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Biomedical subjects

H Scherf

Publications and source records attributed to H Scherf.

At least 19 recordsLinked to original sources
PubMed1999

Amide analogues of trichostatin A as inhibitors of histone deacetylase and inducers of terminal cell differentiation.

Inhibitors of histone deacetylase (HD) bear great potential as new drugs due to their ability to modulate transcription and to induce apoptosis or differentiation in cancer cells. We have described previously analogues of the complex natural HD inhibitors trapoxin B and trichostatin A with activities in the submicromolar range. Here we report structure-activity relationship analyses of further analogues of trichostatin A with respect to in vitro inhibition of maize HD-2 and their ability to induce terminal cell differentiation in Friend leukemic cells. This is the first report that shows the correlation between HD inhibitory activity and action on cancer cells on a larger series of similar compounds. Only the compounds that inhibit HD induce differentiation and/or exert antiproliferative activities in cell culture. Our studies support the use of in vitro systems as screening tools and provide structure-activity relationships that merit further investigation of this interesting target.

Animals↗
PubMed1996

Effects of vitamin E on mammary and blood leukocyte function, with emphasis on chemotaxis, in periparturient dairy cows.

OBJECTIVE: To determine the effect of vitamin E supplementation on the immune system of dairy cows. DESIGN: The following immune parameters were followed: production of chemotactic factors and superoxide by mammary macrophages and chemotactic responsiveness of blood neutrophils. ANIMALS: 16 healthy Holstein dairy cows. PROCEDURE: Dairy cows were assigned to 1 of 2 experimental groups: control (no vitamin E supplementation) and vitamin E supplemented. Supplementation of vitamin E started 4 weeks before and continued up to 8 weeks after parturition, and included oral supplementation of vitamin E at the rate of 3,000 IU/cow/d. In addition, the same group of cows received 1 injection of vitamin E (5,000 IU) 1 week prior to the expected date of parturition. Blood samples were collected weekly throughout the experimental period. RESULTS: Vitamin E supplementation enhanced by 30 to 83% (P < 0.05) chemotactic responsiveness of blood neutrophils beginning 2 weeks before to 4 weeks after parturition, compared with controls. There were no differences in production of superoxide or chemotactic factors by mammary macrophages between control and vitamin E-supplemented cows. CONCLUSIONS: Vitamin E supplementation prevents the periparturient inhibition of neutrophil chemotaxis. It is unlikely that vitamin E affects directly the function of mammary macrophages.

Animal Feed↗
PubMed1995

Effects of vitamin E on immune function of dairy cows.

The effect of vitamin E supplementation on the immune function of dairy cows was studied. Twelve cows were assigned to 1 of the 2 experimental groups: control (no vitamin E supplementation), and vitamin E-supplemented. Supplementation of vitamin E started 4 weeks before and continued up to 8 weeks after parturition and included oral supplementation of vitamin E at the rate of 3,000 IU/cow/d. In addition, the same group of cows received 1 injection of vitamin E (5,000 IU), 1 week prior to the expected date of parturition. Data indicated that blood neutrophils isolated from control cows produced twofold less (P < 0.05) superoxide anion after parturition, compared with the corresponding value before parturition. Furthermore, blood macrophages isolated from control cows produced 15 and 35% (P < 0.05) less interleukin 1 (IL-1) and major histocompatibility (MHC) class-II antigens, respectively, after parturition, compared with the corresponding values before parturition. These data, collectively, indicate that functions of blood macrophages and neutrophils are depressed during the early postpartum period in control cows. In contrast, there were no differences in superoxide anion production by blood neutrophils, or in IL-1 production, and MHC class-II antigen expression by blood macrophages before and after parturition in cows supplemented with vitamin E. There were no differences in lymphocyte proliferation, or IL-1 production and MHC class-II antigen expression by mammary macrophages when control and vitamin E-supplemented cows were compared. We conclude that vitamin E prevented suppression of blood neutrophil and macrophage function during the early postpatum period.

