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Biomedical subjects

C A Holmberg

Publications and source records attributed to C A Holmberg.

At least 55 records · Page 3Linked to original sources

Characterization of rhesus macaque peripheral blood T-lymphocyte subpopulations.

Highly enriched rhesus macaque (Macaca mulatta) peripheral blood T-lymphocytes were separated into functional subpopulations by Fc-receptors. The T-lymphocyte population was comprised of both Fc-IgM (T mu +, 3.4 +/- 1.6) and Fc-IgG (T gamma +, 16.2 +/- 4.0) bearing cells. T-cells depleted of cells bearing Fc-IgG receptors (T gamma -) and T gamma + subpopulations were characterized and assessed for functional activity. T gamma + and T gamma - subpopulations were found to have the following characteristics: 1) T gamma + cells were stimulated by concanavalin-A (Con-A)3, pokeweed mitogen (PWM), and phytohemagglutinin-P (PHA-P), while T gamma - cells were stimulated by Con-A and PWM, but not PHA-P; 2) T gamma - cells were found to mediate PWM induced differentiation of autologous B-cells including EAC+ and EAC- enriched subpopulations, while T gamma + cells did not induce differentiation; 3) T gamma + cells released soluble factors which depressed mitogen stimulation of T gamma- cells; and 4) approximately 8-10% of the T gamma + cells phagocytized IgG sensitized bovine red blood cell (BRBC) immune complexes.

Animals↗

Inhibition of human lymphoma DNA-dependent RNA polymerase activity by 6-mercaptopurine ribonucleoside triphosphate.

6-Mercaptopurine was found to inhibit the growth of cultured human lymphoma P3HR-1 cells and the incorporation of [3H]-uridine into trichloroacetic acid-precipitable materials of the cells. One of the derivatives of 6-mercaptopurine, 6-mercaptopurine ribonucleoside triphosphate (6-thio-ITP), was found to inhibit in vitro RNA synthesis (both engaged and free enzyme activities) of the isolated nuclei from P3HR-1 cells. The alpha-amanitin-resistant RNA polymerase (polymerase I) and alpha-amanitin-sensitive RNA polymerase (polymerase II) of the cells were isolated and partially purified by either diethylaminoethyl cellulose or diethylaminoethyl Sephadex column chromatography, followed by DNA-cellulose affinity chromatography. It was found that these partially purified enzymes were also sensitive to 6-thio-ITP inhibition. Kinetic studies showed that the inhibition of RNA polymerase activities by 6-thio-ITP could be reversed by increasing concentrations of guanosine 5'-triphosphate in the reaction mixture, indicating that 6-thio-ITP may act as a competitive inhibitor of the enzymes by competing with guanosine 5'-triphosphate for its enzyme-binding site. These data suggest that inhibition of RNA transcription by 6-thio-ITP may be considered as one of the mechanisms of the cytotoxic action of 6-mercaptopurine in human tumor cells.

Cell Line↗

Clinicopathological studies of gastrointestinal disease in macaques.

Evaluation of mortality during a two-year period at a primate colony indicated that 34% of nonexperimental deaths in macaques one year of age and older were due to gastrointestinal disease. Of deaths related to gastrointestinal disease, 12% had acute gastric dilatation, 18% had shigellosis, 12% had nontuberculous mycobacterial disease, and 58% were of undetermined cause. Histologic evaluation of the alimentary tract indicated that the large intestine was the most common site of anatomical change in monkeys that had diarrhea at the time of death. Monkeys that had a single terminal episode of diarrhea had less gastric inflammatory lesions than those that had multiple episodes of diarrhea in the last year of life.

Animals↗

Nontuberculous mycobacterial disease in rhesus monkeys.

In a colony of rhesus monkeys (Macaca mulatta), 42 cases of nontuberculous mycobacterial-related disease were identified from 1970 to 1978. The disease affected young and old colony-born and wild-caught monkeys of both sexes. Serotypes 1, 2, 4, 8, and 18 of the Mycobacterium avium-intracellulare group were isolated from different monkeys. The lesions were primarily intestinal in 36 monkeys. Lesions of the large intestine, small intestine, and mesenteric lymph nodes were characterized by diffuse accumulations of large macrophages containing many acid-fast bacteria. Acid-fast bacteria could not be identified histologically in four monkeys with typical histories of diarrhea and weight loss, positive skin reactions to the tuberculin test with M. avium tuberculin, and isolation of the organism from tissues on one or more occasions. Two monkeys had histologically positive lesions limited to the lungs, although chronic colitis of undetermined cause was present.

Animals↗

Clinicopathological studies of gastrointestinal disease in macaques.

