Search PubMed⌕ Search

Biomedical subjects

W J Miller

Publications and source records attributed to W J Miller.

At least 109 records · Page 6Linked to original sources
PubMed1989

Long-term feeding of high zinc sulfate diets to lactating and gestating dairy cows.

Thirty dairy cows, fed a control diet consisting of silage and concentrates, were given either 0, 1000, or 2000 ppm of supplemental Zn (DM basis), from zinc sulfate monohydrate (ZnSO4.H2O) for most of a lactation. Feeding 2000 ppm Zn decreased milk yield and feed intake after several weeks. Some cows were affected more severely than others. Generally, primiparous animals were more tolerant of the high Zn diet than multiparous cows. Milk Zn was materially higher for cows fed 1000 ppm added Zn than controls. With 2000 ppm Zn, milk Zn was elevated further but returned to control values when the high Zn diet was discontinued. Plasma Zn was higher in cows fed supplemental Zn with the increase from 1000 to 2000 greater than that for the first addition. Plasma Cu was lower in cows feed 2000 ppm Zn but milk Cu was not reduced. Milk fat content was not affected, but protein and SNF were reduced by the 12th wk with the 2000 ppm Zn diet. There was no apparent effect on long-term health or performance after the cows were removed from the 2000 ppm Zn diet. Except for lower calf weights with 2000 ppm Zn, reproductive performance was not measurably affected by the dietary treatments. The 1000 ppm added Zn diet had no adverse effect on the cows in any parameter measured.

Animal Feed↗
PubMed1988

Unique promotion of erythrophagocytosis by malondialdehyde.

Modification of the normal erythrocyte membrane by reagent malondialdehyde (MDA) promotes phagocytosis of red blood cells by human macrophages, a phenomenon previously shown to involve both IgG-dependent and IgG-independent mechanisms and to be demonstrable even at micromolar MDA concentrations. In the present studies, we demonstrate this effect using 1mM MDA prepared both by acid hydrolysis of malonaldehyde bis-(dimethyl acetal) and by enzymatic synthesis from 1,3-propanediol. Remarkably, we find that equimolar amounts of other mono- and dialdehydes fail to promote erythrophagocytosis despite similarity to MDA in size and structure and ability to cross link. Authentic MDA seems to be unique among small aldehydes in ability to promote erythrophagocytosis at low aldehyde concentration and, therefore, has a special biologic relevance among the great variety of peroxidation byproducts.

Aldehydes↗
PubMed1988

Allogeneic bone marrow transplantation for acute leukaemia: comparative outcomes for adults and children.

Advances in both allogeneic marrow transplantation and conventional therapy for acute leukaemia have complicated the choice between bone marrow transplantation (BMT) and other remission treatment options. Because older patients may be more susceptible to BMT-related complications, this study analysed the effect of age on clinical outcome for 149 patients with acute leukaemia in remission receiving allogeneic BMT. Overall projected relapse-free survival at 3 years post-transplant is equivalent for 48 adults (18 years or older) and 101 children (less than 18) at 45.4% (31.1-59.6; 95% confidence interval) and 39.9% (30.1-49.7; 95% C.I.), respectively. Among 73 patients with acute lymphocytic leukaemia (ALL) 35.3% of adults and 30.1% of children survive relapse-free at 3 years. Cox multiple regression analysis demonstrated that higher diagnostic white count, but not pre-transplant extramedullary leukaemia, remission number, or age, was important as an independent adverse clinical prognostic factor for patients with ALL. Overall outcome was better for 76 patients with acute myeloid leukaemia (AML) with 51.6% of adults and 52.9% of children surviving relapse-free at 3 years post-transplant. Cox multivariate regression analysis identified first remission status and lower white cell count, but not patient age, as independent predictors of improved relapse-free survival for AML patients. Adults had greater transplant morbidity, predominantly related to a higher incidence of acute graft-versus-host disease (GVHD), resulting in longer hospital stay. Survival at 100 d, long-term survival and clinical performance status were similar in both age groups. These data suggest that results of allogeneic BMT for adults with acute leukaemia compare favourably with those found in children and are superior to most reports of conventional chemotherapy. Allogeneic BMT remains a reasonable option for remission acute leukaemia patients up to the age of 45.

