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Biomedical subjects

F M Collins

Publications and source records attributed to F M Collins.

At least 109 records · Page 6Linked to original sources
PubMed1978

Growth of salmonellae in orally infected germfree mice.

Germfree mice were infected intragastrically, intravenously, or intraperitoneally with 10(3) to 10(9) viable Salmonella typhi Ty2, S. gallinarum 9240, or S. enteritidis 5694. The 50% lethal doses were compared with those for conventionally raised mice. Substantial growth of the salmonellae occurred in the intestinal tract of the germfree mice but, despite the presence of more than 10(9) viable S. typhi or S. gallinarum in the lumen, the liver and spleen cultures remained Salmonella-free, and all of the mice survived the oral challenge. The ileal and cecal Peyer's patches and the mesenteric lymph nodes of these mice contained 10(3) to 10(4) viable salmonellae within 24 h of introduction of the inoculum into the stomach. Despite this local involvement, the infection did not spread systemically even when host resistance was reduced by means of sublethal, whole-body gamma irradiation before oral challenge. Germfree mice infected orally with as few as 10 mouse-virulent S. enteritidis quickly developed severe diarrhea and died within 5 to 8 days as a result of a spreading systemic disease.

Administration, Oral↗
PubMed1978

Cellular antimicrobial immunity.

Acquired resistance to infectious disease may be expressed by a predominantly humoral or a cellular mechanism or, more frequently, by a combination of the two. The cellular interactions which are responsible for the induction of the immune response in the skin, lung, intestinal mucosa, genitourinary tract, conjunctiva, and peritoneal cavity are discussed and the role of living or dead vaccines in the induction of acquired resistance is outlined. The host response involves three different cell types: the phagocytic cell (polymorphs or macrophages), the thymus-dependent (T) lymphocyte, and the thymus-independent (B) lymphocyte-plasma cell line. The normal unstimulated phagocytic cell is capable of killing most nonpathogenic bacteria that gain entry to the tissues. However, the presence of opsonic antibodies and activated macrophages is required to eliminate the pathogenic intracellular parasites. Such immunological activation involves the presence of sensitized T-lymphocytes in the lesion. The cellular response is also characterized by the simultaneous development of a state of delayed-type hypersensitivity (DTH), along with the antimicrobial CMI response. A rising humoral response normally develops subsequently. Killed bacterial cells (except when incorporated into Freund's complete adjuvant) induce the humoral response without the CMI reaction so that such vaccines are not able to fully protect the host against the naturally acquired disease. With the development of cell fractionation methods as well as the identification of distinctive cell surface markers, suspensions of B- and T-cells and macrophages can now be prepared for use in increasingly sophisticated transfer and reconstitution studies. The role of the different cell types in the expression of humoral and cellular immunity has been determined, and the effect of various immunopotentiating and immunosuppressive regimens on the immune system as a whole has been evaluated quantitatively. These studies have led to an appreciation of the role played by suppressor B- and T-cells in the interplay of both humoral and cellular components of the host defense system during the development of immune tolerance, desensitization, anergy, autoimmunity, and the expression of an anamnestic immune response following reinfection.

Adjuvants, Immunologic↗
PubMed1977

Mycobacterium bovis (BCG) infection of the lymph nodes of normal, immune, and cortisone-treated guinea pigs.

Strain-2 inbred guinea pigs were infected intradermally with 10(5)-10(7) viable BCG (Pasteur) organisms by means of multiple scarifications of shaven midflank skin. The spread of the BCG to the draining lymph nodes and on to the spleen was followed quantitatively for 28 days. The population of bacilli at the inoculation site increased as much as tenfold the first 14 days. The number of viable BCG organisms recovered from the primary draining superficial dorsal axillary and inguinal lymph nodes varied from 0.1 to 1.0% of the inoculum, with a further tenfold to 100-fold drop in counts for the secondary subclavian and lumbar lymph nodes. The bacterial counts for the various nodes increased substantially the first 14 days. By 28 days, as many as 1,000 viable bacilli were recovered from the spleen. Increasing the inoculum size or the number of inoculation sites increased the primary node counts and promoted a more extensive and rapid spread by the BCG population to the secondary lymph nodes and spleen. Prior vaccination of the host with living BCG decreased the spread of the BCG inoculum from the scarification site to the various draining lymph nodes. Multiple injections of cortisone tended to reverse this effect.

