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Biomedical subjects

A Hartmann

Publications and source records attributed to A Hartmann.

At least 307 records · Page 17Linked to original sources
PubMed1995

The contribution of excision repair to the DNA effects seen in the alkaline single cell gel test (comet assay).

The alkaline single cell gel test (SCG test or comet assay) was used to study the contribution of excision repair activity to the observed DNA effect after mutagen treatment. The cytotoxicity and genotoxicity of UV-irradiation and the chemical mutagens 4-nitroquinoline-1-oxide (4NQO), benzo[a]pyrene (BP) and 7,12-dimethyl-benz[a]anthracene (DMBA) were compared in a normal human cell line (MRC5CV1) and an excision-deficient xeroderma pigmentosum (XP) cell line (XP12ROSV). The XP cells showed increased cell killing after treatment with all mutagens tested, but did not show a clear increase in DNA migration in the comet assay. DNA effects in MRC5 cells were strongly enhanced by the repair inhibitor aphidicolin (APC), while under the same experimental conditions, APC had no effect on the XP cell line. The enhancing effect of APC on DNA migration in MRC5 cells and the lack of effects in XP cells indicate that the induced DNA effects of 4NQO, BP and DMBA in the comet assay mainly represent the activity of an excision repair process.

4-Nitroquinoline-1-oxide↗
PubMed1995

Contrasting effects of angiotensin converting inhibitor and alpha-1-antagonist on albuminuria in insulin-dependent diabetes mellitus patients with nephropathy.

OBJECTIVE: The main aim of this study was to examine the effects of an angiotensin converting inhibitor, enalapril, and an alpha-1 (alpha-1) antagonist, doxazosin, on albumin excretion, renal haemodynamics and tubular function in insulin-dependent diabetes mellitus patients with nephropathy. DESIGN: The study consisted of a four-week run-in period, a four-week active treatment period, a four-week wash-out period and a second four-week active treatment period. SETTING: The study was performed in the out-patient clinic at a university hospital. SUBJECTS: Ten patients with insulin dependent diabetes mellitus with macroalbuminuria (> 200 micrograms min-1), mild to moderate hypertension (diastolic blood pressure 85-115 mmHg) and serum creatinine level below 200 mumol L-1 were included in the study. MAIN OUTCOME MEASURES: The effect of the drugs on albumin and total protein excretion, beta-2-microglobulin, proximal tubular enzyme markers and renal haemodynamics. RESULTS: Systolic and diastolic blood pressure were equally reduced by both drugs. Enalapril reduced albumin excretion from 1090 +/- 281 micrograms min-1 to 742 +/- 246 micrograms min-1 (P < 0.01) and total protein excretion from 2.0 +/- 0.4 g per 24 h to 1.3 +/- 0.4 per 24 h whereas doxazosin was without effect. Glomerular filtration rate and effective renal plasma flow were unchanged by either drug. Doxazosin increased filtration fraction from 0.21 +/- 0.02 to 0.23 +/- 0.01 (P < 0.05). The urinary excretion of the proximal enzyme markers N-acetyl-beta-glucosaminidase and alkaline phosphatase were elevated as well as urinary excretion of beta-2-microglobulin. However, neither the excretion of beta-2-microglobulin nor the enzyme markers were affected by either drug. CONCLUSIONS: Enalapril, but not doxazosin, reduces albuminuria in insulin dependent diabetes mellitus patients with nephropathy. The drugs exert differential effects on renal haemodynamics.

Adult↗
PubMed1995

In Situ Localization of Azospirillum brasilense in the Rhizosphere of Wheat with Fluorescently Labeled, rRNA-Targeted Oligonucleotide Probes and Scanning Confocal Laser Microscopy.

