Search PubMed⌕ Search

Biomedical subjects

B A Miller

Publications and source records attributed to B A Miller.

At least 91 records · Page 5Linked to original sources
PubMed1992

Effects of alcohol feeding on synthesis and secretion of apolipoproteins by regenerating rat sciatic nerve.

The amounts of apolipoprotein (apo) E and A1 released into the culture medium were examined in the regenerating nerves distal to a crush site following chronic alcohol feeding. Cultured minced segments of regenerating nerves taken from rats fed an alcohol-containing liquid diet for 5 weeks released only 50% of apoE but nearly 200% of apoA1 when compared with rats pair-fed with a control diet. The extent of decrease in medium apoE corresponded to the decrease of apoE mRNA in the nerve. Thus, chronic alcohol ingestion affects apoE synthesis of regenerating nerves by changing its mRNA level. On the other hand, apoA1 mRNA remained undetectable in regenerating and intact nerves whether the rats were fed alcohol or not. Furthermore, the amount of apoA1 released by the regenerating nerve into the culture medium was not significantly larger than that present in the nerve tissue prior to incubation. Therefore, it is most likely that apoA1 released by the injured nerve originated from the bloodstream and the increase in apoA1 content seen in the crushed nerve of alcohol-fed rats is due to an enhanced permeability of the nerve-blood barrier. Since the burst of apolipoproteins in the injured nerve is likely to play a role in nerve regeneration, the perturbation of apolipoprotein contents in regenerating nerves by chronic alcohol consumption may contribute to the pathogenesis of alcoholic neuropathy.

Alcoholism↗
PubMed1992

Ion channels in human erythroblasts. Modulation by erythropoietin.

To investigate the mechanism of intracellular Ca2+ ([Cai]) increase in human burst-forming unit-erythroid-derived erythroblasts by erythropoietin, we measured [Cai] with digital video imaging, cellular phosphoinositides with high performance liquid chromatography, and plasma membrane potential and currents with whole cell patch clamp. Chelation of extracellular free Ca2+ abolished [Cai] increase induced by erythropoietin. In addition, the levels of inositol-1,4,5-trisphosphate did not increase in erythropoietin-treated erythroblasts. These results indicate that in erythropoietin-stimulated cells, Ca2+ influx rather than intracellular Ca2+ mobilization was responsible for [Cai] rise. Both Ni2+ and moderately high doses of nifedipine blocked [Cai] increase, suggesting involvement of ion channels. Resting membrane potential in human erythroblasts was -10.9 +/- 1.0 mV and was not affected by erythropoietin, suggesting erythropoietin modulated a voltage-independent ion channel permeable to Ca2+. No voltage-dependent ion channel but a Ca(2+)-activated K+ channel was detected in human erythroblasts. The magnitude of erythropoietin-induced [Cai] increase, however, was insufficient to open Ca(2+)-activated K+ channels. Our data suggest erythropoietin modulated a voltage-independent ion channel permeable to Ca2+, resulting in sustained increases in [Cai].

Adult↗
PubMed1992

The limited utility of BAC for identifying alcohol-related problems among DWI offenders.

To see if blood alcohol concentration (BAC) is a significant indicator of problem drinking or an alcohol-related diagnosis, the relationships between BAC at arrest for drinking and driving, typical drinking, alcohol-related problems, problem drinking and an alcohol abuse or dependence diagnosis were examined for 235 drinking and driving offenders referred for alcoholism evaluation. BAC and typical drinking correlated weakly and no significant relationship between alcohol-related problems and BAC was found. Further, no significant relationship was found between BAC and alcohol abuse or dependence diagnoses, or between problem drinking and BAC. These findings cast doubt on the usefulness of a single report of BAC for diagnostic and screening purposes.

Accidents, Traffic↗
PubMed1992

Multiple and single location drinking among DWI offenders referred for alcoholism evaluation.

Problem-drinker drivers who drank at multiple locations differ substantially from those who drank at only one location. Persons who drank at more than one location prior to their DWI arrest exhibit the most severe alcohol problems. Multilocation drinkers consumed significantly greater amounts of alcohol--for nearly all alcohol measures including consumption per drinking day, consumption averaged over 30 days, and consumption on the day of the DWI arrest--than single location drinkers. The multilocation group experienced more alcohol problems in their lives, had higher Mortimer-Filkins test scores, were intoxicated more frequently, and had a greater probability of a DSM-III-R alcohol-dependence diagnosis. Compared to the single location drinkers, the multilocation group had more bad driving incidents, frequently (once a week) drove while drunk, and expressed the attitude that the DWI had less of an impact on their lives. The findings suggest that multilocation drinkers require intensive interventions.

Adult↗
PubMed1992

The moderating impact of social support following childhood sexual abuse.

