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Biomedical subjects

M Nakano

Publications and source records attributed to M Nakano.

At least 307 records · Page 17Linked to original sources
PubMed1998

Enhanced engraftment of intravenously transplanted hematopoietic stem cells into bone marrow of irradiated mice treated with AcSDKP.

The effect of the tetrapeptide Acetyl-N-Ser-Asp-Lys-Pro (AcSDKP) on intravenously transplanted hematopoietic stem cell engraftment into the bone marrow (BM) of irradiated mice was studied. When 5 x 10(4) marrow cells were transplanted into lethally irradiated mice given 10 microg AcSDKP, the survival of these animals 4 weeks posttransplantation increased markedly from 20.0 +/- 4.4% to 86.1 +/- 4.8%, the same result as that obtained from mice transplanted with 5 x 10(5) cells without AcSDKP treatment. Increased numbers of hematopoietic stem cells, including spleen colony-forming unit and colony-forming unit granulocyte-macrophage, were observed in the BM of AcSDKP-treated mice 1 and 8 days after transplantation. This finding suggested that AcSDKP influenced homing of hematopoietic stem cells into the BM of lethally irradiated animals. This enhancing activity of AcSDKP was neutralized by the simultaneous administration of an anti-AcSDKP polyclonal antibody. Furthermore, recovery of leukocytes in peripheral blood occurred faster in AcSDKP-treated than in untreated transplanted mice. These findings may provide a basis for the clinical use of AcSDKP in BM transplantation patients.

Animals↗
PubMed1998

Purification and characterization of eugeniin as an anti-herpesvirus compound from Geum japonicum and Syzygium aromaticum.

The hot-water extract of Geum japonicum has been shown to exhibit prophylactic and therapeutic anti-herpes simplex virus (HSV) activity in murine infection models. Eugeniin was purified as an anti-HSV compound from the extract and also was isolated from another herbal extract (Syzygium aromaticum) that had exhibited anti-HSV activity in mice. Thus the anti-HSV action of eugeniin was characterized. The effective concentration (5.0 microg/ml) for 50% plaque reduction of eugeniin for wild HSV type 1 (HSV-1) on Vero cells was 13.9-fold lower than its 50% cytotoxic concentration determined by a yield-reduction assay. Eugeniin also inhibited the growth of acyclovir-phosphonoacetic acid-resistant HSV-1, thymidine kinase-deficient HSV-1 and wild HSV type 2. Eugeniin as well as phosphonoacetic acid inhibited viral DNA and late viral protein syntheses in their infected Vero cells, but not cellular protein synthesis at its inhibitory concentrations. Purified HSV-1 DNA polymerase activity was inhibited by eugeniin noncompetitively with respect to dTTP. Its apparent Ki value for euginiin was 8.2- and 5. 8-fold lower than the Ki values of purified human DNA polymerases alpha and beta, respectively. Thus one of the major target sites of inhibitory action of eugeniin is viral DNA synthesis; the inhibitory action for viral DNA polymerase activity was novel compared with anti-HSV nucleoside analogs.

Animals↗
PubMed1998

Stereoselective uptake of an organic anion across the renal basolateral membrane in isolated perfused rat kidney.

To clarify which process in renal secretion is responsible for the stereoselective renal secretion of organic anions, the renal handling of enantiomers of 5-monomethylsulfamoyl-6,7-dichloro-2, 3-dihydrobenzofuran-2-carboxylic acid (MBCA) was studied by the multiple-indicator dilution method, using isolated perfused rat kidney. After bolus injection of (R)-(+)-[14C]MBCA or (S)-(-)-[14C]MBCA into the renal artery, the outflow patterns for the perfusate and the urinary excretion rate profiles were estimated by statistical moment analysis. AUC values and mean transit times in kidney for the MBCA enantiomers indicated that (R)-(+)-MBCA was excreted much more extensively in urine and that it had a higher affinity for renal tissue than did (S)-(-)-MBCA. A significantly larger intrinsic clearance of secretion for (R)-(+)-MBCA attested to the R-(+)-preferential renal secretion. The uptake rate constant across the basolateral membrane, the ratio of the uptake rate constant to the free fraction in the perfusate, and the intracellular distribution volume were significantly larger for (R)-(+)-MBCA than for (S)-(-)-MBCA, indicating that uptake across the basolateral membrane and intracellular distribution were R-(+)-preferential. However, the mean time across renal epithelial cells for secreted molecules, the single-pass mean residence time in renal epithelial cells, and the rate constant for secretion across the brush-border membrane were not significantly different between enantiomers. The simultaneous presence of (R)-(+)-MBCA decreased the intrinsic clearance of secretion, the ratio of the uptake rate constant to the free fraction in the perfusate, and the intracellular distribution volume for (S)-(-)-[14C]MBCA, although the secretion rate constant, the mean time across renal epithelial cells for secreted molecules, and the single-pass mean residence time in renal epithelial cells were not influenced by (R)-(+)-MBCA, confirming that uptake across the basolateral membrane and intracellular distribution were stereoselective processes.

