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Biomedical subjects

M Paul

Publications and source records attributed to M Paul.

At least 289 records · Page 16Linked to original sources
PubMed1994

Shigellosis in Calcutta during 1990-1992: antibiotic susceptibility pattern and clinical features.

Of 230 cases of bloody diarrhoea studied, 100 (43.5%) were positive for Shigellae by stool culture, of which Shigella dysenteriae type 1 was isolated from 56 cases, S. flexneri from 35, S. boydii from 5 and S. sonnei from 4. The major clinical manifestations of the patients infected with Shigella spp. were abdominal pain, anorexia, vomiting, tenesmus, and fever. Fever of above 100.5 degrees F and frequency of stool of more than 15 per day were noticed more among cases infected with S. dysenteriae type 1 and S. flexneri. Vomiting was more frequently observed in cases infected with S. sonnei or S. boydii (44.4%) as compared to those infected with S. dysenteriae type 1 (10.7%) and S. flexneri (8.6%). All Shigella isolates were uniformly susceptible to norfloxacin and ciprofloxacin but were resistant to streptomycin. S. dysenteriae type 1 isolates were susceptible to nalidixic acid (69.6%), ampicillin (5.4%), TMP-SMX (12.5%), furazolidone (98.2%) and gentamycin (80.4%), whereas all other Shigella isolates (S. flexneri, S. boydii, and S. sonnei) were uniformly susceptible to nalidixic acid, > 94% susceptible to furazolidone, and only moderately susceptible to ampicillin (28.6% to 55.5%) and TMP-SMX (22.2% to 48.6%).

Adult↗
PubMed1994

[Diagnostic value of specific Giardia fecal antigen tests].

Two commercial faecal antigen tests, based on Giardia specific antigens, were compared with traditional microscopical examination of faeces in 40 clinical patients, including 14 patients with a confirmed Giardia infection as well as in a survey among 96 children in four day care centers. The results obtained with these faecal antigen tests were not much better than by using traditional microscopy by a well trained parasitologist. Specific Giardia antigen (GSA 65) has been still detected in faeces up to day 4th after treatment of giardiasis, when microscopical examination of faeces was already for a few days negative. The Giardia antigen detection test was not very useful in examining the unconcentrated duodenal content.

Adolescent↗
PubMed1993

Relationship between environmental tobacco smoke exposure and carcinogen-hemoglobin adduct levels in nonsmokers.

BACKGROUND: A potent bladder carcinogen for workers in the dye industry, 4-aminobiphenyl (4-ABP), is present in environmental tobacco smoke and has been shown to bond covalently with hemoglobin. PURPOSE: The goal of this study was to examine the relationship between exposure to environmental tobacco smoke and levels of 4-ABP-hemoglobin adducts in nonsmoking pregnant women and to compare adduct levels in those women with levels in smoking pregnant women. METHODS: A questionnaire on smoking and exposure to environmental tobacco smoke was administered to 15 pregnant women who smoked cigarettes and 40 who did not smoke. Exposure was quantified for 1 week with a personal diary and by air sampling with a monitor worn by each woman. The monitor collected nicotine by passive diffusion to a filter treated with sodium bisulfate, and the deposit on the filter was analyzed by gas chromatography. Aliquots of maternal blood and cord blood collected during delivery were analyzed for 4-ABP-hemoglobin adducts by gas chromatography with negative ion chemical ionization mass spectrometry. RESULTS: The mean adduct level in smokers (184 pg of 4-ABP per gram of hemoglobin) was substantially higher than that in nonsmokers (22 pg/g). This difference was statistically significant. Among nonsmokers, the levels of 4-ABP adducts increased significantly with increasing environmental tobacco smoke level (P = .009). Those in the lowest exposure category (< 0.5 micrograms/m3 weekly average nicotine) had median 4-ABP-hemoglobin adduct levels of 15 pg of 4-ABP per gram of hemoglobin, while those in the highest exposure category (> or = 2.0 micrograms/m3) had median levels of 26 pg/g. Nonsmokers in this study had a median adduct level of 20 pg/g, and smokers had a median level of 143 pg/g. CONCLUSIONS: 4-ABP-hemoglobin adduct levels in nonsmokers were 14% of the levels in smokers, which is consistent with findings of 20% in two other studies. Nonsmokers may receive a nontrivial dose of carcinogens from environmental tobacco smoke proportional to their exposure to environmental tobacco smoke. IMPLICATION: The relationship between environmental tobacco smoke exposure and 4-ABP-hemoglobin adduct levels supports epidemiologic evidence that environmental tobacco smoke is carcinogenic to passive smokers.

