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Biomedical subjects

A Tomasi

Publications and source records attributed to A Tomasi.

At least 73 records · Page 4Linked to original sources
PubMed1989

[Plasma cell leukemia originating with pleural effusion].

A case of plasma cell leukemia, secreting light kappa chains, is reported. It arose in a 62 year old man and was diagnosed on the basis of a bilateral pleural effusion, which showed many plasma cells and plasmoblasts. The patient also presented multiple osteolytic lesions, no adenopathies, or signs of hepatic or splenic infiltration. Cytological, cytochemical, immunological findings and serum beta 2-microglobulin assays demonstrated a highly aggressive plasmacytic proliferation. The clinical and hematological data, particularly the onset of the disease with pleural effusions, identify the case as an intermediate form between the typical plasma cell leukemia reported in the literature and anaplastic myeloma.

Bone Marrow↗
PubMed1988

Spin trapping of free radical species produced during the microsomal metabolism of ethanol.

Liver microsomes incubated with a NADPH regenerating system, ethanol and the spin trapping agent 4-pyridyl-1-oxide-t-butyl nitrone (4-POBN) produced an electron spin resonance (ESR) signal which has been assigned to the hydroxyethyl free radical adduct of 4-POBN by using 13C-labelled ethanol. The free radical formation was dependent upon the activity of the microsomal monoxygenase system and increased following chronic feeding of the rats with ethanol. The production of hydroxyethyl free radicals was stimulated by the addition of azide, while catalase and OH. scavengers decreased it. This suggested that hydroxyl radicals (OH.) produced in a Fenton-type reaction from endogenously formed hydrogen peroxide were involved in the free radical activation of ethanol. Consistently, the supplementation of iron, under various forms, also increased the intensity of the ESR signal which, on the contrary, was inhibited by the iron-chelating agent desferrioxamine. Microsomes washed with a solution containing desferrioxamine and incubated in a medium treated with Chelex X-100 in order to remove contaminating iron still produced hydroxyethyl radicals, although at a reduced rate. Under these conditions the free radical formation was apparently independent from the generation of OH. radicals, whereas addition of cytochrome P-450 inhibitors decreased the hydroxyethyl radical formation, suggesting that a cytochrome P-450-mediated process might also be involved in the activation of ethanol. Reduced glutathione (GSH) was found to effectively scavenge the hydroxyethyl radical, preventing its trapping by 4-POBN. The data presented suggest that ethanol-derived radicals could be generated during the microsomal metabolism of alcohol probably through two different pathways. The detection of ethanol free radicals might be relevant in understanding the pathogenesis of the liver lesions which are a consequence of alcohol abuse.

Animals↗
PubMed1988

International measles importations United States, 1980-1985.

Between 1980 and 1985, 89-121 international measles importations were reported annually in the US, accounting for 0.7-6.9% of the annual number of reported measles cases. These measles cases were acquired in more than 70 different countries. Three countries accounted for over one third of all imported cases: Mexico, the UK and the Philippines. Thirty-six states reported importations. However, over half of all importations were reported from only six states: California, New York, Maryland, Florida, Texas and Hawaii. Most measles importations did not cause transmission in the US. In 1982 and 1985 only 16% and 29% of importations resulted in any spread cases. Until there is better control of measles worldwide, high immunization levels are crucial for continued measles control in the US.

Adolescent↗
PubMed1988

Measurement of glomerular filtration rate by impulse synthesis: clinical validation and optimization.

Impulse synthesis is a technique which relies upon the logic of continuous infusion but extracts the clearance value from single-injection data by shifting and adding them until an asymptotic value is attained. This study has been aimed at validating and optimizing clinically the measurement of glomerular filtration rate by impulse synthesis. A single intravenous injection of 51Cr-EDTA has been made in 32 patients and plasma activity monitored over the next 6 h. Glomerular filtration rate computed by a single-exponential fit method (GFR-SEF) has been shown to be significantly (p less than 0.001) overestimated when compared with the glomerular filtration rate obtained by the impulse synthesis technique (GFR-IS) in spite of an excellent (r = 0.989) linear correlation between the two sets of data. On the other hand, the comparison between GFR-IS and 24-h creatinine clearance has not shown any significant difference. Moreover, we have found that in patients with severe renal failure GFR-IS is overestimated when the sampling time span is shortened to 3 h. On the other hand, GFR-IS is slightly underestimated in patients with severe renal failure when the convolution time interval is increased over a few minutes.

Adult↗
PubMed1987

Intracellular chromium reduction.

