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Biomedical subjects

Y Shima

Publications and source records attributed to Y Shima.

At least 91 records · Page 5Linked to original sources

Myeloma cells express Fas antigen/APO-1 (CD95) but only some are sensitive to anti-Fas antibody resulting in apoptosis.

To find out which cytokines are involved in the pathogenesis of multiple myeloma, we investigated cytokine receptor expression on myeloma cells using a panel of monoclonal antibodies (MoAbs). Flow cytometric analysis of five myeloma cell lines (RPMI8226, ARH77, KMM-1, U266, and Hs) and myeloma cells freshly isolated from eight patients showed that interleukin-1 receptor (IL-1R) type I and type II, IL-2R alpha and beta chains, IL-4R, IL-6R, IL-7R, IL-8R, granulocyte macrophage colony-stimulating factor receptor (GM-CSFR), c-kit (stem cell factor receptor [SCFR]), membrane bound stem cell factor (MBSCF), and tumor necrosis factor (TNF) receptors type I and type II were not always detected on the myeloma cells. However, interferon-gamma receptor, gp130, and Fas antigen were constitutively expressed, except one sample. To determine the role of Fas antigen on myeloma cells, these cells were cultured with anti-Fas MoAb. Apoptotic changes characterized by loss of cell volume, membrane blebbing, fragmentation of nuclei, and condensed chromatin were observed in three of five myeloma cell lines. When bcl-2 expression was examined, it was seen in all the cell lines regardless of the sensitivity to anti-Fas MoAb. Furthermore, anti-Fas MoAb not only induced apoptosis of freshly isolated myeloma cells but also inhibited the DNA synthesis, although such effects varied from patient to patient. The data indicate that only some myeloma cells undergo apoptosis in response to the signal mediated by the Fas antigen.

Adult↗

Serum interleukin 6 as a predicator of the therapeutic effect and adverse reactions after transcatheter arterial embolization.

To evaluate the value of serum interleukin 6 (sIL-6) for the prediction of therapeutic effect and adverse reaction after transcatheter arterial embolization (TAE), sIL-6 was measured before and after angiography or TAE in 18 patients (three after angiography and 15 after TAE for hepatocellular carcinoma). The three patients with only angiography showed no elevation of sIL-6, while a significant increase was observed after TAE in the 15 hepatocellular carcinoma patients. The sIL-6 levels of patients with a partial response to TAE were higher at 48-72 hours after the procedure than those of patients with no response (P = 0.045), and the sIL-6 levels of patients who showed adverse reactions were higher at 6-24 h than those of patients without adverse reactions (P = 0.019). sIL-6 level at 48-72 h after TAE reflects the efficacy of TAE, whereas the level at 6-24 h after TAE is related to the severity of adverse reactions. Therefore, sIL-6 may be a useful indicator for prediction of the therapeutic effect of TAE as well as adverse reactions.

Aged↗

IS&C (Image Save & Carry) standard: standardized exchange media for medical information.

There has been a strong need for a standardized medical image exchange media. MEDIS-DC in Japan created IS&C as a standard for this purpose, based on 5.25' rewritable magneto-optic discs, with many specifications such as fast speed read/write, independence of apparatus vendor, additional security features, and data format compatible to ACR-NEMA v.2 image format. IS&C is already applied to many institutions, as an alternative for fast expensive networks, long term image casebases and media for teaching file distribution. The IS&C committee hopes this standard will be: 1) used at clinics and hospitals, promoting exchange of information between them, 2) harmonized with other standardization activities, and 3) a basis for future electronic semantic medical records.

Computer Communication Networks↗

Inhibitory effect of all-trans retinoic acid on the growth of freshly isolated myeloma cells via interference with interleukin-6 signal transduction.