Aminobiphenyl Compounds↗
PubMed1993

[In vitro study of leishmanicidal agents with drug carriers].

Antileishmanial chemotherapy is hampered by the location of parasites within lysosomal vacuoles of the macrophages which restricts the bioavailability of many potential antileishmanial compounds. In this study, the effectiveness of pentamidine targeted to the infected cells by a linkage to a colloidal drug carrier, methacrylate polymer nanoparticles was explored. In the same way, polyisoalkylcyanoacrylate nanospheres which have, in vitro, trypanolytic properties were also tested. The study was performed in an in vitro model using Leishmania major amastigote stages within the U 937 human monohistiocytic cell line. The antileishmanial activities of unloaded or pentamidine-loaded nanoparticles were compared to those of the free drugs. The 50% effective concentration of targeted pentamidine was 0.10 microgram/ml, while it was up to 2.7 micrograms/ml with the free drug after a 24-hour incubation time. The pentamidine-bound nanoparticles proved to be 25 times more active than the free drug. Unloaded polyisoalkylcyanoacrylate nanoparticles destroyed intracellular amastigote stages (50% EC = 15 micrograms/ml) but at a level close to the cytotoxic concentration.

Cell Line↗
PubMed1993

Human immunodeficiency virus type 1 RNA detection in peripheral blood mononuclear cells by polymerase chain reaction: enhanced sensitivity after mitogenic stimulation.

The aim of this study was to investigate whether stimulus-induced up-regulation of human immunodeficiency virus type 1 (HIV-1) expression in peripheral blood mononuclear cells (PBMC) could enhance the diagnostic sensitivity of the polymerase chain reaction (PCR). PBMC derived from 11 HIV-1-infected asymptomatic adults were cultured with a stimulus of phytohemagglutinin (PHA) plus phorbol 12-myristate 13-acetate (PMA) for 36 h prior to lysing the cells for PCR. In all 11 patients studied, the intensity of PCR-assisted HIV RNA amplification (RNA-PCR) performed on stimulated cells was significantly (p < 0.001) higher than that obtained on unstimulated cells. A comparison of conventional PCR-assisted DNA amplification (DNA-PCR) with that of RNA-PCR was made on seven patients. The sensitivity of DNA-PCR was also increased by prior stimulation of cells, although not to the same extent as was observed for RNA-PCR. The results of our study indicate that the sensitivity of PCR can be significantly enhanced by prior activation of cells with PHA and PMA.

Adult↗
PubMed1993

Gene expression of cardiac beta 1-adrenergic receptors during the development of hypertension in spontaneously hypertensive rats.

