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Recent evidence suggests that protein encoded by the RNA Binding Motif 10 (RBM10) gene has the ability to modulate apoptosis. The objective of this study was to test this hypothesis by manipulating RBM10 expression levels and examining the downstream consequences. The results showed that transient overexpression of RBM10 correlated with significantly elevated levels of tumour necrosis factor alpha (TNF-α) mRNA and soluble TNF-α (sTNF-α) protein, and increased apoptosis (phosphatidyl serine exposure on the outer cell membrane and nuclear condensation). Stable RNA interference-mediated RBM10 knockdown clones were less susceptible to TNF-α-mediated apoptosis, and had decreased sTNF-α protein levels. Elevated levels of TNF-α associated with RBM10 overexpression resulted from increased TNF-α transcription, not TNF-α mRNA stabilization. These results suggest that RBM10 has the ability to modulate apoptosis, and that it does so via a mechanism involving alterations to TNFR super family-mediated signaling. These data provide the first direct evidence that human RBM10 can function as an apoptosis modulator and cytokine expression regulator.

Background: Infectious diseases of the central nervous system (CNS) remain common and life-threatening, especially in developing countries. Knowledge of the aetiological agents responsible for these infections is essential to guide empiric therapy and develop a rational public health policy. To date most data has come from patients admitted to tertiary referral hospitals in Asia and there is limited aetiological data at the provincial hospital level where most patients are seen., Methods: We conducted a prospective Provincial Hospital-based descriptive surveillance study in adults and children at thirteen hospitals in central and southern Viet Nam between August 2007-April 2010. The pathogens of CNS infection were confirmed in CSF and blood samples by using classical microbiology, molecular diagnostics and serology., Results: We recruited 1241 patients with clinically suspected infection of the CNS. An aetiological agent was identified in 640/1241 (52%) of the patients. The most common pathogens were Streptococcus suis serotype 2 in patients older than 14 years of age (147/617, 24%) and Japanese encephalitis virus in patients less than 14 years old (142/624, 23%). Mycobacterium tuberculosis was confirmed in 34/617 (6%) adult patients and 11/624 (2%) paediatric patients. The acute case fatality rate (CFR) during hospital admission was 73/617 (12%) in adults and to 42/624 (7%) in children., Conclusions: Zoonotic bacterial and viral pathogens are the most common causes of CNS infection in adults and children in Viet Nam.

Background: Internal hernias are uncommon in children and their clinical and imaging findings have not been widely addressed., Objective: To determine the spectrum of clinical and imaging findings of internal hernia (IH) in children and to highlight diagnostic features., Materials and Methods: Review of clinical, imaging and surgical findings in 12 children with surgically proven IH., Results: IH found in seven girls and five boys. Five of the children were neonates and seven were between ages 8-17 years. All neonates presented acutely and had transmesenteric internal hernias (TMIH) (four congenital, one acquired). In the older children, five presented with chronic symptoms and two presented with acute symptoms; the former had paraduodenal hernias (all congenital) and the latter had a congenital pericecal and an acquired TMIH. Only 2/5 neonatal TMIH could be appreciated on GI contrast examination. All five paraduodenal hernias were easily diagnosed on UGI series. CT, in two older children, depicted a paraduodenal hernia and the acquired TMIH. In 7/10 (70%) congenital IH, there was associated malrotation (in all four right paraduodenal hernias)., Conclusion: There is a wide spectrum of clinical and imaging findings of IH in children. TMIH were difficult to appreciate on GI contrast examinations, but paraduodenal hernias were easy to appreciate. One must have a high index of suspicion for right paraduodenal hernia if UGI series shows duodenum and proximal small bowel to the right of the spine.

Introduction: The aim of this study was to validate the use of non-contrast computed tomography (CT) with a ureteral stent in situ instead of ureteroscopy for identification of renal tract stones., Methods: All patients who had stents inserted for renal tract stones and underwent non-contrast CT with the stent in situ followed by ureteroscopy between May 2008 and October 2009 at The Canberra hospital, Australia, were analysed retrospectively. Statistical analysis was performed to compare any differences between CT and ureteroscopy in the identification of stones., Results: Overall, 57 patients were included in the study. The difference between CT and ureteroscopy findings was statistically significant. CT identification of stones with a stent in situ had a sensitivity of 86%, a specificity of 46%, a positive predictive value of 63%, a negative predictive value of 76% and an accuracy of 67%., Conclusions: Our study suggests that non-contrast CT is inferior to the 'gold standard' of ureteroscopy. It lacks sensitivity, specificity, positive predictive value, negative predictive value and accuracy. Therefore, we cannot recommend using non-contrast CT to replace ureteroscopy.

