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Biomedical subjects

M Okada

Publications and source records attributed to M Okada.

At least 1,333 records · Page 74Linked to original sources

Myeloproliferative disorders terminating in acute megakaryoblastic leukemia with chromosome 3q26 abnormality.

Two cases of myeloproliferative disorders terminating in acute megakaryoblastic leukemia are reported. One case began as primary myelofibrosis and the other as chronic myelogenous leukemia. Blast cells in the acute leukemic phase were identified as megakaryoblasts by the presence of platelet peroxidase. The clinical course is described, and the morphology, immunologic studies, and ultrastructure studies of the blast cells are reported. On cytogenetic analysis both cases had a translocation involving the No. 3 chromosome locus q26.2. The present data suggest that 3q26 may be associated with transformation of the megakaryocytic lineage.

Adult↗

Morphological differentiation of human neuroblastoma cell lines by a new synthetic polyprenoic acid (E5166).

The prognosis of patients with advanced neuroblastoma remains poor despite recent progress in chemo/radiotherapy. Therapeutic trials on the induction of differentiation of neuroblastoma by chemical and biological agents have been attempted to improve patients' prognosis. Recently a new synthetic polyprenoic acid, E5166, having retinoic acid properties, has been described. In this study two human neuroblastoma cell lines, KP-N-RT(LN) and SK-N-DZ, were treated in vitro by E5166. Morphological differentiation of KP-N-RT(LN) and SK-N-DZ cells could be induced by E5166 in the presence of 1.7 X 10(-5) M E5166 for 10 days in culture. Levels of catecholamines (dopamine, adrenaline, and noradrenaline) were not elevated in the E5166-differentiated cells. E5166-induced differentiation may not be cyclic AMP dependent, since levels of cyclic AMP did not increase after exposure of cells to this agent. No significant increase in neuron-specific enolase levels could be demonstrated in E5166-treated neuroblastoma as compared to control untreated cells. E5166 treatment of KP-N-RT(LN) and SK-N-DZ cells was found to inhibit colony formation in soft agar in a dose-dependent manner. Colonies of KP-N-RT(LN) cells in the presence of E5166 showed morphological differentiation as defined by the expression of long neurite processes. E5166 is a less toxic reagent than the retinoic acids used for the induction of differentiation, it can be administered to patients p.o., and the concentration of E5166 which induces the morphological differentiation in vitro can be achievable in vivo. Therefore our study suggests that E5166 could be a useful therapeutic agent in advanced neuroblastoma to differentiate residual anaplastic tumor cells to a benign form (ganglioneuroma) after surgery and chemotherapy.

Cell Differentiation↗

Purification and properties of inositol-1,4-bisphosphate 4-phosphohydrolase from rat brain.

Inositol-1,4-bisphosphate 4-phosphohydrolase (inositol-1,4-bisphosphatase) was highly purified from a soluble fraction of rat brain. On SDS-polyacrylamide gel electrophoresis, the purified enzyme gave a single protein band and its molecular weight was estimated to be 42000. The isoelectric point of the enzyme was 4.3. The enzyme specifically hydrolyzed the 4-phosphomonoester linkage of inositol 1,4-bisphosphate. The Km value for inositol 1,4-bisphosphate was 30 microM, and it required Mg2+ for activity. Ca2+ was a competitive inhibitor with a Ki value of 60 microM as regards the Mg2+ binding. Li+, which is known to be a strong inhibitor of inositol 1-phosphatase (EC 3.1.3.25), inhibited the enzyme activity and caused 50% inhibition at a concentration of 1 mM (IC50 = 1 mM). Li+ was an uncompetitive inhibitor of substrate binding with a Ki value of 0.6 mM. These inhibitory parameters of Li+ were quite similar to those for inositol 1-phosphatase (IC50 = 1 mM, Ki = 0.3 mM). Thus, the effect of Li+ on decreasing the free inositol level with a subsequent decrease in agonist-sensitive phosphoinositides, is caused by its inhibition of multiple enzymes involved in conversion of inositol 1,4-bisphosphate to inositol.

