Acoustic trauma and perilymph fistula.
Explore the source record for details and available documents.
Adult↗
Biomedical subjects
J Alexander
Publications and source records attributed to J Alexander.
Resistivity and transverse magnetoresistance in ultrathin films of pure bismuth.
Explore the source record for details and available documents.
Journal Article↗
Effective immunization against cutaneous leishmaniasis with defined membrane antigens reconstituted into liposomes.
The abundant Leishmania promastigote surface Ag gp63 and Leishmania promastigote lipophosphoglycan were reconstituted into liposomes and used as a vaccine against the agent of New World cutaneous leishmaniasis, Leishmania mexicana. The Ag were inoculated s.c., i.p., and i.v. into CBA/ca and BALB/c mice. Even at low Ag dosages, 8 to 10 micrograms/mouse, the Ag induced appreciable levels of protection. In CBA/ca mice complete protection was obtained by s.c. inoculation of antigen-containing liposomes. Protection could be transferred with T cells to naive mice. Interestingly, the Ag-containing liposomes did not cause the disease exacerbation observed in previous vaccine studies with crude parasite extracts.
Animals↗
Evaluation of a low to middle tar/medium nicotine cigarette designed to maintain nicotine delivery to the smoker.
A specific objective of this 6-week crossover study was to determine how 21 regular smokers of middle tar cigarettes changed their smoking behaviour and uptake of smoke constituents, when switching to either lower tar cigarettes capable of delivering amounts of nicotine similar to a conventional middle tar cigarette (maintained nicotine product), or to conventional low tar/low nicotine cigarettes. Subjects visited the laboratory every 2 weeks for detailed assessment of their smoking behaviour. Weekly per capita consumption was similar for all three cigarettes. They were smoked with variable intensities (low tar greater than maintained nicotine greater than middle tar), the tendency being for larger puff volumes, faster puffing and increased puff duration with the low tar cigarettes. The maintained nicotine cigarette was preferred to the middle tar cigarette, although acceptability ratings of the three cigarettes only differed marginally. The nicotine absorbed from the maintained nicotine and middle tar cigarettes was similar and significantly greater than the levels achieved from the low tar cigarettes. Intake of carbon monoxide into the mouth and absorption into the blood stream was lower for the maintained nicotine cigarette than for the middle tar cigarette, with the low tar cigarette occupying an intermediate position. Derived estimates of tar intake suggested reduced intake of tar into the respiratory tract (around 25%) from the maintained nicotine product relative to the middle tar product. The possible advantages of switching to maintained nicotine cigarettes is discussed.
Adult↗
Modulation of the mutagenic effects of 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) and 2-amino-3,4-dimethylimidazo[4,5-f]quinoline (MeIQ) in bacteria with rat-liver 9000 x g supernatant or monolayers of rat hepatocytes as an activation system.
An in vitro protocol was designed to separate the process of metabolic activation from the mutational events. Cultured rat hepatocytes were first incubated with the food mutagens 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) or 2-amino-3,4-dimethylimidazo[4,5-f]quinoline (MeIQ). After the incubation period the medium was removed and further incubated with Salmonella typhimurium TA98. A high direct mutagenic activity of the culture medium was then measured. The half-lives of the mutagenic metabolites formed from IQ and MeIQ were in the order of 45 min. The presence of the cytochrome P450 inhibitors alpha-naphthoflavone and metyrapone during the pre-incubation period reduced the accumulation of mutagenic metabolites. No effects of ascorbate on the mutagenic effects of IQ and MeIQ were seen. (+)-Catechin, another antioxidant and free-radical scavenger, markedly enhanced the number of IQ/MeIQ-induced revertants when added to the hepatocytes. In contrast, (+)-catechin clearly decreased the number of revertants when 9000 X g supernatant from rat liver (S9) was used as an activation system. No marked effect of pentachlorophenol, an inhibitor of hepatocyte sulfation and bacterial O-acetylation, was seen using hepatocytes as an activation system, while the mutagenic activity of both IQ and MeIQ was reduced by 90% in the S9/Salmonella system. The addition of an inhibitor of glucuronidation, galactosamine, or the nucleophile glutathione caused no or only minor decreases in the genotoxic effects of the IQ compounds. With both S9 and hepatocytes as activation systems the relative mutagenic effects observed in the S. typhimurium strains TA98 and TA98 NR were in the same order of magnitude, while a large decrease was seen with TA98/1,8-DNP6. The results show that this in vitro test protocol may be useful as a tool to study mechanisms involved in the formation of mutagenic metabolites.
Animals↗
The ideological construction of risk: an analysis of corporate health promotion programs in the 1980s.
