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Biomedical subjects

R B Moore

Publications and source records attributed to R B Moore.

At least 73 records · Page 4Linked to original sources
PubMed1984

The determination of calcium-binding sites of human erythrocyte membranes.

Calcium binding to leaky erythrocyte plasma membranes was measured by three different procedures: Millipore filtration, equilibrium dialysis, and partition centrifugation. The curve derived from the binding equation, which best fit the means of the raw data, was used to estimate the association constants and capacities of the binding sites. A computer program (Gaushaus) which uses a nonlinear, least-squares regression protocol was also used to confirm these estimates. On the basis of these analyses we propose the presence of three classes of calcium-binding sites with the following apparent association constants and capacities: site 1, Ka = 3 X 10(4) M-1 and n = 30 nmol/mg protein; site 2, Ka = 3 X 10(3) M-1 and n = 200 nmol/mg protein; site 3, Ka = approximately 10(2) M-1 and n = approximately 200 nmol/mg protein. Calcium binding to erythrocyte membranes sealed in a high-salt solution showed the presence of site 3, but not site 2. The influence of phospholipids on the binding of calcium was evaluated by pretreating ghosts with phospholipase C (Clostridium welchii, EC 3.1.4.3). Treatment with this enzyme removed 80% of the total membrane phosphorus, predominantly from sphingomyelin, phosphatidylcholine, and phosphatidylethanolamine. By the method of partition centrifugation two classes of binding sites were identified by computer analysis. Their association constants and capacities are, respectively, 1.1 X 10(5) M-1 and 20 nmol/mg protein for site 1 and 4.4 X 10(3) M-1 and 200 nmol/mg protein for site 2. We speculate that calcium-binding site 1 is composed of acidic phospholipids, calcium-binding site 2 is composed of spectrin and actin, and calcium-binding site 3 is composed of sialic acid.

Binding Sites↗
PubMed1983

Directional ST-segment deviation in graded exercise tests correlated with motion of the individual segments of the left ventricular wall.

An exercise test may be characterized as positive because of the production of either electrocardiographic ST-segment depression or elevation. The relationship of exercise-induced ST-segment deviation to the specific motion abnormalities of the individual segments of the left ventricular wall was investigated. The first 280 subjects to enter the Program of Surgical Control of Hyperlipidemia were studied by treadmill exercise testing and left ventriculography. The results showed that exercise-induced ST-segment elevation could occur without evidence in the resting subject of either dyskinesia or aneurysm of the left ventricle, that the area of left ventricular damage was much greater in subjects with exercise-induced ST-segment elevation than in those with ST-segment depression, and that wall motion abnormalities were concentrated in the inferoposterior area in the group with ST-segment elevation, but were generally scattered throughout the left ventricular wall in the group with ST-segment depression.

Adult↗
PubMed1983

Clinical angiographic regression of atherosclerosis after partial ileal bypass.

Clinical documentation of atherosclerotic plaque regression has been difficult to obtain. This is a report of a patient with severe and early atherosclerotic cardiovascular disease with regression of at least three major atherosclerotic lesions demonstrated by coronary arteriography 10 years after partial ileal bypass operation. The patient's total plasma cholesterol was reduced over these 10 years, ranging from 40% to 23%, from the preoperative level of 757 mg/dl. Sequential arteriograms were assessed independently by several arteriographers and blindly by the Arteriography Review Panel of the Program on Surgical Control of the Hyperlipidemias (POSCH). The readings were analyzed by 4 grading methods. Unanimously, marked regression was read in the proximal left circumflex artery (70% leads to 20%), middle segment of the right coronary artery (45% leads to 20%), and in the distal right coronary artery (80% leads to 50%). Thus, by any and all of the methods used, there was significant regression of arteriographically demonstrated atherosclerotic lesions.

Adult↗
PubMed1982

Overview of randomized clinical trials of lipid intervention for atherosclerotic cardiovascular disease.

