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Biomedical subjects

H Noguchi

Publications and source records attributed to H Noguchi.

At least 19 recordsLinked to original sources
PubMed2007

Activation of c-Jun NH2-terminal kinase (JNK) pathway during islet transplantation and prevention of islet graft loss by intraportal injection of JNK inhibitor.

AIMS/HYPOTHESIS: Although application of the Edmonton protocol has markedly improved the outcome for pancreatic islet transplantation, the insulin independence rate after islet transplantation from one donor pancreas has remained low. During the isolation process and subsequent clinical transplantation, islets are subjected to severe adverse conditions that impair survival and ultimately contribute to graft failure. The aim of this study was to map the c-Jun NH2-terminal kinase (JNK) pathway that mediates islet loss during islet transplantation and to clarify whether intraportal injection with JNK inhibitor during islet transplantation can prevent islet graft loss. METHODS: We measured JNK activity in the liver, fat and muscle of diabetic mice and in the liver immediately after islet transplantation. We examined the effect of intraportal injection of JNK inhibitory peptide at islet transplantation. RESULTS: JNK activity became progressively higher at least until 24 h after transplantation. The cell-permeable peptide of JNK inhibitor was delivered not only in the liver but also in other insulin target organs, preventing JNK activation in the liver at least until 24 h after transplantation and reducing JNK activity in these insulin target organs. Moreover, the peptide inhibitor prevented islet graft loss immediately after transplantation and improved islet transplant outcome. CONCLUSIONS/INTERPRETATION: These findings suggest that control of the JNK pathway is extremely important in islet transplantation and that intraportal injection of JNK inhibitor during islet transplantation (addition of JNK inhibitor to transplant media) could prevent the impairment of islet cells, leading to improved outcome for pancreatic islet transplantation.

Adipose Tissue↗
PubMed2007

Brain-derived neurotrophic factor enhances glucose utilization in peripheral tissues of diabetic mice.

AIMS: Repetitive subcutaneous or intracerebroventricular administration of brain-derived neurotrophic factor (BDNF) ameliorates glucose metabolism and enhances energy expenditure in obese diabetic C57BL/KsJ-db/db mice. To explore the mechanism of action through which BDNF regulates glucose metabolism, we examined the effects of BDNF on glucose utilization and norepinephrine (NE) content in peripheral tissues of diabetic mice. METHODS: [(14)C]2-deoxyglucose ([(14)C]2-DG) uptake into peripheral tissues was analysed after intravenous injection of [(14)C]2-DG in db/db and normal C57BL/6 mice, and [(14)C]2-DG uptake and NE content in peripheral tissues were analysed after subcutaneous administration of BDNF (20 mg/kg) to male db/db and normal mice for 8 days. RESULTS: [(14)C]2-DG uptake in the diaphragm, heart, gastrocnemius, soleus and interscapular brown adipose tissue (BAT) of db/db mice was significantly lower than in normal mice. Repetitive administration of BDNF to db/db mice for 8 days enhanced [(14)C]2-DG uptake in the diaphragm, heart, soleus, BAT and liver. The NE content in heart, skeletal muscle, interscapular BAT and liver of db/db mice given BDNF was high compared with db/db mice given vehicle, whereas no significant change in NE content in peripheral tissues was observed in normal mice given BDNF and those given vehicle. BDNF did not affect [(14)C]2-DG uptake or NE content in the white adipose tissue of db/db mice. CONCLUSIONS: These data indicate that BDNF ameliorates glucose metabolism by enhancement of glucose utilization in muscle and BAT, with this effect caused by modulation of the central and peripheral nervous systems.

Adipose Tissue, Brown↗
PubMed2006

Japanese adult male voxel phantom constructed on the basis of CT images.

