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Biomedical subjects

M Paul

Publications and source records attributed to M Paul.

At least 343 records · Page 19Linked to original sources
PubMed1989

Ocular infections and the industrial use of microscopes.

A cluster of ocular infections occurred in one area of a computer fabrication facility that relied on the use of industrial microscopes. A questionnaire was administered to all employees in this area. Microscope oculars were cultured and compared with control microscopes from a nonindustrial setting. Risk of infection was correlated with the number of hours of microscope use per day and subjective indicators of cleanliness. Bacterial cultures confirmed increased colony counts in industrial oculars compared with control oculars. Hygienic practices were instituted similar to those employed in medical settings. No further outbreaks of conjunctivitis have been reported in a 1-year follow-up.

Conjunctivitis↗
PubMed1989

Role of molecular biology in hypertension research. State of the Art lecture.

In this article we will examine the potential impact of molecular biology on hypertension research. We will review the available molecular techniques, which include gene cloning, transient and stable expressions, as well as the use of transgenic animals. To facilitate our discussion, we will focus primarily on research of the renin gene. Renin provides a useful model that illustrates the power of biotechnology in providing detailed structural and biochemical information on a complex protein that exists in low quantities in vivo. Studies of its messenger RNA and gene expression have resulted in an improved understanding of the biology of the renin system and in generating new hypotheses. These approaches can be generalized to studies of other vasoactive hormones, contractile protein, and other gene products related to cardiovascular regulation. To elucidate the role of a specific gene in genetic hypertension, we will discuss the use of genetic markers in cosegregation or linkage analysis. Finally, we will examine the potential of transgenic animals in the study of regulation of gene expression in the whole animal and the contribution of selective genes to hypertension. We believe that molecular biology complements the biochemical and physiological approaches and provides new opportunities for furthering our concept of hypertension mechanisms.

Animals↗
PubMed1989

A lack of genetic linkage of renin gene restriction fragment length polymorphisms with human hypertension.

Because renin is an important enzyme in blood pressure regulation, we studied the possibility that an alteration in the structure of the human renin gene is genetically linked to human essential hypertension or associated with levels of plasma renin activity or blood pressure. By using specific DNA probes, we have identified four polymorphisms in the human renin gene with the restriction enzymes Taq I, HindIII, Bgl I, and Bgl II. The gene location of all of these polymorphisms except for the Bgl II polymorphism has been determined, and their frequencies were initially estimated in a population of 50 random subjects. To test the clinical significance of these polymorphisms, we studied 68 persons from a large Utah pedigree with a high incidence of hypertension. Among nine relatives with hypertension, genetic linkage without recombination was ruled out by observing several obligate recombinants. We also found no significant association of the restriction fragment length polymorphisms with quantitative measurements of sitting or standing, systolic or diastolic blood pressures, or plasma renin activity in 59 untreated members of this pedigree. Although we found no genetic linkage in this set of study subjects, the characterization of the restriction fragment length polymorphisms for the renin gene may be useful in future studies of other selected pedigrees for the presence of one or more of these to be a genetic marker in hypertension.

Gene Frequency↗
PubMed1989

Cerebrospinal fluid beta 2 microglobulin in patients infected with human immunodeficiency virus.

We prospectively evaluated CSF concentrations of beta 2 microglobulin (beta 2M) in 65 human immunodeficiency virus type 1 seropositive patients. The highest concentrations occurred in those with lymphoma, neurologic opportunistic infections, and acquired immune deficiency syndrome dementia complex (ADC). There was a high correlation between the CSF beta 2M concentration and ADC severity, suggesting that CSF beta 2M may be useful as a marker for the development, progression, and perhaps response to treatment of ADC. Elevated CSF beta 2M was not due to CSF pleocytosis and was usually independent of blood-brain barrier dysfunction.

Acquired Immunodeficiency Syndrome↗
PubMed1989

Dissociation of AIDS-related vacuolar myelopathy and productive HIV-1 infection of the spinal cord.