We have examined the changes in physical properties of aqueous solutions of the plasmid pUC18 that take place on the addition of the cationic oligopeptide penta-arginine. An increase in sedimentation rate and static light scattering, and changes in the nucleic acid CD spectrum all suggest that this ligand acts to condense the plasmid. Dynamic light scattering suggests the hydrodynamic radii of the condensate particles are a few micrometers, ca. 50-fold larger than that of the monomeric plasmid. Condensation of the plasmid also produces a ca. 100-fold decrease in the strand break yield produced by gamma irradiation. This extensive protection against reactive intermediates in the bulk of the solution implies that condensed plasmid DNA may offer a model system with which to study the direct effect of ionizing radiation (ionization of the DNA itself). The use of peptide ligands as condensing agents in this application is attractive because the derivatives of several amino acids (particularly tryptophan and tyrosine) have been shown to modify the radiation chemistry of DNA extensively., (Copyright (c) 2010 Elsevier B.V. All rights reserved.)

Gout is a common metabolic disease but spinal gout is rare. We report a case of gouty arthritis affecting the thoracic spine in a 76-year-old male patient with a long history of tophaceous gout who presented with bilateral lower limb weakness. Magnetic resonance imaging of his thoracic spine revealed erosions in the left pedicles of T8 and T10. The initial imaging diagnosis was metastatic disease. A computed tomography-guided biopsy of the T10 lesion was performed and confirmed the diagnosis of gout. We advocate the use of computed tomography-guided fine-needle aspiration/biopsy for diagnosing spinal gout because the imaging features are non-specific, metastasis and spondylodiscitis being important mimickers.

Objectives: Patients with brain tumours have major disabilities and guarded prognosis but may benefit from inpatient rehabilitation.The objectives were to compare functional outcomes inpatients with glioblastoma multiforme(GBM), brain metastases and other brain tumours, and to determine predictors of survival., Methods: Demographic, clinical,functional, and survival data were collected for 63 patients.Kaplan-Meier and Cox regression were used for survival analyses., Results: Functional Independence Measure(FIM ) scores improved from admission to discharge for patients with GBM, brain metastases and other tumours. Estimated median survival was 141 days for brain metastases, 214 days for GBM and 439 days for other tumours. Low admission dexamethasone dose and high FIM gain predicted better survival in GBM. For brain metastases, high FIM gain, low dexamethasone dose and no organ metastases were positive prognostic factors., Conclusions: Patients with primary and metastatic brain tumours achieved functional gains after rehabilitation. High functional improvement is a significant predictor of longer survival in brain metastases and GBM. This study has implications for rehabilitation in the post-acute management of patients who have disabilities due to brain tumours.

Transcriptional activators work by recruiting transcription factors that are required for the process of transcription to their target genes. We have used the Split-Ubiquitin system to identify eight transcription factors that interacted with both the transcriptional activators Gal4p and Gcn4p in living cells. The over-expression of one of the activator-interacting proteins, Gal11p, partially suppressed GAL4 and GCN4 deletions. We have isolated two point mutants in Gal11p, F848L and F869S that were defective for the dosage compensation. We have identified 35 transcription factors that interacted with Gal11p in living cells, and the only protein-protein interaction affected by the Gal11p mutations was the one between Gal11p and Taf14p. We have further shown that the suppression of a GAL4 deletion by high levels of Gal11p required Taf14p, and that over-expression of Gal11p recruited Taf14p to the GAL1 promoter together with Tbp1p, Swi2p and Srb7p. Gal11p interacted with Mig1p, indicating that Mig1/2p could have recruited Gal11p to the GAL1 promoter in the absence of Gal4p. Our results suggest that transcriptional activators work by raising the local concentration of the limiting factor Gal11p, and that Gal11p works by recruiting Mediator and Taf14p-containing transcription factors like TFIID and SWI/SNF and by competing general repressors like Ssn6p-Tup1p off the target promoters.

End stage renal failure patients requiring long term total parenteral nutrition (TPN) often have multiple central line placements due to line infection or occlusion. Sometimes this can cause central venous stenosis or even occlusion. We present three cases in this consecutive series, in which we have successfully used arteriovenous fistulae for both hemodialysis and long term TPN administration as an alternative route without any complications. We therefore think that native AVF and grafts can be used as dual access for hemodialysis and TPN administration provided careful case selection, counselling and follow-up.

