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Biomedical subjects

H Harada

Publications and source records attributed to H Harada.

At least 487 records · Page 27Linked to original sources

[Malignant histiocytosis with complex chromosomal abnormality: successful treatment with CHOP-E chemotherapy].

A 43 year-old man admitted to our hospital because of fever and splenomegaly. Laboratory findings were as follows: Hb 9.5 g/dl, Plts 4.9 X 10(4)/microliter, LDH 2,348 IU/l. Bone marrow findings showed tumor cell 47% with or without phagocytosis. The tumor cells were stained positive lysozyme and alpha 1 antitrypsin. Cytogenetic study was 47, XY, -7, -8, +9, -11, -12, -19, -21, 3q+, 6p+, +6 markers. This case was diagnosed as malignant histiocytosis. Complete remission was achieved with CHOP-E chemotherapy. Remission has been maintained with repeated this therapy. Etoposide deserves a good evaluation in the treatment of malignant histiocytosis. Some cases of malignant histiocytosis with a t(2; 5) (p23; q35) translocation were often reported in Europe and America, while there was no specific chromosomal abnormalities with malignant histiocytosis in Japan.

Adult↗

Absence of the type I IFN system in EC cells: transcriptional activator (IRF-1) and repressor (IRF-2) genes are developmentally regulated.

Interferons (IFNs) are a heterogeneous family of cytokines that exhibits multiple biological activities. Upon viral infection, expression of type I IFNs (i.e., IFN-alpha and IFN-beta) is induced in a variety of differentiated cells but not in cells of embryonal origin. IRF-1 and IRF-2, which bind to the same cis-elements within the promoters of type I IFN and IFN-inducible MHC class I genes, were identified previously. Here we demonstrate that the expression of both IRF and IFN genes is developmentally regulated in mouse EC cells; these genes become functional only after cell differentiation. Furthermore, cDNA-directed IRF-1 produced in undifferentiated but not differentiated EC cells efficiently activates the transfected IFN-alpha and IFN-beta and endogenous IFN-alpha genes, whereas IRF-2 represses the IRF-1 effects. These findings emphasize the dual function of the IRF-responsive cis-elements as positive and negative regulators, since they can be occupied by transcriptionally active or inactive IRF molecules. This type of regulatory mechanism might operate in other cytokine systems.

Animals↗

Hepatitis C viral cDNA clones isolated from a healthy carrier donor implicated in post-transfusion non-A, non-B hepatitis.

Using a specific hepatitis C virus (HCV) antibody assay, positive blood donors responsible for the transmission of post-transfusion non-A, non-B hepatitis (PT-NANBH) were identified. cDNA fragments were isolated from one of the plasma samples of such healthy HCV carriers by using polymerase chain reactions. Nucleotide (nt) sequence analyses of the cDNA from three different regions of the viral genome revealed that they were derived from a Japanese HCV isolate that was similar but not identical to the prototype HCV previously isolated from a chronically infected chimpanzee. Homology at the nt and amino acid levels was comparatively lower in the presumed structural region than in putative nonstructural regions. This result not only confirms that HCV antibody-positive blood contains infectious HCV, but suggests the existence of different type(s) of HCV.

Amino Acid Sequence↗

The human interleukin-2 receptor beta-chain gene: genomic organization, promoter analysis and chromosomal assignment.

The chromosomal gene for the human interleukin-2 receptor beta-chain (IL-2R beta) was isolated and characterized. The entire IL-2R beta gene is composed of ten exons spanning about 24.3 kilobases, in which the protein is encoded by the exons 2-10. The cysteine rich extracellular region which displays a significant evolutionary resemblance to other cytokine receptors, as well as growth hormone and prolactin receptors, is encoded primarily by exons 3 and 4, whereas the membrane proximal, cysteine poor domain showing a homology with type III modules of fibronectin is encoded by exon 7. Sequence analysis of the 5'-flanking region revealed the presence of potential binding sites for transcription factors such as Octamer binding factors, AP-1, AP-2 as well as the 'GC-clusters'. At least five potential cap sites were identified by S1 mapping analysis. The 850 bp DNA sequence of the 5'-flanking region exhibited constitutive promoter activity when it was linked upstream of the HSV-tk reporter gene and then transfected into YT cells, a human leukemic cell line. By applying the RFLP linkage analysis, the IL-2R beta gene has been assigned to chromosome 22q12-13.