We showed the dose-dependent growth inhibition by alltrans retinoic acid (ATRA) of myeloma cells freshly isolated from patients. ATRA downregulated the cell surface expression of interleukin-6 receptor (IL-6R) and/or glycoprotein (gp) 130. The growth-inhibitory activity of ATRA was well correlated with that of anti-gp 130 antibody in every sample. Furthermore, ATRA inhibited the production of IL-6 from both myeloma cells and marrow stromal cells, and recombinant IL-6 (rIL-6) could partially recover the myeloma cell growth that had been inhibited by ATRA. These data suggest that ATRA may inhibit the proliferation of myeloma cells both by the downregulation of IL-6R and gp130 expression on myeloma cells and by the inhibition of IL-6 production from myeloma and stromal cells. Prednisolone (PSL) and interferon-gamma (IFN-gamma) also inhibited the myeloma growth, while their effects were different from those of ATRA on IL-6 R and gp130 expression, IL-6 production, and morphological change. The inhibitory effect of ATRA on myeloma cell proliferation was observed in 10 of 14 samples obtained from eight patients, which suggests that ATRA may be a potent new therapeutic agent for some myeloma patients.

Antigens, CD↗

Oncostatin M, leukemia inhibitory factor, and interleukin 6 induce the proliferation of human plasmacytoma cells via the common signal transducer, gp130.

We analyzed the stimulatory effect of oncostatin M (OSM), leukemia inhibitory factor (LIF), interleukin 6 (IL-6), IL-11, and the inhibitory effect of anti-IL-6 antibody (Ab), anti-IL-6 receptor monoclonal antibody (mAb), and anti-gp130 mAb on the growth of human plasmacytoma cells freshly isolated from a patient with multiple myeloma. The purified cells showed a plasmacytoid morphology and expressed CD38, CD54, and CD56 antigens but no CD3, CD5, CD10, CD19, CD20, or very late antigen 5. IL-6 receptor (IL-6R) and its signal transducer, gp130, were expressed on their cell surface at a low level. Dose-dependent proliferation of the cells in response to OSM, LIF, and IL-6, but not to IL-11, was observed using [3H]TdR incorporation in vitro. Both anti-IL-6 Ab and anti-IL-6R mAb inhibited the growth of the cells in the presence or absence of exogenous IL-6. These cells release IL-6 but not OSM or LIF into the culture supernatant during short-term culture. Therefore, an autocrine growth mechanism mediated by IL-6, but not by OSM or LIF, was confirmed. Furthermore, anti-gp130 mAb completely inhibited the proliferation of the cells induced by OSM, LIF, as well as IL-6. These data indicate that OSM, LIF, and IL-6 can act as growth factors of human plasmacytoma cells through a common signal transducer, gp130, on their cell surface, and also suggest the potential therapeutic application of anti-gp130 mAb, as well as anti-IL-6R mAb against myeloma/plasmacytomas.

Antibodies, Monoclonal↗

Structure of the L-histidine decarboxylase gene.

Two species of L-histidine decarboxylase (HDC) mRNA were found in the KU-812-F basophilic cell line, but only the 2.4-kilobase (kb) one encodes the functional HDC (Mamune-Sato, R., Yamauchi, K., Tanno, Y., Ohkawara, Y., Ohtsu, H., Katayose, D., Maeyama, K., Watanabe, T., Shibahara, S., and Takishima, T. (1992) Eur. J. Biochem. 209, 533-539). The 3.4-kb one encodes a truncated HDC protein and is also found in human leukemia-derived cell lines HEL and KCL-22. To clarify the mechanisms that regulate transcription of the HDC gene and generate the two species of mRNA, we have isolated genomic DNA clones coding for the HDC from human genomic libraries. Structural analysis of the isolated clones revealed that the human HDC gene is composed of 12 exons spanning approximately 24 kb. Genomic DNA blot analysis suggested that HDC is encoded by a single copy gene. The structural analysis also demonstrated that the heterogeneity of the HDC mRNA is caused by an insertion of the seventh intron sequence and alternative use of the splicing acceptor site at the 12th exon. The transcription start site of the HDC gene and the nucleotide sequences of the promoter and first exon regions were determined. We found a TATA-like sequence, a GC box, four CACC boxes, four GATA consensus sequences, and six leader-binding protein-1 binding motifs in the promoter region of the HDC gene.

