Regulation of CFTR chloride channels by syntaxin and Munc18 isoforms

The cystic fibrosis gene encodes a cyclic AMP-gated chloride channel (CFTR) that mediates electrolyte transport across the luminal surfaces of a variety of epithelial cells. The molecular mechanisms that modulate CFTR activity in epithelial tissues are poorly understood. Here we show that CFTR is regulated by an epithelially expressed syntaxin (syntaxin 1A), a membrane protein that also modulates neurosecretion and calcium-channel gating in brain. Syntaxin 1A physically interacts with CFTR chloride channels and regulates CFTR-mediated currents both in Xenopus oocytes and in epithelial cells that normally express these proteins. The physical and functional interactions between syntaxin 1A and CFTR are blocked by a syntaxin-binding protein of the Munc18 protein family (also called n-Secl). Our results indicate that CFTR function in epithelial cells is regulated by an interplay between syntaxin and Munc18 isoforms.     

Gestational diabetes mellitus in teenage pregnancy: a case-control study

In a retrospective study, teenage Asian pregnancies with gestational diabetes managed over a 4-year period were compared with a group of age and parity matched controls (2 for each study case) to determine the incidence of gestational diabetes and its impact on the pregnancy outcome. The incidence of gestational diabetes in teenage pregnancy was 5.4% (33/611), and accounted for 1.4% of all the cases of gestational diabetes. There was no difference in the maternal anthropometric parameters or antenatal complications, but the study group had a higher incidence of postpartum haemorrhage (p = 0.010), greater amount of estimated blood loss at delivery (p = 0.016), a trend towards a higher incidence of large-for-gestational age infants, a higher incidence of admission to the neonatal unit (p = 0.024), mostly due to meconium-stained liquor for observation (p = 0.014), and a lower first minute Apgar score (p = 0.012). Our findings support the recommendation that in ethnic groups with a high prevalence of diabetes, universal as opposed to age-limited screening for gestational diabetes should be undertaken.     

The synthesis and enzymatic incorporation of sialic acid derivatives for use as tools to study the structure, activity, and inhibition of glycoproteins and other glycoconjugates

Methods have been developed for the enzymatic synthesis of complex carbohydrates and glycoproteins containing in the sialic acid moiety the heavy metal mercury or the transition-state analog phosphonate of the influenza C 9-O-acetyl-neuraminic acid esterase-catalyzed reaction. 5-Acetamido-3, 5-dideoxy-9-methylphosphono-beta-D-glycero-D-galacto-nonulopyra nosidonic acid (1), 5-acetamido-3,5-dideoxy-9-methylphosphono-2-propyl-alpha-D- glycero-D-galacto-nonulopyranosidonic acid triethylammonium salt (2), and 5-acetamido-9-thiomethylmercuric-3, 5,9-trideoxy-beta-D-glycero-D-galacto-nonulopyranosidonic acid (3) were synthesized. Compounds 1 and 2 are proposed transition state inhibitors of an esterase vital for the binding and infection of influenza C. Compound 3 was enzymatically incorporated into an oligosaccharide and a non-natural glycoprotein for use as an aid in the structure determination of these compounds by X-ray crystallography.     

Inability to establish ectopic endometrium in a natural killer cell-deficient murine model. Immunologic, histologic and histochemical assessment

OBJECTIVE: To investigate what effect natural killer (NK) cells have on the implantation of heterologous endometrial scrapings. STUDY DESIGN: Anti-asialo GM1 (AA-GM1) anti-sera have been shown to eliminate NK cell activity in various strains of rats and mice. Either AA-GM1 antibodies (+) or rabbit antiglobulin (-) was administered to beige mice (NK cell deficient) or beige control mice (not NK cell deficient of the same strain). The heterologous endometrial scrapings were prepared by scraping seven pairs of uterine horns from normal mice of the same strain. Beige and normal mice were then injected intraperitoneally every 3 days with the heterologous endometrial scraping and antibodies for a period of 50 days. The four experimental groups (n = 10 per group) can be summarized as being beige (+), beige (-), normal (+) and normal (-). RESULTS: There was no evidence of ectopic endometrial tissue in any of the four test groups by histologic examination or by using immunohistochemical staining techniques. Histologic evidence of an impaired immune response was clearly demonstrated in the beige mice receiving AA-GM1 antibodies. CONCLUSION: Using this model, a deficiency of NK cell activity did not appear to enhance the implantation of endometrial tissue on the abdominal peritoneum of mice.     

