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Biomedical subjects

J L Turk

Publications and source records attributed to J L Turk.

At least 127 records · Page 7Linked to original sources
PubMed1984

Isolation and analysis of circulating immune complexes in leprosy.

Circulating immune complexes (CIC) were isolated by two antigen nonspecific methods from 60 leprosy patients belonging to borderline tuberculoid (BT) and lepromatous (LL) types with and without reactions. CIC were elevated in both BT and LL reactions. CIC from BT in reaction (BTR) were found to consist largely of IgG and C3, whereas, C-reactive protein could be found in CIC from LL reactions (LR). In addition, IgM and rheumatoid factor were demonstrated in the complexes of LR patients who had mainly arthritis. Antimycobacterial antibody was seen in the complexes of two-thirds of LR patients who had predominantly skin manifestations as part of their reaction. The relevance of these findings to the clinical manifestations of different types of reactions is discussed.

Animals↗
PubMed1984

Prostaglandin and thromboxane levels in central nervous system tissues from rats during the induction and development of experimental allergic encephalomyelitis (EAE).

Prostaglandin (PG) and thromboxane levels were measured in the spinal cords and cerebellums of rats during the induction, disease and recovery periods of experimental allergic encephalomyelitis (EAE). In spinal cords PGE and 6-oxo-PGF1 alpha increased to maximum with the onset of neurological symptoms, 11-12 days after inoculation. However, the levels returned to normal at the height of clinical disease, despite the persistence of inflammatory lesions. After an initial fall, PGF2 alpha increased to normal limits, 11-12 days after inoculation, and remained at this level throughout the experiment. In contrast, the cerebellum content of all the eicosanoids decreased prior to the appearance of clinical EAE. PGF2 alpha and 6-oxo-PGF1 alpha concentrations subsequently increased but the PGE and thromboxane levels remained depressed for the duration of the study. The role of the eicosanoids in modulating the immune response to neuroantigen is discussed together with our recent findings in guinea pigs with acute EAE.

6-Ketoprostaglandin F1 alpha↗
PubMed1984

Potentiation of T-lymphocyte function by bleomycin.

Bleomycin, an anti-cancer drug, hitherto thought to have no effect on the immune response, was found to increase contact sensitivity in the guinea pig to 2,4-dinitrofluorobenzene. The drug was given in a single dose (125 mg/kg) on the day of or up to 3 days after sensitization, to achieve this effect. The drug was ineffective if given 3 days before or 4 days after sensitization. In addition, if given 2 or 3 days after sensitization, it caused increased T-cell proliferation in lymph nodes draining the skin sensitization site. It is suggested that the potentiating effect of bleomycin is not on suppressor cell function, as with cyclophosphamide, but might have an effect on local interleukin 2 production, particularly if given when T-cell proliferation is on the increase.

Adjuvants, Immunologic↗
PubMed1984

Prostaglandin levels in cerebrospinal fluid from multiple sclerosis patients in remission and relapse.

Radioimmunoassay (RIA) techniques have been employed to determine prostaglandin (PG) levels in the cerebrospinal fluid (CSF) from multiple sclerosis (MS) patients in remission and relapse and in subjects with other neurological diseases (OND). PGE and PGF2 alpha concentrations in spinal fluid from MS patients in relapse were significantly lower than values estimated during remission and in individuals with OND of the central nervous system (CNS). These observations are discussed in relation to the clinical state of patients with demyelinating disease together with a consideration of the concept that disordered immune mechanisms contribute a central role in the pathogenesis of MS.

Dinoprost↗
PubMed1984

A longitudinal study of the prostaglandin content of central nervous system tissues from guinea pigs with acute experimental allergic encephalomyelitis (EAE).

The levels of prostaglandins (PGs) E, F2 alpha and 6-oxo-PGF1 alpha, in spinal cords and cerebellums of guinea pigs were measured during the development of experimental allergic encephalomyelitis (EAE). The earliest change observed was an elevation of PGE in spinal cords, but not cerebellums , 5-7 days post-inoculation (PI) and prior to the appearance of clinical symptoms. PGE content of spinal cords continued to rise until days 12-14 PI when the animals displayed paralytic EAE. In contrast, PGF2 alpha and 6-oxo-PGF1 alpha levels in spinal cords peaked on days 9-11, when the animals exhibited initial clinical signs, but fell to lower values by days 12-14 PI. In cerebellums , the PGE content increased more slowly than in spinal cords, consistent with the lower numbers of mononuclear cell infiltrates, whereas PGF2 alpha and 6-oxo-PGF1 alpha levels remained unaltered. The relationships between the observed changes in prostanoid levels, lesion development and the appearance of clinical symptoms are discussed.

6-Ketoprostaglandin F1 alpha↗
PubMed1984

Kinetics of the effect of a single dose of cyclosporin-A on antibody and cell mediated immune responses in the guinea pig.

