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Biomedical subjects

J Weber

Publications and source records attributed to J Weber.

At least 271 records · Page 15Linked to original sources
PubMed1995

[Liver transplantation in familial amyloidosis].

A 32-year-old Portuguese with hereditary amyloidosis had been suffering from polyneuropathy for 9 years. It began insidiously with polyneuropathic complaints in the legs which gradually got worse over the years and progressively impaired walking. He also had signs of autonomic neuropathy with severe orthostatic dysregulation, abnormal micturition and impotence. His general state had deteriorated during the last 3 years with a weight loss of 18 kg, due to treatment-resistant diarrhoea. As there is so far no known cure of the amyloidosis, which usually ends fatally from cachexia after an average of 10 years, liver transplantation was performed to reduce amyloid production and thus favourably influence the course of the disease. The patient's general condition has remained stable 32 months after the transplantation.

Adult↗
PubMed1995

Production and analysis of transgenic mice with ectopic expression of parvalbumin.

Transgenic mice expressing rat parvalbumin under the control of the human metallothionein IIA (MTII A), SV-40 early, and neuron-specific enolase (NSE) promoters were produced. Ectopic expression was analyzed by RNA polymerase chain reaction and RNase protection in combination with immunohistochemistry. From a total of 25 transgenic lines 18 were found to express the transgene. Expression strength and tissue specificity were dependent upon the promoter used and varied considerably among animal lines produced with the same construct. Highest constitutive MT IIA-driven expression was found in lung, liver, heart, and kidney, as well as in brain, and lower amounts of transgene expression were found in spleen, testis, and muscle. Immunohistochemistry of tissue sections of metallothionein-parvalbumin transgenic strain 29 in the non-induced state revealed that ectopic PV mRNA is translated into protein. Short-term induction of the MT IIA promoter by CdSO4 or CdCl2 leads to a shift in tissue specificity and does not increase ectopic expression in tissues where the transgene is active in the noninduced state. As expected the NSE promoter showed highest activity in brain. However, NSE-driven expression could also be detected to various degrees in all investigated tissues. SV-40-dependent PV expression showed no tissue preference and varied considerably among different strains. Except for the observation that the SV-40-PV construct showed lower yields in transgenic production and reduced numbers of positive offspring no obvious impairment of growth or behavior as a consequence of transgenic PV expression could be detected.

Animals↗
PubMed1995

Limits of two-dimensional planimetry in the follow-up of glaucomatous optic discs.

BACKGROUND: To test the intra-observer, intra-photographic variability of two-dimensional measurements of the optic nerve head we used computer-assisted planimetry. Depending on the variability, we calculated the confidence intervals of the optic disc parameters which could be indicative of glaucomatous damage on follow-up. METHODS: Slides of the optic disc were taken from 10 eyes of 10 patients (n = 6 open angle glaucoma, n = 4 ocular hypertension) using a Zeiss fundus camera. All eyes were evaluated 10 times within a random sequence on 10 different days. We obtained the absolute values of the disc radii and the cup radii in steps of 1, 10, and 45 deg in predefined quadrants and the mean radii. RESULTS: The confidence interval of the cup radius on follow-up, depending on sector size, ranged between 62 and 38% for small cups (radius 0.2 mm) and between 12 and 7% for large cups (radius 0.8 mm). The confidence intervals of the cup/disc ratio distinguishable from the disc boundary, depending on sector size, ranged between 0.81 and 0.89 for small discs (radius 0.5 mm) and from 0.90 to 0.94 for large discs (radius 1.0 mm). The confidence intervals of the cup/disc ratio indicating an increase on the cup radius in follow-up, distinguishable from the boundary of the disc, ranged, depending on sector size, between 0.57 and 0.75 for small discs (radius 0.5 mm) and from 0.81 to 0.89 for large discs (radius 1.0 mm). CONCLUSION: The smaller the disc, the more difficult is the detection of glaucomatous damage, and the larger the cup, the more difficult is the detection of progression of glaucomatous damage.

