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Biomedical subjects

P Harris

Publications and source records attributed to P Harris.

At least 163 records · Page 9Linked to original sources
PubMed1991

Echocardiography shows persistent thickness of the wall of the right ventricle in infants at high altitude.

We have applied M-mode and two-dimensional echocardiography to infants living at high altitude in La Paz, Bolivia (3800m) and infants living at low altitude in Santa Cruz, Bolivia (400m). At low altitude, the thickness of the anterior wall of the right ventricle decreases during the first month of extrauterine life to a dimension which remains constant for the rest of infancy. At high altitude, the thickness of the anterior wall of the right ventricle at birth is similar to that found at low altitude but does not decrease in the succeeding twelve months. The ratio of the diameter of the aorta to that of the pulmonary artery was higher at low altitude in all age-groups. The observations are consistent with the persistence of a high pulmonary arterial pressure during infancy at high altitude.

Adaptation, Physiological↗
PubMed1990

General practitioners' detection of depression and dementia in elderly patients.

In a study of 11 general practitioners' detection of dementia and depression in 101 elderly patients it was found that general practitioners were more accurate in their detection of dementia than depression. The general practitioners did not identify 12 of the 15 patients assessed as depressed by a Diagnostic Interview for Depression, but their assessments of dementia corresponded quite well with the results of dementia tests. The general practitioners' knowledge of the symptoms and signs of dementia and depression was limited. If the patient talked to the general practitioner about feeling depressed, sad or irritable, the depression recognition rate increased.

Activities of Daily Living↗
PubMed1990

Hereditary spherocytosis associated with deletion of human erythrocyte ankyrin gene on chromosome 8.

Hereditary spherocytosis (HS) is one of the most common hereditary haemolytic anaemias. HS red cells from both autosound dominant and recessive variants are spectrin-deficient, which correlates with the severity of the disease. Some patients with recessive HS have a mutation in the spectrin alpha-2 domain (S.L.M. et al., unpublished observations), and a few dominant HS patients have an unstable beta-spectrin that is easily oxidized, which damages the protein 4.1 binding site and weakens spectrin-actin interactions. In most patients, however, the cause of spectrin deficiency is unknown. The alpha- and beta-spectrin loci are on chromosomes 1 and 14 respectively. The only other genetic locus for HS is SPH2, on the short arm of chromosome 8 (8p11). This does not correspond to any of the known loci of genes for red cell membrane proteins including protein 4.1 (1p36.2-p34), the anion exchange protein (AE1, band 3; 17q21-qter), glycophorin C (2q14-q21), and beta-actin (7pter-q22). Human erythrocyte ankyrin, which links beta-spectrin to the anion exchange protein, has recently been cloned. We now show that the ankyrin gene maps to chromosome 8p11.2, and that one copy is missing from DNA of two unrelated children with severe HS and heterozygous deletions of chromosome 8 (del(8)(p11-p21.1)). Affected red cells are also ankyrin-deficient. The data suggest that defects or deficiency or ankyrin are responsible for HS at the SPH2 locus.

Ankyrins↗
PubMed1990

Effects of temperature and osmolality on the release of atrial natriuretic peptide.

In isolated rat atria a 10 degrees C increase in temperature approximately doubled the output of atrial natriuretic peptide during relaxation and stretch. The effect was not due to the increased rate of contraction. Increasing the osmolality of the superfusate within the physiological range (290 to 320 m osmols) with sodium, potassium or glucose had no appreciable effect on the release of atrial natriuretic peptide.

Animals↗
PubMed1990

Hormonal response in untreated myocardial infarction.

Plasma levels of a variety of hormones have been measured in patients within two hours of the onset of symptoms of myocardial infarction and before commencement of any treatment. Increased plasma concentrations were found for norepinephrine, epinephrine, glucagon, aldosterone, vasopressin, atrial natriuretic peptide, corticotrophin, prolactin, cortisol and substance P while plasma renin activity was raised. The plasma concentrations of insulin, growth hormone, neurotensin, bombesin and vasointestinal peptide were normal.

Female↗
PubMed1990

Identification of a locus which shows no genetic recombination with the autosomal dominant polycystic kidney disease gene on chromosome 16.