A Japanese adult male voxel (volume pixel) phantom (hereinafter referred to as the JM phantom) was constructed on the basis of CT images of a healthy Japanese adult male volunteer. Body characteristics of the JM phantom were compared with those of a voxelised MIRD5 type phantom and a Japanese adult male voxel phantom which was previously developed. The voxel size of the JM phantom is 0.98 x 0.98 x 1 mm(3). The shapes of the organs of the JM phantom, even for small or complicated organs, such as thyroid and stomach, are more realistically reproduced as compared with the previous Japanese voxel phantom (voxel size: 0.98 x 0.98 x 10 mm(3)). Photon self-absorbed fractions (self-AFs) for brain, kidneys, spleen, pancreas, thyroid and urinary bladder wall of JM were evaluated and were compared with those of the other phantoms. In consequence, it was suggested that the mass, shape and thickness of organs are important factors for the determination of self-AFs.

Adult↗
PubMed2006

Evaluation of islet transplantation from non-heart beating donors.

We evaluated islet transplantation from non-heart beating donors (NHBDs) with our Kyoto Islet Isolation Method. All patients had positive C-peptide after transplantation. The average HbA(1C) levels of the five recipients significantly improved from 7.8 +/- 0.4% at transplant to 5.2 +/- 0.2% currently (p < 0.01). Three patients with no or a single autoantibody became insulin independent while the other two patients with double autoantibodies reduced their insulin requirement but did not become insulin independent. C-peptide in patients who became insulin-independent gradually increased after each transplantation whereas C-peptide in patients who did not become insulin-independent from 3 months after the first transplantation to the next transplantation dramatically decreased. The beta-score of the three patients who became insulin independent was the best of eight. In conclusion, our method makes it feasible to use NHBDs for islet transplant into type 1 diabetic patients efficiently.

Adult↗
PubMed2006

Modified two-layer preservation method (M-Kyoto/PFC) improves islet yields in islet isolation.

Islet allotransplantation can achieve insulin independence in patients with type I diabetes. Recent reports show that the two-layer method (TLM), which employs oxygenated perfluorochemical (PFC) and UW solution, is superior to simple cold storage in UW for pancreas preservation in islet transplantation. However, UW solution has several disadvantages, including the inhibition of Liberase activity. In this study, we investigated the features of a new solution, designated M-Kyoto solution. M-Kyoto solution contains trehalose and ulinastatin as distinct components. Trehalose has a cytoprotective effect against stress, and ulinastatin inhibits trypsin. In porcine islet isolation, islet yield was significantly higher in the M-Kyoto/PFC group compared with the UW/PFC group. There was no significant difference in ATP content in the pancreas between the two groups, suggesting that different islet yields are not due to their differences as energy sources. Compared with UW solution, M-Kyoto solution significantly inhibited trypsin activity in the digestion step; moreover, M-Kyoto solution inhibited collagenase digestion less than UW solution. In conclusion, the advantages of M-Kyoto solution are trypsin inhibition and less collagenase inhibition. Based on these data, we now use M-Kyoto solution for clinical islet transplantation from nonheart-beating donor pancreata.

Adenosine↗
PubMed2005

Hippocalcin-deficient mice display a defect in cAMP response element-binding protein activation associated with impaired spatial and associative memory.

Hippocalcin is a member of the neuronal calcium sensor (NCS) protein family that is highly expressed in hippocampal pyramidal cells and moderately expressed in the neurons of cerebral cortex, cerebellum and striatum. Here we examined the physiological roles of hippocalcin using targeted gene disruption. Hippocalcin-deficient (-/-) mice displayed no obvious structural abnormalities in the brain including hippocampal formation at the light microscopic level. Deletion of hippocalcin did not result in up-regulation of the hippocalcin-related proteins; neural visinin-like Ca(2+)-binding proteins (NVP) 1, 2, and 3. The synaptic excitability of hippocampal CA1 neurons appeared to be normal, as estimated by the shape of field excitatory postsynaptic potentials elicited by single- and paired-pulse stimuli, and by tetanic stimulation. However, N-methyl-d-aspartate stimulation- and depolarization-induced phosphorylation of cAMP-response element-binding protein (CREB) was significantly attenuated in -/- hippocampal neurons, suggesting an impairment in an activity-dependent gene expression cascade. In the Morris water maze test, the performance of -/- mice was comparable to that of wild-type littermates except in the probe test, where -/- mice crossed the previous location of the platform significantly less often than +/+ mice. Hippocalcin-deficient mice were also impaired on a discrimination learning task in which they needed to respond to a lamp illuminated on the left or right side to obtain food reinforcement. No abnormalities were observed in motor activity, anxiety behavior, or fear learning. These results suggest that hippocalcin plays a crucial role in the Ca(2+)-signaling pathway that underlies long-lasting neural plasticity and that leads to spatial and associative memory.

