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Biomedical subjects

C Harris

Publications and source records attributed to C Harris.

At least 199 records · Page 11Linked to original sources
PubMed1987

What are health authorities doing about the health problems caused by unemployment?

Unemployment is over three million in Britain, and unemployment is known to be associated with poor health. It has been suggested that health authorities should produce a comprehensive response to the health problems caused by unemployment, and a survey was undertaken to find how many had done so. All the regional and district health authorities in England, the health boards of Wales, Scotland, and Northern Ireland, and the family practitioner committees of England and Wales were asked by letter what they were doing to respond to the health problems of unemployment. A list of suggestions of what they might be doing was enclosed. The overall response rate was 77% (255/331), and 50% (127/255) of the respondents were doing something--33.3% (3/9) of the regional health authorities, 64% (101/158) of the district health authorities and health boards, and 26% (23/88) of the family practitioner committees. The paper describes what they were doing. A relation was sought between the level of unemployment in an area and the extent of the response, and a significant association was found. Half of Britain's health authorities are now responding in some way to the health problems associated with unemployment.

Humans↗
PubMed1987

Regulation of intracellular glutathione in rat embryos and visceral yolk sacs and its effect on 2-nitrosofluorene-induced malformations in the whole embryo culture system.

The dysmorphogenic effects of 2-nitrosofluorene (NF) in vitro were modulated in Day 10 rat embryos by agents which regulate intracellular glutathione (GSH) levels. The incidence of abnormal axial rotation caused by NF alone increased in a dose-dependent manner at NF concentrations in excess of 25 microM. No effects were observed at 15 microM NF and doses of 100 microM resulted in a 100% incidence of mortality. L-Buthionine-S,R-sulfoximine (BSO), an inhibitor of GSH synthesis, produced malformations (50%) in embryos exposed to 15 microM NF but produced no additional effects on embryos at higher NF concentrations. BSO treatment alone resulted in a greater than 50% decrease in GSH content in visceral yolk sacs and had a lesser but likewise significant effect (15% decrease) on the GSH content of embryos. Protein content was inversely affected as embryonic levels were increased by 20% and yolk sac levels were unchanged. When BSO was added in combination with NF at the onset of the culture period, embryonic GSH decreased in a dose-dependent manner, suggesting a relatively low rate of embryonic GSH turnover that could be increased by addition of an exogenous substrate capable of forming adducts with and removing GSH from the cells. 2-Oxothiazolidine-4-carboxylate (OTC), a compound which is enzymatically modified to provide an additional source of intracellular cysteine and increase GSH synthesis, produced no significant changes in embryonic or yolk sac GSH when added alone to the culture medium. When OTC (5 mM) was added in combination with NF, however, NF-elicited malformations were eliminated. This was also the case at 100 microM NF in which OTC not only prevented malformations but completely protected embryos against the loss in viability. The GSH and protein levels were indistinguishable from controls when OTC and NF were added simultaneously except for the 41 microM NF dose at which a highly significant increase in both embryonic and yolk sac protein was observed. This study clearly demonstrates the potential importance of GSH in the modulation of chemical dysmorphogenesis and provides an important new tool for the study of mechanisms of developmental toxicity.

Abnormalities, Drug-Induced↗
PubMed1987

Thermal cataract formation in rabbits.

Intraocularly circulating hot water was used to produce cataracts in nine eyes of seven rabbits by maintaining their retrolental temperatures between 43 degrees C and 45 degrees C. A rapid rate of heating (1.3 degrees C/min) plus a sharp temperature gradient across the eye may have been contributing factors in the consistent production of cataracts at these temperatures. Biomicroscopy and light microscopy showed lens changes similar to those associated with acute exposure to microwave radiation. These findings support the assumption that microwave cataractogenesis is due to the local production of elevated temperatures.

Animals↗
PubMed1987

Platelet-derived growth factor-induced alterations in vinculin distribution in porcine vascular smooth muscle cells.