Adolescent↗
PubMed1988

Effects of diabetes and starvation on skeletal muscle branched-chain alpha-keto acid dehydrogenase activity.

The activation state of branched-chain alpha-keto acid dehydrogenase (BCDH) was studied in rat hindlimb muscles during starvation and insulinopenic diabetes, conditions in which circulating branched-chain amino acids (BCAA) are increased and their oxidation is accelerated. Muscle BCDH is predominantly inactive (phosphorylated) in postabsorptive rats but is activated by increased circulating leucine. Diabetes (streptozotocin-induced and spontaneous BB/W) increased circulating BCAA four- to fivefold and BCDH activity approximately threefold. Insulin treatment caused near normalization of circulating BCAA without correcting BCDH activity. Adrenalectomy of diabetics decreased (without normalizing) circulating BCAA and BCDH activation. Starvation caused mild, progressive increases in circulating BCAA and significant activation of BCDH only after 4 days. Leucine infusion activated BCDH in muscle but the activation by leucine was markedly blunted by diabetes. In isolated perfused hindlimbs (control and diabetic) insulin did not affect BCDH significantly; perfusion with leucine activated BCDH, and this response appeared blunted in diabetics. Activation of muscle BCDH may contribute to increased BCAA catabolism in diabetes; the blunted activation response to hyperleucinemia may spare BCAA and contribute to their persistent elevation in plasma.

3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide)↗
PubMed1988

Influence of a wide range of calcium intakes on tissue distribution of macroelements and microelements in dairy calves.

Sixteen intact male Holstein calves averaging 86 kg and 63 d of age were assigned randomly to four treatment groups. The four treatment diets contained .17, .67, 1.31, and 2.35% Ca on an as-fed basis. The resulting Ca:P ratios with P held constant at about .34% were .47:1, 1.92:1, 3.83:1, and 7.20:1. Calves were fed diets at 3% of their body weights for 4 wk. Magnesium in the bone ash and serum was lowered by the 2.35% Ca treatment. Serum inorganic P was also reduced by the highest Ca diet during the last 2 wk of the experiment. Liver had the highest concentration of Zn in calves fed .67% Ca, and the muscle from calves fed 1.31% Ca diet had the lowest amount of Zn. Copper was reduced in pancreas for 1.31% Ca diet, but Ca was highest in the muscle and heart at the .67% Ca treatment. Weight gains and feed efficiencies were not affected by Ca. Fecal pH was different among treatments and increased as Ca intake increased. Young growing dairy calves can adapt to a wide range of Ca intakes and Ca:P ratios and maintain a moderate growth rate for 4 wk. It appears that excessive dietary Ca may affect concentrations of Zn, Fe, Cu, and Mn in some body tissues, but the magnitude of the effect is relatively small.

Animals↗
PubMed1988

Immunoglobulin and T-cell receptor gene rearrangement in blast crisis of chronic myelocytic leukemia.

Chronic myelocytic leukemia (CML) displays a wide repertoire in its terminal phase, with blast cells showing characteristics of myeloid, B-lymphoid, or T-lymphoid cells in some patients. Blast crisis (BC) cells from 14 patients were studied for immunoglobulin (Ig)- and T-cell-associated gene rearrangements. Five myeloid BC patients had no Ig- or T-cell-associated gene rearrangement. In contrast, all eight patients with pure lymphoid BC displayed C mu rearrangement and two also showed kappa-light chain rearrangement. One patient with mixed (lymphoid and erythroid) BC, however, showed neither Ig- nor T-cell-associated rearrangements. One patient displayed both Ig- (C mu) and T-cell-associated (T beta and T gamma) rearrangements. These cells expressed CD9, CD10, and CD24 surface antigens, but no T-cell antigens. Although most lymphoid blast crises appear to represent an early stage in B-cell differentiation, some cells have undergone apparently inappropriate gene rearrangements during differentiation. Such cells may have been immortalized while undergoing normally occurring nonproductive rearrangement or may, due to their malignant nature, display abnormal genotypic characteristics.