Analysis of Variance↗
PubMed1990

Dietary linoleic acid deprivation: an experimental model of salt-sensitive hypertension.

The present study investigates arterial blood pressure (BP), renal arachidonic acid cyclooxygenase metabolism and excretory function in rats during dietary linoleic acid deprivation and a concomitant low and high NaCl-intake. Four groups of animals were fed isocaloric diets containing 10 energy (en) % saturated fat and either 5 en % linoleic acid (groups I and III) or 5 en % oleic acid (groups II and IV) over six weeks. In addition, groups I and II received a chronic high intake of sodium (5.4 mmol/24 h) while groups III and IV were NaCl-restricted (average NaCl intake of 0.7 mumol/24 h). Systolic BP significantly increased from 97.0 +/- 1.7 to 112.0 +/- 2.2 mmHg (p less than 0.01) in the salt loaded group II fed the diet deficient in linoleic acid and remained unchanged in the three other groups. Renal cyclooxygenase metabolism was significantly stimulated by sodium restriction and suppressed following dietary linoleic acid deprivation. During infusion of 0.45% saline to a stable increase in body weight of 10%, animals in the linoleic acid deprived groups II and IV excreted significantly less sodium, chloride, and potassium than animals in groups I and III. This impairment in renal excretory function occurred without concomitant changes in RPF, GFR, or UPhos V. It was associated, however, with marked decreases in fractional free water excretion (CH2O/GFR), distal delivery of solute [(CH2O + CCl)/GFR] and with an increase in "distal fractional chloride absorption" [CH2O/(CH2O + CCl)]. Furthermore, linoleic acid deprivation was associated with a significantly enhanced papillary osmolality and papillary sodium, chloride, and potassium concentrations in group II animals as compared to group I.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Baroreflex setting and sensitivity in normal subjects: effects of pharmacologic inhibition of the angiotensin I converting enzyme.

Arterial blood pressure, heart rate and the response of these hemodynamic parameters to exogenous norepinephrine were investigated in healthy volunteers (daily sodium intake of 150 mmol) during a control period and after a single oral dose of 5 mg of the angiotensin I converting enzyme (ACE) inhibitor ramipril (HOE 498). Norepinephrine was infused at doses of 0.1, 0.2 and 0.3 micrograms kg-1 min-1, each for 10 minutes, during control and 3 hours after ramipril administration. Exogenous norepinephrine induced a dose-dependent increase in mean arterial blood pressure from 76.4 +/- 0.9 mm Hg during control to 85.6 +/- 1.5, 92.2 +/- 1.8 and 98.4 +/- 2.4 mm Hg, respectively. Ramipril significantly affected the baroreceptor set point with a decrease in mean blood pressure (72.1 +/- 1.7 vs 76.4 +/- 0.9 mm Hg, p less than 0.01) in the presence of unchanged heart rate (71.7 +/- 0.9 vs 73.6 +/- 1.5 min-1). Baroreceptor sensitivity, estimated by the slope of the delta blood pressure versus delta heart rate relation, was not affected by ACE inhibition. Also, the pressor effect of exogenous norepinephrine was unchanged by converting enzyme inhibition. The present results show that ACE inhibition with ramipril in sodium-replete healthy volunteers induces a decrease in blood pressure that is not accompanied by changes in heart rate, pressor sensitivity to exogenous norepinephrine or baroreceptor sensitivity.

Adult↗
PubMed1987

L-platelet activating factor induces changes on renal vascular resistance, vascular reactivity, and renin release in the isolated perfused rat kidney.

