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Biomedical subjects

E Ogris

Publications and source records attributed to E Ogris.

At least 37 records · Page 2Linked to original sources
PubMed1996

Defective endogenous opioid response to exercise in type I diabetic patients.

Plasma beta-endorphin (beta-E) concentration was determined before, during, and after a standardized incremental exercise test to maximal capacity in eight type I diabetic patients and eight normal control subjects. Diabetic patients were studied under normoglycemic and hyperglycemic conditions in a single-blind random fashion to differentiate between the effects of acute hyperglycemia and of diabetes per se on the beta-E response to exercise. The perceived magnitude of leg effort elicited by exercise was evaluated using a category scale. Whereas plasma beta-E concentrations increased in control subjects with increasing workload, causing significantly higher beta-E levels at the end of exercise than at the beginning (P < .001), no such increase could be observed in the diabetic patients under normoglycemic and hyperglycemic conditions. In addition, baseline plasma beta-E concentrations were significantly lower in normoglycemic (P < .01) and hyperglycemic (P < .001) diabetic patients than in control subjects. Even during the recovery period, patients' beta-E levels remained significantly lower than those of control subjects. At submaximal levels of power output, the perceived intensity of leg effort was significantly higher in normoglycemic and hyperglycemic diabetic patients than in control subjects. We conclude that in type I diabetic patients, the ability of the endogenous opioid system to respond to exercise-induced stress is impaired under hyperglycemic and even under normoglycemic conditions. Considering the effect of endogenous opioids on stress tolerance, such changes may compromise exercise performance in diabetic patients.

Adult↗
PubMed1996

Effects of two different enalapril dosages on clinical, haemodynamic and neurohumoral response of patients with severe congestive heart failure.

Angiotensin converting enzyme inhibitors improve symptoms and prolong life in congestive heart failure, but the dose in the individual patient is uncertain. A randomized, 48-week, double-blind study was performed to investigate the safety and efficacy of 'high' in comparison to continued 'low' angiotensin converting enzyme inhibitor therapy in severe heart failure. Eighty-three patients (56 +/- 1.1 years; 69 men, 14 women) in New York Heart Association functional class III/IV on digoxin, furosemide and 'low' angiotensin converting enzyme inhibitors (captopril < or = 50 mg.day-1 or enalapril < or = 10 mg.day-1) were included. After a > or = 14 day run-in on 10 mg.day-1 enalapril, digitalis and furosemide, right heart catheterization at rest and exercise was performed. All patients presented with atrial pressure > 10 mmHg and/or pulmonary artery pressure > 35 mmHg, and/or cardiac index < 2.5 l.min-1.m-2 at rest. Patients then received enalapril 5 mg twice daily (n = 42), or 20 mg twice daily (n = 41) in random order. Thus, patients randomized to low doses of enalapril actually had no change in therapy from baseline to 48 weeks. Forty-three patients (52%) completed the study, 19 patients on the low dose and 24 patients on the high dose. Both dosages equally influenced survival with 15 (18%) deaths, eight on low dose and seven on high dose. After 48 weeks, functional capacity by New York Heart Association class improved more on the high dose than on the low dose (P = 0.04). In contrast, alterations in invasive haemodynamic variables at rest and exercise as well as maximal exercise capacity were comparable in both groups. Diastolic blood pressure decreased and the change between both groups was statistically significant (P = 0.01). Changes in plasma creatinine levels did not differ between high and low dose treatment and no patients had to be withdrawn because of deterioration in kidney function. With regard to neurohumoral activity, a tendency to a discrepant response to both treatments was observed with a blunted increase in noradrenaline on high versus low enalapril dose. Thus, high-dose enalapril treatment proved superior to low dose as regards symptomatology in severe heart failure after long-term treatment, despite similar effects on haemodynamics and on maximal exercise capacity.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1995

TATI (tumour-associated trypsin inhibitor) as a marker of ovarian cancer.

