The response of extracellular signal-regulated kinase (ERK) to androgen-induced proliferation in the androgen-sensitive prostate cancer cell line, LNCaP.
The mechanisms by which androgens stimulate proliferation of prostate cancer cells are poorly understood. It has been proposed that androgen stimulation may induce the mitogen-activated protein (MAP) kinase system in prostate cancer cells and lead to cellular proliferation. We attempted to evaluate the role of the extracellular signal-regulated kinase (ERK) pathway in the stimulation by androgens of prostate cancer cell proliferation. Androgen-sensitive prostate cancer cell line (LNCaP) cells plated on sterile glass coverslips were treated with 10(-8) M dihydrotestosterone (DHT) or epidermal growth factor (EGF) (10 ng/ml) for periods ranging from 1 min to 96 h. The proliferative index of the cells, evaluated by immunoperoxidase staining of cells with an antibody to Ki-67, was increased at least two-fold at all time points from 5 min to 48 h following exposure to either DHT or EGF. Immunohistochemical evaluation of ERK1/2 and pERK (activated ERK) demonstrated high levels of ERK1/2 in untreated LNCaP cells, while pERK was expressed at much lower levels. Following treatment with DHT, no change in staining intensity for either ERK1/2 or pERK was observed, while treatment with EGF resulted in no change in ERK1/2, but significantly increased cytoplasmic staining for pERK at all time points beyond 2 min. These results were confirmed by Western blot analysis of ERK1/2 and pERK expression in these cell lines following treatment with DHT or EGF. Our findings suggest that the proliferative response of prostate cancer cells to androgens, unlike the proliferative response to EGF, is not mediated by the activation of ERK1/2, and that currently undefined pathways other than those involving ERK1/2 are involved.


Long-term follow-up of patients treated with ileoendorectal pull-through and right colon onlay patch for total colonic aganglionosis.
This study was performed to assess the long-term follow-up of five patients who underwent one-stage ileoendorectal pull-through with right colon onlay patch for total colonic aganglionosis (TCA) at Kaiser Permanente Medical Center. A retrospective review of inpatient and outpatient charts and telephone follow-up of all patients were conducted to obtain current data regarding growth, development, bowel function, and postoperative and late complications. Follow-up has ranged from 2 to 11 years. All patients are at or above the 50th percentile for weight by age and are continent with 1 to 5 daily bowel movements. Only two patients required reoperation. A perirectal abscess developed in one patient 2 months postoperatively. In the second patient a functional obstruction was relieved by sphincterotomy. Ileoendorectal pull-through with right colon onlay patch is associated with few early and late postoperative complications; it appears to be superior to other procedures in the early postoperative period because of the more rapid return to acceptable stooling patterns. This method of reconstruction provides an excellent opportunity for normal growth, development, and long-term bowel function.


Trends in Social Work. Nephrology social work meets integrated care: A partnership for the road ahead.
Integrated care has brought changes to the field of nephrology social work. In turn, nephrology social work has brought innovative contributions to the field of integrated care. The new social work service delivery systems described in this article are sure to help the industry reach its goals to keep care patient-centered while maintaining quality and reducing the costs of treating end stage renal disease. Social workers are called to serve the needs of the client, the family, the community and the society at large. Nephrology social workers are right where they belong in the ESRD integrated care environment. They feel right at home.


Structural Basis of Response Regulator Function.
Response regulators function as the output components of two-component systems, which couple the sensing of environmental stimuli to adaptive responses. Response regulators typically contain conserved receiver (REC) domains that function as phosphorylation-regulated switches to control the activities of effector domains that elicit output responses. This modular design is extremely versatile, enabling different regulatory strategies tuned to the needs of individual signaling systems. This review summarizes structural features that underlie response regulator function. An abundance of atomic resolution structures and complementary biochemical data have defined the mechanisms for response regulator enzymatic activities, revealed trends in regulatory strategies utilized by response regulators of different subfamilies, and provided insights into interactions of response regulators with their cognate histidine kinases. Among the hundreds of thousands of response regulators identified, variations abound. This article provides a framework for understanding structural features that enable function of canonical response regulators and a basis for distinguishing noncanonical configurations.


Nonequilibrium thermodynamics and different axioms of evolution.
Proponents of two axioms of biological evolutionary theory have attempted to find justification by reference to nonequilibrium thermodynamics. One states that biological systems and their evolutionary diversification are physically improbable states and transitions, resulting from a selective process; the other asserts that there is an historically constrained inherent directionality in evolutionary dynamics, independent of natural selection, which exerts a self-organizing influence. The first, the Axiom of Improbability, is shown to be nonhistorical and thus, for a theory of change through time, acausal. Its perception of the improbability of living states is at least partially an artifact of closed system thinking. The second, the Axiom of Historically Determined Inherent Directionality, is supported evidentially and has an explicit historical component. Historically constrained dynamic populations are inherently nonequilibrium systems. It is argued that living, evolving systems, when considered to be historically constrained nonequilibrium systems, do not appear improbable at all. Thus, the two axioms are not compatible. Instead, the Axiom of Improbability is considered to result from an unjustified attempt to extend the contingent proximal actions of natural selection into the area of historical, causal explanations. It is thus denied axiomatic status, and the effects of natural selection are subsumed as an additional level of constraint in an evolutionary theory derived from the Axiom of Historically Determined Inherent Directionality.


Human bone marrow stroma cells display certain neural characteristics and integrate in the subventricular compartment after injection into the liquor system.
Because the neural differentiation capacity of bone marrow stromal cells (BMSCs) is still a matter of controversial debate, we performed a thorough investigation into the differentiation capacity of human BMSCs and examined their therapeutic potency. BMSCs were isolated from the femur and kept in cell cultures with various cultivation protocols being applied. In standard culture conditions using a fetal calf serum-enriched medium, while not exhibiting a neural phenotype, the majority of cells expressed a variety of neuronal marker proteins as well as the astrocyte marker GFAP. Only a minority of stem cells expressed nestin, a marker for neural precursor cells. Cultivation in serum-free medium supplemented with specific growth factors resulted in a markedly higher percentage of nestin-positive cells. To establish the therapeutic potency of bone marrow-derived cells, the synthesis of neurotrophic factors such as NGF, BDNF and GDNF was analyzed under non-stimulating standard culture conditions as well as after a neural selection procedure. The therapeutic potency of BMSCs was further examined with regard to their migratory potential in vitro and after transplantation in vivo. After stereotactic engraftment into the lateral ventricle of adult rats, mesenchymal stem cells were seen to adhere to the ependymocytes and cells of the choroids plexus. Afterwards grafted cells passed through the ependymal barrier, locating in the subventricular space. Their BMSCs took up a close host graft interaction without any degenerative influence on the host cells. Furthermore, there was morphological as well as immunohistochemical evidence for a transdifferentiation within the host tissue. In addition, BMSCs could be efficiently transduced using a third-generation adenoviral vector, indicating their potential feasibility for a gene-therapeutic option.


Characterization of two lipoproteins containing apolipoproteins B and E from lesion-free human aortic intima.
Lesion-free areas of aortic intimas from seven men, 30 to 49 years old, were extracted with aqueous buffer within a few hours after an accidental or sudden death. Two lipoprotein fractions could be isolated by density gradient ultracentrifugation from all cases. The mean composition of fraction I (d less than 1.012 g/ml) resembled that reported for the cholesteryl ester-rich, beta-migrating very low density lipoprotein (beta-VLDL); the composition of fraction II (d 1.021-1.046 g/ml) resembled that of plasma low density lipoprotein (LDL). Mean diameter of the particles was 35 +/- 8 nm in fraction I and 25 +/- 5 nm in fraction II (22 +/- 2 nm in plasma LDL). Both fractions contained apolipoproteins B (apoB) and E (apoE), and had increased electrophoretic mobilities and reduced contents of linoleic acid. The immunoreactivity of apoB to a polyclonal and two monoclonal antibodies in both fractions was not different from that of plasma lipoproteins. The apoE isoform patterns in both fractions were similar to those obtained from the respective postmortem plasmas. When incubated with mouse peritoneal macrophages, fractions I and II enhanced the incorporation of radioactive oleate into cholesteryl esters by 10- to 20-fold and 3- to 4-fold, respectively, in comparison to plasma LDL. In conclusion, our results indicate that lesion-free human aortic intima contains two types of apoB- and apoE-containing lipoprotein particles, both of which might be potentially atherogenic.


The derivation of nitrosamines from some therapeutic amines in the human environment.
Five therapeutic drugs which are secondary and tertiary amines were investigated by reaction mechanisms for the derivation of nitrosamines in the human environments. These drugs are chlorpromazine (tranquilizer), methadone (analgesic), chloroquine (antimalarial), primaquine (antimalarial), and phenacetin (analgesic). Phenacetin is an N-acetylated secondary amine; chloroquine and primaquine are secondary amines; methadone and chlorpromazine are tertiary amines; and chloroquine is also a tertiary amine. In the human environments of the gastrointestinal tract, stomach, and bladder which generate the nitrosating agent, the derivation of various nitrosamines from these drugs has been presented. Dimethyl nitrosamine has been derived from methadone and diethylnitrosamine has been generated from chlorpromazine and chloroquine, respectively. Chlorpromazine, methadone, chloroquine, primaquine, and phenacetin have also produced by reaction mechanisms various nitrosamines of hitherto unknown carcinogenicity. The dimethylnitrosamine and diethylnitrosamine derived from methadone, chlorpromazine, and chloroquine are of proven carcinogenicity in experimental animals and they therefore constitute a hazard to humans.


Breed of boar influences the optimal concentration of gamma-oryzanol needed for semen cryopreservation.
The aim of this study was to investigate the influence of boar breed on the optimal concentration of gamma-oryzanol on the qualities of cryopreserved boar semen. Semen was collected from 20 boars (10 Duroc, 5 Large white and 5 Landrace boars). The semen sample was divided into five groups (A-E) according to the concentration of gamma-oryzanol in extender II, that is 0, 0.08, 0.16, 0.24 and 0.32 mM, respectively. The semen was cryopreserved by nitrogen vapour and storage in nitrogen tank (-196°C). After storage for a week, samples were thawed at 50°C for 12 s and evaluated for progressive motility, sperm viability and acrosome integrity. The results demonstrated that gamma-oryzanol significantly improved progressive motility, viability and acrosome integrity of frozen-thawed boar semen. Considering the influence of breeds on the optimal concentration of gamma-oryzanol, for Duroc boar, gamma-oryzanol at 0.16 mM (group C) yielded the highest percentage of progressive motility, sperm viability and acrosome integrity. For Large white and Landrace boars, gamma-oryzanol at 0.24 mM (group D) showed a significantly higher percentage of progressive motility, viability (not significant in Landrace) and acrosome integrity than other concentrations. In conclusion, the optimal concentration of gamma-oryzanol needed for boar semen cryopreservation in lactose-egg yolk (LEY) freezing extender is not only depended on individual boar but also breed of boar, that is 0.16 mM for Duroc and 0.24 mM for Large white and Landrace.


