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Biomedical subjects

G J Smith

Publications and source records attributed to G J Smith.

At least 127 records · Page 7Linked to original sources
PubMed1989

Selenium accumulation by raccoons exposed to irrigation drainwater at Kesterson National Wildlife Refuge, California, 1986.

In February-March 1986, eight raccoons (Procyon lotor) were collected at Kesterson Reservoir (Merced Co., California), which had received selenium-contaminated irrigation drainwater, and four raccoons were collected at the nearby Volta Wildlife Area, which had not. Selenium concentrations in Kesterson raccoons averaged 19.9 ppm (micrograms/g dry wt) in liver, 28.3 ppm (dry wt) in hair, 21.6 ppm (dry wt) in feces, and 2.61 ppm (wet wt) in blood and exceeded Volta concentrations by 12, 30, 21, and 10 times, respectively. Selenium concentrations in livers of Kesterson raccoons were less than those in five of nine other mammal species sampled in 1984. Selenium concentrations in hair provided the strongest statistical separation between study areas. Hemoglobin levels in two Kesterson raccoons equalled levels reported in rats with selenium-induced anemia, but the raccoons showed no illness. Amyloidosis in one Kesterson raccoon may have been selenium-induced. Our data indicate that raccoon births peaked about 2 months later than was previously reported. Based on our sample of 12 raccoons, we found no evidence that contamination by irrigation drainwater had negative effects on raccoons inhabiting Kesterson.

Animals↗
PubMed1989

A decrease in hyaluronic acid synthesis by aging human fibroblasts leading to heparan sulfate enrichment and growth reduction.

Cultured normal human fibroblasts during in vitro aging exhibited increased proportions of heparan sulfate (HS; a glycosaminoglycan (GAG) species) in the cell-associated GAG pool, coincident with decreased cell growth activity. An analysis of GAG metabolism demonstrated that human fibroblasts during aging became relatively rich in HS due to an alteration in the profile of GAG synthesis. HS became relatively enriched and hyaluronic acid (HA) relatively depleted through a decrease in HA synthase activity. An experimental enrichment of human fibroblast cultures with exogenous HS brought about an arrest of the cells in the G0/G1 phase and a decrease in the rate of S phase entry, coincident with aged cell growth behaviour. These results suggest that the change in HA synthesis is responsible, at least to some extent, for the growth reduction during aging of normal human fibroblasts.

Cell Division↗
PubMed1989

Decreased 8N3-[gamma-32P]GTP photolabeling of Gs alpha in tumorigenic lung epithelial cell lines: association with decreased hormone responsiveness and loss of contact-inhibited growth.

The 45-kDa alpha subunit of the signal transducing Gs protein complex, which stimulates receptor-coupled adenylate cyclase, incorporated less of the photoaffinity probe, 8N3-[gamma-32P]GTP, in extracts from tumorigenic cell lines in comparison with nontumorigenic cell lines derived from mouse lung epithelium. Immunoblotting experiments using anti-Gs alpha antibodies demonstrated that tumor cells do not have a decreased amount of Gs alpha and photolabeling of tumor cell Gs alpha increased when the rate of nucleotide exchange was promoted. Therefore, tumor cell Gs alpha function may be altered. Consistent with this hypothesis is the observation that the tumor cells exhibited decreased responsiveness to the beta-adrenergic agonist, isoproterenol. Gs alpha photolabeling in growing nontumorigenic cells was reduced to a level resembling that observed in tumor cells, but photolabeling increased when cells became contact-inhibited. This increase in 8N3-[gamma-32P]GTP incorporation into Gs alpha by normal cells at confluence was not seen in the tumorigenic cells. Since Gs alpha photolabeling was inversely proportional to the percentage of [3H]thymidine-labeled nuclei at confluence, we suggest that the altered Gs alpha in tumor cells is involved in the loss of cell growth regulation.

Affinity Labels↗
PubMed1989

A program for storage and retrieval of demographic, sample, clinical laboratory, and restriction endonuclease map data.

A program, written in dBASE, is described that manages demographic, sample, clinical laboratory, and restriction endonuclease map data. The program exports migration distances of DNA fragments resulting from specified endonuclease digests to a commercially available, but modified, curve fitting program (CURVE-FITTER) where the fragment sizes in base pairs are calculated. The calculated values are imported back into dBASE files for report generation or later analysis. The program will produce hard copy reports for single or multiple individuals.

