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Biomedical subjects

Hiroshi Nakano

Publications and source records attributed to Hiroshi Nakano.

At least 19 recordsLinked to original sources
PubMed2007

The relationship between Helicobacter pylori infection and promoter polymorphism of the Nrf2 gene in chronic gastritis.

The transcription factor Nrf2 regulates the expression of detoxifying and antioxidant genes. Three polymorphisms of the Nrf2 gene have been reported. We attempted to clarify the relationship between Nrf2 gene polymorphism and chronic gastritis in a Japanese population. The study was performed in 159 patients with no evidence of gastric malignancy on upper gastrointestinal endoscopy (mean age, 62.03 years; male:female ratio, 102:57; peptic ulcer diseases in 69 patients, and Helicobacter pylori (H. pylori) positivity in 73.0%). We employed the PCR-SSCP method to detect gene polymorphisms using DNA extracted from peripheral blood cells or from antral biopsy specimens obtained by endoscopy. The severity of the histological chronic gastritis in antral biopsy specimens was classified according to the updated Sydney system. Although the frequencies of the SNP(-686) and SNP(-650) A alleles were decreased in subjects with peptic ulcers or severe mucosal atrophy, no significant differences were seen. However, the number of -686 G alleles was correlated with both neutrophil activity and mononuclear cell infiltration (p=0.036 and p=0.010, respectively), while the -650 C/C genotype was an independent risk factor for mononuclear cell infiltration (p=0.021 by ANOVA). In addition, both the number of -686 G alleles and the -650 C/C genotype showed an interaction with H. pylori infection to promote the infiltration of mononuclear cells (p=0.037 by ANCOVA and p=0.041 by ANOVA, respectively). Nrf2 promoter polymorphisms are significantly associated with the development of gastric mucosal inflammation, either independently or by interacting with H. pylori infection.

Chronic Disease↗
PubMed2006

Protein pattern difference in the colon cancer cell lines examined by two-dimensional differential in-gel electrophoresis and mass spectrometry.

PURPOSE: The pivotal metastatic processes of colorectal cancer (CRC) have yet to be fully investigated by a comprehensive all-inclusive protein analysis. We used two-dimensional differential in-gel electrophoresis (2D-DIGE) and liquid chromatography-tandem mass spectrometry (LC/MS/MS) to investigate the protein pattern changes during the metastasis of CRC. Two CRC cell lines were investigated: SW480 derived from the primary lesion and SW620 derived from lymph node metastasis in the same patient. METHODS: The two cell lines were compared using 2D-DIGE with a maleimide CyDye fluorescent protein labeling technique, which has an enhanced sensitivity for many proteins at a low concentration. A comprehensive proteomics analysis was performed by the dual-labeling method using Cy3 and Cy5 and by LC/MS/MS. In addition, an in vivo experiment of metastasis using nude mice was performed by the injection of the two cell lines into the spleen. RESULTS: Among approximately 1,500 proteins, we detected 9 protein spots with definitively significant changes between the two cell lines. Three out of the nine proteins were validated by a Western blot analysis. Alpha-enolase and triosephosphate isomerase were significantly upregulated in SW620 in comparison to SW480. Annexin A2 (annexin II) was significantly downregulated in SW620 compared to SW480. Neither liver metastasis nor peritoneal dissemination was established in the metastatic experiment using SW480 but some liver and peritoneal metastases occurred in the experiment using SW620. An in vivo metastatic experiment using SW620 showed the expressions of alpha-enolase and triosephosphate isomerase to increase in the liver metastases in comparison to those in the splenic implanted lesion. The expressions of triosephosphate isomerase increased in the peritoneal lesions in comparison to those in the splenic implanted lesion. CONCLUSIONS: 2D-DIGE and LC/MS/MS techniques identified nine proteins that increased significantly more in SW620 than in SW480. The finding of our in vivo metastatic experiment suggests that alpha-enolase and triosephosphate isomerase, at least in part, may be associated with the metastatic process of these two cell lines.

Animals↗
PubMed2006

Multiple myeloma involving the thyroid cartilage.

