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Biomedical subjects

R Grimm

Publications and source records attributed to R Grimm.

At least 109 records · Page 6Linked to original sources
PubMed1996

Cloning of a cDNA encoding a plasma membrane-associated, uronide binding phosphoprotein with physical properties similar to viral movement proteins.

Oligogalacturonides are structural and regulatory homopolymers from the extracellular pectic matrix of plants. In vitro micromolar concentrations of oligogalacturonates and polygalacturonates were shown previously to stimulate the phosphorylation of a small plasma membrane-associated protein in potato. Immunologically cross-reactive proteins were detected in plasma membrane-enriched fractions from all angiosperm subclasses in the Cronquist system. Polygalacturonate-enhanced phosphorylation of the protein was observed in four of the six dicotyledon subclasses but not in any of the five monocotyledon subclasses. A cDNA for the protein was cloned from potato. The deduced protein is extremely hydrophilic and has a proline-rich N terminus. The C-terminal half of the protein was predicted to be a coiled coil, suggesting that the protein interacts with other macromolecules. The recombinant protein was found to bind both simple and complex galacturonides. The behavior of the protein suggests several parallels with viral proteins involved in intercellular communication.

Amino Acid Sequence↗
PubMed1995

Blood pressure and mortality among men with prior myocardial infarction. Multiple Risk Factor Intervention Trial Research Group.

BACKGROUND: The purpose of the present study was to describe the relation between blood pressure (systolic [SBP] and diastolic [DBP]) and death from coronary heart disease (CHD) and all causes for men with a history of myocardial infarction (MI). METHODS AND RESULTS: The study cohort consisted of men aged 35 to 57 years screened for the Multiple Risk Factor Intervention Trial (MRFIT) in 1973 through 1975 and followed for survival for an average of 16 years through 1990. There were 5362 men who reported prior hospitalization for a heart attack of at least 2 weeks' duration at the initial screening of MRFIT. There was a J-shaped relation between SBP and DBP with both CHD and all-cause mortality during the first 2 years of follow-up in older (age, 45 to 57 years) men only. Risk nadirs for SBP were 152 and 145 mm Hg, respectively, for CHD death and all-cause mortality; corresponding DBP risk nadirs were 94 and 90 mm Hg. After the first 2 years, there was a positive association between SBP and death from CHD and all causes. By 15 years, cumulative CHD mortality percentages for men with screening SBP < 120, 120 to 139, 140 to 159, and > or = 160 mm Hg were 19.7%, 21.3%, 27.5%, and 32.0%, respectively. When deaths only after year 2 were considered, although the linear DBP coefficient was significant, the quadratic term for DBP was no longer significant (P > .05). However, the relation still appeared J-shaped as cumulative mortality for those with DBP < 70, 70 to 79, 80 to 89, 90 to 99, and > or = 100 mm Hg was 24.3%, 20.8%, 21.1%, 25.5%, and 29.7%, respectively. When the joint relation of SBP and DBP was considered, there were no survival differences among the four cohorts (SBP > or = 140 and DBP < 80, SBP > or = 140 and DBP > or = 80, SBP < or = 140 and DBP < 80, and SBP < or = 140 and DBP > or = 80) during the first 2 years. After 2 years, both CHD and all-cause mortality rates were approximately 40% higher for participants with SBP > or = 140 mm Hg versus < 140 mm Hg regardless of DBP level (< 80 or > or = 80 mm Hg). CONCLUSIONS: In this large cohort of men with prior MI, the association of SBP and DBP with CHD and all-cause mortality varied over the 16-year follow-up period. During early follow-up, in older men only, J- or U-shaped relations were evident. However, after 2 years, these same relations had become positive and graded. Given the substantial excess mortality risk in this cohort associated with high blood pressure, particularly SBP, efforts to gradually lower blood pressure should receive high priority among hypertensive men with prior MI.

Adult↗
PubMed1995

Cholesterol and Recurrent Events: a secondary prevention trial for normolipidemic patients. CARE Investigators.

