Biomedical subjects

N Hayakawa

Publications and source records attributed to N Hayakawa.

At least 19 recordsLinked to original sources

PubMed2006

Time dependent alterations of co-localization of S100beta and GFAP in the MPTP-treated mice.

S100beta is a calcium-binding peptide produced by astrocytes. This protein is expressed at high levels in brain and is known as a marker of brain damage. However, little is known about the role of S100beta protein during neuronal damage caused by MPTP. To determine exactly changes of expression of S100beta protein in relation to changes of glial cells, we investigated immunohistochemically the expression of S100beta protein using MPTP-treated mice. The present study showed that tyrosine hydroxylase (TH) immunoreactivity was decreased in the striatum and substantia nigra from 5 h and 1 day after MPTP treatment, respectively. Thereafter, a severe reduction in TH immunoreactivity was observed in the striatum and substantia nigra 1, 3 and 7 days after MPTP treatment. In our double-labeled immunostaining, the number of S100-positive/GFAP-negative cells decreased from 1 day up to 7 days after MPTP treatment. In contrast, the number of double-labeled S100/GFAP-immnoreactive cells increased from 1 day up to 7 days after MPTP treatment. The number of S100beta-positive/GFAP-negative cells also decreased 3 and 7 days after MPTP treatment. In contrast, the number of double-labeled S100beta/GFAP-immunoreactive cells increased from 1 day up to 7 days after MPTP treatment. The present study demonstrates that S100beta/GFAP-positive cells may play some role in the pathogenesis of MPTP-induced dopaminergic neurodegeneration in the striatum. The present results also suggest the presence of the S100beta protein in a subpopulation of GFAP-negative astrocytes in the striatum after MPTP treatment. These results suggest that the modulation of astrocytic activation may offer a novel therapeutic strategy of Parkinson's disease.

Animals↗

PubMed2006

Calcium supplementation does not reproduce the pharmacological efficacy of alfacalcidol for the treatment of osteoporosis in rats.

The purpose of this study was to assess whether a nutritional supply of calcium (Ca) could be substituted for alfacalcidol (ALF) administration in preventing bone loss due to estrogen deficiency. Female Wistar-Imamichi rats (8 months old) were ovariectomized (OVX) or sham-operated. OVX rats received ALF administration (0.025, 0.5, or 0.1 microg/kg, p.o., 5 times a week) with standard rodent chow [Ca 1.2%, phosphorus (P) 1.04%], a Ca-enriched diet containing 2%, 4%, or 6% Ca (Ca/P ratio of 2, 4, and 6, respectively), or a Ca/P-enriched diet (Ca/P ratio of 1.2). After 12 weeks of treatment, all rats were killed to harvest the spine, serum, and urine samples. Neither the ALF treatment nor the Ca supplement caused hypercalcemia. In the spine, ALF prevented decreases in bone mineral density (BMD) and compressive strength of lumbar spine induced by OVX. Micro-computed tomographic analysis confirmed that ALF significantly improved the trabecular bone pattern factor and the structure model index and suppressed bone destruction. In contrast, of particular interest, high-dose Ca administration did not have marked effects on bone fragility. Also, when both Ca and P were administered in high doses, BMD and mechanical strength decreased dose-dependently, urinary P excretion significantly increased, and serum parathyroid hormone level increased. Together, it is difficult to adjust the Ca supply through diet alone without disrupting the balance between serum Ca and P levels. Consequently, we conclude that ALF is beneficial for the treatment of osteoporosis, which is not achieved by the use of a Ca supplement.

Amino Acids↗

PubMed2006

Effect of elastic compression stockings on oedema prevention in healthy controls evaluated by a three-dimensional measurement system.