Multiple myeloma, solitary plasmacytoma, and extramedullary plasmacytoma constitute a continuous disease spectrum of plasma cell neoplasms. In the larynx, although extramedullary plasmacytoma in the supraglottic region has been sometimes reported, plasma cell neoplasm with involvement of the thyroid cartilage is extremely rare. We report a case of multiple myeloma involving the thyroid cartilage. A 72-year-old male patient presented with a pathological fracture of the cervical vertebrae. CT scan revealed low-density areas within the thyroid cartilage, but the laryngeal mucosa and submucosal soft tissue were intact. Multiple myeloma was diagnosed, since the tumors in the thyroid cartilage and cervical vertebrae revealed plasmacytoma. Because no other lesion was found, irradiation of the larynx and cervical vertebrae was performed. Neither aggressive change of these lesions nor new lesions have been found over 3-year follow-up following the initial treatment without adjuvant therapy.

Aged↗
PubMed2006

Metformin increases the PGC-1alpha protein and oxidative enzyme activities possibly via AMPK phosphorylation in skeletal muscle in vivo.

AMP-activated protein kinase (AMPK), which was activated by an antihyperglycemic drug metformin, has been hypothesized to mediate metabolic adaptations. The purposes of the present study were 1) to confirm whether acute metformin administration induced AMPK phosphorylation and 2) to determine whether chronic metformin treatment increased the peroxisome proliferator-activated receptor-gamma coactivator-1alpha (PGC-1alpha) protein expression, glycolytic and oxidative enzyme activities, and cytochrome c and glucose transporter-4 (GLUT4) protein expressions in the rat soleus and red and white gastrocnemius muscles. The single oral administration of metformin (300 mg/kg body wt) enhanced the AMPK phosphorylation at 5 and/or 6 h after treatment. In the chronic study, rats were fed either normal chow or chow containing 1% metformin for 14 days. Metformin treatment resulted in a mean daily metformin intake of 631 mg.kg body wt(-1).day(-1). Metformin increased the PGC-1alpha content in all three muscles. Metformin increased the hexokinase activity in the white gastrocnemius, the citrate synthase activity in all three muscles, and the beta-hydroxyacyl-CoA dehydrogenase activity in the soleus. The cytochrome c protein content in the soleus muscle also increased. The GLUT4 content was unchanged by metformin. These results suggest that metformin enhances the PGC-1alpha expression and mitochondrial biogenesis possibly at least in part via AMPK phosphorylation in the skeletal muscle. Metformin has thus been proposed to possibly ameliorate insulin resistance, at least partially, by means of such metabolic effects.

AMP-Activated Protein Kinases↗
PubMed2006

Is omeprazole or misoprostol superior for improving indomethacin-induced delayed maturation of granulation tissue in rat gastric ulcers?

BACKGROUND AND AIMS: Proton pump inhibitors (PPI) and prostaglandin (PG) preparations are believed to both prevent NSAID-induced gastric ulcers and promote the delayed healing of gastric ulcers by NSAIDs, but it remains unclear which of these drugs is superior. The aim of this study was to clarify which achieved better healing of NSAID-induced gastric ulcers, not only with respect to epithelialization but also repair of the submucosal tissues. METHODS: We used acetic acid to induce gastric ulcers in rats, and compared the changes between a control group, NSAID group, NSAID + PPI group and NSAID + PG group. After removing the stomach of each animal, an ulcer index was calculated and the collagen content and type III collagen content of granulation tissue were measured. We also studied fibroblast dynamics, including proliferation, collagen synthesis, differentiation into myofibroblasts, and apoptosis. RESULTS: Indomethacin prevented re-epithelialization of the ulcers, interfered with fibroblast function, and also delayed the replacement of type III collagen. Omeprazole promoted epithelialization, but could not fully reverse the influence of indomethacin on granulation tissue maturation. A concomitant dose with misoprostolreversed it completely. CONCLUSIONS: From our point of view in this study in the use of experimental ulcers, it was thought that compensation of PG should have priority to gastric acid inhibition in terms of healing of NSAID-induced gastric ulcer.

Analysis of Variance↗
PubMed2006

Interleukin-21 triggers both cellular and humoral immune responses leading to therapeutic antitumor effects against head and neck squamous cell carcinoma.

