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Biomedical subjects

M Yamaguchi

Publications and source records attributed to M Yamaguchi.

At least 1,243 records · Page 69Linked to original sources

[T-cell type non-Hodgkin's lymphoma associated with eosinophilia].

A 65-year-old man was admitted to our hospital in January 1990, because of weakness of upper limbs. On admission he was found to have generalized lymphadenopathy and leukocytosis. His WBC count was 40,900/microliters with 88% eosinophils. The bone marrow showed an increased number of eosinophils and their precursors but no other abnormalities. A diagnosis of non-Hodgkin's lymphoma (diffuse, medium sized cell type) was made by biopsy of his inguinal lymph node. The result of marker analysis was consistent with CD3+4+8-. The antibody to human T-lymphotropic virus type I was negative. A stomach biopsy revealed lymphoma cell infiltration. Extensive studies to identify the cause of the eosinophilia were undertaken, with consistently negative results. Combination chemotherapy was begun, and resulted in a dramatic resolution of the eosinophilia and the lymphadenopathy. The association of hypereosinophilia with non-Hodgkin's lymphoma is unusual. We report a patient with eosinophilia and non-Hodgkin's lymphoma, and discussed its possible etiology.

Aged↗

[Genetic study on OPLL in the cervical spine with HLA haplotype].

HLA typing was carried out in 27 families with cases of ossification of the posterior longitudinal ligament (OPLL) in the cervical spine, with haplotype analysis for genetic factors. The results showed a significantly higher incidence of rare haplotypes in probands than in the general Japanese population, suggesting that certain genes linked to HLA are responsible for OPLL. On examination of the distribution of HLA haplotypes in families with members suffering from cervical OPLL, no evidence of OPLL was found in members with only one haplotype in common with the proband. In 9 of 15 siblings with two haplotypes in common, however, OPLL was observed. Further analysis of HLA haplotyping may contribute to the elucidation of the genetic determinants of OPLL linked to two HLA haplotypes, probably based on multifactorial inheritance.

Adult↗

[Results of open heart surgery in neonates--comparison between profound hypothermia with circulatory arrest and deep hypothermic bypass].

To investigate factors affecting surgical outcome of open heart surgery in neonates, a retrospective review was carried out on 38 patients operated in the 9 years period from May 1981 to August 1990, in our institution (TAPVR19, TGA7, HLHS7, and others 5). In the former 3 years and 9 month period, 12 patients were operated with the use of profound hypothermia and circulatory arrest (Group I) and in the latest 5 year and 5 month period, continuous deep hypothermic bypass was used in all but for 7 patients with HLHS (Group II). In the group of neonates with TAPVR, operative mortality improved to 7% (1 of 14) in Group II compared to that of 60% (3 of 5) in Group I. CVP and LAP measured immediately after cessation of cardiopulmonary bypass (CPB) were lower in Group II and the value of CPK-MB was significantly lower in Group II. There was a significant negative correlation (r = -0.695, p less than 0.05) between CPB time and urine volume for 72 hours after operation. A significant negative correlation (r = -0.899, p less than 0.01) was also obtained between CPB time and urine volume in the group of 7 neonates with TGA. There was no significant difference in urine volume between patients with TAPVR and TGA despite of significantly longer CPB time in patients with TGA. It is concluded that, 1) improved protection of cardiac and renal function was obtained in neonates operated with the use of continuous deep hypothermic bypass, 2) surgical outcome was influenced by the method of CPB, CPB time and differences in cardiac function ascribed to primary lesions.

Assisted Circulation↗

[Burkitt's type ALL with numb chin syndrome as an initial manifestation].

A case of Burkitt's type ALL with numb chin syndrome as the initial manifestation is described. A 57-year-old Japanese male was admitted to our hospital in November 14, 1989 because of paresthesia at the chin and lower lip with diplopia and ptosis. Neurological examination revealed oculomotor paralysis of the right side and hypesthesia on the chin, lower lip and buccal mucous membrane. Laboratory findings showed increased leukocyte count. Bone marrow aspirate revealed hypercellular marrow with 92.3% leukemic cells which had vacuoles in the cytoplasm and surface marker of IgM, kappa type. The abnormalities of karyotype included t(8;14). He was treated with chemotherapy and radiation. His conditions were temporarily improved, but relapsed later and died in March 6, 1990. Leukemic infiltrations to the trigeminal nerve were found in autopsy. The relationship between lymphoid malignancies and numb chin syndrome was discussed.