Female↗
PubMed1995

Immunogenicity of the yeast recombinant p17/p24:Ty virus-like particles (p24-VLP) in healthy volunteers.

In this Phase I study, immunisation with the yeast-derived p24 virus-like particles Ty p24-VLP (3 x 100 or 3 x 500 micrograms subcutaneously) in 16 healthy male subjects elicited p24 antibody responses in 4 of 16 (25%) subjects. After a fourth, intramuscular, immunisation (500 micrograms), p24 antibody responses were detected in 11 of 15 (70%) subjects. In addition to p24 antibody responses, T cell proliferative responses were also observed, although no HLA restricted p24-specific cytotoxic T cell responses were detected. The results demonstrate that Ty p24-VLP is immunogenic and well-tolerated in healthy male subjects.

AIDS Vaccines↗
PubMed1995

In vitro effects of low-calcium peritoneal dialysis solutions on peritoneal macrophage functions.

The use of low-calcium peritoneal dialysis solutions (PDS) for continuous ambulatory peritoneal dialysis is becoming widely accepted to reduce the risk of serum hypercalcemia in patients taking calcium salts as phosphate binders. We compared the in vitro effects of low-calcium PDS (1,000 mumol calcium/L), calcium-free buffer, and buffers with increasing calcium concentrations (500 to 5,000 mumol calcium/L) on peritoneal macrophage (PMO) functions. Peritoneal macrophages isolated from 10 continuous ambulatory peritoneal dialysis patients were incubated in the different solutions and tested for phagocytic and killing capacity, superoxide generation (cytochrome-C reduction and lucigenin-enhanced chemiluminescence), and the rate of myeloperoxidase-dependent oxidative metabolism (luminol-enhanced chemiluminescence). All functions of the PMO incubated in calcium-free buffer were significantly suppressed compared with the PMO incubated in calcium buffers. No dose-dependent increase of a single PMO function could be found after incubating the PMO in calcium buffer with increasing concentrations. Incubation of PMO in otherwise identical PDS containing 1,000, 1,450, or 1,750 mumol calcium/L did not result in significantly different PMO functions. Acidic PDS (pH 5.3 to 5.5) suppressed all measured PMO functions as compared with their neutralized counterparts (pH 7.4), irrespective of the calcium concentration. Results of our in vitro study show that low-calcium PDS does not suppress PMO functions any more than standard-calcium PDS (1,750 mumol calcium/L) does.

Acridines↗
PubMed1995

Gene-based sequence-tagged-sites (STSs) as the basis for a human gene map.

Using our data set of 3,143 single pass sequences from human brain cDNA libraries, we have developed a strategy in which gene-based sequence-tagged-sites (STSs), derived from 3'untranslated regions of human cDNAs, are rapidly assigned to megabase-insert yeast artificial chromosomes and somatic cell hybrids to generate regional gene mapping data. Employing this approach, we have mapped 318 cDNAs, representing 308 human genes. Ninety-two of these mapped to regions implicated in human genetic diseases, identifying them as candidate genes. Extension of this strategy has the potential to result in virtually every human gene having, at its 3' end, its own associated STS, with each STS in turn specifying both a corresponding genomic clone and a specific regional location in the genome.

Animals↗
PubMed1995

Evaluation of safety and efficacy of 3TC (lamivudine) in patients with asymptomatic or mildly symptomatic human immunodeficiency virus infection: a phase I/II study.

