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Biomedical subjects

B A Miller

Publications and source records attributed to B A Miller.

At least 109 records · Page 6Linked to original sources
PubMed1990

Aphakic visual fields by automated perimetry.

Accurate testing of the visual field of aphakic patients is demanding due to the optical distortion induced by high plus corrective lenses. This testing procedure can be improved by using an aspheric contact lens instead of a full-aperture loose trial lens. We found that the contact lens enhances the ability of the pattern-deviation printout of the Statpac analysis to identify glaucomatous visual field abnormalities in program 30-2 of the Humphrey Visual Field Analyzer.

Aged↗
PubMed1989

MB-02 cells undergo fetal to adult globin gene switching in response to erythropoietin.

The recently described MB-02 human cell line requires Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) for continuous growth and terminally differentiates into enucleate, hemoglobinized cells in response to erythropoietin. Here, analysis of globin production now demonstrates that uninduced MB-02 cells produce alpha globin and the fetal globin chains G gamma and A gamma in a ratio of 1:3. Addition of erythropoietin results in de novo synthesis of beta globin chains and a marked increase in total Hb/cell. Thus, the MB-02 cell line partially recapitulates the fetal to adult globin switch that occurs during erythroid and human fetal development and provides a new clonal human erythroid progenitor system for investigating the biochemical and molecular events involved in globin gene switching.

Cell Line↗
PubMed1989

Human papillomavirus infection and anal cancer.

To study the association of human papillomavirus (HPV) infection with anal cancer, we examined tissue specimens from 126 patients with malignant lesions of the anal skin or mucosa. The patients were enrolled in a population-based, case-control study of ano-rectal cancer which is being conducted in the state of Washington and the Province of British Columbia. Histologic sections from formalin-fixed, paraffin-embedded tissues were tested for the presence of HPV DNA by in situ hybridization with biotin-labelled HPV 6, 11, 16, 18 and 31 DNA probes. HPV DNA sequences were found in tumor tissues from 24 of the 126 subjects (19.0%). When only squamous neoplasms are considered, 23 of 70 subjects (32.9%) had lesions which contained detectable HPV DNA. One HPV-positive patient had a cloacogenic carcinoma that contained regions of squamous differentiation and it was in these squamous cells that HPV DNA was localized. Of the 23 squamous lesions that harbored detectable HPV DNA, 8 contained HPV 6, 10 contained HPV 16, 1 contained HPV 18 and 4 contained an unclassified virus type(s). HPV DNA was found in tissues from 14 patients with carcinoma-in situ and 10 subjects with invasive carcinoma. These results demonstrate that some malignant tumors of the anus, in both men and women, are associated with HPV infection. We conclude that the anal squamous epithelium is another site where infection with the common genital tract HPVs may carry a risk of malignant transformation.

Adenocarcinoma↗
PubMed1989

Augmentation of influenza antibody response in elderly men by thymosin alpha one. A double-blind placebo-controlled clinical study.

Influenza remains a major cause of illness and death in elderly people despite current vaccination programs. One factor is an immunization failure rate in the elderly that may be as high as 50%. To test whether administration of thymosin alpha 1 would result in greater antibody production, we administered it (900 micrograms/m2 subcutaneously twice weekly for eight doses) in conjunction with the 1986 trivalent influenza vaccine. Ninety men (65-99 years old, mean age 77.3 years) were randomized double-blind to receive thymosin alpha 1 or placebo by the same schedule; the sera from 85 of these men were acceptable for analysis. The two groups were similar with respect to underlying disease, medications, and age. No toxicity was observed in either group. Antibody response rate was defined as a four-fold rise in antibody titer over 3-6 weeks following vaccination and was measured by an enzyme-linked immunosorbent assay (ELISA). Analysis was performed on treatment groups and subgroups divided by the mean age: the older group consisted of subjects aged 77 years and older, and the younger group those aged from 65-76 years. Baseline and change in absolute antibody levels were compared by t test and using age as a continuous variable by multiple regression analysis.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1989

Cancer and other mortality patterns among United States furniture workers.

