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Biomedical subjects

M Bennett

Publications and source records attributed to M Bennett.

At least 127 records · Page 7Linked to original sources
PubMed1995

Hybrid resistance: 'negative' and 'positive' signaling of murine natural killer cells.

Murine NK cells can reject allogenic or parental-strain bone marrow cells (BMC) in vivo and can lyse T lymphoblasts in vitro. The 'missing self' hypothesis states that absence or presence of 'negative signals' from target cell class I antigens (Ag) to NK receptors determines whether or not lysis occurs. Indeed, lysis of parental-strain blasts by purified F1 NK cell subsets occurred only in the presence of anti-receptor antibodies. Evidence for 'positive signaling' to NK cells by class I Ag includes rejection of D8 (Dd) transgene to B6) BMC by B6 hosts. The outcome of other BMC transplants contradict the missing self idea, because donors with identical class I Ag differ in compatibility with certain hosts. Perhaps class I Ag-NK cell receptor interactions dominate over other target-NK cell interactions. These interactions are usually 'negative' but can be 'positive'.

Animals↗
PubMed1995

Ambulatory blood pressure in pregnancy: comparison of the Spacelabs 90207 and Accutracker II monitors with intraarterial recordings.

OBJECTIVE: Our purpose was to compare systolic and diastolic blood pressures obtained with the Spacelabs 90207 (Spacelabs Medical Products, Dee Why, Australia) or Accutracker II (Suntech Medical Instruments, Melbourne, Australia) ambulatory blood pressure monitoring devices with intraarterial blood pressures in pregnant women. STUDY DESIGN: Direct (intraarterial) and resting blood pressures with the ambulatory blood pressure monitoring device were compared in 39 pregnant women (14 Accutracker II and 25 Spacelabs 90207). RESULTS: The Accutracker II device underestimated direct systolic pressure by -9 (-13, -3) mm Hg (median, interquartile range) (p = 0.028) but gave similar diastolic pressure. The Spacelabs 90207 device gave similar systolic pressures but overestimated direct diastolic pressure by 7 (2, 12) mm Hg (p < 0.001). Variability for systolic and diastolic blood pressures within subjects was similar with the two devices. Both received poor gradings by standards of the British Hypertension Society and did not meet criteria of the Association for the Advancement of Medical Instrumentation, with intraarterial recordings used as the reference. CONCLUSIONS: The Accutracker II device significantly underestimated resting direct systolic pressure, whereas the Spacelabs 90207 device significantly overestimated resting direct diastolic pressure in pregnant women. Although poor gradings were achieved for both devices when intraarterial pressures were used as the reference, this is similar to comparisons of routine mercury sphygmomanometry with intraarterial recordings and does not mean these devices are unsuitable for use in pregnancy.

Blood Pressure Monitoring, Ambulatory↗
PubMed1995

Comparison of the susceptibility of the red fox (Vulpes vulpes) to a vaccinia-rabies recombinant virus and to cowpox virus.

Sylvatic rabies can be efficiently controlled by vaccination of foxes with a vaccinia-rabies recombinant virus. However, the risk of recombination between the engineered vaccine virus and other orthopoxviruses endemic in wildlife, such as cowpox virus, still needs to be investigated. In this study, foxes inoculated orally and intradermally with cowpox virus were found to be not very susceptible to cowpox virus, which was isolated from only the oropharynx and tonsils, at low titre and for only five days after inoculation. Thus the risk of recombination between these viruses in foxes is very low.

Animals↗
PubMed1995

Serological evidence for the reservoir hosts of cowpox virus in British wildlife.

The reservoir host of cowpox virus in Western Europe is not known, but epidemiological evidence from human and feline infections indicates that the virus is probably endemic in small wild rodents. Therefore, serum and tissue samples were collected from a variety of wild British mammals and some birds, and tested for evidence of Orthopoxvirus infection. Antibody reacting with cowpox virus was detected in 9/44 (20%) bank voles (Clethrionomys glareolus), 8/24 (33%) field voles (Microtus agrestis), 17/86 (20%) wood mice (Apodemus sylvaticus) and 1/44 house mice (Mus musculus), but in no other animal species tested. Although virus was not isolated from any animal, this serological survey, together with other evidence, suggests that bank and field voles and wood mice are the main reservoir hosts of cowpox virus in Great Britain.

