PubMed HealthSearch

Biomedical subjects

B McCullough

Publications and source records attributed to B McCullough.

At least 19 recordsLinked to original sources

Fetal infection of the baboon (Papio cynocephalus) with lymphocytic choriomeningitis virus.

Recent observations of LCM-induced fetal damage in humans suggested attempts to develop an animal model for studies on viral congenital malformations. We report herein viral studies on three pregnant baboons (Papio cynocephalus) inoculated subcutaneously with LCM virus strain WE3. The first animal, inoculated in the 9th week of pregnancy, aborted 9 days after a high virus dose. Inoculation of the second baboon during a later stage (23rd week) of pregnancy with a moderate virus dose, resulted in the demonstration of virus in the placenta, amniotic fluid, and cord blood. The infant showed only a slight pleocytosis of the spinal fluid, but no virus shedding and no late sequelae. The third baboon inoculated with a high virus dose during the 21st week of pregnancy delivered an underweight, icteric infant that succumbed on the 6th day. All organs of this animal that were tested contained virus. Microscopic examination of these tissues revealed multifocal necrosis, cerebral glial nodules, meningitis, and bilateral choriovasculitis. These results illustrate that fetal damage observed in the LCM-inoculate baboon resembles that seen in humans following infection with LCM virus.

Animals

Lung elasticity in regional and diffuse pulmonary fibrosis.

Static deflation air and saline pressure-volume (PV) curves were performed on five normal excised baboon lungs, four with radiation-induced upper lobe fibrosis, and two with diffuse bleomycin-induced fibrosis. Curves were compared visually and using half-inflation pressures (h). When plotted as percent of observed vital capacity vs. transpulmonary pressure, the radiation-associated curves were similar in shape to control curves. Also, h values were not significantly different between the two groups. The bleomycin-associated curves, however, were shifted rightward and exhibited increased h values. PV curves were correlated with connective tissue data. Elastin concentration was increased in the irradiated upper lobes through loss of associated constituents. Elastin accumulated in the lower lobes of the irradiated animals through compensatory growth and in the bleomycin-associated lungs through excessive production. Collagen followed a similar but less dramatic trend. We conclude connective tissue accumulation may not lead to rightward shifted PV curves if accumulation is present in relatively noninflatable lung units, or as part of compensatory lung growth.

Animals

A rat model of chronic respiratory infection with Pseudomonas aeruginosa.

Chronic, nonlethal, pulmonary infection of rats by Pseudomonas aeruginosa can be initiated by intratracheal inoculation of 10(4) bacteria enmeshed in agar beads. The number of bacteria recoverable from the lung increased to approximately 10(6) within 3 days and remained at that number during 35 days of observation. Histologic examination of the infected lungs revealed lesions resembling those seen in lung tissue of humans with acute or chronic nonbacteremic, Pseudomonas aeruginosa pneumonia, including the presence of goblet-cell hyperplasia, focal areas of necrosis, and acute and chronic inflammatory infiltrate. This model should be useful for investigating the interactions between microbial virulence factors and host defense mechanisms.

Animals

Total lung capacity of baboons and humans determined by planimetry of radiographs.

Total lung capacity and radiographic lung area of 25 young and 7 aged baboons (Papio cynocephalus) and seven nonsmoking young adult men were measured. For all subjects, total lung capacity and radiographic lung area raised to the 3/2 power were shown to be highly correlated (r = 0.995). The regression equation for this relationship was total lung capacity (ml) = 78 + 0.234 x radiographic lung area (1.5) (cm2). A more useful regression equation for predicting values of total lung capacity was found to be log total lung capacity = -0.3819 + 1.4153 x log radiographic lung area (r = 0.993), because the standard error of estimate remains a constant percentage of Y values (+/- 12%). Total lung capacity and radiographic lung area were also highly correlated with height, weight and arm span of young baboons and men (r greater than 0.92), but the lungs of aged baboons were disproportionately larger.

Adult

Bleomycin-induced diffuse interstitial pulmonary fibrosis in baboons.

Pulmonary fibrosis was induced in eight baboons with bleomycin; five untreated animals were controls. After 45-65 U/kg of bleomycin, lung volumes and diffusing capacity were reduced, and static lung pressure-volume curves were shifted to the right. Right middle lobes were resected at this time in five bleomycin-treated and two control animals. Compared to controls, right middle lobes from bleomycintreated animals had increased weight and contained increased amounts of total protein, collagen, elastin, and DNA; synthesis of collagen and noncollagen protein were also elevated. Occasional alveolar septae were edematous and infiltrated by mononuclear inflammatory cells; a slight increase in collagen was demonstrable histologically. Four of six treated animals died with extensive diffuse interstitial fibrosis after 95 U/kg of bleomycin. Biochemical analyses revealed significantly elevated lobar contents of dry weight, protein, elastin, and collagen. Two animals survived 95 U/kg of bleomycin and were terminated 6 mo after treatment. In these animals, physiologic studies were indicative of restrictive lung disease, but lung histology was nearly normal. Lung weight, total protein, and DNA had returned to control values, but collagen and elastin were increased in amount and concentration. Bleomycin induces an intense inflammatory response in the lung. During this inflammation, connective tissue proliferation occurs in concert with proliferation of other tissue components. Cessation of bleomycin treatment is followed by resolution of inflammation manifested by decreases in tissue mass, cellular content, and nonconnective tissue protein. Collagen and elastin deposited during inflammation are less successfully removed during resolution, leading to a stage characterized by increased concentrations of these proteins. A similar sequence of tissue alterations may occur in idiopathic diffuse interstitial fibrosis of man in response to various lung injuries.

