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T Inoue

Publications and source records attributed to T Inoue.

At least 865 records · Page 48Linked to original sources
PubMed1998

P5abc of the Tetrahymena ribozyme consists of three functionally independent elements.

P5abc domain of Tetrahymena LSU intron functions as an activator that is not essential for but enhances the activity of the ribozyme either when present in cis or when added in trans. This domain contains three regions (A-rich bulge, L5b, and L5c) that have been demonstrated to interact with the rest of the intron. Although these regions are presumably important for efficient activation, the role of each element is not understood in the mechanism of activation. We employed circularly permuted introns and examined the roles of each element. The results show that each of the three elements can activate the intron independently. We also found that a correlation between the activation by P5abc and the physical affinity of P5abc to the intron exists.

Animals↗
PubMed1998

Establishment of lymph node metastatic model for human gastric cancer in nude mice and analysis of factors associated with metastasis.

The actual mechanisms responsible for lymph node metastasis in gastric cancer are still unclear. To investigate the mechanisms of lymph node metastasis in gastric cancer, we established a lymph node metastatic model for human scirrhous gastric carcinoma. Lymph node metastasis had frequently developed after orthotopic implantation of OCUM-2M LN derived from a scirrhous gastric cancer cell line, OCUM-2M, which had low capacity for lymph node metastasis. We elucidated the different characteristics including binding ability, migratory capacity and immunoresponses induced by the cell surface molecules of these two cell lines. The binding ability to Matrigel and migratory capacity of OCUM-2M LN cells were significantly greater than those of OCUM-2M cells. On flow cytometric analysis, both OCUM-2M and OCUM-2M LN cells strongly expressed HLA-I (99.5 and 97.1%) and LFA-3 (76.6 and 99.2%) in level of expression between the two cell lines, but neither cell line expressed HLA-II (0.0 and 0.0%), B7-1 (0.0 and 0.0%) or B7-2 (0.4 and 0.3%). ICAM-1 expression in OCUM-2M LN cells was weaker (0.7%) than that in OCUM-2M cells (36.8%). Strong adhesiveness and cytotoxicity of mononuclear lymphocytes for OCUM-2M cells were observed in adhesion and cytotoxic assays, both of which were significantly decreased by the addition of anti-ICAM-1 antibodies. On the other hand, the adhesiveness and cytotoxicity of OCUM-2M LN cells were significantly less than those of OCUM-2M cells, and were not affected by the addition of anti-ICAM-1 antibodies. These findings suggest that decreased ICAM-1 expression in a new gastric cancer cell line with a high rate of lymph node metastasis may in turn decrease immune responses mediated through LFA-1-dependent effector cell adhesion, and that this escape from the immunosurveillance system may be one of the factors inducing lymph node metastasis. In conclusion, we established a gastric cancer cell line, OCUM-2M LN, with a high rate of lymph node metastasis. An in vivo lymph node-metastatic model with this cell line should be useful for analysing the mechanism and therapeutic approach of lymph node metastasis.

Adenocarcinoma, Scirrhous↗
PubMed1998

Serum hepatocyte growth factor as an index of disease status of patients with colorectal carcinoma.

To evaluate the clinical significance of serum levels of hepatocyte growth factor (HGF) in colorectal cancer patients, we measured the venous and portal concentrations of HGF in 60 patients. The tissue concentrations in the tumour and adjacent normal mucosa were also determined. The serum HGF concentration for the peripheral venous blood of the patients was significantly higher than that in normal controls. The content of HGF in cancer tissue was also significantly higher than that in normal mucosa, and it was correlated with the serum HGF concentration for the peripheral venous blood. The serum concentration of HGF reflected pathological features, including tumour size and lymph node or liver metastasis, and it showed an association with various preoperative nutritional parameters and the preoperative haemoglobin level. The serum HGF concentration was also correlated with the serum concentrations of immunosuppressive acidic protein and interleukin-6, indices of the host's immunological condition. Serum HGF seems to be a useful index of the disease status of patients with colorectal carcinoma.

