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Biomedical subjects

J Ishikawa

Publications and source records attributed to J Ishikawa.

At least 37 records · Page 2Linked to original sources
PubMed2000

Limitin: An interferon-like cytokine that preferentially influences B-lymphocyte precursors.

We have identified an interferon-like cytokine, limitin, on the basis of its ability to arrest the growth of or kill lympho-hematopoietic cells. Limitin strongly inhibited B lymphopoiesis in vitro and in vivo but had little influence on either myelopoiesis or erythropoiesis. Because limitin uses the interferon alpha/beta receptors and induces interferon regulatory factor-1, it may represent a previously unknown type I interferon prototype. However, preferential B-lineage growth inhibition and activation of Janus kinase 2 in a myelomonocytic leukemia line have not been described for previously known interferons.

Amino Acid Sequence↗
PubMed2000

Fluvastatin suppresses atherosclerotic progression, mediated through its inhibitory effect on endothelial dysfunction, lipid peroxidation, and macrophage deposition.

Fluvastatin, a potent 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, exerts an inhibitory effect on intimal thickening after mechanical injury in normocholesterolemic rabbit artery at a dose not enough to elicit a known action of lipid lowering. This study was designed to determine whether atherosclerotic progression triggered by hypercholesterolemia can be inhibited by fluvastatin under conditions without its hypocholesterolemic effect. Rabbits were fed a 0.5% cholesterol diet or normal diet for 17 weeks and were treated with either fluvastatin (0.3-2 mg/kg/day, p.o.) or pravastatin (2 mg/kg/day, p.o.). Atherogenic features manifested in the cholesterol-diet group, compared with the normal-diet group; they were the increase in serum lipid peroxide level, in the intraluminal lesion area of the aorta, and in macrophage content of the aortic cross-sectional lesion area; the attenuation of endothelium-dependent relaxing response to acetylcholine in the femoral artery; and the increase in serum lipid level. Treatment with fluvastatin, but not pravastatin, inhibited the manifestation of the atherogenic features without a serum lipid-lowering effect. Thus fluvastatin is likely to reduce the risk of atherosclerotic progression, to which endothelial dysfunction, lipid peroxidation, and macrophage accumulation in the vasculature may contribute, irrespective of changes in serum lipid levels.

Animals↗
PubMed2000

Identification and characterization of the point mutation which affects the transcription level of the chromosomal 3-N-acetyltransferase gene of Streptomyces griseus SS-1198.

We determined the molecular basis for the enhanced expression of the aac(3)-Xa gene encoding an aminoglycoside 3-N-acetyltransferase in Streptomyces griseus. A C-->T substitution was identified at the putative promoter of the mutant gene. RNA analyses demonstrated that the substitution caused a marked increase in the production of the gene-specific transcripts. Therefore, it seemed very likely that the aac(3)-Xa gene was activated by the substitution resulting in the emergence of a stronger promoter.

Arylamine N-Acetyltransferase↗
PubMed2000

Interactions between local anesthetics and Na+ channel inactivation gate peptides in phosphatidylserine suspensions as studied by 1H-NMR spectroscopy.

Interactions between local anesthetics and a sodium channel inactivation gate peptide (Ac-GGQDIFMTEEQK-NH2, MP-1A), which was dissected from the cytoplasmic linker between domains III and IV of the sodium channel alpha-subunit (G1484-K1495 in rat brain type IIA), have been studied by 1H-NMR spectroscopy. Changes in 1H-NMR chemical shifts of the aromatic proton resonances of dibucaine (pH 7.0) and lidocaine (pH 6.0 and 9.0) in phosphatidylserine (PS) suspensions were observed. The effects of substitution of glutamine (F1489Q; MP-2A) or D-phenylalanine (MP-1A') for L-phenylalanine (F1489) in MP-1A and the effects of substitution of neutral amino acid residues for the corresponding acidic amino acid residues (D1487N, MP-1NA; E1492Q, MP-IQEA; E1493Q, MP-IEQA) in MP-1A, on the aromatic 1H-NMR chemical shift changes of dibucaine and lidocaine were also investigated. From these results it was concluded that: the aromatic ring of phenylalanine of MP-1A and the aromatic ring of the cationic form of dibucaine or lidocaine are interacting by pi-pi stacking; the tertiary amine nitrogen of dibucaine is interacting electrostatically with D1487, whereas that of lidocaine is interacting with E1492.

