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Biomedical subjects

E Takeda

Publications and source records attributed to E Takeda.

At least 19 recordsLinked to original sources
PubMed1992

Decrease of pyruvate dehydrogenase phosphatase activity in patients with congenital lactic acidemia.

We developed an assay method for pyruvate dehydrogenase phosphatase activity using [1-14C]pyruvate and measured pyruvate dehydrogenase phosphatase activity in cultured skin fibroblasts from three patients with congenital lactic acidemia due to a defect in activation of the pyruvate dehydrogenase complex. The enzyme activity of their fibroblasts was significantly reduced to 50.7%, 64.6% and 63.1% of that of control fibroblasts. These observations suggest that the defect in activation of the pyruvate dehydrogenase complex in these patients might be due to a reduction in pyruvate dehydrogenase phosphatase activity.

Acidosis, Lactic↗
PubMed1992

Mutation of E1 alpha gene in a female patient with pyruvate dehydrogenase deficiency due to rapid degradation of E1 protein.

A mutation of an insertion of 4 bp in the gene for the alpha subunit of pyruvate dehydrogenase (E1 alpha) was found in a female with pyruvate dehydrogenase deficiency due to the rapid degradation of alpha and beta subunit proteins of pyruvate dehydrogenase. This mutation caused a frameshift that altered the amino acid sequence and created a premature stop codon. This 4-bp insertion has been found in an unrelated female patient with E1 alpha deficiency. It is rare that the same mutation is found in unrelated patients with this rare inborn error of metabolism. Furthermore, short deletions or duplications in the E1 alpha gene of patients with E1 alpha deficiency have been found only in exons 10 and 11. These exons may be hot spots for the mutations by the recombinational processes. This patient was heterozygous for the normal and a mutant allele. However, in most of the cultured skin fibroblasts from this patient, the mutant allele was expressed. These observations suggest that the X chromosome containing the normal allele was predominantly inactivated so that she developed lactic acidaemia and neurological abnormalities despite being heterozygous. The mutant alpha subunit protein failed to form a stable structure of pyruvate dehydrogenase, so that both alpha and beta subunit proteins were degraded rapidly.

Alleles↗
PubMed1992

A female patient with Lesch-Nyhan syndrome.

The authors report the second case of a female with typical Lesch-Nyhan syndrome. She exhibited athetoid movement, self-multilation, mental retardation and spasticity. Laboratory investigations revealed hyperuricaemia, hyperuricosuria and decreased erythrocyte hypoxanthine guanine phosphoribosyl transferase activity. She has normal female external genitalia and karyotype. Her parents are non-consanguineous and there is no family member with gout, nephropathy or any psychoneurological disorder. To prevent self-stimulation, it was necessary to fix the patient's upper extremities to the backrest of her wheelchair. The authors also describe an apparatus that limits elbow flexion.

Child↗
PubMed1992

Suspected distinct activation pathways of human lymphocytes induced by antilymphocyte globulin and anti-CD3 monoclonal antibody result in different secretion of hematopoietic colony-stimulating activities.

We evaluated the activation sequence of peripheral blood lymphocytes from healthy donors using different mitogens, including antilymphocyte globulin (ALG), anti-CD3 monoclonal antibody (OKT3), and phytohemagglutinin (PHA). Blood mononuclear cells stimulated by ALG, OKT3 and PHA incorporated 3H-thymidine in the same way. When enriched T cells were tested in the presence of interleukin-1 alpha (0 to 100 U/ml, incorporation of 3H-thymidine was greater in those cells stimulated by ALG than by PHA. OKT3 did not activate enriched T cells. Thymidine incorporation was reduced to less than 50% of maximum concentrations by the addition of 10(-7) mol/1,25-dihydroxyvitamin D3 (vit D3) in PHA- or OKT3-activated cells. However, the inhibitory effect of vit D3 was not apparent in ALG-activated cells. Production of granulocyte-macrophage colony-stimulating factor and interleukin-3 by lymphocytes upon activation was consistently higher when cells were treated with ALG or PHA than with OKT3. Taken together, the data indicate that there appear to be distinct functional mechanisms between ALG- and OKT3-induced lymphocyte activation that lead to characteristic immunohematologic events.

Antibodies, Monoclonal↗
PubMed1992

[Clinical study on cefprozil fine granules].

Cefprozil (CFPZ, BMY-28100), a new non-ester cephem, was administered to 15 pediatric patients with infectious diseases. The patients included 6 boys and 9 girls from 10 months to 11 years old and they were given oral doses of 18.5-41.7 mg/kg/day for 3 to 8 days. Clinical efficacies were excellent in 3 cases and good in 12 cases, hence the total efficacy rate was 100%. Eosinophilia occurred in 1 case as side effect of the drug, but no other side effects were not found during or after the treatment.

