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H Carpenter

Publications and source records attributed to H Carpenter.

At least 19 recordsLinked to original sources
PubMed2000

Persistent, antigen-specific, therapeutic antitumor immunity by dendritic cells genetically modified with an adenoviral vector to express a model tumor antigen.

Dendritic cells (DC) are potent antigen-presenting cells that play a critical role in the initiation of cellular immune responses. Using a BALB/c syngeneic colon carcinoma cell line expressing a model tumor antigen beta-galactosidase (betagal), we previously reported (Song et al, J Exp Med 1997; 186: 1247-1256) that immunization of mice with a single injection of DCs genetically modified with an adenovirus vector expressing betagal confers potent protection against a lethal intravenous tumor challenge, as well as suppression of pre-established lung tumors, resulting in a significant survival advantage. In the present study, we have addressed the question: how long does the memory of tumor antigen- specific immunity persists after DC priming in vivo using this genetically modified DC-based cancer vaccination strategy? To accomplish this, two groups of mice were evaluated: (1) mice surviving >400 days following protection from an initial intravenous tumor challenge after immunization with DC genetically modified to express betagal; and (2) mice surviving >300 days that had previously demonstrated regression of pre-established lung tumors after treatment with DC immunization. By analyzing the antigen-specific cytotoxic T lymphocyte response and challenging these long-term survival mice with a second subcutaneous tumor administration, the data demonstrate that a single administration of DC genetically modified to express a model antigen induces long-lasting, antigen-specific antitumor immunity in both naive and tumor-bearing hosts, observations that have important implications in the development of genetically modified DC-based antitumor vaccination strategies. Gene Therapy (2000) 7, 2080-2086.

Adenoviridae↗
PubMed2000

Strategies for assessing the implications of malformed frogs for environmental health.

The recent increase in the incidence of deformities among natural frog populations has raised concern about the state of the environment and the possible impact of unidentified causative agents on the health of wildlife and human populations. An open workshop on Strategies for Assessing the Implications of Malformed Frogs for Environmental Health was convened on 4-5 December 1997 at the National Institute of Environmental Health Sciences in Research Triangle Park, North Carolina. The purpose of the workshop was to share information among a multidisciplinary group with scientific interest and responsibility for human and environmental health at the federal and state level. Discussions highlighted possible causes and recent findings directly related to frog deformities and provided insight into problems and strategies applicable to continuing investigation in several areas. Possible causes of the deformities were evaluated in terms of diagnostics performed on field amphibians, biologic mechanisms that can lead to the types of malformations observed, and parallel laboratory and field studies. Hydrogeochemistry must be more integrated into environmental toxicology because of the pivotal role of the aquatic environment and the importance of fates and transport relative to any potential exposure. There is no indication of whether there may be a human health factor associated with the deformities. However, the possibility that causal agents may be waterborne indicates a need to identify the relevant factors and establish the relationship between environmental and human health in terms of hazard assessment.

Animals↗
PubMed1997

Dendritic cells genetically modified with an adenovirus vector encoding the cDNA for a model antigen induce protective and therapeutic antitumor immunity.

Dendritic cells (DCs) are potent antigen-presenting cells that play a critical role in the initiation of antitumor immune responses. In this study, we show that genetic modifications of a murine epidermis-derived DC line and primary bone marrow-derived DCs to express a model antigen beta-galactosidase (betagal) can be achieved through the use of a replication-deficient, recombinant adenovirus vector, and that the modified DCs are capable of eliciting antigen-specific, MHC-restricted CTL responses. Importantly, using a murine metastatic lung tumor model with syngeneic colon carcinoma cells expressing betagal, we show that immunization of mice with the genetically modified DC line or bone marrow DCs confers potent protection against a lethal tumor challenge, as well as suppression of preestablished tumors, resulting in a significant survival advantage. We conclude that genetic modification of DCs to express antigens that are also expressed in tumors can lead to antigen-specific, antitumor killer cells, with a concomitant resistance to tumor challenge and a decrease in the size of existing tumors.

Adenocarcinoma↗
PubMed1997

Circumvention of anti-adenovirus neutralizing immunity by administration of an adenoviral vector of an alternate serotype.

Effective gene transfer and expression following repetitive administration of adenoviral (Ad) vectors in experimental animals is limited by anti-Ad neutralizing antibodies. Knowing that anti-Ad humoral immunity is serotype-specific, we hypothesized that anti-Ad neutralizing immunity could be circumvented using Ad vectors of different serotypes (Ad2, Ad5) within the same subgroup (C) to transfer and express beta-glucuronidase (beta glu) in the lung. Sprague-Dawley rats received an intratracheal administration of either Ad2 beta glu or Ad5 beta glu, and, 14 days later, repeat administration of either the same vector or a vector of a different serotype. Analysis of serum and bronchoalveolar lavage fluid following initial vector administration demonstrated systemic and local serotype-specific neutralizing antibodies. For both the Ad2 and Ad5 vectors, beta glu expression 24 hr following the second administration of the same serotype was < 30% of that of naive animals. In contrast, beta glu expression 24 hr following second administration of a different serotype Ad vector was similar to expression at 24 hr of naive animals receiving a single administration (Ad5 beta glu followed by Ad2 beta glu, as well as Ad2 beta glu followed by Ad5 beta glu; p > 0.2 both comparisons). Although the alternative serotype bypassed anti-Ad neutralizing immunity, persistence of expression was reduced compared to that following administration to naive animals. Compatible with this observation, systemic administration of the same vectors to C57B1/6 mice demonstrated induction of cytotoxic T lymphocytes directed against the beta glu transgene, as well as products of the Ad genome. Interestingly, intratracheal administration of vectors with different serotypes and different transgenes to rats resulted in longer expression (but still not normalized) compared to that achieved with vectors of different serotypes but the same transgene. These observations demonstrate that alternate use of Ad vectors from different serotypes within the same subgroup can circumvent anti-Ad humoral immunity to permit effective gene transfer after repeat administration, although the chronicity of expression is limited, likely by cellular immune process directed against both the transgene and viral gene products expressed by the vector.

