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Biomedical subjects

M Miller

Publications and source records attributed to M Miller.

At least 541 records · Page 30Linked to original sources
PubMed1990

Equine infectious anemia virus (EIAV) humoral responses of recipient ponies and antigenic variation during persistent infection.

Three ponies were inoculated with plasma containing 10(4.8) TCID50 of equine infectious anemia virus (EIAV) and observed for 165 to 440 days. Each pony developed a febrile response within 3 weeks of infection during which a plasma viremia greater than or equal to 10(3.5) TCID50/ml was observed. Analyses of four isolates from sequential febrile episodes in a single pony were conducted by two-dimensional tryptic peptide maps and with monoclonal antibodies in immunoblots. Structural and antigenic alterations were observed in the envelope glycoproteins gp90 and gp45, with greatest variation in gp90. Specific IgG to EIAV gp90, gp45, and p26 of homologous and heterologous isolates was detectable by immunoblots within one month after infection although IgG levels to gp45 at this time were relatively low. The group-specific determinants of gp90 and gp45 were more antigenic than those of p26; however, binding of IgG to these determinants did not correlate with neutralization of EIAV as assayed in fetal equine kidney cells. Neutralizing antibodies were first detectable within two months of infection and only neutralized viruses isolated prior to serum collection. Neutralizing activity of sera collected later in the infection was broadly reactive regardless of the number of clinical episodes the donor had suffered.

Animals↗
PubMed1990

Acylation-stimulatory activity in hyperapobetalipoproteinemic fibroblasts: enhanced cholesterol esterification with another serum basic protein, BP II.

Cultured fibroblasts from patients with familial hyperapobetalipoproteinemia (hyperapoB) were used to determine if a defect in lipid metabolism was present. Three basic proteins (BP I, BP II, and BP III) were isolated from normal human serum by preparative isoelectric focusing, preparative SDS/PAGE, and reversed-phase HPLC. The Mr and pI values of these proteins were 14,000 and 9.10 for BP I, 27,500 and 8.48 for BP II, and 55,000 and 8.73 for BP III. These proteins differed significantly in their content of arginine, cysteine, proline, histidine, serine, and methionine. BP I appears to be the same protein as acylation-stimulating protein, but BP II and BP III appeared different from acylation-stimulating protein and other lipid carrier proteins. BP I, BP II, and BP III stimulated the incorporation of [14C]oleate into lipid esters in normal fibroblasts, an effect that was time and concentration dependent. In hyperapoB cells, BP II markedly increased (up to 9-fold) the incorporation of [14C]oleate into cholesteryl ester compared with that in normal cells; in addition, there was a 50% decrease in the stimulation of triglyceride acylation and cholesterol esterification with BP I. No difference between normal and hyperapoB cells was observed with BP III. In summary, the identification of another serum basic protein, BP II, led to the elucidation of another cellular defect in hyperapoB fibroblasts, enhanced cholesterol esterification, which may be related to the precocious atherosclerosis and abnormal lipoprotein metabolism seen in hyperapoB.

Amino Acids↗
PubMed1990

Increasing ICU staff handwashing: effects of education and group feedback.

This study provides an evaluation of the effectiveness of methods to increase handwashing (HW) by nurses working in an intensive care unit. After baseline observations, two interventions were implemented in sequence: three series of classes conducted by the infection control nurse (ICN); and feedback to staff about handwashing errors on the previous day. Staff were aware that handwashing was being observed throughout the study. The educational intervention produced an immediate increase in HW that was followed by a decline to baseline rates over four weeks. Feedback produced an improvement to 97% compliance that was sustained until completion of the study. Improvement in HW compliance following specified critical procedures was also observed following interventions.

Communication↗
PubMed1990

Isolated low HDL-cholesterol as an important risk factor for coronary heart disease.

