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Biomedical subjects

T Beck

Publications and source records attributed to T Beck.

At least 73 records · Page 4Linked to original sources
PubMed1994

The Raf-1 serine/threonine protein kinase.

Raf-1 belongs to a family of serine/threonine protein kinases which are highly conserved through evolution in multicellular organisms. Raf-1 kinase has gained much attention due to its function as a critical shuttle enzyme that connects stimulation of growth factor receptors and protein kinase C at the cell membrane to changes in the expression of genes involved in the control of cell growth, differentiation and survival. Regulation of Raf-1 activity is complex and involves Ras, as well as several serine/threonine and tyrosine kinases. Through a series of phosphorylation events, extracellular signals are connected through the Raf-1/MAP kinase pathway to activity-regulation of several oncogene-class transcription factors via phosphorylation of specific serine residues. Under ordinary circumstances, the cascade involving Raf-1 eventually leads to changes in gene expression and protein synthesis. Upon constitutive activation of Raf-1 kinase, as a result of genetic changes, a variety of cell types acquire a transformed phenotype.

Animals↗
PubMed1994

Transformation by Raf and other oncogenes renders cells differentially sensitive to growth inhibition by a dominant negative c-jun mutant.

In NIH3T3 cells expressing active Raf-1 protein serine/threonine kinase (PSK) c-jun expression is constitutive while c-fos expression is attenuated. This alteration prompted us to determine whether oncogene transformation would render cells differentially sensitive to growth inhibition by a dominant negative mutant of c-jun, TAM 67. Growth inhibition was observed in three types of assays: (1) transfection of TAM 67 into cells stably transformed by a variety of oncogenes, (2) cotransfection of TAM 67 with oncogene expression plasmids into NIH3T3 cells and (3) titration of oncogene-expressing retroviruses on cells stably expressing TAM 67. The results clearly demonstrate that Raf-1 dependent oncogenes, which include receptor protein tyrosine kinases (PTKs)-, intracellular PTKs- and Ras-derived genes share the Raf phenotype of constitutive c-jun expression, attenuated c-fos induction, and high sensitivity to growth suppression by TAM 67. Additionally, the intracellular PSK oncogene, mos and the nuclear oncogenes c-myc, c-fos, and SV40 T antigen were TAM 67-sensitive for transformation. This universal pattern of altered growth regulation in oncogene transformed fibroblast cell lines highlights the potential usefulness of c-jun based inhibitors for control of tumor cell growth.

3T3 Cells↗
PubMed1994

[The Erlangen Support Ring for management of congenital and acquired acetabular defects. Intermediate term results of 43 implantations].

Between January 1987 and December 1989, at the Department of Trauma Surgery of the University of Erlangen 41 patients were treated at one or both hips with the uncemented hip replacement "Erlanger Modell" including a special supporting ring because of the bad condition of the bone surrounding the acetabular region. In 41 cases the implantation was a revision. 2 patients have not been operated on before. They suffered from congenital hypdysplasia with severe bone destruction at the area of the acetabulum. The supporting ring and the cup are made of the titanium alloy TiAl5 Fe2.5. Using the supporting ring, it is possible to fix the socket within the bone graft and to diminish the pressure exerted on the socket by transferring a lot of stress directly to the iliac bone and the oubic bone. The results of 41 patients (43 joints) ranging from 21 to 57 postoperative months giving an average of 32 months, are very encouraging. 76.6% of the patients feel no or not much pain, 67.4% can walk without hooked stick and 79% can walk a distance of more than 1000 m. The range of movement of the hip joint could be improved, especially abduction and extention. Good results based on patients satisfaction were obtained in 95.4%.

Acetabulum↗
PubMed1993

Assessing chronic brain damage by quantification of regional volumes in postischemic rat brains.