Adult↗
PubMed1998

Pharmacological characterization of a nonpeptide bradykinin B2 receptor antagonist, FR165649, and agonist, FR190997.

1. The nonpeptide bradykinin (BK) B2 receptor antagonist, FR165649 (8-[2,6-dichloro-3-[N-[(E)-4-(N-methylcarbamoyl)cinnamidoacetyl ]-N-methylamino]benzyloxy]-2-methylquinoline), and agonist, FR190997 (8-[2,6-dichloro-3-[N-[(E)-4-(N-methylcarbamoyl) cinnamidoacetyl]-N-methylamino]benzyloxy]-2-methyl-4-(2-pyridyl methoxy)quinoline) have been identified. These compounds have a common chemical structure, and the 2-pyridylmethoxy group is the only structural difference between them. 2. Both FR165649 and FR190997 displaced [3H]-BK binding to B2 receptors in guinea-pig ileum membranes, with an IC50 of 4.7 x 10(-10) M and 1.5 x 10(-9) M, respectively. They also displaced [3H]-BK binding to B2 receptors in human lung fibroblast IMR-90 cells, with an IC50 of 1.6 x 10(-9) M and 9.8 x 10(-10) M, respectively. 3. In guinea-pig isolated ileum-preparations, FR165649 had no agonistic effect on contraction and caused parallel rightward shifts of the concentration-response curves to BK on contraction. Analysis of the data produced a nominal pA2 value of 9.2+/-0.1 (n=5) and a slope of 1.4+/-0.1 (n=5). On the other hand, FR190997 induced concentration-dependent contraction of guinea-pig ilea with a pD2 of 7.9+/-0.2 and the contraction was inhibited by a specific peptide bradykinin B2 receptor antagonist, Hoe 140 (D-Arg-[Hyp3, Thi5, D-Tic7, Oic8]BK) in a non-competitive manner. 4. In IMR-90 cells, FR165649 had no agonistic effect on phosphatidyl inositol (PI) hydrolysis and caused parallel rightward shifts (approximately 200 fold shift at 10(-7) M) of the concentration-response curves to BK on PI hydrolysis. FR190997 induced concentration-dependent PI hydrolysis in IMR-90 cells with a pD2 of 8.4+/-0.1, and this effect was inhibited by Hoe 140. 5. These results indicate that FR165649 and FR190997 are, respectively, a potent bradykinin B2 receptor antagonist and agonist, and that the agonistic activity depends on the small part of the nonpeptide ligand. FR165649 and FR190997 may be useful tools for studying the relationship between ligands and receptors.

Animals↗
PubMed1998

Investigation of glucocorticoid-induced apoptotic pathway: processing of caspase-6 but not caspase-3.

Glucocorticoids (GCs) are essential therapeutic reagents for the treatment of lymphomas and leukemias. GCs cause cell death in certain types of lymphoid cells mediated by the process known as apoptosis. This cell death is completely inhibited by Bcl-2. Here we report that Bcl-2 and benzyloxycarbonyl-Val-Ala-Asp(OMe)-fluoromethylketone (zVAD-fmk), a broad spectrum caspase inhibitor, prevent loss of mitochondrial membrane potential (delta psi m) and the production of reactive oxygen species (ROS) caused by GC, while acetyl-Asp-Glu-Val-Asp-aldehyde (Ac-DEVD-CHO), an inhibitor of the caspase-3 family proteases, does not. This suggests that the inhibition by Bcl-2 and activation of some initiator caspases are upstream events of mitochondrial damage, whereas the activation of caspase-3 family proteases occurs downstream of mitochondrial changes. We also demonstrate that caspase-6 but not caspase-3 is cleaved and activated during GC-mediated apoptosis and that poly(ADP-ribose) polymerase (PARP), a substrate of caspases, also undergoes proteolysis. In addition, we provide the evidence that DNA fragmentation is markedly inhibited by Ac-DEVD-CHO, while cell death, assessed by the damage of the plasma membrane, is marginally inhibited or merely delayed.