OBJECTIVE: To study adrenergic receptors in the heart tissues of genetically hypertensive rats by evaluating the gene expression and the membrane protein density of beta 1-adrenergic receptors using steady-state messenger RNA (mRNA) levels and a radioligand binding assay, respectively. DESIGN: We compared prehypertensive (5-week-old) and early-hypertensive (13-week-old) spontaneously hypertensive rats (SHR) with age-matched Wistar-Kyoto (WKY) normotensive control rats. METHODS: Polyadenylated RNA was extracted from individual hearts and analysed by the slot-blot technique using a beta 1-adrenergic receptor complementary DNA probe. beta-Adrenergic receptors in myocardial membranes were studied by radioligand binding assay using [125I]-cyanopindolol and the beta 1- and beta 2-selective antagonists CGP 207.12A and ICI 118.551, respectively. RESULTS: beta 1-Adrenergic receptor mRNA levels were slightly higher, and membrane protein density was similar in prehypertensive SHR and age-matched WKY rats. However, both beta 1-adrenergic receptor mRNA levels and beta 1-adrenergic receptor density were lower in the hypertensive SHR than in the control rats. beta 1-Adrenergic receptor mRNA was significantly reduced in older rats of both strains, and this reduction was most evident in the SHR. CONCLUSIONS: The absence of downregulation of beta 1-adrenergic receptors in young SHR, despite published data indicating a higher cardiac noradrenaline turnover than in WKY rats, may suggest that the cardiac hyperadrenergic activity observed in prehypertensive SHR is maintained, at least in part, by the participation of peripheral, postsynaptic component(s) involving beta 1-adrenergic receptor dysregulation. In addition, the present data suggest that the previously reported evidence of an age-related decrease in cardiac beta 1-adrenergic receptors in rats may be determined at the transcriptional level.

Animals↗
PubMed1993

Evidence for altered cell-cycle traverse of the non-modal cells of the heteroploid MCa-11 line.

Classic stem cell theory states that the growth of heteroploid cell populations is due to the proliferation of 'main stemline' cells with modal DNA content and chromosome number. Cells with non-modal DNA content and chromosome number are thought to be blocked and/or destroyed at mitosis. To test this, we studied two chromosomally stable cell populations (mouse bone marrow and WCHE-5 cells) and one heteroploid, chromosomally diverse cell line (MCa-11). The heteroploid MCa-11 cells showed significant [3H]dT labelling for cells with DNA contents below the modal G0/G1 peak and above the modal G2 peaks (P < 0.001). This was consistent with the presence of cells with the non-modal DNA content that were engaged in replicative DNA synthesis. A percentage labelled mitosis analysis showed that MCa-11 cells with non-modal DNA content and chromosome number were able to complete mitosis, although with prolonged pre-karyokinetic time. These results suggest that many non-modal cells present in heteroploid cell populations are capable of continued proliferation.

Aneuploidy↗
PubMed1993

Gap junction protein connexin40 is preferentially expressed in vascular endothelium and conductive bundles of rat myocardium and is increased under hypertensive conditions.

Gap junction channels consisting of connexin protein mediate electrical coupling between cardiac cells. Expression of two connexins, connexin40 (Cx40) and connexin43 (Cx43), has been studied in ventricular myocytes from normal and hypertensive rats. Polyclonal affinity-purified rabbit antibodies to Cx43 and Cx40 have been used for immunohistochemical analysis on frozen sections from rat heart. These studies revealed coexpression of Cx43 and Cx40 in ventricular myocytes. In addition, Cx40 is preferentially expressed in three distinct regions: first, in the endothelial layer of the heart blood vessels but not in the smooth muscle layer of the arteries; second, in the ventricular conductive myocardium, particularly in the atrioventricular bundle and bundle branches, where Cx43 is not observed; and third, in the myocyte layers close to the ventricular cavities. These results suggest that Cx40 is preferentially expressed in the fast conducting areas of myocardial tissue. Expression of both Cx40 and Cx43 was also found in immunoblots from normal and hypertensive rat myocardiocytes. Under hypertensive conditions (ie, in spontaneous hypertensive rats and in transgenic rats that exhibit hypertension due to expression of an exogenous renin gene), we found a 3.1-fold increase in Cx40 expression, compared with normal myocardium. Furthermore, we detected a 3.3-fold decrease in Cx43 protein level in transgenic hypertensive rats. The coexpression of Cx40 and Cx43 proteins in rat myocytes, their spatial distribution, and the increased amount of Cx40 protein during cardiac hypertrophy suggest that Cx40 may be involved in mediating fast conduction under normal and pathological conditions. The increased expression of Cx40 in hypertrophic heart may be a compensatory mechanism to increase conduction velocity.

Animals↗
PubMed1993

Gene expression of the renin-angiotensin system in human tissues. Quantitative analysis by the polymerase chain reaction.

