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Biomedical subjects

H Rasmussen

Publications and source records attributed to H Rasmussen.

At least 55 records · Page 3Linked to original sources
PubMed1997

Cyclic nucleotide-dependent vasorelaxation is associated with the phosphorylation of a small heat shock-related protein.

Activation of cyclic nucleotide-dependent signaling pathways leads to the relaxation of various smooth muscles. One of the major phosphorylation events associated with cyclic nucleotide-dependent vasorelaxation in bovine trachealis and carotid artery smooth muscle is the phosphorylation of two 20-kDa phosphoproteins with pI values of 5.7 and 5.9 (previously designated pp8 and pp3, respectively). The present studies sought to determine the identities of pp3 and pp8 in vascular smooth muscle. The phosphopeptide maps for the pp8 and pp3 proteins were similar. Preparative two-dimensional gel electrophoresis and amino acid sequencing of a peptide fragment of the pp3 protein revealed a sequence identical to a 20-kDa heat shock-related protein (HSP20) previously purified from skeletal muscle. Western blot and immunoprecipitation analysis with anti-HSP20 antibodies demonstrated that the pp3 and pp8 proteins are phosphorylated forms of HSP20. In addition, HSP20 could be phosphorylated in vitro by both cAMP-dependent protein kinase and cGMP-dependent protein kinase. These data suggest that the phosphorylation of the heat shock-related protein HSP20 is associated with cyclic nucleotide-dependent relaxation of vascular smooth muscle.

Animals↗
PubMed1997

Human plasminogen binding protein tetranectin: crystallization and preliminary X-ray analysis of the C-type lectin CRD and the full-length protein.

The recombinant human plasminogen binding protein tetranectin (TN) and the C-type lectin CRD of this protein (TN3) have been crystallized. TN3 crystallizes in the tetragonal space group P4(2)2(1)2 with cell dimensions a = b = 64.0, c = 75.7 A and with one molecule per asymmetric unit. The crystals diffract X-rays to at least 2.0 A resolution. A complete diffraction data set has been collected to 2.7 A resolution. The crystals of TN, obtained by the vapour-diffusion reverse salting-in method at 280 K, are rhombohedral, space group R3, with the hexagonal axes a = b = 89.1, c = 75.8 A, and diffract to at least 2.5 A. A full data set has been collected to 3.0 A. The asymmetric unit contains one monomer of TN. Molecular replacement solutions for TN3 and TN have been obtained using the structure of the C-type lectin CRD of rat mannose-binding protein as search model. The rhombohedral space group indicates that trimers of TN are formed in accordance with the observation of trimerization in solution.

Journal Article↗
PubMed1997

Crystal structure of a peptide nucleic acid (PNA) duplex at 1.7 A resolution.

The crystal structure of a PNA duplex reveals both a right- and a left-handed helix in the unit cell. The helices are wide (28A), large pitched (18bp) with the base pairs perpendicular to the helix axis, thereby demonstrating that PNA besides adapting to oligonucleotide partners also has a unique structure by itself.

Base Composition↗
PubMed1997

A randomized phase II study of BB-10010: a variant of human macrophage inflammatory protein-1alpha for patients receiving high-dose etoposide and cyclophosphamide for malignant lymphoma and breast cancer.

Macrophage inflammatory protein-1alpha (MIP-1alpha) is a chemokine that can inhibit the cell cycle progression of both primitive haemopoietic and epidermal progenitor cells. This property could potentially be exploited to attenuate both the myelosuppressive effects of chemotherapy as well as mucositis. We evaluated both the biological and clinical effects of BB-10010, a genetically engineered variant of MIP-1alpha, in patients with malignant lymphoma or breast cancer receiving high-dose etoposide (VP 3.6 g/m2) and cyclophosphamide (Cy 200 mg/kg). 52 patients were randomized to one of three cohorts. Cohort A received no BB-10010; cohorts B and C received 10 microg/kg and 100 microg/kg of BB-10010, respectively. All patients received post-chemotherapy G-CSE BB-10010 was well tolerated. There were no significant differences between groups in recovery to an ANC > 0.5 x 10(9)/l, 1 x 10(9)/l or 1.5 x 10(9)/l, the number of days with an ANC < 0.5 x 10(9)/l, days to a platelet count > 50 x 10(9)/l or 100 x 10(9)/l, or the incidence and severity of mucositis. There was no evidence of any effect of BB-10010 on colony-forming cell (CFC) or long-term culture-initiating cell (LTC-IC) mobilization, cycling activity in the marrow or on chemotherapy-induced changes in CFC or LTC-IC number both of which were in the normal range by 22 d after completion of the chemotherapy. To our knowledge this is the first report of a myelointensive regimen having no apparent long-term effect on the LTC-IC compartment. In summary, BB-10010 is safe when used in patients receiving high-dose therapy but has no effect on reducing the toxicity of such therapy.