The colonization of wheat roots by Azospirillum brasilense was used as a model system to evaluate the utility of whole-cell hybridization with fluorescently labeled, rRNA-targeted oligonucleotide probes for the in situ monitoring of rhizosphere microbial communities. Root samples of agar- or soil-grown 10- and 30-day-old wheat seedlings inoculated with different strains of A. brasilense were hybridized with a species-specific probe for A. brasilense, a probe hybridizing to alpha subclass proteobacteria, and a probe specific for the domain Bacteria to identify and localize the target bacteria. After hybridization, about 10 to 25% of the rhizosphere bacteria as visualized with 4(prm1),6-diamidino-2-phenylindole (DAPI) gave sufficient fluorescence signals to be detected with rRNA-targeted probes. Scanning confocal laser microscopy was used to overcome disturbing effects arising from autofluorescence of the object or narrow depth of focus in thick specimens. This technique also allowed high-resolution analysis of the spatial distribution of bacteria in the rhizosphere. Occurrence of cells of A. brasilense Sp7 and Wa3 was restricted to the rhizosphere soil, mainly to the root hair zone. C-forms of A. brasilense were demonstrated to be physiologically active forms in the rhizosphere. Strain Sp245 also was found repeatedly at high density in the interior of root hair cells. In general, the combination of fluorescently labeled oligonucleotide probes and scanning confocal laser microscopy provided a very suitable strategy for detailed studies of rhizosphere microbial ecology.

Journal Article↗
PubMed1995

Novel pattern of P53 mutation in breast cancers from Austrian women.

Since mutagens produce an extraordinary diversity of mutational patterns, differential mutational exposures among populations are expected to produce different patterns of mutation. Classical epidemiological methods have been successful in implicating specific mutagens in cancers such as those of lung and skin in which one mutagen predominates. In breast cancer, however, no mutagens have been implicated in an unequivocal manner. In an attempt to facilitate epidemiological studies, we have been studying the pattern of p53 gene mutations in breast cancers from multiple populations with high and low breast cancer incidences. We previously reported that breast cancers from Midwest United States, predominantly rural Caucasian women, have a different pattern of p53 gene mutation from populations of Western European women. Herein, we analyze patterns of p53 mutations from Graz, Austria, another population with a high incidence of breast cancer. Among the 60 Austrian breast cancers analyzed, 14 (23%) have a p53 gene mutation in exons 5-9 or in adjacent splice junctions. Analysis of the patterns of mutation shows differences between the "Western European" profile and the Austrian and Midwest United States groups (P = 0.027 and 0.024, respectively). The Austrian pattern is characterized by a high frequency of A:T-->T:A transversions (P = 0.006). The presence of distinct patterns of mutation among the limited number of analyzed populations of Western European origin supports the idea that differential mutagenic exposure and/or genetic differences contribute to breast cancer mutagenesis among geographically distinct Caucasians of Western European origin.

Aged↗
PubMed1995

Rapid and efficient screening for p53 gene mutations by dideoxy fingerprinting.

Dideoxy fingerprinting (ddF) is an efficient method for detecting single base and other sequence changes in PCR-amplified DNA segments. This screening method is a hybrid between single-strand conformation polymorphism analysis (SSCP) and Sanger dideoxy sequencing. It involves a Sanger sequencing reaction with one dideoxynucleotide followed by non-denaturing gel electrophoresis. We are using ddF to screen for mutations in the p53 tumor suppressor gene in primary breast cancers. ddF detected more than 100 mutations in different regions of the gene, including all types of single-base mutations and microdeletions/microinsertions of various sizes. Furthermore, ddF reliably detected heterozygous mutations, if the region of interest was screened in both directions. In a blinded, prospective study, ddF detected all 25 mutations within exons 4-10 and adjacent flanking intronic regions previously found by direct sequencing. ddF was also useful in scoring two common polymorphisms within the p53 gene. Guidelines for preventing false-positive and false-negative results are summarized.

Breast Neoplasms↗
PubMed1995

[High dosage acetylsalicylic acid administration for prevention of acute cerebral ischemia].