Clinical Laboratory Information Systems↗
PubMed1989

Cloned murine non-malignant, spontaneously transformed and chemical tumour-derived cell lines related to the type 2 pneumocyte.

NAL1A is a murine type 2 pneumocyte-related cell line cultured from normal BALB/c adult mouse lung. In vitro spontaneous transformation of 3 out of 7 clones of NAL1A has led to the isolation and establishment in continuous cell culture of sibling-related non-neoplastic (NAL1A) and spontaneously arising neoplastic (NAL1As) cell strains. NAL1As cells exhibited a similar phenotype to cloned NUL1 cells cultured from urethane-induced mouse lung adenomas. All NAL1As and NUL1 clones grew vigorously in 0.3% agar and formed invasive, poorly differentiated carcinomas following subcutaneous inoculation into immunesuppressed mice. Several subcutaneous nodules metastasised preferentially to the lung. All spontaneous and chemically-derived malignant clones were less differentiated than the non-malignant clones as assessed by staining with a type 2 pneumocyte-specific polyclonal antiserum. The clones described in this report form a useful model in the study of spontaneous and chemically-induced neoplastic transformation in mouse epithelial lung cells.

Adenoma↗
PubMed1989

A solar erythemal (sunburn) radiation dosimeter.

Measurement of solar erythemal radiation is a technically demanding task because it is accompanied by a vastly greater flux of other solar radiation. An inexpensive solar erythemal radiation dosimeter has been designed which is based on the photocleavage of an alkyl disulphide. The reaction is carried out in a hydrocarbon solvent which can readily donate hydrogen atoms and as a result no polysulphides with absorptions in the erythemal action spectrum were formed. This avoided non-linearities in the dosimeter arising from inner filtering effects. The amount of alkylthiol produced as a result of exposure of the corresponding dialkyl disulphide solution to solar erythemal radiation was linearly related to the dose of radiation received.

Photochemistry↗
PubMed1989

Facilitation of acquisition and retention in preweanling but not postweanling rats by the presence of familiar home-nest material.

A series of four experiments examined the effect of the presence of stimuli from the home nest on the acquisition and retention of aversively motivated behaviors in preweanling and adult rats. In Experiment 1, training in the presence of home-nest shavings facilitated acquisition of a T-maze discrimination to escape footshock for 16-day-old rats but not for adults. Experiment 2 demonstrated that the extent to which preweanlings were familiar with the home shavings determines the degree to which these stimuli facilitate spatial discrimination learning. When clean shavings were made more familiar than soiled home-nest stimuli (by changing the shavings every day) clean shavings enhanced discrimination performance, whereas no enhancement of learning by home shavings was observed. Experiment 3 extended the generality of the enhancement effect to a conditioned location aversion and examined the extent to which this facilitative effect was due to the tendency for home-nest shavings to elicit approach responses. Expression of the conditioned aversion was enhanced in subjects conditioned in the presence of home shavings, regardless of whether the home shavings were presented with the CS+, the CS-, or both. Experiment 4 determined that the enhanced expression of learning in the context of home-nest stimuli observed for preweanlings did not occur among subjects trained shortly after weaning. Collectively, these data suggest that whereas the enhancement of learning and retention by familiar home-nest stimuli enjoys generality across a number of conditioning situations, the effect may be limited to a relatively brief period during ontogeny.

Aging↗
PubMed1989

Enhanced malignant phenotype of urethane-induced lung adenoma associated with sialoadenectomy in BALB/c mice.

Mouse lung adenoma were induced in adult female BALB/c mice by chronic i.p. urethane injection. Sialoadenectomy of the mice prior to carcinogen treatment did not alter the frequency or size of lung adenoma. However, sialoadenectomized mice exhibited a decrease in the proportion (18 versus 52%) of tumours which exhibited a low nuclear to cytoplasmic ratio and which grew along alveolar septa. Sialoadenectomy was also related to a complementary increase in the proportion (82 versus 48%) of tumours with large vesicular nuclei, prominent nucleoli and generally increased phenotypic features of malignancy. Replacement of epidermal growth factor (EGF) in sialoadenectomized mice restored the tumour-type ratio observed in non-sialoadenectomized mice. These data are discussed with respect to the possible roles of EGF in mouse lung alveologenic carcinoma formation and the cell type of origin for the tumours observed.

