Long noncoding RNA PANDAR promotes progression and predicts poor prognosis via upregulating ROCK1 in prostate cancer.
Recent researches have proved that long noncoding RNAs (lncRNAs) play an important role in tumorigenesis. In this research, lncRNA PANDAR was explored to identify the role it played in the development of prostate cancer and how it achieves. Real-time quantitative polymerase chain reaction (RT-qPCR) was utilized to detect PANDAR expression in both prostate cancer tissue samples and cells. Moreover, the associations between expression level of PANDAR and patients' disease-free survival rate were studied respectively. Then wound healing assay and transwell assay were conducted. Furthermore, RT-qPCR and Western blot assay were used to explore the underlying mechanism. By comparison with PANDAR expression in adjacent tissues, PANDAR expression level was significantly higher in prostate cancer samples, which was closely associated with patients' disease-free survival time. Moreover, after PANDAR was upregulated, cell migration and cell invasion capacities of prostate cancer cells were enhanced in vitro. In addition, after overexpression of PANDAR, the mRNA and protein expression of ROCK1 was upregulated, respectively. Furthermore, it was found that ROCK1 expression was positively correlated to PANDAR expression in prostate cancer tissues. Results above suggest that PANDAR could enhance cell migration and invasion of prostate cancer by upregulating ROCK1, which may offer a potential therapeutic target in prostate cancer.


Impaired platelet-derived growth factor receptor expression and function in cultured lower esophageal sphincter circular smooth muscle cells from W/W(v) mutant mice.
We have previously demonstrated that lower esophageal sphincter (LES) circular smooth muscle (CSM) is functionally impaired in W/W(v) mutant mice that lack interstitial cells of Cajal, and speculated that this could be due to altered smooth muscle differentiation. Platelet-derived growth factor (PDGF) is involved in the maturation and differentiation of smooth muscle. To determine whether PDGF expression and (or) function is altered in W/W(v) mutant mice, PDGF-Rβ expression was measured using RT-PCR, qPCR, and immunocytochemistry, and Ca(2+) imaging and perforated patch clamp recordings performed in isolated LES CSM cells. RT-PCR and immunocytochemistry showed significantly reduced PDGF-Rβ expression in the LES from mutant as opposed to wild-type mice. Quantitative comparison of CSM cell numbers in histological specimens revealed a significantly increased average cell size in the mutant tissue. The specific PDGF-Rβ ligand, PDGF-BB, caused a significant increase in intracellular Ca(2+) in cells from the wild-type mice compared with the mutants. Using a ramp protocol, PDGF-BB caused a 2-fold increase in outward K(+) currents in cells from the wild-type mice, whereas no significant increase was measured in the cells from the mutants. We conclude that the expression and function of PDGF-Rβ in LES CSM from W/W(v) mice is impaired, providing further evidence that LES CSM is abnormal in W/W(v) mutants.


Structural properties of the heparan sulfate proteoglycans of brain.
The heparan sulfate proteoglycans present in a deoxycholate extract of rat brain were purified by ion exchange chromatography, affinity chromatography on lipoprotein lipase agarose, and gel filtration. Heparitinase treatment of the heparan sulfate proteoglycan fraction (containing 86% heparan sulfate and 10% chondroitin sulfate) that was eluted from the lipoprotein lipase affinity column with 1 M NaCl led to the appearance of a major protein core with a molecular size of 55,000 daltons, as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Comparison of the effects of heparinase and heparitinase treatment revealed that the heparan sulfate proteoglycans of brain contain a significant proportion of relatively short N-sulfoglucosaminyl 6-O-sulfate [or N-sulfoglucosaminyl](alpha 1-4)iduronosyl 2-O-sulfate(alpha 1-4) repeating units and that the portions of the heparan sulfate chains in the vicinity of the carbohydrate-protein linkage region are characterized by the presence of D-glucuronic acid rather than L-iduronic acid. After chondroitinase treatment of a proteoglycan fraction that contained 62% chondroitin sulfate and 21% heparan sulfate (eluted from lipoprotein lipase with 0.4 M NaCl), the charge and density of a portion of the heparan sulfate-containing proteoglycans decreased significantly. These results indicate that a population of "hybrid" brain proteoglycans exists that contain both chondroitin sulfate and heparan sulfate chains covalently linked to a common protein core.


Comparing the burden of illness of haemophilia between resource-constrained and unconstrained countries: the São Paulo-Toronto Hemophilia Study.
Although the regular replacement of clotting factor concentrates (prophylaxis) has been well established as the standard of care for severe haemophilia, the high cost of factor concentrates has limited access to prophylaxis in countries with under-developed or developing economies. We studied the health gap that could be addressed by providing unlimited access to clotting factor concentrates with implementation of long-term prophylaxis initiated from an early age in life. We performed a cross-sectional study of a random, representative sample of boys with moderate and severe haemophilia at three haemophilia treatment centres in Sao Paulo, Brazil, and one centre in Toronto, Canada. Canadian subjects were more often treated with prophylaxis, and began treatment at an earlier age. Fewer Canadian subjects had bleeds within the preceding 6 months (19 vs. 34, P = 0.003). Canadian subjects had lower (better) Pettersson radiographic scores (1.5 vs. 6.0, P = 0.0016), lower (better) Hemophilia Joint Health Scores (5.5 vs. 10.5, P = 0.0038), higher (better) Activity Scale for Kids scores (96.6 vs. 92.0, P = 0.033), more time spent in vigorous activity, and higher (better) social participation scores. Our findings suggest that increasing access to clotting factor concentrates for young boys with severe haemophilia is a global imperative.


Spectral domain optical coherence tomography (SD-OCT) assessment of the healthy female canine retina and optic nerve.
To provide normative data for canine whole retinal thickness (WRT), nerve fiber layer thickness (NFL), photoreceptor layer thickness (PR), and outer nuclear layer thickness (ONL) using spectral domain optical coherence tomography. Twelve healthy adult intact female beagles. Horizontal volume scans through the area dorso-temporal from the optic nerve (superior retina), and the area ventro-temporal from the optic nerve (inferior retina) were used to evaluate the thickness of retinal NFL, PR, ONL, and WRT. Peripapillary circular scans were used to evaluate NFL thickness. Statistical analyses were performed to compare the thickness of the individual layers between the superior and inferior retina (paired t-test). One-way analysis of variance (ANOVA) was used to compare the thickness of peripapillary NFL between the superior, inferior, temporal and nasal quadrants of the circle scan. The WRT, PR, and NFL thickness were greater in the superior than in the inferior retina (198.7 ± 9.6 μm vs. 164.4 ± 6.4 μm, P < 0.0001; 95.5 ± 6.5 μm vs. 78.8 ± 7.4 μm, P < 0.0001; and 26.4 ± 1.6 μm vs. 25.0 ± 1.9 μm, P = 0.0236, respectively). No statistical difference was found between the ONL thickness of the superior and inferior retina (50.1 ± 6.4 μm vs. 44.3 ± 3.6, P = 0.0578). Peripapillary NFL thickness showed a similar tendency as the linear scans, with the superior quadrant having the greatest thickness (91.26 ± 7.0 μm) and the inferior quadrant being the thinnest (76.42 ± 9.2 μm) (P < 0.001). Results of our in vivo studies showed significant differences between thickness values for the superior (tapetal) and inferior (nontapetal) retinal regions.


Physiological and psychological correlates of attention-related body sensations (tingling and warmth).
Body sensations play an essential role in the subjective evaluation of our physical health, illness, and healing. They are impacted by peripheral somatic and external processes, but they are also heavily modulated by mental processes, e.g., attention, motor control, and emotion. Body sensations, such as tingling, numbness, pulse, and warmth, can emerge due to simply focusing attention on a body part. It is however an open question, if these sensations are connected with actual peripheral changes or happen "only in the mind." Here, we first tested whether the intensity of such attention-related body sensations is related to autonomic and somatomotor physiological processes and to psychological traits. In this study, attention-related body sensations were not significantly connected to changes in physiology, except warmth sensation, which was linked to decrease in muscle tension. Overall intensity of tingling significantly correlated with body awareness and tendentiously with body-mind practice. This strengthened the hypothesis that attention-related body sensations are more the result of top-down functions, and the connection with peripheral processes is weak. Here, we suggested a novel protocol to examine the effect of manipulating attention on body sensations, which together with our results and discussion can inspire future researches.


Impact of the Gubbio population study on community control of blood pressure and hypertension. Gubbio Study Research Group.
Awareness and treatment of hypertension have markedly increased in the last 30 years in most parts of the world, but a satisfactory control of blood pressure is still infrequent To describe trends in community control of hypertension and blood pressure levels in the small town of Gubbio, Italy. Large samples of the populations (aged 30-79 years) were examined 6 years apart for measurement of blood pressure, other cardiovascular risk factors and knowledge, attitude and practice towards control of hypertension. Data were available from a total of 1125 men and 1445 women with two examinations and 1566 men and 1658 women with at least one examination. Two different definitions of hypertension were used (old definition: systolic blood pressure (SBP) > or = 160 mmHg or diastolic blood pressure (DBP) > or = 95 mmHg or use of antihypertensive drugs; recent definition: SBP > or = 140 mmHg or DBP > or =90 mmHg or use of anti-hypertensive drugs). Awareness, treatment and control of hypertension increased from one survey to the other, whatever definition of hypertension was used. Control rose from 41 to 63% (old definition) and from 12 to 24% (recent definition). In a 6-year period, the average population SBP declined 2-8 mmHg and DBP declined 2-3 mmHg depending on type of analysis, against an expected rise of 9 mmHg for SBP and 2 mmHg for DBP. These trends are partly explained by a marked decline in alcohol consumption and by more common and intensive anti-hypertensive treatment, while change in body mass index, which showed a slight but systematic increase, cannot be considered as a contributor to this trend. An epidemiological study has motivated a population group and its medical profession towards a better control of hypertension.