Animals↗
PubMed1995

Protection against Mycoplasma pulmonis infection by genetic vaccination.

The induction of an immune response against a foreign protein usually requires purification of that protein, which is injected into animals. The isolation of pure protein is time consuming and costly. Recently, a technique called biolistic transformation (biological ballistic system) microparticle injection, gene gun, or particle bombardment was developed. The basic idea is that DNA or biological material coated onto heavy tungsten or gold particles is shot into target cells or animals. We have vaccinated mice by introducing the gene (Mycoplasma pulmonis DNA or a specific fragment) encoding a protein recognized by a protective monoclonal antibody directly into the skin or muscle of mice by two methods: (i) using a hand-held form of the biolistic system that can propel DNA-coated gold microprojectiles (2 micrograms of DNA) directly into the skin; (ii) using a conventional intramuscular injection of the DNA (100 micrograms) into quadricep muscles of transfected mice. HeLa cells were transfected in vitro by the gene gun or by the liposomal delivery system. Indirect immuno-fluorescent antibody (IFA) assay of culture cells indicated that both methods could be successful. Production of antibody and cell-mediated immunity against M.pulmonis were monitored by assaying serum IFA and enzyme-linked immunosorbent assay (ELISA), and delayed type hypersensitivity. In addition, macrophage migration inhibition and lymphocyte transformation to antigen in spleen cells were also tested. Both delivery systems induced humoral and cellular immunity, and vaccinated the mice against infection. Genetic immunization by using the gene gun saves time, money, and labor; moreover, this general method is also applicable to gene therapy.

Animals↗
PubMed1995

2B4, a new member of the immunoglobulin gene superfamily, is expressed on murine dendritic epidermal T cells and plays a functional role in their killing of skin tumors.

Dendritic epidermal T cells (DETC), which are skin-specific members of the tissue-resident gamma delta T-cell family, are characterized by their potential to kill selected tumor targets by a non-major histocompatibility complex (MHC)-restricted mechanism. We have recently identified a new receptor molecule, 2B4, that appears to be associated with non-MHC-restricted recognition of tumor targets by natural killer cells. The purpose of this study was to determine whether DETC express 2B4 molecules, and, if so, to assess their functional roles in DETC-mediated killing of tumor targets. Short-term DETC lines as well as DETC freshly procured from skin expressed surface 2B4, as detected with a specific monoclonal antibody. Removal of interleukin (IL)-2 from DETC cultures caused substantial reduction in 2B4 expression levels as well as a reduction in cytotoxic capacity against YAC-1 targets in a standard 51Cr-release assay. Conversely, exposure to IL-2, but not to IL-7, elevated both 2B4 expression and cytotoxicity. To assess the functional roles played by surface 2B4, we pretreated DETC lines with anti-2B4 antibody and then tested for their killing potential. Anti-2B4, but not the control antibody, augmented their capacity to lyse YAC-1 targets (51Cr-release assays) and to disrupt the monolayers of Pam-212-transformed keratinocytes (visual assessment). Thus, we conclude that DETC express, in an IL-2-dependent manner, 2B4 molecules, which may play a unique role in the killing of skin-derived tumors.

Animals↗
PubMed1995

Immunotoxicity of polyunsaturated fatty acids in serum-free medium.

To test the effect of purified polyunsaturated fatty acids on immune cells in vitro, human peripheral blood mononuclear cells and murine spleen cells were incubated in Opti-MEM medium without serum or even albumin and with 2-mercapto-ethanol, insulin, transferrin and selenium as supplements. The human cells were stimulated with phytohemagglutinin and the murine cells were stimulated with Concanavalin A or lipopolysaccharide. Both human and murine cells were stimulated with recombinant human interleukin-2 to generate lymphokine activated killer cells. Linoleic and linolenic acids inhibited all of the immune responses tested, whereas docosahexaenoic and eicosapentaenoic acids did not. Similar effects were observed with cultured B16 F10 murine melanoma cells. Mixtures of linoleic and docosahexaenoic or eicosapentaenoic acids also inhibited the mitogenic response to phytohemagglutinin. Inhibition of lipid mediator production by indomethacin, quercetin, rutin, or nordihydroguariaretic acid, and addition of vitamins C and E with anti-oxidant activity failed to reverse the effects of linoleic acid. Thus, linoleic and linolenic acids appear to directly inhibit immune and tumor cells, at least under these conditions.

