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Biomedical subjects

M Weber

Publications and source records attributed to M Weber.

At least 379 records · Page 21Linked to original sources
PubMed1996

Reasons for HIV antibody test refusal in a heterosexual sexually transmitted disease clinic population.

OBJECTIVE: To evaluate acceptance of confidential HIV antibody testing and reasons for test refusal among heterosexual clients of Los Angeles County sexually transmitted disease (STD) clinics. METHODS: From January 1993 through June 1994, all blood specimens routinely collected for syphilis serology were tested blindly for HIV antibody at seven STD clinics. Patients were counseled and offered a confidential HIV test. Rate of refusal of confidential testing and primary reason for test refusal were examined by demographic group and HIV serostatus, as determined in the blinded survey, for all heterosexual clients. RESULTS: Of 20,125 persons offered confidential testing, 35.6% refused the test. Test refusal was higher among men (38.7%) than women [31.1%; adjusted odds ratio (OR), 1.4; 95% confidence interval (CI), 1.3-1.4] and among blacks (38.6%) than whites (28.6%; adjusted OR, 1.7; 95% CI, 1.5-2.0). The most common reason for refusal was 'already know my HIV status' (40.6%), followed by 'don't want to know' (23.9%), and 'not at risk' (19.4%). Confidentiality concerns were cited as the primary reason for refusal by 2.2%. Among the 180 (0.9%) persons who tested positive in the blinded survey, 99 (55.0%) refused the confidential test. Of the 44 seropositive persons who refused the confidential test because they "already knew their HIV status', 29 (65.9%) reported their previous test to be negative. CONCLUSIONS: Efforts are needed to increase acceptance of confidential HIV testing in this heterosexual population and should (1) include a client-centered counseling approach that facilitates accurate self-assessment of risk and addresses the misperception that a prior negative test result implies an absence of risk, and (2) highlight the potential benefits of early intervention medical and psychosocial services.

AIDS-Related Opportunistic Infections↗
PubMed1996

Functional cerebral activity during regeneration from entorhinal lesions in the rat.

The consequences of an unilateral electrolytic entorhinal lesion on the functional activity in all major anatomically defined brain regions were evaluated in the rat. The 14C-2 deoxyglucose method served as a tool to quantify alterations of local cerebral glucose utilization (LCGU) ipsilateral and contralateral to the lesion at 4 days, 2 weeks, or 3 months after stereotaxic surgery. Apart from a few minor increases in the contralateral hemisphere, the predominant pattern consisted of reductions in the range of 10-40% in the ipsilateral hemisphere. Ipsilaterally, in extrahippocampal areas, LCGU had regained control levels at 2 weeks postlesion in contrast to hippocampal regions, where reductions were more pronounced than in other brain areas and partially persisted for up to 3 months. Interestingly, the termination zones of entorhinal fibers in the dentate gyrus did not regain control levels within 3 months. We conclude from the data that functional recovery of denervated primary target areas does not occur within 3 months after entorhinal lesions and that altered functional activity may be found beyond the primary target areas predominantly during the acute recovery period after the lesion. The data suggest that sprouting fibers do not reestablish a fully functional neuronal network during the recovery period.

Animals↗
PubMed1996

Production of interleukin-6 by human mast cells and basophilic cells.