Animals↗
PubMed1977

Assessment of typhoid vaccines by using the intraperitoneal route of challenge.

Present laboratory tests for human typhoid vaccines use an intraperitoneal route of challenge given 7 days after injection of increasing doses of standard and test vaccines by the same route. In studies reported here, groups of B6D2 mice were vaccinated intraperitoneally with 2 x 10(8) acetone-killed Salmonella typhi Ty2, with the Vi antigen-free variant O-901, or with Yersinia enterocolitica and Serratia marcescens suspensions. Other groups of mice received 200 mug of purified S. typhi or S. marcescens endotoxin, or their corresponding purified lipid A components. All of the vaccinated mice (except for saline- or thioglycolate-injected controls) exhibited increased protection against the lethal intraperitoneal challenge with S. typhi Ty2. Serial quantitative bacterial counts carried out on peritoneal washouts and on homogenates of the draining mediastinal lymph nodes indicated the development of an antibacterial response by the vaccinated host which was not observed in the control animals. Mice receiving purified endotoxin (lipopolysaccharide) exhibited varying degrees of protection, both in terms of increased host survival and the amount of inactivation of the challenge population in vivo. The response seen when the antigenically unrelated S. marcescens lipopolysaccharide was injected was little different from that seen when the acetone-killed S. typhi Ty2 whole-cell vaccine was used. This suggests that nonspecific inactivation of the intraperitoneal challenge contributes substantially to the immune response seen in mice vaccinated intraperitoneally with specific typhoid antigens.

Animals↗
PubMed1977

Mechanisms of acquired resistance to Pasteurella multocida infection: a review.

Pasteurella multocida is an animal parasite of considerable economic and veterinary importance. The organism produces both capsular polysaccharide and somatic (lipopolysaccharide) antigens used to serotype the organisms. Correlations exist between antigenic structure, host susceptibility and strain virulence. The host response seems to be predominantly polymorphonuclear in nature, with little evidence of a mononuclear component in the host response to infection. In the absence of specific opsonins, phagocytosis rates are very slow, the organisms multiplying freely in an essentially extracellular environment. Passive transfer studies indicate that acquired resistance is humorally modiated, presumably by promoting phagocytosis withing the peritoneal cavity. There is, however, no sign of early increased local bactericidal action within the peritoneal cavity; protection seems rather to be due to an inhibition of the rapid spread by the organisms to the bloodstream and other reticuloendothelial organs. Viable attenuated oral vaccines are effective for chicken and turkey poults, both experimentally and under field conditions. The nature of the protective immunoglobulins and their mode of action against an orally induced infection has not been widely examined as yet. Effective protection can be achieved in birds, cattle and experimental animals with a variety of killed vaccines (especially when presented in a suitable adjuvant). The lack of quantitative growth data in suitably vaccinated animals and the absence of definitive studies of the bactericidal mechanisms involved in the expression of this acquired resistance continue to limit our present understanding of defense against this important animal disease.

Animals↗
PubMed1976

Restoration of T-cell responsiveness by thymosin: development of antituberculous resistance in BCG-infected animals.