The role of social support in moderating the impact of childhood sexual abuse on adult psychological adjustment was examined. Subjects included 475 women, age 18-45, some of whom were currently receiving treatment, others who were not. Women in the treatment group were receiving therapy for either alcoholism, for being battered, or for mental health problems. The comparison group was drawn from two sources: a random household sample and a sample of women attending drinking driver classes. Among both groups, women who had been sexually abused exhibited more psychological symptoms and lower self-esteem compared to those who were not abused. Latency of disclosure of childhood sexual abuse had no impact on long-term consequences of the abuse for either the treatment or the comparison group. However, among women in the comparison group, those who experienced supportive reactions following disclosure of sexual abuse had fewer psychological symptoms and somewhat higher self-esteem relative to those who did not receive support. Social support had no apparent effect on the long-term adjustment of women in the treatment group. Possible explanations for this pattern and directions for future research are discussed.

Adaptation, Psychological↗
PubMed1991

Deficiency of alpha-spectrin synthesis in burst-forming units-erythroid in lethal hereditary spherocytosis.

A child diagnosed in utero with hydrops fetalis and a hematocrit of 6.4% was studied to determine the etiology of the anemia. Fetal red blood cells (RBCs) obtained during in utero transfusion had extremely abnormal osmotic fragility. A maternal history of mild autosomal dominant hereditary spherocytosis was present, and the father, who was hematologically normal, had a slightly abnormal osmotic fragility test. The patient was transfusion dependent after birth, with circulating nucleated RBCs but less than 1% reticulocytes. The patient's anemia failed to respond to splenectomy. Because mature RBCs of the patient were not available for study, progenitor-derived erythroblasts grown in culture were investigated. Immunodot assays of the patient's progenitor-derived cells showed a total cell spectrin content 26% of normal. Immunoprecipitation of whole burst-forming units-erythroid-derived cells and solubilized membranes from cells pulse-labeled with 35S-methionine showed a severe deficiency in alpha-spectrin synthesis and a markedly reduced amount of alpha- and beta-spectrin on cell membranes. No alpha-spectrin degradation products were found within the cells or were produced during membrane preparation. Ankyrin content and band 3 synthesis were not different from control. Inheritance of two genetic defects causing severely reduced alpha-spectrin synthesis is proposed as the cause of the lethal anemia, resulting in cell fragmentation during precursor enucleation or during egress from bone marrow.

Anion Exchange Protein 1, Erythrocyte↗
PubMed1991

Role of pertussis toxin-sensitive guanosine triphosphate-binding proteins in the response of erythroblasts to erythropoietin.

Human progenitor-derived erythroblasts have been recently shown to respond to erythropoietin (Epo) with an increase in intracellular free calcium concentration [Cac]. To explore the role of guanosine triphosphate (GTP)-binding proteins in mediating the rise in [Cac], single day 10 erythroid burst forming unit (BFU-E)-derived erythroblasts loaded with Fura-2 were pretreated with pertussis toxin (PT), stimulated with Epo, and [Cac] measured over 18 minutes with fluorescence microscopy coupled to digital video imaging. The [Cac] increase in day 10 erythroblasts stimulated with Epo was blocked by pretreatment with PT in a dose-dependent manner but not by heat-inactivated PT. These observations provided strong evidence that a PT-sensitive GTP-binding protein is involved. To further characterize the GTP-binding protein, day 10 erythroblast membrane preparations were solubilized, electrophoresed, and immunoblotted with antibodies specific for the known PT-sensitive G-protein subunits: the three subtypes of Gia (1,2, and 3) and Goa, Gia1 or Gia3 and Gia2 were identified but no Goa was found. To examine the influence of Epo on adenylate cyclase activity, day 10 erythroblasts were initially treated with Epo, isolated membrane preparations made, and cyclic adenosine monophosphate (cAMP) production by adenylate cyclase in membrane preparations in the presence of theophylline measured. Epo did not inhibit but significantly stimulated adenylate cyclase activity. However, the mechanism of increase of [Cac] appears to be independent of adenylate cyclase stimulation because treatment of erythroblasts with the cell-permeant dibutyryl cAMP failed to increase [Cac]. In summary, pertussis toxin blocks the increase in [Cac] in erythroblasts after Epo stimulation suggesting that this response is mediated through a pertussis toxin-sensitive GTP-binding protein. Candidate PT-sensitive GTP-binding proteins identified on day 10 erythroblasts were Gia 1, 2, or 3, but not Goa.

Adenylate Cyclase Toxin↗
PubMed1991

The increasing incidence of breast cancer since 1982: relevance of early detection.

