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D Brunner

Publications and source records attributed to D Brunner.

At least 55 records · Page 3Linked to original sources
PubMed1994

Genetic dissection of signal transduction mediated by the sevenless receptor tyrosine kinase in Drosophila.

The specification of the R7 photoreceptor cell fate in the developing eye of Drosophila depends on the local activation of the sevenless (sev) receptor tyrosine kinase by boss, a protein expressed on the membrane of the neighboring R8 cell. Constitutive activation of the sev receptor results in a dosage dependent increase in the number of R7 cells per ommatidium. Genetic screens have been used to identify mutations that alter the efficiency of signal transduction. Subsequent molecular characterization of the corresponding genes has led to the identification of a number of proteins involved in transducing the signal from the receptor to the nucleus. In contrast to the receptor and its ligand, these components are shared between different signal transduction pathways not only in Drosophila but are also homologous to components involved in signal transduction in other organisms.

Animals↗
PubMed1994

Effect of bezafibrate on lipids, lipoproteins, apolipoproteins and platelet aggregation in hypertriglyceridemic patients.

Twenty-seven hypertriglyceridemic patients were recruited for an open placebo-controlled, 7-month study of the effect of bezafibrate (CAS 41859-67-0, Bezalip, Cedur) on lipids, lipoproteins, apolipoproteins, and platelet aggregation. Patients received 3 placebo tablets a day for a stabilization period of 2 months, followed by a treatment period of 5 months during which one group received bezafibrate 200 mg 3 times a day, and a control group continued to receive placebo. Values measured at the end of the stabilization period were considered as the baseline values. Bezafibrate therapy significantly reduced triglycerides by 43%, and increased HDL-cholesterol by 22%. Apolipoprotein A-1 increased by 14%, and apolipoprotein A-2 by 42%. There was a small reduction of cholesterol (6%), and of apolipoprotein B (11%). A small increase occurred in LDL-cholesterol (2%), suggesting increased catabolism of high VLDL levels which were converted to LDL-cholesterol. Platelet aggregation was measured by the degree of light transmission through a platelet suspension. The improvement of the lipoprotein profile was associated with significant reduction of platelet aggregation in vitro, stimulated by adenosine diphosphate (ADP) at concentrations of 1.15 mumol/ml and 0.75 mumol/ml, and by collagen 2.0 micrograms/ml. Average decrease of platelet reactivity was 45%, 30% and 42%, respectively. The decrease of light transmission with ADP concentration of 2.3 mumol/ml was not significant, suggesting that the aggregatonic effect of the higher ADP concentration overcame the attenuating effect of bezafibrate. The control groups, displayed no significant changes in the blood constituents and platelet functions.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Diphosphate↗
PubMed1994

Choice between fixed and variable delays with different reward amounts.

Choice between a variable and a fixed food source was studied in pigeons. The variable source yielded different durations of access to food (changed across experimental conditions) uniquely associated with equiprobable delays of either 20 s or 60 s, timed from the choice point. A comparison, elapsing alternative (time-left procedure, J. Gibbon & R.M. Church, 1981), was associated with fixed access to feeder after a 60-s delay, timed from the beginning of the trial. Preference was best characterized as reflecting an average of the 2 local rates of reinforcement in the variable alternative (the average of the ratio of each standard amount and its associated delay). The averaging rule characterized initial choice link data well, but terminal link responding showed that Ss also remembered the 2 delay-amount combinations separately.

Animals↗
PubMed1993

Genetic analysis of the sevenless signal transduction pathway of Drosophila.

The specification of the R7 photoreceptor cell fate in the developing eye of Drosophila depends on the local activation of the sevenless (sev) receptor tyrosine kinase (RTK) by boss, a protein expressed on the membrane of the neighboring R8 cell. Constitutive activation of the sev receptor results in a dosage dependent increase in the number of R7 cells per ommatidium. Genetic screens have been used to identify mutations that alter the efficiency of signal transduction. Subsequent molecular characterization of the corresponding genes has led to the identification of a number of proteins involved in transducing the signal from the receptor to the nucleus. In contrast to the receptor and its ligand, these components are shared between different signal transduction pathways not only in Drosophila but homologous components are also involved in signal transduction in other organisms.

