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Biomedical subjects

E G Martin

Publications and source records attributed to E G Martin.

16 recordsLinked to original sources
PubMed2004

Tobacco harm reduction: what do the experts think?

OBJECTIVE: To assess experts' opinions about the future of, and potential to improve individual and public health through "tobacco harm reduction" (THR), the use of novel nicotine containing products purporting to reduce the health risks from cigarette smoking. DESIGN: Semi-structured telephone interviews on nine topic areas, with qualitative content analysis of coded transcripts. PARTICIPANTS: 29 professionals with expertise related to tobacco and interest in THR, including prominent tobacco control advocates (7), pharmaceutical (3) and tobacco industry scientists/officials (5), non-industry scientists (12), and Congressional staff (2). RESULTS: Respondents agreed that harm reduction is at minimum theoretically plausible, that characteristics of "good" and "bad" THR products can be identified, that government regulation is essential but not likely in the foreseeable future, and that additional scientific data are very much needed. However, there was no consensus on specifics, such as preferred regulatory strategies or examples of ideal THR products. Disagreement was seen not only across but also within respondent categories. Mistrust of key stakeholders-for example, tobacco control advocates distrust of tobacco industry scientists and vice versa-was pervasive, and cited frequently as a barrier to regulation and collaboration. CONCLUSIONS: Continued dialogue and debate are essential as we enter a new and uncertain era of products purporting to reduce tobacco produced harm. Experts have concluded that effective government regulation is crucial to minimising the risks associated with THR and maximising potential benefits.

Attitude of Health Personnel↗
PubMed2003

The US tobacco control community's view of the future of tobacco harm reduction.

OBJECTIVE: Tobacco harm reduction (THR) has garnered recent attention due to the introduction of novel nicotine delivery products ostensibly intended to reduce risk for inveterate cigarette smokers. This study evaluates the grassroots tobacco control community's knowledge, opinions, and beliefs about THR. DESIGN: A web/mail survey conducted in October and November 2002, with a telephone survey of a sample of non-respondents. SUBJECTS: The 2833 US based registrants for the 2001 National Conference on Tobacco or Health. MAIN OUTCOME MEASURES: Respondents' awareness of THR, perception of its importance, support for regulation, and perception of which THR products should be recommended to inveterate cigarette smokers. RESULTS: 70% of respondents were aware of THR but respondents had low recognition of specific products at the forefront of the debate, such as Swedish snuff. Half believe THR will reduce smoking cessation and cause nicotine experimentation by children; 63% anticipate unintended adverse side effects. More expect THR to have a negative than a positive impact on health. Large majorities support government regulation of THR and conventional tobacco products, but fewer than 30% expect legislation regulating either. Most would recommend nicotine patches (76%) and gum (70%) to inveterate smokers, but no other product was supported by a majority. Scientists are more supportive of THR than activists, while respondents focusing on national/international issues are more supportive than those concentrating on local/state issues. CONCLUSIONS: Many members of the US tobacco control community are unaware of the THR "movement", while others possess only rudimentary familiarity with it. If and as THR achieves an increasingly prominent role on the tobacco-or-health scene, this community will have to become educated about THR, and be prepared to advocate for regulatory policies that will maximise the potential for positive outcomes. The potential for negative outcomes remains significant.

Adult↗
PubMed2002

Simultaneous genotyping of single nucleotide polymorphisms in the IL-6, IL-10, TNFalpha and TNFbeta genes.

Single nucleotide polymorphisms (SNP) in the human IL-6, IL-10, TNFalpha and TNFbeta genes have been associated with gene function and susceptibility to disease. In this study, primers containing mismatches at 1-3 nucleotide positions were designed to incorporate a new restriction site recognized by endonucleases AlwNI, BcgI, BglI, BsaBI, BslI, BstXI, EcoNI or XcmI for genotyping SNPs in the IL-6 gene (position - 174), IL-10 gene (positions -592 and -1082), TNFalpha gene (positions -238, - 308 and -863) and TNFbeta gene (position + 249) by mismatched polymerase chain reaction and restriction fragment length polymorphism (PCR/RFLP). Our results show that appropriately designed BslI-based mismatched PCR/RFLP assays can be successfully used to determine the genotypes for approximately 40% of SNPs. The mismatched PCR strategy can be coupled with multiplex-amplification to enable simple and rapid determination of several SNP genotypes in a single reaction.

Cytokines↗
PubMed2002

Efficient cloning and expression of HLA class I cDNA in human B-lymphoblastoid cell lines.

