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Biomedical subjects

B Hunt

Publications and source records attributed to B Hunt.

At least 37 records · Page 2Linked to original sources
PubMed1993

Direct correlation between MUC18 expression and metastatic potential of human melanoma cells.

The expression of the glycoprotein MUC18 in melanoma biopsies has previously been shown to increase with increasing tumour thickness, and thus to correlate with the probability of metastasis development. We have examined the expression of this molecule by nine human melanoma cell lines with known metastatic ability (both spontaneous and experimental) in nude mice. Examination of the expression of both the MUC18 mRNA and of the glycoprotein on the cell surface revealed a statistically significant correlation (P = 0.040) between its expression and the ability to form metastases in vivo. Although MUC18 shows sequence similarity to neural cell adhesion molecules, no correlation was observed between the site of origin of the metastatic lesions (brain, lymph node) and MUC18 expression.

Animals↗
PubMed1993

Development of a MUMPS-based anticoagulant management system.

A computerised anticoagulant management system written in Digital Standard MUMPS, and incorporated into an ACT Medisys Computer Integrated Laboratory Management System (CILMS), has been developed. The system will automatically adjust and prescribe warfarin dosage for selected patients and set clinic appointments based upon defined criteria. Other significant features include printed patient dosage cards, cumulative worksheets for clinicians, clinic and transport lists, statistical searches, rapid enquiry facilities and operator alerts. After 20 months of successful running, a system has evolved which has greatly improved the efficiency of the anticoagulant clinic and the quality of anticoagulant control. Significant savings have been made in medical staff time, patient waiting times have been greatly reduced and the stability of warfarin control has increased. The service has more recently been extended to patients controlled by their general practitioners, with all the associated benefits.

Anticoagulants↗
PubMed1992

Maxepa versus bezafibrate in hyperlipidemic cardiac transplant recipients.

Accelerated coronary artery disease is the most serious obstacle to long-term survival in cardiac transplant recipients. Lipid abnormalities are found frequently in these patients, and there is growing evidence that even minimally increased levels of cholesterol and triglycerides contribute to the development of accelerated coronary artery disease. However, the optimal lipid-lowering therapy after cardiac transplantation has not been defined. In an open, randomized study, the efficacy and safety of bezafibrate (400 mg/day) and fish oil (Maxepa) (10 g/day) for 3 months were compared in 87 cardiac transplant recipients with serum total cholesterol > 6.5 or triglycerides > 2.8 mmol/liter, or both. After 1 month, bezafibrate reduced total cholesterol by 13%, low-density lipoprotein cholesterol by 20% and apolipoprotein B by 13%. It also increased apolipoprotein A1 and high-density lipoprotein cholesterol by 12 and 20%, respectively, and significantly reduced fibrinogen at 3 months. Maxepa had no significant effect on these variables, but was as effective as bezafibrate in reducing triglycerides (36 and 31%, respectively). Both drugs increased lipoprotein (a) to a similar extent, and bezafibrate significantly increased serum creatinine. These results suggest that bezafibrate has better lipid-, apolipoprotein- and hemostatic modifying properties than does Maxepa, but its potentially adverse effect on renal function needs further investigation.

Apolipoprotein A-I↗
PubMed1991

Reduced tumorigenicity of murine tumor cells secreting gamma-interferon is due to nonspecific host responses and is unrelated to class I major histocompatibility complex expression.

Spontaneous SP1 murine adenocarcinoma cells transfected with the murine gamma-interferon (IFN-gamma) gene expressed IFN-gamma (SP1/IFN-gamma) failed to grow in syngeneic hosts and grew in nude mice. The rejection of SP1/IFN-gamma cells was related to the amount of IFN-gamma produced and appeared to be mediated primarily by nonspecific cellular mechanisms, although some role for T-cells in the afferent arm of this response is possible. SP1 cells are H2-Kk negative but express class I antigens when producing IFN-gamma. However, class I major histocompatibility complex (MHC) expression, while likely necessary, was insufficient in itself to prevent tumor growth since secretion of greater than 64 units/ml IFN-gamma was needed to inhibit tumorigenicity while only 8 units/ml IFN-gamma could induce class I antigens. Similar results were obtained with the murine colon carcinoma CT-26, a tumor that constitutively expresses class I MHC antigens, further supporting the contention that class I MHC expression is not essential for the rejection response induced by IFN-gamma. The failure of SP1/IFN-gamma cells to protect against a challenge with parent SP1 cells argues that factors other than IFN-gamma production or class I MHC expression are needed to induce a protective response against weakly or nonimmunogenic tumor cells.