Animals↗

Activation of interleukin-2 receptor gene by forskolin and cyclic AMP analogues.

Forskolin (FK), a reversible activator of adenylate cyclase, markedly enhanced the expression of interleukin-2 receptor (IL-2-R) on a human natural killer (NK)-like cell line, YT. The FK-induced increase in IL-2-R on YT cells closely correlated with an increase in intracellular cyclic AMP (cAMP) level, and was mimicked by dibutyryl cyclic AMP (dbcAMP). FK induced both high and low affinity IL-2-R on the cells. Using a cDNA for the IL-2-R as a probe, the FK-induced IL-2-R expression was shown to be associated with an increase in IL-2-R mRNA. FK also enhanced the IL-2-R expression on a human T lymphotrophic virus I (HTLV-I) positive T-cell line (YTA-1H) and augmented the phorbol ester-induced expression of IL-2-R on HTLV-I negative T-cell lines (HSB-2 and HPB-ALL). These results suggest the possibility that the stimulation of adenylate cyclase may serve as a pathway leading to activation of the IL-2-R gene in certain types of lymphocytes.

Adenylyl Cyclases↗

Purification of sarcotoxin II, antibacterial proteins of Sarcophaga peregrina (flesh fly) larvae.

Three antibacterial proteins with almost identical primary structures termed sarcotoxin IIA, IIB, and IIC were purified to homogeneity from the hemolymph of third instar larvae of Sarcophaga peregrina. The molecular masses of these proteins were about 24,000. These proteins were found to have common antigenicity, and antibody against sarcotoxin IIA cross-reacted with sarcotoxin IIB and IIC. Radioimmunoassay using this antibody showed that these proteins are induced in the hemolymph in response to injury of the larval body wall.

Amino Acids↗

An alternative method of vascular anastomosis by laser: experimental and clinical study.

In vascular surgery, it is now very difficult to maintain the long-term patency after a conventional vascular anastomosis, especially for small-caliber vessels. A low-energy CO2 laser was experimentally employed to make a vascular anastomosis with only a few sutures. Subsequently, it could be confirmed that optimal conditions for vascular anastomosis by laser were 20-40 mW in output and 6-12 sec/mm in irradiation time. On the other hand, pressure tolerance test as well as tensile strength test and microscopic examinations at the sites of anastomoses by laser were compared with the conventional suture method. There were no significant differences between laser and suture methods. On the basis of the excellent results of this study, the laser was clinically applied for anastomoses of the peripheral vessels in 35 patients. The first clinical laser application in the world was successful in a 44-year-old female patient with chronic renal failure in 1985. All patients are doing well without any complications from vascular anastomosis by laser. From these experimental and clinical studies, it can be concluded that anastomosis by laser should be recommended for small-caliber vessels such as aortocoronary bypass surgery.

Adult↗

Effect of muscle length on surface EMG wave forms in isometric contractions.

To elucidate the influence of muscle length on surface EMG wave form, comparisons were made of surface EMGs of the biceps and triceps brachii muscles during isometric contractions at different muscle lengths. Muscle lengths were altered by setting the elbow joint angle at several intervals between the limits of extension and flexion. The intensity of the isometric contractions was 25% of maximum voluntary contraction at the individual joint angles. Slowing was obvious in the EMG wave forms of biceps as muscle length increased. The so-called 'Piper rhythm' appeared when the muscle was more than moderately lengthened. The slowing trend with muscle lengthening, though less marked, was also seen in triceps. Zero-cross analysis revealed quasi-linear relationships between muscle length and slowing. Frequency analysis confirmed the development of 'Piper rhythm'. An attempt was made to interpret the slowing associated with muscle lengthening in terms of the propagation of myoelectric signals in muscle fibers. given the effect of muscle length on EMG wave forms, a careful control of joint angle may be required in assessing local making fatigue when using EMG spectral indices.