In ovarian cancer patients a 6 kDa polypeptide, the tumour-associated trypsin inhibitor (TATI), can occur at elevated concentrations in both urine and serum. In this study pretreatment serum levels of TATI (cut-off point 21 ng ml-1) and CA 125 (cut-off points 35 U ml-1 and 65 U ml-1) were determined in 152 patients with epithelial ovarian cancer (115 primary and 37 recurrent) and in 267 women with benign pelvic diseases. The data obtained were correlated with the tumor stage, histological type and tumour grade. Overall, TATI showed a sensitivity of 64% and a specificity of 75%. The sensitivity and specificity of CA 125 > 35 U ml-1 were both 80%. Corresponding values for CA 125 > 65 U ml-1 were 70% and 87%. The combination of the two markers increased the sensitivity to 91% (CA 125 > 35 U ml-1) and 86% (CA 125 > 65 U ml-1), while the specificity dropped to 61% and 68% respectively. TATI was clearly superior in mucinous carcinomas of the ovary, the rate of true-positive findings in these neoplasms was 67% vs 42% for CA 125 > 35 U ml-1 and 33% for CA 125 > 65 U ml-1. Unlike CA 125, TATI correlated well with tumour grade. The combination of the two markers had a higher negative predictive value, i.e. 93% (CA 125 > 35 U ml-1) and 90% (CA 125 > 65 U ml-1) respectively. It is concluded that, while TATI cannot replace CA 125 in the diagnosis of malignant epithelial carcinomas of the ovaries, it is a valuable additional marker in cases of mucinous carcinomas and in combination with CA 125.

Adult↗
PubMed1995

Prognostic value of prostate-specific antigen minimum after orchidectomy in patients with stage C and D prostatic carcinoma.

OBJECTIVE: To determine the significance of the minima of prostate-specific antigen (PSA) levels after orchidectomy in patients with advanced carcinoma of the prostate (stage C and D disease), to thereby discriminate patients who have a statistically significant difference in prognosis and thus individualize their adjuvant treatment. PATIENTS AND METHODS: A retrospective analysis of 50 patients (mean age 75.8 years) with extracapsular prostate cancer (58% stage C, 42% stage D disease) was performed. PSA measurement and clinical assessment were continued at 3-monthly intervals until there was evidence of clinical progression. The minimum values of PSA were determined, the patients grouped at intervals of 1 ng/mL and the groups compared statistically on the basis of disease progression. RESULTS: Serum PSA levels decreased in all patients to a minimum after 3-6 months. There was a statistically significant difference in the probability of, and time to, disease progression for PSA minima at 1 ng/mL and 10 ng/mL. Of the 13 patients in group 1 (with PSA minima < 1 ng/mL), 11 stayed in remission during a mean follow-up duration of 45.9 months. Of 25 patients in group 2 (with PSA minima between 1 and 10 ng/mL) 19 developed progression after a mean remission period of 16.7 months, while all 12 patients in group 3 (with PSA minima > 10 ng/mL) progressed after a mean remission period of 12.5 months. CONCLUSION: Post-orchidectomy PSA minima are an excellent prognostic factor with significant predictive value. While patients in group 1 tend to have a favourable prognosis after orchidectomy alone, group 2 and 3 patients need adjuvant treatment as early as possible. Group 3 patients, with their high probability of early progression, also form a uniform cohort for studies concerning new therapeutic modalities. If the PSA minimum was included in further examinations, the results of treatment should improve.

Aged↗
PubMed1994

Polyoma middle tumor antigen interacts with SHC protein via the NPTY (Asn-Pro-Thr-Tyr) motif in middle tumor antigen.

Polyomavirus middle tumor antigen (MT) transforms a large number of cell types by binding to and modulating the activities of cellular proteins. Previous genetic analysis defined in MT an independent motif, NPTY (Asn-Pro-Thr-Tyr), required for transformation. This report demonstrates that NPTY is required for interaction between MT and SHC protein, a Src homology 2 (SH2)-containing protooncogene product implicated in activating Ras via association with GRB2 protein. SHC is phosphorylated on tyrosine and associates with GRB2 in MT-transformed cells. These effects require an intact NPTY motif in MT. SHC immunoprecipitates from MT-transformed cells possess kinase activity that phosphorylates not only SHC and MT but also the 85-kDa subunit of phosphatidylinositol 3-kinase. This result suggests that a complex exists that contains, at a minimum, MT, Src family tyrosine kinases, phosphatidylinositol 3-kinase, and SHC.

