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Biomedical subjects

M Bennett

Publications and source records attributed to M Bennett.

At least 217 records · Page 12Linked to original sources

Susceptibility in cell culture of feline immunodeficiency virus to eighteen antiviral agents.

The in-vitro susceptibilities of two strains of feline immunodeficiency virus to 18 antiviral agents were determined in two cell lines. In terms of inhibiting p24 antigen production, the nucleoside-analogue reverse transcriptase inhibitors were the most effective compounds. Inhibition was also observed with aurintricarboxylic acid, phosphonoformate and butyldeoxynorjirimycin, but not with the other agents tested.

Animals↗

Human cowpox 1969-93: a review based on 54 cases.

This survey of the clinical and epidemiological features of human cowpox, a rare but relatively severe zoonotic infection, is based on 54 cases, many unpublished, which we have studied since 1969. Patients present with painful, haemorrhagic pustules or black eschars, usually on the hand or face, accompanied by oedema, erythema, lymphadenopathy, and systemic involvement. Severe, occasionally fatal, cases occur in eczematous and immunosuppressed individuals, although cowpox has not yet been reported in anyone infected with the human immunodeficiency virus. Variations in the clinical features are described, and the differential clinical diagnosis of cowpox, parapox, herpes virus, and anthrax infections is discussed. The role of the laboratory in diagnosis is described, and the value of electron microscopy in providing rapid confirmation is emphasized. Care in taking a detailed history will assist in the initial clinical diagnosis, and a history of contact with domestic cats, particularly during July-October, is important. The possible influence of smallpox vaccination on the incidence and severity is discussed and discounted.

Adolescent↗

Expression of CZ-1: a CD45RB epitope on progenitors of natural killer and other haematopoietic cells.

CZ-1 is a novel sialic acid-dependent epitope of the murine CD45RB molecule which is expressed on cells that proliferate when cultured in IL-2. Because IL-2 appears to be important in the differentiation of NK cells, the authors examined the expression of CZ-1 on immature NK-lineage cells within the bone marrow. All mature NK1.1+ cells as well as their NK1.1- IL-2 responsive precursors were CZ-1+. Furthermore, IL-2 unresponsive transplantable NK progenitor cells expressed CZ-1 also. To examine expression of CZ-1 on other immature lymphoid progenitor cells, CZ-1+ and CZ-1- marrow cells were transplanted into lightly irradiated scid mice. Transfer of CZ-1+ cells resulted in rapid and sustained generation of thymocytes and splenic B cells, whereas CZ-1- cells caused delayed repopulation. This suggested that the slowly repopulating pluripotent stem cells lacked CZ-1. Therefore, expression of CZ-1 on Ly6+ Lin- c-kit+ cells, highly enriched for pluripotent stem cells, was examined. This population appeared to be homogeneously CZ-1dull. Thus, it appears that expression of CZ-1 is developmentally regulated, with differentiation associated with increased expression. Since CZ-1 is expressed on a protein tyrosine phosphatase, it is likely that this molecule regulates differentiation of NK and other lymphoid cells.

Animals↗

The impact on community palliative care services of a hospital palliative care team.

This retrospective study examined the influence of a hospital palliative care team on the activity of a local hospice home care team over a four-year period from May 1989 to April 1993 in East Leeds. The increasing referral to death interval observed in home care patients over this period appears to be due to the presence of the hospital team. The increasing work-load of the home care team generated by the hospital team is discussed with reference to solutions to meet this increasing demand. A district or regional planning strategy is recommended to co-ordinate existing and potential palliative care services.

England↗

dishevelled is required during wingless signaling to establish both cell polarity and cell identity.

The dishevelled gene of Drosophila is required to establish coherent arrays of polarized cells and is also required to establish segments in the embryo. Here, we show that loss of dishevelled function in clones, in double heterozygotes with wingless mutants and in flies bearing a weak dishevelled transgene leads to patterning defects which phenocopy defects observed in wingless mutants alone. Further, polarized cells in all body segments require dishevelled function to establish planar cell polarity, and some wingless alleles and dishevelled; wingless double heterozygotes exhibit bristle polarity defects identical to those seen in dishevelled alone. The requirement for dishevelled in establishing polarity in cell autonomous. The dishevelled gene encodes a novel intracellular protein that shares an amino acid motif with several other proteins that are found associated with cell junctions. Clonal analysis of dishevelled in leg discs provides a unique opportunity to test the hypothesis that the wingless dishevelled interaction species at least one of the circumferential positional values predicted by the polar coordinate model. We propose that dishevelled encodes an intracellular protein required to respond to a wingless signal and that this interaction is essential for establishing both cell polarity and cell identity.