Base Sequence↗

[Interleukin-6].

Interleukin-6 (IL-6) was found to be a pleiotropic cytokine which plays important roles not only in immune response but also in inflammation and hematopoiesis since the cDNA for IL-6 was originally cloned as a B cell differentiation factor (BCDF). IL-11, leukemia inhibitory factor, oncostatin M, and ciliary neurotrophic factor have similar effects with IL-6. This functional redundancy was well explained by the common signal transducer gp 130. Furthermore, recent studies have revealed the mechanisms to regulate the gene expression of IL-6 and to transduce the signal through IL-6 receptor system. On the basis of these results, elucidation of pathogenic significances of IL-6 and new therapeutic approaches in various diseases are now expected.

Animals↗

[Quantitative study on the effect of oncostatic toxicity on murine fertility].

Oncostatics such as Cisplatin (CDDP), Adriamycin (ADM), and Cyclophosphamide (CPM) were administered to 6-week-old C57BL/6 female mice to destroy 50% (ED50: ED50 treated group) or 80% (ED80: ED80 treated group) of their primordial follicles. Thereafter, they were mated at the age of 11 weeks (group I), and 19 weeks (group II) to study the quantitative oncostatic toxicity to murine fertility. Group I: The maternal body weight before pregnancy in the oncostatics treated group was smaller than the control. The fertile ratios of ED50 (61%) and ED80 (50%) were smaller than that of the control (83%). Six fetal abnormalities (23.2 +/- 10.4%) in ADM.ED50, and 3 (8.1 +/- 2.7%) in CPM.ED80 were regarded as significant (p < 0.05). Group II: Maternal body weight before delivery in CDDP.ED80, ADM.ED50 and ADM.ED80 was less than the control (p < 0.05). The fertile ratios for ED50 (61%) and for ED80 (39%) were smaller than the control (83%). The fetal number for ED80 (7.0 +/- 0.6) was smaller than the control (8.2 +/- 1.1). Fetal birth weight for ED80 and ADM.ED80 was less than the control (p < 0.05). The frequency of IUFD in CDDP.ED50 (9.7 +/- 3.3%) was higher than the control (4.0 +/- 3.6%). In group I, the growing follicles damaged with oncostatics decreased the number of fertile mice and increased IUFD and abnormalities. In group II, the primordial follicles destroyed or decreased by oncostatics led to a decrease in the number of fetuses and birth weight.

Abnormalities, Drug-Induced↗

Neurosteroids in cerebrospinal fluid in neurologic disorders.

In order to investigate the role of "neurosteroids" in the central nervous system (CNS), cerebrospinal fluid (CSF) levels of dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulfate (DHEAS) were determined by radioimmunoassay in 57 patients with various neurologic disorders and 26 patients with non-neurologic disorders. The content of CSF DHEA and DHEAS in patients with Guillain-Barré syndrome (GBS), and the content of CSF DHEAS in patients with carcinomatous meningitis were significantly higher as compared to non-neurological control patients. These changes may be explained by the breakdown of blood-nerve barrier in these disorders. A significant positive correlation was observed between DHEAS and total protein in CSF. In males but not females, a negative correlation was observed between CSF DHEAS and aging. The level of CSF DHEAS, but not DHEA, was significantly higher in males than in females.

Adult↗

Blood flow velocities in the cerebral arteries and descending aorta in small-for-dates infants.

Resistive indices (RI) in the anterior cerebral artery (ACA), basilar artery (BA), middle cerebral artery (MCA) and descending aorta (DA) were obtained in 15 small-for-dates (SFD) infants who were, growth retarded because of maternal pregnancy-induced hypertension and in 20 appropriate-for-dates (AFD) infants matched for gestational age between 24 h and 48 h after birth. The RIs in the MCA, ACA and BA were significantly lower, while the RI in the DA was significantly higher, in the SFD infants than in the AFD infants. These changes in RIs in the SFD infants might be similar to the "brain sparing" effect as reported in growth-retarded fetuses.

Aorta, Thoracic↗

[Incidence and causes of neonatal seizures in the last 10 years (1981-1990)].