Animals↗
PubMed1995

Identification of a recombinational breakpoint at the BAT5 locus in three intra-H-2 recombinant inbred mouse strains.

We have analyzed the S/D region in 14 inbred mouse strains by restriction fragment length polymorphism (RFLP) using human BAT2 and BAT5 genes as probes. In all recombinant strains, the recombinational breakpoint mapped centromeric to Bat-2 (D17H6S51E). In recombinant strains B6.R4, B6.AK1 and B10.BYR1, recombination occurred within or close to the Bat-5 (D17H6S82E) locus. The immunogenicity of B10.BYR1 and B6.R4 bone marrow cell (BMC) grafts differs from that of both sets of parents, as if genes at or just centromeric to Bat-5 are involved. The phenotype of B6.AK1 BMCs (Kb Dk) is similar to that of the H2k parent suggesting no changes occurred. However, RNA blot analysis has shown that the Bat-5 gene is expressed well in bone marrow cells of B10.BR mice but not in B6.AK1 marrow cells. Analysis of a limited number of tumor cells of hemopoietic origin identified a single transcript for Bat-5. Our present data identify a recombinational hot spot at the Bat-5 locus. The expression of Bat-5 or a nearby gene may influence the immunogenicity of BMCs.

Animals↗
PubMed1994

Expression of CD43 on murine and human pluripotent hematopoietic stem cells.

To understand regulation of hemopoiesis, it would be helpful to identify physiologically relevant function-associated molecules on stem cells. Here, we report the detailed examination of CD43 expression on murine and human pluripotent hemopoietic stem cells. Mouse stem cells were found within the Ly6+Lin-CD43high subpopulation of bone marrow. These cells, upon transfer into SCID mice, caused rapid repopulation of thymus, spleen, and bone marrow. Retransfer of bone marrow cells from primary SCID recipients of Ly6+Lin-CD43high cells into secondary recipients resulted in repopulation of lymphohemopoietic cells. All Ly6+Lin-CD43high cells were found to express high levels of c-kit. In contrast, Ly6+Lin-CD43-/low cells caused limited and variable thymic and splenic repopulation. These cells failed to repopulate the marrow cavity and did not contain retransplantable stem cells. These data indicate that murine pluripotent stem cells express high levels of CD43. Examination of human fetal bone marrow cells revealed a population of CD34+CD38-CD43+ cells. When single sorted cells with this phenotype were cultured in vitro, they were able to produce colonies with a dispersed growth pattern. Cells with this growth pattern have previously been shown to have myeloid and lymphoid growth potentials and extensive self-renewal capacity. Furthermore, CD34+CD38-HLA-DR+ cells, recently shown to be highly enriched in stem cell activity, expressed relatively high levels of CD43. Because CD43 has recently been shown to bind to intercellular adhesion molecule-1, these data suggest a possible role for CD43 in the regulation of hemopoiesis.

ADP-ribosyl Cyclase↗
PubMed1994

Integrated control of cell proliferation and cell death by the c-myc oncogene.

Regulation of multicellular architecture involves a dynamic equilibrium between cell proliferation, differentiation with consequent growth arrest, and cell death. Apoptosis is one particular form of active cell death that is extremely rapid and characterized by auto-destruction of chromatin, cellular blebbing and condensation, and vesicularization of internal components. The c-myc proto-oncogene encodes an essential component of the cell's proliferative machinery and its deregulated expression is implicated in most neoplasms. Intriguingly, c-myc can also act as a potent inducer of apoptosis. Myc-induced apoptosis occurs only in cells deprived of growth factors or forcibly arrested with cytostatic drugs. Myc-induced apoptosis is dependent upon the level at which it is expressed and deletion mapping shows that regions of c-Myc required for apoptosis overlap with regions necessary for co-transformation, autoregulation, inhibition of differentiation, transcriptional activation and sequence-specific DNA binding. Moreover, induction of apoptosis by c-Myc requires association with c-Myc's heterologous partner, Max. All of this strongly implies that c-Myc drives apoptosis through a transcriptional mechanism: presumably by modulation of target genes. Two simple models can be invoked to explain the induction of apoptosis by c-Myc. One holds that death arises from a conflict in growth signals which is generated by the inappropriate or unscheduled expression of c-Myc under conditions that would normally promote growth arrest. In this 'Conflict' model, induction of apoptosis is not a normal function of c-Myc but a pathological manifestation of its deregulation. It thus has significance only for models of carcinogenic progression in which myc genes are invariably disrupted.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Effect of 3'azido-2',3'-deoxythymidine (AZT) on experimental feline immunodeficiency virus infection in domestic cats.