Although elevated plasma cholesterol levels represent a well-established and significant risk for developing atherosclerosis, there is a wide spectrum of cholesterol levels in patients with coronary artery disease (CAD). Most secondary prevention studies have generated convincing evidence that cholesterol reduction in patients with high cholesterol levels is associated with improved clinical outcome by reducing risk of further cardiovascular events. However, other risk factors may play a prominent role in the pathogenesis of coronary disease in the majority of patients with near-normal cholesterol values. The Cholesterol and Recurrent Events (CARE) study was designed to address whether the pharmacologic reduction of cholesterol levels with the 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor, pravastatin, would reduce the sum of fatal coronary artery disease (CAD) and nonfatal myocardial infarction (MI) in patients who have survived an MI yet have a total cholesterol value < 240 mg/dl (< 6.2 mmol/liter). The other inclusion criteria for this study were age 21-75 years, low density lipoprotein (LDL) cholesterol levels of 115-174 mg/dl (3.0-4.5 mmol/liter), and fasting serum triglyceride levels < 350 mg/dl (< 4.0 mmol/liter). A total of 4,159 eligible consenting patients without other study exclusions were then randomly assigned to receive either pravastatin 40 mg daily or matching placebo in addition to their individualized conventional therapy. The trial was designed to have a median follow-up of 5 years. Study endpoints will be evaluated with respect to predefined subgroups according to baseline lipid values, age, gender, prior cardiovascular risk factors, and history.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Lifestyle intervention: results of the Treatment of Mild Hypertension Study (TOMHS).

BACKGROUND: Questions regarding the efficacy of nonpharmacologic approaches for the treatment of stage 1 hypertension were addressed as part of the Treatment of Mild Hypertension Study (TOMHS), a 4-year, randomized clinical trial (N = 902). This report describes the lifestyle intervention program used in TOMHS, presents data on the lifestyle changes observed, and focuses on the effect of weight loss on blood pressure and blood lipid levels. METHODS: Participants were randomly assigned to receive either placebo or one of five different antihypertensive medications. All took part in a lifestyle intervention program to reduce weight and sodium and alcohol intake and to increase physical activity. RESULTS: Substantial changes from baseline levels were achieved for all lifestyle intervention variables. Mean weight change was -10.5 lb (-5.6%) at 1 year, -8.5 lb (-4.5%) at 2 years, -7.4 lb (-4.0%) at 3 years, and -5.7 lb (-3.0%) at 4 years. At 4 years, 70% of participants remained below baseline weight and 34% maintained a weight loss of 10 lb or greater. Mean change in urinary sodium excretion was -12.5 mmol/8 hr (-23%) at 1 year, -10.7 mmol/8 hr (-20%) at 2 years, -8.4 mmol/8 hr (-16%) at 3 years, and -4.6 mmol/8 hr (-9%) at 4 years. Alcohol intake declined by 1.6 drinks/week among drinkers at 4 years. Reported leisure physical activity increased by 86% at 1 year and remained 50% above baseline at 4 years. Beneficial changes in blood pressure and serum lipids were associated with these changes. CONCLUSIONS: These results support a role for lifestyle interventions as the initial treatment for stage 1 hypertension and demonstrate that such interventions can be successfully implemented in the clinical setting.

Aged↗
PubMed1995

Contribution of proteasome-mediated proteolysis to the hierarchy of epitopes presented by major histocompatibility complex class I molecules.

Major histocompatibility complex (MHC) class I-restricted cytotoxic T lymphocytes (CTL) recognize peptide epitopes of protein antigens in a hierarchical fashion. We investigated whether proteolytic cleavage, in particular by proteasomes, is important in determining epitope hierarchy. Using highly purified 20S proteasomes, we find preferred cleavage sites directly adjacent to the N- and C-terminal ends of the immunodominant epitope of chicken ovalbumin, Ova257-264, while most of the subdominant epitope, Ova55-62, is destroyed by a major cleavage site located within this epitope. Moreover, we show that variations in amino acid sequences flanking these epitopes influence proteasomal cleavage patterns in parallel with the efficacy of their presentation. The results suggest that proteasomal cleavage within and adjacent to class I-restricted epitopes contributes to their level of presentation.

Amino Acid Sequence↗
PubMed1995

Light-harvesting chlorophyll a/b-binding protein inserted into isolated thylakoids binds pigments and is assembled into trimeric light-harvesting complex.