Amino Acid Sequence↗
PubMed2000

Synthesis of all four possible stereoisomers of 5,9-dimethylpentadecane, the major sex pheromone component of the coffee leaf miner moth, Perileucoptera coffeella.

All of the four possible stereoisomers of 5,9-dimethylpentadecane, the major sex pheromone component of the coffee leaf miner moth (Perileucoptera coffeella), were synthesized by using the methyl esters of (S)- and (R)-3-hydroxy-2-methylpropanoic acid as chiral sources for the purpose of determining the stereochemistry of the pheromone.

Alkanes↗
PubMed2000

Synthesis of four stereoisomers of 1,4-thiazane-3-carboxylic acid 1-oxide via the asymmetric transformation (combined isomerization-preferential crystallization) of 1,4-thiazane-3-carboxylic acid.

In order to synthesize four stereoisomers of 1,4-thiazane-3-carboxylic acid 1-oxide (TCA SO), (S)-1,4thiazane-3-carboxylic acid [(S)-TCA], which is one of the precursors, was prepared by the asymmetric transformation (combined isomerization-preferential crystallization) of (RS)-TCA. This asymmetric transformation was used (2R, 3R)-tartaric acid [(R)-TA] as a resolving agent and salicylaldehyde as the epimerization catalyst in propanoic acid at 110 degrees C to afford a salt of (S)-TCA with (R)-TA in 100% de with a yield of over 90%. Optically pure (S)-TCA was obtained by treating the salt with triethylamine in methanol in a yield of over 80%, based on (RS)-TCA as the starting material. In addition, asymmetric transformation of (R)-TCA gave (S)-TCA in a yield of 60-70%. (S)-TCA was oxidized by hydrogen peroxide in dilute hydrochloric acid to selectively crystallize (1S, 3S)-TCA.SO. (1R, 3S)-TCA SO of 70% de from the filtrate was allowed to form a salt with (R)-TA after a treatment with triethylamine to give (1R, 3S)-TCA SO as a single diastereoisomer. (1R, 3R)- and (1S, 3R)-TCA.SO were also prepared by starting from (R)-TCA that had been synthesized from L-cysteine.

Crystallization↗
PubMed2000

[Colony PCR for rapid detection of antibiotic resistance genes in MRSA and enterococci].

We examined colony PCR that does not use the prepared template DNA but intact cells as the template DNA source for the rapid, simple and reproducible detection of antibiotic resistance genes in strains of methicillin-resistant Staphylococcus aureus (MRSA) and Enterococcus. Two factors turned out to be important; i.e. the transfer size of bacterial cells and the use of DNA Polymerase with high performance. In practice, the tip of a toothpick was lightly touched with a colony on agar plates followed by the PCR mixture (20 microliters) containing KOD-plus-DNA Polymerase and multiplex primers. The cell transfer size ranged from 10(3) to 10(4) cfu and 30 cycles of PCR (95 degrees C, 30 sec.-->50 degrees C, 30 sec.-->72 degrees C, 60 sec.) following the first heating (95 degrees C, 3 min.) resulted in good amplification of the target regions of mecA and aac(6')/aph(2") that are responsible for the resistance to methicillin and arbekacin, respectively.

Aminoglycosides↗
PubMed2000

A novel phosphodiesterase type 4 inhibitor, YM976 (4-(3-chlorophenyl)-1,7-diethylpyrido[2,3-d]pyrimidin-2(1H)-one), with little emetogenic activity.

