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Biomedical subjects

W Schmid

Publications and source records attributed to W Schmid.

At least 91 records · Page 5Linked to original sources
PubMed1990

ACE inhibition improves vagal reactivity in patients with heart failure.

The deranged autonomic control of heart rate was studied in 34 patients with heart failure (New York Heart Association [NYHA] functional class II to III) by examining the carotid sinus baroreflex. The carotid sinus baroreceptors were stimulated by graded suction. The slope of the regression line between increases in cycle length and the degree of neck suction was taken as an index of baroreflex sensitivity. The reflex response is mediated by a selective increase of vagal efferent activity. Baroreflex sensitivity therefore represents a measure of vagal reactivity. Using multiple regression analysis, baroreflex sensitivity (BS) correlated positively to stroke volume index (SVI) and inversely to plasma renin activity (PRA) and to age: BS = 0.47 SVI - 0.38 PRA - 0.23 age + constant (r = 0.74; p less than 0.0005). In addition to digitalis and diuretics, angiotensin-converting enzyme (ACE) inhibitors (captopril or enalapril) were given to 16 patients for a mean of 17 +/- 3 days. The patients with hemodynamic improvement (group A) exhibited improved baroreflex sensitivity (1.4 +/- 0.4 to 3.6 +/- 1.2 msec/mm Hg; p less than 0.01). Baroreflex sensitivity remained unchanged (3.1 +/- 0.8 to 2.4 +/- 1.0 msec/mm Hg; n.s.) in the patients without hemodynamic improvement (group B). The increase in reflex sensitivity did not correlate with hemodynamic alterations. Baroreflex sensitivity during ACE inhibition (BSD) was only related to the baseline baroreflex sensitivity (BSB): BSD = 2.8 BSB - 0.46 (r = 0.84; p less than 0.005). In patients with heart failure, reflex bradycardia decreases with age and with PRA and increases with stroke volume. Chronic therapy with ACE inhibitors enhances vagal reactivity in patients with hemodynamic improvement.

Adult↗
PubMed1990

[Linear versus circular polarization of head coils: comparison on phantoms and in the clinic].

Two different head coils--one with linear polarization and the other with circular polarization--were compared under the same measurement conditions. Comparison was done on a phantom with water-filled and gadolinium-filled pin-holes, as well as on anatomical MR images of 23 volunteers. In three volunteers the whole brain was examined while, in the remaining 20 volunteers the sella region or cerebellopontine angle region was examined. Criteria for comparison were signal-to-noise ratio, background noise, and detail resolution (phantom), as well as subjective criteria--image sharpness, anatomical, contrast, and recognition of anatomical details--, evaluated on anatomical MR images by four radiologists independently of each other. The results show a significant improvement of signal-to-noise ratio, lower background noise and therefore marked improvement of images sharpness, and moderate improvement in the recognition of anatomical details using the circular polarized head coil; as for as detail resolution and anatomical contrast were concerned, however, no significant difference was seen between the two coils. Major advantages of the circular, polarized head coil in clinical application are shorter measurement times (reduced number of acquisitions), as well as thinner slices without loss of signal-to-noise ratio.

Brain↗
PubMed1990

Haemodynamic changes caused by alteration of autonomic activity in patients with heart failure.

In 14 patients with heart failure (New York Heart Association class 2-3) and sinus rhythm the carotid sinus baroreceptors were stimulated to induce a reflex mediated decrease of sympathetic efferent activity and a simultaneous increase in vagal tone. Five patients were in severe heart failure (New York Heart Association class 3) with raised plasma concentrations of noradrenaline at rest (2.99 (0.86) nmol/l (mean (SD)) and nine patients had less severe heart failure (class 2.2 (0.2)) and normal plasma concentrations of noradrenaline at rest. The haemodynamic responses during arterial baroreceptor stimulation were different in both groups. In all five patients with severe heart failure cardiac output increased whereas in the nine patients with less severe heart failure it was unchanged or decreased. The increase of cardiac output in the group with severe heart failure was solely the result of a significant increase of stroke volume index (by 9 (2) ml/m2). In the nine patients with less severe heart failure stroke volume remained unchanged but heart rate decreased significantly by 7 (2) beats/min during baroreceptor stimulation. These data show that an integrated change of autonomic activity consisting of a decrease in sympathetic tone and an increase in vagal activity leads to an increase of stroke volume in patients with severe heart failure and hence to haemodynamic improvement.