Temporal patterns recognized by a network of coordinated time delays and coincidence detectors.
A computational model of a neuronal network is described which performs a fundamental task of general perception: recognition of temporal patterns in continuous and uncued neuronal spike trains. The presented network is able to recognize each pattern element (100 ms interval composed of sets of 10, 20, 30 and 40 ms interspike intervals combined in linear order) as it arrives. Its operation is based upon biologically plausible filtering mechanisms and population neurodynamics.


Color Doppler ultrasonography in prediction of the reducibility of intussuscepted bowel in 15 young dogs.
Color Doppler ultrasonography was performed in 15 young dogs with intestinal intussusception to test the hypothesis that color Doppler findings can be used as a predictor of the manual reducibility of the intussusception at celiotomy. Color flow Doppler ultrasonography indicated blood flow within mesentery of the intussuscepted bowel in 12 of 15 dogs and reduction was achieved in nine of these 12 dogs (75%). In the remaining three dogs and in three dogs where no color Doppler signal were observed, an irreducible intussusception was confirmed at celiotomy. Color Doppler ultrasonography is a useful method for predicting the reducibility of intussusception in dogs.


Inter- and intra-species karyotype variations among microsporidia of the genus Encephalitozoon as determined by pulsed-field gel electrophoresis.
Disseminated infections due to microsporidia of the genus Encephalitozoon are detected increasingly, especially in patients with AIDS. Identification of microsporidia can be achieved by a variety of immunological and molecular methods. This study evaluates the feasibility of pulsed-field gel electrophoresis (PFGE) for the analysis of karyotypes of the 3 known species of this genus (Encephalitozoon cuniculi, Encephalitozoon hellem and Encephalitozoon intestinalis) and of 2 of the 3 known E. cuniculi strains (strains I and III). Eleven chromosomal DNA bands were resolved for E. cuniculi and 10 chromosomal DNA bands for E. hellem and E. intestinalis, with molecular sizes ranging from 231 to 320 kb, from 197 to 288 kb and from 195 to 285 kb, respectively, resulting in estimated genome sizes of about 3.0 Mb, 2.5 Mb and 2.4 Mb. Different PFGE chromosomal banding patterns indicate that not only E. cuniculi, as previously described, but also E. hellem, represent a heterogeneous entity. PFGE is a valuable method of evaluating inter- and intra-species variations among Encephalitozoon species that may enable the identification of environmental sources of infection and modes of transmission.


Antibodies to structural and nonstructural gag-coded proteins of type-D retroviruses in humans with lymphadenopathy and AIDS.
The sera of patients with lymphadenopathies (children, suffering from primary immune deficiencies) and AIDS were analysed for the presence of antibodies against D-type retroviruses by means of radioimmunoprecipitation (RIP) and Western blotting. It was established that these sera contain the antibodies derived against p27, the major structural protein of type-D retroviruses, in a considerable percentage (12/80 for lymphadenopathy (LAP) patients and 9/12 for AIDS patients). Some serum samples reacted in RIP with Pr78gag, the precursor of gag-coded proteins of these viruses. The results obtained for AIDS patients are in contrast with those reported by other research groups. Nevertheless, it seems highly probable that D-type retroviruses are truly associated with human immunodeficiencies, as has been shown for simian ones.


Bacillus invictae sp. nov., isolated from a health product.
A Gram-positive, rod-shaped, endospore-forming Bacillus isolate, Bi.(FFUP1) (T), recovered in Portugal from a health product was subjected to a polyphasic study and compared with the type strains of Bacillus pumilus, Bacillus safensis, Bacillus altitudinis and Bacillus xiamenensis, the phenotypically and genotypically most closely related species. Acid production from cellobiose, D-glucose and D-mannose and absence of acid production from D-arabinose, erythritol, inositol, maltose, mannitol, raffinose, rhamnose, sorbitol, starch and L-tryptophan discriminated this new isolate from the type strains of the most closely related species. Additionally, a significant different protein and carbohydrate signature was evidenced by spectroscopic techniques, matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and Fourier transform IR spectroscopy with attenuated total reflectance. Using a chemometric approach, the score plot generated by principal component analysis clearly delineated the isolate as a separate cluster. The quinone system for strain Bi.(FFUP1) (T) comprised predominantly menaquinone MK-7 and major polar lipids were diphosphatidylglycerol, an unidentified phospholipid and an unidentified glycolipid. Strain Bi.(FFUP1) (T) showed ≥ 99% 16S rRNA gene sequence similarity to B. safensis FO-036b(T), B. pumilus (7061(T) and SAFR-032), B. altitudinis 41KF2b(T) and B. xiamenensis HYC-10(T). Differences in strain Bi.FFUP1 (T) gyrB and rpoB sequences in comparison with the most closely related species and DNA-DNA hybridization experiments with Bi.FFUP1 (T) and B. pumilus ATCC 7061(T), B. safensis FO-036b(T), B. altitudinis 41KF2b(T) and B. xiamenensis HYC-10(T) gave relatedness values of 39.6% (reciprocal 38.0%), 49.9% (reciprocal 42.9%), 61.9% (reciprocal 52.2%) and 61.7% (reciprocal 49.2%), respectively, supported the delineation of strain Bi.(FFUP1) (T) as a representative of a novel species of the genus Bacillus, for which the name Bacillus invictae sp. nov. is proposed, with strain Bi.(FFUP1) (T) ( =DSM 26896(T) =CCUG 64113(T)) as the type strain.


Contrast enhanced magnetic resonance imaging as a method to diagnose early inflammatory changes in the temporomandibular joint in children with juvenile chronic arthritis.
Recent studies have stressed early diagnosis of temporomandibular joint (TMJ) involvement in children with juvenile chronic arthritis (JCA) to initiate treatment before destruction of the condylar head and growth alterations take place. TMJ involvement is often asymptomatic, but studies with contrast enhanced magnetic resonance imaging (MRI) in other joints have shown that it is possible to detect the early inflammatory changes. Thirty TMJ in 15 children with newly diagnosed JCA (mean age 12.0 years) were examined clinically, with radiographs and with MRI enhanced with gadolinium diethylene thiamine pentaacetic acid (Gd-DTPA). A control group of 10 healthy children (mean age 11.5 yrs) were examined clinically and with MRI. The MRI variables included T1 weighted images before and after administration of Gd-DTPA with and without fat suppression. MRI enhanced with Gd-DTPA indicated inflammatory activity in 87% of the patients. Conventional MRI without contrast medium proved to be insignificant in diagnosing early inflammatory changes. Enhanced MRI is very efficient in diagnosing early inflammatory changes of the TMJ and is a more sensitive method than the clinical examination and radiographs.


Three-dimensional photoacoustic imaging using fiber-based line detectors.
For photoacoustic imaging, usually point-like detectors are used. As a special sensing technology for photoacoustic imaging, integrating detectors have been investigated that integrate the acoustic pressure over an area or line that is larger than the imaged object. Different kinds of optical fiber-based detectors are compared regarding their sensitivity and resolution in three-dimensional photoacoustic tomography. In the same type of interferometer, polymer optical fibers yielded much higher sensitivity than glass fibers. Fabry-Perot glass-fiber interferometers in turn gave higher sensitivity than Mach-Zehnder-type interferometers. Regarding imaging resolution, the single-mode glass fiber showed the best performance. Last, three-dimensional images of phantoms and insects using a glass-fiber-based Fabry-Perot interferometer as integrating line detector are presented.


Comparison of meat quality, fatty acid composition and aroma volatiles of dry-aged beef from Hanwoo cows slaughtered at 60 or 80 months old.
The objective of this study was to compare the quality of dry-aged beef from cull Hanwoo cows slaughtered at 60 or 80 months old. A total of eight cull Hanwoo carcasses with a quality grade of 3 (low-grade) were selected and divided into two age groups: 63.5 ± 2.5 months old (n = 4) and 87.8 ± 4.5 months old (n = 4). Whole longissimus thoracis et lumborum from the 11th rib to the last lumbar vertebrae, including the back fat, was removed from the carcass at 24 h postmortem and aged for 50 days in darkness at a temperature of 2°C ± 1°C, a relative humidity of 85% and an air flow of 2 m/s. The sampling was performed aseptically after 0, 20, 24, 40 and 50 days of aging. Regardless of the aging period, aging increased the lightness (p<0.05), redness (p<0.05) and yellowness (p<0.05) at initial blooming (90 min after slicing) and the overall acceptance (p<0.05). No further tenderization effect was found after 20 days of aging, but aging for 50 days significantly increased the lipid oxidation (p<0.05). The generation of aroma volatiles in the roast steak from aged samples was higher (p<0.05) than that of non-aged samples. No significant effect of age at slaughter was found on the color, pH, water-holding capacity, cooking loss, shear force value, bacterial counts, volatile basic nitrogen, consumer acceptance, lipid oxidation, fatty acid composition or aroma volatiles. The quality of dry-aged beef obtained from cull Hanwoo cows slaughtered at either 60 or 80 months old with similar quality grade was comparable, and extending dry aging for more than 40 days is not recommended considering the costs and further lipid oxidation.


[Anesthesia-induced changes in the preload-dependent circulatory reactions in patients with coronary heart disease].
The influence of preload changes (table tilt) on the hemodynamic regulation before and after induction of neuroleptanalgesia was studied in 31 patients with coronary heart disease. The induced preload changes are balanced in the awake patient for the maintenance of normal arterial pressure by regulation of stroke volume and peripheral vascular resistance. This regulation does not exist after induction of anaesthesia. Splitting the patients into sub-groups with good or poor left ventricular function, different ventricular function curves were obtained before and after the induction of anaesthesia. The pharmacologic and ventilatory reasons for the changed regulation of circulation are discussed. For investigations into hemodynamic changes produced by intervention in anaesthesia and intensive therapy, it is recommended to define more exactly the cardiovascular status of patients and the study conditions.