Burkitt Lymphoma↗

[An autopsy case of adult T-cell leukemia complicated with metastatic calcification of the lung].

46-year-old male patient was born in Niigata Prefecture and thereafter lived in Tokyo. In late January 1985, he noticed swelling of the bilateral inguinal lymph-nodes followed by fever and lumbago. In February, he consulted a local doctor and hepatosplenomegaly, marked leukocytosis and renal dysfunction were pointed out and he was referred to our hospital on February 22nd. The clinical laboratory data on admission were as follows; WBC 23,200/microliter, serum-Ca 18.4 mg/dl, BUN 85.3 mg/dl, creatinine 5.4 mg/dl, antibody to ATLV x160. ATL was diagnosed by biopsy of lymph nodes and examinations of peripheral blood and bone marrow hemogram. Remission was achieved in March by the treatment with adriacin. Renal failure and hypercalcemia also improved. However his respiratory dysfunction gradually worsened. The chest radiographies++ showed pulmonary edema, although there was no clinical evidence of heart failure. When his condition became stable, TBLB was performed and revealed extensive deposition of calcium along alveolar septae, suggesting that pulmonary edema was induced by the metastatic calcification of the lung. After the second treatment for ATL, he died of pneumonia. The autopsy showed calcium deposition not only in the lung but in pyramids of the kidney and in sub-serous layer of the small intestine. There was no tumor cell invasion into the bone or parathyroid gland. High urinary c-AMP together with normal levels of PTH suggested that the hypercalcemia in this case was induced by PTH-related protein. It was concluded that careful treatment for hypercalcemia is important as regards the occurrence of pulmonary edema.

Calcinosis↗

Effect of calcium-binding protein regucalcin on hepatic protein synthesis: inhibition of aminoacyl-tRNA synthetase activity.

The effect of regucalcin, a calcium-binding protein isolated from rat liver cytosol, on in vitro protein synthesis in the 5500 g supernatant fraction of rat liver homogenate was investigated. Addition of Ca2+ up to 5.0 microM in the reaction mixture caused a significant decrease in protein synthesis. This decrease was saturated at 10 microM Ca2+. The Ca2+ effect was not reversed by the presence of regucalcin (2.0 microM); the protein caused a remarkable decrease in hepatic protein synthesis, and it enhanced significantly the Ca2+ effect. Meanwhile, calmodulin (2.5-20 micrograms/ml), a calcium-binding protein, did not have an appreciable effect on the Ca2+ (10 microM)-induced decrease in hepatic protein synthesis. [3H]Leucyl-tRNA synthetase activity in the 105000 g supernatant fraction (cytosol) of liver homogenate was markedly decreased by addition of Ca2+ (1.0-50 microM). This decrease was not reversed by the presence of regucalcin (2.0 microM); the protein (1.0-2.0 microM) caused a remarkable decrease in the enzyme activity. The present results suggest that regucalcin can regulate protein synthesis in liver cells.

Animals↗

The primary structure of the rat guanylyl cyclase A/atrial natriuretic peptide receptor gene.

We have isolated and characterized three genomic clones and a genomic fragment amplified by the polymerase chain reaction that contain the rat guanylyl cyclase-A (GC-A)/atrial natriuretic peptide receptor gene. The gene spans about 17.5 kilobases and includes 22 exons and 21 introns. All of the exon-intron junction sequences coincide with the GT/AG consensus. GC-A consists of at least the following four distinguishable domains: extracellular ligand binding, transmembrane, kinase-like, and cyclase catalytic. Exon 7 encodes the putative transmembrane domain. The kinase-like and catalytic domains are encoded by exons 8-15 and 16-22, respectively. The 5' end of the transcript, estimated by primer extension and S1 mapping, is 370 nucleotides upstream of the methionine initiation codon. The initiator sequence (-3 to +5) of CACACTCC has two mismatches when compared with a consensus initiator sequence of CTCANTCT. The 5'-flanking region contains three potential Sp1-binding sites and an inverted CCAAT box, but no apparent TATA box. Three different and short interspersed, repetitive sequences are found within intervening sequences and within the 5'- and 3'-flanking regions of the gene (five rat identifier, two rat type 2 Alu equivalent, and seven Alu-like sequences). They fall between the four major domains suggestive that these may be sites for frequent recombination events. This first reported structure of a gene for a member of this new enzyme/receptor family should facilitate the search for new family members, as well as allow studies to progress on the mechanisms by which the gene is regulated.