BACKGROUND: Interleukin-21 (IL-21) plays important roles in the regulation of T, B, and natural killer (NK) cells. We hypothesized that the cytokine may provide a novel immunotherapy strategy for cancer by stimulating both Th1 and Th2 immune responses. In this context, antitumor immunity induced by IL-21 was examined in mice bearing subcutaneous head and neck squamous cell carcinomas (HNSCC). METHODS: A plasmid vector encoding murine IL-21 was injected intravenously into mice with pre-established HNSCC tumors, either alone or in combination with a vector construct expressing IL-15. Cytotoxic T lymphocyte (CTL) and NK killing activities were evaluated by chrome release assays, while HNSCC-specific antibody was examined by flow cytometry and ELISA. RESULTS: Significant antitumor effects were obtained by repeated transfection with either the IL-21 or the IL-15 gene. Co-administration of both cytokine genes resulted in increased suppression of tumor growth, significantly prolonging the survival periods of the animals. Thirty percent of the tumor-bearing mice that received the combination therapy survived for more than 300 days, completely rejecting rechallenge with the tumor at a distant site. IL-21 induced significant elevation of HNSCC-specific CTL activity, while IL-21 and IL-15 augmented NK activity in an additive manner. IL-21 gene transfer also promoted the production of tumor-specific IgG. CONCLUSIONS: In vivo transduction of the IL-21 gene elicits powerful antitumor immunity, including both humoral and cellular arms of the immune response, and results in significant suppression of pre-established HNSCC. Co-transfer of the IL-15 gene further improved the therapeutic outcome, mainly by augmenting NK tumoricidal activity. The biological effects of IL-21 may be in sharp contrast to those of conventional Th1 and Th2 cytokines, suggesting intriguing implications of this cytokine for the classical concept of Th1 vs. Th2 paradigm.

Animals↗
PubMed2006

Flexible, tapered-tip tube facilitates conventional orotracheal intubation by novice intubators.

Orotracheal intubation is the standard technique for airway management, but several untoward airway complications are possible with this method. To avoid airway trauma caused by the tube tip during intubation, the Parker Flex-Tip tube (PFT), which has a flexible, tapered tip, was developed. It has been reported that the PFT facilitates fiberoptic orotracheal intubation and introducer-guided tracheal intubation. In this study, we compared the PFT to a standard endotracheal tube (SET), regarding the time of intubation during conventional orotracheal intubation and the incidence of postoperative sore throat and hoarseness. One hundred and thirty-four patients scheduled for elective anesthesia using orotracheal intubation were randomized to either the PFT or SET and 132 completed the study. The intubators were classified into three groups: staff anesthesiologists, inexperienced anesthesiologists, and anesthesia trainees. The tube was selected by another anesthesiologist and the time required for intubation was measured. PFT did not shorten the time required for intubation and did not reduce the incidence of sore throat and hoarseness. However, a detailed analysis revealed that the PFT decreased the time required for intubation in the anesthesia trainee group. The PFT may help novice intubators to conduct a smooth intubation.

Adult↗
PubMed2006

Toward zero pancreatic fistula after pancreaticoduodenectomy with pancreaticogastrostomy.

BACKGROUND: Postoperative morbidity after pancreaticoduodenectomy has been associated mainly with the development of pancreatic fistula. However, postoperative complications unrelated to pancreatic fistula cannot be disregarded after pancreaticoduodenectomy. The aim of the present study was to investigate the postoperative morbidity in a large series of pancreaticoduodenectomies with pancreaticogastrostomies without pancreatic fistula. METHODS: The present study analyzed the data from 194 consecutive patients undergoing a pancreaticoduodenectomy with a pancreaticogastrostomy between July 1997 and June 2003 in whom no postoperative pancreatic fistula occurred. RESULTS: The overall rate of postoperative morbidity was 33.5%. Specific and general complications occurred in 16% and 17.5% of the patients, respectively. An American Society of Anesthesiologists (ASA) score of 3 and blood transfusion were the only independent factors associated with postoperative morbidity. CONCLUSIONS: Our study found that the overall morbidity after a pancreaticoduodenectomy with a pancreaticogastrostomy still remains high even in the absence of pancreatic fistula and is associated with the preoperative medical condition (ASA score) of the patients and with blood transfusion.