The present study provides data on fresh volumes of 39 anatomically defined brain regions after a 10 min transient forebrain ischemia in the rat. Ischemia was induced by occlusion of the carotid arteries and simultaneous hypotension. After a survival period of 3 months the rats were transcardially perfusion-fixed with Bodian's solution, and the brains processed for paraffin embedding and serially sectioned. The sections were Nissl-stained for delineation of the brain regions. The volume of a brain region was calculated from 8-10 equidistant sections, using the Cavalieri method and corrected for shrinkage of the brain. Fresh volumes were reduced by 27-50% in the layers of the hippocampal CA1 sector, by 40-46% in the substantia nigra, by 19% in the caudate nucleus, by 13% in the subiculum and the cingulate areas 1-3, by 12-14% in the retrosplenial and temporal areas. The results show that determination of fresh volumes is a sensitive method for quantification and localization of ischemic brain damage in the whole brain.

Animals↗
PubMed1993

Recombinant human erythropoietin and the anemia of multiple myeloma.

The anemia of multiple myeloma (MM) is multifactorial, including physical replacement of normal hemopoiesis by tumor cells, renal failure and cytokines which contribute to the blunted erythropoietin (EPO) response observed in anemias of chronic disease. Recombinant EPO has been evaluated in anemic patients with stable multiple myeloma (< or = 10g% hemoglobin). Responses (> or = 2g% hemoglobin increase) were observed in 78% of 41 patients in two separate studies. Responses were associated with an increase in bone marrow erythropoietic cell compartment and reticulocytosis. Evaluation of potential parameters affecting response identified prolonged cytotoxic therapy for > 12 months, especially with alkylating agents and pre-treatment EPO levels > 100 U/L, both of which seemed to decrease the likelihood of EPO response. EPO is a safe and effective treatment for the anemia associated with MM.

Anemia↗
PubMed1993

Low target birth weight or growth retardation? Umbilical Doppler flow velocity waveforms and histometric analysis of fetoplacental vascular tree.

OBJECTIVE: The placental vascular architecture of small-for-gestational-age fetuses seems to have an impact on the flow patterns in the umbilical arteries. STUDY DESIGN: Blood flow velocity waveforms of the umbilical arteries were measured by Doppler ultrasonography in nine small-for-gestational-age fetuses with elevated systolic/diastolic ratios of the umbilical arteries, seven small-for-gestational-age fetuses with normal flow patterns, and 14 appropriate-for-gestational-age fetuses with normal flow patterns. After delivery histomorphometric placental investigations were performed. RESULTS: Reduced end-diastolic flow velocities were significantly associated with both a reduction of vascularization within the terminal villi and adverse diffusion conditions, indicating insufficient functional maturity. The perfusion and diffusion capacity of small-for-gestational-age placentas with normal umbilical artery flow velocity waveforms was similar or even slightly better compared with the appropriate-for-gestational-age control values. CONCLUSION: These data suggest that Doppler flow velocimetry in the umbilical arteries is predictive of a vascular lesion within the placentas of small-for-gestational-age fetuses.

Blood Flow Velocity↗
PubMed1993

Hereditary palmoplantar keratoderma, type papulosa, in Croatia.

BACKGROUND: Hereditary palmoplantar keratoderma (HPPK), type papulosa, is rare, and epidemiologic data are sporadic and inconsistent. An epidemiologic population study of this disease has not been performed previously. OBJECTIVE: We performed a large population study on prevalence of HPPK, type papulosa, in Croatia. METHODS: The data were collected from medical records of dermatology departments throughout Croatia; 14 patients and their relatives were examined. Histopathologic studies were performed in 11 of these 14 patients. RESULTS: Fifty-five patients were identified and the prevalence was 1.17 per 100,000 inhabitants. All 55 patients belonged to 20 different families. An autosomal dominant mode of inheritance was confirmed in 13 families. All 14 patients examined by the authors had both palmar and plantar lesions; the volar aspects of fingers were also involved. Thickened nails were observed in four patients, and no significant skin lesions were found elsewhere. CONCLUSION: HPPK, type papulosa, is rare, and its prevalence in Croatia is about four times lower than HPPK, Unna-Thost type. It should be considered a distinct entity.

Adolescent↗
PubMed1993

Time course of hippocampal glucose utilization and persistence of parvalbumin immunoreactive neurons after ibotenic acid-induced lesions of the rat dentate area.

