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Biomedical subjects

M Kennedy

Publications and source records attributed to M Kennedy.

At least 235 records · Page 13Linked to original sources
PubMed1984

Altered lymphocyte recognition repertoire during ageing. III. Changes in MHC restriction patterns in parental T lymphocytes and diminution in T suppressor function.

Irradiated C57BL/6 and (C57BL/6 X C3H)F1 mice have been reconstituted with bone marrow prepared from young (2 month) or aged (24 month) C57BL/6 donors. Indirect examination of the T cell receptor for H-2d alloantigens on H-2b splenocytes of these reconstituted mice, using the suppression of the H-2b anti-H-2d response induced by (H-2b X H-2d)F1 anti-(H-2b anti-H-2d) suppressor cells, suggests that the allo-receptor repertoire derived from bone marrow of aged mice is different from that of T cells derived from young bone-marrow precursors. These observations were supported by direct evidence, from rosette formation with murine erythrocytes, for changes in the T cell receptor of these different (radiation-chimaera) sources of H-2b-T cells. Along with these subtle changes in the allo-receptor repertoire of T cells derived from bone marrow of aged mice grown in irradiated F1 hosts, there is a decrease (compared with mice reconstituted with bone marrow from young donors) in the apparent frequency of T cells recognizing antigen in association with the new MHC-restricting elements in these parent F1 chimaeras. Analysis of those cell subsets reported to be involved in the regulation of MLC responses suggests that some of the differences observed between T cell differentiation from bone-marrow stem cells of young or aged donors may in part be explained by a diminution in the production from bone marrow of aged mice of those cells important for homeostasis within the immune system.

Aging↗
PubMed1984

The predictive value of three diagnostic procedures in the evaluation of palpable breast tumours.

In a prospective study of 200 palpable breast tumours of 200 women, the diagnostic specificity and sensitivity of clinical examination, mammography, and fine needle aspiration were compared, alone and in combinations. All tumours were excised and examined histologically, and 38 were malignant. The diagnostic sensitivity of clinical examination was high, 98% (91-99), whereas the specificity was rather low, 48% (36-60). No statistically significant differences were found between the sensitivities or the specificities of the three examinations. When the methods were combined the sensitivity was 100% (96-100) and the specificity was 37% (27-46). Statistically, no improvement of the diagnostic value could be shown. It is concluded that the possibility of distinguishing between malignant and benign palpable breast tumours is not increased by adding mammography and/or fine needle aspiration, but the discovery of two non-palpable malignant tumours by mammography underscores the importance of this method in disclosing subclinical malignant lesions. The study disclosed a statistical possibility of overlooking a few malignant tumours when using these three procedures. Therefore, we advise that all palpable breast tumours should be excised.

Biopsy, Needle↗
PubMed1984

Altered tumor growth in vivo after immunization of mice with antitumor antibodies.

A comparison has been made between the growth patterns of two spontaneously appearing mammary adenocarcinomas in murine bone marrow radiation chimeras and in mice preimmunized with monoclonal antibodies (MAb) detecting embryo-associated antigenic determinants. A correlation was seen between the ability of the embryo-immunized chimeras to produce cytotoxic antibody to the tumors, as assessed by an antibody-dependent cellular cytotoxic assay, and the permissiveness of the mice for growth of a tumor transplant. In addition, mice deliberately preimmunized with cytotoxic MAb (antibody-dependent cellular cytotoxic assay) allowed more rapid growth specifically of that tumor earlier found to be most sensitive to the MAb used for immunization. By comparing the changing antigenic phenotype of tumor cells serially passaged through different immunized, nonimmunized mice, evidence was found suggesting that immunization could cause either antigen modulation of transferred tumor cells or a (transient) selective advantage to antigenically discrete subpopulations within the heterogeneous tumor population. Finally, we have studied the growth pattern of tumor cells transplanted into mice immunized with rabbit antibodies directed against the murine MAb. In this case, tumor growth was slowed preferentially for the tumor reactive with the specific MAb, and again, predictable changes in the antigenic spectrum of tumor cells harvested from these animals were observed. Our overall findings are interpreted in terms of the involvement of networks of antibodies reacting with embryo-associated antigens in the regulation of growth of the murine mammary adenocarcinomas studied.

Adenocarcinoma↗
PubMed1983

Alteration in lymphocyte recognition repertoire during aging. II. Changes in the expressed T-cell receptor repertoire in aged mice and the persistence of that change after transplantation to a new differentiative environment.

