Search PubMed⌕ Search

Biomedical subjects

B A Cooper

Publications and source records attributed to B A Cooper.

At least 55 records · Page 3Linked to original sources
PubMed1988

Identification of a unique type of thrombopathy of human platelets: defect in the exposure of active fibrinogen receptors in a patient with Friedreich's ataxia.

Platelets of a patient with Friedreich's ataxia have been investigated because of a codiagnosis of thrombasthenia. No aggregation occurred in response to adenosine diphosphate, platelet activating factor-acether, a stimulatory antiplatelet monoclonal antibody, or phorbol myristate acetate, although platelet aggregation could be induced with thrombin, the calcium ionophore A23187, or high concentrations of collagen. Shape change, adenosine triphosphate secretion, and the responses of the platelets' protein phosphorylation systems to all agonists were normal. Immunologic analysis of the patient's radiolabeled platelet surface proteins revealed normal levels of glycoproteins IIB and IIIa. However, no iodine 125-fibrinogen binding occurred after stimulation of the patient's platelets with adenosine diphosphate. In contrast, pretreatment of the patient's platelets with the proteolytic enzyme alpha-chymotrypsin resulted in the exposure of active 125I-fibrinogen binding sites. The patient's platelets exhibited normal aggregation to fibrinogen after their pretreatment with chymotrypsin and with elastases derived either from porcine pancreas or from human granulocytes. A murine monoclonal antibody directed against the human platelet membrane glycoproteins IIb and IIIa calcium-dependent epitope and rabbit polyclonal anti-human platelet membrane and human anti-P1A1 antibodies immunoprecipitated glycoproteins IIb and IIIa and a 66 kd cleavage product of glycoprotein IIIa from sodium dodecyl sulfate-Triton X-100 extracts of the patient's proteolytically treated platelets. The patient appears to exhibit a unique type of thrombopathy involving a defect in the exposure of fibrinogen receptors. The association between the neurologic disorder and the platelet defect is still unclear.

Adult↗
PubMed1988

Very low birth weight infants at 8 and 11 years of age: role of neonatal illness and family status.

The intellectual and educational status of 108 children with very low birth weight (less than or equal to 1,500 g), born from 1965 to 1978, was evaluated and tested on standard tests (eight children with severe handicaps were excluded) at 8 years of age. Fifty-seven were further evaluated at 11 years of age. Six categorical outcomes were defined a priori, based on the Wechsler Intelligence Scale for Children-Revised IQ and discrepancies between Verbal and Performance scores and Bender Gestalt Test score. Proportions at 8 years of age were: 4.6% very low IQ (below 70), 13.9% low IQ (70 to 84), and, for those with IQ greater than 84, 12.0% language disability, 12.0% performance disability, 21.4% visual-motor disability, and 36.1% normal. Learning disabilities, determined by discrepancies between IQ and Wide Range Achievement Test scores, included 16.7% of all children. Outcome proportions at 11 years of age were essentially comparable to those at 8 years of age; outcome constancy was present in 52.6%. Ratings of neonatal illness and parent education level strongly influenced the likelihood of outcome at 8 years of age. When ratings were dichotomized (ie, low v high neonatal illness and low v high parent education), the level of neonatal illness primarily influenced the likelihood of normal outcome, whereas the level of parent education influenced the degree of severity of the disability.

Achievement↗
PubMed1988

T-cell depletion with ricin A-chain T101 in allogeneic bone marrow transplantation to prevent severe graft-versus-host disease.

Bone marrow cells from 10 marrow transplant donors were treated with an immunotoxin, which couples A-chain of ricin with a monoclonal anti-T-cell antibody T101 to prevent graft-versus-host disease by the elimination of mature T-cells. Marrow cells treated with the anti human T-cell immunotoxin (IT101) were cultured for erythropoietic colonies, granulocytic colonies, and multilineage hematopoietic colonies (CFU-GEMMT) containing myeloid cells and T-cells, and optimal conditions were defined for the elimination of T-cells present in the harvested donor marrow prior to marrow transplantation. Marrow samples purged with IT101 were examined for residual T-cells by fluorescence activated cell sorting, using anti-T-cell antibodies, [3H]-thymidine incorporation after PHA stimulation, and an assay for clonogenic T-cells. The number of T-cell colonies observed in the treated marrows was less than 5% of the number in comparable unpurged donor marrows. Treatment with IT101 did not alter the plating efficiency of hematopoietic colonies compared to untreated donor marrow cells. These data suggest that multilineage progenitors responsible for the reconstitution of the recipient hematopoietic system are not affected by marrow IT101 purging. The clinical data on 10 patients indicate that the depletion of T-cells in the donor marrow with IT101 is effective in decreasing the severity of acute graft-versus-host disease in allogeneic marrow transplantation and warrants continued investigation.

