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Biomedical subjects

M Costa

Publications and source records attributed to M Costa.

At least 649 records · Page 36Linked to original sources
PubMedDate not supplied

Characterization of a nickel resistant mouse cell line.

Nickel is a potent carcinogen and, at high concentrations, is toxic to mammalian cells. The effects associated with nickel exposure are well-documented but its mechanism of action in the cell has not yet been fully described. In order to understand the metabolic fate of nickel in mammalian cells, a variant cell population has been selected that continues to grow and divide in the presence of nickel chloride concentrations that are toxic to the parental cell line (Balb/c-3T3 mouse fibroblasts). Nickel resistance is not caused by altered uptake of nickel from the medium or increased clearance from the cells and is not associated with changes in metallothionein expression. Compared to the normal cells, the nickel resistant cells have a decreased number of chromosomes and numerous centromeric fusions. The expression of some proteins and the distribution of nickel bound by various proteins are altered in the nickel resistant cells. Preliminary results indicate that the nickel resistant phenotype may be transferred by genomic DNA-mediated transfection into a recipient NIH-3T3 cell line. Current investigations are directed at identifying a gene responsible for nickel resistance.

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The involvement of heterochromatic damage in nickel-induced transformation.

Nickel ions produce selective damage in heterochromatic regions of chromosomes. Male Chinese hamster embryo cells, which have heterochromatin along the entire long arm of the X-chromosome, exhibit an unusually high incidence of nickel-induced transformation compared with female cells of the same species. However, 3-methylcholanthrene, a carcinogen that produces a random distribution of chromosome damage, transforms female and male cells equally. Other species that do not have as much heterochromatin on the X-chromosome exhibit similar incidences of nickel-induced tumors in males and females. Four out of five of the male nickel-transformed Chinese hamster cell lines exhibit a deletion of the heterochromatic long arm of the X-chromosome as the only common karyotypic aberration. This result indicates that a deletion of a heterochromatic chromosomal region may be an important feature of the nickel-induced carcinogenic process. All of the male nickel transformed cells lines are able to form tumors in athymic nude mice.

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Analysis of metal-induced DNA lesions and DNA-repair replication in mammalian cells.

The potency of several metal compounds in causing lesions in DNA either directly or by exposure of intact cultured cells has been examined using the neutral conditions of nucleoid gradient sedimentation. HgCl2 was clearly the most potent inducer of single-strand breakage when added to isolated nucleoids or when nucleoids were prepared from cells treated with this compound. CaCrO4 , however, caused DNA-strand breaks in nucleoids isolated from cells treated with this agent but did not induce DNA strand breaks when added directly to nucleoids. Although less potent than HgCl2, NiCl2 also caused significant single strand breakage in isolated nucleoids or in nucleoids prepared from cells treated with this metal. Since strand breakage of DNA in intact cells may occur secondary to activation of DNA-dependent nucleases during repair replication, CsCl gradient density sedimentation was utilized to examine whether repair processes were induced by exposure of cells to NiCl2, HgCl2 and CaCrO4 . CaCrO4 and NiCl2 induced substantial DNA-repair activity at concentrations and exposure times where DNA lesions could not be detected whereas HgCl2 induced a 10-fold lower level of DNA-repair activity compared to CaCrO4 at optimal concentrations which again were below the concentrations of this metal that produced measurable DNA lesions. Both the induction of DNA-repair activity and DNA-strand breakage by these metals was concentration- and time-dependent. These results demonstrate some unique aspects of the interaction of HgCl2, NiCl2 and CaCrO4 with the DNA of intact cells and point to the possible important correlation of induction of DNA repair to carcinogenesis since nickel and chromate have clearly been implicated as carcinogens and induce considerable repair whereas HgCl2 is not considered a carcinogen and induces the least DNA repair despite its potency in producing DNA lesions.

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Complementary immunohistochemical distribution of the neurofilament triplet and novel intermediate filament proteins in the autonomic and sensory nervous system of the guinea-pig.

We have previously established that immunoreactivity for the triplet of polypeptides that comprise the class IV intermediate filament proteins (NFP-triplet) is localized in specific subpopulations of neurons in guinea-pig sensory and autonomic ganglia. Antibodies to novel neurofilament proteins, including a polyclonal antibody to a 57 kDa neuronal intermediate filament polypeptide (NIF57kD) and a monoclonal antibody (CH1) to a 150 kDa intermediate filament, or associated, protein were used in combination with antibodies to the NFP-triplet for double-labelling immunohistochemistry. The results show that different subpopulations of neurons in the guinea-pig dorsal root ganglia, coeliac ganglion and enteric ganglia can be distinguished by their complementary immunoreactivity for these proteins. In dorsal root ganglia, larger neurons are intensely immunoreactive for the NFP-triplet while immunoreactivity with CH1 and NIF57kD antibodies is restricted to the small to medium-sized neurons. In the coeliac ganglion, two regionally defined subpopulations of neurons can be distinguished by their immunoreactivity for either the NFP-triplet or NIF57kD, whereas CH1 labels all neurons with equal intensity. Three classes of morphologically distinct myenteric neuron subpopulations are also distinguished by their immunoreactivity for either the NFP-triplet, NIF57kD or CH1 antibodies. Two classes of submucous neurons are labelled both with CH1 and NIF57kD antibodies but show faint or no immunoreactivity for the NFP-triplet. It is concluded that intermediate filament protein immunoreactivity marks different subpopulations of neurons, which suggests that these proteins may have specific roles in neuronal function.