Two steps are involved in the uptake of Cr(VI): (1) the diffusion of the anion CrO4(2-) through a facilitated transport system, presumably the non-specific anion carrier and (2) the intracellular reduction of Cr(VI) to Cr(III). The intracellular reduction of Cr(VI), keeping the cytoplasmic concentration of Cr(VI) low, facilitates accumulation of chromate from extracellular medium into the cell. In the present paper, a direct demonstration of intracellular chromium reduction is provided by means of electron paramagnetic (spin) resonance (EPR) spectroscopy. Incubation of metabolically active rat thymocytes with chromate originates a signal which can be attributed to a paramagnetic species of chromium, Cr(V) or Cr(III). The EPR signal is originated by intracellular reduction of chromium since: (1) it is observed only when cells are incubated with chromate, (2) it is present even after extensive washings of the cells in a chromium-free medium; (3) it is abolished when cells are incubated with drugs able to reduce the glutathione pool, i.e., diethylmaleate or phorone; and (4) it is abolished when cells are incubated in the presence of a specific inhibitor of the anion carrier, 4-acetamido-4'-isothiocyanatostilbene-2-2'-disulfonic acid.

Animals↗
PubMed1987

Spin trapping of free radical intermediates produced during the metabolism of isoniazid and iproniazid in isolated hepatocytes.

By the use of spin trapping agents phenyl-t-butyl nitrone (PBN) and 4-pyridyl-1-oxide-t-butyl nitrone (4-POBN) free radical species were detected in isolated hepatocytes incubated with either isoniazid, iproniazid and their respective metabolites acetyl-hydrazine and isopropyl-hydrazine. The addition of bis-nitrophenyl phosphate, an inhibitor of the acylamidase enzymes, to isolated hepatocytes decreased the free radical activation of isoniazid and iproniazid, but not that of acetyl- and isopropyl-hydrazine, confirming that the radical species were originating from the biotransformation of these latter compounds. The ESR spectra were ascribed to the trapping of, respectively, acetyl and isopropyl free radicals on the basis of the analogies of the spectral feature with those of chemically-prepared spin adducts. Comparable ESR spectra were also observed during the metabolism of acetyl- and isopropyl-hydrazines by liver microsomes and their formation was inhibited by the omission of NADP+, anaerobic incubation and enzyme denaturation. In the microsomal preparations inhibitors of the mixed function oxidase system decreased to various extents the free radical formation and a similar effect was also observed following the destruction of cytochrome P-450 induced by pretreating the rats with CoCl2. The addition of reduced glutathione also decreased the radical trapping indicating that GSH can effectively compete with the spin traps for the reaction with the free radicals. The incubation of isolated hepatocytes with isoniazid or acetyl-hydrazine reduced by 20-25% the intracellular GSH content, while a 50% decrease in GSH was present in the cells exposed to iproniazid and isopropyl-hydrazine. In the same hepatocyte preparations stimulation of lipid peroxidation and leakage of LDH were also observed during cell incubation with iproniazid and isopropyl-hydrazine, but not with isoniazid or acetyl-hydrazine and the extent of both phenomena correlated with the susceptibility of the above compounds to the free radical activation.

Animals↗
PubMed1987

Free-radical metabolism of carbon tetrachloride in rat liver mitochondria. A study of the mechanism of activation.

Alterations in liver mitochondria as consequence of rat poisoning with carbon tetrachloride (CCl4) have been reported over many years, but the mechanisms responsible for causing such damage are still largely unknown. Isolated rat liver mitochondria incubated under hypoxic conditions with succinate and ADP were found able to activate CCl4 to a free-radical species identified as trichloromethyl free radical (CCl3) by e.s.r. spectroscopy coupled with the spin-trapping technique. The incubation of mitochondria in air decreased free-radical production, indicating that a reductive reaction was involved in the activation of CCl4. However, in contrast with liver microsomes (microsomal fractions), mitochondria did not require the presence of NADPH, and the process was not significantly influenced by inhibitors of cytochrome P-450. The addition of inhibitors of the respiratory chain such as antimycin A and KCN decreased free-radical formation by only 30%, whereas rotenone displayed a greater effect (approx. 84% inhibition), but only when preincubated for 15 min with mitochondria not supplemented with succinate. These findings suggest that the mitochondrial electron-transport chain is responsible for the activation of CCl4. A conjugated-diene band was observed in the lipids extracted from mitochondria incubated with CCl4 under anaerobic conditions, indicating that stimulation of lipid peroxidation was occurring as a result of the formation of free-radical species.

Animals↗
PubMed1987

Detection of free radical intermediates in the oxidative metabolism of carcinogenic hydrazine derivatives.

