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Biomedical subjects

A Volkman

Publications and source records attributed to A Volkman.

At least 37 records · Page 2Linked to original sources
PubMed1982

Resistance to infections in mice with defects in the activities of mononuclear phagocytes and natural killer cells: effects of immunomodulators in beige mice and 89Sr-treated mice.

Beige mice, which are a homolog of the Chediak-Higashi syndrome, and mice treated with 89Sr to destroy the bone marrow provide animal models of defects in mononuclear phagocyte and natural killer cell functions. The innate resistance of these mice to viruses such as herpes simplex and encephalomyocarditis viruses, however, is normal. Moreover, treatment of the mice with immunomodulators such as Propionibacterium acnes (formerly designated Corynebacterium parvum) and pyran produced a significant increase in resistance to encephalomyocarditis virus. The antiviral effect of P. acnes in 89Sr-treated mice was exhibited during marked monocytopenia and without evidence for an inflammatory influx of macrophages into the peritoneal cavity. Treatment with P. acnes was also effective in increasing the resistance of beige mice to infection with Listeria monocytogenes. Thus, immunomodulators can be effective in mice that exhibit impaired macrophage and natural killer cell functions.

Adjuvants, Immunologic↗
PubMed1982

Resident macrophage proliferation in mice depleted of blood monocytes by strontium-89.

The capacity of resident peritoneal macrophages and alveolar macrophages for self-renewal was studied in CD-1 mice depleted of radiosensitive blood monocyte precursors by irradiation of the bone marrow with the bone-seeking isotope 89Sr. Thermoluminescent dosimetry and studies of DNA synthesis showed that significant levels of radiation were absorbed predominantly in anatomical sites in close proximity to bone. Cell proliferation remote from bone marrow was unaffected when quantitated by DNA precursor uptake. Between 10 and 15 days after injecting mice intravenously with 89Sr at 2 microCi per gm. of body weight, monocytes were only rarely detectable in the peripheral blood as determined by morphology, stains for nonspecific esterase and peroxidase, and by latex phagocytosis. Total numbers of resident peritoneal and alveolar macrophages were not significantly decreased and tritiated thymidine incorporation in vivo persisted at normal levels rather than regressing at a predicted rate during profound monocyte depletion. The data, therefore, suggest that local proliferation by resident macrophages in monocytopenic and intact mice is an important mechanism of population renewal.

Animals↗
PubMed1982

Role of prostaglandins E1, E2, F2 alpha, I2 and thromboxane in salmonella-associated arthritis in rats.

Salmonella-associated arthritis of rats was used as an experimental model for in vivo evaluation of prostaglandins in chronic inflammation. Since the arthritic lesions were localized mainly in the hind paws, femorla vein plasma measurements of prostaglandins were made to estimate the amounts of PGE1, PGE2 alpha, 6-keto-PGF1 alpha and TXB2 produced during the progression of the arthritic disease. PGE1 production was significantly increased in the early phase of infection but these changes were inversely related to the joint swelling in the later stages of the disease. Changes in products of arachidonic acid (20:4 omega 6) were opposite to those observed in PGE1, a product of dihomo-gamma-linolenic acid, (20:3 omega 6), in that measurable levels of these chemicals were lower in the early phase of infection but there was a progressive increase in each compound during the chronic phase of inflammation. Concentrations of PGE2, PGF2 alpha, 6-keto-PGF1 alpha and TXB2 increased proportionately to the severity of the arthritic lesion.

6-Ketoprostaglandin F1 alpha↗
PubMed1982

Ultrastructure of beige mouse peritoneal macrophage lysosomes.

One phenotypic expression of the Chediak-Higashi syndrome in humans and the analogous disorder in the beige mouse (C57BL/6bg/bg) is the presence of anomalous lysosomes identifiable as enlarged cytoplasmic inclusions. This alteration has been used in the study of the circulation and source of certain mononuclear phagocytes in mice. In the present study abnormally enlarged lysosomes are inconsistently demonstrable in the resident peritoneal macrophage of the beige mouse. However, the beige phenotype is also expressed in resident peritoneal macrophages by the presence of anomalous ring form and elongated dumbbell-shaped lysosomes. The former structures resemble those recently described [13] in blood monocytes from patients with the Chediak-Higashi syndrome.

Animals↗
PubMed1980

Intrarenal growth of the Walker 256 tumour and renal vein concentrations of PGE2, PGF 2 alpha, and TXB2: effects of diazepam.

Walker 256 tumours grafted under the left kidney capsules in rats showed enhanced growth following daily treatment with diazepam 500 micrograms (1.7 mg/kg body weight) subcutaneously but not with 1250 micrograms. Thromboxane B2 (the metabolite of TXA2) levels in venous drainage from both the tumour bearing left kidney and from the right control kidney were reduced significantly in all the three groups of tumour bearing rats. Plasma PGE2 was higher in the venous drainage from the tumour bearing left kidney than from the right control kidney. Significantly higher levels were measured following 500 micrograms but not after 1250 micrograms of diazepam. Plasma PGF2 alpha on the other hand, was lower in the plasma from the tumour bearing kidney and was further lowered in animals receiving diazepam treatment.

Animals↗
PubMed1979

The influence of diazepam administration in rats bearing the R3230AC mammary carcinoma.

