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Biomedical subjects

R Bell

Publications and source records attributed to R Bell.

At least 19 recordsLinked to original sources
PubMed1992

Inhibition of metastatic behavior of murine osteosarcoma by hypophysectomy.

BACKGROUND: We recently reported that human osteogenic sarcoma cells are mitogenically responsive in tissue culture to insulin-like growth factor I (IGF-I), a mitogen important in the regulation of cellular proliferation of many tissues, including bone. PURPOSE: The present study was designed to determine whether these in vitro observations could be extended to an in vivo experimental system and whether reduction of IGF-I levels by hypophysectomy could inhibit the aggressive metastatic behavior of osteosarcoma. METHODS: We used standard competitive binding and affinity-labeling techniques to characterize the IGF-I-binding sites of MGH-OGS, a model of human osteosarcoma. Radioimmunoassay of serum, preprocessed to remove IGF-binding proteins, was used to quantitate IGF-I levels. In vitro proliferative response of MGH-OGS cells to IGF-I and other pituitary-dependent factors was determined by thymidine-incorporation experiments. In vivo growth of the neoplasm in 12 hypophysectomized C3H mice and in 14 control C3H mice was determined by serial measurements of implanted tumors and by gross and microscopic examination of the lungs for metastases. RESULTS: MGH-OGS exhibited specific binding sites for 1.39 pmol IGF-I per milligram MGH-OGS cellular membrane protein, a concentration similar to that which we previously reported for human osteosarcoma. In tissue culture, MGH-OGS exhibited mitogenic response to IGF-I (P less than .01) but not to other pituitary-dependent factors. Hypophysectomy reduced levels of circulating IGF-I to 15% of control, significantly inhibited local growth of MGH-OGS tumors (increased time for growth to 1 cm3 from 49 to 84 days, P less than .001), and profoundly inhibited metastatic behavior (decrease in mean number of metastases per host from 16 to less than one; P less than .001). CONCLUSIONS: This study is the first to document the profound inhibitory effect of hypophysectomy on the metastatic behavior of an experimental sarcoma. We conclude that the metastatic behavior exhibited by MGH-OGS osteosarcoma is dependent on pituitary factors, and we suggest that the inhibitory effects of hypophysectomy are related, at least in part, to the reduction of IGF-I levels.

Animals↗
PubMed1992

Hippocampal NCAM180 transiently increases sialylation during the acquisition and consolidation of a passive avoidance response in the adult rat.

Synaptic connectivity change is a consistent anatomical feature of memory formation and the possibility that this is mediated by a replay of neurodevelopmental events has been investigated by measuring change in neural cell adhesion molecule sialylation state during the acquisition and consolidation of a passive avoidance response in the adult rat. The avoidance response was always generated after two to three trials and the animals remained on the platform for the criterion time of 5 min. In all cases training was complete within 5-8 min. Change in sialylation state was monitored following intraventricular infusion of the 3H-ManNAc precursor at 4 hr prior to the reference point. No task-specific change in general glycoconjugate sialylation was apparent in hippocampal P2 pellets at increasing times following training. Increased sialylation state was observed only in neural cell adhesion molecule (NCAM) immunoprecipitates of hippocampal membrane fractions at 12 and 24 hr after training. Change in hippocampal sialylation state could not be attributed to an increased accumulation of NCAM as detected by an immunoabsorbent assay. Immunoblotting of antibody precipitated NCAM demonstrated the 3H-ManNAc to be incorporated into the synapse-specific, 180 kDa isoform of NCAM and a novel 210 kDa isoform. Immunoprecipitation and immunoblotting procedures with an antibody specific for a2-8-polysialic acid showed the 180 and 210 kDa isoforms to be polysialylated. The role of NCAM180 sialylation as a mechanism for synapse selection in information storage is discussed.

Animals↗
PubMed1992

Intraventricular infusions of anti-neural cell adhesion molecules in a discrete posttraining period impair consolidation of a passive avoidance response in the rat.

Intraventricular infusions of anti-neural cell adhesion molecule (anti-NCAM) are demonstrated to inhibit consolidation of a passive avoidance response when administered in the 6-8 h posttraining period. Anti-NCAM was ineffective when administered during training or at any other time up to 10 h thereafter, and no amnesic effects were observed with absorbed anti-NCAM or anti-neurofilament protein. Amnesia was observed only at the 48-h recall time, and this could not be attributed to poor antibody penetration or a prolonged residence time, as studies with 125I-labelled anti-NCAM in trained animals demonstrated a rapid accumulation into all brain regions, and this was marked in the olfactory bulb and hippocampus, areas showing an inherent and paradigm-specific increase in NCAM sialylation state, respectively. The lack of an amnesic action at the 24-h recall time is attributed to anti-NCAM-impaired synapse structuring becoming apparent following the paradigm-specific increases in NCAM sialylation state.

