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M Weis

Publications and source records attributed to M Weis.

At least 73 records · Page 4Linked to original sources
PubMed1995

The perinuclear centriole-containing centrosome is not the major microtubule organizing center in Sertoli cells.

Microtubules are abundant in Sertoli cells and are predominantly arranged parallel to the long axis of the cell. In addition, the centrioles occur in a perinuclear position in the basal one third of the cell. In this study we investigate the importance of the perinuclear centriole-containing centrosome as a microtubule organizing center (MTOC) in Sertoli cells. In all experiments, rat testes were perfusion fixed and then processed for electron and/or fluorescence microscopy. For fluorescence microscopy, fragments or dissected pieces of seminiferous epithelium were labeled for tubulin and actin. The three-dimensional pattern of microtubules in Sertoli cells was determined using data collected with a confocal microscope and analyzed using the NIH-Image program (written by Wayne Rasband at the NIH). The detailed arrangement of microtubules around, and the number of microtubule ends associated with, the centrosome were determined from composite projections constructed from serial thin sections. The nucleating potential of the perinuclear centrosome was determined by perfusing testes for 6 h with 10 micrograms/ml nocodazole and then for up to 3 h with control buffer prior to fixation and analysis with confocal and standard fluorescence microscopy. Microtubules are not organized around a focal perinuclear site and few microtubule ends are associated with the centrosome. Moreover, in cells recovering from nocodazole treatment, microtubules first appear in apical (peripheral) processes. Our data indicate that the centriole-containing perinuclear centrosome is not a significant MTOC in Sertoli cells. Rather, microtubules are nucleated in peripheral regions and project basally. Based on the observations that microtubules appear to "cuff" the nucleus, intermediate filaments are concentrated around the nucleus, microtubules project into the perinuclear intermediate filament network, and microtubules and intermediate filaments are often coaligned, we suggest that microtubules are anchored into position at the base of the cell via linkages with the intermediate filament network. Our nucleation-anchorage model of microtubule organization in Sertoli cells may be applicable to other epithelial systems.

Animals↗
PubMed1994

Further characterization of the events involved in mitochondrial Ca2+ release and pore formation by prooxidants.

Addition of the prooxidant 3,5-dimethyl-N-acetyl-p-benzoquinone imine (3,5(Me)2NAPQI) to Ca(2+)-loaded mitochondria caused a rapid and extensive release of the sequestered Ca2+. Ca2+ release was accompanied by irreversible NAD(P)H oxidation and was followed by the release of adenine and pyridine nucleotides into the extramitochondrial medium; this is evidence of the opening of the pore in the inner mitochondrial membrane. Preincubation of the mitochondria with ADP, cyclosporin A (CSA), m-iodobenzylguanidine (MIBG) or Mg2+ inhibited the prooxidant-induced Ca2+ release and prevented pore-opening. When mitochondria were preincubated with ruthenium red, Ca2+ release was only minimally stimulated by 3,5(Me)2NAPQI. However, increasing the concentration of the prooxidant caused release of an increasing fraction of the sequestered Ca2+. Alternatively, increasing the intramitochondrial Ca2+ load resulted in a lowering of the concentration of 3,5(Me)2NAPQI required for near complete Ca2+ release to occur. In the presence of ruthenium red, 3,5(Me)2NAPQI-induced Ca2+ release was accompanied by irreversible pyridine nucleotide oxidation and followed by the release of nucleotides into the extramitochondrial medium, events which were prevented on preincubation with CSA. Similarly, the addition of CSA, ADP or MIBG during 3,5(Me)2NAPQI-induced Ca2+ release arrested further Ca2+ release. In addition to their inhibitory effect on the 3,5(Me)2NAPQI-induced Ca2+ release, CSA, ADP or MIBG also decreased the rate of the basal, ruthenium red-induced mitochondrial Ca2+ release by 45-70%. It is proposed that the basal, ruthenium red-induced and the prooxidant-induced mitochondrial Ca2+ release occur through a common component that is sensitive to inhibition by CSA, ADP and MIBG and that is involved in mitochondrial pore formation. Furthermore, 3,5(Me)2NAPQI-induced pore opening does not involve Ca(2+)-cycling, but rather involves a site(s) that is (are) synergistically activated by Ca2+ and the prooxidant.

