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Biomedical subjects

K Tada

Publications and source records attributed to K Tada.

At least 505 records · Page 28Linked to original sources

Dihydropteridine reductase deficiency: diagnosis by leukocyte enzyme assay.

An assay procedure for dihydropteridine reductase in peripheral leukocytes is described. The assay utilizes the tetrahydropterin-dependent reduction of ferri-cytochrome C in the presence of NADH and requires a smaller number of cells than assays described for cultured skin fibroblasts. Dihydropteridine reductase activity was not detectable in the peripheral leukocytes nor in the cultured skin fibroblasts from two adolescent patients with malignant hyperphenylalaninemia. The parents of the patients showed approximately 50% of normal dihydropteridine reductase activity in their peripheral leukocytes. Immunochemical experiments using antibodies against bovine liver dihydropteridine reductase suggest that normal leukocytes and skin fibroblasts contain dihydropteridine reductase which is immunologically similar to that of human liver. The present studies indicate that the determination of dihydropteridine reductase activity in peripheral leukocytes can be used to diagnose hyperphenylalaninemia due to a defect in dihydropteridine reductase.

Amino Acid Metabolism, Inborn Errors↗

Establishment and characterization of a human acute monocytic leukemia cell line (THP-1).

A human leukemic cell line (THP-1) cultured from the blood of a boy with acute monocytic leukemia is described. This cell line had Fc and C3b receptors, but no surface or cytoplasmic immunoglobulins. HLA haplotypes of THP-1 were HLA-A2, -A9, -B5, -DRW1 and -DRW2. The monocytic nature of the cell line was characterized by: (1) the presence of alpha-naphthyl butyrate esterase activities which could be inhibited by NaF; (2) lysozyme production; (3) the phagocytosis of latex particles and sensitized sheep erythrocytes; and (4) the ability to restore T-lymphocyte response to Con A. The cells did not possess Epstein-Barr virus-associated nuclear antigen. These results indicate that THP-1 is a leukemia cell line with distinct monocytic markers. During culture, THP-1 maintained these monocytic characteristics for over 14 months.

Cell Line↗

Anterior transfer of the toe flexors for equinovarus deformity of the foot.

Anterior transfer of the long toe flexors was carried out for the treatment of spastic equinovarus foot deformity in both adults and children. Adults included those with hemiplegia subsequent to a stroke, spastic hemiplegia due to cerebral palsy and spastic spinal paraplegia. Most of the children had cerebral palsy. The transfer was indicated for an equinovarus foot with persistent activity of the toe flexors, which produced curling of the toes in the swing phase of the gait or a fixed hammer toe deformity. Fifty six patients were followed up for more than four years. In all cases correction of the equinovarus deformity was achieved and maintained. With satisfactory correction stability of the ankle improved, postural abnormalities during gait decreased and bracing was not required. This study demonstrates the advantage of the long toe flexors for muscle transfer in these patients. The length of tendon available permitted easy transfer to the metatarsal. The defunctioning of the spastic muscles allowed gait improvement and function of the tibialis posterior and tibialis anterior was preserved.

Adolescent↗

Mammary tumorigenic effect of a new nitrosourea, 1,3-dibutyl-l-nitrosourea (B-BNU), in female Donryu rats.

Four groups (groups 1-4) of female Donryu rats were given continuously 400, 200, 100, or 0 ppm solution of 1,3-dibutyl-l-nitrosourea (B-BNU) as their drinking water, and were studied for the development of tumors. The incidence of mammary tumors was 15/19 (79%), 20/24 (83%), 21/26 (81%), and 8/25 (32%) in groups 1, 2, 3, and 4, respectively. In addition, hematopoietic neoplasms, uterine tumors, and vaginal tumors developed in 13, 11, and six rats, respectively in 69 treated rats. Other tumors were infrequent.

Animals↗

A new variant of glycogen storage disease type 1: probably due to a defect in the glucose-6-phosphate transport system.

A new variant of glycogen storage disease (GSD) Type 1, with clinical symptoms and laboratory findings consistent with those of glucose-6-phosphatase (G6Pase) deficiency, is described. Assay of G6Pase in liver from the patient immediately after biopsy by the method of Nordlie and Arion gave low activity (0.8 mumol/min per g liver) in the absence of detergent, but was normal (10.2 mumol/min per g liver) after addition of detergent. Liver stored for a day at -25 degrees C had normal activity (3.4 mumol/min per g liver) without detergent. In patients with GSD Type la, G6Pase activity was very low both with and without detergent. These findings suggest a defect in glucose-6-phosphate transport in the microsomal membrane of the patient's liver. The integrity of microsomal membrane was destroyed by storage at -25 degrees C, when activity of G6 ase in the patient's liver could be demonstrated. This may be the first example of a disorder involving the transport system of an intracellular membrane.

Animals↗

Epstein-Barr virus-induced lymphoblastoid cell lines from patients with primary immunodeficiency diseases.