Continuous circular cycling in bipolar disorder as a predictor of poor outcome.
This prospective study aims to determine if patients with bipolar disorder with a continuous circular course (CCC) are significantly different on clinical characteristics and response to long-term treatment from those with a non-continuous circular course (N-CCC). CCC was defined as the alternation of depression and (hypo)mania without a completely free interval, and N-CCC as the presence of free intervals after the sequence mania-depression or depression-mania. The study sample includes 140 consecutive patients with bipolar I or II disorder according to DSM-IV criteria, aged 18-65 years and receiving prophylactic treatment for. Treatment was based upon international guidelines and clinical experience at the time of patient's enrollment (from January 1998 to January 2006). Primary outcome was the absence of new episodes during the follow-up. Significance level was set at p<0.05. Twenty-eight percent of the sample has CCC. Compared with N-CCC, CCC patients were older, had a later onset, a higher number of total, depressive and (hypo)manic episodes, and of switches, and spent a higher percentage of time ill in the year before entering the study. Polarity at onset and subsequent recurrences were more frequently mixed in N-CCC than in CCC patients. The proportion of patients in the CCC group who had no recurrences during the follow-up was significantly lower than in the N-CCC group. The presence or absence of a free intervals over the course of illness identifies two subtypes of bipolar disorder that differ in clinical presentation, outcome, and response to long-term treatment.


Physalis peruviana L. (Solanaceae) Is Not a Host of Ceratitis capitata (Diptera: Tephritidae): Evidence from Multi-Year Field and Laboratory Studies in Colombia.
Scientifically-based, tephritid fly host status determination lies at the heart of strategic regulatory decisions impinging on international fruit trade. Here we conducted intensive field and laboratory studies with peaches as controls, to determine the host status of Physalis peruviana for the Medfly-Ceratitis capitata, as this fruit is experiencing a consumption boom worldwide. A total of 98,132 Uchuvas (local name), collected in Colombia from the plant or the ground over a three-year period (2016-2018) did not yield a single C. capitata larva or pupa, thus reaching a Probit 9 level with 99.9968% efficacy and 96% confidence level. Field-cage studies with enclosed fruit-bearing Uchuva plants, exposing fruit with an intact, damaged or totally removed husk to the attack of C. capitata, also failed to yield infestations. Highly artificial choice experiments, exposing gravid females to unripe and fully ripe fruit, resulted in an absence of infestations, even when overripe Uchuvas were artificially damaged. The husk and surface resins/waxes inhibit fly landings on fruit and oviposition activity. Considering our results and the fact that the foliage, husk and fruit of P. peruviana are repellent/toxic to insects, we conclude that this plant should be treated as a non-natural and non-conditional host of C. capitata.


Existence and stability of persistent states in large neuronal networks.
We study the existence and stability of persistent states in large networks of quadratic integrate-and-fire neurons. The networks consist of two populations, one excitatory and one inhibitory. The stability of the asynchronous state is studied analytically. Our study demonstrates the role of recurrent inhibition and inhibitory-inhibitory interactions in stable persistent activity in large neuronal networks.


The tale of radioiodine and Graves' orbitopathy.
Autoimmunity against the thyrotropin receptor (TSH-R) is a key pathogenic element in Graves' disease (GD) and the autoimmune aberration may be modified by antithyroid treatment. An association between radioactive iodine (RAI) therapy for GD and the development or worsening of Graves' orbitopathy (GO) is widely quoted. RAI-associated leakage of thyroid antigen(s) leads to an increased production of TSH-R antibodies that may initiate the eye injury. RAI therapy leads to prolonged worsening of autoimmunity against the TSH-R, and the number of patients entering remission of TSH-R autoimmunity is considerably lower than with other antithyroid therapies. Scientific evidence has indicated that RAI treatment for GD is associated with increased risk of occurrence or progression of GO compared with antithyroid drugs (ATD) and thyroid surgery. The risks of developing new GO or worsening of preexisting GO is around 20% after RAI and around 5% after ATD. The risk of developing severe GO after RAI is around 7%. Smoking, high levels of pretreatment serum triiodothyronine, and post-RAI hypothyroidism are associated with increased risk of GO, whereas a high TSH-R autoantibody titer is an independent risk factor for the progression of GO. In patients with mild preexisting GO, steroid prophylaxis is effective in preventing deterioration of GO. Also, routine use of prophylactic oral steroids with RAI therapy should be considered in GD patients without overt GO, but even more so in those at higher risks of eye complications such as smokers, old men, and those with severe hyperthyroidism or high TSH-R antibody titers. In contrast to ATD, remission of TSH-R autoimmunity after RAI therapy is less common, and RAI for GD is associated with definite increased risk of GO. Oral steroids are beneficial for patients with preexisting GO, particularly smokers.


Genetic alterations of serous borderline tumors of the ovary compared to stage I serous ovarian carcinomas.
Borderline tumors of the ovary comprise 10-20% of all epithelial ovarian tumors, and are placed between clearly benign and obviously malignant ovarian tumors. The issue of whether borderline tumors are precursors of invasive carcinoma or distinct clinical entities, however, is still the subject of discussion. To increase our understanding in relation to this issue, the aim of our study was to analyze both serous borderline and invasive ovarian tumors, and to investigate early carcinogenesis in serous ovarian tumors. Using comparative genomic hybridization, we compared cytogenetic changes in borderline ovarian tumors and stage I invasive tumors. The average number of genetic alterations differed significantly between the borderline and the invasive tumors (1.9 and 9.2, respectively). The most common genetic alterations among the borderline tumors were loss of chromosome 17, 20q, and 18p, and gain of 12p13 approximately q23. These changes were also found among the invasive tumors in a similar percentage. In conclusion, we found four distinct cytogenetic alterations that might be early events in serous ovarian tumors, and that might also characterize a subgroup of borderline ovarian tumors that may have the potential to progress and develop malignancy.


Perceiving possibilities for action: on the necessity of calibration and perceptual learning for the visual guidance of action.
Tasks such as steering, braking, and intercepting moving objects constitute a class of behaviors, known as visually guided actions, which are typically carried out under continuous control on the basis of visual information. Several decades of research on visually guided action have resulted in an inventory of control laws that describe for each task how information about the sufficiency of one's current state is used to make ongoing adjustments. Although a considerable amount of important research has been generated within this framework, several aspects of these tasks that are essential for successful performance cannot be captured. The purpose of this paper is to provide an overview of the existing framework, discuss its limitations, and introduce a new framework that emphasizes the necessity of calibration and perceptual learning. Within the proposed framework, successful human performance on these tasks is a matter of learning to detect and calibrate optical information about the boundaries that separate possible from impossible actions. This resolves a long-lasting incompatibility between theories of visually guided action and the concept of an affordance. The implications of adopting this framework for the design of experiments and models of visually guided action are discussed.


Transplantable zebrafish models of neuroendocrine tumors.
Neuroendocrine tumors (NETs) are rare neoplasms whose incidence is increasing. NETs constitute a heterogeneous group of tumors. Their clinical features, functional properties, and clinical course are different on the basis of their site of origin. Due to the heterogeneity of these tumors, a coordinated multidisciplinary approach is required in these patients. However, medical doctor encounters many difficulties when providing care for patients with NETs. This review provides an overview of the state of the art of zebrafish model in the cancer research with a main focus on NETs.


Activation of mouse peritoneal macrophages during infection with Salmonella typhimurium does not result in enhanced intracellular killing.
Our study was performed to investigate whether macrophages become activated during an infection with Salmonella typhimurium and, if so, whether these activated macrophages kill S. typhimurium faster than resident macrophages. Mice received i.v. injections with a sublethal number of S. typhimurium; on about day 12 of the infection the numbers of bacteria in the liver and the spleen were maximal. During the infection, activation of peritoneal macrophages could be demonstrated on the basis of three criteria, i.e., the ability to inhibit the proliferation of Toxoplasma gondii, an enhanced production of H2O2 and an increased expression of Ia Ag. The rate of in vitro intracellular killing of S. typhimurium by these activated macrophages was not increased compared to that for resident macrophages. To determine the growth of S. typhimurium in activated mice a nalidixic acid-resistant mutant strain, called S. typhimurium 510R, was used. The net growth rates of the mutant S. typhimurium 510R in the spleen of S. typhimurium 510-activated and normal mice were similar. However, in the liver of S. typhimurium 510-activated mice the number of S. typhimurium 510R did not change during 3 to 48 h after injection. The role of specific antibodies during the initial phase of the infection was negligible, because only low levels of antibodies were detected during the first 15 days of infection and the growth rates of S. typhimurium 510 in the spleen and liver of mice with high titers of antibodies were not significantly different from the rates in normal mice. The results of this study demonstrate that although macrophages become activated during an infection with S. typhimurium, these cells do not display an enhanced bactericidal activity in vitro and in vivo no significant effect on the growth rate of S. typhimurium in the spleen and a bacteriostatic effect in the liver is found. Hence macrophage activation is probably not very important in the host defense against S. typhimurium.


Nicotine addiction and nicotinic receptors: lessons from genetically modified mice.
The past decades have seen a revolution in our understanding of brain diseases and in particular of drug addiction. This has been largely due to the identification of neurotransmitter receptors and the development of animal models, which together have enabled the investigation of brain functions from the molecular to the cognitive level. Tobacco smoking, the principal - yet avoidable - cause of lung cancer is associated with nicotine addiction. Recent studies in mice involving deletion and replacement of nicotinic acetylcholine receptor subunits have begun to identify the molecular mechanisms underlying nicotine addiction and might offer new therapeutic strategies to treat this addiction.


Diagnosis and treatment of bowel perforation following pediatric orthotopic liver transplantation.
Bowel perforation is a frequent cause of mortality after pediatric orthotopic liver transplantation. The aims of this study were to identify the cause of this phenomenon and to examine current methods of treatment. This is a retrospective analysis of 246 pediatric patients who underwent orthotopic liver transplantation at a large, urban, tertiary care medical center between 1984 and 1992. We examined the frequency of bowel perforations after transplantation and identified predisposing factors and signs. In this series, bowel perforations occurred in 24 of 246 recipients and were common in those who had previous liver-related surgery (22 patients). Clinical signs included fever (13 patients), leukocytosis (14 patients), and free air on abdominal roentgenograms (11 patients). Perforation occurred at the Roux-en-Y limb in 15 of 24 recipients as well as in the right transverse colon (five patients), terminal ileum (three patients), and duodenum (one patient). The repair was resection and/or primary closure (18 patients), or diversion (six patients). Recurrent perforations (nine patients) could not be attributed to the method of the repair. Perforation-related sepsis was the primary cause of death in 12 patients (50%) and was more common among patients who developed recurrent perforation (seven [78%] of nine patients). The occurrence and location of bowel perforation after pediatric orthotopic liver transplantation suggests that the cause is related to bowel injury during difficult hepatectomy. Mortality may be reduced by early second-look operations in high-risk patients.


