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Biomedical subjects

J E Craighead

Publications and source records attributed to J E Craighead.

At least 55 records · Page 3Linked to original sources
PubMed1983

Encephalomyocarditis virus induced diabetes mellitus in mice: long-term changes in the structure and function of islets of Langerhans.

Adult male mice infected with the M variant of encephalomyocarditis virus develop hyperglycaemia acutely as a consequence of B cell injury. The severity of the metabolic disease is variable and many animals become normoglycaemic during convalescence. The islets of Langerhans of these mice exhibit minor structural changes, but there are no significant abnormalities of insulin and glucagon secretion. In contrast, animals with persistent hyperglycaemia exhibit striking morphological alterations in the islets. The A cell mass is prominent, whereas B cells are reduced in number and exhibit striking cytological features. These changes are associated with both hypoinsulinaemia and hyperglucagonaemia.

Animals↗
PubMed1983

Effect of interferon on encephalomyocarditis virus infection of cultured mouse pancreatic B cells.

The M variant of encephalomyocarditis virus (EMC) produces a disease similar to human insulin-dependent diabetes mellitus in some but not all strains of mice. This diabetogenic M variant was found to induce fivefold more interferon than non-diabetogenic strains of EMC in cultures of mouse L 929 fibroblasts. When interferon induced by the M variant was added to monolayers of B cells from both diabetes-'susceptible' CD-1 mice and 'resistant' C57 bl/6 mice before EMC infection, B cell damage and virus replication were delayed. In addition, viral production in B cell cultures from C57 bl/6 mice was reduced five- to tenfold. A similar effect was not found when cultures from CD-1 mice were treated with interferon. Thus, interferon might play an important role in modulating the severity of the initial infection of B cells.

Animals↗
PubMed1983

Use of pancreatic beta cells in culture to identify diabetogenic N-nitroso compounds.

Epidemiological observations suggest that environmental factors play a role in the pathogenesis of insulin dependent diabetes mellitus (1). Several chemicals have been identified as specific beta cell toxins (2-4). We report here studies to determine the feasibility of using monolayer cultures of pancreatic beta cells from neonatal rat to screen potential diabetogenic chemicals. Cytotoxicity was monitored both by phase microscopy and the release of insulin into the culture medium. In comparative studies, cellular protein and release of 51chromium (51Cr) were measured after addition of test compounds to cultures of fibroblasts derived from pancreatic tissue. The nitrosoamides 1 methyl-l-nitrosourea (MNU), 1,3 bis (2-choroethyl) nitrosourea (BCNU), chlorozotocin (CLZ), and the beta cell toxin, streptozotocin (SZ), were examined. CLZ and SZ were more toxic to pancreatic beta cells than to fibroblasts. In contrast, MNU and BCNU damaged both beta cells and fibroblasts at identical concentrations. These results suggest that in vitro techniques can be used to identify chemicals that selectively injure beta cells. Although SZ-induced toxicity was ameliorated with addition of nicotinamide to cultures of beta cells, nicotinamide did not prevent damage caused by CLZ. This observation indicates different mechanisms of drug-induced cytotoxicity.

Animals↗
PubMed1983

Interaction of asbestos with metaplastic squamous epithelium developing in organ cultures of hamster trachea.

The normal mucociliary epithelium of the respiratory tract in chronic cigarette smokers often is replaced focally by a metaplastic squamous epithelium. Because asbestos workers who smoke have a substantially greater risk of bronchogenic carcinoma than nonsmokers, we hypothesized that interaction of asbestos with squamous epithelium might be a contributing factor. To address this question, an in vitro model was developed to study the interaction of asbestos with both mucociliary and squamous epithelium. Explants of tracheas from hamsters were cultured in either a chemically defined minimal essential medium, which maintains a differentiated epithelium, or a nutritionally complex medium, which encourages the development of squamous metaplasia. Scanning electron microscopy (SEM) was used to measure quantitatively the development of a squamous epithelial surface on the explants. The interaction of chrysotile and crocidolite asbestos with cells of the mucociliary and squamous epithelium was studied using both SEM and transmission electron microscopy (TEM). Long fibers of asbestos were cleared, whereas shorter fibers were phagocytized by cells of the mucociliary epithelium. In contrast, asbestos was phagocytized by superficial squamous cells regardless of fiber length, and fibers penetrated between intercellular junctions in the metaplastic epithelium. The relevance of these interactions to the induction of bronchogenic carcinoma is discussed.

