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Biomedical subjects

G L Fisher

Publications and source records attributed to G L Fisher.

At least 19 recordsLinked to original sources
PubMed1992

Characteristics of adult children of alcoholics.

Ninety-seven adult children of alcoholics (ACOAs), 36 adults with dysfunctional family histories, and 41 adults without identified dysfunctional family histories were compared on self-reports of 20 adult characteristics. Significant differences among the groups were found on 4 of the characteristics, with the ACOA group showing the highest frequency of occurrence on 17 of them. No differences due to gender of the alcoholic parent were found, and there was no group by gender interaction. The results suggested that the clinical characteristics attributed to ACOAs may have some empirical validity but the ACOAs seem fairly similar to adults with other types of dysfunctional family histories.

Adaptation, Psychological↗
PubMed1992

Immunosuppression and cancer: the ciclosporin case.

Experimental and clinical data relevant for the evaluation of the carcinogenic potential of the immunosuppressant ciclosporin are reviewed. Ciclosporin binds reversibly to the cytosolic receptor protein ciclophilin. Ciclophilin is likely involved in the blockade of lymphocyte activation-induced gene transcription of various growth factors, especially interleukin-2. The drug has no effect on the transcription of housekeeping genes nor does it activate any gene. Ciclosporin may inhibit tumor cell growth, notably those which are growth factor dependent. At high concentration virus-transformed cells, especially Epstein-Barr-infected B-lymphocytes, may escape the control of specific cytotoxic T-lymphocytes. Ciclosporin has no genotoxic activity, and has no DNA-binding property. In experimental studies ciclosporin did not cause cancer in the absence of an initiating event (e.g. chemical mutagen). However, by its immunosuppressive property, the drug may allow the growth of initiated tumor cells in vivo, an effect which is dose-dependent. In clinical use ciclosporin immunosuppression is associated with an increased incidence of lymphoproliferative disorders and other malignancies particularly of the skin when compared with a normal, not immunosuppressed population. Conventional immunosuppression (azathioprine, antilymphocyte globulin, prednisone) also demonstrates comparable risks to develop tumors. Lymphoproliferative lesions regress after dose reduction or cessation of treatment. Furthermore, combinations of various immunosuppressants with associated 'over-immunosuppression' may result in a higher incidence of viral infection and malignancy. In summary, chemical immunosuppression carries the intrinsic risk of tumor growth. In the case of ciclosporin this effect is dose dependent. Thus, the risk may be reduced by low dosage and by avoiding combination therapies with additional immunosuppressants.

Animals↗
PubMed1990

Arsenic distribution in rabbits after Lewisite administration and treatment with British anti-Lewisite (BAL).

The standard treatment of Lewisite (dichloro(2-chlorovinyl)arsine) poisoning is by chelation with BAL (British anti-Lewisite, dimercaptopropanol). The present study investigated the effect of BAL treatment on the distribution of arsenic after Lewisite administration. Lewisite was administered subcutaneously at the LD10 and LD40 of the compound. Without BAL treatment arsenic was eliminated with a half-life in blood of between 55 and 75 hr and a blood clearance of 120 ml/hr/kg. Arsenic had a large volume of distribution of several liters per kilogram, indicating extensive distribution in tissues. The highest tissue concentrations, more than seven times blood concentrations, were found in the liver, lung, and kidneys. These organs maintained an approximately constant concentration ratio with blood during the sampling period. Concentrations in tissues with a blood-to-tissue barrier, such as the brain and the spinal cord, rose between 4 and 96 hr while blood concentrations declined more than fourfold over the same time period. BAL treatment by four equal, maximally tolerated doses over 12 hr substantially reduced arsenic concentrations in blood and tissues. For example, at 24 hr the concentrations in brain and liver (target organs for arsenic toxicity) were reduced by 65 to 89% over the range of Lewisite doses administered. The total exposure of brain and spinal cord was reduced by more than two-thirds by BAL treatment. Further, the blood clearance of arsenic was increased. BAL treatment enhanced the elimination of arsenic in two ways: by decreasing the tissue-to-blood partitioning which mobilizes arsenic into the blood stream, and by increasing the clearance of arsenic.

Adipose Tissue↗
PubMed1990

Factor analysis of the substance abuse attitude survey with college undergraduates.

Few standardized instruments measure attitudes and beliefs towards substance abuse. The Substance Abuse Attitude Survey, developed for measuring drug attitudes in medical education, was administered to 598 college undergraduates, and a factor analysis was performed. Three coherent and stable factors were identified, e.g., Stereotypes and Moralism, Treatment, and Permissiveness. Internal consistency and 6-wk. test-retest measures indicated moderate to high reliability factor structure. Results are discussed in terms of sample differences between this effort and a previous validation.

Adult↗
PubMed1990

Tumorigenicity of nickel subsulfide in Strain A/J mice.