Anastomosis, Surgical↗
PubMed2006

Serum brain-derived neurotrophic factor level is increased and associated with obesity in newly diagnosed female patients with type 2 diabetes mellitus.

Previous studies have demonstrated that brain-derived neurotrophic factor (BDNF) played a role in the eating behavior and glucose and lipid metabolism. In this study we measured the serum BDNF levels in newly diagnosed female patients with type 2 diabetes mellitus (n = 24, aged 34-59 years) and female subjects with normal glucose tolerance (n = 7, aged 34-56 years). The serum BDNF level was found to significantly increase in diabetic patients in comparison to that in healthy subjects (P < .05). In these patients, the serum BDNF level showed positive correlation with the body mass index (r = 0.535, P < .01), the percentage of body fat (r = 0.552, P < .01), the subcutaneous fat area based on computed tomography scan (r = 0.480, P < .05), the triglyceride level (r = 0.470, P < .05), the fasting blood glucose level (r = 0.437, P < .05), and the homeostasis model assessment of insulin resistance score (r = 0.506, P < .05), whereas it showed a negative correlation with age (r = -0.486, P < .05). The partial correlation coefficients adjusted by age showed significant differences regarding the body mass index (r = 0.423, P < .05), percentage of body fat (r = 0.504, P < .05), and triglyceride level (r = 0.426, P < .05). These results provide the first evidence that an increased BDNF is associated with a prevalence of type 2 diabetes mellitus. In addition, the BDNF is related to the total and abdominal subcutaneous fat mass and energy metabolism in the newly diagnosed female patients with type 2 diabetes mellitus.

Adult↗
PubMed2006

Effects of sucralfate, cimetidine and rabeprazole on mucosal hydroxyproline content in healing of ethanol-hcl-induced gastric lesions.

1. No general consensus has been reached on the treatment of acute gastric lesions. The aims of the present study were to clarify the effects of sucralfate, cimetidine and rabeprazole monotherapies and combination therapies on acute gastric lesions from the viewpoint of connective tissue regeneration. 2. Gastric lesions were experimentally created by the oral administration of 50% ethanol-0.15 mol/L HCl to rats. After 30 min, the anti-ulcer agents sucralfate (100 mg/kg), cimetidine (20 mg/kg) and rabeprazole (2 mg/kg) were administered separately or in combination and the stomach was excised at different times to measure the level of hydroxyproline in the gastric mucosa and determine lesion index. Immunostaining against prolylhydroxylase was performed on some specimens. 3. In the control group, lesion index decreased linearly from 30 min after ethanol-HCl administration and the level of mucosal hydroxyproline peaked between 2 and 4 h later. Although sucralfate significantly promoted lesion healing, it had no effect on mucosal hydroxyproline level. Cimetidine suppressed increases in mucosal hydroxyproline and prolonged lesion healing, but these findings were reversed by combining cimetidine and sucralfate. Rabeprazole had no significant effect on lesion healing, but promoted lesion healing in combination with sucralfate. Immunohistochemical analysis showed that prolylhydroxylase was expressed in spindle cells that lined the glandular cells in a boundary area between normal and injured tissues. 4. Under conditions in which the effects of intragastric pH are minimal, sucralfate is superior to antisecretory agents in promoting the healing of acute gastric lesions.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed2006

Effect of concurrent elemental diet on infliximab treatment for Crohn's disease.

BACKGROUND: Infliximab and elemental diet (ED) have been shown to be effective in the management of Crohn's disease. However, few experiences have been reported regarding their combination therapy. The aim of the present study was to investigate the efficacy and safety of infliximab in Japanese patients, the first such study in Asia, as well as the effect of concomitant ED. METHODS: One hundred and ten consecutive patients receiving infliximab were followed up to week 16 after the last infusion, and clinical response and primary outcome were collected. A response was defined as a reduction in Harvey-Bradshaw Index for inflammatory disease and closure of fistula in fistulizing disease. RESULTS: Out of 75 inflammatory and 35 fistulizing disease patients, 68 (90.7%) and 25 (71.4%) responded at week 4, and 38 (50.7%) and 14 (40.0%) continued to respond until week 16, respectively. Interestingly, inflammatory disease patients with concurrent ED had a significantly higher response rate at week 16 (68.4%) than those without ED (32.4%, P = 0.0026). The effects of ED were independent of the usage of azathioprine and smoking habit. CONCLUSIONS: Infliximab was clinically useful in the treatment of Crohn's disease in Japanese patients as well as in those in Western countries. The efficacy of concurrent ED was suggestive and should be confirmed in a randomized controlled study.