Decreased levels of high density lipoprotein (HDL)-cholesterol are found in patients with hypertriglyceridaemia and in patients who have inherited disorders associated with premature coronary heart disease. Hereditary conditions associated with low levels of HDL-cholesterol and normal total cholesterol levels include familial hypoalphalipoproteinaemia, Tangier disease, fish eye disease, and lecithin: cholesterol acyltransferase deficiency. Secondary causes of low HDL-cholesterol levels include any condition that affects liver metabolism. A recent study of patients with coronary artery disease (CAD) who had normal levels of low density lipoprotein cholesterol and total cholesterol revealed that two-thirds of the men and four-fifths of the women had low HDL-cholesterol levels, suggesting that low HDL-cholesterol may be more prevalent than previously suspected. The high incidence of isolated hypoalphalipoproteinaemia in this group indicates that HDL-cholesterol measurements should be performed on all patients with CAD, regardless of their total cholesterol levels.

Cholesterol, HDL↗
PubMed1990

Effect of age and IGF-I administration on elastin gene expression in rat aorta.

An age-related decrease in elasticity of arteries has been found in clinical and experimental studies done during the past two decades. We have investigated molecular and endocrine aspects of that decrease by examining the effects of age and insulin-like growth factor-I (IGF-I) on rat aorta elastogenesis. For comparison, pulmonary elastogenesis was examined in the same experimental animals. Different aged groups of male Fischer 344 rats (barrier protected) were implanted with minipumps for a two-week infusion of either 0.1 N acetic acid (vehicle solution) or IGF-I (1.2 mg/kg/day). The DNA content (micrograms DNA/g tissue) decreased with age in aorta but remained fairly constant in lung. Administration of IGF-I increased the aortic DNA content in all but the oldest rats. Conversely, the DNA content of pulmonary tissue was significantly increased in only the youngest animals. The steady-state levels of tropoelastin mRNA decreased dramatically in both aorta and lung with increased age. The decrease was greater in lung than aorta. Administration of IGF-I elevated aortic tropoelastin mRNA steady-state levels, whereas lung tropoelastin mRNA levels were unaffected by IGF-I administration. Aortic tissue synthesized decreased amounts of insoluble elastin with increased age. These results establish a direct relationship between aortic tropoelastin mRNA levels and the synthesis of insoluble elastin in aging. Administration of IGF-I increased aortic elastin synthesis throughout the life span of the rat, although the proportionate increase diminished with age.

Aging↗
PubMed1990

The radiographic changes of scleroderma in the hands.

Hand radiographs from 160 patients with scleroderma were reviewed. The presence of calcinosis distal to the metacarpophalangeal joints was significantly associated with the female sex, disease duration over 10 years, digital ulceration, telangiectasia, tuft erosion and the presence of anticentromere antibodies. The presence of calcinosis proximal to the metacarpophalangeal joints was significantly associated with tuft erosions and erosions involving all joints. The lack of distal calcinosis was significantly associated with anti Scl 70 and antinucleolar antibodies. The prevalence of other radiological manifestations of scleroderma such as osteoarthritis, erosions and dorsal tuft modelling was documented. Specific radiological findings correlate with certain clinical and serological characteristics in scleroderma.

Calcinosis↗
PubMed1990

Microsomal glycerolphosphate acyltransferase inactivation by fatty acids.

Glycerolphosphate acyltransferase activity in microsomes from rat adipose tissue is shown to decrease with time upon incubation with adipose tissue cytosolic fraction. The inactivation can be prevented with serum albumin and seems to be caused by an increase in endogenous free fatty acid as a consequence of the action of cytosolic lipase(s) on the membrane lipids. Similar inactivation can be observed after short incubation of microsomes with oleic acid at micromolar concentrations. Diacylglycerol acyltransferase is also inhibited by oleic acid, although to a lesser degree. In contrast, glucose-6-phosphatase and NADPH-cytochrome reductase activities are not changed. The oleic acid effect appears to occur upon binding to the microsomal membranes and can be prevented by bovine serum albumin at protein/fatty acid molar ratios above one. These results suggest that free fatty acids may be involved in the modulation of triacylglycerol synthetic enzymes.