Adolescent↗
PubMed1996

Left ventricular ejection: model solution by collocation, an approximate analytical method.

A differential equation solution method that does not utilize numerical integration is demonstrated on a physiologic model. A previously proposed model of left ventricular ejection incorporating time-varying elastance, internal resistance, aortic inductance, and a three-component windkessel is solved by collocation. Assuming internal resistance to be constant allows simplification to a third order linear differential equation in left ventricular volume. A trigonometric series is used to approximate the solution and the coefficients of the series as well as the duration of ejection and pre-ejection periods are chosen so that the governing differential equation is exactly satisfied at certain times during ejection (the collocation points), as well as the boundary conditions and steady state condition.

Elasticity↗
PubMed1996

Effects of National Cholesterol Education Program Step 2 diets relatively high or relatively low in fish-derived fatty acids on plasma lipoproteins in middle-aged and elderly subjects.

The effects of two National Cholesterol Education Program (NCEP) Step 2 diets (< or = 30% of energy as total fat, < 7% of energy as saturated fat, and < 200 mg cholesterol/d), one relatively high and the other relatively low in fish-derived fatty acids, on plasma lipoprotein concentrations and blood pressure were compared in 22 men and women with a mean (+/- SD) age of 63 +/- 10 y. Subjects were placed on a baseline diet similar to the diet currently consumed in the United States (35% of energy as total fat, 14% of energy as saturated fat, 35 mg cholesterol/MJ) for 6 wk and then on either an NCEP Step 2 diet relatively high in fish (Step 2 high-fish, n = 11) or relatively low in fish (Step 2 low-fish, n = 11) for 24 wk. All food and drinks were provided. Compared with baseline values, consumption of both the Step 2 high-fish and the Step 2 low-fish diets under weight-stable conditions was associated with significant decreases in plasma concentrations of total cholesterol (-14% and -19%, respectively), low-density-lipoprotein (LDL) cholesterol (-15% and -20%, respectively), and high-density-lipoprotein (HDL) cholesterol (-11% and -17%, respectively). Postprandial, but not fasting, triacylglycerol concentrations were significantly reduced during consumption of the Step 2 high-fish diet. There were no significant changes in these indexes after consumption of the Step 2 low-fish diet compared with the baseline diet. LDL particle size decreased significantly (-12%) only in subjects on the Step 2 low-fish diet. Both Step 2 diets caused small but significant reductions in diastolic blood pressure. Our results indicate that NCEP Step 2 diets relatively high or relatively low in fish are both effective in significantly reducing total and LDL-cholesterol concentrations without changes in the ratio of total cholesterol to HDL cholesterol under controlled weight-stable conditions in middle-aged and elderly subjects. A beneficial effect on diastolic blood pressure was also observed.

Aged↗
PubMed1995

Body weight and low-density lipoprotein cholesterol changes after consumption of a low-fat ad libitum diet.

OBJECTIVE: To assess the effects of a diet restricted in fat, saturated fat, and cholesterol, under weight-maintenance and ad libitum conditions on body weight and plasma lipid levels in hypercholesterolemic subjects. DESIGN: Dietary intervention study. SETTING AND PARTICIPANTS: Twenty-seven free-living, healthy middle-aged and elderly men (n = 13, age range, 41 to 81 years) and women (n = 14, age range, 52 to 79 years) with moderate hypercholesterolemia (low-density lipoprotein cholesterol [LDL-C] > or = 3.36 mmol/L [130 mg/dL]) participated in the study. INTERVENTION: Subjects underwent three dietary phases. First, subjects were provided with a diet similar to the average US diet (baseline diet; 35.4% total fat, 13.8% to 14.1% saturated fat, and 30 to 35 mg/1000 kJ [128 to 147 mg/1000 kcal] cholesterol). During the second dietary phase, subjects consumed a low-fat diet (15.1% total fat, 5.0% saturated fat, 17 mg/1000 kJ [73 mg/1000 kcal] cholesterol). During the baseline and low-fat diet phases, which lasted 5 to 6 weeks each, the energy intake was adjusted to keep body weight constant. During the third diet phase (low-fat ad libitum diet) subjects were given the same low-fat diet for 10 to 12 weeks, but could adjust their intake between 66% and 133% of the energy required to maintain body weight. MAIN OUTCOME MEASURES: Body weight and plasma lipid levels. RESULTS: Consumption of the low-fat diet under weight-maintenance conditions had significant lowering effects on plasma total cholesterol (TC), LDL-C, and high-density lipoprotein cholesterol (HDL-C) levels (mean change, -12.5%, -17.1%, and -22.8%, respectively). This diet significantly increased plasma triglyceride levels (+47.3%) and the TC/HDL-C ratio (+14.6%). In contrast, consumption of the low-fat ad libitum diet was accompanied by significant weight loss (3.63 kg), by a mean decrease in LDL-C (124.3%), and by mean triglyceride levels and TC/HDL-C ratio that were not significantly different from values obtained at baseline. CONCLUSIONS: Our results indicate that a low-fat ad libitum diet promotes weight loss and LDL-C lowering without adverse effects on triglycerides or the TC/HDL-C ratio in middle-aged and elderly men and women with moderate hypercholesterolemia.