[A novel approach to the detection of Neisseria gonorrhoeae employing DNA probe method].
The present study was undertaken to establish a novel detection method for Neisseria gonorrhoeae (N. gonorrhoeae). DNA probe obtained from Gen-probe Inc. was employed and clinically isolated strains (18 species, 81 strains) were applied to verify the quality and quantity of the method. The present data revealed that the method is specific to detect N. gonorrhoeae (30/30): neither gram positive nor negative oraganisms were detectable by the method (0/51). It has been shown, further more, that there exists a significant correlation between the number of the bacteria and the relative light units (r = 0.96). The threshold of cell numbers, on the other hand, was found to be 5 X 10(3) cfu/tube. The detection sensitivity for N. gonorrhoeae was not influenced by the presence of other bacteria, and not decreased by using heat-treated or drug-treated N. gonorrhoeae organisms. The present study also provides some experimental evidences that the method can also be applicable for the detection of bacteriolytic action of drugs.


Free fatty acids repress the GLUT4 gene expression in cardiac muscle via novel response elements.
Hyperlipidemia (HL) impairs cardiac glucose homeostasis, but the molecular mechanisms involved are yet unclear. We examined HL-regulated GLUT4 and peroxisome proliferator-activated receptor (PPAR) gamma gene expression in human cardiac muscle. Compared with control patients, GLUT4 protein levels were 30% lower in human cardiac muscle biopsies from patients with HL and/or type 2 diabetes mellitus, whereas GLUT4 mRNA levels were unchanged. PPARgamma mRNA levels were 30-50% lower in patients with HL and/or diabetes mellitus type 2 than in controls. Reporter studies in H9C2 cardiomyotubes showed that HL in vitro, induced by high levels of arachidonic (AA) stearic, linoleic, and oleic acids (24 h, 200 mum) repressed transcription from the GLUT4 promoter; AA also repressed transcription from the PPARgamma1 and PPARgamma2 promoters. Co-expression of PPARgamma2 repressed GLUT4 promoter activity, and the addition of AA further enhanced this effect. 5'-Deletion analysis revealed three GLUT4 promoter regions that accounted for AA-mediated effects: two repression-mediating sequences at -443/-423 bp and -222/-197 bp, the deletion of either or both of which led to a partial derepression of promoter activity, and a third derepression-mediating sequence at -612/-587 bp that was required for sustaining this derepression effect. Electromobility shift assay further shows that AA enhanced binding to two of the three regions of cardiac nuclear protein(s), the nature of which is still unknown. We propose that HL, exhibited as a high free fatty acid level, modulates GLUT4 gene expression in cardiac muscle via a complex mechanism that includes: (a) binding of AA mediator proteins to three newly identified response elements on the GLUT4 promoter gene and (b) repression of GLUT4 and the PPARgamma genes by AA.


Intradiscal administration of osteogenic protein-1 increases intervertebral disc height and proteoglycan content in the nucleus pulposus in normal adolescent rabbits.
A study of the disc height and biochemical changes in the rabbit intervertebral disc after injection of osteogenic protein-1 into the nucleus pulposus. To evaluate the in vivo effects of osteogenic protein-1 administered intradiscally to the intervertebral disc of rabbits. Growth factors, such as osteogenic protein-1 and transforming growth factor-beta, have the ability to stimulate synthesis of proteoglycan and collagen in vitro. No attempts have yet been made to determine the effects of these growth factors in an in vivo model. Twenty-four New Zealand adolescent white rabbits were divided evenly into two subject groups. In one group, three consecutive intervertebral discs were injected with saline; whereas in the other group, they were injected with osteogenic protein-1 in saline. At 2, 4, and 8 weeks after the injection, the intervertebral disc heights of the injected specimens were measured by lateral plain radiographs and compared with preinjection measurements. The change in disc height was expressed as the percent disc height index compared with the preinjection value. After the radiographic measurements were obtained, the intervertebral discs were removed and analyzed for DNA, proteoglycan, and collagen contents. At 2 weeks after the injections, the mean disc height index of the osteogenic protein-1-injected discs was 15% greater than that of the saline group. The increase in disc height with osteogenic protein-1 injection was still statistically significant at the 4- and 8-week time points. The proteoglycan content of the nucleus pulposus in discs injected with osteogenic protein-1 was higher than that in the saline group at the 2-week time point. The osteogenic protein-1-induced effect on the proteoglycan content was also present at the 4- and 8- week time intervals; however, these increases were not statistically significant. There were no significant differences in the DNA content, normalized to noninjected control, of the nucleus pulposus between the saline and osteogenic protein-1 groups. However, a significant increase in the DNA content of the anulus fibrosus in the osteogenic protein-1 group, compared with that of the anulus fibrosus in the saline group, was observed after 4 weeks. To date, no study has demonstrated the potential in vivo effects of growth factors on the intervertebral disc. The present study reports that the intradiscal administration of osteogenic protein-1 in vivo results in an increased disc height present at 2, 4, and 8 weeks and an increase in PG content of the nucleus pulposus at the 2-week time point. Therefore, osteogenic protein-1 may act to stimulate metabolic activity in the nucleus pulposus. Continued research is needed to evaluate the potential of growth factor-induced reversal of age-related disc degeneration in an appropriate animal model. In addition, studies in a nonhuman primate animal model will be essential before considering intradiscal injection of growth factors in humans.


Simultaneous overexpression of multidrug efflux pumps in Pseudomonas aeruginosa non-cystic fibrosis clinical isolates.
The purpose of this study was to examine expression and regulation of 6 multidrug efflux systems, including MexAB-OprM, MexCD-OprJ, MexEF-OprN, MexXY, MexJK, and MexVW, in 13 non-cystic fibrosis (CF) clinical isolates of Pseudomonas aeruginosa. These isolates displayed a high level of resistance to many clinically important antibiotics. Some isolates simultaneously overexpressed up to 4 different Mex systems, as determined by quantitative real-time reverse transcription PCR. None of the isolates overexpressed MexCD-OprJ, and only 1 isolate overproduced MexJK. All the isolates overexpressed MexXY, while overexpression of MexEF-OprN and MexVW was common. DNA sequencing analysis of regulatory genes showed that no clear correlation could be established among (i) the presence of mutations, (ii) the type of mutations, (iii) the expression level of the Mex systems, and (iv) resistance to antibiotic substrates. The results suggest that the concomitant overexpression of some Mex systems may superimpose their antimicrobial drug efflux capabilities, contributing to the multidrug resistance phenotype in the P. aeruginosa non-CF clinical isolates. The existence of uncharacterized regulators for the Mex systems was signified.


The complex thiol-palladium interface: a theoretical and experimental study.
This paper presents a theoretical study of the surface structures and thermodynamic stability of different thiol and sulfide structures present on the palladium surface as a function of the chemical potential of the thiol species. It has been found that as the chemical potential of the thiol is increased, the initially clean palladium surface is covered by a (√3 × √3)R30° sulfur lattice. Further increase in the thiol pressure or concentration leads to the formation of a denser (√7 × √7)R19.1° sulfur lattice, which finally undergoes a phase transition to form a complex (√7 × √7)R19.1° sulfur + thiol adlayer (3/7 sulfur + 2/7 thiol coverage). This transition is accompanied by a strong reconstruction of the Pd(111) surface. The formation of these surface structures has been explained in terms of the catalytic properties of the palladium surface. These results have been compared with X-ray photoelectron spectroscopy results obtained for thiols adsorbed on different palladium surfaces.


Pharmacogenetics of antiangiogenic and antineovascular therapies of age-related macular degeneration.
Age-related macular degeneration (AMD), the most common age-related disease causing irreversible visual loss in industrialized countries, is a complex and multifactorial illness. Researchers have found components of the complement alternative pathway inside drusen and Bruch's membrane of AMD patients, underlying a possible important role of complement factor H in the pathogenesis of AMD. The neovascular (wet) AMD is the most destructive form and it is characterized by invasion of new blood vessels into subretinal spaces with subsequent exudation and bleeding, resulting in scarring of the macular region and loss of the central vision. The hallmark of the neovascular form is the choroidal neovascularization, where VEGF-A has an important role in the pathogenesis of the disease. SNPs of these genes have recently been investigated as potential pharmacogenetic markers of the antiangiogenic and antineovascular therapy of AMD, which includes verteporfin photodynamic therapy and anti-VEGF-A drugs, such as pegaptanib, bevacizumab and ranibizumab. The CFH rs1061170 CT and TT genotypes have been associated with an improvement of visual acuity in bevacizumab or ranibizumab treated patients, whereas patients harboring VEGF-A rs699946 G allele responded better to bevacizumab-based therapy if compared with patients carrying the A allele. In conclusion, the discovery of pharmacogenetic markers for the personalization of the antiangiogenic and/or antineovascular therapy could be, in the future, a key issue in ophthalmology to obtain a personalization of the therapy and to avoid unnecessary costs and adverse drug reactions.


[Prostate cancer screening: an update].
Prostate cancer screening using PSA is controversial because of a low specificity and detection of non clinically relevant cancer. Two important studies have been published recently. One of two studies suggests a 20% lowering in specific prostate cancer mortality due to PSA screening. This benefit is relevant but implies at a high risk of overtreatment and treatment-related complications. Currently PSA screening is only proposed as an individual screening for informed patients.


The coming of age of antibiotics: discovery and therapeutic value.
Origins of antibiotic drug discovery are frequently traced to 1929 when Alexander Fleming recognized the antibacterial activity of a substance secreted by Penicillium notatum on a contaminated culture plate. However, the subsequent development of penicillin as a therapeutic agent was not realized until the early 1940s, after a consortium of academic and pharmaceutical scientists from England and the United States developed sufficiently advanced fermentation technology to produce high-purity penicillin in large enough quantities for medical supplies. It was at this time that the antibiotic era was truly successfully launched. During the following decade, unprecedented antibiotic research and development emerged in academic laboratories and the pharmaceutical industry, resulting in identification of most of the antibiotic classes currently used therapeutically. This short historical commentary describes some of these early events, beginning with a conference held at the New York Academy of Sciences in 1946, the first conference to focus entirely on the latest science related to the identification and characterization of antibacterial substances produced by microorganisms.