Analysis of HLA restriction specificity is one of the important steps in characterizing T cell clones. This usually requires either a panel of HLA-typed cells or HLA cDNA transfectants. Although preparation of HLA cDNA transfectants is laborious, utilization of transfectants is advantageous when a suitable panel is not available due to linkage disequilibrium or rarity of the HLA allele of interest. In this report, we describe an efficient and rapid HLA cloning and expression system. Three sets of PCR primers specific for HLA-A, B and C loci were designed by extensively sequencing 5'- and 3'- untranslated regions of HLA class I genes. The PCR-amplified products were introduced into modified Phoenix retrovirus vectors containing a puromycin resistant gene under the control of a LTR promotor. Gibbon ape leukemia virus (GALV)-pseudotyped retrovirus was produced and infected into B-lymphoid cell lines. Following expansion in selection media, more than 80% of cells expressed transduced HLA at a comparable level to that normally expressed. These results indicate that locus-specific PCR cloning and utilization of GALV-pseudotyped retroviral vector can be an effective and relatively efficient tool for constructing a panel of different HLA transfectants.

Antibodies, Monoclonal↗
PubMed1999

Correlation between disparity for the minor histocompatibility antigen HA-1 and the development of acute graft-versus-host disease after allogeneic marrow transplantation.

Results of a previous study suggested that recipient mismatching for the minor histocompatibility antigen HA-1 is associated with acute graft-versus-host disease (GVHD) after allogeneic marrow transplantation. In that study, most patients received either cyclosporine or methotrexate for GVHD prophylaxis, and a cytotoxic T-cell clone was used to test for HA-1 disparity. To facilitate large-scale testing, we developed a method that uses genomic DNA to identify HA-1 alleles. A retrospective study was conducted to correlate HA-1 disparity and the occurrence of acute GVHD in 237 HLA-A2-positive white patients who had received a marrow or peripheral blood stem cell transplant from an HLA-identical sibling. All patients received both methotrexate and cyclosporine for GVHD prophylaxis. The presence of HLA-A*0201 was confirmed in 34 of the 36 HA-1 disparate pairs by sequencing the HLA-A locus. Grades II-IV GVHD occurred in 22 (64.7%) of these 34 patients, compared with 86 (42.8%) of the 201 patients without HA-1 disparity (odds ratio, 2. 45; 95% confidence interval [CI], 1.15 to 5.23; P =.02). Recipient HA-1 disparity showed a trend for association with acute GVHD (odds ratio, 2.1; 95% CI, 0.91 to 4.68; P =.08) when a multivariable logistic regression model was used to include additional risk factors. These data are consistent with results of the previous study, suggesting an association between HA-1 disparity and risk of acute GVHD, but the strength of this association may be lower in patients who received both methotrexate and cyclosporine than in those who received methotrexate or cyclosporine alone.

Acute Disease↗
PubMed1999

Rapid screening of T-cell receptor (TCR) variable gene usage by multiplex PCR: application for assessment of clonal composition.

The selection of various T-cell receptor (TCR) gene families and complex rearrangements during intra-thymic differentiation provide the basis for the expression of antigen specificity by mature T cells. TCR beta variable (TCRBV) transcripts can be identified by RT-PCR, but multiple reactions are required to detect all genes of the TCRBV subfamilies. We describe here a multiplex PCR method that amplifies 46 functional genes comparing 23 TCRBV families in 5 reactions where each reaction contains 4 to 7 specific primers together with a single fluorescence-tagged TCR beta constant region primer. Between 8 and 10 distinct subtypes within each of the 23 TCRBV families can be identified by analysis of the CDR3 length. Multiplex PCR products isolated from agarose gels can be subjected to direct sequencing for confirmation and definitive clonotyping if necessary. The data illustrated here show that the multiplex PCR technique is useful for screening TCRBV usage and can be easily adapted for analysis of clonal composition in T-cell populations.

Cell Line↗
PubMed1993

Effects of dehydroepiandrosterone in immunosuppressed rats infected with Cryptosporidium parvum.

Cryptosporidium parvum is a coccidian parasite that causes diarrheal disease in animals and humans. Severe cryptosporidial infections were noted in young adult rats immunosuppressed with the glucocorticosteroid dexamethasone (DEX). B-cell and T-cell responses to the mitogens lipopolysaccharide and concanavalin A, respectively, were depressed in the DEX-treated rats. In addition, DEX treatment suppressed serum IgG levels, in vitro IgG production, and natural killer cell activities. Previous results have shown that DEX-immunosuppressed rats treated with dehydroepiandrosterone (DHEA) exhibit significant reductions in cryptosporidiosis as determined by monitoring oocyst shedding in the feces and parasite colonization of the small intestine. Results from this study indicated that B- and T-cell responses to their respective mitogens, serum IgG levels, and in vitro IgG production were greater in DHEA-treated immunosuppressed rats than in untreated DEX-immunosuppressed rats infected with C. parvum. Similar results were demonstrated in DHEA-treated versus normal control rats infected with C. parvum. These results suggest that the effects of DHEA in reducing cryptosporidiosis are the result of a potentiation of the immune system in the immunosuppressed rats.