Evaluation of mortality during a two-year period at a primate colony indicated that 34% of nonexperimental deaths in macaques one year of age and older were due to gastrointestinal disease. Of deaths related to gastrointestinal disease, 12% had acute gastric dilatation, 18% had shigellosis, 12% had nontuberculous mycobacterial disease, and 58% were of undetermined cause. Histologic evaluation of the alimentary tract indicated that the large intestine was the most common site of anatomical change in monkeys that had diarrhea at the time of death. Monkeys that had a single terminal episode of diarrhea had less gastric inflammatory lesions than those that had multiple episodes of diarrhea in the last year of life.

Animals↗

Nontuberculous mycobacterial disease in rhesus monkeys.

In a colony of rhesus monkeys (Macaca mulatta), 42 cases of nontuberculous mycobacterial-related disease were identified from 1970 to 1978. The disease affected young and old colony-born and wild-caught monkeys of both sexes. Serotypes 1, 2, 4, 8, and 18 of the Mycobacterium avium-intracellulare group were isolated from different monkeys. The lesions were primarily intestinal in 36 monkeys. Lesions of the large intestine, small intestine, and mesenteric lymph nodes were characterized by diffuse accumulations of large macrophages containing many acid-fast bacteria. Acid-fast bacteria could not be identified histologically in four monkeys with typical histories of diarrhea and weight loss, positive skin reactions to the tuberculin test with M. avium tuberculin, and isolation of the organism from tissues on one or more occasions. Two monkeys had histologically positive lesions limited to the lungs, although chronic colitis of undetermined cause was present.

Animals↗

Immunosuppressive activity of rhesus monkey pregnancy serum.

Normal pregnancy serum from the rhesus monkey was found to have immunosuppressive activity. Using two-way stimulation, the mixed lymphocyte response was suppressed as much as 80%. Control serum from nonpregnant females was not suppressive. The inhibiting factor was found to have the following characteristics: (1) it was nonspecific in activity; (2) it inhibited the mixed lymphocyte response 20% at in vitro concentrations of 1%; (3) it was heat stable (56 degrees C for 30 minutes) and nondialyzable; (4) it was present in both the IgM- and IgG-containing fractions of pregnancy serum; (5) it was detected in postpartum and second and third trimester serum; and (6) it was at low levels or absent from the serum of two pregnancies which terminated in unexplained stillbirths.

Animals↗

In vitro response of alveolar macrophages to infection with Coccidioides immitis.

Alveolar macrophages obtained from rhesus macaques (Macaca mulatta) by bronchial lavage were observed to phagocytize endospores and arthrospores of Coccidioides immitis. When the macrophages were subsequently maintained in vitro, the phagocytized spores developed into spherules. There was no significant reduction in the viability of C. immitis after phagocytosis by macrophages from normal macaques, nor was killing induced by the addition of immune serum, complement, or lung lining material obtained from the bronchial lavage fluid. The inability of the macrophages to kill C. immitis may in part be explained by the observation that C. immitis appeared to inhibit fusion of the phagosomes containing the fungal spores with the lysosomes within the macrophages.

Animals↗

Histologic classification as a prognostic criterion for canine lymphosarcoma.

Neoplastic tissues from 72 dogs with lymphosarcoma were histologically classified according to the Rappaport schema to determine if the histologic features of the disease had any clinical or prognostic importance. Of 72 dogs, lymphosarcomas in 7 were classified as nodular (9.7%) and 65 were classified as diffuse (90.3%). The two principal cytologic types were lymphocytic, poorly differentiated, and histiocytic, which composed 39% and 56% of the lymphosarcomas, respectively; whereas lymphocytic, well differentiated, mixed, and undifferentiated composed 6%. Clinically, all of the dogs were stage III or IV, according to the accepted criteria for canine lymphosarcoma. The overall complete remission rate was 64% and was defined as no clinical evidence of disease after 9 weeks of chemotherapy. Median remission among nodular histiocytic, diffuse lymphocytic, poorly differentiated, and diffuse histiocytic (DH) groups of dogs was 42 days, 29 days, and 42 days (range, 0 to 1,095), respectively. Median survival for the same groups was 235 days, 190 days, and 173 days (range, 1 to 1,261), respectively. A logarithmic analysis of variance revealed no significant differences among nodular histiocytic, diffuse lymphocytic, poorly differentiated, and DH groups relative to days remission, as well as to days survival. It was observed that those dogs with neoplasms classified as DH had longer remission durations. It would appear that for any one animal, histologic classification according to the Rappaport schema cannot be used as a prognostic criterion in predicting therapeutic response, remission, or survival.

Animals↗

Lymphosarcoma and cryptococcosis in a cat.

