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Biomedical subjects

K Utsunomiya

Publications and source records attributed to K Utsunomiya.

At least 19 recordsLinked to original sources

Effectiveness of an 'half elemental diet' as maintenance therapy for Crohn's disease: A randomized-controlled trial.

BACKGROUND: Although thiopurines have a proven role in maintenance therapy for Crohn's disease, an alternative therapy is needed for patients intolerant or resistant to thiopurines. AIM: To evaluate the effectiveness of home enteral nutrition as a maintenance therapy regimen in which half of the daily calorie requirement is provided by an elemental diet and the remaining half by a free diet. We refer to this home enteral nutrition therapy as 'half elemental diet'. METHODS: Between 2002 and 2005, 51 patients in remission from two hospitals were randomly assigned to a half elemental diet group (n = 26) or a free diet group (n = 25). The primary outcome measure of this study was the occurrence of relapse over the 2-year period. RESULTS: The relapse rate in the half elemental diet group was significantly lower [34.6% vs. 64.0%; multivariate hazard ratio 0.40 (95% CI: 0.16-0.98)] than that in the free diet group after a mean follow-up of 11.9 months. Compliance was similar in the two groups. No adverse event occurred in any of the patients throughout the study. CONCLUSION: This randomized-controlled trial shows the effectiveness of an half elemental diet, which is a promising maintenance therapy for Crohn's disease patients.

Adult↗

Significance of colonoscopy in patients with intestinal graft-versus-host disease after hematopoietic stem cell transplantation.

BACKGROUND AND STUDY AIMS: Patients with intestinal graft-versus-host disease (GVHD) are generally in poor clinical condition. In this study we aimed to establish the clinical significance of endoscopic diagnosis of this condition, observing only the distal section of the large intestine. PATIENTS AND METHODS: Endoscopic and pathological findings at colonoscopy were evaluated retrospectively in 12 patients who were diagnosed with intestinal GVHD after undergoing hematopoietic stem cell transplantation. RESULTS: The main mucosal changes observed at endoscopy were granular change, edema, "spotty redness", and sloughing. These were clearly displayed after enhancement with Indigo carmine staining, and with insertion of the colonoscope only as far as the distal section of the large intestine. A histological diagnosis of intestinal GVHD was made in 50 % of the patients, whose intestinal epithelium specimens showed numerous apoptotic bodies. It was possible to perform total colonoscopy in two patients who were in relatively good condition clinically, but there were no remarkable differences in the endoscopic findings throughout the large intestine, from the terminal ileum to the rectum. In terms of clinical outcomes of the 12 patients, their prognosis was poor in that they all either went on to suffer from chronic GVHD or died. CONCLUSIONS: Endoscopic and histological findings on distal colonoscopy are clinically significant in the diagnosis of intestinal GVHD, and limiting this examination to the distal section of the large intestine avoids causing further clinical deterioration in patients who are already in very poor general condition and the possibility of causing endoscopy-related complications.

Adolescent↗

Usefulness of tc-99m MIBI SPECT in predicting multidrug resistance gene expression levels in non-small cell lung cancer--a preliminary report.

In this study we investigated whether Tc-99m hexakis 2-methoxy isobutyl isonitnile (Tc-99m MIBI) single-photon emission computed tomography (SPECT) has a correlation with the multidrug resistance (MDRI) and multidrug resistance-associated protein (MRP1) gene expression levels in non-small cell lung cancer (NSCLC). Fifteen patients with NSCLC were studied. SPECT images were obtained 15 (early) and 120 (delayed) min after injection of Tc-99m MIBI. We chose only one transverse section and set the region of interest over the tumor and out of the body. The mean counts in the tumor on early and delayed images were corrected by using those in the background and represented as Te and Td, respectively. Resected tumor specimens were frozen with liquid nitrogen and each positive control cell line was cultured. After the total ribonucleic acid (RNA) was extracted from specimens and cell lines, the complimentary deoxyribonucleic acid (cDNA) was amplified by the reverse transcription-polymerase chain reaction (RT-PCR) method. Each product was electrophoresed and fluorointensity was measured. The gene expression level was represented as the ratio of that of the positive control cell line. Te and Td indicated a significant correlation with the MDR1 gene expression level (p = 0.015 and p = 0.022), but not the gene of MRP1 (p = 0.100 and p = 0.145). In conclusion, Te and Td are useful parameters in predicting the MDRI gene expression level, but not MRPI in NSCLC.

Aged↗

Stimulation of catecholamine synthesis in cultured bovine adrenal medullary cells by leptin.