3-Iodobenzylguanidine↗
PubMed1994

Heart rate analysis in 24 patients treated with 150 mg amitriptyline per day.

Twenty-four patients treated with 150 mg amitriptyline per day for an episode of major depression underwent a standardized heart rate analysis (HRA) before therapy and after 14 days. The battery of cardiovascular reflex tests included the determination of the coefficient of variation (CV) while resting and during deep respiration, a spectral analysis of heart rate, the heart rate response to standing, and the Valsalva manoeuvre. The results of the initial HRA did not differ from a group of 24 normal control subjects matched for age and sex. On day 14 of treatment the patients showed significantly reduced values of heart rate variability in all tests (P < 0.0001), probably due to the anticholinergic side effects of amitriptyline. Heart rate increased from 78.1 to 93.6 bpm on average (P < 0.0001). Abnormal CV at rest was registered in 96% of the patients; during deep respiration 29% showed abnormal CV results. An abnormal spectral analysis was found in 100% of the cases (low frequency peak: 42%, mid-frequency peak: 100%, high frequency peak: 79%). The heart rate response to standing was abnormal in 75% and the Valsalva test in 33% of the cases. Eighty-eight percent of the patients fulfilled the criteria of a cardiovascular autonomic neuropathy under the conditions of amitriptyline therapy. As yet, the consequences of these changes for the patients have not been sufficiently elucidated.

Adult↗
PubMed1994

Bioavailability of four oral coenzyme Q10 formulations in healthy volunteers.

The bioavailability of four different Coenzyme Q10 (CoQ) formulations was compared in ten healthy volunteers in a four-way randomised cross-over trial. The included formulations were: A hard gelatin capsule containing 100 mg of CoQ and 400 mg of Emcompress. Three soft gelatin capsules containing: 100 mg of CoQ with 400 mg of soy bean oil (Bioquinon); 100 mg of CoQ with 20 mg of polysorbate 80, 100 mg of lecithin and 280 mg of soy bean oil; and 100 mg of CoQ with 20 mg of polysorbate 80 and 380 mg of soy bean oil, respectively. The result suggests that the soya bean oil suspension of CoQ (Bioquinon has the highest bioavailability. A difference in basic AUC and AUC after p.o. administration of CoQ was observed with respect to sex. A characteristic two peak-pattern was observed at the concentration-time profile.

Administration, Oral↗
PubMed1994

Are affective disorders associated with alterations of heart rate variability?

A standardized heart rate analysis was carried out in unmedicated patients with major depression, melancholic type (n = 16), panic disorder (n = 16), reactive depression with suicide attempts during the preceding 24 h (n = 16) and in 16 normal control subjects. The investigations included time- and frequency-derived measurements of heart rate variability. In the patients with reactive depression, no differences could be detected as compared with the control group. The patients with panic disorder showed a significantly increased low-frequency band of spectral analysis (P < 0.01) and a marginally significant increment of heart rate (P = 0.05), probably indicating predominance of sympathetic control of heart rate. In the patients with major depression, we found significantly lower values of heart's beat-to-beat intervals and of the high-frequency peak of spectral analysis than in the other groups (P < 0.025), indicating decreased parasympathetic activity.

Adjustment Disorders↗
PubMed1994

Heart rate variability in depressed patients and differential effects of paroxetine and amitriptyline on cardiovascular autonomic functions.