Animals↗
PubMed1992

Measurement of converting enzyme activity by antibody-trapping of generated angiotensin II. Comparison with two other methods.

Activity of the angiotensin converting enzyme (ACE) is usually measured in vitro by estimation of products cleaved by the enzyme from synthetic substrates. These substrates have affinities for ACE different from the natural substrate angiotensin I, and insensitive detection systems necessitate millimolar substrate concentrations while physiological angiotensin I concentrations are in the picomolar range. A new assay for ACE activity measurement was developed which reliably quantitates femtomoles of generated angiotensin II in plasma from angiotensin I added at a 17 pmol/mL concentration. The production of high affinity monoclonal antibodies against angiotensin II (Kd = 7 x 10(-11) mol/L) allowed a quantitative trapping (and thus protection from degrading enzymes) of angiotensin II generated during the incubation step and subsequent radioimmunoassay by simple dilution with labelled angiotensin II. Using 40 microL plasma, the detection limit was 20 fmol/mL/min. Normal human plasma has an ACE activity of 335 +/- 83 fmol/mL/min (mean +/- SD). Precision was characterized by coefficients of variation of less than or equal to 11% both within-assay and between-assays. Accuracy of the new method was established by comparing ACE activity with the ratio of plasma angiotensin II/angiotensin I in plasma obtained from normal volunteers 0.5 to 24 h after oral administration of 20 mg enalapril. The percentage of ACE inhibition indicated by both methods was almost identical (r = 0.93, n = 60, P less than .001). Since the latter ratio appears to reflect in vivo ACE activity, these results indicate that accurate measurement in vitro of ACE activity in vivo has been achieved.

Administration, Oral↗
PubMed1992

[Primary closure of traumatically ruptured bursae].

Normally a bursectomy is the choice of therapy when a bursa of a joint is opened through trauma. A primary closure was performed on 10 patients, selected according to certain specific criteria. Nine out of ten cases showed no complications with good short and long-term results.

Adolescent↗
PubMed1991

Isosorbide-5-mononitrate and atenolol in the treatment of stable exertional angina.

Fourteen men and six women, 48-68 years old, with stable angina and effort-induced ST-segment depression (ST-D) were treated with isosorbide-5-mononitrate (IS-5-MN) 2 x 40 mg/day and/or atenolol (AT) 100 mg/day in a double-blind randomized sequence during two 6-week periods. The patients performed ergometer tests. AT caused more decrease of heart rate at rest and at comparable work-load than IS-5-MN. Blood pressure at rest was in the normal range. Decrease of blood pressure at rest and at effort was similar with both agents. Combined administration of the two drugs was not more effective than monotherapy with AT or IS-5-MN in lowering heart rate and blood pressure. The average ST-D at comparable effort was for placebo 2.3 mm, for IS-5-MN after 2, 4, and 6 weeks, 3, 6, and 12 h, respectively, after medication, 1.4, 1.0, and 1.3 mm, and for AT 1.2, 1.4, and 1.4 mm, respectively. Administration of the drugs together caused additional highly significant reduction of ST-D (0.3-0.9 mm). The results indicate that IS-5-MN and AT have a similar beneficial effect on effort-induced myocardial ischemia, which is enhanced by their combined administration. The drugs alone and in combination are effective for as long as 12 h after administration of IS-5-MN, and 24 h after administration of AT. Moderate signs of tolerance to IS-5-MN were found after 6 weeks of therapy.

Aged↗
PubMed1991

[Surgical treatment of diabetic malum perforans by ray resection].

The main cause of the diabetic perforating ulcer is peripheral neuro- and angiopathy. Trivial injuries of the foot, wounds (chiropody), bacterial or mycotic infections often lead to tissue defects in the form of a perforating ulcer (in which neuropathy predominates) or of gangrene (in which angiopathy predominates). The deeply penetrating trophic ulcer with secondary development of osteitis in the foot bones often present us with difficult therapeutic decisions. Several measures for its treatment are given in the literature. We report on 5 patients in whom a plantar perforating ulcer was present beneath the 2nd an 3rd metatarsal heads with radiologically confirmed osteitis. The entire ray, including the corresponding toe, is excised as a wedge from the plantar and dorsal aspects, and the wound left open to heal. The indications, the course of healing, the duration of hospital admission and the complications are described.