Recently, we characterized leptin receptors in bovine adrenal medullary cells (Yanagihara et al. 2000). Here we report the stimulatory effect of leptin on catecholamine synthesis in the cells. Incubating cells with leptin (10 nM) for 20 min increased the synthesis of 14C-catecholamines from [14C]tyrosine, but not from L-3,4-dihydroxyphenyl [3-14C]alanine. The stimulation of catecholamine synthesis in the cells by leptin was associated with the phosphorylation and activation of tyrosine hydroxylase, the rate-limiting enzyme of catecholamine biosynthesis. The incubation of cells with leptin resulted in a rapid activation of the mitogen-activated protein kinases (MAPKs). An inhibitor of MAPK kinase, U0126, nullified the stimulatory effect of leptin on the synthesis of 14C-catecholamines. Leptin potentiated the stimulatory effect of acetylcholine on 14C-catecholamine synthesis, whereas leptin failed to enhance the phosphorylation and activation of tyrosine hydroxylase induced by acetylcholine. These findings suggest that leptin stimulates catecholamine synthesis via the activation of tyrosine hydroxylase by two different mechanisms, i.e., one is dependent on tyrosine hydroxylase phosphorylation mediated through the MAPK pathway and the second is independent of enzyme phosphorylation.

Acetylcholine↗

Utility of Tc-99m GSA whole-body scintigraphy in detecting bone metastases from hepatocellular carcinoma.

Recent advances in the treatment of hepatocellular carcinoma (HCC) have prolonged patient survival. However, the number of patients with bone metastases identified during follow-up examinations has increased. Tc-99m Sn-N-pyridoxy-5-methyltryptophan (Tc-99m PMT) has been reported to accumulate at a high rate in HCC lesions and bone metastases. In the patient described here, whole-body scintigraphy showed accumulation of DTPA galactosyl human serum albumin (Tc-99m GSA) and Tc-99m PMT in bone metastases from HCC. The authors suggest that asialoglycoprotein receptors may be present in bone metastases from well-differentiated HCC. Tc-99m GSA whole-body imaging can be used to detect bone metastases from HCC and to evaluate hepatic reserve.

Albumins↗

Lipoprotein analysis using agarose gel electrophoresis and differential staining of lipids.

We established a strategy to directly measure cholesterol and triglyceride levels of each lipoprotein fraction using a combination of agarose gel electrophoresis and differential staining. The cholesterol and triglyceride levels determined by electrophoresis correlated significantly with those of ultracentrifugation. The correlation coefficients between these methods were, for cholesterol levels 0.975(very low density lipoproteins, VLDL), 0.986(low density lipoproteins, LDL) and 0.965(high density lipoproteins, HDL) and for triglyceride levels 0.994(VLDL), 0.963(LDL) and 0.959(HDL) respectively. Both intra-and inter-assays showed low values of coefficients of variation (CV) (less than 3.57%). We observed a strong linearity between staining and triglyceride concentration. An increased VLDL-cholesterol was observed in type III subjects, a result which enabled distinction between type III and type IIb or type V lipoproteinemia. The method revealed lipoprotein patterns in some samples otherwise unexpected from their corresponding serum lipid parameters. Analyses of these electrophoretic patterns thus provide an effective technique to classify types of hyperlipidemia defined by the WHO. Furthermore, quantitative measurement of chylomicrons, usually difficult, proved to be achievable, providing an additional analysis of postprandial hyperlipidemia and the exact measurement of LDL-cholesterol after diet. Consequently, we recommend this simple and easy method for clinical evaluation of abnormalities in lipoprotein profiles.

Chylomicrons↗

Protective effect of gamma-glutamylethylamide (theanine) on ischemic delayed neuronal death in gerbils.

We examined the protective effect of gamma-glutamylethylamide (theanine) on ischemic delayed neuronal death in field CA1 of the gerbil hippocampus. One microliter of theanine from each three concentrations (50, 125 and 500 microM) was administered through the lateral ventricle 30 min before ischemia. Transient forebrain ischemia was induced by bilateral occlusion of the common carotid arteries for 3 min under careful control of brain temperature at approximately 37 degrees C. Seven days after ischemia, the number of intact CA1 neurons in the hippocampus was assessed. Ischemia-induced neuronal death in hippocampal CA1 region was significantly prevented in a dose-dependent manner in the theanine-pretreated groups. These findings indicate that theanine might be useful clinically for preventing ischemic neuronal damage.

Animals↗

Neovascularization with blood-brain barrier breakdown in delayed neuronal death.