Since mast cells and basophils are thought to play a central role in several types of cutaneous inflammatory and allergic reactions, and since interleukin-6 (IL-6) is an important mediator in these processes, we have studied the ability of the human mast cell line HMC-1, the human basophilic cell line KU812, and human skin mast cells to produce IL-6. All three cell types proved to be potent sources of this cytokine after appropriate stimulation. Transcription of IL-6 mRNA was first detectable 2 h after stimulation with the ester phorbol myristate acetate (PMA) and the calcium ionophore A23187 in both cell lines, as evidenced by semiquantitative reverse transcriptase polymerase chain reaction analysis. Whereas resting cells did not produce IL-6 protein, PMA/A23187-stimulated cells released immunoreactive and biologically active IL-6, as demonstrated and quantitated by enzyme-linked immunosorbent assay and by the use of TEPC 1033 cells, an IL-6-dependent murine plasmacytoma cell line. Stimulated KU812 cells secreted sevenfold more IL-6 (up to 15 ng/ml) than HMC-1 cells (up to 2.4 ng/ml). Immunoblotting of HMC-1- and KU812 cell-derived IL-6 revealed several IL-6 forms in the molecular weight range of 21 to 30 kDa. Immunoelectron microscopic studies of human skin biopsies provided evidence that unstimulated mast cells do not contain preformed IL-6 but accumulate IL-6 in cytoplasmic and extruded granules after IgE-dependent stimulation. These findings suggest that IL-6 secreted by human mast cells and basophils potentially contributes to allergic, other immunologically mediated and nonspecific inflammatory responses.

Basophils↗
PubMed1996

Sequence analysis of the 2nd intron revealed common sequence motifs providing the means for a unique sequencing based typing protocol of the HLA-A locus.

We here present a sequencing strategy for the HLA-A locus which is generally applicable for all HLA class I genes. The typing strategy is based on a group-specific amplification according to the serologically defined antigens. The PCR products carry the typing-relevant polymorphic regions of the 2nd and 3rd exon including the 2nd intron. The sequencing primers were designed to match conserved sequence motifs in the 2nd intron allowing a nested sequencing approach in 3' and 5' direction. These conserved regions were identified after sequence compilation of the 2nd intron of 143 clinical samples and 48 cell lines mostly from the 9th and 10th IHWC representing all serologically defined groups of alleles. This strategy allowed the use of only one 5' and one 3' sequencing primer regardless of the amplified allele. Therefore, it was possible to use dye terminator as well as dye primer sequencing chemistry. The amplification strategy allowed the separation of the haplotypes in almost all cases. Thus, an assignment of heterozygous positions requiring high sequencing quality was not necessary, allowing the application of Sequenase as well as TaqPolymerase as sequencing enzyme. Concerning the resolution of heterozygosity it is obvious that this approach is superior to a typing system using a single pair of generic primers followed by direct sequencing, since the latter technique is not capable of defining the cis/trans linkage of polymorphic sequences and, hence, cannot exclude the presence of unknown alleles.

Alleles↗
PubMed1996

Prevalence of neutralizing antibody to respiratory syncytial virus in sera from mothers and newborns residing in the Gambia and in The United States.

The prevalence of maternal respiratory syncytial virus (RSV)-neutralizing antibodies has been documented in developed countries, but there is little information from developing countries. We assessed the prevalence of RSV-neutralizing antibody in sera from Gambian women and their newborns and compared them with their American counterparts during a similar period. The geometric mean titers of maternal antibodies to RSV subgroup A in the two populations were similar, while titers of antibodies to RSV subgroup B in Gambian mothers were significantly higher (8.7 +/- 1.4 versus 7.9 +/- 1.3 [mean +/- standard deviation], P < 0.001). The titers of neutralizing antibody in newborns in both populations correlated with the neutralizing-antibody titers of their mothers. Thus, the status of neutralizing antibody to both major RSV subgroups was comparable among infants and mothers in a developing country, The Gambia, and those in a developed country, the United States.

Antibodies, Viral↗
PubMed1996

Immune response to hepatitis A virus capsid proteins after infection.