Aged↗
PubMed1989

Multivariate analysis of the twenty-year follow-up of the Donolo-Tel Aviv Prospective Coronary Artery Disease Study and the usefulness of high density lipoprotein cholesterol percentage.

The aim of this study was to assess the role of high density lipoprotein (HDL)-cholesterol percentage and its relation to other variables assumed to be coronary risk factors. The 20-year follow-up involved 2,633 presumably healthy subjects, 1,308 men and 1,325 women, aged 25 to 69 years at the beginning of the study in 1964. Variables determined at entry examination included total cholesterol, HDL cholesterol, systolic and diastolic blood pressures, body mass index and cigarette smoking. During the 20-year period there were 242 fatal and nonfatal definite coronary events in men, and 108 in women. All variables differed in varying degrees between subjects who did and did not have a definite coronary event. Three multiple logistic regression models revealed that among these variables the most important was HDL-cholesterol percentage, which significantly improved the regression, even after total cholesterol was included with all other risk factors. With the first model, goodness-of-fit tests indicated that predicted values fit the observed values well, even after the first step, if HDL-cholesterol percentage is entered. The second and third models significantly fit the predicted values only after entering the HDL-cholesterol percentages. This means that although all the other variables, including total cholesterol, differed significantly between the affected and nonaffected groups, they were insufficient predictors alone. The results reveal that HDL-cholesterol percentage had the highest predictive value for risk of future coronary disease; it significantly improved the predictive capability of the logistic regression model, even after adjustment for all other mentioned variables.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

Infection of peritoneal macrophages in vitro and in vivo with feline immunodeficiency virus.

Macrophages were harvested from the peritoneal cavities of healthy specific-pathogen-free cats by saline lavage. Three days before collection, the peritoneal cavities were stimulated with glutaraldehyde-fixed Saccharomyces cerevisiae cells to induce greater numbers of macrophages and to begin the activation sequence. Peritoneal macrophages from cats stimulated once with yeast consisted mainly of small macrophages and a smaller number of larger activated macrophages. After several days in culture, many of the small macrophages became activated and a portion of the activated macrophages developed into multinucleated giant cells. Peritoneal cells from cats that were stimulated twice or three times with yeast at 3-week intervals consisted of a higher proportion of activated macrophages initially and produced more and larger multinuclear giant cells with time. Cultures of peritoneal cells stimulated once with yeast were easily infected in vitro with feline immunodeficiency virus (FIV) and produced a transient burst of reverse transcriptase activity. After the initial burst of virus replication, the infection became latent. Even more multinucleated giant cells appeared after infection, and many of these cells fused with each other. Replicating virus could be rescued from the latently infected macrophages after 2 to 3 weeks of phorbol myristate acetate stimulation and cocultivation with T-lymphocyte-enriched peripheral blood mononuclear cells. Multiply stimulated peritoneal cells, which contained a much higher proportion of activated macrophages, could also be infected in vitro with FIV. The infection usually became latent, however, without going through an initial replicative stage. Peritoneal cells from chronically FIV-infected specific-pathogen-free cats contained a higher proportion of activated macrophages and were latently infected with FIV from the outset.

Animals↗
PubMed1988

Habituation in the crab Chasmagnathus granulatus: effect of morphine and naloxone.

The escape response decrement shown by the crab Chasmagnathus granulatus as a consequence of repeated shadow presentation, meets five of the seven tested parametric criteria of habituation. Results concerning stimulus generalization and dishabituation strongly suggest that neither motor fatigue nor sensory adaptation can account for the response waning. The effects of morphine and naloxone on performance were also studied. Neither 50 nor 5 micrograms morphine/g exerted any modulatory effect on memory retention. A dose of 50 micrograms morphine/g produced an anterograde detrimental effect on responsiveness but no long-term training effects could be detected after the drug's period of action. A dose of naloxone of 1.6 micrograms/g did not antagonize the effect of morphine. The potential value of the response habituation as a model for studying both habituation dynamics and the mechanisms that subserve it, and also for elucidating the effects of opiates on this memory process, is discussed.

Animals↗
PubMed1988

Lipo- and apolipoproteins in a population survey subset in MONICA-Israel.