Animals↗
PubMed1983

Squamous metaplasia of the respiratory tract. Possible pathogenic role in asbestos-associated bronchogenic carcinoma.

Asbestos workers who smoke have a substantially greater risk of developing bronchogenic carcinoma than nonsmokers. Squamous metaplasia often replaces the mucociliary epithelium in the respiratory tract of chronic users of cigarettes. As a result, clearance mechanisms are altered. Using both scanning and transmission electron microscopy, we examined the interaction of chrysotile and crocidolite asbestos with the metaplastic mucosa found in the bronchi of cigarette smokers and produced in cultures of hamster trachea by enriched, serum-free medium. After deposition on the squamous epithelium, both "long" and "short" fibers were either phagocytosed by, or moved between, the cells of the mucosa. The interaction of asbestos with the mucociliary epithelium differed. Most long fibers were cleared, whereas short fibers were taken up by the mucosa. The apparent increase in uptake of long asbestos fibers by the metaplastic squamous mucosa could contribute to the synergism between this unique mineral and cigarette smoke in the causation of bronchogenic neoplasms.

Animals↗
PubMed1983

Induction of squamous metaplasia in organ cultures of hamster trachea by naturally occurring and synthetic fibers.

Asbestos exhibits many properties of classical tumor promoters. These characteristics include the ability to stimulate proliferation and inhibit normal differentiation of cells. In organ cultures of trachea, crocidolite and amosite asbestos stimulate squamous metaplasia, a pathological process in which a rapidly proliferating squamous epithelium replaces the normal epithelium. We hypothesized that the induction of metaplasia depends upon the fibrous nature of asbestos. Accordingly, several naturally occurring and synthetic fibrous materials and their nonfibrous analogues were assessed for their ability to induce metaplastic changes in tracheal mucosa of the Syrian hamster. Exposure to both crocidolite asbestos and fiberglass resulted in significant increases (p less than 0.05) in squamous metaplasia over a range of dosages (1.0, 4.0, 16.0 mg/ml). Attapulgite (palygorskite) and both "long-" and "short-" fiber preparations of chrysotile asbestos had similar but less marked effects. Nonfibrous analogues of each material (riebeckite, antigorite, and glass particles) failed to produce metaplasia. Asbestos, and fibrous materials in general, appear to stimulate squamous metaplasia because of their fibrous geometry.

Animals↗
PubMed1982

Seasonal incidence of insulin-dependent diabetes (IDDM) in Massachusetts, 1964-1973.

A total of 1142 Massachusetts resident, insulin-dependent diabetics were identified from medical records of the Joslin Clinic. All patients were less than 21 years of age at onset and developed diabetes between 1 January, 1964 and 31 December, 1973. This group consisted of 598 males (52.4%) and 544 females (47.6%) with mean ages at onset (+/- SD) of 11.1 +/- 4.9 and 10.9 +/- 4.6 years respectively. The period between onset and diagnosis was less than two months in 634 cases (81.8%). A first degree family history was noted in 209 cases (18.3%), while an additional 689 cases (60.3%) had more distant relatives with diabetes. The seasonal distribution of onsets was examined in the total group, and in subgroups categorized by sex, type of onset, age of onset, and family history. Significant peaks were noted during the first six months (January-June) in the total group and in all subgroups except those less than five or greater than 14 years of age at onset. Maximum incidence occurred in either January or February. During the second six month period (July-December) strong peaks were noted only in females and in those with no family history. Maximum incidence occurred in late July and in August, respectively. Exceptionally pronounced seasonal variation was demonstrated in a subgroup of 129 diabetics less than 15 years of age with onsets less than two months prior to diagnosis, and with no family history. The distribution of year of onset, in this group, showed considerable variation which did not correlate with year to year fluctuations in the reported incidence of aseptic meningitis, rubeola or mumps.