Animals↗
PubMed2005

Analysis of large-scale nonhuman primate islet isolations.

AIMS: It is important to have clinically relevant large animal models, especially nonhuman primates, to improve the efficacy of islet isolation and transplantation prior to clinical trials. The aim of this study was to improve the efficacy of islet isolation by analyzing large-scale nonhuman primate islet isolations. METHODS: Sixty-one islet isolations were evaluated using nonhuman primates. An automated isolation method was scaled down for islet isolation. Islet yields of prepurification, postpurification, and postculture, purity of islets, viability of islets, and functionality with glucose stimulation test were assessed. Initially, we analyzed relationships between endpoints then analyzed additional factors for successful islet isolation. Those factors included donor characteristics, the two-layer method (TLM) of pancreas preservation, trypsin inhibition during digestion, and digestion and collection time. RESULTS: Prepurification islet yields were strongly correlated with postpurification yields and postculture yields. It weakly but significantly correlated with purity, viability, and functionality. The average prepurification yield was 16,267 IE/g with each case divided into either above-average (high-yield group) or below-average groups (low-yield group). In 8 cases, TLM and trypsin inhibition were used and all cases belonged to the high-yield group. There were no significant differences between high- and low-yield groups in terms of donor age, body weight, pancreas weight, and cold ischemic time. The high-yield group had significantly longer digestion times and shorter collection times. CONCLUSIONS: TLM, trypsin inhibition, complete digestion, and quick collections were key for successful islet isolation. Analysis of nonhuman primate islet isolation techniques provided useful information, which should help to improve clinical islet transplantation.

Animals↗
PubMed2005

Insulin independence of unstable diabetic patient after single living donor islet transplantation.

BACKGROUND: Current success in islet transplantation will lead to a donor shortage. Living donor islet transplantation could be an alternative approach to expand the potential donor pool. In this study we describe the first successful living donor islet transplantation for unstable diabetes, performed at Kyoto University Hospital on January 19, 2005. METHODS: The donor was a healthy 56-year-old woman and mother of the recipient. The recipient was a 27-year-old woman with insulin-dependent diabetes since the age of 15 years. She experienced frequent hypoglycemic unawareness episodes. Her blood glucose concentration was difficult to control and C-peptide level was negative after glucagon stimulation. She needed an average 28 of units of insulin per day. The donor underwent a distal pancreatectomy and islets were isolated from the resected pancreas graft. The total islet yield was 408,114 islet equivalents and isolated islets were immediately transplanted into the recipient's liver. RESULTS: After transplant, the blood glucose level of the recipient was tightly controlled without hypoglycemic episodes. She was discharged on day 37 with a normal oral glucose tolerance test (OGTT). The recipient remained insulin-independent for >3 months, since day 22 posttransplant. The donor's postoperative clinical course was uneventful. She was discharged on postoperative day 18 and returned to her job within 1 month. CONCLUSIONS: We report the first successful living donor islet transplantation for the treatment of unstable diabetes. We believe that living donor islet transplantation may become an option in the treatment of insulin-dependent diabetes.

Adult↗
PubMed2005

Simple evaluation of engraftment by secretory unit of islet transplant objects for living donor and cadaveric donor fresh or cultured islet transplantation.