Adenoma↗
PubMed1989

Identification of normal B-cell counterparts of neoplastic cells which secrete cold agglutinins of anti-I and anti-i specificity.

A monoclonal antibody, which recognizes a cross-reacting idiotypic determinant present on human cold-reactive autoantibodies with anti-I or anti-i binding activity, has been found to specifically inhibit the cold agglutination of red cells. This suggests that an epitope close to the binding site of such autoantibodies is being recognized. The antibody has been used to identify tumour cells in the blood of three patients with cold haemagglutinin disease, and to analyse the heterogeneous nature of the neoplastic B-cell clone present in the bone marrow of one of the patients. Using S-phase analysis, it was found that cell proliferation was occurring in the bone marrow but not in the blood, and that the major proliferating population was that of lymphoplasmacytoid cells containing large vesicular inclusions of idiotypic IgM. It has also been possible to locate normal B-cells which are recognized by the anti-idiotypic antibody. Such cells have been found throughout the normal adult lymphoid tissue where they account for 2.9-10.8% of the B lymphocyte population. They are also present in fetal spleen at 15 weeks gestation, indicating that immunoglobulins bearing this sequence form part of the immature B-cell repertoire.

Agglutinins↗
PubMed1989

Immunohistopathologic localization of Pseudomonas aeruginosa in lungs from patients with cystic fibrosis. Implications for the pathogenesis of progressive lung deterioration.

Despite studies of the pathologic and microbiologic aspects of the lung in cystic fibrosis (CF), there is a lack of information on the lung localization of bacterial pathogens. Bacteriologic data come from cultures of sputum or accessible lung effluent from bronchoscopy. Our objective was to localize Pseudomonas aeruginosa (PA) in situ in order to provide descriptive data on the relationship between the presence of PA and disease of the surrounding tissue. Using stored, uncut blocks of preserved lung, we deparaffinized, cut, mounted, and reacted them with high-titer rabbit sera made to a mucoid strain of PA. The tissues were then reacted with a second antibody, biotinylated goat antirabbit immunoglobulin, developed using a peroxidase technique and counterstained with hematoxylin. PA organisms stained with heavy brown deposits and this was species-specific. In five patients with CF chronically colonized with PA, the organisms could easily be localized in multiple sections. Microscopic study demonstrated that location was generally endobronchiolar and associated with bronchiolar obliterative changes, mainly in small (less than 1 mm) airways. Extraluminal PA organisms were rare even when there was chronic interstitial inflammation. This study demonstrated the presence of PA at the location where physiologic damage in CF is most severe--the small bronchioles--strengthening the association between PA and pulmonary deterioration in CF.

Adolescent↗
PubMed1989

Captopril-induced hypersensitivity lung disease. An immune-complex-mediated phenomenon.

Captopril has not yet been included in the list of drugs causing hypersensitivity lung disease. We report a patient with hypertension, congestive heart failure, and chronic renal failure who, when rechallenged with captopril, developed upper lung field infiltrates associated with productive cough and striking peripheral eosinophilia. Gallium scan, transbronchial biopsy histologic findings, and direct immunofluorescent study were consistent with an immune-complex-mediated hypersensitivity reaction. There was no other etiology discovered for the patient's eosinophilia, nor was there evidence for an infectious etiology to explain his presentation.

Aged↗
PubMed1989

Effects of hyperoxia on surfactant morphology and cell viability in organotypic cultures of fetal rat lung.

Effects of hyperoxia in an organotypic model consisting of well-differentiated fetal rat type 2 pneumocytes have been studied by light and electron microscopy. In cultures exposed to 50% oxygen for 48 h, hyperoxia caused necrosis of cultured lung cells derived from 18- to 19-day gestation fetal rats, less damage in cells derived from 20- to 21-day gestation fetal rats, and no detectable damage of cells derived from newborn rats. After exposure to hyperoxia in organotypic cultures cocultured with fibroblast monolayers, ultrastructural abnormalities of surfactant (large lamellar bodies with disordered lamellae and abnormal shape) were detected in cells from 18- to 19-day gestation fetuses. These abnormalities were not noted when fibroblast monolayers were absent. Fibroblast conditioned medium from fibroblasts exposed to hyperoxia did not cause significant surfactant abnormalities at the ultrastructural level. These changes were less marked in cultures incubated with glutathione's constituent amino acids and with ascorbic acid during exposure to hyperoxia, and in cultures pretreated with dexamethasone (20 nM) before exposure to hyperoxia.

