Search PubMedSearch

Biomedical subjects

A Leonard

Publications and source records attributed to A Leonard.

At least 19 recordsLinked to original sources

Chromosomal aberrations in human lymphocytes induced in vitro by very low doses of X-rays.

This paper presents results of a collaborative experiment between six laboratories which examined the yields of unstable chromosomal aberrations in human lymphocytes induced in vitro by X-rays over the dose range 0-300 mGy. The work included data points of nominal doses of 0, 3, 5, 6, 10, 20, 30, 50 and 300 mGy. Cells from 24 donors were examined and a total of about 300,000 metaphases were scored. The work was undertaken to determine the limits of sensitivity of the system taking into account variations in scoring data due to inter-donor sample and inter-laboratory effects. Despite the existence of these effects, aberration yields significantly in excess of control values were seen at doses greater than 20 mGy and these were consistent with a linear extrapolation from higher doses. Below 20 mGy the observed dicentric yields were generally lower than background, but not significantly so. Excess acentric aberrations, on the other hand, and centric rings, were higher than the controls but the increase was usually not significant. It is concluded that the statistical uncertainties are such that below 20 mGy this technique cannot distinguish between a linear or a threshold model.

Chromosome Aberrations

M3-subtype muscarinic receptor that controls intracellular calcium release and inositol phosphate accumulation in gastric parietal cells.

The muscarinic receptor subtype which triggers acid secretion was investigated in isolated rabbit gastric parietal cells. Cytosolic free Ca2+ concentration ([Ca2+]i), measured with the fluorescent indicator FURA-2, increased rapidly after full agonist (carbachol) stimulation (6-8 sec), then returned to an intermediate sustained value. Other M2-agonists, oxotremorine and arecoline, produced a partial [Ca2+]i increase, whereas M1-agonists, pilocarpine and [4-m-chlorophenylcarbamoyloxyl]-2-butynyl-trimethylammonium, were without any significant effect. [Ca2+]i rise was inhibited by selective muscarinic antagonists: atropine greater than 4-diphenylacetoxy-N-methyl-piperidine methbromide greater than quinuclidinylbenzilate (QNB) greater than pirenzepine greater than 11-[[2-[(diethylamino)methyl]-1-piperidinyl]acetyl]-5,11-dihydro-6H- pyrido[2,3-b][1,4]benzodiazepine-6-one, this sequence being characteristic of the involvement of an M3-subtype. This inhibition was shown to be stereoselective; dexetimide and (-)QNB were more potent than levetimide and (+)QNB. The IC50 values for inhibition of [Ca2+]i increase by muscarinic antagonists were in good agreement with those obtained for inhibition of phospholipase C activation. In conclusion, the muscarinic receptor that controls acid secretion appears to be of the M3-subtype and the biochemical events coupled to the activation of this receptor system are also controlled through the same subtype.

Acetylcholine

Comparative analysis of health risk assessments for municipal waste combustors.

Quantitative health risk assessments have been performed for a number of proposed municipal waste combustor (MWC) facilities over the past several years. This article presents the results of a comparative analysis of a total of 21 risk assessments, focusing on seven of the most comprehensive methodologies. The analysis concentrates on stack emissions of noncriteria pollutants and is comparative rather than critical in nature. Overall, the risk assessment methodologies used were similar whereas the assumptions and input values used varied from study to study. Some of this variability results directly from differences in site-specific characteristics, but much of it is due to absence of data, lack of field validation, lack of specific guidelines from regulatory agencies, and reliance on professional judgment. The results indicate that carcinogenic risks are more significant than chronic non-carcinogenic risks. In most instances polychlorodibenzodioxins, polychlorodibenzofurans, and cadmium contribute more significantly to the total carcinogenic risk from MWC stack emissions than other contaminants. In addition, the contribution to total risk of all indirect routes of exposure (ingestion and dermal contact) exceeds that of the direct inhalation route for most studies reviewed.

Animals

Intracellular coupling of prostaglandin inhibition of acid secretion in isolated rabbit gastric parietal cells.