This study was undertaken to determine the immune response of humans to viral capsid polypeptides of hepatitis A virus (HAV) after natural infection, which is very important for vaccine development. Antiviral capsids in 73 serum samples from patients with acute and chronic HAV infections were analyzed by immunoblotting against individual HAV capsid polypeptides (VP1, VP2, VP3, and VP4) by using a cell culture-based HAV antigen. For reference, total anti-HAV immunoglobulin G (IgG) and anti-HAV IgM were also determined by radioimmunoassay. As a result, a dominant immune response against VP1 (98% IgG, 94% IgM) was found in the acute phase. However, many other sera also reacted with VP0 (88% IgG; 35% IgM) and VP3 (81% IgG and 29% IgM). In contrast to the acute phase, anti-VP1, anti-VP0, and anti-VP3, IgG antibodies against all three viral proteins (29, 29, and 73% respectively), especially those against VP3, were found years after onset of HAV disease and over long periods in the sera of hepatitis patients. These results suggest that antibodies for capsid polypeptides are present over an extended period in the sera of HAV-infected patients. They are likely of importance in maintaining long-term immunity.

Capsid↗
PubMed1996

Evaluation of Pyloriset Dry, a new rapid agglutination test for Helicobacter pylori antibody detection.

We evaluated the performance of a new latex agglutination test, Pyloriset Dry (Orion Diagnostica, Espoo, Finland), in the simultaneous detection of immunoglobulin G (IgG), IgA, and IgM antibodies to Helicobacter pylori and compared it with that of the Pyloristat test (BioWhittaker, Fontenay-sous-Bois, France), an enzyme-linked immunosorbent assay detecting IgG to H. pylori, for 96 untreated dyspeptic patients who had undergone gastroduodenal endoscopy. Infection was diagnosed in 56 cases by positive culture and/or positive Giemsa stain and rapid urease test (antral biopsies) and was associated with chronic gastritis in 52 patients. Forty noninfected patients did not have chronic gastritis. The sensitivity of Pyloriset Dry was 91.1%. The sensitivity of Pyloristat was 91.1 or 82.1%, depending on whether equivocal results were considered positive or negative, respectively. Both tests had a specificity of 87.5%. Their performances were not statistically different. Thus, Pyloriset Dry is an alternative to serological tests for adults, particularly when a small number of serum samples has to be tested.

Adult↗
PubMed1996

T cell involvement in glomerular injury.

The mechanisms of glomerular injury are multiple: one aspect is cell-mediated immunity in inflammatory kidney disease. Its fundamental role has been established within the last decade. T cells seem to play a regulatory role in the course of inflammation not only in the proliferative and crescentic disease, but also in nonproliferative glomerulonephritis. T cells become increasingly important in the pathogenesis of both glomerular and interstitial kidney diseases and seem to determine course and prognosis. The recent advances in understanding the mechanisms of T cell-mediated inflammation in kidney disease offer new approaches in therapy.

Inflammation↗
PubMed1996

Mos is required for MAP kinase activation and is involved in microtubule organization during meiotic maturation in the mouse.

Mos is normally expressed during oocyte meiotic maturation in vertebrates. However, apart from its cytostatic factor (CSF) activity, its precise role during mouse meiosis is still unknown. First, we analyzed its role as a MAP kinase kinase kinase. Mos is synthesized concomitantly with the activation of MAP kinase in mouse oocytes. Moreover, MAP kinase is not activated during meiosis in oocytes from mos -/- mice. This result implies that Mos is necessary for MAP kinase activation in mouse oocytes. Raf-1, another MAP kinase kinase kinase, is already present in immature oocytes, but does not seem to be active when MAP kinase is activated. Moreover, the absence of MAP kinase activation in mos -/- oocytes demonstrates that Raf-1 cannot compensate for the lack of Mos. These results suggest that Raf-1 is not involved in MAP kinase activation. Second, we analyzed the organization of the microtubules and chromosomes in oocytes from mos -/- mice. We observed that during the transition between two meiotic M-phases, the microtubules and chromosomes evolve towards an interphase-like state in mos -/- oocytes, while in the control mos +/- oocytes they remain in an M-phase configuration, as in the wild type. Moreover, after spontaneous activation, the majority of mos -/- oocytes are arrested for at least 10 hours in a third meiotic M-phase where they exhibit monopolar half-spindles. These observations present the first evidence, in intact oocytes, of a role for the Mos/.../MAP kinase cascade in the control of microtubule and chromatin organization during meiosis.