Exposure of porcine vascular smooth muscle cells to platelet-derived growth factor (PDGF; 18-180 ng/ml) but not epidermal growth factor (EGF; 30 ng/ml), somatomedin C (SmC; 30 ng/ml), or insulin (10 microM), results in a rapid, reversible, time- and concentration-dependent disappearance of vinculin staining in adhesion plaques; actin-containing stress fibers also become disrupted following exposure of cells to PDGF. Disappearance of vinculin staining from adhesion plaques is also caused by 12-O-tetradecanoyl-phorbol-13-acetate (TPA; 200-400 nM), though the time course of the disappearance of vinculin staining under these conditions takes longer than in cells exposed to PDGF. The PDGF-induced removal of vinculin from adhesion plaques was inhibited in a concentration-dependent fashion by 8-(N,N-diethylamino) octyl-3,4,5-trimethoxybenzoate (TMB-8; 0.25-4 microM) and leupepetin (2-300 microM), and by n-alpha-tosyl-L-lysine chloromethylketone (TLCK; 100 microM) and trifluoperazine (TFP; 2.5 microM). Addition of PDGF to vascular smooth muscle cells caused a rapid, transient increase in cytosolic free calcium, from a basal resting level of 146 +/- 6.9 nM (SEM, n = 62) to 414 +/- 34 nM (SEM, n = 22) as determined using the calcium-sensitive indicator Fura-2 and Digitized Video Microscopy. This increase in cellular calcium preceded the disappearance of vinculin from adhesion plaques and was partially blocked by pretreatment of cells with TMB-8 but not leupeptin. This rise in cytosolic free calcium was found to occur in approximately 80% of the sample population and displayed both spatial and temporal subcellular heterogeneity. Exposure of cells to TPA (100 nM) did not result in a change in cytosolic free calcium. Both PDGF (20 ng/ml) and TPA (100 nM) caused cytosolic alkalinization which occurred after PDGF-induced disruption of vinculin from adhesion plaques, as determined using the pH-sensitive indicator BCECF and Digitized Video Microscopy. PDGF stimulated DNA synthesis and vinculin disruption in a similar dose-dependent fashion. Both could be inhibited by leupeptin or TMB-8. These results suggest that 1) exposure of vascular smooth muscle cells to PDGF is associated with the disruption of vinculin from adhesion plaques, 2) PDGF-induced vinculin disruption is regulated by an increase in cytosolic calcium (but not cytosolic alkalinization), and involves proteolysis; 3) activation of protein kinase C also causes vinculin removal from adhesion plaques but by a calcium-independent mechanism, and 4) the cellular response to PDGF-stimulated increases in cytosolic free calcium is heterogeneous.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1987

Is yohimbine effective in the treatment of organic impotence? Results of a controlled trial.

Yohimbine is an alpha-adrenoceptor blocker that has been used in the treatment of erectile dysfunction. Adequate trials of this substance in a clearly defined organically impotent population are not available. We conducted a randomized, controlled study with partial cross-over of yohimbine versus placebo in 100 organically impotent men. The first phase of the study showed a positive response in 42.6 per cent of the patients receiving yohimbine versus 27.6 per cent in the placebo group. Although favorable to the test medication these values did not reach statistical significance (p equals 0.42). A similar pattern was noted in the second phase of the study. The over-all response rate of 43.5 per cent was consistent with a previous noncontrolled trial but it was much lower than previous studies. The response rate of organically impotent patients to yohimbine is at best marginal. Owing to its ease of administration, safety and modest effect it still is used in those patients who do not accept more invasive methods. Adrenoceptors are involved in the erectile process, although other neurotransmitter systems also are putative modulators of penile erection, including cholinergic, dopaminergic and vasoactive intestinal polypeptide pathways. It is beyond reasonable expectation that a single agent be of value for all cases of organic impotence. However, yohimbine has shown modest effectiveness at the doses used in this trial (18 mg. per day). Higher doses or a different route of administration may produce different effects.

Clinical Trials as Topic↗
PubMed1987

Evaluation of isradipine (PN 200-110) in mild to moderate hypertension.

