Association between interleukin 4 (IL-4) VNTR, gene polymorphism, and breast cancer susceptibility in Iranian population: experimental and web base analysis.
Breast cancer (BC) is one of the most common types of cancer and the second leading cause of cancer death among women. Epidemiological studies showed that BC is linked to genetic and environmental factors, and inheritance plays a key role in the pathobiology of this disease. Interleukin 4 (IL-4) is a key differentiation cytokine and is produced by Th2 and activates Th2 development. Hence the current study aimed to assess the possible association between interleukin 4 (IL-4) VNTR polymorphism, and BC susceptibility in a sample of Iranian population. IL-4 VNTR polymorphism was evaluated in 150 women with BC and 150 age-matched healthy women by polymerase chain reaction method. Among 3 possible alleles for IL-4 gene, we only observed 2 alleles. Current findings indicate that RP2/RP2 genotypes can be regarded as potent protective factors against breast cancer (OR = 0.929 [95%CI, 0.929-0.995]). Our result showed that the RP2/RP2 genotype of the IL-4 VNTR polymorphism could be a protective factor for BC susceptibility (Tab. 2, Fig. 1, Ref. 46).


IL-6 mediated isotype specific suppression of hapten specific IgE in serum of BPO-KLH sensitized mice: role of IFN alpha in maintainance of hapten specific IgE responses.
The ability of IL-6 or IFN alpha or antibodies to these cytokines to regulate serum levels of hapten specific immunoglobulins (IgM, IgG1, IgE, IgA) was studied in BPO-KLH (benzylpenicilloyl-keyhole limpet hemocyanin) sensitized BALB/c mice at the peak of a hapten specific IgE antibody forming cell (AFC) response. To induce peak IgE responses, mice were injected intraperitonealy (i.p.) with BPO-KLH (10 micrograms) in aluminum hydroxide gel (alum) on days 0, 21, and 42. On day 44, mice were injected s.c. with IL-6 (100-1000 U), IFN alpha (1000-10,000 U), anti-IL-6 (100-1000 neutralizing units [NU]), or anti-IFN alpha (1000-10,000 NU). On day 46, levels of BPO specific IgM, IgG1, IgE and IgA in serum were determined (ELISA). Data are expressed as micrograms/ml. IL-6 suppressed BPO specific IgE in serum in isotype specific fashion (to > 90%), increasing IgA (approximately 3 fold), and leaving IgM and IgG1 unchanged. Since removal of endogenous IL-6 with anti-IL-6 increased serum IgE, and suppressed IgG1 (approximately 50%), with IgM and IgA unchanged, this suggests that IL-6 is an isotype specific suppressor of peak IgE responses and as such may be useful in the therapeutic management of atopic disease. IFN alpha treatment increased serum IgE levels (60%), and potentiated IgA responses (> 30 fold), with IgM and IgG1 unchanged. Since removal of endogenous IFN alpha with anti-IFN alpha decreased IgE levels (approximately 50%), increasing IgA, with IgM and IgG1 unchanged, this suggests a role for IFN alpha as an isotype specific helper of peak IgE responses and in maintenance of IgA responses.


Thematic role properties of subjects and objects.
This paper tests two claims about the thematic roles Agent and Patient: first, that they can be decomposed into more primitive features, as laid out in Dowty's (1991) Proto-Roles Hypothesis; and second, that these properties can be inferred directly from the grammatical roles subject and object. In Experiments 1 and 2, participants rated the Proto-Roles properties of the subject and object of transitive sentences with real verbs. Subjects were rated as more Agent-like than objects, while objects were rated as more Patient-like than subjects. Experiment 3 used transitive sentences with nonsense content words (e.g. "The rom mecked the zarg"). Even in the absence of a known verb, the results were the same. Experiment 4 examined the corollary prediction that subjects and objects should not differ on grammatically irrelevant properties (e.g. "being liquid"); this prediction was confirmed. In Experiment 5, verbs that do not permit objects (e.g. "fall," "erupt") were placed in the transitive frame. Results were the same as in Experiments 1 through 3. Moreover, the semantics of the verb were altered by the frame, indicating that participants tried to fuse the semantics of the verb with those of the frame. Possible sources of these inferences are considered.


[Creatine kinase isoenzymes: idiopathic occurrence of creatine kinase BB activities in patient serum (author's transl)].
By differentiation of creatine kinase isoenzyme activities in sera using immunological methods the published data about occurrence of creatine kinase BB activities in patients with different diseases or after surgical treatment, respectively, cannot be verified in general. With a frequency in the order of magnitude of 1 : 1000 in the serum of old patients (age 57 to 85 years with one exception), however, creatine kinase BB activities can be measured. The range of activities is 15 to 234 U/1, or 19 to 94% of total creatine kinase activities, respectively. At the present time there is no possibility to correlate this phenomenon to any specific disease. These cases are detected by abnormally high results of CK-MB activity measurements with the immunoinhibition test (range 60 to 202% of total creatine kinase activities) which lead to a repeated analysis using immunoprecipitation. The results of all CK-BB patients investigated till now are presented and discussed.


The Effect of Assisted Hatching on Live Birth Rate Following Fresh Embryo Transfer in Advanced Maternal Age.
Assisted hatching (AH) was introduced 3 decades ago as an adjunct method to in vitro fertilization (IVF) and embryo transfer (ET) to improve embryo implantation rate. Limited data are available on the effect of AH on live birth rate (LBR) in advanced maternal age. The objective of this study is to investigate the effect of AH on LBR in women aged 40 years and older. A retrospective study conducted at a single academic reproductive center. Women aged ≥40 years, who were undergoing their first IVF cycle were included. Laser-assisted hatching was the method used for AH and single or double embryos were transferred. Embryo transfer was performed at the cleavage or blastocyst stage. Separate analysis was performed on each ET stage. Live birth rate was the primary outcome. A total of 892 patients were included. Of these, 681 women underwent cleavage ET and 211 underwent blastocyst ET. The clinical pregnancy rate in the entire group was 15.3% and the LBR was 10.2%. Baseline and cycle parameters between the AH group and the control group were comparable. Assisted hatching in the cleavage stage was associated with lower clinical pregnancy rate (odds ratio [OR], 0.52; confidence interval [CI], 0.31-0.86; P = .012) and lower LBR (OR, 0.36; CI, 0.19-0.68; P = .001). Assisted hatching did not have any effect on outcomes in blastocyst ET. Assisted hatching does not improve the reproductive outcomes in advanced maternal age. Performing routine AH for the sole indication of advanced maternal age is not clinically justified.


[Gas gangrene of the hand. A case report].
This is a case report of a 23 year old male, who developed a gas edema of his left hand and forearm 13 days after a stab injury of his finger. Diagnostical procedure and treatment of gas edema are discussed.


Propargylglycine decreases neuro-immune interaction inducing pain response in temporomandibular joint inflammation model.
The mechanisms underlying temporomandibular disorders following orofacial pain remain unclear. Hydrogen sulfide (H2S), a newly identified gasotransmitter, has been reported to modulate inflammation. Cystathionine γ-lyase (CSE) is responsible for the systemical production of H2S, which exerts both pro- and antinociceptive effects through inflammation. In the current study, we investigated whether the endogenous H2S production pathway contributes to arousal and maintenance of orofacial inflammatory pain, through the investigation of the effects of a CSE inhibitor, propargyglycine (PAG), in a rat CFA (Complete Freund Adjuvant)-induced temporomandibular inflammation model to mimic persistent pain in the orofacial region. For this, rats received either CFA or saline in the temporomandibular joints (TMJs), and after 3 or 14 days, they received a single injection of PAG or saline and were evaluated for nociception with the von Frey and formalin test. Also, pro-inflammatory cytokines, tumor necrosis factor-α (TNF-α), and interleukin-1β (IL-1β) were analyzed in TMJs and trigeminal ganglion (TG). In this last one, glial cells reactivity was also verified. Endogenous H2S production rate were measured in both, TMJ and TG. Our results indicated decreased allodynia and hyperalgesic responses in rats submitted to CFA after injection of PAG. Moreover, PAG inhibited leucocyte migration to temporomandibular synovial fluid after 3 and 14 days of inflammation. PAG was able to reduce levels of CBS, CSE, TNF-α, and IL-1β in the TMJ and TG, after 13 days of CFA injection. The observed increased activation of glial cells in the trigeminal ganglia on the 14th day of inflammation can be prevented by the highest dose of PAG. Finally, CBS and CSE expression, and endogenous H2S production rate in the TMJ and TG was found higher in rats with persistent temporomandibular inflammation compared to rats injected with saline and PAG was able to prevent this elevation. Our results elucidated the molecular mechanisms by which H2S exerts its pro-inflammatory and pro-nociceptive role in the orofacial region by alterations in both local tissue and TG.


Is there a field-theoretic explanation for precursor biopolymers?
A Hu-Barkana-Gruzinov cold dark matter scalar field phi may enter a weak isospin invariant derivative interaction that causes the flow of right-handed electrons to align parallel to (inverted delta phi). Hence, in the outer regions of galaxies where (inverted delta phi) is large, as in galactic halos, the derivative interaction may induce a chirality-imbued quantum chemistry. Such a chirality-imbued chemistry would in turn be conducive to the formation of abundant precursor biopolymers on interstellar dust grains, comets and meteors in galactic halo regions, with subsequent delivery to planets in the inner galactic regions where phi and (inverted delta phi) are concomitantly near zero and left-right symmetric terrestrial quantum chemistry prevails.


Developmental differences in childhood motor coordination predict adult alcohol dependence: proposed role for the cerebellum in alcoholism.
The Danish Longitudinal Study of Alcoholism has identified a number of early biological indicators that predicted alcohol dependence 30 years later. In light of recent evidence linking deficits of the cerebellum to certain neuropsychiatric disorders often comorbid with alcoholism, we hypothesized that developmental deficits in the cerebellar vermis may also play a role in the initiation of adult alcohol dependence. The present study evaluated whether measures of motor development in the first year of life predict alcohol dependence three decades later. A total of 241 subjects of the original 330 infants who were entered into this study completed the 30-year follow-up (12 had died). The subjects were men who were drawn from a large birth cohort born in Copenhagen, Denmark, from 1959 to 1961. A comprehensive series of measures were obtained on each subject before, during, and shortly after birth as well as at 1 year of age. Muscle tone at birth and day 5 as well as 1-year measures of motor coordination--age to sitting, standing, and walking--were examined. A DSM-III-R diagnosis of alcohol dependence and a measure of lifetime problem drinking served as the 30-year outcome variables. Several measures of childhood motor development significantly predicted alcohol dependence at 30 years of age. These included deficits in muscle tone 5 days after birth, delays in the age to sitting, and delays in the age to walking. Relationships found between adult alcoholism and early delays in motor development offer support for the theory that cerebellar deficits may play a causal role in the addiction process.