Adult↗
PubMed1987

Vitamin B12 responsive homocystinuria and megaloblastic anemia: heterogeneity in methylcobalamin deficiency.

A male infant with methyl-B12 deficiency (cblE) presented at age 6 weeks with lethargy, staring spells, and vomiting. He later became hypotonic and unresponsive to stimuli and required intubation and ventilation. He had homocystinuria and hypomethioninemia with megaloblastic anemia but normal serum folate and vitamin B12 concentrations. No methylmalonic aciduria was detected. Fibroblasts, cultured from the patient, were unable to grow in medium in which homocysteine replaced methionine and incorporated abnormally small amounts of [14C]-methyl-tetrahydrofolate but normal amounts of [14C]-propionate into protein. Methyl-B12 content of fibroblasts was low, while the adenosyl-B12 content was normal. Methionine synthase activity was decreased when the assay was performed under both optimal and suboptimal reducing conditions, suggesting heterogeneity in the cblE disease. The patient responded dramatically to hydroxocobalamin treatment. Homocystinuria disappeared after 10 days of therapy, and methionine was normalized after 3 weeks. Psychometric testing at age 15 months showed a developmental age of 9 months.

Anemia, Macrocytic↗
PubMed1987

Inherited disorders of vitamin B12 metabolism.

Inherited disorders of vitamin B12 include those which involve the inability of the vitamin to be absorbed from the gut and transported to the appropriate tissues, and those in which the vitamin is not utilised by target cells. The former include intrinsic factor abnormalities, selective malabsorption of vitamin B12 with proteinuria, and deficiencies of transcobalamin I and transcobalamin II. The latter include a defect in the release of free vitamin B12 from lysosomes (cblF), and defects in the formation of both vitamin B12 cofactors (cblC, cblD) or of adenosyl-B12 (cblA, cblB) or methyl-B12 alone (cblE, CblE variant). This article reviews the major clinical manifestations of these diseases, and provides an approach to the diagnosis of transcobalamin II deficiency and the cbl mutations using cultured cells.

Humans↗
PubMed1986

Reconstitution of hematopoiesis after bone marrow purging with ricin A chain immunotoxin.

Bone marrow cells from healthy individuals were treated with an antihuman T cell immunotoxin (IT101). The treated marrow cells were cultured for multilineage hematopoietic colonies (CFU-GEMMT) containing various myeloid cell lineages and T lymphocytes, erythroid colonies (BFU-E), and granulocytic colonies (CFU-C). Optimal conditions were defined for the elimination of clonogenic human T leukemic cells artificially admixed with bone marrow cells. Marrow purging with IT101 led to the restoration of hematopoietic colony formation which was abolished in the presence of T leukemic cells. Mixed colonies grown from bone marrow treated with IT101 contained cells that reacted with monoclonal anti-T-cell antibodies. This suggests that pluripotent stem cells are not affected by marrow IT101 purging and may be able to regenerate lymphoid as well as myeloid lineages.

Antibodies, Monoclonal↗
PubMed1986

Recognition of deficiency of vitamin B12 using measurement of serum concentration.

Of 504 patients with low concentrations of vitamin B12 in serum by microbiologic assay (less than 120 pg/ml) in whom clinical information was available to evaluate vitamin B12 status, 109 (22%) were found to have clinically important deficiency of vitamin B12, and another 10 had pernicious anemia with deficient serum levels of both vitamin B12 and folate. Serum from patients deficient in vitamin B12 was assayed by several commercially available assay techniques. These used either purified or impure preparations of gastric intrinsic factor as binder, extracted cobalamins with either heat or alkali ("no boil") and separated bound from free vitamin B12 either with activated charcoal or by binding the intrinsic factor to glass beads ("solid state"). These kits were purchased commercially from Becton-Dickinson Co. (SimulTrac), BioRad Corp. (Quantaphase), Amersham Corp. (Vitamin B12/folate radioassay) and Corning Medical and Scientific (Immophase). Serum vitamin B12 concentrations assayed in sera from patients deficient in vitamin B12 overlapped the normal range in 6% of all samples assayed by techniques using purified intrinsic factor assays (BioRad, Amersham, and the "blocked" SimulTrac assay), but no such overlap was found between deficient and nondeficient sera assayed with the solid-state pure intrinsic factor assay (Corning), the "unblocked" SimulTrac, or Euglena gracilis. It would appear that (1) radiodilution assays extracting serum by boiling and binding vitamin to binder fixed on a solid matrix may be the most reliable available at this time. These may be as reliable as microbiologic assay for separation of patients with deficiency from those without deficiency.(ABSTRACT TRUNCATED AT 250 WORDS)

Anemia, Pernicious↗
PubMed1986

New disorder of vitamin B12 metabolism (cobalamin F) presenting as methylmalonic aciduria.

