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Biomedical subjects

B A Miller

Publications and source records attributed to B A Miller.

At least 127 records · Page 7Linked to original sources
PubMed1987

Alcohol use by violent and property offenders.

Offenders incarcerated for violent and property crimes were compared with respect to their alcohol and drug use, both chronic and immediately before their crime. There were only slight differences between the groups. The proportions of violent offenders who drank before the crime were greater than the proportion of property offenders, but this was not true for offenders with low education. The disinhibition theory of alcohol involvement in violent crime was not supported.

Adult↗
PubMed1987

Activation of abundant precursors associated with the response of Mlsa H-2k spleens to Mlsc antigen.

We have determined the frequency of splenic interleukin 2-producing T-cell precursors that respond to H-2-identical, Mls-disparate stimulating cells. Gene products of the Mlsa and Mlsd alleles are highly stimulatory in primary mixed lymphocyte reactions and activate substantial numbers of T-cell precursors in normal spleens. Although the product of the Mlsc allele has been described as weakly stimulatory in primary mixed lymphocyte reactions, we detected abundant T-cell precursors responsive to Mlsc under our limiting dilution conditions; H-2k Mlsa T-cell precursors responding to Mlsc were as frequent (2.605 per 1000) as H-2k Mlsb or Mlsc T-cells responsive to Mlsd (1.975 per 1000). In contrast, using the frequency of self-responding cells as a threshold, we were unable to detect precursors for Mlsa, Mlsb, Mlsc, or Mlsd in H-2b mice, for Mlsb in H-2k mice, or for Mlsc in H-2k Mlsb or Mlsd mice. Thus, we conclude that in select strain combinations and under our experimental conditions Mlsc stimulators can activate T-cell precursors that are as abundant as precursors reactive to strong stimulators Mlsa and Mlsd.

Alleles↗
PubMed1987

Gamma-interferon alters globin gene expression in neonatal and adult erythroid cells.

Interferons have the ability to enhance or diminish the expression of specific genes and have been shown to affect the proliferation of certain cells. Here, the effect of gamma-interferon on fetal hemoglobin synthesis by purified cord blood, fetal liver, and adult bone marrow erythroid progenitors was studied with a radioligand assay to measure hemoglobin production by BFU-E-derived erythroblasts. Coculture with recombinant gamma-interferon resulted in a significant and dose-dependent decrease in fetal hemoglobin production by neonatal and adult, but not fetal, BFU-E-derived erythroblasts. Accumulation of fetal hemoglobin by cord blood BFU-E-derived erythroblasts decreased up to 38.1% of control cultures (erythropoietin only). Synthesis of both G gamma/A gamma globin was decreased, since the G gamma/A gamma ratio was unchanged. Picograms fetal hemoglobin per cell was decreased by gamma-interferon addition, but picograms total hemoglobin was unchanged, demonstrating that a reciprocal increase in beta-globin production occurred in cultures treated with gamma-interferon. No toxic effect of gamma-interferon on colony growth was noted. The addition of gamma-interferon to cultures resulted in a decrease in the percentage of HbF produced by adult BFU-E-derived cells to 45.6% of control. Fetal hemoglobin production by cord blood, fetal liver, and adult bone marrow erythroid progenitors, was not significantly affected by the addition of recombinant GM-CSF, recombinant interleukin 1 (IL-1), recombinant IL-2, or recombinant alpha-interferon. Although fetal progenitor cells appear unable to alter their fetal hemoglobin program in response to any of the growth factors added here, the interaction of neonatal and adult erythroid progenitors with gamma-interferon results in an altered expression of globin genes. This supports the concept that developmental globin gene switching can be regulated by environmental factors.

Erythrocytes↗
PubMed1987

Analysis of hemoglobin F production in Saudi Arabian families with sickle cell anemia.

Erythrocytes and progenitor-derived erythroblasts of sickle cell anemia patients from the Eastern Province of Saudi Arabia contain increased fetal hemoglobin and G gamma globin. A distinctive DNA polymorphism haplotype in the beta globin gene cluster (++- +-), tightly coupled to a C----T substitution at position -158 5' to the cap site of the G gamma globin gene, is strongly associated with sickle cell disease in this region. To determine whether the increased fetal hemoglobin production and/or elevated G gamma globin content are tightly linked to this haplotype, we studied 55 members of five Saudi families in which sickle cell disease is present. The results did not suggest a tight linkage of the haplotype to increased fetal hemoglobin production. On the other hand, several sickle trait family members heterozygous for the haplotype had normal fetal hemoglobin production in culture but elevated G gamma to A gamma ratios in peripheral blood. This observation suggests that in this genetic background increased expression of the G gamma globin gene may occur without a measurable increase in total fetal hemoglobin production. The family studies also clearly demonstrate that increased fetal hemoglobin production by erythroid progenitors is dependent on zygosity for the sickle gene in this population. These findings strongly suggest that other factors, such as the products of genes stimulated by hemolytic stress or other genetic determinants associated with the Saudi beta S chromosome, may interact with the -158 C----T substitution and influence gamma globin gene expression in this population.