Aged↗
PubMed1995

["The lucky pill"].

Explore the source record for details and available documents.

Antidepressive Agents↗
PubMed1995

Crystallization and preliminary X-ray analysis of a PNA-DNA complex.

Peptide nucleic acids (PNAs) are DNA mimics with a peptide backbone. PNAs are being intensely investigated owing to a potential as gene-targeted drugs. A PNA (H-GTAGATCACT-NH2)-DNA (5'-AGTGATCTAC-3') complex has been crystallized in a tetragonal space group P4(1)22 with cell dimensions a = b = 79.8, c = 99.9 angstrum. The crystals diffract to about 5 angstrum resolution.

Base Sequence↗
PubMed1995

Kinase activation and smooth muscle contraction in the presence and absence of calcium.

PURPOSE: The intracellular signalling mechanisms that modulate the sustained vascular smooth muscle contractions that occur with vasospasm are not well understood. The purpose of this investigation was to examine cell signalling mechanisms that account for sustained vascular smooth muscle contraction, independent of increases in intracellular Ca2+ concentrations ([Ca2+]i). METHODS: Fresh bovine carotid artery smooth muscles contractile responses were examined in a muscle bath. [Ca2+]i was depleted by use of the extracellular Ca2+ chelator, ethylene glycol-bis(beta-aminoethylether) N,N,N',N'-tetraacetic acid and the intracellular chelator, 1,2-bis(2-aminophenoxy)ethane-N,N,N',N',-tetraacetic acid. RESULTS: In Ca(2+)-free conditions, depolarizing the membrane with high extracellular KCI failed to elicit a contraction. In addition, in Ca(2+)-free conditions the ([Ca2+]i) was less than 10 nmol/L as determined with the Ca(2+)-indicator, Fura 2. The protein kinase C (PKC) activator, phorbol 12, 13-dibutyrate (PDBu), induced slowly developing sustained contractions in bovine carotid artery smooth muscle, and the magnitude of the contractile response to PDBu (10 nmol/L to 10 mumol/L) was the same in the presence and absence of Ca2+. PDBu induced contractions in Ca(2+)-free conditions were not inhibited by the myosin light chain kinase inhibitor, ML-9 (50 mumol/L), but were inhibited by the PKC inhibitor, staurosporine (50 nmol/L). CONCLUSIONS: These data suggest that vascular smooth muscle contractions can occur under conditions where the [Ca2+]i is low and fixed and that these contractions may be mediated by PKC.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1995

PDGF and TGF-beta mediate collagen production by mesangial cells exposed to advanced glycosylation end products.

Deposition of type III collagen protein is increased when cultured rat mesangial cells are cultured in media containing high glucose concentrations. Possible mechanisms for this effect include the production of growth factors, such as PDGF and TGF-beta, and the formation of abnormal glucose-protein adducts called advanced glycosylation end products (AGEs). In our studies, neutralizing antibodies to PDGF and TGF-beta prevented increased type III collagen deposition by mesangial cells exposed either to high glucose media or to low glucose media containing AGEs. Daily addition of PDGF or TGF-beta stimulated type III collagen production. However, while co-incubation with the TGF-beta Ab prevented PDGF-stimulated type III collagen production, the PDGF Ab did not prevent TGF-beta-stimulated type III collagen production. Daily addition of PDGF or TGF-beta stimulated, while AGEs inhibited, mesangial cell proliferation after 96 hours. We propose that high extracellular glucose and AGEs stimulate type III collagen production by pathways that involve the intermediate formation of PDGF and TGF-beta by mesangial cells. PDGF may increase type III collagen production by stimulating the intermediate production of TGF-beta. Exposure to high glucose, AGEs, or TGF-beta also leads to impaired mesangial cell proliferation. The autocrine effects of TGF-beta and PDGF play important roles in the effects of high extracellular glucose and AGEs on cultured mesangial cells.

