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T Suwa

Publications and source records attributed to T Suwa.

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

Gastric pH profiles of beagle dogs and their use as an alternative to human testing.

Gastric pH levels were measured in samples of gastric aspirates from eight fasted beagle dogs. The gastric pH in fasting dogs fluctuated from 2.7 to 8.3, with a mean of 6.8+/-0.2 (SE). Each dog received the following four treatments in randomly-assigned order: (A) distilled water; (B) a placebo capsule; (C) pentagastrin, and (D) ranitidine. The gastric pH remained relatively constant after distilled water administration. In contrast, the treatments with pentagastrin and placebo capsule each lowered gastric pH. Pretreatment with pentagastrin was more successful in lowering gastric pH than that with placebo capsule. On the other hand, the pH rose above 7.0 in all dogs by the first hour after treatment with ranitidine. This animal model may be helpful in evaluating the biopharmaceutics of drugs exhibiting pH-dependent dissolution or decomposition.

Animals↗
PubMed2000

Role of rat adrenal antioxidant defense systems in the aldosterone turn-off phenomenon.

The mechanism(s) of the "aldosterone turn-off phenomenon", hypoaldosteronemia following chronic ACTH administration, remains unclear. Our previous observation that antioxidants prevented turn-off prompted us to evaluate the chronic effect of ACTH on the enzymatic antioxidant system as well as P450aldo activity and expression of CYP11B2 in adrenal zona glomerulosa. Male Wistar rats were administered ACTH-Z for 5 days with or without antioxidants, vitamin E or DMSO. Adrenal capsules were prepared for P450aldo activity measurement and mRNA content determination by competitive RT-PCR, and immunoreactivity of Mn-SOD in whole adrenals was evaluated. ACTH decreased the P450aldo activity and mRNA level of CYP11B2 in adrenal capsules, while co-administration of vitamin E or DMSO partially blocked this inhibition. ACTH increased Mn-SOD mRNA and immunoreactivity but decreased GPx mRNA. These results suggest that prolonged ACTH treatment increases oxidative stress in the zona glomerulosa and an imbalance in the ratio of Mn-SOD to GPx, possibly via corticosterone overproduction in the zona fasciculata, resulting in the downregulation of CYP11B2. Vitamin E and DMSO might thus protect CYP11B2 expression through their antioxidant actions.

Adrenocorticotropic Hormone↗
PubMed2000

Plasma human hepatocyte growth factor concentrations in patients with biliary obstruction.

BACKGROUND: It has been suggested that human hepatocyte growth factor (hHGF) maintains the growth and viability of hepatocytes and biliary epithelial cells. The purpose of this study was to determine plasma hHGF concentrations in patients with obstructive jaundice and to correlate these findings with clinical outcome. METHODS: The study included 22 patients who had biliary obstruction and underwent percutaneous transhepatic biliary drainage. The plasma concentrations of hHGF, standard liver function tests, daily bile flow and the half-life of serum total bilirubin were measured following the drainage. RESULTS: Plasma hHGF concentrations were significantly higher in patients with biliary obstruction compared with a control group (P<0.01). The plasma hHGF concentrations correlated with white cell count, prothrombin time and bilirubin half-life (P<0.05), but not with the values from other liver function tests. Seven patients who died within 3 months after biliary drainage had significantly higher concentrations of plasma hHGF than the 15 patients who survived for at least 3 months (P<0.05). The patients who experienced a poor outcome also had lower bile flows and prolonged bilirubin half-lives compared with the survivors (P<0.05). The plasma hHGF concentrations decreased significantly after biliary drainage in the survivors (P<0.01), but not in the patients with a poor outcome. CONCLUSIONS: These results suggest that systemic inflammation and the hepatic dysfunction caused by obstructive jaundice cause an increase in the plasma concentrations of hHGF. In addition, the plasma concentrations of hHGF may be a predictor of poor outcome in jaundiced patients.

