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J Cormier

Publications and source records attributed to J Cormier.

At least 19 recordsLinked to original sources
PubMed2001

Potential interaction between warfarin and boldo-fenugreek.

A patient was treated with warfarin for atrial fibrillation. During treatment, an increase in international normalized ratio (INR) and her admission that she was taking a variety of natural products, to include boldo and fenugreek, led us to suspect that some of these natural products could alter the effect of warfarin. When she stopped the culpable products, the INR returned to normal after 1 week. The herb-drug interaction was observed a second time after both products were reintroduced a few days later. The imputability of this interaction to both natural products, as determined by the Naranjo algorithm, suggests a probable association between boldo-fenugreek and increased bleeding time in patients treated with warfarin. No undesirable reaction was reported during telephone discussions with the patient. Nevertheless, we recommend that clinicians treating patients with anticoagulant therapy be vigilant when patients also take herbal agents.

Aged↗
PubMed1999

Immune selection after antigen-specific immunotherapy of melanoma.

BACKGROUND: Melanoma antigen (MA)-specific vaccination strongly enhances antitumor reactivity in vivo and is capable of producing strong cytotoxic T lymphocyte responses in vitro. Furthermore, specific human leukocyte antigen-restricted T cell activation is hypothesized to occur in response to peptide-based immunotherapy, which may lead to the preferential killing of tumor cells bearing the relevant MA. The development of melanoma antigen-loss variants may subsequently occur in vivo. METHODS: Analysis of 532 melanoma lesions from 204 patients was performed on fine-needle aspiration biopsy specimens. Lesions were graded for the expression of the MAs gp100 and MART-1 with use of immunocytochemistry. A total of 351 melanoma lesions were divided into cohorts on the basis of the treatment received. The pretreatment group (n = 175) consisted of lesions obtained before any form of gp100 immunotherapy, with the posttreatment group (n = 176) consisting of lesions obtained after vaccination with a modified gp100 epitope, gp209-2M +/- interleukin 2 (IL-2). RESULTS: The percentage of lesions not expressing the gp100 antigen is greater than the percentage not expressing MART-1 (26% vs 14%). The frequency of lesions with high expression (> 75%) of gp100 significantly decreased with therapy (47% vs 34%) and conversely negative lesions increased (18% vs 29%). Treatment of lesions with peptide alone (no IL-2) revealed a significant decrease in gp100 expression (47% vs 32%), enhanced with the addition of IL-2 to therapy (47% vs 35%). The expression of MART-1 remained essentially unchanged unless IL-2 was added (54% vs 54%, MART-1 peptide alone, 54% vs 43%, MART-1 peptide + IL-2). Of 94 patients (181 lesions) assessed for gp100 expression before treatment, 10 patients responded to therapy. Pretreatment lesions in responding patients expressed some level of gp100 in all cases compared with 27% of nonresponding lesions, which were negative for gp100 expression. CONCLUSIONS. This study indirectly demonstrates that vaccination with an MA-derived peptide can result in immune selection in vivo. Furthermore, it provides strong immunologic evidence for the specificity of MA vaccines and to the relevance of MA expression in predicting the response to vaccination.

Antigens, Neoplasm↗
PubMed1998

Validation of capillary electrophoresis for analysis of the X-Y homologous amelogenin gene.

Capillary electrophoresis (CE) is a versatile technology with tremendous potential applications in forensic science. A refinement of the traditional slab-gel, separation occurs in a liquid polymer contained within a capillary. The capillary electrophoresis unit is computer-driven, semi-automating the loading and analysis of samples. As with any new technology, a full performance assessment is required before it may be implemented with confidence. This paper focuses on validation of CE technology for analysis of a portion of the X-Y homologous amelogenin gene used in gender determination. Typical Y/X ratios of peak heights for male samples were determined. Instrument linearity, sample resolution and reproducibility were examined. Samples subjected to contamination, extreme environmental conditions or extracted from a variety of substrates were also tested by CE. All samples typed correctly. Genetic material from a number of common non-primate animals was amplified with amelogenin primers. Some species yielded no product. Products derived from the animal samples that did amplify produced peaks on CE analysis readily distinguishable from those of human origin.