Adult↗

Intracellular localization and transport of three different bovine herpesvirus type 1 glycoproteins involved in neutralization.

Monoclonal antibodies against 3 different glycoproteins of bovine herpesvirus type 1 (BHV-1) involved in virus neutralization were used in indirect immunofluorescence (IIF) tests to characterize the appearance and transport to the plasma membrane of virus antigens in the infected cells. Antibodies against gp 117 and gp 71 glycoproteins first showed pronounced ring-like nuclear fluorescence at 4 hours post-infection (PI), followed by staining of the perinuclear region, presumably the Golgi apparatus. In contrast, antibody against gp 87 produced staining in cell-to-cell junctional areas at 3 hours PI before any staining close to the nucleus. The expression of the 3 glycoproteins at the surface of the infected cells was confirmed by the use of monoclonal antibodies having neutralizing activity, but not by non-neutralizing antibodies against gp 117 and gp 71. Non-neutralizing antibody against gp 87 detected the surface fluorescence only in those cells showing marked degeneration. Inhibition of glycosylation of the viral glycoproteins with tunicamycin (TM) was followed by interference with transport of gp 117 and gp 87 to the plasma membrane. On the other hand, gp 71 was incorporated into the plasma membrane despite the lack of N-linked glycosylation.

Animals↗

Subretinal strands. Tissue culture and histological study.

Subretinal strands in proliferative vitreoretinopathy removed during vitreous surgery in ten cases were studied histologically; tissue culture was taken from five of the ten cases to obtain more material for investigation. Tissue culture was successful in all five cases. The cultured tissue just next to the original strand preserved the characteristics of the original tissue, whereas the portion distal from the original strand did not. Definite and/or suspected retinal pigment epithelial cells (RPE) were found in seven of ten original strands and four of five samples of cultured material. RPE were considered to be a predominant component of subretinal strands.

Culture Techniques↗

Monoclonal antibodies against Drosophila ovaries: their reaction with ovarian and embryonic antigens.

A library of monoclonal antibodies (MAbs) against Drosophila ovarian antigens was established. Each of the MAbs was characterized by its immunohistochemical binding pattern to sections from egg chambers at various stages of oogenesis. Sixteen of the 18 MAbs were found to bind to antigens in mature oocytes. Among the 16 antigens, two were also located in cytoplasm of cell types in the egg chamber other than the oocyte, at all stages of oogenesis. Four made their appearance in nurse cell cytoplasm at mid-vitellogenic stages and shifted to oocyte cytoplasm at a later stage, and ten appeared at the vitellogenic stage and confined their distribution to oocyte cytoplasm. All these antigens were distributed evenly in cytoplasm of mature oocytes. However, some of these antigens were noticed to change their distribution during early embryogenesis as to be localized in a specific region of embryos.

Animals↗

Transcription of IL-2 receptor gene is stimulated by ATL-derived factor produced by HTLV-I(+) T cell lines.

In HTLV-I transformed T-cell lines established from the patients with adult T-cell leukemia (ATL), there is a constitutive activation of the normal IL-2 receptor (IL-2-R) gene. These cell lines continuously produce an ATL-derived factor (ADF), an IL-2-R inducing factor without IL-2 activity. ADF enhances the expression of the IL-2-R through the augmentation of the IL-2-R mRNA in the HTLV-I(+) T-cell line (ED) as well as the NK cell line cells (YT). In YT cells, the transcriptional initiation of the promoter of the IL-2-R gene was enhanced by ADF but not by IL-2. Production of ADF by HTLV-I(+) T-cell lines may be involved in the abnormal expression of IL-2-Rs on these cells.

Cell Line↗

Comparison of efficacy of zotepine and thiothixene in schizophrenia in a double-blind study.