Base Sequence↗

Phosphorylated mu-opioid receptor purified from rat brains lacks functional coupling with Gi1, a GTP-binding protein in reconstituted lipid vesicles.

The effects of phosphorylation of a mu-opioid receptor on signal transduction to G-protein were studied. The mu-opioid receptor purified from rat whole brains was reconstituted with purified Gi1 in phosphatidylcholine vesicles. DAGO, a mu-opioid agonist at 1 microM-1 mM increased GTPase activity by 10-110% of control, in a concentration-dependent manner. When the mu-opioid receptor was phosphorylated by cyclic AMP-dependent protein kinase prior to reconstitution with Gi1, the DAGO-stimulation was markedly reduced (20% increase at 1 mM DAGO).

Animals↗

Taurine deficiency and doxorubicin: interaction with the cardiac sarcolemmal calcium pump.

An anticancer drug, doxorubicin, and a naturally occurring beta-amino acid, taurine, exert opposing actions on myocardial calcium content and lipid peroxidation. Thus, we tested the hypothesis that the two agents may interact to modify cardiac calcium metabolism and indices of lipid peroxidation. Cardiac taurine levels were reduced by half in rats given tap water containing a beta-amino transport inhibitor, beta-alanine. Taurine deficiency was associated with an increased susceptibility of the heart to doxorubicin-mediated calcium accumulation, a phenomenon commonly associated with doxorubicin cardiotoxicity. Taurine deficiency also predisposed the heart to enhanced formation of malondialdehyde caused by doxorubicin administration. While increases in malondialdehyde levels are often associated with lipid peroxidation, the failure of doxorubicin to cause changes in oxidized glutathione content makes peroxidative mechanisms a less likely explanation for the potentiation of doxorubicin-mediated myocardial calcium accumulation in taurine-deficient rats. A more likely possibility is the interaction between taurine deficiency and doxorubicin to inhibit the sarcolemmal calcium pump. The data also suggest that the interaction between doxorubicin and taurine deficiency does not involve alterations in the pharmacokinetics of doxorubicin or the cardiotoxic metabolite, doxorubicinol. It is concluded that reduction in sarcolemmal calcium pump activity by taurine deficiency may contribute to myocardial calcium accumulation in hearts whose calcium homeostasis has been compromised by doxorubicin.

Animals↗

Estimation of biotinylated lectin by isoelectric focusing.

Concanavalin A (Con A) was biotinylated to various degrees using N-biotinyl-omega-aminocaproic-acid-N-hydroxy succinimide ester as the biotinylation reagent, and then analyzed by isoelectric focusing using PhastGel IEF 3-9. The isoelectric points of biotinylated ConAs were found to decrease with increasing concentration of the biotinylation reagent. Analysis by isoelectric focusing followed by dot blotting clearly indicated that the biotinylated ConA with an isoelectric point lower than that of the original ConA by 2.2 +/- 0.6 had the strongest binding activity for ovalbumin.

Biotin↗

Mucin-specific bark lectin from elderberry Sambucus sieboldiana and its applications to the affinity chromatography of mucin.

Three bark lectins were isolated from elderberry Sambucus sieboldiana using fetuin-Sepharose 4B and mucin-Sepharose 4B, and were studied comparatively for their binding to glycoprotein and to clarify various physicochemical features. For each, a unique pattern on isoelectric focusing was noted and their affinity toward various glycoproteins differed, indicating the structures of their carbohydrate binding sites possibly differ. One bark lectin showed specific binding toward porcine mucin. The purity of mucin from a crude porcine stomach mucin or an extract of porcine submaxillary glands could be improved by affinity chromatography on immobilized lectin having binding specificity toward mucin.

Animals↗

Treatment of donor cells with L-leucyl-L-leucine methyl ester prevents induction of graft-vs-host-like reaction in [lpr/lpr----+/+] chimera.