Cause specific mortality was investigated among 36,622 members of a national furniture workers' union who were first employed in unionised shops between 1946 and 1962. Overall mortality for each race and sex group was less than expected when compared with United States death rates (white men SMR = 0.8, black men SMR = 0.7, white women SMR = 0.8, black women SMR = 0.5); however, raised risks were observed among white men employed in specific types of furniture industries and followed up for 20 or more years after first employment. Lymphatic and haematopoietic cancers were significantly raised (SMR = 1.8) among wood furniture workers followed up for at least 20 years due to excess deaths from leukaemia (SMR = 2.0) and non-Hodgkin's lymphoma (SMR = 2.0). Mortality from acute myeloid leukaemia was particularly high in this group (SMR = 4.7) based on six observed cases. Metal furniture workers followed up for at least 20 years experienced a significant excess of all cancers combined (SMR = 1.6), with non-significant increases in cancers of the lung, stomach, and colorectum. This group also had non-significant excesses of liver cirrhosis, arteriosclerotic heart disease, and cerebrovascular disease. Nasal cancer was not found to be significantly raised in this cohort, though the average follow up period may not have been sufficient to detect an excess risk for this uncommon tumour.

Cause of Death↗
PubMed1989

Alcoholism and depressive symptomatology among convicted DWI men and women.

Interrelationships between DSM-III-based alcoholism diagnostic groups and depressive symptomatology were assessed for a sample of 461 convicted DWI offenders. The highest rate of depressive symptomatology was reported by persons diagnosed as alcohol dependent, and such findings were robust across male and female offenders. However, a significant interaction effect was found in which alcohol-dependent women reported higher levels of depressive symptomatology than alcohol-dependent men. With the exception that men reported significantly more previous DWI arrests than women, few differences were found between the gender groups with respect to a range of demographic variables, alcohol use and alcohol-related problems.

Accidents, Traffic↗
PubMed1989

Spousal violence among alcoholic women as compared to a random household sample of women.

The purpose of this study is to examine the relationship between spousal violence and women's alcoholism problems. This study compares two samples: (1) 45 alcoholic women selected from local treatment agencies and Alcoholics Anonymous groups and (2) 40 nonalcoholic women selected randomly from households. Two-hour interview schedules were administered to both samples. The Conflict Tactics Scale was used to assess spouse-to-woman violence. Alcoholic women were found to have higher levels of spouse-to-woman negative verbal interaction, moderate violence and severe violence as compared to the household women. Multivariate analyses revealed that spouse violence scores were strong predictors of type of sample. This was true even after controlling for presence of alcohol problems in the spouse, income, parental violence, parental alcohol problems and changes in parental family. These findings suggest that alcoholism treatment programs should screen for spousal violence among women alcoholics and that victims of spousal violence should be screened for alcohol-related problems.

Adult↗
PubMed1989

Sodium butyrate enhances fetal globin gene expression in erythroid progenitors of patients with Hb SS and beta thalassemia.

Increasing the expression of the gamma globin genes is considered a useful therapeutic approach to the beta globin diseases. Because butyrate and alpha-amino-n-butyric acid (ABA) augment gamma globin expression in normal neonatal and adult erythroid progenitors, we investigated the effects of sodium butyrate and ABA on erythroid progenitors of patients with beta thalassemia and sickle cell anemia who might benefit from such an effect. Both substances increased fetal hemoglobin (Hb F) expression in Bfu-e from 7% to 30% above levels found in control cultures from the same subjects with sickle cell anemia. The fraction of cultured erythroblasts producing Hb F increased more than 20% with sodium butyrate treatment in 70% of cultures. In most cultures, this produced greater than 20% total Hb F and greater than 70% F cells, levels which have been considered beneficial in ameliorating clinical symptoms. Alpha: non-alpha (alpha-non-alpha) imbalance was decreased by 36% in erythroid progenitors of patients with beta thalassemia cultured in the presence of butyrate compared with control cultures from the same subjects. These data suggest that sodium butyrate may have therapeutic potential for increasing gamma globin expression in the beta globin diseases.

Anemia, Sickle Cell↗
PubMed1989

Granulocyte-macrophage colony-stimulating factor reactivates fetal hemoglobin synthesis in erythroblast clones from normal adults.