Animals↗
PubMed1998

[Measurement of thrombomodulin values in the serum and eyes of experimental autoimmune uveoretinitis].

Thrombomodulin (TM) is a protein, present on intact endothelial cell surfaces, that plays a major role in the protein C anticoagulant system. Plasma TM is produced by injured endothelium, and is recognized in circulating blood or urine as a sign of endothelium cell damage. The localization of TM within the eye and its kinetics in the eye and the serum were investigated in rats with experimental autoimmune uveoretinitis (EAU). An immuno-histochemical study showed the presence of TM at sites of fibrin in the anterior chamber and retinal vasculitis. The amount of TM in the eye increased with progression of intraocular inflammation, but the serum level of TM did not significantly differ from the values in the control group. These data suggest that TM may play a role in preventing thrombosis in cases of vasculitis and fibrin formation in the anterior chamber in EAU, thus maintaining blood flow and the fluidity of aqueous humor.

Animals↗
PubMed1998

Characterization of soluble thrombomodulin fragments in human urine.

The soluble thrombomodulin (TM) subspecies in human urine detected by polyclonal anti-human TM IgG were isolated and characterized. 105, 85, 80, 56, 33, 31 and 28 kDa subspecies under reducing conditions was comparable to 78, 66, 56, 200, 52, 30 and 25 kDa under non-reducing conditions, respectively, in the two-dimensional electrophoresis. Each subspecies under non-reducing conditions, except the 200 and 52 kDa molecules, was constituted of single subspecies, whereas the 200 and 52 kDa molecules were constituted of the tetramer of the 56 kDa subspecies of reducing conditions and a dimer of the 33 kDa subspecies, respectively. NH2-terminal amino acid sequences of the 105, 85 and 80 kDa subspecies maintained Ala1-Pro2-Ala3- of intact human TM, however, 56, 33, 31 and 28 kDa subspecies started from Glu137-Gln138-, Gln214-Gly215-, Ser228-Val229- and Ala240-Ile241-, respectively. All subspecies obtained under non-reducing conditions exhibited cofactor activity for thrombin-dependent protein C activation ranging from 58 to 162 pmol APC/min/nmol TM at 0.4 mM Ca2+ indicating that all of the subspecies maintained the fourth to sixth repeat of epidermal growth factor-like structure of intact TM. 85, 80, 56, 33, 31 and 28 kDa subspecies were suggested to lack both chondroitin sulfate glycosaminoglycan (CSGAG), transmembrane and cytoplasmic domains of intact TM, while 105 kDa subspecies lack only CSGAG from the results of kinetic properties and the interaction with phospholipid vesicles composed from phosphatidylcholine and phosphatidylethanolamine.

Humans↗
PubMed1998

[Pharmaceutical and pharmacological development of antitumor prostaglandins].

Antitumor Prostaglandins such as delta 12PGJ2 and delta 7PGA1 possess a cross-conjugated dienone unit and exhibit unique antitumor effect. Lipid microshere (w/o type emulsion) was selected as pharmaceutical formulation because of physicochemical properties of prostaglandin. 13,14-Dihydro-15-deoxy-delta 7-PGA1 methyl ester (TEI-9826) were selected as a candidate for clinical trial. In a rat and mouse serum in vitro, TEI-9826 rapidly metabolized to 13,14-dihydro-15-deoxy-delta 7-PGA1 (TOK-4528), but TOK-4528 is stable as well as delta 12PGJ2. Lipid microshere containing TEI-9826 at the content of 5 mg/ml exhibited administration route and schedule dependent antitumor effect in vivo using Colon 26 bearing mouse model, which suggested that duration of serum concentration was important for antitumor effect. One of the antitumor mechanism of antitumor PG might be an induction of the cyclin-dependent kinase inhibitor p21. PPAR gamma also might be important. New type homogenizer, high pressure jet flow type homogenizer was developed in the study of antitumor prostaglandin.

