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Biomedical subjects

M Bennett

Publications and source records attributed to M Bennett.

At least 307 records · Page 17Linked to original sources

Effect of the venodilated state on sympathetic-induced venoconstriction in normal subjects.

The interaction between venoconstriction induced by application of ice to the forehead and nitroglycerin-induced venodilation was examined in 19 healthy male volunteers, ages 25 +/- 5 years (mean +/- standard deviation). Venous tone was determined by the equilibration technique. Mercury-in-silastic plethysmography was used to measure changes in forearm volume before and after ice application during control conditions, and before and after ice application in the venodilated state (nitroglycerin spray, 0.8 mg). Venous tone and arterial pressure increased significantly after the application of ice to the forehead in both the control and venodilated states, indicating that ice increased sympathetic tone. Nitroglycerin increased venous volume by 0.28 cc/100 cc arm. The venoconstrictive effect of ice after nitroglycerin (a decrease in venous volume of 0.53 cc/100 cc arm) was quantitatively similar to the venoconstrictive effect of ice during control conditions (a decrease in venous volume of 0.54 cc/100 cc arm). These results suggest that sympathetic-induced venoconstriction is not attenuated in the venodilated state.

Adult↗

Effector cell expression of NK1.1, a murine natural killer cell-specific molecule, and ability of mice to reject bone marrow allografts.

The rejection of Hh-1 incompatible bone marrow cells in irradiated mice is mediated by NK cells and is genetically regulated. We tested the role of the NK-specific gene, NK1.1, in regulating the rejection of allogeneic bone marrow cell grafts. NK1.1+ mice, that are known to display strong resistance against Hh-1 incompatible grafts, were crossed to H-2/Hh-1 identical NK1.1-, poor responder mice, and the progeny were backcrossed to the poor responder parent. The segregating mice were individually typed for their expression of NK1.1 and the ability to resist Hh-1 incompatible bone marrow cells (BMC). A strong correlation was noted between expression of NK1.1 and rejection of H-2d/Hh-1d BMC. Our results support the idea that NK1.1 is one of the genes responsible for strong resistance to Hh-1d (determinant 2) but not for Hh-1j (determinant 3) BMC grafts. We suggest that the NK1.1 molecule functions as an accessory molecule in the cellular interactions involving the recognition of Hh-1 determinants.

Animals↗

Regulation of B lymphocytes by natural killer cells. Role of IFN-gamma.

Using a co-culture system of fractionated B cells and highly purified NK cells, we have demonstrated direct interactions between B lymphocytes and NK cells. B cells are able to stimulate the production of IFN-gamma by NK cells. This stimulatory ability is restricted to a subpopulation of large, presumably in vivo activated B lymphocytes. The secreted IFN-gamma in turn inhibits polyclonally induced B cell proliferation. Small resting B cells neither stimulate IFN-gamma production nor are they measurably affected by NK cells.

Animals↗

Natural killer cells and their precursors in mice with severe combined immunodeficiency.

Our studies with scid mice have clarified the relationship between T cells and NK cells. C.B-17 scid mice have normal frequency of transplantable NK progenitors in their bone marrow which develop into fully functional NK cells. Spleens of scid mice contain mature NK cells which are phenotypically and functionally indistinguishable from NK cells found in normal mice. These cells retain their TCR genes in germline configuration and do not transcribe the CD3 genes. Thus, NK cells are distinct from the earliest identifiable cells committed to the T-lineage. In addition to the spleen, the thymus of scid mice also contains mature NK cells. These cells constitute a small proportion of the thymus cell population and can be clearly distinguished from the majority of cells, which have the phenotype and molecular characteristics of very early T-lineage cells. There is no evidence that NK cells within the thymus are derived in situ from a common NK/T precursor. Together these data support the hypothesis that NK cells form an independent lineage.

Animals↗

Studies on poxvirus infection in cats.

The development of clinical disease and the pathogenesis of cowpox were studied in domestic cats inoculated by a variety of routes. Intradermal titration in two cats demonstrated that as little as five pfu of cowpox virus caused a primary skin lesion. Intradermal inoculation of greater than or equal to 10(5) pfu cowpox virus resulted in severe systemic disease. Large amounts of virus (greater than or equal to 10(3) pfu/g) were isolated from skin lesions and the turbinates of cats killed at eight and 11 days post-inoculation (dpi). Lesser amounts of virus (congruent to 10(2) pfu/g) were isolated from lymphoid tissues and the lung, and small amounts of virus were isolated from various other tissues. A white cell-associated viraemia was detected from 5 dpi onwards. Skin scarification with 10(3) or 50 pfu cowpox virus enabled reproduction of the naturally-acquired disease. Cat-to-cat transmission was demonstrated from cats inoculated by skin scarification, but caused only subclinical infection in sentinel cats. Oronasal inoculation resulted in transient coryza and milder generalized disease than skin inoculation, and no transmission to sentinel cats. Preliminary investigations showed vaccinia virus (Lister strain) to be of low infectivity in cats while inoculation of ectromelia virus (Mill Hill strain) did not cause any clinical signs.

