Search PubMed⌕ Search

Biomedical subjects

W Weber

Publications and source records attributed to W Weber.

At least 199 records · Page 11Linked to original sources
PubMed1993

Crystallization and preliminary X-ray analysis of leukemia inhibitory factor.

Leukemia inhibitory factor (LIF) is a polyfunctional molecule with significant and diverse biological activities. LIF is a glycoprotein secreted by a number of different cell types in vitro. It is induced in fibroblasts, lymphocytes, monocytes and astrocytes by various inducers such as serum, TNF, interleukin-IP and EGF. Due to extensive and variable glycosylation the molecular weight can range from 38 to 67 kDA. The biological functions of LIF are mediated through a receptor and a signal transducer, gp130, which is also used by factors like interleukin-6 (IL-6), cilliary neurotropic factor (CNTF), and oncostatin M (OSM). Here, we report the crystallization of the non-glycosylated human-like LIF expressed in E. coli. The present crystals diffract to 2.0 A using synchrotron radiation. They belong to the monoclinic space group C2, and the cell dimensions are a = 61.5 A, b = 45.3 A, c = 77.7 A and beta = 112.3 degrees.

Cloning, Molecular↗
PubMed1993

The alpha 2-macroglobulin receptor/low density lipoprotein receptor-related protein binds lipoprotein lipase and beta-migrating very low density lipoprotein associated with the lipase.

Lipoprotein lipase (LPL) causes a marked increase in the cellular binding of beta-migrating very low density lipoprotein (beta-VLDL) to a large receptor compatible with the alpha 2-macroglobulin receptor (alpha 2MR)/low density lipoprotein receptor-related protein (LRP) (Beisiegel, U., Weber, W., and Bengtsson-Olivecrona, G. (1991) Proc. Natl. Acad. Sci. U. S. A. 88, 8342-8346). Here we demonstrate that LPL binds to the alpha-chain of purified alpha 2MR/LRP immobilized on microtiter plates. The binding, apparently to multiple sites, was blocked by heparin and inhibited by the alpha 2MR-associated protein (alpha 2MRAP) and by EDTA. Immobilized LPL bound alpha 2MR/LRP in solution as well as beta-VLDL prepared from cholesterol-fed rabbits. Both binding reactions were dependent on an intact carboxyl-terminal folding domain of LPL, but were independent of its dimeric structure and intact catalytical function. Dimeric LPL could mediate binding of beta-VLDL to immobilized alpha 2MR/LRP and to cells, e.g. monocytes. In contrast, LPL monomers were not able to mediate binding to immobilized alpha 2MR/LRP, presumably because of cross-inhibition due to close relation between the binding regions for the lipoprotein and for the receptor in the carboxyl-terminal domain of the LPL monomer. Heparin, but not alpha 2MRAP, inhibited cellular binding of 125I-LPL or 125I-beta-VLDL supplemented with LPL. However, alpha 2MRAP inhibited degradation of the two ligands by about 90% and 40-50%, respectively. The results show that LPL is a ligand for alpha 2MR/LRP and, because of its affinity for lipoprotein particles, dimeric LPL can mediate or strengthen binding of beta-VLDL to this receptor. It is proposed that LPL binds primarily to cell surface heparan sulfate in monocytes and is presented for endocytosis and degradation by alpha 2MR/LRP. Moreover, beta-VLDL may be further supplemented with LPL at the cell surface and achieve affinity for alpha 2MR/LRP.

Animals↗
PubMed1993

[Hereditary p53 mutation in a patient with multiple tumors: significance for genetic counseling].