Background: Parenteral nutrition (PN) is a common supportive care therapy in patients undergoing hematopoietic stem cell transplantation (HSCT). Inadequate oral dietary intake may necessitate prolonged courses of PN, which have been associated with metabolic, infectious, and hepatobiliary complications. The objective of this study was to identify demographic, clinical, and nutrition factors associated with the resumption of oral dietary intake following HSCT., Methods: This was an observational cohort study of 37 children undergoing allogeneic HSCT. Repeated-measures regression analysis was performed to identify factors associated with the resumption and macronutrient composition of oral nutrient intake after HSCT., Results: Mean oral dietary intake during the first 2 weeks after HSCT was <280 kcal/d. At all times, oral carbohydrate intake was high, ranging from 58% to 74% of oral energy. Age, time since transplant, degree of oral mucositis, and severity of graft-vs-host disease (GVHD) were all significantly correlated with the resumption of oral energy intake, as well as oral intake of carbohydrates. Oral protein and fat intake were also associated with elapsed time since HSCT, severity of mucositis, and GVHD. Factors not associated with oral dietary intake included gender, pre-HSCT nutrition status, diagnosis, type of donor, and infections., Conclusions: Children undergoing HSCT exhibit a marked reduction in oral dietary intake and a preference for a diet high in carbohydrates. Careful attention should be directed to the oral dietary intake and nutrient requirements of children during HSCT, especially in younger patients and those who experience severe mucositis or GVHD.

Cutaneous involvement is a rare manifestation of tuberculosis (TB). The correct diagnosis is often significantly delayed because cutaneous TB is not routinely considered in the differential diagnosis or because investigations fail to reveal the presence of Mycobacterium tuberculosis. The clinical features of cutaneous TB are diverse, and result from exogenous and endogenous spread of M. tuberculosis and from immune-mediated mechanisms. The recognition of cutaneous TB is important, as the diagnosis is frequently overlooked resulting in delayed treatment.

Leptin, an adipocyte-derived hormone, acts directly on the brain to control food intake and energy expenditure. An important question is the identity of first-order neurons initiating leptin's anti-obesity effects. A widely held view is that most, if not all, of leptin's effects are mediated by neurons located in the arcuate nucleus of the hypothalamus. However, leptin receptors (LEPRs) are expressed in other sites as well, including the ventromedial hypothalamus (VMH). The possible role of leptin acting in "nonarcuate" sites has largely been ignored. In the present study, we show that leptin depolarizes and increases the firing rate of steroidogenic factor-1 (SF1)-positive neurons in the VMH. We also show, by generating mice that lack LEPRs on SF1-positive neurons, that leptin action at this site plays an important role in reducing body weight and, of note, in resisting diet-induced obesity. These results reveal a critical role for leptin action on VMH neurons.

Activation of melanocortin-4-receptors (MC4Rs) reduces body fat stores by decreasing food intake and increasing energy expenditure. MC4Rs are expressed in multiple CNS sites, any number of which could mediate these effects. To identify the functionally relevant sites of MC4R expression, we generated a loxP-modified, null Mc4r allele (loxTB Mc4r) that can be reactivated by Cre-recombinase. Mice homozygous for the loxTB Mc4r allele do not express MC4Rs and are markedly obese. Restoration of MC4R expression in the paraventricular hypothalamus (PVH) and a subpopulation of amygdala neurons, using Sim1-Cre transgenic mice, prevented 60% of the obesity. Of note, increased food intake, typical of Mc4r null mice, was completely rescued while reduced energy expenditure was unaffected. These findings demonstrate that MC4Rs in the PVH and/or the amygdala control food intake but that MC4Rs elsewhere control energy expenditure. Disassociation of food intake and energy expenditure reveals unexpected divergence in melanocortin pathways controlling energy balance.

Atherosclerosis, now considered an inflammatory process, is the leading cause of death in the Western world and is manifested by a variety of diseases in multiple organ systems. Because of its prevalence and associated morbidity, novel therapies directed at arresting this progressive process are urgently needed. The inflammatory mediator TNF-alpha, which is known to contribute to apoptosis in vascular smooth muscle cells, has been shown to be intimately involved in the atherosclerotic process, being present at elevated levels in human atheroma as well as possibly being responsible for plaque rupture, a clinically devastating event. In light of our earlier finding that p73 is a proapoptotic protein in vascular smooth muscle cells, which are involved in plaque progression as well as rupture, we asked whether TNF-alpha mediates apoptosis in these cells through p73. We now show that p73 is present in spindle-shaped cells within human atheroma, and p73beta, an isoform that is pivotal in both apoptosis and growth suppression, is induced in vascular smooth muscle cells in vitro by serum but not by PDGF-BB. In addition, TNF-alpha, when added to these cells in the presence of serum-containing media, increases p73beta expression and causes apoptosis in both rat and human vascular smooth muscle cells. Inhibition of p73 activity with a dominant inhibitory NH2-terminally deleted p73 plasmid results in markedly decreased TNF-alpha-induced apoptosis. Thus p73beta is likely a mediator of the apoptotic effect of TNF-alpha in the vasculature, such that future targeting of the p73 isoforms may ultimately prove useful in novel atherosclerosis therapies.