Activation of tissue-specific gene expression of the components of the renin-angiotensin system (RAS) in humans may play an important role in cardiovascular regulation and pathophysiology. Studies of human tissue RAS expression, however, have been limited by the lack of availability of sufficient amounts of fresh human tissues and a sensitive method for detecting specific mRNAs. To demonstrate the presence of components of local RASs in humans we used the polymerase chain reaction (PCR) after reverse transcription to detect renin- angiotensinogen-, and angiotensin-converting enzyme-mRNA in small quantities of human tissues. Results indicated that all components of the RAS were widely expressed in human organ samples. In order to study changes of gene expression in small tissue samples (e.g., renal biopsies) obtained from patients, we established a competitive PCR assay for quantification of renin, using a 155-basepair deletion mutant of the human renin cDNA as an internal standard. Renin-mRNA concentration was quantitated in the kidney (1.74 +/- 0.2 pg renin/micrograms total RNA), adrenal gland (1.15 +/- 0.15 pg renin/micrograms total RNA), placenta (0.7 +/- 0.1 pg renin/micrograms total RNA), and saphenous vein (0.02 +/- 0.01 pg renin/micrograms total RNA). The method described here may serve as a highly sensitive tool to quantify alterations in gene expression in man under various pathophysiologic conditions. This study should provide the methodological basis for future studies of tissue RAS in human physiology and disease.

Adrenal Glands↗
PubMed1993

Improving education and resources for health care providers.

Workers and citizens are turning increasingly to the health care system for information about occupational and environmental reproductive hazards, yet most primary care providers and specialists know little about the effects of occupational/environmental toxicants on the reproductive system or how to evaluate and manage patients at potential risk. Although it is unrealistic to expect all clinicians to become experts in this area, practitioners should know how to take a basic screening history, identify patients at potential risk, and make appropriate referrals. At present, occupational and environmental health issues are not well integrated into health professional education in the United States, and clinical information and referral resources pertaining to reproductive hazards are inadequate. In addressing these problems, the conference "Working Group on Health Provider Education and Resources" made several recommendations that are detailed in this report. Short-term goals include enhancement of existing expertise and resources at a regional level and better integration of information on occupational/environmental reproductive hazards into curricula, meetings, and publications of medical and nursing organizations. Longer term goals include development of a comprehensive, single-access information and referral system for clinicians and integration of occupational and environmental medicine into formal health professional education curricula at all levels.

Curriculum↗
PubMed1993

Smell dysfunction and related factors in diabetic patients.

OBJECTIVE: To analyze smell function in diabetic patients and healthy control subjects, with reference to individual characteristics and major complications of the disease. RESEARCH DESIGN AND METHODS: A cross-sectional study of smell recognition in 68 diabetic patients and 30 control subjects without known cause of smell impairment was conducted. Smell was studied using a kit of flavors that patients were asked to recognize, leading to a smell recognition score ranging from 0 (no recognition) to 20 (perfect recognition). Demographic and clinical data, and the electrogustometric threshold were recorded in both groups. Metabolic control and degenerative complications were studied in diabetic patients. RESULTS: The SRS was significantly lower in diabetic patients than in control subjects (12.4 +/- 0.5 vs. 15.1 +/- 0.5, P < 0.001). By use of univariate and multivariate analyses, this difference could not be explained by individual factors such as age, sex, body mass index, blood pressure, or tobacco or alcohol consumption but was related to diabetes. SRS correlated with EGT (r = 0.70, P < 0.001). In the diabetic group, SRS was associated with age (r = 0.29, P < 0.05), duration of diabetes (r = 0.27, P < 0.05), microalbuminuria (12.2 +/- 0.8 vs. 14.4 +/- 0.9, P < 0.05), peripheral neuropathy (10.3 +/- 1.0 vs. 14.1 +/- 0.9, P < 0.01), and EGT (r = 0.39; P < 0.001). By use of multivariate analysis, the strongest association was found with EGT (R2 = 0.15). CONCLUSIONS: These results suggest that smell recognition is impaired in patients with diabetes mellitus. Smell dysfunction is associated with age and degenerative complications of diabetes, suggesting a degenerative mechanism related to diabetes.