Anemia, Sickle Cell↗
PubMed1987

Influence of hydroxyurea on fetal hemoglobin production in vitro.

Cytotoxic drugs increase circulating fetal hemoglobin levels. We examined the mechanism by measuring the fetal hemoglobin produced per BFU-E-derived erythroblast following hydroxyurea treatment in vivo and in vitro. Treatment of four sickle cell patients increased the percentage of circulating F reticulocytes. The frequencies of bone marrow or peripheral blood BFU-E or CFU-E-derived colonies and their fetal hemoglobin content were unaffected. In all cases, the number of erythroid cells/progenitor-derived colony increased. To explore further the effect of hydroxyurea on fetal hemoglobin production, we added 50 mumol/L hydroxyurea to cultures of peripheral blood BFU-E-derived erythroblasts on 1 of 9 days (day 5 through 13) to nine samples. These BFU-E were derived from the peripheral blood of normal donors, sickle trait donors, and sickle cell anemia patients and from the bone marrows of monkeys. This concentration of hydroxyurea was selected so that the frequency of BFU-E and their size was moderately decreased. Addition of hydroxyurea to these progenitor-derived erythroid cells had no effect on fetal hemoglobin content per cell. Neither did transient exposure of progenitors to hydroxyurea prior to culture in nontoxic concentrations (0 to 500 mumol/L) result in a significant increase in fetal hemoglobin content in progenitor-derived erythroblasts. These data suggest that hydroxyurea does not directly alter the HbF program expressed by progenitor-derived erythroid cells. Instead, it enhances hemoglobin F content secondarily, possibly by inducing alterations in erythropoiesis.

Anemia, Sickle Cell↗
PubMed1987

The role of childhood sexual abuse in the development of alcoholism in women.

The effects of childhood sexual abuse on the development of alcoholism in women were examined by comparing a sample of 45 alcoholic women selected from local treatment agencies and Alcoholics Anonymous groups with a group of 40 nonalcoholic women selected randomly from a household population. Face-to-face interview schedules were administered to both samples. Sexual abuse was defined as any unwanted sexual contact with a person at least five years older than the respondent, or with any family relative, regardless of age difference. Types of sexual contact included both nonphysical contact (e.g., invitations, exposure) and physical contact (e.g., fondling, intercourse). Results showed that alcoholic women were more likely to have experienced sexual abuse, had a greater number of different types of sexual abuse experiences, and endured sexual abuse over a longer period than the comparison group. The presence of any childhood sexual abuse experience was sufficient to discriminate between the alcoholic women and the comparison group, even controlling for demographic variables and the presence of a parent with alcohol-related problems. Although alcoholic women were more likely to report that a parent had alcohol-related problems, relatively few of the sexual abuse incidents were perpetrated by a parent. The data suggest that vulnerabilities to sexual abuse were attributable to environmental or psychological factors in homes in which a parent was reported as having alcohol-related problems.

Adolescent↗
PubMed1987

Childhood experiences of parental physical violence for alcoholic women as compared with a randomly selected household sample of women.

The effects of childhood experiences of parental violence on the development of alcoholism in women were examined by comparing a sample of 45 alcoholic women selected from local treatment agencies and Alcoholics Anonymous groups with 40 nonalcoholic women selected randomly from the population. Two-hour person-to-person interview schedules were administered to both samples. The Conflict Tactics Scale (CTS) assessed both father-to-daughter and mother-to-daughter relationships. Type of sample was regressed on each CTS subscale, controlling for presence of parental alcoholism, number of childhood changes in family structure, present age of respondent, and present income source. Alcoholic women were found to have higher father-to-daughter negative verbal interaction, moderate violence, and serious violence than household women. Father-to-daughter positive verbal interaction was found unrelated to membership in the alcoholism sample. None of the mother-to-daughter subscales were found to predict membership in the alcoholism sample.