Antigens, Surface↗
PubMed1987

In vitro correlates of low dose ara-C efficacy: clinical, cytogenetic, and bone marrow culture analysis.

Low-dose Ara-C (10 mg/m2 subcutaneously bid) has been used as an alternative therapy for acute nonlymphocytic leukemia (ANLL) and myelodysplastic syndromes. We sought to define its therapeutic mechanism by assessing clinical and cytogenetic responses to treatment in conjunction with careful in vitro study of both morphologic and functional characteristics of bone marrow cells cultured with Ara-C. Sixteen patients (12 ANLL, four myelodysplastic syndrome) were treated. All developed pancytopenia and 11 of 12 had bone marrow hypoplasia during treatment. Four had a meaningful clinical response while five more showed in vivo leukemic cell sensitivity to low-dose Ara-C. Seven showed no response. Cells with cytogenetic abnormalities were either decreased in number or eradicated during clinical improvement. Liquid culture of marrow mononuclear cells with Ara-C (.033-.333 micrograms/ml X 7 days) produced little evidence of morphologic or functional differentiation (ten of 11 studied). No functional maturation was observed in cells from clinically responding patients. We conclude that low-dose Ara-C is modestly effective for some patients with ANLL or myelodysplasia. However, no evidence for in vivo leukemic differentiation is suggested by either in vitro culture studies or cytogenetic correlates of clinical response. In vitro marrow culture studies failed to predict clinical response to Ara-C.

Acute Disease↗
PubMed1987

Effect of added dietary cobalt on metabolism and distribution of radioactive selenium and stable minerals.

Retention of 75Se following a single oral dose and stable Co, Cu, Zn, and Mg were determined in tissues of calves fed a diet containing 0, 10, or 40 ppm supplemental Co for 21 d. Concentrations of 75Se in tissue were numerically higher with 10 ppm Co than with the other two diets, but the effect was significant only in small intestine tissues of calves fed 40 ppm Co. Dietary Co did not affect fecal 75Se. Average total fecal 75Se excretion was 53, 48, and 51% of the dose over 6 d in calves fed 0, 10, and 40 ppm added Co. Concentrations of Co in tissues increased with increased supplementation. Dietary Co did not significantly affect growth, feed intake, tissue Zn, tissue Cu, blood hemoglobin, packed cell volume, plasma alkaline phosphatase, or plasma glutamic oxaloacetic transaminase. Magnesium in heart and skeletal muscle was increased in calves fed 40 ppm Co. Although high amounts of added dietary Co had some influence on metabolism of Se, the magnitude and extent of the effects appeared to be too small to be of practical concern.

Animals↗
PubMed1987

Influence of high dietary lead on selenium metabolism in dairy calves.

Metabolism of orally dosed 75Se was studied in 10 intact male Holstein calves that were fed ad libitum a control diet containing no added Pb or supplemented with 1000 ppm Pb as PbSO4 for 4 wk. Lead-supplemented calves did not exhibit any clinical signs of Pb toxicity. Voluntary feed intake was reduced by 9.5% and average daily gain by 23%. Lead content of rib, liver, and kidney increased. Serum glutamic oxaloacetate transaminase activity was increased during the last 2 wk of the experiment in calves fed Pb. In calves receiving supplemental Pb, 75Se absorption, blood concentration, and urine concentration were reduced by 26, 21, and 42%, respectively. Tissue 75Se concentrations were significantly lower in kidney, liver, testicle, pancreas, small intestine, heart, spinal cord, and muscle in calves fed Pb. There was a significant negative correlation (r = -.78) between 75Se and stable Pb concentrations in the liver. It is not clear whether the ingestion of subclinical amounts of Pb could affect the absorption and utilization of Se in dairy calves to the extent of Se deficiency when dairy calves are kept in areas known to be low in Se.