Various kinds of acute pathological events in the central nervous system, such as ischemia, hemorrhage, and trauma, often cause brain edema. The edema may advance for days or weeks while inducing extensive damage in neural function, regardless of the extent of the original damage, and often results in death. Delayed edema is thought to be vasogenic; however, the mechanism underlying edema induction remains unknown. We found delayed vascular cell proliferation with a blood-brain barrier breakdown in and around the gerbil CA1 hippocampus, a region known to be involved in delayed apoptotic neuronal death 2-6 days after transient ischemia. Vascular cell proliferation, assessed by (3)H-thymidine incorporation, was most prominent 4-6 days after ischemia, and extravasation of exogenously applied dye or endogenous serum albumin from blood vessels was observed concomitantly. We propose neovascularization in delayed neuronal death as a cause of brain edema advancing days after neurological events.

Animals↗

Characterization and functional role of leptin receptor in bovine adrenal medullary cells.

We report here the characterization and functional roles of the leptin receptor (ObR) in bovine adrenal medullary cells. The plasma membranes isolated from bovine adrenal medulla showed a single class of specific binding sites of (125)I-leptin with an apparent K(d) of 6.6 nM and B(max) of 62 fmol/mg protein. ObRa but not ObRb mRNA was detected in bovine adrenal medulla by reverse transcriptase-polymerase chain reaction. Incubation of cultured adrenal medullary cells with leptin (3-30 nM) for 20 min resulted in a significant increase in [(14)C]catecholamine synthesis from [(14)C]tyrosine without any change in catecholamine secretion. These findings suggest that leptin stimulates catecholamine synthesis through its receptors in bovine adrenal medullary cells.

Adrenal Medulla↗

Technetium-99m MIBI single photon emission computed tomography as an indicator of prognosis for patients with lung cancer-preliminaly report.

PURPOSE: We performed technetium-99m hexakis-2-methoxyisobutylisonitrile (Tc-99m MIBI) single photon emission computed tomography (SPECT) in 23 patients with primary lung cancer between July 1993 and March 1996. We evaluated the relationships among the uptake ratio, retention index and the prognosis after radiation therapy and/or chemotherapy. MATERIALS AND METHODS: Tc-99m MIBI SPECT was performed at 30 minutes and at 3 hours after intravenous injection of 600 MBq of Tc-99m MIBI with three gamma camera detectors (GCA-9300A/HG) on transverse SPECT images. Regions of interest were set in the area of abnormal uptake of Tc-99m MIBI and in the contralateral normal lung. The ratio of uptake in the lesion to that in the contralateral normal lung was obtained on early images (early ratio; ER) as well as delayed images (delayed ratio: DR). The retention index (RI) was calculated as follows: RI = (DR - ER)/ER x 100. The ratio was compared with survival time and prognostic factors. RESULTS: There was no correlation between ER and DR. The patients with high RI survived longer than those with low RI (median survival, 19.4 months vs. 9.4 months; p = 0.0104 by the Mantel-Cox test). CONCLUSION: These results suggest that RI is the most useful among Tc-99m MIBI indices of primary lung cancer in predicting prognosis.

Adult↗

Comparison of the accumulation and efflux kinetics of technetium-99m sestamibi and technetium-99m tetrofosmin in an MRP-expressing tumour cell line.

The potential clinical use of technetium-99m labeled sestamibi (Tc-MIBI) and tetrofosmin (Tc-Tfos) to image tumours is currently being evaluated. In this study. the accumulation and efflux of Tc-MIBI and Tc-Tfos in the nasopharyngeal carcinoma cell line CNE-1 were examined in the presence or absence of various inhibitors of P-glycoprotein (PGP) and/or multidrug resistance associated protein (MRP) activity [GG918, PSC833, verapamil (Vrp), cyclosporin A (CsA) and buthionine sulfoximine (BSO)]. Reverse-transcriptase polymerase chain reaction analysis and immunodetection of the CNE-1 cells detected expression of MRP, MRPI and MRP2 but not PGP. Tc-MIBI and Tc-Tfos accumulation was increased (P < 0.0001) and efflux decreased (P < 0.05) in the presence of BSO, CsA, Vrp and PSC833 but not GG918, which is a specific inhibitor of PGP. The absolute accumulation of Tc-MIBI was approximately twofold higher than that seen with Tc-Tfos, whereas the addition of inhibitors caused a much greater suppression of Tc-Tfos transport (>2 times greater than for Tc-MIBI). However, no qualitative differences in inhibitors were seen between Tc-MIBI and Tc-Tfos. These results suggest that both Tc-MIBI and Tc-Tfos are substrates for the MRP transporter and that PSC833, Vrp, CsA and BSO but not GG918 can inhibit MRP activity. These results indicate that Tc-MIBI and Tc-Tfos may be suitable imaging agents for detecting MRP-mediated drug resistance in human cancers.