Aged↗
PubMed2000

Interleukin-6 induces demargination of intravascular neutrophils and shortens their transit in marrow.

Recombinant human interleukin-6 (IL-6) causes both a thrombocytosis and leukocytosis. The thrombocytosis is caused by an accelerating thrombocytopoiesis, but the mechanism of the leukocytosis is unknown. This study was designed to determine the relative contributions of marrow stimulation and intravascular demargination to the IL-6 induced neutrophilia. IL-6 (2 microgram/kg), administered intravenously to rabbits, caused a biphasic neutrophilia with an initial peak at 3 h and a second peak at 9 h. Using the thymidine analog 5'-bromo-2'-deoxyuridine (BrdU) to label dividing polymorphonuclear leukocytes (PMNs) in the bone marrow, we showed that IL-6 treatment mobilizes PMNs from the marginated pool into the circulating pool at 2-6 h with a decrease in L-selectin expression on PMNs and also accelerates the release of PMNs from the postmitotic pool in the bone marrow at 12-24 h. We have concluded that IL-6 causes a biphasic neutrophilia wherein the first peak results from the mobilization of PMNs into the circulating pool from the marginated pool and the second peak results from an accelerated bone marrow release of PMNs.

Animals↗
PubMed2000

Overt congestive heart failure with mitral and aortic regurgitation due to antiphospholipid syndrome in a patient with systemic lupus erythematosus.

A 51-year-old woman with overt congestive heart failure with pleural and pericardial effusion was treated with furosemide and nifedipine, leading to improvement in her condition and a decrease in effusions. An echocardiography demonstrated mitral and aortic regurgitation with mitral valve prolapse, which caused the congestive heart failure. Since leukocytopenia and lymphocytopenia with arthralgia could be observed, serological investigations were performed. She was diagnosed as having systemic lupus erythematosus (SLE) with antiphospholipid syndrome, and started on a treatment of prednisolone and aspirin. Based on the treatment, the pleural and pericardial effusion went into complete remission, indicating that the serositis related to SLE had overlapped the heart failure. Since there was no evidence of any other diseases that could be responsible for the valvular lesions, we concluded that they were due to antiphospholipid syndrome. The administration of prednisolone had no significant effect on valvular morphology or function as demonstrated by echocardiography. When patients with valvular disease are seen, a valvulopathy related to antiphospholipid syndrome should be considered as part of the differential diagnosis.

Antiphospholipid Syndrome↗
PubMed2000

Transplantation of normal and genetically modified adrenocortical cells.

Cell transplantation techniques have been applied to the study of the biology of the adrenal cortex and to adrenocortical cell proliferation, differentiation, and senescence. Primary bovine adrenocortical cells, primary human adrenocortical cells and genetically modified bovine adrenocortical cells have been transplanted. Successful methods include transplantation of cells beneath the kidney capsule and several subcutaneous cell transplantation procedures. In successful transplants the cells form a functional vascularized tissue structure that allows the host animals to survive adrenalectomy. We show here that subcutaneous cell transplantation does not depend on embedding cells in collagen gel before introduction into the host animal. Subcutaneous transplants secrete both cortisol and aldosterone. However, the variability of plasma aldosterone levels indicates that the factors that determine glomerulosa-type and fasciculata-type cell function in transplant tissues are not well understood.

3T3 Cells↗
PubMed2000

What's new in imaging? New magnetic resonance imaging of esophageal cancer using an endoluminal surface coil and antibody-coated magnetite particles.

