Search PubMed⌕ Search

Biomedical subjects

U Walter

Publications and source records attributed to U Walter.

242 records · Page 14Linked to original sources

Signal transduction by cGMP in heart.

Early studies in whole heart indicated that cGMP antagonized the positive inotropic effects of catecholamines and cAMP. However, the regulation of cGMP levels by a variety of agents was not always consistent with their effects on contractility. It is now clear that at least two major cell types in whole heart, cardiac myocytes and vascular smooth muscle cells, differ markedly in their mechanisms of cGMP regulation and response to cGMP. Furthermore, experiments on isolated cardiac myocytes indicate that the mechanism of cGMP action even in this single cell type can be multifaceted. Cyclic GMP inhibits the L-type calcium channel current (ICa), which is the major source of Ca++ entry into heart cells, and which plays a predominant role in the initiation and regulation of cardiac electrical and contractile activities. Patch-clamp measurements of ICa indicate that in isolated frog myocytes cGMP inhibits ICa by stimulation of cAMP phosphodiesterase (cGS-PDE), whereas in purified rat ventricular myocytes, cGMP predominantly inhibits ICa via a mechanism involving cGMP-dependent protein kinase (cGMP-PK). Under certain conditions, cGMP can also inhibit a cGMP-inhibited cAMP phosphodiesterase (cGI-PDE) and thereby produce a stimulatory effect on ICa. Biochemical characterization of the endogenous PDEs and cGMP-PK in purified cardiac myocytes provided further evidence in support of these mechanisms of cGMP action on ICa.

Animals↗

Neonatal platelets from cord blood and peripheral blood.

The haemostatic system in neonates is different from that of adults, possibly contributing to an increased incidence of bleeding disorders, such as intracranial hemorrhage. In this study, we analyzed platelets from cord blood and peripheral blood, collected at three time points after delivery from 20 term and 37 preterm neonates as well as blood from 20 healthy adults. Platelet membrane glycoproteins (GP) were quantified and P-selectin expression and PAC-1 binding ability before and after stimulation with TRAP were analyzed by whole blood flow cytometry. We found no significant differences in neonatal platelets from cord blood and peripheral blood within the first 24h of life. Platelets from infants less than 30 weeks of gestation expressed lower levels of GP (33271+/-9381 vs. 44085+/-17287 for GPIIIa, P<0.05) and were less reactive than platelets from term newborns (4.3+/-3.3 vs. 20.1+/-11.8% PAC-1 positive platelets after stimulation with TRAP, P<0.05). A significantly lower level of GPIIb/IIIa expression on platelets from peripheral blood was seen in term newborns as well as preterm infants, compared to adults. There was only a partial enhancement in the degranulation ability (alpha-granules) (13.4+/-12.3 vs. 50.3+/-16.1% P-selectin positive platelets, P<0.05) and no significant increase for PAC-1 binding (13.6+/-10.9 vs. 15.3+/-5.9% PAC-1 positive platelets, P=0.8) during the first 12 days of life. In conclusion, we could demonstrate that neonatal platelet reactivity increases with gestational age.

Acid Phosphatase↗

Correlation between mononuclear infiltration and changes in VASP phosphorylation patterns after heterotopic cardiac transplantation in the rat.

Chronic cardiac transplant vasculopathy still remains the major cause of late graft failure after the 1st postoperative year, with iNOS playing a central role in the progression of this disease. Since VASP, a recently identified microfilament-associated protein in smooth muscle cells, endothelial cells, and platelets, is phosphorylated by cyclic nucleotide dependent protein kinases, changing amounts of NO-producing mononuclear infiltration cells during cardiac rejection are supposed to change platelet VASP phosphorylation patterns. We investigated whether platelet VASP Ser(157) phosphorylation (VASP shift) after coronary passage of rat cardiac allografts correlates with graft infiltration. The Lew-F344 heterotopic rat cardiac transplantation model was used. Native hearts and grafts were harvested 3-150 days after transplantation and were used for Langendorff perfusion. The platelet VASP shift after native heart and graft perfusion was identified. Additional iNOS stimulation and iNOS inhibition were achieved pharmacologically. Immunohistology revealed graft mononuclear infiltration. Platelet VASP Ser(157) and Ser(239) phosphorylation significantly increased after coronary passage of native hearts and grafts (p < 0.01). Though platelet VASP Ser(157) phosphorylation failed to directly express graft infiltration, we showed a significant correlation between changes of platelet VASP shift and extent of grafts' mononuclear infiltration after competitive iNOS inhibition (p < 0.01). The platelet VASP shift is modified during coronary perfusion, and this modification correlates with mononuclear infiltration in the graft. This emphasizes the influence of mononuclear infiltration cells on microfilamental structures of the cytoskeleton in adjacent cells.