We describe molecular genetic findings in a patient who initially presented with an intermediate teratoma of the testis and who many years later presented with an oligodendro-astrocytoma. In addition he developed a malignant histiocytoma over the scapula, an adenocarcinoma of the stomach and a late stage adenoma of the sigmoid colon. Due to the development of several neoplasms the possibility of either ataxia telangiectasia or Li-Fraumeni syndrome was considered in differential diagnosis. A molecular genetic investigation revealed that both he and his brother carried a germline p53 tumor suppressor gene mutation at codon 248. From this result we conclude that this family belongs to the Li-Fraumeni syndrome. Once characterized as belonging to the Li-Fraumeni syndrome, the remaining members of the family were typed to determine if they too carried the same mutation. The two children of the index patient were shown not to carry the mutation and are therefore at no increased risk of developing any of the Li-Fraumeni spectrum of malignancies. A molecular genetic investigation into similar families could help to prevent the development of additional malignancies as seen in the index patient, as radiotherapy may interfere with the normal function of the p53 protein and this may in turn help to orchestrate DNA repair after radiation.

Adult↗
PubMed1993

Serum biochemical changes in dogs competing in a long-distance sled race.

Fifty-five blood samples were collected from 28 dogs competing in the 1991 Yukon Quest International Sled-Dog Race to examine race-induced changes in serum biochemical values. Blood was collected after a 36-hour mandatory rest at the midpoint of the race, and again at 2 subsequent checkpoints. The mean speed of dogs between checkpoints was approximately 4.5 mph. There were no significant increases in PCV, or in serum total protein, sodium, or creatinine concentrations during the race. Mean serum potassium concentration decreased significantly (P < 0.05) from 4.8 +/- 0.4 to 4.4 +/- 0.3 to 3.9 +/- 0.3 mEq/L, as did the serum triglyceride concentration (138 +/- 52, 88 +/- 25, 81 +/- 16 mg/dl). Plasma cortisol concentration did not change significantly. Increases in the mean serum activity of creatine kinase (167, 420, 344 U/L), and aspartate aminotransferase (55, 79, 62 U/L) during the race were significant (P < 0.05). Participation in a long-distance sled race was associated with mild changes in routinely measured serum biochemical values in dogs.

Animals↗
PubMed1993

Flumazenil kinetics in the elderly.

In an open design, randomised, two-way cross-over study, a single 2 mg i.v. dose and a single 30 mg oral dose of flumazenil were each administered to a group of healthy young (n = 6) and elderly (n = 12) volunteers (male: female 2/1). Plasma samples were collected at intervals and intact drug was assayed. Both the i.v. and oral doses of flumazenil were very well tolerated by both age groups and no severe or unexpected adverse effects were observed. The main complaints were dizziness and headache, mainly after oral dosing, probably due to the higher Cmax and AUC following this route of administration. After 2 mg i.v. the disposition parameters in the two age groups (elderly/young) were very similar: volume of distribution (Vss): 0.88/0.90 l.kg-1; total body clearance (ClPL): 0.86/0.99 l.min-1; terminal elimination half-life (t1/2 beta): 1.02/0.91 h. After the 30 mg oral dose the mean Cmax of 87.6 ng.ml-1 (elderly) and 78.4 ng.ml-1 (young) were generally reached within 0.5 to 1 h. In 26% (elderly) and 23% (young), the absolute bioavailability of flumazenil was very similar. It is concluded that the absorption and disposition parameters of flumazenil were not significantly affected by aging.

Administration, Oral↗
PubMed1993

Population kinetics of gentamicin in neonates.

A population kinetic analysis was carried out on sparse plasma gentamicin (GE) concentration data from 469 neonates obtained as part of a routine therapeutic drug monitoring (TDM) programme in the hospital neonatology unit. The best predictors of the kinetic parameters of the monoexponential model, volume of distribution (Vd) and clearance (CL), were the weight (WT) and gestational age (GA). Vd of the neonates was only related to WT, whereas the half-life was only related to the GA. The clinical implications of the findings are that the initial dose per WT administered to premature infants should be larger than that for term infants, because of a larger Vd per unit WT, and the intervals between maintenance doses should extended due to the prolonged half-life. Apart from these general guidelines, specific dose recommendations are also given.

Body Weight↗
PubMed1993

Percutaneous ultrasonic angioplasty: initial results of an in-vitro study on normal and atherosclerotic human vessel segments.