Animals↗
PubMed1998

[The measurement of antioxidant activity in human plasma using cumene hydroperoxide].

We describe a new method using cumene hydroperoxide to determine antioxidant activity (AO) in human plasma. We used a kit (Determiner LPO: Kyowa Medex Co., LTD. Tokyo Japan) for the determination of lipid peroxides in plasma or serum. 30 microliters 1 of sample was mixed with 70 microliters 1 of cumene hydroperoxide (50 nmol/ml) and incubated at 30 degrees C for 120 min before analysis. Samples were mixed with 1.0 ml of reagent-I (Determiner LPO) and incubated at 30 degrees C for 5 min. Then 2.0 ml of reagent-II (Determiner LPO) was added and incubated at 30 degrees C for 10 min, at which time the absorbance at 675 nm was measured. AO were calculated using the following formula: AO nmol/ml = 35 nmol/ml-(Es-Eb)/(Estd-Eb) x 35 nmol/ml (Es = sample abs., Eb = blank abs., Estd = standard abs.). Within-run precision for plasma AO was 2.3%. AO in plasma samples stored for 4 h at 4 degrees C was decreased by 1 nmol/ml. After 3 h at room temperature, AO was decreased by the same amount. Because this method measured ascorbic acid, alpha-tocopherol, glutathione peroxidase and quercetin as antioxidant compounds, we were able to measure antioxidant activity in human plasma. Our reference values were calculated from the volunteers group which consisted of 172 students and 82 soldiers. The reference intervals for plasma AO by this procedure were 15.4-20.9 nmol/ml.

Adult↗
PubMed1998

[A case of solitary retroperitoneal neurofibroma].

A 70-year-old woman was admitted to our hospital complaining of epigastralgia. Computed tomography, ultrasonography and magnetic resonance imaging revealed a round tumor measuring 6 cm in diameter, which was located in the medial side of the right kidney. It was successfully removed without injury to the surrounding large vessels and organs. Histological diagnosis was benign neurofibroma. This is the 27th case of solitary retroperitoneal neurofibroma reported in Japan.

Aged↗
PubMed1998

Prevalence and conditions of urinary incontinence among the elderly.

In Japan, elderly disorders and diseases have markedly increased in recent years, because of rapid aging and an increasing number of older persons. The situation is creating serious social and community problems. These disorders, particularly dysuria and urinary incontinence (UI), disturb the quality of life (QOL) in latelife. Few reports on UI have been published, but precise investigation into the community level remains to be made. Our presentation is the development, implementation and evaluation of elderly UI in Kumamoto Prefecture. This study includes 2,304 people (male: 856, female: 1,448), over 65 years of age, living in two different communities; one is an urban (K) and the other is a typical rural area (S). The rate of UI was in homebound elderly persons, male: 4.7%, female: 11.3%, and in nursing home residents, male: 16.2%, female: 23.2%. The condition of UI was: almost Urinary Urgency in male (61.5%), and Stress Incontinence (such as, caused by coughing, sneezing, and exercise) in female (46.3%). The influence of UI on the activity of daily life was investigated. Most of the male cases were giving concerns for family and community. In contrast, females hesitated to participate in group excursions and outdoor exercise, and had a tendency to live alone or indoors. However, most persons (81.5%) with UI did not visit a physician. From this investigation, we conclude that a community health care program and public support system are essential for proper understanding and solution of the elderly UI problem.

Activities of Daily Living↗
PubMed1998

[Intraarterial chemotherapy via reservoir system for far-advanced bladder and prostate cancer].