Acyltransferases↗
PubMed1990

Alzheimer's disease and depression: neuropsychological impairment and progression of the illness.

The authors longitudinally evaluated the cognitive functions of patients with probable Alzheimer's disease who also met criteria for major depression and compared them with matched patients with Alzheimer's disease who were not depressed. They found no significant difference in the pattern of neuropsychological deficits between the two groups; composite scores on attention, language, memory, learning, and visuospatial functions did not differentiate the two groups at baseline or at 1-year follow-up. The results of this preliminary report suggest that depression does not modify the neuropsychological features and the rate of progression of Alzheimer's disease.

Aged↗
PubMed1990

Identification of committed mononuclear precursors for osteoclast-like cells formed in long term human marrow cultures.

Nonadherent marrow mononuclear cells enriched for hematopoietic progenitor cells were cultured in semisolid medium with recombinant human granulocyte-macrophage colony-stimulating factor for 9 days to form colony forming unit-granulocyte macrophage (CFU-GM) colonies. 1,25-Dihydroxyvitamin D was then gently layered over the cultures. After 2 weeks, approximately 30% of the colonies that formed were composed of cells with a unique polygonal morphology. One hundred percent of the polygonal cells in these colonies crossreacted with the monoclonal antibody 23c6, which preferentially recognizes osteoclasts. Homogenous populations of these polygonal cells formed multinucleated cells (MNC) in suspension culture, 100% of which cross-reacted with the 23c6 monoclonal antibody, and greater than 90% of the MNC contracted in response to calcitonin. Approximately 20% of these MNC formed resorption lacunae on calcified matrices. These results suggest that 1) early osteoclast precursors are derived from CFU-GM, the committed granulocyte-macrophage progenitor; 2) committed mononuclear osteoclast precursors have a distinct polygonal morphology and cross-react with monoclonal antibodies that recognize mature osteoclasts; and 3) these mononuclear precursors are capable of forming multinucleated cells which fulfill the functional criteria for osteoclasts.

Antibodies, Monoclonal↗
PubMed1990

A Veterans Administration Cooperative Study of biphasic calcium phosphate ceramic in periodontal osseous defects.

One hundred thirty-seven V.A. patients were randomized to one of three treatment groups to evaluate the efficacy of biphasic calcium phosphate (BCP) ceramic in the treatment of periodontal osseous defects. This material was tested against both autogenous bone implant and open flap curettage procedures. Baseline probing attachment level, Navy plaque index, and gingival index were recorded for all patients. These parameters were monitored for 3 years. At the end of this period, 101 patients had completed the study. Although the plaque and gingival indices steadily increased with time, there were no statistically significant differences among the treatment groups. Patients in the ceramic group had a gain in attachment level of 1.0 mm; those in the curettage group, 0.9 mm; and 0.4 mm for those in the bone implant group. Although the BCP patients had a greater gain, the difference was not statistically significant. In this veteran population, not only did BCP patients fail to outperform those in the control groups, all three treatment groups were similarly ineffective.

Adolescent↗
PubMed1990

Lowering of plasma glucose concentrations with bezafibrate in patients with moderately controlled NIDDM.