BACKGROUND/AIMS: The degree of oedema may differ at various sites on the leg. This study evaluated the degree of oedema at the calf, ankle and foot using a three-dimensional measurement system. METHODS: By three-dimensional measurement system using the grid pattern projection method, the effects of four different types of elastic compression stockings on oedema prevention were compared in healthy subjects. RESULTS: Without stockings, a significant increase in the circumference and volume was seen at the ankle and foot in the evening compared with morning values. The average increase in circumference was greater at the foot than that at the ankle. A significant increase in circumference and volume in the evening after a day without stockings disappeared when elastic compression stockings were worn during the day. The coefficient of variation was greater for measurements at the foot than for those at the calf and ankle. CONCLUSION: Oedema develops easily in order of the foot, the ankle and the calf in healthy populations. Elastic stockings, even with a pressure as low as 8 mmHg, are effective on oedema prevention. In measurement at the foot, further developments are necessary to improve this system.

Adult↗

PubMed2004

Individual and joint impact of family history and Helicobacter pylori infection on the risk of stomach cancer: a nested case-control study.

We used 202 cases of stomach cancer and 394 controls nested within the Japan Collaborative Cohort Study For Evaluation of Cancer Risk (JACC study) to investigate whether family history has an independent effect on the risk of stomach cancer after controlling for the Helicobacter pylori infection. A positive history of stomach cancer in one or more first-degree relatives was associated with an increased risk of the disease in women, but not in men after controlling for H. pylori infection and other confounding variables. Women with both a family history and H. pylori infection were associated with more than five-fold increased risk of the disease (OR 5.10, 95% CI 1.58-16.5) compared to those without these factors. These results suggest the existence of inherited susceptibility to the disease in women, and that measurements of H. pylori infection together with the family history allow meaningful evaluation of risk beyond that provided by either factor alone.

Adult↗

PubMed2004

Bowel movement frequency and risk of colorectal cancer in a large cohort study of Japanese men and women.

The relationship between bowel movement (BM) frequency and the risk of colorectal cancer was examined in a large cohort of 25 731 men and 37 198 women living in 24 communities in Japan. At enrolment, each participant completed a self-administrated questionnaire on BM frequency and laxative use. Incidence rate ratios (IRR) with 95% confidence intervals (CI) were estimated using Cox's proportional-hazard model. During the follow-up period (average length 7.6 years), 649 cases of colorectal cancer, including 429 cases of colon cancer, were identified. Among women, subjects who reported a BM every 2-3 days had the lowest risk of developing colorectal (IRR=0.71, 95% CI=0.52-0.97) and colon cancer (IRR=0.70, 95% CI=0.49-1.00), whereas those reporting a BM every 6 days or less had an increased risk of developing colorectal (IRR=2.47, 95% CI=1.01-6.01) and colon cancer (IRR=2.52, 95% CI=0.93-6.82) compared with those reporting >or=1 BM per day. A similar, but nonsignificant, association between the frequency of BM and cancer risk was observed in men. There was no association between colorectal or colon cancer risk and laxative use. Regulating BM frequency might therefore have a role in the prevention of colorectal cancer.

Adult↗

PubMed2004

A nested case-control study of stomach cancer in relation to green tea consumption in Japan.

To evaluate whether green tea consumption provides protection against stomach cancer, the relative risks (RRs) were calculated in the Japan Collaborative Study for Evaluation of Cancer Risk, sponsored by the Ministry of Health and Welfare (JACC Study). The study was based on 157 incident cases and 285 controls aged 40-79 years. Cox proportional hazards regression analysis was used to estimate the RRs for stomach cancer. It was found that green tea consumption had no protective effect against stomach cancer. After adjustment for age, smoking status, H. pylori infection, history of peptic ulcer, and family history of stomach cancer along with certain dietary elements, the risks associated with drinking one or two, three or four, five to nine, and 10 or more cups of green tea per day, relative to those of drinking less than one cup per day, were 1.3 (95% confidence interval (CI): 0.6-2.8), 1.0 (95% CI: 0.5-1.9), 0.8 (95% CI: 0.4-1.6), and 1.2 (95% CI: 0.6-2.5), respectively (P for trend=0.899). We found no inverse association between green tea consumption and the risk of stomach cancer.

Adult↗

PubMed2004

A prospective study of body size and colon cancer mortality in Japan: The JACC Study.