Adult↗
PubMed1986

Cancer risk among artistic painters.

An association between bladder cancer and employment as an artistic painter was found in two study populations. A proportionate mortality analysis of death certificates of professional artists indicated a greater than twofold excess for bladder cancer mortality among painters. This association was further investigated in a large case-control interview study of bladder cancer patients where an overall relative risk estimate of 2.5 was found among artistic painters. Excess deaths from leukemia and arteriosclerotic heart disease also occurred in the proportionate mortality study. Information was not available to determine exposure to specific substances that may have been responsible for these observations; however, efforts should be made to limit exposure to art materials known to be hazardous.

Art↗
PubMed1986

Alcoholism diagnoses for convicted drinking drivers referred for alcoholism evaluation.

The types and extent of alcohol-related problems were determined for a sample of 461 convicted drinking drivers who were referred to an alcoholism treatment facility for evaluation and possible treatment. Using responses to questionnaire and structured interview questions on alcohol-related problems, DSM III diagnoses are constructed; approximately three-quarters of the sample are diagnosed with sufficient severity for a DSM III diagnosis of abuse or dependence. Self-reported consumption levels and drinking/driving incidents increase as the level of the alcohol problem increases; persons in the Alcohol Abuse category are heavier consumers and drive more frequently after drinking than are persons who are not diagnosed by the DSM III as having an alcohol problem. Persons in the Alcohol Dependence category are heavier consumers than either the Alcohol Abuse or Undiagnosed Problem categories and report more drinking/driving incidents. The DSM III provides useful subcategories of convicted drinking drivers referred for alcoholism evaluation and distinguishes groups differing in quality, frequency, and self-reported DWI measures, independent of basic demographics. These analyses suggest that drinking/driving countermeasures should include intervention efforts to address alcohol-related problems. Serious alcohol problems exist among some drinking drivers, and drinking/driving incidents are more frequent among these individuals.

Adult↗
PubMed1986

High fetal hemoglobin production in sickle cell anemia in the eastern province of Saudi Arabia is genetically determined.

Homozygous sickle cell disease in the eastern province of Saudi Arabia is clinically mild. Circulating fetal hemoglobin levels of 16.0 +/- 7.4% were found in these anemic patients, but only 1.09 +/- 0.97% in their sickle trait parents. To determine whether these sickle cell anemia patients inherit an increased capacity to synthesize fetal hemoglobin, a radioimmunoassay of fetal and adult hemoglobin was performed on erythroid progenitor (BFU-E)-derived erythroblasts from Saudi Arabian sickle cell patients and their parents. Mean fetal hemoglobin content per BFU-E-derived erythroblast from Saudi Arabian sickle cell patients was 6.2 +/- 2.4 pg/cell or 30.4 +/- 8.6% fetal hemoglobin (normal 1.1 +/- 0.7 pg/cell and 5.1 +/- 1.8%). Linear regression analysis of % HbF in peripheral blood versus % HbF per BFU-E-derived cell showed a positive correlation with an r of 0.65. The variance of the intrinsic capacity to produce HbF may account for almost 40% (r2) of the variance of circulating fetal hemoglobin but other factors, particularly selective survival of F cells, must also contribute significantly. Despite virtually normal HbF levels in sickle trait parents of these Saudi patients, mean fetal hemoglobin production per BFU-E-derived erythroblast in these individuals was elevated to 3.42 +/- 1.79 pg/cell or 16.1 +/- 6.4% fetal hemoglobin, and the magnitude of fetal hemoglobin production found in parents correlated with that of the patients. These data indicate that the high fetal hemoglobin in Saudi sickle cell disease is genetically determined but expressed only during accelerated erythropoiesis. Further evidence of such genetic determination was provided by analysis of DNA polymorphisms within the beta-globin gene cluster on chromosome 11. This revealed a distinctive 5' globin haplotype (+ + - + +) on at least one chromosome 11 in all high F SS and AS tested. The precise relationship of this haplotype to HbF production in this population remains to be defined.

Anemia, Sickle Cell↗
PubMed1985

Thy-1 is a differentiation antigen that characterizes immature murine erythroid and myeloid hematopoietic progenitors.

