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Biomedical subjects

R Vogel

Publications and source records attributed to R Vogel.

At least 127 records · Page 7Linked to original sources
PubMed1989

Cytogenetic studies on preimplantation mouse embryos exposed to methylnitrosourea in vivo.

Since exposure of mice to methylnitrosourea (MNU) during the preimplantation period can induce malformations and an increased postnatal death rate, direct embryotoxic effects were studied in preimplantation embryos shortly after treatment of pregnant mice on days 2 and 3 of gestation with single i.p. injections of 2.5, 5.0, and 10.0 mg/kg MNU. Embryos exposed to MNU for 24 h after treatment on day 2 showed a significant reduction of cell number and induction of sister chromatid exchange (SCE) frequency, but no structural chromosomal aberrations or inhibition of development during culture. Embryos exposed to MNU in vivo for 3 h on day 3 showed significantly reduced cell numbers, a significant inhibition of development in culture, and an increase in structural chromosome aberrations. Due to the high cytotoxicity of MNU, determination of SCE was not possible. The results indicate that MNU reaches preimplantation mouse embryos shortly after maternal treatment and that malformations seen at term and postnatal effects are probably induced by the direct action of MNU on early embryos. Furthermore, the importance of the time interval chosen for evaluation of toxicologic endpoints in preimplantation embryos is demonstrated.

Animals↗
PubMed1989

Abnormal development of mouse embryos exposed to methylnitrosourea before implantation.

On day 2 of gestation mice were exposed to single i.p. injections of 5, 10, 20, and 40 mg/kg methylnitrosourea (MNU). Evaluation at term revealed 100% embryolethality in the 40 mg/kg group but no signs of maternal toxicity (LD50 = 400 mg/kg). In mice treated with 5 and 10 mg/kg, no malformations could be detected at term. In contrast, 40% of the live fetuses exposed to 20 mg/kg MNU showed developmental abnormalities of vertebrae, ribs, long bones, and kidneys. Analysis of postnatal development 3 weeks after birth indicated a significant increase in mortality in the offspring of all animals exposed to MNU on day 2 of pregnancy. Further developmental or morphologic anomalies could not be detected in the offspring up to the age of 6 months, when autopsy was performed. The data show that exposure to MNU before implantation has embryolethal and teratogenic effects in a dose range one order of magnitude lower than the toxic dose range for adult animals.

Abnormalities, Drug-Induced↗
PubMed1989

Maternal factors influencing development of embryos from mice superovulated with gonadotropins.

In NMRI mice superovulation with pregnant mare serum gonadotropin (PMSG) and human chorionic gonadotropin (hCG) increased mating rate, number of implantation sites, rate of advanced and delayed resorptions, as well as retarded sternebral ossification and cleft palate. On day 3 of gestation in preimplantation embryos, cell number and mitotic index were lower after superovulation than after spontaneous ovulation. However, when preimplantation embryos from superovulated and control females were transferred on day 3 of pregnancy to pseudopregnant recipients (10 embryos per female) no differences could be detected between the two groups of fetuses at term. The results of the embryo transfer experiments indicate that abnormal embryonic development after superovulation with gonadotropins is predominantly induced by effects of the hormone treatment on the maternal uterine environment.

Abnormalities, Drug-Induced↗
PubMed1989

The visual field in chronic simple glaucoma and ocular hypertension; its character, progress, relationship to the level of intraocular pressure and response to treatment.

Nine hundred and twenty-nine patients with chronic simple glaucoma or ocular hypertension were followed for one to thirteen years using the King's College Hospital glaucoma data base. The 30 degree visual field was divided into twelve clinical zones. The field sensitivity and its change as measured by the mean differential threshold both in these zones and overall was followed to determine the pattern and progress of field loss in eyes diagnosed initially as chronic simple glaucoma or ocular hypertension. The findings were related to other similar analyses in which the mean differential threshold in chronic glaucoma was found to correlate significantly with the initial intraocular pressure and its progress with the mean follow-up intraocular pressure under treatment. Inferences were drawn regarding the nature of chronic simple glaucoma and ocular hypertension and their management.

Adult↗
PubMed1989

Fibroblast growth factor enhances type beta 1 transforming growth factor gene expression in osteoblast-like cells.