The major site for mutations leading to autosomal dominant polycystic kidney disease (ADPKD) is at the PKD1 locus, previously mapped to 16p13. Three additional probes have now been mapped within an existing array of genetic markers flanking this locus. One of these, CMM65b (D16S84), shows no recombination with PKD1 in 201 informative meioses. The others, Fr3-42 (D16S21) and EKMDA2 (D16S83), are shown to be the closest telomeric flanking markers. Somatic cell hybrids containing derivative chromosome 16s were used to construct a physical map of the region. Cosmid overlap cloning of the D16S84 region allowed a t(16;1) translocation breakpoint to be mapped at the molecular level, orientating the extended D16S84 locus with respect to the chromosome. The new markers and physical map described here provide an improved framework for attempts to clone the PKD1 region and to identify polycystic kidney disease mutations.

Animals↗
PubMed1989

Effects of platelet-derived growth factor on phosphorylation of the epidermal growth factor receptor in human skin fibroblasts.

Heterologous regulation of the epidermal growth factor (EGF) receptor by platelet-derived growth factor (PDGF) was studied in FS4 human skin fibroblasts. The addition of PDGF to FS4 cells inhibited high affinity binding of 125I-EGF and stimulated phosphorylation of the EGF receptor. Phosphopeptide analysis by high performance liquid chromatography revealed that PDGF treatment of cells increased phosphorylation at several distinct sites of the EGF receptor. However, PDGF did not stimulate phosphorylation of threonine 654, a residue previously shown to be phosphorylated when protein kinase C is activated. The tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) also stimulated phosphorylation of the same peptides from the EGF receptor as PDGF, and, in addition, induced phosphorylation of threonine 654. TPA inhibited both high and low affinity 125I-EGF binding by these cells. PDGF treatment of cells had no effect on EGF-dependent, tyrosine-specific autophosphorylation of the receptor, whereas TPA treatment was inhibitory. TPA, but not PDGF, stimulated phosphorylation of a Mr = 80,000 protein, known to be a substrate for protein kinase C, even though PDGF appeared to mediate breakdown of phosphoinositides. These data suggest that regulation of EGF receptor function by PDGF and TPA are distinct in these cells, even though some elements of regulation are shared. The results differ from those previously reported for a human lung fibroblast isolate, indicating that cell type-specific differences may exist in metabolism of the EGF receptor.

Binding, Competitive↗
PubMed1989

Hemodynamic, hormonal, and renal effects of atrial natriuretic peptide in untreated congestive cardiac failure.

We report the effects of intravenous infusion of the atrial natriuretic peptide analogue, met-ANP-26 (2 micrograms/min for 2 to 4 hours), in four patients with cardiomyopathy and severe congestive cardiac failure who had not received any previous cardiac therapy. The average cardiac index before infusion was 1.8 L/min/m2. Severe sodium and water retention was confirmed by high levels of total body water and extracellular liquid, whereas renal blood flow and glomerular filtration rate were reduced. Plasma concentration of ANP, norepinephrine, cortisol, and growth hormone were significantly increased before infusion. The infusion had no significant hemodynamic effect. After 2 hours urine volume had increased significantly from 51 to 76 ml/hr, urinary concentration of sodium from 72 to 90 mmol/L, and sodium excretion from 4.5 to 8.2 mmol/hr. The infusion was accompanied by a significant increase in plasma ir-ANP from 193 to 980 pg/ml. There were no significant effects on the plasma concentrations of norepinephrine, epinephrine, aldosterone, vasopressin, cortisol, growth hormone, or prolactin and no significant change in plasma renin activity. After 2 hours of infusion one patient had a severe sinus tachycardia and another had a sinus bradycardia. Both arrhythmias disappeared without harmful effects soon after the infusion was stopped.

Adult↗
PubMed1989

Stretch-induced centrifugal movement of atrial specific granules--a preparatory step in atrial natriuretic peptide secretion.

Atrial natriuretic peptide (ANP) is a circulating hormone produced by atrial muscle cells which acts upon renal vascular smooth muscle to raise glomerular filtration pressure, thereby increasing salt and water excretion and reducing blood pressure [2, 5, 8]. As in other peptide hormone-secreting cells, ANP is packaged and stored in dense Golgi-derived secretory granules [4-6]. These atrial specific granules [6] occur predominantly in large clusters deep in the myocyte's interior, associated with Golgi cisternae in myofibril-free cytoplasm at the nuclear poles [5, 6]. Smaller clusters and individual granules are distributed beneath the sarcolemma and between myofibrils [6, 10]. Expansion of the blood volume raises the level of circulating ANP [7], a response mediated by mechanical stretch of the atrial wall [1, 3, 9]. The mechanism by which cell stretch induces release of ANP from atrial myocytes is, however, unknown. We show here that one component of this unusual secretory mechanism involves a sudden centrifugal movement of atrial specific granules toward the cell surface.