6 studies with a placebo-controlled, double blind, randomized protocol on the effect of acetylsalicylic acid (ASA) in a dosage of higher than 100 mg/day have been published. The preventive effect for TIA was obvious without a significant difference between males and females. The effect on secondary cerebral ischemic attacks after completed infarcts has not been sufficiently proven with the ASA. The preventive effect for cerebral ischemic attacks in normals without preceding strokes or TIA has not been shown.

Aspirin↗
PubMed1994

Risk of endomyocardial biopsy in immunosuppressed patients after cardiac transplantation.

OBJECTIVES: Central venous puncture is required for endomyocardial biopsy to identify rejection after cardiac transplantation. We evaluated our use of the Seldinger technique to determine the safety of this invasive method. METHODS: In 42 immunosuppressed patients central venous puncture was performed after cardiac transplantation using the Seldinger technique for right heart biopsy. Together with physical examinations, chest X-ray and cardiac ultrasonography were performed during the inhospital follow-up. Outpatient follow-up continues and all reported adverse effects were evaluated by the attending cardiologist. RESULTS: There were a total of 620 central venous punctures, most via the right internal jugular vein (77.9%). The planned puncture could not be performed in 3.2% of the cases and an alternative site was used. The femoral approach was associated with the longest radiation time. No severe adverse effects were observed and no complications (infection, large haematoma, pneumothorax, severe rhythm disorders) were recorded. CONCLUSION: Even in immunosuppressed patients frequently requiring central venous puncture, right heart endomyocardial biopsy can be safely performed to evaluate rejection.

Adult↗
PubMed1994

Novel pattern of p53 gene mutations in an American black cohort with high mortality from breast cancer.

The pattern of acquired mutations in the p53 gene can be used to study differences in factors contributing to carcinogenesis. We investigated mutations in exons 5-9 and adjacent intronic regions in 47 breast cancers of black women from Michigan, a population with the highest breast-cancer mortality in the US. The 16 mutations detected differed from those of other populations. In particular, the black women had an excess of A:T-->G:C transitions compared with rural white US midwest women. While the causes of the different pattern of acquired mutation remain to be determined, this molecular epidemiological approach detects the consequences of mutagenic processes in specific populations. Mutation patterns will constrain hypotheses to mechanisms consistent with the observed biochemical alterations.

Base Sequence↗
PubMed1994

Comparative investigations of the genotoxic effects of metals in the single cells gel (SCG) assay and the sister chromatid exchange (SCE) test.

Sodium arsenite (NaAsO2) and cadmium sulphate (CdSO4) were tested for their ability to induce genotoxic effects in the single cell gel (SCG) assay and the sister chromatid exchange (SCE) test in human blood cultures in vitro. Both metals induced DNA damage in white blood cells that was expressed and detected as DNA migration in the SCG assay. Dose dependent effects were seen for cadmium in concentrations from 5 x 10(-4)-5 x 10(-3) M and for arsenic in concentrations from 2 x 10(-4)-1.5 x 10(-3) M. The distribution of DNA migration among cells, a function of dose, revealed that the majority of exposed cells expressed more DNA damage than cells from control cultures and that with increasing length of DNA migration the variability in migration among cells increased as well. Treatment of cells for 2 hr or 24 hr beginning 48 hr after the start of the blood cultures did not increase the SCE frequency in the case of cadmium but caused a small but significant SCE induction with arsenic at the highest concentration. The metal concentrations which could be investigated in the SCE test were much lower due to a strong toxic effect. Metal concentrations which were toxic in the SCE test were without visible effect in the SCG assay. Thus the two endpoints for the determination of genotoxic effects in vitro differed markedly with respect to the detection of genotoxicity induced by metals. These differences and the biological significance of the findings are discussed.

Arsenites↗
PubMed1994

Carotid artery stenosis and tachyarrhythmias: regional cerebral blood flow during high-rate ventricular pacing after one vessel occlusion in rats.