Effect of lesser tuberosity osteotomy size and repair construct during total shoulder arthroplasty.
Lesser tuberosity osteotomy has been shown to decrease postoperative subscapularis dysfunction. The purpose of this study was to determine the effect of osteotomy thickness and suture configuration on repair integrity. One side of 12 matched-pair cadaveric shoulders was randomly assigned to either a thick osteotomy (100% of lesser tuberosity height) or a thin osteotomy (50% of height). Both sides of the matched pairs were given the same repair, either (1) compression sutures or (2) compression sutures plus 1 tension suture. This created 4 groups of 6 paired specimens. Computed tomography imaging was used to measure tuberosity dimensions before and after osteotomy to validate fragment height and area. The repairs were loaded cyclically and then loaded to failure. A video system measured fragment displacement. The percent area of osteotomy contact was calculated from the computed tomography and displacement data. The average initial displacement was less in the thin osteotomy groups (P = .011). Adding a tension suture negated this difference. A significant number of thin repair sites compared with thick repair sites remained intact during load-to-failure testing (P = .001). No difference occurred because of maximum load between the repair groups (P = .401), and construct stiffness was greater when a tension suture was used (P = .032). The percent area of osteotomy contact showed no differences between the osteotomy (P = .431) and repair (P = .251) groups. The study showed that thin osteotomies displaced less than thick osteotomies. Adding a tension band improved construct stability and eliminated some failure modes. Our ideal repair was a thin wafer with both tension and compression sutures. This construct had smaller total displacement, a high osteotomy percent contact area, and a high maximum load.


[Multidisciplinary treatment of superior sulcus (Pancoast) tumors].
Ten patients with a Pancoast tumour, seven with pulmonary carcinoma, three with a soft tissue tumour, were treated surgically with or without preoperative chemotherapy or external radiotherapy, and with postoperative external radiotherapy mostly in combination with brachytherapy using a flexible intraoperative template. The results were highly variable, e.g. one patient died after three months, another was still alive without tumour after 36 months. Optimal treatment requires cooperation of experienced surgeons, radiotherapists and medical oncologists.


Does a cytoplasmic bridge connect the CNS axon with the inner loop of myelin?
Sarah Luse (1959) reported over 30 years ago on the presence of a bridge connecting the axon to the myelin sheath in the central nervous system (CNS). This notion has not been accepted in the literature. Wolman (1992) found that the progress of demyelination in some viral diseases affecting the CNS fits the concept of Luse, as the process occurred primarily along the major dense line of myelin, which is in continuity with the cytoplasm of the oligodendroglial cell. Injection of Lucifer yellow (LY) and horseradish peroxidase (HRP) into the vitreous of guinea pigs, with and without iontophoresis, resulted in labeling of the nerve axons and myelin. Labeling of myelin by HRP occurred along the major dense line which indicated that a transient or permanent cytoplasmic bridge connects axons and myelin in the optic nerve.


Role of vagal afferent C fibres in the bradycardiac response to an increase in arterial blood pressure in ferrets.
The effects on baroreceptor reflexes of bilateral application of the C fibre neurotoxin, capsaicin, to the cervical vagi have been investigated in decerebrate ferrets. Baroreflex sensitivity was estimated from the relationship between cardiac interval and systolic blood pressure following I.V. infusion of phenylephrine. Control responses to phenylephrine were fitted by two linear slopes with an initial shallow slope, a, followed by a steeper slope, b. Capsaicin abolished slope b and the resulting relationship was best fitted by a single regression with a slope not significantly different from that of the control response a. This suggests that a significant proportion of the baroreflex response induced by phenylephrine is mediated by cardiopulmonary receptors attached to vagal afferent C fibres.


Serotyping of human astrovirus strains by immunogold staining electron microscopy.
Human astrovirus strains were propagated in CaCo-2 cell cultures, and virus multiplication was demonstrated by immunosorbent electron microscopy (ISEM). Serotyping of the virus strains was carried out in cell culture fluids or directly in faecal extracts by an indirect immunogold staining (IGS) electron microscopy technique, using specific rabbit antisera against astrovirus types 1-6 as primary antibodies and goat anti-rabbit IgG gold conjugate as secondary antibody. Thirty-seven astrovirus strains were examined, of which 26 grew in the cell cultures in several passages. IGS of the cell-derived viruses showed that 16, 3, 3, and 4 of the strains were types 1, 2, 3, and 4 respectively. Types 5 and 6 were not demonstrated. Eleven strains did not grow in cell cultures, and attempts to serotype these strains by IGS directly in the faecal extracts were unsuccessful, except for one strain which was found to be type 1. The results indicate that IGS may be a specific and suitable method for serotyping astroviruses grown in cell cultures.


Reducing and filtering point clouds with enhanced vector quantization.
Modern scanners are able to deliver huge quantities of three-dimensional (3-D) data points sampled on an object's surface, in a short time. These data have to be filtered and their cardinality reduced to come up with a mesh manageable at interactive rates. We introduce here a novel procedure to accomplish these two tasks, which is based on an optimized version of soft vector quantization (VQ). The resulting technique has been termed enhanced vector quantization (EVQ) since it introduces several improvements with respect to the classical soft VQ approaches. These are based on computationally expensive iterative optimization; local computation is introduced here, by means of an adequate partitioning of the data space called hyperbox (HB), to reduce the computational time so as to be linear in the number of data points N, saving more than 80% of time in real applications. Moreover, the algorithm can be fully parallelized, thus leading to an implementation that is sublinear in N. The voxel side and the other parameters are automatically determined from data distribution on the basis of the Zador's criterion. This makes the algorithm completely automatic. Because the only parameter to be specified is the compression rate, the procedure is suitable even for nontrained users. Results obtained in reconstructing faces of both humans and puppets as well as artifacts from point clouds publicly available on the web are reported and discussed, in comparison with other methods available in the literature. EVQ has been conceived as a general procedure, suited for VQ applications with large data sets whose data space has relatively low dimensionality.


Aerosol-assisted synthesis of thiol-functionalized mesoporous silica spheres with Fe3O4 nanoparticles.
Thiol-functionalized mesoporous silica spheres having Fe3O4 nanoparticles are fabricated in one-pot by aerosol-assisted synthesis. A TEM image shows that Fe3O4 nanoparticles are successfully embedded within the mesoporous silica spheres. SEM images and SAXS profiles reveals that the encapsulating Fe3O4 nanoparticles do not affect the ordering of a mesoporous structure. The spherical morphologies are also well retained. The presence of cage-type mesopores with uniform size is confirmed by N2 adsorption-desorption isotherms and TEM observations. The spray-dried thiol-functionalized particles with Fe3O4 nanoparticles effectively adsorb mercury (II) ions due to their strong interaction to thiol groups embedded in the framework. The particles with the amount of Fe3O4 nanoparticles (3.5 wt%) show a saturated magnetization (over 1.0 emu/g). This magnetic property is useful for practical collection with magnet.


Influence of nuclear factor kappaB activation on inflammatory mediators of alveolar macrophages in rats with acute necrotizing pancreatitis.
To investigate the potential influence of nuclear factor kappaB (NF-kappaB) activation on the inflammatory mediators secreted by alveolar macrophages (AMs) in rats with acute necrotizing pancreatitis (ANP) and to evaluate the effect of an inhibitor of NF-kappaB-N-acetylcysteine (NAC). Ninety male Sprague-Dawley rats were randomly divided into 3 groups, 30 of each: control, ANP, and ANP plus NAC groups. The ANP rat models were established by a retrograde injection of 5% sodium taurocholate into the pancreatic duct. In addition to sodium taurocholate, the ANP plus NAC group received intravenous infusion of NAC (25 mg/100 g). At the sixth hour after modeling, the protein content of the bronchoalveolar lavage fluid, the myeloperoxidase in the lung tissue, and the transforming growth factor alpha and the nitric oxide (NO) secreted by AMs were determined. The histopathologic changes of the pancreas and the lung were observed under light microscope, and NF-kappaB activation of AMs was detected. The protein content of the bronchoalveolar lavage fluid and the myeloperoxidase level of the lung tissue showed a significant increase in the ANP group as compared with the NAC-administered group. The levels of transforming growth factor alpha and NO secreted by AMs in the ANP and the ANP plus NAC group rose significantly over that in the control group, and there was a significant difference between them. Although they were still higher than those in the control group, the pancreas destruction and the lung injury were slighter in the ANP plus NAC group and the activation of NF-kappaB was lower in the ANP plus NAC group as compared with that in the ANP group. The correlation between the NF-kappaB activation, the up-regulation of the inflammatory mediators secreted by AMs, and the tissue damage suggests a key influence of NF-kappaB in the pathogenesis of ANP. Inhibition of NF-kappaB activation may reverse the lung injury of ANP.


Subclinical left ventricular dysfunction and correlation with regional strain analysis in myocarditis with normal ejection fraction. A new diagnostic criterion.
The diagnosis of myocarditis is challenging, especially in case of normal left ventricular systolic function. The aim of this study is to test the hypothesis that 2D speckle tracking echocardiography (2DSTE) can detect subclinical left ventricular (LV) dysfunction in patients with myocarditis and preserved LV function without regional wall motion abnormalities and that regional strain analysis can correlate with cardiac magnetic resonance (CMR) findings. Study population consisted of 25 consecutive patients with myocarditis and 19 controls. All patients underwent a full echocardiographic study at the first day of their admission and in addition to conventional echocardiographic measurements, global longitudinal and circumferential strain of the left ventricle (LVGLS, LVCS accordingly), as well as regional strains of the lateral wall, were estimated. Moreover, all patients underwent a CMR scan during the first week from their admission. Although there was no statistical difference between the two groups of patients in systolic function, myocarditis patients demonstrated significantly impaired LVGLS (-16.5 ± 2.2 vs -20.5 ± 1.3%, p < 0.0001) and LVCS (-16.4 ± 3.7 vs -20.9 ± 2%, p = 0.002), as well as segmental longitudinal strains of the lateral wall. CMR in all myocarditis patients revealed late gadolinium enhancement in the lateral left ventricle free wall. In patients with acute myocarditis with preserved ejection fraction, 2DSTE evaluation appears to be a promising, useful noninvasive and inexpensive tool in addition to existing methods used for the diagnosis of acute myocarditis, since it seems to be able to identify myocardial fibrosis early in the setting of the disease.


The 5T4 oncofetal glycoprotein does not act as a general organizer of the CXCL12 system in cancer cells.
The chemokine, CXCL12, promotes cancer growth and metastasis through interaction with either CXCR4 and/or CXCR7. This tumor-specific organization of the CXCL12 system obscures current therapeutic approaches, aiming at the selective inactivation of CXCL12 receptors. Since it has been previously suggested that the cellular use of CXCR4 or CXCR7 is dictated by the 5T4 oncofetal glycoprotein, we have now tested whether 5T4 would represent a general and reliable marker for the organization of the CXCL12 system in cancer cells. The CXCR4 antagonist, AMD3100, as well as the CXCR7 antagonist, CCX771, demonstrated that the cancer cell lines A549, C33A, DLD-1, MDA-231, and PC-3 use either CXCR7 and/or CXCR4 for mediating CXCL12-induced chemotaxis and cell proliferation. The use of CXCL12 receptors as well as their subcellular localization remained unchanged in most cell lines following siRNA-mediated depletion of 5T4. In distinct cell lines, inhibition of 5T4 expression, however, modulated tumor cell migration and proliferation per se. Collectively our analyses fail to demonstrate general organizational influences of 5T4 of the CXCL12 system in different cancer cell lines, and, hence, dismiss its future use as a diagnostic marker.