Amino Acid Chloromethyl Ketones↗
PubMed1998

Homozygous missense mutation (band 3 Fukuoka: G130R): a mild form of hereditary spherocytosis with near-normal band 3 content and minimal changes of membrane ultrastructure despite moderate protein 4.2 deficiency.

The characteristics of phenotypic expression were studied in a Japanese family with hereditary spherocytosis and an extremely rare homozygous missense mutation of the band 3 gene (band 3 Fukuoka: G130R). The homozygous unsplenectomized proband was a 29-year-old male with compensated haemolytic anaemia (red cell count 4.21 x 10(12)/l, reticulocytes 278 x 10(9)/l, and indirect bilirubin 44 micromol/l). His red cell band 3 (B3) protein demonstrated a 9.3% reduction and his protein 4.2 (P4.2) level was substantially reduced (45.0%), compared to normal subjects. P4.2 protein was composed mostly of a wild type (72 kD) with a trace of 68 kD peptide. The binding properties of the mutated B3 to normal P4.2 were significantly impaired, which probably resulted in the substantial reduction of P4.2 in this proband, since no abnormalities were detected on the P4.2 gene. Electron microscopy (EM) using the freeze-fracture method demonstrated a mild decrease in intramembrane particles (IMPs) of near-normal size (8 nm in diameter) with no substantial increases in their oligomerization. Their distribution on the membrane P face was almost normal, although most of the IMPs could represent the homozygously mutated B3 protein. EM (quick-freeze deep-etching method) disclosed a skeletal network of near-normal size and size distribution of the skeletal units, suggesting that the mutated B3 protein itself did not have much effect on the skeletal network in situ. Therefore the reduced P4.2 content (45% of that of normal subjects), which remained on the red cell membrane of this proband, appeared to be nearly sufficient for maintaining the normal structure of the skeletal network and IMPs in situ, contrary to the marked abnormalities in both IMPs and the skeletal network in complete P4.2 deficiencies.

Adult↗
PubMed1998

Plasma leptin level and its relationship with body composition in hemodialysis patients.

Leptin is a newly found hormone secreted by adipocytes that regulates food intake, thermogenesis, and body fat. We measured plasma leptin levels in 103 patients with chronic renal failure treated by hemodialysis and 167 age- and gender-matched healthy control subjects to examine the impact of renal failure on plasma leptin levels and the influence of leptin on body composition measured by dual-energy X-ray absorptiometry. Hemodialysis patients showed a significant decrease in both body fat mass and lean body mass compared with those of the control subjects. Plasma leptin was significantly elevated in the hemodialysis group over the controls. In both groups, leptin was higher in female than male subjects, and it correlated positively with percent body fat. The subjects were divided into six categories according to percent body fat, and plasma leptin levels were compared between the two groups in the same category. Leptin of hemodialysis patients was significantly higher than that of the control subjects in the percent body fat categories of 30 or greater, whereas there was no statistically significant difference in leptin concentrations in the lower percent body fat categories. This was also true in the comparison in each gender, and leptin levels in female subjects showed a more remarkable difference between the hemodialysis and control groups in obese categories. Multiple regression analysis in all subjects indicated that plasma leptin levels were independently affected by percent body fat, plasma insulin concentration, gender, and renal failure. The positive impact of renal failure on leptin remained significant in the subjects with percent body fat of 30 or greater in the multiple regression model, whereas it was no longer significant in the remaining lean subjects. In multiple regression analysis of factors affecting fat mass index and lean mass index, leptin level was selectively associated with fat mass index, but not with lean mass index, regardless of percent body fat ranges. These results indicate that renal failure is an important factor affecting plasma leptin levels, especially in obese female subjects, and that hyperleptinemia was closely related to fat mass but not to lean body mass in hemodialysis patients.

Body Composition↗
PubMed1998

Urinary collagen crosslinks reflect further bone loss of femoral neck in osteoporotic patients undergoing vitamin D therapy.