Adenoviridae↗
PubMed1996

DR human leukocyte antigens and disease severity in chronic hepatitis C.

BACKGROUND/AIMS: Immune mechanisms may modulate disease severity in chronic hepatitis C and the DR human leukocyte antigens may affect these mechanisms. Our aims were to evaluate the association between the DR antigens and disease severity at presentation and to seek correlation between these antigens, disease severity and autoantibodies in this condition. METHODS: Sixty-four patients were assessed prospectively and classified as having mild, moderate and severe disease by clinical, laboratory and histologic criteria. Fourteen DR antigens were determined by restriction fragment length polymorphism or polymerase chain reaction-sequence specific primers. Eighty normal subjects were typed in a similar fashion. RESULTS: Patients with mild (16), moderate (32) and severe (16) disease at presentation were indistinguishable from each other and from normal subjects by the frequencies of each DR antigen. Subsets of patients with different laboratory and histological findings had DR frequencies comparable to those without these findings and to those of normal subjects. Patients with autoantibodies and/or concurrent immunologic diseases had mild (19% versus 32%, p = 0.4), moderate (50% versus 50%) and severe (31% versus 18%, p = 0.4) disease as commonly as other patients. The frequencies of the DR antigens were similar in each category of disease severity. Patients with autoimmune features differed from patients without these features (3% versus 32%, p = 0.002) and normal subjects (3% versus 25%, p = 0.003) by having a lower frequency of HLA DR1. CONCLUSIONS: The DR antigens are not associated with any index of disease severity at presentation. Immunologic manifestations do not identify patients with a different disease severity or a distinctive genetic predisposition for disease activity. The presence of DR 1 is associated with a lower frequency of immune manifestations.

Antibodies, Antinuclear↗
PubMed1994

A survey of hepatitis B among health workers in Jamaica.

One thousand, five hundred and thirty-seven health staff, presenting for hepatitis B vaccination in Jamaica, were surveyed in 1990/91 for hepatitis B markers and/or exposure to blood or hepatitis. Antibodies to either hepatitis B surface antigen (HBsAg) or hepatitis B core (HBc) were found in 19.8% of 817 persons tested. Males were more likely to have antibodies to Hepatitis B Virus (HBV) than females (29% compared with 18%, Odds Ratio 1.6; 95% CI 0.98-2.9). HBsAg was found in 5.3% of 562 persons tested compared with 1% of blood donors. One or more needlestick accidents were reported by 60% of the sample, and blood or liquor splashing on the face was reported by 48%. Jaundice and hepatitis were reported by 1.2% and 3.5% of health staff, respectively. HBsAg carrier status was associated with years of service (p = 0.039). Prevalence of antibodies to HBV increased with age (p = 0.004) and years of service (p = 0.028). The effect of age and years of service appears to be largely independent (r = 0.44). This survey reaffirms the importance of health workers being immunized with hepatitis B vaccine, and adhering rigorously to universal precautions in patient care and laboratory practice.

Adolescent↗
PubMed1992

Hugh Carpenter. International general practitioner.

Hugh Carpenter's interests in general practice have been cosmopolitan and challenging. After seven years as a solo country general practitioner in Tasmania and then as State Director of the Family Medicine Programme in Tasmania, he was appointed to positions in China (1987-1990) and Moscow. His special interests are medical education and bilateral international medical relations, especially between China and Australia, and Great Britain with Russia, Bulgaria and Romania.

China↗
PubMed1987

Becoming a general practitioner.

Becoming a general practitioner is too much a matter of chance. The curriculum 'walks in through the door'. This is informal and unlikely to be comprehensive. Cognitive, not behavioural skills predominate. Many tutors have little or no grounding in adult education. The career intentions of trainees tend to be overshadowed by their immediate service role. This essay explores the integrated structure of general practice training. The author draws on his experience of 10 years as tutor in Sydney suburban and Tasmanian country practice, and now as State Director of training. He is a student in the University Centre for Education. Four essentials to be considered are: a highly motivated vocational trainee, a comprehensive negotiated curriculum emphasizing behaviour, a wealth of selected experience in refined training positions, and skilled tutors. The essay makes no attempt at an exhaustive analysis of becoming a general practitioner. The purpose is to address these critical features of training, and to argue for an approach in tune with the trainee's vision; comprehensive, valid and reliable; not a matter of chance.

Attitude of Health Personnel↗
PubMed1987

Teamwork.

Explore the source record for details and available documents.

Delivery of Health Care↗