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Biomedical subjects

R Gasser

Publications and source records attributed to R Gasser.

At least 91 records · Page 5Linked to original sources
PubMed1993

Vasodilative response to hypoxia and simulated ischemia is mediated by ATP-sensitive K+ channels in guinea pig thoracic aorta.

Local vasodilation in response to hypoxia or ischemia improves perfusion and O2 supply of the affected tissue. This local vasodilation thus constitutes the most important mechanism in the prevention of ischemic cell injury. The regulation of vascular tone has mainly been attributed to changes of cytoplasmatic Ca2+ ((Ca2+)i) concentrations in vascular smooth muscle cells. The mechanism underlying these changes has not, however, been elucidated so far. Using aortic strips of guinea pigs (transversally cut in spirals; normal Tyrode, in mM: NaCl 150, KCl 4.5, MgCl2 2, CaCl2 2.5, glucose 10; buffered with 10 mM HEPES at pH 7.4; equilibrated with 100% O2 at 31 degrees C) the authors could show that metabolic blockade (glucose replaced by 10 mM 2-deoxyglucose (DOG) led to a relaxation of the preparation. Thus, in four experiments, resting tension decreased from 0.75 g by 27% +/- 12% within two hours (% of maximal contractile force developed by each preparation when depolarized with 43 mM KCl and 101.5 mM NaCl). When the same experiment was carried out in the presence of 1 mM tolbutamide (a known blocker of ATP-dependent K+ channels) in vascular smooth muscle no such relaxation could be seen (n = 4). Furthermore, in the same type of preparation, similar results have been obtained upon hypoxic relaxation (100% O2 replaced by 100% N2), where 1 mM tolbutamide also prevented vasodilation. Thus, hypoxic/ischemic vasodilation in response to glycolytic inhibition (DOG) and hypoxia (N2) is based upon the opening of K+ ATP channels and hence can be prevented by sulfonylureas (the opening of K+ ATP channels would lead to hyperpolarization (increased K+ conductance, Goldmann equation), thus diminishing the open probability of voltage-gated Ca2+ channels with subsequent vasodilation). This inhibition by sulfonylureas of vasodilative response to ischemia may also constitute the so far unknown cause of the increased cardiovascular mortality seen under sulfonylurea treatment.

Adenosine Triphosphate↗
PubMed1993

Observations on plasma ANP levels during short-term transient myocardial ischemia produced by PTCA in patients with LAD stenosis.

Ten patients with coronary artery disease and stable angina (mean age fifty-seven) were included in the study. Five of the patients had normal left ventricular function, 5 had local hypokinesia or akinesia; 8 had one-stem and 2 had two-stem disease, but all had left anterior descending (LAD) lesions ranging from 75% to 100%. Ejection fraction varied between 35% and 75% (mean 59%). Immunoreactive atrial natriuretic polypeptide (ANP) levels in the femoral vein (FV) and the coronary sinus (CS) were measured before, immediately after, and up to twenty-four hours after percutaneous transluminal coronary angioplasty (PTCA) of the LAD. ANP secretion increased by 83% (FV) and 11% (CS) within minutes after PTCA and reached control levels after thirty to sixty minutes. In patients with hypokinesia of the anterior wall, ANP secretion was significantly lower, 48% (FV) and 11% (CS) respectively. ANP secretion during PTCA was higher in patients with concomitant increase in pulmonary capillary pressure (PCP) but was also observed without an increase of PCP, suggesting ventricular ANP secretion. IN conclusion, transient myocardial ischemia leads to immediate ANP secretion even in the absence of significant pressure elevation in the left atrium. As a part of the continuous medical education program of the American College of Angiology the second part of the paper reviews the mechanisms that allow the ischemic heart to counteract the ischemic condition and thus to escape from myocardial infarction. A review of this subject is presently not available in the literature.

Angina Pectoris↗
PubMed1993

Left-sided laparoscopic adrenalectomy.

Laparoscopic transperitoneal adrenalectomy was performed in a 42-year-old female with a left adrenocortical adenoma causing Conn's syndrome. No technical problems occurred during surgery and the patient recovered quickly.

Adrenal Cortex Neoplasms↗
PubMed1993

[Calcium antagonists and coronary heart disease. An overview].

