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Biomedical subjects

F M Collins

Publications and source records attributed to F M Collins.

At least 91 records · Page 5Linked to original sources
PubMed1981

The effect of combined chemotherapy on suppressor T-cell activity in Mycobacterium simiae-infected mice.

Specific pathogen-free B6D2 mice were infected with 10(6) or 10(8) viable Mycobacterium bovis (BCG Pasteur) or Mycobacterium simiae and the in vivo growth curves were correlated with the levels of delayed hypersensitivity developed against a cytoplasmic protein antigen (CPA) injected into a hind footpad at increasing time intervals after infection. Half of the heavily infected, anergic mice were placed on a regimen of 10 mg of rifampin, 5 mg of amikacin and 2 mg of clofazimine per 100 ml of drinking water 2 or 8 weeks into the infection. The number of viable mycobacteria recovered from the lungs and spleens of the treated mice (compared with the corresponding drug-free controls) were reduced by up to 10,000-fold over a 3-month treatment period. Spleen cells were harvested at increasing time intervals from the drug-treated and control mice and T-cell enriched suspensions were tested for blastogenic responsiveness to phytohaemagglutinin (PHA) and to the specific CPA mitogen. The early (day 14) peak in tritiated thymidine ([3H]-TdR) uptake was followed by a sharp drop to near background levels. Cell-mixing experiments demonstrated the presence of a suppressor T-cell population in the heavily infected spleens of the M. simiae-infected mice. The suppressor-cell effect was substantially reduced following combined drug therapy although the specific CPA-mediated response was less affected than the non-specific PHA-mediated response.

Amikacin↗
PubMed1981

Suppressor and helper T-cell populations in Mycobacterium kansasii-infected spleens.

Specific pathogen-free B6D2 F1 hybrid mice were infected intravenously with increasing numbers of Mycobacterium kansasii TMC 1203 or 1214 and blastogenic responsiveness of the splenic T cells to phytohaemagglutinin (PHA), Con A or to a mixed lymphocyte reaction (MLR) were compared. Mice which had been infected 30 days earlier with M. kansasii strain 1203 exhibited substantial suppression whereas those infected with 1214 showed enhanced tritiated thymidine uptakes when exposed to mitogenic or allogeneic stimulation. Spleen cells harvested from mice infected 10 days earlier with either M. kansasii 1203 or 1214 exhibited substantially enhanced levels of helper T-cell activity in vitro compared with normal spleen cells. As the M. kansasii 1203 infections progressed, increasing suppressor T-cell activity was observed so that by day 30, the helper T-cell response had been largely ablated. On the other hand, the M. kansasii 1214-infected spleens exhibited little or no suppressor T-cell activity at any time during the infection. However, helper T-cell activity doubled over this same time period relative to that for the 1203-infected spleens when the responses were compared on a cell-to-cell basis.

Animals↗
PubMed1981

Antimycobacterial activity of 2-acetylpyridine thiosemicarbazones in relation to their antileprosy activity.

Antimycobacterial assays were carried out on sixteen 2-acetylpyridine thiosemicarbazones using a number of culturable mycobacteria in vitro. The resulting MIC determinations were plotted against the lipophilicity (log P) values for the various test compounds. Plots of log MIC vs log P values conformed to a parabolic regression curve having a log Pmax of 4.0 for the slow-growing mycobacteria and 3.0 for the rapid grower, M. smegmatis. Ten thiosemicarbazone compounds covering a log P range of 1.0 to 4.5 were tested for their antileprosy activity in M. leprae-inoculated mouse foot pads. The resulting activity curve had a log Pmax of 2.0. The significance of these findings is discussed in terms of the role played by limiting diffusional factors within the tissue so far as the penetration of these thiosemicarbazones into the intracellular environment is concerned.

Animals↗
PubMed1980

Mechanism of cellular suppression induced by oral tilorone treatment of mice.

Specific-pathogen-free B6D2 F1 hybrid mice were treated orally with tilorone hydrochloride (100 mg/kg of body weight per day) and infected with sublethal doses of Listeria monocytogenes, Salmonella enteritidis, Mycobacterium bovis (BCG Pasteur), or M. tuberculosis Erdman. Daily tilorone treatment inhibited the cell-mediated response to all of the intracellular parasites, and most of the mice succumbed to the challenge. Tilorone suppressed delayed hypersensitivity responses to the microbial sensitins as well as to sheep erythrocytes. However, humoral responses (immediate hypersensitivity reactions) were stimulated. The types of growth curves obtained in the tilorone-treated mice were quite different from those observed in T-cell-depleted mice and tended to resemble those seen in sublethally irradiated (400 rads) animals. Leukocyte counts were depressed 10-fold by daily tilorone treatment. Both monocyte and granulocyte (but not large-lymphocyte) counts were depressed. There was an initial drop in small-lymphocyte counts with a later recovery phase. Tilorone treatment reduced the granulomatous response within the Salmonella-infected liver, suggesting that the drug interferes with the mobilization of the mononuclear defenses within the normal host.