Administration, Oral↗
PubMed1992

[A case of periodic ataxia].

We report a sporadic case of periodic ataxia characterized by recurrent attacks of vertigo and ataxia. A 62-year-old male was known to have nystagmus at the age of 18. He has had recurrent episodes of vertigo and ataxia since the age of 48. During an attack remarkable downbeat nystagmus, limb ataxia predominant in the lower extremities and ataxic gait were present. MRI demonstrated an atrophy of the anterosuperior region of the cerebellar vermis. Vertical nystagmus, dysesthesia of gloves and stocking type and deep sensory disorder persisted during interictal intervals. There is no finding which supports this case to be vascular disorder, congenital anomaly, tumor, infection or demyelinating disease. We thought this case to be periodic ataxia and to belong to vestibulocerebellar ataxia reported by Farmer and his colleagues.

Cerebellar Ataxia↗
PubMed1991

Screening for disorders of pyruvate metabolism by measuring the ratio of the rates of lactate production and pyruvate decarboxylation in cultured skin fibroblasts.

We assayed the rates of lactate production from [1-14C]pyruvate and decarboxylation of [1-14C]pyruvate in cultured skin fibroblasts from 8 patients with disorders of pyruvate metabolism and 16 control subjects. The disorders of pyruvate metabolism could be more readily detected by measuring the ratio between the rates of lactate production and pyruvate decarboxylation by cultured skin fibroblasts than by measuring either the rate in isolation.

Acidosis, Lactic↗
PubMed1991

Clinical and biochemical findings in parents of children with vitamin D-dependent rickets Type II.

Vitamin D-dependent rickets type II is a rare disease caused by a disorder of the receptor for 1, 25-dihydroxyvitamin D (1, 25(OH)2D). Several parameters of this receptor-effector system were investigated to obtain biochemical information on the presumed heterozygotes of vitamin D-dependent rickets type II in parents of five patients and in their age-matched controls. It was found that the serum concentrations of 1, 25-(OH)2D and 24,25-dihydroxy-vitamin D (24,25(OH)2D), and the ratio of 1,25-(OH)2D/24,25-(OH)2D differed significantly in the parents from those of the patients and the respective control groups. In the parents' cultured skin fibroblasts, the activity of 25-hydroxyvitamin D-24-hydroxylase induced by 10(-8) mol/L 1, 25-(OH)2D3 ranged from 50 to 82% of that of their controls (versus 1-13% of controls for the patients). The binding capacity of the parents' [3H]1, 25-(OH)2D3 to the nucleus was 38-54% of that of their control subjects (versus 7-27% of controls for the patients). The parents' values were thus in a range between those of the patients and the control groups. These findings suggest that, in the parents, a partial impairment of the receptor system for 1, 25-(OH)2D led to an imbalance of vitamin D metabolism, thus confirming that vitamin D-dependent rickets type II is an autosomal recessive inherited disease. Serum concentrations of 1, 25-(OH)2D and 24, 25-(OH)2D may provide useful parameters for detecting heterozygotes of this disease.

24,25-Dihydroxyvitamin D 3↗
PubMed1991

Effects of deoxyadenosine on ribonucleotide reductase in adenosine deaminase-deficient lymphocytes.

To explore the relationship between ribonucleotide reductase and immunodysfunction in adenosine deaminase deficiency, the effects of deoxyadenosine on ribonucleotide reductase in ADA-deficient lymphocytes was investigated. An assay system for ribonucleotide reductase in intact permeabilized lymphocytes was developed to approximate physiological conditions. The activity of cytidine diphosphate (CDP) reductase in resting but not in proliferating lymphocytes in culture was inhibited by 1 to 10 mumol/L deoxyadenosine. The resting cells were protected from the toxicity of 1 mumol/L deoxyadenosine by 5 mmol/L nicotinamide or 30 mumol/L deoxycytidine and from that of 10 mumol/L deoxyadenosine by 30 mumol/L deoxycytidine. These findings suggest that depletion of nicotinamide adenine dinucleotide might be the principal cause of death in resting lymphocytes with ADA deficiency. It is concluded that the mechanism of deoxyadenosine toxicity on non-replicating lymphocytes, which may not be mediated by ribonucleotide reductase inhibition, is closely related to the mechanism of immunodysfunction in patients with ADA deficiency.

Adenosine Deaminase↗
PubMed1991

The effect of 1,25-dihydroxyvitamin D3 on the growth and differentiation of cultured human outer root sheath cells from normal subjects and patients with vitamin D-dependent rickets type II with alopecia.