Ionized calcium and the in vivo response of normal and hyperplastic parathyroid glands to beta-adrenergic agents.
We compared ionized serum calcium and parathyroid hormone (PTH) responses to the beta-adrenergic agents, isoproterenol and propranolol, in 14 patients with hyperparathyroidism following renal transplantation and 8 normal volunteers. Following isoproterenol, PTH rose in normal subjects concurrent with a significant (p less than 0.01) fall in ionized but not total, calcium. In the hyperparathyroid patients the PTH concentration decreased (p less than 0.001) coincident with a significant (p less than 0.01) increase in ionized, but not total, calcium. Changes in both PTH (p less than 0.05) and ionized calcium (p less than 0.05) were significantly different in hyperparathyroid patients compared to normal subjects. Propranolol did not affect PTH, ionized or total calcium in either group. We conclude that beta-adrenergic stimulation of PTH secretion may be mediated, in part, by antecedent changes in ionized calcium and not solely a direct effect of the agonist. Concurrent assessment of changes in ionized calcium is necessary for proper interpretation of investigations involving the sympathetic nervous system's regulation of PTH secretion.


Intrinsic denervation of the colon is associated with a decrease of some colonic preneoplastic markers in rats treated with a chemical carcinogen.
Denervation of the colon is protective against the colon cancer; however, the mechanisms involved are unknown. We tested the hypothesis that the denervated colonic mucosa could be less responsive to the action of the chemical carcinogen dimethylhydrazine (DMH). Three groups of 32 male Wistar rats were treated as follows: group 1 (G1) had the colon denervated with 0.3 mL 1.5 mM benzyldimethyltetradecylammonium (benzalkonium chloride, BAC); G2 received a single ip injection of 125 mg/kg DMH; G3 was treated with BAC + the same dose and route of DMH. A control group (Sham, N = 32) did not receive any treatment. Each group was subdivided into four groups according to the sacrifice time (1, 2, 6, and 12 weeks after DMH). Crypt fission index, ss-catenin accumulated crypts, aberrant crypt foci, and cell proliferation were evaluated and analyzed by ANOVA and the Student t-test. G3 animals presented a small number of aberrant crypt foci and low crypt fission index compared to G2 animals after 2 and 12 weeks, respectively. From the second week on, the index of ss-catenin crypt in G3 animals increased slower than in G2 animals. From the 12th week on, G2 animals presented a significant increase in cell proliferation when compared to the other groups. Colonic denervation plays an anticarcinogenic role from early stages of colon cancer development. This finding can be of importance for the study of the role of the enteric nervous system in the carcinogenic process.


Epidemiological aspects of pulse pressure and arterial stiffness.
Systolic and diastolic blood pressure are considered to be exclusive haemodynamic predictors of cardiovascular risk in humans. If high blood pressure is characterized as a mechanical factor which acts on the arterial wall with deleterious consequences, then the totality of the blood pressure curve should be investigated to determine the risk. The purpose of this review is to show that, in addition to systolic and diastolic blood pressure, other haemodynamic variables should be taken into account; namely, brachial pulse pressure, pulse pressure amplification, aortic pulse wave velocity, and carotid incremental elastic modulus. These new components might modify our conventional views on antihypertensive agents and may serve to identify new potentially active molecules.


Body fluid compartments in humans during acute high-altitude exposure.
Body fluid compartments were studied in a group of sea level residents at sea level and during 12 d of acute exposure to an altitude to 3,500 m. Measurements of total body water and extracellular water were done on the third and 12th days of exposure, while plasma volume was measured on 12th day only. The intracellular water, blood volume, and red cell mass were computed from the above parameters. Total body water and extracellular water decreased progressively, the decrease being 4.7% (p less than 0.001) and 6.0% (p less than 0.05) respectively on the 12th day. Plasma volume and blood volume decreased significantly with a slight increase in red cell mass. Intracellular water, computed from total body water and extracellular water, decreased by 4.3% on 12th day. This study suggested hypohydration on acute altitude exposures.


A retrospective comparative study of aortic valve replacement with St. Jude medical and medtronic-hall prostheses: a 20-year follow-up study.
To compare the long-term clinical outcome of patients who underwent aortic valve replacement with St. Jude Medical and Medtronic-Hall mechanical prostheses. From June 1978 to June 1982, 43 Medtronic-Hall and 48 St. Jude Medical mechanical valves were implanted in 90 consecutive patients with aortic valve disease, and their clinical outcome was retrospectively assessed. At 20 years in the St. Jude Medical group and in the Medtronic-Hall group the actuarial rates of overall survival were 50 and 49% (p = NS), of cardiovascular survival 66 and 63% (p = NS), of valve-related survival 95 and 91% (p = NS), of freedom from major valve-related complications 83 and 45% (p = 0.005), from major cerebrovascular events 93 and 71% (p =0.06), from valve thrombosis 97 and 89% (p = NS), from aortic valve reoperation 93 and 88% (p = NS), from major bleeding 96 and 82% (p = 0.04), and from endocarditis 93 and 82% (p = NS), respectively. The linearized rate of overall major aortic valve prosthesis-related complications was 3.47%/year in the Medtronic-Hall valve group and 1.53%/year in the St. Jude Medical valve group (p = 0.003). Multivariate analysis showed that the type of prosthesis was predictive of freedom from valve-related complications (p = 0.01; 2.849; C.I. 95%: 1.246-6.516). The aortic St. Jude Medical mechanical valve seems to be associated with a slightly lower rate of long-term valve-related morbidity than the aortic Medtronic-Hall mechanical valve. Because of the small patient population and the retrospective nature of the study, the choice between these two prostheses should not be made only on the basis of these findings. However, these results suggest a reappraisal for further comparative studies with such an extended follow-up.


Effects of a paraspinal-lumbar tape application during 7 days on the perceived area of tape contact.
The study aimed to investigate the changes of the perceived area of tape contact during a lumbar tape application that lasted 7 days. Single group, repeated measures study. University research laboratory. Twenty-three healthy collegiate students in sports science. Perceived area of tape contact was collected by preparing a drawing of their individual perceived tape outline into a printed body image. Measurements were obtained immediately after fixation of the tape (day 0), at day 3 and day 7 during application and 5 min after the release of the application (day 7). There was no significant change of the perceived area of tape contact after 3 days of tape application. A significant decrease in the perceived area of tape contact was detected 7 days after application (p < 0.05) and after detaching the tape (p < 0.01) compared to the first measurement. Our results indicate that the perception of the area of tape contact of healthy sport students is decreased at 7 days. This effect could not be observed at 3 days. These results provide relevant information for the use of elastic tapes concerning the duration of application in medical therapy.


Three dimensional printing technology and materials for treatment of elbow fractures.
3D printing is a rapid prototyping technology that uses a 3D digital model to physically build an object. The aim of this study was to evaluate the peri-operative effect of 3D printing in treating complex elbow fractures and its role in physician-patient communication and determine which material is best for surgical model printing. Forty patients with elbow fractures were randomly divided into a 3D printing-assisted surgery group (n = 20) and a conventional surgery group (n = 20). Surgery duration, intra-operative blood loss, anatomic reduction rate, incidence of complications and elbow function score were compared between the two groups. The printing parameters, the advantages and the disadvantages of PLA and ABS were also compared. The independent-samples t-test was used to compare the data between groups. A questionnaire was designed for orthopaedic surgeons to evaluate the verisimilitude, the appearance of being true or real, and effectiveness of the 3D printing fracture model. Another questionnaire was designed to evaluate physician-patient communication effectiveness. The 3D group showed shorter surgical duration, lower blood loss and higher elbow function score, compared with the conventional group. PLA is an environmentally friendly material, whereas ABS produce an odour in the printing process. Curling edges occurred easily in the printing process with ABS and were observed in four of ten ABS models but in only one PLA model. The overall scores given by the surgeons about the verisimilitude and effectiveness of the 3D model were relatively high. Patient satisfaction scores for the 3D model were higher than those for the 2D imaging data during physician-patient discussions. 3D-printed models can accurately depict the anatomic characteristics of fracture sites, help surgeons determine a surgical plan and represent an effective tool for physician-patient communication. PLA is more suitable for desktop fused deposition printing in surgical modeling applications.


Abnormal hypothalamic-pituitary-adrenal function in anorexia nervosa. Pathophysiologic mechanisms in underweight and weight-corrected patients.
To study the pathophysiology of hypercortisolism in patients with anorexia nervosa, we examined plasma ACTH and cortisol responses to ovine corticotropin-releasing hormone before and after correction of weight loss. We also studied patients with bulimia whose weight was normal, since this disorder has been suspected to be a variant of anorexia nervosa. Before their weight loss was corrected, the anorexic patients had marked hypercortisolism but normal basal plasma ACTH. The hypercortisolism was associated with a marked reduction in the plasma ACTH response to corticotropin-releasing hormone. When these patients were studied three to four weeks after their body weight had been restored to normal, the hypercortisolism had resolved but the abnormal response to corticotropin-releasing hormone remained unchanged. On the other hand, at least six months after correction of weight loss their responses were normal. The bulimic patients whose weight was normal also had a normal response to corticotropin-releasing hormone. We conclude that in underweight anorexics, the pituitary responds appropriately to corticotropin-releasing hormone, being restrained in its response by the elevated levels of cortisol. This suggests that hypercortisolism in anorexics reflects a defect at or above the hypothalamus. The return to eucortisolism soon after correction of the weight loss indicates resolution of this central defect despite persistence of abnormalities in adrenal function.


Child pedestrian fatalities in Diyarbakir, Turkey.
As there is an increase in modernization, transportation, unskilled, and drunk drivers, injuries from traffic accidents have taken on an epidemic form all over the world. The present study aims to describe the demographic data of childhood pedestrian fatalities in a large urban area in Turkey. The demographic data of childhood pedestrian fatalities in a large urban area in Turkey was described retrospectively, with respect to age, gender, injury pattern and location. Cases less than 16 years of age were collected retrospectively from the files of the Branch of the Council of Forensic Medicine in Diyarbakir between 1998 and 2003. There were 232 childhood pedestrian fatalities among a total of 267 children involved in lethal traffic accidents. The mean age of the victims was 7.2 years, most of them being in the 6-10 years of age group (49.1%). Male predominated among our victims (76.3%). With regard to injury location, the most common site was the head (73.7%). There was an increase in pedestrian fatalities in the summer season (33.6%). There was no difference in rates of pedestrian deaths between years. Child pedestrian deaths have constituted a significant percentage of all child fatalities due to traffic accidents in our region. There were 6.4 deaths per 100,000 populations, and this rate was also higher than in other populations.