Animals↗
PubMed1980

Development of delayed hypersensitivity in gnotobiotic mice.

Germ-free mice develop low levels of delayed hypersensitivity following exposure to sensitizing doses of sheep erythrocytes, compared to that seen in conventionally raised mice. Infection of the germ-free animal with either Salmonella gallinarum or Salmonella pullorum was followed by extensive growth of the organisms within the intestine and the gut-associated lymphoid organs. As many as 5,000 viable Salmonellae were recovered from the cecal and ileal Peyer's patches as well as the mesenteric lymph nodes. However, neither strain spread significantly beyond the lymph nodes to the blood stream or to the liver and spleen. The gnotobiotic mice developed significant levels of delayed hypersensitivity to the Salmonella protein antigen and could be more readily sensitized to sheep erythrocytes than the germ-free host, despite the fact that Salmonellae were only able to infect the gut-associated lymphoid tissues.

Animals↗
PubMed1980

Microscopic counts carried out on Mycobacterium leprae and M. tuberculosis suspensions. A comparison of three staining procedures.

Standard smears of heat-killed Mycobacterium leprae and M. tuberculosis H37Rv were counted microscopically following staining by the Ziehl-Neelsen, auramine, and silver-methenamine methods. The numbers of stained bacillary bodies were consistently higher in the silver-methenamine stained smears compared to the Ziehl-Neelsen and auramine stained smears. The auramine smears were examined under ultraviolet illumination and permitted the enumeration of the brightly fluorescent bacilli against a black background. The auramine counts were not as high as those obtained using the silver-methenamine stained preparations but were consistently higher than those obtained with the Ziehl-Neelsen preparations. Both the auramine and silver-methenamine stained preparations clearly outlined the cell walls of the bacilli in the smears and this greatly facilitated the counting process, especially if the cell suspension was badly clumped.

Mycobacterium leprae↗
PubMed1980

Effect of chemotherapy on suppressor T cells in BCG-infected mice.

Specific pathogen-free B6D2 mice infected intravenously with 10(6) or 10(8) viable BCG Pasteur develop an anti-tuberculous immune response resulting in a progressive decline in viable BCG counts for the spleen and lung. Mice infected with 10(8) bacilli did not develop detectable levels of tuberculin hypersensitivity. Spleen cells harvested from both groups of mice at increasing time intervals after infection were T-cell enriched by nylon wool passage and tested for blast transformation following exposure to PHA or PPD. An early peak in tritiated thymidine uptake was observed following PPD exposure of cells from both the 10(6) and 10(8) groups. Cells from the latter group of animals developed a profound suppression to responsiveness to PPD throughout the remainder of the experiment. If the heavily infected mice were exposed to a regimen of 10 mg isoniazid plus 10 mg rifampin per 100 ml of drinking water for 30 days, the viable BCG population present within the lungs and spleen declined to near undetectable levels. This drop was associated with a decline in supressor T-cell activity demonstrated by appropriate cell-mixing experiments in vitro. The blastogenic responses to both PHA and PPD were substantially restored after 30 days of drug treatment. Treatment of the BCG infected mice within the first 7 days of infection prevented the development of the suppressor T-cell population.

Animals↗
PubMed1980

Development of suppressor T cells in mice heavily infected with mycobacteria.

Specific pathogen-free B6D2 mice were infected intravenously with 10(8) viable BCG, M. habana or M. simiae and the level of tuberculin hypersensitivity to 2.5 micrograms PPD or cytoplasmic protein antigens (CPA) prepared from the other organisms was determined using the footpad swelling test with increasing time after infection. This was correlated with the growth or persistence of mycobacterial populations within the liver. Spleen cells were removed from these infected mice and the level of blast transformation following exposure to PHA, PPD or M. habana or M. simiae CPA was measured in vitro. Early in the mycobacterial infections (day 14) thymidine incorporation by the spleen cells was significantly enchanced followed by a profound depression in incorporation rates as the infection progressed. The mechanism of this depressed response involved the production of suppressor T cells in the spleen. In the case of the M. simiae or M. habana infection, cells capable of mediating suppression were still present even after 12 months of infection. In the BCG infection, suppressor T cells declined with time so that by 4 months incorporation rates were back to normal and suppressor cells were no longer detectable in the spleens of the infected animals.

Animals↗
PubMed1979

Mucosal defenses against Salmonella infection in the mouse.