Leptin is required for normal energy and glucose homeostasis. The hypothalamic arcuate nucleus (ARH) has been proposed as an important site of leptin action. To assess the physiological significance of leptin signaling in the ARH, we used mice homozygous for a FLPe-reactivatable, leptin receptor null allele (Lepr(neo/neo) mice). Similar to Lepr(db/db) mice, these mice are obese, hyperglycemic, hyperinsulinemic, infertile, and hypoactive. To selectively restore leptin signaling in the ARH, we generated an adeno-associated virus expressing FLPe-recombinase, which was delivered unilaterally into the hypothalamus using stereotaxic injections. We found that unilateral restoration of leptin signaling in the ARH of Lepr(neo/neo) mice leads to a modest decrease in body weight and food intake. In contrast, unilateral reactivation markedly improved hyperinsulinemia and normalized blood glucose levels and locomotor activity. These data demonstrate that leptin signaling in the ARH is sufficient for mediating leptin's effects on glucose homeostasis and locomotor activity.

Neuroanatomical and electrophysiological studies have shown that hypothalamic POMC neurons are targets of the adipostatic hormone leptin. However, the physiological relevance of leptin signaling in these neurons has not yet been directly tested. Here, using the Cre/loxP system, we critically test the functional importance of leptin action on POMC neurons by deleting leptin receptors specifically from these cells in mice. Mice lacking leptin signaling in POMC neurons are mildly obese, hyperleptinemic, and have altered expression of hypothalamic neuropeptides. In summary, leptin receptors on POMC neurons are required but not solely responsible for leptin's regulation of body weight homeostasis., (Copyright 2004 Cell Press)

Two studies investigating the psychological, family and interpersonal correlates of adolescent violent behavior are reported in this paper. In Study 1, secondary school students (N = 1,519) responded to established scales assessing their psychological attributes, family functioning, parenting qualities and psychosocial support and conflict. Results of Study 1 showed that: a) adolescents who showed higher levels of perceived stress and psychological symptoms displayed more signs of adolescent violence; b) adolescents who had a higher sense of mastery and existential mental health displayed less signs of violence; c) adolescents' attitudes towards poverty and traditional Chinese beliefs about adversity were significantly related to adolescent violence; d) higher levels of family functioning, positive parenting styles as well as interpersonal support and lower levels of interpersonal conflicts were associated with a lower level of adolescent violence. Results further showed that some of the above factors were more strongly related to adolescent violence in adolescents experiencing economic disadvantage than in adolescents who did not experience economic disadvantage. Some of the findings of Study 1 were replicated in Study 2, where adolescents from 229 families (either families on welfare or low income families) were recruited. These studies suggested that several psychological, family and interpersonal factors are related to adolescent violent behavior, particularly in adolescents with economic disadvantage.

Analyses of adolescent suicide statistics in Hong Kong for the period 1980 to 2000 revealed several phenomena. First, while adolescent suicide rates (10-24 age group) in Hong Kong were relatively stable for the period under study, there was a gradual rising trend where adolescent suicide rates in the 1990s were higher than those in the 1980s. Second, suicide rates for adolescents aged 10-24 were lower than those of other adult age groups. Third, while adolescent suicide rates in Hong Kong were lower than those reported in some English-speaking countries and Mainland China, the figures were higher than those reported in Taiwan. Fourth, suicide rates among teenagers in early adolescence were lower than those among adolescents in late adolescence. Fifth, although male adolescent suicide rates were in general higher than female adolescent suicide rates (10-24 age group), gender differences in suicide rates appeared to be moderated by age. Sixth, there was a gradual rising trend in adolescent proportional mortality rates for suicide in the 1990s. Seventh, proportional mortality rates for suicide among teenagers in early adolescence were lower than those among adolescents in late adolescence. Finally, while jumping from a height was a common method of adolescent suicide, there was a rising trend of using other methods such as taking drugs, hanging and charcoal burning. The observed adolescent suicide phenomena are discussed with reference to the socio-cultural context of Hong Kong.

Bone-morphogenetic proteins (BMP)-2 and -7, multifunctional members of the transforming growth factor (TGF)-beta superfamily with powerful osteoinductive effects, cause cell cycle arrest in a variety of transformed cell lines by activating signaling cascades that involve several cyclin-dependent kinase inhibitors (CDKIs). CDKIs in the cip/kip family, p21(Cip1/Waf1) and p27(Kip1), have been shown to negatively regulate the G1 cyclins and their partner cyclin-dependent kinase proteins, resulting in BMP-mediated growth arrest. Bone morphogens have also been associated with antiproliferative effects in vascular tissue by unknown mechanisms. We now show that BMP-2-mediated inhibition of platelet-derived growth factor (PDGF)-stimulated human aortic smooth muscle cell (HASMC) proliferation is accompanied by increased levels of p21 protein. Antisense oligodeoxynucleotides specific for p21 attenuate BMP-2-induced inhibition of proliferation when transfected into HASMCs, demonstrating that BMP-2 inhibits PDGF-stimulated proliferation of HASMCs through induction of p21. Whether p21-mediated induction of cell cycle arrest by BMP-2 sets the stage for osteogenic differentiation of vascular smooth muscle cells, ultimately leading to vascular mineralization, remains to be investigated.