The light-harvesting chlorophyll a/b-binding protein (LHCP) is largely protected against protease (except for about 1 kD on the N terminus) in the thylakoid membrane; this protease resistance is often used to assay successful insertion of LHCP into isolated thylakoids in vitro. In this paper we show that this protease resistance is exhibited by trimeric light-harvesting complex of photosystem II (LHCII) but not by monomeric LHCII in which about 5 kD on the N terminus of LHCP are cleaved off by protease. When a mutant version of LHCP that is unable to trimerize in an in vitro reconstitution assay is inserted into isolated thylakoids, it gives rise to only the shorter protease digestion product indicative of monomeric LHCII. We conclude that more of the N-terminal domain of LHCP is shielded in trimeric than in monomeric LHCII and that this difference in protease sensitivity can be used to distinguish between LHCP assembled in LHCII monomers or trimers. The data presented prove that upon insertion of LHCP into isolated thylakoids at least part of the protein spontaneously binds pigments to form LHCII, which then is assembled in trimers. The dependence of the protease sensitivity of thylakoid-inserted LHCP on the oligomerization state of the newly formed LHCII justifies caution when using a protease assay to verify successful insertion of LHCP into the membrane.

Amino Acid Sequence↗
PubMed1995

Goals of antihypertensive therapy.

Antihypertensive therapy has been used for almost 40 years to reduce blood pressure and to prevent morbidity and mortality related to the hypertensive state. Cardiovascular events are related to the initial elevation of blood pressure; the benefits of treating malignant, severe or moderate hypertension are well established. Although large scale clinical trials have demonstrated a decrease in morbid events when mildly elevated blood pressures is treated, the benefits are neither universal or dramatic and treatment is certainly less cost effective than no treatment. Recently it has been emphasised that the absolute risk of cardiovascular events is determined only in part by blood pressure, and that it is also influenced by age, gender, race and the presence of other cardiovascular risk factors. For example, in older individuals where the absolute risk of vascular complications is greater than in younger individuals for any given level of blood pressure, the benefits of therapy will be greater. It has been suggested that in younger individuals with mild hypertension and a low absolute risk of developing cardiovascular morbid events it may be more appropriate to monitor the effects of drug therapy on measures of cardiac and vascular damage that are associated with the hypertensive state. Drug therapy has been shown to be extremely effective in reducing the incidence of stroke, congestive cardiac failure and renal failure associated with elevated blood pressure. Meta-analysis of randomised large scale clinical trials indicates that drug therapy may not reduce coronary events to the extent expected in patients with hypertension. One plausible explanation is that the trials have been of insufficient duration to detect the benefit of blood pressure lowering on coronary heart disease. It has also been suggested that certain adverse metabolic effects associated with the use of thiazide diuretics and beta-blockers employed in these trials may have partially offset the benefits of blood pressure reduction. However, the clinical significance of these drug-induced metabolic disturbances remains unclear. Experimental data suggesting differences in the ability of antihypertensive drugs to inhibit atherosclerosis in animal models are also of interest, but again the relation of the findings to the clinical situation is unknown. Thiazide diuretics, beta-blockers, calcium antagonists, angiotensin-converting enzyme (ACE) inhibitors and alpha-blockers can produce regression of left ventricular hypertrophy (LVH). While LVH is clearly a strong and independent predictor for coronary disease, it remains to be shown that a lower risk for coronary morbid events exists in patients whose LVH has undergone regression over and above that attributable to blood pressure reduction.(ABSTRACT TRUNCATED AT 400 WORDS)

Adrenergic alpha-Antagonists↗
PubMed1994

Identification of tryptophan and tyrosine residues in peptides separated by capillary electrophoresis by their second-derivative spectra using diode-array detection.

The use of diode-array detection allows the non-destructive identification of tryptophan and tyrosine residues in complex peptide mixtures separated by capillary electrophoresis. Second-order derivative spectra of both amino acids show significant differences while zero-order spectra are overlapping to a great extent. A mixture of peptides containing tryptophan and/or tyrosine residues was used to evaluate this method. Tryptic peptide maps of carbonic anhydrase and of the bacterial chaperonin protein GroEL, and of an autodigest of trypsin were characterized for tryptophan- and tyrosine-containing peptides. Automated spectra library search was performed successfully.

Amino Acid Sequence↗
PubMed1994

Sequence-specific impairment of learning by c-jun antisense oligonucleotides.