Amelogenin↗
PubMed1997

Immunocytochemical detection of MART-1 in fresh and paraffin-embedded malignant melanomas.

MART-1 is a transmembrane protein that appears to be melanocyte specific. This study evaluated the use of a new monoclonal antibody, directed against MART-1, in fresh and paraffin-embedded specimens. Twenty-three paraffin-embedded tumors were evaluated for MART-1 immunoreactivity both before and after microwave-based antigen retrieval. After this comparison, 53 fine-needle aspirates from 43 patients with malignant melanoma were assessed for MART-1 immunoreactivity. Immunocytochemistry was performed on both cytospins and paraffin-embedded tissues that were pretreated with antigen retrieval. Seventeen (74%) of 23 tumors evaluated for immunoreactivity before and after antigen retrieval showed a significant increase in both staining intensity and the number of cells stained. When cytospins and antigen-retrieved cell blocks from 53 fine-needle aspirates were compared. 38 (72%) showed good correlation. In 13 (25%) of 53 tumors, MART-1 immunoreactivity was more intense in the cytospins, although the differences were marked in only two cases: Microwave-based antigen retrieval renders paraffin-embedded tissues nearly as sensitive as fresh material for use in the immunocytochemical detection of MART-1. This technique will allow the evaluation of MART-1 immunoreactivity in archival malignant melanomas.

Antibodies, Monoclonal↗
PubMed1997

Dendritic cells infected with poxviruses encoding MART-1/Melan A sensitize T lymphocytes in vitro.

Dendritic cells (DC) are potent professional antigen-presenting cells that can activate naive T lymphocytes and initiate cellular immune responses. As adjuvants, DC may be useful in enhancing the immunogenicity of tumor antigens and mediating tumor regression. Endogenous expression of antigen by DC offers the potential advantage of allowing prolonged constitutive presentation of endogenously processed epitopes and exploitation of multiple restriction elements for the presentation of the same antigen. In this report, we show that human DC are (a) capable of infection by recombinant poxviruses encoding melanoma-associated antigen (MAA) genes and (b) capable of efficiently processing and presenting these MAA to cytotoxic T cells. In 6/6 HLA A*0201-expressing melanoma patients tested, the virally driven expression of MART-1/Melan A MAA by DC was sufficient to generate CD8+ T lymphocytes that could recognize naturally processed epitopes on tumor cells. In most cases, specific anti-MART-1 reactivity could be detected after a single stimulation. Analysis of epitope dominance revealed that the amino acid sequence recognized by these cytotoxic T lymphocytes (CTL) corresponded to the MART-1(27-35) residues previously shown to be most commonly recognized by cytotoxic T lymphocytes expanded from metastatic melanoma lesions. These data show that the virally driven expression of MAA by DC can be exploited for the efficient induction of clinically relevant cytotoxic T-cell responses. This has clinical implications for active immunization therapy, and currently vaccine trials have been proposed for patients with metastatic melanoma.

Antigen Presentation↗
PubMed1996

Analysis of expression of the melanoma-associated antigens MART-1 and gp100 in metastatic melanoma cell lines and in in situ lesions.