Adult↗
PubMed1993

A little help, a lot of independence. Retirement community advances the cause of aging with dignity.

Sometimes the elderly need only a little extra help to make it on their own. When this is the case, it behooves providers of healthcare and social services to meet those needs and allow these individuals to maintain the dignity of independent living as they age. At Resurrection Retirement Community, an independent living facility on Chicago's northwest side, the Garden Annex fills this niche in a unique model of independent living with additional services. Services include three meals a day in the common dining room, laundry service for household linen, and weekly maid service. Residents enjoy varied activities, exercise sessions, and socialization with friends and neighbors. They also have access to such amenities as daily religious services, a library, a beauty salon, and banking facilities. To live in the Garden Annex, prospective residents must meet certain physical and mental criteria and be able to function somewhat independently. In contrast to assisted living facilities, the Garden Annex does not provide nursing care or assistance with personal care. However, residents may take advantage of the continuum of care offered by Resurrection Health Care Corporation. They are afforded access to a medical center, a long-term care facility, and physicians' services.

Activities of Daily Living↗
PubMed1993

Tissue renin-angiotensin systems. Their role in cardiovascular disease.

BACKGROUND: The identification of the components of the renin-angiotensin system (RAS) in various extrarenal tissues suggested the existence of local renin-angiotensin systems with organ-specific functions that may act independently from the plasma RAS. These findings have led to the hypothesis of paracrine-autocrine functions of the RAS, which implies that locally generated angiotensin II mediates effects within one tissue or within one cell. Whereas the circulating endocrine RAS appears to be responsible for acute effects, the tissue RAS seems to participate in more chronic processes such as secondary structural changes and therefore may contribute to the pathogenesis of hypertension as well as other cardiovascular disorders such as cardiac hypertrophy, coronary artery disease, and atherosclerosis. METHODS AND RESULTS: The use of molecular biological techniques has demonstrated that all components of the RAS-renin, angiotensinogen, converting enzyme, and angiotensin receptors-are expressed in several tissues that participate in the regulation of cardiovascular homeostasis. CONCLUSIONS: The therapeutic importance of inhibitors of the RAS, such as converting enzyme inhibitors, is based on their cardioprotective as well as antiproliferative effects and points to a direct involvement of the RAS in the development and preservation of primary hypertension, a pathological condition in which normal or even low plasma renin activity is a common finding. Reversal of cardiovascular structural changes and enhancement of renal sodium excretion by converting enzyme inhibitors are important long-term antihypertensive actions possibly mediated by inhibition of the tissue RAS.

Animals↗
PubMed1993

The renin-angiotensin system in the brain. Localization and functional significance.

Many neuropeptides have been localized in brain areas involved in cardiovascular regulation. In some cases, regulatory systems which have been originally described in other organs have been found in the brain. A prominent member of this group is the renin-angiotensin system. All of its known components have been localized in the central nervous system and angiotensin II has numerous actions in the central regulation of cardiovascular homeostasis. In addition there are actions which go beyond an active role in the control of blood pressure; these include behavioural actions and the regulation of thirst. The brain renin angiotensin system interacts with other neurotransmitters such as the catecholaminergic system and may act as a neuromodulator.

Animals↗
PubMed1992

Effects of angiotensin-converting enzyme inhibitors on tissue renin-angiotensin systems.