Zymographic techniques for the analysis of matrix metalloproteinases and their inhibitors.
The balance between matrix metalloproteinases (MMPs) and their inhibitors, the tissue inhibitors of metalloproteinases (TIMPs), is largely responsible for the remodeling of tissues. Deregulation of this balance is a characteristic of extensive tissue degradation in certain degenerative diseases. To analyze the role of MMPs and TIMPs in tissue remodeling under normal and pathological conditions, it is important to have reliable detection methods. This review will focus on zymographical techniques for the analysis of MMPs and TIMPs. MMPs can be analyzed with several zymographical techniques, but substrate zymography is the most commonly used. This technique identifies MMPs by the degradation of their preferential substrate and by their molecular weight. Several substrates that can be used for zymography are described. Reverse zymography, which detects TIMPs by their ability to inhibit MMPs, is also discussed. Finally, in situ zymography is described, which is used to localize MMPs in tissue sections. Common problems encountered during sample preparation, zymography itself and the data analysis are discussed. Hints are given to improve the sensitivity and accuracy of zymographical methods. In conclusion, zymography is a valuable tool for research purposes and for the development of new diagnostic techniques and therapies for pathological conditions such as rheumatoid and osteoarthritis, and tumor progression.


Human CD46 aberrant splicing in transgenic mice.
RNA analysis of mice transgenic for human CD46 reveals almost undetectable levels of the expected transcript and the accumulation of a 900 nt shorter species. cDNA cloning and sequence analysis of this variant demonstrate an aberrant splicing of the transgene RNA. This aberrant splicing is present at low levels in cells that normally express the gene, suggesting that the transgene is lacking regulatory elements influencing the abundance of the shorter transcript.


Streamwise-localized solutions at the onset of turbulence in pipe flow.
Although the equations governing fluid flow are well known, there are no analytical expressions that describe the complexity of turbulent motion. A recent proposition is that in analogy to low dimensional chaotic systems, turbulence is organized around unstable solutions of the governing equations which provide the building blocks of the disordered dynamics. We report the discovery of periodic solutions which just like intermittent turbulence are spatially localized and show that turbulent transients arise from one such solution branch.


Prehispanic (Guanches) mummies and natrium salts in burial caves of Las Cañadas del Teide (Tenerife).
The prehispanic population of Tenerife (Guanches) buried their dead in caves. Many corpses are totally or partially mummified. Embalming procedures are largely unknown, besides some information recorded by chroniclers and the general idea that environmental conditions in some areas may favour natural mummification. Detailed observation of burial caves containing mummified corpses revealed the presence of a white mineral in form of crusts or powder that was not present in the vast majority of non-burial caves, especially in basaltic and trachybasaltic lava flows. We analysed these crusts and they consist of natrium carbonate salts. Therefore, we conducted a search visiting 30 caves, 3 of them harbouring mummified corpses, and made analyses if there were natrium salts in these caves and their amount. One burial cave was located in trachyphonolitic lava flow, and two further caves in trachybasaltic and basaltic lava flows. There was a significant association between presence of natrium salts and use of the cave as a burial site (χ2 = 9.37; p = 0.0259). The semiquantitatively assessed amount of natrium salts was also by far higher in burial caves than in non-burial ones (Z = 2.58, p = 0.01). There are no reports that support the use of natrium salts in the embalming process among the Guanches, but we found a clear-cut relationship between the presence and/or amount of natrium salts in caves and their use as burial sites by the prehispanic population buried in the central highlands, suggesting an intentional use of caves containing this mineral as burial caves, based perhaps on the observation of the ability of natrium salts to preserve corpses.


Understanding the origin of liquid crystal ordering of ultrashort double-stranded DNA.
Recent experiments have shown that short double-stranded DNA (dsDNA) fragments having six- to 20-base pairs exhibit various liquid crystalline phases. This violates the condition of minimum molecular shape anisotropy that analytical theories demand for liquid crystalline ordering. It has been hypothesized that the liquid crystalline ordering is the result of end-to-end stacking of dsDNA to form long supramolecular columns which satisfy the shape anisotropy criterion necessary for ordering. To probe the thermodynamic feasibility of this process, we perform molecular dynamics simulations on ultrashort (four base pair long) dsDNA fragments, quantify the strong end-to-end attraction between them, and demonstrate that the nematic ordering of the self-assembled stacked columns is retained for a large range of temperature and salt concentration.


Mechanisms of breast cancer resistance to anthracyclines or taxanes: an overview of the proposed roles of noncoding RNA.
Anthracyclines and taxanes are the two most active classes of cytotoxic agents that are commonly used for the treatment of breast cancer. However, resistance to these agents has become a major clinical obstacle. The aim of the present review is to define the roles of noncoding RNA (ncRNA) in breast cancer progression and the development of chemotherapy resistance. The ultimate goal is to exploit ncRNAs as new therapeutic tools to overcome resistance. Two important types of ncRNA include microRNA (miRNA) and long noncoding RNA (lncRNA). Both miRNA and lncRNA have recently impacted the field of breast cancer research as important pieces in the mechanistic puzzle of the genes and pathways involved in breast cancer development and progression. Herein, we review the roles of miRNA and lncRNA in breast cancer progression and the development of chemotherapy resistance. Future research should include identification of ncRNAs that could be potential therapeutic targets in chemotherapy-resistant tumors, as well as ncRNA biomarkers that facilitate more tumor-specific treatment options for chemotherapy-resistant breast cancer patients.


Effects of Lexical Competition and Dialect Exposure on Phonological Priming.
A cross-modal lexical decision task was used to explore the effects of lexical competition and dialect exposure on phonological form priming. Relative to unrelated auditory primes, matching real word primes facilitated lexical decision for visual real word targets, whereas competing minimal pair primes inhibited lexical decision. These effects were robust across two English vowel pairs (mid-front and low-front) and for two listener groups (mono-dialectal and multi-dialectal). However, both the most robust facilitation and the most robust inhibition were observed for the mid-front vowel words with few phonological competitors for the mono-dialectal listener group. The mid-front vowel targets were acoustically more distinct than the low-front vowel targets, suggesting that acoustic-phonetic similarity leads to stronger lexical competition and less robust facilitation and inhibition. The multi-dialectal listeners had more prior exposure to multiple different dialects than the mono-dialectal group, suggesting that long-term exposure to linguistic variability contributes to a more flexible processing strategy in which lexical competition extends over a longer period of time, leading to less robust facilitation and inhibition.


Efficacy and tolerability of amlodipine/valsartan combination therapy in hypertensive patients not adequately controlled on amlodipine monotherapy.
ABSTRACT (ARB), in essential hypertensive patients not adequately controlled by amlodipine monotherapy. This was a multi-centre, randomised, double-blind, active-controlled study in patients with essential hypertension. After a washout period followed by a single-blind amlodipine 10 mg run-in period, patients with mean sitting diastolic blood pressure (msDBP) > or =90 mmHg and <110 mmHg were randomised to receive amlodipine/valsartan (10/160 mg o.d.) or amlodipine (10 mg o.d.) for 8 weeks. NCT00171002. The primary efficacy variable was change from baseline in msDBP at study endpoint. Secondary efficacy variables were change from baseline in mean sitting systolic blood pressure (msSBP), responder rate (msDBP <90 mmHg or > or =10 mmHg reduction from baseline) and DBP control rate (msDBP <90 mmHg). Of the 1283 patients enrolled in single-blind period, 944 were randomised to receive amlodipine/valsartan 10/160 mg (n = 473) and amlodipine 10 mg (n = 471). Statistically significant greater reductions (p < 0.0001) from baseline in msSBP/msDBP were observed with combination therapy (12.9/11.4 mmHg) compared to monotherapy (10.0/9.3 mmHg). Responder rate was significantly greater (p = 0.0011) with combination therapy (79.0%) compared to monotherapy (70.1%). The percentage of patients with controlled DBP was also significantly (p < 0.0001) higher with combination therapy (77.8%) compared to monotherapy (66.5%). Incidence of peripheral oedema was slightly higher with amlodipine monotherapy (9.4%) compared to combination therapy (7.6%). The combination of amlodipine/valsartan in this 8-week double-blind study provided additional BP control and was well tolerated in patients inadequately controlled with amlodipine monotherapy. Results should be interpreted with the knowledge that study entry criteria may limit application to a wider population.


Sorbic Acid as a Triplet Probe: Reactivity of Oxidizing Triplets in Dissolved Organic Matter by Direct Observation of Aromatic Amine Oxidation.
Sorbic acid (2,4-hexadienoic acid; HDA) isomerization is frequently used to probe triplet-state dissolved organic matter (3CDOM*) reactivity, but there remain open questions about the reaction kinetics of 3CDOM* with HDA due to the difficulties of directly measuring 3CDOM* quenching rate constants. Using our recently developed approach based on observing the radical cation of N,N,N',N'-tetramethyl-p-phenylenediamine (TMPD) formed through oxidation of TMPD by 3CDOM*, we studied 3CDOM* quenching kinetics with HDA monitored via transient absorption spectroscopy. A competition kinetics-based approach utilizing formation yields of TMPD•+ was developed, validated with model sensitizers, and used to determine bimolecular rate constants between 3CDOM* oxidants and HDA for diverse DOM isolates and natural waters samples, yielding values in the range of (2.4-7.7) × 108 M-1 s-1. The unquenchable fraction of TMPD-oxidizing triplets showed that, on average, 41% of 3CDOM* oxidants cannot be quenched by HDA. Conversely, cycloheptatriene quenched nearly all TMPD•+-forming triplets in CDOM, suggesting that most 3CDOM* oxidants possess energies greater than 150 kJ mol-1. Comparing results with our companion study, we found slight, but noticeable differences in the 3CDOM* quenching rate constants by HDA and unquenchable triplet fractions determined by oxidation of TMPD and energy transfer to O2 (1O2 formation) methods.


Male pattern baldness: current treatments, future prospects.
Male pattern baldness affects up to half of the male Caucasian population by middle age, and almost all Caucasian men by old age. Especially in younger men, this heritable form of hair loss can have significant psycho-social consequences. Although approved pharmacological agents exist to manage the condition, none of the currently available options are highly efficacious. New treatments under development, and acceleration in our understanding of the underlying molecular genetic aetiology of this condition provide increased hope for future targeted treatment strategies.