Animals↗
PubMed1989

Emergence of neoplastic transformants spontaneously or after exposure to N-methyl-N'-nitro-N-nitrosoguanidine in populations of rat liver epithelial cells cultured under selective and nonselective conditions.

Many studies have shown that cultured rat liver epithelial cells can be neoplastically transformed by repeated or long-continued exposure to chemical carcinogens. These cells also may transform spontaneously in the absence of carcinogen treatment after long-term, continuous passage in culture or after chronic maintenance in a confluent state in vitro. In this study, we have compared the times of emergence and rates of accumulation of transformed cells in populations of rat hepatic epithelial cells exposed either to a single dose of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG, 3 micrograms/ml culture medium for 30 minutes) or to acetone vehicle alone (3 microliters/ml culture medium for 30 minutes). Transformation was compared in cell populations that were passaged continuously once a week as they attained a confluent density (nonselective growth conditions), or that were maintained at a confluent density for 3 weeks between passages once a month (selective growth conditions). Emergence of both spontaneous transformants and transformants induced by MNNG was facilitated by selective growth conditions, as compared with non-selective growth conditions. Transformants were detected both in cultures exposed to MNNG and in cultures exposed only to acetone (solvent controls), but they always emerged earlier in cultures exposed to MNNG (nine population doublings earlier when grown under selective growth conditions and 22 population doublings earlier when grown under nonselective growth conditions). Once transformants were detected, they replaced the nontransformed population more quickly under selective than under nonselective conditions of culture. Cells possessing the ability to grow in soft agar and to produce tumors in syngeneic rats were detected (at about 12 population doublings after treatment) under selective conditions much earlier than under nonselective growth conditions (at about 90 population doublings after treatment). Among MNNG-treated cultures, the fraction of aneuploid cells in the population was correlated significantly with tumorigenicity. In contrast, among acetone-treated control populations, aneuploidy and tumorigenicity were not correlated; populations of aneuploid acetone-treated cells often were not tumorigenic. These observations suggest that MNNG treatment produced a specific type of aneuploidy that was associated with tumorigenicity.

Animals↗
PubMed1989

Cell cycle perturbation and cell death after exposure of a human lymphoblastoid cell strain to N-methyl-N'-nitro-N-nitrosoguanidine.

The mechanisms involved in cell death caused by carcinogens that methylate DNA are poorly understood. In this study, the cytotoxicity of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) was studied in exponentially growing T5-1 human lymphoblastoid cells. MNNG exposure killed cells and inhibited proliferation of the remaining viable cells. Reduction in cell viability, which coincided with the accumulation of cells in the late S phase of the cell cycle, was not apparent until the population had completed one doubling. Fluorescence-activated cell sorting of fluorescein diacetate-stained, MNNG-treated cells into live and dead subpopulations revealed that all cycle phases were well represented in the live fraction, whereas the dead fraction consisted primarily of cells with a sub-G1 DNA content. Thus, cell death after MNNG exposure occurred during the second cell cycle after treatment apparently as a consequence of perturbation of DNA replication and the degradation of nuclear DNA.

Cell Cycle↗
PubMed1988

Induction of foci of morphologically transformed cells in synchronized populations of 10T1/2 cells by N-methyl-N'-nitro-N-nitrosoguanidine and the effect of spontaneous transformation on calculated transformation frequency.