7-Oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridines as novel inhibitors of human eosinophil phosphodiesterase

High-throughput file screening against inhibition of human lung PDE4 led to the discovery of 3-ethyl-1-(4-fluorophenyl)-6-phenyl-7-oxo-4, 5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine (11) as a novel PDE4 inhibitor. Subsequent SAR development, using an eosinophil PDE assay, led to analogues up to 50-fold more potent than 11 with IC50 values of 0.03-1.6 microM. One such compound, CP-220,629 (22) (IC50 = 0.44 microM), was efficacious in the guinea pig aerosolized antigen induced airway obstruction assay (ED50 2.0 mg/kg, po) and demonstrated a significant reduction in eosinophil (55%), neutrophil (65%), and IL-1beta (82%) responses to antigen challenge in atopic monkeys (10 mg/kg, po).     

Back to the future: from knowledge management to the management of information and data

This paper argues for a return to fundamentals and for a balanced assessment of the contribution that Information Technology can make as we enter the new millennium. It argues that the field of Information Systems should no longer be distracted from its natural locus of concern and competence, or claim more than it can actually achieve. More specifically, and as a case in point, we eschew IT-enabled Knowledge Management, both in theory and in practice. We view Knowledge Management as the most recent in a long line of fads and fashions embraced by the Information Systems community that have little to offer. Rather, we argue for a refocusing of our attention back on the management ofdata, since IT processes data-notinformation and certainly notknowledge. In so doing, we develop a model that provides a tentative means of distinguishing between the terms. This model also forms the basis for on-going empirical research designed to test the efficacy of our argument in a number of case companies currently implementing ERP and Knowledge Management Systems.     

Trauma and pregnancy

The effects of macrophage stimulation with interferon-gamma (IFN-gamma) before or after infection on the intracellular growth of Mycobacterium avium complex (MAC) were investigated. Treatment of murine peritoneal macrophages before infection with IFN-gamma (50 U/ml) for 24 h and 48 h, but not for 72 h, was associated with 41% and 52% significant MAC growth inhibition, respectively. NG-monomethyl-L-arginine (NMA) did not affect the preinfection antimycobacterial activity of IFN-gamma, thus indicating that nitric oxide was not involved in this phenomenon. In contrast, treatment of macrophages with IFN-gamma (50 U/ml) for 24 h and 48 h after infection was ineffective, whereas treatment for 72 h caused some MAC growth promotion. The use of NMA suppressed the IFN-gamma-mediated MAC growth, suggesting that nitric oxide may affect postinfection microbicidal function of macrophages. These results suggest that activation of macrophages with IFN-gamma before or after infection may direct the course of the infection and that nitric oxide may be detrimental more than beneficial for MAC-infected macrophages.     

Asteroid hyalosis and vision loss after posterior capsulotomy

We describe the case of a 77-year-old man with asteroid hyalosis who had phacoemulsification and implantation of a plate-haptic intraocular lens (IOL). Intraoperatively, a tear occurred in the anterior capsule, and vision loss occurred 3 months after a neodymium:YAG posterior capsulotomy. Because of the asteroid hyalosis, a posteriorly dislocated IOL, which occurred after the capsulotomy, was difficult to diagnose. Careful retinoscopy established the aphakic condition of the eye, and the B-scan ultrasonography indicated the IOL's location.     

Transcranial Doppler ultrasound battery reliably identifies severe internal carotid artery stenosis

BACKGROUND: The clinical significance of plasma concentration of matrix metalloproteinase 9 (MMP-9) was investigated in patients with gastric cancer. METHODS: Plasma was obtained from 138 healthy individuals and 70 patients who underwent gastrectomy for gastric cancer at Aichi Cancer Centre between August 1994 and July 1995. Plasma concentrations of MMP-9 were measured using a one-step sandwich enzyme immunoassay employing monoclonal antibodies. RESULTS: Patients with gastric cancer had plasma higher concentrations of MMP-9 than normal subjects. Postoperative concentrations of MMP-9 were lower than preoperative levels. In addition to patients with advanced cancer, those with early gastric cancer also exhibited higher mean values of and positivity rates for MMP-9 than healthy individuals. Preoperative plasma MMP-9 concentration correlated closely with Union Internacional Contra la Cancrum tumour node metastasis (pTNM) stage, severity of T, N and M classification, and tumour size. CONCLUSION: Plasma MMP-9 concentration can be used for detection of primary or recurrent gastric cancer, and for estimation of tumour extent.