Animals↗
PubMed1996

Identification of 17 mutations in ten exons in the COL4A5 collagen gene, but no mutations found in four exons in COL4A6: a study of 250 patients with hematuria and suspected of having Alport syndrome.

Conditions for polymerase chain-reaction amplification of ten exon regions (Exons 3, 7, 11 through 13, and 15 through 19) of the collagen COL4A5 gene and four exon regions (Exons 2, and 12 through 14) of the COL4A6 gene were sequenced and established in this study. These Type IV collagen genes contain 51 and 48 exons, respectively. The sequences of these exons were determined in the two genes in 250 male patients with hematuria and suspected Alport syndrome. Seventeen mutations were found in nine of the ten exons studied in the COL4A5 gene in 17 patients, whereas no mutations were identified in COL4A6. One mutation was identical in two patients known to be unrelated. The results indicate that mutations in COL4A5 that leading to renal failure are more frequent than those involved in classic Alport syndrome, and also that mutations in COL4A6 are not likely to cause this disease. Furthermore, mutations in COL4A5 are distributed quite randomly and no "hot spots" were found.

Adolescent↗
PubMed1996

Monosialoganglioside GM1 reduces ischemia--reperfusion-induced injury in the rat retina.

PURPOSE: Gangliosides are normal components of cell membranes, contribute to structural rigidity and membrane function, and have been shown to protect against various insults to the brain. This study evaluates the effect of exogenously administered monosialoganglioside GM1 on retinal damage induced by transient retinal ischemia and reperfusion. METHODS: Retinal ischemia was induced unilaterally in Long Evans rats by increasing intraocular pressure to 160 mm Hg for 60 minutes. GM1 (30 mg/kg, intraperitoneally) or buffer controls were administered at 48 hours, and 15 minutes before ischemia, and survival time after ischemia was either 8 or 15 days. The degree of retinal damage was assessed by histopathologic study according to Hughes' quantification of ischemic damage. RESULTS: Retinal ischemia led to significant reductions in thickness and cell number, principally in the inner retinal layers (30% to 80%), and to a lesser extent in the outer retinal layers (18% to 42%). Pretreatment with intraperitoneally injected monosialoganglioside GM1 conferred significant protection against retinal ischemic damage either 8 or 15 days after ischemic survival time. After 8 days reperfusion, the ischemic-induced loss in overall retinal thickness was reduced by 70%, and those of the inner nuclear and plexiform layers were reduced by 77% and 44%, respectively. Ischemic-induced ganglion cell, inner nuclear, and outer nuclear layer cell density losses were reduced by 45%, 40%, and 57%, respectively. After 15 days of reperfusion, approximately the same statistically significant differences could be observed in comparison with the 15-day ischemic--reperfusion group. CONCLUSIONS: Monosialoganglioside GM1 protects the rat retina from pressure-induced ischemic injury when administered intraperitoneally 2 days before insult. This protection afforded by GM1 can be observed even after 8 days or 15 days of reperfusion.

Animals↗
PubMed1996

IGF-I receptor signalling: lessons from the somatotroph.