Twenty-four unmedicated patients with episodes of major depression (DSM-III-R) and an age- and sex-matched group of 24 normal subjects underwent a heart rate analysis. The battery of cardiovascular reflex tests included the coefficient of variation while resting (CVr) and during deep breathing (CVdr), a spectral analysis of heart rate variability, the Valsalva test, and the posture index. The depressed patients showed no significant abnormalities in any of the tests as compared to the healthy subjects. The 24 patients were randomly allocated for treatment with either amitriptyline or paroxetine. During treatment with 20 mg paroxetine per day, patients showed no changes in cardiovascular autonomic function tests after 14 days. However, treatment with 150 mg amitriptyline per day decreased all heart rate parameters significantly due to anticholinergic side effects, except heart rate, which increased significantly. As autonomic side effects are a potential hazard of antidepressant therapy, the data suggest that paroxetine is an appropriate antidepressant for cases with pre-existing cardiovascular autonomic neuropathy.

Adult↗
PubMed1994

Endothelium-dependent and endothelium-independent vasomotion in large coronary arteries and in the microcirculation after cardiac transplantation.

Endothelium-dependent and endothelium-independent vasodilation of the epicardial conduit vessels and the microcirculatory coronary vessels was investigated with cumulative doses of acetylcholine (ACh 50 micrograms and 100 micrograms i.c.), nitroglycerin (0.3 mg i.c.) and dipyridamole (0.56 mg.kg-1 i.v.) in 17 patients (3 female/14 male; age: 47 +/- 3.6 years) with angiographically normal coronary arteries 40 +/- 5.1 months after cardiac transplantation. The effect of ACh on large conduit arteries was evaluated angiographically. Coronary blood flow velocity changes were measured utilizing an 8F Judkins style 20 MHz Doppler catheter positioned in the left main coronary artery. A coronary flow index was calculated from the mean Doppler flow velocity and the computed cross-sectional vascular area. After 50 micrograms of ACh the diameter of proximal, middle and distal segments of the left anterior descending coronary artery decreased significantly by 7.6 +/- 2.06% (P < 0.05), 10.6 +/- 3.5% (P < 0.01) and 12.6 +/- 3.29% (P < 0.01) and after 100 micrograms ACh by 10.5 +/- 2.4% (P < 0.05), 13.0 +/- 3.7% (P < 0.01) and 15.3 +/- 3.9% (P < 0.01). The endothelium-independent vasodilator nitroglycerin (0.3 mg i.c.) induced an increase in vascular diameter of 14.4 +/- 3.1% (P < 0.01), 18.6 +/- 4.1% (P < 0.01) and 20.8 +/- 2.9% (P < 0.01) in proximal, mid and distal segments of the left anterior descending coronary artery.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗
PubMed1994

[Partnership status in long-term home ventilation of amyotrophic lateral sclerosis patients].

Described is the development of the intrapartnership dynamics in a case of home ventilation of a spouse having amyotrophic lateral sclerosis. Led in a heated manner until recently, the ethical discussion on the pros and cons of long-term (home) ventilation could be greatly enriched by introducing relevant systemic views and reasoning. So far, however, there are no published observations in this field.

Amyotrophic Lateral Sclerosis↗
PubMed1994

[Disorders of autonomic heart rate regulation in patients with brain stem lesions].

The present study investigates the frequency of alterations of autonomic cardiac innervation in patients with brain stem lesions by testing cardio-vascular reflexes tests. In the neurological ICU, we tested 22 patients aged 19 to 78 years (mean age 54 +/- 17 years) suffering from ischemic brain stem lesions. The variability of heart rate was at first evaluated at rest. Mean heart rate, coefficient of variation (VK) and RMSSD (root mean square of successive differences) were calculated. In addition, a spectral analysis of the heart frequency was computed by a fast fourier transformation and the spectral powers in the frequency bands 0.02-0.09 Hz, 0.09-0.15 Hz and 0.20-0.30 Hz, respectively were determined. An atropine test was then carried out. 5 minutes after the beginning of injection of atropine sulfate, further rate and spectral analyses were again computed. The VK was pathologically diminished in 59% of the patients, the RMSSD in 55% and both, VK and RMSSD, in 45%. In 32% of the patients VK and RMSSD were within normal range. Spectral power was diminished in all three frequency bands in 4 out of 22 patients with pathological heart rate variability. Most abnormal results in spectral analysis could be obtained in the frequency band 0.09-0.15 Hz (73%), followed by the frequency band 0.20-0.30 Hz (45%) and the 0.02-0.09 Hz frequency band (32%). There were significant correlations between the heart rate variability; the spectral power in the 0.09-0.15 Hz and 0.20-0.30 Hz frequency bands (p < 0.05; Spearman). 88% of the patients with abnormal results at rest had diminished heart rate responses to atropine.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Accessibility of hepatocyte protein thiols to monobromobimane.

