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Biomedical subjects

N Nishi

Publications and source records attributed to N Nishi.

At least 91 records · Page 5Linked to original sources
PubMed1996

Granulocyte-colony stimulating factor and stem cell factor are the crucial factors in long-term culture of human primitive hematopoietic cells supported by a murine stromal cell line.

The findings that murine marrow stromal cell line MS-5 supported the proliferation of human lineage-negative (Lin-) CD34+CD38- bone marrow cells in long-term culture have been reported. In this study, we analyzed this proliferating activity of MS-5-conditioned medium (CM) on human primitive hematopoietic cells. When Lin-CD34+CD38- cells of normal human cord blood cells were co-cultured with MS-5, colony forming cells (CFCs) were maintained over 7 weeks in vitro. Prevention of contact between MS-5 and Lin-CD34+CD38- cells by using membrane filter (0.45 micron) was negligible for this activity. This indicated that the activity of MS-5 on human primitive hematopoietic cells is a soluble factor(s) secreted from MS-5, which is not induced by the contact between MS-5 and Lin-CD34+CD38- cells. We tried to purify this soluble activity. An active material with a molecular weight of about 150 kDa, determined by gel filtration chromatography, solely supported the growth of Lin-CD34+CD38- cells and Mo7e, a human megakaryocytic cell line. This activity not only reacted with anti-mouse stem cell factor (mSCF) antibody on Western blots, but it was also neutralized in the presence of anti-mSCF antibody. Another active material with a molecular weight of about 20-30 kDa synergized with mSCF to stimulate the growth of Lin-CD34+CD38- cells but failed to do so alone, although this synergy was inhibited in the presence of soluble mouse granulocyte-colony stimulating factor (mG-CSF) receptor, which is a chimeric protein consisting of the extracellular domain of mG-CSF receptor and the Fe region of human IgG1. In addition, the latter molecule supported the growth of the G-CSF dependent cell line FD/GR3, which is a murine myeloid leukemia cell line, FDC-P2, transfected with mG-CSF receptor cDNA. Adding of anti-mSCF antibody and soluble mG-CSF receptor to the culture completely abrogated the activity of MS-5-CM. Recombinant (r) mSCF and rmG-CSF had synergistic activity on the growth of Lin-CD34+CD38- cells. These results indicated that the activity on Lin-CD34+CD38- cells included in MS-5-CM is based upon the synergistic effects of mSCF and mG-CSF.

ADP-ribosyl Cyclase↗
PubMed1995

Synthesis and conformational investigation of tandem repeat sequence in RNA polymerase II.

The largest subunit of RNA polymerase II has a very interesting sequence in the C-terminus; that is, a tandem repeat sequence of Ser-Pro-Thr-Ser-Pro-Ser-Tyr consisted of proline residues and three kinds of residues having side-chain hydroxyl groups. Although lack of this tandem repeat is a lethal event in vivo, its functional role is unclear. The sequential polypeptide corresponding to this tandem repeat, poly(Ser-Pro-Thr-Ser-Pro-Ser-Tyr), was synthesized and its conformation was investigated by circular dichroism comparing to the monomeric heptapeptide. In addition, the theoretical conformational analysis based on the molecular mechanics was tried for the heptapeptide in the repeating unit and the periodic polyheptapeptide corresponding to the tandem repeat sequence. These results suggested the possibility that the tandem repeat contains a kind of super conformation composed of the repetitive turn structure in the native state. The characteristic repetitive turn structure would be the key of its function mechanism.

Amino Acid Sequence↗
PubMed1995

Hematopoietic stem cells found in lineage-positive subsets in the bone marrow of 5-fluorouracil-treated mice.