3T3 Cells↗
PubMed1994

Different regulation of thymidine kinase during the cell cycle of normal versus DNA tumor virus-transformed cells.

We compared the cell cycle regulation of thymidine kinase (TK) after centrifugal elutriation in normal human and mouse cells (primary cells, diploid fibroblasts) with its expression in cells transformed with different DNA tumor viruses. Normal cells showed a rise of TK enzyme activity near the G1/S boundary, which peaked in S phase, and in G2 returned approximately to the level of G1. Conversely, in cells derived from viral transformation, TK activity remained high throughout S and G2 phases, although it was induced to a comparable extent at the onset of DNA replication. In addition, transformed cells exhibited much more enzyme activity during all phases of the cell cycle. The observed differences in expression were due neither to different rates of protein turnover nor to differences in enzyme stability. Enzyme activity was always totally paralleled by the protein level. In all normal cells, the pattern of TK mRNA variation during the cell cycle was similar to that of enzyme activity. In all transformed lines, however, mRNA levels were higher and did not fluctuate throughout the cell cycle. Recently we showed (Ogris et al., 1993) that the E2F binding site present in the TK promoter is a target for trans activation of the TK gene by polyoma virus large T antigen. Using cells expressing this antigen under the control of a hormone-inducible promoter, we were able to switch TK cell cycle expression from the normal to the transformed status. Obviously, DNA tumor viruses suppress transcriptional down-regulation of the endogenous DNA precursor pathway enzyme TK during the eukaryotic cell cycle, maybe to improve conditions for their own replication.

Animals↗
PubMed1994

Coordinated trans activation of DNA synthesis- and precursor-producing enzymes by polyomavirus large T antigen through interaction with the retinoblastoma protein.

Previously constructed Swiss mouse 3T3 fibroblasts producing polyomavirus large T antigen after addition of dexamethasone were used to study the transcriptional activation by the viral protein of five genes coding for enzymes involved in DNA synthesis and precursor production, namely, dihydrofolate reductase, thymidine kinase, thymidylate synthase, DNA polymerase alpha, and proliferating-cell nuclear antigen. It was found that all these genes, whose expression is stimulated at the G1/S boundary of the cell cycle after growth stimulation by serum addition, are coordinately trans activated when T antigen is induced in cells previously growth arrested by serum withdrawal. Cell lines carrying the information for a mutant form of large T antigen, in which a glutamic acid residue in the binding site for the retinoblastoma protein was changed into aspartic acid, were constructed to test the involvement of an interaction of T antigen with the retinoblastoma protein in this reaction. It was found that the mutated T protein is incapable of stimulating transcription of any one of the genes. The promoter of three of the genes (dihydrofolate reductase, thymidine kinase, and DNA polymerase alpha) unequivocally carries binding sites for transcription factor E2F, suggesting that complexes forming with this growth- and cell cycle-regulating transcription factor are the targets for T antigen. Although there is so far no evidence that thymidylate synthase and proliferating cell nuclear antigen are regulated via E2F, our data indicate that the retinoblastoma protein still is involved in the control of these genes. mRNA for E2F itself increases in amount at the G1/S border in serum-stimulated cells but not during polyomavirus T antigen-induced transcriptional activation of DNA synthesis enzymes in arrested cells.

3T3 Cells↗
PubMed1993

Plasma big endothelin-1 concentrations in congestive heart failure patients with or without systemic hypertension.

Plasma endothelin concentrations were evaluated in 53 chronic, congestive heart failure (CHF) patients with or without history of systemic hypertension, as well as in 9 with hypertension only and in 22 healthy control subjects. Plasma renin, aldosterone and atrial natriuretic peptide, as well as clinical and hemodynamic data were determined. In patients with CHF, big endothelin-1 was, independent of hypertension history, significantly greater than in hypertensive patients with normal cardiac function and in control subjects (both p < 0.0001). Patients with severe CHF had significantly greater big endothelin-1 values than did those with moderate CHF. During 12-month follow-up, 11 patients with CHF underwent heart transplantation, and 9 died; these patients had significantly greater big endothelin-1 concentrations than did the 33 clinically stable patients (p < 0.001). Big endothelin-1 and atrial natriuretic peptide correlated with right atrial pressure, pulmonary capillary wedge pressure, left ventricular ejection fraction, effort capacity and severity of CHF (New York Heart Association functional class).