The renin-angiotensin system (RAS) plays a major role in the control of blood pressure and cardiovascular homeostasis and is involved in the pathogenesis of a number of cardiovascular disorders. The efficacy of angiotensin-converting enzyme (ACE) inhibitors in the treatment of hypertension and congestive heart failure has led to the widespread clinical use of ACE inhibitors in primary or secondary prevention of heart disease. The demonstration of the expression of the components of the RAS in several extrarenal tissues, as well as local generation of angiotensin II, has confirmed the existence of a tissue RAS that may serve organ-specific functions and act independently from the plasma RAS. The concept of paracrine/autocrine functions of the local RAS has changed our understanding of the functions of the RAS and suggests that tissue ACE inhibition may be of greater importance than inhibition of circulating ACE in the treatment of congestive heart failure and other cardiovascular disorders. Whereas the circulating endocrine RAS appears to be responsible for mediation of acute effects, the tissue RAS seems to be involved in more chronic situations, such as secondary structural changes of the cardiovascular system, and therefore could contribute to the pathogenesis of hypertension as well as other cardiovascular disorders, such as cardiac hypertrophy, coronary artery disease, and atherosclerosis. Several experimental and clinical findings suggest that reversal of cardiovascular structural changes secondary to cardiovascular disease and enhancement of renal sodium excretion by ACE inhibitors are important long-term antihypertensive actions possibly mediated by inhibition of the tissue RAS.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1992

Species specificity of renin kinetics in transgenic rats harboring the human renin and angiotensinogen genes.

The renin-angiotensin system (RAS) is the most important regulatory system of electrolyte homeostasis and blood pressure. We report here the development of transgenic rats carrying the human angiotensinogen TGR-(hAOGEN) and human renin TGR(hREN) genes. The plasma levels and tissue distribution of the transcription and translation products from both genes are described. A unique species specificity of the enzyme kinetics was observed. The human RAS components in the transgenic rats did not interact with the endogenous rat RAS in vivo. Instead, infusions of exogenous human RAS components specifically interacted with human transgene translation products. Thus, infusion of human renin in TGR(hAOGEN) led to an increase of angiotensin II and an elevation of blood pressure, which could not be antagonized by the human-specific renin enzyme inhibitor Ro 42-5892. Rat renin also elevated blood pressure and angiotensin II in TGR(hAOGEN); however, this effect was not antagonized by the human renin inhibitor. Compared to mice, rats offer the advantage of chronic instrumentation and repetitive, sophisticated, hemodynamic, and endocrinological investigations. Thus, transgenic rat models with human-specific enzyme kinetics permit primate-specific analyses in non-primate in vivo and in vitro experimental systems.

Angiotensin II↗
PubMed1992

Identification of a negative regulatory element involved in tissue-specific expression of mouse renin genes.

The 5' flanking region of the mouse renin genes (Ren-1d and Ren-2d) contains two motifs that are homologous to known negative regulatory elements (NREs). Ren-2d has a 150-base-pair (bp) insertion 5' to the upstream putative NRE (NRE-1), which is lacking in Ren-1d. We tested the functionality of these sequences by using site-directed mutagenesis to delete individually each putative NRE from Ren-1d and to delete the 150-bp insertion from Ren-2d. We examined the effect of these mutations on the expression of the reporter gene chloramphenicol acetyltransferase, which was expressed from a truncated thymidine kinase promoter fused to the renin regulatory region. This plasmid was transfected into human choriocarcinoma JEG-3 cells. Only the upstream NRE (positions -619 to -597) was found to be functional in Ren-1d. The deletion of a 150-bp insertion from Ren-2d resulted in the suppression of chloramphenicol acetyltransferase activity to the level of Ren-1d expression. These data suggest that the upstream NRE that is functional in Ren-1d, but not in Ren-2d, may be partly responsible for differential expression of the renin genes in various tissues. The molecular mechanism of the NRE was examined by studying its interaction with nuclear proteins in submandibular gland and JEG-3 cells by gel-mobility-shift assays. Specific nuclear protein binding was observed only to the upstream NRE and the molecular mass of this protein was approximately 72 kDa as determined by Southwestern blot analysis. Thus our results suggest that both Ren-1d and Ren-2d conserve a cis-acting NRE in the 5' flanking region. In Ren-1d, this NRE could bind a specific nuclear protein resulting in the inhibition of Ren-1d expression in these tissues. On the other hand, the NRE in Ren-2d is nonfunctional due to interference by an adjacent 150-bp insertion.

Animals↗