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Biomedical subjects

M A Marshall

Publications and source records attributed to M A Marshall.

14 recordsLinked to original sources
PubMed2001

Mice infected with Schistosoma mansoni develop a novel non-T-lymphocyte suppressor population which inhibits virus-specific CTL induction via a soluble factor.

We previously observed that Schistosoma mansoni-infected mice were deficient in their ability to mount a CTL response to unrelated viral antigens and to clear a vaccinia viral infection. Here, we explore the mechanism of that deficiency. Mixing experiments showed that splenocytes from S. mansoni-infected mice actively suppress stimulation in vitro of both viral-peptide specific CTL in spleen cells from virus-infected mice, and allospecific CTL. The mechanism of suppression involves at least in part a soluble factor, in that it can occur across a 0.4-microm membrane which prohibits direct cell contact. However, the inhibition is not alleviated by blocking with antibodies to IL-4, IL-10 or TGF-beta. Fractionation of the splenocyte population from S. mansoni-infected mice shows that the suppression is mediated by a non-B, non-T cell that expresses CD16 and Mac-1, but not FcepsilonR or NK1.1. This represents a novel suppressor population that is distinct from the FcepsilonRI(+) populations of non-B, non-T cells in the spleens of S. mansoni-infected mice that provide a major source of IL-4 in these animals. Similar cells in schistosome-infected humans could affect susceptibility to other infections or responsiveness to vaccines.

Animals↗
PubMed2000

Growth-inhibiting antibody responses of humans vaccinated with recombinant outer surface protein A or infected with Borrelia burgdorferi or both.

Serial serum samples from a 2-year human trial of outer surface protein (Osp) A vaccine were analyzed by Borrelia burgdorferi growth-inhibition assay (GIA) and anti-OspA ELISA to assess the antibody responses of vaccine recipients and subjects with Lyme disease. Although 74% of OspA recipients had a reciprocal GIA titer >/=64 after 3 vaccinations, none of the placebo recipients, even those with Lyme disease, had a GIA titer this high. The correlation between GIA and ELISA titers after 3 doses of vaccine was.84; however, more vaccine recipients had an elevated ELISA titer paired with low GIA titer than had a low ELISA titer with a high GIA titer. OspA-vaccine recipients who acquired Lyme disease had significantly lower serum GIA and ELISA titers after 3 immunizations than did age- and sex-matched OspA recipients without Lyme disease. Thus, vaccinated subjects had antibodies to native antigen on viable cells, and antibody assays with this specificity may predict protection of vaccinees against infection.

Aged↗
PubMed2000

Factors associated with the vaccination of international travelers: a multivariate analysis.

Travel medicine practice in the United States has not been extensively studied. This study included 1078 consecutive patients who presented to a university-based travel medicine clinic from 1990 through 1994. Analyses of patient demographics, clinic attendance, itineraries, and vaccinations were conducted. Mean patient age (+/- SD) was 37.4 +/- 16.2 years; 626 (58.1%) of the patients were male. Travel duration was 103.1 +/- 242.3 days (median, 21 days), and lead time (defined as the time between clinic presentation and departure for the purpose of this study) was 23.8 +/- 26.5 days (median, 16 days). Destination was the strongest independent factor affecting vaccination practices. A lead time of 31 or more days was associated with significantly elevated odds ratios for all immunobiologicals except immune globulin. These findings underscore the need to educate the traveling public, healthcare providers, and the travel industry about the benefits of seeking medical consultation at least 1 month prior to international travel.

Adolescent↗
PubMed1996

Interleukin 2 production in vitro by peripheral lymphocytes in response to human papillomavirus-derived peptides: correlation with cervical pathology.

Human papillomavirus (HPV) is believed to be the major cause of cervical cancer. To investigate whether a cellular immune response, especially a T helper type 1 response, is related to the natural defense against HPV-related cervical lesions, the interleukin 2 response of peripheral blood lymphocytes in vitro to overlapping peptides from HPV-16 E6 and E7 oncoproteins was compared with the degree of cervical cytological abnormality among 140 women in a cross-sectional study. We compared 66 women diagnosed with low-grade squamous intraepithelial lesions (LSIL), 21 with high-grade squamous intraepithelial lesions (HSIL), and 28 with invasive cervical cancer with 25 women who were cytologically normal but previously HPV-16 DNA positive. The fraction showing strong interleukin 2 production against HPV-16 peptides was greatest among cytologically normal women (35%) and declined with increasing disease severity [LSIL] (20%), HSIL, (17%), and cancer patients (7%); X2 test P for the trend = 0.02], whereas the responses against a recall influenza antigen were not significantly different among groups. Our finding suggests that a T helper lymphocyte type 1 response to HPV antigens is associated with disease status. This result may reflect a targeted effect of the disease on immune function or a protective effect of the immune response against disease progression.