The pulmonary tumor response of Strain A mice has been reported to be a rapid and efficient predictor of carcinogenic potential for a variety of chemicals. The route of exposure has usually been by intraperitoneal injection (i.p.) of solubilized materials. We compared intratracheal (i.t.) instillation as a more representative route typical of human exposures, with i.p. injection of nickel subsulfide, a potent animal carcinogen. Animals were sacrificed either 20 weeks after the first dosing, or were held until 45 weeks after the first dosing. Urethane, a positive control, produced a significant increase in pulmonary tumor response after i.t. instillation as well as i.p. injection. For nickel subsulfide treated animals, there was no evidence of a dose-related increase in pulmonary tumor response in any i.p. or i.t. treatment group when compared with age-matched controls.

Adenoma↗
PubMed1990

Pulmonary adenomas in A/J mice treated with silica.

This study was designed to test the pulmonary tumor response to intratracheally instilled silica in Strain A mice. Urethane was used as a positive control. Silica treatment was utilized to evaluate the effect of a potent fibrinogen on pulmonary adenoma formation in this unique animal model. Urethane produced an increase in pulmonary tumor response in this study in agreement with previous investigations. Also, the background incidence of adenomas was comparable to other studies. Silica treatment did not affect tumor incidence either in terms of percent of mice with adenomas or average number of adenomas per mouse.

Adenoma↗
PubMed1990

Effects of mainstream and environmental tobacco smoke on the immune system in animals and humans: a review.

This review evaluates the available information on the effects of mainstream and environmental tobacco smoke on the immune system in animals and humans. The primary emphasis is on mainstream smoke since little information is available on the effects of environmental smoke. The effects of mainstream tobacco smoke on the immune system in humans and animals are similar. Animals exposed to mainstream tobacco smoke for periods of a few weeks generally exhibit a slight immunostimulation. However, subchronic and chronic exposure studies indicate that immunosuppressive changes develop. Lymphocyte proliferation in response to the mitogens PHA and LPS is decreased, suggesting compromise of cell function. Antibody production can be suppressed. Smoke-exposed animals that are challenged with metastasizing tumors or viruses have been shown to exhibit a higher incidence of tumorigenic and infectious diseases, respectively. Localized immunological changes in the lung can include reduction of bronchus-associated lymphoid tissue and immunoglobulin levels. Smoking-related changes in the peripheral immune system of humans have included elevated WBC counts, increased cytotoxic/suppressor and decreased inducer/helper T-cell numbers, slightly suppressed T-lymphocyte activity, significantly decreased natural killer cell activity, lowered circulating immunoglobin titers, except for IgE which is elevated, and increased susceptibility to infection. The effects of environmental tobacco smoke on the immune system, in contrast to mainstream tobacco smoke, have just begun to be investigated and information available in the literature, to date, is limited. Immunoreactive substances are known to be present in environmental tobacco smoke, but to date, environmental tobacco smoke has been more closely associated with irritation than sensitization. A few studies have indicated a potential for environmental smoke-induced hypersensitivity and suppression of immunoregulatory substances. In contrast, other investigators have failed to detect immunological or other biological changes associated with environmental smoke. Clearly, more research is needed to resolve these differences.

Animals↗
PubMed1989

In vitro effects of fibrous and nonfibrous silicon nitride on bovine pulmonary macrophages.

Bovine pulmonary macrophages were exposed in vitro to 0.3, 0.1, 0.03, or 0.01 mg/ml of a fibrous silicon nitride, nonfibrous (milled) silicon nitride comminuted from the fibrous powder, alpha-quartz (an active control), or glass beads (an inert control). Functional evaluation of the exposed cells indicated that the fibrous silicon nitride was as cytotoxic as quartz, while the nonfibrous silicon nitride was relatively inert. To further evaluate the mechanisms of cytotoxicity, the cells were exposed to 1 mg/ml of the control and test materials and biochemical studies were performed. Quartz increased release of both the cytoplasmic enzyme, lactate dehydrogenase (LDH), and the lysosomal enzyme, acid phosphatase (AP), consistent with both cell membrane and lysosome lysis. In addition, total protein levels were significantly depressed, suggesting significant impairment of cellular synthetic processes. LDH, but not AP, values were increased with fibrous silicon nitride treatment, but not with the nonfibrous silicon nitride. In contrast to quartz, which increased LDH levels by 65%, the fibrous silicon nitride only increased LDH levels by 11%. Scanning electron micrographs further indicated that the fibrous silicon is cytotoxic and poorly tolerated by macrophages. These studies provide further evidence of morphology as a primary determinant of cytotoxicity since the milled powder test article was comminuted from the fibrous material.

Acid Phosphatase↗
PubMed1989

Pre-service teachers use of and attitudes toward alcohol and other drugs.

Drug attitude and use assessment of 598 undergraduate students revealed attitudinal differences between anticipated occupation groups and drug use patterns that paralleled prior studies which used college student samples. Results are discussed as they pertain to the education of those planning to enter the teaching profession.

Adolescent↗
PubMed1987

In vitro models of lung toxicity.