An infant with vitamin B12-responsive methylmalonic aciduria and no homocystinuria or megaloblastic anemia presented with stomatitis, glossitis, convulsions, and developmental delay. Cultured fibroblasts showed defective incorporation of both [14C]5-methyltetrahydrofolate and [14C]propionate into protein by whole cells and a decrease of methionine synthase activity in cell extracts. Despite excessive incorporation of [57Co]cyano-B12 by fibroblasts from the patient, free vitamin B12 was unable to efflux from lysosomes, and, therefore, synthesis of both adenosyl-B12 and methyl-B12 was impaired.

5-Methyltetrahydrofolate-Homocysteine S-Methyltran↗
PubMed1986

The use of color in the environment of the elderly to enhance function.

Empirical evidence suggests that the functional level of the institutionalized elderly is favorably affected by enriching the environment with the specific use of color and light. Evidence of the validity of this supposition would form a worthwhile contribution to geriatric rehabilitation by promoting the independence of the elderly in the area of activities of daily living. The quality of literature on the appropriate use of environmental color for an institutionalized geriatric population is limited, being primarily descriptive in nature. In general, visual enhancement by the selective use of color is advocated to minimize the adverse effects of sensory deprivation and to enhance mood, whereas color coding and cueing are directed toward improving function. Faced with a variable literature base and a scarcity of studies that scientifically approach the question of what effect visual enhancement might have on function in the elderly, the authors of this paper are conducting a pilot study with the following objectives: To demonstrate that color cueing (in the form of color contrast applied to key objects in the environment) and increased lighting can enhance the performance of activities of daily living in an institutionalized elderly population. To study the concept that improvement in activities of daily living corresponds with improvement in the patient's mood and feelings of self-worth. To evaluate the effect of color and lighting changes in the environment on various aspects of behavior. It is hypothesized that improvement in behavior will accompany increased functional independence. Thus, we would expect to see a relationship between aspects of behavior and those aspects of mood and activities of daily living currently under investigation.

Aged↗
PubMed1985

Defect in vitamin B12 release from lysosomes: newly described inborn error of vitamin B12 metabolism.

Cultured diploid fibroblasts from a patient with a previously undescribed inborn error of cobalamin metabolism accumulate unmetabolized, nonprotein-bound vitamin B12 in lysosomes. These cells are able to endocytose the transcobalamin II-B12 complex and to release B12 from transcobalamin II. The freed vitamin B12 is not released from lysosomes into the cytoplasm of the cell. This suggests that there is a specific lysosomal transport mechanism for vitamin B12 in the human.

Biological Transport↗
PubMed1985

Prenatal vitamin B12 therapy of a fetus with methylcobalamin deficiency (cobalamin E disease).

A child presented early in life with homocystinuria and megaloblastic anaemia which responded to hydroxocobalamin (OH-B12) therapy. Mental development has been subnormal since birth. Fibroblasts from this patient contained low levels of methylcobalamin (CH3-B12) and incorporated less 14C from labelled 5-methyltetrahydrofolate (14CH3H4PteGlu) into methionine. Methionine synthase activity was more thiol-dependent in the patient's fibroblasts than it was in normal cells. Studies on fibroblasts from the parents confirmed that both are heterozygous for this disorder. When the mother became pregnant again, prenatal diagnosis was attempted by use of cultured amniocytes obtained at 16 weeks' gestation. Values for incorporation of 14CH3H4PteGlu into methionine by intact cells and the thiol requirement of methionine synthase were abnormal in these amniocytes but these features did not conclusively identify the fetus at risk as being homozygous for the abnormality. Only 8% of the 57Co vitamin B12 incorporated by the fetal amniocytes was present as CH3-B12 compared with 29% and 40% in two control amniocyte lines and 37% and 32% in fibroblasts from the parents who are obligate heterozygotes. These studies suggested that the fetus had CH3-B12 deficiency. The mother was treated with OH-B12 (1 mg twice weekly, intramuscularly) from 25 weeks' gestation. The baby was clinically normal at birth without any evidence of homocystinuria or anaemia, and has been maintained on OH-B12 (1 mg twice weekly). Studies on fibroblasts from the baby confirmed the diagnosis of CH3-B12 deficiency (cobalamin E disease). At 6 months of age, growth and development remain normal.