Adult↗
PubMed1993

99mTc-DTPA aerosol for same-day post-perfusion ventilation imaging: results of a multicentre study.

A multicentre study was performed in an attempt to evaluate a submicronic technetium-99m diethylene triamine penta-acetic acid aerosol generated by a newly developed delivery system, the aerosol production equipment (APE nebulizer), for same-day post-perfusion ventilation imaging in patients with clinically suspected pulmonary embolism. Quantitative comparison between the DTPA aerosol and krypton gas demonstrated a close correlation with respect to regional pulmonary distribution of activity and peripheral lung penetration (n = 14, r = 0.94, P < 0.001 and r = 0.75, P < 0.0025, respectively). In 169 consecutive patients, DTPA aerosol images performed immediately following perfusion (inhalation scan I) were compared to those carried out on the next day (inhalation scan II) with respect to image quality and assessment of perfusion-ventilation matches or mismatches. Agreement between inhalation scans I and II with respect to perfusion defects matched or mismatched to ventilation was found in 166/169 (98%) studies. The image quality of inhalation scan I was equal to that of scan II in 72%; inhalation scan I was superior in 11% of cases, while scan II was superior in 17%. This submicronic 99mTc-labelled DTPA aerosol is well suited for fast same-day post-perfusion ventilation imaging in patients with clinical suspicion of pulmonary embolism.

Aerosols↗
PubMed1993

Clinical and neurohumoral response of patients with severe congestive heart failure treated with two different captopril dosages.

Although angiotensin converting enzyme inhibitor therapy is an established approach in the treatment of chronic heart failure, the required dosage remains unclear. This open 6 month study investigated the influence of different captopril dosages on the clinical course and neurohumoral activity of patients with severe heart failure (left ventricular ejection fraction < or = 20%). Eighty-five patients in New York Heart Association class II-IV despite treatment with digitalis, diuretics, and captopril (mean dose +/- SEM 28 +/- 2 mg.day-1 at baseline) for > or = 3 months received either 'low dose' captopril (< 75 mg.day-1, mean 32 +/- 2 mg.day-1; n = 46) or 'high dose' captopril (> or = 75 mg.day-1, mean 99 +/- 4 mg.day-1; n = 39) during the follow-up period. Both groups were comparable in clinical, haemodynamic and neurohumoral parameters at baseline. Functional state improved significantly only in the high dose group (P < 0.0001). Of 31 low dose and 20 high dose patients considered as heart transplantation candidates at baseline, 21 low dose and only six high dose patients remained on the waiting list (P < 0.0001). In patients in the low dose group, eight deaths were observed (P < 0.001). Seven patients remained on low dose captopril due to adverse effects. The initially elevated plasma levels of aldosterone and atrial natriuretic peptide decreased significantly only in high dose patients (P < 0.01). Renin increased significantly in both groups. These observations underline the necessity of suppressing neurohumoral overactivation with adequate doses of captopril reflected by sequential humoral plasma determination.

Aldosterone↗
PubMed1993

A binding site for transcription factor E2F is a target for trans activation of murine thymidine kinase by polyomavirus large T antigen and plays an important role in growth regulation of the gene.

The promoter of the murine thymidine kinase gene contains a binding site for transcription factor E2F. Using cell lines (3T3-LT) conditionally expressing polyomavirus large T antigen from a hormone-responsive promoter and reporter gene constructs carrying the thymidine kinase promoter with intact or mutated E2F sites, we show that this E2F site is the target for trans activation by the viral protein. Transcription of the growth-regulated endogenous thymidine kinase gene can be activated in serum-starved, quiescent 3T3-LT cells by induction of T antigen. Activation of transcription from the thymidine kinase promoter requires an intact binding site for the retinoblastoma protein in the T antigen. The same promoter region was furthermore shown to play a major role in growth regulation of the gene. As several other DNA synthesis enzymes also carry E2F binding sites in their promoters, our observations suggest a common mechanism of growth regulation of these genes and that they all might be targets for trans activation by DNA tumor virus proteins.