Background: Clear cell change, which may occur in a variety of thyroid neoplasms, is an uncommon finding. A fine needle aspirate of a follicular neoplasm showing extensive clear cell morphology is even more rarely described in the literature., Case: We report the fine needle aspiration cytology of a case of follicular neoplasm undergoing clear cell change due to intracellular accumulation of lipid and mucin. The cytology showed cohesive sheets of nondescript, round to oval cells having ample, pale-staining cytoplasm. Many of the tumor cells tended to cluster around branching capillaries. Adipocytelike cells with discrete cell borders, eccentric nuclei and cytoplasm distended by fat globules were frequently found. The cell block sections also showed scattered ghost outlines of these adipocytelike cells in a mucoid background. Similar findings were noted in the crush preparation of the freshly excised surgical specimen. Histologic examination confirmed the presence of a minimally invasive follicular carcinoma with clear cell change., Conclusion: Though the cytologic features of this peculiar morphologic variant of follicular neoplasm may mimic those of mesenchymal lesions or metastatic tumors, recognition of other subtle changes, together with ancillary investigations, is useful in arriving at a correct preoperative diagnosis.

Reduced neuronal NOS (nNOS) expression and biochemical activity was found in the striatum (P<0.05) and cerebellum P<0.05) of late-stage R6/1 Huntington's disease (HD) mice. The changes in NOS biochemical activity correlated with body weight (P<0.001), abnormal clasping (P<0.05) and motor functioning (P<0.05) scores. HD transgenic mice missing both copies of the nNOS gene showed accelerated disease progression relative to HD transgenic mice wildtype or heterozygous for the nNOS gene. On the other hand, mice with one copy of the nNOS gene had delayed onset of their HD-related symptoms relative to HD transgenic mice wildtype for nNOS. Administration of an iNOS inhibitor had no effect on behavioral progression. The effects of nNOS genotype on behavior may be related to abnormal expression of nNOS during development, which was increased relative to controls in R6/2 mice 3 weeks of age (presymptomatic), but decreased in R6/2 mice relative to controls at 6 (around the time of symptom onset) and 11 (late-stage disease) weeks of age. Finally, protein expression of calmodulin kinase II and IV, both of which are regulators of nNOS transcription and activation, had a pattern of increased expression early in development, and decreased expression late in development, similar to that seen for nNOS. These findings indicate that nNOS activity is altered in a complex manner in HD transgenic mice and suggest that these abnormalities occur in the setting of a more global disturbance of calcium-regulated proteins.

Background: A new rapid urine test was developed to detect anti-Helicobacter pylori antibody in urine using the principle of immunochromatography. The accuracy of this test in the Chinese population remains to be defined., Aim: To evaluate a new rapid urine test for the diagnosis of H. pylori infection in the Chinese population., Methods: Eligible patients without previous treatment of H. pylori were recruited. In-house rapid urease test and histology were used as the gold standard. The rapid urine test (RAPIRUN H. pylori antibody) was performed and the results were compared with the gold standard., Results: One hundred and twenty-three patients were eligible for analysis and 61 (50%) were H. pylori positive by the gold standard. The rapid urine test showed a sensitivity, specificity, positive predictive value, negative predictive value and accuracy of 96.7%, 95.2%, 95.2%, 96.7% and 95.9%, respectively. Results were obtained within 20 min and no special laboratory support was required., Conclusions: The rapid urine test by immunochromatography is highly accurate for the diagnosis of H. pylori infection in untreated Chinese patients.

Background: Numerous serological tests for the detection of Helicobacter pylori infection have been developed. However, many perform poorly when evaluated in the Chinese population., Aim: To search for optimal serological tests for the detection of H. pylori infection in Chinese patients., Methods: Consecutive dyspeptic patients referred for upper endoscopy were recruited. During endoscopy, gastric biopsies were taken for the CLOtest and histological examination. Patients were then given a 13C-urea breath test. Sera were used to test for H. pylori infection, employing three commercial enzyme-linked immunosorbent assay kits (pylori DTect, HP IgG and GAP IgG). Results were compared with the gold standard defined by the CLOtest, histology and 13C-urea breath test., Results: Among the 142 patients (47 male, 95 female; mean age, 49 years) recruited, 81 (57%) were H. pylori-positive, 57 (40%) were H. pylori-negative and four (3%) were defined to be indeterminate. Using a self-defined cut-off value after calculation, the best accuracies for the pylori DTect, HP IgG and GAP IgG tests were 97%, 91% and 80%, respectively., Conclusions: The pylori DTect test is an optimal serological test for the detection of H. pylori infection in Hong Kong Chinese patients. The HP IgG test may be used as an alternative.

