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Biomedical subjects

J E Craighead

Publications and source records attributed to J E Craighead.

At least 73 records · Page 4Linked to original sources

Legionnaires' pneumonia after intratracheal inoculation of guinea pigs and rats.

We have developed a model of legionnaires' pneumonia in guinea pigs and rats. A reproducible population of Legionella pneumophila was obtained in late exponential growth phase and inoculated into the trachea of young animals. Either immunologic or microbiologic evidence of infection was demonstrated in 27 or 28 guinea pigs and 19 of 20 rats that had been inoculated with 10(5) to 10(7) colony-forming units. An acute pneumonia that resembled human legionnaires' disease was produced in both species, and Legionella antigen was closely related to inflammation in the distal air spaces. A fatal illness was produced in guinea pigs, and pneumonia was more extensive than in rats. Extrapulmonary inflammatory lesions, particularly splenic necrosis, were more frequent in guinea pigs than in rats. Each rodent species has potential advantages for testing specific questions and both should be useful for future investigations.

Animals↗

Viral diabetes mellitus in man and experimental animals.

Accumulating evidence strongly suggests that viruses may play an etiologic role in some cases of diabetes mellitus. The importance of environmental factors in the pathogenesis of the disease is suggested by genetic and epidemiological observations. Group B Coxsackie viruses and mumps virus have been implicated, and the evidence suggests that several other agents also could play a role in the disease. In experimental animals, a picornavirus similar to the Coxsackie viruses exhibits specific tropism for the beta cells of the islets of Langerhans, causing a disease in mice that is similar to juvenile-onset diabetes. In these animals, genetic and metabolic factors appear to influence the severity of beta cell injury. Immunopathologic considerations also may be important. In man, histocompatibility genes are important determinants of juvenile-onset diabetes and abberations of immune responsiveness to beta cells have been demonstrated. In experimental animals, cell-mediated immunity develops subsequent to the occurrence of viral-induced lesions in the islets. Viewed in concert, the evidence supports the notion that certain "wild" viruses may possess specific tropism for beta cells and destroy them during the course of a systemic infection. Host factors clearly play a role, but their relative importance in the pathogenesis of the disease remains to be defined.

Animals↗

Giant cell pneumonia associated with parainfluenza virus type 3 infection.

Giant cell pneumonia associated with parainfluenza virus type 3 infection and chronic poliovirus type 2 meningoencephalomyelitis are documented in an infant with combined immunologic deficiency (Swiss type). Caution should be exercised in attributing cases of giant cell pneumonia to measles virus without serologic or virologic evidence.

Humans↗

Pulmonary pathology in workers exposed to nonasbestiform talc.

We studied pulmonary tissue from seven men employed in the mining and milling of talc that contained minimal amounts of crystalline silica and asbestiform minerals. The lungs exhibited varying degrees of fibrosis, located either adjacent to the vessels and bronchi or diffusely. Semiquantitative estimations of talc in the lung tissue indicated that the extent of the pulmonary lesions corresponded to its concentration in the tissue. Histopathologic findings were evaluated with regard to duration of occupational exposure and radiographic changes in the chest. In three of the seven workers with exposures of 26, 27, and 27 years chest roentgenographic changes were consistent with pneumoconiosis. The lung tissues from four other patients with exposure histories of four, five, 13, and 19 years exhibited focal and diffuse fibrosis with accumulations of talc, but the chest x-ray films were negative. Crystallographic studies of digestates of lung tissue indicated that the talc contained few mineral impurities. An increase in dust load in the lungs was associated with duration of employment.

Adult↗

Effect of genetic obesity in mice on the induction of diabetes by encephalomyocarditis virus.

The "M" variant of the encephalomyocarditis (EMC) virus causes a diabetes-like disease in some, but not all, strains of mice. The genetic basis for either resistance or susceptibility to the diabetogenic effect of the virus is not known. After infection with EMC, C57BL/6 mice seldom develop hyperglycemia and the insular lesions are subtle. To explore the possible effects of metabolic influences on the viral susceptibility of the islets, we studied C57BL/6 mice that were carriers of the ob gene. After virus inoculation, obese homozygous C57BL/6-ob/ob mice consistently developed hyperglycemia during the acute stages of infection, whereas nonobese littermates did not. Infection induced more severe lesions in the pancreatic islets of obese mice than in islets of the lean littermates. These studies suggest that the functional activity of the beta-cells influences the severity of the viral injury to the beta-cell, and the consequent occurrence of diabetes.

Animals↗

Effect of cholera toxin on secretion of mucin by explants of guinea pig trachea.

Cholera toxin (CT) elicits a dosage-dependent increase in mucin secretion by explants of guinea pig trachea. Concomitantly, the mucin in goblet cells of the mucosa and submucosal glands is depleted. This effect is realized in the absence of cell injury, as assessed morphologically and by the assay of culture medium for the release of acid phosphatase. Mucosal concentrations of cyclic AMP increase after exposure to CT. However, the stimulatory effects on secretion appear to be independent of the cyclic nucleotide, as exogenous dibutyryl cyclic AMP and cyclic GMP fail to increase secretion, and theophylline, a phosphodiesterase inhibitor, also is ineffective. The stimulatory effect of CT is decreased by preincubation of the explants with inhibitors of microtubules (nocodazole) and microfilaments (cytochalasin D) in a dosage-dependent manner. Addition of the calcium chelator, ethylene glycol bis(beta-aminoethyl ether)-N,N'-tetraacetic acid, with CT also inhibits the secretory response. CT appears to stimulate mucin secretion by tracheal epithelial cells by a mechanism independent of cyclic nucleotide activation but requires intact microtubules, microfilaments, and exogenous calcium ions.