The growth of the R3230AC mammary carcinoma was studied in female Fisher 344 rats that were treated with diazepam. Diazepam at 250 micrograms/animal/day (2.5 mg/kg body weight) and 500 micrograms/day was administered for 4 weeks, starting 2 days before subcutaneous transplantation of uniform pieces of the tumour. Tumour size was significantly increased in the group receiving 250 micrograms but was below the levels observed in the saline treated controls in those given 500 micrograms diazepam. Plasma PGE2 and PGF2 alpha concentrations were comparable in control and diazepam treated animals.

Animals↗
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↗
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↗
PubMed1975

The elaboration of leukotactic mediators during the interaction between parental-type lymphocytes and F1 hybrid cells.

Mixed leukocyte cultures consisting of white blood cells from (Lewis times BN) F1 hybrids and Lewis parents produced monocyte chemotactic factor. Elaboration of this material preceded incorporation of 3H-thymidine. Local graft vs host (GVH) reactions were induced by subcapsular injection of parental thoracic duct cells into F1 hybrids. Homogenates from these kidneys, but not from kidneys injected with syngeneic thoracic duct cells, contained monocyte chemotactic factor. Little or no neutrophil chemotactic factor was present. Ultracentrifugal analysis of the monocyte chemotactic factor indicated a distribution similar to that found previously in culture fluids of lymphoid cells stimulated by soluble antigens. Differential counts of inflammatory cells extracted in suspension form from kidneys undergoing a GVH reaction indicated the majority of cells to be lymphocytic in type, but with a significant proportion of monocytes. Virtually no neutrophils were present. These findings indicate that a monocyte chemotactic factor is produced by cultures of parental leukocytes stimulated by semiallogeneic cells and that a similar factor appears in GVH reactions in the rat kidney. This chemotactic factor may be relevant to the character of the cellular exudates.

Animals↗
PubMed1974

The cytokinetics of monocytosis in acute salmonella infection in the rat.

The mechanisms responsible for monocytosis occurring in acute Salmonella infection were studied by means of isotopic labeling and autoradiography. Male (Lewis x BN)F(1) hybrid rats (160-180 g) were pulse-labeled with [(3)H]TdR at varying intervals with respect to the time of i.v. injection of about 10(6) living Salmonella enteritidis. The half time for monocytes in the blood was estimated from the exponential decline in the percentage of labeled monocytes. The average generation time for dividing monocyte precursors in bone marrow was estimated by fitting a regression line to the decline in median grain counts (halving-time = T(G)). After an initial fall, the absolute number of blood monocytes rose to a plateau about 2.5 x normal on day 5, suggesting the reimposition of steady state conditions. The half time of monocytes in the blood of infected rats was shortened to 25 h throughout the infection, compared with 61 h estimated in uninfected rats. T(G) was reduced to 15 h (days 1-3) but later reverted to the preinfection level of 34 h (days 4-8). Another early response to infection was the release of immature monocytes into the blood. These cells, however, were too few to offset the initial monocytopenia. Under these conditions, with little or no division of blood monocytes, the sustained monocytosis (days 4-8) must have been due to enlargement of the dividing precursor pool. Excessive loss of monocytes from the blood thus appears to activate a feedback mechanism. However, a more direct stimulating effect on monocyte production by endotoxin could have contributed substantially to the monocytosis.

Animals↗
PubMed1973

Polyarthritis associated with Salmonella infection in rats.

Rats infected intravenously with Salmonella enteritidis develop a chronic destructive polyarthritis. The joint lesions resemble those of human rheumatoid arthritis in distribution and pathology. On the basis of histological and microbiological studies, involvement does not appear to be the result of intra-articular sepsis. Instead, the data favor the view that transient infection incites an immunological response that localizes in the joint and becomes destructive.

Animals↗
PubMed1972

The host cell response in the local graft-versus-host reaction induced in the kidneys of F 1 rats by parental thoracic duct lymphocytes.

Radioautographs of infiltrative cells in the kidneys of (Lewis x BN)F(1) rats labeled with tritiated thymidine (TdR(3)H) before the subcapsular injection of parental (Lewis) thoracic duct lymphocytes (TDL) showed a predominantly host-proliferative response by 4 days after grafting. The immediate renal incorporation of TdR(3)H was used to measure the local graft-vs.-host (GVH) reactions. Substantial reactions could still be induced in the face of the considerable degree of leukopenia after 400 R whole body gamma-irradiation. These results suggest that radioresistant cells are capable of carrying on the appropriate host activities and that the weakness of GVH reactions induced after higher doses of irradiation may be due to impairment of the mitotic mechanism of host cells. The importance of circulating leukocytes as a source of immunogenic stimulation was nevertheless substantiated by inducing local GVH reactions with Lew TDL in chimeric parental-type rats that had been repopulated with F(1) bone marrow. This result also emphasizes the nonspecific nature of tissue destruction in the renal GVH reaction in confirmation of Elkins. In this and other situations in which B cells were the predominant F(1) type elements available for interaction with parental-type TDL the reactions were nearly equivalent or equivalent to those in the appropriate controls. Typical local GVH reactions could be induced in heavily irradiated hosts by an inoculum of combined parental and F(1)-type TDL in the apparent absence of mononuclear phagocytes. The possible relationship between the activation of host lymphocytes, the involvement of B cells, and the nonspecific nature of tissue damage in the renal GVH is discussed.

Animals↗