Biomedical subjects

K Tada

Publications and source records attributed to K Tada.

At least 217 records · Page 12Linked to original sources

PubMed1992

[Clinical evaluation of effects of KRN8601 (rhG-CSF) on neutropenia].

Clinical effects of KRN8601 (recombinant human granulocyte colony-stimulating factor:rhG-CSF) were studied in 26 patients with chronic neutropenia including 4 Kostmann's disease, 1 Shwachman's syndrome, 1 Lonsdale's syndrome, 1 glycogen storage disease Ib-associated, 6 chronic benign, 5 chronic hypoplastic, 2 cyclic, 4 autoimmune and 2 miscellaneous neutropenia. The patients were given rhG-CSF intravenously at doses of 20-540 micrograms/m2 or subcutaneously at doses 20-400 micrograms/m2, over the periods of 2-32 weeks. Increases in neutrophil counts occurred after rhG-CSF administration in 23 of the 26 patients. Patients with Kostmann's disease, Shwachman's syndrome and chronic hypoplastic neutropenia responded poorly compared to patients with other types of neutropenia. There were no serious side effects which caused interruption of the study. These results indicated a beneficial effect of KRN8601 in various types of chronic neutropenia.

Adolescent↗

PubMed1992

[Prenatal diagnosis of inborn error of amino acid metabolism].

Prenatal diagnosis of inborn errors of amino acid metabolism was discussed from the viewpoints of its purpose, ethical problems, analysis methods, and sampling methods of the fetal tissues. In addition to the general discussion, our results of the prenatal diagnosis of 20 cases with nonketotic hyperglycinemia (NKH) were also reported. Nineteen cases were diagnosed by the enzymatic method, while one Finnish case was successfully diagnosed by DNA analysis, which is based on our observation that a missense mutation we identified accounts for 70% of the mutant alleles in Finland. The DNA analysis would be a great help for the prenatal diagnosis in Finland where the incidence of NKH is unusually high (1: 12,000 births).

Amino Acid Metabolism, Inborn Errors↗

PubMed1992

[Inherited amino acid transport disorders].

Disorders due to inherited amino acids transport defect are reviewed. The disorders were categorized into three types of transport defects, namely, brush-border membrane of epithelial cells of small intestine and kidney tubules (Hartnup disease, blue diaper syndrome, cystinuria, iminoglycinuria and lysine malabsorption syndrome), basolateral membrane (lysinuric protein intolerance) and membrane of intracellular organelles (cystinosis and hyperornitinemia-hyperammonemia-homocitrullinuria syndrome). Pathogenesis, clinical feature, laboratory findings, diagnosis, genetics and treatment of these disorders are described, briefly. There is not much data for the transport systems themselves, so that further investigation in molecular and gene levels for transport systems is necessary to clarify the characteristics of the transport and heterogeneity of phenotypes in inherited amino acids transport disorders.

Amino Acid Metabolism, Inborn Errors↗

PubMed1992

[Pulmonary infection caused by Mycobacterium gordonae (M. gordonae) in a healthy middle-aged male].

A 51-year-old man was admitted to our hospital in July 1989 because of an abnormality in his chest radiograph. On his yearly health check-up, an abnormality of his chest radiography was first noted in June 1988. At that time, examinations including bronchoscopy were performed but no specific diagnosis was made. On admission, his chest radiograph revealed new infiltrates at the apex of the right lung which were not present in June 1988. Three out of 5 consecutive sputum specimens after admission produced a pure growth of 100 colonies to 1+ of acid-fast bacilli (AFB). This AFB was scotochromogenic, and hydrolysis of Tween 80 at 5 days was positive. It did not reduce nitrate, and niacin test was negative. It was sensitive to ethambutol at a concentration of 5 micrograms/ml, and was not tolerant to 0.2% picric acid. We thus identified this AFB to be M. gordonae. The patient was treated with rifampicin (450 mg/day), isoniazid (400 mg/day), and ethambutol (1000 mg/day) for 9 months. After 2 months of treatment the sputum cultures became negative, and the chest radiograph showed improvement of the infiltrates. M. gordonae is considered to be one of the least pathogenic AFB to man. Most recent reports of M. gordonae infection have been in immunocompromized hosts or patients with a history of pulmonary tuberculosis. The present case is a very rare example of this organism affecting a healthy male, and thus yields new information on the pathogenesis of M. gordonae in man.

Drug Therapy, Combination↗

PubMed1991

Glycine cleavage system in astrocytes.