The aim of the present study was to investigate the effect of hypotensive tachycardias on cerebral blood flow (CBF) in the presence of significant carotid stenosis. The experiments were performed in 57 spontaneously breathing rats during arterial normoxia and normocapnia anesthetized with thiobarbital. CBF was determined with radiolabeled microspheres during control conditions (normofrequent sinus rhythm, normotension; group A; n = 15), during high-rate left ventricular pacing (660-840 ppm) at normotension (group B1; n = 13), borderline hypotension (group B2; n = 15) and severe hypotension (group B3; n = 7). In addition, CBF measurements were performed during borderline hypotension induced by hemorrhage (group C; n = 7). Global CBF was 1.09 +/- 0.29 ml g-1 min-1 in group A, 0.93 +/- 0.40 in group B1, 0.68 +/- 0.31 in group B2 (P < 0.05 vs. A), 0.42 +/- 0.16 in group B3 (P < 0.05 vs. A) and 0.83 +/- 0.2 in group C. The highest CBF values were found in the cerebellum (A; 1.43 +/- 0.5 ml g-1 min-1) and the lowest in the postocclusive tissue of the ipsilateral hemisphere (A; 0.74 +/- 0.2 ml g-1 min-1). In all groups a 15% mean CBF reduction in the right hemispherical cerebrum in comparison to the left hemisphere was observed (P < 0.01). In contrast, hemispherical CBF of the cerebellum did not differ. The CBF blood pressure relationship shifted to lower CBF values, the threshold of CBF regulation shifted to higher blood pressure values in the tissue regions distal to the occluded vessel during hypotensive tachycardias.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Specific recognition of arteriovenous malformations using Xenon-133 RCBF technique.

With respect to the methodology of the atraumatic Xenon-133 technique the problem whether or not the proposed and introduced arterial artifact (AA) truely represents radiation from intravascular volume and to what extent it affects regional cerebral blood flow (rCBF) calculation is unresolved. We performed rCBF measurements in 22 patients with angiomas to clarify this issue in those patients known to have pathologically enlarged intracranial vessels. P4--the parameter suggested to represent the AA--as well as the conventional blood flow parameter for gray matter (F1) were compared to those of 50 volunteers using four criteria of abnormality: 1. intrahemispheric distribution, 2. interhemispheric differences of homologous detector pairs, 3. differences of mean hemispheric values, 4. visual evaluation of CBF maps. 19 of the 22 patients with angioma fulfilled at least two of the four criteria of abnormality, in comparison to 1 of 50 volunteers. P4's sensitivity for detecting angiomas proved to be higher (86%) than the perfusion parameters of gray matter. Focal increase of P4 proved to be highly specific for the presence of arteriovenous malformation (AVM, specifity 98%). A true arterial artifact exists in most instances in the presence of an AVM. Disregarding AA in the algorithm for calculation rCBF leads to an artificial overestimation of tissue flow in the region of the AVM.

Adult↗
PubMed1994

Time course of myocardial and cerebral blood flow during stable but hemodynamically compromising ventricular tachycardias. Laboratory investigations.