Adult↗
PubMed1989

Glucocorticoid receptor binds cooperatively to adjacent recognition sites.

In order to define the mechanism of synergistic induction mediated by multiple glucocorticoid response elements (GRE), the affinity of the glucocorticoid receptor to a single or duplicated GRE was analyzed by gel retardation, nitrocellulose filter binding and by footprinting experiments. Direct measurement of the relative affinity and indirect determination by competition showed greater than 10-fold higher affinity of the glucocorticoid receptor to a duplicated GRE when compared to a single element. Maximal stability of the GRE-receptor complex was obtained using two closely spaced GREs positioned on the same side of the DNA helix. Increasing the distance or changing the helical position of the GREs considerably increased the off rate of the receptor. DNase I footprinting shows in addition to the protection of the GRE region, an altered pattern in the nonprotected intervening DNA indicating structural alteration of the DNA helix by the receptor bound to adjacent GREs.

Animals↗
PubMed1989

Hepatocyte differentiation in vitro: initiation of tyrosine aminotransferase expression in cultured fetal rat hepatocytes.

A fetal rat hepatocyte culture system has been used to study the molecular mechanisms of tyrosine aminotransferase (TAT) gene expression during development. It has previously been shown that TAT activity can be detected in 19-d, but not 15-d, gestation hepatocytes on the first day of culture (Yeoh, G. C. T., F. A. Bennett, and I. T. Oliver. 1979. Biochem. J. 180:153-160). In this study enzyme activity, synthesis, and mRNA levels were determined in hepatocytes isolated from 13-, 15-, and 19-d gestation rats maintained in culture for 1, 2, or 3 d and exposed to dexamethasone. TAT expression is barely detectable in 13-d gestation hepatocytes even after 3 d in culture. Hepatocytes isolated from 15-d gestation fetuses have undetectable levels of enzyme activity and synthesis on the first day of culture; both can be assayed by days 2 and 3. TAT mRNA levels in these hepatocytes, measured by hybridization with a specific cDNA, increase substantially during culture. TAT activity, synthesis, and mRNA are evident on the first and subsequent days of culture in 19-d gestation hepatocytes. Transcription measurements in isolated nuclei indicate that the increase in TAT mRNA in 15- and 19-d gestation hepatocytes is associated with an increase in transcription of the gene. Immunocytochemical studies demonstrated that the increase in TAT expression correlated with an increase in the proportion of hepatocytes expressing the enzyme, rather than a simultaneous increase in all hepatocytes. These results support the proposal that a subpopulation of 15-d fetal hepatocytes undergo differentiation in culture with respect to TAT.

Animals↗
PubMed1989

Unorthodox diagnostic procedure in a rare case of intrapericardial malignant schwannoma.

To establish preoperatively the cytology of a large right atrial tumour, an echoguided transcutaneous thin needle aspiration using a transhepatic approach was performed. Cytology suggested myxoma, which had been mimicked by regressive changes within the tumour, while the histologic examination of the removed specimen revealed a malignant pericardial Schwannoma. In spite of this discrepancy we think that solid tumours located at the free atrial wall are accessible to ultrasound guided puncture without great risk.

Adult↗
PubMed1988

Synergistic action of the glucocorticoid receptor with transcription factors.

Steroid responsive elements (SRE) have been mapped at variable positions relative to the transcription start site and are often adjacent to binding sites of transcription regulatory proteins. In order to define the role of these transcriptional control sequences in the induction process, we inserted the previously defined 15-bp glucocorticoid response element (GRE) or 15-bp estrogen response element (ERE) immediately upstream of the TATA box of the thymidine kinase promoter, deleting all distal promoter elements. Both ERE and GRE confer inducibility by the respective hormone to the truncated promoter. These data suggest that the steroid receptor protein, possibly in conjunction with the TATA box binding protein, is able to form an active transcription complex. In contrast, the GRE when inserted 351 bp upstream of the start site of transcription of the tyrosine aminotransferase gene (TAT) is not capable of mediating hormone inducibility. Inducibility can be attained at this position by either two GREs or a single GRE in combination with a CCAAT motif. A cluster of point mutations in the CCAAT box abolishes hormone inducibility, strongly suggesting a synergistic action between the glucocorticoid receptor and the factor recognizing the CCAAT motif. The CCAAT box can be replaced by a CACCC box, an NF I and an SP1 binding site, thus demonstrating that synergistic action is not restricted to the CCAAT box binding protein. These combinations of a GRE with different transcription factor binding sites show a pronounced cell-type-dependent glucocorticoid induction of expression.