Analysis of Variance↗
PubMed1995

Impaired cyclic nucleotide-dependent vasorelaxation in human umbilical artery smooth muscle.

Activation of either the adenylate cyclase pathway with forskolin or the guanylate cyclase pathway with sodium nitroprusside fails to induce active relaxation of serotonin-precontracted human umbilical artery smooth muscle (HUASM) but causes active relaxation of serotonin-precontracted bovine carotid artery smooth muscle (BCASM). This difference in response appears to be unique to HUASM in that all other vascular muscles exhibit relaxation in response to these substances. Forskolin and sodium nitroprusside stimulation leads to respective increases in intracellular adenosine 3',5'-cyclic monophosphate (cAMP) and guanosine 3',5'-cyclic monophosphate (cGMP) concentrations in HUASM and BCASM. cAMP- and cGMP-dependent protein kinases are both present in HUASM and can be activated in homogenates of HUASM by the addition of exogenous cAMP and cGMP, respectively. When either forskolin or nitroprusside acts in BCASM, two low-molecular-weight proteins display an increase in the extent of phosphorylation. Neither protein shows such an increase when HUASM is treated with either agent. Thus the inability of HUASM to display active relaxation appears to be secondary to impaired activation of cyclic nucleotide-dependent protein kinases. The refractoriness to active relaxation may contribute to the vasospasm that occurs in the umbilical vasculature with parturition.

1-Methyl-3-isobutylxanthine↗
PubMed1995

Periodic high extracellular glucose enhances production of collagens III and IV by mesangial cells.

We examined the effects of periodic changes in extracellular glucose concentration on matrix production and proliferation using three groups of cultured rat mesangial cells (MCs): 1) MCs in medium with continuous 5 mM glucose (CL), 2) MCs in medium alternating daily between 5 and 25 mM glucose (PH), and 3) MCs in medium with continuous 25 mM glucose (CH). MCs cultured in PH for 10 days produced 329 and 110% more type III collagen protein than MCs cultured in CL and CH, respectively. MCs cultured in PH induced 31 and 14% more type IV collagen than MCs cultured in CL and CH, respectively. Extracellular glucose concentration had no effect on the amount of type I collagen produced. MCs cultured in PH or CH for 5 days also expressed increased levels of type I, III, and IV collagen mRNA compared with MCs cultured in CL. MCs cultured in PH for 8-10 days also produced significantly more DNA than MCs in CL or CH. These data suggest that the temporal pattern of exposure to high extracellular glucose plays a role in regulating matrix formation and cellular proliferation by MCs. Furthermore, periodic elevations of extracellular glucose had a greater stimulatory effect on collagen production than a sustained elevation. These results suggest that decreasing the variability of blood glucose concentration may decrease the adverse effect of elevated glucose levels on MC matrix production and the progression of diabetic glomerulopathy.

Analysis of Variance↗
PubMed1995

Serotonin activates phospholipase D in rat mesangial cells.

We tested the hypothesis that serotonin activates phospholipase D (PLD) in cultured rat mesangial cells. The formation of phosphatidylethanol (PET) in ethanol was used as a measure of PLD activity. Serotonin [5-hydroxytryptamine (5-HT)] stimulated PET production, with an initial 10-fold increase in PET content within 15-30 s, followed by a decrease in PET to values only sixfold above baseline at 45-60 s. Thereafter, the values increased again at 5 min to a plateau 10-fold above baseline. The decrease in PET values, following the initial increase, was due to metabolism of PET, possibly by a phosphatidic acid phosphohydrolase, which led to a 76% decrease in PET within 1 h. Inhibition of phosphohydrolase with propranolol increased the phosphatidic acid and decreased the 1,2-diacylglycerol (DAG) content of 5-HT-stimulated cells. Finally, exogenous PLD induced mesangial cell proliferation as well as increases in phosphatidic acid, PET, and DAG. We conclude that phosphatidic acid contributes to DAG formation in mesangial cells. Furthermore, we suggest that PLD is involved in 5-HT-mediated mesangial cell proliferation.

Animals↗
PubMed1995

Efficacy of a National Cholesterol Education Program Step 2 diet in normolipidemic and hypercholesterolemic middle-aged and elderly men and women.