The nature of theoretical knowledge about health promotion and disease prevention programs at the worksite is examined in the context of knowledge as ideological construction. The emergence of the discourse about health promotion is linked to corporate attempts to reduce their share of medical expenditures and solve problems of productivity and absenteeism which plague the American workforce. Although not always evident, corporate managers choose selectively from a body of knowledge about medical costs and illness and disease in contemporary America. That knowledge reinforces the notion of risk: individual propensity to the risk of disease or the attempts of the firm to minimize risk. Three examples of ideological construction: (1) the corporate construction of the cost problem in terms of employee demand and overutilization; (2) the construction of disease etiology as individual risk; and (3) entrepreneurial activity in health promotion, all provide evidence for the dominance of the risk discourse.
Cost Control↗
Sex differences and cross-immunity in DBA/2 mice infected with L. mexicana and L. major.
Female DBA/2 mice were found to be highly resistant to Leishmania mexicana and rarely developed lesions even when inoculated subcutaneously with high numbers (5 x 10(6] of amastigotes. Male DBA/2 mice, on the other hand, were much more susceptible to this parasite and often developed non-healing lesions even when inoculated subcutaneously with comparatively few (5 X 10(4] amastigotes. Conversely, although both male and female DBA/2 mice developed ulcerating lesions when inoculated subcutaneously with L. major amastigotes, lesions invariably healed in males but did not heal in females. Male DBA/2 mice recovered from L. major infection subsequently were found to be resistant to subcutaneous challenge with L. mexicana. Conversely female DBA/2 mice that had failed to develop lesions when infected with L. mexicana developed lesions which healed following subcutaneous challenge with L. major. Thus there is bilateral cross-immunity between L. mexicana and L. major in DBA/2 mice which overrides differences in sex-determined susceptibility to both organisms.
Animals↗
(Acyloxy)alkyl carbamates as novel bioreversible prodrugs for amines: increased permeation through biological membranes.
(Acyloxy)alkyl carbamates of the type R1R2N-CO-O-CHR3-OCO-R4 are described as novel bioreversible prodrugs for primary and secondary amines. These were prepared either by a one-step reaction involving nucleophilic attack on p-nitrophenyl alpha-(acyloxy)alkyl carbonates with displacement of p-nitrophenol or by reaction of alpha-haloalkyl carbamates with silver or mercury salts of carboxylic acids. Enzymatic hydrolysis of the ester bond in these ester carbamates leads to a cascade reaction resulting in rapid regeneration of the parent amine. Permeability measurements of such nonionic derivatives of atenolol, betaxolol, pindolol, propranolol, and timolol through fuzzy rat skin and rabbit cornea mounted on diffusion cells show that derivatization of the hydrophilic beta-blockers results in several-fold increase in permeation through these biological membranes. However, prodrug modification of the lipophilic beta-blockers leads to little advantage in permeability characteristics.
Adrenergic beta-Antagonists↗
Genotoxic activity of the N-acetylated metabolites of the food mutagens 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) and 2-amino-3,4-dimethylimidazo[4,5-f]quinoline (MeIQ).
The genotoxic potential of the food mutagens 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) and 2-amino-3,4-dimethylimidazo[4,5-f]quinoline (MeIQ) and their N-acetylated metabolites (AcIQ and AcMeIQ, respectively) has been studied, in order to evaluate whether an initial N-acetylation of IQ or MeIQ is important for the overall in vivo genotoxicity of the compounds. When incubated with uninduced (control) rat hepatocytes, both the acetylated and the unacetylated compounds appeared to be relatively stable, whereas water-soluble metabolites (i.e. not extractable by ethyl acetate at alkaline pH) were rapidly formed with hepatocytes from PCB-induced animals. No DNA damage was induced by IQ or MeIQ in hepatocytes isolated from control rats, as measured by alkaline elution. In hepatocytes from PCB-pretreated rats, IQ, MeIQ, AcIQ and AcMeIQ induced DNA damage at low (10(-6) M) concentrations, with AcIQ being more potent than IQ whereas AcMeIQ was less potent than MeIQ. Similar patterns were observed when unscheduled DNA synthesis was measured in hepatocytes. The compounds induced sister chromatid exchanges in Chinese hamster V79 cells with PCB-induced hepatocytes as activation system; IQ and AcIQ were equal while AcMeIQ had less activity than MeIQ. The compounds were also compared in bacterial mutagenesis test systems (Salmonella typhimurium TA98). With hepatocyte activation, AcIQ was slightly more potent than IQ, whereas AcMeIQ was markedly less mutagenic than MeIQ. With subcellular fractions as activation system (rat liver S9 or microsomes), the N-acetylated compounds were similar to or less mutagenic than their parent compounds. The mutagenic effects of AcIQ and AcMeIQ in bacteria with microsomal activation were markedly reduced by the deacetylase inhibitor paraoxon.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Fatal necrotizing fasciitis following suction-assisted lipectomy.