Bone mineral density (BMD) of the lumbar (L2-LA) spine and femoral neck was measured annually for 2 years (3 times beginning at the beginning of year 1 and after each subsequent year) in 39 female patients with osteoporosis undergoing 0.5 or 1.0 microg daily doses of vitamin D therapy. At the time of the first BMD measurement, biochemical markers including serum alkaline phosphatase (ALP), urinary pyridinoline (Pyr), deoxypyridinoline (Dpyr) and hydroxyproline (Hyp) were also measured. Urinary Pyr and Dpyr correlated with the percent changes of femoral neck BMD measurements taken the year following the sampling (Pyr: r=-0.622, p<0.001, Dpyr: r=-0.385, p<0.05). Only urinary Pyr correlated with the percent changes of femoral neck BMD measurements taken the following 2 years (r=-0.532, p<0.05). Neither serum ALP nor urinary Hyp correlated with the percent changes of spine or femoral neck BMD measurements taken the year or 2 years after the sera and urine sampling. In summary, we believe urinary Pyr and Dpyr can reflect subsequent bone loss of the femoral neck BMD having been measured only once during the course of a year.

Alkaline Phosphatase↗
PubMed1998

Patterns of care study of radiation therapy for esophageal cancer in Japan: influence of the stratification of institution on the process.

BACKGROUND: To improve the quality of radiation therapy in Japan, Patterns of Care Study (PCS), a widely known QA program in the USA, was introduced in Japan. The feasibility was tested by collecting nationwide data by extramural audit for esophageal cancer. METHODS: From July 1996 through February 1997, PCS audits were performed for 29 institutions. Based on the facility survey by Tsunemoto, 13 institutes were classified as A1 (university hospital/cancer center treating > 300 patients/year), 10 as B1 (other institutes > 120 patients/year) and six as B2 (other institutes < 120 patients/year). Medical charts for 455 patients with thoracic esophageal cancer between 1992 and 1994 were reviewed based on the data format of PCS in the USA. RESULTS: Concerning external beam equipment, linear accelerators of > or = 10 MV were used for 73% of patients in A1, whereas in B1-2, 60Co machines were still used for 13% of patients (P < 0.0001). The median number of full-time equivalent (FTE) radiation oncologists was 2.7 in A1, 0.65 in B1 and 0.2 in B2. Forty-five percent of patients had received surgery in A1 and 34% in B1-2 (P = 0.0068). In the non-surgery group, a higher radiation dose of > 60 Gy was delivered in A1 than in B1-2 (P = 0.0008). Chemotherapy was administered to 51% of the patients in A1 and to 30% in B1-2 (P < 0.0001). Brachytherapy was utilized for 17% in A1 and only for 5% in B1-2 (P = 0.0001). CONCLUSION: Institutional stratification, including equipment and personnel, significantly affected the patterns of care for esophageal cancer. Therefore, to improve the quality of radiation therapy nationwide, improvement of equipment and supply of FTE personnel is extremely important. PCS was found to have great potential for the practical evaluation of how much will be required in Japan.

Adult↗
PubMed1998

Membrane-bound carboxypeptidase-M is expressed on human ovarian follicles and corpora lutea of menstrual cycle and early pregnancy.

We have previously reported that membrane-bound aminopeptidases were expressed on human follicles and corpora lutea (CL) and we showed that these aminopeptidases are involved in follicular growth, probably by regulating extracellular peptide concentrations. In this study, the expression of membrane-bound carboxypeptidase-M (CP-M), which cleaves carboxyl-terminal amino acids from peptides extracellularly, on human follicles and CL was examined. In growing and pre-ovulatory follicles, CP-M was immunohistochemically detected with weak or moderate intensity on theca interna cells. Although CP-M was not detected on granulosa cells in growing and pre-ovulatory follicles, it was strongly detected on the cell surface of luteinizing granulosa cells isolated from patients undergoing in-vitro fertilization treatment, indicating that CP-M was rapidly expressed on granulosa cells during ovulation. In menstrual and pregnant CL, CP-M was clearly detected on luteal cells. In menstrual CL, the expression of CP-M mRNA was observed by reverse transcription-polymerase chain reaction (RT-PCR). Western blotting analysis revealed that the molecular mass of the CP-M extracted from mid-luteal CL was 62 kDa. These results indicate that CP-M is a cell surface differentiation-related molecule of human granulosa, theca, and luteal cells. The rapid expression on granulosa cells during ovulation strongly suggests the involvement of CP-M in the ovulation and CL formation processes.