Animals

Experimental infection with Schistosoma intercalatum (Fisher, 1934) in the chimpanzee (pan troglodytes) and the gibbon (Hylobates lar).

Two young chimpanzees (Pan troglodytes) and two adult gibbons (Hylobates lar), each exposed to 1,000 cercariae of Schistosoma intercalatum (Cameroon), were examined at 79 and 82 wk and 61 and 69 wk, respectively, post-infection. Based upon worn returns and tissue egg deposits, these primates can be employed as hosts for experimental schistosomiasis intercalata. However, no histopathology was detected in the urogenital system.

Animals

C19-steroid metabolism by spontaneous adenocarcinoma of the A X C rat ventral prostate.

Specimens of ventral prostate from 37- to 46-month-old Andradurin-treated A X C rats demonstrated three primary morphologic patterns, each being divisible into two sub-groups based upon the extent of glandular alteration. The principal groups were: group 1, hyperplasia; group 2, atypical hyperplasia; and group 3, adenocarcinoma. The secondary classifications were: subgroup (+), few glands involved; and subgroup (++), most glands involved. Multiple parameters of ventral prostate testosterone metabolic potential failed to distinguish the morphologically diverse prostate specimens of groups (1+). 1(++), 2(+), 2(++), and 3(+) which predominantly metabolized testosterone to 5alpha-reduced 17beta-hydroxysteroids. By contrast, testosterone metabolism by ventral prostate specimens predominantly composed of neoplastic epithelium, group 3(++), was distinct from all other prostate specimens. The distinguishing feature was a shift to more prominent elaboration of 17-ketosteroids, principally delta4-androstenedione, and a cteroids. The change in this biochemical parameter of prostate epithelial cell function was indicated to be an early manifestation of the neoplastic transformation.

17-Ketosteroids

Multifocal candidiasis in a capuchin monkey (Cebus apella).

Candidiasis involving nasal, pharyngeal, and intestinal mucosal surfaces and a pharyngeal lymph node was demonstrated microscopically in a young adult female capuchin monkey (Cebus apella) experimentally infected with Schistosoma haematobium (Iran strain). Persistent nasal exudation and weight loss characterized the clinical disease preceding the animal's death.

Animals

Clinical, virological, and pathological features of herpesvirus SA8 infection in conventional and gnotobiotic infant baboons (Papio cynocephalus).

The pathogenicity of a strain of simian herpesvirus SA8 in one month old conventional and gnotobiotic baboons was investigated. Intratracheal inoculation resulted in a mortality rate of 1/5 in the conventional and 1/4 in the gnotobiotic group. Disease became apparent after 3 days and was characterized by respiratory distress, reduced formula intake, weight loss and fever in both groups. Isolation of herpesvirus from the respiratory tract, lymphoid organs, kidneys, adrenals, and CNS was more frequent by explant culturing than by routine procedures. Although there was a significant difference in total white blood counts (WBC), with higher values in conventional vs. gnotobiotic infants, the absolute number of lymphocytes was not different. The lower number of WBCs apparently was due to fewer polymorphonuclear leukocytes in the gnotobiotic baboons. Infection resulted in a leukopenia 5 days post infection (p.i.) and a leukocytosis 10 days p.i. in both groups. The animals, which succumbed, had acute necrotizing fibrinous pneumonia. Intranuclear inclusion bodies typical for herpesviruses were present. All the surviving infant baboons had subacute interstitial pneumonia, when sacrificed 35 days p.i.

Animals

Serologic response to canine distemper viral antigens in gnotobiotic dogs infected with canine distemper virus.

The humoral immune response to canine distemper viral antigens in gnotobiotic dogs experimentally infected with canine distemper virus was studied by the complement fixation and serum neutralization tests. Antibody titers measured by both serologic methods varied inversely with the severity of disease produced. Recovered dogs demonstrated the highest titers of antibody, whereas fatally infected dogs had little or no antibody activity in their sera. A third group of dogs, characterized by chronic persistent infection, had intermediate levels of anitbody to canine distemper virus. Preliminary characterization of the viral antigens involved in the complement fixation test indicated that at least two antigenic components were involved. One antigen was soluble in ether and was heat-labile, whereas the other was relatively heat-stable and was unaffected by treatment with ether. No evidence for serologic cross-reaction between viral and central nervous system components was found. A vigorous antibody response to envelope antigen determinants in addition to core determinants distinguished immune dogs from persistently infected dogs. The results of this study suggest that the inability to produce antibodies to envelope antigens may be a crucial factor in the establishment of a persistent infection with canine distemper virus in these dogs.

Animals

Spontaneous adenocarcinomas of the ventral prostate of aged A X C rats.

Spontaneous adenocarcinomas of the ventral prostate were present in 7 of 41 aged (34- to 37-month-old), virgin, untreated male A X C rats. The only consistent gross evidence of possible neoplastic involvement was intraprostate hemorrhage. The principally intraglandular neoplasms were composed of markedly anaplastic epithelial cells which retained a moderate propensity to form glandular patterns. The nuclei of the neoplastic cells were pleomorphic, vesiculated, enlarged, and hyperchromatic. Mitotic figures were frequent. Interglandular connective tissue was invaded in one rat; however, metastases were not demonstrated.

Adenocarcinoma