In a phase I/II study, 7 levels of 3TC therapy (from 0.5 to 20.0 mg/kg/day) were studied in 104 asymptomatic and mildly symptomatic human immunodeficiency virus-infected patients with CD4 cell counts < or = 400 x 10(6)/L. Mild and transient episodes of diarrhea, headache, fatigue, nausea, and abdominal pain were the most frequent events reported. No dose-limiting toxicities were observed. Small and transient increases in CD4 cell counts were detected during the first 4 weeks of treatment. These were followed by progressive declines during prolonged therapy. Sustained decreases in beta 2-microglobulin, neopterin, and p24 antigen levels were seen over the 52-week study. There was no consistent dose-response correlation for any surrogate marker. Penetration of 3TC into cerebrospinal fluid (CSF) was in the same range as reported for ddC and ddI; the mean CSF-to-serum ratio was 0.06. These findings indicate that 3TC exhibits an excellent safety profile and has antiretroviral activity at the dosages studied.

Adult↗
PubMed1995

Vitamin D metabolites modulate osteoblast activity by Ca+2 influx-independent genomic and Ca+2 influx-dependent nongenomic pathways.

Previous studies have shown that 1,25(OH)2D3 activates multiple signaling pathways in osteoblasts, including rapid nongenomic and long-term genomic pathways. Genomic pathways are mediated by the vitamin D receptor (VDR), a member of the steroid receptor superfamily, and involve transcriptional regulation of target genes. Nongenomic pathways involve lipid turnover, activation of Ca+2 channels and elevation of intracellular Ca+2, all of which occur within seconds after addition of seco-steroid. The interaction of other physiological metabolites of vitamin D, such as 24,25(OH)2D3, with target cells such as osteoblasts is much less clear. We have used a combination of electrophysiological, biochemical, molecular and ion tracer studies to dissect the physiological responses of osteoblast-like osteosarcoma cells (ROS 17/2.8) to 1,25(OH)2D3 and related metabolites. We conclude the following: 1) the structural requirements for activation of genomic vs. nongenomic pathways by seco-steroid are distinct and likely to involve separate receptors; 2) activation of rapid nongenomic pathways is independent of the long-term regulation of target genes; and 3) 1,25(OH)2D3 and 24,25(OH)2D3 interact at the level of the plasma membrane to regulate Ca+2 permeability. Present studies are aimed toward the understanding of the role of both genomic and nongenomic pathways in osteoblast physiology.

Calcitriol↗
PubMed1995

Phase I/II study of 3TC (lamivudine) in HIV-positive, asymptomatic or mild AIDS-related complex patients: sustained reduction in viral markers. The Lamivudine European HIV Working Group.

OBJECTIVE: To evaluate the efficacy of 3TC (lamivudine), a synthetic nucleoside analogue that inhibits HIV reverse transcriptase in vitro, as treatment for HIV-positive, asymptomatic or mild AIDS-related complex patients. DESIGN: Open-label, multinational and multicentre, non-comparative, escalating dose study. METHODS: Patients who meet the selection criteria (n = 104) were enrolled in three European countries. Ten to 15 patients were included at each of the six dose levels of 3TC (0.5, 1.0, 2.0, 4.0, 8.0, 12.0 and 20.0 mg/kg daily in two divided doses every 12 h). Virological parameters--immune-complex dissociation (ICD) assay for HIV p24 antigenaemia, plasma HIV RNA load, whole blood assay and cellular viraemia--were evaluated at weeks 0, 4, 12 and 24. RESULTS: Sustained reductions in HIV RNA load and in ICD p24 antigen levels were observed and maintained over the 12-week assessment period. Greater reductions were noted at higher doses but this trend did not reach statistical significance. In 38 patients, reductions of cell viraemia were significantly greater at 4 weeks for patients treated at higher doses of 3TC. CONCLUSION: These virological data show that 3TC is a potent inhibitor of HIV replication in HIV-positive, asymptomatic or mild ARC patients as assessed by ICD p24 antigenaemia, plasma HIV RNA load and cell viraemia.

AIDS-Related Complex↗
PubMed1995

Biological dosimetry after extensive diagnostic x-ray exposure.

The yield of chromosome aberrations (dicentric and ring chromosomes) was determined for five patients who had been extensively exposed to diagnostic x rays. Remarkably high aberration yields were obtained for each of them leading to correspondingly high equivalent whole body doses ("biological dosimetry"). The contribution of iodized contrast media and computing tomography to the biologically estimated doses is discussed.