The localization of the glycine cleavage system was examined in the rat brain by immunohistochemistry using an antibody to P-protein (a constituent of the system). In all sites studied, the enzyme was confined to the astrocytes. The intensity of astrocyte staining varied in different brain regions, with the strongest staining being noted in the hippocampus, the cerebellar cortex, the Bergmann glia in the cerebellum and the Muller cells in the retina. The weakest staining was seen in the brainstem and spinal cord. P-protein was found to be located in the mitochondria by an ultrastructual study.

Aminomethyltransferase↗

PubMed1991

Low-density particles (W-particles) containing catalase in Zellweger syndrome and normal fibroblasts.

By both histological and biochemical criteria, peroxisomes in patients with Zellweger syndrome appear to be absent or severely deficient. By using 15-30% (wt/vol) Nycodenz/sucrose gradients to study the subcellular localization of extraperoxisomal catalase activity, a commonly used marker for mature peroxisomes, we detected a single peak of activity in Zellweger syndrome fibroblasts at an equilibrium density of 1.13 g/cm3, lower than the expected 1.17 g/cm3 of mature peroxisomes. Upon recentrifugation in either the original gradient or one with a higher salt concentration, essentially all catalase activity was recovered in fractions of the original densities. The activity of the catalase peak was further analyzed by a digitonin titration and filtration assay in combination with Triton X-100 treatment. The catalase activity passed through 0.1-microns and 0.22-microns but was retained on 0.025-microns membrane filters (mean pore size). After treatment with Triton X-100 nearly all catalase activity passed through the filters. The results from fractionations data, digitonin latency measurement, and the detergent effect on the filtration behavior suggest that catalase is not free in the cytosol of Zellweger syndrome fibroblasts as commonly thought but in particles (W-particles). Similar low-density catalase-containing particles, distinct from peroxisomes, are also found in normal fibroblasts. We found that L-alpha-hydroxyacid oxidase, another peroxisomal matrix enzyme, is also present in W-particles derived from normal and Zellweger syndrome fibroblasts. We speculate that the low-density catalase-containing W-particle may represent an immature or incomplete form of peroxisome distinct from previously described "peroxisomal ghosts" in Zellweger syndrome fibroblasts.

Biomarkers↗

PubMed1991

An immunohistochemical study of MAP2 and clathrin in gerbil hippocampus after cerebral ischemia.

Changes in MAP2 and clathrin immunoreactivity were studied in gerbil hippocampus after transient cerebral ischemia. MAP2 immunoreactivity decreased significantly by 1 h in the subiculum-CA1 and CA2 areas which correspond to reactive change, while no decrease was observed in CA1 until day 4. Before the initiation of delayed neuronal death, MAP2 immunoreactivity was not changed in CA1. On the other hand clathrin immunoreactivity increased in the pyramidal cell layer of CA1 by 3 h after ischemia and remained high for 2 days. Clathrin immunoreactivity in the pyramidal cell layer of CA1 diminished after delayed neuronal death. The transient change of clathrin was noted especially in CA1 in the period prior to delayed neuronal death. These results imply an abnormal change in clathrin turnover after ischemia, which may participate in the pathogenesis of delayed neuronal death.

Animals↗

PubMed1991

Abnormal distribution of cathepsins in the brain of patients with Alzheimer's disease.

Formalin-fixed paraffin-embedded hippocampal sections of brains with early-onset and late-onset Alzheimer's disease were studied immunohistochemically with antisera against cathepsin D and cathepsin B. In addition to the staining of neuronal perikarya, some of the senile plaques visualized by Bielshowsky silver staining and some of reactive astrocytes were positively stained with the antisera against cathepsin D and cathepsin B in brains with Alzheimer's disease. Abnormal localization of cathepsin D and cathepsin B immunoreactivity in neuronal perikarya was observed in brains with early-onset Alzheimer's disease. These findings demonstrate that the distribution of lysosomal proteases was altered in brains with Alzheimer's disease, suggesting the primary and/or secondary involvement of the lysosomal proteases in the pathological process of Alzheimer's disease.

Alzheimer Disease↗

PubMed1991

Retrospective survey of urea cycle disorders: Part 2. Neurological outcome in forty-nine Japanese patients with urea cycle enzymopathies.

We analyzed neurological data, including DQ or IQ, EEG, and CT scan, in 49 patients with urea cycle enzymopathies, all of whom were included in a retrospective survey from 1978-1988 in Japan. We classified 3 groups depending on age-at-onset: group 1 (0-28 days, N = 11), group 2 (29 days-5 years, N = 31), and group 3 (greater than 5 years, N = 7). The least DQ or IQ score and the highest CT score, representing the most severe brain damage was found in group 1, and the highest DQ or IQ and the least CT score was found in group 3. Intermediate scores of both parameters were found in group 2. There was a negative correlation between these 2 parameters (r = -0.82, P less than 0.01). Abnormal EEG during the attack-free period was predominantly observed in patients with CT abnormalities compared to those with a normal CT scan (P less than 0.01). Approximately 40% of the patients, mostly in groups 2 and 3 (92.8%) had normal findings in all 3 parameters. Thus, the magnitude of developmental abnormalities is clearly related to the degree of brain damage and to the age-at-onset of these diseases.