Changes in the T-lymphocyte alloreceptor repertoire associated with aging by exploring the frequency of cytotoxic T-lymphocyte precursors (CTLp) available for activation by various major histocompatibility complex (MHC) haplotypes in mice of different ages have been investigated. There was no consistent pattern of change in CTLp frequencies. Thus, for instance, while the frequency of responder C57B1/6 CTLp for ATH alloantigen decreased with age, the frequency for C3H alloantigen increased. There was no significant change in the overall frequency of splenic CTLp (assessed irrespective of antigen specificity). No evidence was found that CTL produced by activated CTLp of aged mice were less specific in their lytic capacity that CTL produced by CTLp of young mice. However, by assaying responder CTLp cultures at limiting dilution we obtained evidence that the "burst size" (mean lytic capacity per responder well assayed at limiting dilution) was diminished with age of the donor of the CTLp pool. Furthermore, we obtained evidence that the apparent affinity of CTL for their target antigen was consistently decreased when those effector cells were derived from a pool of CTLp of aged mice. All of these changes reflected in mature T cells derived from aged mice were already apparent in the bone marrow stem cell pool of aged individuals and were not due to environmental influences alone, as assessed by the phenotype of T cells derived from young or old bone marrow stem cells transplanted to young or aged recipient mice. A final study has examined evidence for more subtle changes in the T-cell alloreceptor repertoire, reflecting heterogeneity in young or aged mice in the recognition repertoire associated with a given antigenic specificity. By preparing F1 anti (parent anti-F1)-suppressor cells directed against CTL from young parental mice (a, b, c), or aged parental mice (x, y, z), we have explored the heterogeneity in the anti-C3H alloreceptor repertoire in individual young or aged C57B1/6 mice. Suppression by immunized F1 animals was assessed in tissue culture (inhibition of mixed lymphocyte culture (MLC) responses) or in vivo (inhibition of lethal GvHD induced by inoculation of parental lymphocytes into sublethally irradiated F1 hybrid mice). Irrespective of the assay system used, the data suggests that the receptor repertoire of aged T lymphocytes uses recognition structures different from those of young individuals, and that there is less individual-to-individual variation in the receptor repertoire of aged mice than in young mice.

Aging↗
PubMed1983

Recognition specificities, development, and possible biological function of natural killer cells in the mouse. I. Spleen focus forming assay for natural killer activity and analysis of lectin-like recognition structures on the surface of murine natural killer cells.

A number of simple sugars have been tested and found to be effective in blocking lysis of YAC-1 tumor target cells by nonimmune murine natural killer (NK) effector cells. Using a spleen fragment culture system an assay has been developed which allows us to compare the inhibition of lysis observed in replicate culture wells prepared from cells contained in one spleen fragment (less than or equal to 1 X 10(6) cells). The inhibition pattern of any well was found to fall naturally into 1 of 25 (of the total 128 possible tested) patterns. Using this panel analysis of NK activity in individual mice of the same or different strain has been compared. Our data suggest that within any given strain the inhibition pattern of NK effector cells is quite uniform. Consistent differences are seen between strains which are interpreted in terms of a genetic control of the final expression of the NK recognition repertoire. In adult F1 hybrid individuals the pattern of recognition by NK cells is best considered a result of the codominant expression of genes contributed by each parent.

Animals↗
PubMed1983

IgM paraproteins with immunological specificity for a Schwann cell component and peripheral nerve myelin in patients with polyneuropathy.

The sera of 9 patients with benign IgM paraproteinaemia and chronic sensorimotor neuropathy were tested for reactivity to human peripheral nerves by the indirect immunoperoxidase method. They reacted in very high titre (10(-3)-10(-6) with a cytoplasmic Schwann cell component, and to lesser degree, with peripheral nerve myelin (10(0)-10(-3). The Schwann cell staining was in the form of perinuclear cytoplasmic granules and was only seen with adult nerve. The distribution of the antigen was similar to that of the metachromatically staining Pi-granules of Reich, which accumulate in the peripheral nerves with age. Specific activity was present in the IgM and F(ab)2 fractions and could be absorbed out with peripheral nerve tissue, but not with liver. Reactivity is not a simple function of the IgM level, since many IgM paraproteins do not react. The antibody is species specific and binds to human, but not to any component of rabbit, rat or guinea pig sciatic nerves. Antigenicity is removed by pretreatment of the nerve with chloroform-methanol or periodate, but not protease or trypsin. Reactivity is restored, after periodate treatment, by exposure to sodium borohydride. It is suggested that some IgM paraproteins have a specificity for a myelin glycolipid or glycoprotein, which normally accumulates in the Pi-granules of the Schwann cell cytoplasm as a function of age.

