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Biomedical subjects

J E Craighead

Publications and source records attributed to J E Craighead.

At least 37 records · Page 2Linked to original sources
PubMed1988

Chromosomal translocations with specific breakpoints in asbestos-induced rat mesotheliomas.

Cytogenetic analysis was conducted on cells of 15 rat mesotheliomas induced in rats by the i.p. inoculation of crocidolite or chrysotile asbestos. These tumor cells were diploid, triploid, or tetraploid. All tumor lines exhibited aneuploidy and marker chromosomes. Loss of at least one copy of the X chromosome was observed in each of the tumors analyzed, and loss of copies of chromosomes 8, 16, 20, or 18 characterized at least six of the tumors. Translocations were observed in 12 tumors, with six chromosome rearrangements present in at least two different tumors. However, the breakpoints were not always identical. On the other hand, translocations involving chromosomes 5, 10, and 13 exhibited repeated breakage at the same loci. Such specific and repetitive translocations may be involved in the process of asbestos-induced tumor development.

Aneuploidy↗
PubMed1988

1987 H. P. Smith award lecture. Eyes for the epidemiologist: the pathologist's role in shaping our understanding of the asbestos-associated diseases.

Asbestosis was first recognized as an entity at autopsy by a pathologist in 1900. Pathologists also discovered the unique relationship of mesothelioma and bronchogenic carcinoma with exposure to asbestos. The observations of preceding pathologists have provided insights that have served as the basis for epidemiologic studies associating asbestos with disease in humans.

Asbestos↗
PubMed1987

Intermediate filament proteins in asbestos-induced mesotheliomas of the rat.

Abdominal diffuse malignant mesotheliomas develop in rats administered asbestos by the intraperitoneal route. A latency period of 6 to 24 months precedes tumor development; the biological and morphological features of these tumors resemble mesotheliomas in humans. Using one- and two-dimensional gel electrophoresis and immunoblotting, rat mesotheliomas (n = 24) were shown to express two classes of intermediate filament (IF) proteins. The tumors contained both vimentin and at least one of six keratins (p40, Mr 40,000; Dm, Mr 50,000; p53, Mr 53,000; Bm, Mr 53,000; Cm, Mr 54,000; Am, Mr 54,000). Vimentin predominated in 15 of 16 tumors exhibiting either sarcomatous or mixed (epithelial and mesenchymal) appearance. One of eight mixed lesions and six of eight epithelial tumors had a complement of IF proteins in which cytokeratins predominated. A similar pattern has been reported in mesotheliomas in humans (Blobel et al., Am. J. Pathol. 121: 235, 1985). Epithelial tumors often contain comparable amounts of vimentin and low molecular weight cytokeratins, while vimentin is the most actively expressed IF protein in sarcomatous tumors. Thus, tumors induced by asbestos in the rat peritoneum express IF proteins in a manner that resembles human mesotheliomas, supporting the notion that these lesions are appropriate models of human mesothelioma.

Animals↗
PubMed1987

Helper-inducer T-lymphocytes mediate diabetes in EMC-infected BALB/c ByJ mice.

Diabetes mellitus developing in BALB/c ByJ mice infected with the M variant of encephalomyocarditis (EMC) virus is dependent on thymic immune mechanisms. We treated mice with the anti-T-lymphocyte monoclonal anti-L3T4 and anti-Lyt2.2 antibodies before virus inoculation and monitored the infection and occurrence of diabetes thereafter. Mice depleted of L3T4+ cells exhibited a reduced incidence and severity of diabetes compared with both untreated and anti-Lyt2.2-treated animals. All mice sustained pancreatic infections, but islet lesions with beta-cell degranulation only occurred in control infected and anti-Lyt2.2-treated animals. These data support the conclusion that the induction of diabetes in EMC-infected BALB/c mice is immune mediated and controlled by the L3T4 T-lymphocyte subpopulation.

Animals↗
PubMed1987

Characteristics of tumors and tumor cells cultured from experimental asbestos-induced mesotheliomas in rats.

Mesotheliomas developed in rats in the abdominal cavity 6-23 months after peritoneal introduction of chrysotile and crocidolite asbestos. The tumors were strikingly similar to those occurring in man both with regard to histologic features and growth patterns. The authors have cultured cells from these tumors and established epithelial lines with a variety of karyologic features and doubling times shorter than those of normal mesothelial cells. Lines of diploid or near-diploid tumor cells required serum in the medium to replicate, whereas most aneuploid cell lines were maintained in a serum-free medium. In serum-free medium, the aneuploid line monolayers produced anchorage-independent excrescent masses of cells which "bud" and float free. These spheroids, which strikingly resemble the papillary structures in human mesotheliomas, are composed of mesothelial-like cells that produce hyaluronic acid and have a rich complement of intermediate filaments, predominantly cytokeratins. Aneuploid cells also replicated in soft agar with high efficiency, whereas the diploid and near-diploid cells did not. All but one cultured cell line, regardless of karyotype, produced tumors after subcutaneous or intraperitoneal inoculation (or both). Aneuploid cells caused lung tumors sporadically when introduced intravenously. Comparative analysis of the nuclear DNA of primary tumors and cultured cells demonstrated a high degree of chromosomal instability and selection among cells during early passage in vitro.

Abdominal Neoplasms↗
PubMed1986

Contrasting features of T-lymphocyte-mediated diabetes in encephalomyocarditis virus-infected Balb/cBy and Balb/cCum mice.