We tested the effects of a National Cholesterol Education Program (NCEP) Step 2 diet (30% of calories or less as total fat, less than 7% saturated fat, and less than 200 mg cholesterol per day) on plasma lipid levels in normocholesterolemic and hypercholesterolemic middle-aged and elderly men and women. Thirty-two subjects were studied. Eight normolipidemic subjects (6 men and 2 women, mean age 56 +/- 13 years) with LDL cholesterol levels of less than 4.14 mmol/L (160 mg/dL) were given a baseline diet similar in composition to the diet currently consumed in the United States (35% of calories as total fat and 14% as saturated fat, with 147 mg cholesterol per 1000 kcal) for 6 weeks. Subjects were then placed on an NCEP Step 2 diet (26% total fat, 4% saturated fat, 45 mg cholesterol per 1000 kcal) for 24 weeks. In addition, 24 subjects (12 men and 12 women, mean age 62 +/- 12 years) with moderate hypercholesterolemia (LDL cholesterol levels of 4.14 mmol/L or above) were given a baseline diet for 6 weeks and then the NCEP Step 2 diet for 6 weeks. Energy intakes were adjusted to keep body weight constant throughout the study. In both normolipidemic and hypercholesterolemic subjects, consumption of the NCEP Step 2 diet was associated with significant changes in levels of total cholesterol (-20% and -16%, respectively), LDL cholesterol (-21% and -18%, respectively), and HDL cholesterol (-16% and -15%, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1995

Metabolic activation of Ca(2+)-independent phosphoinositide hydrolysis in beta-cells and its role in the control of insulin secretion.

Recent studies have led to the proposal that the oxidative metabolism of glucose leads to the generation of messengers, in addition to ATP, that are important in the ability of changes in extracellular glucose concentration to stimulate insulin secretion from pancreatic beta-cells. In particular, there is now evidence that glucose induces both a Ca(2+)-dependent and Ca(2+)-independent increase in phosphoinositide (PI) hydrolysis. To explore the relationship between oxidative metabolism and PI hydrolysis, we examined the effect of low concentrations (2.5 mM) of alpha-ketoisocaproate (KIC) and monomethylsuccinate (MMSucc) either alone or in combination on insulin secretion and PI hydrolysis in isolated rat pancreatic islets incubated with either no glucose, 5 mM glucose, or 20 mM glucose. A combination of KIC and MMSucc leads to a marked increase in largely (80%) Ca(2+)-independent PI hydrolysis in either the absence or presence of 5 mM glucose. When glucose is absent, this combination of substrates induces a very small and transient first phase of insulin secretion but no significant second phase of secretion. In the presence of 5 mM glucose, either KIC or MMSucc alone induces a first phase of insulin secretion with a peak secretory rate 10-fold greater than the basal rate but only a small second phase of secretion approximately 5-fold above control. However, in the presence of 5 mM glucose, the combination of KIC plus MMSucc induces a large biphasic increase in insulin secretion: peak first-phase secretion is increased 30-fold, and second-phase 40-fold. These response are comparable to those induced by 20 mM glucose and are completely inhibited by 0.5 microM nitrendipine. In contrast, KIC plus MMSucc do not enhance the insulin secretory response induced by 20 mM glucose. Previous data showed that when 20 mM glucose acts, the resulting increase in PI hydrolysis is only partially Ca2+ dependent. A reanalysis of these data shows that raising the glucose concentration from 5 to 7 mM causes a 2-fold increase in Ca(2+)-independent PI hydrolysis, and a further increase to 20 mM leads to a further 2-fold increase in Ca(2+)-dependent PI hydrolysis. These data show that these two pathways are regulated by different ranges of glucose concentration. They raise the interesting possibility that these distinct pathways have different signaling functions. In particular, raising the glucose concentration from 5 to 7 mM is known to alter the responsiveness of beta-cells to a variety of neurohumoral agonists and to tolbutamide.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1995

Intracellular signaling: from simplicity to complexity.

The field of intracellular signaling is barely a half-century old (Robison et al, 1971). In that span of time, our concepts concerning the organization and function of intracellular signaling have gone from viewing such signaling events in terms of a few simple models, to viewing them in terms of highly complex models that display both spatial and temporal domains of signal action. It has become apparent that even apparently simple processes, such as the secretion of the peptide hormone, insulin, from the beta-cell involves highly complex, interacting networks of signaling molecules to which the terms synarchic regulation and crosstalk have been applied. In this brief survey of cell signaling an attempt will be made to provide a global view of our present understanding of some aspects of their complexity. In doing so, I shall start with a consideration of the basis of all signaling, and a presentation of some early simple models as a means of providing a framework for what follows.

Adenylyl Cyclases↗