The compound 3'azido-2',3'-deoxythymidine (AZT) inhibits the replication of feline immunodeficiency virus (FIV) in cell culture, and treatment with the compound has been reported to induce some clinical improvement in some cases of feline FIV infection. In order to determine the effect of prophylactic treatment with AZT on experimental FIV infection, cats were treated with the compound at 0.2, 1.0, 5, 25 or 50 mg kg-1 day-1 for 29 days. One day after the treatment was started, they were inoculated with 150 cat infectious doses of FIV. All the cats became viraemic, seroconverted and developed lymphadenopathy, although the onset of each was delayed in the cats given higher doses of AZT. Anaemia developed in the cats given high doses of AZT. Virus re-isolated from the cats given 50 mg kg-1 day-1 was as susceptible to AZT in cell culture as the inoculated virus. Thus AZT is much less effective in cats than might have been expected from the results of in vitro studies.

Animals↗
PubMed1994

Acute arthritis of cats associated with feline calicivirus infection.

Twelve specific pathogen-free cats were infected either by intra-articular inoculation or by contact exposure to one of two strains of feline calicivirus (FCV), either F65, a field strain originating from an outbreak of lameness in a group of cats, or a vaccine strain. Following either route of exposure, both strains induced signs typical of FCV infection including oral and nasal ulceration, conjunctivitis and ocular discharge. These signs were of equal severity for both virus strains, but overall, following either route of infection, F65 induced more severe disease than the vaccine strain, with marked pyrexia, lethargy and lameness. Vaccine virus only induced a relatively mild lameness following intra-articular inoculation. Gross pathological and histopathological lesions were seen in some of the joints, but again changes were more severe in the F65-exposed cats. Virus was isolated from both normal and affected joints from both groups of F65-exposed cats, and from a joint from each cat inoculated intra-articularly with vaccine virus. Mild transient lameness was also seen in one of two control cats inoculated intra-articularly, but no pathological changes were seen or virus isolated from joints. A cDNA probe used in RNA dot blot hybridisation experiments was found to be specific and more sensitive than virus isolation in detecting FCV in selected tissues. This may be useful in future studies on the pathogenesis of FCV disease and in studies on viral persistence in FCV carriers.

Acute Disease↗
PubMed1994

Protection of mice against experimental murine mycoplasmosis by a Mycoplasma pulmonis immunogen in lysogenized Escherichia coli.

A construct of the Mycoplasma pulmonis (MP) genomic library, using randomly sheared DNA, was cloned in lambda gt11 and transfected into C600 Escherichia coli organisms. Clones of E. coli expressing a fusion protein reactive with anti-MP and monospecific serum were transferred orally or intravenously into Balb/c mice. Expression of the fusion protein was induced by adding isopropyl-beta-D-thiogalactopyranoside to the drinking water. This vaccination protocol led to local and systemic antibody formation, to generation of immune lymphocytes and to protection against large numbers of virulent MP organisms. This approach might be generally successful in preventing infectious disease.

Administration, Oral↗
PubMed1994

Apramycin-resistant Escherichia coli isolated from pigs and a stockman.

Escherichia coli serotype O147:K89:K88a,c was found to be associated with outbreaks of diarrhoea in preweaner pigs of up to 4 weeks of age on a pig unit. Resistance to apramycin, gentamicin, netilmicin, tobramycin and other antibiotics was associated with conjugative plasmids of approximately 62 kb. The presence of a gene which encoded for the aminoglycoside acetyltransferase enzyme AAC(3)IV was confirmed by DNA hybridization. Samples collected during the following 12 months revealed widespread dissemination of these resistance plasmids in non-serotypable, non-haemolytic E. coli throughout the farm. Apramycin-resistant E. coli were also isolated from a stockman and it appeared from plasmid profile analysis and antibiotic sensitivity testing that the human isolates carried the same plasmid as that carried by the porcine E. coli. Klebsiella pneumoniae, with a slightly smaller conjugative plasmid and similar resistance pattern, was isolated from the stockman's wife.

Agricultural Workers' Diseases↗