Hybridization studies revealed a differential accumulation of c-jun and jun B mRNA in the hippocampus and cerebral cortex of rats trained on a foot-shock-motivated brightness discrimination. Supposing that early gene expression is functionally significant for plastic changes in the brain, we used antisense phosphorothioate oligodeoxynucleotides (S-ODN) in vivo to study effects of specific inhibition of c-jun and jun B gene expression on learning and memory formation in rat brain. Discrimination performance of rats was impaired after intrahippocampal injection of anti-c-jun S-ODN but not of anti-jun B S-ODN. These results imply that topically injected antisense oligonucleotides affect processes involved in learning and memory in a sequence-specific manner.

Animals↗
PubMed1994

The amino acid sequence previously attributed to a protein kinase or a TCP1-related molecular chaperone and co-purified with phytochrome is a beta-glucosidase.

A 60 kDa protein (P60) co-purified with phytochrome was identified as avenacosidase, a beta-glucosidase which is part of the defense system of Avena sativa. An antiserum raised against P60 was used to isolate a cDNA clone coding for the complete amino acid sequence of P60. The cDNA-derived amino acid sequence contained the partial sequences described before for a protein kinase [(1989) Planta 178, 199-206] and for a TCP1-related molecular chaperone [(1993) Nature 363, 644-647] co-purified with phytochrome. We conclude that these activities were related to minor contaminants and that only sequences of avenacosidase had been obtained.

Amino Acid Sequence↗
PubMed1994

Cholesterol lowering in the elderly. Results of the Cholesterol Reduction in Seniors Program (CRISP) pilot study.

BACKGROUND: Total and lipoprotein cholesterol levels continue to be predictors of coronary heart disease risk in men and women over 65 years old. Cholesterol-lowering trials, however, while sometimes including such subjects, have not concentrated on this age group. The Cholesterol Reduction in Seniors Program was a five-center pilot study to assess feasibility of recruitment and efficacy of cholesterol lowering in this age group. METHODS: The study was a randomized, double-masked clinical trial with placebo, 20-mg lovastatin, and 40-mg lovastatin arms. Major efforts were made to recruit women and minorities. Participants were followed up for 1 year on a cholesterol-lowering diet plus placebo or study drug. End points were changes in blood lipid levels. Data on other blood chemistry values, as well as quality-of-life measures and coronary heart disease morbidity and mortality, were also collected. RESULTS: Four hundred thirty-one subjects with low-density lipoprotein cholesterol levels greater than 4.1 and less than 5.7 mmol/L (159 and 221 mg/dL) were randomized, of whom 71% were women and 21% were African Americans; the mean age was 71 years. In the 20- and 40-mg lovastatin groups, total cholesterol levels fell 17% and 20%; low-density lipoprotein cholesterol levels fell 24% and 28%; triglyceride levels fell 4.4% and 9.9%, respectively. High-density lipoprotein cholesterol levels rose 7.0% and 9.0%, respectively. No changes were observed in the placebo group. Gender, race, and age did not significantly affect responses. Coronary heart disease morbidity and mortality data were collected but not analyzed for this study. CONCLUSION: Older subjects of both genders and a variety of racial and ethnic groups can be successfully recruited into a cholesterol-lowering trial. Lovastatin has effects similar to those reported in younger subjects in previous controlled trials. There is little advantage to the higher lovastatin daily dose. Side effects were remarkably low in all groups.

Aged↗
PubMed1993

A TCP1-related molecular chaperone from plants refolds phytochrome to its photoreversible form.

Folding of the major cytoskeletal components in the cytosol of mammalian cells is mediated by interactions with t-complex polypeptide-1 (TCP1) molecular chaperones, a situation analogous to the chaperonin 60-aided folding of polypeptides in bacteria, chloroplasts and mitochondria. We have purified a TCP1-related molecular chaperone from etiolated oat seedlings that has a unique structure. Although immunologically related to TCP1, and having amino-acid sequence similarity, its quaternary structure is different from animal TCP1 proteins. Electron microscopy and image analysis reveals that the chaperone has two stacked rings of six subunits each, and is distinct in size and configuration. The chaperone copurifies with the soluble cytosolic photoreceptor phytochrome, and can stimulate refolding of denatured phytochrome to a photoactive form in the presence of Mg-ATP. We propose that this protein is the cytosolic chaperone involved in phytochrome biogenesis in plant cells.

