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Biomedical subjects

M Bennett

Publications and source records attributed to M Bennett.

At least 109 records · Page 6Linked to original sources

Cowpox: a re-evaluation of the risks of human cowpox based on new epidemiological information.

Human cowpox is a rare but relatively severe infection of interest because of its links with Edward Jenner and the introduction of smallpox vaccine and, more recently, because of re-evaluation of the epidemiology of the infection. This indicates that cowpox is not enzootic in cattle, relegates the cow to a minor role, and emphasizes the importance of feline cowpox as a source of human infection and of wildlife as virus reservoirs. The evidence available suggests that the virus is of low infectivity for humans and should not become an increasing problem despite the cessation of smallpox vaccination and increasing numbers of immunocompromised individuals.

Animals↗

Progressive neurosarcoidosis: a case report.

Neurosarcoidosis affects 3% to 5% of patients with sarcoidosis. It involves primarily the central nervous system and/or the peripheral nervous system. The treatment of a patient with neurosarcoidosis is difficult, and functional improvement following intensive rehabilitation has not been described. We report a middle-aged man who presented initially with ophthalmologic and pulmonary symptoms consistent with sarcoidosis and who later developed progressive weakness of the lower extremities, with impaired ambulation. The patient's clinical presentation, assessment, and rehabilitation management are presented. Also, the different pharmacologic treatments used to control the disease, and that may alter the long-term functional improvement of patients with neurosarcoidosis, are discussed.

Activities of Daily Living↗

Cowpox in British voles and mice.

Serosurveys indicate that bank voles, field voles and woodmice are probably reservoir hosts of cowpox virus in western Europe, although virus has not yet been isolated from these species. In this study, bank voles, field voles, woodmice and laboratory mice were shown to be susceptible to combined intradermal and subcutaneous inoculation with 3-20 plaque-forming units (pfu) of cowpox virus. Bank and field voles, but not laboratory mice, were also susceptible to combined oral and nasal inoculation with 50 pfu. Few clinical signs were seen and virus was generally recovered only from inoculation sites. Bank voles were not susceptible to injection of ectromelia virus (5000 pfu) into the skin (as described above). These results provide information on which further pathogenesis and transmission studies can be based, and support the view that the orthopoxvirus antibody detected in British wild voles and woodmice indicates infection with cowpox virus. However, further investigation of the pathogenesis of cowpox in these species is needed to understand better the epidemiology of the disease.

Administration, Intranasal↗

Role of murine NK cells and their receptors in hybrid resistance.

Hybrid resistance refers to the rejection of parental strain bone marrow cells by natural killer cells of mice that are F1 hybrids derived from two inbred parental strains. This pattern of rejection is not seen in solid organ transplants. Progress in understanding this exception to the laws of transplantation genetics has occurred with the recent discovery of negative signaling receptors for MHC class I molecules. In the last year the discovery of natural killer cell subsets with non-overlapping inhibitory receptors for parental class I molecules has provided an explanation for hybrid resistance. In some instances, however, positive rather than negative signaling seems to be the basis for rejection of allogeneic as well as parental marrow cell grafts.

Animals↗

Cavernous lymphangioma in the adult parotid.

Cavernous lymphangioma is a benign congenital lesion that usually appears in childhood. It rarely presents in the adult but may be diagnosed at this late stage due to the slow growing nature of the tumour. It is rarely found in the salivary glands and when it does occur, the gland is usually incorporated by lymphangioma of surrounding tissue. We present and discuss the case of a cavernous lymphangioma in the parotid gland of an adult male.

Adult↗

Sequences of the ribonucleotide reductase-encoding genes of felid herpesvirus 1 and molecular phylogenetic analysis.