Reactivation of fetal hemoglobin (HbF, alpha 2 gamma 2) synthesis was previously reported in normal human adult erythroblast colonies ("bursts") generated by erythroid progenitors (BFU-E) in fetal calf serum-supplemented (FCS+) semisolid cultures stimulated with erythropoietin (Ep). Our studies focused on the reactivation of HbF synthesis in normal adult erythroid bursts generated by peripheral blood mononuclear cells (PBMCs) seeded in FCS+ methylcellulose culture. Reactivation is almost totally suppressed when (a) PBMCs are grown in optimized FCS- culture, or (b) PBMCs are first stringently depleted of monocytes and then plated in FCS+ medium (ie, BFU-E growth in FCS+ Mo- culture). In both experimental conditions, the proliferation of lymphocytes and macrophages interspersed among colonies is drastically reduced, and the cloning efficiency of granulocyte-macrophage (GM) progenitors is sharply diminished. In either case, addition of biosynthetic GM colony-stimulating factor (GM-CSF) induces a dose-related increase of HbF synthesis up to the level in FCS+ culture, with even more elevated values on delayed addition of Ep. A dose-related increase was also observed in erythroblast clones generated by highly purified BFU-E. These results suggest that reactivation of HbF synthesis in normal adults is at least in part mediated by GM-CSF. Furthermore, they imply intriguing hypotheses on the mechanism(s) of perinatal Hb switching. Finally, they raise the possibility of reactivation of HbF synthesis in beta-thalassemia and sickle cell anemia by GM-CSF therapy.

Biological Factors↗
PubMed1989

Erythropoietin stimulates a rise in intracellular-free calcium concentration in single BFU-E derived erythroblasts at specific stages of differentiation.

Human cord blood progenitor-derived erythroblasts have recently been shown to respond to erythropoietin (Epo) or granulocyte-macrophage colony-stimulating factor (GM-CSF) with a transient increase in intracellular free calcium concentration [Cac]. However, the importance of [Cac] changes in mediating cell proliferation and/or differentiation is undefined. In the present study, the response of erythroid precursors at different stages of differentiation to Epo was examined. Erythroblasts were derived from adult blood erythroid progenitors (BFU-E) at day 7 or day 10 of culture. [Cac] was measured in individual Fura-2 loaded cells with fluorescence microscopy coupled digital video imaging. The dynamic range (Rmax/Rmin) of intracellular Fura-2 was similar to that measured in free solution, suggesting insignificant amounts of intracellular Ca insensitive forms of Fura-2. Baseline [Cac] of erythroid cells calculated with an in vitro calibration method was 44 +/- 4 nmol/L and with an in vivo method was 46 +/- 4 nmol/L. Treatment of day 7 BFU-E derived erythroblasts with Epo resulted in no significant increase in [Cac]. In contrast, in more mature erythroblasts (day 10 of culture), Epo stimulated a large increase in [Cac] from 49 +/- 11 nmol/L at baseline to 279 +/- 47 nmol/L. This [Cac] increase occurred in phosphate buffered saline (PBS) containing no added calcium. The increase in [Cac] persisted for 18 minutes and was dose dependent. Day 7 and day 10 control cells treated with either insulin or media showed no significant change in [Cac] during 18 minutes of observation. Our data demonstrate that early (day 7) and late (day 10) erythroblasts display different responses to Epo, at least in terms of intracellular Ca++ fluxes. The differential [Cac] response observed in early and late erythroid precursors to growth factor stimulation suggests that [Cac] may be an important signal in cell differentiation.

Adult↗
PubMed1988

Erythropoietin stimulates a rise in intracellular free calcium concentration in single early human erythroid precursors.

Erythropoietin and granulocyte-macrophage colony-stimulating factor (GM-CSF) stimulate the differentiation and proliferation of erythroid cells. To determine the cellular mechanism of action of these growth factors, we measured changes in intracellular free calcium concentration [( Cac]) in single human erythroid precursors in response to recombinant erythropoietin and GM-CSF. [Cac] in immature erythroblasts derived from cultured human cord blood erythroid progenitors was measured with fluorescence microscopy digital video imaging. When stimulated with erythropoietin, [Cac] in the majority of erythroblasts increased within 3 min, peaked at 5 min, and returned toward baseline at 10 min. The percentage of cells that responded to erythropoietin stimulation increased in a dose-dependent manner. Additional stimulation with GM-CSF in cells previously exposed to erythropoietin resulted in a second [Cac] increase. Immature erythroblasts treated with GM-CSF followed by erythropoietin responded similarly to each factor with a rise in [Cac]. The source of transient calcium is intracellular since erythroblasts were incubated in medium devoid of extracellular calcium. Our observations suggest that changes in [Cac] may be an intracellular signal that mediates the proliferative/differentiating effect of hematopoietic growth factors.

Body Fluids↗
PubMed1988

Thymic influence on the T-lymphocyte self MHC repertoire. I. Helper T-lymphocyte precursors.