Animals↗

Abnormal sodium efflux in erythrocytes of patients with essential hypertension.

Erythrocyte sodium efflux as well as sodium, potassium, and water content were studied in 12 untreated men with uncomplicated essential hypertension and in 18 normotensive control subjects. In the patients with essential hypertension, the rate constant for total sodium efflux was significantly lower than in the normotensives (5.96.10(-3) +/- 0.45.10(-3) min-1 vs 6.69.10(-3) +/- 0.49.10(-3) min-1; p less than 0.005), which was due to a reduced ouabain-sensitive sodium efflux rate constant. Significant differences in total sodium efflux and ouabain-sensitive sodium efflux, however, could not be demonstrated, since intracellular sodium concentrations, although insignificant, were higher in the patients with essential hypertension (6.11 +/- 0.74 mmole/liter vs 5.97 +/- 0.66 mmole/liter. The rate constants for ouabain-insensitive sodium efflux, for ouabain-insensitive furosemide-sensitive sodium efflux, and for passive (ouabain-insensitive furosemide-insensitive) sodium efflux were similar in hypertensives and in normotensives. The cause of the reduced rate constant for ouabain-sensitive sodium efflux is not clear. However, as suggested for other types of altered erythrocyte transport mechanisms described recently, it might be determined genetically.

Adult↗

[Morphometric findings of a peculiarity in the aging of the lymphatic system].

The size of sections of lymph follicles in the pharyngeal tonsils of sixty-four children and juveniles between two and twenty-one years of age was determined histomorphometrically. The measurements were followed by linear regression and correlation analyses and determinations of mean differences by Student's t-test. It was possible to show that lymph follicles start decreasing in size already from the third year of life onward. Moreover, lymph follicle size decreases with the frequency of infections, and there is a positive correlation between the histomorphometrically determinable follicle size and the macroscopic size of the organ.

Adolescent↗

Erythrocyte phosphate release in essential hypertension.

In this study erythrocyte phosphate release depended on the intracellular hydrolysis of organic phosphate esters. Total phosphate release was increased in essential hypertension, which suggests an elevated phosphate ester metabolism. Ouabain-sensitive phosphate release was decreased, and the ratio of intracellular Na+/K+ concentrations was increased, a finding consistent with a diminished Na-K-ATPase activity. Furosemide in a concentration of 1.0 mmol/L inhibited erythrocyte phosphate release by half, probably owing to nonspecific membrane effects. The combination of ouabain and furosemide reduced phosphate transfer to a higher degree than did each substance individually. Because of the nonspecific alteration of erythrocyte membrane permeability by furosemide in a concentration of 1.0 mmol/L, ouabain-insensitive, furosemide-sensitive phosphate release and ouabain-insensitive, furosemide-sensitive Na+ efflux (Na-K cotransport) must not be regarded uncritically as specific transport systems.

Adolescent↗

[Typology of illness in aging--consequences for prevention concepts].

Conventional dichotomy or three-part classifications for disease and age are not very helpful for practical application. The article presents a typology of disease, which we developed further into four categories. It considers the relation between physiological processes of aging and pathological developments as well as the courses of disease in old age. Adequate prevention strategies can be derived. Category I (physiological changes in old age which are only possibly a disease) demonstrates the importance of the context in illness. Physiological processes of aging with a high plasticity can be influenced by prevention strategies. Category II (age-related disease with a long latency period) demonstrates the problem of early recognition and secondary prevention. The category III (disease with different physiological process in old age because of reduced homeostatic regulation and repair mechanism) is not receptive to preventative concepts, but only to tertiary prevention and rehabilitation. In the category IV (disease as a result of long term exposure, increasing with lifetime) population-based prevention strategies are sensible.

Aged↗