Zotepine and thiothixene were compared for clinical efficacy and safety in a double-blind trial. Using overall improvement ratings and Gorham's BPRS, zotepine rated higher improvement in motor retardation, suspiciousness, mannerisms and posturing symptoms, suggesting that it has both activating and antipsychotic activities. Thiothixene produced higher improvement ratings in symptoms such as hallucinatory behavior, somatic concerns, anxiety, guilt feelings, tension, depressive mood and uncooperativeness. As for side effects, there was a significantly lower frequency of dry mouth and insomnia with zotepine when compared with thiothixene. The lower incidence of insomnia is interesting in view of zotepine's clinical activating effects. There were no abnormal laboratory findings.

Adult↗

Phosphotyrosine phosphatase: a novel phosphatase specific for phosphotyrosine, 2'-AMP and p-nitrophenylphosphate in rat brain.

A unique phosphatase that selectively hydrolyzed phosphotyrosine and 2'-AMP at alkaline pH and p-nitrophenylphosphate at neutral pH was isolated from a cytosolic fraction of rat brain. The purified enzyme appeared homogenous on SDS-polyacrylamide gel electrophoresis and its molecular weight was estimated to be 42,000. The molecular weight of the native enzyme was 45,000 as determined by molecular sieve chromatography. These findings indicate that the native enzyme is a monomer protein. At pH 8.6, the enzyme hydrolyzed L-phosphotyrosine, D-phosphotyrosine, 2'-AMP, p-nitrophenylphosphate, 3'-AMP, 2'-GMP, and 3'-GMP; the ratio of its activities with these substrates was 100:96:115:68:39:25:16. Its Km values for L-phosphotyrosine, 2'-AMP, and p-nitrophenylphosphate were 0.8 X 10(-4) M, 1.4 X 10(-4) M, and 1.7 X 10(-4) M, respectively. At pH 7.4, the enzyme hydrolyzed p-nitrophenylphosphate, L-phosphotyrosine, and D-phosphotyrosine; the ratio of its activities with these compounds was 100:17:17, and its Km values for L-phosphotyrosine and p-nitrophenylphosphate were 1.8 X 10(-4) M and 2.0 X 10(-4) M, respectively. The enzyme activity was dependent on Mn2+ or Mg2+, and was strongly inhibited by 5'-nucleotides, pyrophosphate, and Zn2+. The enzyme was not sensitive to inhibitors of some well-characterized phosphatases such as NaF, molybdate, L(+)tartrate, tetramisole, vanadate, and lithium salt. The physiological role of the enzyme is discussed with respect to its activities toward phosphotyrosine, 2'-AMP, and p-nitrophenylphosphate.

Adenosine Monophosphate↗

Purification of sarcotoxin III, a new antibacterial protein of Sarcophaga peregrina.

A glycine-rich antibacterial protein with a molecular mass of 7,000 termed sarcotoxin III, was purified to homogeneity from the hemolymph of third instar larvae of Sarcophaga peregrina. When the hemolymph was fractionated, this protein was recovered in the same fraction as sarcotoxin I, a group of potent antibacterial proteins that have been purified. But, it was clearly different from sarcotoxin I in amino acid composition and molecular mass. Sarcotoxin III was shown to be induced in the hemolymph in response to injury of the larval body wall.

Amino Acids↗

Synthetic partial extension peptides of P-450(SCC) and adrenodoxin precursors: effects on the import of mitochondrial enzyme precursors.