Hydrazine derivatives are widely used in agriculture, in industry, as rocket propellants, and in medicine. Hydrazines also occur naturally in tobacco and mushrooms. Many hydrazines tested in animal studies appear to be carcinogenic and induce tumors in various target tissues in mice, hamsters, and rats. The use of hydrazine derivatives in humans is often complicated by adverse side-effects such as liver injury and rheumatoid arthritis. A number of studies have demonstrated that hydrazine derivatives are activated to reactive intermediates, such as free radicals, through a variety of cellular oxidative metabolic pathways. The aim of this work is to demonstrate the occurrence of free radical intermediates during the metabolic activation of various hydrazine derivatives and to characterize the enzymatic system(s) responsible for the activation to free radical species. The hydrazines studied are acetylhydrazine, isoniazid, isopropylhydrazine, iproniazid, methylhydrazine, 1,1-dimethylhydrazine, and 1,2-dimethylhydrazine. The model systems chosen are those of rat liver microsomes and isolated hepatocytes. Free radical intermediates have been demonstrated by the electron spin resonance spectroscopy coupled to spin trapping technique. The activation mechanism has been characterized using inhibitors of the mixed function oxidase system and of the FAD-dependent oxygenase system. Glutathione was able to scavenge, with high efficiency, the free radicals produced.

Animals↗
PubMed1987

Measles hospitalizations, United States, 1977-84: comparison with national surveillance data.

Trends in measles discharges from hospitals participating in the Commission on Professional and Hospital Activities, Professional Activities Study (CPHA-PAS) from 1977 to 1984 reflected the rapid decline in measles morbidity indicated by national surveillance data with an 88 per cent decrease in hospitalizations and a 95 per cent decrease in reported cases from 1977 to 1984. Overall trends in number, age, and seasonal distribution were also generally similar. Thirty-four per cent of the hospitalizations listed respiratory complications, 8.5 per cent otitis media, and 3.4 per cent neurologic complications.

Adolescent↗
PubMed1987

Free radical metabolism of alcohols by rat liver microsomes.

By using e.s.r. spectroscopy coupled with the spin trapping technique we have detected the formation of free radical intermediates by rat liver microsomes incubated with either ethanol, 2-propanol or 2-butanol in the presence of a NADPH regenerating system and 4-pyridyl-l-oxide-t-butyl nitrone (4-POBN) as spin trap. The e.s.r. spectra have been identified as due to the hydroxyalkyl free radical adducts of 4-POBN. The free radical formation depends upon the activity of the microsomal monoxygenase system and is blocked by omitting NADP+ from the incubation mixture, by anaerobic incubation or by enzyme denaturation. The involvement of hydroxyl radicals (OH.) produced through a Fenton-type reaction from endogenously formed hydrogen peroxide is suggested by the opposite effects exerted on the e.s.r. signal intensity by azide and catalase. Consistently, iron chelation by desferrioxamine inhibits the free radical formation, while the supplementation of EDTA-iron increases it by several fold. Inhibitors of cytochrome P450-dependent monoxygenase system reduce to various extents the production of free radical intermediates suggesting that reactive oxygen species might be formed at the active site of cytochrome P450 where they react with alkyl alcohol molecules. The data presented support the hypothesis that free radical species are generated during the microsomal metabolism of alcohols and suggest the possibility that ethanol-derived radicals might play a role in the pathogenesis of the liver lesions consequent upon alcoholic abuse.

1-Propanol↗
PubMed1987

Electron spin resonance studies on isolated hepatocytes treated with ferrous or ferric iron.

Isolated rat hepatocytes incubated with iron salts in the presence of the spin trapping agent alpha-4-pyridyl-l-oxide N-tert-butyl nitrone (4-POBN) generate a clear electron spin resonance signal; this signal is not detectable in the absence of exogenous iron. The hyperfine splitting constants are identical whether ferrous or ferric iron is used. The free radical trapped does not appear to be an active oxygen species but rather a carbon-centred radical, which we here ascribe to a lipodienyl radical on the basis of its hyperfine splitting features. Support to this interpretation is lent by the fact that no such radical could be generated in hepatocytes fully protected against lipid peroxidation by pretreating the donor rats with alpha-tocopherol.

Animals↗
PubMed1986

Effect of spin traps in isolated rat hepatocytes and liver microsomes.