A clinical study was performed on the efficacy of intraarterial chemotherapy using reservoir system for far-advanced urological malignancy. The reservoir system was indwelled in the femoral subcutaneous layer using Seldinger's method. Fifteen cases with inoperable complicated advanced bladder cancer and ten cases with postoperative local recurrent bladder cancer received intraarterial chemotherapy using the reservoir system. Then, 23 cases with local relapsed prostate cancer and two cases with endocrine-resistant prostate cancer received chemotherapy. The administered anti-cancerous agents were methotrexate, cis-platinum and adriamycin, and 5-FU or carboplatin were administered as maintenance therapy. The mean courses of chemotherapy were six for bladder cancer and four for prostate cancer. During stabilization of the local lesion, no distant deterioration was recognized. Overall clinical efficacy was as follows: PR:18 cases and NC:7 cases for bladder cancer; then, PR:11 cases and 14 cases for prostate cancer. The median duration of stabilization was as follows: 23 months for bladder cancer and 12 months for prostate cancer. Complications were fewer than with systemic chemotherapy.

Adenocarcinoma↗
PubMed1998

Analysis of renal pathology and drug history in 158 Japanese patients with rheumatoid arthritis.

To clarify the characteristics of renal pathology and its correlation with disease-modifying antirheumatic drugs (DMARDs) in patients with rheumatoid arthritis (RA), renal biopsy findings from 158 Japanese RA patients with urinary abnormalities and/or renal dysfunction were analyzed retrospectively in the period between 1979 and 1996. Urologic abnormality and urinary tract infection were ruled out in all patients. Light and immunofluorescence (IF) microscopy were performed in all patients. Mesangial proliferative glomerulonephritis (MesPGN) was diagnosed in 54 patients, membranous nephropathy (MN) in 49, and secondary amyloidosis (AM) in 30. Renal dysfunction was more frequent in patients with AM (22/30) than in patients without (40/128). Forty of 49 MN patients developed renal disorders during DMARDs therapy. The prevalence of DMARD-related MN increased during the period of observation. The fact that DMARDs are of very frequent use in recent Japanese RA patients may reflect the prevalence of MN in this study. Two thirds of patients with MesPGN developed renal disorders when no DMARDs were used. One half of 54 MesPGN patients demonstrated IgA glomerulonephritis (GN) by IF. The prevalence of primary renal diseases in Japan may reflect the frequency of IgA GN in Japanese RA patients. Furthermore, diffuse thinning of the glomerular basement membrane (GBM) was observed in 30 of 81 patients with electron microscopy. RA itself may underlie the pathogenesis of GBM thinning, and drugs used for RA treatment may also accelerate the development of this lesion. In conclusion, although MesPGN, MN, and AM may be relatively more common, IgA GN and GBM thinning also were other frequent entities in Japanese RA patients. No correlation was observed between DMARDs and renal disorders excepting MN.

Adolescent↗
PubMed1998

[Macrocytic anemia with anisocytosis due to alcohol abuse and vitamin B6 deficiency].

Megaloblastic anemia due to folic acid deficiency and ringed sideroblastic anemia have been reported in alcohol abusers. It has also been reported that vitamin B6 deficiency causes ringed sideroblastic anemia as well as microcytic anemia that is not associated with ringed sideroblasts. We encountered a case of macrocytic anemia with anisocytosis in a 75-year-old alcohol abuser who suffered vitamin B6 deficiency. Neither megaloblastic changes nor ringed sideroblasts were observed in specimens of the patient's bone marrow. Analyses of porphyrin content and heme biosynthetic enzyme activity suggested a decline in ALA-synthase activity (an enzyme that depends on vitamin B6) as well as decreased ferrochelatase activity or abnormal iron metabolism. Abstention from alcohol led to a reduction in mean corpuscular volume and the disappearance of Pappenheimer bodies commonly observed in the red blood cells of drinkers. Follow-up supplements of vitamin B6 resolved the patient's anisocytosis and anemia.

Aged↗
PubMed1997

Mutations in the gyrA and parC genes associated with fluoroquinolone resistance in clinical isolates of Citrobacter freundii.

We determined partial sequences of the gyrA and parC genes of Citrobacter freundii type strain, and then examined 38 C. freundii clinical strains isolated from patients with urinary tract infections for the association of alterations in GyrA and ParC with susceptibility to fluoroquinolones. Our results suggest that in C. freundii DNA gyrase may be a primary target of quinolones, that an amino acid change at Thr-83 or Asp-87 in GyrA is sufficient to decrease susceptibility to fluoroquinolones, and that accumulation of changes in GyrA with the simultaneous presence of an alteration at Ser-80 or Glu-84 in ParC may be associated with the development of high-level fluoroquinolone resistance in C. freundii clinical isolates.