OBJECTIVE: To determine whether body size measurements are risk factors for colon cancer death among the Japanese. DESIGN AND SUBJECTS: A nationwide prospective study, the Japan Collaborative Cohort (JACC) Study from 1988 to 1999. The present analysis included 43 171 men and 58 775 women aged 40-79 y who respond to a questionnaire on current weight and height, weight around 20 y of age, and other lifestyle factors. Body mass index (BMI) at baseline and 20 y of age (B-BMI and 20-BMI, respectively) were calculated. RESULTS: We identified 127 deaths from colon cancer during the follow-up of 424 698 person-years among men and 122 deaths during the follow-up of 591 787 person-years among women. After adjustments for the lifestyle factors known to modify the risk of colon cancer, weight at baseline showed a significant positive association in women, while no such association was seen in men. There was also a significant trend of increasing risk with the increase in B-BMI among women. Women with B-BMI >/=28 kg/m(2) had a relative risk (RR) of 3.41 (95% confidence interval (CI): 1.44-8.06) compared with those with BMI of 20-<22 kg/m(2). 20-BMI also presented the same trend of increasing risk as B-BMI. Women with 20-BMI of <22 and B-BMI of >26 kg/m(2), that is, excessive BMI gain, had a high RR of 3.41 (95% CI 1.29-9.02) compared with those with 20-BMI of <22 and B-BMI of <22 kg/m(2). There were no corresponding trends of colon cancer risk for B-BMI, 20-BMI, or BMI change among men. CONCLUSIONS: These study data suggest that obesity and excessive weight gain are associated with the risk of colon cancer death in Japanese women but no such relationship was found in Japanese men.

Adult↗

PubMed2004

A stable prostacyclin analogue reduces high serum TNF-alpha levels in diabetic patients.

AIMS: To confirm whether a prostacyclin (prostaglandin I (2)) affects the increased TNF-alpha concentration in sera of diabetic patients, we measured serum TNF-alpha concentration and treated these patients with oral administration of the stable prostacyclin analogue (Beraprost). Twelve of 20 type II diabetic patients were investigated for follow up-study and 6 of those patients were for therapy with Beraprost for diabetic neuropathy. SUBJECTS AND METHODS: Serum TNF-alpha concentration was quantified by EASIA using monoclonal antibodies directed against distinct epitopes of TNF-alpha. RESULTS: In diabetic patients, serum TNF-alpha concentration was significantly increased compared with that of healthy subjects. The augmented TNF-alpha concentration in these patients was not decreased by diabetic control using antihyperglycemic agents for 8 weeks but was reduced with oral administration of a stable prostacyclin (prostaglandin I (2)) analogue for 5 weeks without any changes of blood glucose levels. CONCLUSIONS: Stable prostacyclin analogue administration for a short term period reduced increased TNF-alpha levels in diabetic patients, not through the improved hyperglycemic condition but another pathway, probably a cAMP system. These results imply that treatment with the prostacyclin analogue may contribute to the prevention of progression in diabetic complications.

Adult↗

PubMed2004

Possible role of VEGF in the progression of kidney disease in streptozotocin (STZ)-induced diabetic rats: effects of an ACE inhibitor and an angiotensin II receptor antagonist.

Two endothelium-derived factors, endothelin (ET), a vasoconstrictor, and vascular endothelial growth factor (VEGF), an angiogenic factor are thought to be involved in the pathogenesis of diabetic vascular complications. The aim of this study was to determine the effects of an angiotensin II type I (AT-1) receptor antagonist and an ACE inhibitor on the pathogenesis of VEGF and ET-1-mediated kidney disease in STZ-induced diabetic rats. Two days after STZ administration, diabetic rats were treated for 8 weeks with enalapril maleate, an ACE inhibitor, candesartan cilexetil, an AT-1 receptor antagonist, or saline. Urinary albumin and N-acetyl beta-D glucosaminidase (NAG) excretion as well as the VEGF protein content in the kidney were all found to be elevated in diabetic rats. Administration of enalapril maleate or candesartan cilexetil decreased the level of microalbuminuria and NAG excretion in diabetic rats. Administration of enalapril maleate also suppressed the elevated renal VEGF protein content in these animals while candesartan cilexetil treatment had no effect. Serum ET-1 and VEGF levels were unchanged by these treatments. These data support a role for AT-1 receptor antagonists and ACE inhibitors in the prevention of diabetic nephropathy, and suggest that the former may work by reducing renal VEGF levels.