Calcium antagonists (Ca-antagonists) have been used for 2 decades in the treatment of coronary heart disease. Their use has initially been promoted with variant angina, but soon has expanded to all forms of coronary heart disease, entailing both stable and instable angina. Based on promising experimental findings, these drugs have also been given in myocardial infarction, however, with disappointing results. The same was true for secondary prevention. The basic principle underlying Ca-antagonistic therapy of ischaemic heart disease is the improvement of myocardial oxygen balance. On the one hand, Ca-antagonists (in particular verapamil and diltiazem) reduce myocardial oxygen demand via negative inotropic and chronotropic action--on the other hand, the afterload is reduced by peripheral vasodilation. In addition, coronary dilation improves oxygen delivery, especially during exercise. Ca-antagonists inhibit transsarcolemmal Ca-influx, thus preventing deleterious myocardial Ca-overload as seen during ischaemia and atherosclerosis. Indeed, recent human studies have proven a preventive effect of Ca-blockers against atherosclerosis.

Calcium Channel Blockers↗
PubMed1993

A physiological oral magnesium supplement does not influence total serum magnesium, left ventricular ejection fraction and prognosis in patients with dilated cardiomyopathy.

It has been postulated that patients with congestive heart failure (CHF) benefit from physiological oral magnesium supplements. In order to study the effect of such supplements upon patients with idiopathic dilated cardiomyopathy (IDC) we studied a group of 23 patients with the salient characteristics of IDC (18 male, 5 female; mean age 51 +/- 13 years [range: 23-72]; Mg group), who received oral magnesium supplements (15 mmol/day). All patients received oral ACE inhibitors and 22 were receiving digitalis and diuretics. A control group of 27 patients, matched for age, sex, symptoms, and additional treatment (22 male, 5 female; mean age 52 +/- 13 years [range 22-71]) were not given oral magnesium supplements. All these patients also received oral ACE inhibitors, 25 were receiving digitalis, and 23 were receiving diuretics. Mean serum magnesium concentration (total serum Mg) in the Mg group was 0.83 +/- 0.06 mmol/litre [mean +/- SD, range 0.69-0.99], while in the control group it was 0.83 +/- 0.07 mmol/litre [range 0.70-0.96], P = NS. Left ventricular ejection fraction (LV-EF) improved from 32 +/- 11 per cent [range 13-51] to 42 +/- 14 per cent [range 15-66] in the Mg group and from 30 +/- 13 per cent [range 10-52] to 42 +/- 11 per cent [range: 25-64] in the control group. We found that physiological oral Mg supplements did not influence serum magnesium, LV-EF, or prognosis. Furthermore, we found that 56 per cent of all patients improved when subjected to strict guidance and therapy with ACE inhibitors, digitalis, and diuretics.

Adult↗
PubMed1992

mu-crystallin is a mammalian homologue of Agrobacterium ornithine cyclodeaminase and is expressed in human retina.

mu-Crystallin is the major component of the eye lens in several Australian marsupials. The complete sequence of kangaroo mu-crystallin has now been obtained by cDNA cloning. The predicted amino acid sequence shows similarity with ornithine cyclodeaminases encoded by the tumor-inducing (Ti) plasmids of Agrobacterium tumefaciens. Until now, neither ornithine cyclodeaminase nor any structurally related enzymes have been observed in eukaryotes. RNA analysis of kangaroo tissues shows that mu-crystallin is expressed at high abundance in lens, but outside the lens mu-crystallin is preferentially expressed in neural tissues, retina, and brain. An almost full-length cDNA for mu-crystallin was cloned from human retina. In human tissues, mu-crystallin mRNA is present in neural tissue, muscle, and kidney. This pattern of expression and relationship to an enzyme involved in unusual amino acid metabolism suggests the interesting possibility that mammalian mu-crystallins could be enzymes participating in processes such as osmoregulation or the metabolism of excitatory amino acids.

Amino Acid Sequence↗
PubMed1992

Frequency of magnetic resonance signal abnormalities of the brain in patients aged less than 50 years with idiopathic dilated cardiomyopathy.