It is known that treatment of mice with 5-fluorouracil (5-FU, 150 mg/kg) confers radioprotection. To investigate this effect, we performed bone marrow transplantation (BMT) using C57BL/6-Ly5 congenic mice treated with 5-FU five days prior to experiments. The mononuclear cells (MNC) in 5-FU-treated bone marrow (BM) were 10 times more radioprotective than those in untreated BM. Moreover, the number of BM MNC expressing c-kit on their surface from 5-FU-treated mice was markedly decreased relative to those from untreated controls. These results showed that the surface characteristics of cells that contributed to this radio-protective effect differ from those of stem cells as reported recently. BM MNC of mice treated with 5-FU were separated on the basis of expression of the lineage-specific antigens (Lin), c-kit, and Ly6A/E. When injected into lethally irradiated mice, 1,000 Lin+ and Lin-c-kit+Ly6A/E+ cells showed radioprotective effects such that 100% and 60% survived, respectively. Flow cytometric analysis 165 days after BMT showed that 88.8% and 65.1% of peripheral blood (PB) in mice transplanted with Lin+ and Lin-c-kit+Ly6A/E+ was derived from donor mice, respectively. After six months, donor-derived Lin-c-kit+Ly6A/E+ cells which showed radioprotective effects on a secondary irradiated host were detected from mice transplanted with Lin+ cells from 5-FU-treated mice. Taken together, these findings demonstrated that stem cells expressing Lin+ present in the BM of mice treated with 5-FU other than Lin-c-kit+Ly6A/E+ cells and these Lin+ cells play an important role in the recovery of myeloablative mice.

Animals↗
PubMed1995

Improvement of anemia in W/WV mice by recombinant human erythropoietin (rHuEPO) mediated through EPO receptors with lowered affinity.

We studied the effects of recombinant human erythropoietin (rHuEPO) on anemic W/WV mice which manifested severe anemia accompanied by mutation of the W gene encoding tyrosine kinase type receptor (c-kit gene) of bone marrow hematopoietic cells. Nine-week-old male W/WV mice or normal littermates (+/+) were used. Since serum EPO concentration in W/WV mice increased in proportion to severity of anemia, EPO production in the kidneys of these animals was found to be regulated normally. Hematocrit in +/+ mice increased and a maximal response was also obtained with 2,000 IU/kg of rHuEPO. On the other hand, hematocrit in W/WV mice increased in a dose-responsive manner by administration with 2,000 and 10,000 IU/kg, showing different responses to rHuEPO in these two types of mice. The responsiveness of W/WV mice to rHuEPO was low in terms of increases in erythroblastic precursor cells (CFU-E), and immature cells in the bone marrow. Scatchard analysis of the specific binding of 125I-rHuEPO against bone marrow cells revealed that the different responsiveness to rHuEPO between W/WV and +/+ mice may be correlated with differences in affinity of EPO receptor of bone marrow cells in these mice. From these results, a high dose of rHuEPO is capable of improving the anemia in W/WV mice that had EPO receptors with lowered affinity, indicating the possible effectiveness of rHuEPO in anemic patients with EPO receptor abnormality.

Anemia↗
PubMed1995

[Effect of efonidipine hydrochloride, a calcium channel blocker, on the experimental cerebral ischemia/anoxia].

The anti-ischemic and anti-anoxic effects of efonidipine, a dihydropyridine calcium antagonist, were studied in several models for cerebral ischemia and anoxia in mice and rats, and the effects were compared with those of nicardipine and flunarizine. Both efonidipine and flunarizine showed protective effects in the models of KCN-induced anoxia and complete ischemia induced by decapitation in mice 6 hr after the treatment, while nicardipine did not show such a long-lasting effect. Efonidipine (1 mg/kg, i.p.), but not nicardipine and flunarizine, prolonged the tolerance times in the asphyxic anoxia model. In mice, efonidipine (4 mg/kg, i.p.) significantly reduced the cumulative mortality rate after bilateral carotid artery ligation. The survival rates at 20 hr after bilateral carotid artery ligation were 33% in the group treated with efonidipine, significantly higher than that in the control group, 0%. On the other hand, the treatment with nicardipine or flunarizine did not increase the rates at 20 hr after the ligation. Moreover, efonidipine attenuated the disturbance of cerebral energy metabolism induced by decapitation in rats. These effects of efonidipine observed in this study were on the whole superior to those of the reference drugs, strongly suggesting the improving effect of efonidipine on cerebral ischemia and anoxia.

Animals↗
PubMed1994

Identification of probasin-related antigen as cystathionine gamma-lyase by molecular cloning.