An endoluminal surface coil: Esophageal cancer was studied by high resolution magnetic resonance imaging (MRI) to determine the histopathologic basis for signal intensity in these lesions and to determine the potential of this modality for evaluating the depth of cancer invasion. In a basic study, 14 tumors were examined with a 1.5-T superconductive MR system using a surface coil. The esophageal wall could be differentiated into four layers on the T1-weighted images and seven layers on the T2-weighted images. The signal intensity of the tumor varied from low to intermediate on the T1- and T2-weighted images. The submucosal layer is important in evaluating cancer invasion on the T2-weighted images. In a clinical study, 30 patients with esophageal cancer were examined with a 1.5-T superconductive MR system using an endoluminal surface coil. In terms of depth of cancer invasion, the accuracy rate of MRI using the endoluminal surface coil was 83%. In conclusion, MRI with an endoluminal surface coil will be a useful examination for esophageal cancer in the future. Antibody-coated magnetite particles: A highly specific and effective MRI contrast agent was prepared by coating superparamagnetite particles with monoclonal antibodies (MAbs) directed against epidermal growth factor receptors (EGFRs), which are overexpressed in esophageal squamous cell carcinoma. The agent was shown to have EGFR-specific MRI contrast capacity in vivo in athymic rats bearing TE8 or H69 tumors. Immunospecific MRI using magnetite particles coated with MAbs against EGFR seems to be useful in the diagnosis of squamous cell carcinoma of the esophagus.

Animals↗
PubMed2000

Population pharmacokinetics and pharmacodynamics of TS-943 for selective nonpeptide platelet glycoprotein IIb/IIIa receptor antagonist in normal healthy subjects.

The pharmacokinetics and pharmacodynamics of TS-943 were evaluated with use of NONMEM in 36 healthy male subjects after constant infusion of five different single-dose regimens. Population analysis showed the plasma concentration-time profiles of TS-943 to be best-fit characterized by a two-compartment open model with constant infusion and first-order elimination. The pharmacodynamic model that best fitted the platelet aggregation was a sigmoid Emax model. The final estimates for baseline effect, 50% inhibitory concentration (IC50), and the Hill coefficient were 79.4%, 23.4 ng/mL and 1.63, respectively. The maximum effect (Emax) was fixed at 80% (submaximal aggregation response). In addition, correlations between TS-943 plasma concentration and extension of template bleeding time were examined by fitting with an exponential model. The model estimates that the TS-943 plasma concentration necessary to double template bleeding time is approximately 63 ng/mL (ie, 2.7-fold greater than the IC50). The population approaches for pharmacokinetic-pharmacodynamic investigation can be useful for the analysis of concentration-effect relationships and concentration-adverse event relationships for a platelet glycoprotein IIb/IIIa receptor antagonist.

Adult↗
PubMed1999

Obstructive jaundice caused by a huge liver cyst riding on the hilum: report of a case.

A 71-year-old man presented to our hospital with obstructive jaundice, found to be caused by a huge liver cyst which was centrally located and riding on the hilum. Percutaneous transhepatic cyst drainage was performed, following which obstruction of the bile duct was relieved and the jaundice subsided. As jaundice recurred after removal of the drainage tube, the patient underwent deroofing, since when he has remained well. Only 13 cases of liver cysts producing obstructive jaundice have been reported in the English literature, most of which were characteristically enormous, located centrally, and riding on the hilum. Liver cysts possessing such features are likely to cause obstructive jaundice by compressing the hepatic hilum. Cyst drainage is helpful for ameliorating the jaundice and making an accurate diagnosis; however, subsequent deroofing or injection therapy is necessary to prevent recurrence.

Aged↗
PubMed1999

Cerebral germinoma with syncytiotrophoblastic giant cells: feasibility of predicting prognosis using the serum hCG level.

