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Biomedical subjects

M J Colston

Publications and source records attributed to M J Colston.

At least 127 records · Page 7Linked to original sources
PubMed1985

Susceptibility of Mycobacterium leprae to the bactericidal activity of mouse peritoneal macrophages and to hydrogen peroxide.

Macrophages from athymic nude mice were infected in vitro with Mycobacterium leprae to study the intracellular fate of this organism. Using the proportional bactericidal test, we have shown that the viability of M. leprae declines rapidly within these macrophages, although results of clearance experiments demonstrate that live and killed organisms are cleared at comparable rates. We have also shown that M. leprae is susceptible to the bactericidal effects of hydrogen peroxide and we suggest that hydrogen peroxide generated by macrophages is responsible for the killing of intracellular M. leprae.

Animals↗
PubMed1984

The regulation of macrophage activity in congenitally athymic mice.

It has been suggested that non-T cell-mediated cellular immune mechanisms might be elevated in nude mice, which could contribute to their partial resistance to intracellular infectious agents and to the development of spontaneous tumors. In this study we have examined macrophages (M phi) from athymic, euthymic and athymic T cell-reconstituted mice in terms of their phagocytic capacity, microbicidal and tumoricidal activity, and the production of hydrogen peroxidase and superoxide anions. These studies have demonstrated the presence of activated M phi in nude mice and suggest that this activation is associated with the absence of T cell-mediated suppression. We have also compared M phi activation levels in germ-free nude mice which have received a defined intestinal bacterial flora. We have found M phi activity to be significantly elevated in microbiologically defined nude mice when compared to germ-free nude mice, indicating that a resistant gut flora is capable of nonspecifically stimulating nude mouse M phi.

Animals↗
PubMed1983

Mycobacterium leprae infection in nude mice: bacteriological and histological responses to primary infection and large inocula.

Previous studies have demonstrated that congenitally athymic, nude mice are highly susceptible to infection with Mycobacterium leprae. In this study, we showed that footpad inoculation of nude mice with different inoculum sizes of M. leprae resulted in exponential growth of bacilli until bacillary numbers reached approximately 10(10) bacilli per footpad. There was dissemination of the infection from approximately 10 months after inoculation. When nude mice were compared with thymectomized and irradiated mice and normal intact mice for the ability to detect growth from large inocula of low viability, nude mice were the most sensitive, permitting the detection of 10(2) viable M. leprae among 10(7) irradiation-killed organisms. There was widespread dissemination of the infection throughout the reticuloendothelial system and the tissues of the cooler body sites from approximately 10 months after inoculation. Histologically, the lesions resembled those seen in lepromatous leprosy, although the bacillary load appeared larger and was similar to that seen in heavily infected tissues of the nine-banded armadillo. An unusual feature was the presence of numerous foci of neutrophil polymorphs in the footpads and liver of infected nude mice.

Animals↗
PubMed1983

Infection of the congenitally athymic rat with Mycobacterium leprae.