Acid secretion from isolated rabbit gastric parietal cells can be stimulated by gastric secretagogues, histamine (cyclic-AMP pathway) and carbachol (inositol phosphate pathway). Prostaglandins (PG) from E series are potent inhibitors of acid secretion. The intracellular mechanism of this inhibition was examined by using a stable PGE1-analogue, misoprostol. Aminopyrine (AP) accumulations due to histamine, IBMX and forskolin were dose-dependently inhibited by misoprostol, whereas a weak but significant biphasic effect on carbachol-induced AP accumulation was observed. The cyclic-AMP formation induced by histamine and IBMX were also inhibited by misoprostol in a non-competitive way. The potent effect of forskolin on cyclic-AMP levels was not modified by misoprostol in parietal cells, whereas it was potentiated in non-parietal cells. The inhibitory effect of misoprostol on AP accumulation was reduced by incubation of parietal cells with Bordetella pertussis toxin (IAP) but not with Cholera toxin (CT). Pretreatment of the cells with IAP did not alter cyclic-AMP levels of resting and histamine-stimulated parietal cells but abolished the inhibitory effect of misoprostol. Treatment with CT increased basal and histamine-stimulated cyclic-AMP levels and masked the inhibitory effect of misoprostol. The biphasic effect of misoprostol on carbachol-stimulated AP accumulation in parietal cells was confirmed on carbachol-stimulated phospholipase C activity and on [Ca2+]i stimulated by carbachol. These data confirm a direct and specific effect of the prostanoid on the Gi-subunit of the adenylate cyclase coupled to the histamine H2-receptor, and a biphasic effect on the phospholipase C pathway of the parietal cells.

1-Methyl-3-isobutylxanthine

Calcium involvement in the muscarinic response of the gastric parietal cell.

The influence of extracellular Ca2+ on the mediation of carbachol stimulation in isolated rabbit gastric parietal cells was studied. Removing Ca2+ from extracellular medium caused a 42% decrease of the aminopyrine accumulation due to carbachol with the same EC50 value (approximately 5 microM). A short time depletion in extracellular calcium suppressed the carbachol-dependent Ca2+ influx without affecting Ca2+ release from internal stores (fura-2 measurements). Similarly, the production of inositol phosphates under cholinergic stimulation was reduced by 29%. A rapid increase in Ins(1,4,5)P3 was obtained 5 s after carbachol stimulation, and this increase was not changed in Ca2(+)-depleted medium. In contrast, a 20 min incubation with carbachol caused a 50% reduction in both basal and carbachol-stimulated inositol phosphate accumulations. In conclusion, phospholipase C activation, intracellular Ca2+ release and aminopyrine accumulation were sequentially observed following carbachol stimulation of the isolated gastric parietal cell and extracellular calcium contributed to sustain this acid secretory response.

Aminopyrine

Risk factors for PTSD and other diagnoses in a general sample of Vietnam veterans.

This study examined the contribution of premilitary, military, and postmilitary risk factors to posttraumatic stress disorder (PTSD) and other postwar diagnoses in a sample of Vietnam veterans. PTSD was explained primarily by war stressors, including threat to life and exposure to grotesque death, but premilitary and postmilitary factors also contributed to the likelihood of a current diagnosis of PTSD. Panic disorder was also highly predicted by war experiences, whereas prewar functioning played a stronger role in several non-PTSD diagnoses. The study supported the notion that PTSD is specifically linked to intense stressors. Mechanisms for interactions among risk factors are discussed.

Adult

Spontaneous perforation of the extrahepatic biliary tree in infancy. A case report.

Spontaneous perforation of the bile duct in infancy is rare, with less than 55 cases described in the literature to date. The authors report the case of a 30-day-old neonate who presented with a 2-week history of progressive abdominal distension and intermittent jaundice. Disofenin technicium 99m sequential scintiscanning provided a preoperative noninvasive confirmation of the diagnosis of biliary ascites secondary to spontaneous perforation of the extrahepatic biliary tract. Distal common bile duct atresia was identified intraoperatively, and end-to-side Roux-en-Y hepaticojejunostomy was performed, with an uneventful postoperative recovery. The etiology, diagnosis, and treatment of spontaneous neonatal biliary perforation is discussed.

Ascites

Global aphasia without hemiparesis following prerolandic infarction.

Acute global aphasia without hemiparesis (GAWH) is said to result from the association of 2 separate lesions in the anterior and posterior left hemisphere language areas. We present 2 unusual cases of GAWH whose CTs revealed only a single lesion of the posterior part of F2 and F3. There was good recovery of verbal communicative abilities. Functional disconnection of posterior language areas seems responsible for this syndrome in such cases.

Aged

Inverted papilloma of bladder: clinical significance.

Based on 15 cases of inverted urothelial papilloma, we present the clinical significance of these lesions in view of the current literature. An inverted papilloma should raise suspicion with respect to the whole urothelial surface. However, approaching every lesion of this type as a (pre-)neoplastic tumor does not seem justified, since 90 percent of all cases reported so far do not present any clinical or histologic feature of malignancy. Some factors, such as the patient's history, eventually associated urothelial carcinomas, or histologic features of malignant transformation within an inverted papilloma, must be taken into consideration. If no single indication in favor of malignancy has been disclosed, we believe follow-up with yearly endoscopic investigations, in addition to regular urine cytologies, may suffice.

