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Biomedical subjects

A Hartmann

Publications and source records attributed to A Hartmann.

At least 235 records · Page 13Linked to original sources
PubMed1997

G proteins in Ustilago maydis: transmission of multiple signals?

In the phytopathogenic fungus Ustilago maydis, cell fusion is governed by a pheromone signalling system. The pheromone receptors belong to the seven transmembrane class that are coupled to heterotrimeric G proteins. We have isolated four genes (gpa1 to gpa4) encoding alpha subunits of G proteins. Gpa1, Gpa2 and Gpa3 have homologues in other fungal species, while Gpa4 is novel. Null mutants in individual genes were viable and only disruption of gpa3 caused a discernible phenotype. gpa3 mutant strains were unable to respond to pheromone and thus were mating-deficient. A constitutively active allele of gpa3 (gpa3(Q206L)) was generated by site-directed mutagenesis. Haploid strains harbouring gpa3(Q206L) were able to mate without pheromone stimulation, indicating that Gpa3 plays an active role in transmission of the pheromone signal. Surprisingly, Gpa3 is also required for pathogenic development, although pheromone signalling is not essential for this process.

Calcium-Calmodulin-Dependent Protein Kinases↗
PubMed1997

The contribution of cytotoxicity to DNA-effects in the single cell gel test (comet assay).

We evaluated genotoxic and cytotoxic effects of the three non-mutagenic and non-carcinogenic compounds p-nitrophenol, D-menthol and sodium N-lauroyl sarcosine which have previously been shown to induce DNA double strand breaks (DNA dsb) secondary to induced cytotoxicity. We tested whether genotoxic effects in the alkaline single cell gel test (comet assay) may be confounded by cytotoxicity-induced DNA dsb. Cell viability was determined at the end of the treatment using the fluorescein diacetate/ethidium bromide-assay and plating efficiency was used as an indicator of long-term survivability. Experiments with V79 Chinese hamster cells and human white blood cells revealed negative results in the comet assay despite strong cytotoxic effects. However, cells with extremely fragmented DNA ('clouds') occurred but were excluded from the evaluation under the principle that they represent dead cells. We also noticed a significant loss of cells at cytotoxic concentrations that might be attributed to the induction of highly fragmented DNA which is lost during electrophoresis. Since the comet assay allows the determination of DNA effects on the single cell level, a confounding effect of cytotoxicity on test results can be avoided.

Animals↗
PubMed1997

Biological degradation of cyclophosphamide and its occurrence in sewage water.

The mutagenic and cancerogenic antineoplastic agent cyclophosphamide (CP) is released into sewage water by cancer patient excretion. To assess the biological degradability of CP two standardized test systems, the Zahn-Wellens/EMPA test (OECD 302B) and a laboratory scale sewage treatment plant, were used. In both test systems the agent exhibited only poor degradability. To verify the expected occurrence of CP in hospital sewage, water samples were analyzed for CP with GC/MS after enrichment by solid-phase extraction. CP could be detected in concentrations ranging from 20 ng/L to 4.5 micrograms/L. The occurrence of the agent could also be proved in samples from the influent and the effluent of the communal sewage treatment plant into which the hospital's sewage water is shed. Concentrations ranged from 7 to 143 ng/L. In an attempt to assess the contribution of CP to the genotoxicity detected in hospital waste water in a recent study, the effects of CP in the umuC test, a bacterial genotoxicity assay, were investigated. However, no genotoxic effects of CP were found up to concentrations of 1 g/L.

Antineoplastic Agents, Alkylating↗
PubMed1997

[Association of hypertension and diabetes mellitus with microangiopathic cerebral infarct patterns].

OBJECTIVE: To test the hypothesis of a positive association of hypertension and diabetes mellitus with cerebral small-vessel disease infarct patterns. METHODS: Using a prospective stroke database, the 152 patients with computertomographic signs of small-vessel disease (lacunes and/or leucoaraiosis)--including as a subgroup of 85 cases with multiple lacunes and/or leucoaraiosis-were compared with 106 patients featuring pial artery infarcts. Statistical analyses of the rates of hypertension and diabetes included univariate tests (odds ratios) and a logistic regression model comprising the additional variables hypercholesterolemia, cigarette smoking, carotid stenosis, atrial fibrillation, and left cardiac thrombus. RESULTS: Multivariate testing revealed a significant association of hypertension and diabetes with multiple lacunar infarcts and/or leucoaraiosis (hypertension: odds ratio 2.0; 95% confidence interval 1.04-3.7; diabetes: odds ratio 1.9; 95% confidence interval 1.01-3.8), whereas for the total group of patients with small-vessel disease lesions no such effect was found. Among the other tested variables, only atrial fibrillation/left cardiac thrombus showed a significant negative association (odds ratio 0.5; 95% confidence interval 0.2-0.9) with lacunes/leucoaraiosis. CONCLUSION: Independent of other risk factors and other possible causes of stroke, both hypertension and diabetes appear to be strong determinants of multiple lacunar infarcts and/or leucoaraiosis.