3T3 Cells↗
PubMed1993

Endogenous opioid system during inspiratory loading in patients with type I diabetes.

To investigate the activity of the endogenous opioid system in patients with insulin-dependent diabetes mellitus during ventilatory stress situations, we measured plasma beta-endorphin levels in six male and five female diabetic patients breathing against fatiguing inspiratory resistive loads. The patients had to generate with each inspiration an esophageal pressure (Pes) 80% of maximum until they were exhausted and could no longer develop target Pes. The loaded breathing run was repeated three times with a 1-min interval between each run. Duty cycle, tidal volume, and breathing frequency were constant in all tasks. For each run plasma beta-endorphin levels were measured, inspiratory effort sensation assessed using a modified Borg scale, and inspiratory muscle endurance evaluated by the length of time the task could be maintained (Tlim). A group of 11 sex-, age-, height-, and weight-matched healthy individuals served as control subjects. Tlim was significantly lower in the diabetic patients. Evaluating respiratory effort during the three test runs in control subjects at a time corresponding to the break point of loaded breathing in patients showed significantly lower Borg ratings in the control group than in the patient group. Baseline plasma beta-endorphin was significantly lower in the diabetic patients (10.6 +/- 2.1 versus 27.0 +/- 4.2 pg/ml, p < 0.01). Additionally, whereas resistive loaded breathing caused a further increase in plasma beta-endorphin concentration in the control group (p < 0.005), absolutely no increase was found in the diabetic patients. We conclude that the endogenous opioid system in insulin-dependent diabetic patients does not respond to stress caused by breathing against fatiguing inspiratory resistive loads.

Adult↗
PubMed1993

Effect of clodronate treatment on bone scintigraphy in metastatic breast cancer.

Because of their high affinity for bone, bisphosphonates are used both in the treatment of benign and malignant bone disease and in radiopharmaceutical bone imaging. A prospective study was undertaken to evaluate whether intravenous clodronate (dichloromethylene bisphosphonate) therapy might affect the results of bone scintigraphy with 99mTc-labeled methylene diphosphonate (MDP). In 11 female patients with breast cancer and metastatic bone disease, quantitative bone scans were obtained using a region of interest (ROI) method on Days 0 and 22. After intravenous clodronate therapy from Day 1 to Day 21, all metastatic bone lesions were still detectable, and median ROI ratios did not differ to a statistically significant extent from baseline values. Serum calcium levels decreased (p = 0.0449), whereas parathyroid hormone concentrations showed an increase (p = 0.0053). Mean serum levels of creatinine, inorganic phosphorus, osteocalcin, gamma glutaminyl-transpeptidase and alkaline phosphatase remained unchanged. However, a more than twofold rise in the serum activity of alkaline phosphatase was measured in three patients. We conclude that 3 wk of intravenous clodronate treatment did not impair the sensitivity of 99mTc-MDP bone scintigraphy in detecting bone lesions in patients with metastatic breast cancer.

Bone Neoplasms↗
PubMed1993

Distinct amounts of polyomavirus large T antigen are required for different functions of the protein.

Many cellular and some virally coded proteins regulating key events in higher cells have been found to be multifunctional. One example of such a protein is the polyomavirus large T antigen, which is involved not only in viral DNA replication and gene expression but also in the induction of the S phase in host cells, in the immortalization of various cell types and in the transactivation of some cellular genes. We recently constructed cell lines in which T antigen was synthesized under the control of a hormone-inducible promoter. This allowed us to induce different concentrations of the protein in the cell and to investigate the levels of large T antigen required for replication, S-phase induction and transactivation of a growth-regulated promoter. We found that significantly higher concentrations of large T antigen are required for the replication function of the protein than for either S phase induction or transactivation. These observations for the first time provide clear evidence for a potential regulation of different functions of a pleiotropic protein by the amount of that protein produced in the cell.

