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Biomedical subjects

G J Smith

Publications and source records attributed to G J Smith.

At least 145 records · Page 8Linked to original sources
PubMed1988

Mutagenic potency at the Na+/K+ ATPase locus correlates with cycle-dependent killing of 10T1/2 cells.

Perturbation of DNA replication by chemical-DNA adducts produced by exposure to mutagenic/carcinogenic chemicals results in mutagenic or cytotoxic damage in the DNA. Demonstration of a correlation between cell cycle dependency of cytotoxicity and point mutation at the Na+/K+ ATPase gene could suggest that the two consequences of chemical exposure are caused by the same damage in the template DNA and that both are mediated through DNA replication-associated mechanisms. N-methyl-N'-nitro-N-nitrosoguanidine, N-ethyl-N'-nitro-N-nitrosoguanidine, 4-nitroquinoline-1-oxide, and benzo(a)pyrene-trans-7,8-dihydrodiol-9,10-epoxide demonstrated cell cycle-related patterns of cytotoxicity in 10T1/2 cells, with maximal cell killing produced by exposure in early S phase, and were highly efficient mutagens of the Na+/K+ ATPase gene relative to their cytotoxic potential. In contrast, methyl methanesulfonate and N-acetoxy-N-2-fluorenylacetamide were maximally cytotoxic in cell populations exposed in early G1 phase and were weak mutagens of the Na+/K+ ATPase gene at comparable levels of cytotoxicity. These data suggest that mutagenic/carcinogenic chemicals that are effective at producing mutations by misreplication kill cells by a related mechanism that may be associated with the perturbation of DNA replication.

Animals↗
PubMed1988

Evaluation of the developmental toxicity of nicotine and cotinine with frog embryo teratogenesis assay: Xenopus.

The teratogenic potential of nicotine and a primary metabolite, cotinine, was examined with FETAX (Frog Embryo Teratogenesis Assay: Xenopus). Early embryos of Xenopus laevis were exposed for 96 hr to nicotine or cotinine in two separate static renewal tests of each compound without addition of the metabolic activation system (MAS). Two static renewal tests of nicotine with the MAS were also conducted. Addition of the MAS to nicotine reduced the LC50 from an average of 136 to 20 mg/L. However, the EC50 (malformation) was increased from 0.4 to 5.8 mg/L upon activation. The LC50 and EC50 values for cotinine averaged 4,340 and 720 mg/L, respectively. Based on mortality/malformation index values, growth end points, and the types and severity of the induced malformations, nicotine and cotinine scored as potential teratogens. Metabolism of nicotine to more polar metabolites increased the nicotine concentration required to induce terata. The results are indicative of the versatility of FETAX in developmental toxicity testing.

Animals↗
PubMed1988

A cell culture model of chemically and spontaneously derived mouse lung alveologenic carcinoma.

Malignant cell lines related to mouse lung alveologenic carcinoma have been established from urethane-induced tumors and after in vitro spontaneous transformation of preneoplastic cell lines. Both the chemically and spontaneously transformed cell lines formed invasive, poorly differentiated carcinomas with secondary lung deposits when implanted subcutaneously in immune-suppressed mice. They differed from the related preneoplastic cell line in coordinately exhibiting anchorage-independent growth, reduced epidermal growth factor receptor activity and absence of pericellular fibronectin. These data suggest that similar molecular events may occur in type 2 pneumocyte-related cells in order to generate mouse lung alveologenic adenomas and carcinomas by both spontaneous and chemical carcinogen induction mechanisms. A reduced level of pericellular fibronectin was also demonstrated in an in situ compressive urethane-induced mouse lung adenoma. Loss of pericellular fibronectin may therefore be an early and persistent phenotypic alteration during transformation to the alveologenic adenoma and carcinoma.

Adenoma↗
PubMed1988

Magnetic resonance, pathology and physiology of the BA1112 rhabdomyosarcoma in vivo.

We studied histology, findings on H-1 magnetic resonance (MR) imaging, and correlations of P-31 MR spectroscopy with microelectrode pH and pO2 measurements in the BA1112 rhabdomyosarcoma in WAG/Rij/Y rats. Intratumoral hemorrhage was a prominent feature on MR images and pathologic specimens. Eosinophilic necrosis could be seen microscopically but was not discernible on images. The peaks seen on P-31 MR spectra were similar to those reported in other tumors. The intratumoral pH was neutral despite low pO2 values and P-31 MR evidence for impaired metabolic status.

Animals↗
PubMed1988

Post-diction of suicide in a group of depressive patients.

Prediction of suicides was made on the basis of 99 psychiatric patients included in a study of anti-depressive therapy during 1961-63. These patients were followed up until 31 December 1984. Eight of them committed suicide. The prediction was based on two test methods, the Serial Colour-Word Test (CWT), which registers style of adaptation to a conflicting situation, and the Meta-Contrast Technique (MCT), where incongruous or threatening stimulation is introduced by degrees into neutral pictures and various defense misrepresentations of the threat are spotted. Both tests could predict suicide, but MCT was most successful. The sensitivity of the test was 0.80 and the specificity 0.75. The main risk symptom appeared to be depressive retardation together with lack of functional defensive structures.

Adult↗
PubMed1988

Use of a cross reacting anti-idiotype to identify normal counterparts of neoplastic cells.

We have established that 9G4, a cross reacting monoclonal anti-idiotype identifies an epitope close the binding site of anti-I cold agglutinins. 9G4 positive lymphocytes comprise around 5% of B cells and are widely represented in all lymphoid tissue. They may be detected in 15 week fetal spleen at the time of the earliest appearance of B cells and thus form part of the basic B cell repertoire. Such antibodies are derived largely from CD5 positive B cells. 9G4 is thus a useful tool to investigate the normal counterpart of the CLL cell.