ATP Binding Cassette Transporter, Subfamily B↗

Intraductal ultrasonographic assessment of coagulation depth during endoscopic microwave coagulation therapy in a canine model.

In order to examine the feasibility of endoscopic microwave coagulation therapy (MCT) for the treatment of common bile duct cancer in humans, we investigated the safety and effectiveness of endoscopic MCT with the assistance of intraductal ultrasonography (IDUS). We performed MCT in the canine small intestine as a model because of its similarity in size to the obstructed human common bile duct. Multiple coagulation lesions were made in anesthetized dogs, with the endoscope inserted through a jejunostomy. Under condition "A", the tip of the MCT probe was kept in a fixed position in contact with the mucosa of the intestine, and coagulation was performed with an output of 30 or 50 W for 30 or 10 s, respectively. Under condition "B", the tip of the MCT probe was moved along the intestinal mucosa, and coagulation was performed with an output of 50, 40, or 30 W, all for 10 s. After coagulation, a thin-caliber ultrasonic probe was inserted endoscopically for observation of the effects of coagulation. Each coagulation under condition "A" resulted in degeneration of all layers of the intestine. Coagulation under condition "B" resulted in more localized degeneration, extending from the mucosal layer to the proper muscle layer. By comparison with histologic observations, the accuracy of IDUS in assessing depth of degeneration was 87.5%. Endoscopic microwave coagulation was considered safe and effective, and IDUS was able to accurately assess the effects of microwave coagulation.

Animals↗

A case of local recurrent pheochromocytoma: usefulness of I-123 MIBG early SPECT and maximum intensity projection images.

It has been reported that 10% of patients with pheochromocytoma experience recurrence despite surgery. The authors administered I-123 MIBG to patients with recurrent pheochromocytoma and found that early images are more useful than delayed images to detect recurrence. Early imaging with I-123 MIBG is useful for postoperative follow-up studies in patients with pheochromocytoma and those with possible tumor recurrence.

3-Iodobenzylguanidine↗

Ischemia-induced glutamate release in the dentate gyrus. A microdialysis study in the gerbil.

The levels of extracellular glutamate were measured in the dentate gyrus by using an in vivo brain microdialysis method to determine whether the ischemia-induced glutamate release might be correlated with the neuronal vulnerability to ischemia. A microdialysis membrane was placed in CA4 (vulnerable to ischemia) and the molecular and granule cell layers of the dentate gyrus (resistant to ischemia) of gerbils. A significant increase in glutamate levels was induced in the normal dentate gyrus during 10-min ischemia. The increase was completely suppressed during the first 5 min of ischemia when CA4 neurons were eliminated. Thus, it was indicated that during the first 5 min of ischemia glutamate was released mostly from CA4 neurons but not from granule cells of the dentate gyrus. During the second half of 10-min ischemia, a significant increase in glutamate release was induced even in the dentate gyrus where CA4 neurons were eliminated; this increase was significantly suppressed by inhibiting proliferation of astrocytes. A large part of glutamate that was released during the second half of 10-min ischemia was considered to be attributable to glutamate release from astrocytes.

Animals↗

A vitamin D analog regulates mesangial cell smooth muscle phenotypes in a transforming growth factor-beta type II receptor-mediated manner.

Mesangial cells share features with contractile smooth muscle cells and mechanically support the capillary wall. The role of vitamin D compounds and the transforming growth factor-beta (TGF-beta) type II receptor in modulating the smooth muscle phenotype of cultured mesangial cells was examined. Cell proliferation was significantly inhibited by the vitamin D analog 22-oxa-1,25-dihydroxyvitamin D(3) (22-oxacalcitriol; OCT) rather than by 1,25-dihydroxyvitamin D(3) (1, 25(OH)(2)D(3)) in a dose-dependent manner. OCT-treated early passage mesangial cells (MC-E cells) had increased expression levels of type IV collagen and smooth muscle alpha actin mRNA, but 1, 25(OH)(2)D(3)-treated MC-E cells did not. The addition of a TGF-beta(1)-neutralizing antibody to the OCT-treated MC-E cells blocked this inhibitory effect for cell proliferation and attenuated the up-regulated mRNA levels. However, after exposure to 1, 25(OH)(2)D(3) or OCT, there was no significant difference in the secretion of active TGF-beta. We next investigated whether TGF-beta type II receptor (RII) was involved in this regulation. OCT treatment significantly increased the expression of the RII mRNA in MC-E cells. These results suggest that the vitamin D analog OCT induces smooth muscle phenotypic alterations and that this phenomenon was mediated through the induction of RII in cultured mesangial cells.

Animals↗