Although merging clinically within the spectrum of the AIDS dementia complex, vacuolar myelopathy is a pathologically distinct entity detected in up to 30% of autopsied patients succumbing to the late complications of human immunodeficiency virus type 1 (HIV-1) infection. Using immunohistochemistry and in situ hybridization to detect an HIV-1 core protein and viral mRNA, respectively, in tissue sections, and culture isolation to assess infectious virus in tissue homogenates, we found that vacuolar myelopathy was independent of productive HIV-1 infection of the spinal cord and brain. These results indicate that AIDS-associated vacuolar myelopathy is either not related directly to spinal cord HIV-1 infection or involves nonproductive infection and pathobiological processes distinct from those responsible for the multinucleated-cell inflammatory infiltrates that serve as histopathologic markers of productive CNS HIV-1 infection.

Acquired Immunodeficiency Syndrome↗
PubMed1989

Effect of potential antidotes on the acute toxicity, tissue disposition and elimination of selenium in rats.

Treatment of male Wistar rats with sodium selenate (2.24 mg Se/kg, s.c.) inhibited their body weight gain for 24 hr, after which the animals recovered. Intraperitoneal injections of sodium-2,3-dimercaptopropane-1-sulphonic acid (60 mg/kg), meso-2,3-dimercaptosuccinic acid (50.9 mg/kg) and calcium disodium ethylenediamine-tetraacetate (500 mg/kg) 15 min after Se had no protective effect, whilst 2,3-dimercaptopropanol (15 mg/kg) inhibited the recovery of the Se-treated animal. Sodium diethyldithiocarbamate (DDTC, 70 mg/kg, i.p.) reduced the Se-induced loss of body weight but had no effect on the tissue disposition of 75Se when injected 15 min, 3 hr or 6 hr after a s.c. injection of sodium [75Se] selenite (50 microCi, 17.4 micrograms Se/kg). The citrate salts of bismuth (2.5 and 5 mg Bi/kg, s.c.), antimony (1.5 and 3 mg Sb/kg, s.c.) and germanium (40 mg Ge/kg, s.c.) also reduced the selenate-induced loss of body weight, whilst germanium citrate (40 mg Ge/kg) and bis-carboxyethyl germanium sesquioxide (80, 200 and 400 mg Ge/kg) promoted significant dose-related increases in the 24 hr urinary excretion of 75Se when given 15 min after sodium [75Se] selenite (30 microCi, 0.5 mg Se/kg, s.c.).

Animals↗
PubMed1989

Cellularity of bone marrow--a comparison of trephine biopsies and aspirate smears.

The estimation of cellularity of bone marrow was done on 212 trephine biopsies and their corresponding aspirate smears by a single observer using the visual scanning method. On applying the statistical test of agreement, it was found that the trephine biopsies and the aspirate smears were equally reliable in assessing marrow cellularity.

Biopsy, Needle↗
PubMed1988

Different secretory pathways of renin from mouse cells transfected with the human renin gene.

Mammalian cells in culture, transfected with human renin gene, can provide a useful tool for studying renin biosynthesis and secretion. We transfected fibroblast cells (mouse L929 and Chinese hamster ovary cells) and pituitary tumor cells (mouse AtT-20) with the human renin gene and a selectable plasmid (pSV2Neo). Transfected fibroblasts synthesize prorenin only. Prorenin is secreted by fibroblasts constitutively and the secretion is not influenced by 8-bromo-cAMP. On the other hand, transfected AtT-20 cells synthesized both prorenin and mature active renin. Transfected AtT-20 cells release prorenin by constitutive secretion but mature renin is secreted by a regulated mechanism since the secretion of the former is not influenced by 8-bromo-cAMP but the release of the latter is significantly stimulated. Our studies demonstrate that human renin may be secreted by at least two cellular pathways: prorenin by a constitutive pathway and mature renin by a regulated pathway. These transfected cells may provide useful models for studies of human renin synthesis, processing, and secretion.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1988

Mapping of the human renin transcription start site: evidence for a single functional promoter.

The 5' flanking region of the human renin gene contains two putative promoter sequences (TATA boxes), named P1 and P2. These are located in positions -77 to -71 and -29 to -23 respectively, each followed by a possible translational start site (AUG). In order to identify whether these sequences are functional in the kidney, we employed the RNAse protection assay. Total RNA extracted from human kidney cortex was hybridized with labeled cRNA probes complementary to the 5' flanking region of the human renin gene. After digestion with RNAse, protected hybrids were identified by electrophoresis on polyacrylamide/urea gels and autoradiography. Results showed that only P2 is active in human kidney resulting in a single transcript. This suggests that human kidney renin is synthesized as a single preproform.