Cryptococcosis and lymphosarcoma were diagnosed in a 3-year-old Domestic Shorthair cat. The cat was studied immunologically, and abnormal findings included absolute lymphopenia, with a low percentage of the lymphocytes having cell surface markers of normal T and B cells, decreased responsiveness to mitogens, and low immunoglobulin concentrations in serum. Necropsy revealed cryptococcal lesions in the facial area. The cortex of the left kidney was replaced by a diffuse pattern of undifferentiated large cells compatible with those of histiocytic cell type lymphosarcoma.

Animals↗

Virus detection in monkeys with diarrhea: the association of adenoviruses with diarrhea and the possible role of rotaviruses.

To explore the role of viruses in the etiology of diarrhea in colony-reared monkeys, direct electron microscopy, the fluorescent virus precipitin test and cell culture inoculation were used to examine the stools of monkeys with and without diarrhea. The animals were predominantly rhesus with a few macaques of other species, and included infants, juveniles and adults. Adenoviruses were isolated from a higher proportion of specimens from rhesus monkeys with diarrhea (73% of specimens from infants and 78% of specimens from juveniles and adults) than from control monkeys without diarrhea (22% of specimens from infants and 26% of specimens from juveniles and adults). SV 20 was the most frequently isolated simian adenovirus type; SV 17 and SV 32 also were recovered. Noncultivable adenoviruses detectable only by electron microscopy were not seen. Although adenovirus excretion was associated with diarrhea, the causal role of adenoviruses was difficult to assess. When serial specimens from animals with chronic or intermittent episodes of diarrhea were examined, sequential infections with different viruses were found to be common. Rotaviruses were detected by electron microscopy and isolated in cell cultures from two infant rhesus monkeys with diarrhea. However, the low detection rate, together with negative serologic data on 40% of infant monkeys with diarrhea, suggested that rotaviruses were not the major cause of gastroenteritis in the monkeys under study.

Adenoviridae↗

Rotavirus antibody assays on monkey sera: a comparison of enzyme immunoassay with neutralization and complement-fixation tests.

An enzyme immunoassay (EIA) for the detection of rotaviral antibodies was developed, using a purified, cell culture-grown SA 11 viral antigen and alkaline phosphatase as an enzyme label. This technique was evaluated by comparative testing with tube neutralization and complement-fixation assays on a collection of simian sera. There was close correlation between positive and negative results obtained by EIA and by neutralization. The EIA was as easy to perform as complement fixation testing, but showed greater sensitivity and fewer nonspecific reactions. Thus, EIA was shown to be a very suitable test for routine detection of rotaviral antibodies in serum. Results of neutralization tests suggested that the monkeys (mostly rhesus macaques) in the present study were infected with viruses varying in their antigenic relatedness to SA 11 virus and to a British isolate of calf rotavirus.

Animals↗

Dysgerminoma in a rhesus monkey: morphologic and biological features.

A female Macaca mulatta was observed for 31 months after the initial surgical removal of an ovarian tumor. Solitary metastatic lesions were surgically removed 26 and 28 months after excision of the primary tumor. The animal was killed after 31 months because of additional metastatic lesions. Histological evaluation by light microscopy was not conclusive in determining the origin of neoplasm. Transmission electron microscopy, lymphocyte marker studies, and hormone assays were utilized to confirm the diagnosis of dysgerminoma.

Animals↗

Cellular immunologic studies of malignant lymphoma in rhesus macaques.

Cells from malignant lymphoma in 10 rhesus macaques were examined for lymphocyte surface markers. Three had features of T cells, 5 had features of B cells, and 2 lacked evidence of either B- or T-cell differentiation. Correlation between the histologic classification of cell type and the B- or T-cell nature of the neoplasms was not evident. Evaluation of serum electrophoresis, mitogen responses tests, and previous histologic studies suggest that the development of the neoplastic lymphocyte proliferation occurred following or during an abnormal immunologic response.

Animals↗

Isolation of simian virus 40 from rhesus monkeys (Macaca mulatta) with spontaneous progressive multifocal leukoencephalopathy.

Isolates of virus from the brain tissue of two naturally occurring cases of progressive multifocal leukoencephalopathy in rhesus monkeys (Macaca mulatta) have been characterized. Both isolates were demonstrated to be simian virus 40 (SV40) by serological tests and analysis of cleavage fragments of viral deoxyribonucleic acid produced by restriction endonuclease from Haemophilus influenzae. SV40 virions and the nonvirion T antigen were demonstrated in the brain lesions of one monkey by the fluorescent antibody staining technique. SV40 was not demonstrated in the brain of normal rhesus monkeys from the same colony with use of the same methods of viral isolation or demonstration of antigen.

Animals↗