As the biological behaviour of germinoma with syncytiotrophoblastic giant cells (STGC) is not well established, the present study was undertaken to ascertain the prognostic significance of serum hCG level in affected patients. Of a total of 23 cases studied, 12 patients were regarded as pure germinomas and 11 were germinomas with STGC. All but one of the former demonstrated an excellent outcome. The exception developed subarachnoid metastases, but the tumour disappeared on radiation therapy and the patient is enjoying a normal social life 13 years after the initial treatment. With the germinoma complicated by STGC, 3 cases showed local recurrence which were followed by a poor outcome. Their pretreatment hCG levels were 15.0, 26.0 and 29.6 mIU/ml respectively. The study showed a tendency, in germinomas with STGC, for a positive association between serum hCG, and the likelihood of a poor outcome. Germinomas with STGC and serum hCG levels higher than 15 mIU/ml thus have a high recurrence rate, and more aggressive treatment is indicated for the affected patients.

Adolescent↗
PubMed1999

Cerebellar clear cell ependymoma mimicking hemangioblastoma: its clinical and pathological features.

BACKGROUND: As the clinical and pathological significance of cerebellar clear cell ependymoma (CCE) has not been recognized in the past, eight cases of cerebellar CCEs were studied. METHODS: Subjects were six men and two women, and their ages ranged from 23 to 64 years old. Their neuroradiological, operative, and pathological features were reviewed. RESULTS: The tumors frequently showed high vascularity on angiography and marked enhancement on computerized tomography. Grossly, six tumors exhibited a "cyst with mural nodule" and two were mostly solid containing small cysts. At operation, the tumor nodules were dark red in color and the cysts contained xanthochromic fluid. Microscopically, all tumors displayed mostly clear round cells and abundant blood vessels. Although they commonly lacked the characteristic features of ependymomas, immunostaining and electron microscopy confirmed their ependymal origin. CONCLUSIONS: The results indicate that cerebellar CCEs closely mimic hemangioblastoma both clinically and pathologically, which suggests CCE should be considered in the differential diagnosis of vascular tumors of the cerebellum. Some diagnostic clues to differentiate CCE from hemangioblastoma are discussed.

Adult↗
PubMed1998

Increased invasiveness of MUC1 and cDNA-transfected human gastric cancer MKN74 cells.

MUC1 mucin is an anti-adhesion molecule expressed in a wide variety of tumors. To examine whether MUC1 mucin is involved in tumor invasion, we have prepared MUC1 transfectants using the human gastric cancer cell line MKN74 and performed an in vivo tumor assay by transplanting these into nude mice. Tumor weight at 71 days after s.c. injection of transfectants was measured, showing that the in vivo growth of MUC1 transfectants was increased compared to that of mock transfectants. Furthermore, MUC1-transfectant tumors invaded into the muscle layer, whereas mock-transfectant tumors did not. In vitro invasion, adhesion to extracellular matrix components and phagokinetic track motility were then evaluated to analyze the mechanisms for the in vivo invasiveness of the transfectants. MUC1 transfectants exhibited an increased in vitro invasiveness, decreased binding to laminin, fibronectin, type I collogen and type IV collagen and increased motility. These effects of MUC1 mucin over-expression in MKN74 cells were abolished by the treatment of transfectants with an inhibitor of O-glycan biosynthesis, benzyl-alpha-GalNAc. Our data suggest that MUC1 mucin could be related to the increased invasive ability of MKN74 cells, whereas O-glycan might play an essential role.

Animals↗
PubMed1998

Magnetic resonance imaging of esophageal squamous cell carcinoma using magnetite particles coated with anti-epidermal growth factor receptor antibody.

A highly specific and effective magnetic resonance imaging (MRI) contrast agent was prepared by coating super-paramagnetite particles with monoclonal antibodies (MAbs) directed against epidermal growth factor receptors (EGFRs), which are over-expressed in esophageal squamous cell carcinoma. The preparation maintained both the immunoreactivity of the MAbs and the full relaxing capability of the magnetite particles. The particles of this EGFR-specific contrast agent are 13.2 +/- 1.9 nm in size, and thus, it is assumed that they are smaller than capillary pores and, hence, able to escape scavenging by reticulo-endothelial system cells. The EGFR-specific T2-relaxing ability of this contrast agent was ascertained first in vitro, using the EGFR-expressing cell line TE8 and the EGFR-deficient cell line H69. The results in athymic rats bearing TE8 or H69 tumors revealed that the agent has EGFR-specific MRI contrast capacity in vivo. The electron-microscopic findings in TE8 tumor-bearing rats revealed that the magnetite particles had been taken up by their lysosomes. In conclusion, immuno-specific MRI using magnetite particles coated with MAbs against EGFR appears to be useful in the diagnosis of squamous cell carcinoma of the esophagus.