The effects of ibotenic acid induced lesions of the dentate gyrus on hippocampal glucose utilization and parvalbumin-positive neurons were evaluated in male Wistar rats. Ibotenic acid was injected in the right dorsal dentate gyrus. Quantification of glucose utilization was performed 3 days, 3 weeks, or 3 months after the lesion using the 14C-2-deoxyglucose method. Nissl-stained sections and sections stained for acetylcholinesterase were used as references for anatomical delineation of the hippocampal cytoarchitecture. Additional sections were stained for parvalbumin. The results revealed widespread reductions of glucose utilization in all layers and sectors of the hippocampus in the ipsilateral lesioned hemisphere and also in the nonlesioned contralateral hemisphere. The reductions occurred as early as 3 days after the lesion and persisted up to 3 months. In neither hippocampal structure did glucose utilization return to control levels. Immunohistochemical visualization of parvalbumin-containing neurons revealed that these putatively inhibitory neurons persisted in the otherwise granule-cell-depleted area. The data show that interruption of the excitatory trisynaptic pathway from the entorhinal cortex to the CA1 at the level of the dentate gyrus affects hippocampal glucose utilization irreversibly and uniformly. Since some inhibitory neurons seem to survive the ibotenic acid lesion, we suggest that the reductions of hippocampal glucose utilization reflect an imbalance in favor of inhibitory neurons in the ipsilateral hippocampus after the lesion, which manifests also in the contralateral hemisphere via the commissural pathways.

Animals↗
PubMed1993

[Follow-up of tumor markers in evaluating the effectiveness of chemo- or hormone therapy in metastatic breast cancer].

We compared the course of the tumour markers CEA and CA 15-3 with the clinical course of 62 patients with metastasising breast cancer. The patients were treated by an aggressive chemotherapy (FAC-regimen) or high-dose hormonal therapy (1000 mg MPA/day). The markers were determined after a well-defined schema. In patients treated with aggressive chemotherapy, the markers were determined 4, 8 and 12 hours as well as 7 days after each course. In patients treated with hormonal therapy, the markers were determined weekly from the first to 12th week as well as 4, 8 and 12th week after onset of therapy. The course of the tumour markers was compared with the results of the radiological and clinical staging three months after beginning of therapy. For patients treated with aggressive chemotherapy CEA withdrawn 4 hours after the first and second cycle resulted in medium predictive values of 88% for marker increase and 93% for marker decrease. In comparison, the predictive values of CA 15-3 were 81% for marker increase and 71% for marker decrease. Both markers obtained better results when withdrawn four hours after therapy compared to values withdrawn 7 days after therapy. In high-dose hormonal therapy, the determination of markers collected four weeks after onset of therapy is sufficient for predicting the clinical course. The medium predictive values of CEA after 4 and 8 weeks amount to 83% for marker increase and 87% for marker decrease. In comparison, the predictive values of CA 15-3 are 95% vs. 85%.(ABSTRACT TRUNCATED AT 250 WORDS)

Antigens, Tumor-Associated, Carbohydrate↗
PubMed1992

Morphological, immunohistochemical and biochemical characterization of 6 newly established human ovarian carcinoma cell lines.

Six permanent human tumor cell lines (OV-MZ-1 to 6) were established from 6 patients with serous adenocarcinomas of the ovary. These cell lines were derived from both solid tumors and ascites, from pre-treated and untreated patients, and are available over a range of in vitro passage numbers. The tumor cells grow as monolayers and develop foci of "piled-up' cells in confluent cultures. Flow cytophotometry showed that all the lines exhibited DNA hyperdiploidy with DNA tetraploidy in one cell line and DNA aneuploidy in the other cell lines. The mean population doubling time ranged from 24 to 52 hr. Transmission electron microscopy demonstrated that the tumor cells of all cell lines exhibited features of epithelial differentiation such as desmosomes and intracellular gland-like lumina. Immunocytochemical analysis showed that the co-expression of cytokeratins and vimentin, which is a feature of ovarian serous cystadenocarcinomas in situ, was fully preserved in the majority of cell lines. The main cytokeratin polypeptides expressed were numbers 7, 8, 17, 18 and 19. The tumor-associated antigen CA-125, but not CEA, was shed in the culture supernatant. This was in accordance with FACScan analysis of the cell lines and the level of CA-125 and CEA in the patients' serum. The estrogen and progesterone receptors were negative both in the cell lines and in the original tumors. These new ovarian carcinoma cell lines will be valuable models for further investigations into a variety of biological properties.