Albuminuria↗

PubMed2002

A prospective study of stomach cancer death in relation to green tea consumption in Japan.

To evaluate whether green tea consumption provides protection against stomach cancer death, relative risks were calculated using Cox proportional hazards regression analysis in the Japan Collaborative Study for Evaluation of Cancer Risk, sponsored by the Ministry of Health and Welfare (JACC Study). The study was based on 30 370 men and 42 481 women aged 40-79. After adjustment for age, smoking status, history of peptic ulcer, family history of stomach cancer along with certain dietary items, the risks associated with drinking one or two, three or four, five to nine, and 10 or more cups of green tea per day, relative to those of drinking less than one cup per day, were 1.6 (95% CI: 0.9-2.9), 1.1 (95% CI: 0.6-1.9), 1.0 (95% CI: 0.5-2.0), and 1.0 (95% CI: 0.5-2.0), respectively, in men (P for trend=0.669), and 1.1 (95% CI: 0.5-2.5), 1.0 (95% CI: 0.5-2.5), 0.8 (95% CI: 0.4-1.6), and 0.8 (95% CI: 0.3-2.1), respectively, in women (P for trend=0.488). We found no inverse association between green tea consumption and the risk of stomach cancer death.

Adult↗

PubMed2002

Effect of elastic compression stockings in patients with varicose veins and healthy controls measured by strain gauge plethysmography.

BACKGROUND/AIMS: Oedema is one of the most frequent signs of chronic venous insufficiency and may be present at all stages of this disorder. The aim of this study was to compare the effects of four different types of elastic compression stockings on oedema prevention in patients with varicose veins. METHODS: An increase in foot volume after elevation of the leg was evaluated by strain gauge plethysmography in 20 limbs with varicose veins and 14 normal limbs, and the effects of four different compression stockings--8, 14, 22 and 30-40 mmHg--were compared. RESULTS: All stockings significantly reduced the foot volume increase compared with the no stockings patient group and the normal group. There was no significant difference in the volume increase in the normal group for all four stockings, while there was a significantly smaller volume increase in the 22 mmHg stocking compared to the 14 mmHg stocking in the patient group. Between the 22 mmHg and 30-40 mmHg stockings or between the 14 mmHg and 8 mmHg stockings, there was no significant difference in the volume increase. CONCLUSION: Elastic stockings, even with a pressure as low as 8 mmHg, can prevent oedema in patients with varicose veins, as well as in normal controls. However, the 22 mmHg and 30-40 mmHg stockings were better at preventing foot oedema in patients with varicose veins than those exerting less compression.

Bandages↗

PubMed2002

Extensive surgery for carcinoma of the gallbladder.

BACKGROUND: The purpose of this study was to clarify the efficacy of, and define the indications for, extensive surgery for gallbladder carcinoma. METHODS: Between 1979 and 1994, 116 patients with gallbladder carcinoma underwent operation. Radical resection was performed in 80 patients. RESULTS: In 68 patients with stage III or IV disease, extensive resection including extended right hepatectomy (n = 40), pancreaticoduodenectomy (n = 23) and/or portal vein resection (n = 23) was employed to achieve complete tumour excision. The hospital mortality rate was 18 per cent. The postoperative 3- and 5-year survival rates were 44 and 33 per cent respectively in the patients with stage III disease (n = 9), and 24 and 17 per cent respectively in patients with stage IV (M0) disease (n = 29). In contrast, the postoperative survival rate for the 30 patients with stage IV (M1) disease (7 per cent at 3 years and 3 per cent at 5 years) was worse than that for patients with stage III and stage IV (M0) disease (P = 0.009 and P = 0.062 respectively). CONCLUSION: Radical resection should be undertaken for stage III and stage IV (M0) gallbladder cancer. Although portal vein resection and/or pancreaticoduodenectomy did not contribute to long-term survival, better survival was obtained than that for the unresected patients.