The effect of 100 mg/kg cyclosporin-A (CS-A), given as a single dose either before or after immunization, on antibody levels and skin test reactivity was investigated. CS-A was found to suppress both primary and secondary anti-hapten and anti-carrier IgG1 and IgG2 antibodies. However, CS-A was also capable of inducing enhanced anti-hapten antibodies. CS-A showed a similar effect on contact sensitivity reactions to 2,4-dinitrofluorobenzene (DNFB) as has been shown for cyclophosphamide (CY) in that, given before sensitization, skin reactions were enhanced, whereas given after sensitization they were suppressed. However, the effect of CS-A on the T-cell proliferation in the lymph node, draining the site of sensitization to DNFB, differed from that of CY. Although CS-A induced a depression of T-cell proliferation, this suppression was more prolonged than that found in CY treated animals. Also, these draining lymph nodes never showed increased T-cell proliferation as did those in animals treated with CY before sensitization. This work demonstrates that a single dose of CS-A can both suppress or enhance antibody production and delayed hypersensitivity. The timing of the dose of CS-A in relation to the time of primary immunization is important. However, both IgG1 and IgG2 primary and secondary antibody responses can be altered. Comparison with the effect of CY on antibody levels and contact sensitivity would indicate that in some ways CS-A reacts similarly to antimitotic agents and in other ways is different.

Animals↗
PubMed1984

Studies on migration inhibitory factors of non-lymphoid origin.

A large number of mouse fibrosarcoma and adult guinea pig fibroblast cultures were examined for their ability to produce migration inhibitory activity. In most cases culture supernatants were found to inhibit macrophage migration, in a dose-dependent manner. Toxicity of the tested material could be excluded by: a) experiments using colchicine as a stimulator of macrophage migration and, b) examination of the effect of test materials on macrophage monolayer cultures. Additionally, migration inhibitory activity was found in fibroblast, but not fibrosarcoma frozen and thawed extracts. Furthermore, incubation of cells with puromycin could only inhibit production by fibrosarcoma, thus suggesting that the fibroblast activity was due to preformed cellular constituents. Fractionation of concentrated culture supernatants by Sephadex G-200 gel filtration showed that the activity derived from fibrosarcoma cells could be eluted in a narrow molecular weight fraction (18,000-22,500), whereas the fibroblast activity was heterogenously distributed over a wide range. Migration inhibitory activity in fibroblast extracts was mainly associated with higher molecular weight material. Differences could be demonstrated between these activities and lymphocyte migration inhibitory factor, including inhibition by methyl-pentoses and the presence of macrophage aggregating activity.

Animals↗
PubMed1984

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↗
PubMed1984

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↗
PubMed1984

Comparison of DNFB and K2Cr2O7 'flare-up' reactions in the guinea pig.

A comparison has been made of the 'flare-up' of 2,4-dinitrofluorobenzene (DNFB) contact reactions with that of 'flare-up' of potassium dichromate (K2Cr2O7) contact sensitivity reactions following the intravenous injection of dinitrobenzenesulphonic acid (DNBSO3) or K2Cr2O7. Differences in time course were noted and these were confirmed by increase in vascular permeability and histological appearance. Failure to influence the reactions with indomethacin would appear to exclude the participation of an Arthus-type phenomenon, despite evidence of a drop in the circulating antibody levels. Increased numbers of basophils were found particularly in the DNFB/DNBSO3 reaction during its resolution. These reactions could therefore be broadly included among the cutaneous basophil hypersensitivities.

Animals↗
PubMed1984

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↗
PubMed1984

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.

Animals↗
PubMed1984

The effect of cyclophosphamide on immunological control mechanisms.

Cyclophosphamide (CY) given three days before immunization with a range of antigens increases the intensity of cell-mediated immune responses. CY given around the time of immunization also reverses immunological tolerance, blocks antigenic competition and modifies desensitization. The effect on antibody production is not so predictable. However, it may increase the IgE response without affecting IgG1 or IgG2 response to the same antigen and may abolish immunological memory. The action of CY is on rapidly-turning-over cell populations. Lymphocytes are maximally at risk 48 hours before they transform into large pyroninophilic cells, that is just before the S phase of cell division. CY has a preferential effect on both T- and B- suppressor cells. The application of these findings to experimental cancer models is discussed. These findings are not restricted to CY, as a wide range of cytotoxic drugs with different actions at the cellular level may have similar profound effects on the regulation of the immune response.

Animals↗
PubMed1983

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.

Animals↗
PubMed1983

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↗
PubMed1983

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.

Animals↗
PubMed1983

The effect of cyclophosphamide on immunological memory.

The intradermal injection of bovine gammaglobulin (BGG) anti-BGG immune complexes, in antibody excess, in Freund's complete adjuvant, induced strong delayed hypersensitivity and a state of priming which was recognized by an antihapten and anticarrier humoral immune response following injection of DNP9-BGG nine days later. Cyclophosphamide (CY), given either as small multiple doses over the first seven days after sensitization, or as a single dose on various days, had a strongly selective effect on the antihapten and anticarrier response. The drug treatment, using multiple doses, suppressed the development of a priming for the antihapten IgG2, but not for IgG1 production. Pretreatment with a large dose of CY (250 mg/kg) led only to an enhanced production of anti-DNP IgG2 and not of IgG1 antibodies. This suggests that CY inhibits the suppressor cells regulating the IgG2, but not the IgG1, antibody response. CY, given on day +3 but not on days 0 and +7 impaired both the IgG1 and the IgG2 response. Anticarrier-specific IgG1 could not be detected and the IgG2 was completely suppressed by the drug, given either as multiple doses or as a single large dose administered on days 0, +3 or +7. The selective influence of CY given about the time of the initial immunization suggests that the IgG1 and IgG2 responses involve memory cells with different susceptibilities to CY. Moreover, these memory cells appear to have a different susceptibility to CY as compared with that of the effector cells involved in delayed hypersensitivity.

Animals↗