Fibroblast growth factor (FGF) and type beta transforming growth factor (TGF beta) are potent modulators of proliferation and differentiation in many types of cells. TGF beta acts in an autocrine manner, and the regulation of TGF beta gene expression is one of the crucial events in the control of cellular functions. This study examines FGF regulation of TGF beta 1 gene expression in osteoblast-like cells. Bovine basic FGF (bFGF) increased the steady-state level of 2.5-kb TGF beta 1 mRNA two- to threefold in rat osteosarcoma (ROS17/2.8) cells in a dose-dependent manner, starting at 0.1 ng/ml. The increase of the message was detectable within 3 h after the addition of bFGF, peaked at 6 h, and lasted at least up to 48 h. This effect was blocked by a protein kinase inhibitor, K252a, indicating the involvement of phosphorylation. bFGF increased the rate of TGF beta 1 gene transcription estimated by nuclear run-on assay, while the stability of TGF beta 1 mRNA was not altered. bFGF increased the TGF beta activity in the conditioned media, estimated by DNA synthesis inhibition assay using mink lung epithelial (CCL-64) cells. Parathyroid hormone reduced the abundance of TGF beta 1 mRNA in ROsS17/2.8 cells and opposed the bFGF effect on TGF beta 1 mRNA. bFGF also increased the steady-state level of TGF beta 1 mRNA in mouse calvaria-derived MC3T3E1 and human osteosarcoma SaOS-2 cells. These findings indicate that FGF enhances the expression of TGF beta 1 gene in osteoblast-like cells and point to the tight relationship of the two growth factors involved in the control of cellular functions.

Animals↗
PubMed1989

Co-administration of ascorbic acid with cyclophosphamide (CPA) to pregnant mice inhibits the clastogenic activity of CPA in preimplantation murine blastocysts.

Cyclophosphamide (CPA) administered at a dose of 15 mg/kg body weight to pregnant inbred CBA/CaH mice 60 h after copulation significantly elevated the incidence of structural chromosomal aberrations and sister-chromatid exchanges in 96 h blastocysts. When ascorbic acid (800 mg/kg body weight) was co-administered with CPA (15 mg/kg) using different injection sites, the incidence of structural chromosomal aberrations and the number of aberrant metaphases were significantly lower as compared to the CPA-exposed embryos, but still significantly higher than untreated controls. Sister-chromatid exchanges were not significantly different in embryos exposed to CPA only when compared to those exposed to CPA and ascorbic acid. In terms of the developmental potential of embryos, pregnant mice injected with both CPA and ascorbic acid had significantly fewer resorptions per mouse, and a significantly higher number of viable fetuses retrieved on the 18th day of gestation when compared to mice injected with CPA alone. The data in this study demonstrate that the co-administration of ascorbic acid with CPA to pregnant mice ameliorates the CPA-induced clastogenicity and improves the developmental potential of these embryos. This study suggests that some of the CPA-induced genotoxicity is due to the generation of reactive oxygen molecules, but further research is necessary before this can be firmly concluded.

Animals↗
PubMed1989

Effect on the 24-hour diurnal curve of intraocular pressure of a fixed ratio combination of timolol 0.5% and pilocarpine 2% in patients with COAG not controlled on timolol 0.5%.

Eight patients with chronic open-angle glaucoma who had an intraocular pressure greater than 24 mm Hg at some time during the day while taking timolol 0.5% twice daily were given the fixed ratio combination of timolol 0.5% with pilocarpine 2% (TP2) twice daily. By comparing full 24-hour diurnal curves on timolol with those on TP2 it was possible to show that all patients except one (at a single timepoint) had an IOP less than 22 mm Hg when changed to TP2. The mean IOPs, the area under the diurnal pressure curve, and the diurnal variation were all significantly lower on TP2 twice daily than on timolol 0.5% twice daily.

Aged↗
PubMed1989

Mortality and rate of suicide of first admission psychiatric patients. A 5-year follow-up of a prospective longitudinal study.

Patients who commit suicide in a psychiatric hospital are, in general, patients who have had previous admission or who have already made at least one suicide attempt. The following study focuses upon an earlier time within the course of a psychiatric illness, that is the time of first admission, and examines the rate of suicide of 258 patients after 5 years. Two control groups were selected: first admitted psychiatric patients who did not commit suicide, and patients who died a 'natural death'. We analyzed how the suicides were integrated into the vocational, social and medical areas of life before they were admitted to the hospital. Further it was possible to identify predictors of future suicide.

Female↗
PubMed1989

Suicide and mental illness in the elderly.