Lipo- and apolipoproteins in a population survey subset in MONICA-Israel. A group of 169 healthy men and women selected at random from the population survey of the MONICA-Israel Project were screened for baseline values of serum lipoproteins and apolipoprotein A-I and B concentrations. The apolipoprotein measurements were obtained using a recently developed immunoturbidimetric assay. The study population was subdivided into age groups of 25-44 years and 45-64 years. It was found that women aged 45-64 years had significantly higher levels of apolipoprotein A-I, apolipoprotein B, total cholesterol (TC), LDL cholesterol (LDL-c) and a lower ratio of HDL-cholesterol (HDL-c) to TC (HDL-c%) than did their younger counterparts. These parameters did not differ significantly between younger and older men. The results suggest that the HDL of women over the age of 45 years contains relatively less cholesterol and more protein than the HDL of younger women. Further studies will show to what degree apolipoprotein concentrations, and their relation to lipoproteins will sharpen the assessment of coronary risk.

Adult↗
PubMed1988

Effects of glibenclamide on serum lipids, lipoproteins, thromboxane, beta-thromboglobulin, and prostacyclin in non-insulin-dependent diabetes mellitus.

A study was conducted to determine the effects of glibenclamide on serum lipoproteins, apolipoproteins, thromboxane (TXA2), prostacyclin (PGI2), and beta-thromboglobulin (B-TGL) in patients with newly diagnosed non-insulin-dependent diabetes mellitus (NIDDM). In 20 NIDDM patients, aged 34 to 67 (mean, 53.6) years, without clinical signs of atherosclerotic disease and whose blood sugar level was over 140 mg/dl after four weeks of dietary treatment, fasting blood samples were taken before the beginning of the trial, after four weeks of dietary treatment, and after four and eight weeks of combined dietary and glibenclamide treatment. Pretrial levels of total serum cholesterol (TC), triglycerides (TG), and low-density lipoprotein cholesterol (LDL-C) in the diabetic patients did not differ from those in nondiabetic controls, whereas high-density lipoprotein cholesterol (HDL-C) levels and the percentage of TC bound to HDL (HDL-C%) were significantly lower in the patients than in controls. After combined dietary and glibenclamide treatment and the normalization of blood sugar, both HDL-C (mg/dl) levels and HDL-C% levels increased significantly. TC, TG, and LDL-C levels decreased. Levels of apolipoproteins A1 and A2 rose and apolipoprotein B fell, but differences were not significant. TXB2 and 6-keto-PGF1-alpha (the inert metabolites of TXA2 and PGI2) and B-TGL were determined by radioimmunoassay. TXB2 and B-TGL levels decreased significantly after glibenclamide administration, indicating attenuation of platelet aggregation. No changes in PGI2 were observed. The results demonstrate the favorable effect of glibenclamide on lipoproteins and apolipoproteins in NIDDM patients, especially in increasing HDL-C levels and HDL-C%, and in attenuating platelet aggregation as indicated by reduction of TXB2 and B-TGL.

Adult↗
PubMed1988

Effects of glyburide treatment on serum lipoprotein and apolipoprotein concentrations and ratios in non-insulin-dependent diabetes mellitus.

Lipoproteins and apolipoproteins were studied in 28 patients with newly detected non-insulin-dependent diabetes mellitus (NIDDM) before and after combined dietary and glyburide treatment. The patients, aged 33 to 67 years and without coronary or other atherosclerotic diseases, displayed fasting blood sugar levels of over 140 mg/dl after four weeks of dietary treatment. Overnight fasting blood samples were collected before the beginning of the trial, after four weeks of dietary treatment, and after four and eight weeks of combined dietary and glyburide treatment. The pretrial levels of total serum cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), apolipoprotein A1 and A2, and apolipoprotein B were similar to or even lower than those of nondiabetics; however, high-density lipoprotein cholesterol (HDL-C) levels and HDL-C% (the percentage of TC bound to HDL) were significantly lower in the diabetic patients. After combined dietary and glyburide treatment and normalization of blood sugar, apolipoprotein A1 and A2, HDL-C levels, and HDL-C% increased significantly. TC, TG, and LDL-C levels, although not exceeding the normal range, decreased significantly. HDL-C2 and HDL-C3 levels also increased, but the differences did not reach significance. Among the lipid, lipoprotein, and apolipoprotein ratios in the patients, only the ratios HDL-C:LDL-C, apolipoprotein A1:apolipoprotein B, and HDL-C: apolipoprotein B increased significantly as a result of the opposing responses of the protective lipoprotein HDL-C and apolipoprotein A1 and the atherogenic lipoprotein LDL-C and apolipoprotein B. The results demonstrate the favorable effects of combined dietary and sulphonylurea drug treatment on lipoproteins and apolipoproteins in NIDDM patients, thereby reducing coronary and atherosclerotic risks.