Blotting, Western↗
PubMed1998

Trans-activation of the Tetrahymena ribozyme by its P2-2.1 domains.

The Tetrahymena group I self-splicing intron contains peripheral domains P2-2.1. Mutant introns lacking these domains are hardly active. We found that if an independently prepared P2-2.1 RNA is added in trans, it efficiently enhances the catalytic activity of an intron lacking the domains. P2-2.1 RNA together with the previously identified activator, P5abc RNA, of the Tetrahymena intron can activate the intron lacking both of them. The trans-activation depends on the long-range interaction between P2.1 and P9.1 domains.

Animals↗
PubMed1998

Type 1 Cu structure of blue nitrite reductase from Alcaligenes xylosoxidans GIFU 1051 at 2.05 A resolution: comparison of blue and green nitrite reductases.

The crystal structure of the blue nitrite reductase from Alcaligenes xylosoxidans GIFU 1051 (AxgNIR) has been determined at 2.05 A resolution. AxgNIR contains both type 1 and 2 Cu sites, the geometry of the former being distorted tetrahedral. The superpositioning of the type 1 Cu sites in the blue enzyme and a green nitrite reductase revealed that the orientation of the Met150 side chain differed. The deviation of the Sdelta(Met150) atom from the axial position of the NNS plane formed by two Ndelta(His95 and His145) and one Sgamma(Cys136) atom caused the difference in the colors of the enzymes, i.e. blue and green.

Alcaligenes↗
PubMed1998

The effects of menopausal status and disease activity on biochemical markers of bone metabolism in female patients with rheumatoid arthritis.

The effects of menopause and disease activity on bone metabolism in rheumatoid arthritis (RA) were studied by using biochemical markers of bone metabolism. We measured osteocalcin, bone-specific alkaline phosphatase, urinary total pyridinoline and deoxypyridinoline, and urinary free deoxypyridinoline in 78 female patients with RA (39 pre-menopause, Pre-RA; 39 post-menopause, Post-RA) and 54 female normal controls (28 pre-menopause, Pre-NC; 26 post-menopause, Post-NC). In Pre-RA, although bone formation was equal to Pre-NC, bone resorption increased. In Post-RA, however, bone formation was lower while bone resorption was higher than in Post-NC. The high disease activity RA group showed higher bone turnover than the low disease activity RA group. We conclude that menopause affects the bone turnover in RA as well as in normal controls. In Pre-RA, osteopenia is caused by the increase in bone resorption. In Post-RA, osteopenia is caused by the increase in uncoupling between bone formation and bone resorption. Furthermore, the high disease activity of RA induces high bone turnover.

Adult↗
PubMed1998

The effect of electroconvulsive treatment on thermal hyperalgesia and mechanical allodynia in a rat model of peripheral neuropathy.

UNLABELLED: We tested the ability of electroconvulsive treatment (ECT) to block thermal hyperalgesia and mechanical allodynia in rats with peripheral neuropathy. Repeated ECT (six times daily) significantly reduced thermal hyperalgesia 48 h after the end of the final treatment but had no significant effects on mechanical allodynia. Single ECT had no significant effect on thermal hyperalgesia or mechanical allodynia. Neither single nor repeated ECT had any significant effect on the withdrawal response of sham-operated paws and untreated rats to thermal and mechanical stimuli. The anti-thermal hyperalgesic effect of repeated ECT was reversed by the previous administration of nifedipine (L-type Ca2+ channel blocker). We conclude that, due to effects on the voltage dependent calcium channel, ECT modified one of the pain behaviors induced by nerve injury. ECT may be of use in the treatment of human neuropathic pain. IMPLICATIONS: We showed that repeated electroconvulsive treatment reduced pain responses to heat stimulation after sciatic nerve injury in rats. This study implies a possible therapeutic effect of electroconvulsive treatment on neuropathic pain.