Adult↗
PubMed1992

Chronic infusion of nerve growth factor does not rescue pyramidal cells after transient forebrain ischemia in the rat.

Male Wistar rats received chronic intracerebroventricular infusions of nerve growth factor (NGF) starting immediately before induction of a transient forebrain ischemia and continuing until 7 days after the infarct. Ischemia was induced by carotid occlusion and simultaneous hypotension. Seven days after the infarct the brains were examined histologically and the number of necrotic cells in the hippocampus were counted. The results did not reveal any difference in treated vs. untreated animals. The data suggest that application of exogenous NGF does not prevent ischemic cell death in the hippocampus.

Animals↗
PubMed1992

C-erbB-2-oncogene expression in breast carcinoma: analysis by S1 nuclease protection assay and immunohistochemistry in relation to clinical parameters.

The c-erbB-2 mRNA was detected by the S1 nuclease protection assay and Northern blotting in breast cancer tissues. In contrast to the Northern blot analysis which has been used in all recent publications concerning c-erbB-2 expression on the level of RNA, the S1-nuclease protection assay has distinct advantages with respect to sensitivity, reproducibility, and handling of radioactive probes. We compared the expression of c-erbB-2 in 120 breast carcinomas which were operated in the years 1989-1990 on the level of the mRNA (S1 nuclease protection assay) and the protein (immunohistochemistry), respectively. In general, results obtained with both methods were in good agreement. Only minor differences in classification were observed with 18 samples, all of them belonging to either the moderate or the weak c-erbB-2 expression phenotype. In addition, the level of c-erbB-2-protein was investigated by immunohistochemistry in 271 breast carcinomas which were operated in the years 1984-1987. Comparison of the level of c-erbB-2 expression with the patient history indicates that patients whose tumors had already metastasized to the axillary nodes showed a reduced overall and disease-free survival in the group with pronounced expression of the c-erbB-2 protein. Thus the strong expression of c-erbB-2 oncogene in primary breast cancers appears to be an additional and particular prognostic factor in lymph node positive patients.

Blotting, Northern↗
PubMed1992

[Placental morphometry in diastolic zero and negative flow of the umbilical arteries].

Macromorphometric and histometric placental data, in cases with enddiastolic zero flow or reverse flow (dZRF), reveal a lower placental weight and smaller attachment area as well as bigger terminal villi with a reduced amount of epithelial plates with comparable vascularisation. In cases with reverse flow, all parameters were worse, either compared to the controls or to the zero flow cases. With advancing duration of clinical observation, we find a maturation of the terminal villi, with the cross-sectional areas getting smaller, diffusion distances becoming shorter and vessels bigger. This proves the dependence of foetal outcome by dZRF on the compensatory capacity of the terminal villi. The planimetric area in the forward flow channel depends on the foetal intravillous blood volume.

Blood Flow Velocity↗
PubMed1992

Infarct reduction by the platelet activating factor antagonist apafant in rats.

BACKGROUND AND PURPOSE: Recent findings suggest a key role for platelet activating factor in neuroinjury. For this reason we evaluated the effects of the platelet activating factor antagonist apafant (4-(2-chlorophenyl)-9-methyl-2[3(4-morpholinyl)-3-propanol-1- yl[6H-thieno[3.2-f[[1.2.4]triazolo]4,3-1]]1.4]diazepine on farct volume and local cerebral blood flow following irreversible occlusion of the left middle cerebral artery in rats to assess the direct and vascular components of apafant's action. METHODS: We measured infarct volume 48 hours after middle cerebral artery occlusion. The effect of multiple doses of apafant (30 mg/kg p.o.) was tested in both pretreatment (n = 8) and posttreatment (n = 8) groups. In the pretreatment group apafant was given 30 minutes before and 2, 6, and 18 hours after occlusion. Rats of the posttreatment group received apafant 1, 6, and 18 hours after middle cerebral artery occlusion. We also examined the effect of a single dose of apafant given 30 minutes prior to occlusion (n = 9) on local cerebral blood flow determined 2 hours after middle cerebral artery occlusion. RESULTS: Both regimens of apafant effectively decreased infarct volume. The reduction in cortical infarct volume was 59% (p less than 0.01; H test, U test) when the rats were treated before and after vessel occlusion whereas the decrease was 47% (p less than 0.05; H test, U test) when treatment began 1 hour after occlusion. Apafant did not change local cerebral blood flow after occlusion compared with controls. CONCLUSIONS: We suggest that the cytoprotection afforded by apafant occurs mainly via a direct effect on brain tissue and has no major vascular component.