BACKGROUND: Evaluation of engraftment is important to assess the success of islet transplantation. Recently we developed secretory unit of islet transplant objects (SUITO) index for simple evaluation of engraftment. Assuming that normal subjects aged <40 years have 100% pancreatic beta-cell function, SUITO index was calculated by the formula: 1500 x fasting C-peptide immunoreactivity [ng/dL]/(fasting blood glucose [mg/dL] - 63). In this study, we compared the efficacy of islet transplantation from cadaveric and living donors using the SUITO index. METHODS: We performed eight islet transplantations with non-heart-beating donors (NHBDs) into five patients. Two patients received fresh islets once, one patient received fresh islets twice, one patient received cultured islets once, and one patient received cultured islets twice plus fresh islets once. In addition, one patient received fresh islets from a living donor. We calculated the SUITO index from postoperative days 3 to 30 for each case. RESULTS: Mean SUITO index after one fresh islet transplant was 11.7 +/- 1.0, after two fresh islet transplants was 28.5 +/- 3.4, after one cultured islet transplant was 2.1 +/- 0.4, after two cultured islet transplant was 12.1 +/- 1.9, and after two cultured islet transplant plus one fresh islet transplant was 26.7 +/- 1.7. The mean SUITO index after single living donor islet transplant was 40.7 +/- 2.6, which was significantly higher compared with all other groups. Insulin independence was obtained when the SUITO index was >26, which might reflect that 26% beta-cell mass was required for insulin independence. CONCLUSION: SUITO index is useful to evaluate islet engraftment and to predict the possibility of insulin independence.

Blood Glucose↗
PubMed2005

In situ cooling of pancreata from non-heart-beating donors prior to procurement for islet transplantation.

BACKGROUND: The specific aim of this study was to develop an effective technique for pancreas procurement for islet transplantation from a non-heart-beating donor (NHBD). METHODS: Between January 2004 and November 2004, 11 human pancreata were procured and processed for islet isolation at a cell processing center. After confirmation of brain-death status, a double-balloon catheter was inserted to prevent warm ischemic damage to the donor pancreas by using an in situ regional organ cooling system that was originally developed for kidney procurement. RESULTS: Warm ischemic time was controlled with the modified in situ regional cooling system at 6.0 +/- 0.9 minutes (mean +/- SE). The operations for procurement of the kidneys and pancreata lasted 48.1 +/- 3.6 minutes and 9.9 +/- 4.8 minutes, respectively. The islet yield per isolation was 396,767 +/- 142,842 IE (islet equivalents). Ten of the 11 cases met the criteria for pancreatic islet transplantation based on the Edmonton protocol. CONCLUSIONS: We developed a novel procurement technique in cooperation with our kidney procurement team. This protocol for the procurement of pancreas and kidney from an NHBD enabled us to transplant islets into a type 1 diabetic patient and kidney into a renal failure patient.

Brain Death↗
PubMed2005

Kyoto islet isolation method: the optimized one for non-heart-beating donors with highly efficient islet retrieval.

The availability of pancreata for clinical cadaveric islet transplantation is restricted to non-heart-beating donors (NHBDs) in Japan. This forced us to modify the current standard islet isolation protocol that was made up for brain-dead donors and make it suitable for NHBDs. The Kyoto islet isolation method is the one with induction of several steps based on the ideas both already reported literally and invented originally by ourselves. Using this islet isolation method, we isolated islets from 13 human pancreata of NHBDs and transplanted 11 preparations to six type-1 diabetic patients. The rate to meet release criteria of Edmonton protocol was 84.6%. Establishment of this method allowed us to begin a clinical islet transplantation program in Japan and to continue to perform the preparation of islets from NHBDs with high rate to meet the release criteria of the Edmonton protocol.

Brain Death↗
PubMed2005

Varus-valgus balance and range of movement after total knee arthroplasty.

We performed a randomised, prospective study of 80 mobile-bearing total knee arthroplasties (80 knees) in order to measure the effects of varus-valgus laxity and balance on the range of movement (ROM) one year after operation. Forty knees had a posterior-cruciate-ligament (PCL)-retaining prosthesis and the other 40 a PCL-sacrificing prosthesis. In the balanced group (69 knees) in which the difference between varus and valgus was less than 2 degrees, the mean ROM improved significantly from 107.6 degrees to 117.7 degrees (p < 0.0001). By contrast, in the 11 knees which were unbalanced and in which the difference between varus and valgus laxity exceeded 2 degrees, the ROM decreased from a mean of 121.0 degrees to 112.7 degrees (p = 0.0061). We conclude that coronal laxity, especially balanced laxity, is important for achieving an improved ROM in mobile-bearing total knee arthroplasty.