[Manuel P. García and the history of the laryngoscope].
Many people have never heard of Manuel García; others know him as an artist and singing teacher of exceptional qualities; yet others had heard of him as an extraordinary researcher and the first scientist to investigate the voice. Manuel Patricio García is chiefly known as the man who invented the laryngeal mirror, the first person to carry out a dynamic assessment of phonation, and therefore the founder of laryngology. The main facts in his extensive biography are reviewed, covering his career as a singer, a teacher and a scientist; The invention of the laryngoscope and the "failed attempts"; his famous family, including his father, Manuel García, and his sisters María Malibrán and Paulina Viardot; and his extensive oeuvre.


Effects of cholestatic agents on the structure and function of bile canaliculi in neonatal rat hepatocytes in primary culture.
The effects of cytochalasin B and colchicine on the structure and function of bile canaliculi were studied in neonatal rat hepatocytes in primary culture. Cellular contacts of neonatal hepatocytes were not as tight as those of adult hepatocytes. There was no remarkable difference in the ultrastructure of bile canaliculi between neonatal and adult hepatocytes. Neonatal hepatocytes treated with cytochalasin B were round in shape and aggregated in groups of several cells. Actin filaments stained by rhodamine-phalloidin were disrupted and condensed at the cell periphery or around dilated bile canaliculi. Markedly-dilated bile canaliculi with less microvilli were observed by transmission electron microscopy while the secretory function of horseradish peroxidase, which was used as a marker for uptake, transport and secretion into bile canaliculi, were maintained. The lumen of dilated bile canaliculi was found close to the undersurfaces of hepatocytes by scanning electron microscopy after turning over the cultured cells. By colchicine treatment, the filamentous structure of microtubules in neonatal hepatocytes disappeared. The ultrastructure of the bile canaliculi was not affected by the treatment, but transport and secretion of horseradish peroxidase into bile canaliculi were inhibited. The development of strict cellular polarity in neonatal hepatocytes may be suppressed in neonatal hepatocytes; however, cholestatic agents which rearrange the cytoskeleton caused the same morphological or functional changes of bile canaliculi as in adult hepatocytes.


A study of the kinetic behaviour of glucose based on simultaneous estimates of influx and phosphorylation in brain regions of rats in different physiological states.
Results from the application of a procedure that allows simultaneous estimation of the rates of glucose transport from blood and of glucose phosphorylation in discrete regions of the brain are given for groups of rats displaying chemically induced motor disturbances. The procedure is based on sequential injections of [14C]- and [3H]-2-deoxyglucose followed a few minutes later by focused microwave irradiation to the head. Control conscious rats were used and rats displaying either whole body tremors, hind-limb rigidity or choreoathetotic movements induced by synthetic pyrethroid compounds. For individual rats estimates of 5 parameters were obtained in up to 16 brain regions. In addition brain tissue and plasma glucose concentrations were determined. The 5 parameters were: (1) rate of total glucose influx from plasma; (2) rate of glucose phosphorylation (equivalent to net influx); (3) rate of glucose efflux; (4) half-life of free glucose in brain; and (5) PS-product expressed as the ratio of the rate of glucose influx to plasma glucose concentration. For each parameter significant differences between regions were found in all groups of animals including conscious controls. The mean values for the somatosensory cortex of control rats were parameter: (1) 2.02 mumol/g/min; (2) 1.11 mumol/g/min; (3) 0.91 mumol/g/min; (4) 0.94 min; and (5) 0.196 ml/g/min. A high correlation was observed between the rate of total glucose influx and the rate of glucose phosphorylation for all brain regions in all groups of rats. This finding is discussed in terms of a synchronized regulatory mechanism on the glucose transport carrier of capillary endothelial cells and on the functional hexokinase Vmax activity within brain cells.


[Acral erythema after allogeneic graft of the bone marrow].
Acral erythema (AE) is a painful, erythematous bullous eruption of the palms and soles which is chemotherapy-induced. To the numerous chemotherapies which induce AE we must add, perhaps, a new drug, Vépéside. AE is followed by graft-versus-host-disease in all patients receiving bone marrow transplantation. AE and early GVH disease being very similar, we discuss the differential diagnosis which can be very difficult.


Detection of Escherichia coli O157, Salmonella enterica serovar Typhimurium, and staphylococcal enterotoxin B in a single sample using enzymatic bio-nanotransduction.
Enzymatic bio-nanotransduction is a biological detection scheme based on the production of nucleic acid nano-signals (RNA) in response to specific biological recognition events. In this study, we applied an enzymatic bio-nanotransduction system to the detection of important food-related pathogens and a toxin. Escherichia coli O157:H7, Salmonella enterica serovar Typhimurium, and staphylococcal enterotoxin B (SEB) were chosen because of the implications of these targets to food safety. Primary antibodies to each of the targets were used to functionalize magnetic beads and produce biological recognition elements (antibodies) conjugated to nano-signal-producing DNA templates. Immunomagnetic capture that was followed by in vitro transcription of DNA templates bound to target molecules produced RNA nano-signals specific for every target in the sample. Discrimination of RNA nano-signals with a standard enzyme-linked oligonucleotide fluorescence assay provided a correlation between nano-signal profiles and target concentrations. The estimated limit of detection was 2.4 x 10(3) CFU/ml for E. coli O157:H7, 1.9 X 10(4) CFU/ml for S. enterica serovar Typhimurium, and 0.11 ng/ml for SEB with multianalyte detection in buffer. Low levels of one target were also detected in the presence of interference from high levels of the other targets. Finally, targets were detected in milk, and detection was improved for E. coli 0157 by heat treatment of the milk.


rhIL-1Ra reduces hepatocellular apoptosis in mice with acute liver failure mainly by inhibiting the activities of Kupffer cells.
In clinic, there is still no drug that can significantly improve the survival rate of patients with acute liver failure (ALF). We have confirmed that recombinant human IL-1 receptor antagonist (rhIL-1Ra) significantly improves the survival rate of acetaminophen (APAP)-induced ALF mice by reducing hepatocellular apoptosis. Here, we investigated the mechanism of this and the key target cells of rhIL-1Ra. In vivo, APAP-induced ALF mice were treated with rhIL-1Ra and gadolinium chloride (Gdcl3), respectively. Survival rates of mice, serum IL-1Ra and IL-1β levels, IL-1 receptor type I (IL-1RI) and CD163 expression in the livers, and the phagocytic activities of Kupffer cells (KCs) were investigated. Additionally, the proliferation of hepatocytes and KCs in co-culture conditions with the serum of ALF mice were investigated in vitro. In this study, a large number of activated large KCs were found in liver lobe region III. Both GdCl3 and rhIL-1Ra significantly decreased the quantity of large KCs. In all of the mice, hepatocytes and liver non-parenchymal cells other than KCs expressed low levels of IL-1RI, whereas large KCs expressed high levels of IL-1RI. The high ratio of endogenous IL-1Ra/IL-1β was related to rhIL-1Ra function. Additionally, the phagocytic activities of KCs were significantly inhibited by GdCl3 and rhIL-1Ra. In vitro, the proliferation of hepatocytes in co-culture conditions were significantly inhibited by KCs. In conclusion, large KCs were the key target cells of rhIL-1Ra, and rhIL-1Ra could play its role of reducing hepatocellular apoptosis mainly by inhibiting the activities of KCs.


Myocardial troponin T levels in patients with diabetic nephropathy.
We investigated myocardial troponin T (TnT) level as a marker for myocardial injury at various stages of diabetic nephropathy, including end-stage renal failure. One hundred and four diabetic patients were included in this study. These patients were divided into 5 groups as follows: Group I, composed of 41 patients without nephropathy who served as controls; Group II, composed of 15 patients with micro-albuminuria; Group III, composed of 15 patients with macroalbuminuria; Group IV, composed of 8 patients with renal failure who were not receiving hemodialysis; and Group V, composed of 25 patients who were receiving hemodialysis for renal failure. The following markers of myocardial injury were measured in these patients: myocardial TnT, creatine kinase (CK), myoglobin (Mb), and myosin light chain-1 (MCL-1). Our results showed that as the disease state of diabetic nephropathy advanced to renal failure, myocardial TnT levels became elevated. Group V showed significantly higher myocardial TnT levels than either Group I, Group II or Group III. Group IV showed significantly higher myocardial TnT levels than either Group II or Group III. The rate of ischemic changes on electrocardiograms also tended to increase with advance to renal failure in these patients. However, there was no correlation between myocardial TnT levels and serum Cr levels, used as an index for renal function. Myocardial TnT levels had a higher specificity for cardiac muscle than other markers for myocardial injury and are not significantly influenced by renal function. Myocardial TnT may be useful as a marker of myocardial injury for patients with chronic renal failure.


A model of brain function: its implications for psychiatric research.
Much current research in psychiatry proceeds in the absence of an integrated model of brain function. It is based instead on the effort to relate clinical syndromes to single, localised abnormalities in the brain. Such an approach is inconsistent with existing data, inadequate for linking research findings with clinical practice, and, probably, fundamentally misdirected. A model of brain function is presented that is based on Luria's notion of cerebral functional systems and on the proposition that the neural substrates of emotion are those processes that integrate different brain regions. Some of the implications of this model for research are discussed.


Examining the Bidirectional Associations between Adolescents' Disclosure, Parents' Solicitation, and Adjustment Problems among Non-Hispanic White and Hispanic Early Adolescents.
Research indicates that parents' solicitation and adolescents' disclosure of information are negatively associated with adjustment problems (depressive symptoms and conduct problems). However, few studies examine the bidirectional associations between these variables with early adolescents in the United States or the race/ethnic group differences in these bidirectional associations. We examined cross-lagged associations and race/ethnic group differences between parents' solicitation, adolescents' disclosure and adjustment problems among 209 non-Hispanic White (61.2%) and Hispanic (38.8%) early adolescents (67.5% female) across a 1-year period. The findings indicated that adolescents' disclosure was negatively associated with subsequent depressive symptoms, while parents' solicitation was positively associated with subsequent depressive symptoms. No significant race/ethnic group differences were indicated. Family-based interventions should encourage adolescents to disclose information to parent(s) due to its promotive capabilities.