Animals↗
PubMed1992

The effect of antenatal intravenous immunoglobulin on ascending intrauterine infection after preterm premature rupture of the membranes: a pilot study.

Ascending infection is a serious threat in pregnancies complicated by preterm premature rupture of the membranes (PROM). In a controlled randomized prospective pilot study (n = 18) we have evaluated the effect of intravenous IgM enriched immunoglobulin given to the mothers 24-48 hours after preterm PROM in reducing ascending infection. Using a validated infection score from laboratory and clinical data at birth, we found a significant reduction of probable infection in the neonates of the treatment group compared to the control group (p = 0.0022). Histopathological investigation of the placentas, membranes and umbilical cords revealed significantly lower stages and grades of chorioamnionitis in the treatment group (p = 0.036). From these preliminary results we conclude, that intravenous broad spectrum immunoglobulin given antenatally to patients with preterm PROM may reduce ascending infection. However, studies with a much larger cohort of patients are necessary to confirm these preliminary results and to detect potential clinical benefits from this treatment mode.

Adult↗
PubMed1991

The effects of two 21-aminosteroids on overt infarct size 48 hours after middle cerebral artery occlusion in the rat.

The lipid peroxidation inhibitors U74006F (21-[4-(2,6-di-1-pyrrolidinyl-4-pyrimidinyl)-1-piperazinyl]-16 alpha-methylpregna-1,4,9]-(11)-triene-3, 20-dione) and U74512E (21-[4-(3-ethylamino-2-pyridinyl)-1-piperazinyl]-16 alpha-methylpregna- 1,4,9]-(11)-triene-3,20-dione) were tested for cerebroprotective properties in the rat. Focal cerebral ischemia was induced by irreversible occlusion of the middle cerebral artery (MCA-O). The 21-aminosteroids U74006F (1 mg/kg or 10 mg/kg, i.p.) and U75412E (1 mg/kg or 30 mg/kg, i.p.) were injected 30 min prior and 2, 6, and 24 h after MCA-O. The higher doses of U74006F or U75412E caused reductions in cortical infarct size ranging from 28 to 34%. The data suggest the 21-aminosteroids to be mildly effective after irreversible occlusion of the MCA but possibly to be more beneficial as part of a combined drug therapy in conjunction with Ca2+ or NMDA antagonists.

Animals↗
PubMed1991

The effects of dizocilpine (MK-801), phencyclidine, and nimodipine on infarct size 48 h after middle cerebral artery occlusion in the rat.

The effects of the calcium channel blocker nimodipine and the non-competitive NMDA-antagonists MK-801 and phencyclidine (PCP) on infarct size 48 h after occlusion of the middle cerebral artery (MCA-O) were evaluated in the rat. Nimodipine was given at a dose of 0.3 mg/kg s.c. 30 min prior and 8, 16, and 24 h after MCA-O. MK-801 (1 mg/kg i.p. or 10 mg/kg i.p.) or PCP (0.3, 1.0, 3.0, 10, or 30 mg/kg i.p.) were administered 30 min prior to ischemia. In additional experiments 30 mg/kg PCP was given 1, 3, or 5 h post ischemia. Nimodipine and 1 mg/kg MK-801 reduced cortical infarct volumes significantly by 50% and 55%, respectively, while cortical infarct size fell by 32% and total infarct volume was not altered significantly after administration of 10 mg/kg MK-801. Pretreatment with 10 or 30 mg/kg PCP reduced cortical infarction by 47-53% and total infarct volumes by 39-42%. Posttreatment with PCP was effective if started at 1 or 3 h post ischemia.

Animals↗