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Subpopulations of neurons in the guinea-pig inferior mesenteric ganglia distinguished by the differential distribution of neurofilament triplet epitopes.

The distribution of the neurofilament protein triplet was examined in neurochemically identified subpopulations of neurons in the guinea-pig inferior mesenteric ganglion. A majority of the catecholamine-containing nerve cell bodies also contained the neurofilament protein triplet. However, a major proportion of the noradrenergic, neuropeptide Y-immunoreactive neurons did not contain neurofilament protein triplet immunoreactivity. Furthermore, a specific subpopulation of neurons that lacked catecholamines and were associated with the hypogastric nerve could be distinguished by the unusual feature of cell body content of post-translationally modified neurofilament protein triplet epitopes. These studies indicate that neurons in the inferior mesenteric ganglia can be distinguished by the presence of specific neurofilament protein triplet epitopes, and thus this class of intermediate filament proteins may confer specific properties to the neurons in which it is contained.

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Bovine respiratory syncytial virus: first serological evidence in Uruguay.

Bovine respiratory syncytial virus (BRSV) is a major cause of respiratory disease in calves resulting in a substantial economic loss for the cattle industry worldwide. In order to determine the presence of BRSV in Uruguay, an immunoenzymatic test was set up, using a recombinant BRSV nucleocapsid (N) protein as the antigen. The N protein was produced in Sf9 insect cells by a recombinant baculovirus expressing the N protein. Serum samples collected from one hundred cattle from four different geographic regions of Uruguay were analyzed. Antibodies against the N protein of BRSV were detected in 95% of the serum samples analyzed. These results show for the first time the presence of BRSV antibodies and suggest a widespread BRSV infection in the cattle population of Uruguay.

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Preliminary report on a simple new assay for DNA-protein cross-links as a biomarker of exposures experienced by welders.

A method originally developed to detect topoisomerase DNA complexes has been adapted to determine DNA-protein cross-links formed in cells following their exposure in vitro and in vivo to cross-linking agents. A preliminary study on welders and controls has been carried out to assess the feasibility of this assay to detect human exposure to chromium (Cr) and nickel (Ni) that are associated with increased DNA-protein cross-links. The percentage of cross-link was significantly higher among welders (1.85% +/- 1.14) than among controls (1.17% +/- 0.46; p = .01) Cross-links were not affected by age, weight, or smoking status. The assay developed has substantial advantages over previous methods, being considerably more simple, inexpensive, and sensitive.

Adult↗
PubMedDate not supplied

Ambulatory blood pressure monitoring is associated with reduced physical activity during everyday life.

OBJECTIVE: The objective of this study was to assess the impact on noninvasive ambulatory blood pressure monitoring on physical activity measured objectively by use of triaxial accelerometers. METHODS: Twenty-four working men and women performed ambulatory blood pressure plus activity monitoring for 1 working day and evening and activity monitoring alone for a separate day and evening. Blood pressure measures were taken at 20-minute intervals during the day and 30-minute intervals in the evening and were accompanied by diary assessments of mood, location, and posture. Comparisons were made of energy expenditure on the 2 days and of activity levels during the minutes surrounding each blood pressure reading and diary completion. RESULTS: Energy expenditure assessed in terms of activity calories per hour was significantly lower during blood pressure plus activity monitoring compared with activity monitoring alone (mean 37.3, SD = 16.3 vs. mean = 43.0, SD = 18.7 kcal, respectively: p = .02). Energy expenditure was lower during the 4 minutes surrounding each blood pressure reading than in the intervals between blood pressure readings. However, energy expenditure was also lower in the intervals between blood pressure readings than during comparable times on the activity only monitoring day. Blood pressure, heart rate, and physical activity were moderately correlated within individuals. CONCLUSIONS: Ambulatory blood pressure recording using automated sphygmomanometers is associated with reduced physical activity during the monitoring day. This is due partly to regular periods of immobility during cuff inflation and deflation and diary completion and partly to more general self-imposed restrictions on activity. This pattern has implications for the representativeness of ambulatory blood pressure monitoring, and the construction of ambulatory monitoring diaries.