Gallbladder Neoplasms↗

PubMed2002

Isolation and characterization of human monoclonal autoantibodies to glutamic acid decarboxylase.

Production of human monoclonal autoantibodies to glutamic acid decarboxylase M(r) 65,000 (GAD65), characterization of their isotype, binding affinity, V region sequences and competition with autoantibodies in patients' sera is described. Lymphocytes from a patient with Addison's disease who had GAD65 autoantibodies without diabetes were immortalised and fused to a mouse/human hybridoma. In addition, mouse monoclonal antibodies to GAD65 were produced using standard techniques. F(ab')2S from our monoclonals and the GAD6 mouse monoclonal were used in competition with intact monoclonals and sera from diabetic patients for binding to 125I-labelled GAD65 (amino acids 46-586). Reactivities of the human monoclonals with GAD 65,000/67,000 M(r) chimeras were also studied. Variable region genes of human monoclonals were sequenced and analysed. The human monoclonals (n = 3) had affinity constants for GAD65 of 2.2 x 10(9), 5.8 x 10(9), 1.3 x 10(10) mol/l(-1); affinities of the mouse monoclonals (n = 5) ranged from 1.1 x 10(8) to 5.4 x 10(10) mol/l(-1). The binding of each of the human monoclonals was inhibited by GAD6 F(ab')2 and the binding of GAD6 antibody was inhibited by the human monoclonal F(ab')2S suggesting that the epitopes for these antibodies were overlapping. Studies with GAD65/GAD67 chimeras indicated that the human monoclonals reacted with C-terminal epitopes. The human monoclonals, GAD6 and 3/5 mouse monoclonals inhibited serum autoantibody binding to 125I-labelled GAD65. Overall, the human monoclonals were of high affinity, reacted with C-terminal epitopes and showed evidence of antigen driven maturation; they represented only a proportion of the repertoire of autoantibodies to GAD65 in the donor's serum and in the sera of patients with type-1 diabetes.

Addison Disease↗

PubMed2001

Complications of hepatectomy for hilar cholangiocarcinoma.

We retrospectively reviewed postoperative complications in 105 patients with hilar cholangiocarcinoma who underwent hepatectomy at Nagoya University Hospital from January 1990 through March 1999. Of the 105 subjects, 97 (92.4%) underwent resection of two or more Healey's segments of the liver. Combined portal vein resection was performed in 33 (31.4%) patients and pancreatoduodenectomy in 10 (9.5%). Twenty (19.0%) patients had no postoperative complications, another 39 (37.1%) patients had minor complication(s) only, and the remaining 46 (43.8%) developed major complication(s). The morbidity rate reached as high as 81.0%. Major complications required relaparotomy in 11 (10.5%) patients. Of the 46 patients with major complication(s) 36 recovered; the remaining 10 patients died of liver failure with other organ failure(s) or of intraabdominal bleeding 12, 14, 18, 21, 57, 75, 75, 87, 93, or 134 days after surgery. Thus the 30-day mortality was 3.8% and the overall mortality 9.5%. Pleural effusion was the most frequent complication found in 66 (62.9%) patients, followed by wound sepsis in 39 (37.1%), and then liver failure in 29 (27.6%). Liver failure developed in 16.7% of 48 patients with less than 50% liver resection and in 36.8% of 57 patients with 50% or more resection (P < 0.05). Other organ failures, including renal, respiratory, gastrointestinal, and hematologic failures, developed as a sign of multiple organ failure following liver failure in most patients or preceding liver failure in a few patients. None of the six patients with four or more organ failures survived. Hepatectomy for hilar cholangiocarcinoma is risky owing to impaired hepatic functional reserve in jaundiced patients and the technical difficulty associated with hepatobiliary resection. Our goal is to reduce mortality to less than 5% while keeping a high resectability rate (above 80%).