Amino Acid Sequence↗

Cloning and characterization of the 2B4 gene encoding a molecule associated with non-MHC-restricted killing mediated by activated natural killer cells and T cells.

We have recently described a signal transducing molecule, 2B4, expressed on all NK and T cells that mediate non-MHC-restricted killing. The gene encoding this molecule was cloned and its nucleotide sequence determined. The encoded protein of 398 amino acids has a leader peptide of 18 amino acids and a transmembrane region of 24 amino acids. The predicted protein has eight N-linked glycosylation sites, suggesting that it is highly glycosylated. Comparison of 2B4 with sequences in the databanks indicates that 2B4 is a member of Ig supergene family, and it shows homology to murine and rat CD48 and human LFA-3. Northern blot analysis has shown at least three transcripts for 2B4 in adherent lymphokine-activated killer cells of several mouse strains and TCR-gamma/delta dendritic epidermal T cell lines but not in allospecific T cell clones. These three mRNA are the products of differential splicing of heterogeneous nuclear RNA. Southern blot analysis of genomic DNA from several mouse strains revealed that 2B4 belongs to a family of closely related genes. The 2B4 gene has been mapped to mouse chromosome 1 by analysis of 2B4 expression in recombinant inbred mouse strains.

Amino Acid Sequence↗

Correspondence between a mammalian spliceosome component and an essential yeast splicing factor.

None of the mammalian splicing factors that have been cloned corresponds to the yeast pre-messenger RNA splicing factors, the PRP proteins. Here, a generalizable strategy was used to isolate a complementary DNA encoding the mammalian spliceosome-associated protein (SAP) SAP 62. It is demonstrated that SAP 62 is the likely functional homolog of the yeast PRP11 protein. Both PRP11 and SAP 62 associate stably with the spliceosome, contain a single zinc finger, and display significant amino acid sequence similarity. Unlike PRP11, SAP 62 contains 22 proline-rich heptapeptide repeats at the carboxyl-terminus.

Amino Acid Sequence↗

Use of newborn liver cells as a murine model for cord blood cell transplantation.

There is current interest in using umbilical cord blood cells as a substitute for bone marrow cells (BMC) in human transplantation. However, T cell-depleted BMC are more susceptible to rejection. Because CBC lack mature T cells, mouse newborn liver cells (NLC) were used as a model to investigate the role of T cells in engraftment. BALB/c BMC, C.B-17 scid/scid (SCID) BMC, and BALB/c NLC were transplanted into lethally irradiated BALB/c and (B6 x DBA/2) F1 (B6D2F1) hosts. Splenic 125IUdR incorporation 5 days later assessed engraftment. BALB/c BMC, NLC, and SCID BMC grew well in BALB/c hosts, but only BALB/c BMC grew in B6D2F1 hosts. This suggests that T cells are necessary for engraftment of H-2d stem cells in the B6D2F1 host. Addition of BALB/c thymocytes to SCID BMC or NLC allowed engraftment in the F1 hosts. It appears that NK cells mediated the resistance because their depletion by mAb increased engraftment of SCID BMC or NLC. Anti-NK1.1 mAb and -asialo GM1 serum eliminate all NK cells, although anti-5E6 mAb eliminate a subpopulation of NK cells that responds to Hh-1d (determinant 2+) stem cells. Treatment of F1 hosts with any of these mAb prevented rejection of SCID BMC or BALB/c NLC. Also, activation of NK cells by poly I:C caused rejection of donor cells in the F1 that could not be overcome by the presence of thymocytes. This effect of the poly I:C could also be reversed by mAb depletion of host NK cells. Thus, engraftment of stem cells is influenced by the presence of donor T cells and the activation level of host NK cells.

Animals↗

Typing of feline calicivirus isolates from different clinical groups by virus neutralisation tests.