We examined the effect of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) on the growth and differentiation of cultured human hair outer root sheath cells (ORSC) from normal subjects and patients with vitamin D-dependent rickets type II (DDR-II) with alopecia. 1,25(OH)2D3 dose-dependently suppressed the plating efficiency, clonal growth, and DNA synthesis of normal ORSC. It enhanced the cornified envelope formation and caused morphological changes in the cells. All results indicated the existence of specific receptors for 1,25(OH)2D3 in the ORSC, and suggest that 1,25(OH)2D3 is a potent inhibitor of proliferation of ORSC as well as a stimulator of terminal differentiation. However, the cells from DDR-II patients with alopecia did not respond to 1,25(OH)2D3, suggesting a lack of the specific receptors in the cells. The differences in the cellular response to the hormone between the normal ORSC and those from the patients were apparent and easily distinguishable, therefore this experiment may be a rapid and simple diagnostic test for DDR-II patients with alopecia. Large number of hairs were difficult to obtain from patients with alopecia, and we developed a new culture method to accomplish these studies from a few plucked hair follicles. Our system may be useful in the culture of ORSC from limited number of follicles, and could be utilized to analyse the cellular characteristics of ORSC in patients with hair diseases.

Alopecia↗
PubMed1991

Therapeutic effect of sodium dichloroacetate on visual and auditory hallucinations in a patient with MELAS.

We report a patient with mitochondrial myopathy, encephalopathy, lactic acidosis, and strokelike episodes who experienced visual and auditory hallucinations. His blood and cerebrospinal fluid lactate levels were remarkably elevated. Sodium dichloroacetate was administered orally at doses of 12.5 to 100 mg/kg/day. On normalization of the lactate levels, the hallucinations disappeared.

Acidosis, Lactic↗
PubMed1991

Diagnosis of atlantoaxial subluxation in Morquio's syndrome and spondyloepiphyseal dysplasia congenita.

Compression of the spinal cord due to atlantoaxial subluxation was diagnosed in a patient with Morquio's syndrome and in another with spondyloepiphyseal dysplasia (SED) congenita by cervical radiography and magnetic resonance imaging (MRI). The patient with Morquio's syndrome, a 15 year old boy, had no neurologic symptoms and his somatosensory evoked potential (SSEP) was normal. However, MRI demonstrated spinal cord compression at C1-C2. In contrast, the patient with SED congenita, an 11 year old girl, had neck pain, hyperreflexia and loss of vibration sense in both legs. These findings were explained by the absence of P3 and later waves in SSEP and by compression of the spinal cord observed on MRI. Both SSEP and MRI should be used for evaluating disorders in which atlantoaxial subluxation might be present.

Adolescent↗
PubMed1991

Demonstration of an unstable variant of pyruvate dehydrogenase protein (E1) in cultured fibroblasts from a patient with congenital lactic acidemia.

The deficiency of pyruvate dehydrogenase enzyme complex causes congenital lactic acidemia and devastating neurologic abnormalities in newborns and children. In the majority of cases, the basic defect appears to be in the pyruvate dehydrogenase (E1) component, which consists of two subunits, alpha and beta. Whereas some patients are deficient of a single subunit, in other patients both subunits of E1 are missing. To find out why two proteins were deficient, we investigated the cultured fibroblasts of a female patient who had missing E1-alpha and E1-beta protein bands on Western blot. Radiolabeling-immunoprecipitation studies with 35S-methionine revealed that patient fibroblasts synthesized normal sized precursor E1-alpha and E1-beta proteins, which were presumably transported into mitochondria and processed into normal sized mature proteins. However, pulse-chase analysis showed that alpha- and beta-proteins were degraded rapidly compared to normal. Our findings proved that alpha- and beta-subunits were synthesized and processed normally but failed to form a stable structure for incorporation into the pyruvate dehydrogenase complex.

Cells, Cultured↗
PubMed1991

A unique mutation in the vitamin D receptor gene in three Japanese patients with vitamin D-dependent rickets type II: utility of single-strand conformation polymorphism analysis for heterozygous carrier detection.

