Interaction of bladder glycoprotein GP51 with uropathogenic bacteria

PURPOSE: A major component of bladder surface mucin is a glycoprotein GP51 (molecular weight 51 kD.). GP51, which has previously been isolated from rabbit mucosa, appears to function as part of the defense mechanism in an in vivo infection model. GP51 coats the epithelium and is secreted into the urine, as detected by immunohistochemical testing and enzyme-linked immunosorbent assay (ELISA). Increased urinary GP51 occurs during urinary tract infection. To elucidate the role of GP51 as a component of the primary defense mechanism we studied interactions with uropathogenic bacterial isolates and urine from symptomatic patients with urinary tract infection. MATERIALS AND METHODS: ELISA was performed to demonstrate the binding of GP51 and various uropathogens. Immunochemical studies were done using monoclonal antibodies to GP51 to determine the interaction of GP51 with certain uropathogenic isolates, including Escherichia coli, Enterobacter cloacae, Klebsiella pneumoniae, Proteus vulgaris, Pseudomonas aeruginosa, Serratia marcescens, Staphylococcus aureus, S. epidermidis and Streptococcus faecalis. Infected urinary sediments and uropathogenic bacterial cultures were examined by immunocytochemical testing to localize GP51. Antigen inhibition ELISA was done to quantitate urinary GP51 in the urine of 17 normal controls and 19 patients with urinary tract infection. RESULTS: ELISA revealed that GP51 binds to a wide spectrum of gram-positive and gram-negative uropathogens in semiquantitative fashion. Immunochemical methods confirmed that purified GP51 binds to bacteria, encapsulating and aggregating the bacteria. Clinical specimens showed GP51 localized to bacteria and uroepithelial cells. We observed a significant increase in urinary GP51 in urinary tract infection compared to uninfected urine (p = 0.0003). CONCLUSIONS: These studies suggest that GP51, a component of bladder mucin, may be a strategic factor in the primary defense mechanism of the bladder.     

Current status of magnetic resonance imaging (MRI) and ultrasonography fusion software platforms for guidance of prostate biopsies

Prostate MRI is currently the best diagnostic imaging method for detecting PCa. Magnetic resonance imaging (MRI)/ultrasonography (US) fusion allows the sensitivity and specificity of MRI to be combined with the real‐time capabilities of transrectal ultrasonography (TRUS). Multiple approaches and techniques exist for MRI/US fusion and include direct ‘in bore’ MRI biopsies, cognitive fusion, and MRI/US fusion via software‐based image coregistration platforms.     

Coagulation factor activity and clinical bleeding severity in rare bleeding disorders: results from the European Network of Rare Bleeding Disorders

Summary. Background: The European Network of Rare Bleeding Disorders (EN‐RBD) was established to bridge the gap between knowledge and practise in the care of patients with RBDs. Objectives: To explore the relationship between coagulation factor activity level and bleeding severity in patients with RBDs. Patients/Methods: Cross‐sectional study using data from 489 patients registered in the EN‐RBD. Coagulation factor activity levels were retrieved. Clinical bleeding episodes were classified into four categories according to severity. Results: The mean age of patients at data collection was 31 years (range, 7 months to 95 years), with an equal sex distribution. On linear regression analysis, there was a strong association between coagulation factor activity level and clinical bleeding severity for fibrinogen, factor (F) X, FXIII, and combined FV and FVIII deficiencies. A weaker association was present for FV and FVII deficiencies. There was no association between coagulation factor activity level and clinical bleeding severity for FXI. The coagulation factor activity levels that were necessary for patients to remain asymptomatic were: fibrinogen, > 100 mg dL^?1; FV, 12 U dL^?1; combined FV + VIII, 43 U dL^?1; FVII, 25 U dL^?1; FX, 56 U dL^?1; FXI, 26 U dL^?1; FXIII, 31 U dL^?1. Moreover, coagulation factor activity levels that corresponded with Grade III bleeding were: undetectable levels for fibrinogen, FV and FXIII, < 15 U dL^?1 for combined FV + VIII; < 8 U dL^?1 for FVI; < 10 U dL^?1 for FX; and < 25 U dL^?1 for FXI. Conclusions: There is a heterogeneous association between coagulation factor activity level and clinical bleeding severity in different RBDs. A strong association is only observed in fibrinogen, FX and FXIII deficiencies.     

Mandibular advancement for pediatric obstructive sleep apnea: A systematic review and meta-analysis

Objectives

Mandibular distraction osteogenesis and mandibular advancement, collectively referred to as mandibular advancement surgeries (MAS), have been used to treat children with mandibular insufficiency and obstructive sleep apnea (OSA). The objective is to perform a systematic review and meta-analysis for MAS as treatment for obstructive sleep apnea.