Adult↗
PubMed1985

Endogenous folate of normal fibroblasts using high-performance liquid chromatography and modified extraction procedure.

The endogenous levels of the various folate monoglutamate compounds in cultured human fibroblasts were determined using high-performance liquid chromatography for the separation of folate monoglutamate. Endogenous folates were converted to monoglutamate forms using conjugase enzyme present in rat serum and incubation was carried out at pH 6.5. This minimized folate coenzyme interconversion during processing. Using methanol for precipitation of protein instead of heat minimized degradation of labile folates. Recovery of all folates except 10-formyltetrahydrofolic acid (10-CHO H4PteGlu) using this procedure was more than 90%. Disruption of cells by boiling appeared to cause less postextraction changes of cell folates than did freezing and thawing or sonication. When heat to release endogenous folate, conjugase treatment with rat serum at pH 6.5, and precipitation of protein with methanol were used, more than half of the intracellular folate of normal fibroblasts in confluent growth was 5-methyltetrahydrofolic acid (5-CH3 H4PteGlu), and 10-CHO H4PteGlu and tetrahydrofolic acid (H4PteGlu) comprised 29 and 6%, respectively.

Cells, Cultured↗
PubMed1985

A model for implementing color contrast in the environment of the elderly.

Much has been written on the use of color as a functional facilitator in the environment of the elderly, but little information is available on how to implement it. This paper a) restates the main age-acquired visual defects, b) critically examines the literature on the use of environmental color, and then c) proposes a model which incorporates the factors that enhance visual clarity and Johannes Itten's rules of color contrast. Implicit in the application of color to enhance vision is a clear understanding of the main functional purpose of the area to be heightened.

Activities of Daily Living↗
PubMed1985

Interaction of 3-deaza-adenosine, a phospholipid methyltransferase inhibitor, on the production of pluripoietins from human peripheral T cells.

The formation of mixed colonies is dependent upon the addition of leucocyte-conditioned medium prepared with the mitogenic lectin phytohemagglutinin (PHA). The activation of peripheral T cells by PHA revealed an increase in methylated phospholipids and subsequently led to the release of stimulatory activities into the media. Stimulatory activities supporting mixed colony formation could not be detected when peripheral T cells were preincubated with the methyltransferase inhibitor 3-deaza-adenosine for 60 min before PHA stimulation. The addition of 3-deaza-adenosine to the culture at day 0 demonstrated no inhibitory effect on multilineage colony formation. The data suggest that the activation of human peripheral T cells from healthy volunteers by the mitogenic lectin PHA causes an increase in methylated phospholipids and might be an important signal for the mitogenesis of T-lymphocytes, which subsequently lead to the production of stimulatory activities promoting the growth of pluripotent stem cells.

Humans↗
PubMed1984

Homocystinuria and megaloblastic anemia responsive to vitamin B12 therapy. An inborn error of metabolism due to a defect in cobalamin metabolism.

We describe an inborn error of vitamin B12 metabolism in an infant who had severe developmental delay, megaloblastic anemia, and homocystinuria. There was no evidence of methylmalonic aciduria or deficiency of folate or vitamin B12. Treatment with hydroxocobalamin, but not with cyanocobalamin and folic acid, resulted in rapid clinical and biochemical improvement. Cultured fibroblasts showed an absolute growth requirement for methionine, defective incorporation of radioactivity from [14C]5-methyltetrahydrofolate into protein, and normal incorporation of radioactivity from [14C]propionate, thus assigning the intracellular defect to methionine synthesis. The proportion of intracellular methylcobalamin in the fibroblasts was decreased, but that of 5'-deoxyadenosylcobalamin was normal. Methionine synthetase activity in cell extracts was normal, as was cobalamin incorporation into cultured cells. This defect differs from those described previously in being limited to methylcobalamin accumulation and defective use of 5-methyltetrahydrofolate by intact cells with normal activity of methylmalonyl CoA mutase.

5-Methyltetrahydrofolate-Homocysteine S-Methyltran↗