The aim of the present study was to assess the efficacy and safety of a new ultrasound catheter system in vitro before employing it in humans. Ultrasound energy was applied to 141 normal and atherosclerotic human vessel segments, obtained at autopsy. Macroscopical and histological examination of the treated vessel segments revealed that ultrasound energy is atraumatic to the normal vessel wall. In atherosclerotic vessel segments, there was macroscopically significant reduction in the size of plaques. In 7/10 completely occluded femoral arterial segments, recanalization could be achieved. The resulting lumen approximated the diameter of the wire probe. Therefore, ultrasound energy is an appealing form of energy for recanalization of completely obstructed atherosclerotic vessels and for disintegration of atherosclerotic plaques. Clinically, ultrasonic angioplasty may become an adjunctive modality to balloon angioplasty.

Angioplasty, Balloon↗
PubMed1993

Familial occurrence of cancer in Basel city.

The Basel Familial Cancer Study was established in 1982. Data collection and statistical analysis suggest that genetic mechanisms play an important role in most cancer types. This is illustrated in breast and colorectal cancer patients whose first degree relatives were studied. The establishment of a familial cancer registry is most helpful for cancer risk determinations, surveillance and management programmes, identification of new cancer prone genotypes and etiological family studies. The family history should be included into future cancer control activities.

Adult↗
PubMed1992

Determination of the relative configuration of 5,6,7,8-tetrahydromethanopterin by two-dimensional NMR spectroscopy.

The relative configuration of the pterin moiety of 5,6,7,8-tetrahydromethanopterin 1, a coenzyme isolated from methanogenic archaea, has been determined by two-dimensional NMR spectroscopy of N5,N10-methenyl-5,6,7,8-tetrahydromethanopterin 2 to be rel-(6R; 7S; 11R). The complete proton resonance assignment of the pterin moiety of N5,N10-methylene-5,6,7,8-tetrahydromethanopterin 3 is described including the relative stereospecific assignment of the C(14a) methylene protons.

Magnetic Resonance Spectroscopy↗
PubMed1992

[Cancer research in clinical practice. The attentive physician and the family anamnesis].

Astute physicians play an important role in the detection of cancer causes. Their most powerful tool is the family history. It permits the identification of families with unusual cancer clusters. The members of such families can be recruited for research in prevention and molecular genetics. The potential of research in medical practice should be exploited more extensively in the future.

Algorithms↗
PubMed1992

Binding of the H-ras p21 GTPase activating protein by the activated epidermal growth factor receptor leads to inhibition of the p21 GTPase activity in vitro.

There is strong, albeit indirect, evidence for a mitogenic signal transduction pathway comprising growth factors, growth factor receptors, the GTPase activating protein (p120-GAP), and p21ras. To demonstrate a direct physical association between these proteins in the absence of other cell constituents, their interaction was studied in vitro. Our results obtained with homogeneous protein preparations show that the activated epidermal growth factor (EGF) receptor phosphorylates p120-GAP at one site. Phosphorylated p120-GAP remains firmly bound to the receptor at physiological salt concentration; this leads to product inhibition of the receptor kinase activity as shown by diminished autophosphorylation activity and lack of turnover in p120-GAP phosphorylation. Phosphorylated p120-GAP is as active in stimulating the p21ras.GTPase as unphosphorylated GAP. p120-GAP, however, when bound to the EGF receptor is by a factor of 2 less active in stimulating the p21ras.GTPase than free p120-GAP. This effect might contribute to regulate the steady-state level of p21-GTP.

Enzyme Activation↗
PubMed1992

[The significance of the family anamnesis in women with breast carcinoma].

A cancer-related family history was ascertained in 600 women with breast cancer. Prevalence data in the families were compared to the data of the population-based Basel cancer registry. Breast cancer occurrence was increased in first degree female relatives (relative risk: 1.7; 95% confidence interval: 1.4-1.9; p less than 0.0001). Breast cancer risk in relatives decreased with increasing age of the probands. Women at elevated breast cancer risk can be identified by obtaining a family history of breast cancer patients.

Adult↗