One hundred and thirteen isolates of feline calicivirus originating from seven different clinical groups were typed by virus neutralisation tests using eight different cat antisera. The clinical groups comprised 'healthy' cats, cases of acute oral/respiratory disease, chronic stomatitis, acute febrile lameness syndrome, vaccine reactions (clinical disease seen within 21 days of vaccination) and vaccine breakdowns (clinical disease seen more than 21 days after but within one year of vaccination). Isolates from the vaccine reaction cases were grouped into those associated with acute oral/respiratory disease alone and those associated with the lameness syndrome, and the latter group was further subdivided according to the vaccine used. Two groups appeared significantly different from others with some of the antisera. Thus the lameness vaccine reaction isolates associated with vaccine B were significantly different from the isolates from all the other clinical groups, including other lameness isolates, with a number of the antisera. In addition, the chronic stomatitis isolates were significantly different from those from the 'healthy' and the acute oral/respiratory disease groups with one or two of the antisera. Eighty-five to 88 per cent of the isolates were neutralised by antisera raised against F9 or F9-like vaccine strains at a dilution of 1 in 2. Twenty antibody units of such antisera neutralised 42 to 80 per cent of the isolates. A bivalent antiserum raised against a vaccine F9 strain and field strain LS015 neutralised 96 per cent of the isolates at a dilution of 1 in 2, and 20 antibody units neutralised 68 per cent of isolates. Antisera to field strain F65 neutralised all the remaining isolates at a dilution of 1 in 2 and 44 per cent of the remaining isolates at a dilution of 20 antibody units. Therefore, strains LS015 and F65 may be of use in the production of a polyvalent feline calicivirus vaccine, together with the widely used strain F9.

Animals↗

A novel function-associated molecule related to non-MHC-restricted cytotoxicity mediated by activated natural killer cells and T cells.

NK cells and IL-2-propagated splenic T cells mediate non-MHC-restricted cytotoxicity. The molecules involved in this process are not well defined. We describe a novel 66-kDa cell surface molecule called 2B4 that is expressed on cells that mediate non-MHC-restricted cytotoxicity. All resting and rIL-2 cultured NK cells and a significant number of T cells cultured in high doses of rIL-2 are 2B4+. In fresh as well as cultured spleen cells, all non-MHC-restricted cytotoxicity is contained within the 2B4+ population. In addition to defining cells capable of non-MHC-restricted killing, the 2B4 molecule is also involved in modulation of their function. In the presence of anti-2B4, the lytic activity of cultured NK cells and non-MHC-restricted T cells against a wide variety of FcR- and FcR+ targets is greatly augmented. Anti-2B4 is also able to transduce other signals in IL-2-activated NK cells such as IFN-gamma secretion and granule exocytosis. In addition, 2B4+ T cells can specifically lyse the 2B4 hybridoma cells. Unlike many other activation and adhesion molecules (such as murine CD2, LFA-1, and CD16), 2B4 expression is restricted to cells that mediate NK-like killing. Conversely, highly activated T cells that do not express 2B4 do not mediate non-MHC-restricted killing. Together these data suggest that the 2B4 molecule is likely to be a part of a receptor complex or a component of signal-transducing complex on cells that mediate non-MHC-restricted killing.

Animals↗

Investigation of vaccine reactions and breakdowns after feline calicivirus vaccination.

The clinical and epidemiological features of feline calicivirus associated vaccine reactions and breakdowns were investigated. Twenty per cent of 123 vaccine reactions were associated with acute oral/respiratory disease alone, and 80 per cent were associated with lameness either alone or in association with other clinical signs. Feline calicivirus was isolated from oropharyngeal swabs from 69 per cent of the vaccine reaction cases. Twenty-four of 31 vaccine breakdowns were associated with acute oral/respiratory disease and only seven with lameness; the virus was isolated from 28 of the 31 breakdowns. Some of the viruses isolated from the vaccine reactions were compared with the appropriate vaccine virus in virus neutralisation tests; the majority appeared to be different from the vaccine virus and were presumably field viruses. However, some appeared more similar to the vaccine virus and the majority of these were associated with lameness after the first vaccination.

Animals↗

Induction of murine hepatic glutathione S-transferase by dietary dehydroepiandrosterone.