Background: There is a substantial genetic heterogeneity among Helicobacter pylori strains, and certain genotypes have been suggested to be associated with the virulence of this pathogen. The aim of this study was to investigate the distribution of H. pylori vacA, cagA and iceA genotypes and their association with duodenal ulcer disease in Hong Kong., Materials and Methods: Gastric biopsies of 72 H. pylori infected patients were analyzed by specific polymerase chain reactions., Results: Of the 72 cases, 69 (95.8%) had vacA signal sequence s1c strains, and three (4.2%) had s1a strains. vacA middle region sequences, m1b and m2, were detected in 23 (31.9%) and 46 (63.9%), respectively. Six (8.3%) cases contained multiple vacA subtypes. vacA s2 allele was only observed in three (4.3%) cases, which were also infected with s1c subtype. cagA was present in 64 (88.9%) of 72 patients, and iceA1 subtype was detected in 46 (63.9%) cases. Neither cagA nor vacA and iceA were associated with duodenal ulcer disease., Conclusion: The distribution of vacA, cagA and iceA alleles in H. pylori strains in Hong Kong is similar to that in east Asia. There is a difference in the distribution of genotypes between strains in Hong Kong and those in mainland China, although strains in the two regions exhibit a very close relation. The association of these virulence genes and duodenal ulcer disease needs reappraisal, particularly under geographic considerations.

Background and Aim: The PyloriTek Test Kit (a 1-h rapid urease test) was developed for the rapid diagnosis of Helicobacter pylori (H. pylori) during endoscopy. Most studies were performed in Western populations. The aim of this study was to evaluate the PyloriTek test for the diagnosis of H. pylori infection in Chinese population., Methods: Eligible patients without prior treatment or who had had recent eradication of H. pylori were recruited. During endoscopy, biopsies were taken from the antrum and corpus for an in-house rapid urease test (RUT), histology and for the PyloriTek test (one antral and one corpus biopsy). Results of the PyloriTek test were compared with the gold standard (RUT and histology)., Results: Analysis of PyloriTek test results from the antrum alone (101 patients before eradication and 52 patients after eradication) showed a sensitivity, specificity, and accuracy of 96.3, 97.9, and 97.0%, respectively, for cases before eradication, and an accuracy of 100% for cases after eradication. The benefit of an additional body biopsy was marginal and only occurred in the pre-eradication group., Conclusion: The PyloriTek test was highly accurate for the diagnosis of H. pylori infection before and after eradication therapy, with a final result available at 1 h, which is unmatched by any invasive test so far. It enhances clinical decision-making by allowing the clinicians or endoscopists to start therapy on the same day of an endoscopy visit. One biopsy from the antrum is highly reliable for this purpose.

Thioredoxin expression within the reproductive tissues of the female mouse was analysed during the oestrous cycle stages of dioestrus, oestrus and metoestrus by Western blot analyses and immunocytochemistry. From Western blot analyses the expression of thioredoxin was found to be increased in oestrus compared to dioestrus and metoestrus. Localisation of thioredoxin within the reproductive organs of the mouse during the oestrous cycle has shown that the expression of thioredoxin is specific for distinct areas within the reproductive organs. These areas are the stratified squamous epithelium of the vagina, the simple columnar epithelium and the uterine glands of the uterus, the ciliated columnar epithelium of the oviduct, the corpus lutea, the interstitial cells and the secondary follicles of the ovary. The discrete cellular localisation and oestrous dependence of thioredoxin expression are suggestive of specific roles in various reproductive processes.

Background: Different tests are available for diagnosing Helicobacter pylori infection., Aim: To compare the most commonly used tests either alone or in combination in Chinese patients with respect to routine clinical use or research purpose., Methods: A total of 294 consecutive dyspeptic patients without previous H. pylori treatment were recruited. During upper endoscopy, biopsies were taken from the antrum and corpus, for a commercially available CLO-test, an in-house rapid urease test, culture, polymerase chain reaction and histological examination. Patients then received a 13C-urea breath test. The H. pylori status of each patient was determined by a concordance of test results., Results: For routine clinical use, histology (antral plus corpus biopsies) had an accuracy of 100%, whilst the rapid urease test had an accuracy of 99.7%. The 13C-urea breath test was equally reliable, with an accuracy of 94.5%. Combinations of two tests did not confer additional advantage over the most accurate single test. For research purposes, the accuracy of using the criteria of two positives out of three diagnostic tests was 100% and equivocal results were not found., Conclusion: Histology with or without a rapid urease test was highly accurate for routine clinical use. Alternatively, the 13C-urea breath test was an equally reliable non-invasive test. The two positives out of three tests approach was highly reliable in predicting H. pylori status of untreated Chinese patients in a research setting.

