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Biomedical subjects

R Peters

Publications and source records attributed to R Peters.

At least 109 records · Page 6Linked to original sources
PubMed1998

The Tight skin mouse: demonstration of mutant fibrillin-1 production and assembly into abnormal microfibrils.

Mice carrying the Tight skin (Tsk) mutation harbor a genomic duplication within the fibrillin-1 (Fbn 1) gene that results in a larger than normal in-frame Fbn 1 transcript. In this study, the consequences of the Tsk mutation for fibrillin-containing microfibrils have been examined. Dermal fibroblasts from Tsk/+ mice synthesized and secreted both normal fibrillin (approximately 330 kD) and the mutant oversized Tsk fibrillin-1 (approximately 450 kD) in comparable amounts, and Tsk fibrillin-1 was stably incorporated into cell layers. Immunohistochemical and ultrastructural analyses of normal and Tsk/+ mouse skin highlighted differences in the gross organization and distribution of microfibrillar arrays. Rotary shadowing of high Mr preparations from Tsk/+ skin demonstrated the presence of abundant beaded microfibrils. Some of these had normal morphology and periodicity, but others were distinguished by diffuse interbeads, longer periodicity, and tendency to aggregate. The presence of a structurally abnormal population of microfibrils in Tsk/+ skin was unequivocally demonstrated after calcium chelation and in denaturating conditions. Scanning transmission electron microscopy highlighted the presence of more mass in Tsk/+ skin microfibrils than in normal mice skin microfibrils. These data indicate that Tsk fibrillin-1 polymerizes and becomes incorporated into a discrete population of beaded microfibrils with altered molecular organization.

Animals↗
PubMed1998

Lactamase live!

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Cephalosporins↗
PubMed1998

Droplet discovery.

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Carrier Proteins↗
PubMed1998

Steady-state pharmacokinetics of zonisamide, an antiepileptic agent for treatment of refractory complex partial seizures.

A 56-day pharmacokinetic study of zonisamide was conducted in 24 healthy volunteers. Steady state was achieved in 29 days including two dose escalations, and in an average of 15 days from the last dose adjustment. Twice-daily administration of 200 mg every 12 hours produced a 14% serum level fluctuation at steady state. After once-daily administration of 400 mg, a 27% serum level fluctuation was observed. The terminal-phase half-life after the last dose was 63 to 69 hours, which is consistent with the half-life of 52 to 60 hours found in single-dose studies. This result demonstrates that zonisamide is not an autoinducer. Serum oral clearance of 0.60 to 0.71 L/hr (0.121-0.132 mL/min/kg) was similar to that observed in other multiple-dose studies.

Anticonvulsants↗
PubMed1998

Chronic tophaceous gout in the elderly.

Gout in the elderly seems to represent a special subgroup. The presentation is often atypical and drug treatment poses special difficulties. We present two elderly patients with large subcutaneous tophi leading to grotesque deformities. Their clinical features, risk factors, diagnosis and treatment are discussed. Although the appearance and radiographic changes caused by tophi are characteristic, the definitive diagnosis of tophaceous gout is made by aspiration and crystal analysis, as is illustrated by colour photographs.

Age Factors↗
PubMed1998

Extensive phenotypic analysis of CD34 subsets in successive collections of mobilized peripheral blood progenitors.

The transplantation of mobilized progenitor cells after high-dose chemotherapy shortens haemopoietic engraftment. CD34 cell subsets were examined in 20 consecutive mobilized progenitor cell collections obtained from patients with solid tumours that had not been previously treated. The analysis of CD34 cells was based on the expression of intracellular antigens, surface antigens including CD38, and cell size using multi-dimensional flow cytometry. We also correlated the numbers of stem cell subsets reinfused to haemopoietic recovery. The majority of CD34+ cells expressed CD13 and CD33. A significant proportion was cytoplasmic myeloperoxidase (cMPO) positive. CD34+ MPO+ cells increased significantly in late collections. MPO expression was related to cell size. Cells expressing CD13 also increased in late collections in parallel to CFU-GM count. Small subpopulations of CD34+ CD38+ were committed to B cells, T cells and erythroid cell lineages. A small population expressing the megakaryocytic antigen had a small size and were predominantly CD38-. A minor subpopulation expressed stem cells antigens. These were significantly higher in late collections (CD34+ Thy-1+ and CD34+ CD33-). After mobilization, patients received three cycles of intensive chemotherapy followed by reinfusion of mobilized progenitors (5.45 x 10(6)/kg CD34+ cells, range 3.4-11.88). The numbers of reinfused CD34 cells or the individual subsets did not influence recovery of leucocytes (9 d) or platelets (9 d). In conclusion, the numbers of stem cells and their subsets differed between collections and, in unpretreated patients receiving intensive chemotherapy, there was no delayed engraftment when sufficient numbers of stem cells were reinfused. The recovery period was short and not correlated to any stem cell subsets.