Brain↗

PubMed1991

Prevalence of K329E mutation in medium-chain acyl-CoA dehydrogenase gene determined from Guthrie cards.

Medium-chain acyl-CoA dehydrogenase (MCAD) deficiency is an autosomal recessive disorder that has been associated with sudden infant death syndrome and a condition resembling Reye's syndrome. The point mutation K329E is thought to be the commonest mutation causing MCAD deficiency in caucasian patients. The prevalence of this mutation was determined by use of dried blood spots on Guthrie cards obtained during neonatal screening programmes. 12 carriers were identified among 479 newborn babies in Britain, 5 among 353 in Australia, and 5 among 536 in North America but none among 500 in Japan. Since presymptomatic diagnosis and appropriate dietary management can prevent life-threatening episodes in MCAD deficiency, population-based DNA screening for this potentially fatal disorder might be justified in countries with a high frequency of this mutation.

Acyl-CoA Dehydrogenases↗

PubMed1991

Glutamate triggers internucleosomal DNA cleavage in neuronal cells.

Glutamate neurotoxicity is responsible for neuronal loss associated with numerous obstinate disorders. In this report, the mechanism of glutamate neurotoxicity was investigated on a viewpoint of DNA degradation. We found that chromosomal DNA of cultured neurons was degraded into nucleosomal-sized DNA fragments by the addition of glutamate, prior to the glutamate-induced neuronal death. Both the neuronal death and DNA fragmentation were prevented by the inhibitors of endonucleases and mRNA synthesis. Furthermore, an injection of glutamate into the rat hippocampi resulted in DNA fragmentation with the similar time course observed in neuronal death in vitro. These results suggest that the glutamate neurotoxicity involves an active suicide process which leads to neuronal death through internucleosomal DNA cleavage.

Animals↗

PubMed1991

Monoclonal antibodies defining distinct epitopes of the human IL-2 receptor beta chain and their differential effects on IL-2 responses.

We have established and characterized five new monoclonal antibodies (mAbs) which specifically immunoprecipitate the human interleukin-2 receptor beta chain (IL-2R beta). One of them, TU30, recognizes the intracytoplasmic 'serine-rich region' of IL-2R beta that is critical for IL-2 signal transduction. The others, TU12, TU21, TU23 and TU25, completely inhibit IL-2 binding, as does the previously characterized TU27. However, reciprocal binding competition assays show that the epitopes recognized by the individual mAbs are different from each other. The mAbs inhibit the growth of IL-2-dependent cells. The magnitude of their inhibitory effects is dependent on not only the affinities of the mAbs for IL-2R beta but also upon the number of IL-2R alpha subunits expressed on IL-2-dependent cells. These mAbs should be useful in studying the structure and function of the IL-2R.

Animals↗

PubMed1991

Buffy coat from families of Alzheimer's disease patients produces intracytoplasmic neurofilament accumulation in hamster brain.

Buffy coat of three members from a family with Alzheimer's disease was inoculated into hamster brains. Eighteen months after the inoculation, all experimental animals were sacrificed for the neuropathological study. Hematoxylin-eosin staining showed no gross vacuolar degeneration, or neuronal loss in the cortex. The spongiform degeneration was minimum. Immunostaining with antibodies against neurofilament 200 kDa subunit protein revealed massive immuno-positive intracytoplasmic inclusion bodies within neurons of the brainstem nuclei. By electron microscopy, the intracytoplasmic inclusion body was shown to be composed of proliferated 10 nm neurofilaments. The intra-cytoplasmic neurofilament proliferation was observed with the hamsters inoculated with the buffy coat from Alzheimer's disease patients as well as an apparently normal member of the family.

Alzheimer Disease↗

PubMed1991

Structural and expression analyses of normal and mutant mRNA encoding glycine decarboxylase: three-base deletion in mRNA causes nonketotic hyperglycinemia.

Full-length cDNA clone encoding human glycine decarboxylase (P-protein) was isolated from the human placental lambda gt11 expression library using specific antibodies. This clone was 3,705 bp in length and encoded 1,020 amino acids. We studied the structure of the mutant P-protein mRNA expressed in the liver of a patient with nonketotic hyperglycinemia (NKH) deficient of P-protein. A three-base deletion, which resulted in deletion of Phe756, was found. Cos7 cells in which normal P-protein cDNA was expressed presented an activity of 6.9 +/- 0.41 nmole/milligram of protein/hour, which was almost equivalent to that of human liver. In contrast, Cos7 cells in which the mutant cDNA was expressed showed no activity, indicating that the three-base deletion could cause NKH.