Forty-eight hours following extensive blunt suction lipectomy with 3,000 cc of tissue removed, a 36-year-old woman presented to an emergency room with necrotizing fasciitis of both lower extremities extending over the buttock and to the lower third of the back. Tissue cultures and blood culture grew out a pure culture of beta-hemolytic streptococci. The patient rapidly progressed into a comatose state and, despite extensive debridement and appropriate antibiotic therapy, in addition to hyperbaric oxygen treatments, she died on day 9 of her hospitalization (day 11 following the suction lipectomy). To our knowledge this is the first published mortality reported in the United States following this procedure.
Adipose Tissue↗
Regulation of the distribution of tissue iron. Lessons learned from the hypotransferrinemic mouse.
Explore the source record for details and available documents.
Animals↗
The therapeutic effect of sodium stibogluconate in BALB/c mice infected with Leishmania donovani is organ-dependent.
A study of the antileishmanial efficacy of sodium stibogluconate was carried out in BALB/c mice. The drug was administered to Leishmania donovani-infected animals on days 7 and 8 post-infection in one of three forms; free (40-50 mg Sbv Kg-1), liposomal, or niosomal (6.4-8.0 mg Sbv Kg-1) drug. On day 14 post-infection counts of the number of parasites present in the liver, spleen and bone marrow of treated and control animals showed that although all three drug preparations significantly reduced parasite numbers in the liver (approximately equal to 99% suppression) they had little effect on those residing in the spleen or bone marrow. The carrier forms of the drug were therefore significantly more effective than free drug in reducing liver parasite burdens. Increasing the concentration and the number of doses of free drug (maximum of 500 mg Sbv Kg-1), and reducing the size of the vesicles used to deliver the drug had a minimal effect on parasite numbers in the spleen and bone marrow. It is proposed that because of the resistance of spleen and bone marrow parasites to drug therapy, the BALB/c mouse infected with L. donovani provides an excellent model system for the study of drug delivery to these deeper tissue sites.
Animals↗
Interrelation between end-systolic pressure-volume and pressure-wall thickness relations.
We predicted the shape of the end-systolic pressure-thickness relationship (ESPTR) by modeling the left ventricle as thick-walled sphere. To test the validity of the predicted relationships, we then measured the ESPTR over wide volume ranges in seven isolated blood-perfused canine hearts. Both simulation and experiments demonstrated that the ESPTR is curvilinear. However, within a physiological left ventricular systolic pressure range (80-150 mmHg), the ESPTR was described reasonably well by a straight line. Within that pressure range, changes in left ventricular contractile state, assessed by slope changes of the end-systolic pressure-volume relationship, were associated with almost parallel shifts in the ESPTR. In contrast, in a low pressure range (less than 80 mmHg), contractility changes were associated with slope changes of the ESPTR. We conclude that, in general, there are limitations in the application of ESPTR for assessing left ventricular contractility, but if the limitations are recognized and accounted for, then the ESPTR may be useful for assessing contractility changes in vivo.
Animals↗
Assessment of Windkessel as a model of aortic input impedance.
To facilitate the analysis of aortic-ventricular coupling, simplified models of aortic input properties have been developed, such as the three-element Windkessel. Even though the impedance spectrum of the Windkessel reproduces the gross features of the real aortic input impedance, it fails to reproduce many of its details. In the present study we assessed the physiological significance of the differences between real and Windkessel impedance. We measured aortic input impedance spectra from five anesthetized open-chest dogs under a wide range of conditions. For each experimentally determined spectrum we estimated the corresponding values of the best-fit Windkessel parameters. By computer simulation we imposed both the real and best-fit Windkessel impedances on a model left ventricle and assessed the differences in seven different coupling variables. The analysis indicated that the Windkessel model provides a reasonable representation of afterload for purposes of predicting stroke volume, stroke work, oxygen consumption, and systolic and diastolic aortic pressures. However, the Windkessel model significantly underestimates peak aortic flow, slightly underestimates mean arterial pressure, and, of course, does not provide realistic aortic pressure and flow waveforms.
Animals↗
CEO-board relationships under hospital corporate restructuring.
Corporate restructuring has been increasing among the nation's hospitals, but little research has been devoted to assessing how, if at all, this phenomenon affects hospital management and policymaking. This study examines CEO-board relationships in corporately restructured hospitals in relation to more traditionally structured institutions. Analysis of survey responses from 1,179 restructured and 2,010 nonrestructured hospitals indicates that boards of restructured hospitals provide CEOs with greater operational flexibility and control but, at the same time, hold them more accountable for their performance.
Data Collection↗
A model system for studying covalent binding of food carcinogens MeIQx, MeIQ and IQ to DNA and protein.