We synthesized a novel phosphodiesterase type 4 (PDE4) inhibitor, YM976, that is structurally different from the other PDE4 inhibitors like rolipram. In the present study, the pharmacological profile of YM976 was investigated. YM976 exhibited a strong and competitive inhibition against PDE4 purified from human peripheral leukocytes with an IC(50) of 2.2 nM. IC(50) values of rolipram and RP73401 were 820 and 0.43 nM, respectively. Test compounds had no effects on the other PDE isozymes, PDE1, -2, -3, and -5. YM976 potentiated prostaglandin E(2)-induced cAMP accumulation in a human mononuclear cell line, U937, and inhibited tumor necrosis factor-alpha production from human peripheral blood mononuclear cells stimulated by lipopolysaccharide. Anti-inflammatory activities of PDE4 inhibitors were compared in rat carrageenan-induced pleurisy models. YM976, rolipram, and RP73401 inhibited the cell infiltration into the pleural cavity with oral ED(30) values of 9.1, 10, and 7.4 mg/kg, respectively. YM976 produced no emesis up to 10 mg/kg, whereas rolipram and RP73401 induced emesis at oral doses of 3 mg/kg. To evidence the dissociation of anti-inflammatory activity from emesis, the anti-inflammatory effect of YM976 was examined in ferrets. YM976 dose dependently reduced carrageenan-induced leukocyte infiltration at the doses of 1, 3, and 10 mg/kg, p.o. On the other hand, rolipram failed to show obvious inhibition at doses that do not induce emesis. In conclusion, YM976 is a novel and orally active PDE4 inhibitor and possesses a good separation of emetogenicity from anti-inflammatory activity.

Animals↗
PubMed2000

Early onset of hemophagocytic syndrome following allogeneic bone marrow transplantation.

We report a 40-year-old man who presented with acute onset of hemophagocytic syndrome (HPS) after allogeneic bone marrow transplantation (alloBMT) for acute myelogenous leukemia. On day 8 after alloBMT, the patient suddenly manifested high-grade fever, transfusion-resistant severe anemia, and thrombocytopenia. Neither veno-occlusive disease nor thrombotic microangiopathy was documented. The level of ferritin in serum was elevated to 1192 ng/mL. A bone marrow aspiration test on day 16 showed a markedly increased number of activated macrophages showing massive hemophagocytosis. Serum levels of interferon-gamma, soluble interleukin-2 receptor, interleukin-6, tumor necrosis factor-alpha, and macrophage colony-stimulating factor (M-CSF) were elevated. From these findings, we determined his transfusion-resistant cytopenias to be attributable to HPS. No viruses (including cytomegalovirus, Epstein-Barr virus, human herpes-virus-6, parvovirus B19, and adenovirus B11) were detected in serum or urine by polymerase chain reaction amplification. We speculate that in addition to the administration of M-CSF, hypercytokinemia during the early phase post-alloBMT might have contributed to the onset of HPS in this patient. Methylprednisolone pulse therapy was very effective for the treatment of the HPS. This case reveals that HPS could develop after alloBMT, even when engraftment of hematopoietic cells is not confirmed.

Adult↗
PubMed2000

[Prognostic factors of hepatocellular carcinoma: analysis by the proportional hazard model].

Five hundred fifty patients hospitalized to our hospital during 1990 to 1999 were studied. Subjects consisted of 413 males and 102 females and mean age was 62.1 years. Association with HBV infection, HCV infection and both infection was 11.1%, 78.4% and 2.5% respectively. According to the criteria based in Liver Cancer Study of Japan, 5 year survival rate in clinical stage I, II, III was 42.3%, 38.8% and 17.5%. Tumor morphology was nodular type in 78.9%, massive type in 9.1% and diffuse type in 10.5% of cases. Portal tumor thrombus and distal metastasis were observed in 19.9% and 6.3% of all cases. The 1-, 3- and 5-year survival rate in patients received any therapy was 80.8%, 44.6% and 28.7%, respectively. Analysis by the proportional hazard model showed that HBV infection, advanced clinical stage, multiple tumors, a tumor diameter in excess of 5 cm and AFP positivity were shown as significant factors on poor prognosis.

Carcinoma, Hepatocellular↗
PubMed1999

Differential susceptibility of C57BL/6 and DBA/2 mice to ovalbumin-induced pulmonary eosinophilia regulated by Th1/Th2-type cytokines.