Amino Acid Metabolism, Inborn Errors↗

PubMed1991

Retrospective survey of urea cycle disorders: Part 1. Clinical and laboratory observations of thirty-two Japanese male patients with ornithine transcarbamylase deficiency.

In a retrospective survey done from 1978-1988 in Japan, 32 male patients with ornithine transcarbamylase (OTC) deficiency were identified. We classified a neonatal and 2 late-onset groups, depending on clinical manifestations and the age at onset; group 1 (0-28 days; N = 10), group 2 (29 days-5 years; N = 13), and group 3 (greater than 5 years; N = 9). Compared to findings in the group 2 patients, there was a higher rate of mortality and a higher incidence of mental retardation in association with a great decrease in enzyme activity in group 1. In group 3, the mortality rate and enzyme activities were similar to those in group 1. However, patients in this group were asymptomatic prior to the first episode. Enzyme activities were measured mostly in autopsy samples. The serum citrulline levels (enzyme product) were highest in this group. Thus, the mutant enzymes were apparently labile with greater activities in vivo than in vitro. Treatments, including a protein-restricted diet, arginine supplementation, and sodium benzoate administration, resulted in a favorable prognosis for survivors with partial enzyme deficiency. We wish to emphasize that the incidence of late onset of this disease is higher than heretofore considered.

Child, Preschool↗

PubMed1991

Assembly, disassembly, and exchange of glial fibrillary acidic protein.

The kinetics and dynamics of glial fibrillary acidic protein (GFAP) assembly was explored by a fluorescence energy transfer assay method. Purified GFAP was stoichiometrically labeled at a single cysteine residue with fluorescein-maleimide. Soluble labeled GFAP in a low ionic strength buffer was assembled into 10 nm filaments by rapidly increasing the ionic strength, and the kinetics of GFAP assembly was monitored by the reduction in fluorescence due to self-quenching of fluorescein. The extent of fluorescence quench correlated with both the formation of 10 nm filament morphology and the amount of protein pelleted at 12,000g. The assembly of GFAP is critically dependent upon both protein and magnesium ion concentration, and at the critical concentration for GFAP assembly is approximately 40 micrograms/ml. Disassembly of GFAP filaments was also observed as a relief of fluorescence quenching after dilution of labeled GFAP filaments. When labeled GFAP filaments were mixed with an excess of unlabeled filaments, a rapid increase of fluorescence was observed, which is due to an exchange of subunits between labeled and unlabeled GFAP filaments. These results indicate that GFAP filaments are dynamic structures and that a small pool of kinetically active unassembled GFAP subunits are in a dynamic equilibrium with assembled GFAP filaments. The ability of GFAP to assemble, disassemble, and undergo subunit exchange has important implications for the organization and dynamics of astroglia cell cytoskeleton during development and in response to injury.

Animals↗

PubMed1991

First-trimester prenatal diagnosis in quintuplets: a practical approach using step-by-step embryo reduction.

A multiple pregnancy of high rank may occur in a couple at risk for a Mendelian disorder. Prenatal diagnosis is hampered by the difficulty of (1) obtaining chorionic villi from each zygote and (2) unequivocally relating each sample to the corresponding embryo. The calculation of the genetic risk according to the number of zygotes led us to propose a diagnostic strategy based on embryo reduction, a technique initially designed to improve the perinatal outcome of multiple pregnancies with normal embryos. We report a case in which this approach allowed rational use of first-trimester chorionic villus sampling in a quintuplet pregnancy at risk for non-ketotic hyperglycinaemia, resulting in the selective birth of unaffected twins.

Abortion, Therapeutic↗

PubMed1991

Dystrophin immunohistochemistry in a symptomatic carrier of Becker muscular dystrophy.

Immunohistochemical localization of dystrophin was studied in a symptomatic carrier of Becker muscular dystrophy (BMD). Muscle biopsy specimens from a female carrier showed findings compatible with slowly progressive muscular dystrophy by ordinary histochemical examinations. Immunohistochemical study, using an antiserum raised against a synthetic peptide fragment of dystrophin, demonstrated a mixture of staining patterns, including continuous but faint positive fibres, partially disrupted fibres and negative fibres. These findings were identical to those of patients with BMD and appear to differ from previous findings in female carriers of Duchenne muscular dystrophy. This report is the first immunohistochemical study of a symptomatic female proven by molecular genetic analysis to be a carrier of BMD.

Adult↗