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Biomedical subjects

A B Hill

Publications and source records attributed to A B Hill.

At least 19 recordsLinked to original sources
PubMed1992

Loss of HLA class-I alleles, heavy chains and beta 2-microglobulin in colorectal cancer.

Using immunohistochemical methods, we have analysed colorectal biopsies of normal mucosa, metaplastic polyps (5 cases), adenomas (15 cases) and adenocarcinomas (70 cases) with 13 monoclonal antibodies (MAbs) to allelic products of the HLA-A, B, C loci. Nine of the 70 carcinomas showed total loss of HLA Class-I molecules due to an underlying defect regarding not only the expression of beta 2-microglobulin (beta 2-m), but also the heavy chains of HLA A, B and C loci, or both. Much commoner was a loss of one or more Class-I alleles as follows: A1/Aw36 (completely lost in 4 of 29 cases and focally lost in another 2), A2 (in 1 of 37 cases), A3 (in 2 of 14 cases), A1 1/28/31/33 (in 3 of 11 cases), B7 (in 3 of 13 and focally in 1 other case), B17 (in 1 case), Bw4 (in 8 of 45 and focally in another 6), Bw6 (in 9 of 62 and focally in another 3). Focal selective loss (Bw6 and a combined A1-Bw6), was observed in 2 adenomas. Normal colonic mucosa, as well as stromal and lymphoid cells present between the neoplastic glands, were studied in each case as a control. A particular allele was only considered to be lost by the malignant cells if it was still expressed on these adjacent tissues.

Alleles↗
PubMed1992

Restimulated memory Tc cells have a higher apparent avidity of interaction with targets than primary virus-immune Tc cells as indicated by anti-CD8 blocking.

Previous experiments have shown that whereas a secondary in vitro Kunjin-immune cytotoxic T (Tc) cell population lysed equally well targets infected with either native flavivirus or a recombinant vaccinia virus expressing the immunodominant determinant, primary in vivo Kunjin-immune Tc cells were able to lyse only the recombinant vaccinia virus-infected targets. Using CD8 blockade to assess the avidity of T cell-target interaction, recombinant-infected targets express antigen more efficiently than native flavivirus infected targets and secondary in vitro Kunjin-immune Tc cells have a higher avidity for targets than do primary in vivo Kunjin-immune Tc cells. Secondary in vivo influenza-immune Tc cells are also of higher avidity than primary in vivo influenza-immune Tc cells. Thus, a restimulated memory Tc cell population interacts with targets with greater avidity than does a recently activated naive population.

Animals↗
PubMed1992

Relationships between attributions and emotions in a laboratory-based sporting contest.

A series of one-vs-one fencing contests was staged in a laboratory to investigate the nature and extent of relationships between attributions and emotions. The experimenter had full control over the outcome and created a substantial defeat for one subject. A pre-contest measure of the importance of winning was obtained via a questionnaire. After the contest, questionnaire ratings of 12 attributions for outcome (winning/losing), 28 adjectives describing emotions, and a rating of satisfaction with performance were elicited. Factor analysis of emotion ratings revealed three factors of 'positive self-esteem', 'depression-frustration' and 'intropunitiveness'. Relationships between emotion factors and attributions involved primarily internal attributions. Multiple regression analyses showed that positive self-esteem for winners was best predicted by performance satisfaction, outcome importance and attributions, whereas depression-frustration was predicted only by attributions. For losers, positive self-esteem was predicted from attributions. These results suggest that attributions and emotions are related after sports competition but that non-attribution variables are also important predictors of sport-related emotion.

Adolescent↗
PubMed1992

Radiation resistance in a doxorubicin-resistant human fibrosarcoma cell line.

In clinical practice, cancers refractory to chemotherapy can appear relatively radioresistant. Recent work in multidrug-resistant cell lines has yielded conflicting results concerning the relationship between drug resistance and radiation resistance. The current study examines the radiation response of a human fibrosarcoma (HT1080) and a doxorubicin-resistant subline (HT1080/DR4). Using soft-agar colony formation after graded doses of x-rays as an endpoint, HT1080/DR4 had an increased D0 (D0 = 2.1 Gy) and a broader initial shoulder (n = 2.7, Dq = 2.1 Gy) than the parental HT1080 line (D0 = 0.7, Gy, n = 1.2, Dq = 0.3 Gy), suggesting that HT1080/DR4 has an increased capacity to repair radiation-induced DNA damage. This possibility was tested by comparing the cell lines' ability to accumulate sublethal damage. In split-dose recovery experiments, HT1080/DR4 demonstrated increased ability to repair sublethal radiation damage following fractionated irradiation, compared with the HT1080 parental line. The mechanism for this radiation resistance is not clear, but a variety of cellular alterations seen in drug-resistant cell lines are discussed with reference to areas of further study.