Rat kidneys were isolated and perfused with a modified Krebs-Henseleit buffer containing 4% albumin. Perfusate recirculated except during L-platelet activating factor (L-PAF), angiotensin II (ang II), and norepinephrine (NE) infusions. L-PAF caused a dose-dependent decrease in renovascular resistance (RVR): -6 +/- 3% at 10(-9)M, -12 +/- 6% at 10(-8)M, -18 +/- 3% at 10(-7) and -20 +/- 7% at 10(-6)M. L-PAF increased immunoreactive PGE (iPGE) and thromboxane (iTXB) release into the venous effluent from 2.4 +/- 0.2 to 3.9 +/- 0.4 ng/min (p less than 0.05) and from 2.1 +/- 0.4 to 3.5 +/- 0.5 ng/min (p less than 0.05), respectively. Vasodilation by L-PAF (10(-7) M) in the presence of indomethacin (INDO) (5 microM) was enhanced compared to the non-INDO response (RVR change: L-PAF = -18 +/- 3% vs. L-PAF = -26 +/- 3%; p less than 0.05). As a control for specificity, the was infused at 10(-9) M, 10(-8) M, and 10(-7) M. None of these concentrations changed renal vascular resistance. To study the vascular receptor responsible for L-PAF-induced vasodilation, dose-response curves to NE and ang II were established with and without L-PAF (10(-7) M). The NE dose-response curve was unchanged by L-PAF, whereas the ang II dose-response curve was shifted to the right by one order of magnitude. In kidneys pretreated with INDO (5 microM), the L-PAF-induced shift of the ang II dose-response relation was increased to 2-3 orders of magnitude.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin II↗
PubMed1986

Converting enzyme inhibitor ramipril stimulates prostacyclin synthesis by isolated rat aorta: evidence for a kinin-dependent mechanism.

The present study was performed to investigate the effect of the angiotensin I-converting enzyme inhibitor ramipril on vascular synthesis of prostacyclin (PGI2). Administration of ramipril (Hoe 498) to rats significantly stimulated prostacyclin (PGI2) synthesis, quantified by radioimmunoassay of its stable hydrolysis product 6-keto-PGF1 alpha, by portions of the animals' isolated aorta. This effect was maximal at a dose range of 10(-7) mol/kg ramipril. The addition of the active ramipril metabolite ramipril diacid directly into the incubation buffer at final concentrations of 10(-9), 10(-6), and 10(-4) M resulted in a dose-dependent stimulation of 6-keto-PGF1 alpha released by isolated aortic tissue. Pretreatment of rats with aprotinin (40,000 U s.c. 60 min before the incubations) attenuated the ramipril-induced effect on aortic 6-keto-PGF1 alpha synthesis. Our results show that the angiotensin I-converting enzyme inhibitor ramipril stimulates PGI2 synthesis in vascular tissue and that this effect may be secondary to changes in the activity of the kinin system.

6-Ketoprostaglandin F1 alpha↗
PubMed1986

Hemodynamic effects of platelet activating factor in the dog kidney in vivo.

The effect of platelet activating factor (PAF) on renal hemodynamics and function was examined in anesthetized dogs. The infusion of PAF into the renal artery at 5, 10, and 20 ng X min-1 X kg-1 body weight resulted in dose-dependent reductions in renal blood flow, glomerular filtration rate, urine volume, and urinary sodium excretion, whereas the infusion of vehicle alone in the contralateral kidney did not result in significant changes in these parameters. The maximum decrease expressed as the percent change from baseline was 22.2 +/- 1.7% for renal blood flow, 50.8 +/- 11% for glomerular filtration rate, 67.3 +/- 4.2% for urine volume, and 69.0 +/- 8.5% for urinary sodium excretion, respectively. These renal effects were not accompanied by significant alterations in systemic arterial blood pressure and heart rate. Pretreatment with indomethacin to block prostaglandin synthesis enhanced the effect of PAF on kidney function. Our data demonstrate that, unlike the rat kidney, intrarenal PAF infusion into the intact dog results in vasoconstriction and serve reduction in glomerular filtration rate.

Animals↗
PubMed1984

Further studies on the mechanism of increased blood pressure during dietary linoleic acid deprivation.