We reported previously that a monoclonal antibody against probasin (rat prostatic secretory protein) recognizes a 40-kDa protein localized in rat liver and kidney. The protein (probasin-related antigen, PRB-RA) may participate in a specific differentiated function of these tissues. To clarify the molecular nature of PRB-RA, a series of cDNA clones coding for the protein were isolated from a rat liver expression library using an affinity-purified polyclonal antibody. The amino acid sequence deduced from the determined cDNA sequence included sequences identical with those of proteolytic fragments of PRB-RA, which covered about 70% of the deduced sequence. Northern blot hybridization of poly(A)+ RNA isolated from rat tissues showed the presence of predominant and minor mRNA species of about 2.0 and 4.3 kilobases, respectively, in the liver and kidney. A sequence homology search revealed that PRB-RA is almost completely identical to rat cystathionine gamma-lyase (cystathionase) and that it does not show overall homology with probasin. Three candidates for an epitope common to probasin and PRB-RA were found on close examination of the amino acid sequences of the two proteins. A synthetic peptide, TYFRRI, corresponding to one of the candidates, neutralized the reactivity of the anti-probasin monoclonal antibody to both probasin and PRB-RA on Western blot analysis. These results show that PRB-RA/cystathionase is neither structurally nor functionally related to probasin except for a common epitope and that cystathionase, a cystein-producing enzyme, is localized in urinary tubular epithelial cells in a highly restricted region of the kidney in addition to in liver parenchymal cells.

Amino Acid Sequence↗
PubMed1994

Combination therapy consisting of arterial infusion chemotherapy (EPF, EAP) and transcatheter arterial embolization (TAE).

From January 1988 to January 1993, 45 patients with unresectable advanced hepatocellular carcinoma (HCC) were treated with a new combination therapy consisting of arterial infusion chemotherapy and TAE. The combination therapy was performed according to our treatment schedule as follows: two courses of arterial infusion chemotherapy were given first, and then transcatheter arterial embolization (TAE) using a mixture of Lipiodol and cisplatin powder was performed. Two arterial infusion chemotherapeutic regimens were employed: EPF (etoposide, cisplatin, and 5-fluorouracil) and EAP (etoposide, Adriamycin or Epi-adriamycin, and cisplatin). The anticancer drugs were infused through a catheter inserted into the proper or common hepatic artery. Assessment was made of the anticancer effect and survival rate of each treatment method. The response to each therapy was evaluated on the basis of CT performed prior to and after the treatment. In the EPF.TAE group, the response rate was about 46%, whereas in the EAP.TAE group it was 48%. Overall, 21 of 45 patients attained a regression rate of 50% or more. Furthermore, daughter nodules decreased in size or disappeared in about 67% of 15 patients. Additionally, tumor thrombi tended to show a similar response. In all of the cases, the average duration of survival was 30.3 months, and the 1-year survival value was 68%, the 2-year survival value was 44%, and the 3-year survival value was 35%. These results were superior to those obtained with TAE therapy alone.

Adolescent↗
PubMed1994

Biosynthesis of a novel polysaccharide by Acetobacter xylinum.

An Acetobacter xylinum adapted to a medium containing N-acetylglucosamine (GlcNAc) has been used to prepare a novel polysaccharide containing residual GlcNAc in cellulose. The maximum amount of incorporation was found to be 4 mol% in cellulose, when a mixed medium containing 1.4% glucose (Glc) and 0.6% GlcNAc was used for the culture of A. xylinum. The resulting polysaccharide was lysozyme-susceptible. The aminosugar residue incorporated into bacterial cellulose was found to be only GlcNAc, even if galactosamine (GalN) and glucosamine (GlcN) were applied, whereas there was little effect by mannosamine (ManN). As the major component of the resulting polysaccharide was Glc residues, even if the only carbon source in the culture medium was GlcNAc, it was suggested that there must be several enzyme systems to convert GlcNAc into Glc in the bacteria. Several ammonium salts were also found to be effective for the incorporation of GlcNAc residues when the incubation system was converted to rotatory and aerobic incubation from static incubation. The amount of residual GlcNAc was remarkably increased by the addition of lysozyme-susceptible phosphoryl-chitin (P-chitin) and increased slightly with addition of P-chitin that was less lysozyme-susceptible. However, little effect was found on addition of highly substituted P-chitin.

Acetylglucosamine↗
PubMed1994

Inhibition of acto-myosin subfragment-1 ATPase activity by peptides corresponding to various segments of the 20-kDa domain of myosin heavy chain.