Effect of 6-dimethylaminopurine on germinal vesicle breakdown of bovine oocytes.
The effect of 6-dimethylaminopurine (6-DMAP) on germinal vesicle breakdown (GVBD) and maturation in bovine oocytes was investigated in this study. This puromycin analog has been shown to be an inhibitor of phosphorylation. Whereas GVBD occurred in nearly all oocytes (96.8%, 120/124) in control medium, presence of 6-DMAP (2 mM) blocked this process almost completely, irrespective of the presence (98.3% GV, 349/355) or absence (97.1% GV, 165/170) of cumulus cells. When lower concentrations of 6-DMAP were used (100-500 microM), GVBD was observed in 87.9% of oocytes, but their maturation was arrested at late diakinesis-metaphase I stage. The inhibition of GVBD was fully reversible, but most of the metaphase II plates were abnormal (80%). To assess whether the action of 6-DMAP is different from the inhibitors of protein synthesis, metaphase II oocytes were exposed to either cycloheximide or 6-DMAP, respectively. Whereas in cycloheximide-supplemented medium approximately 80% of the oocytes were activated, parthenogenetic activation was much less frequent after incubation in 6-DMAP (14.5%). Fusion studies showed that, even if GVBD occurs in 6-DMAP supplemented medium, the level of the maturation-promoting factor (MPF) is decreased. These experiments may indicate the importance of phosphorylation for GVBD in cattle oocytes.


[Assessment of changes in levels of interleukin 6 and C reactive protein in patients with breast tumors].
Serum concentrations of interleukin 6 (IL-6) and C-reactive protein (CRP) were determined in 74 patients with various histological types and clinical stages of breast carcinoma, recurrent breast carcinoma and of benign breast tumor. The concentrations of IL-6 and CRP were significantly increased in carcinoma patients relative to control group and to benign breast tumor group. The frequency of higher levels and absolute value of IL-6 and CRP showed tendency to significant increase with the stage of disease. A positive correlation was observed between the concentrations of IL-6 and CRP. Our results suggest that of IL-6 assay may be useful in estimation of progress disease in patients with breast carcinoma.


Crystal structure of the archaeal asparagine synthetase: interrelation with aspartyl-tRNA and asparaginyl-tRNA synthetases.
Asparagine synthetase A (AsnA) catalyzes asparagine synthesis using aspartate, ATP, and ammonia as substrates. Asparagine is formed in two steps: the β-carboxylate group of aspartate is first activated by ATP to form an aminoacyl-AMP before its amidation by a nucleophilic attack with an ammonium ion. Interestingly, this mechanism of amino acid activation resembles that used by aminoacyl-tRNA synthetases, which first activate the α-carboxylate group of the amino acid to form also an aminoacyl-AMP before they transfer the activated amino acid onto the cognate tRNA. In a previous investigation, we have shown that the open reading frame of Pyrococcus abyssi annotated as asparaginyl-tRNA synthetase (AsnRS) 2 is, in fact, an archaeal asparagine synthetase A (AS-AR) that evolved from an ancestral aspartyl-tRNA synthetase (AspRS). We present here the crystal structure of this AS-AR. The fold of this protein is similar to that of bacterial AsnA and resembles the catalytic cores of AspRS and AsnRS. The high-resolution structures of AS-AR associated with its substrates and end-products help to understand the reaction mechanism of asparagine formation and release. A comparison of the catalytic core of AS-AR with those of archaeal AspRS and AsnRS and with that of bacterial AsnA reveals a strong conservation. This study uncovers how the active site of the ancestral AspRS rearranged throughout evolution to transform an enzyme activating the α-carboxylate group into an enzyme that is able to activate the β-carboxylate group of aspartate, which can react with ammonia instead of tRNA.


Acute massive rhabdomyolysis due to prolonged inhalation of liquid gas.
A very rare case of non-fatal acute massive rhabdomyolysis caused by unintentional prolonged inhalation of liquid gas (consisting of butane and propane) in a previously healthy adult is presented. The immediate diagnosis and intensive symptomatic therapy prevented any other severe complications of rhabdomyolysis, and the patient made a complete recovery without any sequelae.


Renovation of a "sick building": the challenge of attaining the confidence of occupants.
This case study focused on the renovation of a building with severe mold and HVAC problems. The users did not trust the success of the planned remedies, and the situation became conflict-prone. The aims of the study were to improve communication and cooperation between experts participating in the renovation process and the future users of the building and monitor the success of the remedies. An intervention was implemented with the aim of making the renovation easily understood by the future users of the building and preventing the escalation of unnecessary concern among them. The follow-up methods comprised a questionnaire study, technical inspections, quality measurements of the indoor air, structural follow-up measurements, and interviews of key persons. The renovation itself seems to have been successful, and the model to improve communication and cooperation appears to be a promising one. The confidence of the future users was attained, and the relocation took place as planned. In order to succeed in the renovation of a "sick building," both technical expertise and investment in information and communication are needed.


Survival of patients with non-small cell lung cancer having leptomeningeal metastases treated with immune checkpoint inhibitors.
Patients with non-small cell lung cancer (NSCLC) experience leptomeningeal metastases (LM) in 3-9% of cases. Because overall survival (OS) and performance status are very poor, they are mostly excluded from clinical trials. Here, we evaluated survival of patients with NSCLC having LM treated with immune checkpoint inhibitors (ICIs). A prospectively collected list of patients with advanced NSCLC treated with ICIs between November 2012 and July 2018 in 7 European centres was merged. All patients with LM before ICI start were selected, data were retrospectively added and patients were classified according to the National Comprehensive Cancer Network (NCCN) LM prognostic classification (good/poor). Progression-free survival (PFS) and OS on ICIs were evaluated. Nineteen of 1288 (1.5%) patients had LM; 73.7% had synchronous brain metastases; 73.7% had neurological symptoms at the start of ICIs and 52.6% were in the NCCN LM good prognosis group. Programmed death ligand-1 (PD-L1) expression was known for 42.1% of patients (87.5% positive). Median follow-up was 13 months from the start of ICIs, and median (95% confidence interval [CI]) PFS on ICIs was 2.0 (1.8-2.2) months. Six-month PFS rate was 21.0% and was significantly higher in the NCCN good versus poor prognostic group: 40% vs 0% (p = 0.05). Twelve-month PFS rate was 0%. Median (95% CI) OS from the start of ICIs was 3.7 (0.9-6.6) months. Six-month OS rate was 36.8%, and 12-month OS rate was 21.1%; both were not statistically significantly different for the good versus poor NCCN prognostic group (p = 0.40 and p = 0.56, respectively). Some patients with NSCLC having LM do benefit from ICI treatment; specifically, those in the NCCN LM good prognosis group can obtain a long survival.


Strong inhibition of crystal-cell attachment by pediatric urinary macromolecules: a close relationship with high urinary citrate secretion.
To investigate other reasons for the low incidence of pediatric urolithiasis, we evaluated the difference in the crystal-cell adhesion inhibitory activity of urinary macromolecules (UMMs) between children and adults. We also evaluated whether citrates influence the above inhibitory activity, because citrates are important in pediatric urine. Urine samples were collected from children and healthy male adults during a 24-hour period, and urinary components with a molecular weight of 3 kDa or greater were extracted as UMMs to compare their inhibitory activity during the adhesion of calcium oxalate monohydrate crystals to cultured Madin-Darby canine kidney cells between children and adults. Subsequently, various concentrations of citrates were added to adult UMMs to evaluate the changes in the crystal-cell adhesion inhibitory activity of UMMs. Pediatric UMMs more strongly inhibited the adhesion of calcium oxalate monohydrate crystals to cultured Madin-Darby canine kidney cells at a concentration of 0.1 mg/mL compared with adult UMMs. In addition, pediatric UMMs contained higher proportions of fibronectin and glycosaminoglycans, both of which exhibit crystal-cell adhesion inhibitory activity. When citrates were added to adult UMMs, the crystal-cell adhesion inhibitory activity of UMMs was increased in a dose-dependent manner. However, citrates alone did not result in any differences in the inhibitory activity at any of the three different concentrations. We speculate that the incidence of pediatric urolithiasis is low because pediatric UMMs more potently inhibit the adhesion of calcium oxalate crystals to renal tubular cells or because the higher proportion of citrates in pediatric urine enhances the crystal-cell adhesion inhibitory activity of UMMs in a dose-dependent manner.


[Radical Operation Performed on a Gastric Cancer Patient with Cold Agglutinin Disease - A Case Report].
A 56-year-old man with no abnormalmedicalhistory was admitted to our hospitalfor gastric cancer surgery. The preoperative laboratory tests indicated anemia, hyperbilirubinemia, hemagglutinin reaction, and a markedly high cold agglutinin titer; thus, we diagnosed the patient with cold agglutinin disease(CAD). Although perioperative complications caused by cold stimulation were suspected, we decided that it was possible to perform the operation under robust intraoperative conditions avoiding exposure to cold temperatures, and thus performed the radical operation. Intraoperatively, we performed blood transfusion because the anemia of the patient progressed owing to bleeding; however, no other complications were noted. Postoperatively, the clinical course was good without any complications, and the patient was discharged 13 days after the operation. The present case demonstrated that CAD patients requiring surgery can safely be operated on if their conditions, including perioperative body temperature management, are adequately considered during surgical preparation.


Pharmacokinetics of recombinant factor IX in relation to age of the patient: implications for dosing in prophylaxis.
The aims of this study were to investigate possible age-related changes in the disposition of factor IX procoagulant activity (FIX:C) after administration of recombinant factor IX (rFIX) and to translate the pharmacokinetic findings into suggestions for dosing of rFIX during prophylactic treatment of haemophilia B. Pharmacokinetic data were available from a previous study on 56 patients, aged 4-56 years (one of whom was excluded from analysis). FIX:C curves during prophylactic dosing were computer-simulated from the single-dose data. Clearance and volume of distribution at steady state of FIX:C increased linearly with body weight of the patients, consequently increasing during childhood and adolescence but remaining fairly constant during adulthood. The terminal half-life of FIX:C showed no correlation with age, while in vivo recovery (in U dL(-1) per U kg(-1) given) tended to increase. Computer-predicted trough levels of exogenous FIX:C during repeated doses of rFIX (50 U kg(-1)) and, conversely, doses (in U kg(-1)) needed to maintain a 1-U dL(-1) trough level showed little or no dependence on age. There was considerable interindividual variation in disposition and required doses of rFIX, emphasizing the need for individual dose titration. Dosing of rFIX according to lean body mass instead of body weight did not reduce this variability. During prophylaxis a 1-U dL(-1) trough level can normally be maintained by dosing every 2-3 days, the former schedule resulting in, on average, a 45% lower consumption of rFIX.


Laboratory demonstrations of interferometric and spotlight synthetic aperture ladar techniques.
A variety of synthetic-aperture ladar (SAL) imaging techniques are investigated on a table-top laboratory setup using an ultra-broad bandwidth (>3 THz) actively linearized chirp laser centered at 1.55 microns. Stripmap and spotlight mode demonstrations of SAL in monstatic and bistatic geometries are presented. Interferometric SAL for 3D topographical relief imaging is demonstrated highlighting the coherent properties of the SAL imaging technique.


