Biomedical subjects

H Haller

Publications and source records attributed to H Haller.

312 records · Page 18Linked to original sources

PubMedDate not supplied

Diapedesis of leukocytes: antisense oligonucleotides for rescue.

Ischemia-reperfusion injury is an acute inflammatory process during which leukocytes are intimately involved. In this review, we summarize the current data on the leukocyte cell adhesion cascade in ischemia-reperfusion injury, focus upon studies which have demonstrated specific cell adhesion molecule interactions which mediate the leukocyte involvement in ischemia-reperfusion injury, and suggest future avenues of therapeutic interventions. The increased adhesion between activated vascular endothelium and peripheral blood leukocytes is central to the structural and the functional impairment in ischemia-reperfusion injury. Several families of adhesion molecules, namely the selectins, the intercellular adhesion molecules (ICAMs), and the integrins expressed either on the endothelium or on the leukocytes, are involved the cascade of events. Sequential and overlapping cellular interactions between the members of the three gene families of adhesion receptors result in adhesion of the leukocytes to the endothelium and extravasation at the site of ischemia. The functional importance of ICAM-1 and its beta2 integrin ligands in ischemia-reperfusion of the kidney has been demonstrated by monoclonal antibody blockade studies, in knockout mice and by treatment with antisense oligodeoxynulceotides (ODN). We have shown that antisense ODN for ICAM-1 protected the kidney against ischemic renal failure. In addition, in transplanted kidneys, ICAM-1 inhibition by antisense ODN ameliorates ischemia-reperfusion injury and prevents delayed graft function. Recent developments in antisense ODN technology make this a promising therapeutic approach, and antisense ODN treatment of donors or donor organs for ICAM-1 may be useful for the prevention of reperfusion injury in human renal transplantation and could influence acute and chronic graft function.

Animals↗

PubMedDate not supplied

Nuclear protein transport pathways.

Nuclear proteins like transcription factors and ribosomal proteins are synthesized in the cytoplasm and have to be transported into the nucleus to fulfill their functions. The transport of proteins >20-60 kD through the nuclear pore complex (NPC) into the nucleus is an active, energy-requiring process. Transport substrates are recognized by their transport proteins via certain signals. The best-characterized protein import pathway is the 'classical' nuclear localization signal-dependent pathway with importin alpha and beta carrying the substrate to the NPC. The transport of the importin-substrate complex into the nucleus is regulated by the small GTPase Ran/TC4. During the last years more than ten proteins have been discovered which have already been proven or are very likely to be nuclear transport factors of distinct import pathways: members of the importin alpha protein family are very similar and transport in complex with importin beta nuclear localization signal-bearing proteins into the nucleus. Members of the Ran-binding protein family show some weak similarity to importin beta. Sharing a common domain at the amino terminus, they are able to bind RanGTP, a prerequisite for their function as nuclear import or export factors for distinct proteins or RNAs. However, Ran/TC4 seems to play a key regulatory role in all nuclear transport pathways described so far, although the molecular mechanism of the translocation step through the NPC is still unclear.

Animals↗

PubMedDate not supplied

Pituitary adenylate-cyclase-activating peptides relax human coronary arteries by activating K(ATP) and K(Ca) channels in smooth muscle cells.

Pituitary adenylate-cyclase-activating peptides (PACAPs) are potent dilators of arteries, including human coronary arteries. We tested the importance of specific K+ channel regulatory mechanisms in human arterial smooth muscle relaxation induced by PACAPs, using contraction and patch clamp measurements on human coronary artery vascular smooth muscle cells. PACAP27 and PACAP38 produced dose-dependent relaxations of 5 microM PGF2alpha-preconstricted rings, with half-maximal relaxations at 1.0 nM and 2.0 nM, respectively. Both peptides induced complete relaxation at 100 nM. Pretreatment of the vessels with the ATP-dependent K+ (K(ATP)) channel blocker glibenclamide (1 microM) or with the Ca2+-activated K+ (K(Ca)) channel blocker iberiotoxin (100 nM) inhibited PACAP27-induced relaxation in an additive manner. Moreover, in the patch clamp experiments on freshly isolated cells from human coronary arteries, PACAP27 (100 nM) induced a large, nonrectifying, outward (I(K)(ATP)) K+ current in a proportion of cells and a voltage-dependent outward (I(K)(Ca)) K+ current in other cells. The PACAP27-induced I(K)(ATP) was blocked by glibenclamide (3 microM), while the PACAP27-stimulated I(K)(Ca) was blocked by iberiotoxin (100 nM). These findings provide the first evidence that relaxation of arterial smooth muscle cells by PACAPs is mediated by opening of K(ATP) and K(Ca) channels. The data indicate that both K(ATP) and K(Ca) channels in vascular smooth muscle cells may serve as final common pathway to induce vasorelaxation by endogenous vasoactive signals in man.