In vitro assays that emphasize cellular components critical to the host defense system have been developed to evaluate pulmonary toxicity and define deleterious changes in parenchymal cell populations. Assays that employ pulmonary alveolar macrophages (PAM) have demonstrated good correlation between macrophage toxicity and pulmonary fibrogenicity for many inorganic compounds. The PAM assays provide simple and inexpensive screens of potential respiratory tract toxicity. Many investigators screen chemicals for their ability to alter the mucosal epithelial cell conducting airways by performing tracheal organ cultures. The tracheal assays have also provided useful screens for Vitamin A analogues required for epithelial cell differentiation. Most recently, in vitro respiratory tract models have been extended to include whole-lung explants, an approach that allows for development of fibrosis and epithelial cell toxicity after in vitro exposure to inorganic and organic fibrogens. The whole-lung explant system appears to duplicate the in vivo response to a variety of lung toxins, including bleomycin, silica, and crocidolite asbestos. Together, these assays provide a description of potential toxicity to key components of the lung, emphasizing the pulmonary macrophage, conducting airways, and alveolar septae. It is expected that continued research in these models will enhance their predictive abilities and utility in risk assessment.

Animals↗
PubMed1987

Adult peripheral lung organ culture--a model for respiratory tract toxicology.

This report describes procedures to culture 1- to 2-mm-thick cross sections of lung lobes for periods of 4 to 6 weeks. Normal morphologic and macromolecular composition are maintained. Previous attempts to maintain adult peripheral lung cultures for periods beyond 7-10 days or to examine respiratory disorders in vitro other than acute changes have been generally unsuccessful. Eight different, supplemented, serum-free media, mixed with heated liquid agarose were infused into the airways of hamster and rat lungs. Cross sections were explanted onto squares of porous surgical packing material, placed in medium, and incubated for 4 to 6 weeks. The ability of each medium to maintain normal lung was assessed microscopically by quantitative image analysis and by biochemical analyses. The optimal medium formulation for each species is described. The adult peripheral lung culture system may provide toxicologists with a unique model for mechanistic and safety evaluations of potential lung toxicants.

Animals↗
PubMed1987

A possible mechanism of chrysotile asbestos toxicity.

In vitro evaluations of heat treated and/or irradiated chrysotile asbestos indicate the importance of electron transfer in determining the biological outcome of asbestos exposure. Regardless of the assay system used, all show the same trends. Namely, heat treatment reduces cytotoxicity while heat treatment in combination with irradiation increases activity over heat treatment alone. Furthermore, studies of BSA and DNA binding consistently indicate a lower molecular adsorption for heated asbestos. BSA and DNA adsorption are similar for untreated, irradiated and heated or irradiated samples. Physical and chemical analyses indicate that the size and elemental composition are unaffected by the treatment processes. X-ray diffraction indicates no change in the crystal structure of chrysotile asbestos. IR spectroscopy suggests that heat treatment affects the external hydroxyl group population while heat treatment and irradiation may repopulate this functional group. A proposed mechanism consistent with the biological and physical characterization is based upon electron transfer from the chrysotile asbestos matrix to biological receptors.

Adsorption↗
PubMed1979

Physical factors affecting the mutagenicity of fly ash from a coal-fired power plant.

The two finest, most respirable coal fly ash fractions collected from the smokestack of a power plant were more mutagenic than two coarser fractions. Mutagenicity was evaluated in the histidine-requiring bacterial strains TA 1538, TA 98, and TA 100 of Salmonella typhimurium. Ash samples collected from the hoppers of an electrostatic precipitator in the plant were not mutagenic. The mutagens in coal fly ash were resistant to x-ray or ultraviolet irradiation, possibly as a result of stabilization by fly ash surfaces. All mutagenic activity is lost with heating to 350 degrees C.

Air Pollutants↗
PubMed1979

Abnormal canine bone development associated with hypergravity exposure.

Chronic centrifugation of 85- to 92-day-old Beagles at 2.0 X g and 2.6 X g for 26 weeks during the time of active skeletal growth caused skeletal abnormalities in the radius and the ulna of ten of 11 dogs. The pattern of change mimicked that found in naturally occurring and experimentally induced premature distal ulnar physeal closure or delayed growth at this physis. Minimal changes in bone density were detected by sensitive photon absorptiometric techniques. Skeletal abnormalities also were found in five of the six cage-control dogs, although the run-control dogs were radiographically normal.

Animals↗
PubMed1978

Hypothesis for the mechanism of elevated serum copper in cancer patients.

Neoplastic growths seem to interfere with normal processes regulating the serum level of ceruloplasmin, a copper-containing oxidase, which accounts for 96% of serum copper. Normal catabolism of ceruloplasmin in the liver follows desialylation. However, in patients with tumors, ceruloplasmin may be resialylated at the tumor cell surface or in peripheral blood. Decreased catabolism due to resialylation of asialo-ceruloplasmin could account for the increased concentration of serum copper noted in patients with neoplasia.

Ceruloplasmin↗