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Biomedical subjects

D Franks

Publications and source records attributed to D Franks.

At least 19 recordsLinked to original sources
PubMed1991

Randomised controlled trial of day and in-patient psychiatric treatment. 2: Comparison of two hospitals.

Acutely ill patients presenting for admission in two district psychiatric services were randomly allocated to day-hospital or in-patient care. In both services a quarter of all admissions could not be allocated because they were too ill (half of these were compulsory admissions); these patients were predominantly manic and schizophrenic patients with pronounced psychotic symptoms and disturbed behaviour. In one service 80% (41/51) of patients randomly allocated to day-hospital treatment were successfully engaged in treatment compared with 54% (19/35) in the other service. This difference arose because only patients with mildly disturbed behaviour could be treated at the second day hospital. For patients who were successfully allocated, the outcome of treatment was similar in terms of psychiatric symptoms and social functioning. The results of a treatment trial for acutely ill patients in one district service cannot be generalised to other district services without due attention to the factors, such as staffing levels, which determine the degree of disturbed behaviour that can be tolerated in the day hospital.

Acute Disease↗
PubMed1989

Healing potential of the anulus fibrosus.

The purpose of this study was to investigate the healing of surgically created defects in the anulus fibrosus in an effort to determine the healing potential of this structure. Four identical lesions were made in the anulus fibrosus of ten dogs at levels L2-L5. Two dogs were killed at 3, 6, and 9 weeks. Four dogs were killed at 12 weeks. The spines were harvested during a 3- to 12-week period and evaluated grossly and microscopically. Our study demonstrated that a stab wound of the anulus has a limited healing potential and the persisting defect could provide a pathway for irritating nuclear fluid escape onto perineural tissue, possibly resulting in persistent low-back pain.

Animals↗
PubMed1985

Failure of scalp hypothermia to prevent hair loss when cyclophosphamide is added to doxorubicin and vincristine.

Scalp hypothermia can prevent alopecia caused by low doses of doxorubicin alone or in simple combinations. The technique was used in 60 patients with breast cancer (24 receiving adjuvant therapy; 36 with advanced recurrent disease) receiving chemotherapy with iv doxorubicin (40 mg/m2) and vincristine (1.4 mg/m2) on Day 1 together with oral cyclophosphamide (200 mg/m2) on Days 2-5. The patients' desire to continue scalp hypothermia, reflecting their perception of benefit, and an objective assessment of hair retention were the study end points. The mean number of cycles of chemotherapy given (6.1 in patients receiving adjuvant therapy; 3.8 in those with advanced disease) exceeded the number of cycles with hypothermia (2.1 in patients receiving adjuvant therapy; 1.6 in those with advanced disease); no patients retained enough hair to encourage them to continue scalp hypothermia throughout chemotherapy. All patients were rated as having poor hair retention. Scalp hypothermia is ineffective when used with combinations of drugs, each causing alopecia, or with high doses of doxorubicin.

Alopecia↗
PubMed1984

Serological and bacteriological survey of three horse studs for contagious equine metritis.

A bacteriological and serological survey for evidence of contagious equine metritis (CEM) was made during the 1980 breeding season on 3 horse studs in South Australia with a history of previous infection. Swabs from the clitoral sinus and the cervix were cultured for Haemophilus equigenitalis and serum was screened for antibody using the complement fixation test (CFT) and the enzyme-linked immunosorbent assay (ELISA). The specificity of both tests was greater than 0.99 but the ELISA was more sensitive in detecting antibody in infected mares. On the evidence presented it was concluded that H. equigenitalis is no longer present in the horse studs investigated.

Animals↗
PubMed1984

Surface proteins of the human eosinophil. I. Isolation of eosinophil IgG binding proteins.

Proteins involved in the attachment of eosinophils to immobilized antigen-antibody complexes were isolated. Eosinophils, purified from normal human peripheral blood, were surface labelled with 125I-iodide in the presence of lactoperoxidase and hydrogen peroxide. Immobilized immune complexes were prepared by covalent coupling of tetanus toxoid antigen to cellulose and treatment of the fixed antigen with human anti-tetanus IgG. Intact cells were allowed to interact with the antigen-antibody complex and the cells were then lysed in situ with a salt solution containing the non-ionic detergent NP40. After exhaustive washing to remove unattached proteins, the bound proteins were eluted with a buffer containing mercaptoethanol with or without SDS. A major protein of mol. wt 16K and a minor protein of mol. wt 18K were isolated. These proteins were unaffected by the temperature of attachment of eosinophils to the fixed IgG antigen complexes or by the presence of protease inhibitors and did not therefore appear to be proteolytic cleavage products.