Patient selection for ventricular assist devices: a moving target.
The number of patients with advanced heart failure that has become unresponsive to conventional medical therapy is increasing rapidly. One of the most promising new alternatives to heart transplantation is use of ventricular assist devices (VADs). To date, there are no guidelines for appropriate selection for use of these devices that are approved by national societies in the field. This review addresses all of the general criteria for clinicians to keep in mind regarding when to refer a patient for evaluation and the specific issues addressed in patient selection. The field of mechanical circulatory support has advanced significantly over the past 10 years, resulting in rapid expansion of patients with advanced heart failure who can benefit from implantable devices. With progress of technology, limitations associated with age, body size, and comorbidities gradually become less prohibitive. The continuing simplification of design along with continued reduction in size of the devices, plus eventual elimination of the external drive line will make the use of VADs a superior option to heart transplant and even to medical management in many patients. We anticipate that the patient selection process outlined in the present review will continue to shift toward less advanced cases of heart failure.


Long-term follow-up of 5262 breast cancer patients with negative sentinel node and no axillary dissection confirms low rate of axillary disease.
It is established that axillary dissection (AD) can be safely avoided in breast cancer patients with a negative sentinel node (SN). In the present study we assessed whether the rate of axillary disease was sufficiently low on long term follow-up to consolidate the policy of AD avoidance. We retrospectively analysed data on 5262 consecutive primary breast cancer patients with clinically negative axilla and negative SN, treated from 1996 to 2006, who did not receive AD. We used univariate and multivariate analyses to assess the influence of patient and tumour characteristics on first events and survival. The primary endpoint was the development of axillary disease as first event. After a median follow-up of 7.0 years (interquartile range 5.4-8.9 years) survival for the series was high (91.3%; 95% CI 90.3-92.3 at 10 years) and only 91 (1.7%) patients developed axillary disease as first event. Axillary disease was significantly more frequent in patients with the following characteristics: <35 years at diagnosis, tumour >1 cm, multifocality/multicentricity, G3, ductal histotype, Ki67 ≥ 30%, peritumoral vascular invasion, luminal B-like subtype, HER2 positivity, mastectomy, and not receiving radiotherapy. Long-term follow-up of our large series confirms that axillary metastasis is infrequent when AD is omitted in SN-negative breast cancer patients, and has low impact on overall survival.


Squamous cell carcinoma of the external auditory canal. Therapeutic prognosis based on a proposed staging system.
To determine the adequacy of the proposed TNM staging system and evaluate the therapeutic modalities used at our institution in an attempt to synthesize guidelines for therapy of primary squamous cell carcinoma (SCC) of the temporal bone. Case series of 22 patients with previously untreated or residual SCC of the temporal bone treated between 1970 and 1990. Mean follow-up of the surviving patients was 124.5 months (range, 46 to 210 months). University of Texas M. D. Anderson Cancer Center, Houston, an ambulatory and hospitalized care referral center. The hospital charts of 41 patients with carcinoma of the temporal bone seen between 1970 and 1990 were retrospectively reviewed. Twenty-two of these patients had previously untreated or residual SCC of the external auditory canal and were chosen for this study. Information was collected regarding symptoms, tumor location, treatment methods, pathologic diagnosis, and patient outcomes. Accuracy of proposed staging system in predicting 5-year survival. Effect of surgery alone, radiotherapy alone, and surgery combined with radiotherapy on survival. Using the Pittsburgh staging system, the conditions of eight patients (36%) were staged at T1, four (18%) were staged at T2, six (27%) were staged at T3, and four (18%) were staged at T4. (The 19 patients with either recurrent disease or non-SCC were also treated, but their conditions were not staged). Statistical validation is impossible owing to the small sample sizes. Combination therapy with surgery and radiotherapy provided a higher 5-year survival rate than surgery or radiotherapy alone. Extrapolation of our data confirms that a staging system is useful in planning therapy. Surgical resection followed by radiotherapy is the preferred treatment for SCCs of the external auditory canal.


Bananas--physiology and biochemistry of storage and ripening for optimum quality.
Bananas (Musa spp.) are a major food crop of the humid tropics, and although edible cultivars are diverse and numerous, most of our knowledge of the physiology and biochemistry of these fruits relates to a few dessert cultivars of the AAA type, mainly of the Cavendish subgroup, which dominate the export trade between tropical and temperate zones. The preclimacteric period of banana fruits after harvest determines their transportability, and its duration is very sensitive to changes in fruit maturity, storage temperature, ethylene concentration, and other factors; progress in measurement and resolution of each of these effects is described. Changes in composition of the ripening fruits, especially in the development of flavor volatiles, are reviewed. Progress in understanding the integration of the biochemical changes controlling ripening in banana fruits is discussed. Recent work on storage, ripening, and factors relating to sensory assessment of fruit quality is discussed for cultivars of Musa types not used in major export trades.


Transgenic alfalfa that accumulates piceid (trans-resveratrol-3-O-beta-D-glucopyranoside) requires the presence of beta-glucosidase to inhibit the formation of aberrant crypt foci in the colon of CF-1 mice.
Plants have been genetically enhanced to produce a number of products for agricultural, industrial and pharmaceutical purposes. This technology could potentially be applied to providing chemoprevention strategies to the general population. Resveratrol (3,5,4'-trihydroxystilbene) is a compound that has been shown to have protective activity against a number of cancers and could be an ideal candidate for such an application. Alfalfa that was genetically modified to express resveratrol-synthase was used as a model in applying biotechnological approaches to cancer prevention. The transgenic alfalfa, which accumulates resveratrol as a glucoside (piceid = trans-resveratrol-3-O-Beta-D-glucopyranoside) (152 +/- 17.5 microg piceid/g dry weight), was incorporated into a standard mouse diet at 20% of the diet by weight and fed for 5 wk to 6-wk-old, female CF-1 mice (N = 17-30) that were injected with a single dose of azoxymethane (5 mg/kg body weight). While the addition of resveratrol-aglycone (20 mg/kg diet) to the basal diet reduced the number of aberrant crypt foci/mouse, the transgenic alfalfa did not inhibit the number, size, or multiplicity of aberrant crypt foci in the colon of the CF-1 mice relative to control alfalfa which does not accumulate resveratrol-glucoside. However, diets containing transgenic alfalfa with an exogenous Beta-glucosidase (860 U/kg diet) did significantly inhibit the number of aberrant crypt foci in the distal 2 cm of the colon of the mice relative to mice fed diets containing the transgenic alfalfa without the enzyme (P < 0.05; Fisher's Combination of p-values). The Beta-glucosidase alone appeared to have no effect on the inhibition of aberrant crypt foci. These results suggest that piceid in transgenic piceid-accumulating alfalfa was not bioavailable.


Emerging zoonotic encephalitis viruses: lessons from Southeast Asia and Oceania.
The last decade of the 20th Century saw the introduction of an unprecedented number of encephalitic viruses emerge or spread in the Southeast Asian and Western Pacific regions (Mackenzie et al, 2001; Solomon, 2003a). Most of these viruses are zoonotic, either being arthropod-borne viruses or bat-borne viruses. Thus Japanese encephalitis virus (JEV), a mosquito-borne flavivirus, has spread through the Indonesian archipelago to Papua New Guinea (PNG) and to the islands of the Torres Strait of northern Australia, to Pakistan, and to new areas in the Indian subcontinent; a strain of tick-borne encephalitis virus (TBEV) was described for the first time in Hokkaido, Japan; and a novel mosquito-borne alphavirus, Me Tri virus, was described from Vietnam. Three novel bat-borne viruses emerged in Australia and Malaysia; two, Hendra and Nipah viruses, represent the first examples of a new genus in the family Paramyxoviridae, the genus Henipaviruses, and the third, Australian bat lyssavirus (ABLV) is new lyssavirus closely related to classical rabies virus. These viruses will form the body of this brief review.


[Plasma potassium concentrations during N2O-enflurane anesthesia in patients on chronic hemodialysis].
Plasma potassium concentrations during anesthesia with N2O and enflurane in O2 were measured in 12 patients on chronic hemodialysis (HD) who underwent HD for about 2 hours just before anesthesia. Pre-HD and pre-anesthetic plasma potassium concentrations were 5.0 +/- 0.2 and 4.3 +/- 0.2 mEq.l-1, respectively. The potassium levels decreased slightly following induction of anesthesia, but increased significantly during and after surgery; and at the end of anesthesia the levels were similar to those measured just before HD. None of the patients developed acidosis, hypoxia or hypercapnia. Based on our results, we consider that plasma potassium levels should be measured frequently during surgery in patients who have high potassium levels just before HD and are subjected to HD just before anesthesia, because hyperkalemia may occur.


Preparative isolation and purification of psoralen and isopsoralen from Psoralea corylifolia by high-speed counter-current chromatography.
Psoralen and isopsoralen were separated from Psoralea corylifolia by high-speed counter-current chromatography (HSCCC). A two-phase solvent system composed of n-hexane-ethyl acetate-methanol-water (5:5:4.5:5.5, v/v) was used for HSCCC separation, and yielded, from 100 mg of crude extract, 39.6 mg of psoralen and 50.8 mg of isopsoralen each at over 99% purity as determined by high performance liquid chromatography (HPLC). The identification of psoralen and isopsoralen were performed with 1H NMR and 13C NMR.


Daily distribution of sleep states in the jackdaw, Corvus monedula.
Polygraphic and behavioral studies of the jackdaws Corvus monedula have revealed a strong influence of the natural day-night cycle on their daily wakefulness-sleep activity. The jackdaws were behaviorally active during the light part of the photoperiod. The daily distribution of slow wave sleep (SWS) was symmetric and that of paradoxical sleep (PS) was asymmetric. The amount of PS was greater in the second half of the night than in the first. Short and intermediate length episodes occurred almost homogeneously throughout the night. The longest sleep episodes clustered toward the middle part of the night and did not occur in the periods following onset of sleep and before the end of sleep.


Factors associated with development and mortality of pulmonary hypertension in systemic lupus erythematosus patients.
Objectives This study aims to identify the factors associated with the development and mortality of pulmonary hypertension (PH) in systemic lupus erythematosus (SLE) patients. Methods We conducted a prospective study of SLE patients in a single tertiary center. PH was defined as a systolic pulmonary arterial pressure ≥30 mmHg on transthoracic echocardiography. We assessed potential associated factors contributing to the development and mortality of PH in SLE patients. Results Of 1110 patients with SLE, 48 patients were identified to have PH. Multivariable analysis indicated that pleuritis or pericarditis (odds ratio (OR) = 4.62), anti-RNP antibody (OR = 2.42), interstitial lung disease (ILD) (OR = 8.34) and cerebro-cardiovascular disease (OR = 13.37) were independently associated with the development of PH in SLE. Subgroup analysis among patients with PH demonstrated that there were no statistically significant factors associated with PH mortality in SLE. Conclusions The prevalence of PH was 4.3% in our cohort. There were significant associations with pleuritis or pericarditis, anti-RNP antibody, ILD, and cerebro-cardiovascular disease in SLE, which may contribute to the development of PH. However, there were no statistically significant factors associated with PH mortality in SLE.