Antibodies specific for capsular polysaccharides play a central role in immunity to encapsulated Streptococcus pneumoniae, but little is known about their genetics or the variable (V) region polymorphisms that affect their protective function. To begin to address these issues, we used combinatorial library cloning to isolate pneumococcal polysaccharide (PPS)-specific Fab fragments from two vaccinated adults. We determined complete V region primary structures and performed antigen binding analyses of seven Fab fragments specific for PPS serotype 6B, 14, or 23F. Fabs were of the immunoglobulin G2 or A isotype. Several V(H)III gene segments (HV 3-7, 3-15, 3-23, and 3-11) were identified. V(L) regions were encoded by several kappa genes (KV 4-1, 3-15, 2-24, and 2D-29) and a lambda gene (LV 1-51). Deviation of the V(H) and V(L) regions from their assigned germ line counterparts indicated that they were somatically mutated. Fabs of the same serotype specificity isolated from a single individual differed in affinity, and these differences could be accounted for either by the extent of mutation among clonal relatives or by usage of different V-region genes. Thus, functionally disparate anti-PPS antibodies can arise within individuals both by activation of independent clones and by intraclonal somatic mutation. For one pair of clonally related Fabs, the more extensively mutated V(H) was associated with lower affinity for PPS 14, a result suggesting that somatic mutation could lead to diminished protective efficacy. These findings indicate that the PPS repertoire in the adult derives from memory B-cell populations that have class switched and undergone extensive hypermutation.

Background: Oleoyl-estrone administration induces the rapid loss of fat preserving body protein., Aim of the Study: We intended to check whether the fat-shedding effect of oleoyl-estrone arrests growth in young rats, limiting the buildup of protein and fat., Methods: Oleoyl-estrone diluted in a powdered hyperlipidic diet (33 mumol/kg) was given for 30 days to 30-day old Zucker lean (Fa/?) rats. Their body weight and food consumption were followed daily; on day 30 of treatment (60-day old rats), whole body composition (lipid, protein) was determined, and plasma energy parameters and leptin were measured., Results: Oleoyl-estrone-treated rats grew more slowly than controls fed the hyperlipidic diet alone, and on day 60 their lipid content was about half that of controls. Protein content per kg was identical in both groups, but treated rats tended to accumulate less nitrogen and energy because of their smaller size. No changes in plasma glucose, urea, triacylglycerols or total cholesterol were observed, but oleoyl-estrone-treated rats showed lower circulating leptin than controls., Conclusion: Despite limiting the accumulation of lipids, oleoyl-estrone slowed, but did not arrest growth of young rats, nor elicit a loss of fat or protein.

Objective: The clinicopathologic features of splenic metastases have seldom been investigated. The aim of this study was to evaluate the clinical and pathological impact of splenic metastases., Case Material: We reviewed the clinical/autopsy records and pathologic features of 92 Chinese patients (58 men, 34 women) with secondary nonlymphoid splenic tumors recorded during a 25-year period., Results: The incidence of splenic secondary tumors at autopsy was 0. 6% and at splenectomy, 1.1%. The lesions were often seen in elderly patients (mean age, 60 years). Seven (8%) of the splenic lesions were symptomatic. The symptomatic splenic lesions, as compared with asymptomatic lesions, were bigger and were found more often in women and younger patients. Two patients experienced spontaneous splenic rupture because of metastatic carcinoma. Eighty-seven (95%) of the secondary splenic tumors were carcinomas. Lung was the most common primary tumor site (21%), followed by the stomach (16%), pancreas (12%), liver (9%), and colon (9%). Rarely reported sources of primary tumor, such as esophageal carcinomas, nasopharyngeal carcinoma, and choriocarcinoma, were also found. Splenic metastases could be identified macroscopically in 74 (80%) of our patients. Grossly, splenic metastases involved the splenic capsule (n = 8) or were solitary (n = 31), multiple (n = 30), or diffuse (n = 8) lesions in the splenic parenchyma. Isolated splenic metastases were noted in 5.3% of the metastases found at autopsy. Many of the metastatic lesions in the spleen were identified shortly after primary tumors were detected (mean latent period, 6.7 months). The time from diagnosis of the primary tumor to metastasis to the spleen was more than 2 years in 14 patients., Conclusions: Splenic metastases are uncommon. A variety of clinical and pathologic patterns were noted in our series.