To test the effect of genotype on immune response, C57BL/6 and DBA/2 mice were sensitized with aluminum hydroxide gel (alum)-precipitated ovalbumin (OVA) and challenged with aerosolized OVA. The serum immunoglobulin (Ig) E and IgG1 levels in C57BL/6 mice were higher than those in DBA/2 mice. In contrast, IgG2a levels in C57BL/6 mice were lower than that in DBA/2 mice. C57BL/6 mice were also much more susceptible than DBA/2 mice to OVA-induced pulmonary eosinophilia. Furthermore, patterns of cytokine generation in lung tissue were different between C57BL/6 and DBA/2 mice after OVA challenge. Th2-type cytokine interleukin (IL-) 4 and IL-5 generation in C57BL/6 mice was higher than that in DBA/2 mice, while Thl-type cytokine interferon-gamma (IFN-gamma) generation in C57BL/6 mice was lower than that in DBA/2 mice. Similar patterns of IL-4 and IL-5, and IFN-gamma production in splenocytes from both strains after OVA stimulation in vitro were also observed. The participation of IL-4 and IL-5, and IFN-gamma in the regulation of eosinophil infiltration into the lung was confirmed by injection of anti-IL-5, -IL-4 and -IFN-gamma monoclonal antibodies. These results indicate that C57BL/6 mice preferentially induce IL-4 and IL-5-mediated Th2-type response, while DBA/2 mice induce IFN-gamma-mediated Thl-type response. Thus, the genotype of laboratory strains partially determines whether Th1- or Th2-type immune responses are elicited.

Animals↗
PubMed1999

FramePlot: a new implementation of the frame analysis for predicting protein-coding regions in bacterial DNA with a high G + C content.

FramePlot is a web-based tool for predicting protein-coding regions in bacterial DNA with a high G + C content, such as Streptomyces. The graphical output provides for easy distinction of protein-coding regions from non-coding regions. The plot is a clickable map. Clicking on an ORF provides not only the nucleotide sequence but also its deduced amino acid sequence. These sequences can then be compared to the NCBI sequence database over the Internet. The program is freely available for academic purposes at http://www.nih.go.jp/jun/cgi-bin/frameplot.pl.

Amino Acid Sequence↗
PubMed1999

Stromal cell CD9 regulates differentiation of hematopoietic stem/progenitor cells.

CD9 belongs to the transmembrane 4 superfamily, and has been shown to influence cell proliferation, motility, and adhesion. We show here that ligation of CD9 modifies proliferation and/or differentiation of hematopoietic stem/progenitors. Pluripotent EML-C1 hematopoietic cells were cocultured with MS-5 stromal cells in the presence of KMC8.8, an anti-CD9 antibody. Numbers of recovered EML-C1 cells were slightly reduced and the antibody caused the hematopoietic cells to migrate beneath the adherent stromal cell layer. Of particular interest, EML-C1 cells recovered from CD9-ligated cultures had undifferentiated properties. Separate pretreatment of the two cell types with antibody showed that stromal-cell CD9 mediated these responses. Spontaneous expression of erythroid marker was completely blocked and there was a shift towards undifferentiated clonogenic progenitors. Immunoprecipitation studies showed that stromal-cell CD9 associates with the beta1 subunit of integrin, as well as a novel 100 kD protein. Antibody cross-linking of cell surface CD9 increased the amount of 100 kD protein that was subsequently coprecipitated with CD9. These observations show that stromal-cell CD9 influences physical interactions with hematopoietic cells and may be one factor that determines the degree of stem cell differentiation.

Animals↗
PubMed1999

Enhanced growth of human vascular endothelial cells on negative ion (Ag-)-implanted hydrophobic surfaces.

Silver negative ions (Ag-) were implanted to an insulator, polystyrene, in a relatively low ion energy ranging from 5 to 30 keV, and in a dose ranging from 10(14) to 6 x 10(16) ions. cm-2. Surfaces of Ag--implanted polystyrene were studied by means of secondary ion mass spectrometry, X-ray photoelectron spectroscopy, Fourier transform infrared spectroscopy, and micro-Raman spectroscopy, and contact angle measurement. As a result of Ag- implantation, the polystyrene surfaces underwent degradation, thereby becoming more hydrophilic with increasing dose and ion energy except an ion energy of 30 keV. The Ag- implantation in polystyrene led to enhanced growth of human vascular endothelial cells, which grew to more extent with increased hydrophilicity of Ag--implanted surfaces except an ion energy of 30 keV. Polystyrene surfaces on which Ag- were implanted up to an ion energy of 30 keV caused the same hydrophobic level as polystyrene surface itself. Nevertheless, the Ag--implanted polystyrene showed relatively good biocompatibility different from polystyrene. Such an improvement in cell adhesion may be related to the formation of a graphite-like structure on polystyrene surfaces by a Ag--implanted process. Moreover, upon plating in a high cell density, human vascular endothelial cells survived even on the polystyrene region of Ag--implanted polystyrene for longer than 1.5 months, while the cells did not grow on untreated polystyrene in the same culture conditions.