Adolescent↗
PubMed1994

Increased susceptibility of mice infected with Schistosoma mansoni to recombinant vaccinia virus: association of viral persistence with egg granuloma formation.

BALB/c mice infected 7 weeks previously with Schistosoma mansoni and challenged with a recombinant vaccinia virus vPE16 expressing the human immunodeficiency virus envelope protein gp160 show a marked delay in hepatic viral clearance as compared to mice infected with vPE16 alone. This increase in viral persistence is accompanied by reduced gp120-specific Th1-associated cytokine responses as well as by impaired cytotoxic T lymphocyte (CTL) activity against targets expressing epitopes of the same antigen. To investigate the contribution of these defects to the observed delay in clearance of recombinant vaccinia virus, animals were challenged with vPE16 at different times following S. mansoni infection, and virus titers in tissues and viral-specific immune responses were measured simultaneously in the same animals. While normal resolution of virus occurred in schistosome-infected mice prior to parasite egg deposition, persistence within the liver was observed in animals challenged during the onset and peak phase of granuloma formation (6 to 8 weeks after S. mansoni infection). At later times, when schistosomiasis is in its chronic phase, normal viral clearance returned. This time course of viral resolution correlated in part with the observed pattern of decreased Th1 cytokine production toward viral antigens but was clearly less temporally related to the defect in virus-specific CTL activity. Immunohistochemical staining of liver sections from vaccinia/S. mansoni co-infected mice with polyclonal anti-vaccinia antibodies revealed that viral epitopes are localized primarily within granulomas. These experiments suggest that egg granulomas, by providing a microenvironment for viral expression, in combination with the cytokine imbalance present during schistosome infection, can promote the expansion of vaccinia virus and possibly other viral agents.

Animals↗
PubMed1991

Aspergillus nidulans wetA activates spore-specific gene expression.

The Aspergillus nidulans wetA gene is required for synthesis of cell wall layers that make asexual spores (conidia) impermeable. In wetA mutant strains, conidia take up water and autolyze rather than undergoing the final stages of maturation. wetA is activated during conidiogenesis by sequential expression of the brlA and abaA regulatory genes. To determine whether wetA regulates expression of other sporulation-specific genes, its coding region was fused to a nutritionally regulated promoter that permits gene activation in vegetative cells (hyphae) under conditions that suppress conidiation. Expression of wetA in hyphae inhibited growth and caused excessive branching. It did not lead to activation of brlA or abaA but did cause accumulation of transcripts from genes that are normally expressed specifically during the late stages of conidiation and whose mRNAs are stored in mature spores. Thus, wetA directly or indirectly regulates expression of some spore-specific genes. At least one gene (wA), whose mRNA does not occur in spores but rather accumulates in the sporogenous phialide cells, was activated by wetA, suggesting that wetA may have a regulatory function in these cells as well as in spores. We propose that wetA is responsible for activating a set of genes whose products make up the final two conidial wall layers or direct their assembly and through this activity is responsible for acquisition of spore dormancy.

Amino Acid Sequence↗
PubMed1989

Genetic engineering of filamentous fungi.

Filamentous fungi are important in medicine, industry, agriculture, and basic biological research. For example, some fungal species are pathogenic to humans, whereas others produce beta-lactam antibiotics (penicillin and cephalosporin). Industrial strains produce large amounts of enzymes, such as glucoamylase and proteases, and low molecular weight compounds, such as citric acid. The largest and most economically important group of plant pathogens are fungi. Several fungal species have biological properties and genetic systems that make them ideally suited for basic biological research. Recently developed techniques for genetic engineering of filamentous fungi make it possible to alter their detrimental and beneficial activities in novel ways.

Aspergillus nidulans↗