Distal femoral replacement by custom-made prostheses. Clinical follow-up and survivorship analysis.
We report the long-term clinical follow-up and survivorship analysis of 40 distal femoral replacements performed between 1964 and 1980 for traumatic, locally aggressive and malignant conditions. Custom-made prostheses with fully-constrained knee joints were used to replace a mean of 42% of the length of the femur. Survivorship analysis showed a cumulative success rate of 80% at eight years, with no subsequent deterioration at 18 years. Clinical assessment revealed 78% excellent or good results. Failure was due to infection in three cases, and in two to fracture of a now-outmoded femoral stem.


Basilar bifurcation aneurysms associated with persistent primitive hypoglossal artery.
We report two cases of ruptured basilar bifurcation aneurysm associated with a persistent primitive hypoglossal artery. Angiograms revealed low-positioned aneurysms; in both cases bilateral vertebral arteries and posterior communicating arteries were hypoplastic or aplastic. Both aneurysms were successfully clipped via subtemporal transtentorial approach through the craniotomy ipsilateral to the side of the primitive hypoglossal artery. The ipsilateral craniotomy and exposure of the cervical carotid artery were helpful for obtaining the proximal control of the basilar artery needed to perform the clipping procedure with safety.


BRAF inhibition in hairy cell leukemia with low-dose vemurafenib.
The activating mutation of the BRAF serine/threonine protein kinase (BRAF V600E) is the key driver mutation in hairy cell leukemia (HCL), suggesting opportunities for therapeutic targeting. We analyzed the course of 21 HCL patients treated with vemurafenib outside of trials with individual dosing regimens (240-1920 mg/d; median treatment duration, 90 days). Vemurafenib treatment improved blood counts in all patients, with platelets, neutrophils, and hemoglobin recovering within 28, 43, and 55 days (median), respectively. Complete remission was achieved in 40% (6/15 of evaluable patients) and median event-free survival was 17 months. Response rate and kinetics of response were independent of vemurafenib dosing. Retreatment with vemurafenib led to similar response patterns (n = 6). Pharmacodynamic analysis of BRAF V600E downstream targets showed that vemurafenib (480 mg/d) completely abrogated extracellular signal-regulated kinase phosphorylation of hairy cells in vivo. Typical side effects also occurred at low dosing regimens. We observed the development of acute myeloid lymphoma (AML) subtype M6 in 1 patient, and the course suggested disease acceleration triggered by vemurafenib. The phosphatidylinositol 3-kinase hotspot mutation (E545K) was identified in the AML clone, providing a potential novel mechanism for paradoxical BRAF activation. These data provide proof of dependence of HCL on active BRAF signaling. We provide evidence that antitumor and side effects are observed with 480 mg vemurafenib, suggesting that dosing regimens in BRAF-driven cancers could warrant reassessment in trials with implications for cost of cancer care.


Occurrence of phosphate acquisition genes in Prochlorococcus cells from different ocean regions.
The cyanobacterium Prochlorococcus is the numerically dominant phototroph in oligotrophic parts of the oceans. Recently, it was shown that the distribution of phosphate acquisition genes did not match the 16S rRNA phylogeny among isolates from this group but rather appeared related to phosphate availability where the strains had been isolated. To further understand adaptation to phosphate limitation in Prochlorococcus, the distribution of phosphate acquisition genes was investigated in different ocean regions and related to local ortho-phosphate concentration. In regions characterized by less than 0.1 microM phosphate, most Prochlorococcus cells contain genes involved in phosphate uptake, regulation and utilization of organic phosphates. In contrast, most of these genes are absent in regions with more than 0.1 microM phosphate with the exception of genes involved in transport of phosphate (phoE and pstABCS) and three genes of unknown function. This pattern of phosphate acquisition genes showed no significant correspondence to the distribution of rRNA phylotypes. In addition, it was demonstrated that several genes in a separate genomic island were commonly present in low-P sites while absent in high-P sites. Overall, this study further demonstrates a linkage between environmental conditions in the ocean and genome content of Prochlorococcus.


Screening low fire blight susceptible Crataegus species for host suitability to hawthorn leaf-curling aphids (Dysaphis spp.).
The group of hawthorn leaf-curling aphids (Dysaphis spp.) hosted by the common hawthorn Crataegus monogyna Jacq. may play an important role in the biological control of the rosy apple aphid, Dysaphis plantaginea (Passerini), by increasing reproduction opportunities for the indigenous hymenopteran parasitoid Ephedrus persicae Froggatt. Unfortunately, most fruitgrowers hesitate to introduce the common hawthorn in their orchards because they fear fire blight infections which may be transmitted by this highly susceptible hawthron species. This potential hazard led us to investigate the suitability to leaf-curling aphids of alternative Crataegus species. As representative for these closely-related aphids, the species Dysaphis apiifolia petroselini (Börner) was used in the trials. Ten Crataegus species characterized by their very low susceptibility to fire blight were examined from two angles. Firstly, aphid sexuals were introduced in autumn onto the different species to verify whether egg laying could take place. Secondly, the development of fundatrices and gall formation were followed the next spring. Although eggs and mature fundatrices could be obtained on almost all species, no fundatrice-hosting galls were recorded in spring. The possible causes of these negative results with respect to the geographical origin of the particular Crataegus species involved in this work are discussed.


Linkage disequilibrium and selection response in two-stage marker-assisted selection of dairy cattle over several generations.
A stochastic simulation was carried out to investigate the advantage of marker-assisted selection (MAS) in comparison with traditional selection over several generations. The selection goal was a sex-limited trait or a linear combination of traits with a polygenic component, two unlinked additive QTL and a non-genetic component. The simulated QTL were moderate or large and the allele frequencies were varied. Two stages of selection among the male offspring were carried out. In the first stage marker information was used to select among full sibs (MAS) or one full sib was chosen at random. In the second stage young bulls were selected based on a progeny test. The response in total genetic gain was faster with MAS than with traditional selection and persisted over several generations. With a QTL of moderate size and initial allele frequencies of the favourable allele of 0.05 the response with MAS was 6% higher than with traditional selection in the sires selected after progeny test. MAS in a within-family two-stage selection scheme improved the genetic merit of selected bulls even when linkage disequilibrium between QTL and polygenes was initially increased.


Morphological and functional changes of blood-brain barrier in kindled rats with cortical dysplasia.
Cortical dysplasia (CD) is one of the major causes contributing to epileptogenesis associated with blood-brain-barrier (BBB) disturbances. The current study investigated the functional and ultrastructural changes of BBB in pentylenetetrazole (PTZ)-kindled rats with CD. Pregnant rats on E17 were exposed to 145 cGy of gamma-irradiation and offspring were used for experiments. The rats were given PTZ three times per week to induce kindling. The permeability of BBB was determined by using sodium fluorescein (NaFlu). Immunohistochemistry for occludin, GFAP and c-fos, western-blot analysis for occludin and electron microscopy for the ultrastructural alterations in BBB were performed. The brain level of NaFlu did not increase in rats with CD and/or kindling. Following administration of a convulsive dose of PTZ, a significant increase in BBB permeability was observed in kindled rats with CD. Occludin immunoreactivity and expression remained essentially unchanged in all groups. Slightly enhanced immunoreactivity for GFAP was observed in all groups except control. c-fos immunoreactivity in brain sections of kindled rats with CD displayed a striking increase by convulsive PTZ challenge. Tight junctions were ultrastructurally intact, whereas markedly increased number of pinocytotic vesicles was noted in brain endothelium of kindled rats with CD by convulsive dose of PTZ. The present study showed that epileptic seizures induced by convulsive PTZ challenge during kindling-mediated epileptogenesis in the presence of CD changed both functional and ultrastructural properties of the BBB and considerably enhanced transendothelial vesicular transport, while paracellular pathway was apparently not involved in this setting.


Pulmonary pressure/volume relationships during the last phase of delivery and the first postnatal breaths in human subjects.
Intrathoracic pressure and volume changes during delivery and the first postpartum breaths were measured in 17 term infants. The following findings emerged: (1) Infants were often exposed to high pressures during delivery, when significant volumes of lung fluid were expressed. (2) Despite this, none of the infants' lungs reinflated by passive "elastic recoil." (3) The active inspiratory effort required for reinflation was usually small or moderate, and an "opening pressure" did not appear to be necessary for the initial rise in volume. It is believed that diaphragm and intercostal muscle tone falls or disappears during delivery and returns during the first breath.


Understanding Gunshot Residue Evidence and Its Role in Forensic Science.
Gunshot residue, or GSR, can be a valuable tool in forensic science, but its importance depends greatly on how it is utilized during an investigation and applied in criminal courts. This comprehensive review defines what constitutes GSR resulting from a discharged firearm. Sampling methods and analytical testing instrumentation will be discussed along with data interpretation and limitations of analysis.


Zebrafish Embryonic Lipidomic Analysis Reveals that the Yolk Cell Is Metabolically Active in Processing Lipid.
The role of lipids in providing energy and structural cellular components during vertebrate development is poorly understood. To elucidate these roles further, we visualized lipid deposition and examined expression of key lipid-regulating genes during zebrafish embryogenesis. We also conducted a semiquantitative analysis of lipidomic composition using liquid chromatography (LC)-mass spectrometry. Finally, we analyzed processing of boron-dipyrromethene (BODIPY) lipid analogs injected into the yolk using thin layer chromatography. Our data reveal that the most abundant lipids in the embryo are cholesterol, phosphatidylcholine, and triglyceride. Moreover, we demonstrate that lipids are processed within the yolk prior to mobilization to the embryonic body. Our data identify a metabolically active yolk and body resulting in a dynamic lipid composition. This provides a foundation for studying lipid biology during normal or pharmacologically compromised embryogenesis.


The effects of quercetin protect cardiomyocytes from A/R injury is related to its capability to increasing expression and activity of PKCε protein.
Quercetin is a ubiquitous flavonoid found in vegetable foods. Epidemiological and animal studies have reported an inverse association between quercetin intakes and occurrence and development of various cardiovascular diseases. Some researchers have inferred that the mechanisms of quercetin to protect cardiomyocytes from ischemia/reperfusion injury may be involved in modulation of intracellular signal pathways and regulation of proteins expression beyond its antioxidant activity. The aim of this study was to investigate whether quercetin protect cardiomyocytes from anoxia/reoxygenation injury through PKCε pathway. Neonatal rat primary cardiomyocytes were pretreated with quercetin or quercetin plus εV1-2, a selective PKCε inhibitor, prior to A/R treatment. Western blotting analysis showed that the level of PKCε and phosphor-PKCε Ser297 in the quercetin pretreatment group were all increased significantly compared to the control or A/R group. Subsequent assays showed that pretreated with quercetin could increase the viability of neonatal rat primary cardiomyocytes suffered A/R, decrease the apoptosis and ROS and alleviate the loss of mitochondrial membrane potential induced by A/R injury. However, the protective effects of quercetin disappeared in the group pretreated with εV1-2. Thus, for the first time, we revealed that one of the mechanisms of quercetin protecting cardiomyocytes from A/R injury might be increase the expression of PKCε protein and then enhance the activity of its downstream pathway.