Adult↗
PubMed1987

Relation of serum total cholesterol and high-density lipoprotein cholesterol percentage to the incidence of definite coronary events: twenty-year follow-up of the Donolo-Tel Aviv Prospective Coronary Artery Disease Study.

This 20-year follow-up report presents the incidence of definite coronary events and its relation to serum total cholesterol (TC) and alpha-lipoprotein cholesterol percentage (percentage of serum TC bound with alpha-lipoprotein), now usually called high-density lipoprotein cholesterol percentage (HDL-C%). The cohort consists of 1,454 men and 1,481 women, presumably healthy, aged 35 to 64 years at the time of entrance examination in 1964. During the follow-up period 123 men and 44 women died from coronary disease. Ninety-six men and 42 women had nonfatal myocardial infarctions. The incidence of definite coronary events increased from 6% in men with TC levels of less than 200 mg/dl to 25% in men with levels of more than 264 mg/dl. The corresponding figures in women were 3% and 10%. The incidence of definite coronary events was inversely correlated to HDL-C%. The incidence of definite coronary events in 225 men with HDL-C% of less than 14% was 28%, and in 669 men with HDL-C% of 21% or more, 7%. The corresponding figures in 234 women with HDL-C% of less than 17% was 14%, and in 853 women with HDL-C% of 23% or more, 2%. Two HDL-C% subsets were assessed: "low" and "high" subsets refer to HDL-C% of less than 21% and 21% or more, respectively, in men and less than 23% and 23% or more in women.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1987

The efficacy of isosorbide-5-mononitrate on effort-induced electrocardiographic ischemic changes in patients with angina pectoris.

The efficacy of isosorbide-5-mononitrate 40 mg twice a day was tested in 10 patients suffering from effort-induced angina pectoris. Patients were studied with ergometer testing 6 hours after drug administration on the first treatment day, and again 8 and 12 hours after medication at 3 weeks and 6 months of therapy. At comparable and maximal workloads the patients expressed significantly less ST segment depression on treatment than prior to treatment. No tolerance was observed. Isosorbide-5-mononitrate treatment was demonstrated to have a beneficial effect on exercise tolerance in patients suffering from stable angina in effort.

Angina Pectoris↗
PubMed1986

Effects of short- and long-term treatment with transdermally and orally administered nitroglycerin (a double-blind crossover study).

The efficacy of a once daily transdermally applied nitroglycerin system and of sustained release nitroglycerin capsules was assessed by ergometer stress testing in 12 patients with stable angina pectoris in a double-blind crossover study. In the morning the patients received transdermally applied nitroglycerin (TDS) which delivered 5.0 mg nitroglycerin in 24 hours together with a placebo capsule, respectively 1 nitroglycerin (NTR) capsule of 2.5 mg together with a plaster placebo. In the evening the first treatment group received 2 placebo capsules, and the second group 1 NTR capsule and 1 placebo capsule. Each period lasted 14 days. The patients performed a pre-medication ergometer stress test and repeated the test on the first and 14th day of each treatment period, 1 and 24 hours after medication. At the end of the second period all patients continued in an open study with TDS once a day for a further three months. Minor degrees of ST-segment depression, and in fewer patients, were observed at comparable workloads in the treatment tests compared with the pre-medication tests. The improvement after TDS on the first and last day of each period, 1 and 24 hours after medication, was significant and more marked than with NTR. The latter did not reach significance. Furthermore, increase of work capacity and elevation of angina threshold was greater with TDS than with NTR. Similar results were found at the end of the open study after 3 months' treatment with TDS. No development of tolerance was observed.

Administration, Cutaneous↗