Spin traps are increasingly employed in the detection of free radicals in biological systems, including liver microsomes and isolated hepatocytes. Two spin traps phenyl-t-butyl nitrone (PBN) and 4-pyridyl-l-oxide-t-butyl nitrone (4-POBN) have been tested for their effects on hepatocyte viability and mixed-function oxidase activity. High concentration of PBN but not of 4-POBN proved to moderately affect liver cell integrity, without interfering with intracellular ATP or cytochrome P-450 content. PBN also decreased hepatocyte GSH content, probably as the result of its metabolism to benzaldehyde. The two spin traps were found to inhibit aminopyrine demethylase and ethoxycoumarin deethylase activity in hepatocytes and microsomes. At low concentrations (1-5 mM) PBN enhanced aniline hydroxylase while high concentrations of the spin trap inhibited this activity. The inhibition of the monooxygenase system was not caused by damage of microsomal enzymes, but rather by competition with other substrates for the binding to the haemoprotein. The effects of spin traps on mixed function oxidase systems should be taken into account when evaluating the results of spin trapping experiments.

Animals↗
PubMed1986

Decrease of hepatic mitochondrial glutathione and mitochondrial injury induced by 1,2-dibromoethane in the rat in vivo: effect of diethylmaleate pretreatment.

Diethylmaleate (DEM) potentiated the 1,2-dibromoethane (DBE)-induced hepatic morphological lesion in fasted male Wistar rats, as revealed by light and electron microscopy examination. The subcellular structures involved in such lesions were the mitochondria. The potentiating effect of DEM appeared to be due to enhancement of the depletion of hepatic mitochondrial glutathione (GSH) caused by DBE. DEM, however, failed to potentiate the DBE-induced release in the plasma of hepatic enzymes. The relationship between loss of mitochondrial GSH, mitochondrial injury, and the importance of the mitochondrial lesion in DBE-induced hepatotoxicity is discussed.

Animals↗
PubMed1986

Appropriate age for measles vaccination in the United States.

The appropriate age for measles vaccination is determined by weighing the risk of measles disease and complications at a given age with vaccine efficacy at that age. In the United States, measles vaccine was initially used in children as young as 9 months of age because the disease was common and complications were greatest in persons less than 1 year of age. In 1965, when it became apparent that vaccine failure was unacceptably high in children less than 1 year and when epidemiologic analysis indicated that children greater than or equal to 1 year, particularly schoolchildren, were the primary focus of measles transmission, the vaccination age was raised to 12 months. In 1976, further studies showed efficacy was slightly higher at 15 months of age versus 12 months or 12-14 months of age. Because the risk of acquiring measles in children less than 15 months was low, the age for routine vaccination was increased to 15 months. This age recommendation may be appropriate for developed countries where the epidemiology of measles may be similar to the epidemiology in the United States. However, this age is inappropriate for many countries in the developing world where the risks of measles and complications from measles are high in young preschool children. In those countries, the recommended age for routine vaccination against measles is generally 9 months.

Age Factors↗
PubMed1985

The role of pentachlorophenol in causing mitochondrial derangement in hexachlorobenzene induced experimental porphyria.

Hexachlorobenzene feeding to rats for 60 days to induce experimental porphyria resulted in partial and constant uncoupling of oxidative phosphorylation of liver mitochondria from the early phase (i.e. 20 days) of treatment. Direct experimental evidence has been presented that this uncoupling is completely due to the action of pentachlorophenol endogenously formed by metabolism of hexachlorobenzene. The complete restoration of membrane potential by albumin under these conditions indicates that no irreversible damage occurs in the mitochondrial membrane. No appreciable correlation between concentrations of pentachlorophenol and the degree of porphyria has been observed.

Animals↗
PubMed1985

The effect of medroxyprogesterone acetate on premature labor in the sheep.

The ability of medroxyprogesterone acetate to delay premature delivery was investigated in nine chronically catheterized pregnant sheep (125 to 130 days' gestation). Catheters were placed for measurement of intrauterine pressure and uterine vein concentrations of progesterone, 17 beta-estradiol, and 15-keto-13,14-dihydroxyprostaglandin F2a. Premature parturition was induced in all animals by infusion of dexamethasone (1 mg/24 hours) to the fetus. Three ewes served as controls, three ewes received oral medroxyprogesterone acetate (5 mg/kg/day) 48 hours prior to the start of and during dexamethasone (early medroxyprogesterone acetate), and the remaining three animals received oral medroxyprogesterone acetate 12 hours after the onset of dexamethasone infusion (late medroxyprogesterone acetate). The lengths of time from dexamethasone until the onset of labor and from dexamethasone until delivery were compared, and were significantly longer for each group compared to control times. Of all endocrine events analyzed, the fall in plasma progesterone was the most consistent in all groups, showing that animals with rapid falls in progesterone levels (control group) tended to deliver earlier. These results demonstrate that medroxyprogesterone acetate can delay premature parturition in the sheep. Also medroxyprogesterone acetate appears to delay the endocrinologic events that normally occur at this time.

Animals↗