[Examination strategies in the preparative phase for cataract operations and artificial lens implantation].
The extraordinary increase in the number of posterior chamber intraocular lenses (IOLs) implanted in recent years has completely changed our attitude towards cataract patients. A few years ago, the goal of preoperative evaluation was to select ideal candidates for implantation. In the meantime, contraindications to IOLs have become very rare and many tests have been developed to objectify and quantify lens opacities in patients with good visual acuity (glare disability tests, contrast sensitivity tests), or to predict the functional clinical result (macular function tests). The value of these tests is reduced by the rate of false-positive or false-negative results. A meticulously recorded history and careful enlightenment of the patient are indispensable to avoid postoperative disappointment. Slit-lamp observation and biometry are the only mandatory tests for establishing the presence of a cataract and planning the surgical approach. All modern tests attempt to substitute automatic or semi-automatic measurements for clinical judgment, but indication for cataract surgery nevertheless remains a clinical act.


Abscisic acid response element binding factor 1 is required for establishment of Arabidopsis seedlings during winter.
Abscisic acid (ABA) plays a crucial role in abiotic stress response apart from its influence on growth and development of a plant. Our studies on abscisic acid response element binding factor 1 (ABF1) gene in Arabidopsis demonstrate that it is required for seedling establishment during winter. ABF1 is also involved in regulating seed dormancy and seed germination to some extent. Analysis of transcriptional activity of ABF1 promoter reveals that ABF1 expresses specifically in trichomes of young leaves and constitutively in cotyledons, roots, older leaves and flowers. The expression is induced upon exposure to ABA, cold and heat. The alignment of cDNAs of ABF1 (At1g49720) and At1g49730 (encodes a protein kinase of unknown function), reveals an overlap of 88 bp at their 3' UTR region suggesting that they can potentially form natural cis-antisense mRNAs pair in a tail-to-tail manner. Analysis by Genevestigator microarray stress response viewer further supports the regulatory role of these genes. An inverse proportion is observed in the transcription the two loci in number of stress responses. The abf1 mutants do not show any seedling establishment defects when grown under standard growth conditions. The mutant seedlings exhibit growth defects during winter in the western Himalayan region. Our study also signifies the importance of functional analysis for mutant phenotypes in natural habitats by reverse genetic approaches, in order to identify specific function of particular gene/s whose expression level is altered upon exposure to changes in environmental cues such as temperature and light.


[Possibilities and results of "immunotherapy" in children with acute leucosis (author's transl)].
In the introduction we are giving an overview about the possibilities of treatment of acute leucemias in childhood with an adjuvant immunotherapeutic component. Our own ten-years-experiences from 25 a. 1.1. children with BCG-application are useful for testing this kind of adjuvant therapy under clinical conditions in future, too.


Transperitoneal laparoscopic adrenalectomy: experience in 100 patients.
Between July 1992 and October 1996, 100 transperitoneal laparoscopic adrenalectomies were performed on 99 patients at our hospital and affiliated hospitals. The clinical diagnoses were primary aldosteronism (41 patients), Cushing's syndrome (15), pre-Cushing's syndrome (6), pheochromocytoma (7; 8 adrenal glands), adrenal cancer (2), nonfunctioning adenoma (22), myelolipoma (3), and complicated adrenal cyst (3). Ninety-seven glands were removed laparoscopically. The mean operative time was 240 +/- 76 (SD) minutes and the mean blood loss 68 +/- 80 mL for the series. The mean blood was 77 +/- 113 mL when the three operations that were converted to open surgery are included. The mean times for the return to a normal diet and unassisted ambulation were 1.3 +/- 0.6 and 1.4 +/- 0.8 days, respectively. The mean duration of the use of analgesics was 1.5 +/- 1.3 days, including the day of surgery. In contrast, in the latest 10 open adrenalectomies done at Kyoto University Hospital, the mean operative time was 186 +/- 53 minutes and the mean blood loss 220 +/- 170 mL. The mean times for return to a normal diet and for unassisted ambulation and the mean duration of the use of analgesics were 1.9 +/- 0.3, 2.9 +/- 1.1, and 2.9 +/- 1.7 days, respectively. Thirty-six operations, excluding one converted to open surgery, performed at Kyoto University Hospital were selected to look at the learning curve for transperitoneal laparoscopic adrenalectomy and evaluated for operative time and blood loss. The mean operative time and mean blood loss in the first 10 procedures performed at Kyoto University Hospital were 256 +/- 63 minutes and 89 +/- 57 mL; however, these values were reduced to 177 +/- 39 minutes and 48 +/- 32 mL in the next 10 procedures at the same hospital. Laparoscopic adrenalectomy via the transperitoneal anterior approach can be equivalent to open adrenalectomy in efficiency with a shorter convalescence.


Checklist of Cerambycidae (Coleoptera) primary types of the Museu Nacional, Rio de Janeiro, Brazil, with a brief history of the collection.
A checklist of the Cerambycidae (Coleoptera) primary types deposited in the Museu Nacional, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil is given. There are 1,044 primary types. Lectotype designation for Megacyllene castroi (Prosen, 1947) is proposed. A brief history of the collection of Cerambycidae of the Museu Nacional is presented.


[Intramuscular juvenile xantogranuloma].
Deep or intramuscular juvenile xanthogranuloma (JXG) is very rare. There are, however, some clinical and histological similarities between the case we present and the few cases that have been published in the literature. Although most of them will need histologic confirmation to establish the final diagnosis, surgeons who are operating tumors of infancy should consider it in the differential diagnosis of well circumscribed, rapidly growing dorsal masses in children under 3 years of age. Macroscopic appearance upon excision can help to support the diagnosis. Knowledge of this variant of JXG may avoid aggressive diagnostic or therapeutic procedures.


Analysis of risk factors for gastric dilatation and dilatation-volvulus in dogs.
The Veterinary Medical Data Base was usd to conduct an epidemiologic study of gastric dilatation and dilatation-volvulus (GDV) to describe changes over time in frequency of canine hospital admissions, to identify risk factors, and to estimate their relative importance. Cases in this case-control study included 1,934 dogs with GDV that were admitted to 12 participating veterinary hospitals from 1980 to 1989. The controls were 3,868 dogs with other diagnoses that were randomly selected from the same hospitals. Frequency of GDV per 1,000 canine hospital admissions ranged from 2.9 to 6.8. The case fatality rate was 28.6 and 33.3% for gastric dilatation alone and for gastric dilatation with volvulus, respectively. Using logistic regression analysis, the odds ratio (OR) and its 95% confidence limits (95% CL) for GDV associated with purebred vs mixed-breed dogs were 2.5 and 2.1, 3.0, respectively. The risk of GDV was associated with increasing age (chi 2 = 305.6, P < 0.0001) and increasing weight (chi 2 = 627.8, P < 0.0001). Significant association of GDV risk with sex or neuter status was not found. The 5 breeds having at least 10 cases and 8 controls and with the highest risk of GDV were Great Dane (OR, 10.0; 95% CL, 6.4, 15.6), Weimaraner (OR, 4.6; 95% CL, 2.3, 9.2), Saint Bernard (OR, 4.2; 95% CL, 2.3, 7.4), Gordon Setter (OR, 4.1; 95% CL, 1.8, 9.3), and Irish Setter (OR, 3.5; 95% CL, 2.4, 5.0). The effect of increasing body weight on GDV risk was less than that of increasing ideal adult breed weight, determined by published breed standards.(ABSTRACT TRUNCATED AT 250 WORDS)


Bleomycin-induced DNA lesions are dependent on nucleosome repeat length.
Treatment of cells or nuclei with bleomycin induces DNA lesions. We detect the presence of lesions as the release of fragments from bulk DNA when cells (or nuclei) are lysed in dilute alkali. To further characterize the lesions we have altered experimentally the average nucleosome repeat length and probed the lysate with nuclease S1 in order to remove single-stranded DNA. In salt-incubated nuclei with short average nucleosome repeat length (140-145 base pairs) (and also with long nucleosome-free stretches of DNA) one can induced fewer DNA lesions in the nucleosome-containing DNA as compared to nuclei with 190-195 base pairs average nucleosome repeat length. Hence the ability of bleomycin to induce DNA lesions is dependent on nucleosome repeat length.


CD8(+) T-cell responses to adeno-associated virus capsid in humans.
Hepatic adeno-associated virus (AAV)-serotype 2 mediated gene transfer results in transgene product expression that is sustained in experimental animals but not in human subjects. We hypothesize that this is caused by rejection of transduced hepatocytes by AAV capsid-specific memory CD8(+) T cells reactivated by AAV vectors. Here we show that healthy subjects carry AAV capsid-specific CD8(+) T cells and that AAV-mediated gene transfer results in their expansion. No such expansion occurs in mice after AAV-mediated gene transfer. In addition, we show that AAV-2 induced human T cells proliferate upon exposure to alternate AAV serotypes, indicating that other serotypes are unlikely to evade capsid-specific immune responses.


[AIDS and HIV infection in 1998].
Last years number of notified and registered AIDS cases was quite stable. Some increasing of HIV infections number was observed. Quality of collected epidemiological data will depend--among other things--on: easy access to HIV testing, completeness of data and diagnosis of AIDS indicator diseases by definitive methods.


Determination of renal molar concentrations of phosphorus-containing metabolites in vivo using 31P NMR.
A technique to determine absolute metabolite concentrations of the kidney in vivo using 31P NMR is described. The technique is based on the use of methylphosphonic acid (MPA), which gives rise to a well-resolved peak upfield from in vivo phosphorous metabolite resonances, as an "internal standard." The method involves acquisition of a fully relaxed kidney spectrum with an implanted coil followed by intravenous infusion of MPA (4 ml of 150 mM) for a period of 30 min. The animal is then sacrificed to insure a steady state level of renal MPA and another spectrum is obtained. From these two spectra the ratio of intensities of MPA to beta-ATP was derived. In the method used here, no significant contribution from tissues outside the kidney was observed. In addition, a relatively homogeneous distribution of MPA throughout the kidney was achieved. The amount of MPA per gram wet weight of kidney was also obtained through NMR methods by placing the excised organ in a phosphate-calibrated solenoidal coil. The calibration spectra along with the ratio of intensities for MPA/beta-ATP were used to calculate the number of micromoles of ATP per gram wet weight of kidney. Infusion of a higher concentration of MPA (1.25 M) produced a visible MPA resonance in other organs besides the kidney. Thus, MPA could be useful in determining phosphate metabolite concentrations in other tissues.