T-cell-depleted (adult thymectomized, lethally irradiated, bone marrow-reconstituted [THXB]), sham-thymectomized (XB) and normal control mice were injected daily with 3 mg of calf thymosin for 16 days. On day 8 of the treatment, the mice, together with untreated controls, were infected intravenously with 4 X 10(6) viable Mycobacterium bovis (BCG Montreal). Growth of the BCG in the lungs and spleens was compared quantitatively for up to 100 days. Thymosin treatment reversed the progressive weight loss seen in BCG-infected THXB mice and prevented their death due to the ongoing mycobacteriosis that developed in the T-cell-depleted animal. There was a late-developing anti-mycobacterial response in the thymosin-treated THXB mice, which resulted in a progressive decline in viability for the lung and spleen populations over the 40- to 80-day period, when the corresponding counts for the untreated THXB mice remained relatively constant. The histopathology of the lung and the increased antibacterial activity seen in the thymosin-treated THXB mice correlated with decreased [3H]deoxyribonucleic acid levels seen in the lungs and spleen compared with that present in the T-cell-depleted controls.

Animals↗
PubMed1976

Restoration of delayed hypersensitivity to sheep erythrocytes by thymosin treatment of T-cell-depleted mice.

Calf thymosin was injected subcutaneously in daily doses of 0.1 to 3 mg for 12 to 15 days into adult thymectomized, irradiated, bone marrow-reconstituted (THXB) mice. Thymosin partially restored the ability of the T-cell-depleted host to develop delayed-type hypersensitivity to sheep erythrocytes. The degree of restoration varied from 50 to 75% of control values. Thymosin treatment of normal mice potentiated the footpad responsiveness to sheep erythrocytes by as much as 50% over that of untreated controls. The optimum dosage of thymosin seemed to be in the 200- to 500-mug range, and multiple injections were essential for a significant response. Tweleve daily injections of 100 to 500 mug of thymosin restored T-cell reactivity to the THXB mouse, but the responsiveness decayed relatively rapidly once the treatment was stopped. The restoration of immune responsiveness to sheep erythrocytes in T-cell-depleted mice provides a convenient means of demonstrating activity in thymosin preparations in vivo.

Animals↗
PubMed1976

Immune mechanism in Pasteurella multocida-infected mice.

Various immunizing procedures were tested for their effect on the growth of Pasteurella multocida in specific pathogen-free CD-1 mice. Two injections with killed vaccine incorporated into Freund complete adjuvant gave excellent protection against parenteral challenge, but less to control the growth of an aerogenic inoculum. Protection with adjuvant-treated preparation was always superior to that seen with non-adjuvant-treated vaccines. A killed saline-suspended vaccine introduced aerogenically marginally increased resistance to small (2 to 5 mean lethal doses) aerogenic challenges. Live mycobacterium bovis (BCG) vaccine immunopotentiated a single dose of heat-killed P. multocida vaccine in terms of the protective immune response against a subsequent footpad challenge. Hyperimmune mouse serum, administered intraperitoneally, intramuscularly, or intravenously 1 to 7 days prior to subcutaneous challenge with 500 to 5,000 P. multocida, was highly protective. Mice injected in the thigh with 0.2 ml of hyperimmune serum prior to footpad challenge frequently developed a severe inflammatory response with local swelling within 48 h; these lesions often became severly abscessed with time. The passively protected, footpad-infected mice developed active immunity against a subsequent challenge given into the opposite footpad.

Administration, Intranasal↗
PubMed1976

Role of host factors in the pathogenesis of Salmonella-associated arthritis in rats.

To evaluate the roles of the infectious agent and the host in the pathogensis of Salmonella-associated arthritis (SAA), 1O(3) to 10(6) heat-killed Salmonella enteritidis were injected directly into involved carpal joints in normal and actively immunized rats and in hosts adoptively immunized by the intravenous transfer of spleen cells from syngeneic donors with ongoing SAA. As many as 10(6) living Salmonellae invariably failed to generate more than a transient inflammatory response in normal rats. The regression of acute joint swelling was accelerated in both types of immunized hosts. The intensity and duration of acute inflammation evoked in normal rats by 10(6) and 10(9) heat-killed Salmonellae did not exceed the response elicited by 10(3) living organisms. In sharply contrasting results, however, a chronic arthritis became established in a significant number of actively and adoptively sensitized rats after the intra-articular injection of 10(9) heat-killed organisms. No Salmonellae were recovered from these adoptively sensitized rats although small numbers of organisms has been present among the spleen cells in the transfer inocula. Taken together, these results indicate the obligatory involvement of host factors in the mediation of this chronic arthritis and virtually eliminate any likelihood that joint damage in SAA is due to the directly destructive effects of intra-articular infection.

