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H Haller

Publications and source records attributed to H Haller.

At least 217 records · Page 12Linked to original sources
PubMed1992

Superoxide anion release induced by platelet-activating factor is increased in human alveolar macrophages from smokers.

This study was designed to investigate the effects of the platelet-activating factor (PAF) on the superoxide anion production (O2.) of human alveolar macrophages (AM) from nonsmoking (n = 18) and smoking (n = 30) subjects. Freshly isolated cells were stimulated with (PAF) or with a phorbol ester (phorbol 12-myristate 13 acetate (PMA)). Stimulation with PAF led to a dose-dependent increase of O2. production by AM in both groups. The median effective dose (EC50) for PAF action on O2. production of smoker AM was 0.5 x 10(-8) M, compared to nonsmoker AM with an EC50 of 1.0 x 10(-7) M. This effect of PAF was blockable by the PAF-antagonist WEB 2086 in a dose-dependent manner. Comparison of the relative increase of O2. production after PAF-stimulation showed that smoker cells were significantly more sensitive to PAF than nonsmoker cells (p less than 0.01). In contrast to the findings with PAF, the relative increase of O2. production after PMA-stimulation showed no differences between smoker and nonsmoker AM. Our data suggest that AM from smoking subjects are more sensitive to PAF than AM from nonsmokers.

Bronchoalveolar Lavage Fluid↗
PubMed1991

Thyrotropin-releasing hormone induces opposite effects on Ca2+ channel currents in pituitary cells by two pathways.

Thyrotropin-releasing hormone (TRH) stimulates pituitary secretion by steps involving a cytosolic Ca2+ rise. We examined various pathways of Ca2+ elevation in pituitary GH3 cells. By using the patch clamp technique in the whole-cell configuration and Ba2+ as divalent charge carrier through Ca2+ channels, TRH (1 microM) reversibly reduced the current by about 55%. This hormonal effect was prevented by infusing guanine 5'-[beta-thio]diphosphate (GDP[beta S]) intracellularly but not by pretreating the cell with pertussis toxin (PT). Since PT-insensitive guanine nucleotide-binding regulatory (G) proteins are known to mediate a hormone-stimulated inositol trisphosphate-mediated Ca2+ release from intracellular stores, we assume that the inhibitory effect of TRH on Ba2+ currents through Ca2+ channels is caused by the increased intracellular Ca2+. To prevent a Ca(2+)-release-dependent inhibition of Ca2+ channels, we preincubated GH3 cells in a medium free of divalent charge carriers and measured the Na+ current through Ca2+ channels. When fura-2 was used as indicator for the cytosolic Ca2+, TRH induced a release from intracellular stores only once and had no effect on the intracellular Ca2+ concentration during further applications. In line with this observation, TRH initially reduced the Na+ current through Ca2+ channels but stimulated it during subsequent applications. The stimulation was sensitive to GDP[beta S] and was abolished by pretreatment with PT, suggesting that the stimulatory action of TRH is mediated by a G protein different from the one that functionally couples the receptor to phosphatidylinositol 4,5-bisphosphate hydrolysis. In conclusion, the present data suggest that TRH increases the intracellular Ca2+ concentration by two interacting pathways, that release from intracellular stores causes a secondary blockage of Ca2+ channels, and that, especially with empty intracellular Ca2+ stores, Ca2+ channels are stimulated by a PT-sensitive G protein.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1991

Evidence for a platelet-activating factor receptor on human alveolar macrophages.

In this report we demonstrate evidence which strongly suggests that human alveolar macrophages possess receptor for the platelet activating factor (PAF). We investigated the effects of PAF by measuring (a) the intracellular free calcium concentration [Ca2+]i, using the fura-2 method in single isolated cells and (b) the production of superoxide anion. PAF increased [Ca2+]i in a dose-dependent manner (EC50 = 1 x 10(-8) M), whereas lyso-PAF had no effect. The initial increase of [Ca2+]i was followed by a slow decrease to a sustained elevation of [Ca2+]i significantly above basal values. While the initial rise in [Ca2+]i was only slightly reduced in Ca(2+)-free medium (1 mM EGTA), the sustained phase was totally abolished. The sustained calcium increase was also blocked after preincubation of AM with the calcium-channel blocker nitrendipine. PAF increased the production of superoxide anion (O2-) by human alveolar macrophages in a dose- dependent manner. The effects of PAF on [Ca2+]i and (O2-) could be blocked by the PAF-specific antagonist WEB 2086 dose dependently, indicating a receptor-mediated event.