Adult↗
PubMed1997

[Progressive cerebral parenchyma damage caused by recurrent arterial hypotension].

To date clinical and experimental investigations have focused on acute strokes and complete infarctions. Histological and immunological staining in animal experiments and improved imaging techniques in patients suggest that selective or incomplete infarction is a common pathomechanism. Incomplete infarction can manifest as laminar necrosis at autopsy and as leukoaraiosis in imaging studies. An important mechanism in the genesis of leukoaraiosis is vascular pathology of the long penetrating arteries of the deep white matter combined with episodes of decreased perfusion pressure or hypotension. We demonstrate that the cumulative effect of repetitive, moderate hypotensive episodes on cognitive performance or cerebral tissue has not been adequately studied and appreciated.

Animals↗
PubMed1997

Variations of segmental endothelium-dependent and endothelium-independent vasomotor tone after cardiac transplantation (qualitative changes in endothelial function).

Endothelial dysfunction is a common phenomenon after cardiac transplantation. However, qualitative differences in endothelial vasoregulation at different coronary segments and at different postoperative times have rarely been explored. To uncover the functional variations of endothelium responses we infused the endothelium-dependent vasodilator acetyl-choline (50 micrograms) followed by the endothelium-independent vasodilator 3-morpholinosydnonimine (SIN-1) (1 mg; 16 patients) or nitroglycerin (0.3 mg; 14 patients) sequentially into the left coronary artery. We investigated the responses of 120 nonstenotic coronary segments (proximal and distal left anterior descending and right circumflex coronary arteries) in 30 patients with quantitative angiography (group 1: 13 patients, 12 +/- 1 months after cardiac transplantation; group 2: 17 patients, 55 +/- 3 months after cardiac transplantation). Continuous-flow measurement was performed to exclude significant reduction of microvascular response influencing epicardial dilation. Five responses to acetylcholine administration followed by nitrates were observed. On the one end of the spectrum, segments dilate to acetylcholine administration with no further dilation to exogenous nitric oxide, indicating completely preserved endothelial function. On the other end, segments constrict to acetylcholine with no change after endogenous nitric oxide, reflecting a defective endothelial and defective smooth muscle function. The different patterns of coronary vasomotor lone responses to endogenous nitric oxide followed by exogenous nitric oxide represent different degrees of endothelial function after cardiac transplantation. In addition, the functional assessment of endothelial integrity shows qualitative time-dependent differences between proximal and distal coronary parts. The existence of coronary segments with functioning endothelium indicates that the latter is not diffusely disturbed in all cardiac transplant recipients and that the endothelial damage is perhaps not irreversibly lost.

Acetylcholine↗
PubMed1997

Successful thrombolysis after prosthetic pulmonary valve obstruction under aspirin monotherapy.

In a 22-year-old woman with recent onset of left-sided chest pain and exertional dyspnea, echocardiography revealed obstruction of a St. Jude Medical bileaflet prosthetic valve (size 23 mm) in the pulmonary position. Oral anticoagulation had been replaced for the previous 7 years by aspirin as the sole antithrombotic treatment. The valve had been inserted 16 years ago for pulmonary atresia. Valve function was restored by systemic application of 9 million units of urokinase.

Adult↗
PubMed1997

The molecular epidemiology of p53 gene mutations in human breast cancer.

The P53 tumor-suppressor gene is an advantageous tool for analyzing the molecular epidemiology of cancer. We describe the utility of the P53 gene as a 'mutagen test' and a prognostic indicator in breast cancer. Aspects of study design and methodology are discussed. Two major conclusions emerge: (1) there is an extraordinary diversity of mutational patterns among cohorts, hinting that the unique biology of mammary cells results in exposure to high doses of a diversity of ingested lipophilic mutagens; and (2) mutations in the P53 gene predict poor outcome in breast cancer.

Breast Neoplasms↗
PubMed1997

Hypertension prophylaxis with omega-3 fatty acids in heart transplant recipients.