Animals↗
PubMed1989

Femoro-popliteal versus femoro-distal bypass grafting for limb salvage in patients with an "isolated" popliteal segment.

In a prospective, multicentre trial, 59 patients with an ischaemic limb and an "isolated" popliteal segment on angiography were randomised to undergo infrainguinal bypass grafting to either the popliteal segment or to a reconstituted distal vessel lower in the calf. Limb salvage was attained with 88% of the femoro-popliteal grafts and 80% of the femoro-distal grafts. There was no difference in the one year graft patency rate between the femoro-popliteal group (79%) and the femoro-distal group (70%). Mean postoperative increase in ankle/brachial pressure index was similar in the two groups despite the presence of occluded or significantly diseased vessels distal to the popliteal anastomoses. Technical difficulties were encountered in 8% of the popliteal group and 24% of the distal group. Femoro-distal bypass grafting confers no apparent benefit over femoral bypass grafting into a patent popliteal segment, even though the popliteal run-off is impaired or occluded.

Aged↗
PubMed1989

Pulmonary blood vessels and endocrine cells in subacute infantile mountain sickness.

A male infant of 16 months, of the Han race, died from subacute infantile mountain sickness in Lhasa (3600 m). At necropsy there was right ventricular hypertrophy secondary to muscularization of the pulmonary arteries and arterioles thought to have been induced by hypobaric hypoxia. In addition, there was intimal proliferation of myofibroblasts in the pulmonary arterioles, venules and veins. There were increased numbers within the bronchioles of pulmonary endocrine cells, containing calcitonin and bombesin, which could be related to hypoxia or trophic effects on the pulmonary vasculature. The relation of delayed effects of hypoxia to primary pulmonary hypertension is considered in this study.

Altitude Sickness↗
PubMed1989

Noradrenaline, atrial natriuretic peptide, bombesin and neurotensin in myocardium and blood of rats in congestive cardiac failure.

Rats given monocrotaline develop severe right ventricular hypertrophy often accompanied by ascites and pleural effusions. In rats with right ventricular hypertrophy and no serous effusions ("hypertrophy" group), ventricular concentrations of noradrenaline were reduced but ventricular contents were unchanged. Atrial concentrations of noradrenaline were unaffected. Those with more severe right ventricular hypertrophy and serous effusions ("failure" group) had greatly reduced concentrations of noradrenaline in all four chambers, particularly on the right side; the right and left ventricular contents of noradrenaline were also diminished. The distributions of ir-ANP, ir-bombesin and ir-neurotensin in the normal rat heart are presented. ANP concentration fell to 33% in the right atrium and 46% in the left atrium of "failure" animals and to 57% in the right atrium of "hypertrophy" animals. Right ventricular content of ANP, normally low, increased more than two-fold in both groups, the concentration remaining unchanged. Left ventricular content of ANP decreased in the "failure" group. Concentrations of bombesin and neurotensin fell in both ventricles of both groups. Ventricular contents of bombesin did not change, but ventricular contents of neurotensin decreased, especially on the right side. Plasma ANP rose nearly six-fold while plasma bombesin and neurotensin fell in the "failure" group. Plasma peptide concentrations were unchanged in the "hypertrophy" group. The studies show the utility of the monocrotaline model in distinguishing between the effects of hypertrophy and those associated specifically with the syndrome of congestive cardiac failure.

Animals↗
PubMed1989

Treatment of heart failure with diuretics: body compartments, renal function and plasma hormones.

Body fluid compartments, renal function and plasma hormones were measured in 13 patients with severe chronic heart failure, when the referring physician considered the patient to be appropriately treated. Although renal function was substantially impaired and plasma noradrenaline, aldosterone and renin activity were elevated, fluid compartments were within the normal range. These results show that careful clinical assessment of patients by an experienced physician is a reliable method of assessing restoration of 'normal' body fluid volumes with diuretics.

Adult↗