As reported previously, the synthetic heptapeptide having the amino acid sequence around the reactive Cys (SH1) of myosin heavy chain, IRICRKG-NH2, inhibited acto-myosin subfragment-1 (S-1) ATPase activity and half inhibition (K1/2) was observed at a peptide concentration of 0.06 mM. The inhibitory ability of the peptide was found to be decreased to one-fifth by acetylation of its N-terminal alpha-amino group. A similar effect of N-acetylation was observed with a nonapeptide, EGIRICRKG-NH2, and an undecapeptide, VLEGIRICRKG-NH2. These results indicate that N-terminal-free synthetic peptides do not act as proper analogs of the corresponding segment of S-1 heavy chain against F-actin. We isolated a longer peptide extending from Thr682 to Lys709 in S-1 heavy chain, with two Cys residues corresponding to SH1 and SH2. This peptide, having 28 residues (28peptide), inhibited acto-S-1 ATPase activity with a K1/2 of 0.23 mM. A cosedimentation binding assay indicated that the 28peptide completely dissociated acto-S-1 in the presence of ATP. This behavior is different from that observed with the N-terminal-free synthetic heptapeptide, and thus the 28peptide might be an analog of the corresponding segment. There is a possibility that the region corresponding to the 28peptide in S-1 heavy chain may bind directly with F-actin and may be involved in determining the acto-S-1 link during the steady state of the acto-S-1 ATPase reaction.

Acetylation↗
PubMed1994

[Analysis of tuberculosis cases among students reported from Osaka prefectural high schools and counter--measures for tuberculosis].

The number of newly registered cases of tuberculosis has been increasing in the age group 15-19 year-old and over. To investigate the prevention of tuberculosis among young people under 20 years old, a survey was conducted on reported cases of tuberculosis among Osaka Prefectural high school students during the period from April, 1989 to May, 1994. Altogether 67 cases were reported from their schools during this period. Although there was a decrease in the total number of students since 1990, there was no corresponding decrease in the number of cases of tuberculosis. Of the total number of cases among high school students registered at public health centers in Osaka, only 23% were reported from the high schools. Cases confirmed bacteriologically positive consisted 13% of all cases. Male students accounted for 61% of reported cases. The methods of detection included medical consultation due to symptoms (75%), mass radiography (18%) and pre-employment health checkup (7%). 46% of cases reported during the first school year were discovered by mass radiography. While 24% of all cases were detected in April, no less than 46% of cases among those in the first school year were detected in April. Compared with those detected in any other school years, cases detected in the first school year showed some characteristic differences with regards to detection and bacteriological results. There has been one tuberculosis epidemic which accounted for six cases during the past five years.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1994

A highly enhanced thrombopoietic activity by monomethoxy polyethylene glycol-modified recombinant human interleukin-6.

Interleukin-6 (IL-6) is a novel cytokine with activities that can affect hematopoietic cells including those of the megakaryocytic lineage. We have examined the effects of monomethoxy polyethylene glycol-modified recombinant human interleukin-6 (Peg-IL-6) on thrombopoiesis in vivo. To compare the thrombopoietic activity between Peg-IL-6 and unmodified IL-6, each was administered subcutaneously to mice every 24 hours at various doses. A dose-response experiment showed that Peg-IL-6 and IL-6 increased platelet counts in a dose-dependent fashion at a plateau stimulation level of 0.5 micrograms/day and 10 micrograms/day, respectively. This dose of Peg-IL-6 and IL-6 induced the elevated platelet counts by approximately 140% to 160% and 50% to 60%, respectively. Peg-IL-6 treatment (0.5 micrograms/day) for x-ray (6.0 Gy) irradiated mice induced an increase in the rate of platelet recovery, and a higher dosage (5 micrograms/day) completely blocked the induction of thrombocytopenia in this model. In contrast, IL-6 (10 micrograms/day) could not protect the animals from platelet nadir but reduced the period of thrombocytopenia after x-ray irradiation. Furthermore, when administered to 5-fluorouracil-treated mice, 5 micrograms/day of Peg-IL-6 diminished the platelet nadir and increased platelet counts on individual days during the recovery phase. The potent thrombopoietic activity of Peg-IL-6 were due to prolongation of circulating IL-6 levels that were reverted from Peg-IL-6 in vivo. These findings indicate that reduction of total body clearance of IL-6 induces potent thrombopoiesis and that Peg-IL-6 may be a useful thrombopoietic agent.