Adenocarcinoma↗
PubMed1991

Immunogenicity of a non-class I MHC expressing murine tumor transfected with the influenza virus hemagglutinin or murine interleukin-2 genes.

The transfection of murine SP1 tumor cells with the hemagglutinin (HA) gene of influenza virus results, after fluorescent-activated cell sorting (FACS), in the selection of high-HA-expressing cell lines called H4A and H4B. Both lines fail to grow in syngeneic animals at doses that result in 100% tumor take of non-transfected tumor cells. Both grow in immunosuppressed mice. SP1 and H4A or H4B cells express few class I major histocompatibility complex (MHC) antigens but do express class II IAk antigens. H4A or H4B cells engender a cytotoxic T lymphocyte (CTL) response but cannot protect against a challenge with SP1 cells. This CTL response is inhibited by anti-CD4 but not anti-CD8 antibodies. Using FACS, we were able to select a population (called H5AK5) with high class-I MHC antigen expression. Like H4A and H4B, H5AK5 cells fail to grow in syngeneic animals but do grow in immunosuppressed mice. However, unlike H4A or H4B, H5AK5 can induce protection against a challenge with 1 x 10(5) SP1 cells. These studies indicate that the immunogenicity of HA-transfected SP1 cells may correlate with the cell-surface expression of class II MHC antigens. However, HA-expressing SP1 cells seem able to induce a protective response against a parent SP1 cell challenge only if they also express class I MHC antigens. This view is supported by the observations that SP1 cells expressing murine interleukin-2 do not express class I MHC antigens, fail to grow in syngeneic animals, do grow in immunosuppressed mice but do not protect against a challenge with parental SP1 cells.

Animals↗
PubMed1991

Expression of ABH blood group antigens in human heart tissue and its relevance to cardiac transplantation.

Blood group antigen expression was assessed in cardiac tissue taken during heart transplantation. The samples were from ten donors and nine recipients, of whom seven were blood group A, three were group B, two were group AB, and seven were group O. Cryostat sections were studied by immunofluorescence microscopy. Blood group antigens were confined to the mesothelial cells on the surface of the epicardium and the cardiovascular endothelium where they were consistently demonstrated according to erythrocyte blood group using a rabbit anti-A serum, monoclonal antibodies against A and B antigens, and the H antigen-specific lectin Ulex europaeus. The cardiac muscle itself was negative for blood group antigen. The results indicate that there is some variation in antigen expression between individuals, which may explain why transplants have occasionally been successful in breaching the blood group ABO barrier.

ABO Blood-Group System↗
PubMed1990

Synergistic cytotoxicity using 2'-deoxy-5-azacytidine and cisplatin or 4-hydroperoxycyclophosphamide with human tumor cells.

The combined use of 2'-deoxy-5-azacytidine with cisplatin or 4-hydroperoxycyclophosphamide in vitro frequently resulted in synergistic cytotoxicity against a panel of six human cell lines. This enhanced cell killing occurred at drug concentrations that are clinically achievable. Synergy was also seen if the sequence of drug administration was altered, implying that a temporal overlap between the drugs was necessary, but that the actual biochemical lesions induced by each agent were probably unique, and interacted in an as yet undefined manner. Of further interest was the observation that at least one of the synergistic pairs was active against five of the six cell lines tested. 2'-Deoxy-5-azacytidine incorporation as assessed by the level of gross genomic DNA methylation did not appear to correlate with the synergistic cytotoxicity observed. Thus, we could not discern a clear relationship between the degree of DNA hypomethylation and the observed synergies, although DNA hypomethylation frequently occurred when synergy was demonstrated. The practical usefulness of these drug combinations has not yet been tested and awaits appropriate clinical trials both to assess the tumoricidal effects and possible increased toxicity.