Background: Near patient tests for Helicobacter pylori were developed to assist in the management of dyspepsia patients in general practice. Most studies were performed in western populations., Aim: To evaluate the rapid whole blood test (Flexpack HP) for H. pylori in the Chinese population., Methods: Consecutive dyspeptic patients referred for upper endoscopy were recruited. During upper endoscopy, biopsies were taken from the antrum and corpus for rapid urease test (CLO test) and histological examination. After endoscopy, the whole blood test (FlexPack HP) was performed according to the manufacturer's instruction. Patients then received a 13C-urea breath test. Results of the whole blood test were compared with the gold standard (CLO test, histology and 13C-urea breath test)., Results: A total of 294 consecutive patients gave a valid Flexpack HP result for interpretation. The mean age of patients was 47.7 (range 15-85) years. Analysis showed a sensitivity, specificity, positive predictive value, negative predictive value and accuracy of 58%, 92%, 91%, 63% and 73% respectively., Conclusion: The FlexPack HP whole blood test showed good specificity but lacked sensitivity. It is not sensitive enough to be used in a general practice setting for the test-and-treat approach in the Chinese population.

Background: Estrone is a relatively abundant hormone widely distributed in tissues of animal and plant origin. It is a mild estrogen that induces increases in body weight in experimental animals. The relative abundance of estrone esters in animal tissues suggests that it may also be found in foods, from which it may alter the mechanisms of body weight control., Aim of the Study: To measure the total estrone content in food and to determine whether this may affect body weight., Methods: In the first part of the study, a method was devised for the measurement of total estrone content in food. This was applied to the analysis of estrone content in a variety of food. Finally, hyperlipidic diets (18.6 MJ/kg) with a total estrone content 0.89 +/- 0.21 mumol/kg (control group) and 1.37 +/- 0.13 mumol/kg (laced with estrone fatty esters) were given to rats during 15 days, in order to determine the influence of dietary estrone on the body mass. Zucker lean (Fa/?) rats weighing initially 200-215 g were used. The total estrone (essentially as fatty esters) content of food was investigated by combining a dried methanol extraction with saponification and measurement of the free estrone evolved through radioimmunoassay., Result: The content of estrone was zero in some vegetables, but significant in fruits, meats, and especially fats, both of plant and animal origin. The application of these analyses to a standard recommended diet for humans may result in intakes of more than 1 mumol of estrone per day, a figure comparable to the estrogen production by women. When rats were exposed to a raised estrone content in a fat-rich diet, they significantly increased their body weights, doubling their rate of growth (1.99 g/day) compared with controls (0.81 g/day), but maintaining their plasma composition and the proportions of lipid, water, and protein in their carcasses., Conclusion: The widely distributed estrone esters in food and their relatively high concentrations may result in high free hormone intakes in humans. The continued and massive intake of estrone may enhance tissue deposition and lead to obesity.

Interdigitating dendritic cell tumor is an extremely rare neoplasm that mainly occurs in lymph nodes. An example of such a tumor in the testis, a hitherto unreported site, is described. Grossly, the tumor was light tan with a uniform solid appearance, replacing virtually the entire testis. Microscopically, it was formed by whorls and fascicles of spindle cells intermingling with small lymphocytes. Such a histologic appearance can, however, mimic a wide variety of other tumors and tumor-like lesions, among which mesenchymal sarcoma, spindle cell carcinoma, follicular dendritic cell tumor, and inflammatory pseudotumor are the main differential diagnoses. Immunohistochemical studies showed that the spindle tumor cells were strongly and diffusely positive for S-100 protein and vimentin. They were also focally positive for CD68 and CD4, but were uniformly negative for leukocyte common antigen, CD1a, CD3, CD20, CD21, CD23, CD34, CD35, actin, desmin, HMB45, cytokeratins, and placental alkaline phosphatase. Ultrastructurally, the tumor cells possessed complex interdigitating cytoplasmic dendritic processes, with abundant rough endoplasmic reticulum and mitochondria in their cytoplasm. An in situ hybridization study for Epstein-Barr virus was negative. The pathologist should be aware of such an entity and consider it in the list of differential diagnoses for unusual spindle cell lesions with a significant background population of small lymphocytes. However, because of its nonspecific histologic appearance, additional immunohistochemical and electron microscopic studies are generally required for its definitive diagnosis.

Nine patients with premature ovarian failure, one of whom had the associated autoimmune disorders rheumatoid arthritis, Hashimoto's thyroiditis, and vitiligo, were examined for the presence of a serum factor which would interfere with gonadotropin-receptor interaction in a bovine testicular membrane system. Sera from nine premenopausal and nine postmenopausal women served as control subjects. Mean displacement of radiolabeled follicle-stimulating hormone (FSH) and luteinizing hormone (LH) from receptors was not significantly different among the three groups. However, the greatest interference with FSH-receptor interaction was detected in the patient with both premature ovarian failure and autoimmune diseases. No differences in mean serum levels of IgG, IgM, and IgA were found among the premature ovarian failure and the two control groups, nor were immunoglobulin levels different in the otherwise unique subject (premature ovarian failure and autoimmunity). Our study suggests that anti-gonadotropin receptor factors are unlikely to be involved in the majority of patients with premature ovarian failure. However, an anti-FSH receptor factor, possibly an antibody, may be present in some patients, particularly those who have concomitant autoimmune disorders.