Various portions of the extension peptides of P-450(SCC) precursor were chemically synthesized. The effects of these peptides on the import of enzyme precursors into mitochondria were examined. Peptides SEP1-15 and SEP1-20, corresponding to the amino terminal portion of the extension peptides, strongly inhibited the import of P-450(SCC) precursor into mitochondria. These peptides were effective at concentrations above 30 microM, and complete inhibition was observed at 100 microM. SEP1-11, which is shorter than SEP1-15 and SEP1-20, showed very weak inhibition. SEP25-39, which corresponds to the carboxy terminal portion of the extension peptide, did not affect the import of the precursor. The import of P-450(11 beta) and adrenodoxin precursors were also inhibited by SEP1-15. Another peptide, AEP1-14, which corresponds to the amino terminal portion of the extension peptide of adrenodoxin precursor, was also synthesized. The peptide inhibited the import of both adrenodoxin and P-450(SCC) precursors into mitochondria. The import of malate dehydrogenase was also inhibited by SEP1-15 and AEP1-14. The rate of the internalization of the precursor into mitochondria was decreased by the peptides. The amount of the precursor bound to the surface of mitochondria and the processing of adrenodoxin precursor were not affected. The respiratory activities of isolated mitochondria were not influenced by SEP1-15 even at 100 microM. We conclude that the inhibitory activities of the synthetic partial extension peptides on the import of enzyme precursors into mitochondria require the presence of about fifteen amino acid residues in the amino terminal portion of the extension peptides, and the inhibition of the import by the peptides was dependent on the blockage of the internalization of the precursors into mitochondria.

Adrenodoxin↗

Anatomical involvement and clinical features in 91 Japanese patients with Crohn's disease.

Ninety-three patients with Crohn's disease who had not undergone bowel resection at the time of diagnosis (during the years 1969-1983) were selected for the study, to elucidate whether initial anatomical involvement correlates with clinical manifestations, complications, laboratory findings, and prognosis. Forty-one patients had isolated small intestine disease (44%), 37 ileocolic (40%), 13 colonic disease alone (14%), and two rectal or appendix involvement (2%). Statistically significant symptoms were fever and rectal bleeding with colon involvement, and number of liquid or very soft stools in 1 week with ileocolic or colon involvement. Statistically significant complications included intestinal obstruction with ileocolic disease, perianal fistulas, and arthritis with colonic disease. Increases in ESR, C-reactive protein, and white blood cell in patients with colon involvement were among the statistically significant laboratory findings. Gammaglobulin was significantly higher in patients with ileocolic or colon involvement than in those with small intestine disease. Red cell count and hemoglobin were significantly lower in patients with ileocolitis than in patients with small intestine involvement. Crohn's disease activity index (CDAI) was significantly higher in patients with ileocolic or colon involvement than in those with small intestine involvement only. These findings confirm that colonic involvement renders the disease more severe than involvement of the small intestine. Surgery was required for 22 patients (24%) during a 2.8-year follow-up, but the difference among the three groups was not significant.

Adolescent↗

The efficacy of biological response modifiers against murine cytomegalovirus infection in normal and immunodeficient mice.

The host-mediated antiviral effect of two biological response modifiers (BRM), OK-432 and PS-K, against murine cytomegalovirus (MCMV) was evaluated in normal and immunologically deficient mice of the same litters. In normal littermate mice, BALB/c (nu/+) or C57BL/6 (bg/+), the BRM-induced resistance against MCMV infection was evidenced by increase in fifty percent lethal doses, decrease in titers of viruses replicated in the target organs and augmentation of natural killer (NK) cell activity of the spleen cells. In T cell-deficient, athymic nude mice, BALB/c (nu/nu), the protective effect was manifested by prolongation of the survival, decrease in the virus titers, and increase in the NK-cell activity, but without decrease in mortality. In NK cell-deficient, beige mutant mice, C57BL/6 (bg/bg), the BRM-induced protection was nullified or minimized, and there was little difference in those parameters between BRM-treated and untreated mice. However, with higher doses of OK-432, but not PS-K, or with sublethal doses of MCMV, the NK cell activity was slightly augmented in the beige mutant mice. Thus both NK cell and T cell activity are essential for mice to overcome acute MCMV infection and it is likely that the protective effect of BRM manifests itself fully, at least in immunologically intact mice.

Adjuvants, Immunologic↗