Animals↗

Successful treatment of patients in whom germ cell tumour masses enlarged on chemotherapy while their serum tumour markers decreased.

Enlargement of tumour masses with a fall or no change in tumour marker levels was noted in eight of 287 patients during chemotherapy for NSGCT at the Charing Cross and Mount Vernon Hospitals between 1977 and 1988. These eight patients had elements of differentiated teratoma in the primary specimen and in five the enlarging masses showed cystic change on CT scan. The increase in tumour mass occurred within 6 months of starting treatment. At surgery, four patients were found to have differentiated teratoma and have been followed for 15 months to 5 years without relapse. Two patients who also had some areas of embryonal carcinoma in the resected specimens had post-operative chemotherapy and are alive disease free at 8 and 24 months respectively. Two patients died: one post-operatively of uncontrolled haemorrhage secondary to aortic rupture and the second of acute myeloid leukaemia following 8 years of intermittent therapy for unresectable differentiated teratoma. The successful outcome in six of these eight patients suggests that enlarging teratomatous masses on chemotherapy can be managed by surgical resection and, when active tumour is present, by the use of post-operative chemotherapy.

Adolescent↗

Pan natural killer cell monoclonal antibodies and their relationship to the NK1.1 antigen.

The study of natural killer (NK) has been difficult because they account for a small percentage of peripheral blood and splenic lymphocytes and the paucity of NK specific antigens that have been identified. We have isolated pure populations of C57BL/6 (H-2b) NK cells using the IgG2b monoclonal antibody PK136 (anti-NK1.1). These NK1.1+ cells were used to immunize 129/J (H-2b) mice, and in this report, we describe three new NK specific monoclonal antibodies (SW3A4(IgM), SW4B12(IgG1), and SW2B4(IgG2b] and their relationship to the known murine NK antigen NK1.1. We have further characterized the NK1.1 antigen as a 39 kd molecule which is coded for by a gene which appears to map to chromosome 6.

Animals↗

Recombinant vaccinia virus expressing the herpes simplex virus type 1 glycoprotein C protects mice against herpes simplex virus challenge.

The gene encoding the herpes simplex virus type 1 (HSV-1) glycoprotein C (gC) was isolated and cloned into a vaccinia virus insertion vector, and the resulting vaccinia-gC vector was used to construct a recombinant vaccinia virus that expressed gC (VVgC5). Infection of cells with VVgC5 resulted in cell surface expression of authentic HSV-1 gC. HSV-1 gC-specific neutralizing antibodies were produced in VVgC5-immunized mice, and lymphocytes exhibited an HSV-1-specific proliferation response in vitro following infection. More importantly, VVgC5-immunized mice were resistant to subsequent lethal HSV-1 challenge.

Animals↗

Self-disclosure in a clinical context by Asian and British psychiatric out-patients.

A study is described in which self-reported self-disclosure levels of Asian and British out-patients to psychiatrists are examined as a function of racial and gender match to psychiatrist. Analysis of self-disclosure scores for 77 subjects revealed no overall differences between Asian and British subjects, or between men and women. Asian subjects, however, reported being prepared to disclose significantly more to a psychiatrist of the same sex as themselves, regardless of race; no such effect was found for British subjects. British women reported being prepared to reveal significantly more to a psychiatrist of the same race as themselves; this effect was not observed in any of the other three subgroups. Implications of these findings for clinical practice are discussed.

Adult↗

Bone marrow cell transplants involving intra-H-2 recombinant inbred mouse strains. Evidence that hemopoietic histocompatibility-1 (Hh-1) genes are distinct from H-2D or H-2L.

Hemopoietic histocompatibility (Hh) Ag are noncodominantly expressed on bone marrow stem cells and other normal and neoplastic cells of hemopoietic origin. H-2/Hh-1 allogeneic or parental-strain bone marrow grafts are eliminated in a determinant specific manner by NK cells. In inbred mouse strains, seven Hh-1 alleles representing combinations of five different Hh-1 antigenic determinants are described. Each Hh-1 allele maps in the vicinity of H-2D, and the genes that map to Hh-1 are transacting regulatory genes. The expression of a particular determinant depends on the absence of the regulatory gene and the presence of the appropriate structural gene. The primary focus of this study is to ascertain whether the Hh-1 phenotype and the serologic H-2DL typing are always correlated or whether recombinant can separate the two. To achieve this, we used a panel of irradiated hosts that are able to recognize the different Hh-1 determinants on the bone marrow cells of congenic intra-H-2 recombinant donors. We report: 1) the majority of strains show a correlation between Hh-1 and H-2DL: 2) B10.RQDB and B10.WB strains dissociate Hh-1 from Lb: 3) nine H-2S/D interval recombinant strains exhibit no correlation between the H-2DL type and Hh-1 phenotype; and 4) in two strains from this group, B10.D2 (R106) and B10.RSF5, H-2S/D crossovers occurred within Hh-1r, (Hh-1 regulatory). We conclude that Hh-1r is a distinct regulatory locus mapping telomeric of H-2S and centromeric of, although probably closer to, H-2D.