The naturally occurring steroid dehydroepiandrosterone (DHEA), when administered as a supplement to the diet of mice and rats, produces alterations in the relative concentrations of specific liver proteins; among these, a protein of Mr approximately 28 K is markedly induced by DHEA action. In the present study we identified the murine hepatic approximately 28 kDa protein as glutathione S-transferase subtype GT-8.7. Glutathione S-transferases belong to a gene superfamily that encode closely related proteins which are induced in liver and other tissues by various chemicals, including carcinogens and chemoprotective agents such as dietary antioxidants. Based on the above finding, we evaluated glutathione S-transferase activity in cytosols and microsomes prepared from liver tissue of mice fed either a control diet or a DHEA-containing diet (0.45%, by weight). The specific activity of hepatic cytosolic glutathione S-transferase in mice treated with DHEA up to 7 days was either unchanged or slightly decreased when compared to controls; however, treatment for 14 days or longer resulted in significant increases in activity. The specific activity of microsomal glutathione S-transferase also was increased by long-term DHEA treatment; however, its activity was approximately one-tenth of that in corresponding cytosols.

Administration, Oral↗

Human isolates of apramycin-resistant Escherichia coli which contain the genes for the AAC(3)IV enzyme.

Gentamicin-resistant Escherichia coli isolated at different periods from patients in two hospitals were tested for resistance to the aminoglycoside antibiotic apramycin. Twenty-four of 93 (26%) gentamicin-resistant isolates collected from the Royal Liverpool Hospital between 1981 and 1990 were resistant to apramycin. Thirteen isolates were highly resistant to apramycin (minimal inhibitory concentration (MIC) > or = 1024 micrograms/ml), were also resistant to gentamicin, netilmicin and tobramycin, and hybridized with a DNA probe derived from the aminoglycoside acetyltransferase (3)IV (AAC(3)IV) gene. The proportion of gentamicin-resistant isolates which had high level resistance to apramycin increased from 7% in 1981-5 to 24% in 1986-90. Twelve gentamicin-resistant E. coli from Guy's and St Thomas's Hospital isolated between 1977 and 1980 were also tested for resistance to apramycin. For five of these isolates the MICs of apramycin was 32-256 micrograms/ml. None was shown to have a conjugative plasmid carrying resistance to apramycin and only one hybridized with the DNA probe for the AAC(3)IV enzyme.

Acetyltransferases↗

Children's understanding of conflicting emotions: a training study.

Notwithstanding a substantial body of evidence indicating that young children have difficulty in understanding conflicting emotions, we predicted that training would likely be effective in promoting an ability to understand. This prediction was made in the light of recent research that has demonstrated young children's competence in understanding conflicting beliefs and desires, a competence that is seen as contingent upon the possession of a representational theory of mind (Perner, 1991). The experiment involved two groups of 6-year-olds, one of which had undergone brief training. Ten weeks following training, both groups watched a video recording of an event that could be seen to give rise to both positive and negative emotions. As predicted, children in the experimental group gave significantly more evidence of understanding conflicting emotions than did those in the control group. Surprisingly, even within the control group, many children understood conflicting emotions. Possible explanations for the precocious performance of children in the control group are discussed, as are caveats relating to the major findings of the study.

Child↗

Genetic control of resistance to Mycoplasma pulmonis infection in mice.

The differences in susceptibility of various inbred strains of mice to a highly pathogenic strain of Mycoplasma pulmonis CT (T2) has been known for some time. We assessed the genetic control of resistance to T2 infection. Tracheolung lavage samples and lungs of mice were assessed for T2 organisms after intratracheal injection of T2. We found that H-2b (C57BL/6 (B6) and H-2k B10.BR mice were resistant, whereas H-2b A.By, H-2k C3H/Bi, H-2k C3H/HeJ (C3H), and H-2b BALB.B mice were susceptible. We also typed individual B6C3F2 mice for H-2 and for resistance to T2 and observed that resistance to T2 infections is controlled by a single dominant gene not linked to H-2. Histologic examination revealed severe lung lesions typical of M. pulmonis infections in susceptible C3H mice, in contrast to minimal lung lesions in resistant B6 mice. No significant titers of local or systemic antimycoplasma antibodies were detected in either resistant or susceptible mice at 5 days postinfection. Macrophages taken from uninfected B6 or C3H mice failed to inhibit growth of T2 in vitro. However, macrophages from B6 mice did inhibit growth of T2 much better than C3H macrophages when harvested on day 5 of infection. Thus, there is an association between activation of macrophage bactericidal function and genetic resistance to growth of T2 organisms.

Animals↗