Breast cancer incidence in the United States has been rising dramatically since 1982, as shown in data collected by the Surveillance, Epidemiology, and End Results (SEER) Program. In women aged 50 and older, incidence rates for in situ and localized invasive tumors have increased over the period 1982-86, while rates for regional and distant tumors have remained stable. The incidence of localized tumors less than 1.0 cm, 1.0-1.9 cm, and 2.0-2.9 cm in size has increased more rapidly than that of tumors 3.0 cm or more in size among women over age 50. Survival rates also have improved among cases diagnosed over this time period. These data suggest that early detection may be playing a role in the recent increase in female breast cancer incidence, though other factors cannot be ruled out. Conclusions regarding improved cancer control await confirmation by reduced breast cancer mortality.

Breast Neoplasms↗
PubMed1991

Electrogenic uptake of sulphur-containing analogues of glutamate and aspartate by Müller cells from the salamander retina.

1. The effect of sulphur-containing analogues of glutamate and aspartate on the membrane current of glial cells was studied by whole-cell clamping Müller cells isolated from the salamander retina. 2. L-Cysteic acid (CA), L-cysteinesulphinic acid (CSA), L-homocysteic acid (HCA), L-homocysteinesulphinic acid (HCSA) and S-sulpho-L-cysteine (SC) all evoked an inward membrane current that was large at negative potentials, and was smaller (but did not reverse) at more positive potentials up to +30 mV. 3. Removal of external sodium ions abolished the amino acid-evoked currents. Whole-cell clamping with pipettes containing no potassium led to a rapid suppression of the currents, that did not occur when potassium was included in the pipette. 4. The dependence of the currents on sulphur-containing amino acid concentration obeyed first-order Michaelis-Menten kinetics. The current evoked by co-application of L-glutamate and a sulphur-containing analogue was smaller than the sum of the currents produced by glutamate alone and by the sulphur analogue alone. 5. These data are consistent with the sulphur amino acid-evoked current being caused by uptake on the electrogenic glutamate uptake carrier, which co-transports an excess of Na+ ions into the cell, and counter-transports one K+ ion out of the cell. 6. The apparent Km (Michaelis-Menten constant) values for activation of uptake by CA (6 microM) and by CSA (60 microM) are low enough for uptake on the glutamate uptake carrier to be a plausible mechanism for terminating the postulated neurotransmitter action of these agents. However, the apparent Km values for uptake of HCA (2.95 mM), HCSA (1.65 mM) and SC (greater than 1 mM) are much higher than the EC50 (half-maximal effective concentration) concentrations for these agents' activation of NMDA (N-methyl-D-aspartate) channels. 7. Comparing the concentrations of sulphur amino acids needed to activate NMDA channels with their rate of uptake suggests that their potency for causing excitotoxic damage should follow the sequence HCA greater than SC greater than HCSA greater than Glu greater than CSA greater than Asp greater than CA.

Amino Acids, Sulfur↗
PubMed1991

Benign mucous membrane pemphigoid: a case report.

A relatively rare systemic disease, benign mucous membrane pemphigoid (cicatricial pemphigoid) usually starts in the mouth and is clinically characterized by bullae that rupture and form an ulcer. A distinctive Nikolsky's sign is apparent using gentle air blasts or finger pressure. The pharynx, larynx, nose, esophagus, genitals and eyes can also be affected. Involvement of the conjunctivae can lead to scarring and ensuing blindness. The following case of a healthy 77-year-old man, diagnosed as suffering from mucous membrane pemphigoid, is of particular interest since several confusing clinical observations, including poor oral hygiene, the possibility of a contact dermatitis or an adverse antibiotic reaction, made the diagnosis more difficult. A careful medical history, examination and consultation process is paramount to initiating proper treatment and subsequent relief of symptoms. Benign mucous membrane pemphigoid must always be considered in any patient with desquamative epithelium of the oral mucosa.

Aged↗
PubMed1991

Psychiatric symptoms and DWI offenders.

The utility of psychiatric symptoms for identifying potential DWI recidivists was examined. Results indicated that psychiatric symptoms were more related to whether the individual would have qualified for a DSM-III-R alcohol dependent diagnosis than to offender status. A second finding of importance was the high rate of alcohol dependence found for the first-time offenders. The implications for these findings are discussed in this report.

Alcoholic Intoxication↗
PubMed1990

Problem drinking and depression among DWI offenders: a three-wave longitudinal study.

Longitudinal data collected at 3 occasions of measurement from a convicted driving-while-intoxicated sample (n = 302) were used to study the interrelations between problem drinking and depressive symptomatology. Time intervals between occasions of measurement were approximately 9 months. Cross-lagged latent variable models indicated that higher levels of depression at Time 1 were significantly associated with lower levels of problem drinking at Time 2. Similarly, higher levels of problem drinking at Time 1 were significantly associated with lower levels of depression at Time 2. However, the direction of effects for the cross-lagged coefficients were reversed for the Time-2-Time-3 relations. Higher levels of depression at Time 2 were significantly associated with higher levels of problem drinking at Time 3, and higher levels of problem drinking at Time 2 were associated with higher levels of depression at Time 3. The results are interpreted to reflect a biphasic process.