To determine the role of Thy-1 antigen in murine hematopoietic differentiation, bone marrow was treated with anti-Thy-1.2 antibody and complement or complement alone. Growth of immature hematopoietic progenitors, erythroid burst-forming units (BFU-E), and granulocyte/macrophage colony-forming units (CFU-GM) was greatly reduced following antibody and complement treatment and was not restored by mitogen-stimulated spleen cell supernatants. In contrast, more mature erythroid and myeloid progenitors, the erythroid colony-forming unit (CFU-E) and the macrophage progenitor stimulated by L-cell-conditioned media (LCM), were spared by anti-Thy-1.2 antibody and complement treatment. Here, to separate the effects of anti-Thy-1.2 antibody treatment on accessory cells from those on progenitors, splenic T cells and thymocytes were added to treated marrow at ratios of up to 200%. Growth of BFU-E and CFU-GM was not restored. To more precisely replace required accessory cells, male complement-treated marrow was cocultured with female anti-Thy-1.2 antibody and complement-treated marrow. Even marrow cells failed to restore female BFU-E and CFU-GM growth. Fluorescent-activated cell sorting (FACS) and immune sheep red cell rosetting with anti-Thy-1.2-labeled marrow were then performed to determine if immature hematopoietic progenitors bear Thy-1.2. These techniques revealed enrichment of BFU-E and CFU-GM in the Thy-1.2-positive fraction, demonstrating the presence of Thy-1.2 on early murine hematopoietic progenitors. CFU-E and CFU-M were present in the Thy-1.2-negative fraction following FACS separation. These data demonstrate that Thy-1.2 is a differentiation antigen, present on at least some murine BFU-E and CFU-GM and lost as they mature to CFU-E and CFU-M.

Animals↗
PubMed1985

Sequential development of distinct clonal chromosome abnormalities in a patient with preleukaemia.

Preleukaemia has been identified as a clonal haemopathy in which progression to acute leukaemia involves conservation of the preleukaemic karyotype in the blast cells or the development of new abnormalities superimposed on the original clone. In this report, a case of childhood preleukaemia is presented in which two cytogenetically distinct clones developed over 2 years in a dysplastic marrow that was initially karyotypically normal. One clone with 47 chromosomes (47,XY,+21), disappeared without therapy. Predominance of the cytogenetically abnormal clone, 45,XY,-12,-17,t(12;17)(p11;q11) was associated with the development of acute myelogenous leukaemia and myelofibrosis. The development of independent clonal abnormalities in the unstable preleukaemic marrow may occur more commonly than has been previously recognized. Implications of the progression of the karyotypic abnormalities are discussed.

Antigens, Neoplasm↗
PubMed1985

Effect of glucagon on hepatic taurocholate uptake: relationship to membrane potential.

Since glucagon can hyperpolarize hepatic plasma membrane and stimulate biliary bile acid secretion in vitro, we studied the effect of glucagon on taurocholate uptake and its relationship to plasma membrane potential in isolated rat hepatocytes. [14C]taurocholate uptake was linear through 1 min and contained a saturable sodium-dependent and a nonsaturable sodium-independent component. Km of taurocholate uptake by the sodium-dependent system was 18.4 microM. Hill coefficient for Na+ was 2.59 and for taurocholate was 1.1, suggesting that the stoichiometry is 2 Na+:1 bile acid. Stimulation of taurocholate uptake by glucagon was limited to the sodium-dependent component, detected within 5 min of hormone exposure, and was maximum at 30 min. Glucagon, from 10(-8) to 10(-5) M, stimulated taurocholate uptake and hyperpolarized concurrently the plasma membrane potential. Because valinomycin produced a dose-related depolarization of plasma membrane potential, this agent was used to counteract the effects of glucagon. With 10(-6) M glucagon, valinomycin (10(-10) M) depolarized membrane potential from -35.50 to -28.00 mV and inhibited taurocholate uptake from 60% above the control rate to 5% below. These data strongly suggest that taurocholate uptake by isolated hepatocytes is an electrogenic process, and its stimulation by glucagon may be mediated by changes in plasma membrane potential.

Animals↗
PubMed1985

Influence of cell cycle phase-specific agents on simian fetal hemoglobin synthesis.