Adenosine Triphosphate↗
PubMed1993

Chaperonin-mediated reconstitution of the phytochrome photoreceptor.

The native phytochrome photoreceptor was purified to homogeneity from etiolated seedlings of oat (Avena sativa L.) and used for renaturation experiments. Light scattering measurements showed that the GroEL molecular chaperone interacts with non-native phytochrome to suppress aggregation of the refolding polypeptide, following its dilution from a chaotrope. The binary complex formed between non-native phytochrome and GroEL was stable and could be isolated by size exclusion chromatography. Discharge of the photoreceptor from GroEL was obtained with 2 mM MgATP, although 6 mM adenosine 5'-O-(3-thiotriphosphate) was also effective. Phytochrome released from GroEL with MgATP was found primarily in the form of 124-kDa monomers, as judged by size exclusion chromatography and nondenaturing gel electrophoresis, although dimers and other oligomeric forms were also observed. The reconstituted dimers, and other oligomeric forms, preferentially cross-reacted with a monoclonal antibody that recognizes native-like epitopes. In vitro folding reactions, using chemically denatured phytochrome, revealed that successful reconstitution of the photoreceptor required the presence of the GroEL chaperonin and MgATP under the conditions tested. Reconstitution in the presence of GroEL yielded phytochrome that could exhibit photoreversibility between the red-light absorbing and far-red absorbing forms.

Adenosine Triphosphate↗
PubMed1993

Chlorthalidone attenuates the reduction in total cholesterol and small, dense LDL cholesterol subclass associated with weight loss.

Thiazide diuretics are known to raise total and LDL cholesterol. To assess whether chlorthalidone affected levels of putatively atherogenic small, dense LDL (LDL 3), we conducted a 12 week double blind randomized, placebo controlled clinical trial in 34 nonsmoking men aged 35 to 57 years with mild hypertension (DBP 90 to 104 mm Hg). Our a priori hypothesis that chlorthalidone raised LDL 3 levels was not confirmed. However, the fall in LDL 3 (P = .03) and total cholesterol (P = .08) associated with weight loss was attenuated by chlorthalidone. Since weight loss is commonly prescribed during the clinical management of hypertensives with concomitant hypercholesterolemia, consideration should be given to the attenuating effect of chlorthalidone on cholesterol reduction in the management of these patients.

Adult↗
PubMed1993

Echocardiographic correlates of left ventricular structure among 844 mildly hypertensive men and women in the Treatment of Mild Hypertension Study (TOMHS).

BACKGROUND: Echocardiography provides a noninvasive means of assessing left ventricular (LV) structure and evidence of LV wall remodeling in hypertensive persons. The relation of demographic, biological, and other factors with LV structure can be assessed. METHODS AND RESULTS: LV structure was assessed by M-mode echocardiograms for 511 men and 333 women with mild hypertension (average blood pressure, 140/91 mm Hg). Measurements of LV wall thicknesses and internal dimensions were made, and estimates of LV mass indexes and other derivations of structure were calculated. LV hypertrophy criteria were based on previously reported echocardiographic population studies of normal subjects. These measures were compared by age, sex, race, body mass index, systolic blood pressure, antihypertensive drug use, physical activity, alcohol intake, cigarette smoking, and urinary sodium excretion. Despite virtual absence of ECG-determined LV hypertrophy, 13% of men and 20% of women had echocardiographically determined LV hypertrophy indexed by body surface area (g/m2), and 24% of men and 45% of women had LV hypertrophy indexed by height (g/m). Black participants had slightly higher mean levels of wall thickness than nonblack participants but similar LV mass. Systolic blood pressure and urinary sodium excretion were significantly and independently associated with LV mass index and LV hypertrophy using both g/m2 and g/m. Body mass index was significantly related to LV mass index and LV hypertrophy using g/m. Smoking was significantly associated with LV mass index, i.e., using continuous measurement but not using the dichotomy for LV hypertrophy. CONCLUSIONS: This study of a large population of men and women with mild primary hypertension, largely without ECG evidence of LV hypertrophy, showed a substantial percentage of participants with echocardiographically determined LV hypertrophy. LV mass indexes correlated positively with systolic blood pressure, body mass index, urinary sodium excretion, and smoking.

Aging↗