Irradiated C57BL/6 (B6) mice which had received spleen cells from autoimmune-prone C57BL/6J-lpr/lpr (B6-lpr) mice underwent a graft-versus-host (GvH)-like reaction early after the spleen cell transfer, although both strains have the same background genes, including MHC and Mls gene, but differ only in a lpr gene. We analyzed the changes in this GvH-like reaction when the donor spleen cells had been treated with L-leucyl-L-leucine methyl ester, which has been reported to have an inhibitory effect on the early GvH reaction in allogeneic or semiallogeneic chimeras. The treatment of donor spleen cells completely abrogated the induction of the early phase of the GvH-like reaction in [B6-lpr----B6] chimeras. The results suggest that the GvH-like reaction in these chimeras is caused by a mechanism(s) similar to that operating in allogeneic or semiallogeneic chimeras.

Animals↗

Brain abscess associated with congenital pulmonary arteriovenous fistula.

A case of brain abscess associated with congenital pulmonary arteriovenous fistula was presented and 52 reported cases were reviewed. The brain abscess was successfully treated with repeated aspiration and drainage, and the pulmonary arteriovenous fistula, located in the right lower lobe, was resected. The arteriovenous fistula occurs as a common pulmonary manifestation of hereditary hemorrhagic telangiectasia; however, no symptoms suggesting these two were noted in this case. Brain abscesses can be an initial clinical manifestation in asymptomatic pulmonary arteriovenous fistula. This possible association should be borne in mind in cases of brain abscesses of unexplained etiology.

Arteriovenous Fistula↗

Inhibition of influenza virus infection by pine cone antitumor substances.

The anti-influenza virus activity of polysaccharides and other high molecular weight fractions from pine cone extract (PCE) of Pinus parviflora Sieb. et Zucc. was investigated. None of the fractions affected the growth of MDCK cells. The acidic PCE substances markedly suppressed the growth of the influenza virus in MDCK cells. Significant inhibition of both the viral protein synthesis in infected cells and virion-associated RNA-dependent RNA polymerase activity was observed with these acidic fractions. Although amantadine inhibited virus plaque formation as effectively as PCE fractions, it was less effective in inhibiting the RNA polymerase activity. These results suggest that PCE, which has been shown to contain antitumor substance(s), also contains anti-influenza virus substance(s).

Amantadine↗

Orally potent human renin inhibitors derived from angiotensinogen transition state: design, synthesis, and mode of interaction.

A three-dimensional structure of the complex of human renin and the scissile site P4 Pro to P1' Val of angiotensinogen was deduced in order to design potent human renin inhibitors rationally. On the basis of this structure, an orally potent human renin inhibitor (1a) was designed from the angiotensinogen transition state and synthesized. The inhibitor 1a contains a (2R)-3-(morpholinocarbonyl)-2-(1-naphthylmethyl)propionyl residue (P4-P3) with a retro-inverso amide bond, L-histidine, and a novel amino acid, (2R,3S)-3-amino-4-cyclohexyl-2-hydroxybutyric acid, named cyclohexylnorstatine (2a). The optically pure cyclohexylnorstatine was efficiently prepared from Boc-L-cyclohexylalaninol (3), and the stereochemistry of 1a was established by X-ray crystal analysis. The analyses of interaction between 1a and human renin using modeling techniques indicated that (1) the cyclohexyl group of P1 and the naphthyl group of P3 were accommodated in large hydrophobic subsites S1 and S3, respectively; (2) the imidazole of P2 His was hydrogen bonded to the side chain OH of Ser-233 to contribute to the selectivity of renin inhibition; (3) cyclohexylnorstatine isopropyl ester residue was accommodated in S1-S1'. The importance of the stereochemistry in the potent and specific inhibitor was clearly shown. Oral administration to monkeys of this inhibitor resulted in a drop of 10-20 mmHg in mean blood pressure and a reduction of plasma renin activity for a 5-h period.

Administration, Oral↗

Hepatitis C virus infection is associated with the development of hepatocellular carcinoma.