Biocompatible Materials↗
PubMed1999

Persistent tolerance induced after portal venous injection of allogeneic cells plus cyclophosphamide treatment.

The injection of allogeneic cells via the portal vein (p.v.) is known to reduce responses to donor-alloantigens. In the present study, we have obtained persistent tolerance across Mls and multiple minor histocompatibility complexes by p.v. preimmunization followed by the administration of cyclophosphamide (CY). A hundred percent survival of (BALB/c x DBA/2)F1 (CDF1) skin grafts for more than 200 days was observed when BALB/c mice were preimmunized with spleen cells of CDF1 (3 x 10(7)) via the p.v. and administered 300 mg/Kg CY 2 days after the p.v. injection. Comparable survival of the skin graft was observed when bone marrow cells instead of spleen cells were p.v. preimmunized. However, the survival rate was significantly decreased when LPS-stimulated blastic cells were p.v. preimmunized. Microchimerism has been observed in the liver, thymus, bone marrow and peripheral blood of recipients. V beta 6+ cells decreased in CD4+ cells of recipients of the p.v. preimmunization plus CY treatment. However, there was no difference in the decrease in V beta 6+ cells between recipients accepting the CDF1 skin grafts and recipients that had rejected the skin grafts. Furthermore, no intrathymic depletion of the V beta 6+ cells was observed. From these results, it is suggested that, rather than clonal deletion, other mechanisms such as clonal anergy or suppression may be involved in the induction of persistent tolerance after the p.v. preimmunization plus CY treatment.

Animals↗
PubMed1999

The effects of wrist distraction on carpal kinematics.

Changes in carpal kinematics under wrist distraction were studied in fresh cadaveric specimens. A magnetic tracking device measured kinematic motions of the scaphoid, lunate, and third metacarpal relative to the fixed radius in 3 planes of passive motion (coronal, sagittal, and "dart throwers") under progressive distraction loads. The change in percent contribution of the radiocarpal and midcarpal joints was calculated. Radiocarpal motion during extension was decreased as increasing traction was applied, but it increased with flexion. Motion of the scaphoid relative to the lunate was smaller in the oblique plane, resulting in less radiocarpal motion than in the sagittal plane. In the coronal plane, traction had little effect on radial deviation, but ulnar angulation of the scaphoid was greater with ulnar deviation of the wrist. These results suggest that different degrees of tension exist in the palmar and dorsal ligaments with the wrist under traction and during different planes of wrist motion. If wrist motion is desired during fixed traction, such as used clinically with external fixation, the dart-throwers motion (wrist extension with radial deviation and wrist flexion with ulnar deviation) appears to have the least impact on radiocarpal motion. If greater radiocarpal motion is desired, however, such as during postoperative mobilization, flexion-extension and radioulnar deviation will create more radiocarpal motion than the dart-thrower's motion.

Biomechanical Phenomena↗
PubMed1999

Inhibitory effects of citrus essential oils and their components on the formation of N-nitrosodimethylamine.

Twenty-eight kinds of citrus essential oils and their components were studied for inhibitory effects on the formation of N-nitrosodimethylamine (NDMA). The reaction mixture consisted of dimethylamine and sodium nitrite adjusted at pH 3.6, in addition to essential oils and an emulsifying agent. The quantification was determined by high-performance liquid chromatography monitored at 220 nm. All of the essential oils inhibited the formation of NDMA in the range of 20-85%. The oils of ujukitsu (Citrus ujukitsu Hort. ex Shirai), yuzu (C. junos Tanaka), mochiyu (C. inflata Hort. ex Tanaka), and ponkan (C. reticulata Blanco cv. F-2426) inhibited the formation of NDMA much more effectively than other citrus oils. The inhibitory proportions of components of citrus essential oils such as myrcene, alpha-terpinene, and terpinolene were as high as 80%.

Anticarcinogenic Agents↗