Adult↗
PubMed1990

Interferon-gamma modulates fetal hemoglobin synthesis in sickle cell anemia and thalassemia.

Interferon-gamma (IFN-gamma) has been shown to influence globin gene expression in cord blood and normal adult progenitor-derived erythroblasts. To explore the influence of IFN-gamma on fetal hemoglobin (HbF) synthesis in the hemoglobinopathies, erythroid progenitors (BFU-E, burst forming unit-erythroid) from patients with sickle cell anemia (SCA) and thalassemia were co-cultured with or without IFN-gamma. Hemoglobin content in progenitor-derived erythroblasts was assessed by radioligand assay (RIA). Co-culture of erythroid progenitors from 12 SCA patients with 200-400 U/ml of IFN-gamma resulted in a significant decrease in picograms of HbF and percent HbF per BFU-E-derived erythroblast. The mean decrease (+/- SEM) of picograms of HbF per cell and percent of HbF was by 42 +/- 9% and 35 +/- 8% of control cultures, respectively. Co-culture of erythroid progenitors from 10 patients with thalassemia major or thalassemia variant (HPFH/thalassemia, sickle/beta 0-thalassemia) with 200 U/ml IFN-gamma also resulted in a significant decrease in picograms and percent of HbF per BFU-E-derived erythroblast. IFN-gamma treatment also inhibited the enhancement in gamma-globin synthesis induced in culture by butyric acid. Erythroid progenitors from 2 patients with SCA, 1 patient with sickle/beta 0-thalassemia, and 1 patient with HbE/beta 0-thalassemia were co-cultured with IFN-gamma, L-alpha-amino-n-butyric acid, or both. HbF content (expressed as picograms HbF/cell) was decreased in samples co-cultured with IFN, increased in cultures with L-alpha-amino-n-butyric acid, but remained at control values in cultures treated with IFN plus L-alpha-amino-n-butyric acid. These data demonstrate that IFN-gamma is an environmental factor that influences gamma-globin gene expression in the beta hemoglobinopathies in vitro.

Aminobutyrates↗
PubMed1990

Stopping the biologic clock for globin gene switching.

The developmental switch from production of fetal (gamma) to adult (beta) globin occurs on a normally set biologic clock which proceeds even if expression of the adult (beta) globin genes is defective and produces little or no protein, as in the beta-thalassemias. Preventing or reversing the globin gene switch could provide a way of keeping the abnormal globin genes "silent" and maintaining expression of the fetal globin gene. We have identified a class of agents which, when present in elevated plasma concentrations during gestation, inhibits the gamma----beta-globin gene switch in developing humans. Further investigation has shown that butyric acid and related compounds can increase gamma-globin and decrease beta-globin expression in cultured erythroid cells of patients with beta-thalassemia. Butyrate compounds were therefore infused in an in vivo fetal animal model, and the globin switch was inhibited and even reversed in some fetal lambs. Histone hyperacetylation, which maintains active chromatin structure, and an effect on the gamma-globin promoter appear to be mechanisms of action involved. These data suggest that inhibiting expression of abnormal beta-globin genes by pharmacologic means may in the future be possible for treatment of individuals with beta-globin disorders.

Anemia, Sickle Cell↗
PubMed1990

Three-dimensional intracellular calcium gradients in single human burst-forming units-erythroid-derived erythroblasts induced by erythropoietin.

We have previously shown that the intracellular free Ca2+ increase induced by erythropoietin is likely related to differentiation rather than proliferation in human BFU-E-derived erythroblasts (1989. Blood. 73:1188-1194). Since cell differentiation involves transcription of specific regions of the genome, and since nuclear endonucleases responsible for single strand DNA breaks observed in cells undergoing differentiation are Ca2+ dependent, we investigated whether the erythropoietin-induced calcium signal is transmitted from cytosol to nucleus in this study. To elucidate subcellular Ca2+ gradients, the technique of optical sectioning microscopy was used. After determining the empirical three-dimensional point spread function of the video imaging system, contaminating light signals from optical planes above and below the focal plane of interest were removed by deconvolution using the nearest neighboring approach. Processed images did not reveal any discernible subcellular Ca2+ gradients in unstimulated erythroblasts. By contrast, with erythropoietin stimulation, there was a two- to threefold higher Ca2+ concentration in the nucleus compared to the surrounding cytoplasm. We suggest that the rise in nuclear Ca2+ may activate Ca2(+)-dependent endonucleases and initiate differentiation. The approach described here offers the opportunity to follow subcellular Ca2+ changes in response to a wide range of stimuli, allowing new insights into the role of regional Ca2+ changes in regulation of cell function.

Calcium↗