Adult↗
PubMed1991

Trauma involving the proximal tibial epiphysis.

Thirty injuries involving the proximal tibial epiphysis were treated during a period of 28 years. The epiphysis was displaced in 16 cases (53%). Three patients presented with peripheral ischemia on admission, and one patient with associated ipsilateral femoral fracture developed delayed thrombosis of the popliteal artery. The treatment results were satisfactory in 21 of the 27 (74%) who were reassessed according to Shelton's evaluation criteria after an average post-traumatic interval of 11.6 years. Three of the six patients with unsatisfactory outcome had a discrepancy in leg length of more than 2.5 cm after concomitant ipsilateral fracture of the femur or the tibia. One patient had a positive 3-cm anterior drawer sign, one patient had a 10 degree valgus deformity of the tibia, and one had to undergo above-knee-amputation because of delayed diagnosis of the vascular lesion.

Adolescent↗
PubMed1991

The effect of adding copper onto Lippes Loop IUDs: results from a ten-year study in Yugoslavia.

The present study is the first randomized ten-year comparison of the standard, non-medicated Lippes Loop D and the same device with the addition of 200 mm2 of copper in the form of copper sleeves. The devices were randomly inserted immediately after first trimester medical termination of pregnancy. Out of 400 postabortal IUD insertions, 371 were followed for up to ten years. Gross cumulative life-table accidental pregnancy rates after one year of use were 0.56 for the copper-bearing Lippes Loop and 4.63 for the standard Lippes Loop. After two, four and ten years, these rates were 1.24, 2.70 and 3.62 and 6.03, 7.58 and 14.94, respectively (in all comparisons, rates were significantly different at the 0.05 level or lower). At each time interval, expulsion/displacement rates were 4.49, 4.49, 5.23 and 6.32 for the copper-bearing Lippes Loop and 12.61, 13.29, 15.46 and 19.79 for the standard Lippes Loop (rates were significantly different at the 0.01 level or lower). Differences in removal rates for bleeding and/or pain were not significantly different at any of the follow-up intervals. The lower event rates for copper-bearing Lippes Loop D users indicates that the addition of copper to the Lippes Loop IUD may result in better long-term efficacy profiles for this device among postabortal women. The results also suggest that large, medicated IUDs may be more efficacious for women with larger uteri who often experience higher failure rates due to expulsion or displacement of smaller IUDs into the lower uterine segment.

Adolescent↗
PubMed1991

Endothelin increases [Ca2+]i, protein phosphorylation, and O2-. production in human alveolar macrophages.

The goal of the present study was to investigate whether endothelin (ET) increases O2-.production in alveolar macrophages and to establish which second messengers are activated by ET. We measured the effects of ET on cytosolic free calcium concentration [Ca2+]i, protein phosphorylation, and O2-.production in human alveolarmacrophages (HAM). Human macrophages were obtained by bronchoalveolar lavage. [Ca2+]i was measured by the fura-2 method both in cell suspensions and in isolated single macrophages. Protein phosphorylation was assessed by gel electrophoresis and autoradiography after labeling the cells with 32P. ET increased [Ca2+]i in a dose-dependent manner (50% effective concentration = 1 x 10(-7)M). At a concentration of 10(-6)M ET, [Ca2+]i rose from basal values of 121 +/- 23 to 456 +/- 41 nM. This increase was comparable with the increase of [Ca2+]i induced by N-formyl-L-methionyl-L-leucyl-L-phenylalanine and platelet-activating factor (PAF; 1-O-alkyl-2-acetyl-sn-glyceryl-3-phosphorylcholine). The initial rise in [Ca2+]i and the sustained phase were significantly reduced in calcium-free medium (1 mM ethyleneglycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid) and after preincubation of HAM with the calcium channel blocker nitrendipine (10(-7)M). Exposure of 32P-labeled HAM to ET for 1 min induced the phosphorylation of a group of 48-kDa proteins and of a 35-kDa protein. The ET-induced 32P incorporation into the 48-kDa proteins was less pronounced than the 12-O-tetra-decanoylphorbol-13-acetate or PAF-induced response (168 +/- 24 vs. 356 +/- 68 and 278 +/- 61% of control).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

Protein kinase C translocation in intact vascular smooth muscle strips.