The amino-acid residue specificity of monobromobimane (mBBr) and its accessibility to cellular protein cysteine residues were investigated. mBBr reacted selectively with the sulfhydryl group of both the free amino acid cysteine and bovine serum albumin. Incubation of isolated hepatocytes with mBBr resulted in a concentration-dependent formation of protein-bound mBBr fluorescence in the cytosolic, mitochondrial and microsomal fractions, which was not fully saturated with up to 16 mM mBBr. SDS-PAGE resolution of the proteins revealed that the major portion of increased protein-bound mBBr fluorescence that occurred at high mBBr concentrations was due to covalent binding to proteins. A minor portion (10-16% in the microsomal fraction) of protein-bound mBBr fluorescence was removed by SDS-PAGE and is therefore concluded to be due to physical entrapment of fluorescent mBBr reaction products. The accessibility of mBBr, assayed as the degree of depletion of total protein cysteine residues, was similar to N-ethylmaleimide (NEM) in isolated microsomes. By contrast, in the cytosol a markedly lower amount of protein cysteine residues were labelled by mBBr as compared to NEM. In both organelle fractions p-BQ was the most efficient thiol-depleting reagent. It is concluded that mBBr is a suitable reagent for the analysis of the cellular protein thiol status and of its xenobiotic-induced alterations when used at high concentrations; however, it should be considered that, (i) the relative accessibility of mBBr and a particular xenobiotic to cellular protein thiol residues may be different, and (ii) physically entrapped fluorescent reaction products of mBBr should be removed when quantitating protein thiol levels.

Amino Acids↗
PubMed1993

Influence of repetitive magnetic stimuli on verbal comprehension.

The influence of repetitive magnetic transcranial stimulation over the temporo-parietal cortex on verbal comprehension was investigated in 44 healthy subjects. In right-handed subjects, trains of 50 Hz magnetic stimuli over the left hemisphere produced more errors than stimulation over the right hemisphere. The result is not very clearcut, however; thus the test cannot be used for diagnostic investigation of language dominance.

Adolescent↗
PubMed1992

N-acetyl-p-benzoquinone imine-induced protein thiol modification in isolated rat hepatocytes.

Incubation of isolated rat hepatocytes with N-acetyl-p-benzoquinone imine (NAPQI) or 3,5-dimethyl-N-acetyl-p-benzoquinone imine (3,5-Me2-NAPQI) resulted in a concentration-dependent decrease in the protein thiol content of the mitochondrial, cytosolic and microsomal fractions. On a concentration basis, 3,5-Me2-NAPQI induced a more marked depletion of protein thiols than did NAPQI. Sodium dodecyl sulphate-polyacrylamide gel electrophoretic separation of the proteins of each fraction showed that different proteins had different susceptibilities to modification of their cysteine residues by the quinone imines. A few protein bands showed a decreased protein thiol content following incubation with non-toxic concentrations of quinone imines, whereas other proteins were affected by higher concentrations. Concentrations of quinone imines that were highly cytotoxic induced a general loss of protein thiols. NAPQI-induced protein thiol depletion occurred within 5 min and remained essentially unchanged for at least 30 min. In contrast, protein thiol depletion induced by 3,5-Me2-NAPQI increased over the 30-min time course of the experiment. Toxic concentrations of 3,5-Me2-NAPQI caused the formation of high molecular mass aggregates in all three subcellular fractions after 30 min of incubation. The observed crosslinking was not due to protein disulfide formation. However, no aggregate formation was observed after exposure of hepatocytes to NAPQI. One of the major target proteins of quinone imine-induced protein thiol depletion was a 17 kDa microsomal protein that was identified as the microsomal glutathione S-transferase. Exposure of hepatocytes and isolated liver microsomes to the quinone imines resulted in an up to four-fold increase in the specific activity of the microsomal glutathione S-transferase. In conclusion, our results are consistent with the suggestion of a critical role of protein thiol depletion in quinone imine-induced cytotoxicity.