Coronary Vessels↗

PubMedDate not supplied

Multiple pathways for ATP-induced intracellular calcium elevation in pheochromocytoma (PC12) cells.

Extracellular ATP excites neurons in both the peripheral and central nervous system. To elucidate the mechanisms involved, we used spectrofluorometric analysis to study the pathways by which extracellular ATP elevates the intracellular Ca2+ concentration ([Ca2+]i) in individual, fura-2-loaded, rat pheochromocytoma PC12 cells. ATP (> 1 microM) increased [Ca2+]i. The ATP effect on [Ca2+]i was completely abolished by a nominally Ca(2+)-free extracellular medium, which indicates that the ATP-induced increase in [Ca2+]i was due to an influx of extracellular Ca2+. We next applied specific blockers of voltage-dependent Ca2+ channels and used experimental protocols with depolarizing external K(+)-rich solutions. Our results show that ATP induces influx of extracellular Ca2+ through (a) dihydropyridine-sensitive (Ln-type) Ca2+ channels, (b) Ca(2+)-permeable, voltage-independent, Cd(2+)-insensitive cation channels, and (c) an as yet unidentified, voltage-dependent, Cd(2+)-sensitive Ca2+ influx system.

Adenosine Triphosphate↗

PubMedDate not supplied

Elimination of lipofundin S during the intravenous fat tolerance test in patients with low, medium, and high fasting triglyceride concentrations.

The intravenous fat tolerance test with Lipofundin S (0.5 ml of 20% emulsion/kg body weight) was performed in 22 male nondiabetic patients. According to their fasting triglycerides (TG), the patients were arranged into three groups: low (less than 2.8 mmol/liter), medium (2.8-5.7 mmol/liter), and high (greater than 5.7 mmol/liter) concentrations. Fractional elimination rates of injected Lipofundin S decreased from 11.08 in low TG to 4.57%/min in high TG; they were positively correlated with fasting levels of high-density lipoprotein cholesterol but negatively with those of TG. The same pattern of correlations was observed with fractional catabolic rates of endogenous TG as measured after injection of tritium-labeled glycerol. The intravenous Lipofundin S load effected transient TG and free fatty acid elevations which were delayed in high TG. The elimination mechanisms of injected Lipofundin S and of endogenous TG are compared.

Adult↗

PubMedDate not supplied

[Health risks in intrauterine contraception].

From 1968 till 1987, 8514 first insertions of different IUDs were performed; 7315 IUD users were regularly followed-up. In 4269 cases non-medicated and in 3046 cases medicated IUDs were inserted. All women were classified according to age, parity and the number of previous abortions. In the women analysed only one cervical perforation was found 3 months after the insertion of TCu 380 Ag (secondary perforation). In the group of non-medicated IUD users till the cut off date (February 29, 1988) 377 (8.8%) pregnancies were registered of which 10 were ectopic; at the same time there were 104 (2.4%) cases of PID. In the group of medicated IUD users 160 (5.3%) pregnancies with 11 ectopic and 90 (3.0%) cases of PID were observed. According to the age of users, in the group of women in their teens pregnancies appeared more often than in the older users, independent of the type of the IUD used. This difference was statistically significant (p less than 0.05). The highest percent age of PID was registered in mulliparous medicated IUD users: the difference in the PID appearance in nulliparous and multiparous medicated IUD users has also shown a statistical significance. Gross cumulative rates after 10 years of use fo non-medicated IUDs were 12.5 for pregnancy and 4.6 for PID, and after 15 years 14.6 and 6.2, respectively. For medicated IUDs after 10 years of use these rates were 9.4 for pregnancy and 8.3 for PID.

Female↗