The susceptibility of congenitally athymic rats to Mycobacterium leprae infection has been investigated. Following inoculation of small numbers of M. leprae (5 X 10(3] into the foot pad, the organisms replicated and attained a maximum of 2.6 X 10(8) per foot pad at 294 days; there was limited dissemination to the tail. In similarly inoculated neonatally thymectomized Lewis rats (NTLRs) a ceiling of 2 X 10(7) organisms was reached. When a larger inoculum (10(7] was given, the number of bacilli in athymic rat foot pads peaked at 6.7 X 10(8) and after approximately 240 days a plateau of between 2 X 10(8) and 6 X 10(8) per foot pad was reached. Dissemination to superficial tissues occurred approximately nine months after inoculation, when significant numbers of bacilli were recovered from the foot pads, ears, snout, and tail. Following intravenous inoculation of 10(7) M. leprae into athymic rats, significant numbers of bacilli were recovered from the superficial tissues by 300 days post inoculation. The numbers of organisms reached a plateau of about 10(8) by one year. Autopsy of infected animals from 1-2 years after inoculation revealed no gross abnormalities except for a purulent bronchitis and bronchopneumonia. Although normal grossly, the ears, tail, snout and foot pads showed a varying degree of infiltration by histiocytes. In some this was almost imperceptible, in others there were large accumulations of foamy macrophages reminiscent of lepromatous leprosy. The numbers of mycobacteria present in Fite stains ranged from 2+ (several organisms or clusters of organisms) to 5+ (very numerous). The lymph nodes contained numerous non-caseating granulomata composed of activated macrophages which contained large (4+) or very large (5+) numbers of bacilli. Mycobacteria were present in the cells of the mononuclear-phagocyte series in the liver and spleen of animals killed 12-15 months post inoculation, but were absent from these cells in animals killed later. M. leprae were also numerous in the smooth muscle of the scrotum. It is concluded that congenitally athymic rats are highly susceptible to M. leprae infection. Despite their lack of thymic-dependent T cell function, it appears that they possess the defense mechanism(s) capable of limiting the infection.

Animals↗
PubMed1982

Biological characteristics and viral susceptibility of a stable dog kidney cell line.

A cell line derived in 1956 from normal dog kidney is described. The cells are epithelial, contact-inhibited, and can be maintained in the same culture vessels for period of more than 2.5 yr. Karyologically, the cells are hypodiploid with a modal number of 72 as opposed to the diploid number of 78. The karyotype indicates male origin of the cells and clonal derivation of extant cultures due to the presence of two marker chromosomes in all metaphases observed. At the 159th passage the dog kidney (DK) cells did not produce tumors in athymic rats. At least 13 viruses of various types produced transmissible cytopathogenic effects in the DK cells, including all of the human influenza viruses investigated.

Animals↗
PubMed1982

1,25-dihydroxyvitamin D3 receptors in human epithelial cancer cell lines.

Specific, high-affinity cytosolic receptors for 1,25-dihydroxyvitamin D3 have been demonstrated in five human cancer cell lines. The cell lines were derived from tumors of breast, lung, cervix, and melanotic and amelanotic melanomas. Binding affinity (Kd) of the receptors for 1,25-dihydroxyvitamin D3 were all approximately 0.2 nM, and receptor content ranged from 21 to 174 fmol/mg cytosol protein. The receptors from all five cell lines sedimented at 3.2S on sucrose density gradients and exhibited preferential affinity for 1,25-dihydroxyvitamin D3 compared to other vitamin D metabolites.

Breast Neoplasms↗
PubMed1981

The effect of body temperature and cell-mediated immunity on the growth of Mycobacterium marinum and Mycobacterium leprae in mice.

Evidence is presented that the high susceptibility of armadillos to infection with Mycobacterium leprae cannot be explained solely in terms of body temperature because mutant mice maintained with a body temperature similar to that of armadillos do not become heavily infected with M. leprae. The depression of cell-mediated immunity accompanying the low body temperature is not sufficient to produce an overwhelming infection. The results obtained with M. marinum suggest that whereas lack of cell-mediated immunity or a low body temperature result in a moderately enhanced infection in the mouse a combination of both of these factors is required to produce an overwhelming infection involving the internal organs.

Adipose Tissue↗
PubMed1981

1,25-dihydroxyvitamin D3 and malignant melanoma: the presence of receptors and inhibition of cell growth in culture.

In this study we demonstrate the presence of specific, high-affinity receptors for 1,25-dihydroxyvitamin D3 in malignant melanoma. Receptors are present both in cultured melanoma cells and in melanoma tumor tissue produced by inoculation of cells into athymic rats. The receptor sediments at 3.25 on sucrose density gradients, possesses a preferential affinity for 1,25-(OH)2D3 and has an apparent Kd of 0.18 nM by Scatchard analysis. We also demonstrate that human melanoma cells are responsive to 1,25-(OH)2D3 in vitro. Inclusion of 1,25-(OH)2D3 in the culture medium produced a marked increase in cell doubling time. This inhibitory effect of the hormone on melanoma cell proliferation was dose-related and represents the first demonstration of a 1,25-(OH)2D3 mediated action on tumor cells.