Amnesia↗
PubMed1992

Low birthweight and socioeconomic status, Victoria 1982 to 1986.

The aim of this study was to evaluate the association between the incidence of low birthweight and socioeconomic status, in particular whether the relationship was different for very low birthweight (less than 1500 g) and moderately low birthweight (1500 to 2499 g). The study population was births from 1982 to 1986 to women resident in Victoria (300,704). Data on socioeconomic status were derived from an indicator developed by the Australian Bureau of Statistics from the 1981 census and applied to postcodes. Using the rates of very low birthweight and moderately low birthweight in the highest socioeconomic status decile as the reference value we found that the relative risk for very low birthweight was significantly raised in only the lowest socioeconomic status decile (relative risk = 1.29, 95% confidence interval (CI) 1.17 to 1.42). The relative risk for moderately low birthweight was increased in the two lowest deciles: 1.19 (CI 1.12 to 1.26) and 1.09 (CI 1.01 to 1.17) respectively. Women not married at the time of the birth had a higher rate of low birthweight and were more likely to live in the lower socioeconomic status postcode areas. The relationships between very low birthweight, moderately low birthweight and socioeconomic status were attenuated but still significant when this factor was taken into account. Differences in low birthweight by socioeconomic status decile were not apparent for nonsmoking women. The relationship between smoking and low birthweight was different in the two lowest socioeconomic status deciles: the relative risk of low birthweight in smokers was 2.60 (CI 1.73 to 3.91) compared with a relative risk of 1.64 (CI 1.33 to 2.03) in deciles 3 to 10.

Australia↗
PubMed1992

All-trans retinoic acid in the treatment of acute promyelocytic leukaemia.

All-trans-retinoic acid (ATRA) is known to induce differentiation of promyelocytes in vitro and also to induce remission of acute promyelocytic leukaemia in vivo. We treated 11 patients with poor prognosis acute promyelocytic leukaemia (APL) with ATRA and obtained seven complete and one partial remission. Remissions took one to three months to achieve and were associated with adverse effects including dry skin and bone pain. In eight patients the white cell count rose above 20 x 10(9)/L within the first ten days of retinoic acid treatment and this was associated with the development of pulmonary leukostasis in three patients which was fatal in one. Another two patients died of intracranial haemorrhage also within the first ten days. ATRA is a promising new agent in the induction therapy of this particular category of acute leukaemia.

Adult↗
PubMed1991

T-cell receptor V beta gene expression differs in tumor-infiltrating lymphocytes within primary and metastatic melanoma.

Expression of T-cell receptor (TCR) gene rearrangements in tumor-infiltrating lymphocytes (TILs) within primary and metastatic melanoma specimens was studied. In order to analyze TCR gene transcription in TILs within these tissues, we analyzed reverse transcribed complementary DNA from mRNA directly from tissues using the polymerase chain reaction. The polymerase chain reaction-amplified products were confirmed by dot or Southern blot hybridization with C alpha or C beta oligoprobes. First, we investigated the diversity of TCR V alpha and V beta gene usage in human malignant melanoma patients with multiple metastasis. We found in one patient, bearing multiple skin lesions, that the patterns of TCR V alpha and V beta repertoires in different sites of the skin (leg and chest wall) were almost the same. However, in another patient with skin and brain melanomas, different TCR repertoires were presented. Next, we examined the usage of murine TCR V beta genes in TILs within the primary and metastatic sites (liver, lung, and brain) of C57BL/6 mice bearing B16-F10 murine melanoma. The population of TILs in each primary and metastatic site expressed from one to four TCR V beta genes. In each metastatic site, the profile of TCR V beta gene expression was different. A different TCR V beta usage in TILs distributed within metastases of various organs may reflect differences in tumor antigenicity at these sites or may be due to differential homing patterns to these tumors.

Animals↗
PubMed1991

Observations on the effect of chimeric anti-CD4 monoclonal antibody in patients with mycosis fungoides.

Chimeric (murine/human) anti-CD4 monoclonal antibody was infused into seven patients with mycosis fungoides. Successive patients received doses of 10, 20, 40, and 80 mg of antibody twice a week for 3 consecutive weeks. All patients had some clinical improvement, but responses were of relatively short duration. Serum levels of chimeric antibody varied as a function of dose. At the 80-mg dose level, antibody was readily observed in biopsied skin lesions. Although there was coating by antibody of most CD4 positive cells in the blood, there was no significant depletion of CD4 positive cells. Low-level antibody responses against the mouse Ig variable region and human Ig allotypic constant region determinants were observed in several patients, but none were of clinical significance. All but two patients made primary antibody and T-cell proliferative responses to a simultaneously administered foreign protein test antigen. However, there was marked suppression of the mixed lymphocyte reaction. We conclude that at the dose levels studied, a chimeric anti-CD4 monoclonal antibody (1) had some clinical efficacy against mycosis fungoides; (2) was well tolerated; (3) had a low level of immunogenicity; (4) had immediate immunosuppressive effects; and (5) did not induce tolerance to a co-injected antigen.