Humans↗
PubMed1983

Physiological concentrations of prolactin can promote the growth of human breast tumor cells in culture.

There is only indirect evidence at present to suggest a role for PRL in either the genesis or progression of human breast cancer. Here, we report the results of experiments in primary cultures of breast tumor cells from a hyperprolactinemic breast cancer patient who had an elevated mean 24-h PRL concentration but a normal diurnal variation of PRL release. The effects of PRL and GH on the growth of the dispersed cells from the breast tumor was evaluated in monolayer culture using a recently developed microculture technique. Pharmacological quantities of GH produced significant increases in the number of population doublings of the breast tumor cells. Also, PRL concentrations present in the patient's circulation were demonstrated to significantly increase the number of population doublings of the breast tumor cells obtained in primary cultures. Thus, physiological concentrations of PRL stimulated the growth of breast tumor cells from this premenopausal patient.

Adult↗
PubMed1983

A possible maternal effect in the abnormal hyporesponsiveness to specific alloantigens in offspring born to neonatally tolerant fathers.

Newborn CBA mice were inoculated i.p. with 1 X 10(8) adult (CBA X A)F1 lymphoid cells with 5 X 10(7) F1 hybrid lymphoid cells thereafter inoculated i.v. at 14-day intervals. The mice were subsequently grafted with A/J tail skin at 24 days of age. At 8 wk of age, individual tolerant males with intact skin grafts were each mated with similar tolerant skin-grafted females or with 8-wk-old control normal CBA females. Approximately 0.4 ml of peripheral blood from 7-wk-old progeny born to these crosses, along with the blood from age-matched progeny born to normal CBA incrosses, were used for in vitro mixed leukocyte cultures (MLC). All progeny received skin grafts of (CBA X A)F1 tail skin at 7 1/2 wk of age. In this study, we show i) that MLC hyporesponsiveness to histocompatible cells is an acquired phenotype expressed by lymphoid cells of the progeny of tolerant male mice, and ii) that these progeny also show delayed rejection of (CBA X A)F1 skin grafts. The continued breeding of the first generation animals established that a similar transmission of hyporesponsiveness can be observed in the second generation progeny. When putatively normal females, however, which had borne several litters after mating with neonatally tolerant males, were mated with "normal" (nontolerant) males; their offspring also exhibited a specific hyporesponsiveness in MLC to the initial tolerizing allodeterminants. This suggests that there may ultimately be a maternally derived origin for the transmission of characters from tolerant males.

Animals↗
PubMed1982

Prophylactic cefuroxime in total joint replacement.

Cefuroxime was given during operation to 95 patients undergoing 106 total joint replacements (hip 69: knee 37). Two regimes were used. Either 1 g was given intravenously with induction of anaesthesia and then two intramuscular injections of 1 g 6 and 12 h later, or 1.5 g was given intravenously with induction and two injections of 750 mg each intramuscularly 6 and 12 h later. The concentrations of cefuroxime in bone, capsule and blood were measured in 77 patients. The assays were carried out independently in two laboratories. In most instances concentrations in the bone were above the MICs for likely pathogens, even after allowing for any contaminating blood. Concentrations in synovial capsule were generally higher than in bone. After a follow-up period of 2 years, two patients developed deep infections. The overall infection rates are comparable with the best results reported in the literature using other prophylactic antibiotics or with ultra-clean air systems.

Adult↗
PubMed1982

Conditioned immune response associated with allogeneic skin grafts in mice.

Groups of CBA mice were given sham skin grafts (conditioned stimulus, CS) or alloantigen only (unconditioned stimulus, US; C57BL/6 lymphoid cells inoculated i.p.). A further group of animals received simultaneous US and CS (alloantigen (US), in this case actually given in the context of a C57BL/6 skin graft). The peripheral blood leukocyte (PBL) pool of all animals was analyzed in tissue culture for the frequency of cytotoxic T lymphocyte precursors (CTLp) specific for alloantigens on the grafted tissue. After three "conditioning" trials, spaced at intervals to allow recovery in all groups of the CTLp frequency to that of naive control mice, individuals in all groups were sham-grafted (given CS alone). PBL of these mice were tested 2 days after removal of the casts. Only group CS + US, and only some 50 to 60% of these, were able to show a "conditioned" increase in the CTLp frequency specific for alloantigens of the grafted tissue after sham-grafting. When these "responder" mice were subdivided into two groups that were subsequently given two trials of CS only or CS + US, followed by retesting with CS alone, either extinction or reinforcement of the previously conditioned response was observed.

Animals↗