Humans↗
PubMed1988

Quantification of renin mRNA in various mouse tissues by a novel solution hybridization assay.

A new solution hybridization assay was established for the measurement of renin mRNA. The assay makes use of a radioactively labelled renin complementary RNA as hybridization probe and allows rapid and sensitive detection of renin mRNA in amounts as low as 0.5 pg. With this assay it was possible to quantify renin mRNA in tissues with low-gene expression such as brain and heart as well as in testis, kidney and the submandibular gland (SMG) of mice. The concentrations in these organs were 0.03, 0.07, 1, 5.2 and 164 pg renin mRNA/micrograms RNA, respectively. These results are in agreement with Northern blotting experiments. The general applicability and ease of the solution hybridization assay described here should greatly improve the rapidity of mRNA measurements in future functional studies.

Animals↗
PubMed1988

Glycosylation influences intracellular transit time and secretion rate of human prorenin in transfected cells.

The mouse pituitary tumour (AtT-20) cell transfected with the human renin gene has been shown to be a useful model system to study human renin biosynthesis. To investigate the influence of glycosylation on secretion of human renin from these cells, we performed pulse labelling experiments on transfected cells in the presence or absence of tunicamycin, a potent inhibitor of n-linked glycosylation. Intracellular and secreted renins were characterized by immunoprecipitation, sodium dodecyl sulphate (SDS) gel electrophoresis and fluorography. Our data showed that blockade of n-linked glycosylation reduced the intracellular transit time and increased the rate of prorenin secretion from transfected cells. We conclude that the carbohydrate moiety influences the kinetics of human renin secretion. This result provides one possible explanation for the observation that the secretion of glycosylated human renin is considerably slower than that of the unglycosylated mouse renin-2.

Cell Line↗
PubMed1988

Renin gene expression in rat tissues: a new quantitative assay method for rat renin mRNA using synthetic cRNA.

A genomic renin exon 9 fragment was subcloned into vector pSPT18 and used for in vitro transcription to obtain 32P-labeled rat renin cRNA. Using this cRNA, we established quantitative solution hybridization and specific Northern blotting assays for renin mRNA. We were able to detect renin mRNA in the kidney, heart ventricle and atrium, brain, testis, and adrenal gland of male rats in the concentrations of 430 +/- 8.1, 110 +/- 1.9, 43 +/- 0.9, 64 +/- 1.1, 47 +/- 0.9 and 11 +/- 0.2 pg mRNA/mg of total RNA, respectively.

Animals↗
PubMed1988

Reproductive hazards in the workplace: what the practitioner needs to know about chemical exposures.

A growing body of scientific evidence implicates occupational chemical exposures in the etiology of human adverse reproductive outcomes. Most reproductive toxins that have been investigated in sufficient detail have been shown to exert multiple effects on and through both men and women. In the face of growing public awareness, it is essential that clinicians develop a knowledgeable and effective approach to patient concerns about reproductive hazards in the workplace. Of vital importance is the accurate characterization of exposure at the worksite. Intervention strategies for worrisome situations include amelioration of worksite exposure or, as a last resort, temporary, compensated job modification or transfer. The clinician can obtain assistance in addressing the problem from several resources, including local regulatory agencies and occupational health clinics. Widespread involvement of knowledgeable health professionals can have a dramatic impact on improving this important contemporary public health problem.

Abnormalities, Drug-Induced↗
PubMed1987

The measurement of ethylenethiourea and ethyleneurea in the rat and common marmoset Callithrix jacchus after zineb (zinc ethylenebisdithiocarbamate) dosing.

The metabolism of the fungicide zineb, (zinc ethylenebisdithiocarbamate), has been studied in the rat and the marmoset. 2. It was found in both species that a relatively large proportion (21-22%) of the original zineb administered was detectable in the excreta as ethylenethiourea (ETU) a known mutagen, teratogen and carcinogen. 3. A further proportion (2-5%) was determined to be ethyleneurea which is a metabolite of ETU. 4. Results of comparative experiments in marmosets revealed that ETU was photolabile in the presence of excreta, thus showing the importance of conducting the studies in the dark.

Animals↗