Adult↗
PubMed1991

Diagnosing personality disorders in psychiatric inpatients.

This study investigated assumptions made by DSM-III and DSM-III-R regarding Axis I-Axis II associations and sex differences for the 11 personality disorders (PD). A total of 112 patients formed 4 Axis I diagnostic groups: recent-onset schizophrenia (n = 35); recent-onset mania (n = 26); unipolar affective disorder (n = 30); and a mixed diagnostic group (n = 21). The prevalence of PD was determined using the Structured Interview for DSM-III Personality Disorders (SIDP). Schizophrenia was associated with antisocial PD and schizotypal PD; manic disorder was associated with histrionic PD; and unipolar affective disorder was associated with borderline, dependent and avoidant PD. Some of these results were consistent with DSM-III/DSM-III-R postulates. However, there was little support for the DSM-III/DSM-III-R statements on sex differences in the prevalence of PD, except for antisocial PD. The implications of the results for DSM-III/DSM-III-R assumptions are discussed.

Adult↗
PubMed1991

Elevated intracranial pressure and computed tomography of the brain in fulminant hepatocellular failure.

Cerebral herniation is a leading cause of death in patients with fulminant hepatocellular failure. Classical signs of elevated intracranial pressure are often absent in these patients. A reliable noninvasive method by which the presence of cerebral edema could be determined is much needed. To assess the efficacy of computed tomography of the brain in this setting, we compared the radiographic findings to the intracranial pressure measured by an epidural monitor in patients with fulminant hepatic failure. Unfortunately, a considerable difference existed between the presence of cerebral edema diagnosed by computed tomography of the brain and elevation of the intracranial pressure. Our observations suggest that in patients with fulminant hepatic failure and advanced hepatic encephalopathy, computed tomography of the brain is of little value in detecting cerebral edema. Pressure monitoring is most important to establish the presence and guide the therapy of intracranial hypertension.

Brain↗
PubMed1991

Effect of different pump mechanisms on transfusion of blood.

Sometimes infusion pumps are used to deliver whole blood to patients. However, in doing so there is a potential for damage to red cells from mechanical stresses in the pump, resulting in haemolysis. In order to investigate the degree of haemolysis caused by different pumps and therefore their suitability for whole blood infusion, we compared the performances of commonly used volumetric pumps (AVI 400; IVAC 560; IVAC 631 and IMED 927) with different pumping mechanisms. Our results show that the maximum haemolysis (3.9 mg/100g) was caused by the IVAC 560 and the least (1.08 mg/100g) by the AVI 400.

Blood Transfusion↗
PubMed1990

A comparative trial of three agents in the treatment of acute migraine headache.

STUDY OBJECTIVES: A study was conducted to evaluate the relative efficacy of three non-narcotic agents, chloropromazine, lidocaine, and dihydroergotamine, in the treatment of migraine headache in an emergency department setting. DESIGN: The trial was randomized and single blinded. SETTING: The study was conducted in two university-affiliated EDs. TYPE OF PARTICIPANTS: All patients had an isolated diagnosis of common or classic migraine. INTERVENTIONS: Patients were pretreated with 500 mL (IV) normal saline before randomization. Study drugs as administered were dihydroergotamine 1 mg IV repeated after 30 minutes if the initial response was inadequate; lidocaine 50 mg IV at 20-minute intervals to a maximum total dose of 150 mg as required; or chloropromazine 12.5 mg IV repeated at 20-minute intervals to a total maximum dose of 37.5 mg as required. Patients were asked to grade headache severity on a ten-point scale before and one hour after the initiation of therapy. Follow-up by phone was sought the following day. MEASUREMENTS AND MAIN RESULTS: Of 76 patients completing the trial, 24 were randomized to receive chloropromazine, 26 to receive dihydroergotamine, and 26 to receive lidocaine. Reduction in mean headache intensity was significantly better among those treated with chloropromazine (P less than .005). Persistent headache relief was experienced by 16 of the chloropromazine-treated patients (88.9%) contacted at 12 to 24 hours follow-up compared with ten of the dihydroergotamine-treated patients (52.6%) and five of the lidocaine-treated group (29.4%). CONCLUSION: The relative effectiveness of these three antimigraine therapies appears to favor chloropromazine in measures of headache relief, incidence of headache rebound, and patient satisfaction with therapy.

Adult↗