The efficacy and safety of isradipine (PN 200-110), a new dihydropyridine calcium antagonist, was evaluated in 87 hypertensive patients in a placebo-controlled, double-blind, randomized multicenter trial. After a 3-week single-blind washout phase, isradipine (or matching placebo) was administered for 4 weeks, beginning at 2.5 mg b.i.d. with increments of 2.5 mg b.i.d. at weekly intervals if supine diastolic blood pressure remained greater than or equal to 90 mm Hg. At the end of 1 week average supine blood pressure in the isradipine group (n = 45) fell from a baseline of 156 +/- 13/104 +/- 4 mm Hg to 146 +/- 14/97 +/- 7 mm Hg. By week 4 blood pressure was reduced by 19/14 mm Hg compared with 4/5 mm Hg in the placebo group (P less than 0.001 between groups). Supine and standing pulse rates were slightly increased initially with isradipine therapy but returned to baseline with increasing isradipine doses. Blood pressure responses at week 4 were good or excellent (supine diastolic less than or equal to 90 mm Hg or greater than or equal to 10 mm Hg decrease from baseline) in 87% of isradipine-treated patients and in 26% of placebo-treated patients. Headache, edema, abdominal discomfort, and constipation occurred slightly more frequently in isradipine-treated patients than in placebo-treated control subjects. The results indicate that isradipine, administered as monotherapy in doses of 2.5 to 10 mg b.i.d., is safe and effective in patients with mild to moderate essential hypertension.

Adult↗
PubMed1987

Stereoselectivity of cytosolic glutathione S-transferases with arene and alkene oxide substrates in various tissues and isolated hepatic and pulmonary cells of the rabbit.

The specific activity and stereoselectivity of cytosolic glutathione S-transferases (GST) from various rabbit tissues and isolated cells were determined as an initial step in characterizing GST isoenzymes in the rabbit. Of the five tissues examined, liver cytosol had the highest specific GST activity with the polycyclic arene oxides (+/-)-benzo[a]pyrene 4,5-oxide (BPO), pyrene 4,5-oxide (PO) and (+/-)-benz[a]-anthracene 5,6-oxide (BAO), and kidney cytosol had the second highest. Lung, intestine and testis had relatively low activities with all three substrates. With the alkene oxide (+/-)-styrene 7,8-oxide (SO), testicular cytosol had the highest GST activity while liver cytosol had only half the activity of the testis. Cytosolic GST from liver and kidney were highly stereoselective for reaction of glutathione with the S-configured oxirane carbon atoms of BPO, PO and BAO, and all tissues but the intestine were enantioselective for (4R,5S)-BPO and (5S,6R)-BAO. With SO, the liver, kidney and testis preferentially catalyzed the reaction of glutathione with the benzylic carbon atom of (7S)-SO. There was virtually no enantioselectivity in lung cytosol with SO but a preference for reaction with (7R)-SO was noted in the intestine. The stereoselectivities found in the intestine with each of the four substrates were markedly different from the other tissues. Cytosol from isolated hepatocytes showed almost identical patterns of stereoselectivity with BPO and PO to those of whole liver cytosol. Similarly, the stereoselectivity of cytosol prepared from alveolar type II cells isolated from rabbit lung was the same as that of whole lung cytosol with these substrates, whereas cytosol of alveolar macrophages differed substantially from lung cytosol in both cases. There were marked differences in stereoselectivity of cytosol from freshly isolated Clara cells with BPO versus PO as substrate. With BPO, Clara cells were very similar to whole lung cytosol, but with PO they were not. The data are consistent with the differential tissue and cellular distribution of multiple GST isoenzymes in the rabbit.

Animals↗
PubMed1987

Serologic, immunologic, and clinical features of parenteral drug users from contrasting populations.