Animals↗
PubMed1988

Postmortem stability of DNA.

High-molecular-weight DNA was recovered postmortem in sufficient quantities from various human organ tissues as well as from blood, although not all organs were equally well suitable. Good DNA stability was found in brain cortex, lymph nodes and psoas muscle over a period of three weeks postmortem. Spleen and kidney showed good DNA stability up to five days postmortem but after longer periods, rapid degradation was observed. Yields of DNA from blood were not consistent because of the non homogeneity of samples. Blood clots were rich with DNA. Generally, the amount of degraded DNA correlated directly with the duration of the postmortem period. However in some cases, DNA degradation was already prominent after a short period. However in some cases, DNA degradation was already prominent after a short period. Case histories showed that high environmental temperature at the site of death and/or infectious diseases prior to death were the main factors for rapid autolysis. Gradual disappearance to complete loss of the long fragments (15-23 kb) was observed in DNA fingerprinting using the minisatellite probe 33.15. No extra-bands were noted, thus excluding erroneous conclusions. However, evidentiary value of older samples was lower.

Cerebral Cortex↗
PubMed1988

Expression of neuroendocrine markers (neuronspecific enolase, synaptophysin and bombesin) in carcinoma of the lung.

The value of immunoreactivity of antibodies against neuronspecific enolase (NSE), bombesin (GRP), and synaptophysin (SY 38) as markers for various human lung carcinoma has been assessed. One hundred-forty-two primary bronchus carcinomas (small cell anaplastic carcinoma, epidermoid carcinoma, adeno carcinoma, and large cell anaplastic carcinoma) were studied by the indirect immunoperoxidase method (PAP). SY 38 was found to react positively in 49/68 (79%) of the small cell anaplastic carcinoma (SCCL) and in 6/74 (8%) of the non-small cell carcinoma of the lung (NSCCL). Positive immunohistochemical data with antibody SY 38 showed in some cases an immunoreactive polypeptide of Mr = 40.000 obtained by immunoblotting similar in molecular weight as described for synaptophysin in other tumours. Reactivity of NSE was observed in 41/68 (61%) of the SCCL and in 8/74 (10%) of the NSCCL. Positive reactivity to GRP was similar to NSE in 42/68 (62%) of SCCL and in 7/74 (10%) of NSCCL. All cases of NSCCL reacting positively to SY 38 were found to react positively to NSE, and to GRP. Prognostic value of SY 38 was calculated vp = 0.71 for positive prediction and vn = 0.91 for negative prediction. The data indicate that SY 38 represents the broadest marker for neuroendocrine carcinoma of the lung since in addition to the majority of SCCL about 10% of NSCCL are recognized by the antibody SY 38.

Antibodies, Monoclonal↗
PubMed1988

[Comparison of captopril with enalapril in the therapy of heart failure: effect on hemodynamics and kidney function].

24 patients with severe heart failure (NYHA III) were randomly assigned to an additional therapy with captopril or enalapril. The mean daily dose of captopril was 56 +/- 2 mg and of enalapril, 9.6 +/- 0.9 mg. After a mean of 9 days, the influence of both inhibitors of the angiotensin converting enzyme (ACE-inhibitors) on hemodynamics and renal function was evaluated. The mean arterial pressure in the group treated with captopril (group A) fell by 11 +/- 2 mm Hg (p less than 0.001), with enalapril (group B) by 13 +/- 3 mm Hg (p less than 0.01), the difference between the groups not being significant. Heart rate decreased in both groups to a similar degree. The change was significant only in the patients treated with enalapril (13 +/- 4/min; p less than 0.05 vs. 11 +/- 5/min in group A). Stroke volume index increased by 10 +/- 2 ml/m2 in group A vs. 12 +/- 2 ml/m2 in group B; both increases were highly significant (p less than 0.001). Mean decreases in pulmonary artery and right atrial pressure were comparable in both groups. The hemodynamic improvement was not different with both ACE-inhibitors. Serum sodium and potassium before therapy were 137 +/- 1 mmol/l and 4.1 +/- 0.2 mmol/l in group A and 139 +/- 1 mmol/l and 3.8 +/- 0.1 mmol/l in group B and serum creatinine was 1.2 +/- 0.1 mg/dl in both groups. Neither serum electrolytes nor serum creatinin were changed significantly by therapy with captopril or enalapril.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1988

[Reflex regulation of heart rate in patients with heart failure].