Animals↗

Polymorphism of Hh-1, the mouse hemopoietic histocompatibility locus.

The major goal of these studies is to more fully assess the polymorphism of the hemopoietic histocompatibility (Hh) genetic system. H-2 homozygosity is required for optimal immunogenicity of bone marrow cell (BMC) grafts, and "hybrid resistance" to grafts of parental strain BMC by irradiated H-2 heterozygous F1 hybrid mice suggests that Hh-1 antigens are inherited recessively. The Hh-1 antigens are also expressed on other normal hematopoietic cells and lymphoid tumors, and natural killer cells are the effectors which mediate the elimination of BMC grafts in an Hh-specific manner. Previous studies have demonstrated three different antigens mapping to the Hh-1 locus near H-2D. We test the expression of Hh-1 on BMC of all nonrecombinant H-2 haplotypes of independent origin and H-2j, a presumed natural recombinant. Hh-1 typing is based on the pattern of growth and rejection in a panel of hosts. F1 hybrids with H-2b, H-2d, and H-2k are produced and used as donors and hosts to confirm the phenotype. Grafts of b, d-, and j-haplotype marrow serve as prototypical examples of determinants that are provisionally designated as 1, 2, and 3, respectively. We describe a new determinant, 4, in the k haplotype. It is non-codominantly expressed, maps to H-2D, and is also expressed on H-2b BMC. NZW, H-2z grafts exhibit a phenotype similar to k, but express a unique determinant 5 which can be distinguished from determinant 4. This additional determinant is also expressed by the b haplotype. The d, f, and p haplotypes all express determinant 2, and grafts of j-haplotype marrow are found to express determinants 2 and 5 in addition to determinant 3. The q and r haplotypes are null for all known determinants. Finally, we describe a phenotype which is a new combination of previously described determinants: s-haplotype grafts express determinants 1, 2, and 4. The polymorphism of Hh-1 detected thus far consists of seven alleles which are combinations of five distinct determinants.

Animals↗

Gallium-67 renal uptake in Sjogren's syndrome.

This case report describes a 61-year-old male with Sjogren's syndrome. Diffuse Ga-67 uptake in the kidneys was seen due to renal involvement with this disorder. Sjogren's syndrome should be considered in the differential diagnosis of diffuse bilateral Ga-67 accumulation in the kidneys.

Gallium Radioisotopes↗

Mechanism of anti-asialo GM1 prevention of graft-vs-host disease: identification of allo-antigen activated T cells.

The purpose of this study was to begin to dissect the mechanism whereby anti-asialo GM1 (alpha ASGM1) prevents otherwise lethal graft-vs-host disease (GVHD) across multiple minor histocompatibility barriers in mice. Phenotypic characterization of cells from the peak proliferative time of the graft-vs-host reaction (C57BL/6J lymph node cells----irradiated LP/J, days 5-7) revealed the alpha ASGM1 and alpha Thy 1.2 identified cells with an approximate 80% concordance and that NK-1.1 staining was negligible. Because resting T cells do not label with alpha ASGM1, the epitope recognized by alpha ASGM1 on GVHR T cells is an activation antigen. Because asialo GM1 has been previously found on the surface of activated macrophages, we wanted to distinguish between the two most likely targets for the in vivo effect of alpha ASGM1 infusions (T cells or macrophages). We compared the effects of alpha ASGM1 infusions on alloantigen-stimulated T-cell proliferation versus antigen presentation: T-cell proliferation was markedly reduced by alpha ASGM1 infusions, whereas antigen presentation function was not diminished. We conclude that the mechanism whereby alpha ASGM1 prevents GVHD does not involve NK cells or antigen presenting cells, but does involve activated donor T cells. The potential therapeutic advantage of such an antibody for use in human disorders compared to pan-immunosuppression lies in its ability to eliminate selectively those T cells involved in the immunologic process (i.e. activated T cells) while sparing the remainder of the T-cell repertoire.

Animals↗

Kinetics and location of bone marrow cell graft rejection by irradiated mice.

Natural killer (NK) cells were eliminated with rabbit anti-Asialo GM1 (anti-ASGM1) serum to test the kinetics and location of bone marrow cell (BMC) rejection. Anti-ASGM1 serum was injected intravenously in mice at various times before or after irradiation (8.6 Gy) and transfer of parental-strain or allogeneic BMC. Growth of BMC was determined by measuring splenic 5-iodo-2'-deoxyuridine-125I incorporation 5 days after cell transfer. Anti-ASGM1 serum weakened hybrid resistance even if injected intravenously as late as 24 h post-BMC transfer and even in recipients injected with polyinosinic:polycytidylic acid so as to boost NK activity. If regenerating spleen cells (higher rate of cell cycling) were used as donor cells instead of BMC, the length of time required for rejection was unaffected. Anti-ASGM1 serum injected intravenously rapidly inhibited splenic NK activity and lung clearance of YAC-1 tumor cells, but when injected intratracheally, it only inhibited lung NK activity. Thus, BMC rejection occurs in the hematopoietic tissue and requires at least 24 h.

Animals↗