A possible causative role for the recently discovered hepatitis C virus (HCV) in the development of hepatocellular carcinoma (HCC) was investigated by assay of sera from HCC patients in Japan for antibodies to a recombinant HCV antigen and to hepatitis B virus (HBV) antigens. Among the 253 HCC patients examined, 156 (61.7%) had no serum markers of either a previous or a current HBV infection (group I), 46 (18.2%) were negative for HBV surface antigen but positive for anti-HBV surface and/or anti-HBV core antibody, indicating the occurrence of a previous, transient HBV infection (group II), and 51 (20.2%) were chronically infected HBV carriers as evidenced by positivity for HBV surface antigen (group III). The prevalence of HCV antibody in group I (68.6%) and II (58.7%) patients was significantly higher than for group III (3.9%) or in 148 additional patients with other (non-HCC) cancers (10.1%) (P less than 0.01). Thus, there appears to be a strong association between HCV infection and the development of HCC, particularly in patients for which HBV infection cannot be implicated as a causative factor. The data also suggest an additional mode of transmission for HCV other than blood transfusion, since a history of blood transfusion was shown in only about 30% of the HCV antibody-positive HCC patients in groups I and II. A high prevalence of HCV antibody was also shown among patients with HCC whose disease was originally thought to be due to very high ethanol consumption.

Blood Transfusion↗

Effect of viscous indigestible polysaccharides on pancreatic-biliary secretion and digestive organs in rats.

Effects of viscous indigestible polysaccharides on the pancreas exocrine function were investigated in growing rats. Rats were fed a nonfiber diet or a diet containing approximately 5% of one of the following fibers: apple pectin, lambda-carrageenan, locust bean gum, gum xanthan, guar gum or sodium (Na) alginate. Pancreatic-bile secretion was found to be elevated in rats fed for 2 wk the highly viscous polysaccharides, sodium alginate, locust bean gum, gum xanthan and guar gum. The polysaccharides may have interfered with the digestion and absorption of nutrients, resulting in a decreased digestibility and an enlargement of digestive organs. When alginic acid and calcium alginate, insoluble polysaccharides that did not contribute to viscosity, were given to rats, they had no effect on pancreatic and biliary secretion compared with sodium alginate. The results demonstrate that consumption of viscous indigestible polysaccharides leads to changes in the exocrine pancreatic-biliary function and may depress the process of digestion and absorption. Rats may compensate for the inefficiency of digestion and absorption with a hyperplasia/hypertrophy of digestive organs and an increased secretion of digestive juice.

Alginates↗

Isolation and characterization of a novel nuclear protein from pollen mother cells of lily.

Pollen mother cells of the lily (Lilium speciosum) were found to have a histone-H1-like protein (PMCP) not detected in other tissues. The PMCP appears from the late S-G(2) period of premeiosis and is present in mature pollen. PMCP and H1 were extracted from pollen mother cells with 5% perchloric acid and isolated by reverse-phase high-performance liquid chromatography. The amino acid composition of PMCP differs from that of somatic H1. However, PMCP is similar to H1t in mammalian testis with regard to amino acid composition.

Journal Article↗

Beta-adrenoceptor control of peroxidase synthesis in nasal glands.

Endogenous peroxidase activity was observed in the cisternae of the rough-surfaced endoplasmic reticulum (r-ER), including the nuclear envelope, Golgi complex, and secretory granules of the cat's nasal glands. A single injection of propranolol resulted in a decrease of peroxidase-positive secretory granules, an increase of electron-lucent granules, and no change in the level of peroxidase activity in the r-ER and Golgi complex at either 5 or 9 hours after the injection. Continuous administration of propranolol over 7 hours led to the disappearance of peroxidase activity from the r-ER and secretory granules. These data would indicate that propranolol inhibits only the synthesis of peroxidase. Twenty minutes after a single injection of isoproterenol, the rate at which the granule content containing the peroxidase reaction product was discharged into the acinar lumen increased sharply. However, 60 minutes after the injection, the secretion rate of peroxidase-positive granules decreased. The same experiment then was repeated, but this time before the isoproterenol was injected, propranolol was administered to the cats. This time no change in peroxidase activity appeared in the acinar cells. It was concluded, therefore, that the stimulation of beta-receptors enhances the synthesis of peroxidase.

Animals↗