We report the incidence of neonatal seizures in the last 10 years. Between 1981-1990, 28,925 infants were born in the Japanese Red Cross Medical Center. Very low-birth-weight infants (< 1,500 g) were excluded in this study. Seizures were identified in 67 infants (0.23%) during the first 7 days of life. Seizures occurred more frequently in low-birth-weight infants (1,500-2,499 g) than in normal-birth-weight infants (> 2,499 g). Fifty-one infants (0.19%) of 27,276 normal-birth-weight infants and 16 (0.97%) of 1,649 low-birth-weight infants developed seizures. The frequency of seizures was 0.25% during the first 5 years and 0.20% during the second 5 years. In low-birth-weight group, the frequency of seizures decreased form 1.49% to 0.48% during the 5-year periods, and seizures due to post asphyxial hypoxic-ischemic encephalopathy also decreased from 0.14% to 0.06%. The decreased incidence in neonatal seizures during the last 10 years was probably achieved by the progress in intervention of low-birth-weight infants in NICU and by the obstetrical prevention of intrapartum asphyxia.

Female↗

[The clinical and pharmacokinetic evaluation of two-route chemotherapy with cisplatin and sodium thiosulfate in combination with angiotensin II].

Thirty-six courses of chemotherapy with cisplatin (CDDP) and sodium thiosulfate (STS) were performed in 31 patients with gynecologic cancer 2 weeks after operation under the hypertensive condition induced by angiotensin II (AT-II). One hundred-fifty mg of CDDP/body was intraperitoneally administered while the usual systolic blood pressure was increased to 130-140% by AT-II. The hypertension was maintained for 15 minutes after finishing CDDP infusion, then 8g of STS was intravenously infused immediately after the cessation of AT-II. The urinary Pt level measured 15 minutes after finishing CDDP infusion was extremely low at 1.37 +/- 0.47 micrograms/ml, in spite of the significantly high levels of plasma total Pt (7.83 +/- 0.85 micrograms/ml) and filtrable Pt (4.02 +/- 0.55 micrograms/ml). This suggests that, during renal vasoconstriction induced by AT-II, the renal blood flow as well as renal uptake of CDDP was decreased. Plasma filtrable Pt levels were measured at 15, 30, 60 and 120 minutes after intraperitoneal administration of CDDP. At 15 and 30 minutes a significantly higher blood concentration was found than in the control group (p less than 0.05). However, CDDP-induced toxicities of the bone marrow, liver, kidney and alimentary tract were not increased. The extreme vasoconstriction in the kidneys and other organs induced by AT-II might have protected these organs from the toxicities of CDDP despite the fact that STS infusion was delayed by 15 minutes after CDDP infusion. STS infused immediately after the cessation of AT-II could neutralize the CDDP preventing the occurrence of toxicities.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin II↗

Sequence and properties of beta-xylosidase from Bacillus pumilus IPO. Contradiction of the previous nucleotide sequence.

The nucleotide sequence of the beta-xylosidase (xynB) gene from Bacillus pumilus has been reported previously [Moriyama, H., Fukusaki, E., Crespo, J.C., Shinmyo, A. & Okada, H. (1987) Eur. J. Biochem. 166, 539-545]. However, the sequence identified in the present study is quite different from the previously reported one. The total length of the PstI--EcoRI fragment of a plasmid pOXN295 containing the xynB gene is 2201 bp from our sequencing, while the length of the fragment in the previous data was 2466 bp. The sequences are similar in the N-terminal (500 bp) and C-terminal (260 bp) regions, but those in the central region are completely different. From the following observations, the previous sequence seems to have no reliable experimental basis. First, the restriction sites observed for pOXN295 are quite different from the sites deduced from the sequence. Second, the amino acid composition deduced from the sequence and the composition identified by amino acid analysis of the purified beta-xylosidase are very different. It is confirmed, on the other hand, that our new sequence agrees well with these experimental data. The enzyme was purified to homogeneity from Bacillus pumilus and Escherichia coli harboring a hybrid plasmid which highly expresses the xynB gene. The molecular mass of the enzyme was estimated to be 190 kDa by high performance gel filtration chromatography using TSK-G3000SW and 56 kDa by SDS/polyacrylamide gel electrophoresis. The pH optimum was 7.0, and the optimum temperature was 40 degrees C. The Vm value was estimated to be 1.23 +/- 0.14 mukat/mg (or p-nitrophenyl beta-D-xyloside) and 0.14 +/- 0.011 mukat/mg (for xylobiose), while Km was estimated to be 3.9 +/- 0.59 mM (for p-nitrophenyl beta-D-xyloside) and 8.9 +/- 1.19 mM (for xylobiose).