Regulation of the TGFbeta signalling pathway by ubiquitin-mediated degradation.
The transforming growth factor-beta (TGFbeta) superfamily controls a plethora of biological responses, and alterations in its signalling pathway are associated with a range of human diseases, including cancer. TGFbeta superfamily ligands signal through a heteromeric complex of Ser/Thr kinase receptors that propagate the signal to the Smad family of intracellular proteins. The ubiquitin-mediated proteasomal degradation pathway is an evolutionary conserved cascade that tightly regulates TGFbeta superfamily signalling. Both the size of the Smad pool in unstimulated cells and Smad protein levels subsequent to the activation of the pathway are controlled by ubiquitination. E3 ligases are components of the ubiquitin-degradation complex that specifically recognize targeted proteins and the E3 ligases, Smad ubiquitination-related factor 1 (Smurf1), Smurf2 and SCF/Roc1 have been implicated in Smad degradation. The Smurfs are of particular importance to TGFbeta signalling, as Smads also function as adapters that recruit the Smurfs to various pathway components including the TGFbeta receptor complex and the transcriptional repressor, SnoN, and thereby regulate the degradation of these Smad-associating proteins. Thus, by controlling the level of Smads as well as positive and negative regulators of the pathway, Smurfs provide for complex and fine control of signalling output. Finally, growing evidence demonstrates that ubiquitination and proteasomal degradation is also implicated in the turnover of tumor-derived Smad mutants and may thus contribute to disease progression.


[Effect of reperfusion after local ischaemia on the M receptor density in rat brains].
To study the dynamic changes in the density of muscarinic acetylcholine receptor in different areas of rat brains during reperfusion after local ischaemia. The rat cerebral focal ischemia/reperfusion model after middle cerebral artery occlusion was made by the intraluminal suture method. Using 3H-QNB as radioligand, after binding with M receptor on the brain slice of the rat model, the brain samples were exposed on the hypersensitive film [H-3] to complete autoradiography, and the density of M receptor in different areas on the film of autoradiography was measured. There were no changes in the M receptor density in 2 hours' ischaemia group and 2 hours' reperfusion group, M receptor densities in the area of occipital cortex (OC) and temporal cortex (TC) were observed to decrease significantly in 8 hours' reperfusion group, but the degree of decrease was lower than 24 hours' and 72 hours' reperfusion groups, there was significant decrease in the density of M receptor in the areas of caudate putamen (CP), frontal cortex (FC), TC, OC of the 24 hours' and 72 hours' reperfusion groups and no difference was found between these two groups, and the imaging of M receptor in the domains with decreased receptor was obvious. The quantity of M receptor did not change right after ischaemia or reperfusion. It decreased gradually after an interval of time; Imaging of the M receptor could assess the changes of the density of viable cholinergic neurons and be a marker of diagnosis, therapy, and prognosis of brain ischaemia.


Integrated portable genetic analysis microsystem for pathogen/infectious disease detection.
An integrated portable genetic analysis microsystem including PCR amplification and capillary electrophoretic (CE) analysis coupled with a compact instrument for electrical control and laser-excited fluorescence detection has been developed. The microdevice contains microfabricated heaters, temperature sensors, and membrane valves to provide controlled sample positioning and immobilization in 200-nL PCR chambers. The instrument incorporates a solid-state laser and confocal fluorescence detection optics, electronics for sensing and powering the PCR reactor, and high-voltage power supplies for conducting CE separations. The fluorescein-labeled PCR products are amplified and electrophoretically analyzed in a gel-filled microchannel in <10 min. We demonstrate the utility of this instrument by performing pathogen detection and genotyping directly from whole Escherichia coli and Staphylococcus aureus cells. The E. coli detection assay consists of a triplex PCR amplification targeting genes that encode 16S ribosomal RNA, the fliC flagellar antigen, and the sltI shigatoxin. Serial dilution demonstrates a limit of detection of 2-3 bacterial cells. The S. aureus assay uses a femA marker to identify cells as S. aureus and a mecA marker to probe for methicillin resistance. This integrated portable genomic analysis microsystem demonstrates the feasibility of performing rapid high-quality detection of pathogens and their antimicrobial drug resistance.


Burden of care and quality of life in relatives of opioid dependent male subjects.
The aim of this study was to compare the quality of life (QoL) and family burden in relatives of patients with heroin dependence with that of healthy controls. A total of 50 heroin dependent patients and 50 of their relatives and 50 healthy subjects and 50 of their relatives were included in the study. The Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders (SCID-I) was used to determine the heroin dependence and other Axis I psychiatric disorders. Family burden and QoL levels in the relatives were assessed with the Zarit Burden Interview (ZBI) protocol and the World Health Organization Quality of Life Assessment-Brief (WHOQOL-BREF), respectively. There were no significant differences in demographic characteristics between the groups. When compared with healthy controls, family members of heroin dependence patients had significantly higher ZBI scores and significantly lower all subscale scores of the WHOQOL-BREF. ZBI score was positively correlated with duration of the illness. All WHOQOL-BREF subscale scores were negatively correlated with duration of the illness. The study suggests that heroin dependence not only affects the lives of patients but also the lives of their family members. Heroin dependence leads to high burden on the family and also impairs the QoL of relatives.


Safety and efficacy of the terminal complement inhibitor eculizumab in Japanese patients with paroxysmal nocturnal hemoglobinuria: the AEGIS clinical trial.
Paroxysmal nocturnal hemoglobinuria (PNH) is a progressive and life-threatening disease characterized by complement-mediated chronic hemolysis, resulting in serious life-threatening complications and early mortality. Eculizumab, a humanized anti-C5 monoclonal antibody that inhibits terminal complement activation, has been shown to reduce hemolysis in PNH patients. The pivotal open-label, 12-week phase II registration study (AEGIS) was designed to evaluate the efficacy and safety of eculizumab in Japanese patients with PNH. This trial achieved its primary endpoint of reducing intravascular hemolysis with high statistical significance. Twenty-seven of the 29 patients responded to eculizumab treatment, resulting in an 87% reduction in hemolysis (P < 0.0001) and subsequent improvement in anemia (P = 0.0003) despite reduction in transfusion requirements (P = 0.006). Fatigue and dyspnea significantly improved within 1-2 weeks of eculizumab treatment and the improvement was independent of changes in hemoglobin. Chronic kidney disease (CKD) was common (66%) and eculizumab treatment improved CKD in 41% of patients at 12 weeks (P < 0.001). Elevated thrombotic risk was evident in Japanese PNH patients and eculizumab treatment normalized D: -dimer levels in 45% of patients with elevated D: -dimers at baseline (P < 0.001). The AEGIS results demonstrate that eculizumab is effective, safe and well tolerated in Japanese patients with PNH.


Morphometric analysis of pulpal myelinated nerve fibers in human teeth with chronic periodontitis and root sensitivity.
The reasons why root sensitivity occurs in some periodontally diseased teeth are still unknown. It is possible that root sensitivity may be related to changes of intradental myelinated nerve fibers, which are responsible for dentine sensitivity. The aim of this study was to define the pattern of myelinated nerve fiber changes in the pulps of teeth with and without root sensitivity in the presence of chronic periodontitis. A total of 33 cross-sectioned human dental pulp specimens were collected from noncarious, intact, permanent teeth sensitive to electric and thermal (cold) stimulus (10 hypersensitive teeth with chronic periodontitis (HTPP group), 15 nonsensitive teeth with chronic periodontitis (NTPP group), and 8 nonsensitive teeth with healthy periodontium (control group)). The morphometric parameters were estimated using light microscopy and image-analyzing computer program Image-Pro Plus. The means of myelinated nerve fiber density, fiber and axon diameter, area, perimeter, length, width, g ratio, index of circularity, and myelin sheath thickness in NTPP group significantly differed from HTPP group and the control group teeth (p<0.001). The great reduction in the density of myelinated nerve fibers in NTPP group was accompanied by unequal decrease in the number of very large-diameter myelinated nerve fibers. The mean values of morphometric parameters of all myelinated nerve fibers in HTPP group were almost the same as those in the control teeth, and no significant difference was observed. The findings of the present study suggest that the reason for enhanced root sensitivity has likely nothing to do with changes of the innervation of myelinated nerves in the dental pulp. While, decreased sensitivity of periodontally diseased teeth may be related to the degeneration of myelinated nerve fibers in the pulp.


Critical regulation of Th17 cell differentiation by serum amyloid-A signalling in Behcet's disease.
The current understandings on cellular and molecular biology suggest that Th17 axis plays a pivotal role in Behcet's disease (BD) pathogenesis. Recently the role of serum amyloid-A (SAA) as a potential marker of disease activity in BD patients has been explored, and it has been reported that the occurrence of specific clinical features are significantly associated with high serum levels of this inflammatory mediator. The aim of this study was to investigate the cytokine-like activity of SAA in inducing Th17 differentiation from CD4 + T naive cells in BD. Purified peripheral monocytes from BD and healthy control (HC) were stimulated with SAA "in vitro", and secreted IL-8, TNF-α, IL-18, IFN-α, IFN-γ, IL-1β and IL-6 were measured using a Bio-Rad multiplex cytokine immunoassay. To assess Th17 differentiation, purified CD4 + T cells were challenged with anti-CD3/CD28 antibodies, while cultured with supernatant derived from SAA stimulated monocytes, and intracellular staining of IL-17A and IFN-γ was evaluated by flow-cytometry. Furthermore, peripheral blood mononuclear cells (PBMCs) were stimulated with SAA and transcript levels of RAR-related orphan nuclear receptor (ROR)-γt and IL-17A were assessed by Real-time PCR. Upon stimulation with SAA, monocytes obtained from both HC and BD groups released large amounts of IL-8, IL-6, TNF-α, IL-1β and IFN-α. Monocytes-derived supernatants from BD patients, but not HC, were capable of promoting Th17 but not Th1 differentiation from CD4 + T cells. However, SAA did not induce up-regulation of Th17 specific mRNA transcript such as IL-17A and (ROR)-γt in PBMCs from both HC and BD. In BD patients SAA induced Th17 polarization rather than Th1 differentiation from CD4 + T cells. These data suggest that a critical regulation of Th17 may be the functional link between acute SAA increase and the induction of Th17 mediated inflammatory response in BD.