3T3 Cells↗
PubMed1992

Polyomavirus large and small T antigens cooperate in induction of the S phase in serum-starved 3T3 mouse fibroblasts.

The induction of an S phase in the host cell is a prerequisite for the lytic replication cycle of polyomavirus. This function was attributed to proteins coded for by the early region of the viral DNA, the T antigens. A consideration of the role of the T antigens in the initiation of a mitogenic response of the host cell has to take into account the recent discovery that virus adsorption is sufficient to induce the synthesis of proteins which are known to appear early after quiescent cells are stimulated by the addition of serum, namely fos, jun, and myc (J. Zullo, C.D. Stiles, and R.L. Garcea, Proc. Natl. Acad. Sci. USA 84:1210-1214, 1987; G. M. Glenn and W. Eckhart, J. Virol. 64:2193-2201, 1990). This induction is followed by an initiation of DNA synthesis. It is therefore important to dissociate the effects of the T antigens on the host cell from those of virus adsorption. To do so, we used dexamethasone-regulated versions of the large and small T antigens of polyomavirus stably integrated into the genome of Swiss 3T3 cells to study their function in S-phase induction. When the production of the large or small T antigen in serum-starved 3T3 mouse fibroblasts was activated, only a small fraction of cells was able to leave G0/G1 despite the synthesis of considerable amounts of the respective T antigen. Activation of both T antigens within the same cell, on the other hand, resulted in S-phase induction in a notable percentage of cells, suggesting that the two proteins cooperate in this activity. Polyomavirus T antigens appear to bypass the pathway of growth regulation involving the activation of c-fos. These results are discussed in relation to other known functions of the two virally coded proteins.

3T3 Cells↗
PubMed1991

Rapid changes of atrial natriuretic peptide concentration during percutaneous transluminal coronary angioplasty.

In 34 patients undergoing routine coronary angioplasty, concentrations of atrial natriuretic peptide (ANP), plasma renin (PR), and plasma aldosterone (PA) were estimated before, during, and after vessel occlusion and were correlated with hemodynamic changes. For the group as a whole, averaged right atrial pressure rose significantly (p less than 0.001) from 4.4 +/- 1.8 mm Hg at baseline to 6.7 +/- 3.0 mm Hg during vessel occlusion, and average right atrial ANP concentrations increased significantly (p less than 0.005) from 50.1 +/- 18.8 pg/ml to 59.7 +/- 21.4 pg/ml during balloon inflation. Data analysis of subgroups did not show any differences in right atrial pressure elevations between patients with left anterior descending artery (LAD) or right coronary artery (RCA) disease; ANP elevation was significant only in patients with LAD occlusion (p less than 0.001). In individual patients no statistically significant correlations were found to be present between changes in right atrial pressures and changes in atrial ANP concentrations. During vessel occlusion, PR dropped from 0.86 +/- 1.11 ng/ml/hr to 0.65 +/- 0.85 ng/ml/hr (p less than 0.001) in all patients, and PA decreased from 63.0 +/- 50.9 ng/ml to 52.2 +/- 43.4 ng/ml (p less than 0.01). Our data support the concept that, although an increase in right atrial pressure leads to ANP release in the majority of patients, atrial pressure and stretch are not the only regulatory factors of ANP release in humans.

Aldosterone↗
PubMed1990

Bidirectional promoter activity of the 5' flanking region of the mouse thymidine kinase gene.

The 5' flanking region of the gene coding for cytoplasmic thymidine kinase (TK) in the mouse (a total of 490 bp upstream of the initiation codon) was tested for promoter activity using the chloramphenicol acetyltransferase gene as reporter. It was found that the region can be divided into two parts, one of which carries promoter activity in the direction of TK, whereas the 5'-half has promoter activity in the opposite direction. A fragment of 140 bp was sufficient for growth-dependent promoter activity in the direction of TK, although about 100 bp further upstream, enhanced the activity. Expression from the divergent promoter was independent of cell growth.

Animals↗