Exclusive and inclusive semileptonic decays of B mesons to D mesons.
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Journal Article↗
Biomedical subjects
J Alexander
Publications and source records attributed to J Alexander.
Loculated fluid. A previously undescribed fluorescein angiographic finding in choroidal neovascularization associated with macular degeneration. Macular Photocoagulation Study Reading Center.
The Foveal Photocoagulation Study, a component of the Macular Photocoagulation Study, is designed to evaluate whether laser treatment can reduce the risk of severe visual loss in eyes with well-defined choroidal neovascular membranes associated with macular degeneration that extend through the foveal center. On one third of the 554 baseline angiograms of study patients enrolled in and whose eyes were graded in the study as of January 31, 1990, the Reading Center staff has noted an unusual pattern of hyperfluorescence in the late-transit frames that has not been described previously. This pattern, which we call "loculated fluid," consists of a well-demarcated area of hyperfluorescence that appears to represent pooling of fluorescein in a compartmentalized space anterior to the choroidal neovascular leakage. Although the loculated fluid may conform to a pattern of typical cystoid macular edema, it can also pool within an area deep to the sensory retina in a shape that does not bear any resemblance to cystoid macular edema. This pattern is important to recognize because it (1) should not be confused with the angiographic pattern or extent of choroidal neovascularization and (2) should be differentiated from a serous detachment or tear of the retinal pigment epithelium.
Body Fluids↗
Pretreatment fundus characteristics as predictors of recurrent choroidal neovascularization.
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Choroid↗
Effect of a bradycardic agent on the isolated blood-perfused canine heart.
Bradycardic agents could limit the consequences of myocardial ischemia via two mechanisms: by decreasing myocardial oxygen demand (MVO2) and by increasing diastolic coronary blood flow (CBF). We investigated whether the benzazepinone UL-FS 49 affects only sinus node cells or also smooth muscle and/or myocardial cells. To avoid confounding interactions with the periphery, we performed experiments on 11 isolated, blood-perfused canine hearts. Injection of UL-FS 49 (1 mg/kg i.c.) significantly reduced heart rate (HR) from 104 +/- 7 to 93 +/- 7 min-1 (mean +/- SEM) and increased stroke volume (n = 6: 9.8 +/- 1.1 vs. 13.2 +/- 1.6 ml), so that cardiac output remained unchanged (n = 6: 1.1 +/- 0.1 vs. 1.2 +/- 0.1 l/min). The contractile state, assessed by isovolumic peak systolic pressure, was unaltered by UL-FS 49 (n = 5: 72 +/- 6 vs. 72 +/- 6 mmHg). At a constant coronary arterial pressure (CAP) of 80 mmHg, mean CBF was slightly decreased (102 +/- 11 vs. 97 +/- 10 ml/[min.100 g]) by UL-FS 49, such that mean coronary resistance remained unchanged (0.9 +/- 0.1 vs 1.0 +/- 0.1 mmHg.min.100 g/ml). The slight decreases in arteriovenous oxygen content difference (n = 6: 6.6 +/- 0.7 vs. 6.5 +/- 0.7 ml/100 ml) and in CBF lead to a calculated, significant decrease in MVO2 (n = 6: 6.9 +/- 0.5 vs. 6.0 +/- 0.4 ml.100 g/min). In conclusion, UL-FS 49 at the dose used decreases MVO2 by reducing HR in isolated canine hearts. In the absence of negative inotropic and vasodilating effects, cardiac output is maintained via increased stroke volume, and CAP will likely be preserved in situ. Thus, this specific bradycardic agent could be useful in treating ischemic myocardial disease.
Animals↗
Genotoxic effects of 2-amino-3,4-dimethylimidazo(4,5-f)quinoline (MeIQ) in rats measured by alkaline elution.
The alkaline elution method was used to examine genotoxic effects of MeIQ in various organs of rats after in vivo exposure. No DNA damage could be observed in the stomach, small and large intestine, liver, kidney or testis of male Wistar rats 2 h after a single intraperitoneal dose of 80 mg/kg MeIQ. In rats that had been pretreated with Aroclor 1254 (PCB), MeIQ induced significant DNA damage in the liver after both oral and intraperitoneal injection. MeIQ induced DNA damage in the large intestine, liver and kidney of male F344 rats given a single intraperitoneal dose of 80 mg MeIQ/kg or fed 0.03% MeIQ for 13 days. The DNA damage did not seem to accumulate during the feeding period.
Animals↗
(Acyloxy)alkyl carbamate prodrugs of norfloxacin.