Animals↗
PubMed1993

Inhibition of tumor metastasis by Arg-Gly-Asp-Ser (RGDS) peptide conjugated with sulfated chitin derivative, SCM-chitin-RGDS.

We have synthesized a new compound in which Arg-Gly-Asp-Ser (RGDS) was conjugated with 6-O-sulfated and 6-O-carboxymethyl-chitin (SCM-chitin), i.e. SCM-chitin-RGDS, and tested the inhibitory effect on lung and liver metastases of three different types of tumors in mice. SCM-chitin-RGDS was more effective for the inhibition of liver metastasis of L5178Y-ML25 lymphoma and lung metastases of colon 26 M3.1 cells than SCM-chitin, RGDS or their mixture. GRGDS peptide, however, required a higher dose (3000 micrograms) to obtain a sufficiently antimetastatic effect. Intermittent i.v. administration of SCM-chitin-RGDS before or after the i.v. inoculation of L5178Y-ML25 cells caused significant inhibition of liver metastasis as compared with the multiple administration of RGDS, SCM-chitin or untreated control. Co-injection of lymphoma cells with SCM-chitin-RGDS or multiple treatment of SCM-chitin-RGDS after tumor inoculation showed significantly enhanced survival rate. SCM-chitin-RGDS also showed the spontaneous lung metastasis produced by intrafootpad injection of B16-BL6 melanoma cells by the multiple i.v. administrations. These results demonstrate that the conjugation of RGDS peptide with SCM-chitin led to augmentation of therapeutic potential to cancer metastasis, thus implying an importance of the conjugation of cell-adhesive RGDS peptide with structurally heparin-like SCM-chitin, which possess binding ability to the heparin-binding domain of fibronectin or laminin and extremely low anticoagulant properties.

Amino Acid Sequence↗
PubMed1993

Primary structure of scombrine gamma, protamine isolated from spotted mackerel (Scomber australasicus).

Spotted mackerel protamine, scombrine, was isolated from the sperm of a spotted mackerel (Scomber australasicus) by extraction with sulfuric acid and fractionated into one major (scombrine II) and one minor (scombrine I) components by chromatography on CM-Sephadex C-25. Scombrine II gave a single band, whereas scombrine I gave three bands upon PAGE. Scombrine II (scombrine gamma) consists of 34 amino acid residues, and its sequence is: Pro-Arg-Arg-Arg-Arg-Arg-Ala-Ser-Arg-Pro-Val-Arg-Arg-Arg-Arg-Arg- Ala-Arg-Arg-Ser-Thr-Ala-Val-Arg-Arg-Arg-Arg-Arg-Val-Val-Arg-Arg-Arg-Arg. The ion spray mass spectrum shows that scombrine gamma has a molecular mass of 4,532.13 Da. The other minor component (scombrine I) is considered to be a mixture of degradation products of scombrine gamma based on the results of PAGE and ion spray mass spectrometry. Scombrine gamma has a similar sequence to sardaine Z2 from striped bonito except for two positions.

Amino Acid Sequence↗
PubMed1992

An anti-probasin monoclonal antibody recognizes a novel 40-kDa protein localized in rat liver and a specific region of kidney urinary tubule.

Immunoblotting with a monoclonal antibody against probasin (rat prostatic secretory protein) showed that a 40-kDa protein antigenically related to probasin was localized in rat liver and kidney. The contents of probasin in these organs were negligible. Immunostaining revealed that the 40-kDa protein (probasin-related antigen: PRB-RA) was expressed in the liver parenchymal cells and the kidney urinary tubular epithelial cells in outer stripe. The content of PRB-RA in the kidney was low during 0 to 2 weeks of age, then rapidly increased about 10-fold from 2 to 8 weeks of age. The content in the liver increased about 2-fold during the period, reaching a value of 10-12 ng/micrograms protein, which was ten times higher than that in the kidney. PRB-RA was purified from rat liver by ion-exchange chromatography, gel filtration and fast protein liquid chromatography on a hydroxyapatite column. The purified protein formed insoluble aggregates in the absence of a detergent, and it had a blocked amino terminal. The amino acid sequence of a peptide generated by tryptic digestion of alkylated PRB-RA was determined. Computer analysis showed that there was no protein having a significant homology with the peptide. These results indicate that a novel 40-kDa protein with a structural similarity to probasin is localized in rat liver and kidney, and might bear a function specific to these organs.