Adult↗
PubMedDate not supplied

Emotions and stress increase respiratory resistance in asthma.

OBJECTIVES: Clinical reports suggest that various emotions and types of stress can precipitate asthmatic symptoms, but there is little experimental evidence to substantiate this claim. We studied the impact of different emotional states and stress on respiratory resistance in asthmatic and nonasthmatic individuals. METHODS: Participants (24 asthmatic and 24 nonasthmatic patients) viewed short film sequences selected to induce anxiety, anger, depression, elation, happiness, contentment, or a neutral affective state and completed two stressful tasks, mental arithmetic to induce active coping efforts and viewing of medical slides to induce passive coping efforts. Oscillatory resistance, heart rate, blood pressure, baroreflex sensitivity, skin conductance level, respiration rate and volume, and self-reported affective state were measured throughout the session. RESULTS: Uniform increases in oscillatory resistance were found in all emotional states compared with the neutral state and during mental arithmetic in both groups. Asthmatic patients showed stronger reactions to the medical slides than healthy control subjects, with significant increases in oscillatory resistance, blood pressure, skin conductance level, and minute volume, as well as higher levels of self-reported depression, arousal, and shortness of breath. Changes in oscillatory resistance were inconsistently correlated with other physiological indices. CONCLUSIONS: Various emotional states and stress increase oscillatory resistance largely independently of concurrent increases in autonomic or ventilatory activity. The particular sensitivity of asthmatics to passive coping demand requires additional research.

Adult↗
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The participation of enteric inhibitory nerves in accommodation of the intestine to distension.

1. The amounts by which various weights distended isolated segments from the distal colons of guinea-pigs were measured. 2. Tetrodotoxin substantially reduced the distensibility of the intestine, but bretylium, guanethidine, hyoscine and methysergide had no significant effect. 3. It is concluded that a local reflex involving enteric inhibitory nerves causes an accomodation of the intestine to stretch.

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Adrenaline synthesizing nerve cells in the medulla of normotensive and hypertensive rats.

1. We have studied the number and distribution of adrenaline synthesizing nerve cells in the medulla oblongata of the rat, using a combination of immunofluorescence to visualize the enzyme phenylethanolamine-N-methyltransferase (PNMT) and catecholamine fluorescence to detect central catecholamines. 2. The distribution of adrenaline synthesizing nerve cells was similar in normotensive (Wistar Kyoto) rats, spontaneous hypertensive rats, and stroke-prone rats. Few of the cells visualized by PNMT immunofluorescence were detected by the Faglu fluorescence method for catecholamines. The C1 (ventrolateral) and C2 (dorsomedial) groups of PNMT cells were anatomically distinct from the A1 and A2 groups of catecholamine fluorescent cells and lay rostral to these cells within the medulla. There was a third group of adrenaline synthesizing cells close to the midline in the rostral medulla, and we have called this the C3 group. 3. There was a 32% increase in the number of PNMT cells in the medulla of 4-week-old stroke-prone rats. 4. PNMT enzyme activity in a cross-segment of the medulla containing the adrenaline synthesizing cells was also increased by 30% in both spontaneous hypertensive rats and stroke-prone rats.

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Modeling the impact of prostate cancer early diagnosis on managed care plans.

Efforts to improve decisions about the appropriate use of new and existing technologies have prompted the development of technology assessment committees and advisory panels within managed care plans. As part of this development, plans are using a variety of sophisticated tools to aid their decision making. One such tool is the actuarial model, a method of quantitatively estimating the risk associated with providing care to specified populations.

Actuarial Analysis↗
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An actuarial model approach to assessing the impact of serial testing for prostate cancer using the Tandem PSA assay.

This article summarizes an analytical approach to modeling prostate cancer detection scenarios that health-care plans, i.e., managed care organizations, can use to assist them in making early detection policy decisions. The actuarial modeling approach incorporates current variations in clinical practice with costs for the purpose of generating per member per month outputs. The intent of this approach is to provide laboratories with a tool to provide a value-added service to their managed care customers. The model can be tailored to an array of managed care plans and payer financial arrangements. Included here is a summary of an oral presentation from the Outcomes Conference at the CLMA meeting in Minneapolis, Minnesota in August of 1995. This material was presented by Robert Parson.

Actuarial Analysis↗
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[Progressive multifocal leukoencephalopathy. Role of imaging in its diagnosis. Perspectives].

We review five cases of Progressive Multifocal Leukoencephalopathy (PML), confirmed by biopsy in three cases and by LCR JC virus research by PCR (polymerase chain reaction) in two cases. We analysed the lesions and different forms of imagiological presentation, concerning location, mass effect, contrast enhancement and progress, and emphasize the importance of some atypical patterns. Reference is also made to the role of imaging in its diagnosis and new techniques, such as Spectroscopy and Transfer Magnetization, to avoid brain biopsy.

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