To determine the influence of cell cycle-specific agents on primate hematopoiesis and fetal hemoglobin production, two juvenile cynomolgus monkeys (Macaca fascicularis) were repeatedly bled to maintain their hemoglobins at approximately 6.5 g/dl and fetal hemoglobin levels at 3-5%. Six separate 5-d courses of hydroxyurea at 100 mg/kg per d were then administered over the next 200 d while phlebotomy was continued. These courses of hydroxyurea progressively raised the fetal hemoglobin levels to 17 and 18%, respectively. The drug had very little effect on the frequency of immature erythroid progenitors (BFU-E) in the bone marrow, but caused a marked reduction in the frequency of later progenitors (CFU-E) and a transient fall in the reticulocyte count. Following the courses of hydroxyurea, the number of F cells and the fetal hemoglobin level fell to base line over a period of 4 wk. Two control animals which were not phlebotomized showed no detectable increase in F cells or fetal hemoglobin when treated with the same regimen of hydroxyurea. A 5-d course of 5-azacytidine at 8 mg/kg per d was then given to each of the phlebotomized animals. This produced a more profound, albeit transient, reticulocytopenia, a fall in the CFU-E/BFU-E ratio, and a prompt increase in the fetal hemoglobin to levels even higher than were seen following a single 5-d course of hydroxyurea at 100 mg/kg/d. Subsequently, the animals were given a single dose of vinblastine at 0.4 mg/kg which reduced reticulocytes and CFU-E to the same extent as hydroxyurea; however, vinblastine at this dose had no effect on hemoglobin F (HbF) production. In contrast, when vinblastine was administered to the phlebotomized monkeys as a 5-d course at 0.2 mg/kg/d, prolonged reticulocytopenia followed by dramatic F cell and HbF responses were seen. Combinations of single dose vinblastine and a 5-d course of hydroxyurea were subsequently administered using two different schedules. When the animals received vinblastine on the first day of a 5-d course of hydroxyurea, the F cell response was double that seen following hydroxyurea treatment alone. In contrast, when vinblastine was administered on the final day of hydroxyurea treatment, the magnitude of the F cell response was the same as that which occurred following hydroxyurea treatment alone, but the onset of the rise was delayed for 4 d and HbF/F cell response was much higher. These results establish several important features of the fetal hemoglobin response to cytotoxic agents in the primate model. The response requires accelerated erythropoiesis and is preceded by transient reticulocytopenia. The response is produced by S phase- and M phase-specific agents when given in sufficient doses and at appropriate schedules. Passage of erythrocyte progenitors through M phase appears to be necessary for expression of the effect produced by S phase agents. The fetal hemoglobin response induced by cytotoxic drug administration occurs during the recovery of erythropoiesis following marrow suppression.

Animals↗
PubMed1985

Identification of cell surface antigens present on murine hematopoietic stem cells.

Nine antigens found on murine bone marrow cells were examined to define their pattern of expression in murine hematopoietic differentiation. Lymphocyte function antigen (LFA-1), heat stable antigen (recognized by M1/69), common leukocyte antigen (CLA, T200, Ly-5) and Lgp100a (recognized by 30-C7) were present on early hematopoietic progenitors, BFU-E, CFU-E, CFU-GM, and CFU-M. All antigens found on progenitors were found on some immature precursor cells, myeloblasts, erythroblasts, or monoblasts, but their pattern of expression on identifiable hematopoietic cells varied. Three of these antigens, LFA-1, heat stable antigen recognized by M1/69, and CLA, were expressed on leukocytes of all stages of maturity but were lost from the erythroid lineage during differentiation. MAC-1, Forssman antigen, heat stable antigen (recognized by M1/75), anti-P-95 (recognized by M5/113), and Ia (recognized by M5/114) were found only on differentiated hematopoietic precursors or mature cells. The expression of these antigens was more lineage-specific. MAC-1 and heat stable antigen (recognized by M1/75) were restricted to either mature myeloid or erythroid cells, respectively. The marked differences in distribution of these antigens suggest that they may be useful in negative or positive selection experiments to enrich progenitors, and that some of them may have a functional role in differentiation.

Animals↗
PubMed1984

T-cell acute lymphoblastic leukaemia with late developing Philadelphia chromosome.

A case of childhood T-cell acute lymphoblastic leukaemia (ALL) is presented in which the only chromosome abnormality at diagnosis was a deletion of part of the short arm of one chromosome 9 (9p-). Cytogenetic studies at relapse showed, in addition to 9p-, a partial deletion of the long arm of one chromosome 6 (6q-) and the Philadelphia chromosome (Ph1) produced as a result of the classical translocation t(9q+;22q-). All metaphases from haemopoietic colonies grown from a cryopreserved specimen of this patient's marrow at relapse were normal, in contrast to haemopoietic colonies cultured from patients with chronic myelogenous leukaemia (CML) which contained the Ph1. A hypothesis which incorporates T-cell ALL with late development of the Ph1 into the overall family of Ph1 positive diseases is suggested.

Bone Marrow↗