Using intact muscle strips from the bovine carotid artery, the time course of translocation of protein kinase C (PKC) from the cytosol to the membrane fraction was measured in response to various agonists that induce contractile responses. PKC activity was assessed by Ca2+/phospholipid-dependent phosphorylation of histone. Exposure of the muscle strips to phorbol ester (12-deoxyphorbol 13-isobutyrate) induced a rapid and sustained translocation of PKC from the cytosol to the membrane fraction, and a slowly developing but sustained contractile response. Histamine induced a comparable initial translocation of PKC to the membrane which then decreased somewhat to a stable plateau significantly above basal values. Histamine also led to a rapid and sustained increase in tension. Angiotensin I, which caused a rapid but transient contraction, induced a rapid initial translocation of PKC to the membrane. The membrane-associated PKC then declined to a stable plateau significantly lower than that seen after a histamine-induced response, and only slightly above the basal value. Endothelin, which induced a sustained contraction, caused a sustained translocation of PKC from the cytosol to the membrane. In contrast, although exposure to 35 mM-KCl induced a rapid and sustained contraction, it caused only a transient translocation of PKC; the membrane-associated PKC returned to its basal value within 20 min. These results demonstrate that PKC in intact smooth muscle can be rapidly translocated to the membrane and remains membrane-bound during sustained phorbol ester- or agonist-induced contractions, but that such a sustained translocation of PKC does not occur during prolonged stimulation with KCl.

Angiotensin II↗
PubMed1990

Cells adherent to copper-bearing intrauterine contraceptive devices determined by monoclonal antibodies.

The presence of nucleated cells adherent to copper-bearing IUDs removed from successful IUD users, as well as from those IUD users with accidental pregnancy, was determined by a panel of monoclonal antibodies. A significant decrease in the percentage of CD3+ cells-mature T lymphocytes was found in the cell population adherent to IUDs removed from pregnant compared to non-pregnant uteri (43 +/- 2.6 vs 34 +/- 1.5). Among these cells, the percentage of CD4+ cells was increased (from 22.9 +/- 1.9 to 30.4 +/- 2.0), and CD8+ was decreased (from 23 +/- 0.9 to 10.8 +/- 1.2). The percentage of HLA-DR+ cells was also decreased (from 24.3 +/- 1.7 to 16.7 +/- 1.8). B4+ cells (B lymphocytes) were present in a similar percentage on IUDs removed from pregnant as well as from non-pregnant uteri. Thus, the uterine cavity in the presence of an IUD, contains a consistent population of immunologically competent cells. The question still remains, whether the change in the number of nucleated cells present in the uterine cavity with an IUD could contribute to its antifertility effect.

Adhesiveness↗
PubMed1989

Endothelin depolarizes membrane voltage and increases intracellular calcium concentration in human ciliary muscle cells.

The ciliary muscle which is involved in accommodation and regulation of aqueous humour outflow resistance resembles smooth muscle in other parts of the body. In the present investigation we used an established primary cell line (H7CM) to study the effects of endothelin, a novel vasoconstrictor peptide, on membrane voltage (V) and intracellular calcium in cultured human ciliary muscle cells. Membrane voltage was measured in confluent monolayers of H7CM cells using conventional microelectrodes. Intracellular calcium concentration [( Ca]i) was measured in single H7CM cells using the fluorescent calcium indicator fura-2. Under resting conditions V averaged -66.9 +/- 0.7 mV (mean +/- SEM, n = 125). Endothelin (10(-10)-10(-6)M) induced a dose-dependent reversible membrane voltage depolarization and a dose-dependent rise in [Ca]i. The initial calcium peak was followed by a recovery phase during which oscillations of [Ca]i occurred. The initial calcium peak was not dependent on the presence of extracellular calcium and was not abolished in the presence of the calcium antagonist verapamil (10(-4)M). Thus it is probably mediated by a release of calcium from intracellular reservoirs. We conclude that cultured human ciliary muscle cells express a functional endothelin receptor.

Benzofurans↗
PubMed1989

[Coronary heart diseases and associated risk factors in newly manifested type II diabetic patients over the course of 5 years].

Using the baseline data of the diabetes intervention study (DIS) from 1126 newly manifested type II-diabetics our analysis demonstrates higher mean-values of some components of the so-called metabolic syndrome in patients with ECG-abnormalities indicating coronary heart disease (CHD) in diagnosis of diabetes compared with subjects without ECG-findings. The impact of general risk factors for the prevalence of CHD in diagnosis and after a 5-year follow-up is obviously different in both sexes. In multivariate analysis only systolic blood pressure was persistently a significant predictor in both sex groups. With increasing age life-duration gets as time-related factor importance for the development of CHD. The mathematically demonstrated association of triglyceride levels to the presence of ECG-abnormalities agrees with the results of WHO multinational study of vascular disease in diabetes mellitus. In the interventions as well as in the control-groups diabetic subjects with CHD after 5 year follow-up showed in comparison to diabetics without CHD higher levels of investigated risk factors which develop their pathogenetic effect probably by their clustering impact, because the differences of their mean-values are only in some cases significant. The common lower level of the most risk factors at the intervention group compared with the conventionally treated group is the result of the intervention measures.