Amino Acid Sequence↗

Interleukin 6, a possible autocrine growth and differentiation factor for the human megakaryocytic cell line, CMK.

CMK is a human cell line derived from a megakaryoblastic leukaemia. It has characteristics of the megakaryocytic lineage, such as the presence of platelet peroxidase, membrane glycoproteins (GP)Ib and GPIIb/IIIa, alpha-granules, and demarcation membranes. The cell line proliferates autonomously in serum-containing medium. Here we report that the cell line expresses the gene for IL-6 and releases small quantities of the cytokine into the medium. Addition of exogenous IL-6 to cultures seeded into medium was found to promote growth of the cells. Conversely, addition of a neutralizing anti-IL-6 antibody inhibited cell growth. These data support the notion that autocrine IL-6 is one of the factors accounting for autonomous growth of the cell line.

Blotting, Northern↗

Effects of the consumption of cigarettes, alcohol and foods on serum concentrations of carotenoids, retinol and tocopherols in healthy inhabitants living in a rural area of Hokkaido.

The relationship between serum concentrations of carotenoids, tocopherols and retinol and the consumption of cigarettes, alcohol and foods was investigated in 835 healthy inhabitants (aged 35-79 years) of a rural area of Hokkaido. Serum concentrations of beta-carotene (BC), alpha-carotene (AC), lycopene (LY), beta-cryptoxanthin (BX), zeaxanthin (including lutein, ZX), canthaxanthin (CX) and beta-tocopherol (including gamma-tocopherol, BT) were higher in females than in males, while serum retinol (RE) concentrations were lower. Serum alpha-tocopherol (AT) concentrations were the same for both sexes. The serum values of BC, BX, AC, LY and ZX for males were inversely associated with the consumption of cigarettes in multiple-regression analysis. The serum values of BC, AC and BX for males were inversely associated with alcohol consumption, while serum RE values were positively related to alcohol consumption for both sexes. There were significant relations between serum values of BC, AC, and ZX and the intake frequencies of carrots, tomatoes, milk and/or green-leaf vegetables, especially for females, and between serum BX values and the intake of oranges, juices and fruits. Serum RE and AT concentrations were not associated with any food intake, and BT concentrations were associated with the intake of tomatoes and juices for males.

Adult↗

[Prophylactic effect of allopurinol mouthwash against stomatitis induced by the chemotherapy (PMUE regimen) for gastrointestinal malignancies].

For prevention of the chemotherapy-induced stomatitis we administered allopurinol mouthwash to 15 out of 38 patients who underwent PMUE regimen. The severity of stomatitis was graded on five scales according to the criteria of Japan Society For Cancer Therapy. The incidence of stomatitis was defined as patients number with stomatitis above Grade 2/all patients number. Six of 23 patients which were not given allopurinol mouthwash (control group) developed stomatitis of Grade 1 (three patients), Grade 3 (two), or Grade 4 (one). Only one patient given allopurinol mouthwash (AMW group), however, suffered from Grade 1 stomatitis. The incidence of stomatitis was 13.0% for a control group and 0% for an AMW group. The average graded toxicity was 0.07 for the AMW group significantly lower than 0.57 for the control group. There was no significant difference between the two groups in other clinical adverse effects or abnormal laboratory data. These results suggested that allopurinol mouthwash regimen was well tolerated and effective for prevention of the chemotherapy induced stomatitis.

Allopurinol↗