We measured the frequencies of helper T-cell precursors in spleens of allogeneic thymus-grafted nude mice to determine whether allogeneic thymus engraftment resulted in clonal deletion of helper T-cells reactive to thymic major histocompatibility complex alloantigens, thereby producing tolerance to the thymic alloantigens. C3H thymus-grafted nudes had nearly normal numbers of C3H-reactive helper T-cell precursors, whereas C57BL/6 thymus-grafted nudes had significantly reduced numbers of C57BL/6-reactive helper T-cell precursors. Additional evidence suggested that tolerance was not due to a paucity of helper T-cell precursors: a) there was no correlation between the helper T-cell precursor frequency and the ability to mount cytotoxic responses against the thymic alloantigens, and b) exogenous helper factors did not break cytotoxic T-lymphocyte tolerance to thymic alloantigens. Thus, we conclude that immune tolerance resulting from engraftment of allogeneic thymic tissue is not necessarily due to clonal deletion of specific helper T-cell precursors.

Animals↗
PubMed1988

Thymic influence on the T-lymphocyte self MHC repertoire. II. Cytotoxic T-lymphocyte precursors.

We measured the frequency and specificity of thymic alloantigen-reactive cytotoxic T-lymphocyte precursors in spleens of allogeneic thymus-grafted nude mice tolerant to thymic alloantigens. Under our conditions of limiting dilution analysis we found no selective loss of cytotoxic T-lymphocyte precursors in allogeneic thymus-grafted mice. Upon analysis of individual cytotoxic T-lymphocyte clones, we found that lysis of specific and third party targets was mediated by distinct clones specific for H-2 antigens. Precursors from allogeneic thymus-grafted nudes stimulated at limiting dilutions with thymic alloantigens tended to lyse fewer targets than were lysed by normal cytotoxic T-lymphocytes or allogeneic thymus-grafted nude precursors stimulated with third party alloantigens, but the reduction in lytic activity was not statistically significant. Specific suppression was not demonstrated, but could not be ruled out unequivocally. We conclude that intrathymic deletion of thymic alloantigen-reactive pCTL is not necessary to achieve specific tolerance to thymic alloantigens.

Animals↗
PubMed1987

Butryic acid analogues augment gamma globin gene expression in neonatal erythroid progenitors.

The gamma----beta globin gene switch in humans is normally on a set developmental clock but is delayed in infants of diabetic mothers. We cultured cord blood erythroid progenitors and assayed globin produced in the presence and absence of metabolites that are elevated in such infants. Analogues of butyric acid at supranormal concentrations significantly augmented gamma and inhibited beta globin expression. The uptake of alpha-amino-n-butyric acid into colony-derived erythroblasts was increased in the presence of supranormal insulin. These findings suggest that elevated levels of alpha-amino-n-butyric acid and insulin in the developing fetus delay the globin switch and may offer potential for augmenting gamma globin expression in the beta globin chain diseases.

Butyrates↗
PubMed1987

Molecular analysis of the high-hemoglobin-F phenotype in Saudi Arabian sickle cell anemia.

Patients from the eastern province of Saudi Arabia who have sickle cell anemia have high circulating levels of fetal hemoglobin (hemoglobin F, 17 percent), and they therefore have a mild form of the disease. To examine the molecular basis of the elevated production of hemoglobin F, we searched for mutations in the promoter regions of the two hemoglobin F gamma-globin genes (G gamma and A gamma). The DNA sequences 450 bp (base pairs) upstream of both the G gamma and A gamma globin genes were normal except for a single-base cytosine-to-thymidine (C----T) substitution at -158 bp 5' to the cap (preinitiation) site of the G gamma-globin gene of the high-hemoglobin-F chromosome. We searched for an association between this -158 C----T substitution and the production of hemoglobin F and G gamma in normal Saudis and Saudis with sickle cell disease or trait. The substitution was present in nearly 100 percent of the patients with sickle cell disease or trait, and in 22 percent of the normal Saudis. Homozygosity for this mutation had no demonstrable effect on hemoglobin F production in the normal Saudi population. We conclude that this mutation is not uniquely responsible for the increase in hemoglobin F in Saudi patients. It may nevertheless have an important role in regulating hemoglobin F production, but its expression is complex and requires interaction with additional factors, such as hemolytic stress or other molecular determinants, possibly linked to the sickle cell gene.

Anemia, Sickle Cell↗