High Performance Flexible Actuator of Urchin-Like ZnO Nanostructure/Polyvinylenefluoride Hybrid Thin Film with Graphene Electrodes for Acoustic Generator and Analyzer.
A bass frequency response enhanced flexible polyvinylidene fluoride (PVDF) based thin film acoustic actuator is successfully fabricated. High concentrations of various zinc oxide (ZnO) is embedded in PVDF matrix, enhancing the β phase content and the dielectric property of the composite thin film. ZnO acts as a nucleation agent for the crystallization of PVDF. A chemical vapor deposition grown graphene is used as electrodes, enabling high electron mobility for the distortion free acoustic signals. The frequency response of the fabricated acoustic actuator is studied as a function of the film thickness and filler content. The optimized film has a thickness of 80 μm with 30 wt% filler content and shows 72% and 42% frequency response enhancement in bass and midrange compared to the commercial PVDF, respectively. Also, the total harmonic distortion decreases to 82% and 74% in the bass and midrange regions, respectively. Furthermore, the composite film shows a promising potential for microphone applications. Most of all, it is demonstrated that acoustic actuator performance is strongly influenced by degree of PVDF crystalline.


[Diagnosis and treatment of primary malignant fibrous histiocytoma of bone].
Eleven cases of primary malignant fibrous histiocytoma of bone treated surgically were reported. There were 7 males and 4 females, with age ranged from 29 to 50 years (mean age 35.3 Yrs). The sites of involvement were femur (3 cases), tibia (3), humerus (2), radius (1) temporal bone, (1) and maxilla (1). The prominent findings in these cases were pain and swelling associated with regional mass. Differential diagnosis should be made from giant cell tumor, fibrosarcoma, osteosarcoma reticulum cell sarcoma and osteomyelitis. We in order to improve survival rate, think the ablative surgery should be the therapy of choice with post operational adjuvant chemotherapy. The five-year survival was 44% in these cases.


[Comparative study of several processes of multivariate statistics in the morphologic analysis of the facial profile. Specificity and limits].
Upon 5 cutaneous angles and 4 bony angles, measured in facial profile, several (mono and plurivariate) methods were used for research of sexual differences. We explain why discriminant analysis is the only one to bring a very significant result.


[Birth readiness of the uterine cervix. II. Cervix readiness score and its problems because of the variability of individual criteria].
Cervical ripeness was scored in nulliparous and parous women not in labor at term according to Bishop's pelvic score. The frequency distributions of the scores for the single criteria as well as of the total score reveal the problems of all those scoring systems caused by the grouping process as sequelae of the choice of width of the classes as well as of their limits. E.g. for cervical dilatation in none case 2 or 3 points had been reached and similar findings had to be stated concerning station of the presenting part. An other point of discussion erases from the results of the analysis for linear correlation of the single criteria between each other and between the single criteria and the total score. The total score is mostly influenced by the consistency (r = 0,81 in nulliparous and parous women) and the effacement (r = 0,80 and r = 0,81) of the cervix, whereas for dilatation and station lower correlation coefficients were found. In contrast, when labor had started spontaneously, even if the status of cervix was not advanced, a significant change in the correlative influence of the total score by the single criteria could be stated with high correlation coefficients for dilatation and station and lower one's for consistency and effacement.


Association between sap flow-derived and eddy covariance-derived measurements of forest canopy CO2 uptake.
The carbon sink intensity of the biosphere depends on the balance between gross primary productivity (GPP) of forest canopies and ecosystem respiration. GPP, however, cannot be directly measured and estimates are not well constrained. A new approach relying on canopy transpiration flux measured as sap flow, and water-use efficiency inferred from carbon isotope analysis (GPPSF ) has been proposed, but not tested against eddy covariance-based estimates (GPPEC ). Here we take advantage of parallel measurements using the two approaches at a semi-arid pine forest site to compare the GPPSF and GPPEC estimates on diurnal to annual timescales. GPPSF captured the seasonal dynamics of GPPEC (GPPSF = 0.99 × GPPEC , r(2) = 0.78, RMSE = 0.82, n = 457 d) with good agreement at the annual timescale (653 vs 670 g C m(-2) yr(-1) ). Both methods showed that GPP ranged between 1 and 8 g C m(-2) d(-1) , and the GPPSF /GPPEC ratio was between 0.5 and 2.0 during 82% of the days. Carbon uptake dynamics at the individual tree scale conformed with leaf scale rates of net assimilation. GPPSF can produce robust estimations of tree- and canopy-scale rates of CO2 uptake, providing constraints and greatly extending current GPPEC estimations.


Anthropogenic-driven rapid shifts in tree distribution lead to increased dominance of broadleaf species.
Over the past century, major shifts in the geographic distribution of tree species have occurred in response to changes in land use and climate. We analyse species distribution and abundance from about 33 000 forest inventory plots in Spain sampled twice over a period of 10-12 years. We show a dominance of range contraction (extinction), and demographic decline over range expansion (colonization), with seven of 11 species exhibiting extinction downhill of their distribution. Contrary to expectations, these dynamics are not always consistent with climate warming over the study period, but result from legacies in forest structure due to past land use change and fire occurrence. We find that these changes have led to the expansion of broadleaf species (i.e. family Fagaceae) over areas formerly dominated by conifer species (i.e. family Pinaceae), due to the greater capacity of the former to respond to most disturbances and their higher competitive ability. This recent and rapid transition from conifers to broadleaves has important implications in forest dynamics and ecosystem services they provide. The finding raises the question as to whether the increasing dominance of relatively drought-sensitive broadleaf species will diminish resilience of Mediterranean forests to very likely drier conditions in the future.


Effectiveness of the iodine prophylaxis model adopted in Poland.
Most of the Polish territory has been classified as an iodine-deficient and endemic goiter area according to the International Council for Control of Iodine Deficiency (ICCIDD) criteria. In 1997 the obligatory model of iodine prophylaxis was implemented. Our investigations were aimed at the effectiveness of iodine prophylaxis in Poland. We assessed urinary iodine excretion and goiter prevalence in 5663 children aged 6-12 yr. The population of children from the same 27 schools was investigated from 1992 to 1994 (1406 girls and 1244 boys) and from 1999 to 2005 (1563 girls and 1450 boys) using identical laboratory and ultrasound methods. We found significant increase in iodine urinary concentration (median 52 microg/l vs 93 microg/l, p<0.001) with accompanying drop in goiter prevalence (29.6% vs 5.2%, p<0.001) after implementation of iodine prophylaxis. Iodine excretion distribution changed significantly after 1997 with an increase in the percentage of children with iodine urinary concentration above 100 microg/l from 10.8% to 45.4%, respectively. A significantly higher iodine urinary concentration was observed in lowlands compared to uplands both before and after implementation of iodine prophylaxis (median, 50 microg/l vs 57 microg/l and 86 microg/l vs 114 microg/l, respectively, p<0.001). The goiter prevalence did not differ between girls and boys from 1992 to 1994 (28.8% vs 30.5%, p=0.35) and 1999 to 2005 (5.5% vs 4.9%, p=0.45). Implementation of the new model of iodine prophylaxis in Poland in 1997 has led to significant increase in iodine urinary concentration and decrease in goiter prevalence among Polish schoolchildren. In the youngest group of children (6-8 yr olds), prevalence of goiter decreased to 3.2%--i.e. below endemic levels.


Numb and Numbl act to determine mammary myoepithelial cell fate, maintain epithelial identity, and support lactogenesis.
Mammary epithelium is comprised of an inner layer of luminal epithelial cells and an outer layer of contractile myoepithelial cells with mesenchymal properties. These two compartments interact throughout mammary morphogenesis to form branching ducts during puberty and terminate in secretory alveoli during lactation. It is not known how the myoepithelial cell lineage is specified, nor how signals in myoepithelial cells contribute to lactogenesis. Here, we show that Numb and Numbl are enriched in mammary myoepithelial cells, with their expression peaking during pregnancy. We use conditional Numb- and Numbl-knockout mouse models to demonstrate that loss of Numb/Numbl compromised the myoepithelial layer and expanded the luminal layer, led epithelial cells to undergo epithelial-to-mesenchymal transition, and resulted in lactation failure as a result of abnormal alveolar formation during pregnancy. Numb and Numbl function via repression of the Notch signaling pathway and of the p53-p21 axis during mammary gland development. These findings highlight the importance of Numb and Numbl in the control of myoepithelial cell fate determination, epithelial identity, and lactogenesis.-Zhang Y., Li, F., Song, Y., Sheng, X., Ren, F., Xiong, K., Chen, L., Zhang, H., Liu, D., Lengner, C. J., Xue, L., Yu, Z. Numb and Numbl act to determine mammary myoepithelial cell fate, maintain epithelial identity, and support lactogenesis.


Requirement for myeloid growth factors in the differentiation of acute promyelocytic leukaemia.
It is well known that the differentiation of acute promyelocytic leukaemia (APL) cells by all-trans-retinoic acid (ATRA) may be enhanced by myeloid growth factors, but the requirement for growth factors in this process is unclear. Our previous studies in multiple myeloma and non-APL acute myeloid leukaemia demonstrated that lineage-specific growth factors are required for the maximal activity of many pharmacologic differentiating agents in vitro. Thus, we studied whether the differentiation of APL is similarly dependent on growth factors. We found that the myeloid growth factors granulocyte colony-stimulating factor or granulocyte-macrophage colony-stimulating factor markedly increased the differentiation of NB4 cells or APL blasts from clinical samples treated with ATRA, arsenic trioxide (ATO), or bryostatin-1 as evidenced by the enhanced expression of myeloid surface antigens and the inhibition of clonogenic growth. Furthermore, myeloid growth factors were necessary for the differentiation of APL cells since the activity of each pharmacologic agent could be blocked by specific growth factor-neutralizing antibodies. Each differentiating agent was active only at concentrations that inhibited cell cycling, suggesting that this property is also required for differentiation. These data demonstrate that both pharmacologic differentiating agents and myeloid growth factors are required, but neither sufficient, for the differentiation of APL cells. The combined use of pharmacologic differentiating agents and growth factors may improve the clinical efficacy of differentiation therapy in APL.