Failure of coffee to inhibit the pharmacodynamic activity of morphine in vivo.
High doses of caffeine-containing as well as decaffeinated instant coffee neither inhibited morphine-induced analgesia in mice nor the morphine-induced fall of blood pressure, heart rate and respiratory rate in rats. On the contrary, caffeine-containing coffee even enhanced the analgesic effects of morphine in mice. Coffee thus does not exhibit opiate-antagonizing activity in the whole organism in vivo. The very weak morphine-antagonistic efficacy of coffee powder in the myenteric plexus-longitudinal muscle preparation from the guinea pig ileum is of no practical importance.


Release of ovarian progesterone during the rat oestrous cycle by ganglionic cholinergic influence: the role of norepinephrine.
The coeliac ganglion neurons, whose axons constitute the superior ovarian nerve (SON), contain cholinergic receptors. The aim of this work was to study the effect of cholinergic agents added to the coeliac ganglion on the release of ovarian progesterone in the coeliac ganglion-SON-ovary in vitro system. We also analyzed the release of norepinephrine in the ovarian compartment and its possible relationship with the release of progesterone. After the addition of cholinergic agents in the ganglion compartment, progesterone release was determined by radioimmuneassay (RIA) and norepinephrine by catecholamine assay (HPLC). The release of progesterone and norepinephrine in the ovary compartment was studied during period of 180 min in pre-oestrus (PE), oestrus (E), dioestrus day 1 (D1) and dioestrus day 2 (D2) rats. The most relevant results concerning the action of acetylcholine were found on PE and dioestrus. On PE, the pre-ovulatory peak of progesterone, which is known to respond to the endocrine action, was not modified by neural effect of acetylcholine in our scheme. On the other hand, the progesterone peak occurs in the afternoon of D1, which has been described as independent of the gonadotrophic action but was inhibited by neural effect of acetylcholine in our experimental scheme. This action on D1 was accompanied by a decrease of norepinephrine release in the ovary compartment. We conclude that the action of cholinergic agents varies according to the oestrous cycle stage and constitutes one of the factors governing the secretory activity of the ovarian steroids, in this case, progesterone.


Enzyme linked immunosorbent assay for potency testing of vaccines containing Clostridium perfringens type D epsilon-toxoid.
For ethical, economic and technical reasons in vivo assays need to be replaced in routine laboratory procedures. Based on a method which is already accepted by the British authorities, an indirect ELISA has been developed and evaluated for Clostridium perfringens type D-containing vaccines. Individual and pooled sera of vaccinated rabbits were tested at a single dilution level, the results transferred into IU/ml, and compared with the conventional toxin neutralization test in mice. The ELISA was found to give reproducible estimates of antitoxin levels and showed good correlation with the conventional in vivo test in mice.


Introduction: RNA and the treatment of human cancer.
Epigenetic events are important in carcinogenesis and for the susceptibility of malignant cells to chemotherapy, and this knowledge has identified a new generation of oncogenes and thereby also a new class of possible therapeutic targets for anticancer treatment. RNA reflects gene expression and can thereby be used for identification of therapeutic targets through global gene expression analysis or siRNA screening. However, molecular events at the RNA level are important regulatory mechanisms (i.e., the small regulatory RNAs) and a level for posttranscriptional modification of proteins through alternative RNA splicing. Recent publications have described RNA repair mechanisms that may be involved in carcinogenesis as well as chemosensitivity of human cancer. Most available clinical studies try to target gene expression and thereby RNA-associated regulatory mechanisms mainly through non-specific targeting of gene expression by histone deacetylase inhibition or demethylating agents, but the use of bcl-2 antisense represents an example of specific therapy. Future RNA-targeting studies have to focus on the development of new therapeutic strategies: (i) new therapeutic agents should possibly be more specifically directed towards the target molecules rather than towards more general molecular mechanisms with effects on a wide range of intracellular regulators; and (ii) drug delivery systems have to be developed so that the treatment can be directed towards the localization of the malignant disease to reduce the risk of serious side effects.


Acute and chronic toxicity of copper to the euryhaline rotifer, Brachionus plicatilis ("L" strain).
This article presents data from original research, intended for the use in the development of copper (Cu) criteria for the protection of estuarine and marine organisms and their uses in the United States. Two 48-h static-acute toxicity tests-one with and one without added food-and a 96-h static multigeneration life-cycle test (P1-F2 generations) were performed concurrently using the euryhaline rotifer Brachionus plicatilis ("L" strain) to develop a Cu acute-to-chronic ratio (ACR) for this species. Tests were performed at 15 g/L salinity, at 25°C, and the exposure concentrations of dissolved Cu were verified. Supplemental chemical analyses were performed and reported for the development of a Cu-saltwater biotic ligand model (BLM). Supplemental analyses included alkalinity, calcium, chloride, dissolved organic carbon (DOC), hardness, magnesium, potassium, sodium, and temperature. The acute toxicity test measurement end points were the dissolved Cu median lethal concentration (LC₅₀) values based on rotifer survival. The chronic measurement end points were the dissolved Cu no-observed-effect concentration (NOEC), lowest-observed-effect concentration (LOEC), EC₂₅, EC₂₀, and EC₁₀ based on the intrinsic rate of rotifer population increase (r). The 48-h LC₅₀(Fed), 48-h LC₅₀(Unfed), 96-h NOEC, 96-h LOEC, EC₂₅, EC₂₀, and EC₁₀ were 20.8, 13.4, 6.1, 10.3, 11.7, 10.9, and 8.8 μg Cu/L, respectively. The ACRs were calculated as ratios of each 48-h LC₅₀ value [fed and unfed) and each of the 96-h chronic values (ChV; geometric mean of NOEC and LOEC)], EC₁₀, EC₂₀, and EC₂₅. The ACRs ranged from 1.15 to 2.63.


Variational calculation of highly excited rovibrational energy levels of H2O2.
Results are presented for highly accurate ab initio variational calculation of the rotation-vibration energy levels of H2O2 in its electronic ground state. These results use a recently computed potential energy surface and the variational nuclear-motion programs WARV4, which uses an exact kinetic energy operator, and TROVE, which uses a numerical expansion for the kinetic energy. The TROVE calculations are performed for levels with high values of rotational excitation, J up to 35. The purely ab initio calculations of the rovibrational energy levels reproduce the observed levels with a standard deviation of about 1 cm(-1), similar to that of the J = 0 calculation, because the discrepancy between theory and experiment for rotational energies within a given vibrational state is substantially determined by the error in the vibrational band origin. Minor adjustments are made to the ab initio equilibrium geometry and to the height of the torsional barrier. Using these and correcting the band origins using the error in J = 0 states lowers the standard deviation of the observed-calculated energies to only 0.002 cm(-1) for levels up to J = 10 and 0.02 cm(-1) for all experimentally known energy levels, which extend up to J = 35.


Plant development: PXY and polar cell division in the procambium.
The vascular stem-cell tissue known as procambium generates phloem cells on one side and xylem cells on the other. The Arabidopsis PXY gene encodes a leucine-rich repeat receptor-like kinase that is required for polar divisions of procambial cells.


A combination of PLP and DM20 transgenes promotes partial myelination in the jimpy mouse.
Mutations in the myelin proteolipid protein (PLP) gene, such as that found in the jimpy mouse, result in an abnormal structure of the myelin, severe dysmyelination, and a reduction in the number of mature oligodendrocytes. To examine the functions of the two alternatively spliced isoforms of proteolipid protein, transgenic mice were generated that express either PLP or DM20 cDNAs placed under control of the PLP upstream regulatory region. The transgenes were bred into jimpy mice, and the effect of the transgenes on the dysmyelinating phenotype was analyzed. Neither the PLP transgene nor the DM20 transgene alone had an effect on myelination in the jimpy mice. Combining the two transgenes substantially increased the number of myelinated axons, suggesting that the two alternatively spliced products of the PLP locus perform distinct functions in oligodendrocytes. The enhanced myelination was not sufficient, however, for completely correcting the dysmyelinating phenotype of the jimpy mice, nor was it accompanied by the restoration of normal levels of myelin gene expression. The inability to rescue the jimpy phenotype is most likely attributable to a dominant negative action of the abnormal proteolipid proteins present in jimpy mice. These results demonstrate the complexity of proteolipid protein function in myelination.


Vibrational spectroscopic studies and DFT calculations on NaCH3CO2(aq) and CH3COOH(aq).
Aqueous solutions of sodium acetate, NaCH3CO2, and acetic acid, CH3COOH, were studied using Raman and infrared spectroscopy. The spectra were recorded over a large concentration range, in the terahertz region and up to 4000 cm(-1). In the isotropic Raman spectrum in R-format, a polarized band at 189 cm(-1) was assigned to the ν1Na-O stretch of the hydrated Na(+)-ion and a shoulder at 245 cm(-1) to the restricted translation band, νsO-H···O* of the hydrated acetate ion, CH3CO2(-)(aq). The CH3CO2(-)(aq) and the hydrated acetic acid, CH3COOH(aq), possess pseudo Cs symmetry. Geometrical parameters for the species in the gas phase and for CH3CO2(-)(aq) and CH3COOH(aq) are reported. Characteristic bands for CH3CO2(-)(aq) and CH3COOH(aq) were assigned under the guidance of the DFT vibrational frequency calculations and discussed in detail. In aqueous NaCH3CO2 solutions, at high concentrations, no contact ion pairs could be detected, but instead solvent separated ion pairs were found. In LiCH3CO2(aq), however, contact ion pairs are formed which is indicated by the appearance of a shoulder at 939 cm(-1) and the shift of the symmetric stretching mode of the -CO2(-) group to higher wavenumbers.


Single-Stage Repair of an Unusual Association: Congenital Gerbode Defect, Hypoplastic Aortic Arch, and Partially Anomalous Pulmonary Venous Return in an Infant.
We present the case of a two-month-old male with congenital Gerbode defect, hypoplastic aortic arch, and left-sided partially anomalous pulmonary venous return. The patient underwent single-stage surgical repair, which consisted of aortic arch advancement with resection of the coarctation segment, pulmonary vein repair, and primary closure of the Gerbode defect. The anomalous pulmonary vein posed a particular challenge due to its size and distance from the left atrium, which we approached with a posterior atrial wall trapdoor baffle technique, without mobilizing the affected vein. Postoperatively and at one year follow-up, there was no evidence of residual lesions and there was unobstructed flow pattern across the aortic arch and the affected pulmonary vein.