Hepatitis B virus subgenotypes and basal core promoter mutations in Indonesia

AIM： To identify the distribution of hepatitis B virus （HBV） subgenotype and basal core promoter （BCP） mutations among patients with HBV-associated liver disease in Indonesia.
METHODS： Patients with chronic hepatitis （CH, n =61）, liver cirrhosis （LC, n = 62）, and hepatocellular carcinoma （HCC, n = 48） were included in this study. HBV subgenotype was identified based on S or preS gene sequence, and mutations in the HBx gene including the overlapping BCP region were examined by direct sequencing.
RESULTS： HBV genotype B （subgenotypes B2, B3, B4, 85 and B7） the major genotype in the samples, accounted for 75.4%, 71.0% and 75.0% of CH, LC and HCC patients, respectively, while the genotype C （subgenotypes C1, C2 and C3） was detected in 24.6%, 29.0%, and 25.0% of CH, LC, and HCC patients, respectively. Subgenotypes B3 （84.9%） and C1 （82.2%） were the main subgenotype in HBV genotype B and C, respectively. Serotype adw2 （84.9%） and adrq＋ （89.4%） were the most prevalent in HBV genotype B and C, respectively. Double mutation （A1762T/G1764A） in the BCP was significantly higher in LC （59.7%） and HCC （54.2%） than in CH （19.7%）, suggesting that this mutation was associated with severity of liver disease. The T1753V was also higher in LC （46.8%）, but lower in HCC （22.9%） and CH （18.0%）, suggesting that this mutation may be an indicator of cirrhosis.
CONCLUSION： HBV genotype B/B3 and C/C1 are the major genotypes in Indonesia. Mutations in BCP, such as A1762T/G1764A and T1753V, might have an association with manifestations of liver disease.     

Evidence for direct action of human biosynthetic (recombinant) GM-CSF on erythroid progenitors in serum-free culture

The biologic activity of human biosynthetic granulocyte-monocyte colony stimulating factor (GM-CSF) was investigated in serum-free culture of erythroid progenitors derived from adult peripheral blood. The morphology of erythroid bursts and the cloning efficiency of BFU-E under serum-free conditions were similar to those observed in dishes with fetal bovine serum (FBS). For these experiments, progenitor cells were partially purified by Ficoll-Paque density centrifugation, adherence to a plastic surface, and complement-mediated cytotoxicity of Leu-1+ elements. For some studies, blastlike cells were harvested directly from 6-day-old semisolid cultures. In serum-free culture of the light-density cell fraction, biosynthetic erythropoietin (Ep) was sufficient for formation of pure and mixed erythroid colonies whereas GM-CSF was required for granulocyte-monocytic colonies. When adherent and Leu-1+ cells were removed, or when in vitro differentiated blast cells were used as a source of progenitors, neither Ep or GM-CSF alone induced colony formation. In dishes supplemented with both growth factors, erythroid bursts were detected. Although the presence of GM- CSF alone did not induce formation of any colony or clusters, BFU-E were recorded when Ep was added 8 days later, suggesting that BFU-E could be maintained. Terminal maturation of the resulting erythroid bursts was delayed by 8 days. These results provide evidence that GM- CSF acts directly on early erythroid progenitors. Furthermore, they suggest that both Ep and GM-CSF are necessary to start the differentiation process.     

Treatment of compulsive behaviour in eating disorders with intermittent ketamine infusions

We have previously shown that eating disorders are a compulsive behaviour disease, characterized by frequent recall of anorexic thoughts. Evidence suggests that memory is a neocortical neuronal network, excitation of which involves the hippocampus, with recall occurring by re-excitement of the same specific network. Excitement of the hippocampus by glutamate-NMDA receptors, leading to long-term potentiation (LTP), can be blocked by ketamine. Continuous block of LTP prevents new memory formation but does not affect previous memories. Opioid antagonists prevent loss of consciousness with ketamine but do not prevent the block of LTP. We used infusions of 20 mg per hour ketamine for 10 h with 20 mg twice daily nalmefene as opioid antagonist to treat 15 patients with a long history of eating disorder, all of whom were chronic and resistant to several other forms of treatment. Nine (responders) showed prolonged remission when treated with two to nine ketamine infusions at intervals of 5 days to 3 weeks. Clinical response was associated with a significant decrease in Compulsion score: before ketamine, mean +/- SE was 44.0 +/- 2.5; after ketamine, 27.0 +/- 3.5 (t test, p = 0.0016). In six patients (non-responders) the score was: before ketamine, 42.8 +/- 3.7; after ketamine, 44.8 +/- 3.1. There was no significant response to at least five ketamine treatments, perhaps because the compulsive drive was re-established too soon after the infusion, or because the dose of opioid antagonist, nalmefene, was too low.      

Chemokine expression and leucocyte infiltration in Sjogren's syndrome

OBJECTIVE: To investigate the expression and source of chemokines in minor salivary gland biopsies (MSGs) in patients with Sjogren's syndrome (SS). METHODS: Immunohistochemical analysis was used to determine the pattern of chemokine expression in MSGs from patients with (n=6) and without (n=5) SS, as well as to examine the phenotype of both resident and infiltrating cells expressing chemokines. RESULTS: Significant differences in the number of infiltrating mononuclear (MN) cells in patients with and without SS were noted. Ductal epithelial cells of SS biopsies expressed significantly increased levels of macrophage inflammatory protein (MIP)-1alpha, MIP-1beta, interleukin-8 (IL-8) and RANTES (Regulated upon Activation, Normal T cell Expressed and Secreted). Biopsies from patients with SS showed that MIP-1beta was expressed by 51% of infiltrating cells, while 41% expressed MIP-1alpha, whereas 22 and 7% expressed RANTES and IL-8, respectively. CONCLUSION: Chemokines expressed by ductal epithelial cells may attract circulating leucocytes, in particular CD4+ T cells, towards the site of inflammation, thereby orchestrating the influx of MN cells characteristically seen in MSGs in SS. Chemokines may be induced directly by a putative triggering agent for SS, or secondary to the release of pro-inflammatory cytokines produced by epithelial cells. These findings further implicate epithelial cells as playing a major role in the pathogenesis of SS and implicate chemokines in the leucocyte recruitment in this setting.