Insulin-like growth factor 1 (IGF-I) is a major feedback regulator of pituitary GH secretion, with defined actions occurring at both the hypothalamus and pituitary. The IGF-I gene is expressed in the anterior pituitary in a GH-dependent manner thus providing for both endocrine-as well as autocrine-mediated GH regulation. In turn, IGF-I selectively and specifically inhibits GH gene transcription and secretion, its attenuating effects on nascent GH mRNA synthesis being demonstrable within 1 h. Binding of IGF-I to its pituitary cell surface receptor is followed by rapid activation of the intrinsic tyrosine kinase activity of the receptor beta-subunit and phosphorylation of insulin receptor substrate 1 (IRS-1). Structure-function studies of the human IGF-I receptor were performed in stable, GH-secreting transfectants expressing either the cDNA encoding the wild-type (WT) human IGF receptor and exhibiting enhanced IGF-I responsiveness, or cDNAs encoding IGF-I receptor mutants and a truncated, kinase-deficient receptor (952STOP). 950Tyr situated on the submembrane receptor domain was found to be critical for transducing the IGF-I signal to the GH gene. IGF-I failed to suppress GH secretion by signalling endogenous rat IGF-I receptors when hybrid receptors were formed with kinase-deficient human receptors and rat hemi-receptors. This dominant negative effect on hormone secretion was also evidenced when mitogenic IGF-I signals were blocked in vitro and in vivo by these hybrid receptors. Using similar doses of IGF-I, the IGF-I receptor cell transfectants also demonstrated ligand-dependent activation of ERKs in pituitary cells. In conclusion, the pituitary IGF-I receptor mediates the negative feedback regulation of GH. Thus, IGF-I receptor mass may determine GH responses to malnutrition, pregnancy, and refeeding. IGF-I receptor mutations may also prove useful to abrogate the growth of IGF-I-dependent tumors. These structure-function studies of the human IGF-I receptor provide mechanistic insights into both metabolic control of the GH axis, as well as target tissue proliferative characteristics.

Animals↗
PubMed1996

[In vitro susceptibility of Pasteurella and related bacteria to five orally administered antibiotics].

Tetracyclines and beta-lactam antibiotics are usually recommended for the treatment of pasteurellosis following bite wounds. However other oral antimicrobial agents could be proposed. In vitro susceptibility of 94 Pasteurella strains [P. multocida (79), P. stomatis (11), P. dagmatis (2), P. canis (1), P. "SP" (1)], 20 group EF-4 strains and 28 Neisseria weaveri strains (formerly group M-5), that are bacteria often isolated after animal-inflicted wounds, was studied towards five antibiotics: clarithromycin, azithromycin, pristinamycin, trimethoprim-sulfamethoxazole and ciprofloxacin. MICs were determined by the agar dilution method using HTM medium (Oxoïd), and for pristinamycin using both HTM and Mueller-Hinton agar supplemented with 5% horse blood (BMH). Most of Pasteurella isolates showed intermediate susceptibility to clarithromycin (63%) and to azithromycin (90.5%) with lower MICs for azithromycin. Fourty-two and thirty-two percent of Pasteurella strains were susceptible to pristinamycin respectively on HTM and on BMH. EF-4 and N. weaveri were more sensitive than Pasteurella to macrolides and to pristinamycin. Trimethoprim-sulfamethoxazole was active against all isolates, with higher MICs for EF-4 and N. weaveri. On all strains tested, the lowest MICs were observed for ciprofloxacin. Trimethoprim-sulfamethoxazole and ciprofloxacin could be proposed as a therapeutic alternative in case of pasteurellosis following animal bites.

Administration, Oral↗
PubMed1996

[Bleomycin in Kaposi disease in a patient with heart transplantation].

INTRODUCTION: Kaposi's disease is increasingly frequent in transplant recipients. The therapeutic approach in heart transplantation is not fully established. CASE REPORT: A 61-year-old male transplant recipient (June 1992) presented Kaposi's disease on the legs. Immunosuppressive therapy was reduced, cyclosporin by 20 p. 100, withdrawal of azathioprine and 40 p. 100 reduction in prednisone was insufficient to control the disease. Due to the extension of the lesions and the major functional handicap, bleomycin was given and led to complete regression of the lesions within 6 months. DISCUSSION: This case illustrates the difficult therapeutic situation encountered in heart transplant recipients. The situation may be life-threatening with organ rejection. The first step is to reduce immunosuppressive therapy. If this is insufficient or the Kaposi is particularly aggressive, bleomycin may be used. The efficacy of bleomycin observed in our case requires confirmation in multicenter studies.

Antibiotics, Antineoplastic↗