Calcitriol↗
PubMed1981

Growth and regression of human tumor cell lines in congenitally athymic (rnu/rnu) rats.

Athymic rats were inoculated with cells from nine human tumor tissue culture cell lines. Tumor growth was seen with seven of the cell lines; histologically, the tumors resembled the tumors from which the cell lines were originated. Only one cell line--a malignant melanoma--grew progressively. The remaining sex cell lines grew to a short period of time and then regressed.

Animals↗
PubMed1981

Relationship between T-cell population in neonatally thymectomized Lewis rats and susceptibility to infection with mycobacterium leprae.

The neonatally thymectomized Lewis rat (NTLR) is highly susceptible to infection with M. leprae. However, a significant percentage of NTLR respond to infection with M. leprae in much the same way as do intact rats, yet show no evidence of residual thymus. To determine whether there was a correlation between the number of remaining T-cells and susceptibility to infection with M. leprae, a direct fluorescent antibody test was performed using a highly specific, absorbed antithymocyte globulin labeled with fluorescein isothiocyanate. Both total circulating white blood cells and T-cells were significantly depressed in all NTLR examined. Although the greatest numbers of M. leprae were found in NTLR from the groups having the lowest percentage of circulating T-cells, these groups also contained NTLR infected with small numbers of M. leprae. The groups containing NTLR with the highest percentages of circulating T-cells also contained animals with both moderate and severe M. leprae infection. The response of cultured splenic lymphocytes from NTLR and normal rats to the T-cell mitogen concanavalin A was investigated to determine whether there was any correlation between T-cell activity and susceptibility to M. leprae infection. The mean stimulation index for normal rats was five to ten times greater than indices for NTLR, but there were no significant differences between NTLR with a well developed, generalized infection and those with a poorly developed infection. it was concluded that since there was no apparent relationship between T-cell depletion and susceptibility to infection with M. leprae, an additional, unknown mechanism was also involved.

Animals↗
PubMed1980

Intermittent chemotherapy of experimental leprosy in mice.

In this study we assess the degree of prolonged bacteriostasis of Mycobacterium leprae after temporary exposure to ehtionamide or thiacetazone, and relate this to their efficacy when administered intermittently to mice with experimental leprosy infections. The results show that temporary exposure of M. leprae to either of these drugs results in a prolonged bacteriostatic effect, but that efficacy is rapidly lost as the interval between doses is increased. Using the mouse foot pad system, growth of M. leprae is not inhibited by thiacetazone when the frequency of administration is less than three times weekly. When ethionamide is administered once weekly, growth of M. leprae is inhibited but bactericidal activity is lost. When ethionamide is administered in combination with continuous dapsone therapy, either continuously or three times weekly, the bactericidal activity of the drug combination is greater than when either drug is administered alone. However, when ethionamide is administered once weekly in combination with continuous dapsone treatment, the bactericidal effect is identical to that when dapsone is given alone: that is, ethionamide makes no contribution to the combination.

Animals↗
PubMed1979

The effect of freezing and storage in liquid nitrogen on the viability and growth of Mycobacterium leprae.

The effects of rapid and slow rates of freezing in liquid nitrogen, storage in liquid nitrogen for 12 months, and the rate of subsequent thawing on the viability and growth of M. leprae in the mouse footpad were studied. Some loss of viability of M. leprae was detected, and this was found to be associated with the freezing process, rather than with storage or thawing. Slow freezing was less deleterious than quick freezing, with a loss of viability of 90% compared with 98%. The growth pattern of M. leprae was unaffected except for a delay in the appearance of growth caused by the loss of viability, though there was some evidence of an increased lag phase of one strain, possibly due to the repair of sub-lethally damaged organisms.

Freezing↗