The present studies investigate the changes in blood pressure and excretory renal function in rats during dietary linoleic acid deprivation. Four groups of animals were fed isocaloric diets containing 10 en % saturated fat and either 5 en % linoleic acid (groups I and III) or 5 en % oleic acid (groups II and IV). In addition, groups I and II received a chronic high intake of Na (greater than 5 mmol/day) while groups III and IV were Na restricted with an average Na intake of 0.7 mumol/day. Blood pressure significantly increased in the high salt, linoleic acid deprived group II and was unchanged in all three other groups of animals. De novo synthesis of prostaglandin E2 in rat kidney inner medullary homogenates in the four groups of animals at the end of the dietary protocol showed a marked dependency on Na balance with significantly (p less than 0.01) higher values in the Na restricted animals as well as on linoleic acid intake with significantly (p less than 0.01) higher values in the linoleic acid substituted animals. Urinary excretion of NaCl during acute expansion of the extracellular fluid volume with hypotonic saline was significantly impaired in the animals receiving oleic acid instead of linoleic acid. In a metabolic study, linoleic acid deprived animals retained Na from the first day of linoleic acid deprivation and blood pressure started to rise only after a substantial amount of Na had been retained. Our results show that linoleic acid deprivation suppresses renal arachidonic acid cyclooxygenase metabolism and impairs the renal ability to excrete an acute salt load. Impaired renal excretory function precedes the increase in blood pressure. Thus suppressed renal cyclo-oxygenase metabolism which impairs renal excretory function may be a crucial mechanism in the rise of blood pressure during dietary linoleic acid deprivation.

Animals↗
PubMed1984

Cholesterol-induced growth stimulation, cell aggregation, and membrane properties of ascites tumor cells in culture.

Ascites tumor cells can be cultivated at a reduced serum concentration if cholesterol (2.50 mg per 100 ml of medium) is added to the culture medium. At serum concentrations of 3%, optimal growth properties are obtained; below 3%, cell cultures usually perish after a few days. Cells grown in the presence of added cholesterol have an elevated content of this molecule per cell as well as in the plasma membrane, and they also show a cholesterol concentration-dependent rate of proliferation. Precursors of the cholesterol-biosynthetic pathway like mevalonic acid, added in mM amounts, or squalene and lanosterol cannot be substituted for cholesterol itself. This is due to the observation that the biosynthetic pathway is blocked at the stage of lanosterol conversion to cholesterol. Cholesterol de novo synthesis from acetate is regulated by the cholesterol content of the cells, which also affects the production of ubiquinone and dolichol. Growth factors such as insulin, prostaglandin F2 alpha, and transferrin added to the medium do not mimic the cholesterol-induced effect. Distribution of DNA during cell cycle and the cell density-dependent reduction in macromolecule synthesis is very similar to the control cells. In contrast, cells without added cholesterol show reduced growth properties accompanied by the accumulation of cells in the mitotic and G2 phase. The cholesterol/phospholipid ratio of the plasma membranes of cholesterol-rich cells is about 15% lower than of the control cells and 40% higher compared to the cholesterol-poor cells, which, however, does not significantly alter the membrane fluidity between the cholesterol-rich and -poor cells as revealed by fluorescence polarization measurements. The most dramatic behavior of the cholesterol-rich cells is their tendency to form aggregates, which is demonstrated either by concanavalin A-induced agglutination or by cell density-dependent aggregation shown by interference microscopy in vivo.

Agglutination↗
PubMed1982

[Sterile vesiko-ureteral reflux. Radiological kidney surface measurements as follow-up criteria].

33 patients with 46 sterile vesicoureteral refluxes were followed by repeated clinical-urological and radiological studies over a period from 1 to more than 6 years. The results of the evaluation, obtained by only looking at the urograms, were compared with the following measurements: the length of each kidney, the length ratio right to left, and the parenchymal area. At the end of the follow-up period, 2 out of 32 initially normal kidneys (about 6%) had pathologically low values, whereas 3 out of 14 already initially damaged kidneys (21,5%) showed a further decrease of these values. Preceding urinary tract infections with consecutive pyelonephritis, leading to a progressive shrinkage of the organ over many years, are thought and discussed to be more responsible for these results than the sterile reflux itself.

Adolescent↗