MART-1 and gp100 melanoma associated antigens (MAA) are expressed by cells of the melanocytic lineage and are recognized by the majority of HLA-A2 restricted tumor-infiltrating lymphocytes. Heterogeneity of expression of MAA in tumor deposits may affect the natural history or response to therapy of patients with melanoma. In this study, we evaluated the expression of these MAA with a new monoclonal antibody (mAb) directed against MART-1 (M2-7C10) and the commercially available HMB45 mAb directed against gp100. Expression was tested in vitro by intracellular fluorescence analysis and in vivo by immunophenotyping of tissue specimens. Nine melanoma cell lines and 25 tissue specimens from metastatic melanoma were analyzed. One cell line did not express MART-1 or gp100. The expression of both antigens was more heterogeneous and significantly reduced (p < 0.01) in melanoma cell lines compared with melanocytes, suggesting progressive loss of expression of MAA by neoplastic cells. None of the nonmelanoma cancer lines tested stained for MART-1 or gp100. Analysis of melanoma lesions by immunohistochemistry showed significant heterogeneity of expression of both MART-1 and gp100 MAA either as a percentage of cells expressing MAA or as intensity of expression. Ten of 25 frozen sections expressed MART-1 in < 50% of the cells. In 6 of 25 lesions, immunoreactivity for MART-1 was totally absent. Fine needle aspiration of metastatic lesions seemed to yield information accurately about amount and heterogeneity of expression of MAA in tumor lesions in vivo. Heterogeneity of expression of MAA may be one of several mechanisms leading to tumor escape from immune recognition, and pretreatment evaluation of tumor lesion for expression of these antigens may help in selecting patients best suited to antigen-specific vaccine therapies.

Antigens, Neoplasm↗
PubMed1995

HLA associations in the antitumor response against malignant melanoma.

In this study we analyzed the human leukocyte antigen (HLA) pattern of North American Caucasian patients with metastatic melanoma as compared with the North American Caucasian (NAC) population. We also investigated whether the HLA type of melanoma patients had an effect on their tolerance and response to interleukin-2 (IL-2)-based therapy. Four hundred twelve serologic phenotypes of Caucasian melanoma patients referred to the National Cancer Institute, National Institutes of Health, from February 1989 through December 1993 were collected by typing the patient's peripheral blood lymphocytes. Furthermore, 74 melanoma patients were typed for HLA class II by high-resolution sequence specific primer-polymerase chain reaction. Response rate and treatment-related toxicity in those patients receiving IL-2-based treatment (N = 272) were compared with HLA serologic types. The frequency of four HLA-B alleles was significantly different in the melanoma compared with the NAC population: of these, HLA-B5, -B8, and -B15 had a frequency falling between the NAC and the Northern European population. No other significant differences between melanoma patients and NAC population were noted for other HLA loci. A correlation was noted between HLA-DR3 and -DR4 alleles and decreased tolerance to IL-2, whereas homozygosity for HLA-DR decreased the chance of response. There were no significant associations between HLA type and response. It is unlikely that the associations noted between some HLA-B alleles and melanoma bear significantly on the etiology of the disease. The differences seen between American melanoma patients and the NAC population are probably best explained by geographical ancestry. The association between HLA-DR and tolerance to IL-2 therapy noted in this study may offer insight toward the understanding of mechanisms regulating the cascade of events after the systemic administration of IL-2.

Gene Frequency↗
PubMed1993

Athletic trainer utilization in sports medicine clinics.

Increased use of athletic trainers in sports medicine clinics has created a need for information related to actual and ideal use of these professionals in these settings. The purposes of this study were to 1) describe the characteristics of sports medicine clinics and their personnel, 2) determine whether there were differences between opinions of certified athletic trainers (ATCs), physical therapists (PTs), and professionals with dual credentials (PT/ATCs) about the ideal role of the ATC in sports medicine clinics, and 3) determine whether there were differences in actual usage of ATCs between states with and without athletic training laws. Subjects included 46 PTs, 43 PT/ATCs, and 73 ATCs from six different states. A questionnaire ascertained opinions about ideal ATC utilization and about current practice of ATCs with respect to 28 different clinical procedures. For 27 of the 28 procedures, there were significant differences of opinion about ideal ATC utilization between individuals with the three credentials. No significant differences in actual athletic trainer use in sports medicine clinics were found between states with and without athletic training laws.

Adult↗
PubMed1992

Structure-function studies of peptides inhibiting the ribonucleotide reductase activity of herpes simplex virus type I.