We screened inpatient and outpatient parenteral drug users with no clinical evidence of AIDS for immunodeficiency and antibodies to HTLV-III by ELISA. Among 20 outpatient drug users, 5 (25%) were seropositive. Three of these (and 2 who were seronegative) had low T-cell ratios. Over 6 months, 1 seropositive patient with a low ratio developed oral thrush and weight loss. We also studied 13 parenteral drug users hospitalized for conditions other than AIDS. Eight had low T-cell ratios, and at least 6 of these developed AIDS or ARC within 4 months. Serum from 8 of 13 inpatients was available for HTLV-III testing: 6/8 were seropositive and 3 of these 6 were among those developing AIDS or ARC. Abnormal T-cell ratios among all patients were associated with abnormal HTLV-III serology (p = .02). Of the 7 patients who developed AIDS or ARC, 4 were tested for both antibodies and T-cell ratios: all 4 were seropositive and had low ratios. A low ratio (p = .0004), a positive ELISA (p = .014), and abnormalities of both tests (p = .001) were associated with the development of AIDS or ARC. Of the 26 patients without AIDS or ARC, 3 were lost to follow-up and 23 did not develop AIDS or ARC. Six of these 26 had abnormal ratios. Of the 21 patients who did not develop AIDS or ARC and who were tested for HTLV antibodies, 2 were lost to follow-up. Seven of 21 were seropositive and 2/21 were both seropositive and had a low ratio. One of these 2 seropositive patients with low ratios also had lymphadenopathy, but he was lost to follow-up. The other had no adenopathy and remained well until her death from trauma a year later. This study found two populations with very different risks. Six of 13 hospitalized parenteral drug users and only 1 of 20 healthy outpatients developed AIDS or ARC.

Acquired Immunodeficiency Syndrome↗
PubMed1987

Medical records.

Explore the source record for details and available documents.

Medical Records↗
PubMed1986

Differential glutathione depletion by L-buthionine-S,R-sulfoximine in rat embryo versus visceral yolk sac in vivo and in vitro.

L-Buthionine-S,R-sulfoximine (L-BSO), a selective inhibitor of glutathione synthesis, exhibited the capacity to deplete embryonic and visceral yolk sac glutathione (GSH) after administration in vivo and also after addition of L-BSO to a whole embryo culture system. Administration of L-BSO to pregnant dams at 2.5 or 18 hr prior to the explantation of day 10 conceptuses resulted in greater than 55% GSH depletion relative to control values in both the yolk sac and the embryo proper. The levels of GSH returned to normal in all embryos and in the corresponding visceral yolk sacs pretreated at 2.5 hr (but not at 18 hr) after culturing for 24 hr in L-BSO-free medium. GSH content was significantly lower in yolk sacs but not in embryos of conceptuses cultured for 24 hr in medium containing 1 mM L-BSO. This treatment, however, significantly increased the amount of protein and DNA in the embryo. The differential sensitivity of the yolk sac versus embryo and the demonstration of the ability to modulate tissue levels of GSH during organogenesis promise to provide important new tools for the study of embryonic protective mechanisms in chemical teratogenesis.

Animals↗
PubMed1986

Effect of wedging on the flow characteristics past tilting disc aortic valve prosthesis.

To evaluate the efficacy of implanting a tilting disc aortic valve prosthesis in an angulated (wedged) supra-annular position, an in vitro experimental study was performed. The aortic valve prosthesis was mounted in an axi-symmetric valve chamber in a wedged position and incorporated in a mock circulatory system. Measurements were obtained on the transvalvular pressure gradient, percent regurgitation as well as velocity profiles and turbulent normal stresses distal to the valve. Our results showed that there was no significant reduction in the pressure gradient in mounting a larger sized valve in the wedged supra-annular position. On the other hand, the percent regurgitation increased with increase in heart rate and wedge angle. The valve failed to function properly above 110 beats min-1 at any wedge angle with the normal flow rate. The velocity profiles also showed significant changes with an increase in the turbulent normal stress with increase in wedge angle. Hence our study suggests that implanting the tilting disc prosthesis in a wedged supra-annular position in the aorta is not advisable.

Aortic Valve↗
PubMed1986

Evidence for kinetic heterogeneity among human low density lipoproteins.

The kinetics of low density lipoprotein apolipoprotein B (LDL apo B) metabolism are usually determined using turnover techniques in which radioiodinated LDL apo B is injected as a bolus into plasma, and serial plasma and urinary radioactivity samples are taken. The metabolic parameter of interest usually estimated from such data is the fractional catabolic rate (FCR). Two methods are normally employed to obtain an estimate of the FCR. One, the so-called Matthews' analysis, assumes plasma LDL apo B metabolism can be described by a single plasma pool while the other is determined by calculating the ratio of urinary radioactivity excreted to mean plasma radioactivity per day. Both of these methods assume LDL apo B is kinetically homogeneous, thus ignoring the evidence that LDL is biochemically heterogeneous in some individuals. If this biochemical heterogeneity manifests itself as kinetic heterogeneity, then the use of these data to estimate the FCR will not permit the resolution of the finer details of potential metabolic defects. This paper addresses the question of kinetic homogeneity and heterogeneity of LDL apo B within the context of several integrated kinetic models of increasing complexity. Each model fits reasonably the turnover data and hence cannot be rejected on the basis of failure to be compatible with the data. However, the models have strikingly different physiologic interpretations while providing essentially the same estimate for the FCR. Thus LDL apo B metabolism appears to be more complex than originally believed, and the models provide a framework within which to design new experiments to distinguish among them.