Cell Cycle↗
PubMed1992

Broad cross-reactivity with marked fine specificity in the cytotoxic T cell response to flaviviruses.

Cytotoxic T (Tc) cells were generated in mice of five H-2 haplotypes against the flaviviruses Kunjin and West Nile (WNV). A panel of recombinant vaccinia viruses which between them expressed cDNA of the entire Kunjin virus genome were used to infect targets. Anti-Kunjin virus responses to determinants derived from non-structural proteins, especially NS3, NS4A and NS4B, were dominant in most mouse strains; usually only one class I major histocompatibility complex (MHC) restriction element was involved. WNV-immune Tc cells showed similar but not identical patterns of antigen recognition to Kunjin virus-immune Tc cells. The extent to which WNV-immune Tc cells recognized Kunjin virus-encoded determinants varied considerably between mice of different MHC haplotypes.

Animals↗
PubMed1992

Peritonitis.

Intraperitoneal infections or inflammatory disease in elderly patients are a diagnostic challenge that will be encountered with increasing frequency in the aging population of the United States. Diagnostic clues are not overt and frequently appear late in the course of the disease. Confusion and subtle changes in clinical status are important signals. A high index of suspicion is required to initiate diagnostic procedures. Therapy will frequently be modified not only to the disease process but also to the patient to incorporate concepts of minimally invasive procedures. The advent of laparoscopic surgery may be a great advance in the diagnosis and treatment of intra-abdominal crisis in geriatric patients. It also may make elective surgery conform more to the goals of the geriatric patient and thus prevent the high morbidity and mortality associated with emergency surgery in this age group.

Aged↗
PubMed1992

Effects of v-src oncogene activation on radiation sensitivity in drug-sensitive and in multidrug-resistant rat fibroblasts.

Recent work has implicated the activated ras oncogene, whose gene product is a G-protein located in the plasma membrane, as well as the activated raf oncogene, whose gene product is a membrane-associated protein kinase, in contributing to radioresistance. Another transforming oncogene whose gene product is localized to the plasma membrane is v-src. We have examined a rat fibroblast line (RAT-1) infected with an avian sarcoma virus carrying a temperature-sensitive mutation in the v-src tyrosine kinase domain (LA-24). At 40 degrees C, LA-24 cells have a flat morphology and grow as a contact-inhibited monolayer, while at 35 degrees C, LA-24 cells have a transformed morphology, lose contact inhibition, grow in soft agar, and exhibit 3.5-fold higher tyrosine kinase activity. The parental RAT-1 line, not infected by the virus, grows at both temperatures as a contact-inhibited monolayer. This well-characterized system represents a good model for examining the effect of v-src transformation on radiosensitivity. RAT-1 and LA-24 cells grown at 35 and 40 degrees C were irradiated with graded doses of radiation, and clonogenic survival was assayed. For LA-24 cells grown at 35 and 40 degrees C, and for RAT-1 cells grown at 35 and 40 degrees C, calculated D0, n, alpha, and beta values did not differ significantly. To determine whether there might be differences in radiation damage repair capacity too subtle to detect by comparing radiation survival curves, sublethal damage repair capacity was assessed. There was no difference in sublethal damage repair capacity for LA-24 cells grown at 35 or 40 degrees C. Other studies have associated multidrug resistance with radioresistance. We have examined the radiation sensitivity of two colchicine-resistant LA-24 clones with four- to fivefold amplification of the P-glycoprotein gene, which are four-to fivefold more resistant to colchicine than the parental LA-24 line. In these multidrug-resistant clones, v-src activation does appear to increase radiation resistance. This did not appear to be due to alteration in cell cycle kinetics. We conclude that oncogene activation, or even protein kinase activity per se, does not necessarily lead to radiation resistance. Rather, radiation resistance following oncogene activation depends upon the oncogene and cell line studied, and perhaps upon specific protein phosphorylation.

Animals↗
PubMed1991

Alloreactive cytotoxic T cells recognize MHC class I antigen without peptide specificity.