Existence of a connecting system in the flagellar apparatus and the accessory structures of Trypanosoma evansi.
The three-dimensional architecture of a quartet of microtubules (QM) of Trypanosoma evansi and its related structures was examined with a transmission electron microscope (TEM). The initiation of the QM as a successive bundle of microtubules was confirmed at the juxtaposition of the second barren body (SBB). After connecting with the distal part of the basal body (BB), the QM ascended to the level of the terminal plate (TP) and gained access most closely to the inner membrane of the flagellar pocket (FP) and formed the special structure together with macula adherens (MA) and the electron dense linear substance (EDLS); then it follows its way around the FP from the posterior to the anterior and fills the subpellicular space at the underneath of the flagellum. This special structure disappeared when the associated-flagellum became the extracellular flagellum (EF), where the QM intervened into the row of the subpellicular microtubules (SM). This EDLS is suggested to represent a demarcating line (DL). In the deep cytoplasm of the flagellar root, connections via several microtubules between the BB and the SBB and via electron zonal substance (EDZS) between the BB and the mitochondrion (M) were observed. As a result, a connecting system among the flagellar apparatus and its accessory structures seems probable.


Inactivation of Escherichia coli O157:H7 on stainless steel upon exposure to Paenibacillus polymyxa biofilms.
We investigated the potential use of biofilm formed by a competitive-exclusion (CE) microorganism to inactivate Escherichia coli O157:H7 on a stainless steel surface. Five microorganisms showing inhibitory activities against E. coli O157:H7 were isolated from vegetable seeds and sprouts. The microorganism with the greatest antimicrobial activity was identified as Paenibacillus polymyxa (strain T5). In tryptic soy broth (TSB), strain T5 reached a higher population at 25 °C than at 12 or 37 °C without losing inhibitory activity against E. coli O157:H7. When P. polymyxa (6 log CFU/mL) was co-cultured with E. coli O157:H7 (2, 3, 4, or 5 log CFU/mL) in TSB at 25 °C, the number of E. coli O157:H7 decreased significantly within 24h. P. polymyxa formed a biofilm on stainless steel coupons (SSCs) in TSB at 25 °C within 24h, and cells in biofilms, compared to attached cells without biofilm formation, showed significantly increased resistance to a dry environment (43% relative humidity [RH]). With the exception of an inoculum of 4 log CFU/coupon at 100% RH, upon exposure to biofilm formed by P. polymyxa on SSCs, populations of E. coli O157:H7 (2, 4, or 6 log CFU/coupon) were significantly reduced within 48 h. Most notably, when E. coli O157:H7 at 2 log CFU/coupon was applied to SSCs on which P. polymyxa biofilm had formed, it was inactivated within 1h, regardless of RH. These results will be useful when developing strategies using biofilms produced by competitive exclusion microorganisms to inactivate foodborne pathogens in food processing environments.


Involvement of lysine residues in the binding of ovine prolactin and human growth hormone to lactogenic receptors.
The lactogenic activity (L.A.) of oPRL and hGH derivatives obtained by chemical modifications of lysine residues was studied by radioreceptor assay. Control treatment with borohydride had a slight effect on the L.A. of hGH but drastically reduced the oPRL activity; this latter was preserved in the presence of iodoacetamide. Methylation, ethylation, guanidination and acetimidination affected the L.A. of both hormones as a function of the degree of modification. The structure-binding relationships to the lactogenic receptors are discussed, suggesting that the lysine or arginine residues in homologous positions 42, 51, 73, 128, 146 of oPRL and 47, 50, 73, 128, 147 of hGH might be particularly involved.


Formation of proteinaceous capsules on plastic lens implants--by mouse macrophages under tissue culture conditions.
Formation of continuous proteinaceous capsule-like layers is demonstrated in tissue culture on plastic lens implants as part of cellular membranes created by mouse macrophages after 48, 56, and 96 hours of incubation. The capsules resemble similar formations seen on lens implants removed from human eyes and their existence is considered part of a clinically beneficial adaptation of man-made materials to the inner eye.


Ocular health myths among a hospital staff.
In order to evaluate their common beliefs in the field of ocular health, an exploratory survey was carried out among 122 professionals belonging to different ranks and specialty areas of the University of Campinas Clinical Hospital (UNICAMP-CH), São Paulo, Brazil. The non-structured questionnaire used asked about common ophthalmologic problems as well as the presence of popular myths about ocular health, such as: 'cure' of visual problems by the use of glasses; reading under insufficient lighting or watching TV too much close to the apparatus is harmful; consequences from the intensive use of the eyes; or special food being needed for better vision. The results indicated the existence of various misconceptions, even among health professionals, such as: belief in the cure of refractive problems by the use of glasses (40.0%); or damage to vision due to insufficient lighting, watching TV too much close to the apparatus or from the intensive use of the eyes (86.7%). Among the professionals performing activities within the ophthalmology department, 62.5% admitted believing in visual damage as a result of conditions such as those mentioned above and 37.5% stated that reading in a moving vehicle is detrimental to vision. From these data, one is entitled to conclude that misconceptions continue to be present, even among professionals in the health area; this indicates that educational programs in ocular health should be provided, especially for individuals working within a hospital ophthalmological service.


Effects of amygdaloid and olfactory tubercle stimulation on efferent activities of the vesical branch of the pelvic nerve and the urethral branch of the pudendal nerve in dogs.
In 69 dogs with divided hypogastric nerves anesthetized with ketamine and chloralose the outflows of the pelvic vesical branch (PV) and pudendal urethral branch (PU) were recorded, and effects of amygdaloid and olfactory tubercle stimulation on them were studied. Stimulation (2-100 Hz, 3 ms, 0.2 mA) was applied to the amygdaloid body and olfactory tubercle. When the bladder contraction was induced by amygdaloid stimulation, the increased PV and decreased PU appeared after latencies of about 115 and 110 ms, respectively. When the bladder relaxation was, oppositely, elicited by stimulation, the decreased PV and enhanced PU occurred after latencies of 110 and 90 ms, respectively. The PV excitation was elicited by medial parts of the intermediate principal nucleus, medial parts of the medial principal nucleus, a part of cortical nucleus and of pericortical nucleus. Inhibition of PV was induced by lateral parts of the medial principal nucleus, medial nucleus, central nucleus and a part of the pericortical nucleus. Olfactory tubercle stimulation elicited PV excitation and PU inhibition with latencies of about 100 ms. The vesicopressor response from the tubercle was not abolished by section of the medial preoptic area, medial hypothalamus and periaqueductal gray, but was abolished by added section of the lateral preoptic area, lateral hypothalamus and lateral mesencephalic tegmentum. At the rostral pontine level, the response was abolished by partial section of the lateral part of the pontine reticular formation ipsilateral to the stimulation.


Molecular imaging of drug-eluting coronary stents: method development, optimization and selected applications.
A molecular imaging application was developed to characterize the drug distribution on CYPHER® and NEVO™ Drug-eluting Stents using MALDI Qq-ToF analytical methodology. The coating matrix, laser energy, laser frequency, spatial resolution (related to rastering speed) and mass spectrometer parameters were optimized to analyze drug distribution in both durable and biodegradable polymer matrices. The developed method was extended to generate data from stents explanted from porcine coronary arteries. Due to the method's intrinsic specificity, it offers a significant advantage over other techniques in that it allows low-level detection of the target molecule without biological interferences from the blood or tissue. The method is also capable of detecting drug-related degradation products both from the finished stent product and from explanted stents.


Mucocutaneous granulocytic sarcomas of the head and neck.
Granulocytic sarcomas are malignant solid tumors composed of poorly differentiated myeloid cells that occur in association with myelocytic leukemia. The clinicopathologic characteristics of granulocytic sarcomas that presented in the oral mucosa and in the facial, scalp and neck skin of 8 patients in the acute phase of myelocytic leukemia are described and discussed. Although most of the tumors were demonstrably sensitive to cytosine arabinoside, alone or in combination with other antineoplastic drugs, the prognostic portent of these lesions was extremely poor.


A prospective evaluation of iodinated contrast flow patterns with fluoroscopically guided lumbar epidural steroid injections: the lateral parasagittal interlaminar epidural approach versus the transforaminal epidural approach.
Lumbar midline interlaminar and transforaminal (TF) epidural steroid injections are treatments for low back pain with radiculopathy secondary to degenerative disk disease. Since pain generators are located anteriorly in the epidural space, ventral epidural spread is the logical target for placement of antiinflammatory medications. In this randomized, prospective, observational study, we compared contrast flow patterns in the epidural space using the parasagittal interlaminar (PIL) and transforaminal approaches with continual fluoroscopic guidance. Sixty adult patients with low back pain and unilateral radiculopathy from herniated or degenerated discs were enrolled. Subjects were randomly assigned to one of two groups: TF or PIL (30 in each). All procedures were performed using continual fluoroscopic guidance and 5 mL of contrast. Contrast spread was rated (primary outcome measure) by the interventionalist. Spread was scored 0-2, with 0 = no anterior spread; 1 = anterior spread, same level as needle insertion; and 2 = anterior spread at > or = 1 segmental level. The secondary outcome measure was analgesia at 2 wk, 1, 3, and 6 mo. One hundred percent (29 of 29) patients in the PIL group and 75% (21 of 28) patients in the TF group demonstrated anterior epidural spread. The mean spread grade was 1.93 (95% confidence interval [CI], 1.83-2.0) in the PIL group and 1.46 (95% CI, 1.17-1.46) in the TF group (P = 0.003). Mean fluoroscopy time was 28.96 s (95% CI, 23.9-34.1 s) in the PIL group and 46.25 s (95% CI, 36.27-56.23 s) in the TF group (P = 0.003). Visual analog scale scores were equivalent between groups. The PIL approach is superior to the TF approach for placing contrast into the anterior epidural space with reduction in fluoroscopy times and an improved spread grade. With increasing attention to neurological injury associated with TF, the PIL approach may be more suitable for routine use.


Design, implementation, and evaluation of a thrice-daily cartfill process.
Efficiencies achieved through a redesign of the central pharmacy cartfill process at a large academic medical center are reported. In an initiative to expand clinical pharmacy services in a budget-neutral manner, pharmacists at the University of Wisconsin Hospital and Clinics (UWHC) led the transition from a once-daily to a thrice-daily medication cartfill model designed to better align pharmacy operations with patterns of medication ordering, delivery, and order discontinuation. A pre-post analysis demonstrated several benefits of the shift to thrice-daily cartfill, including a 32.7% decrease in the mean daily number of extemporaneously prepared oral doses. Overall, the new cartfill process resulted in reduction in lead times for three of four peak delivery periods, roughly a 55-65% reduction. During the postimplementation period, the frequency of requests for missing medication doses through the electronic medical record (EMR) system increased from 1.13% to 1.43%; however, this increase may have been the result of improved nurse adherence to EMR protocols for requests for missing medications. Implementation of a thrice-daily cartfill process and ancillary changes at UWHC resulted in a 2.1% increase in cartfill doses dispensed, a 44.1% decrease in first doses dispensed, and a 42.9% decrease in the number of medications returned to the central pharmacy. This resulted in a reduction in waste within pharmacy operations and allowed for redeployment of two technician full-time equivalents to expand pharmacy services.