This paper is a review of the scientific and economic (when possible) impact of 15 randomized clinical trials of lipid intervention for atherosclerotic cardiovascular disease. No effort has been made to be all-inclusive and certain smaller and first generation studies have been omitted. No effort has been made to offer detailed analyses of protocols; we have limited discussion to summaries of the salient features of each study presented. After stating the data, we introduce certain reflections and raise some of the more obvious questions that emerge.

Arteriosclerosis↗
PubMed1982

The Program on the Surgical Control of the Hyperlipidemias: a status report.

The Program on Surgical Control of the Hyperlipidemias (POSCH) is a multicentered secondary coronary heart disease intervention trial utilizing maximal plasma lipid reduction as achieved by the partial ileal bypass operation. With over 500 patients recruited into this trial at present, the 4-year sequential lipid changes are statistically highly significant and include an approximate 30% plasma total cholesterol and 40% low density lipoprotein (LDL)-cholesterol reduction, with a slight increase in the high density lipoprotein (HDL)-cholesterol and a marked increase in the HDL-cholesterol:LDL-cholesterol ratio of about 75% or higher. A definitive answer to the lipid-atherosclerosis theory corollary--whether a decrease in the plasma cholesterol engenders a reduction in the incidence or severity of atherosclerotic cardiovascular disease--can be expected from these marked lipid changes in POSCH.

Adult↗
PubMed1981

Myotonic dystrophy: calcium-dependent phosphatidic acid synthesis in erythrocytes.

Recently it was reported that calcium-dependent phosphatidic acid synthesis in erythrocyte of patients with myotonic muscular dystrophy (MyD) is markedly impaired when compared to that in control subjects. Using 32P-loaded erythrocytes, we found no significant difference in the levels of 32P-phosphatidic acid synthesized after exposure to calcium and its ionophore A23187 between patients with MyD and controls. In a batch experiment typical of the experiments with 32P, and a twofold increase of phosphatidic acid in both groups was determined by inorganic phosphate measurements. Thus, the specific activity of the 32P-phosphatidic acid increased four- to five-fold in response to calcium Analyses of 32P-polyphosphoinositide breakdown in ghosts and in adenosine triphosphate-depleted erythrocytes also appeared normal for patients with myotonic muscular dystrophy. Possible discrepancies between the results presented here and those reported previously are discussed.

Adenosine Triphosphate↗
PubMed1981

Patterns of activity evoked in cerebellar interpositus nuclear neurones by natural somatosensory stimuli in awake cats.

1. Stable extracellular unitary recordings were made from 138 cerebellar interpositus nuclear neurones (IPNs) in awake cats. Mean background discharge, in animals in a state of relaxed wakefulness and in the absence of overt movement, was 41.0+/-2.6 impulses/sec (mean+/-s.e.m).2. Animals were trained to accept a variety of sensory testing procedures without producing detectable motor reactions. Mechanical taps (1 mm amplitude; 20 msec overall duration) applied to the main pads or dorsal surfaces of the forepaws and/or hind paws modified discharge in forty-eight of 110 IPNs tested. Response patterns to taps generally comprised one or more of three basic components, namely: short-latency excitation, e(1), at onset latencies of 13.0+/-0.9 msec (mean+/-s.e.m.) for ipsilateral forepaw (iF) and 17.0+/-0.7 msec for ipsilateral hind paw (iH); a period of reduced discharge, at latencies 25.6+/-2.6 msec for iF and 32.3+/-2.1 msec for iH; a delayed acceleration of discharge, e(2), at latencies 47.4+/-4.6 msec for iF and 46.4+/-4.1 msec for iH. The component e(1) was the most common (present in 80% of responses) and e(2) the least common (present in 18% of responses).3. The majority (> 70%) of responses of IPNs to tap stimulation of the paws comprised net excitation.4. Convergence of tap-evoked sensory input from iF and iH on to individual IPNs was evident in eight of the thirty-five units tested with stimulation of both afferent sites.5. Approximately one third of IPNs so tested were sensitive to passive manipulation of limb joints in the quiet, awake cat. Sixteen of the forty-three IPNs so tested responded to displacement of the ipsilateral wrist and/or elbow joints and three of ten IPNs so tested responded to movement of contralateral forepaw joints. Corresponding proportions of IPNs responding to passive ankle and/or knee joint displacements were sixteen of thirty-six units tested and three of three units tested for ipsilateral and contralateral hind paws respectively. Convergence of input generated by manipulation of iF and iH joints on to individual IPNs was apparent in only three of twenty-four units tested at each site.6. Tactile stimulation (brushing fur, gentle pressure on the skin) of iF influenced discharge in twelve of thirty-seven IPNs tested and comparable iH-related cutaneous sensory fields were found for fourteen of twenty-eight IPNs tested.7. The modulations of discharge of IPNs associated with active movements of the stimulated limb were usually far more pronounced than those elicited by somatosensory stimulation in the quiet, relaxed animal.8. Responses of IPNs to natural somatosensory stimulation in the awake cat are compared with those previously described for anaesthetized or decerebrate preparations and with those found for electrical stimulation of cutaneous nerves in awake cats. In general IPN response patterns to precisely timed tap stimulation of the paws in the awake animal closely resembled those that would have been predicted from the earlier studies, although the time course of responses differed in certain respects.