Animals↗
PubMed1987

Effects of varying the amounts of dietary calcium on selenium metabolism in dairy calves.

Influence of dietary Ca on Se metabolism was studied with 16 intact male Holstein calves averaging 86 kg. Calves were assigned randomly and fed one of four diets containing, .17, .67, 1.31, and 2.35% Ca at 3% of their body weight for 4 wk. The diets contained .062 ppm Se and .34% P. Four days prior to the end of the experiment, calves were dosed orally with radioactive 75Se. Dietary Ca had no significant effect on 75Se absorption. There was a slight curvilinear relationship between apparent 75Se absorption and dietary Ca intakes. Urinary excretion of 75Se and stable Se tended to decrease with increasing dietary Ca, but differences were not significant. No significant differences were found in concentration of 75Se in several tissues. Kidney and liver had the highest concentration with that in kidney being about four times that of liver. Apparent 75Se absorption was decreased 10 to 6%, respectively, in calves fed extremely low and high amounts of Ca, compared with those receiving the requirement (.67% Ca). These small reductions along with a small R2 suggest that dietary Ca probably is of little practical importance relative to Se metabolism in calves.

Animals↗
PubMed1987

Bioavailability of phosphorus from defluorinated and dicalcium phosphates and phosphorus requirement of calves.

Bioavailability of P from defluorinated phosphate and dicalcium phosphate and the P requirement were studied with 63 male Holstein calves. A P depletion diet containing .08% total P on a dry matter basis was fed to all animals for 4 wk beginning at 6 wk of age and 61 kg weight. Calves developed typical signs of P deficiency. The depletion period was followed by a 6-wk experimental period in which the same depletion diet was used as a control. Phosphorus from each of the two sources was added to make diets containing .14, .20, and .32% total P. Source of supplemental P did not affect weight gains, feed consumption, feed efficiency, serum inorganic P, serum alkaline phosphatase, or bone ash.

Animals↗
PubMed1987

Metabolism of manganese in calves as affected by dietary manganese and intravenous or duodenal manganese-54 dosing.

Fifteen intact male Holstein calves averaging 101 d of age were utilized to determine the effects of dietary Mn concentration and routes of administration on its metabolism. They were fed a practical grain diet containing 23 ppm Mn with 0, 100, or 1000 ppm supplemental Mn (MnSO4.H2O) for 7 d prior to intravenous or duodenal dosing with 54Mn. Animals were killed 4 h later. With added Mn there was a significant decrease in 54Mn content of some small intestine parts. However, in most tissue, including organs, bones, intestinal tract tissues, and blood, added Mn did not have a significant effect on 54Mn concentrations. Concentrations of 54Mn in tissues, except in small intestine, were far higher following intravenous dosing than with duodenal dosing. This further confirms that absorption of Mn is very low. Dosing method had a sizable effect on the relative amounts of 54Mn in different tissues. This suggests that intravenously administered Mn, at least initially, is not metabolized in the same way as that absorbed. In most tissues, unlabeled Mn was not affected greatly by supplemental Mn. This is in contrast to earlier results with very young calves and indicates that Mn metabolism changes sharply before 3 to 4 mo of calf age.

Animals↗
PubMed1987

Molecular genetic rearrangements distinguish pre- and post-bone marrow transplantation lymphoproliferative processes.