Adult↗
PubMed1998

An optical method for recording the activity of single transporters in membrane patches.

We have previously introduced an optical technique for recording the transport of fluorescent substrates by single membrane transporters. Referred to as optical single-transporter recording (OSTR), the method was restricted to cases in which membrane transporters occurred at extremely small densities, namely at one or a few transporters per cell. Here we describe the extension of OSCR from whole cells harbouring a small number of transporters to small membrane patches containing transporters at normal densities. A technique was developed for firmly attaching cells to isoporous filters, i.e. very thin transparent sheets containing homogeneous populations of cylindrical pores. The flux of fluorescent transport substrates across the tiny membrane pieces spanning the filter pores was measured by scanning microphotolysis, a combination of fluorescence microphotolysis and confocal laser scanning microscopy. The technique was tested by attaching erythrocytes to filters containing pores of 1.2, 2.0 or 3.0 microns diameter. After treating filter-attached erythrocyte membranes with streptolysin O, the transport of the fluorescent protein B-phycoerythrin through single streptolysin O pores was observed. From the flux data the functional radius of the streptolysin O pore was derived to be 12.5 +/- 0.9 nm, in very good agreement with previous electron microscopic estimates. The new technique features a number of unique properties: (i) the size of the membrane patch can be chosen within wide limits according to transporter density, (ii) transport can be recorded on many membrane patches in parallel, (iii) both influx and efflux may be analysed employing either photobleaching of fluorescent or photorelease of caged nonfluorescent substrates, (iv) two or more transport substrates may be monitored simultaneously. The new technique can be used, for instance, for analysing the activity of protein/particle pumps, a membrane transport domain not previously accessible to a single-transporter analysis.

Bacterial Proteins↗
PubMed1998

The cutaneous microfibrillar apparatus contains latent transforming growth factor-beta binding protein-1 (LTBP-1) and is a repository for latent TGF-beta1.

The transforming growth factors-beta1 and beta2 (TGF-beta) stimulate synthesis of extracellular matrix proteins in vitro and appear upregulated in fibrotic conditions, in scar formation, and in wound healing. The extracellular matrix in turn might also act as a scavenger or repository for TGF-beta. We therefore studied the in situ distribution of latent TGF binding protein-1 (LTBP-1) and latent TGF-beta1 on extracellular matrix elements of normal human skin and skin regenerating from cultured keratinocyte autografts. We localized both LTBP-1 and latent TGF-beta1 to fibrillin-containing (elastic) microfibrils. Both LTBP-1 and latent TGF-beta1 were already present during the earliest stages of the de novo formation of the microfibrillar apparatus, i.e., on fusiform, randomly oriented microfibrils that later coalesced to form the typical candelabra-like structures in the papillary dermis. We show herewith that LTBP-1 exerts a dual role as a component of fibrillin-microfibrils of the skin and in targeting latent TGF-beta1 to the cutaneous microfibrillar apparatus. Thus, this major connective tissue structure does not only serve as a force bearing element and scaffold for elastin deposition in the dermis, but also as an important repository for latent TGF-beta in the skin.

Adult↗
PubMed1998

A community-based clinic survey of antidepressant use in persons with schizophrenia.

OBJECTIVE: To determine the rates of antidepressant and antipsychotic use in the treatment of schizophrenia. METHOD: The primary therapists at 8 community mental health centres in a metropolitan Canadian city completed a survey questionnaire for all of their active clients. Information was collected about diagnoses, medication treatments, and clinical variables. RESULTS: There were 3555 clients, 1552 (43.7%) of which had a diagnosis of schizophrenia. Of clients with schizophrenia, 94% were prescribed antipsychotic medications, and 11.6% of these were also prescribed antidepressant medications. There were differences between the combination-treatment group and the antipsychotic-alone group in gender ratio, rates of concurrent diagnoses of mood disorder, level of current functioning, and total number of hospitalizations. CONCLUSION: In this community-based sample of clients with schizophrenia, antidepressants and antipsychotics are commonly prescribed in combination, even though the rate of concurrent mood disorders diagnoses is low. Further studies should clarify the efficacy and indications for antidepressant use in this population.

Antidepressive Agents↗