Adult↗
PubMed1989

Saturable first-pass kinetics of propranolol.

Reduced bioavailability (F) due to hepatic first-pass extraction of an oral dose (D) is a well-known pharmacokinetic phenomenon. An integrated solution for Michaelis-Menten kinetics of the first-pass effect is derived from the maximal metabolic rate (Vm), volume of distribution (Vd), first order absorption rate constant (ka), Michaelis constant (Km), and liver blood flow (Q). F = 1 - VmVd/kaD ln (1 + kaD/QKm) This equation for single dosage can also be extended to steady state kinetics after multiple dosing in which the amount of a drug present in the hepatic circulation is considered. According to the literature, the bioavailability of a single 80 mg oral dose of propranolol (F = 0.22) increases after multiple doses Fss = 0.36). Based on the first pass equations for single dosage and multiple dosing, the maximal metabolic rate (Vm = 0.043 mg l-1 h-1) corresponding to 310 mg per day and the Michaelis constant (Km = 0.10 mg/l) were calculated for propranolol. Incorporation of nonlinear plasma protein binding in this concept may explain the lack of threshold phenomenon for a single dose of less than 40 mg propranolol. Zero order absorption kinetics could explain why cumulation kinetics seem linear even at an excessive dosage of 960 mg propranolol per day. From these derivations it may be concluded that multiple dosing, increase in plasma protein binding, high absorption rate, and increased portal venous blood flow will increase bioavailability, whereas slow release formulations, fractional drug dosage, and saturable absorption kinetics will decrease bioavailability of first-pass drugs like propranolol.

Absorption↗
PubMed1989

Increased intracellular free calcium and sensitivity to angiotensin II in platelets of preeclamptic women.

Preeclampsia is characterized by a generalized vasoconstriction and increased vascular sensitivity to angiotensin II. Intracellular free calcium, implicated in vascular smooth muscle contraction, has been found to be elevated in platelets of other hypertensive disorders. We therefore measured intracellular free calcium concentrations by using the fluorescent probe quin-2 in platelets of six patients with preeclampsia and compared them to measurements in ten normotensive pregnant women and ten age-matched nonpregnant women. Intracellular free calcium was also determined in the preeclamptic women after delivery. We found that intracellular free calcium was slightly elevated in normal pregnancy (102 +/- 13 nmol/L v 87 +/- 17 nmol/L) but was markedly increased in preeclampsia (138 +/- 13 nmol/L, P less than .05). This increase disappeared six weeks after delivery (84 + 10 nmol/L, P less than .01). To investigate whether the increased intracellular free calcium was related to angiotensin II, the platelets were exposed to thrombin and angiotensin II in vitro. Exposure to thrombin and angiotensin II caused a dose-dependent increase in intracellular free calcium. The intracellular response to thrombin was not significantly different in the three groups. However, stimulation with angiotensin II revealed an increased response in intracellular free calcium in preeclampsia (P less than .05) that disappeared after delivery. Our findings show a sustained increase in platelet intracellular free calcium in preeclampsia and suggest a functional alteration of the angiotensin II receptor in this disease.

Adult↗
PubMed1989

Continuous membrane voltage recordings in A10 vascular smooth muscle cells: effect of AVP.

Continuous membrane voltage (V) recordings were obtained in A10 vascular smooth muscle cells (rat aorta) using glass microelectrodes. Resting membrane voltage in 262 impalements averaged 54.0 +/- 0.4 (SE) mV. Relative K+ conductance was characterized, and the contribution of electrogenic Na+-K+-ATPase to membrane voltage was investigated. Action potentials could be induced by application of 1 mM barium or 10(-4) M acetylcholine. In a few recordings, spontaneous spike activity occurred, and this could be abolished by 5 mM MgCl2 or by removal of extracellular Ca2+. Barium-induced action potentials were not dependent on the presence of extracellular Na+ and not inhibitable by 10(-6) M tetrodotoxin. Application of 10(-6) M [Arg8] vasopressin (AVP) for 30 s caused a typical biphasic membrane voltage response with an initial transient hyperpolarization of -9.5 +/- 1.1 mV and a more sustained subsequent depolarizing response averaging 28.2 +/- 1.3 mV (mean +/- SE, n = 58). The effect of AVP on membrane voltage was blocked by the V1-antagonist [beta-mercapto-beta,beta-cyclopentamethylenepropionyl1,O-Me- Tyr2,Arg8]vasopressin. The initial hyperpolarizing component of the membrane voltage response to AVP became more prominent when V was predepolarized, for example, by a preceding AVP application. However, when AVP was applied during high K+ depolarization or in the presence of quinidine (1 mM), the initial hyperpolarizing response was practically abolished. The time course of the initial hyperpolarization was shown to be similar to the calcium transient observed in fura-2-loaded A10 cell suspensions after the application of AVP. We conclude that the initial AVP-induced hyperpolarization in A10 cells corresponds to an activation of Ca2+-activated K+ channels.