Aged

Chronic bacterial prostatitis: 10 years of experience with local antibiotics.

Direct transperineal infiltration of the prostate with antibiotics was performed in 24 selected patients with refractory chronic bacterial prostatitis. Diagnosis had been made following a modification of the classical lower tract localization studies. Remission periods of at least 6 months were obtained in 71 per cent of these patients after 1 or 2 infiltrations, while 6 of 24 (25 per cent) required several procedures to assume a long-term remission state and 1 (4 per cent) failed therapy (patient 24490). Seven patients had relapse after remission periods ranging from 13 months to 7 years. The last culture in 3 patients was positive. The value of the method compared to other therapeutic alternatives in the management of chronic bacterial prostatitis is discussed.

Adult

Seminal vesiculography in chronic bacterial prostatitis.

A total of 15 patients with proved chronic bacterial prostatitis underwent bilateral seminal vesiculography to determine the morphological appearance of the seminal vesicles and the ampulla ducti deferentis in this condition. A pathological condition, such as segmental stenosis or complete shriveling of the seminal vesicles, was obvious in 21 of 24 vesiculograms (87.5 per cent), while malformations of the ampulla were seen in 7 (29.1 per cent). The role of chronic bacterial prostatitis as an important pathogenetic factor in the history of epididymo-orchitis is discussed.

Adult

Characteristics of hazardous material spills from reporting systems in California.

Data on hazardous material releases that occurred between January 1, 1982 and September 30, 1983 in California were obtained from the California Highway Patrol (CHP) and the US Department of Transportation (DOT). The majority of incidents involved highway transport of hazardous materials, although some information was available on air, rail, and stationary facility releases. Vehicle accidents and failure of or damage to the container were the most frequent causes of releases. Proportionately more hazardous materials incidents occurred in early summer than at other times of the year, during weekdays, and daytime hours. The largest proportions of incidents involved the chemical categories of corrosives and fuels. Reported exposures and injuries to response personnel and other people at the scene were relatively few; no fatalities were reported. Few incidents were reported in both data sources, suggesting that the examination of only one data source would yield a gross underestimate of the total number of hazardous materials incidents in California. The lack of available denominator data limits the interpretation of the findings.

Accidents

Dissociation of the receptor for immunoglobulin E in mild detergents.

We previously showed that, in the absence of phospholipids, exposure of the tetrameric receptor for immunoglobulin E to mild detergents dissociates the intact beta chain and two gamma chains from the alpha chains. Having developed a practical method for assaying the dissociation, we have now explored a variety of different detergents, detergent concentrations, temperatures, times, salts, pHs, and other factors that influence the detergent-induced dissociation. Our findings should be useful for optimizing the stability of the receptor and for future studies on recombination of the subunits. The data suggest the following: (1) The critical perturbant is micellar detergent. (2) Unlike solubilization of membranes, where a molar ratio of micellar detergent:lipid of 2 is adequate, dissociation of the receptor is incomplete even at molar ratios of micellar detergent:receptor of greater than 10(5) and may be limited by a reversible component. (3) Detergents that are best for solubilizing membranes are also best for dissociating the receptors. (4) The latter observation and other data implicate bound lipid as stabilizing the receptor. Our findings may be applicable to the study of interactions between membrane proteins in general.

Animals

Effect of an enhanced natural radioactivity on mammal fertility.

Male and female mice of the BALB/c strain were placed on the floor of a hut built at a site of the Permian Basin of Lodève (Southwest France) where the dose rate of gamma radiation amounts to about 10 mrad/h. In previous experiments such high natural radioactivity was shown to induce point mutations in plant material as well as chromosome aberrations in somatic cells of experimental mammals. Controls were kept near the radioactive site under comparable conditions. After the exposure period, the animals were mated in our laboratory, with control mice of the same strain. Due to the high radiosensitivity of mouse oocytes, the fertility of the exposed females was drastically reduced in spite of the fact that the dose received did not exceed 13.8 rad. The fertility of the males exposed to 13 rad, 15 rad or to 45 rad was increased above the control values but was reduced for the animals receiving 63 rad. Analysis of the results show that the differences in fertility are mainly due to a decrease in the number of sterile pairs when males have been exposed to doses upto 45 rad and to an inverse effect when animals received 63 rad. Since histology and weight of the testes suggest that the germ cell population was normal, one has to conclude that the variations in fertility result from physiological effects.

Animals