Characterisation of Dichelobacter nodosus isolates from Norway.
An outbreak of ovine footrot in Norway in 2008, the first reported since 1948, prompted action to investigate Norwegian isolates of Dichelobacter nodosus. A total of 579 isolates from 124 different farms were characterised. These included 519 isolates from sheep, 52 isolates from cattle and 8 isolates from goats. The potential virulence of the isolates was assessed by the gelatin gel test (GG-test) and the elastin agar test, that test the heat stability and elastase activity of bacterial proteases, respectively. The isolates were also tested for the presence of intA by PCR, and allocated to serogroups by differentiation of fimA variants using multiplex PCR or sequencing. Thirty of the isolates were also serogrouped by slide agglutination. Three hundred and five isolates were defined as virulent by the GG-test. All these were from sheep from 52 farms located in the county of Rogaland in the south west of Norway. All isolates from cattle and goats were defined as benign by the GG-test. IntA was only detected in 6 (2.0%) of the virulent isolates. All serogroups except D and F were detected. Three hundred and seventy-two (64.3%) of the isolates belonged to serogroup A, and 96% of the virulent isolates belonged to this serogroup. On the grounds that virulent isolates were only found in one county, and that the majority belonged to the same serogroup (A), it is believed that a virulent D. nodosus strain was introduced to Norway relatively recently and that so far it has only spread locally.


Human disorders in N-glycosylation and animal models.
Genes that cause human disorders in N-linked oligosaccharide biosynthesis have appeared much faster than animal model systems to study them. In most models, a single gene is altered or deleted while other genes and the environment are held constant. Since humans have variable genetic backgrounds and environments, model systems may only partially mimic the actual disorders. Mutations in seven of the 30-40 genes needed for the synthesis and transfer of oligosaccharides from the lipid donor to the nascent protein acceptors in the endoplasmic reticulum cause Type I Congenital Disorders of Glycosylation (CDG). Since all of these gene products ultimately contribute to the same final step, one might suspect that all the diseases would be very similar. However, even patients with mutations in the same gene show considerable phenotypic variability. Modifier, or susceptibility genes in the background likely explain some variations of the "primary" gene chosen for study. Add to this the stress of infections, dietary insufficiencies, and the demands of growth itself. These issues are particularly important during development when the temporal and spatial specific interplay of cell adhesions and signals has only a single opportunity. Multiple hypomorphic alleles of genes in the same pathway may have synergistic effects. Investigators designing model systems to study human glycosylation disorders may want to construct strains with several heterozygous hypomorphic alleles in rate-limiting steps in the glycosylation pathway.


[Protective effects of inhibitors of oxygen free radicals on the ischemic and reperfused heart. Applications to cardioplegia].
Oxygen free radicals play an important role in the induction of myocardial lesions by the sequence ischaemic-reperfusion. The aim of this study was to determine whether the protection afforded by a cardioplegic solution could be improved by the addition of different anti-oxygen free radical agents. Forty isolated, perfused, rat hearts' isovolumic contraction systems were divided into 5 groups of 8. In 4 groups, cardioplegia was stopped for 90 minutes in normothermia and then reperfused for 45 minutes. These hearts received a single initial injection of either standard cardioplegic solution or a solution enriched with dismutase peroxide (200,000 U/l), reduced glutathione (0.1 mM) or peroxidase (6,000 U/l). The fifth group of hearts was continually aerobically reperfused and served as a non-ischaemic control group. Based on post-ischaemic values of the pressure developed (maximal systolic-diastolic pressure), LVdP/dt, diastolic pressure and coronary flow, the best myocardial protection was observed in those hearts given cardioplegic solution enriched with peroxidase, the haemodynamic indices being comparable to those of the non-ischaemic controls. These results confirm that myocardial protection with cardioplegic solutions can be improved by the addition of anti-oxygen free radical agents, especially peroxidase which inactivates both hydrogen peroxide (precursor of the very cytotoxic hydroxyl radical) and some hydroperoxides, so interrupting the self-sustaining chain of lipidoperoxidation and limiting the damaging effects of this reaction on the cardiac cell membranes.


Testes function and feedlot performance of bulls actively immunized against gonadotropin-releasing hormone: effect of age at immunization.
Testes function, feedlot performance, and carcass traits were evaluated in bulls actively immunized against gonadotropin-releasing hormone (GnRH) at different ages. Bull calves were randomly assigned to one of seven treatment groups (n = 15 calves/group). Calves were unimmunized (Group 1), immunized at 1.5, 4, 7, or 12 mo of age with a GnRH-keyhole limpet hemocyanin (KLH) conjugate (Groups 2 to 5, respectively), or castrated at 4 mo of age (Groups 6 and 7). Immunized bulls did not receive a secondary, or booster, immunization. Calves in group 6 received Synovex-C at castration and Synovex-S at weaning and feedlot entry. Anti-GnRH titer was evident at slaughter in all immunized bulls. However, the final immune response of bulls immunized at 1.5 mo was significantly lower than the response of bulls immunized at later stages of development. Final scrotal circumference and testis weight in bulls immunized at 4, 7, or 12 mo of age were significantly reduced relative to unimmunized bulls. The final live weight, feedlot gain, and carcass weight of immunized and unimmunized bulls did not differ (P > .05) from the same parameters in steers implanted with Synovex. Longissimus muscle area, marbling score, and backfat thickness did not differ between immunized and unimmunized bulls. The sex class score of the carcasses of immunized bulls did not differ from the score of steer carcasses. In contrast, a significantly higher proportion of carcasses from unimmunized bulls graded as bullock carcasses. Taken together, these data indicate that a single immunization against GnRH at 4 to 12 mo of age results in significant attenuation of testicular growth in bulls. These data also demonstrate that immunization against GnRH reduces the masculinity of carcasses from bulls, but does not affect feedlot performance, longissimus muscle area, marbling score, or backfat thickness. These results suggest that single immunization with the GnRH-KLH conjugate may have practical utility as a noninvasive alternative to surgical castration in management of beef cattle.


Effect of surrounding tissue on propagation of axisymmetric waves in arteries.
A model of an artery consisting of a thin-walled flexible tube filled with a Newtonian incompressible liquid and surrounded by an external viscoelastic tissue is studied. The dispersion relations and attenuation lengths are determined for the lowest axially symmetric propagation modes: the Young, Lamb, and torsional modes. The numerical calculations confirm a low attenuation of the Young mode and a relatively weak dependence of its phase velocity on the elastic parameters of the surrounding medium. The Lamb and torsional modes show a nonzero frequency (a gap) at zero wave vector except for the limiting case of the absence of surroundings. The attenuation of the Lamb mode at zero frequency and the gap frequency turns out to be particularly sensitive to the elastic parameters of the surroundings. However, the spatial attenuation of the Lamb mode extends over a length of the order of 10cm at the viscoelastic parameters corresponding to human tissues. Such lengths are comparable to the size of human organs. Three kinds of local axially symmetric perturbations have been studied, and the corresponding amplitude ratios of the Lamb to the Young mode calculated. The amplitude of the Lamb mode turns out to exceed that of the Young mode by a factor of ten at some frequencies with perturbations involving axial motions. Physiological consequences of this effect are discussed.


Comparison of reading speed in normal observers through different forms of equivalent power low vision devices.
Compensation at near for vision loss can be achieved using a variety of equivalent forms of low vision magnifiers. Each has inherent advantages and disadvantages in terms of field, working distance, etc. We compared the reading speed of 60 trained, normal observers with 4 commonly prescribed types of low vision devices of +12 D equivalent power (spectacles, hand magnifier, stand magnifier, and telemicroscope) to their normal reading speed. Although there was individual variance in performance, reading speed with all the devices was generally within 20% of normal reading speed. Implications are that in terms of differences in reading speed for normals, the form of the low vision device is not as significant as acquiring proficiency in the use of the selected device.


[Medium-term effects of intravitreal bevacizumab for macular edema associated with central retinal vein occlusion].
To report the medium term effects of intravitreal injection of bevacizumab for central retinal vein occlusion (CRVO) with macular edema. Twenty-two eyes of 22 patients receiving intravitreal injections of 1.25 mg/0.05 ml of bevacizumab (IVB) were included. All patients were followed up for 6 months or longer after the final IVB. The visual acuity and central retinal thickness (CRT) were measured at baseline, one week and every three months after the first IVB. The mean follow-up after the final IVB was 12.5 months (6-30 months). The mean visual acuity (baseline : 0.63 +/- 0.39) temporarily improved at one week (0.38 +/- 0.33 : p=0.0002), but there was no significant visual improvement at the final visit (0.73 +/- 0.67 : p=1.0). The mean CRT significantly decreased at one week, three months and six months after IVB and at the last visit. There were no differences in either visual or anatomical outcomes between the ischemic type and non-ischemic type. Intravitreal injections of bevacizumab should be initially considered as a possible treatment in eyes with macular edema associated with central retinal vein occlusion.


Three types of simultaneous pancreas and kidney transplantation.
The purposes of this study were to study and compare clinical and functional outcomes after simultaneous deceased donor pancreas and kidney transplantation (SPK DD), simultaneous deceased donor pancreas and living donor kidney transplantation (SPK DL), and simultaneous living donor pancreas and kidney transplantation (SPK LL). From January 1, 1996 to September 1, 2005, 8918 primary, simultaneous pancreas and kidney transplantation (SPK) procedures were reported to the International Pancreas Transplant Registry. Of these, 8764 (98.3%) were SPK DD, 115 (1.3%) were SPK DL, and 39 (0.4%) were SPK LL. We compared these 3 groups with regard to several endpoints including patient and pancreas and kidney graft survival rates. The 1-year and 3-year patient survival rates for SPK DD were 95% and 90%, 97% and 95% for SPK DL, and 100% and 100% for SPK LL recipients, respectively (P ≥ .07). The 1-year and 3-year pancreas graft survival rates for SPK DD were 84% and 77%, 83% and 71% for SPK DL, and 90% and 84% for SPK LL recipients, respectively (P ≥ .16). The 1-year and 3-year kidney graft survival rates for SPK DD were 92% and 84%, 94% and 86% for SPK DL, and 100% and 89% for SPK LL recipients, respectively (P ≥ .37). Patient survival rates and graft survival rates for pancreas and kidney were similar among the 3 groups evaluated in this study.