Animals↗
PubMed1976

Mycobactericidal activity of glutaraldehyde solutions.

Aqueous solutions of alkaline glutaraldehyde (buffered at pH 8.5) inactivated a standard suspension of Mycobacterium tuberculosis H37Rv faster than the corresponding acid (pH 3.7 preparation. Quantitative differences in the rate of inactivation of eight other species of Mycobacterium were determined using a 1% solution of alkaline glutaraldehyde and inactivation of residual glutaraldehyde with 1% sodium bisulfite solution. Variations in the rate of kill were observed between the various mycobacterial species tested, but such differences were probably not sufficiently large to be of practical importance. A 2% alkaline glutaraldehyde solution inactivated 10(5) viable M. tuberculosis cells present on the surface of porcelain penicylinders within 5 min at 18 degrees C. This rate of inactivation was faster than in the acidic solution.

Aldehydes↗
PubMed1976

Distribution of mycobacteria grown in vivo in the organs of intravenously infected mice.

Suspensions of 35-day-old Mycobacterium tuberculosis H37Rv prepared from stirred liquid cultures and injected intravenously into CD-1 mice accumulated in the lungs at a significantly higher concentration that that seen with logarithmically growing cells. Mice were infected with logarithmic 8-day-old or stationary phase 35-day-old suspensions of H37Rv, and 24 hours later, the bacilli within pooled lung and splenic homogenates were recovered by differential centrifugation. The bacilli were then homogenized in Tween saline and injected intravenously into fresh mice. The partitioning of the 4 inocula into the lungs and spleens of the secondary recipients was compared to that for the original suspensions grown in vitro. There was a significant increase in the number of lung-adapted H37Rv that could again be recovered from the lungs of the secondary recipients compared to that observed for the corresponding splenic preparations. This effect was not due to bacterial clumping or to size differences in the organisms grown in vivo. Homogenation of H37Rv with normal lung increased the relative accumulation of viable bacilli in the lungs compared to the spleens of recipient mice.

Animals↗
PubMed1975

Involvement of the upper respiratory tract in orally induced salmonellosis in mice.

The possible involvement of the tissues of the head and neck during the early pathogenesis of orally or intragastrically induced murine salmonellosis was examined. Viable counts of Salmonella in the local lymphoid tissues and draining nodes indicated that the ileal Peyer's patches were primarily involved in the development of a subsequent enteric fever, irrespective of the method of oral challenge. Contamination of drinking water with a high concentration of salmonellae produced infection of the ileal Peyers patches and the eventual development of systemic disease. The cervical lymph nodes were sporadically involved early in the infection, but this involvement soon became general, with large numbers of salmonellae in the cervical nodes by 36 hr. A lower concentration of salmonellae in drinking water led to primary involvement of the ileal Peyers patches; upper respiratory tract involvement was detected much later in the infection. Intragastrically invected mice exhibited the same low-level infection of the cervical lymph nodes as that in mice infected via drinking water. Thus systemic infection apparently results from infection of the ileal Peyers patches; a small percentage of the animals develop a concurrent upper respiratory tract infection that may be responsible for the development of carrier states after enteric infection.

Animals↗
PubMed1975

Effect of tilorone treatment on intracellular microbial infections in specific-pathogen-free mice.