The felid herpesvirus 1 (FHV-1) genes encoding the two ribonucleotide reductase (RR) subunits (RR1, large subunit and RR2, small subunit) were cloned and their nucleotide (nt) sequence determined. The RR1 open reading frame (ORF) is 2358 nts long and is predicted to encode a protein of 786 amino acids (aa). In common with herpesviruses in the Varicellovirus genus of the alphaherpesvirus subfamily, FHV-1 RR1 lacks the N-terminal serine threonine protein kinase region present in herpes simplex virus (HSV)-1 and -2. FHV-1 RR1 has a predicted aa identity of 47-64% with other alphaherpesvirus RR1 peptides, falling to 26-29% for gammaherpesviruses. The RR2 ORF is 996 nts long, predicted to encode a protein of 332 aa and has aa identities of 64-70% with alphaherpesviruses and 38-39% with gammaherpesviruses. Molecular phylogenetic analysis groups FHV-1 with equid herpesviruses 1 and 4 (EHV 1 and 4), pseudorabies virus (PRV) and bovid herpesvirus 1 (BHV 1) within the genus Varicellovirus.

Alphaherpesvirinae↗

Expression of avrPphB, an avirulence gene from Pseudomonas syringae pv. phaseolicola, and the delivery of signals causing the hypersensitive reaction in bean.

Protein production encoded by the avirulence gene avrPphB from Pseudomonas syringae pv. phaseolicola was examined. Incorporation of [35S]-labeled methionine into the AvrPphB protein indicated processing of the full-length peptide in Escherichia coli to give a major 28-kDa product. The 28-kDa native peptide was isolated from E. coli following over-expression of avrPphB and found not to elicit the hypersensitive response (HR) after infiltration into bean leaves. Antiserum raised to the 28-kDa peptide allowed expression of avrPphB and processing of AvrPphB protein to be examined in P. syringae pv. phaseolicola; immunoreactive peptides of both 35 and 28-kDa were detected in races 3 and 4 (which contain avrPphB) only after induction in minimal medium + 10 mM sucrose. Antiserum raised to a synthetic peptide, derived from the sequence of the 62 amino acids found to be cleaved from the full-length AvrPphB protein, revealed the accumulation of peptides corresponding to the smaller cleavage products, in both E. coli and P. syringae pv. phaseolicola. Biochemical localization experiments showed that all AvrPphB peptides were cytoplasmic in P. syringae pv. phaseolicola. No AvrPphB peptides were produced in a hrpL mutant unless expression of the gene was directed by a strong vector promoter; induction kinetics similar to wild type were observed in a hrpY- strain, although it also failed to cause a confluent HR. Growth of P. syringae pv. phaseolicola under inducing conditions removed the requirement for rifampicin-sensitive mRNA synthesis by bacteria to allow HR development (the induction time) in bean and lettuce leaves. Constitutive expression of hrpL reduced but did not remove the induction time. Expression of the hrp gene cluster of P. syringae pv. phaseolicola from plasmid pPPY430 in E. coli enabled phenotypic expression of avrPphE (also carried by pPPY430) and avrPphB (if over-expressed from pPPY3031). Despite constitutive expression of the hrp and avr genes in E. coli, a protein synthesis dependent induction time was still required for development of the HR in bean genotypes with matching resistance genes. The significance of processing for the function of AvrPphB peptides and the delivery of elicitors of the HR are discussed.

Amino Acid Sequence↗

Allorecognition by murine natural killer cells: lysis of T-lymphoblasts and rejection of bone-marrow grafts.

Natural killer (NK) cells of inbred mice reject allogeneic bone-marrow cells, and NK cells of F1 hybrid mice can reject parental bone-marrow cells (hybrid resistance). In some cases these patterns of rejection can be mimicked in vitro by utilizing IL-2 cultured NK effector cells and allogeneic or parental T-lymphoblasts as target cells. Lysis of allogeneic and parental targets in vitro can be explained on the basis of the missing self hypothesis. Subsets of NK cells that bear non-overlapping MHC class I inhibitory receptors belonging to the Ly49 family lyse allogeneic targets because they do not express self class I molecules of the NK cell donor. Parental strain targets are lysed because they do not express all of the self class I antigens of the F1 hybrid, and hence fail to deliver inhibitory signals to all subsets of F1 NK cells. The expression of Ly49 receptors on NK cells is regulated by host MHC to ensure maximal sensitivity to alterations in self class I molecules and to prevent autoreactivity. In many instances, however, the rejection of allogeneic bone marrow cells in vivo cannot be readily explained by the missing self hypothesis. In these instances, it appears that rejection is initiated by class I MHC receptors on NK cells that recognize allogeneic class I molecules as non-self, and activate rather than inhibit NK cell function.