OBJECTIVES: This study sought to determine whether omega-3 fatty acids act as hypertension prophylaxis in heart transplant recipients and have an impact on vascular reactivity. BACKGROUND: Cyclosporine-induced hypertension is probably related to endothelial dysfunction. Suggested vasodilatory mechanisms of omega-3 fatty acids may therefore be particularly beneficial in heart transplant recipients. METHODS: Heart transplant recipients were randomized to receive either 4 g of omega-3 fatty acids (treatment group, n = 14) daily or corn oil (placebo group, n = 14) from the fourth postoperative day. Twenty-four hour blood pressure monitoring was performed at day 12 and 1,2,3 and 6 months postoperatively. Microvascular endothelium-dependent vasodilation, evaluated by skin laser Doppler perfusion measurements of postocclusive reactive hyperemia, was determined preoperatively and at the end of the study. RESULTS: With comparable characteristics at the time of randomization, blood levels of cyclosporine did not at any point differ between the groups. After 6 months, systolic blood pressure decreased 2 +/- 4 mm Hg (mean +/- SEM) in the treatment group and increased 17 +/- 4 mm Hg in the placebo group (p < 0.01), whereas diastolic blood pressure increased 10 +/- 3 and 21 +/- 2 mm Hg (p < 0.01), respectively. The decrease in systolic blood pressure was inversely proportional to increases in concentrations of serum eicosapentaenoic and docosahexaenoic acid (p = 0.01). After 6 months, five patients in the treatment group and nine in the placebo group needed additional antihypertensive treatment. Although the endothelial-dependent phase of the reactive hyperemic response remained unchanged in the treatment group, it decreased significantly in the placebo group. CONCLUSIONS: Postoperative daily administration of 4 g of omega-3 fatty acids in heart transplant recipients is effective as hypertension prophylaxis, depending on increases in serum eicosapentaenoic and docosahexaenoic acids. Preservation of microvascular endothelial function, demonstrated by a more pronounced response to forearm skin ischemia in the treatment group, may contribute to the hypotensive role of omega-3 fatty acids.

Blood Pressure↗
PubMed1997

Modeling psychotherapy outcome as event in time: an application of multistate analysis.

Standard survival analysis (SA) and multistate analysis (MSA) are methods for modeling categorical psychotherapy outcome events over time. The underlying principles, mathematical details, and indications for using each technique are discussed, and data from an anorexia nervosa psychotherapy outcome study comparing psychodynamic psychotherapy with psychodynamic psychotherapy plus cognitive-behavioral techniques are used to illustrate the use of SA and MSA techniques. MSA includes multiple competing outcome states in a single model. A single MSA model includes reaching target weight and treatment dropout before reaching target weight as competing events. It is concluded that MSA is an informative analytic technique in the domain of psychotherapy research.

Adult↗
PubMed1997

Characterization and application of a strain-specific monoclonal antibody against the rhizosphere bacterium Azospirillum brasilense Wa5.

A hybridoma cell line producing a rat monoclonal antibody (MAb Bo-33) directed against lipopolysaccharide of Azospirillum brasilense Wa5 has been established and characterized. Whole bacteria were used as immunogens. The number of antigens per cell was about 1500. The number of antigens per cell of reisolates from the rhizosphere of what was similar to the number of antigens of bacteria cultivated in rich medium. The sensitivity of detection using MAb Bo-33 was about 100 bacteria/ml. Therefore, the MAb was suitable for in situ immunofluorescence detection and a sensitive direct quantification of Azospirillum brasilense Wa5 in rhizosphere extracts.

Animals↗
PubMed1997

Serum amyloid A protein is a clinically useful indicator of acute renal allograft rejection.

BACKGROUND: Early diagnosis of acute rejection after renal transplantation is important. There is evidence that measurement of the acute phase proteins, C-reactive protein (CRP) and serum amyloid A protein (SAA) is helpful. METHODS: In 64 consecutive patients, CRP was measured in a routine clinical system (Technicon RA1000, Bayer) and SAA in a new sensitive automated immunoassay on the Abbott IMx instrument, daily or on alternate days for 30 days after renal transplantation. RESULTS: Patients all received triple immunosuppression with cyclosporin, azathioprine, and prednisolone and all mounted a post-surgical acute phase response of SAA, but the CRP response was reduced or absent. Serum creatinine rose significantly in 36 patients, leading to treatment for first rejection. Thirty of these episodes were confirmed rejection, three were definitely not and three were uncertain. SAA. normally < 10 mg/l, rose to more than 100 mg/l in all episodes except when rejection was definitely absent. In six cases SAA rose above 100 mg/l 1-3 days before the rise in creatinine leading to antirejection therapy, and only twice did creatinine rise 1 day before SAA. In contrast, CRP responses to rejection were modest or absent. In four patients there were SAA and CRP responses unrelated to rejection, three associated with intercurrent infection and one with administration of antilymphocyte globulin. There were also two unexplained isolated spikes of SAA. CONCLUSIONS: SAA is a sensitive marker of acute renal allograft rejection. It is not specific, but the differential behaviour of CRP in patients receiving cyclosporin helps to distinguish infection from rejection. Availability of rapid assays for these analytes should facilitate management of renal allograft recipients.