Exposure of synchronized C3H10T1/2 (clone 8) cell populations of various sizes to N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) at a concentration of 2 micrograms/ml for 30 min at 24 h after release from confluence-induced arrest of proliferation produced neoplastic transformation (formation of foci of morphologically altered cells) by a random but episodic process in a small fraction of the cells at risk soon after treatment. The fraction of dishes that contained type II or type III foci increased as the number of cells at risk increased. In contrast, the development of spontaneous foci is a stochastic process that depends on the number of new cells that form during population growth and is independent of the number of cells that are plated (J. W. Grisham et al., Cancer Res., 48: 5969-5976,1988). When there were small numbers of cells at risk, spontaneous formation of foci was a source of considerable error in evaluating MNNG-induced transformation frequency. In surviving cell populations of less than 1000-3000 cells/100-mm dish, the frequency of induction of foci by MNNG could not be distinguished statistically from the frequency with which foci were expected to form spontaneously. When the fraction of MNNG-treated dishes that contained foci was adjusted for the fraction of pooled control dishes that contained foci, the number of foci induced by a uniform dose of MNNG was found to vary with the number of surviving cells. However, the MNNG-induced transformation frequencies calculated by the Poisson method were independent of the size of the population of cells at risk, provided the population of cells at risk was of sufficient size to allow spontaneous and induced transformation to be distinguished statistically. The results of this study show that the frequency of MNNG-induced transformation can be quantitated in cultures of 10T1/2 cells that contain varying but sufficient numbers of cells at risk when spontaneous transformation is considered. Furthermore, these observations suggest that MNNG-induced transformation of 10T1/2 cells occurs with the frequency and characteristics of a mutation-like change involving a single gene.

Animals↗
PubMed1988

Spontaneous formation of foci of morphologically transformed cells in populations of C3H 10T1/2 (clone 8) cells.

Spontaneous formation of morphologically altered foci of types II and III (neoplastic transformation) was examined in populations of C3H 10T1/2 (10T1/2) cells. Initial surviving cell densities ranged from 3 to 3 x 10(5) cells/100-mm dish and the final cell density was approximately 2 x 10(6) cells/dish, yielding widely differing numbers of population doublings but similar numbers of cell births from the time of cell plating to the attainment of confluence. Spontaneous formation of foci was independent of the initial surviving cell densities (and, therefore, of the number of population doublings) but was related to the number of cell divisions (cell births) between the time the cell population was plated and when suppression of proliferation of wild-type cells occurred in confluent cultures. In 418 pooled asynchronously proliferating cultures in 100-mm dishes the 95% confidence limits for the fraction of dishes containing foci was 0.041-0.089 for type II foci and 0.008-0.036 for type III foci; for cell populations in 2041 pooled cultures in 100-mm dishes, the proliferation of which was synchronized by release from confluence-induced arrest of proliferation, the 95% confidence limits for the fraction of dishes containing foci were 0.150-0.166 for type II foci and 0.017-0.032 for type III foci. Using the Poisson method, the 95% confidence limits for rates of spontaneous transformation in asynchronously proliferating populations of 10T1/2 cells were 1.4-3.2 x 10(-8)/cell/division for type II foci and 0.28 to 1.3 x 10(-8)/cell/division for type III foci; in populations in which proliferation was initially synchronized by release from confluence-induced arrest, spontaneous transformation rates were 5.6-6.3 x 10(-8)/cell/division for type II foci and 0.59-1.1 x 10(-8)/cell/division for type III foci. Spontaneous transformation occurred in populations of wild-type 10T1/2 cells at the rates and with the characteristics expected of the mutation of a single gene locus.

Animals↗
PubMed1988

Expression of fibronectin on clonally related transformed and control sublines from an epithelial cell strain and a tumor line of mouse alveolus.

The cellular expression of fibronectin and the importance of fibronectin for the morphology of cultured cells were studied in a lung epithelial cell system. The cells used were clonally related control NAL1A, spontaneously transformed NAL1AS cells of the NAL1A cell strain, and transformed clonal sublines of the cell line NAL1AM and the tumor cell line NUL1. Fibronectin was detected on the surface of NAL1A cells by surface iodination; fibronectin synthesis, secretion, and pericellular accumulation were detected in each of the control sublines by immunoblot assay, immunoprecipitation of metabolically labeled cell extracts and conditioned medium, and was confirmed by immunofluorescence microscopy. Fibronectin synthesis, secretion, or accumulation could not be detected by these methods in NAL1AS and NAL1AM sublines, or the sublines of NUL1. The control NAL1A cells showed enhanced cell spreading on culture substrata of fibronectin or extracellular matrix from bovine endothelial cells, as compared to plastic. The transformed NAL1AS and NAL1AM cells had the same cell shape when cultured on the three different substrata. For these cultured epithelial cells, cellular fibronectin expression and sensitivity to the presence of adhesive glycoproteins in the culture substrata are seen in the control, anchorage-dependent cells, but the transformed cells appear not to express fibronectin and to have a cell shape that is unaffected by the nature of the culture substratum.

Animals↗