Adult↗
PubMed1986

Distribution of 15- and 137-mu diameter microspheres in the dog lung in the axial plane.

Oleic acid infusion, as a model of fat embolism, produces a predominantly peripheral lesion in the dog lung. The lung injury corresponds to the peripheral distribution of labeled oleic acid. The basis for this distribution of oleic acid is not known. Our hypothesis for this nonuniform distribution is that particle diameter plays a role in the subsequent distribution of infused oleic acid and the resulting lung injury. We injected 15-mu microspheres 85Sr and then 137-mu microspheres (141Ce) into the right atria of seven dogs, which were killed and the lungs removed. Analysis of the distribution of the two different diameter microspheres within axial slices from the left caudal lobe of each dog revealed a peripheral distribution of the larger diameter microspheres not seen with the smaller microspheres.

Animals↗
PubMed1986

Mechanism of action of gonadotropin releasing hormone.

GnRH interacts with a plasma membrane receptor to provoke gonadotropin release, as well as regulate numbers of its own receptor and target cell responsiveness. Receptor numbers are altered in different physiological states of the animal. Microaggregation of the GnRH receptor mimics all known actions of the releasing hormone, and therefore is viewed as an early step in the molecular mechanism of hormone action. Internalized hormone is neither necessary nor sufficient for stimulation of known releasing hormone actions. Evidence summarized in the present work suggests that Ca2+ serves a role as a second messenger for GnRH-stimulated gonadotropin release, and that it may be involved in receptor up-regulation in response to the releasing hormone. In the former role, diacylglycerols by their action on protein kinase C, in a fashion independent of the Ca2+ -calmodulin system, may act as a signal amplifier.

Animals↗
PubMed1986

Programming for special groups through closed-circuit television.

At Winnipeg's Children's Hospital Television (CHTV), there was concern that the closed-circuit alternative television station was not realizing its full potential in helping to meet the special needs of the adolescent and native Canadian patients. Consequently, CHTV hired workers to produce programming targeted at these two groups. This article documents the underlying philosophy and structure of this programming. It also discusses how other children's health care institutions might adapt this kind of programming to suit their own groups with special needs.

Adolescent↗
PubMed1986

The potential role of redox cycling as a mechanism for chemical teratogenesis.

A survey of the literature indicates that several chemicals whose reduced metabolites are capable of undergoing redox cycling in biological systems also possess significant teratogenic properties when tested in vivo. We have initiated investigations to determine whether the embryotoxic effects of such chemicals could result from their redox cycling properties and whether redox cycling could be an important mechanism in chemical teratogenesis. In order to obviate the potentially confounding influences of maternal factors, our initial studies have been performed with a whole embryo culture system with redox cycling agents added directly to the culture medium. Several representative redox cycling agents including doxorubicin, paraquat, a series of nitroheterocycles, nitrosofluorene, and diethylstilbestrol (converted metabolically to redox cycling quinone/semiquinone radicals) have been investigated thus far. The nitroheterocycles which bear nitro groups with comparatively high redox potentials produced a striking, asymmetric defect involving primarily the right half of the prosencephalic and mesencephalic regions. The effect was exacerbated under conditions of low O2 tension. Accumulated data to date strongly suggest that reduction of the nitro group is an essential feature in the embryotoxic mechanism. Quinones (doxorubicin, paraquat) and compounds metabolically converted to quinones (diethylstilbestrol) appeared to produce embryotoxic effects via mechanisms not associated with redox cycling. Nitrosofluorene embryotoxicity was markedly exacerbated by changes in both intra- and extracellular glutathione levels, but definitive dependence on a radical-mediated effect or redox cycling was not demonstrated.

Abnormalities, Drug-Induced↗