Chronic myelocytic leukemia (CML) may display a lymphoproliferative phase (lymphoid blast crisis) that is generally of B cell phenotype. Since lymphoproliferative disorders may occur following bone marrow transplantation (BMT), it may be difficult to distinguish posttransplant relapse of CML lymphoid blast crisis from de novo lymphoproliferation. Lymphoid blast crisis cells from a patient with CML displayed immunoglobulin heavy chain gene (C mu) rearrangement before BMT. Following BMT the patient developed a lymphoproliferative disorder involving multiple organs. Clonal rearrangement of C mu was demonstrated in several involved tissues. The rearranged C mu restriction fragment was distinct from that displayed before BMT. Additionally, rearrangement of the breakpoint cluster region (bcr) was demonstrated in the pretransplant blast crisis sample, but not in the posttransplant lymphoproliferation samples, thus confirming that these lymphoproliferative disorders were distinct. Molecular genetic techniques offer powerful diagnostic tools for monitoring the course of patients with CML undergoing BMT.

Blast Crisis↗
PubMed1986

The safety of the hepatitis B vaccine. Inactivation of the AIDS virus during routine vaccine manufacture.

In the United States, one hepatitis B vaccine (Heptavax-B) has been licensed for the prevention of hepatitis B virus infections. Even though this vaccine has been shown to be highly effective and well tolerated in controlled trials and has been recommended for use in those at risk for acquiring infection by hepatitis B virus, many individuals have been reluctant to be immunized for fear of contracting acquired immunodeficiency syndrome (AIDS). In this study, we demonstrate that each of the three inactivation steps used in the manufacture of Heptavax-B independently will inactivate the infectivity of high-titered preparations of the AIDS virus; recipients of the hepatitis B vaccine do not develop antibodies to the AIDS virus; the hepatitis B vaccine does not contain detectable levels of nucleic acids related to the AIDS virus. These observations clearly demonstrate that vaccination with the currently available hepatitis B vaccine poses no demonstrable risk for acquiring AIDS.

Antibodies, Viral↗
PubMed1986

An inactivated hepatitis A viral vaccine of cell culture origin.

Hepatitis A virus (HAV) strain CR326, adapted to grow in LLC-MK2 cells, was highly purified, inactivated with formalin, adsorbed to alum, and tested for capacity to induce antibody to HAV in both mice and marmosets. The minimum dose of HAV antigen necessary to produce antibody in 50% of mice was 10 ng. As little as three doses of 1 ng each produced antibody in 50% of marmosets. Further, all marmosets with any detectable antibody to HAV, as a result of vaccination, were protected against virulent infection on challenge with HAV. Thus a highly efficacious, inactivated hepatitis A vaccine can be produced from virus grown in cell culture. Although LLC-MK2 cells are unacceptable for use in human vaccine preparation, HAV can also be prepared in a similar manner in MRC-5 cells, which are acceptable for human vaccine manufacture.

Animals↗
PubMed1986

Unusually high-level expression of a foreign gene (hepatitis B virus core antigen) in Saccharomyces cerevisiae.

As a model system for the study of factors affecting gene expression, hepatitis B virus core antigen (HBcAg) has been expressed in the yeast Saccharomyces cerevisiae. The singularly high levels of expression achieved are approx. 40% of the soluble yeast protein. The HBcAg polypeptides are present as 28-nm particles which are morphologically indistinguishable from HBcAg particles in human plasma and are highly immunogenic in mice. The plasmid construction employed to achieve these very high levels of expression utilizes the constitutively active yeast promoter from the GAP491 gene which is fused in a way that all non-translated sequences flanking the HBcAg coding region are yeast-derived. Hybrid constructions containing 3'-nontranslated viral DNA (yeast 5') or 5'-nontranslated viral DNA (yeast 3') as well as a construction with both 5'- and 3'-nontranslated viral DNA also have been made. A comparison of these constructions for levels of HBcAg expression indicates that the strongest contributor to the high levels of protein is the presence of 5'-flanking sequences which are yeast-derived; secondarily, a significant improvement can be achieved if the 3'-flanking sequences also are yeast-derived. The high abundance of HBcAg in the highest producer is explicable in part on the basis of the very high stability in yeast cells of HBcAg polypeptides. Analysis of the HBcAg coding sequence reveals a very low index of codon bias for S. cerevisiae, largely discounting codon usage as a contributor to the high level of protein obtained.

Genes↗