利福昔明：有效维持肝性脑病缓解

肝性脑病是的一种慢性消耗性的肝硬化并发症。利福昔明（rifaximin）,一种口服的抗生素,治疗急性肝性脑病的疗效已有报道,但其预防此病疗效未知。     

Cellular orientation of atrial natriuretic peptide in the human brain

Many peptide hormones and neurotransmitters have been detected in human neuronal tissue. The localisation of atrial natriuretic peptide (ANP) in the human brain was considered to be both interesting and relevant to the understanding of neurochemistry and brain water–electrolyte homeostasis. This vasoactive peptide hormone has been localised in rat and frog neuronal tissue. In the present study, we report the immunohistochemical localisation of ANP in autopsy samples of human brain tissue employing the avidin–biotin–peroxidase complex technique, using an antibody against a 28 amino acid fragment of human ANP. The most intense staining of immunoreactive ANP was detected in the neurones of preoptic, supraoptic and paraventricular nuclei of the hypothalamus, epithelial cells of the choroid plexus and ventricular ependymal lining cells. Immunoreactive neurones were also observed in the median eminence, lamina terminalis, infundibular and ventromedial nuclei of the hypothalamus, and in neurones of the brain stem, thalamic neurones and some neurones of the caudate nucleus. The network of ANP cells in numerous hypothalamic centres may regulate the salt and water balance in the body through a hypothalamic neuro-endocrine control system. ANP in the brain may also modulate cerebral fluid homeostasis by autocrine and paracrine mechanisms.     

Human chorionic gonadotrophin-beta gene sequences in women with disorders of HCG production

Women with recurrent abortion, primary unexplained infertility, and gestational trophoblastic neoplasia (GTN) manifest disordered human chorionic gonadotrophin (HCG) secretion. Mutations in the HCG beta/luteinizing hormone (LH) beta gene complex could cause aberrant HCG production in these disorders. The purpose of this study was to determine whether HCG beta gene deletions occur in women with recurrent abortion or primary unexplained infertility, and whether HCG beta gene duplications are present in women with GTN. DNA was extracted from 10 patients with unexplained recurrent abortion, 10 patients with unexplained primary infertility, 12 patients with GTN, three partners of women with GTN, and 30 controls. Southern blots were constructed and hybridized with DNA probes for HCG beta-5 and the LH beta gene. No gene deletions were identified in patients with recurrent abortion or primary unexplained infertility. Likewise, no gene duplications were identified in women with GTN. A previously described Mbol restriction fragment length polymorphism (RFLP) was identified in both patients and controls. A new Pstl RFLP was also characterized, but was present in patients and controls. Deletion/duplication mutations in the HCG beta/LH beta gene complex do not appear to be common causes of aberrant HCG production in humans with these disorders.      

Reduced Ia-afferent-mediated Hoffman reflex in streptozotocin-induced diabetic rats

Familial amyloidotic polyneuropathy (FAP) is a late-onset inherited disease characterized by the deposition of amyloid fibrils. FAP is associated with mutations on the transthyretin (TTR) gene. A monoclonal antibody, MAb 39-44, reacting with high molecular weight aggregates of TTR but not with tetrameric TTR has recently been generated and characterized. This antibody recognizes a cryptic epitope that is expressed in isolated recombinant amyloidogenic mutants and in ex vivo amyloid. In the present work we show that this amyloid-specific antibody specifically recognizes in a direct enzyme-linked immunoassay (ELISA) plasma TTR from carriers of various mutations associated with FAP, both in asymptomatic individuals and in patients. In contrast, it does not react with plasma TTR from healthy individuals or that from carriers of nonpathogenic mutations. Using the ELISA developed in this study we identified three different TTR mutations in Portuguese patients with neuropathy of unknown cause, later shown to have amyloid tissue deposition. This antibody recognizes conformations that express cryptic epitopes shared by amyloidogenic TTR variants associated with FAP, not present among nonpathogenic TTR molecules. This antibody will contribute to further identify and characterize intermediates of the amyloidogenic cascade. In addition, it will also be useful for screening amyloidogenic TTR mutations in patients with neuropathy of unknown cause, prior to precise molecular diagnosis using protein and/or DNA analysis.     