As a new prodrug approach to norfloxacin (NFLX) we prepared the acetoxyalkyl carbamates of the type NFLX-CO-OCHR-OAc by the reaction of sodium or mercuric acetate on NFLX alpha-chloroalkyl carbamates. These produrgs did not have the bitter taste of NFLX. In vitro, the acetoxyethyl carbamate exhibited activity only against Staphylococcus spp. and was inactive against Gram-negative organisms. However, in the presence of serum and intestinal homogenate, esterase-catalyzed hydrolysis of the ester bond in these modified carbamates led to a cascade reaction resulting in the rapid regeneration of NFLX. At high oral doses of the prodrug, the acetaldehyde produced as a side product in the breakdown of the promoiety caused a slight decrease in alcohol metabolism in a mouse model. The bioavailability of NFLX from the acetoxyethyl carbamate was lower compared to an equivalent dose of NFLX when given as an oral suspension in rhesus monkeys, presumably because of the lower aqueous solubility of the prodrug.
Animals↗
Formation of a glutathione conjugate and a semistable transportable glucuronide conjugate of N2-oxidized species of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) in rat liver.
We have previously shown that 2-hydroxamino-1-methyl-6-phenylimidazo[4,5-b]pyridine(2-h ydroxamino-PhIP) is the principal metabolite leading to mutations in Salmonella typhimurium TA98 and DNA damage in mammalian cells. In rat hepatocytes this metabolite can be further conjugated to 2-(N-beta-D-glucuronopyranosyl (hydroxamino)-1-methyl-6-phenylimidazo[4, 5-b]pyridine[N(OH)-gluc-PhIP]. Its rate of formation was increased in hepatocytes from polychlorinated biphenyl (PCB)-pretreated animals. This metabolite is the main metabolite of PhIP in bile and it is hydrolyzed both by human and rat intestinal bacteria. Smaller amounts are excreted into urine. The evidence for the proposed structure is based on 1H- and 13C-NMR, beta-glucuronidase-lability giving 2-hydroxamino-PhIP upon hydrolysis and on the results obtained by using biochemical enzyme inhibitors. N(OH)-gluc-PhIP may be important for genotoxic lesions and tumors of 2-amino-1methyl-6-phenylimidazo [4,5-b]pyridine (PhIP) in extrahepatic tissue. In hepatocytes and bile from PCB-pretreated rats a PhIP-glutathione conjugate, 2-glutathionyl-1-methyl-6-phenylimidazo[4,5-b]pyridine (GSH-PhIP) was also found. The evidence for the proposed structure is based on 1H-NMR and high-resolution mass spectrometry. The metabolite can also be produced by a direct nucleophilic substitution of the nitro group in 2-nitro-PhIP by glutathione (GSH) in vitro. The metabolite did not form from 2-hydroxamino-PhIP and GSH either directly or in the presence of glutathione S-transferase. The formation of GSH-PhIP in rat liver and isolated cells only at a high rate of 2-hydroxamino-PhIP formation (PCB-treated animals) indicates that 2-nitro-PhIP may be formed in the liver during such N-oxidation of PhIP.
Animals↗
The effect of dose and enzyme inducers on the metabolism of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) in rats.
Male Fischer 344 rats were given a single dose of 0.03-30 mg/kg of [2-14C]2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine ([14C]PhIP), the radioactivity in urine and feces was determined over 48 h, and the major metabolites were identified and quantified. Dose had little effect on the profile of metabolites in the urine but did influence the profile in the feces. PhIP was more efficiently metabolized at higher doses. In addition, rats were pretreated with Aroclor 1254 (PCB), 3-methylcholanthrene (MC), phenobarbital (PB), PhIP and corn oil prior to a single dose of [14C]PhIP, and compared with a control group receiving [14C]PhIP only. The major metabolites in the urine and feces were quantitated for each group, as well as PhIP binding to serum proteins, hemoglobin and selected tissues. Pretreatment with MC and PCB resulted in an increase in the amount of 4'-hydroxylation of PhIP and a decrease in the amount of N-hydroxylated metabolites in the urine. Pretreatment with PB resulted in an increase in the amount of N-hydroxylated metabolites, but a decrease in 4'-hydroxylation. Pretreatment with either MC or PCB resulted in an increase in PhIP binding to the liver and kidney, while reducing the binding in other tissues. Animals pretreated with PhIP showed few significant differences from the untreated group, while pretreatment with PB in general resulted in a decrease of PhIP binding in tissues.
Animals↗
Immunochemical detection of rodent hepatic and urinary metabolites of cooking-induced food mutagens.