Autoimmune pancreatitis: pathological findings.
In recent years, autoimmune pancreatitis has been established as a special type of chronic pancreatitis. It is characterized by its histopathological and immunological features. The morphological hallmarks are periductal infiltration by lymphocytes and plasma cells and granulocytic epithelial lesions with consequent destruction of the duct epithelium and venulitis. Autoimmune pancreatitis has therefore also been called lymphoplasmacytic sclerosing pancreatitis, duct-destructive chronic pancreatitis, or sclerosing pancreatitis. Autoimmune pancreatitis most commonly involves the head of the pancreas and the distal bile duct. Occasionally, masses are formed and it has been described as an inflammatory myofibroblastic tumor.


[Clinical aspects of diabetic nephroangiopathy (author's transl)].
Diabetic nephropathy is a dangerous and insidious complication of diabetes mellitus. The course is variable and from the statistical point of view usually unfavorable. The pathogenesis of the complaint is not fully known. Of the numerous hypotheses, the one most favored is a defective glucose metabolism with uncontrolled inundation of the kidney cells with glucose. The predominant symptom is proteinuria. Early recognition and optimal correction of the metabolic disorder may possibly delay the manifestation of diabetic nephropathy for a time. The use of Somatostatin is attracting great attention today. With such a preparation, the stabilization of diabetes could be facilitated.


A practical way to diagnosis personality disorder: a proposal.
General criteria for the diagnosis of personality disorder are provided based on rating a few items describing four core features of personality disorder: (a) low Self-directedness, (b) low Cooperativeness, (c) low Affective Stability, and (d) low Self-transcendence. These core features correspond closely with the basic concept of personality disorder in DSM-IV and are based on specific items easy for clinicians to rate in a short time. Criteria are also provided for rating severity of personality disorganization and for subtyping based on a profile of three additional dimensions corresponding to core features of DSM-IV clusters A, B, and C. This approach should facilitate efficient screening in clinical practice, encourage an understanding of the development of comorbidity as a self-organizing process, and provide a theory-driven basis for therapeutic planning with drugs and psychotherapy.


Content of Asthmagen Natural Rubber Latex Allergens in Commercial Disposable Gloves.
The use of natural rubber latex (NRL) gloves in many occupations may lead to latex sensitization, allergic asthma, and skin reactions. Due to their good properties and environmental safety NRL gloves are still being used in the healthcare setting, but also in the food industry, by hairdressers, cleaners, etc. The aim of our study was to assess the protein and NRL allergen content in commercial gloves by different methods, including a new assay. Twenty commercially available NRL gloves were analyzed. Protein extraction was performed according to the international standard ASTM D-5712. Total protein content was measured with a modified Lowry method, NRL content with the CAP Inhibition Assay, the Beezhold ELISA Inhibition Assay, and an innovative ELISA with IgY-antibodies extracted from eggs of NRL-immunized hens (IgY Inhibition Assay). We found a high protein content in a range of 215.0-1304.7 μg/g in 8 out of the 20 NRL gloves. Seven of the 20 gloves were powdered, four of them with a high protein content. In gloves with high protein content, the immunological tests detected congruently high levels of NRL allergen. We conclude that a high percentage of commercially available NRL gloves still represent a risk for NRL allergy, including asthma. The modified Lowry Method allows to infer on the latex allergen content.


"If I had been given that information back then": An interpretive description exploring the information needs of adults with cerebral palsy looking back on their transition to adulthood.
Young people with cerebral palsy (CP) and their families have identified lack of information received during the transition to adulthood as a barrier to successful outcomes. To date, few studies have explored the information needs, preferences, timing, and method of provision from the perspective of individuals with CP. The methodological approach to this qualitative study was interpretive description. Nine adults living with CP, between the ages of 20 and 40, were purposively recruited in Ontario, Canada, to explore, retrospectively, their information needs during the transition to adulthood. Participants completed a 1-hour interview that explored their experiences seeking and receiving information. Interviews were transcribed verbatim, and data were analysed to create a thematic description of adults' experiences with information. Three themes emerged: (a) "Recognizing and supporting information needs," which highlighted the importance of support systems to assist young people in receiving and seeking information throughout the transition; (b) "Getting creative," which highlighted strategies young people use when confronted with environmental barriers when seeking information; and (c) "Gaps and advice for the future," which highlighted the need for real-life opportunities, during the transition to adulthood, to experience some of the responsibilities of adult life. Clinicians assisting young people with CP need purposefully to foster knowledge and skills during the transition to adulthood. They should be not only providers of information but also enablers of opportunities for immersion in real-life experiences to prepare for adult life. It is important for young people to have the opportunity to discuss challenges and exchange information with their peers.


Fludarabine-containing chemotherapy as frontline treatment of nongastrointestinal mucosa-associated lymphoid tissue lymphoma.
Mucosa-associated lymphoid tissue (MALT) lymphoma is a specific clinicopathologic entity with gastric and nongastrointestinal site involvement. The authors reported the clinical outcome of patients with Stage IE nongastrointestinal MALT lymphoma treated with a frontline fludarabine-containing regimen or with a regimen containing cyclophosphamide, vincristine, and prednisone (CVP). Between 1998 and 2001, 31 patients with Stage IE disease were referred to the Seràgnoli Institute of Hematology and Medical Oncology at the University of Bologna (Bologna, Italy). Presenting sites included periorbital soft tissue (n = 8), lung (n = 5), skin (n = 5), salivary glands (n = 5), lacrimal glands (n = 5), and thyroid (n = 3). Twenty patients were treated with fludarabine and mitoxantrone (FM), and 11 were treated with the CVP regimen. The median follow-up was 3 years. All patients achieved complete responses (CR). Four patients, all treated with CVP, experienced disease recurrence and then achieved a second CR after FM salvage treatment. No tumor recurrence was observed in patients with thyroid, lacrimal gland, or pulmonary lymphoma. The projected 5-year overall survival and disease-free survival rates were 100% and 85%, respectively. The fludarabine-containing FM regimen provided a relatively effective frontline (or salvage) treatment option for patients with nongastrointestinal Stage IE MALT lymphoma and probably was superior to CVP in terms of efficacy.


A death in the life of a therapist and its impact on the therapy.
Several years ago, each of the authors experienced the death of a close family member. In the months after our return to work, we found ourselves discussing with each other our losses, the process of mourning, our families, and gradually, our patients. We became aware that we both were struggling privately with the problem of being a therapist in the wake of a deep personal loss. We began to discuss our cases in greater detail with each other, reviewed the literature pertinent to upheaval in the lives of therapists, and spoke with colleagues who had also experienced the death of a loved one. This paper explores the problems and opportunities that may arise in this common clinical situation. Our principal finding is that the interaction between patient and therapist often repeats an earlier trauma for the patient in which the therapist unwittingly reenacts a pathogenic parental response. The therapist should be sensitive to this possibility and attempt to deal with the problem interpretively. Rather than focusing on whether or not to reveal his or her loss to the patient, the therapist should address the broader issue of the meaning that revealing or not revealing will have for the patient. Overall, we hope to further the dialogue about the impact of a therapist's loss on the patient.


Uracil-DNA glycosylase in insects. Drosophila and the locust.
It has been reported that Drosophila lacks a uracil-DNA glycosylase but that a direct incising activity on uracil-containing DNA appeared developmentally only in third instar larvae. In contrast we have found by two independent assays, that uracil-DNA glycosylase exists in both Drosophila eggs as well as in third instar larvae. The first assay shows the liberation of [3H] uracil from a d(AT)n polymer randomly substituted with [3H]uracil by its synthesis in the presence of [3H] dUTP. The second fluorometric assay for uracil-DNA glycosylase depends on the unique topological properties of circular DNAs and has the advantage of detecting apyrimidinic/apurinic (AP) endonuclease activity as well. To test one other insect, locust eggs were also assayed for uracil-DNA glycosylase. The amount of uracil-DNA glycosylase correlated well with the amount of DNA in actively replicating cells.


Regulation of prostaglandin synthesis by antiinflammatory drugs.
The prostaglandins (PG), thromboxanes, and leukotrienes (LT) are potent groups of mediators derived from arachidonic acid. The functions of these compounds are numerous and involve every organ system, but their roles in physiology and pathology are not completely understood. PG and LT are important mediators of inflammatory reactions. Convincing evidence supports the hypothesis than inhibition of PG synthesis accounts for both the major therapeutic antiinflammatory and toxic side effects of the nonsteroidal antiinflammatory drugs. New research has revealed that PG are synthesized by 2 forms of the enzyme cyclooxygenase, COX-1 and COX-2. Since COX-1 generally produces PG responsible for cytoprotective functions and COX-2 produces PG in inflammatory reactions, it is a reasonable hypothesis that drugs that are selective inhibitors of COX-2 should be effective antiinflammatory agents with few toxic side effects.


In vivo and in vitro studies on the neurotoxic potential of 6-hydroxydopamine analogs.
In an attempt to determine which physical and biological properties could best be correlated with neurotoxic potential, seven analogs of 1-(2,4,5-trihydroxyphenyl)-2-aminoethane (1), better known as 6-hydroxydopamine, were synthesized and compared to 1 in a variety of ways both in vivo and in vitro. The analogs, in combination with the standard 1, include all eight of the 2,4,5-trisubstituted-phenyl derivatives of phenethylamine and alpha-methylphenethylamine in which the substitution is of the trihydroxy or aminodihydroxy form. Low (60 nmol) and high (300 nmol) intracerebroventricular doses of all analogs produced long-term (7 day) reduction of mouse whole brain norepinephrine (NE) and lesser depletions of dopamine (DA), and effects on serotonin were varied. The analog 1-(5-amino-2,4-dihydroxyphenyl)-2-aminopropane (8) was both more complete and more selective than the standard 1 in depleting NE. Using a histofluorometric glyoxylic acid method and Fink-Heimer silver degeneration stain, it was determined that overt neural degeneration was produced by 8. In vitro, the ease of oxidation of the eight analogs was found to be represented by a formal potential range of -130 to -212 mV vs SCE. However, there was no obvious relationship between ease of oxidation and the extent of monoamine depletion from mouse brain. Using kinetic analysis of synaptosomal accumulation of [3H]NE and [3H]DA, it was found that the standard 1 is more potent in its interaction with the DA uptake site (Ki = 12 +/- 0 microM) than the NE uptake site (Ki = 51 +/- 1 microM). A correlation analysis was used to determine that differences in NE and DA depletion by each analog could not be explained by differences in potency for in vitro uptake blockade. However, there was a correlation between the Ki for [3H]NE uptake blockade and the EC50 for synaptosomal release of preloaded [3H]NE for the eight analogs (R2 = 0.96; for log:log plot, R2 = 0.54), indicating that the results for these two in vitro tests both reflect interaction with the same NE neuronal membrane transport site. A similar correlation between Ki and EC50 was shown for all eight analogs using [3H]DA (R2 = 0.92; for log:log plot, R2 = 0.52), indicating interaction with the same DA neuronal membrane transport site. These findings demonstrate that there is no single property that can account for selectivity of action and/or potency of catecholamine neurotoxins related to 6-hydroxydopamine.