Animals↗
PubMed1998

A new postoperative management scheme for preventing sacral pressure sores in patients with spinal cord injuries.

Although the reliability of pressure sore surgery has improved with the advent of many different types of flaps, it is well known that the recurrence rate of pressure sores is still remarkably high in spinal cord-injured patients. This article reports the very low relapse rate of postsurgical pressure sores using air mattresses, which also helps relieve manpower requirements for care. We measured interface pressures at the sacrum for 18 spinal cord-injured patients with a ROHO air mattress (ROHO International, Inc, Belleville, IL). Based on the results, we used this mattress immediately after surgery for 19 spinal cord-injured patients with sacral pressure sores. Minimal repositioning was performed for each patient during the hospital stay. Minimal repositioning was similarly performed at home. All pressure sores healed, regardless of the type of surgical procedure, size, and degree of sore. No relapse has been found, with an average of 33.4 months after surgery. With this management, we could achieve a very low recurrence rate, require less manpower for postoperative management, as well as minimize stress for the patients.

Adult↗
PubMed1998

Corneal infiltration and CMV retinitis in a patient with AIDS.

PURPOSE: To describe the clinical features of stromal keratitis in a patient with cytomegalovirus (CMV) retinitis and acquired immunodeficiency syndrome (AIDS). METHODS: Case report. RESULTS: Human CMV genome was detected in plasma, urine, and aqueous humor by polymerase chain reaction. CMV retinitis subsided and the corneal infiltrate was scarred within 4 weeks of systemic ganciclovir treatment. CONCLUSION: This is the first report of the corneal infiltration seen in an AIDS patient with CMV retinitis. Etiological significance of the finding is discussed.

AIDS-Related Opportunistic Infections↗
PubMed1998

Effects of growth hormone and insulin-like growth factor I on opsonin receptor expression on local and systemic phagocytes in a lethal peritonitis model.

OBJECTIVE: To investigate the effects of pretreatment with growth hormone (GH) and insulin-like growth factor I (IGF-I) on phagocyte exudation and bacterial clearance, focusing on CD11b and CD32/CD16 expression on local and systemic phagocytes, in a lethal peritonitis model. DESIGN: Prospective randomized experimental study. SETTING: Research laboratory in a university hospital. SUBJECTS: Balb/c mice (n = 21). INTERVENTIONS: Mice were challenged intraperitoneally with 1 x 10(8) Escherichia coli, after 6 days of pretreatment with saline (control), GH (4.8 mg/kg/day), or IGF-I (24 mg/kg/day). Samples were harvested at 4 hrs after the challenge. MEASUREMENTS AND MAIN RESULTS: Viable bacterial counts in peritoneal lavage fluid (PLF) and blood were determined. Peritoneal exudative cells and peripheral blood leukocytes were counted and analyzed for receptor expressions by flow cytometry. GH reduced viable bacterial counts in PLF, as compared with the saline control. GH (three-fold) and IGF-I (two-fold) increased the number of peritoneal exudative neutrophils (PENs), as compared with the saline control. The number of PENs showed an inverse correlation with PLF viable bacterial counts. By contrast, there were no differences in peripheral blood neutrophil (PN) counts among the three groups, nor was there a correlation between PN and PEN counts. CD11b expression was greater on PENs than on PNs in all three groups. CD11b expression on PNs did not differ among the three groups. However, GH increased CD11b expression on PENs, as compared with saline and IGF-I, and this expression showed a positive correlation with PEN numbers and an inverse correlation with PLF viable bacterial counts. CD11b expression on peritoneal macrophages and peripheral blood monocytes did not differ among the three groups. There were no differences in phagocyte CD32/CD16 expression among the three groups. CONCLUSIONS: GH pretreatment enhanced CD11b expression on PENs, but not PNs, possibly in association with enhanced neutrophil recruitment, phagocytosis, and bacterial elimination by PENs, without activation of PNs. GH prophylaxis may be useful for reducing the frequency rate and severity of septic complications, via modulation of CD11b expression on local and systemic neutrophils.

Animals↗