Amino Acid Sequence↗

Determination of alpha-keto acids including phenylpyruvic acid in human plasma by high-performance liquid chromatography with chemiluminescence detection.

A highly sensitive method for the determination of alpha-keto acids including phenylpyruvic acid in human plasma is investigated. The method employs high-performance liquid chromatography with chemiluminescence detection. The acids and alpha-ketocaproic acid (internal standard) in human plasma are isolated by anion-exchange chromatography on a Toyopak DEAE cartridge, and then converted into the corresponding chemiluminescent derivatives with 4,5-diaminophthalhydrazide dihydrochloride, a chemiluminescence derivatization reagent for alpha-keto acids. The derivatives are separated within 50 min on a reversed-phase column, TSKgel ODS-120T, with isocratic elution, followed by chemiluminescence detection; the chemiluminescence is produced by the reaction of the derivatives with hydrogen peroxide in the presence of potassium hexacyanoferrate(III). The detection limits for the acids are in the range 9-92 pmol/ml in plasma (signal-to-noise ratio = 3). This sensitivity permits precise determination of several alpha-keto acids including phenylpyruvic acid, which cannot be determined by other HPLC methods, in 10 microliters of normal human plasma. The chemiluminescent product from phenylpyruvic acid was characterized as 3-benzyl-7,8-dihydropyridazino[4,5-g]quinoxaline-2,6,9(1H)-trione.

Adult↗

Enhancement of human basophil histamine release by interleukin 5.

Substantial evidence indicates a close relationship between eosinophils and basophils. We examined whether interleukin 5 (IL-5), known to be eosinophilopoietic and capable of selectively regulating eosinophil functions, has an affect on basophil functions. IL-5 enhanced basophil histamine release evoked by anti-IgE, formyl-methionyl-leucyl-phenylalanine, or ionophore A23187 at picomolar concentrations. Direct action of IL-5 on human basophils was confirmed using highly purified basophil populations. These observations reveal the novel fact that IL-5 is able to modulate basophil functions as well as eosinophil functions, and suggest that normal human basophils possess functional receptors for IL-5.

Basophils↗

Striking similarity of the distribution patterns of the poly(ADP-ribose) polymerase and DNA polymerase beta among various mouse organs.

The expression level of poly(ADP-ribose) polymerase mRNA as well as the level of enzymatic activity were examined in various mouse organs by northern blot and activity gel analyses. High levels of the mRNA expression and enzymatic activity were observed in testis, thymus, spleen, and brain. On the other hand, low levels of the mRNA expression and enzymatic activity were observed in liver and kidney. These findings suggest that the expression of the poly(ADP-ribose) polymerase is mainly regulated by transcription. Striking similarity was observed between the patterns of organ distribution of enzymatic activities of poly(ADP-ribose) polymerase and DNA polymerase beta in various mouse organs.

Animals↗

Dipalmitoylphosphatidylcholine (L-alpha-lecithin) stimulates phospholipase A2 activity in human amnion.

In order to investigate the mechanism of dipalmitoylphosphatidylcholine (DPPC, L-alpha-lecithin) stimulation of the prostaglandin E (PGE) production of the amniotic membrane, effects of DPPC (50-800 micrograms/ml) on phospholipase A2 (PLA2), phospholipase C (PLC), PG endoperoxide synthase, and PGE synthase activities of human amniotic membrane were studied. Only PLA2 activity was increased by DPPC, suggesting that lecithin, the major surfactant component, increases the PGE production of the amniotic membrane by activating PLA2.

1,2-Dipalmitoylphosphatidylcholine↗

Detection of a fast isoform of C-protein with an antiserum directed against the N-terminal portion of dystrophin.

An antiserum raised against the N-terminal actin-binding portion of dystrophin cross-reacted with a 130-kDa protein in fast skeletal muscle. The results of purification and two-dimensional gel electrophoresis and its immunological properties demonstrated that this protein is identical to a 130-kDa basic isoform of fast-C-protein. These results suggest that the actin-binding domain of dystrophin shares one or more antigenic determinants with those of C-protein.

Antibodies↗

Mitochondrial energy-linked nicotinamide nucleotide transhydrogenase: effect of substrates on the sensitivity of the enzyme to trypsin and identification of tryptic cleavage sites.