Animals↗
PubMed1980

The effect of partial ileal bypass on plasma lipoproteins.

Plasma lipids and lipoprotein cholesterol concentrations were determined before and at 3 months and 1 year after partial ileal surgery in 28 male survivors of first myocardial infarction (eight normolipidemic subjects and eight type II-A, two type II-B, eight type IV and two type V hyperlipoproteinemic subjects). All subjects had marked reductions in plasma total cholesterol (average 45% and 33% in the type V subjects and 37% and 31% in the other 26 subjects at 3 months and 1 year after surgeryyy). Except for the two type V subjects, all had even more marked reductions in low-density lipoprotein (LDL)-cholesterol than in the total plasma cholesterol, averaging 51% at 3 months and 49% at 1 year after surger. There were no significant changes in high-density lipoprotein (HDL)-cholesterol levels. The hypertriglyceridemic subjects had marked reductions in plasma triglycerides and very low density lipoprotein-cholesterol, whereas the normotriglyceridemic subjects (normals and II-A) had slight increases in these two measurements after surgery. Partial ileal bypass tends to normalize elevated plasma lipid and lipoprotein levels and results in a maximal lowering in LDL-cholesterol concentrations without altering the HDL-cholesterol level.

Adult↗
PubMed1980

Effect of nolinium bromide, cimetidine, and oxyphencyclimine on gastric hypersecretion induced by some secretagogues in the rat.

Gastric hypersecretion was induced in the pylorus-ligated rat by histamine, pentagastrin, carbachol, or insulin following the peroral administration of either nolinium bromide, a new non-anticholinergic antisecretory drug, cimetidine, an H2-histamine receptor antagonists, or oxyphencyclimine hydrochloride, a specific anticholinergic drug. Nolinium bromide cimetidine or oxyphencycline. Nolinium bromide and cimetidine weakly antagonized hypersecretions in response to carbachol and to insulin while oxyphencyclimine caused profound antagonism. It was concluded that there was incomplete parallelism in inhibitory efficacy among the three antagonist drugs suggesting that their modes of action in blocking gastric hypersection differed. The findings with nolinium bromide were consistent with its lack of specific anticholinergic action and in keeping with its gastric acid antisecretory activity.

Aniline Compounds↗
PubMed1979

Plasma lipoproteins and coronary arteriography in subjects in the program on the surgical control of the hyperlipidemias. Preliminary report.