Adult↗
PubMed1987

Malignant epithelial cell strains cultured from BALB/c mouse lung adenoma.

Urethane-induced lung adenomas from adult BALB/c mice were explanted onto a plastic substratum and cultured in order to establish the epithelial cell strain NUL1. The cell strain exhibited a polygonal morphology with high nuclear to cytoplasmic ratio and osmiophilic lamellar bodies characteristic of lung adenoma cells. A reproducible large and small cell heterogeneity was preserved despite multiple cell cloning. NUL1 was malignant at all passage numbers tested exhibiting anchorage-independent growth and subcutaneous formation of carcinomas in immune-suppressed mice. The cell strain was diploid at low passage numbers and became pseudo-diploid with increasing passages.

Adenoma↗
PubMed1987

Description and rationale of a new operation for chronic pancreatitis.

An operation is described that is useful in the management of patients with chronic pancreatitis and its complications. The operation features duodenal-preserving resection of the head of the pancreas combined with longitudinal pancreaticojejunostomy of the body and tail of the pancreas. The operation has application to patients with pain or complications of chronic pancreatitis with dilated ducts in the body and tail of the pancreas who have small strictured ducts and/or small pseudocysts or ducts impacted with calculi in a markedly enlarged fibrotic pancreatic head. It also has application to patients with chronic pancreatitis complicated by common duct obstruction from small pseudocysts, fibrosis, or inflammation in the head of the pancreas. With this procedure, the common duct can often be freed up from the structures compressing it within the substance of the pancreas doing away with the necessity of a separate biliary bypass. The operation also has application to patients with a previous longitudinal pancreaticojejunostomy who have recurrent or persistent pain associated with small strictured ducts in an enlarged fibrotic pancreatic head with or without common bile duct obstruction.

Adult↗
PubMed1987

Lymphokine-induced phenotypic changes in cells of a type 2 pneumocyte-related strain: characterization of activity in mitogen-stimulated spleen cell supernatants.

Supernatants from concanavalin A-stimulated spleen cells contain a factor which induces morphological alterations, inhibition of replication, and altered phospholipid biosynthesis in cells of a type 2 pneumocyte-related strain designated NAL 1A. This study has demonstrated that the active factor is generated by nonadherent spleen cells in the presence of supernatants from cultures of stimulated adherent cells. The active factor inhibits proliferation of NAL 1A cells in a dose-dependent fashion, exerts an irreversible effect following overnight exposure of these cells to stimulated supernatants, and appears to be continuously synthesized by stimulated spleen cells in culture. It is stable at pH 2 for 4 hours, does not bind to Blue Sepharose CL-6B, and exhibits molecular heterogeneity on gel filtration chromatography, with maximal activity recovered in fractions of molecular size 34,000 and 43,000. Comparable inhibition of growth was induced by exposure of NAL 1A cells to recombinant murine and human interleukin 2, as well as by recombinant murine interferon-gamma. These findings provide evidence for an interaction between type 2 pneumocytes and lymphokines such as interleukin-2 and interferon-gamma. The possible implications of a similar interaction occurring in vivo and its effects on type 2 pneumocyte morphology and function are discussed in the context of chronic interstitial inflammatory lung disease.

Animals↗
PubMed1987

Pulmonary tumor embolism: a critical review of clinical, imaging, and hemodynamic features.

Pulmonary tumor embolism is a common finding at autopsy but is generally perceived as a difficult diagnosis to make ante mortem. After a retrospective review of 164 reported cases of pulmonary tumor embolism, we identified a typical profile of clinical, laboratory, and imaging features that may permit confident clinical diagnosis in most patients with this condition. The clinical features include a documented or suspected underlying malignancy, acute to subacute onset of dyspnea, and signs of cor pulmonale. Supportive laboratory features are hypoxemia or increased alveolar-arterial oxygen gradient, and invasive or noninvasive evidence of pulmonary artery hypertension. Typical imaging findings are normal chest radiographs; multiple, subsegmental, peripheral perfusion defects on ventilation-perfusion lung scans; and delayed filling with or without subsegmental filling defects but without a thrombus on pulmonary angiogram. Radiolabeled monoclonal antibody imaging and pulmonary microvascular cytology sampling techniques are promising diagnostic tests for early diagnosis of pulmonary tumor embolism.

Adult↗
PubMed1987

Pulmonary response to atmospheric pollutants. 3. The role of pulmonary collapse in the induction of aberrations of the type 2 pneumocyte.

Type 2 pneumocyte responses were studied in the rat after experimental right apical lobe collapse induced by surgical occlusion of the apical bronchus. After initial degranulation, type 2 pneumocytes underwent proliferation, and exhibited large numbers of well formed and densely staining intracytoplasmic surfactant lamellar bodies. The proliferative response, which was diffuse in the initial 3 to 25 days, became focal by 50 days and thereafter subsided. These results are discussed in relationship to the responses of the type 2 pneumocyte to toxic injury as previously reported.

Air Pollutants↗
PubMed1986

Characterization of an alveolyn-like protein associated with mouse type 2 pneumocytes using immunochemical methods.

Delipidated proteins from a fraction of mouse lung homogenate enriched for lamellar bodies of type 2 pneumocytes were characterized by a combination of gel filtration and enzyme immunoassay for the presence of a surfactant-associated antigen. Immunoreactivity was associated with a protein of Mr 250-270,000 as well as its multimers and proteolytic fragments. The characteristics of the antigenic protein closely resembled those of a surfactant-associated protein termed alveolyn which is reported to be secreted by type 2 pneumocytes of various other species. Surfactant-associated proteins of M 32-38,000 in bronchoalveolar lavage fluid may be derived from this molecule by proteolysis.

Animals↗