Adult↗
PubMed2006

Blood glucose-lowering activity of colestimide in patients with type 2 diabetes and hypercholesterolemia: a case-control study comparing colestimide with acarbose.

BACKGROUND: An anion exchange resin has been reported to lower blood glucose levels in patients with type 2 diabetes. AIM: To examine, in comparison with an alpha-glucosidase inhibitor, the usefulness of colestimide in lowering blood glucose levels in patients with type 2 diabetes and hypercholesterolemia. METHODS: Thirty-three patients with type 2 diabetes and hypercholesterolemia were more or less randomly assigned to receive either colestimide (17 patients) or acarbose (16 patients). At 10 time points before and after administration, plasma glucose levels and serum lipid concentrations were measured in all subjects, and the J-index and M-value were calculated. RESULTS: Patients receiving colestimide showed significant decreases in glucose levels 2 hours after breakfast (from 216.9 +/- 37.2 mg/dl before treatment to 191.1 +/- 40.9 mg/dl after treatment; p=0.008), in the J-index (from 42.6 +/- 14.5 to 32.6 +/- 9.8; p<0.001), and in the M-value (from 23.1 +/- 12.1 to 14.6 +/- 7.1; p<0.001). CONCLUSION: In patients with type 2 diabetes and hyperlipidemia, colestimide was suggested to have blood glucose-lowering activity as does acarbose.

Acarbose↗
PubMed2006

[Epidemiology of elderly diabetes mellitus in Japan].

Glucose tolerance progressively declines with age, and there is a high prevalence of type 2 diabetes and post challenge hyperglycemia in the older population. Diabetes in the elderly is not a single entity, but a heterogeneous group of conditions. A further 9% may have undetected/asymptomatic hyperglycemia. Several studies have also shown that fasting blood glucose rises with age (about 1-2 mg/dl/decade) and postprandial glucose by about 15 mg/dl/decade, leading to a mild glucose intolerance. Age-related glucose intolerance in humans is often accompanied by insulin resistance. The relative contribution of decreased insulin secretion vs. increased insulin resistance to the pathogenesis of type 2 diabetes mellitus has been the subject of long-standing controversy.

Aged↗
PubMed2006

[Clinical pathophysiology of the elderly onset diabetes mellitus].

Several studies have shown that fasting blood glucose rises about 1-2 mg/dl/decade and post-prandial glucose by about 15 mg/dl/decade, leading to mild glucose intolerance with insulin resistance associated with aging. There appears to be a distinct group of individuals on an accelerated trajectory to clinically impaired glucose intolerance or frank type 2 diabetes mellitus. There are several characteristics of elderly onset type 2 diabetes as describe below. The incidence and progression of retinopathy were suggested to be rare. Several studies of the association between body mass index and cardiovascular mortality suggested the increased mortality associated with weight loss and underweight. Hypoglycemia is an underappreciated and potentially fatal complication of insulin and sulfonylurea treatment.

Age of Onset↗
PubMed2006

[Clinical review on patients who developed seizures during theophylline administration: relationships with seizure-predisposing factors].

OBJECTIVE: In recent years, attempts have been made to broadly deem seizures developing during theophylline administration as theophylline-related seizures. Consequently, a tendency to consider all the seizures attributable to theophylline has occurred. We investigated background factors in pediatric patients with seizures to examine the involvement of theophylline in the event. METHODS: Of adverse events developing during theophylline administration which were reported by two theophylline preparation manufacturers between October 1987 and April 2004, we investigated underlying disease, regimen, outcome, and other items in 255 patients with seizures provoked by oral preparations and in 79 patients with seizures provoked by intravenous preparations. RESULTS: The most predominant factors were represented by neurological predispositions, e.g., epilepsy, and by a history of fits prior to the onset of seizures in not less than two-thirds of pediatric patients with seizures who were receiving theophylline. Furthermore, not less than 90% of pediatric patients who remained with sequelae and who died had the factors. Our investigation revealed that the factors developed predominantly when the relevant patients presented fever, aged under 3 years and had history of seizures. CONCLUSIONS: Therefore, we consider that advertence to this point is most important in administering theophylline safely.

