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Biomedical subjects

J Curtis

Publications and source records attributed to J Curtis.

At least 127 records · Page 7Linked to original sources

Resistance to subcutaneous infection with Mycobacterium lepraemurium is controlled by more than one gene.

The resistance of C57BL (high) and BALB/c (low) mice, their F1 hybrids, and the offspring derived from backcrosses of the F1 to both parental strains was assessed at 20 weeks after subcutaneous infection with 10(7) Mycobacterium lepraemurium organisms. The numbers of bacilli recovered from the infected foot and draining lymph node indicated that resistance to subcutaneous infection is controlled by more than one non-H-2-linked gene of intermediate dominance. In general, female mice were more resistant than males.

Animals↗

H-2-linked genes which modify resistance of C57BL/10 mice to subcutaneous infection with Mycobacterium lepraemurium.

Strains of C57BL/10 mice with recombinants within the H-2 complex were used to map the genes which control the mononuclear cell response at the infection site and modify resistance to subcutaneous infection with Mycobacterium lepraemurium. Strains with b in the K-E beta regions of the H-2 complex mounted a more rapid cellular response in the infected footpad and were more resistant than mice with d or k in the K-E beta regions. Significant differences between strains with k in the K-E beta regions appeared to be controlled by a gene in the D region.

Animals↗

T cell proliferation in Mycobacterium lepraemurium infection. I. Lack of correlation between antigen-specific proliferation of Lyt 1 + 23- cells and resistance in lethal infections.

Antigen specific T lymphocyte proliferation and Lyt phenotypes of the T lymphocytes were studied in BALB/c and C57BL/6 mice infected with 10(9) M. lepraemurium organisms intravenously. A highly disseminated form of the disease developed to which all mice succumbed by 17 weeks. Maximal antigen-specific T lymphocyte proliferation was detected at 4 weeks after the infection and persisted thereafter even when the mice started to die of the infection. Accessory cells of phagocytic and adherent type did not appear to be a requirement for this proliferation. The T lymphocytes generated during the course of the infection were mostly of the Lyt 1 phenotype. However, there appeared to be no correlation between sensitized Lyt 1 cells capable of antigen-induced T lymphocyte proliferation and protective immunity.

Animals↗

T cell proliferation in Mycobacterium lepraemurium infection. II. Characterization of cells that transfer resistance in subcutaneously infected mice.

T lymphocyte proliferation, Lyt phenotypes and their role in the evolution of protective immunity were studied in BALB/c and C57BL/6 mice infected subcutaneously with Mycobacterium lepraemurium. Antigen-induced proliferation was not demonstrable with T-enriched cells obtained from the spleens. However, these cells were capable of spontaneously proliferating in the absence of added antigen for a limited period. This proliferation was dependent on the presence of a phagocytic and adherent accessory cell. During the period when the T cells proliferated spontaneously they consisted of a mixture of Lyt-1 and Lyt-23 and were able to transfer protection to syngeneic recipient mice. Furthermore, the multiplication of the organisms was curbed during the same period demonstrating a strong association between the ability to proliferate spontaneously Lyt-1/Lyt-23 cells and protective immunity. T cells from normal BALB/c mice showed a marked suppressive effect on protection suggesting that these cells may be responsible for the susceptibility of this strain to a moderate subcutaneous infection.

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The histopathology of tissues in "resistant" and "susceptible" strains of mice infected with a moderate dose of Mycobacterium lepraemurium.

A systematic study by light and electron microscopy of tissues from BALB/c and C57BL/6 mice infected subcutaneously with 10(7) Mycobacterium lepraemurium organisms was carried out at various times throughout the infection. The relatively resistant C57BL/6 mice had an earlier inflammatory response at the site of the infection than did the susceptible BALB/c mice. The infiltration in the former strain contained fibroblast-like cells and epithelioid cells early on in the infection. Few lymphocytes were observed in both strains throughout the infection. The spread of acid-fast bacilli was slower in the resistant strain (C57BL/6). The findings indicated that the rate of cellular infiltration at the infection site and the nature of the cells in the infiltration may determine the outcome of this infection.

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Macrophage specific antigen is expressed by resting microglia in the CNS but not by Langerhans cells in the skin.

Controversy exists as to whether Langerhans cells in the epidermis and resting microglia in the brain should be included among cells of the mononuclear phagocyte series (MPS). A monoclonal anti-guinea-pig macrophage antibody has been prepared that is specific for a macrophage membrane antigen and does not react with Fc receptors or Ia antigens. This antibody fails to react with Langerhans cells despite reacting with peritoneal exudate macrophages, alveolar macrophages, Kupffer cells and macrophages in infectious granulomas. It does, however, react with resting microglia in the brain. This could suggest that Langerhans cells, despite a similar bone marrow origin, are not typical cells of the MPS, whereas resting microglia share features with this cell system.

Animals↗

High-amplitude peristaltic contractions in a patient with esophageal intramural pseudodiverticulosis.

In their initial radiographic description of esophageal intramural pseudodiverticulosis (EIP) in 1960, Mendl and coworkers suggested that elevated esophageal intraluminal pressure might be etiologically important. Chronic inflammation and moniliasis have also been implicated. A patient is reported with EIP and a primary esophageal motility disorder characterized by esophageal contractions of increased amplitude and duration. Features confusing the interpretation of esophageal motor abnormalities in previously reported cases, such as diabetes mellitus, fungal esophagitis, and stricture formation, were not present in this case.

Diverticulum, Esophageal↗

The resistance of C57BL/6 mice to subcutaneous infection with Mycobacterium lepraemurium is dependent on both T cells and other cells of bone marrow origin.