幽门螺杆菌感染患者血清可溶性幽门螺杆菌抗原及其 IgG,IgA型免疫复合物测定

目的　测定血清可溶性幽门螺杆菌抗原(S-Hp)和其特异性免疫复合物(Hp-IC)并评价它们对幽门螺杆菌感染诊断的意义.方法　采用双抗体夹心式酶免疫测定法.结果　66例Hp感染患者血清S-Hp阳性率90.91%,显著高于28例阴性对照组阳性率0%,P<0.001.S-Hp含量与Hp感染菌量呈成比,但43例Hp阳性患者治疗前后S-Hp 含量无显著改变（P>0.05）.血清 S-Hp抗原均以IgG和/或IgA型特异性免疫复合物形式存在,Hp-IC对Hp感染诊断特异性85.71%,敏感性77.23%. 结论　S-Hp和Hp-IC测定可用于临床Hp感染诊断,对阐明Hp致病机理有重要意义.     

Hydrolysis of kininogens by degranulated human neutrophils and analysis of bradykinin as chemotactic factor for cells isolated from peripheral blood

Human neutrophils play a pivotal role in acute inflammation including the regulation of vascular permeability. We have examined the capacity of neutrophil enzymes to hydrolyse human kininogens in vitro and have also explored the potentiality of bradykinin to induce chemotactic migration on neutrophils isolated from peripheral blood. Isolated neutrophils were stimulated with either f-Met-Leu-Phe, thrombin or silica particles coated with human IgG. Neutrophil enzymes obtained by degranulation produced, after 45 min of incubation with high and low molecular weight kininogens, the complete transformation of both proteins in polypeptides ranging from 20 to less than 10 kDa in molecular mass. Supernatants obtained from nonstimulated neutrophils did not modify the molecular size of kininogens. The assay used to test the chemoattractant capacity of synthetic bradykinin on human neutrophils showed that this peptide has no chemotactic activity on cells isolated from healthy subjects. Our results show that stimulation of human neutrophils with opsonized silica, thrombin and the chemotactic peptide f-Met-Leu-Phe induces release of kininogen-hydrolyzing enzymes from these cells.     

Endothelin-1 and endothelin receptor status in kidney transplants undergoing acute rejection

Endothelin-1 (ET-1) is a potent vasoconstrictor with vasopressor and mitogenic effects. Blood samples were collected from 21 renal transplant patients undergoing acute rejection at the time of diagnostic kidney biopsy: there were 20 men and one woman, mean age 35.6 years. All patients were on triple immunosuppressive therapy with cyclosporine A, azathioprine and methylprednisolone. Twenty living kidney donors pre-uninephrectomy (11 men and nine women, mean age 34 years) served as controls. Control kidney was obtained from fresh autopsy material and normal kidney tissue from nephrectomies for malignancy. Mean plasma ET-1 was significantly increased at 1.56 +/- 0.2 pg ml(-1) during acute rejection compared to 0.74 +/- 0.06 pg ml(-1) in donors (p = 0.0009 unpaired t-test). ET(A) receptor immunolabelling was visualised in distal tubules and collecting ducts with minimal labelling in the glomeruli and blood vessels of control kidney tissue ET(A) receptor labelling was similar in kidney biopsies with acute rejection. ET(B) receptor immunolabelling was significantly increased in glomeruli (p = 0.002) and decreased in distal tubules (p = 0.004) in kidneys with acute rejection compared to control kidney tissue. While these findings may account for the oedema and hypertension observed during acute rejection, the exact significance needs to be studied further.     

Diabetes insipidus, diabetes mellitus, optic atrophy and deafness (DIDMOAD) caused by mutations in a novel gene (wolframin) coding for a predicted transmembrane protein

Wolfram syndrome is an autosomal recessive disorder characterized by juvenile diabetes mellitus, diabetes insipidus, optic atrophy and a number of neurological symptoms including deafness, ataxia and peripheral neuropathy. Mitochondrial DNA deletions have been described in a few patients and a locus has been mapped to 4p16 by linkage analysis. Susceptibility to psychiatric illness is reported to be high in affected individuals and increased in heterozygous carriers in Wolfram syndrome families. We screened four candidate genes in a refined critical linkage interval covered by an unfinished genomic sequence of 600 kb. One of these genes, subsequently named wolframin, codes for a predicted transmembrane protein which was expressed in various tissues, including brain and pancreas, and carried loss-of- function mutations in both alleles in Wolfram syndrome patients.