We have studied the covalent binding of carcinogenic aminoimidazoazaarene compounds to macromolecules in a microsomal model system. The 14C-labelled compounds were incubated with rat-liver microsomes, and binding to macromolecules was measured after their precipitation on glass filters, which were washed several times in organic solvents. The amount of radioactivity was determined by liquid scintillation counting. Covalent binding was dependent on the addition of NADPH, with an optimal concentration of about 1 mM. The binding appeared to follow saturation kinetics when carcinogen concentrations were lower than 200 microM, with Km values of less than 20 microM. At 50 microM, 2-amino-3,4-dimethylimidazo[4,5-f]-quinoline (MeIQ) and 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) bound more effectively than 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx). When DNA was included in the incubations, binding to this macromolecule was ten-fold less per milligram than binding to proteins. In comparison with microsomes from untreated animals, those from rats treated with beta-naphthoflavone caused up to nine-fold more binding of MeIQx, six-fold more of IQ and three times as much of MeIQ. Induction by Aroclor 1254 caused up to 17-fold more binding, whereas induction by phenobarbital caused up to three-fold more binding. The effects of the inducers were greatest for MeIQx and IQ, while smaller effects were seen for MeIQ. The results are most consistent with cytochrome P450-dependent metabolic activation of the carcinogens to hydroxylamine metabolites, for which an isoenzyme(s) inducible by polyaromatic and polychlorinated hydrocarbons is most effective. To our knowledge, this is the first report that MeIQx is metabolized to reactive species capable of covalent binding to macromolecules.
Animals↗
Effect of nisoldipine on coronary resistance, contractility and oxygen consumption of the isolated blood-perfused canine left ventricle.
Nisoldipine reportedly has little direct myocardial effect. However, because of interactions between the heart and vascular load, the effects on myocardial contractility and left ventricular oxygen consumption (LVO2) have not been established. The authors performed experiments on six isolated, blood-perfused canine left ventricles that were isovolumically contracting and paced at constant rate. Coronary arterial pressure (CAP) and coronary blood flow were measured for evaluation of coronary vascular resistance, and coronary arteriovenous oxygen difference was measured for determination of LVO2. Intracoronary injection of 1 and 10 micrograms of nisoldipine decreased coronary vascular resistance by 16.9 and 36.8% (CAP approximately 40 mm Hg), respectively, and by 21.5 and 47.7% (CAP approximately 80 mm Hg). At both doses, nisoldipine caused no decrease in peak systolic pressure as long as CAP was kept constant at 80 mm Hg. However, when CAP was decreased to 40 mm Hg, peak systolic pressure was significantly decreased even without nisoldipine. This impaired contractile state was associated with a decreased coronary blood flow and a slight decrease in LVO2, whereas 10 micrograms of nisoldipine at CAP approximately 80 mm Hg increased LVO2 significantly. Using the end-systolic pressure-volume relationship as an index of contractility, the authors found nisoldipine not to change the contractile state at CAP approximately 80 mm Hg. They conclude that nisoldipine decreases coronary vascular resistance over a wide range of CAP. It neither depresses the contractile state nor decreases LVO2 in the canine left ventricle. Nisoldipine might effectively counteract anginal attacks by dilating the coronary vessels without depressing myocardial contractility as found in this study on normal ventricle.
Animals↗
Mutagenic activation of 2-amino-3-methylimidazo[4,5-f]-quinoline (IQ) and 2-amino-3,4-dimethylimidazo[4,5-f]-quinoline (MeIQ) by subcellular fractions and cells isolated from small intestine, kidney and liver of the rat.
The mutagenic activity of the pyrolysis products 2-amino-3-methyl-imidazo[4,5-f]-quinoline 2-amino-3,4-dimethylimidazo[4,5-f]-quinoline in Salmonella typhimurium TA98 using rat intestinal and renal subcellular fractions as activation systems was approximately 1 and 5 revertants per nmol, respectively. This was 1,000 times less than the activity with a subcellular fraction from rat liver. The mutagenic activity of both compounds was considerably increased using intestinal, renal and hepatic preparations isolated from PCB (Aroclor 1254)-pretreated rats, compared to preparations from control animals. In addition, both compounds displayed a moderate direct-acting mutagenic activity at concentrations above 10(-5) M. Isolated cells from small intestine, kidney and liver incubated in nucleopore chambers were able to convert both compounds into products which mutated bacteria outside the chambers. The concentrations of chemicals required to yield responses of a similar magnitude were approximately 3 orders of magnitude higher in the intestinal and renal systems compared to the hepatic system. The formation of metabolites mutagenic for Salmonella typhimurium by hepatic subcellular and cellular systems was shown to be superior to the respective intestinal and renal systems.
Animals↗