Limited sensitivity of pigment photo-oxidation in isolated thylakoids to singlet excited state quenching in photosystem II antenna.
Light-induced pigment oxidation and its relation to excited state quenching in photosystems antennae have been investigated in isolated thylakoids. The results indicate that (i) chlorophyll oxidation takes place in two sequential steps. A slow initial phase is followed by a steep increase in the bleaching rate when more than one quarter of the chromophores are oxidised. (ii) During the initial slow phase, the carotenoid pool is bleached with an apparent rate which is about three times faster than that found for chlorophyll a and more than six times faster than that of chlorophyll b. (iii) Pigment bleaching has been observed both in photosystem I and photosystem II, and it has been possible to estimate a similar carotenoid bleaching rate in the two photosystems. (iv) The protection conferred by singlet state quenchers in the initial slow phase of pigment oxidation is modest. Taking into consideration that both the photosystems are subjected to the oxidative treatment, a somewhat larger protective effect than those estimated for photo-inhibition in thylakoids [S. Santabarbara, F.M. Garlaschi, G. Zucchelli, R.C. Jennings, Biochim. Biophys. Acta 1409 (1999) 165-170] can be computed, although it is less than 50% of the expected level on the basis of the observed reciprocity to the number of incident photons. (v) Pigment oxidation is associated with the loss of membrane ultra-structure, which is interpreted as originating from a decrease in grana stacking. The dynamics of loss of membrane ultra-structure parallel the phases observed for chlorophyll photo-bleaching.


Towards a global IT system for personalized medicine: the Medicine Safety Code initiative.
The availability of pharmacogenomic data of individual patients can significantly improve physicians' prescribing behavior, lead to a reduced incidence of adverse drug events and an improvement of effectiveness of treatment. The Medicine Safety Code (MSC) initiative is an effort to improve the ability of clinicians and patients to share pharmacogenomic data and to use it at the point of care. The MSC is a standardized two-dimensional barcode that captures individual pharmacogenomic data. The system is backed by a web service that allows the decoding and interpretation of anonymous MSCs without requiring the installation of dedicated software. The system is based on a curated, ontology-based knowledge base representing pharmacogenomic definitions and clinical guidelines. The MSC system performed well in preliminary tests. To evaluate the system in realistic health care settings and to translate it into practical applications, the future participation of stakeholders in clinical institutions, researchers, pharmaceutical companies, genetic testing providers, health IT companies and health insurance organizations will be essential.


Comparisons of outcomes and survivals for two central venous access port systems.
This study compares the outcomes and survivals between two central venous access port systems. Medical records from 298 cancer patients who had received open-end (Deltec, N = 159) or closed-end (Groshong, N = 139) port catheter insertions were retrospectively reviewed. The infection, thrombosis, and surgical complication rates (chi-square test), as well as mean catheter-indwelling-days (t-test) were compared. Kaplan Meier analysis and stratified log rank test were used to compare actuarial survival rates. Cox proportion hazard model was applied to analyze the outcomes predictors. The total catheter-indwelling-day was 116,603 days in general for this cohort. The Groshong catheters (569 +/- 386.1 days) had longer (P < 0.001) mean catheter-indwelling-day than did Deltec catheters (239 +/- 235.6 days). But the per 1,000 catheter day infection (Deltec 0.18, Groshong 0.16), thrombosis (Deltec 0.07, Groshong 0.06), and surgical complication rates (Deltec 0.07, Groshong 0.02) were equivalent (P > 0.05) between two groups. Patients with leukemia were at higher risk (odds ratio 13.4, P = 0.009) to develop adverse events. However, two types of catheters had similar actuarial survival rates at end of follow up (P > 0.05). We found infection, thrombosis occlusion, surgical complication, and actuarial device survival rates were similar between Deltec and Groshong groups. Hematogenous malignancy was a risk factor for catheter failure.


Rebuttal to Nelson et al. 'Response to Bodin and Grote regarding postdoctoral recruitment in clinical neuropsychology'.
Nelson et al. provided a response to our commentary on the postdoctoral match in clinical neuropsychology. In this brief rebuttal, we will focus on statements from Nelson et al. that we believe are factual inaccuracies or misunderstandings of some of the points we made in our commentary. In addition, we will comment briefly on the proposed guidelines offered in their response.


Serotonin suppresses N-methyl-D-aspartate responses in acutely isolated spinal dorsal horn neurons of the rat.
In acutely isolated spinal dorsal horn neurons of the rat, effects of serotonin (5-hydroxytryptamine, 5-HT) on inward current induced by excitatory amino acids were studied under whole-cell voltage-clamp condition. 5-HT suppressed the response to N-methyl-D-aspartate (NMDA), but not the response to kainate or quisqualate. This inhibitory effect of 5-HT on NMDA response was present at 5-HT concentrations as low as 10(-15) M. Although the 5-HT effect exhibited similar pharmacology to the 5-HT1A-type receptors, it was not mimicked by increasing intracellular concentration of adenosine 3',5'-cyclic monophosphate that is the common second messenger for 5-HT1A receptors in the mammalian central nervous system. Glycine strongly antagonized this inhibitory effect of 5-HT, and 5-HT reduced opening of NMDA-gated single channels recorded from the outside-out membrane patch. These lines of evidence are consistent with a possibility that 5-HT might directly modulate the NMDA receptor-ion channel complex, either by interacting with the regulatory site(s) or by acting on a distinct site.


Individuation among bedouin versus urban arab adolescents: ethnic and gender differences.
Three scales assessing individuation (Objective Measure of Ego-Identity Status [OMEIS], Separation-Individuation Test of Adolescence [SITA], and Multigenerational Interconnectedness Scale [MIS]) were administered to 40 female and 38 male Bedouin Arab adolescents and to 39 female and 38 male urban Arab adolescents in Grade 12. It was hypothesized that Bedouin Arab adolescents and female adolescents would manifest less individuation than urban Arab adolescents and male adolescents, respectively. Results from the OMEIS revealed that the identity foreclosed mean of the Bedouin adolescents was higher than that of the urban adolescents. As for the SITA, significant differences were found between Bedouin and urban Arabs in terms of dependency denial, separation anxiety, teacher enmeshment, peer enmeshment, and rejection expectancy. Significant gender differences were found in regard to dependency denial, and a borderline difference was found for separation anxiety. Significant effects of ethnicity and gender were found on the financial interconnectedness subscale of the MIS. The results support the present hypotheses concerning ethnicity differences and indicate that urbanization seems to narrow the differences in individuation between male and female adolescents.


Selective determination of orthophosphate and total inorganic phosphates in detergents by flow injection photometric method.
A flow injection photometric system was developed for the determination of orthophosphate and total inorganic phosphates in detergents. While orthophosphate was directly determined in the presence of other phosphates by utilizing the kinetic discrimination of flow injection analysis, total inorganic phosphates was analyzed after on-line hydrolysis of polyphosphates in 2.5 mol l(-1) sulfuric acid for 50 s under 145 degrees C. Sodium dodecyl sulfate (SDS) was added to mask the interference of non-ionic surfactants. The detection limits and the sampling rates were 2.5 mg l(-1) P(2)O(5) and 40 h(-1) for total inorganic phosphates, and 1.0 mg l(-1) P(2)O(5) and 80 h(-1) for orthophosphate determination. The proposed method was applied to analyze orthophosphate and total inorganic phosphates in washing powders. The experimental results are in good agreement with those obtained by the Chinese national standard methods.


Ultrastructural localization of peroxidatic catalase in human peripheral blood leukocytes.
Localization of peroxidatic catalase in human peripheral blood leukocytes was accomplished by the assessment of alkaline diaminobenzidine reaction in the cytoplasmic granules of normal and acatalasemic leukocytes. A modified cytochemical procedure of Novikoff and Goldfischer (Novikoff AB, Goldfischer S: J Histochem Cytochem 17:675, 1969) and of Fahimi (Fahimi HD:J Cell Biol 43:275, 1969) was employed to improve the specificity of alkaline diaminobenzidine test for catalase. Diaminobenzidine-positive reaction for peroxidative catalase was observed in large and medium-sized granules in the cytoplasm of normal neutrophils, but a striking and notable absence of this reaction was observed in acatalasemic neutrophils. The test for myeloperoxidase, with the diaminobenzide reaction performed at neutrality, disclosed positively stained granules in both normal and acatalasemic neutrophils. Similarities in size and configuration of the positively stained granules for these enzymes suggest that catalase is sequestered in organelles which may be primary or azurophilic granules. Myeloperoxidase has been shown to be localized in the primary granules by others. It is possible that catalase and myeloperoxidase may be sequestered together or separately in these granules, but the present data do not permit us to draw this distinction. The ultrastructural localization of peroxidatic catalase and myeloperoxidase has been attempted in eosinophils, lymphocytes, and platelets, and the observations are compared with those of neutrophilic granules. The localization of peroxidatic catalase in monocytes could not be assessed satisfactorily because of the difficulties encountered in proper sampling of these cells.


Tissue inhibitor of matrix metalloproteinase-2 regulates matrix metalloproteinase-2 activation by modulation of membrane-type 1 matrix metalloproteinase activity in high and low invasive melanoma cell lines.
Activation of pro-matrix metalloproteinase (MMP)-2 on the surface of malignant cells by membrane-bound MT1-MMP is believed to play a critical role during tumor progression and metastasis. In this study we present evidence that MT1-MMP plays a key role for the in vitro invasiveness of malignant melanoma. Melanoma cell lines secreted latent MMP-2 when cultured on plastic. However, when cells were grown in floating type I collagen lattices, only high invasive melanoma cells activated proMMP-2. Activation could be inhibited by antibodies against MT1-MMP, by addition of recombinant tissue inhibitor of metalloproteinases (TIMP)-2 and by inhibition of MT1-MMP cleavage. MT1-MMP protein was detected as an inactive protein in all cell lines cultured as monolayers, whereas in collagen gels, active MT1-MMP protein was detected in the membranes of both high and low invasive melanoma cells. Production of TIMP-2 was about 10-fold higher in low invasive cells as compared with high invasive melanoma cells and was further increased in the low invasive cells upon contact to collagen. Thus, in melanoma cells TIMP-2 expression levels might regulate MT1-MMP-mediated activation of proMMP-2. High invasive melanoma cells displayed increased in vitro invasiveness, which was inhibited by TIMP-2. These data indicate the importance of these enzymes for the invasion processes and support a role for MT1-MMP as an activator of proMMP-2 in malignant melanoma.