Acute Disease↗
PubMed1997

Pulse-dosing and conventional application of doxepin: effects on psychopathology and hypothalamus-pituitary-adrenal (HPA) system.

It has been shown that a single pulse-dosing (PD) dose of clomipramine improves depressive symptoms. However, so far PD and conventional (CONV) application of antidepressants have never been directly compared for an extended period. We performed a double-blind study of PD and CONV application of doxepin (DOX) in depressed patients. After a 1-week placebo treatment, nine parents in the PD group received 250 mg of DOX every 6 days and placebo on the other days until day 39. Ten patients in the CONV group received increasing dosages of DOX until day 7 and 250 mg DOX on the other days for 39 days. Three dexamethasone (DEX)-suppression/corticotropin-releasing hormone (CRH)-stimulation tests were completed: (1)during the initial placebo period; (2)on day 9; and (3)on day 21. In the PD group, scores on the Hamilton Rating Scale for Depression (HAM-D) differed from baseline only after day 36 (17.1 +/- 7.0 vs. 22.7 +/- 2.8, p < 0.03). In the CONV group, however, HAM-D scores improved significantly after 2 days (22.8 +/- 7.2 vs. 26.5 +/- 5.7, p < 0.02) and continued to improve until day 39 (7.3 +/- 5.8). From day 25 to 39, there were significant differences between the HAM-D scores of the two groups. In the PD group, the decline of cortisol after DEX pretreatment was nonsignificant (NS) at both follow-up test occasions (35.9 +/- 40.7 vs. 24.0 +/- 20.7 vs. 23.6 +/- 26.6 micrograms/mL). In the CONV group, a significant decrease was observed at the second test (61.8 +/- 61.9 vs. 10.7 +/- 4.2 vs. 19.8 +/- 19 micrograms/mL, p < 0.05, respectively, NS). The area-under-the-curve cortisol response after CRH was attenuated in the PD group (5,667 +/- 2,910 vs. 1,883 +/- 2,178 vs. 2,239 +/- 2,583 [arbitrary unit], p < 0.01, respectively, p < 0.01) and in the CONV group (5,710 +/- 4,734 vs. 1,267 +/- 2,053 vs. 445 +/- 1,016 [arbitrary unit], NS, respectively, p < 0.02. We conclude that CONV application of DOX is clinically superior compared with PD and that both modes of application have attenuating effects on hypothalamus-pituitary-adrenal system activity.

Adult↗
PubMed1997

Possibilities for therapeutic drug monitoring of azathioprine: 6-thioguanine nucleotide concentrations and thiopurine methyltransferase activity in red blood cells.

The objectives of this study were to establish monitoring of azathioprine (AZA) treatment in renal allograft recipients by red blood cell (RBC) 6-thioguanine nucleotide (6-TGN) measurements and to characterize the variability of RBC thiopurine methyltransferase (TPMT) activity and the effects on 6-TGN levels and the incidence of rejection episodes. In 82 renal allograft recipients, the effect of standard AZA dosage (3 mg/kg tapered to 1 mg/kg) was compared with higher dosages (3 mg/kg for several days) under 6-TGN monitoring. The authors measured TPMT in these patients and in a group not receiving AZA. The authors did not find an inverse correlation between RBC TPMT activity and 6-TGN concentrations, and baseline TPMT activity did not predict the incidence of rejection episodes The slight increase in RBC TPMT activity after transplant was associated with the use of furosemide rather than AZA; in the five patients receiving furosemide for less than 10 days, TPMT activity declined. The higher AZA dosage in the 6-TGN monitored group was not sufficient to increase RBC 6-TGN to target levels (100 to 200 pmol/8 x 10(8) RBC); median 6-TGN levels were similar in the two groups, as was the incidence of rejection episodes. Based on these findings, the authors suggest that higher dosages be studied in conjunction with 6-TGN monitoring, to explore the possibilities for therapeutic improvements.

Adolescent↗