Aged↗
PubMed2004

DNA sequence and comparative analysis of chimpanzee chromosome 22.

Human-chimpanzee comparative genome research is essential for narrowing down genetic changes involved in the acquisition of unique human features, such as highly developed cognitive functions, bipedalism or the use of complex language. Here, we report the high-quality DNA sequence of 33.3 megabases of chimpanzee chromosome 22. By comparing the whole sequence with the human counterpart, chromosome 21, we found that 1.44% of the chromosome consists of single-base substitutions in addition to nearly 68,000 insertions or deletions. These differences are sufficient to generate changes in most of the proteins. Indeed, 83% of the 231 coding sequences, including functionally important genes, show differences at the amino acid sequence level. Furthermore, we demonstrate different expansion of particular subfamilies of retrotransposons between the lineages, suggesting different impacts of retrotranspositions on human and chimpanzee evolution. The genomic changes after speciation and their biological consequences seem more complex than originally hypothesized.

Animals↗
PubMed2004

Re-emission of heavy water vapour from soil to the atmosphere.

The re-emission process of tritiated water (HTO) deposited on a soil surface is an important process to assess tritium doses to the general public around nuclear fusion facilities in future. A field experiment using heavy water (HDO) as a substitute for HTO was carried out in the summertime to investigate the re-emission process of HTO from soil to the atmosphere. In the experiment, the time variations of depth profiles of HDO concentrations in soil exposed to HDO vapour and soil mixed with HDO were measured during the re-emission process on the field. The HDO concentrations in soil water in top soil layers of both the exposed and mixed soil rapidly decreased with time during the re-emission. However, the decrease of exposed soil was much greater than that of mixed soil. The re-emission process was analysed using a model including the evaporation of HDO from soil, the exchange between soil HDO and air H2O, and the diffusion of HDO in soil. It was found that the model is applicable to calculating the time variations of detailed depth profiles of HDO concentration in soil water in surface soil layers, using an estimated exchange velocity.

Deuterium Oxide↗
PubMed2003

Isolation and characterization of a dopa decarboxylase cDNA and the induction of its expression by an insect cytokine, growth-blocking peptide in Pseudaletia separata.

Parasitization by the wasp, Cotesia kariyai, elevates the concentration of an insect cytokine, growth-blocking peptide (GBP), in hemolymph of last instar Pseudaletis separata larvae. The increase of epidermal and hemolymph dopamine level is associated with the GBP increase. Both GBP and dopamine disturb host development and metamorphosis (Hayakawa, 1995). Dopa decarboxylase (DDC) converts Dopa to dopamine, and its cDNA was isolated from P. separata, and the deduced amino acid sequence showed that it was highly homologous to other lepidopteran DDCs, showing 96, 90 and 86% identity with those of Mamestra brassicae, Bombyx mori, and Manduca sexta, respectively. A 3.2 kb DDC mRNA transcript was constitutively expressed at low levels in the epidermis, brain-nerve cord and hemocytes, and the expression was enhanced by injection of GBP in these tissues. Detailed characterization of the DDC mRNA expression in the epidermis showed that its expression reached a plateau 3 hr after the injection. DDC activity and DDC protein (55 kDa) level mirrored the mRNA expression. Immunocytochemistry with anti-DDC antibody confirmed that the enhanced DDC expression was localized in the epidermal cells. Dopamine concentration in the epidermis gradually increased and reached maximum 6 hr after the injection. When the epidermis of Day 1 last instar larvae was cultured in vitro in the presence of GBP, DDC mRNA increased, indicating that GBP acted on the epidermal cells directly to induce expression of the DDC gene.

Amino Acid Sequence↗