The diffuse neuroendocrine system and the apud concept: related "endocrine" peptides in brain, intestine, pituitary, placenta, and anuran cutaneous glands.
A number of peptides, closely related in terms of their amino acid sequences, have been found to occur in the gastroenteropancreatic system on the one hand and in the brain on the other. A common range of peptides links the pituitary gland and the placenta and 4 groups of peptides, found in anuran cutaneous glands, are related to the brain and intestinal peptides of mammals. The cells responsible for the production of these peptides, in whatever situation they occur, belong to the APUD ("Amine Precursor Uptake and Decarboxylation") series and they share a number of cytochemical and ultrastructural characteristics which reflect their functional similarities. It was originally suggested that the production of common peptides could be explained on the basis of the origin of the cells from a common ancestor. It is now postulated rather that, being derived at different periods of time from the embryonic epiblast--or perhaps, more accurately, ectoblast--they share a common neuroendocrine programme which is manifested by their possession of the acronymous amine-handling characteristics of the series and whose final expression is determined by microenvironmental circumstances. The APUD concept thus links together a whole spectrum of peptides some of which are hormones, or local hormones, others neurotransmitters and yet others probably exotoxins. Its implications are widespread, and far reaching, affecting most disciplines in the field of medical biology.


Serum Concentration of Anti-TNF Antibodies, Adverse Effects and Quality of Life in Patients with Inflammatory Bowel Disease in Remission on Maintenance Treatment.
High serum concentrations of infliximab [IFX] and adalimumab [ADA] may be associated with adverse effects in patients with inflammatory bowel disease [IBD]. We aimed to investigate whether high anti-tumour necrosis factor [TNF] trough levels [TLs] were associated with toxicity and impaired quality of life [QoL]. We conducted a prospective cohort study in IBD patients in clinical and biochemical remission on IFX or ADA maintenance therapy. Trough serum concentrations and antidrug antibodies were measured in addition to biochemical markers of inflammation in serum and stool to confirm quiescent disease. QoL was assessed using the Inflammatory Bowel Disease Questionnaire and 36-item short form]. Side effects such as fatigue and arthralgia were measured with a visual analogue score [VAS]. Skin toxicity was reported with a European Organization for Research and Treatment of Cancer-derived score. In all, 252 IBD patients on maintenance anti-TNF therapy were screened, of whom 95 [73 with Crohn's disease, 22 with ulcerative colitis; 72 on IFX, 23 on ADA] were in clinical and biochemical remission and were included. Median TLs were 5.5 µg/ml and 6.6 µg/ml for IFX and ADA, respectively. Patients with anti-TNF TLs above median had lower IBDQ scores than patients with lower TLs [IBDQ 176 vs 187, p = 0.02], particularly regarding systemic symptoms and emotional status. A trend towards lower SF-36 and higher fatigue scores was observed in the higher anti-TNF TL group. Skin and arthralgia scores were not significantly different between the groups. IBD patients with higher anti-TNF serum concentrations had significantly lower disease-specific QoL. Fatigue, arthralgia, and skin lesions do not occur more often in these patients. These data are reassuring that high serum concentrations of anti-TNF antibodies are not toxic.


Comparison of dipyridamole-echocardiography with dipyridamole-thallium scintigraphy for the diagnosis of myocardial ischemia.
After an intravenous infusion of dipyridamole (0.56 mg/kg), we performed both echocardiography and thallium scintigraphy in 63 patients who were referred for known or suspected coronary artery disease. Of those patients, 25 returned for coronary arteriography within 1 month after the tests, thus forming the study group for this report. Sensitivity for detection of coronary artery disease, when analyzed region-by-region, was 80% for thallium scintigraphy and 57% for echocardiography, whereas specificity was 85% and 98%, respectively. When evaluating individual patients for the presence or absence of ischemia, we found a sensitivity of 95% for scintigraphy and 58% for echocardiography; corresponding specificities were 50% and 100%. By using arteriography as the gold standard for comparison, it appears that thallium scintigraphy has a significantly higher sensitivity but lower specificity for the detection of coronary artery disease than does echocardiography. Echocardiography may, however, be a useful adjunct to thallium scintigraphy in the evaluation of patients with coronary artery disease.


Investigation of tracheoesophageal voice prosthesis leakage patterns: patient's self-report versus clinician's confirmation.
This study investigated the patient's self-report and clinician's confirmation of tracheoesophageal voice prosthesis leakage patterns (through or around) with or without the cough reflex and whether prosthesis diameter affected the leakage route. Sixty-six consecutive participants with a total of 200 patient-initiated reasons for prosthesis changes were enrolled prospectively. Patient's self-report of leakage and cough reflex were recorded prior to clinician's confirmation. One-hundred eight (54%) of the 200 patient-initiated reasons for prosthesis changes were leakage through or around the voice prosthesis. Leakage was unrecognized in 21 (23%) of 92 instances, even though 15 (71%) of those 21 instances exhibited a cough reflex. Clinician's confirmed leakage in 118 (59%) of 200 patient-initiated reasons for prosthesis changes. Coughing occurred significantly less with leakage around (9 [53%] of 17 instances) than that with leakage through the voice prosthesis (80 [88%] of 91 instances) (chi(2) [1, N=108], p< .05). Leakage around the voice prosthesis occurred more with 20-Fr diameter prostheses (16 [76%] of 21 instances). Patient education is important for reliable identification of leakage for prompt prosthesis replacement. Leakage around the voice prosthesis can be minimized or avoided by initially fitting and continuing the use of smaller diameter (16 Fr) voice prostheses.


3(3) factorial design-based optimization of the formulation of nitrofurantoin microcapsules.
A microcapsule form of nitrofurantoin was prepared by a simple coacervation method with carboxymethylcellulose and aluminium sulfate. 3(3) factorial design was performed for three independent variables, namely, the particle size of the drug, the size of the microcapsules and the pH of the dissolution medium. The dissolution tests with the formulated microcapsules were carried out according to the United States Pharmacopeia XXII rotating basket method at pH 1.2, 5, and 7.5, which represent the pH of gastrointestinal fluids. Release data were examined kinetically and the ideal kinetic models were estimated and t(63.2) values obtained from RRSBW distribution were used in the factorial design experiment. The influence of the independent variables on the dissolution of nitrofurantoin microcapsules could be expressed as the pH of the dissolution medium > particle size of the microcapsule > particle size of nitrofurantoin. The other aim of this study was to evaluate microcapsule formulation in terms of the United States Pharmacopeia criteria with a minimum of experiments. Our findings suggest that dosage forms which comply with the pharmacopoeia criteria for dissolution can be prepared and selected by factorial design.


Giant stick insects reveal unique ontogenetic changes in biological attachment devices.
A strong modification of tarsal and pretarsal attachment pads during the postembryonic development is described for the first time. In the exceptionally large thorny devil stick insect Eurycantha calcarata a functional arolium is only present in the immature instars, enabling them to climb on smooth surfaces, especially leaves. Nymphs are also characterized by greyish and hairy euplantulae on tarsomeres 1-4. The gradual modifications of the arolium and the euplantula of tarsomere 5 in the nymphal development are probably mainly related to increased weight. The distinct switch in the life style between the leaf-dwelling nymphal stages and the ground-dwelling adults results in the final abrupt change of the adhesive devices, resulting in a far-reaching reduction of the arolium, the presence of a fully-developed, elongated euplantula on tarsomere 5, and white and smooth euplantulae on tarsomeres 1-4. The developmental remodelling of attachment pads also reflects a phylogenetic pattern. The attachment devices of the earlier instars are similar to those found in the basalmost lineage of extant stick insects, Timema, which is characterized by a very large pan-shaped arolium and a hairy surface of the tarsal and pretarsal attachment pads.


Validating the UNICEF/Washington Group Child Functioning Module for Fijian schools to identify seeing, hearing and walking difficulties.
This study investigated the seeing, hearing and walking questions of the UNICEF/Washington Group Child Functioning Module and the inter-rater reliability between teachers and parents as proxy respondents. Cross-sectional diagnostic accuracy study, two-gate design with representative sampling, comparing Module responses to reference standard assessments for 472 primary aged students in Fiji. Receiver operating characteristic curves were constructed to determine the area under the curve and optimal cut-off points. Areas under the curves ranged from 0.823 to 0.889 indicating "good" diagnostic accuracy. Inter-rater reliability between parent and teacher responses was "good" to "excellent". The optimal cut-off determined by the Youden Index was "some difficulty" however a wide spread of impairment levels were found in this category with most children either having none or substantial impairments. The diagnostic accuracy of the Module seeing, hearing and walking questions appears acceptable with either parents or teachers as proxy respondents. For education systems, use of the cut-off "some difficulty" with accompanying clinical assessment may be important to capture children who require services and learning supports and avoid potentially misleading categorization. Given the high proportion of the sample from special schools research is required to further test the Module in mainstream schools. Implications for rehabilitation Identification of children who are at risk of disability in Fiji is important to enable planning, monitoring and evaluating access to quality inclusive education. The UNICEF/Washington Group Child Functioning Module appears to be a practical and effective tool that can be used by teachers to identify children at risk of disability. Children identified on the UNICEF/Washington Group Child Functioning Module as having "some difficulty" or higher levels of difficulty in relation to vision, hearing or walking should be referred for further assessment and services. Rehabilitation services in Fiji need to prepare for greater numbers of referrals as the Ministry of Education increasingly rolls out the inclusive education policy, which includes identification by schools of children at risk of disability.