Lung deposition and clearance of microparticle and nanoparticle C60 fullerene aggregates in B6C3F1 mice and Wistar Han rats following nose-only inhalation for 13 weeks.
C60 fullerenes (C60) are spherical structures consisting of 60 carbon atoms that are generated via combustion from both natural and anthropogenic sources. C60 are also synthesized intentionally for industrial applications. Individual C60 structures have an approximate diameter of 1nm; however, C60 readily forms aggregates and typically exist as larger particles that range from nanometers to micrometers in diameter. In this report, lung and extrapulmonary tissue deposition and lung clearance of C60 nanoparticles (nano-C60, 50nm) and microparticles (micro-C60, 1μm) were examined in Wistar Han rats and B6C3F1/N mice after nose-only inhalation for 90 days. Exposure concentrations were 0.5 and 2mg/m(3) (nano-C60) and 2, 15, and 30mg/m(3) (micro-C60). For both C60 particle sizes, the C60 lung burden increased proportionally to exposure concentration. The C60 lung burden was greater in both species at all time points following exposure to nano-C60 particle exposure compared to micro-C60 exposure at the common exposure concentration 2mg/m(3). The calculated C60 particle lung retention half-times were similar for both nano-C60 and micro-C60 exposure at 2mg/m(3) in male mice (15-16 days). In contrast, in male rats, the half-time of C60 particles following nano-C60 exposure (61 days) was roughly twice as long as the half-time following micro-C60 exposure (27 days) at the same exposure concentration (2mg/m(3)) and was similar to the clearance following micro-C60 exposure at higher exposure concentrations (15 and 30mg/m(3)). C60 was detected in bronchial lymph nodes but the burden was not quantified due to the high variability in the data. C60 concentrations were below the experimental limit of quantitation (ELOQ) in liver, spleen, blood, brain and kidney tissues. These tissue burden data provide information for comparison between nanometer and micrometer sized C60 particle exposure and will aid in the interpretation of toxicity data.


False-positive diagnosis of adrenal pheochromocytoma on iodine-123-MIBG scan.
1-123 metaiodobenzylguanidine (1-123 MIBG) scintigraphy is known for its high specificity in detecting pheochromocytoma and other tumors of neural crest origin. In this rare case report, we describe a definite adrenocortical adenoma that demonstrated false-positive uptake at I-123 MIBG scintigraphy and a remarkable accumulation of 75-SE-6-beta-selenomethyl-norcholesterol.


Evaluation of the genotoxic potential of soil contaminated with mineral coal tailings on snail Helix aspersa.
Coal remains an important source of energy, although the fuel is a greater environmental pollutant. Coal is a mixture of several chemicals, especially inorganic elements and polycyclic aromatic hydrocarbons (PAH). Many of these compounds have mutagenic and carcinogenic effects on organisms exposed to this mineral. In the town of Charqueadas (Brazil), the tailings from mining were used for landfill in the lower areas of the town, and the consequence is the formation of large deposits of this material. The purpose of this study was to evaluate the genotoxic potential of soil samples contaminated by coal waste in different sites at Charqueadas, using the land snail Helix aspersa as a biomonitor organism. Thirty terrestrial snails were exposed to different treatments: 20 were exposed to the soil from two different sites in Charqueadas (site 1 and 2; 10 in each group) and 10 non-exposed (control group). Hemolymph cells were collected after 24h, 5days and 7days of exposure and comet assay, micronucleus test, oxidative stress tests were performed. Furthermore, this study quantified the inorganic elements present in soil samples by the PIXE technique and polycyclic aromatic hydrocarbons (PAH) by HPLC. This evaluation shows that, in general, soils from sites in Charqueadas, demonstrated a genotoxic effect associated with increased oxidative stress, inorganic and PAH content. These results demonstrate that the coal pyrite tailings from Charqueadas are potentially genotoxic and that H. aspersa is confirmed to be a sensitive instrument for risk assessment of environmental pollution.


Low-level self-assembly of open framework based on three different polyhedra: metal-organic analogue of face-centered cubic dodecaboride.
Dinuclear paddlewheels linked by 5-methylisophthalate and dabco act as 5-connecting nodes to form a highly symmetric open framework based on three different Archimedean polyhedra.


Cloning and functional study of a novel aromatic-ring-hydroxylating dioxygenase gene.
The aromatic-ring-hydroxylating dioxygenase is a key enzyme that initiates the biodegradation of polycyclic aromatic hydrocarbons in bacteria. In the present study, a novel dioxygenase sequence was cloned from Terrabacter sp. FLO using a genome walking method. The dioxygenase was cloned into pET17 and actively expressed in E.coli BL21 (DE3) in co-expression with electron transfer chain proteins. The recombinant dioxygenase was found to transform phenanthrene, fluorene, pyrene and fluoranthene into the cis-dihydrodiol metabolites.


Eucapnic voluntary hyperventilation of compressed gas mixture. A simple system for bronchial challenge by respiratory heat loss.
Eucapnic voluntary hyperventilation (EVH) of cold, dry air has been shown to be an effective stimulus for bronchoconstriction in people with reactive airways. The system for respiratory heat exchange (RHE) challenge can be greatly simplified from what is presently used. A relationship was derived which predicts that a single fraction of inspired CO2 (0.0489) will produce near normal alveolar CO2 over a wide range of voluntary hyperventilation. This relationship was verified in 19 normal subjects who performed a total of 110 periods of hyperventilation with minute ventilation (VE) randomly distributed between 40 and 105 L/min. The experimentally determined CO2 production of the voluntary hyperventilation was found to be 3.72 ml/min per L/min over a range of VE from 40 to 105 L/min. Next, a group of 10 patients with exercise-induced asthma (EIA) were challenged with a standard exercise protocol, ventilating ad libitum from a source of dry air at room temperature. On another day, the same pattern of VE, and hence RHE, was required of them using the simplified EVH scheme. The average decreases in forced expiratory volume in one second and specific airway conductance were 32 +/- 10% and 66 +/- 13%, respectively, after the exercise challenge, and 33 +/- 12% and 73 +/- 12% after EVH. The difference between corresponding mean values was not significant. We conclude that a simplified EVH challenge can be done using a single dry gas mixture without the need for cooling inspired gas or monitoring end-tidal fraction of CO2. This test can be used to identify and study patients with EIA without the requirement for an exercise challenge or the need for elaborate gas conditioning and monitoring equipment.


Transferrin-polyethylenimine conjugate, FuGENE6 and TransIT-LT as nonviral vectors for gene transfer to the corneal endothelium.
To investigate the efficacy and pathogenicity of three commercially available nonviral DNA vectors for gene transfer to the corneal endothelium. Corneas obtained from New Zealand White rabbits were cultured ex vivo. For cell culture, the corneal endothelial cells were removed and cultured in vitro under standard conditions. Using the vectors, culture cells or ex vivo corneas were transfected with plasmid DNA coding for green fluorescent protein (GFP). Expression of the transduced gene was monitored by fluorescence microscopy. Transfection efficiency was estimated as the percentage of GFP-positive cells identified. The viability and morphology of the endothelium were also examined. Transferrin-polyethylenimine conjugate was effective in vitro but not ex vivo. FuGENE6 and TransIT-LT mediated the transfer of GFP gene both in in vitro and in ex vivo culture. Their efficiency estimated at day 3 was 28.8% and 38.8% in vitro, and 8.1% and 8.8% ex vivo, respectively. Viability staining revealed no dead cells. Morphological study showed no apparent alteration. FuGENE6 and TransIT-LT are safe, simple to use, and may be useful alternative methods for gene transfer to the corneal endothelium, avoiding certain side effects of viral vectors. As the efficiency could be enhanced, these nonviral vectors may be promising for practical application.


Inhibition of chemiluminescence response of human mononuclear cells and suppression of mitogen-induced proliferation of spleen lymphocytes of mice by hispolon and hispidin.
The effects of two phenolic compounds, hispolon and hispidin isolated from fruit bodies of the basidiomycete Inonotus hispidus (Bull. ex Fr.) Karst, were investigated on the chemiluminescence response by LPS- or zymosan-activated human mononuclear cells (MNC) and on the concanavalin A-induced proliferation of spleen lymphocytes of mouse in vitro. Both compounds showed inhibitory activity in the chemiluminescence-test with an IC50 (the concentration of test compound causing 50% effect) ranging from 4.4 to 4.6 micrograms/ml (20.3 to 21.2 microM) for hispolon and < 0.1 to 1.5 micrograms/ml (from < 0.4 microM to 6.0 microM) for hispidin. Antiproliferative effects have been achieved in the lymphocyte transformation test (LTT) by hispolon with an IC50 of 3.4 micrograms/ml (15.5 microM).


[Characteristics of the response of vestibular evoked myogenic potentials to different stimulus modes].
Vestibular evoked myogenic potential (VEMP) has been utilized in clinic to test the function of saccule. In the present study, 3 stimulus modes were applied to 21 normal adults and intended to draw in a clinical test protocol. The normal latency and amplitude of VEMPs of 21 normal subjects were recorded and the ratio of bilateral amplitudes and asymmetry were calculated. The response to binaural clicks were similar to the response of the monaural clicks. The interindividual variation in amplitude were large, but the latency varied little. VEMPs is a stable myogenic potentials. Monaural and binaural clicks stimulus can be used in clinical practice. The latter is appropriate for normal hearing subjects. Amplitude measurement is probable to evaluate the asymmetry of bilateral saccular function and may reveal saccule lesion.


[Meningitis caused by Haemophilus influenzae type B, resistant to ampicillin and chloramphenicol].
Authors present three cases of ampicillin and chloramphenicol resistant Haemophilus influenzae type b meningitis, and one case with resistance to ampicillin and allergy to chloramphenicol. These multiresistant Haemophilus influenzae strains create very important therapeutic problems. They have used first (cefacetrile), second (cefamandole) and third (cefotaxime an moxalactam) generation cephalosporins, in order to their disponibility. There was an excellent evolution in every case. They conclude that third generation cephalosporins are useful in cases of ampicillin and chloramphenicol resistant Haemophilus influenzae type b meningitis.