Animals↗
PubMed1998

Enhancement of reactivity of anti-MUC1 core protein antibody and killing activity of anti-MUC1 cytotoxic T cells by deglycosylation of target tissues or cells.

MUC1 mucin core protein contains an important tumor-associated peptide antigen that can induce cytotoxic T cells (CTLs) in vivo, although this antigen is generally masked by mucin-type glycans. To reveal the precise expression pattern of MUC1 protein in normal and neoplastic gastric tissues, we performed immunohistochemical staining of periodic acid-treated tissue sections with an anti-MUC1 core protein monoclonal antibody (mAb), MUSE11. In non-cancerous tissues, the deep portion of fundic glands and the luminal surface were predominantly immunostained in normal and metaplastic glands, respectively. In cancerous tissues, the incidence of positivity for MUC1 protein varied from 67% to 88%, depending on histological type. This frequent expression of MUC1 protein in cancer tissues after periodic acid treatment suggested that deglycosylation may be of use for exposing the target antigen of anti-MUC1 CTLs. Accordingly, we then examined the effect of benzyl-alpha-GalNAc, an inhibitor of O-glycan biosynthesis, on the expression of MUC1 protein and sensitivity to an anti-MUC1 CTL line, designated TS, in gastric cancer JRST cells. After incubation with benzyl-alpha-GalNAc, the reactivity of mAb MUSE11 with JRST cells and their sensitivity of TS were clearly increased. These findings suggest that deglycosylation may offer an important strategy for enhancing anti-tumor immunity in patients with gastric cancer.

Acetylgalactosamine↗
PubMed1998

Plasma concentration of cytokine antagonists in patients with infection following liver resection.

BACKGROUND: The interactions between endogenous cytokine antagonists, surgical injury and perioperative infection are poorly understood. METHODS: Perioperative plasma concentrations of soluble tumour necrosis factor receptor p55 (STNFR p55), interleukin (IL) 1 receptor antagonist (IL-1ra) and IL-6 were measured by immunoassay in 29 consecutive patients undergoing liver resection. RESULTS: Plasma concentrations of STNFR p55, IL-1ra and IL-6 showed a striking increase immediately after operation (day 0) and on postoperative day 1. STNFR p55 concentrations correlated significantly with operating time (P< 0.05); IL-1ra levels with operating time, blood loss and weight of resected liver (P < 0.05); and IL-6 concentrations with operating time and blood loss (P< 0.05). Eight of the 29 subjects developed postoperative infections, of whom four had positive cultures of enteric organisms. Plasma STNFR p55 and IL-6 concentrations were significantly higher in the infected group than in the uninfected group (P < 0.05). STNFR p55 and IL-6 concentrations on day 0 differentiated between the two groups with a diagnostic accuracy of 79 and 83 per cent respectively. CONCLUSION: These results suggest that STNFR p55, IL-1ra and IL-6 are produced during operation in response to surgical stress. This production of STNFR p55 and IL-6 may be enhanced further by intraoperative bacterial translocation. Measurement of plasma STNFR and IL-6 concentrations may predict the development of postoperative infectious complications.

Adult↗
PubMed1998

In vivo and in vitro effects of AVP and V1a receptor antagonist on Cushing's syndrome due to ACTH-independent bilateral macronodular adrenocortical hyperplasia.