In this report, experiments are described to differentiate between three potential models of class I MHC allorecognition, namely 1) recognition of peptide-free MHC, 2) peptide-MHC-specific recognition, and 3) peptide-MHC-nonspecific recognition. Using a nucleoprotein peptide (NPP) with a sequence derived from influenza virus nucleoprotein with high affinity for Kd class I MHC molecules, it is shown that target cells rapidly become lysable by Kd-NPP self-restricted cytotoxic T (Tc) cells, and retain sufficient Kd-NPP complexes for at least 72 h. Kd-specific alloreactive Tc cells at the clonal and polyclonal level do not show decreased lysis of Kd-bearing targets in the continuous long term (48 h) presence of NPP. Kd-stimulator cells modified with NPP are able to induce potent Kd-NPP-specific self-restricted Tc cells, however Kd-NPP stimulator cells do not generate Kd-NPP specific alloreactive Tc cells from CBA and B10.A (5R) mouse strains as tested by limiting dilution split clone experiments. Human cells infected with the vaccinia virus recombinant coding for the murine Kd class I MHC Ag can be lysed by murine Kd-specific alloreactive Tc cells. In addition the rate of reemergence of alloreactive and self-restricted Tc cell epitopes on virally infected target cells that had their cell-surface class I MHC Ag removed is identical. These results are consistent with model 3 namely that the majority of Tc precursor and effector cells recognize class I MHC Ag without peptide specificity.

Animals↗
PubMed1991

Chest trauma in a Canadian urban setting--implications for trauma research in Canada.

The trauma registry at the Montreal General Hospital was reviewed to provide basic epidemiologic data on chest trauma in Canada and to compare these data with the minimal data available in the literature. Chest trauma in multiply injured patients resulted in higher Injury Severity Scores (ISSs) than the average. This was reflected in higher mortality for patients with chest trauma. The majority of injuries were caused by blunt trauma. Less than 9% of patients admitted to the hospital required thoracotomy for thoracic vascular and cardiac trauma. Outcome (measured by mortality) was better than that predicted from the literature based on admission ISS. The etiology of trauma in this Canadian setting and the resulting injury profiles were substantially different from those obtained from the predominantly American epidemiologic data available in the literature. This suggests the need for gathering more Canadian population-based trauma data for the planning of trauma prevention and care in this country.

Adolescent↗
PubMed1991

Effects of melatonin on the cell cycle kinetics and "estrogen-rescue" of MCF-7 human breast cancer cells in culture.

Melatonin has been shown to have a direct inhibitory action on the proliferation of estrogen-responsive MCF-7 human breast cancer cells in culture. In the present study, we examined by flow cytometry whether this inhibitory effect might be exerted on the G1 phase of the cell cycle, thus causing a transition delay into the S phase. In order to further verify this hypothesis we tested the ability of estradiol to "rescue" MCF-7 cells from melatonin inhibition, and the potential of this indoleamine to block the ability of estradiol to rescue the cells from tamoxifen inhibition. Following five days of incubation, melatonin (10(-9)M) increased the fraction of cells in G1 of the cell cycle while simultaneously causing a 50% reduction in the proportion of cells in S phase. The antiproliferative effect of melatonin (10(-5)M) was prevented by the simultaneous treatment of the cells with estradiol (10(-8)M) in clonogenic soft agar culture, or reversed by the addition of estradiol to cells previously incubated with and inhibited by melatonin (10(-9)M) in monolayer culture. Additionally, melatonin blocked the estrogen-rescue of tamoxifen-inhibited cells in both types of culture systems. These results support the hypothesis that the antiproliferative effect of melatonin, like tamoxifen, is cell cycle specific by causing a G1-S transition delay. These results also indicate an important interaction of melatonin with estrogen-mediated mechanisms of MCF-7 cell proliferation.

Cell Cycle↗
PubMed1989

Dynamic cardiomyoplasty for treatment of heart failure.

Dynamic cardiomyoplasty is a new surgical procedure proposed for treatment of the failing heart. Clinically, the latissimus dorsi muscle is raised as a pedicled flap and wrapped around the heart. The skeletal muscle is transformed to produce a myocardium-like fatigue-resistant muscle. It is stimulated to contract in synchrony with the heart in hope of assisting the myocardial contraction. An R-wave synchronous pacemaker provides a pulse-train form of stimulation to simulate, for the skeletal muscle, the contractile characteristics of the myocardial syncytium. We have undertaken a critical review of the clinical results of dynamic cardiomyoplasty reported to date. Objective evidence of clinical improvement after dynamic cardiomyoplasty resulting from the contractile assistance of the myoplasty has been modest. Many of the beneficial results reported could be explained by concomitant procedures done, such as aneurysmectomy or coronary artery bypass grafting. Hemodynamic studies have failed to demonstrate consistent and convincing improvement as a result of the cardiomyoplasty stimulation. We have, however, identified an interesting subgroup of patients, in whom a striking hemodynamic response to cardiomyoplasty stimulation has been reported. These patients all possess large resting heart volumes characteristic of dilated cardiomyopathy. Thus, case selection may ultimately be one of the most important factors in determining the success of dynamic cardiomyoplasty for the treatment of heart failure.