Adult↗
PubMed1995

Naturally occurring variants of human T-cell leukemia virus type I Tax protein impair its recognition by cytotoxic T lymphocytes and the transactivation function of Tax.

There is a high degree of intraisolate sequence heterogeneity in the tax gene of human T-cell leukemia virus type I (HTLV-I), although the sequence variation between patients is small compared with that of human immunodeficiency virus type 1. In the present study, we investigated whether naturally occurring amino acid substitutions changed the properties of the Tax protein in two respects: first, recognition of the protein by cytotoxic T lymphocytes (CTL), and second, the ability of the Tax protein to transactivate various promoters. We found that (i) all of the observed amino acid substitutions that occur in known CTL epitopes abolished the recognition of the synthetic peptide representing the respective epitope; (ii) these substitutions occurred significantly more frequently in subjects carrying HLA-A2; and (iii) most of the amino acid substitutions severely reduced the ability of Tax protein to transactivate three promoters: the HTLV-I long terminal repeat, the c-fos promoter, and the interleukin-2 receptor alpha chain promoter.

Amino Acid Sequence↗
PubMed1995

Effects of the German 1993 health reform law upon primary care practitioners' individual performance: results from an empirical study in sentinel practices.

An empirical study in Lower Saxony aimed to investigate any changes in primary care physicians' diagnostic and therapeutic strategies as a result of Germany's 1993 health reform act (known as the Gesundheitsstruktur Gesetz or GSG), which included the countrywide implementation of a strict drug budget. A sentinel network consisting of a 37% sample of 350 randomly selected doctors (n = 130, GPs, general internists) was established in Lower Saxony. Four cross sectional surveys, each focussing on one group of health problems, were carried out during 1993. These aimed to show whether sentinel practice networks are suitable for reporting physicians' attitudes towards health care cost containment policies and, secondly, changes in physicians' quantitative and qualitative assessments of the 1993 reform act during its first year of implementation. Participating physicians reported patient consultations (n = 3728). Standardised questionnaires ascertained sociodemographic variables and major reasons for the patients' visit. Data on the diagnoses associated with the patient's main reason for the consultation, the doctor's assessment of the severity of the problem, and diagnostic and treatment strategies were also recorded. The questionnaire focussed on changes in therapy made by the physician together with the reasons for these changes. A number of treatment changes made with regard to cost containment were recorded. During the course of 1993 a decrease in reported changes in treatment was noticed. As expected, some doctors recorded a reduction in successful outcomes of treatment and ascribed this to the reform act. Differences between the four surveys with regard to the influence of the health reform act on the frequency of changes in treatment and the physicians' expectations cannot be explained sufficiently by the physicians' adaptation to the cost containment policies within the year.

Adult↗
PubMed1995

Novel tools for the study of development, migration and turnover of nematocytes (cnidarian stinging cells).

The rhodamine derivatives tetramethyl-rhodamine-5/6-maleimide (TROMI) and tetramethyl-rhodamine-6-isothiocyanate (TRITC) were allowed to react with living Hydra vulgaris. The two fluorescent dyes stain the polyps to different degrees, apparently without impairing their viability and behaviour. Concerning nematocytes, TROMI preferentially couples to cytoskeletal elements only of mounted nematocytes whereas TRITC selectively reacts with structural components of cysts of late nematoblasts, which thereafter develop apparently normally into mature nematocytes. Hence TROMI-labelling indicates that nematocytes are mounted and ready for discharge; TRITC-labelling can be used as a tool to investigate the final maturation, migration and installation of nematocytes in Hydra. Together with a new non-fixative method to dissociate Hydra polyps into single, identifiable cells, the two labelling methods allow direct quantitative dynamic studies of nematocyte turnover and open new possibilities of investigating the regulation and the mechanisms of nematocyte supply and migration.

Animals↗