Monoclonal antibodies, previously selected to bind either 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) or 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) were evaluated to determine their binding properties with several known metabolites of these compounds purified from rat hepatocyte cultures. Both 2-N- and 5-substituted MeIQx metabolites were recognized by antibodies AIA-2 and AIA-11, while antibodies AIA-1 and AIA-12 bound N-substituted metabolites only. Anti-PhIP antibodies bound N-hydroxy-PhIP, N-sulfinamide-glutathione-PhIP and N-hydroxy-glucuronide-PhIP. Immunoaffinity columns incorporating these antibodies were used to concentrate and purify both the unmetabolized parent compounds and several relatively non-polar metabolites from the urine of rats exposed either to MeIQx or PhIP. Several of these metabolites corresponded with available standards of previously identified polar conjugate metabolites, e.g. N-sulfamate-MeIQx and N(OH)-gluc-PhIP, while others are as yet unidentified. Immunoaffinity chromatography is demonstrated as a promising means of selectively concentrating metabolites of PhIP and MeIQx from urine.
Animals↗
Reductive metabolism and protein binding of chromium(VI) by P450 protein enzymes.
The cytochrome P450-dependent reduction of Cr(VI) using reconstituted phospholipid vesicles containing purified preparation of various forms of rabbit and rat liver microsomal cytochrome P450 has been investigated. The alcohol-induced form of the rat, P450IIE1, was the most efficient enzyme, 7.2 +/- 0.40 nmol Cr/nmol P450/min, whereas the corresponding rates for rat P450IA1, rat IIB1, rabbit IIB4, rabbit IA2 and rabbit IIE1 were 1.7 +/- 0.09, 2.5 +/- 0.08, 1.6 +/- 0.08, 2.5 +/- 0.15 and 1.6 +/- 0.08 nmol Cr/nmol P450/min respectively. NADPH-cytochrome P450 reductase had Cr(VI) reductase activity which was dependent on enzyme concentration. Below 0.15 nmol P450 reductase/ml the sp. act. was low and constant, while at a higher concentration the activity was markedly dependent upon the amount of enzyme present. In a quantitative binding assay it was shown that binding of [51Cr]Cr(VI) to the catalytic enzymes was proportional to the enzyme concentration up to 0.8 nmol P450/ml, which caused binding of 70% of the total radioactivity. Analysis by SDS-PAGE and autoradiography exhibited binding to the individual catalytic proteins of [51Cr]Cr. EDTA treatment removed the radioactivity from the bands matching P450 and P450 reductase, indicating that Cr(III) is bound to the proteins. The reducing activity of both P450 and P450 reductase was potently inhibited by oxygen. The inhibitory effect of oxygen is not due to reoxidation of the reduced Cr and redox cycling. Rat P450IA1 ethoxycoumarin O deethylase activity was inhibited after preincubation with chromate (CrO4(2-). The P450 reductase inhibitor 2'-AMP stimulated the anaerobic P450 reductase dependent Cr(VI) reductase rate approximately 2-fold. Both CO and CCl4 inhibited the different P450 enzymes to various extents. With rabbit P450IIE1 CCl4 stimulated the Cr(VI) reduction approximately 4-fold, whereas the activity of the other enzymes was inhibited when the reconstituted system was incubated with CrO4(2-) and CCl4 prior to NADPH addition. Neither CO nor CCl4 affected the Cr(VI) reducing activity of the P450 reductase. The difference in CrO4(2-) reducing activity of the P450 enzymes and binding to the enzymes may be important for in vivo endoplasmic catalytic metabolism of CrO4(2-).
7-Alkoxycoumarin O-Dealkylase↗
New Zealand black mice are immunologically resistant to high-dose, but not low-dose Leishmania mexicana infection.
The course of infection following s.c. inoculation of a wide dose range of L. mexicana stationary-phase promastigotes (SPP) was examined in sexually mature and immature NZB mice of both sexes. Infection with a high dose (greater than 10(7) SPP) was able to induce a protective in vivo response, which could be adoptively transferred with parasite-immune T cells, into naive, syngeneic recipients. In contrast, s.c. infection with a low dose (less than 10(7) SPP) induced non-healing lesions; disease susceptibility could also be transferred into naive animals with T cells from non-immune donors. When the ability to mount a delayed-type hypersensitivity (DTH) reaction was tested in these two groups, the high-parasite dose group gave a significantly higher response. The in vivo protection and high DTH response were reflected in the ability of cells derived from the high-dose resistant (but not low-dose susceptible) mice to mount an antigen-specific T cell response in vitro. The possible immunological effector mechanisms underlying high-dose resistance and low-dose susceptibility are discussed.
Animals↗
CD8+ T cells are the major lymphocyte subpopulation involved in the protective immune response to Toxoplasma gondii in mice.