Animals↗
PubMed1992

N-acetyl-p-benzoquinone imine induces Ca2+ release from mitochondria by stimulating pyridine nucleotide hydrolysis.

The mechanism of N-acetyl-p-benzoquinone imine (NAPQI)-induced release of Ca2+ from rat liver mitochondria was investigated. The addition of NAPQI or 3,5-Me2-NAPQI (a dimethylated analogue of NAPQI with only oxidizing properties) to mitochondria resulted in the rapid and extensive oxidation of NADH and NADPH. High-performance liquid chromatographic analysis of mitochondrial pyridine nucleotides revealed that the formation of NAD+ and NADP+ was followed by a time-dependent net loss of total pyridine nucleotides as a result of their hydrolysis, with the formation of nicotinamide. Preincubation of the mitochondria with cyclosporin A completely prevented the quinone imine-stimulated release of sequestered Ca2+ from mitochondria. Cyclosporin A did not affect the ability of NAPQI or 3,5-Me2-NAPQI to oxidize NAD(P)H but prevented the quinone imine-induced hydrolysis of the pyridine nucleotides. Although there was no detectable change in total protein-bound ADP-ribose content during quinone imine-induced Ca2+ release from mitochondria, meta-iodobenzylguanidine, a competitive inhibitor of protein mono(ADP-ribosylation), prevented Ca2+ release by NAPQI and 3,5-Me2-NAPQI; meta-iodobenzylguanidine did not inhibit the quinone imine-induced NAD(P)H oxidation and only partially blocked hydrolysis of the oxidized pyridine nucleotides. It is concluded that NAPQI causes the oxidation of mitochondrial NADH and NADPH, and stimulates Ca2+ release as a result of the further hydrolysis of the oxidized pyridine nucleotides and protein mono(ADP-ribosylation).

3-Iodobenzylguanidine↗
PubMed1992

The natural history of intimal flaps caused by angioscopy.

UNLABELLED: This study tried to determine the natural history of angioscopy-induced arterial intimal flaps as assessed by video angioscopy, light and transmission electron microscopy. Eight mongrel dogs were anesthetized and bilateral femoral and carotid arteries surgically exposed. A 3.0 mm American Edwards angioscope was inserted into each artery and passed vigorously until an intimal flap was visualized by angioscopy. The location of intimal flaps was externally marked with 6-0 polypropylene adventitial sutures. Animals were then recovered and follow-up angioscopy performed at one, two, three, and four week intervals. Following repeat angioscopy, all animals were sacrificed and vessels perfusion-fixed in situ with 2.5% glutaraldehyde in 0.1 M sodium cacodylate. A total of 37 intimal injuries were created (immediate, n = 10; one week, n = 8; two weeks, n = 4; three weeks, n = 8; four weeks, n = 7). No arterial thrombosis occurred following intimal flap formation. Only one of 37 (2.7%) lesions progressed to a hemodynamically significant stenosis. Histology of immediate lesions demonstrated deep intimal fractures extending into the tunica media. Complete healing of intimal flaps was observed by follow-up angioscopy in zero of eight lesions by one week, zero of four lesions by two weeks, one of eight lesions by three weeks, and four of seven lesions by four weeks (p = 0.02). Light and electron microscopy confirmed the angioscopic intimal fractures and regrowth of denuded endothelium. CONCLUSION: follow-up angioscopy and microscopy one month after angioscopy-induced arterial intimal trauma demonstrated a significant trend towards complete endothelial healing.

Animals↗