Ac-Tyr298-Ala299-Gly300-Thr301-Val302-I le303-Asn304-Asp305-Leu306-OH (Ac-VZV R2-(298-306)) represents the acetylated form of the C-terminus of varicella-zoster virus (VZV) ribonucleotide reductase subunit 2 (R2). This peptide possesses a high degree of homology with the C-terminus nonapeptide of the herpes simplex virus (HSV) type I and II ribonucleotide reductase R2 protein and is 15 times more potent than the latter in its in vitro inhibition of HSV-1 reductase activity. Accordingly, a new series of analogues based on this structure was studied in vitro. The replacement of Asp305 by Asn, Glu, Gln, Ser, or Cys; of Asn304 by Gln or Ser; of Ile303 and Val302 by D-Val; and of Tyr298 by Cha induced an important loss of inhibitory potency. The substitution of Asn304 by Asp; of Thr301 by Cys, Ser, or Val; of Gly300 by Ala or Val; of Ala299 by Val; or of Tyr298 by homoPhe, 4'-fluoro-Phe, 4'-chloro-Phe, 3'-iodo-Tyr, Me-Tyr, or For-Trp led to a moderate decrease of the Ac-VZV R2-(298-306) potency. The replacement of Val302 by Ile; Ala299 by Cys, Ser, or Thr; or the insertion of a six- or eight-carbon chain between Tyr298 and the NH2 terminus either preserved or slightly increased the inhibitory potency of Ac-VZV R2-(298-306). Finally, the substitution of Tyr298 by Trp or the addition of 4'-nitro-Phe at the amino terminus resulted in a 3-fold increase of potency. Altogether, these results stress the importance of the structural integrity of the minimum active core 302-306 in preserving the inhibitory potency and suggest that further studies on monosubstitutions could be directed at the portion 298-301 of the peptide.

Amino Acid Sequence↗
PubMed1990

Prevention of diabetes in the BB rat by essential fatty acid deficiency. Relationship between physiological and biochemical changes.

Essential fatty acid (EFA) deficiency exerts a striking protective effect in several animal models of autoimmune disease. We now report that EFA deprivation prevents diabetes in the BB rat, an animal model of human insulin-dependent diabetes mellitus. In diabetes-prone (DP)-BB rats, the incidences of spontaneous diabetes and insulitis (the pathological substrate of autoimmune diabetes) were greatly reduced by EFA deficiency. This beneficial effect of the deficiency state was also seen in diabetes-resistant (DR)-BB rats that, after treatment with antibody to eliminate RT6+ T cells, would otherwise have become diabetic. The susceptibility of EFA-deprived DP-BB rats to spontaneous diabetes was restored when they were given dietary supplements of linoleate at 70 d of age (during the usual period of susceptibility), but not when they were repleted beginning at 120 d (after the peak incidence of diabetes). EFA deficiency did lead to growth retardation, but calorically restricted control rats demonstrated that the protective effect of the deficiency state was not a function of decreased weight. To examine the relationship between the biochemical changes of EFA deficiency and its physiological effects in this system, we compared the fatty acid changes that occurred in EFA-deficient animals that did and did not develop diabetes. Nondiabetic animals had significantly lower levels of (n-6) fatty acids (i.e., linoleate and arachidonate) and higher levels of oleate, an (n-9) fatty acid, than did diabetic animals. Levels of 20:3(n-9), the fatty acid that uniquely characterizes EFA deficiency, were similar in both groups, however. Among diabetic EFA-deficient rats, the age at onset of diabetes was found to correlate inversely with the level of (n-6) fatty acids, the least depleted animals becoming diabetic earliest, whereas there was no correlation with levels of 20:3(n-9). Among animals repleted with linoleate beginning at 70 d, restoration of susceptibility to diabetes correlated with normalization of the level of arachidonate. In summary, EFA deprivation reduced the frequency of diabetes in both DP and RT6-depleted DR-BB rats. This protective effect was strongly associated with depletion of (n-6) fatty acids, particularly arachidonate, but not with accumulation of the abnormal 20:3(n-9). Conjecturally, arachidonate and/or a metabolite may play a key role in mediating inflammatory injury in this animal model of autoimmune diabetes.

Animals↗