Two closely related sublines of the Balb/c strain, Balb/cBy and Balb/cCum mice respond differently when inoculated with the diabetogenic M variant of the encephalomyocarditis (EMCM) virus. Although genetically similar, Balb/cBy mice develop severe hyperglycemia, whereas Balb/cCum animals exhibit only modest alterations in glucose tolerance. Virus concentrations in the pancreases of animals of both sublines are equivalent 3 days after inoculation and decrease rapidly to undetectable levels within 10 days, at a time when hyperglycemia in Balb/cBy mice peaks. These results support two conclusions: 1) direct virus-induced injury to the beta cells probably is not responsible for hyperglycemia in Balb/c mice, and 2) virus replication in the pancreas does not predict diabetes susceptibility. Diabetes in Balb/cBy mice is immunologically mediated. These animals generate cytolytic T lymphocytes specific for beta cells during periods corresponding to glucose intolerance, and anti-thymocyte serum treatment of infected mice prevents the development of hyperglycemia. The pathogenesis of diabetes in Balb/cCum mice is not clear. Although cytolytic T cells appear concomitant with glucose intolerance, anti-thymocyte serum has not consistently prevented the development of the metabolic disease.

Animals↗
PubMed1985

Genetic influences on the immunologic pathogenesis of encephalomyocarditis (EMC) virus-induced diabetes mellitus.

DBA/2 and Balb/cBY mice were infected with approximately 30 plaque-forming units of the M-variant of encephalomyocarditis (EMC-M) virus. Seven days after inoculation the majority of the animals of both strains were hyperglycemic. A significant correlation between increased concentrations of virus in the pancreas and hyperglycemia was found among individual DBA/2 animals, but not among Balb/cBY mice. T-lymphocyte depletion of DBA/2 mice before infection failed to alter the incidence or severity of hyperglycemia in comparison to intact animals. Conversely, hyperglycemia in T-lymphocyte-depleted Balb/cBY mice was reduced substantially in comparison to infected immunocompetent animals. There appears to be at least two genetically influenced pathogenic mechanisms of diabetes in EMC-M virus-infected mice. In some strains of animals, hyperglycemia results exclusively from viral infection and the consequent injury to the beta cells, whereas in other animals, viral damage to the islets is compounded by immunologic events.

Animals↗
PubMed1985

Chlorozocin. A diabetogenic analogue of streptozocin with dissimilar mechanisms of action on pancreatic beta cells.

Chlorozotocin (chlorozocin, CLZ), the 2-chloroethyl analogue of streptozocin (STZ), was evaluated in three species of rodents. The drug is currently being used in phase II chemotherapeutic trials in man, and appears to be effective in the treatment of certain tumors. In our studies, hyperglycemia was induced in hamsters as early as 2 days after a single intraperitoneal (i.p.) injection of 30-60 mg/kg and was most striking at 4 days. Greater concentrations of CLZ (greater than or equal to 50 mg/kg) were required to produce hyperglycemia in CD-1 mice. Degranulation and necrosis of beta cells developed in hamsters and mice, whereas alpha and acinar cells of the pancreas revealed no morphologic changes. Hyperglycemia was not induced in rats at any concentration tested; however, animals showed abnormal carbohydrate tolerance after administration of 100 mg/kg CLZ (LD50 dosage). The nature of damage by CLZ to beta cells was investigated both in vivo and in vitro. Pretreatment of hamsters with nicotinamide (500 mg/kg, i.p.) failed to alter the extent of CLZ-induced beta cell injury and associated hyperglycemia, but decreased the amount of beta cell necrosis and hyperglycemia in animals receiving STZ. The nonmetabolizable sugar, 3-O-methylglucose (3-O-MG), and 3-aminobenzamide, an inhibitor of the nuclear enzyme, polyADPribose synthetase, prevented STZ-associated damage to beta cells in islet cell cultures, but only 3-O-MG reduced CLZ-induced toxicity. Thus, in comparison to STZ, CLZ appears to be a diabetogenic agent with different species specificity and alternative mechanisms of cytotoxicity. The glucose moiety of both drugs appears critical in the induction of beta cell damage.

3-O-Methylglucose↗
PubMed1984

Interaction of Mount St. Helens' volcanic ash with cells of the respiratory epithelium.

Respirable-sized dust from the Mount St. Helens (MSH) eruption of Spring 1980, and minerals similar to the major components of the volcanic ash, were examined comparatively for interactions with epithelial cells of rodent respiratory airways in vitro. MSH dust, Na feldspar, cristobalite, and alpha-quartz, in concentrations of 0.4 to 40 mg/ml, had neither significant effects on mucin release by tracheal explants nor acute toxic effects after exposure for 2 hr. Long-term incubation (1 and 3 weeks) of explants after a 1-hr exposure to MSH dust failed to elicit widespread toxic or proliferative changes in airway epithelial cells. In contrast, long-term exposure to Na feldspar, cristobalite, and alpha-quartz caused significant toxicity to the explants, although metaplastic changes were not observed. Ultrastructural evidence of associations (e.g., phagocytosis) between particulates and respiratory epithelium was not observed. The results of these studies suggest that volcanic ash from MSH interacts minimally with cells of the respiratory mucosa.

Animals↗
PubMed1983

Stimulatory effect of Pseudomonas aeruginosa on mucin secretion by the respiratory epithelium.

Cell-free filtrates of broth cultures from 11 of 18 strains of Pseudomonas aeruginosa isolated from patients with cystic fibrosis (CF) (or from patients without CF) increased substantially the secretion of mucin by explants of trachea from guinea pigs and human tracheal tissue obtained at autopsy. The effect was not related to the mucoid nature of the isolates, was not destroyed by heating at 90 degrees C for 30 minutes, and was not dependent on serotype. As P aeruginosa commonly infects the respiratory tracts of persons with CF, elaboration of an extracellular product that stimulates mucin secretion could play a role in the pathogenesis of the disease in the airways.

Animals↗