Administration, Oral↗
PubMed2005

Plaunotol prevents the progression of acute gastric mucosal lesions induced by compound 48/80, a mast cell degranulator, in rats.

We examined the preventive effect of plaunotol, an antiulcer drug, on acute gastric mucosal lesion progression in rats treated once with compound 48/80 (C48/80). Rats treated with C48/80 (0.75 mg/kg BW, i.p.) received plaunotol (10, 25 or 50 mg/kg BW, p.o.) 0.5 h after the treatment at which time gastric mucosal lesions appeared. The gastric mucosa of C48/80-treated rats showed progressed lesions and had increased myeloperoxidase (an index of neutrophil infiltration) activity and thiobarbituric acid reactive substances (an index of lipid peroxidation) content and decreased ascorbic acid and adherent mucus contents and Se-glutathione peroxidase activity at 3 h after C48/80 treatment. Postadministered plaunotol attenuated all these changes dose-dependently. These attenuating effects of plaunotol were not counteracted by pretreatment with indomethacin (5 mg/kg BW, i.p.), a prostaglandin synthesis inhibitor. These results indicate that plaunotol prevents the progression of C48/80-induced acute gastric mucosal lesions in rats possibly by its anti-inflammatory and antioxidant actions, but not by affecting gastric mucosal prostaglandin levels.

Animals↗
PubMed2005

A critical role of gastric mucosal ascorbic acid in the progression of acute gastric mucosal lesions induced by compound 48/80 in rats.

AIM: To study the role of gastric mucosal ascorbic acid (AA) in the progression of acute gastric mucosal lesions induced by compound 48/80 (C48/80), a mast cell degranulator, in rats. METHODS: C48/80 (0.75 mg/kg) was intraperitoneally injected to fasted Wistar rats. Oral administration of AA (10, 50 or 100 mg/kg) was performed 0.5 h after C48/80 treatment. Determinations for gastric mucosal lesion severity and blood flow, and assays for gastric mucosal total AA, reduced AA, oxidized AA, vitamin E, thiobarbituric acid reactive substances (TBARS), adherent mucus, nitrite/nitrate (NOx), non-protein SH (NPSH), and myeloperoxidase (MPO), and serum total AA, reduced AA, oxidized AA, and NOx were conducted 0.5 and 3 h after C48/80 treatment. RESULTS: Gastric mucosal lesions occurred 0.5 h after C48/80 treatment and progressed at 3 h. Gastric mucosal blood flow decreased 0.5 h after C48/80 treatment but the decrease was recovered at 3 h. Gastric mucosal total AA, reduced AA, vitamin E, and adherent mucus concentrations decreased 3 h after C48/80 treatment. Gastric mucosal oxidized AA concentration remained unchanged after C48/80 treatment. Gastric mucosal NPSH concentration decreased 0.5 h after C48/80 treatment, but the decrease was recovered at 3 h. Gastric mucosal TBARS concentration and MPO activity increased 0.5 h after C48/80 treatment and further increased at 3 h. Serum total AA and reduced AA concentrations increased 0.5 h after C48/80 treatment and further increased at 3 h, while serum oxidized AA concentration increased at 0.5 h. Serum and gastric mucosal NOx concentrations increased 3 h after C48/80 treatment. AA administration to C48/80-treated rats at 0.5 h after the treatment prevented the gastric mucosal lesion progression and the changes in gastric mucosal total AA, reduced AA, vitamin E, adherent mucus, NOx, and TBARS concentrations and MPO activity and serum NOx concentration found at 3 h after the treatment dose-dependently. The AA administration to C48/80-treated rats caused further increases in serum total AA and reduced AA concentrations at 3 h after the treatment dose-dependently. CONCLUSION: Gastric mucosal AA plays a critical role in the progression of C48/80-induced acute gastric mucosal lesions in rats.

Animals↗