Back↗
PubMed1988

Cytogenetic and molecular characterization of tumors in nude mice derived from a multidrug-resistant human leukemia cell line.

We have evaluated whether selection of a human tumor leukemic line for resistance to vinblastine (Velban; VLB) alters its tumorigenicity. To address this question, CEM and CEM/VLB100 cells [which express the multiple drug-resistant (MDR) phenotype via amplification of the P-glycoprotein gene] were characterized by several techniques including chromosome banding, in situ hybridization, Southern blotting, RNA dot blotting, in vitro drug sensitivity, and tumorigenicity in nude mice. Analysis of the chromosome banding patterns of both drug-sensitive CEM cells and the MDR CEM/VLB100 cells revealed that the two lines differed primarily by the presence of a large metacentric marker chromosome associated with the acquisition of VLB resistance. In situ hybridization of a P-glycoprotein complementary DNA to metaphase chromosomes showed that the amplified P-glycoprotein genes in the CEM/VLB100 cell line were localized to this large marker. Tumorigenicity of both the CEM and CEM/VLB100 cell lines was measured after injection of 10(7) cells/nude mouse. The results showed that 4 of 4 drug-sensitive and 4 of 5 drug-resistant cell lines formed tumors in 5-10 wk. By comparison with the parental line, three of the four tumors arising from the CEM/VLB100 line retained their drug-resistance properties as measured by vinblastine resistance in vitro and elevated P-glycoprotein mRNA expression associated with P-glycoprotein gene amplification. In addition, tumors retaining the MDR phenotype also retained the large metacentric marker chromosome. One tumor arising from CEM/VLB100 reverted to the drug-sensitive phenotype, with a resultant decrease in P-glycoprotein mRNA expression and loss of P-glycoprotein gene amplification. This revertant was also missing the large metacentric marker present in all cells from the CEM/VLB100 parent. Our experiments show that the acquisition of the MDR phenotype resulting from overexpression of P-glycoprotein in the plasma membrane does not effect the tumorigenicity of human CEM cells.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1988

Radiation resistance in a multidrug resistant human T-cell leukemia line.

In clinical practice, cancers refractory to chemotherapy commonly appear to be comparatively radioresistant. One mechanism by which cancer cells become resistant to chemotherapy is pleiotropic multidrug resistance, characterized by cross resistance to a number of otherwise unrelated heterocyclic antineoplastic agents, including vinca alkaloids, anthracyclines, dactinomycin, and others. We have studied a drug sensitive human leukemia cell line, CEM; a pleiotropic multidrug resistant subline of CEM, CEM/VLB100; VLB-1, a drug sensitive revertant subline arising during in vivo passage of CEM/VLB100; and a methotrexate resistant subline of CEM, CEM-MTX. Using soft-agar colony formation after graded doses of X rays as an endpoint, we found that CEM, CEM-MTX, and CEM/VLB100 had similar terminal slopes (D0 = 0.66 Gy). However, the CEM/VLB100 survival curve had a broader initial shoulder (n = 3.0, Dq = 0.75 Gy) than did CEM (n = 1.6, Dq = 0.25 Gy) or CEM/MTX (n = 1.0, Dq = 0 Gy), suggesting that CEM/VLB100 has an increased capacity to repair radiation-induced DNA damage. This was tested by comparing the cell lines' abilities to accumulate sublethal damage. In split dose recovery experiments, CEM/VLB100 demonstrated increased ability to repair sublethal radiation damage following fractionated irradiation compared with the CEM parental line. Although it no longer demonstrated multidrug resistance, VLB-1 still displayed diminished radiation sensitivity. On the basis of these and other investigators' results, we suggest that diminished radiation sensitivity is separate from, but can be closely associated with, the multidrug-resistant phenotype.

Antineoplastic Agents↗
PubMed1987

Anxiety responses to subliminal experience of mild stress.

Two groups of undergraduates (n = 14 in each) matched for level of trait anxiety participated in the experiment. One group (E) was presented with 20 'emotional' words 10 per cent below detection threshold while the other group (N) was presented with 20 emotionally neutral words under the same conditions. Ratings of seven psychological variables were taken before and after stimulation and two psychophysiological measures, heart and respiration rate, were also taken. MANOVA and subsequent ANOVA analyses showed ratings of sweating and anxiety increased in the E group and decreased in the N group following stimulation. Ratings of shaking and muscular tension increased significantly in both groups but the increase was significantly greater in the E group. Ratings of palpitations and difficulty in breathing increased significantly in both groups as did measures of actual heart and respiration rate, but these increases appeared to be an artifact of task demands. It is concluded that manifest anxiety and some features of anxiety having somatic referents can be induced by subliminal experience of mild stress.

Adolescent↗