Vitamin D-dependent rickets type II is a hereditary disease resulting from a defective vitamin D receptor. In three Japanese patients with vitamin D-dependent rickets type II whose fibroblasts displayed normal cytosol binding and impaired nuclear uptake of 1,25-dihydroxyvitamin D3, western, Southern, and northern analyses failed to disclose any abnormalities in vitamin D3 receptor protein and its gene. Exons 2 and 3 of the vitamin D receptor cDNA, which encode the DNA-binding domain consisting of two zinc fingers, were amplified by PCR and sequenced to identify the specific mutations in the vitamin D receptor gene. In the three patients and one normal control a T-to-C transition was found in the putative initiation codon, while this transition was not observed in another normal control. This finding suggested that an original initiation codon was located at positions 10-12 in the human vitamin D receptor cDNA sequence reported previously. In contrast, a unique G-to-A transition at position 140 in exon 3, resulting in substitution of arginine by glutamine at residue 47, was revealed only in these three patients. The arginine at 47 is located between two zinc fingers and is conserved within all steroid hormone receptors. Therefore, it is highly conceivable that this amino acid substitution is responsible for the defect of the vitamin D receptor in the patients. Single-strand conformation polymorphism analysis of amplified DNA confirmed that all patients were homozygous and that parents from one family were heterozygous carriers for this mutation.

Amino Acid Sequence↗
PubMed1990

Effect of long-term treatment with massive doses of 1 alpha-hydroxyvitamin D3 on calcium-phosphate balance in patients with vitamin D-dependent rickets type II.

Three patients with vitamin D-dependent rickets type II were given massive doses of 1 alpha-hydroxyvitamin D3 for 29 to 36 months and their calcium-phosphate balance was studied during treatment and one month after cessation of treatment. During treatment fasting hypercalciuria was observed in patient 1 and an increased rate of calcium excretion after calcium loading in patients 1 and 2. In these patients, calcium excretion was parallel with the serum 24,25-dihydroxyvitamin D concentration, which may reflect the level of receptor for 1,25-dihydroxyvitamin D. These findings suggested that the responsiveness to 1,25-dihydroxyvitamin D improved during long-term treatment of these two patients with vitamin D-dependent rickets type II.

Calcium↗
PubMed1990

25-Hydroxyvitamin D-24-hydroxylase in phytohemagglutinin-stimulated lymphocytes: intermediate bioresponse to 1,25-dihydroxyvitamin D3 of cells from parents of patients with vitamin D-dependent rickets type II.

A method for assay of 25-hydroxyvitamin D-24-hydroxylase (24-hydroxylase) activity in phytohemagglutinin (PHA)-stimulated lymphocytes was applied to determine whether vitamin D-dependent rickets type II (VDDR II) is hereditary. In normal lymphocytes incubated with PHA for 3 days, maximal and half-maximal responses of 24-hydroxylase were observed after exposure to 10(-8) mol/L and (1.3 +/- 0.4) x 10(-9) mol/L 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3], respectively. These responses were similar to those of cultured skin fibroblasts. In contrast, after exposure to 10(-8), 10(-7), and 10(-6) mol/L 1,25-(OH)2D3, no 24-hydroxylase activity was detected in cells from patients with VDDR II, and intermediate activity was observed in cells from their parents. These findings indicated the presence of an intracellular receptor-effector system for 1,25-(OH)2D3 in peripheral lymphocytes. Heterozygotes of VDDR II could be identified, and autosomal recessive inheritance of the disease was demonstrated. Detection of heterozygotes of this disease was not possible by assay of inhibition of thymidine incorporation, another marker of the function of 1,25-(OH)2D3 in PHA-stimulated lymphocytes. Therefore, assay of 24-hydroxylase induction reflected the receptor status more closely than assay of inhibition of DNA biosynthesis. The assay of 24-hydroxylase activity in PHA-stimulated lymphocytes described here will be useful for diagnosis of VDDR II and study of families of patients with this disease.

24,25-Dihydroxyvitamin D 3↗
PubMed1990

[The effect of 1, 25-dihydroxyvitamin D3 on cultured human hair follicle cells from a patients with vitamin D-dependent rickets type II with alopecia].

We examined the effects of 1, 25-dihydroxyvitamin D3 on the growth and differentiation of cultured human hair follicle cells from a patient with vitamin D-dependent rickets type II [DDR-II] with alopecia. In the presence of 100 nM 1, 25-dihydroxyvitamin D3, the clonal growth of normal hair follicle cells was inhibited and terminal differentiation was markedly stimulated. However, the cells from a patient with DDR-II with alopecia did not respond to the hormone, suggesting a lack of the specific receptors in the cells. The difference in the cellular response to the hormone between the normal hair follicle cells and those from a patient were clear and easily distinguished, and these studies may provide a basis for the rapid diagnosis of DDR-II. Large number of hairs were difficult to obtain from patients with alopecia, and we developed a new culture method to accomplish these studies. Our system may be useful in the culture of HFC from only a few hair follicles.

Alopecia↗