Myocardial infarction as the presenting manifestation of systemic lupus erythematosus with antiphosphatidylserine antibodies.
The presence of antiphospholipid antibodies has been associated with thrombotic events in systemic lupus erythematosus and other diseases. Antiphosphatidylserine antibodies have been shown more recently to have clinical implications being noted in thrombocytopenia, positive VDRL test, prolonged partial thromboplastin time, and recurrent fetal loss. To report a patient with systemic lupus erythematosus who presented with a myocardial infarction resulting from a single clot in the distal left anterior descending coronary artery and to discuss the merits of evaluating such patients for the presence of antiphospholipid antibodies. Case report and review of the literature. A 55-year-old woman with no risk factors for coronary artery disease presented with a myocardial infarction. A distal left anterior descending coronary artery clot was seen on angiography. Evaluation for the presence of a hypercoagulable state revealed evidence for systemic lupus erythematosus. Although lupus anti-coagulant and anticardiolipin antibody titers were negative, antiphosphatidylserine IgA antibodies were detected. Because antiphosphatidylserine antibodies of the IgA isotype have been shown to be associated with thrombosis and other manifestations of systemic lupus erythematosus, a complete evaluation for antiphospholipid antibodies should include testing for all three isotypes.


Effects of vegetative-periodic-induced rhizosphere variation on the uptake and translocation of metals in Phragmites australis (Cav.) Trin ex. Steudel growing in the Sun Island Wetland.
To evaluate the vegetative periodic effect of rhizosphere on the patterns of metal bioaccumulation, the concentrations of Mg, K, Ca, Mn, Zn, Fe, Cu, Cr, Ni, Cd and Pb in the corresponding rhizosphere soil and tissues of Phragmites australis growing in the Sun Island wetland (Harbin, China) were compared. The concentrations of Zn, Fe, Cu, Cr, Ni, Cd and Pb in roots were higher than in shoots, suggesting that roots are the primary accumulation organs for these metals and there exists an exclusion strategy for metal tolerance. In contrast, the rest of the metals showed an opposite trend, suggesting that they were not restricted in roots. Harvesting would particularly be an effective method to remove Mn from the environment. The concentrations of metals in shoots were generally higher in autumn than in summer, suggesting that Ph. australis possesses an efficient root-to-shoot translocation system, which is activated at the end of the growing season and allows more metals into the senescent tissues. Furthermore, metal bioaccumulation of Ph. australis was affected by vegetative periodic variation through the changing of physicochemical and microbial conditions. The rhizospheric microbial characteristics were significantly related to the concentrations of Mg, K, Zn, Fe and Cu, suggesting that microbial influence on metal accumulation is specific and selective, not eurytopic.


Cardioperipheral vascular effects of inversion on humans.
The purpose of this study was to identify the cardioperipheral vascular effects of inversion on humans. Twenty healthy volunteer subjects (10 men, 10 women), aged 20 to 40 years, participated in this study. Variables of heart rate, blood pressure, and intraocular pressure were measured in four positions: sitting, standing, bent knee inversion, and straight leg inversion. Three trials were recorded in each of the four positions. Data were analyzed by two-way analyses of variance for repeated measures. The results indicated that heart rate increased significantly from the sitting position to the bent-knee-inversion position (p less than .05). Systolic and diastolic blood pressure (observed and corrected) and intraocular pressure (left and right) increased significantly from the sitting and standing positions to the bent-knee-inverted and straight-leg-inverted positions (p less than .01). Intraocular pressure also was significantly higher during straight leg inversion as compared with bent knee inversion (p less than .01). These findings reflect the need for additional research to establish better safety standards for the use of inversion devices.


Gardnerella vaginalis diversity and ecology in relation to vaginal symptoms.
Gardnerella vaginalis was first described in 1953, and subsequently identified as the causative agent of a cluster of vaginal symptoms currently known as vaginosis. Research has so far failed to confirm whether and by which mechanism G. vaginalis initiates vaginosis, with, consequently, poor diagnostics and treatment outcomes. Recent molecular analyses of protein-coding genes demonstrate that the taxon G. vaginalis consists of at least four distinct species. This development may represent a critical turning point in clarifying ecological interactions and virulence factors contributing to symptoms and/or sequelae of vaginosis.


Melanocytoma of the choroid: angiographic and histopathologic findings.
A juxtapapillary choroidal melanocytoma that was clinically confused with a choroidal melanoma is described. The clinical examination of a 40-year-old female patient included ultrasonography, fluorescein, and indocyanine green angiography. Histopathologic and immunohistochemical study of the enucleated eye resulted in the identification of a markedly pigmented, 3.8 mm elevated choroidal melanocytic tumor observed nasally to the disk. A-scan ultrasonography showed a high initial spike with a low to medium internal reflectivity with decreasing amplitude. On fluorescein angiography, the tumor was surrounded by a rim of retinal pigment epithelium depigmentation with a well-defined comet-tail. The lesion was hypofluorescent in the early phases of the indocyanine green angiogram, but from the late venous phase appeared ill-defined hyperfluorescence. Histopathologic study revealed a juxtapapillary choroidal melanocytoma The pigmented tumor cells stained positive for HMB45 and vimentin but negative for S100, GFAP, NSE, and MNF116. No tumor cells stained positive for the proliferation marker Ki67. These findings conclude that choroidal melanocytoma may mimick choroidal melanoma. Abnormalities on fluorescein angiography may be a clinical hint to suspect a pigmented tumor different from a choroidal melanoma.


Myelination in the developing human brain: biochemical correlates.
To delineate the biochemical sequences of myelination in the human brain, we analyzed the protein and lipid composition of white matter in 18 baseline cases ranging in age from midgestation through infancy, the critical period in human myelination when the most rapid changes occur. Three adult cases were used as indices of maturity, and 4 cases with major disorders of CNS myelination (maple syrup urine disease, severe periventricular leukomalacia, idiopathic central hypomyelination, and metachromatic leukodystrophy) were analyzed. Brain samples were obtained < or = 24 hours after death. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis and high performance thin-layer chromatography were used to separate and identify proteins and polar and neutral lipids in an average of 10 sites/brain; computer-based densitometry was used to quantify polar lipids. Biochemical sequences, as manifested by the appearance of the myelin-associated lipids and myelin-specific proteins, closely followed previously described anatomic sequences both temporally and by region, and were identical in all sites sampled: sphingomyelin was followed simultaneously by cerebrosides, MBP, PLP, and nonhydroxy-sulfatide, followed by hydroxy-sulfatide. The onset and tempo of the expression of individual constituents, however, were quite variable among sites, suggesting a wide differential in vulnerable periods to insult in biochemically-specific pathways in early life. Cholesterol ester was transiently elevated during late gestation and early infancy, prior to and around the time of the appearance of cerebrosides, sulfatides, PLP, and MBP. Distinctive lipid and protein abnormalities were detected in idiopathic central hypomyelination and metachromatic leukodystrophy. This study underscores the feasibility of the combined biochemical approaches in pediatric brains and provides guidelines for the assessment of disorders of myelination in early human life.


[Role of endogenous sex steroids in the genesis of precancers and cancer of the cervix uteri in endocrine diseases].
The causes and characteristics of the pathogenesis of various background, precancerous processes and cervical cancer have not been fully studied, and research in this area is currently ongoing. Nevertheless, the role of certain factors of the external and internal environment that have a direct impact on the development of cervical pathology is firmly defined.


Synchronous lymphomas arising in ipsilateral parotid and submandibular glands: video-assisted surgery.
The incidence of lymphomas in salivary glands is 5%, and it represents 10% of malignant salivary tumors. Synchronous tumors arising in different major salivary glands are not only very infrequent but also extremely rare; on the other hand, synchronous lymphomas in ipsilateral major salivary glands have not been reported previously. This article reports a case of synchronous lymphomas in mucosa-associated lymphoid tissue in the ipsilateral parotid and submandibular glands. Parotidectomy with facial nerve conservation and resection of the submandibular gland by video-assisted surgery using only a Blair-modified classic incision was performed. One year after the surgical procedure, the patient was followed up at regular intervals, and residual mucosa-associated lymphoid tissue lymphoma did not appear. This case illustrates the importance of the diagnostic possibility of synchronous primary tumors after identification of a simple one; this also reports the video-assisted resection of the submandibular gland using only a Blair incision, when a parotidectomy must be also made.


Interferon therapy in intravenous drug users with HIV-associated idiopathic thrombocytopenic purpura.
There is no generally accepted treatment for human immunodeficiency virus (HIV)--associated idiopathic thrombocytopenic purpura (ITP). recombinant alpha interferon (rIFN) has been used in classic ITP with conflicting results. We have tested its activity in a group of intravenous drug users (IVDUs) with HIV-associated ITP, who also had a high prevalence of chronic liver disease. Nine patients were treated with a short course of rIFN-2b (3 MU s.c. three times a week for four weeks), and their hematological and biochemical parameters were monitored before (t0), at the end (t1), and one month after discontinuation of rIFN therapy (t2). Platelet counts increased significantly from 15.9 +/- 7.3 x 10(9)/L at t0 up to 67.0 +/- 38.8 x 10S(9)/L at t1 (p < 0.005), but returned to 24.7 +/- 12.7 x 10(9)/L at t2 (t1 vs t2: p < 0.005). The other parameters did not change, with the exception of the alanine aminotransferase levels, which decreased from 105 IU/L at t0 to 42 IU/L at t1 (p < 0.05). A short course of rIFN is an effective treatment for HIV-associated ITP in IVDUs and may also be beneficial for the frequently concomitant chronic liver disease. Since the efficacy of rIFN on the platelet count is short-lived, long-term rIFN administration would be worth testing.


The induction of a regenerative propensity in sensory neurons following peripheral axonal injury.
Injury of the peripheral axons of primary sensory neurons has been previously shown to increase the probability that the corresponding central axons would grow from the injured spinal cord into a peripheral nerve graft. This phenomenon has been used to investigate the nature of extrinsic cues from injured nerves that enhanced regenerative propensity within sensory neurons. In 13 groups of rats, a segment of the right sciatic nerve was grafted to the dorsal columns of the spinal cord and the left sciatic nerve was subjected to mechanical injury, injection of colchicine or infusion of nerve growth factor. Subsequently, neurons in lumbar dorsal root ganglia with axons growing from the spinal cord into a graft were identified by retrograde perikaryal labelling and compared for the two sides. The aim was to mimic or modify the inductive effect of nerve transaction by alternative or additional manipulation of the nerve. Growth of central axons was less enhanced by peripheral axonal interruption if the length of the proximal stump was increased or if a distal stump was present to permit rapid regeneration. However, the regenerative response following nerve transection was altered little by crushing the proximal stump or injecting it with colchicine or nerve growth factor. It is suggested that sensory neurons are stimulated to regenerate by peripheral axonal injuries that reduce some normal retrograde regulatory influence of Schwann cells.