We examined the possibility that AVP and V1a receptors were involved in regulating cortisol production in a 49 year old man with ACTH-independent bilateral macronodular adrenocortical hyperplasia (AIMAH), and investigated the effects of a V1a receptor antagonist. An i.v. injection of a small dose (0.1 or 0.3 U) of AVP, insulin-induced hypoglycaemia, upright posture tests, and oral administration of a V1a receptor antagonist (OPC-21268; 300 mg), and its repeated administration at a dose of 600 mg/day for 8 days were performed. An in vitro study of dispersed cells obtained from resected AIMAH tissue was also conducted. Plasma ACTH, AVP and cortisol levels and 24-h urinary free cortisol excretion were measured in the in vivo studies and cortisol concentrations in incubation media in the in vitro study. Injection of small doses of AVP stimulated cortisol secretion without any elevation of plasma ACTH. Insulin-induced hypoglycaemia caused a rise in plasma AVP followed by an increase in plasma cortisol. Although plasma cortisol levels were not affected by single or repeated administrations of OPC-21268, 24-h urinary free cortisol excretion was significantly decreased by the repeated treatment. In the in vitro study, more cortisol was stimulated by AVP from adrenal cells of the AIMAH tissue than from those of a normal adrenal gland, and this secretion was completely suppressed by OPC-21268. These results suggested that hypersensitivity to AVP may have contributed to overproduction of cortisol in this case of ACTH-independent bilateral macronodular adrenocortical hyperplasia, and may have contributed to its pathogenesis.

Adrenal Cortex↗
PubMed1998

End-tidal sevoflurane concentration for tracheal extubation and skin incision in children.

UNLABELLED: We sought to determine minimum alveolar anesthetic concentrations for skin incision (MAC) and for tracheal extubation (MAC(Ex)) for sevoflurane and its associated awakening time and respiratory complications during emergence from sevoflurane anesthesia in children. We studied 40 (20 in each group) unpremedicated pediatric patients ranging in age from 2 to 8 yr. For MAC(Ex) determination, anesthetic induction, tracheal intubation, and maintenance of anesthesia were performed with sevoflurane and N2O in oxygen. However, N2O administration was discontinued at the end of surgery. The ratio of the predetermined end-tidal to inspiratory concentration was maintained at 0.95-1.00 for at least 15 min. The trachea was gently extubated, and smooth tracheal extubation was defined by the absence of gross purposeful muscular movements. In addition, the respiratory complications and awakening time were investigated during emergence from anesthesia for each patient. For MAC determination, anesthesia induction and tracheal intubation were performed with 5% sevoflurane in oxygen. After the predetermined end-tidal sevoflurane concentration had been established and maintained for at least 15 min, skin incision was attempted. Patients' responses to skin incision were described as "no movement" or "movements." The MAC or MAC(Ex) for sevoflurane was 2.22% +/- 0.13% (mean+/-SD) or 1.70%+/-0.12%, and the 95% effective dose (ED95) for smooth extubation was 1.87% (95% confidence limits 1.75%-2.62%), respectively, in children. During emergence from anesthesia, none of patients held their breath or experienced laryngospasm in the current study. One patient in a subgroup at 1.5% coughed before tracheal extubation. All 10 patients with smooth tracheal extubation had hemoglobin oxygen saturation levels of > or =98% in this study. Awakening time was 9.7+/-3.7 min in the subgroup that received 1.75% sevoflurane. In conclusion, the MAC(Ex) and ED95 values of sevoflurane were 1.64% and 1.87%, respectively, in children. The MAC(Ex) to MAC ratio for sevoflurane was 0.8 in children within the same age range and mean age. IMPLICATIONS: Because tracheal extubation of anesthetized patients may be advantageous in certain clinical situations, we performed this study. The ratio minimum alveolar anesthetic concentrations for skin incision and for tracheal extubation for sevoflurane was 0.8 in children within the same age range and mean age. No patient in the current study had laryngospasm.

Anesthesia, General↗