Antigen-Antibody Complex↗
PubMed1983

Importance of oxidative metabolism in T cell cytotoxicity: a comparison of cloned T cells and spleen cells.

To distinguish between direct and indirect involvement of oxygen metabolites in CTL cytotoxicity a comparison was made of cloned CTLs and mixed cells from mouse spleen. Tumour cells could be protected from cloned CTLs and from spleen CTLs by the thiol protecting reducing agents DTT and DETC. Cytotoxic activity was inhibited by diversion of reducing power from NAD(P)H to artificial electron acceptors and by the inhibitor of NAD(P) linked enzymes cibacron blue. Although H2O2 formation could be detected during the lysis of P815 by spleen CTLs it did not prove to be a necessary requirement for cytolysis since it was not formed when glutaraldehyde-treated P815 cells were lysed. Of the scavengers of toxic oxygen metabolites tested only the hydroxyl radical scavenger sodium benzoate inhibited cytotoxicity.

Animals↗
PubMed1982

Immunological studies in patients with rheumatoid arthritis receiving azathioprine and myocrisin in combination.

Thirty-one patients with classical or definite rheumatoid arthritis (RA), on treatment with azathioprine and sodium aurothiomalate in combination were studied. Absolute lymphocyte counts and IgA levels were reduced but this did not reach statistical significance. Lymphocyte transformation with phytohaemagglutinin (PHA) showed no significant difference from a control group. However, antibody dependent cell-mediated cytotoxicity was significantly impaired compared to rheumatoid controls (p less than 0.001). There was no relation to the degree of impairment of ADCC and the current dose of azathioprine nor to the total dose or duration of therapy. Inhibiting material to cell-mediated cytotoxicity was present in the sera of 23 patients but its presence showed no relation to the degree of cytotoxicity exhibited by cells in the same patient. Our studies of cellular cytotoxicity have revealed alterations in cellular function possibly attributable to azathioprine.

Adolescent↗
PubMed1982

The mechanism of Fc-mediated interaction of eosinophils with immobilized immune complexes. II. Identification of two membrane proteins, modified by the interaction.

Human peripheral blood eosinophils attach to and flatten down onto antibody-coated surfaces and subsequently degranulate. An antibody-coated surface was prepared by treating a layer of agar, containing tetanus toxoid antigen and eosinophil chemotactic factor (ECF), with human anti-tetanus immunoglobin. Changes in eosinophil surface proteins during attachment to the antibody-coated agar layer were detected by lactoperoxidase catalysed iodination. Purified eosinophils were pre-treated with unlabelled iodide, lactoperoxidase and hydrogen peroxide to block pre-existing accessible tyrosine residues on the cell surface. They were then allowed to interact with the agar layer, and subsequently treated with lactoperoxidase and 125I-labelled iodide to label newly accessible surface proteins. Separation of the radioactive proteins by sodium dodecyl sulphate/polyacrylamide gel electrophoresis revealed that, while incubation of the cells in suspension restored the major proteins to the cell surface, interaction with the antibody-coated agar layer caused the appearance of additional proteins of apparent molecular weight 55K, 30K, 28K and 18K. The 55K, 28K and 18K proteins were greatly reduced when antibody was absent, but the 55K protein was distinguishable from immunoglobulin G (IgG) heavy chain, since it could be detected in low amounts even in the absence of antibody. It was found in purified plasma membranes and it could be separated from IgG heavy chain by iso-electric focusing. The possibility is discussed that this protein is either linked to the receptor for the Fc portion of IgG, or that it is itself the receptor. The 18K protein required both antibody and ECF for maximum expression, but was seen in limited amounts with ECF alone. Possibly it is concerned with an ECF-mediated recognition of IgG. Unlike the 55K protein, it binds concanavalin A. Plasma membranes were prepared from eosinophils by lysis in borate, followed by purification on a glass-bead column. Both the 55K and the 18K proteins were found to be major components of the eosinophil membrane.

Antigen-Antibody Complex↗
PubMed1982

Role of sulphydryl groups in T lymphocyte-mediated cytotoxicity.

The role of thiols in T cell-mediated cytotoxicity was investigated by studying the thiols of the target cell and cytotoxic cell separately. Agents which protect the reduced thiols of the target cell inhibit their lysis by the cytotoxic T cells; thiol reactive reagents may be directly toxic to the target cell. The thiol groups of the effector cell are also important, since pre-treatment with thiol reactive reagents inhibits killing.

Animals↗
PubMed1981

The interaction in vitro between bovine immunoglobulin and juvenile Fasciola hepatica.