The mitochondrial nicotinamide nucleotide transhydrogenase catalyzes hydride ion transfer between NAD(H) and NADP(H) in a reaction that is coupled to proton translocation across the inner mitochondrial membrane. The enzyme (1043 residues) is composed of an N-terminal hydrophilic segment (approximately 400 residues long) which binds NAD(H), a C-terminal hydrophilic segment (approximately 200 residues long) which binds NADP(H), and a central hydrophobic segment (approximately 400 residues long) which appears to form about 14 membrane-intercalating clusters of approximately 20 residues each. Substrate modulation of transhydrogenase conformation appears to be intimately associated with its mechanism of proton translocation. Using trypsin as a probe of enzyme conformation change, we have shown that NADPH (and to a much lesser extent NADP) binding alters transhydrogenase conformation, resulting in increased susceptibility of several bonds to tryptic hydrolysis. NADH and NAD had little or no effect, and the NADPH concentration for half-maximal enhancement of trypsin sensitivity of transhydrogenase activity (35 microM) was close to the Km of the enzyme for NADPH. The NADPH-promoted trypsin cleavage sites were located 200-400 residues distant from the NADP(H) binding domain near the C-terminus. For example, NADPH binding greatly increased the trypsin sensitivity of the K410-T411 bond, which is separated from the NADP(H) binding domain by the 400-residue-long membrane-intercalating segment. It also enhanced the tryptic cleavage of the R602-L603 bond, which is located within the central hydrophobic segment. These results, which suggest a protein conformation change as a result of NADPH binding, have been discussed in relation to the mechanism of proton translocation by the transhydrogenase.

Amino Acid Sequence↗

The mechanism of antifungal action of (S)-2-amino-4-oxo-5-hydroxypentanoic acid, RI-331: the inhibition of homoserine dehydrogenase in Saccharomyces cerevisiae.

We have explored the mechanism by which an antifungal antibiotic, (S)-2-amino-4-oxo-5-hydroxypentanoic acid, RI-331, preferentially inhibits protein biosynthesis in Saccharomyces cerevisiae, by inhibiting the biosynthesis of the aspartate family of amino acids, methionine, isoleucine and threonine. This inhibition was effected by inhibiting the biosynthesis of their common intermediate precursor homoserine. The target enzyme of RI-331 was homoserine dehydrogenase (EC.1.1.1.3) which is involved in converting aspartate semialdehyde to homoserine in the pathway from aspartate to homoserine. The enzyme is lacking in animals. So the antibiotic is selectively toxic to prototrophic fungi.

Alcohol Oxidoreductases↗

Biosynthesis of the trypanosomatid metabolite trypanothione: purification and characterization of trypanothione synthetase from Crithidia fasciculata.

Trypanothione synthetase from Crithidia fasciculata has been purified ca. 14,500-fold to homogeneity in an overall yield of 40%. The pure enzyme catalyzed the synthesis of N1- and N8-glutathionylspermidine and N1,N8-bis(glutathionyl)spermidine (trypanothione) from ATP/magnesium, glutathione (GSH), and spermidine, N1- and N8-glutathionylspermidines being intermediates of trypanothione synthesis. The enzyme showed a sharp pH optimum of 7.5-7.75 for the synthesis of both mono- and diglutathionylspermidine conjugates. It was highly specific for its physiological substrates ATP/Mg2+, GSH, spermidine, and N1- and N8-glutathionylspermidine with Km values of 400 microM, 914 microM, 1.07 mM, 20 microM, and 7 microM, respectively. Trypanothione synthetase was active in the monomeric form with Mr = 87,000 and absorption maxima lambda max = 225 and 280 nm (A280/A260 = 1.85). Trypanothione synthetase is a new member of the ATP-dependent class of ligases which form amide linkage with concomitant production of ADP and orthophosphate.

Amide Synthases↗

Behavioural effects of 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) in monkeys.

Subcutaneous injections of a 5-HT1A receptor agonist, 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), in monkeys induced distinct behavioural changes characterized by head weaving, hindlimb extension and upper limb fluttering. The effects were dose-dependent and were similar to the 5-HT syndrome induced in rats by 8-OH-DPAT. The 5-HT receptor antagonist, metergoline, attenuated the behavioural syndrome seen in response to 8-OH-DPAT. These results suggest that 8-OH-DPAT induces a 5-HT1A receptor-mediated behavioural syndrome in monkeys as well as in rodents.

8-Hydroxy-2-(di-n-propylamino)tetralin↗