This report deals with the relation of suicide to mental illness in the elderly. Our investigation of this relation proceeds from the following two points of view: First, we asked whether the fact that the elderly are most at risk of committing suicide is confounded with their increased psychiatric morbidity. Second, we asked to what extent suicides of older mentally ill persons are definitely created by their mental illness. The sample includes 310 suicides of psychiatric in-patients. There were explored in the course of a multicentre study of 6 psychiatric state hospitals in the south of the Federal Republic of Germany. The method of analysis involved the motives of the suicidal acts. Results demonstrate that the age is an autonomous risk factor and not to be confounded with the psychiatric morbidity. Psychiatric morbidity of older suicides is not sufficient to explain the suicidal act. Moreover, we found that if mental illness played a part, motives reflecting aspects of chronicity predominated motives reflecting psychopathology (i.e. feeling of being persecuted, loosing mind) of the suicidal patients. Results are discussed with special reference to preventing and managing suicides in the elderly.

Aged↗
PubMed1989

[The course of Crohn disease and side effect profile with long-term treatment using metronidazole].

In a prospective study 21 patients with Crohn's disease not responding to standard treatment (salazosulfapyridine and/or corticosteroids) received metronidazole in a dose of 12 to 20 mg per kg body weight over 6 and 12 months respectively. The objectives were documentation of side effects and pharmacokinetic behaviour of metronidazole in relation to the course of the disease. In 3 months intervals and 3 months after the end of treatment activity indices were determined, the side effects of metronidazole were recorded and the drug plasma concentration was measured. Compliance of drug intake was excellent (94%). Best-Index decreased to a minimum after 6 months, orosomucoid after 3 months. Side effects from metronidazole (black tongue, dark urine, paraesthesia, metallic taste, epigastric pain, skin reactions, nausea) were reported by over 80% of the patients at any time of the study. Nearly 50% of patients developed paraesthesia, which was still present 3 months after the end of treatment. A mean dose of 15.4 mg per kg corresponded to a mean plasma concentration of 10.9 micrograms/ml of metronidazole. Plasma concentrations were not related to treatment success nor to the incidence of side effects. Treatment of Crohn's disease with metronidazole for longer than 3 months is not recommended both because of lack of additional therapeutic gain and because of the increasing risk of side effects.

Adolescent↗
PubMed1988

Isolation of a human cDNA of urokinase and its expression in COS-1 cells.

The cDNA encoding human urokinase (UK) has been isolated from a cDNA library prepared from human normal fibroblast (WI38) cells, which had been stimulated by endothelial cell growth factor and heparin. This cDNA was sequenced and found to contain a few silent substitutions, thus encoding the same amino acids as deduced from the published genomic sequence of UK. After modification, the cDNA of UK was inserted into a transient expression vector and used to transfect COS-1 cells. The recombinant UK protein (rUK) in the serum-free medium of transfected COS-1 cells was characterized by biochemical and functional assays. These studies indicated that rUK from COS-1 cells is glycosylated, enzymatically active, and very similar to native single-chain plasminogen activator (scuPA). Therefore, such rUK can be a convenient source of scuPA for any further studies.

Amino Acid Sequence↗
PubMed1988

Proteinase-sensitive regions in the heavy chain of low molecular weight kininogen map to the inter-domain junctions.

Low molecular weight kininogen from human plasma was subjected to limited proteolysis with trypsin, chymotrypsin, elastase, and bromelain, and the resulting fragments of 20,000 or 40,000 Da were isolated. Amino-terminal sequence analysis of the fragments disclosed for the various proteinases eight independent cleavage sites distinct from the typical kallikrein cleavage sites flanking the kinin region. All the identified cleavage sites cluster in two stretches of 11-12 residues of the kininogen heavy chain. These short segments represent the primary attack sites for proteinases ("proteinase-sensitive regions") in the heavy chain portion of human low molecular weight kininogen. The amino acid sequences of the two proteinase-sensitive regions are mutually homologous; they are further characterized by the presence of a single copy each of the consensus tetrapeptide Cys-X-Gly-Cys known to form a narrow disulfide loop (Kellermann, J., Thelen, C., Lottspeich, F., Henschen, A., Vogel, R., and Müller-Esterl, W. (1987) Biochem. J. 247, 15-21). The proteinase-sensitive regions are located at the junctions of the three cystatin-like domains constituting the kininogen heavy chain. Proteolytic cleavage at the sensitive regions dissects the kininogen heavy chain and releases single domains of 20,000 Da and combined domains of 40,000 Da which can function as cysteine proteinase inhibitors. The presence of kininogen heavy chain domains in plasma samples under pathologic conditions suggests that cleavage of the proteinase-sensitive regions might also occur in vivo.

Amino Acid Sequence↗