Antineoplastic Agents↗
PubMed1990

A comparison of AIDS and STD knowledge between sexually active alcohol consumers and abstainers.

Effective curricula should influence knowledge levels of all students, including high-risk populations. In this study, a modified version of the National Adolescent Student Health Survey was administered to a group of eighth and 10th grade students (N = 3,803) exposed to a curriculum designed to improve AIDS and STD knowledge levels. The analysis examined the influence of gender, ethnicity, alcohol use, and sexual activity as they related to AIDS and STD knowledge. Findings indicated poor knowledge scores on STD items, with no significant differences on group comparisons. Comparisons of AIDS knowledge scores indicated significant differences based on gender, ethnicity, and behavior. Females scored higher than males, whites scored higher than blacks, and abstainers from sexual activity and alcohol scored higher than their active counterparts. Results suggest current educational efforts are not equally effective. Future educational initiatives should be sensitive to group membership.

Acquired Immunodeficiency Syndrome↗
PubMed1990

The entrainment of low frequency breathing periodicity.

It has been predicted by mathematical models of the respiratory control system that the delay between the lung and the respiratory controller may determine the cycle time found in periodic breathing. We examined cycle time of periodic breathing and circulation time in 11 patients known to have circulation delay due to heart failure. We did not find a significant relationship between the amount of periodic breathing and circulation delay, but found a very high correlation between circulation delay and the cycle time of periodic breathing (r2 = 0.825; p = 0.0001).

Blood Circulation↗
PubMed1989

Genotypic and phenotypic evidence of clonal interactions in murine tumor cells.

The stability of mixed tumor cell populations has been described in terms of phenotypic characteristics such as metastatic potential, immunogenicity, and drug resistance. We have extended these analyses to the molecular level in a model that uses transfection of the hemagglutinin antigen (HA) gene of influenza virus into murine CT-26 colorectal carcinoma cells. Transfection was followed by fluorescence-activated cell sorting (FACS) to select a parent population with expression of high levels of HA. We characterized this population (FACS-3) and four derived clones (5, 6, 9, and 18) over time with regard to phenotypic characteristics: immunogenicity and cross-protection against tumor challenge, cell surface expression of HA, evidence of HA gene amplification, and levels of HA mRNA. During 6 months in culture, the FACS-3 parent cells remained stable, but the individual clones varied for all of the parameters assessed. Among the clones, all possible molecular variations occurred, including changes in HA gene copy number (increased in clone 5 and decreased in clone 18), gene rearrangement (clone 5), decrease in HA mRNA (clones 6, 9, and 18), increase in HA mRNA (clone 5), and an abnormality in translational control or a posttranslational error. In all cases, the molecular changes correlated with cell surface HA expression, immunogenicity, and cross-protective potential. We conclude that in vitro clonal interactions play a role in stabilizing heterogeneity in this system. These studies show that even in the absence of selection, clonal interactions may alter the phenotype of tumors by increasing malignant progression or impeding tumor growth.

Animals↗
PubMed1989

Retention of immunogenicity after X-irradiation of mouse colon tumor cells expressing the transfected influenza virus hemagglutinin gene.

We have previously demonstrated that murine colon tumor cells transfected with the gene coding for the hemagglutination antigen (HA) of influenza virus acquire an inherent immunogenicity, fail to grow in syngeneic mice, and demonstrate an ability to cross-protect against a challenge with parental nontransfected cells. In the present study the immunogenic potential of HA-transfected cells correlated with cell-surface HA expression, as measured both by a fluorescence-activated cell sorter and by radio-labeled antibody binding. HA-transfected immunogenic cells had a median lethal dose (LD50) that was 10,000-fold greater than that of nontransfected cells. Most importantly this study demonstrated that HA-transfected cells retained their immunogenicity after X-irradiation with 12,000 rad. This characteristic makes their potential usefulness in treating human neoplasia more plausible.

Animals↗
PubMed1988

Induction in a murine tumor of immunogenic tumor variants by transfection with a foreign gene.

