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Biomedical subjects

P Harris

Publications and source records attributed to P Harris.

At least 217 records · Page 12Linked to original sources
PubMed1987

Regional blood flow and hemodynamics in the rabbit with adriamycin cardiomyopathy: effects of isosorbide dinitrate, dobutamine and captopril.

We have studied the effects of captopril, nitrates and dobutamine on hemodynamics and regional blood flow in the conscious rabbit with adriamycin cardiomyopathy. Rabbits were injected twice weekly with adriamycin (1 mg.kg-1 bw.) for 8 weeks and subsequently maintained for 2 weeks without adriamycin in order to allow recovery from any noncardiac effects. Doses of drug for investigation (captopril, 300 micrograms.kg-1.min-1; isosorbide dinitrate, 10 micrograms.kg-1.min-1; and dobutamine, 10.9 micrograms.kg-1.min-1) were chosen in anticipation of a 20% increase of cardiac output in animals with heart failure. In animals with heart failure myocardial blood flow was increased by dobutamine and to a lesser extent by captopril. Renal blood flow was increased only by captopril and nitrates. Cerebral blood flow was reduced by captopril in control animals but unaltered in animals with heart failure. The observed alterations of blood flow were similar to those known to occur in humans and indicate that this is a useful model of heart failure for the evaluation of new drugs.

Animals↗
PubMed1986

Mapping by chromosome sorting of several gene probes, including c-myc, to the derivative chromosomes of a 3;8 translocation associated with familial renal cancer.

In eight members of a single family a constitutional translocation t(3;8) (p14.2;q24.1) is associated with the development of renal cancer. Chromosomes isolated from a cell line established from a subject with this translocation were analysed in flow with a fluorescence-activated cell sorter (FACS II). Nearly six million chromosomes from the flow karyotype region containing the der(8) and 5.5 million from the region containing the der(3) were sorted, the DNA extracted, digested with EcoRI, size fractionated by electrophoresis, and transferred to nitrocellulose. Hybridization with gene probes for c-mos, which has been localized to 8q11-q22 and somatostatin, which has been mapped to 3q28, confirmed that the sorted fractions contained, respectively, the der(8) and der(3) chromosomes. The cellular oncogenes c-raf-1 (3p25) and c-myc (8q24) were found to be translocated to the der(8) and der(3) chromosomes, respectively. The possible role that the relocation of c-myc might have on the development of renal carcinoma in carriers of this 3;8 translocation was further studied by analysis of the region surrounding the c-myc gene. By the use of cosmid cloning, no rearrangement 31 Kb 5'(or 19 Kb 3') of the translocated gene was found, indicating that the break-point is not immediately adjacent to c-myc. In an associated study, the DNA fragment D3S2 from chromosome 3 was found to map to 3p14.2-pter. This assignment in conjunction with published somatic cell hybrid data enabled D3S2 to be mapped more precisely to the interval 3p14.2-3p21.

Carcinoma, Renal Cell↗
PubMed1986

The thickness of the alveolar capillary wall in the human lung at high and low altitude.

An ultrastructural study of lung biopsy specimens from an adult mestizo highlander from La Paz (3800 m) and three lowlanders from London showed no significant difference in the thickness of the alveolar capillary wall, the thickness in the highlander being 0.65 micron and the range in the lowlanders being 0.57-0.69 micron. The thickness of the blood-air barrier in a mestizo girl of 4 years born and living in La Paz was 0.47 micron. These findings suggest that the alveolar capillary wall in the acclimatized highlander does not differ in thickness from the lowlander. This contrasts with our previous findings in native high altitude guinea pigs which indicate that the alveolar capillary wall is thinner in such indigenous mountain species which are adapted genetically rather than acclimatized to hypobaric hypoxia.

Adult↗
PubMed1986

The thickness of the alveolar capillary wall in guinea-pigs at high and low altitude.

The thickness of the alveolar-capillary wall was measured in the lungs of seven guinea-pigs born and living at La Raya, in the Peruvian Andes, at an altitude of 4200 m and in seven sea-level representatives of the same species. This was achieved by carrying out morphometric studies on electron micrographs to obtain the so-called arithmetic and harmonic mean thicknesses. The arithmetic mean thickness was always the larger, this being due to the greater emphasis which the technique employed places on the copious amounts of connective tissue in the interstitial space of the alveolar capillary wall in this species. These thicker portions of the alveolar wall are not concerned with gaseous diffusion. The harmonic mean thickness probably gives a more physiologically realistic estimate of the magnitude of the diffusion barrier to oxygen. This proved to be smaller in the animals from high altitude and may facilitate diffusion of oxygen from alveolar spaces to blood, thus making less steep the "oxygen cascade" from inspired air to mitochondria.

Altitude↗
PubMed1986

St. Etheldreda and the death of Gervase.

We have discovered an interesting account of sudden death reported in the Liber Eliensis, a Latin compendium of twelfth century happenings in the environs of Ely, the cathedral town found just north of Cambridge in the fenlands of England. The account tells how Gervase, a Norman official of the Sheriff, oppressed the local Saxons. The abbot took the people's part and was summoned before Gervase. However, during the night before the abbot arrived, Gervase dreamed that the local Saxon saint of the shrine, St. Etheldreda, struck him with her staff in the chest. He woke with pain, crying out that St. Etheldreda was about to strike him again, and died.

Death, Sudden↗
PubMed1986

Identification of cDNA clones for the human microtubule-associated protein tau and chromosomal localization of the genes for tau and microtubule-associated protein 2.