Animals↗

Facilitation of parental-strain marrow engraftment by T cells of neonatally-tolerant mice.

T cells present in bone marrow cell (BMC) grafts promote engraftment in histoincompatible hosts, but they or other T cells may also initiate lethal graft-vs.-host disease (GVHD). The purpose of this study was to determine whether T cells from donors tolerant of host alloantigens were able to prevent natural killer (NK) cell-mediated rejection of BMC grafts without causing GVHD. Previous studies have shown that H2d C.B-17 SCID BMC grafts were rejected by (BALB/c x B6)F1 (CB6F1,H2d/b) host NK cells, and that this rejection was reversed by adding H2d T cells to the donor inoculum. T cells tolerant of H2d/b alloantigens were produced by irradiating (3 Gy) BALB/c newborn mice, and infusing CB6F1 BMCs. Tolerance was assessed by donor (H2b+) cell chimerism, acceptance of CB6F1 skin grafts, the inability of adoptively transferred lymphocytes to initiate GVHD in irradiated CB6F1 mice, and the inability of spleen or thymus cells to generate cytolytic T lymphocytes against H2b target cells in vitro. Whole or H2-Kb-depleted BMCs isolated from tolerant donors were able to proliferate in both BALB/c and H2b/d (C57BL/6 x DBA/2)F1 hosts as determined by incorporation of a radiolabelled DNA precursor in the spleen. Furthermore, thymocytes from tolerant donors were able to prevent rejection of H2d SCID BMCs. Because the percentage of donor F1 cells was so high in these chimeras, we generated BALB/c to CB6F1 SCID BMC chimeras; the percentage of BALB/c cells was approximately 100%, the BMCs grew well in irradiated CB6F1 hosts, and their lymph node cells failed to cause a graft-vs.-host (GVH) reaction in CB6F1 hosts. Thus, GVHD may be prevented without inhibiting the ability of donor T cells to promote engraftment. Perhaps separate T cells, or separate functions of a common T cell subset, induce GVHD and enhance engraftment of stem cells.

Animals↗

IL-15 can substitute for the marrow microenvironment in the differentiation of natural killer cells.

NK cells require an intact bone marrow microenvironment to acquire lytic function. In mice rendered osteopetrotic by 17beta-estradiol treatment, NK1.1 positive cells are arrested in a nonlytic state. Culture with as little as 2 ng/ml of murine IL-15 (mIL-15), a cytokine produced by macrophages and stromal cells, causes these immature NK1.1+ cells to acquire lytic activity. By contrast, approximately 10- to 50-fold greater amount of mIL-2 was required to induce similar level of cytotoxicity. After culture with mIL-15, the relatively low expression of B220, CD11b, and Ly-49 molecules on immature NK1.1+ cells was increased to levels comparable to those of mature splenic NK1.1+ cells. mIL-15 also caused a greater expansion of NK1.1+CD3- cells as compared with NK1.1+CD3+ cells. We conclude that IL-15 is a specific maturation factor for NK cells and that it can mimic the marrow microenvironment in vitro.

Animals↗

Serological survey for orthopoxvirus infection of wild mammals in areas where a recombinant rabies virus is used to vaccinate foxes.

Several fox vaccination campaigns against rabies have been undertaken in Belgium by using a vaccinia-rabies recombinant virus distributed in baits in the field. However, foxes and other wild animals that may ingest the baits could be infected at the same time by another orthopoxvirus, such as cowpox virus, which circulates in wildlife. Recombination between the two viruses could therefore occur. A serological survey for antibodies to orthopoxvirus, and particularly to cowpox virus, was undertaken in foxes and in several other wild species. Antibodies were detected only in two rodent species, in 16 of 25 bank voles (64 per cent) and in two of 29 woodmice (7 per cent). The risk of virus recombination in wildlife can therefore be considered to be extremely low.

Animals↗