Specific pathogen-free ICR (Institute of Cancer Research) mice were challenged with Salmonella orally, aerogenically, or parentally 24 hr after they received sublethal whole-body irradiation. The early growth for the sublethal inoculum was identical in irradiated and control mice. In the irradiated group, Salmonella multiplied in the liver and spleen until death of the host. Increasing the dose of irradiation reduced the size of the mean lethal dose for the intravenous, intraperitoneal, and aerogenic challenges. However, in the orally challenged mice, the 50% lethal dose dropped only 100-fold when the radiation was increased from 0 to 400 rad, with little further decrease even when the dose was increased to 800 rad. Presumably, the local gut defenses were responsible for this considerable disparity in the lethal effects of an oral vs. parenteral challenge. No evidence was found for enhanced local infection of the gut or increased involvement of the gut-associated lymphoid organs in the irradiated host. The increased mortality seen in the irradiated group seemed to be associated with a continued unrestricted growth of Salmonella in the liver and spleen when the number of peripheral blood leukocytes was at a minimum. Resistance to the sublethal salmonella challenge was eventually restored as the total counts of white blood cells returned to normal.

Administration, Oral↗
PubMed1979

Restoration of T-cell responsiveness by thymosin: expression of anti-tuberculous immunity in mouse lungs.

Specific pathogen-free, adult thymectomized, irradiated, and bone marrow-reconstituted (THXB) B6D2 mice were infected aerogenically with 1 X 10(3) to 5 X 10(3) live BCG Pasteur. Seven days later a group of the mice was placed on a 14-day regimen of 20 mg of calf thymosin per kg per day, and the growth of the BCG in the lungs, spleen, inguinal lymph node, bone marrow, and blood was determined for up to 90 days. The thymosin treatment was followed by a decline in the BCG counts for the lungs and spleens of the THXB mice, whereas the saline-treated controls showed no such decline with time. The thymosin-treated mice did not develop progressive BCG infections in the test lymph nodes or in the bone marrow, both of which became positive in the THXB mice. Spleen cells were harvested from thymosin-treated THXB donors, filtered through nylon wool, and infused three times into BCG-infected THXB recipients. The lung BCG counts declined approximately 10-fold by day 90 compared with THXB mice which received THXB spleen cells. The transferred immune response was only slightly smaller numerically than that seen in THXB mice infused with BCG-immune lymphocytes from normal donors.

Animals↗
PubMed1979

Delayed hypersensitivity responses in mice and guinea pigs to Mycobacterium leprae, Mycobacterium vaccae, and Mycobacterium nonchromogenicum cytoplasmic proteins.

Antigenic relationships between Mycobacterium vaccae, M. nonchromogenicum, and M. leprae were examined in mice and guinea pigs injected with M. vaccae or M. nonchromogenicum suspensions. The growth of both organisms in outbred ICR and four inbred mouse strains was followed up to 30 days. M. nonchromogenicum persisted in the livers and spleens of the inbred mice substantially better than did the M. vaccae population in the same mouse strains. A translucent colony variant of M. vaccae isolated from the opossum survived in vivo better than the opaque colony isolated from opossums and cattle. Persistence of M. vaccae and M. nonchromogenicum was not markedly increased in T-cell-depleted (nude) mice. Normal mice infected with increasing numbers of M. vaccae did not develop delayed-type hypersensitivity to the homologous M. vaccae cytoplasmic protein antigen. When heat-killed M. vaccae were incorporated into Freund adjuvant, both mice and guinea pigs developed delayed hypersensitivity to cytoplasmic antigens prepared from M. vaccae, M. nonchromogenicum and M. vaccae vaccines cross-sensitized guinea pigs to the M. leprae cytoplasmic antigens.

Animals↗
PubMed1979

Suppressor T-cells in BCG-infected mice.

Specific pathogen-free B6D2 hybrid mice were infected with high (10(8) cells, intravenous), moderate (10(6) cells, intravenous), and low 10(3) cells, aerogenic) doses of viable BCG Pasteur. The growth of the BCG in the lungs and spleens of the three groups was followed over a 90-day period and correlated with the level of tuberculin hypersensitivity. Spleen cells were harvested from the three groups of mice at increasing time intervals and filtered through nylon wool to remove adherent cells, and the level of blast transformation after exposure to phytohemagglutinin and purified protein derivative was determined. Early in the BCG infection both the high- and the intermediate-dose groups showed enhanced thymidine incorporation by the spleen cell cultures, followed by a profound depression late in the infection. At this time, both groups of mice were anergic to purified protein derivative injected into footpads. Cell mixing studies demonstrated the presence of a population of suppressor cells in the spleens of the anergic animals. The suppressive abilities of these cells would be ablated by treatment with anti-Thy-1 antiserum and complement. The aerogenically infected mice were unresponsive to purified protein derivative but showed no evidence of suppressor T-cells. The lack of tuberculin sensitivity in these mice seemed to be due to a lack of sensitized T-cells in the spleen rather than to active immunosuppression.