Freshly excysted Fasciola hepatica possess an outer glycocalyx which stimulates an antibody response in cattle infected with F. hepatica metacercariae. Sera from animals receiving either a single or a double infection were examined for levels of IgM, IgG1 and IgG2 specific for the outer glycocalyx of intact live juvenile F. hepatica. High levels of specific IgG1 were found to predominate. Using positive sera in an indirect fluorescent antibody assay, the bovine immunoglobulins labelled the outer glycocalyx in a characteristic reticulated pattern. On incubation at 37 degrees C this pattern rapidly broke up into discrete clumps and progressed until the entire antibody-outer glycocalyx complex was shed. The shedding phenomenon was shown to be continuous and, by using preparations of Fab fragments, was not due to the bivalent binding of the sensitizing antibody.

Animals↗
PubMed1981

Evasion of the oxidative microbicidal activity of human monocytes by trypomastigotes of Trypanosoma dionisii.

Trypomastigotes of Trypanosoma dionisii, a stercorarian trypanosome from bats, are effectively killed by neutrophils from human peripheral blood but are less sensitive to the cytotoxic action of human monocytes. The mechanism of killing appears to involve peroxidase and hydrogen peroxide. Trypomastigotes are as effective as epimastigotes in inducing the formation of hydrogen peroxide by effector cells. They are, however, less sensitive than epimastigotes to the cytotoxic effect of peroxidase and hydrogen peroxide. They are therefore susceptible to the high concentrations of peroxidase found in the phagosome of the neutrophil, but resist the lower levels encountered in monocytes.

Humans↗
PubMed1980

Role of hydrogen peroxide in the cytotoxic reaction of T lymphocytes.

Evidence is presented that T lymphocyte cytotoxicity is mediated by hydrogen peroxide (H2O2). At a concentration of 5 x 10(-4) M H2O2 induced 51Cr release from pre-labelled P815 mastocytoma cells. H2O2 was generated when T lymphocytes from mouse spleen were exposed to P815 cells. The concentration of H2O produced was apparently one thousand times lower than the concentration required to lyse the P815 cells. This suggests that the H2O2 is produced and acts at a highly localized site on the target cell. Sulphydryl groups on the target cell were particularly sensitive both to H2O2 and to spleen cell attack. The activity of the spleen cells was inhibited by cyanide and azide and by reducing agents which protected the target cells. Cytotoxicity was enhanced by agents which prevented H2O2 breakdown.

Animals↗
PubMed1980

In vitro effect of immune serum and bovine granulocytes on juvenile Fasciola hepatica.

Cattle, infected with Fasciola hepatica metacercariae, produce antibodies against the outer glycocalyx of freshly excysted juvenile F. hepatica. Using 51Cr-release and viability assays such antibodies in the presence or absence of bovine complement did not cause discernible damage to the parasite. The presence of excess antibody caused the build-up of large aggregates of antigen--antibody complexes over the parasite surface; these aggregates were eventually shed into the medium. Neutrophils and eosinophils were obtained by selective stimulation of the mammary gland of heifers, and attached in large numbers to flukes coated with either IgG1 or IgG2. Attachment was dependent on Fc receptors although the adherence of the eosinophils was more prolonged than that of the neutrophils. Using 51Cr-release and viability assays no damage occurred to the flukes using either eosinophils or neutrophils in antibody-dependent cell-mediated cytotoxicity; adherent granulocytes were eventually shed. It is suggested that the rapid turnover and excretion of the outer glycocalyx of juvenile flukes prevents the intimate attachment of granulocytes to the helminth parasite, which is perhaps a prerequisite for cell-mediated damage to occur.

Animals↗
PubMed1979

Phagocytosis and killing of Trypanosoma dionisii by human neutrophils, eosinophils and monocytes.

The cell-mediated resistance of human leucocytes to Trypanosoma dionisii, a bat parasite related to T. cruzi, was investigated. Human peripheral blood neutrophils and monocytes were cytotoxic to T. dionisii as assessed by electron microscopy and by induction of 99mTc release from trypanosomes pre-labelled with [99mTc] pertechnetate. The enhancement of cytotoxicity by specific antiserum varied considerably from one individual to another. Neither blood lymphocytes nor blood eosinophils induced 99mTc release from T. dionisii. The trypanosomes were readily phagocytosed by neutrophils and monocytes even in the absence of added antiserum but the rate was enchanced when antiserum was present. Eosinophils also phagocytosed T. dionisii but only in the presence of antiserum. Investigation by electron microscopy revealed that T. dionisii is rapidly destroyed in the phagocytic vacuole of enutrophils and monocytes and by eosinophils. Phagocytosis, ultrastructural damage and induction of 99mTc release occurred more rapidly in neutrophils than in monocytes.