We have previously identified a partial human cDNA for MAP2, and we now report the isolation of human cDNA clones for tau. The RNA species recognized by the tau clones is a 6 kilobase (kb) message that is expressed in the human brain but not in other human tissues, and exhibits a developmental shift in size. We also report the human chromosomal localization of the MAP2 and tau genes. The MAP2 cDNA pKN7 was used to localize the MAP2 gene to chromosome 2q34-35. The tau cDNAs were used to confirm the presence of a tau gene on chromosome 17q21 and an additional region of homology on chromosome 6p21.

Chromosome Mapping↗
PubMed1986

GDP activates rabbit heart adenylate cyclase, but does not support stimulation by isoproterenol: a re-appraisal of the control mechanism.

The effect of GDP on rabbit heart adenylate cyclase has been determined under conditions where only 0.08% to 0.26% of an added 100 microM was converted to GTP in the course of the assay. At concentrations of 100 microM, GDP stimulated basal cyclase activity to the same extent as GTP and guanosine-5'-O-(2-thiodiphosphate) (GDP beta S). Isoproterenol increased activity in the presence of GTP or guanylyl-imidodiphosphate (Gpp(NH)p), but not in the presence of GDP or GDP beta S. It is suggested that the hydrolysis of GTP to GDP is the "turn-off" mechanism for beta-receptor stimulation of cardiac adenylate cyclase, but not for stimulation by GTP alone. The effects of GDP and GDP beta S are readily removed by washing, implying that their binding to Ns (the guanine nucleotide binding protein) is weak. GDP beta S initially competes with Gpp(NH)p, reducing Gpp(NH)p-stimulated activity. As stimulation of cyclase activity by Gpp(NH)p develops, in the course of 30 min, Gpp(NH)p becomes no longer displaceable by GDP beta S. Isoproterenol does not release 3H-Gpp(NH)p or reduce Gpp(NH)p-stimulated activity, once the nucleotide has become tightly bound. Nor does isoproterenol change the relative affinities of GDP beta S and Gpp(NH)p when these analogs are given together. There is, therefore, no evidence that isoproterenol acts by releasing tightly bound GDP from Ns, or that it 'unlocks' the guanine nucleotide binding site in the myocardial sarcolemma. In this, the cardiac adenylate cyclase system differs from the avian erythrocyte system. The action of isoproterenol is best explained by an increased dissociation of alpha(GTP) and beta,gamma-subunits of the Ns protein.

Adenylyl Cyclases↗
PubMed1986

Pluripoietin alpha: a second human hematopoietic colony-stimulating factor produced by the human bladder carcinoma cell line 5637.

We have identified a factor constitutively produced by the human bladder carcinoma cell line 5637, which has the following capacities: to induce the differentiation of the human promyelocytic leukemic cell line HL-60; to induce the expression of chemotactic peptide receptors in leukemic cells as well as in normal peripheral blood granulocytes; to function as a chemoattractant for neutrophils as well as, under certain conditions, inhibiting their migration; to support the growth of eosinophil and granulocyte/macrophage progenitors, which is maximal when scored at day 14; and to support the growth of human mixed pluripotent progenitors and erythroid bursts from normal human bone marrow. This factor has a molecular size of 32 kDa by gel filtration and 16.5 kDa by NaDodSO4/PAGE. We have termed this factor pluripoietin alpha.

Bone Marrow Cells↗
PubMed1986

The molecular actions of beta-agonists in the cardiac sarcolemma.

Although alpha-receptors are known to exist in the myocardium, the predominant effect of catecholamines on the force of contraction of the heart is mediated through beta-receptors. This review deals only with the latter, and is particularly concerned with the sarcolemmal molecular mechanisms by which beta-stimulation increases the rate of cyclic adenosine monophosphate (cAMP) production by adenylate cyclase.

Adenylyl Cyclases↗
PubMed1986

Pulmonary haemodynamics of the yak, cattle, and cross breeds at high altitude.

The pulmonary arterial pressure of Ladakhi yaks, at an altitude of about 4500m, was not significantly different from that found in yaks bred at low altitude. The pulmonary arterial resistance, however, was slightly but significantly increased in the high altitude group. It is concluded that the yak has adapted genetically to high altitude by largely eliminating the hypoxic pulmonary vasoconstrictor response. The pulmonary arterial pressure and resistance were significantly higher in indigenous Himalayan cattle than in the yaks. The dzo (cow X yak) had pulmonary haemodynamics similar to those of the yak. Half of the stols (dzo X bull) had pulmonary haemodynamics similar to those of the yak, while in the other half the findings resembled those in the cow. The results suggest that the genetic attenuation of the hypoxic vasoconstrictor response is transmitted as a simple autosomal dominant.

Altitude↗
PubMed1986

Determination of the DNA content of human chromosomes by flow cytometry.

The mean relative DNA content of each human chromosome was calculated from flow karyotypes of ethidium bromide-stained chromosomes obtained from healthy, normal individuals. These values were found to correlate closely with previously published data obtained by photometric scanning of stained, fixed chromosomes. Calculations of the normal variation in DNA content of each human chromosome indicated that chromosomes 1, 9, 16, and Y (chromosomes with large centric heterochromatic regions) were the most variable, followed by the acrocentrics, 13, 14, 15, 21, and 22. Chromosomes 2, 3, 18, and 19 were also found to vary significantly in DNA content. Chromosomes from a number of subjects with extreme heteromorphisms were flow karyotyped to obtain an estimate of the extent of variation in DNA content of each chromosome. The greatest difference between extreme variants was found for chromosome 1 (which differed by 0.82% of the total genomic DNA), followed by 16 and 9. The largest Y-chromosome variant was 85.9% bigger than the smallest. The precise karyotype analysis produced by flow cytometry resolved many differences between chromosome homologs, including some that cannot be readily distinguished cytogenetically. The implications of these findings for detection of chromosome abnormalities by flow karyotype analysis are discussed.

Chromosome Banding↗