Specific-pathogen-free CD-1 mice were treated orally with the drug tilorone (2,7-bis[2-diethylaminoethoxy]fluoren-9-one hydrochloride) at dosages of 10 or 100 mg per kg of body weight. Drug was given 24 h before challenge and then every other day for up to 15 days. Growth of sublethal doses of Listeria monocytogenes, Mycobacterium bovis (BCG Montreal), M. tuberculosis H37Rv, and Salmonella enteritidis in the livers and spleens of intravenously challenged mice was significantly increased compared with that in control animals receiving distilled water orally. Tilorone given every other day at a dosage of 10 mg/kg reduced (but did not completely ablate) the tuberculin response to the mycobacterial infections. Both tuberculin hypersensitivity and anti-mycobacterial resistance returned to normal values within days of stopping the drug treatment. Tilorone treatment at the 100-mg/kg dose level increased the growth of S. enteritidis in both intravenously and intragastrically challenged mice; this effect seemed to be due to the reduced ability of the host to express the normal granulomatous response to the microbial infection within the liver and spleen.

Animals↗
PubMed1975

Effect of oral niridazole treatment on some bacterial infections in mice.

Treatment of specific-pathogen-free CD-1 mice with oral doses of 10 or 100 mg of niridazole per kg of body weight given 24 h before challenge and then every other day for up to 15 days altered the growth curves for Listeria monocytogenes, Mycobacterium bovis (BCG Montreal), M. tuberculosis H37Rv, and Salmonella enteritidis seen in the livers and spleens of the treated animals. Niridazole in an oral dosage of 10 mg/kg reduced (but did not eliminate) tuberculin hypersensitivity in the mycobacteria-infected mice. Both delayed hypersensitivity and antimycobacterial resistance quickly returned to normal levels once the drug treatment was stopped. Niridazole treatment reduced the growth of S. enteritidis in both intravenously and intragastrically challenged mice; this seemed to be due to the antibacterial action of the drug on the salmonellae both in vitro and in vivo.

Animals↗
PubMed1975

Growth of mycobacterium bovis (BCG) in T lymphocyte-depleted mice.

BCG Montreal (10-6 viable bacilli) injected intravenously into adult thymectomized, irradiated, and bone marrow-reconstituted (THXB) C57Bl times C3H F1 hybrid mice induced a progressive systemic infection which killed 95% of the animals within 60 days. Control mice infected with this dose of BCG did not die. The infected THXB mice failed to develop detectable levels of tuberculin hypersensitivity although they did show considerable Arthus (3 h) reactivity. The BCG-infected THXB mice lost weight progressively, and the root spleen and root lung indices increased substantially as the infection proceeded. None of the THXB mice developed an antibacterial immune response to the systemic BCG infection, and this was reflected by the continued persistence of macroscopic lung granuloma in these animals. The BCG-infected control mice developed as many surface tubercles as did the THXB animals, but the granulomas rapidly regressed in size and numbers in the normal mice. The lung changes correlated with the amount of tritiated thymidine incorporated by the lung cells in the later stages of the BCG infection. T cell depletion depressed the early splenic peak normally seen in BCG-infected controls, but, on the other hand, there was a progressive increase in lung counts in the THXB mice as the infection progressed and this late peak was not seen in the control animals. The significance of these findings is discussed in relation to the development of antituberculous immunity by BCG-infected mice.

Animals↗
PubMed1975

Pathogenesis of Salmonella-associated arithritis in the rat.

The distribution of joint lesions in rats with Salmonella-associated arthritis (SSA), as determined in a detailed survey, resembles to a great extent the pattern of small joint involvement in human rheumatoid arthritis. Such lesions, though regularly induced in the rat by the intravenous injection of live S.enteritidis, could not be evoked by the heat-killed organisms injected by various routes with and without extrinsic adjuvants. Efforts to transfer SAA from sensitized donors to either normal or primed recipients, employing lymphoid ce-ls from several sources, also failed repeatedly. Two observations, however, virtually exclude the possibility that joint damage in SAA can be the direct result of sustained intra-articular sepsis. First, the inoculation of as many as 10-3 viable inflammation. Second, the incidence of SAA was significantly lower in weanling rats in the adult controls although the growth and distribution of intravenously injected S. enteritidis was virtually identical in the two groups. Together these observations indicate that the joint damage occurring in SAA is determined by the host and not by the infecting organism. From this, it seems fair to conclude that the destructive arthritis characteristic of this syndrome is immunologically mediated.

Age Factors↗