Animals↗
PubMed1978

Role of hydrogen peroxide and peroxidase in the cytotoxicity of Trypanosoma dionisii by human granulocytes.

The mechanism of the cytotoxic reaction of leukocytes to Trypanosoma dionisii was investigated. Cytotoxicity was measured by release of [99mTc]pertechnetate from labeled protozoa. Both granulocytes and lymphocytes were found to be cytotoxic to antibody-coated T. dionisii. The reaction was inhibited by diethyldithiocarbamate and by potassium cyanide, both of which inhibit myeloperoxidase. Myeloperoxidase from azurophil granules was toxic to T. dionisii, provided that hydrogen peroxide was also present. Hydrogen peroxide formation was induced in granulocytes and, to a lesser extent, in lymphocytes by antibody-coated T. dionisii. Inhibition of this hydrogen peroxide formation by treatment of the effector cell surface with p-diazobenzenesulfonic acid inhibited cytotoxicity. It is therefore concluded that granulocytes, and probably also lymphocytes, kill T. dionisii with hydrogen peroxide by a peroxidase-mediated reaction. Although hydrogen peroxide and myeloperoxidase alone were also cytotoxic to the lymphoblastoid cell line CLA4, it seems unlikely that this is the cytotoxic mechanism for this process because these cells were unable to induce hydrogen peroxide formation.

Animals↗
PubMed1978

Antibody-dependent cell-mediated cytotoxicity in cattle: activity against 51Cr-labeled chicken erythrocytes coated with protozoal antigens.

Bovine mononuclear cells in the presence of bovine anti-chicken erythrocyte sera at high dilutions induce release of chromium-51 from labeled chicken erythrocytes. Bovine effector cells are capable of recognizing both bovine immunoglobulin G(1) and bovine immunoglobulin G(2); in contrast, human effector cells only recognize immunoglobulin G(1). Effector cell activity of bovine mononuclear cells is equally distributed between peripheral blood and spleen. As in other species, thymus and lymph node cells exert no antibody-dependent effect, although some direct cytotoxicity by lymph node cells may be observed. Antibody-dependent cell-mediated cytotoxicity against a bovine cell line can also be detected. By using a tannic acid technique, it was found that chicken erythrocytes coated with Theileria parva piroplasm antigen or with Trypanosoma rhodesiense variant-specific coat antigen form suitable targets for bovine antibody-dependent cell-mediated cytotoxicity assays. By using such targets, a moderate degree of direct cytotoxicity by bovine mononuclear cells, in the absence of antibody, is always observed; this may be reduced by choosing optimal conditions of tannic acid treatment and antigen sensitization and by the use of short incubation periods for the cytotoxicity assay. Observations have been made on the variant specificity, time course of appearance, and association with immunoglobulin G(1) of the antibody activity responsible for cell-dependent cytotoxicity against chicken erythrocytes coated with T. rhodesiense antigens. The potential usefulness of this technique in the analysis of protective immune responses against protozoal infections is discussed.

Animals↗
PubMed1977

Antibody-dependent eosinophil-mediated damage to 51Cr-labeled schistosomula of Schistosoma mansoni: damage by purieid eosinophils.

After earlier observations that antibody-dependent, cell-mediated damage to 51Cr-labeled schistosomula can be ablated by pretreatment of a mixed preparation of human peripheral blood leukocytes with an anti-eosinophil serum and complement, we investigated the cytotoxic effects of eosinophil-enriched cell preparations. Preparations containing up to 98.5% eosinophils and devoid of neutrophils were effective in mediating antibody-dependent damage to schistosomula. Preparations enriched in mononuclear cells or in neutrophils, and devoid of eosinophils, were inactive. Eosinophils from some patients with eosinophilia induced by schistosomiasis were less active on a cell-to-cell basis than cells from normal individuals. The possibility that such cells were initially blocked by immune complexes was considered, and it was found that reasonable cytotoxicity by purified eosinophils from patients with eosinophilia could be generated by overnight cultures. A possible requirement for cooperation between eosinophils and other cell types was also studied. Lymphocytes, neutrophils and monocytes failed to enhance eosinophil-mediated cytotoxicity. These results provide further evidence that the eosinophil is the only cell in man responsible for antibody-dependent, complement-independent damage to schistosomula in vitro. Eosinophils from individuals, however, differ in their cytotoxic potential by a mechanism yet to be elucidated. The possible relationship of these findings to immunity in vivo is discussed.

Animals↗