Coronary arteriographic findings, plasma lipid and lipoprotein levels, and cigarette smoking history are reported for the first 101 male post myocardial infarction survivors who have been entered into the POSCH clinical trial. Estimates of the extent of stenosis in the major coronary arteries were made using 4 models ranging from a simple determination of the number of the 3 major vessels having significant (i.e. 50% or greater stenosis) disease to more complex methods of determining overall extent of disease in 14 major segments of the coronary arteries. Age was shown to be an important factor in the extent of vessel disease. When controlling for age, plasma cholesterol and LDL-cholesterol levels were shown to be related to the extent of disease, especially in Type II hyperlipoproteinemia subjects. Multiple linear regression analysis demonstrated that age and LDL-cholesterol had positive associations and HDL-cholesterol had an inverse association with the coronary artery disease indices. In this comparatively "healthy" subgroup of the overall population of first MI survivors the major CHD risk factors are limited to plasma lipids and cigarette smoking. This preliminary report of 10% of the recruitment objective of the project supports the currently held views of the lipid--atherosclerosis hypothesis regarding the effects of age-total plasma cholesterol, LDL--cholesterol, and HDL--cholesterol on the extent of coronary atherosclerotic plaques, as determined by coronary arteriography.

Adult↗
PubMed1977

Maximum lipid reduction by partial ileal bypass: a test of the lipid-atherosclerosis hypothesis.

Atherosclerosis is the process responsible for our national epidemic of coronary heart disease. A primary and proven atherosclerotic risk factor is the plasma cholesterol concentration. Yet, proof that a reduction in plasma cholesterol level results in a reduction in the incidence or severity of atherosclerosis and atherosclerotic cardiovascular disease still requires conclusive documentation. The controversial methods of operation and inconclusive results of concluded first and second generation trials are reviewed. These data clearly demonstrate that a definitive test of the lipid hypothesis has not been reported. Evidence is presented to show that the partial ileal bypass operation most nearly fulfills the six features of an "ideal" lipid lowering trial modality: maximum effectiveness (50% cholesterol reduction); known mechanism of action; no response "escape" or "rebound"; obligatory effect without patient cooperation; minimal side effects; and relative safety. The basic design and protocol of the National Heart and Lung Institute Program on Surgical Control of the Hyperlipidemias, a secondary intervention trial using a combination of diet therapy and partial ileal bypass surgery, are outlined.

Arteriosclerosis↗
PubMed1976

Effect of thyroid status on spontaneous and induced surges of luteinizing hormone.

This study was designed to describe the effects of thyroid status on the preovulatory surge of LH and to determine the site(s) at which these effects are exerted. The treatment of normal 4-day cycling rats with a hyperthyroid dose of thyroxine (T4, 20 mug/100 g BW/day) for 8 days resulted in surges of LH on proestrus which were depressed to 25% of control levels. In ovariectomized (OV) or ovariectomized-thyroidectomized (OV-Tx) rats maintained on a physiological regimen of T4 (2 mug/100 gBW/day), the amount of estrogen required to induce an LH surge was far greater than that required in OV-TX rats receiving no T4 replacement. These data suggest that T4 attenuates preovulatory surges of LH by acting at the hypothalamic-pituitary axis. However, the pituitary might be eliminated as a site of action since hyerthyroid proestrous rats responded to a challenge of LH-releasing hormone (500 ng) by secreting a quantity of LH equivalent to that in euthyroid animals. Similarly, there was no difference in the quantity of LH released by hyperthyroid and euthyroid proestrous rats in response to electrochemical stimulation (100 muA, 60 sec) of the medial preoptic area of the hypothalamus. On the other hand, hyperthyroid rats secreted significantly less LH in response to stimulation of the arcuate nucleus-median eminence area (ARN-ME) than did controls. Thus, T4, apparently modifies LH release by depressing the response of the ARN.

Animals↗
PubMed1975

The partial ileal bypass operation in treatment of the hyperlipidemias.

Partial ileal bypass is, today, the single most effective means available for lowering the plasma lipids, in particular the plasma cholesterol concentration. The cholesterol lowering effect of this procedure is universally lasting; response escape or rebound of lipid levels has not occurred. The operation is safe. In addition, the obligatory benefits of this mode of therapy make it attractive as a therapeutic alternative, especially in a young and asymptomatic population. We do not advocate this operation as the treatment of choice for all hyperlipidemic individuals. It may be the treatment of choice for certain patients with hyperlipidemia.

Cholesterol↗