Twenty patients with idiopathic dilated cardiomyopathy (IDC) aged less than 50 years (mean 41) and an age-matched group of 20 healthy volunteers were studied. All subjects were free of cerebrovascular symptoms and risk factors for stroke. Magnetic resonance imaging of the brain, extracranial Doppler ultrasonography, heart catheterization and echocardiography were performed. In patients with IDC, a higher frequency of ventricular enlargement (p less than 0.02), cortical atrophy (p less than 0.01) and white matter lesions (p less than 0.05) was observed. Cerebral infarcts were found in 4 patients (p less than 0.05) who showed clinically severe limitation of functional capacity (New York Heart Association class III or IV). The extent of cortical atrophy, and the duration of clinical evidence of IDC showed a significant correlation (p less than 0.04). The data indicate a high incidence of parenchymal abnormalities of the brain in young, neurologically asymptomatic patients with IDC.

Adolescent↗
PubMed1992

Fibrinogen values in patients with and without restenosis following percutaneous transluminal coronary angiography.

Fibrinogen has turned out to be an independent risk factor for coronary heart disease (CHD). It is not known whether or not this parameter could be a prognostic factor for restenosis following percutaneous transluminal coronary angioplasty (PTCA), which represents the main problem limiting the long-term efficacy of this procedure. Therefore, we studied fibrinogen concentrations in a series of 50 males (mean age: 55, range: 38-70 years) with CHD and successful PTCA. Follow-up coronary angiography was performed 12 months following PTCA. Twenty-two patients had restenosis, and 28 patients were without restenosis. Both groups did not differ significantly in medical history (smoking habits, hypertension, positive family history for cardiovascular diseases), in routine lipid profile (total cholesterol, HDL cholesterol, LDL cholesterol, triglycerides, apolipoproteins A1 and B). Fibrinogen values were 405 +/- 128 mg/dl (range: 202-725) in patients with restenosis and 352 +/- 94 mg/dl (range: 187-568) in patients without restenosis (not significant). Elevated fibrinogen levels of more than 400 mg/dl were found in 8 patients in each group. Although fibrinogen is a proven marker for CHD in men, fibrinogen is not a risk factor for restenosis following PTCA.

Adult↗
PubMed1991

The major alpha-class glutathione S-transferases of rabbit lung and liver. Primary sequences, expression, and regulation.

The complete primary structures of two distinct rabbit alpha-class glutathione S-transferase (GST) subunits, rbGST alpha I and rbGST alpha II, have been derived from cDNA sequences. Clones encoding rbGST alpha I were isolated from both hepatic and pulmonary cDNA libraries, whereas clones encoding rbGST alpha II were isolated only from the hepatic library. Immunochemical and peptide sequence data confirmed that rbGST alpha I corresponds to the 27-kDa alpha-class subunit purified from rabbit lung (Serabjit-Singh, C. J., and Bend, J. R. (1988) Arch. Bioch. Biophys. 267, 184-194). Expression of rbGST alpha II in liver but not in lung and expression of rbGST alpha I in both liver and lung was substantiated by Northern and immunochemical analyses. rbGST alpha I and rbGST alpha II are composed of 223 and 221 amino acids, respectively, and are 78% identical in amino acid sequence. Compared to published GST sequences, both proteins are most closely related to the human Ha subunit (greater than 80% identity). On the basis of sequence comparison and Northern and Southern analyses, we conclude that rbGST alpha I and rbGST alpha II are products of different genes that are independently regulated. Further, the regulatory elements of the alpha-class GST genes may be significantly different in the rabbit as compared to the rat, as evidenced by the lack of induction by phenobarbital of rabbit hepatic or pulmonary alpha-class GST subunits, enzymatic activity, or mRNA. This tissue- and species-dependent expression of the predominant class of cytosolic GST implies unique functions for each isozyme and may contribute to the differential susceptibility of tissues and animals to toxicants.

Amino Acid Sequence↗
PubMed1991

Chromogranin A and B in parathyroid tissue of cases of primary hyperparathyroidism: an immunohistochemical study.

Routinely processed parathyroid tissues from 26 cases with primary hyperparathyroidism (19 adenomas, 7 multiglandular hyperplasia) and 8 normal human parathyroid glands were investigated with antibodies against chromogranin A and B and parathyroid hormone (PTH). Normal parathyroids were immunohistochemically positive for PTH and chromogranin A but negative for chromogranin B. Hyperplastic glands showed a focal staining for PTH and chromogranin A without correlation of the staining pattern on serial sections. Adenomas were either uniformly positive for both PTH and chromogranin A or showed a staining pattern similar to that seen in hyperplastic glands. Focal chromogranin B positivity (less than 10% of cells) was found in 3 cases (1 hyperplastic gland and 2 cases of parathyroid adenoma with an immunohistochemical staining pattern similar to hyperplastic glands). Our immunohistochemical results may support previously published findings that most parathyroid adenomas are monoclonal neoplasms whereas hyperplastic glands are of polyclonal origin.