Animals↗

Actin-containing cells in human pulmonary fibrosis.

Lung tissue from five patients with varying degrees of diffuse pulmonary fibrosis was examined for the presence of nonmuscle cells containing the contractile protein actin. Histochemical studies using light- and electron-microscopic techniques suggested that the fibrotic tissue, in areas lacking smooth muscle, had within it numerous cells with cytoplasmic microfilaments composed of actin. Similar cells rarely were observed in control lung tissue. The orientation of these cells within the parenchyma, as well as the arrangement and density of the filaments in the cell, suggests a contractile function. Cells with contractile properties might play a role in the altered dynamics of the lung in diffuse fibrotic pulmonary disease.

Actins↗

Asbestos-induced epithelial changes in organ cultures of hamster trachea: inhibition by retinyl methyl ether.

The epithelium of the hamster trachea in organ culture undergoes hyperplasia and squamous metaplasia after exposure to the amphibole types of asbestos, crocidolite and amosite. These changes are inhibited when the synthetic vitamin A analog, retinyl methyl ether, is incorporated into the culture medium. These findings suggest a possible use for retinoids in the prevention and treatment of respiratory tract disease associated with environmental exposure to asbestos.

Animals↗

Testosterone effect on experimental diabetes mellitus in encephalomyocarditis (EMC) virus infected mice.

A diabetes mellitus-like disease occurs in male DBA/2 mice infected with the M variant of the encephalomyocarditis virus. Female mice of this strain sustain systemic infection, but rarely exhibit hyperglycaemia. The diabetogenic effects of the virus were studied in 3 groups of adult DBA/2 males-castrates, castrates treated with testosterone, and sham-operated controls. After infection, pancreatic insulin concentrations decreased precipitously to approximately 10% of control values in intact males and castrates treated with testosterone; hyperglycaemia occurred concomitantly in both groups. In contrast, untreated castrates failed to develop hyperglycaemia and the effect on the insulin content of the pancreas was less striking.

Animals↗

Exfoliation of respiratory epithelium in hamster tracheal organ cultures infected with Mycoplasma pneumoniae.

Hamster tracheal organ cultures were infected with M. pneumoniae and examined sequentially by transmission and scanning electron microscopy to correlate surface with intracellular alterations. Infection was established by culture and the demonstration of morphologically compatible organisms on the mucosal surface. Ciliated epithelial cells developed vacuolization of the apical and subnuclear cytoplasm and eventually fragmented along planes formed by coalescing vacuoles. Non-ciliated cells showed apical swelling and loss of microvilli during the course of infection. After degeneration and sloughing of both ciliated and non-ciliated cells, a flattened layer of intact basal cells covered the submucosa. It is likely that progressive vacuolization of epithelial cells leads to exfoliation of both cells and cell fragments in M. pneumoniae infection. Since organisms frequently are associated with these exfoliated cells, their potential presence in sputum and lavage specimens could prove to be of diagnostic importance.

Animals↗

Comparative studies on the cytotoxicity of amphibole and serpentine asbestos.

The chemical and physical properties of serpentine and amphibole asbestos are considered in the context of their interaction with tissue of the tracheobronchial tree and lungs. In vitro studies in cultures of several types are evaluated and work with the erythrocyte hemolysis system is reviewed. Although fibers of the two major mineral types differ substantially, it is likely they are modified by secretions and membranes of cells after inhalation to the respiratory tract. Investigations using virgin asbestos might not provide an accurate picture of events in vitro.

Animals↗

Isolation and spontaneous transformation of cloned lines of hamster tracheal epithelial cells.

In respiratory carcinogenesis studies using rodents, the tracheal epithelium is the target tissue for the induction of tumors after exposure of animals to chemical carcinogens. In the studies described below, tracheal epithelial cells were isolated to evaluate their biological and biochemical features. Epithelial cells derived from the tracheal mucosa of Syrian golden hamsters were established in culture. Three morphological types of polygonal cells were observed as mixed populations in four clonally derived lines. One type of cell is mucin secreting since membrane-bound vesicles that stain positively using the alcian blue:periodic acid-Schiff reaction are present in the cytoplasm and increased amounts of mucin constituents are demonstrable in the culture medium. Cells of a second type possess both intracytoplasmic and surface cilia, but they lack mucin vesicles. The third type exhibits no differentiating features. Four density-dependent inhibited cloned cell lines were established. After repeated passage, these cells: (a) grew in soft agar; (b) released proteases that were activators of plasminogen; (c) demonstrated measurable basal and inducible aryl hydrocarbon hydroxylase activity; and (d) produced anaplastic carcinomas in syngeneic hamsters. Factors affecting the transformation and differentiation of respiratory epithelial cells have not been elucidated. The availability of these cell lines will permit studies that focus on these questions.

Animals↗

Fatal massive hepatic necrosis from varicella-zoster hepatitis.

An unusual case of varicella-zoster hepatitis is reported which resulted in fatal massive hepatic necrosis in a 64-year old white female. The patient had had chickenpox 30 years prior to death but no cutaneous zoster at any time. The liver showed typical eosinophilic intranuclear inclusions and herpesvirus virions were demonstrated by electron microscopy. Indirect immunofluorescent serologic studies confirmed remote and recent infection by varicella-zoster virus. The potential significance of an incidental splenectomy performed 14 months before death and the general role of immunosuppression in the incidence and dissemination of varicella-zoster are discussed. The features of 13 reported cases of herpes simplex hepatitis are briefly reviewed.

Female↗