Transfection of the undifferentiated murine colon carcinoma line CT-26 with the gene coding for the hemagglutination antigen (HA) of influenza virus resulted in the generation of highly immunogenic tumor cells. CT-26 cells transfected with HA not only failed to grow in syngeneic mice but also protected normal animals against a challenge with otherwise lethal doses of parental nontransfected cells. The immunogenicity of HA-transfected cells appeared to correlate with surface HA expression in that tumorigenic clones of HA-transfected CT-26 cells expressed little HA, while immunogenic clones were high expressers of HA. Irradiation of immunogenic HA clones did not abrogate their immunogenicity. These observations demonstrate that immune recognition of a poorly immunogenic tumor can be produced by immunization with tumor cells expressing a defined, foreign cell surface antigen.

Animals↗
PubMed1988

The prevalence of ouabain-resistant variants after mutagen treatment. Lack of correlation between the frequency of variant expression and the metastatic phenotype.

In order to test the hypothesis that tumor cells with greater malignant potential should have an increased sensitivity to mutagens, four individual murine cell lines, each paired for their metastatic and nonmetastatic potentials, were compared with respect to the prevalence at which ouabain-resistant mutants could be obtained after treatment of the cells with the mutagen MNNG. No increase in the prevalence of induced mutation in metastatic cells was observed; and, in fact, in two cases (h-ras-transfected 3T3 and SP1 cells), nonmetastatic cells had a higher prevalence of mutations after MNNG treatment than did their metastatic counterparts. We suggest that the absolute level of genomic instability, measured by this means, is not critical to malignant potential and tumor progression.

Animals↗
PubMed1987

Selection of metastatic variants with identifiable karyotypic changes from a nonmetastatic murine tumor after treatment with 2'-deoxy-5-azacytidine or hydroxyurea: implications for the mechanisms of tumor progression.

Experiments were undertaken to explore whether in vitro exposure of a nonmetastatic murine tumor to chemotherapeutic drugs would affect the ability of this tumor to metastasize spontaneously. The tumor chosen was an aneuploid (near-tetraploid) spontaneously arising intraductal mammary adenocarcinoma (CBA-SP1), which normally fails to give rise to microscopic or macroscopic metastases after s.c. inoculation of cells. The drugs tested were 5-aza-2'-deoxycytidine (5-aza-dCyd) and hydroxyurea. We found that the injection of 1 X 10(5) uncloned drug-treated cells s.c. resulted in the emergence of gross and/or microscopically detectable metastases in the lungs of CBA mice. Individual clones derived from hydroxyurea-treated cells all produced metastases in a manner similar to the bulk culture injections. Clones of 5-aza-dCyd-treated cells also produced metastases, but fewer of these produced macroscopic metastases. In addition, only 9 of 15 5-aza-dCyd-treated clones produced tumor takes because of the ability of 5-Aza-dCyd to engender Imm+ variants in CBA-SP1 cells. Lung metastases obtained after the injection of uncloned cells retained their metastatic phenotype for three generations, indicating that the phenotypic change was a heritable characteristic. Although the genetic or epigenetic mechanism for this change is unknown, we observed karyotypic changes of a similar nature in the drug-treated cell lines established from micrometastases. These involved the detection of extra copies of chromosome 8. It is possible that exposure of tumors to therapeutic agents may in some cases increase their aggressiveness through genetic or epigenetic mechanisms that lead to high frequency heritable phenotypic alterations associated with distinguishable chromosomal changes.

Animals↗
PubMed1987

A cluster of patients with a chronic mononucleosis-like syndrome. Is Epstein-Barr virus the cause?

A cluster of 134 patients who had undergone Epstein-Barr virus (EBV) serological testing because of suspected chronic EBV syndrome was investigated in Nevada. Fifteen case-patients were identified who had severe, persistent fatigue of undetermined etiology for more than two months. When compared with the remaining 119 patients who had less severe illnesses and with 30 age-, sex-, and race-matched control-persons, these 15 patients had significantly higher antibody titers against various components of EBV and against cytomegalovirus and herpes simplex and measles viruses. Epstein-Barr virus serology could not reliably differentiate individual case-patients from the others, and the reproducibility of the tests within and among laboratories was poor. As a group, the case-patients appear to have had a syndrome that is characterized by chronic fatigue, fever, sore throat, and lymphadenopathy. The relationship of this fatigue syndrome to EBV is unclear; further studies are needed to determine its etiology.

Adolescent↗