The carotid sinus baroreceptors were stimulated in 34 patients with heart failure (NYHA II-III) and sinus rhythm. We found that reflex bradycardia is caused by a selective increase in parasympathetic activity and the increase in cycle length depends on the degree of baroreceptor stimulation, therefore a regression line could be calculated for each patient. The slopes of these regression lines were used as an index of baroreflex sensitivity. Initial heart rate, age, stroke volume index, and plasma-noradrenaline concentration correlated with baroreflex sensitivity. However, according to multiple regression analysis (r = 0.64, p less than 0.001), only age correlated negatively (p less than 0.05), and the stroke volume index correlated positively (p less than 0.001) with baroreflex sensitivity: the lower the stroke volume index the smaller the baroreflex sensitivity. This indicates that reflex increases in parasympathetic activity depend on the degree of heart failure.

Adult↗
PubMed1988

Gene deletion in a patient with chronic granulomatous disease and McLeod syndrome: fine mapping of the Xk gene locus.

In a patient suffering from X-linked chronic granulomatous disease (X-CGD)--a disorder of phagocytesuperoxide generation--and McLeod syndrome, characterized by the absence of the red cell Kell antigen, we identified a deletion of the entire X-CGD gene by means of DNA hybridization with a cDNA probe. Our findings suggest that the X-CGD and McLeod loci are physically close in the p21 region of the X chromosome proximal to the Duchenne muscular dystrophy locus.

Anemia, Hemolytic, Congenital↗
PubMed1987

[DNA diagnostics].

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Chromosome Aberrations↗
PubMed1987

[DNA diagnosis of Huntington's chorea. Application and genetic counseling in 4 involved families].

The discovery of linked DNA markers permits presymptomatic and prenatal diagnosis of autosomal-dominant Huntington's disease. However, family members born at 50% risk can find out if they have inherited the mutant gene only if family analyses are possible. Many individuals at risk lack a sufficient number of living relatives for presymptomatic testing. However, prenatal exclusion testing in pregnancy can be offered to most probands. In four case reports we demonstrate the first clinical use of these markers for genetic counselling in Switzerland. The method was used for both presymptomatic testing and prenatal diagnosis. Prenatal exclusion testing is described in one family. The general practitioner should be informed of the potentialities of DNA technology, since competent advice to his patients and follow-up of positive probands are part of his duties.

Adult↗
PubMed1987

Transcription activation of the tyrosine aminotransferase gene by glucocorticoids and cAMP in primary hepatocytes.

The expression of the tyrosine aminotransferase (TAT) gene of the rat was analyzed in primary hepatocytes. The TAT gene remains active in primary cultured cells at a level similar to that in liver cells. Expression can be induced by glucocorticoids and cAMP, glucocorticoids lead to a 8-10-fold increase in TAT mRNA level, cAMP to a 20-30-fold increase. The elevation of the TAT mRNA is preceeded by a rise in the relative rate of transcription of the gene. Surprisingly transcription of the albumin gene, which steadily declines with the age of the culture, can also strongly be stimulated by glucocorticoids in primary hepatocytes. cAMP antagonists, which act as competitive inhibitors of the cAMP-dependent protein kinase, prevent induction of transcription of the tyrosine aminotransferase gene by cAMP suggesting that the effect of cAMP on expression of the tyrosine aminotransferase gene is mediated by a cAMP-dependent protein kinase. The cAMP antagonist does not interfere with induction by glucocorticoids which suggests that phosphorylation of the glucocorticoid receptor by the cAMP-dependent protein kinase is not required for its function. We thus conclude that the two inducers affect transcription by independent mechanisms.

Animals↗