Adolescent↗
PubMed1982

Legionnaires' pneumonia after aerosol exposure in guinea pigs and rats.

We developed an animal model of Legionnaires' pneumonia to permit study of aerosol infection, pathogenesis, and pulmonary host defense mechanisms in this disease. Guinea pigs and rats were exposed in a nose-only inhalation facility for 30 min to an aerosol of Burlington serogroup 1 Legionella pneumophila. Lungs contained 10(3) to 10(4) L. pneumophila immediately after exposure. Both guinea pigs and rats developed pneumonia, with 100% infectivity by microbiologic, histologic, and serologic criteria. Guinea pigs demonstrated illness, fever, and 56% mortality; rats showed little illness and 11% mortality. In both species, diffuse patchy pneumonitis coalesced and consolidated as the disease progressed. Aerosol challenge with 3H-L. pneumophila showed exponential growth of the bacteria in the lungs of both species. Guinea pigs and rats can be infected by aerosol exposure to L. pneumophila to produce a disease that closely simulates human Legionnaires' pneumonia. Rapid initial intrapulmonary growth suggests that resident lung defense mechanisms are quite ineffective against L. pneumophila, and that recruited or immunospecific defenses may be more critical in the outcome of infection. The difference in severity of illness between guinea pigs and rats may be exploited for different experimental designs.

Aerosols↗
PubMed1982

Metabolic and underlying causes of diabetes mellitus.

It is emphasized that animal models should be used to study specific genotypic or phenotypic expressions associated with diabetes rather than assuming a single animal model can reflect diverse forms of the human disease. Diabetic and normal animals are reviewed on the basis of their usefulness as models of genetic, viral, and chemically induced diabetes, including the often associated immune phenomena. Characteristics of spontaneously diabetic animals with and without obesity are also described with an emphasis on both genetics and metabolic derangements. Recommendations for future animal experimentation include: more longitudinal studies evaluating the role of sex, prenatal environment, diet, and viral or chemical attack on B-cell function; characterization of the immune phenomena associated with B-cell lesions (and insulitis) in diabetic and immunologically incompetent lines; clarification of relationships between obesity and islet-cell function with emphasis on the role of fuel metabolism, vitamins, and minerals; and, finally, the development of new models with specific genetic aberrations placed in normal or diabetic lines.

Alloxan↗
PubMed1982

Porcine tracheal goblet cell ultrastructure: a three-dimensional reconstruction.

In order to study specific anatomical relationships among organelles involved in the movement and secretion of mucin granules by airway epithelium, a three-dimensional replica of a single goblet cell from porcine trachea was constructed by means of transmission electron microscopy of serially prepared ultrathin sections. Many features of the goblet cell that could not be deduced from single planes of section were revealed. The cell is columnar in configuration. The cytoplasm contains not one, but several discrete clusters of mucin granules, each associated with a separate Golgi apparatus. Microtubules and microfilaments often are observed in close association with both mucin granules and coiled filamentous mitochondria, suggesting a role in the intracellular movement of these organelles. These morphological observations are in agreement with previous functional studies of airway mucin secretion, and elucidate further the cellular biology of airway mucosal goblet cells and the secretory process.

Animals↗
PubMed1982

"Hazardous" wastes of the clinical chemistry laboratory.

The authors of this article highlight recent government initiatives in the field of hazardous waste management, and present data on the hazardous wastes of a representative clinical chemistry laboratory. They cite a number of reasons why pathologists should begin addressing this issue, and hope that the results of the study will stimulate the much needed discussion.

Laboratories↗