The goal of this study was to investigate whether treatment with bezafibrate improves glucose tolerance in non-insulin-dependent diabetes mellitus (NIDDM). The study included 37 NIDDM patients with HbA1 concentrations greater than 8.5% and normal kidney and liver function who were being treated with diet alone or diet together with a sulfonylurea drug. One patient withdrew because of constipation. At randomization and after 3 mo of treatment, patients were given a standard mixed-test-meal tolerance test (MTT; 500 cal) after an overnight fast, and plasma glucose, insulin, C-peptide, metabolite, nonesterified fatty acid (NEFA), and triglyceride concentrations were measured at 15- to 30-min intervals. Serum lipid, HbA1, and fructosamine concentrations were measured at monthly intervals. Glucose, NEFA, and triglyceride concentrations were significantly lower throughout the second MTT in bezafibrate patients (P less than 0.01-0.001) but not in the placebo group. Fasting serum insulin and C-peptide levels, but not postprandial concentrations, were reduced only in bezafibrate patients (P less than 0.05). After 3 mo, mean fasting serum triglyceride concentrations fell from 2.2 to 1.4 mM (P less than 0.001), total serum cholesterol concentrations from 6.3 to 5.5 mM (P less than 0.001), and low-density lipoprotein cholesterol concentrations from 4.2 to 3.5 mM (P less than 0.001) in bezafibrate patients. There were no changes in serum lipid concentrations in the placebo group. Treatment of patients with moderately controlled NIDDM with bezafibrate improves glucose tolerance and the serum lipid profile. Bezafibrate treatment may be a useful adjunct to hypoglycemic therapy in patients with NIDDM.

Bezafibrate↗
PubMed1990

Transformation of early erythroid precursor cells (BFU-E) by a recombinant murine retrovirus containing v-erb-B.

Avian erythroblastosis virus (AEV) is a replication-defective retrovirus that transforms erythroid and fibroblast cells in vitro and in vivo. The transforming ability of AEV is due primarily to the oncogene v-erb-B. A recombinant murine retrovirus has been constructed by inserting a chimeric gag-v-erb-B gene into a Moloney murine leukemia virus based vector. This retrovirus was used to examine v-erb-B-induced transformation of murine hematopoietic cells. Infection of murine primary fetal liver, adult bone marrow or adult spleen cells with the recombinant virus generated large hemoglobinized erythroid colonies in the absence of exogenous growth factors. Generation of such colonies usually requires the presence of erythropoietin (Epo) and interleukin-3 (IL-3). These growth-factor independent colonies were shown to be derived from early (BFU-E) and not late (CFU-E) erythroid progenitor cells, and the effect was not attributable to growth factors elicited by the virus-producing cell lines. In order to confirm that the recombinant virus was responsible for this transformation of BFU-E to growth factor independence, bone marrow cells from post 5-fluorouracil treated mice were infected and used to repopulate lethally-irradiated mice. Growth factor-independent BFU-E were obtained in up to 30% of day-13 spleen colonies and it was shown by DNA analysis that cells from these colonies contained integrated provirus. Our results indicate that v-erb-B transforms early erythroid progenitors to growth factor independent growth and subsequent differentiation to erythrocytes -a process that normally requires Epo plus either IL-3 or granulocyte-macrophage colony stimulating factor (GM-CSF).

Alpharetrovirus↗
PubMed1990

Peroxidase-dependent oxidation of sulfonamides by monocytes and neutrophils from humans and dogs.

The hydroxylamine and nitroso metabolites formed by N4-oxidation of sulfonamides are thought to be involved in the pathogenesis of idiosyncratic reactions to this class of drugs. Idiosyncratic reactions to sulfonamides are characterized by multisystemic toxicity, including hepatitis, nephritis, dermatitis, and blood dyscrasias (aplastic anemia, agranulocytosis). We have previously shown that cytochrome P-450 in the liver metabolizes sulfamethoxazole to its hydroxylamine metabolite. In this paper we report the N4-oxidation of sulfamethoxazole by activated monocytes and neutrophils (human and canine) to form sulfamethoxazole hydroxylamine and nitrosulfamethoxazole. The presumed nitroso intermediate was not detected. Purified myeloperoxidase and prostaglandin H synthase were also capable of mediating the oxidation of sulfamethoxazole. The present studies suggest that myeloperoxidase is responsible for the observed oxidation by phagocytic cells. Oxidation by neutrophils may play a role in agranulocytosis, and oxidation by monocytes may facilitate antigen presentation. Extrahepatic bioactivation of sulfonamides by peroxidases in phagocytic cells and other tissues may be important in determining the range of adverse reactions to sulfonamides that occur.

Animals↗