Animals↗
PubMed1989

Independent learning in pathology. Does it work?

The sophomore pathology course at the University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, Piscataway, was substantially modified with the intention of promoting guided, independent learning. The emphasis has been shifted from lectures to other modalities of instruction. This article delineates the curricular changes made, describes the instructional modalities used, and reports student performance after two year's experience with the new curriculum.

Education, Medical, Undergraduate↗
PubMed1986

Prostaglandins modulate baroreflex-induced changes in blood pressure and myocardial function in anesthetized dogs.

The purpose of our study was to investigate the role of prostaglandins in the changes in myocardial function and peripheral and coronary vascular resistance which accompany a generalized increase in sympathetic tone caused by carotid baroreflex unloading in the anesthetized dog. Bilateral carotid artery occlusion (BCO) with heart rate held constant by electrical pacing (150 beats/min) resulted in increases in systolic, (33%) diastolic (40%), and mean (35%) arterial pressures, LV systolic pressure (33%) and left ventricular (LV) dP/dt (37%). After blockade of prostaglandin synthesis with indomethacin (N = 11) or meclofenamate (N = 6) the increases in systolic (41%), diastolic (45%), and mean (41%) arterial pressures, LV systolic pressure (39%), LV dP/dt (52%), and cardiac work caused by BCO were significantly greater, in spite of the initially higher baseline values (11-18%) following the administration of the drugs. In contrast, the changes in circumflex coronary blood flow and coronary vascular resistance to BCO were essentially the same before and after inhibition of prostaglandin synthesis. Systemic prostaglandin synthesis may, therefore, play a significant role in the control of systemic arterial pressure and myocardial function, most probably by modulating the release of norepinephrine from adrenergic nerve terminals, without adversely affecting coronary blood flow regulation.

Animals↗
PubMed1982

Thromboxane mediates acute pulmonary hypertension in sheep extracorporeal perfusion.

We measured serial plasma concentrations of thromboxane B2 (TXB2), the stable metabolite of the putative pulmonary vasoconstrictor thromboxane A2 (TXA2), and 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha), the stable metabolite of the pulmonary vasodilator prostacyclin (PGI2) by double-antibody radioimmunoassay during partial venovenous bypass in 25 awake sheep. The onset of bypass caused mean pulmonary artery pressure (PAP) to increase from 16 +/- 1 to 28 +/- 2 mmHg at 12 +/- 2 min, due to an increase of pulmonary vascular resistance, followed by a return to control within 45 min. There was no systemic hypoxia. TXB2 increased simultaneously with the onset of pulmonary hypertension (PH) (236 +/- 36 to 700 +/- 120 pg/ml at 0 and 5 min) and peaked at 1,724 +/- 172 pg/ml 10 min after maximum PAP was achieved. Positive pulmonary artery-to-aortic differences of TXB2 were measured. 6-Keto-PGF1 alpha increased from 51 +/- 3 to 842 +/- 367 pg/ml at 35 min. PGF2 alpha was unchanged (130 +/- 45 pg/ml). PH, TXB2, and 6-keto-PGF1 alpha increases were blocked by pretreatment with indomethacin or ibuprofen. PH and TXB2 increases were prevented with an imidazole derivative. PH caused by a continuous infusion of an endoperoxide analog did not induce lung release of TXB2 or PGF2 alpha. We conclude that 1) transient pulmonary vasoconstriction is caused by thromboxane; 2) the lung is the primary site of thromboxane synthesis; and 3) bypass causes selective alterations in arachidonic acid metabolism rather than general activation of the cascade.

6-Ketoprostaglandin F1 alpha↗
PubMedDate not supplied

Effects of dexamethasone and dehydroepiandrosterone in immunosuppressed rats infected with Cryptosporidium parvum.

Treatment of rats immunosuppressed with dexamethasone and inoculated with Cryptosporidium parvum oocysts were treated with dehydroepiandrosterone. A significant reduction in cryptosporidial activity was observed as determined by oocyst shedding and colonization of host tissue by parasites. Dexamethasone treatment alone resulted in decreases in T-, B- and natural killer (NK) cell responses and antibody production that, with the exception of NK-cell activity, were all reversed after administration of dehydroepiandrosterone.

Animals↗