Animals↗
PubMed1979

Development of suppressor T-cells in Mycobacterium habana-infected mice.

Mice were infected intravenously with increasing numbers of Mycobacterium habana (simiae serotype II), and the levels of delayed-type hypersensitivity to purified protein derivative and M. habana cytoplasmic protein antigen were determined after 14, 30, and 90 days. A footpad delayed-type hypersensitivity response was seen in 14-day-infected mice and was followed by a persisting anergy. T-cell-enriched suspensions collected 30 and 90 days into the infection (anergic donors) showed depressed transformation indexes after phytohemagglutinin and M. habana cytoplasmic protein antigen treatment in vitro. The corresponding B-cell mitogen (lipopolysaccharide) responses were not affected. Mixing experiments with T-cell-enriched suspensions from day-90 M. habana-infected donors adoptively suppressed lymphocyte transformation by normal and day-14 spleen cells. This effect could be ablated by anti-theta serum and complement treatment of the day-90 cells, indicating that the lack of in vitro responsiveness to cytoplasmic protein antigen was mediated by a population of suppressor T-cells present in the heavily infected spleens. There was no evidence that similar cells were present in the spleens of the 14-day-infected animals. Suppressor T-cells could be induced in vitro by exposure of day-14 spleen cells to concanavalin A or M. habana cytoplasmic protein antigen before they were mixed with normal or day-14 indicator splenic lymphocytes. The timing of the appearance of suppressor T-cells in the infected spleens corresponded to a loss of footpad hypersensitivity by the M. habana-infected animals.

Animals↗
PubMed1979

Inactivation of Pasteurella multocida within the mouse peritoneal cavity.

Normal ICR mice were injected intraperitoneally with 0.5 ml of thioglycollate broth or 5 x 10(8) heat-killed Pasteurella multocida vaccine and the number of polymorphs, lymphocytes and macrophages in the peritoneal washout suspensions were determined at intervals up to 72 hours. The stimulated mice were challenged intraperitoneally with opsonized or unopsonized P. multocida at increasing time intervals and the rate of growth by the organisms in the washout suspension was determined up to 60 minutes later. The opsonized bacilli were taken up by the 6 hr. exudate cells (50-60% PMNs) and their growth inhibited more effectively than when the 72 hr exudate cells were tested (only 10% PMNs). When the challenge inoculum was introduced into the peritoneal cavities of mice stimulated 6 hrs previously with 5 x 10(8) heat-killed P. multocida vaccine, up to 80% of the bacilli were inactivated over a 30 minute period. However, when 72 or 250 hr peritoneal exudate cells were tested, the inoculum was not inactivated, but showed an increasingly lethal effect.

Animals↗
PubMed1979

Host responses to infection with Yersinia enterocolitica.

The mechanism of protective systemic immunity to Y. enterocolitica infection in mice was studied. It was determined that active immunization of mice with heat-killed yersiniae would induce a protective immune response against an intravenous challenge. This protective response was proven to be humoral in nature when it was demonstrated that passively transferred serum, but not cells, protected normal recipients against a lethal challenge. It was also shown that the immune serum caused opsonization of the microorganisms resulting in enhanced phagocytosis and killing of yersiniae by reticuloendothelial organs.

Animals↗
PubMed1978

Immune response to persistent mycobacterial infection in mice.

Mycobacterium marinum has been recommended as a possible model of M. leprae for use in laboratory studies of antileprosy immunity. M. marinum introduced into the footpads of normal mice underwent a steady decline in viability, with less than 1% survival after a 30-day period. Small numbers of viable bacilli were recovered from the footpads of these mice up to 12 months later. Similarly, mice infected with M. simiae exhibited bacterial populations that persisted for up to 18 months with little change in viability. Injection of M. simiae into the footpads was followed by an extensive redistribution of the organisms in the tissues. Eventally, bacterial counts for footpads and draining lymph nodes stabilized, with small numbers of bacilli still present in the footpads 18 months later. Persistent growth, with little sign of any immune response, was also observed in mice infected with several strains of M. avium, as well as with one strain of M. intracellulare. Other strains of M. intracellulare, as well as M. vaccae and M. nonchromogenicum, failed to establish persistent infections in normal mice, regardless of whether they were introduced by an intravenous or subcutaneous (footpad) route. The relevance of these findings is discussed in relation to antileprosy immunity in experimental animals and in humans.

Animals↗