Acetylcholine↗
PubMed1989

Factors influencing the response to hepatitis B vaccination of hemodialysis patients.

The response rate and HBsAG antibody concentrations were examined after hepatitis B vaccination in 78 hemodialysis patients aged between 29 and 79 years. The values were related to age, duration of hemodialysis, body weight, creatinine, urea nitrogen, serum concentrations of beta 2-microglobulin and soluble interleukin-2 receptor (IL-2R). Patients with low anti-HBsAG antibody concentrations (10-100 mU/ml) had significantly higher IL-2R serum concentrations than those with high anti-HBsAG antibody concentrations (greater than 3,000 mU/ml; p less than 0.05). Discriminant multivariate analysis (p = 0.032) revealed the influence (62%) of IL-2R on the response rate while other factors were similar in all patient groups. It is concluded that preactivation of T cells with an increased release of IL-2R may contribute to impaired immune response after hepatitis B vaccination.

Adult↗
PubMed1989

Multivariate analysis of aminoglycoside levels in hemodialysis patients.

Multivariate discriminant analysis was performed on data for 50 consecutive hemodialysis patients who had received aminoglycoside treatment because of severe bacterial infections. The 10 of the 60 clinical parameters considered to be most important were survival of patients (28/50 patients), success of treatment (27/50 patients), acute or chronic renal failure (15 vs. 35), age (54 +/- 17 years), creatinine level (675 +/- 298 mumol/l), artificial ventilation (21/50 patients), need for catecholamines (19/50 patients), continuous arteriovenous hemofiltration (9/50 patients), duration of therapy (12 +/- 8 days) as well as aminoglycoside peak (7.5 +/- 2.7 mg/l) and trough levels (3.6 +/- 1.3 mg/l). The 4 of the 10 parameters investigated by multivariate analysis significantly contributing to survival of patients were clinical success of aminoglycoside treatment (p = 0.0001), no need for catecholamines (p = 0.0001), duration of dosage (p = 0.003) and aminoglycoside peak levels (p = 0.009).

Adolescent↗
PubMed1989

Effect of acetylcholine on membrane potential of cultured human nonpigmented ciliary epithelial cells.

Human nonpigmented ciliary epithelial cells (NPE) were grown in tissue culture after transformation with an origin-defective mutant of SV-40 DNA. In these cells membrane potentials (V) were measured using the microelectrode technique. Addition of 10(-4) M acetylcholine led to a bisphasic voltage response. An immediate, transient hyperpolarization was followed by a sustained depolarization below the steady state level. These responses were irreversibly blocked by 10(-5) M atropine. In Ca2+-free media the initial addition of acetylcholine resulted in an unchanged voltage response. A second application of acetylcholine in Ca2+-free solution evoked only an abortive response of V, and further addition had no effect on V. In the presence of Ca2+ channel blockers (10(-5) M verapamil, 1 mM Co2+) the acetylcholine-induced response of the membrane potential was not changed. The initial hyperpolarization induced by acetylcholine was reduced by 33 +/- 3% (n = 6) in the presence of 2 mM Ba2+ and by 79 +/- 6% (n = 6) in the presence of 1 mM quinidine. Moreover, the amplitude of the hyperpolarization was dependent on the extracellular K+ concentration. With increasing extracellular K+ concentration (and decreasing transmembrane K+ gradient) the acetylcholine-induced hyperpolarization was reduced. To further elucidate the role of Ca2+ in the acetylcholine-induced responses, we measured cytoplasmic Ca2+ activity using the fluorescence of intracellularly trapped Fura-2. Cytoplasmic Ca2+ activity increased immediately and transiently upon addition of acetylcholine. We conclude that acetylcholine transiently hyperpolarizes V in cultured human NPE by activation of K+ channels mediated by mobilization of Ca2+ from intracellular stores.

Acetylcholine↗