Amino Acid Sequence↗
PubMed1997

Generation of neutralizing antibody to the reverse transcriptase of human immunodeficiency virus type 1 by immunizing of mice with an infectious vaccinia virus recombinant.

Antibodies inhibiting the reverse transcriptase (RT) of human immunodeficiency virus type-1 (HIV-1) were found to be generated in the serum of mice repeatedly infected with a vaccinia virus recombinant, WRRT, expressing the enzyme. A monoclonal antibody (mAb), 7C4, which specifically and almost completely inhibits the RNA-dependent DNA polymerase activity of HIV-1 RT was produced from a mouse repeatedly immunized with WRRT. 7C4 seems to be specific for HIV-1 among retroviruses: 7C4 inhibited RT activity of three strains of HIV-1 (IIIB, Bru, and IMS-1) but not of two strains of HIV-2 (GH-1 and LAV-2) or two strains of SIV (MAC and MND). The immunoglobulin isotype of three out of four mAbs produced from spleen cells of the immunized mouse were IgG2a. This immunization method that avoids protein denaturation may preferentially induce a T helper type-1 immune response and increase the chances of producing the only occasionally obtainable mAb capable of recognizing a conformational epitope and completely inhibiting enzyme activity.

Animals↗
PubMed1997

Identification of an N-glycosylated region of pig zona pellucida glycoprotein ZPB that is involved in sperm binding.

ZPB, one of the pig zona pellucida glycoproteins, can be purified after removal of sialylated and/or sulfated N-acetylpolylactosamine from the nonreducing region of its carbohydrate chains by digestion with endo-beta-galactosidase. Among the components produced, only ZPB shows sperm-binding activity after the digestion. Recently, we have shown that N-linked carbohydrate chains of endo-beta-galactosidase-digested ZPB (EbetaG-ZPB) are predominantly involved in sperm binding [Yonezawa, N., Aoki, H., Hatanaka, Y. & Nakano, M. (1995) Eur. J. Biochem. 233, 35-41]. In this study, to define the sperm-binding region in EbetaG-ZPB, glycopeptides were purified from lysyl endopeptidase digests of EbetaG-ZPB and analyzed for sperm-binding activity by an in vitro competition assay. The locations of the glycopeptides were determined from partial amino acid sequences, amino acid and sugar composition analyses, and apparent molecular masses after SDS/PAGE. The N-terminal fragment (amino acid residues 137-247), which contains two N-linked carbohydrate chains, showed a significant inhibition of sperm-egg binding. However, the fragment that had one N-linked carbohydrate chain (residues 325-341) and the fragment that had two or three O-linked carbohydrate chains (residues 248-324) did not inhibit sperm-egg binding. Thus, the two N-linked carbohydrate chains in the N-terminal fragment of EbetaG-ZPB are important for sperm binding of pig zona pellucida.

Amino Acid Sequence↗
PubMed1997

1,2-Diacylglycerol hydroperoxides induce the generation and release of superoxide anion from human polymorphonuclear leukocytes.

We examined the effect of 1-palmitoyl-2-linoleoylglycerol (PLG), PLG hydroxide (PLG-OH), and PLG hydroperoxide (PLG-OOH) on the release of superoxide anion from human PMNs monitored by the chemiluminescence generated by the superoxide anion-sensitive reagent, 2-methyl-6-(p-methoxyphenyl)-3,7-dihydroimidazo[1,2-a]pyrazin++ +-3-one (MCLA). PLG-OOH at low micromolar concentrations stimulated human PMNs whereas PLG and PLG-OH did not. 1,3-Dilinoleoylglycerol hydroperoxide, 1-palmitoyl-2-linoleoylphosphatidylcholine hydroperoxide, and linoleic acid hydroperoxide were much less efficient in stimulating human PMNs than PLG-OOH. The PKC inhibitors, chelerythrine chloride and staurosporine, inhibited the stimulation of PMNs. Possible pathophysiological role of 1,2-diacylglycerol hydroperoxides is discussed.

Diglycerides↗