Thymectomized or sham-thymectomized C57BL/6 mice were irradiated and reconstituted with either C57BL/6 bone marrow cells or bone marrow cells from H-2 matched BALB/B mice. The ability to limit organism multiplication at the site of infection in response to a moderate dose of Mycobacterium lepraemurium is shown to be T-cell mediated and not dependent on the type of bone marrow cells used for reconstitution. Dissemination of the organisms on the other hand appeared to be dependent on both T cells and cells of bone marrow origin.

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Successful renal transplantation in hyperoxaluria. A report of two cases.

Two patients with documented primary hyperoxaluria have received renal allografts with successful function for 10 years and 25 months. The patient in case 1 required a ureterolithotomy 6 years post-transplantation to remove a renal calculus of calcium oxalate. This case illustrates that despite recurrence of oxalate stones in the allograft, satisfactory renal function can be maintained by careful follow-up and appropriate interventions. Factors that may be important in successful graft function include the occurrence of acute rejection episodes, avoidance of ischemic graft damage, trials of pyridoxine therapy to decrease oxalate excretion, and frequent evaluation with appropriate interventions as necessary. Renal transplantation is a suitable and possibly the preferred form of therapy of end stage renal disease in patients with primary hyperoxaluria.

Adult↗

Analysis of cells of the mononuclear phagocyte series in experimental mycobacterial granulomas by monoclonal antibodies.

Two distinct types of granulomas were produced in the draining lymph nodes by immunizing guinea pigs with Mycobacterium bovis BCG or Mycobacterium leprae, as reported earlier (Narayanan et al., J. Pathol. 134:253-265, 1981). In the BCG-induced granuloma there is successful containment, killing, and degradation of the organisms with the presence of epithelioid cells and fibrosis. M. leprae, on the other hand, induces a granuloma where there is an absence of organization of the cells, failure to completely degrade the organisms, absence of epithelioid cells, and minimal fibrosis. By using a macrophage-specific monoclonal antibody and an anti-Ia monoclonal antibody and applying the immunoperoxidase, immunofluorescence, and fluorescence-activated cell sorter analysis techniques, the epithelioid cells of the BCG granuloma were found to have macrophage-specific antigen, but not detectable amounts of Ia antigen. This suggests that these cells have a close relationship to other cells of the mononuclear phagocyte series with which they share a common antigen. The absence of Ia antigen, on the other hand, suggests that epithelioid cells may not be involved in antigen presentation or other accessory cell functions where the presence of Ia antigen is crucial. The macrophages in the M. leprae-induced granuloma expressed both macrophage-specific and Ia antigens.

Animals↗

Role of the major histocompatibility complex in resistance and granuloma formation in response to Mycobacterium lepraemurium infection.

Resistance to a subcutaneous infection with a moderate dose of Mycobacterium lepraemurium was investigated in C57BL/6 mice and in three congenic strains with the BALB background (BALB/c, BALB/B, and BALB/K). Resistance after 10 weeks of infection was found not to be linked to the major histocompatibility complex. The ability to develop a delayed hypersensitivity response to an ultrasonicate of M. lepraemurium was associated with the background genes, and this ability had no influence on resistance to M. lepraemurium. Granuloma formation at the infection site in the early stages appeared to be linked to the H-2b haplotype. The types of cells involved in the granulomas were also investigated.

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Comparison of mycobacterial granulomas in guinea-pig lymph nodes.

A study was made of mycobacterial-induced granulomas in guinea-pig lymph nodes. Live BCG (Pasteur) induced a granuloma containing epithelioid cells while Cobalt irradiated Mycobacterium leprae induced a granuloma comprised of phagocytic macrophages. The granulomas were quantitated by measurement of lymph node weight and the areas of infiltration in histological sections. The time course of granuloma formation induced by Co-irradiated M. leprae was veary different from the time course of the granuloma formation induced by BCG. Collagen synthesis assessed by incorporation of 14C-proline into collagenase sensitive protein was greater in lymph nodes draining the site of injection of Co-irradiated BCG than those draining the site of injection of Co-irradiated M. leprae during the first 10 weeks. Collagen synthesis was delayed in the nodes from animals injected with live BCG for at least 10 weeks. Single cell suspensions of draining lymph nodes containing granulomas consisted of lymphocytes and large cells (epithelioid cells and macrophages). A high proportion of the large cells were found to be non-adherent in the live BCG-induced epithelioid cell granuloma. In contrast, M. leprae-induced granulomas contained a high percentage of adherent large cells. In both the granulomas, the majority of large cells were esterase positive and showed the presence of fibronectin. Most of the large cells in the granulomas did not carry receptors for the Fc component of IgG or the C3 component of complement and did not exhibit peroxidase activity.

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H-2 linkage control of resistance to subcutaneous infection with Mycobacterium lepraemurium.

The H-2 linkage of the gene or genes controlling resistance to subcutaneous infection with 10(7) Mycobacterium lepraemurium organisms was investigated by using H-2 congenic strains on BALB and B10 backgrounds. Resistance was assessed by counting the organisms present at the infection site in the footpad and in the draining (right popliteal) lymph node 20 weeks after infection. When mice of BALB and B10 backgrounds with the same H-2 haplotype were compared, the BALB mice were always more susceptible. However, BALB/K (H-2k) mice were more susceptible than BALB/B (H-2b) mice, and BALB/B mice were more susceptible than BALB/c (H-2d) mice. There was no detectable difference in the resistance of B10.D2/n (H-2d) mice and B10 (H-2b) mice, but B10.BR (H-2k) mice were more susceptible than mice of the other two B10 strains. BALB/K was the only strain in which a high proportion of mice showed significant dissemination of organisms to the liver and spleen.

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