Peripheral lymphocytes from eight patients with congenital immunodeficiency diseases were infected with Epstein-Barr virus (EBV) in an attempt to establish B lymphoblastoid cell lines (LCL). These patients included three boys with congenital agammaglobulinaemia, two girls with hypogammaglobulinaemia, one boy with common variable immunodeficiency, one boy with severe combined immunodeficiency with adenosine deaminase deficiency, and one boy with DiGeorge syndrome. Five of the patients bore no surface immunoglobulins (sIg) on their peripheral lymphocytes. LCL were established from seven of the eight patients. All the LCL established formed rosettes with EAC3 and had the ability to produce cytoplasmic immunoglobulins (cIg) of various classes. Culture supernatants concentrated up to 100-fold developed precipitin bands by Ouchterlony's method with antisera to human Ig in all the established LCL. These results suggested that both sIg-, cIg- and C3+ cells and sIg+, cIg- and C3+ cells might be the target cells for EBV and that sIg-, cIg- and C3+ cells might be the precursor cells of B lymphocytes.

Adolescent↗

A sibling case of hyperphenylalaninemia due to a deficiency of dihydropteridine reductase: biochemical and pathological findings.

Three siblings with hyperphenylalaninemia were described, who showed convulsions and severe mental retardation despite dietary control of blood phenylalanine. The cultured skin fibroblasts from two patients revealed a markedly low activity of dihydropteridine reductase. These patients showed low levels of serum folate and of 5-hydroxyindoleacetic acid and homovanillic acid in cerebrospinal fluid. The postmortem examination on one of these siblings exhibited the dysmyelination in the cerebrum and spongy lesions of the white matter in the cerebellum, pons, medulla oblongata and spinal cord. Many minute foci of calcification were found in the cerebrum, which were located in the perivascular space of the small blood vessels. Such calcification was observed on CT scanning of the brain in the other two living siblings as well.

Adult↗

Immunoglobulin production in Epstein-Barr virus-induced human monoclonal lymphoblastoid cell lines.

In order to establish clonal human lymphoblastoid cell lines, human tonsillar lymphocytes infected with Epstein-Barr virus were directly seeded in semi-solid agar. After four weeks, resulting colonies were randomly isolated and transferred to suspension culture. At around three months after the initiation of the culture, immunoglobulin (Ig) production of 17 clones thus established was determined. Cytoplasmic and membrane Ig were detected by immunofluorescence staining and secretory Ig in the culture supernatants was detected by double immunodiffusion. The patterns of Ig production by these cell lines were clear-cut. Each clone produced and secreted one class of heavy chains and one type of light chains, i.e., a single Ig. Of 17 clones, 13 clones were IgM producers, 3 clones were IgA producers and one clone was an IgG producer. Membrane Ig of these clones was also identical with cytoplasmic/secretory Ig with the exceptions of three IgM producers in which membrane IgD as well as IgM was detected and the one IgG producer in which no membrane Ig was detected.

Cell Line↗

[Studies on regeneration and adhesion of the tendon. Part 7: Influence of the vincula on regeneration of the tendon (author's transl)].

Repair of the flexor digitorum profundus (FDP) of the chicken was studied by light microscopic and microangiographic examination. The effects of altered circulation in the vincula breve were related to repair processes of tendon. Sixty young-adult chickens weighing 2 to 3 kg were used. The FDP tendons of the third toes were incised and sutured without anesthesia, then the vincula breve was cut and ligated. In the control group, no procedure was performed to the vincula breve. Samples were obtained at the fixed time intervals up to 8 weeks after the operation. For microangiography, Micropaque solution was injected into the femoral artery after perfusion of physiological saline. The amputated legs were fixed in 10% formalin, subcutaneous tissues removed, then soft X-ray examination performed using Softex-CMB. Histological specimens were stained with hematoxylin-eosin. The results were as follows: 1) In the group with ligated vincula, delay of cellular reaction in the repair process was histologically evident in the early stages. There were little granulation and proliferation of the dorsal epitenon, which formed adhesion with surrounding tissues in the later stages. 2) In the angiographic examination, the sutured site of the tendon was not avascular, and compensatory proliferation of the periosteal and capsular vessels was found around the suture although the vincula breve had been ligated. However, there was a somewhat impaired circulatory pattern in the group with ligated vincula during the early stages. Later, normalization of the circulation was delayed compared to the control samples. 3) Damage of the vincula was thought to delay regeneration in tendon injuries. Poor circulation, if present, may also influence the healing process by inducing adhesion of the surrounding tissues.

Animals↗

Development of spinal motoneuron innervation of the upper limb muscle in the rat.

Horseradish peroxidase was injected into the biceps brachii muscle of rats at various stages of development, from 10 days to 50 weeks. The retrogradely labeled neurons were found in the ipsilateral ventro-lateral column of the cervical cord, C4--C8, of all stages studied, but the number of labeled neurons decreased according to exponential curve as the age advanced. A striking finding was that the contralateral ventral horn cells were also labeled in the 10- and 14-day-old rats.

Animals↗

A new method for screening for hyperammonemia.

A new method for the detection of hyperammonemia, using a kit based on the principle of microdiffusion of ammonia, is described. The method requires only one drop of blood and takes only 15 min to complete. Experiments for recovery and reproducibility were satisfactory, and good correlation was obtained when compared with an enzymatic method for blood ammonia determination. The new method is considered to be useful for routine, low-cost mass-screening of newborn infants for hyperammonemia. It will also be useful for monitoring blood ammonia levels at the bedside in cases with hepatic disease or receiving parenteral nutrition.

Amino Acid Metabolism, Inborn Errors↗