The ability of the major T cell subsets to adoptively transfer resistance to T. gondii infection was studied. Spleen cells harvested from mice with a 3-month T. gondii infection and cells from uninfected mice were enriched for T cells by nylon/wool purification. Adoptive transfer of these cells from both groups of donor mice led to a significant increase in the survival of syngeneic recipient mice infected intraperitoneally with 20 T. gondii cysts. Increased survival was mediated particularly by CD4-depleted but also, to a lesser extent, CD8-depleted subpopulations. These results were confirmed in T cell reconstituted athymic nude mice. Unfractionated T cells from chronically infected donors produced a significant inhibition of cyst formation in the brains of recipient mice measured 10 weeks after infection compared with control mice. The inhibition of cyst formation was ablated by pretreating T cells with anti-CD8 antibody and complement, but not anti-CD4 antibody and complement. Mice receiving cells from infected donors produced an early increase in their IgG1 and IgG2a antibody titres compared with mice given cells from uninfected animals. The depletion of either CD8+ or CD4+ immune cells appeared to have little effect on the antibody responses in recipient mice and there was no correlation between antibody levels and immunity. The results indicate that CD8+ T lymphocytes from convalescent T. gondii-infected BALB/c mice are the principal mediators of resistance to T. gondii, although CD4+ T cells appear to be involved during the acute phase of infection.
Animals↗
An unusual solitary circumscribed neuroma (palisaded encapsulated neuroma) of the skin--with observations on the nature of pseudo-epitheliomatous hyperplasia.
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Aged↗
Effect of in vivo chromate, acetone and combined treatment on rat liver in vitro microsomal chromium(VI) reductive activity and on cytochrome P450 expression.
Cytochrome P450 (P450IIE1) in rat has previously been shown to exhibit high chromate [Cr(VI)] reductase activity (Mikalsen et al. 1991). The present study reports on the effect of chromate treatment in vivo in rats and on the modulating effect of acetone + fasting on chromium(VI) toxicity. No effect of intraperitoneal injection with 5 mg chromate/kg was observed, whereas 15 mg chromate/kg decreased the liver microsomal Cr(VI) reductase activity by about 30% in in vitro microsomal incubations. In addition, the P450 and cytochrome b5 contents were decreased by about 30% and 25% respectively. Acetone + fasting caused increases of total microsomal P450 and cytochrome b5 contents, associated with similar increases in apoproteins P450IIE1 and P450IIB1 + 2, and their corresponding mRNA, and apoprotein NADPH-P450 reductase, as well as NADPH-P450 reductase and microsomal Cr(VI) reductive activities. Related to acetone + fasting alone, when given in combination with chromate (15 mg/kg) the Cr(VI) reductive activity was decreased by about 30%, associated with decreases in the P450 and cytochrome b5 contents, 65% and 35% respectively. This further reduced the apoprotein levels of P450IIB1 + 2, P450IIE1, and NADPH-P450 reductase to 90%, 60%, and 40%, respectively, and the mRNA levels of P450IIB2 and P450IIE1. No effect was observed on NADPH-P450 reductase activity. This dose also caused some macroscopic alterations in the liver. In contrast, the P450IIE1 apoprotein level in the lung was apparently stabilized or even increased by chromate in rats treated with acetone + fasting.(ABSTRACT TRUNCATED AT 250 WORDS)
Acetone↗
Autoregressive analysis of aortic input impedance: comparison with Fourier transform.
We evaluated the advantages of the autoregressive (AR) model over the conventional Fourier transform in estimating aortic input impedance. In 10 anesthetized open-chest dogs, we digitized aortic pressure and flow at 200 Hz for 51.20 s under random ventricular pacing and subdivided them into five segments. We obtained aortic input impedance over the frequency range of 0.1-20 Hz both by AR model and by Fourier transform for various lengths of data, i.e., from one to four consecutive segments. For any given data length, the impedance spectrum estimated by the AR model was smoother than that obtained by the Fourier transform. To evaluate the accuracy of the estimated impedance, we predicted instantaneous aortic pressure of the fifth segment by convolving corresponding aortic flow with the impulse response of aortic input impedance. The prediction error was less with the AR model than that resulting from Fourier transform as long as the number of the segments was less than four. We conclude that the AR model provides a more accurate estimate of aortic input impedance than does the Fourier transform when data length is limited.
Animals↗
Study reveals nature of board-CEO relations.
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Contract Services↗
Medical administration and health education needs.
The purpose of this paper is to describe the role of the Royal Australian College of Medical Administrators in the training of medical graduates who wish to pursue a career in health services management. The Royal Australian College of Medical Administrators, founded in May 1968 with an initial membership of 279, is a specialist educational body conducted along similar lines to the other medical colleges in Australia and the United Kingdom. The development of the educational requirements of the college, and the evolution of its training program over the past twenty years, is examined, as well as the appropriateness of the British college model for the training of medical administrators, and the impact that the changes in Australian health care services may have on future educational programs.
Australia↗
Chemotherapy: uses and safety considerations.
Topical chemotherapy is used for treating specific skin diseases. Dermatology nurses must understand topical chemotherapy use to minimize exposure for staff and patients.
Administration, Topical↗