Aging↗
PubMed1992

Induction of avascular yolk sac due to reduction of basic fibroblast growth factor by retinoic acid in mice.

Vasculogenesis depends on autocrine secretion of basic fibroblast growth factor (bFGF) from capillary endothelial cells. Retinoic acid (RA) induced avascular yolk sac (AVY) of mouse embryos of dams given 60 mg/kg of RA orally on Day 8 of gestation and sacrificed 3 days later. We studied the localization and transcriptional expression of bFGF and FGF-receptor (flg), heparin-binding growth factor (HBGF) activity, localization of lysosomal enzymes and alpha 1-antitrypsin (AAT), and electron microscopy of the normal mouse visceral yolk sac (VYS) and AVY. bFGF, which is normally present in the endoderm of the VYS of 8-day-old embryos and in all components of the VYS by Day 11 of gestation, was reduced in the AVY. However, in the presence of bFGF in vitro capillary nets were restored in the AVY. The mRNA for bFGF was not detectable in either VYS or AVY, while flg mRNA was detected equally in both organs in Northern blotting. The characteristic distribution pattern of lysosomal enzymes, acid phosphatase, lysozyme, and cathepsin D, and AAT was altered in the AVY. The level of acid phosphatase and AAT was reduced to 10% in the AVY. Electron microscopy revealed a partial or total loss of lysosomal membranes where the contents of lysosomes fused with adjacent lysosomes and the external organelles. These results suggest that vitelline blood vessels are not developed by endogenous autocrine bFGF but by exogenous transcellular bFGF from absorptive endodermal cells. Retinoic acid does not affect the angiogenic capacity of the VYS mesenchyme but destroys lysosomes, which release hydrolytic enzymes, leading to degradation of AAT in the endodermal cells and then digestion of endocytosed bFGF.

Acid Phosphatase↗
PubMed1992

Relationships of site of infarction and history of previous infarction with short- and long-term prognosis after acute myocardial infarction in Japan.

We studied the outcome in 308 patients with acute myocardial infarction (MI) admitted to the coronary care unit of Kobe General Hospital. Short-term outcome (within 28 days after MI) and long-term outcome (more than 28 days) were examined with survival curves to find any relationship with a history of previous MI and with the site of the MI. In the short term, 38 of the 308 patients died of cardiac causes. The group with anterior MI tended to have higher mortality than the group of patients with inferior MI, and among patients without a previous MI, patients with anterior MI had significantly higher mortality (p = 0.01). In multivariate analysis by the logistic regression model, the site of the MI was found to be independently associated with the short-term outcome. In the long term, with a mean follow-up of 3.4 years, 23 of the 308 patients died of cardiac causes. Different sites of the MI did not result in different outcomes in patients with or without a previous MI. Of patients with anterior or inferior MI, those with a previous MI tended to have higher mortality, and of patients with an inferior MI, the difference was significant (p = 0.001). In multivariate analysis by the proportional hazards model, a history of MI was more predictive than the site of the MI. In conclusion, the site of the MI was associated more with the short-term outcome than with the long-term outcome, and a history of MI was associated more closely with the long-term outcome.

Aged↗
PubMed1992

Studies on the function mechanism of a Formosan grey mullet protamine-mugiline beta M6: interaction of the M6 and M6 fragments with DNA.

The interaction of three peptide segments of one component of Formosan grey mullet protamine (mugiline beta M6), obtained by chemical and enzymatic cleavage, with DNA was studied by spectroscopic measurement, thermal denaturation and circular dichroism. The data obtained were then compared with those of whole M6 and other fish protamines such as salmine of salmon and clupeine of herring. M6-B-I, which lacks C-terminal 11 amino acids in M6, showed significantly different properties. It showed remarkably high DNA aggregating ability which was due to a conformational change of DNA from B to A form. The conformational change of DNA induced by the binding of M6-B-I was reproduced by the carboxypeptidase B digestion of DNA-M6 complex. From these results, the arginine-rich, C-terminal domain of the M6 molecule was estimated to be essential for natural DNA binding.

Amino Acid Sequence↗