Adenoma↗
PubMed1991

Chromogranin A and B in adenomas of the pituitary. An immunohistochemical study of 42 cases.

Forty-two pituitary adenomas (10 prolactinomas; three ACTH-, nine GH-, two FSH- and two TSH-secreting adenomas; and 16 clinically nonfunctioning null cell adenomas) were investigated immunohistochemically with antibodies against chromogranin A and B as well as ACTH, GH, prolactin (PRL), FSH, LH, TSH, and alpha-HCG antibodies. For the demonstration of chromogranin B, two different antibodies were used--e.g., a polyclonal antihuman antibody and an antiserum against a synthetic peptide (DK-21, chromogranin B 306-326) present in the chromogranin B amino acid sequence. All tumors were positive for both chromogranin B antibodies. Chromogranin A was found in FSH- (two of two) and TSH- (two of two) secreting adenomas; it was also found in a focal distribution in ACTH- (one of three) and GH- (four of nine) secreting adenomas. Thirteen of 16 null cell adenomas contained chromogranin A, whereas no chromogranin A was found in prolactinomas. We conclude that null cell adenomas may arise either from FSH/LH or TSH cells (null cell adenomas with both chromogranin A and B positivity) or from ACTH, GH, or PRL cells (the respective tumors are only positive for chromogranin B). Chromogranin B may be used as a universal marker for pituitary adenomas.

Adenoma↗
PubMed1991

New concepts in ischemia prevention.

Transient myocardial ischemia may result from obstruction to flow in the large epicardial coronary arteries or diminished flow reserve due to small vessel disease or left ventricular hypertrophy. In patients with coronary heart disease, calcium blockers have proven to reduce stress induced ischemia in patients with normal left ventricular function and in those with ischemic cardiomyopathy. However, recent studies indicate a need for caution when giving calcium antagonists to patients with postinfarction left ventricular systolic dysfunction. Moreover, calcium antagonists that reduce heart rate (diltiazem) are able as a monotherapy to reduce total ischemic burden. Calcium antagonists that may increase rate (dihydropiridines) have to be combined with beta-blockers to achieve this goal. For 24-h control of ischemia the ischemic threshold should be determined for a differentiated therapy in the individual patient. Is the ischemic threshold of the majority of episodes lower than the exercise threshold, a calcium blocker should work. Angiotensin-converting enzyme (ACE) inhibitors are not effective in stress-induced ischemia, but may reduce total ischemic burden, although this effect is not significant. In patients with left ventricular hypertrophy and/or small vessel disease, calcium blockers and ACE inhibitors are probably effective in regression of left ventricular hypertrophy and vascular hypertrophy. However, it remains to be shown that ischemia is reduced by these drugs.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1991

[Coronary artery anomalies in adulthood].

In a series of 3000 consecutive coronary angiographies carried out in adults (period October 1988 through February 1991) the incidence of coronary artery anomalies was investigated. Among these there were 7.2% of patients with left-, 3.8% with right-sided and 89% with bilateral coronary artery supply. 10 cases revealed a double left anterior descendent artery (LAD), whereas in 2 patients the left circumflex artery (CX) was missing. In approximately 1% of patients origin anomalies of coronary arteries were observed, above all of the right coronary artery (RCA). A pronounced kinking of the coronaries was seen in 22 cases (11 LAD, 11 RCA) and a bridging in 2.5% of patients (74 LAD, 1 CX, 1 RCA). Of the latter, there were 21 hemodynamic active stenoses (more than 75% diameter stenosis) of which in 12 cases this narrowing was the sole cause for the heart complaints. During the same period there were 8 patients with coronary anomalies leading to shunt development out of which a 30-year-old female revealed clinically a coronary steal phenomenon. Aneurysms of the coronary arteries were observed in 54 cases (2%) whether congenital or acquired could not be ascertained. In total, there were 194 coronary anomalies in the total series (6.5%) being clinical significant in 22 cases (0.7%).

Adult↗