Myocardial and cerebral blood flow were determined with radiolabeled microspheres in 20 Sprague-Dawley rats during sinus rhythm and during stable but hemodynamically compromising ventricular tachycardias. In addition, in 10 animals the measurements were performed at hypotension induced by exsanguination. In controls (n = 10), myocardial and cerebral blood flow were 5.14 +/- 0.6 and 1.03 +/- 0.3 ml/g per minute, respectively. The range of myocardial blood flow values was markedly enlarged after onset of tachycardia induced by epicardial pacing. The mean values of myocardial blood flow were 5.80 +/- 1.9 ml/g per minute (n.s.) after 1 min and 7.46 +/- 3.9 ml/g per minute (n.s.) after 5 min. Cerebral blood flow, however, significantly decreased after 1 min (0.57 +/- 0.1 ml/g per minute, P < 0.01) and after 5 min (0.71 +/- 0.3 ml/per minute, P < 0.05). In contrast, 1 min after exsanguination myocardial blood flow significantly decreased (4.03 +/- 1.5 ml/g per minute, P < 0.05) and recovered after 5 min (6.06 +/- 1.2 ml/g per minute, n.s.) Cerebral blood flow was below control levels 1 min (0.70 +/- 0.2 ml/g per minute, P < 0.05) after onset of hypotension due to exsanguination and returned to normal values with the next 4 min (0.90 +/- 1 ml/g per minute, n.s.). The results suggest that stable but hemodynamically compromising ventricular tachycardias markedly affect cerebral blood flow, whereas in most cases myocardial blood flow is maintained within normal ranges, or even increases. An augmented myocardial autoregulation can be concluded from the autoregulatory index. This maintainance of regulatory ability might be due to the increase of myocardial oxygen consumption at decreased coronary perfusion pressure during tachycardias. In contrast, during hypovolemic hypotension, myocardial as well as cerebral blood flow decreased. During stable but hemodynamically compromising ventricular tachycardias, cerebral blood flow initially drops drastically and recovers slowly over the next 5 min. This finding contrasts with the results of hypovolemic and drug-induced hypotension models.

Animals↗
PubMed1994

Improvement of blood glucose control in IDDM patients retards the progression of morphological changes in early diabetic nephropathy.

We investigated in a randomized, prospective study the influence of improved blood glucose control during 2-3 years in young insulin-dependent diabetic (IDDM) patients with microalbuminuria, which is indicative of early nephropathy. Patients were randomized either to intensive treatment by continuous subcutaneous insulin infusion (CSII) (n = 9) or CT (n = 9). Kidney biopsies were taken at baseline and after 26-34 months. End points were structural changes in the glomeruli. Sensitive, quantitative, morphometric methods were used. The blood glucose control improved significantly (p = 0.01) during the study in the CSII-group as glycated haemoglobin (HbA1c) fell from 10.1% ([95% CI] 8.9-11.3) to 8.6% (7.9-9.2), but not in the CT-group, 10.1% (8.3-11.9) vs 9.7% (8.7-10.8). Mean HbA1c during the study period was significantly lower in the CSII-group than in the CT-group, 8.7% (8.1-9.3) vs 9.9% (8.5-11.3), p = 0.04. Basement membrane thickness (BMT) increased in both groups, most (CT vs CSII, p = 0.03) in the CT-group: 140 nm (50-230) vs CSII: 56 nm (27-86). In the CT-group only an increase was seen in matrix/mesangial volume fraction (p = 0.006) and matrix star volume (p = 0.04). Furthermore, a positive correlation between mean HbA1c during the study and change from baseline in BMT (r = 0.70, p = 0.001) and matrix/glomerular volume fraction (r = 0.33, p = 0.09, NS) was demonstrated. Albumin excretion rate correlated significantly to BMT and most of the matrix parameters.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1994

A comparison of the DNA-damaging, the cytotoxic and genotoxic properties of tetracycline in human fibroblasts in the presence and absence of light.

The reduction of the colony-forming ability, the induction of DNA strand breaks and DNA repair were determined in human fibroblasts after treatment with tetracycline (TC) in the presence and absence of light. In all experiments human fibroblasts were more sensitive to incubations of TC in the light than in the dark. Induction of DNA single-strand breaks and DNA repair were detected in the cells after a 1-h incubation with TC under light but not in the dark. In contrast to these results, TC induced single-strand breaks in isolated PM2 DNA in the dark, however, to a lower extent than in the presence of light. In both cases strand break formation was totally suppressed by adding catalase. The formation of a TC-derived radical by ESR and a decomposition product by UV-vis spectroscopy was observed in the presence and absence of light; their rate of formation in the dark was much smaller than in the light.

Cell Line↗