Adult↗

PubMed2001

Five-year survivors after aggressive surgery for stage IV gallbladder cancer.

PURPOSE: To describe 5-year survivors after radical surgery for stage IV gallbladder cancer and to determine the characteristics leading to potential long-term survival. METHODS: Of 59 patients undergoing radical resection for stage IV disease between 1979 and 1994, 6 patients who have survived for more than 5 years were followed up. RESULTS: Three patients had developed obstructive jaundice due to involvement of the hepatic hilum, but the other three had not. The jaundiced patients had remarkable tumor spread over the bile duct and right hepatic artery within the hepatoduodenal ligament. However, the proper and left hepatic arteries and the portal trunk and its left branch were free from tumor involvement. The nonjaundiced patients had N1 or N2 lymph node metastasis. However, none underwent bile duct resection or pancreatoduodenectomy to establish radical lymphadenectomy. CONCLUSIONS: Selected patients with stage IV gallbladder cancer may be candidates for 5-year survival when the primary tumor is fairly localized even if it forms a large mass and involves neighboring organs including the hepatic duct, lymph node metastasis is limited to N1 and N2 except for the celiac and superior mesenteric nodes and is less infiltrative, and distant metastasis including that in the paraaortic area is absent.

Adult↗

PubMed2001

Advanced gallbladder carcinoma with biliobiliary fistula, resected by hepatopancreatoduodenectomy, in an aged patient.

We report a 78-year-old man with a gallbladder carcinoma and biliobiliary fistula, diagnosed by percutaneous transhepatic cholangioscopic biopsy through the fistula. The impacted stones in the common hepatic duct were crushed, and then selective cholangiography under percutaneous transhepatic cholangioscopy (PTCS) revealed a biliobiliary fistula. Cholangioscopic biopsy tissues taken from the gallbladder revealed adenocarcinoma, but biopsies taken from the fistula revealed no evidence of malignancy. Further investigations indicated that the gallbladder carcinoma involved the duodenum and the distal common bile duct. A hepatopancreatoduodenectomy, including both an extended right hepatic lobectomy with resection of the caudate lobe and a pancreatoduodenectomy, was performed. Despite the patient's advanced age, he made an unremarkable postoperative recovery and was able to enjoy an active social life for 8 months after the surgery. We discuss biliobiliary fistula associated with gallbladder carcinomas and the use of hepatopancreatoduodenectomy for advanced biliary cancer in aged patients.

Aged↗

PubMed2001

Hepatocellular carcinoma with biliary tumor thrombi: aggressive operative approach after appropriate preoperative management.

BACKGROUND: The aim of this study was to clarify clinicopathologic characteristics of, and to evaluate an aggressive treatment strategy for, hepatocellular carcinoma with biliary tumor thrombi. METHODS: From 1980 to 1999, a total of 132 patients underwent hepatectomy for hepatocellular carcinoma. Of these, 17 patients had macroscopic biliary tumor thrombi and were retrospectively analyzed. RESULTS: The operative procedures included right hepatic trisegmentectomy (n = 1), right or left hepatic lobectomy (n = 11), and segmentectomy or subsegmentectomy (n = 5). In 13 patients, tumor thrombi extended beyond the hepatic confluence and was treated by thrombectomy through a choledochotomy in 8 patients and extrahepatic bile duct resection and reconstruction in 5 patients. The 3- and 5-year survival rates were 47% and 28%, respectively, with a median survival time of 2.3 years. These survival rates were similar to those achieved in 115 patients without biliary tumor thrombi. In a multivariate analysis, expansive growth type and solitary tumors were independent prognostic variables for favorable outcome after operation, whereas biliary tumor thrombi was not a significant prognostic factor. CONCLUSIONS: Surgery after appropriate preoperative management of hepatocellular carcinoma with biliary tumor thrombi yields results similar to those of patients without biliary involvement. Hepatectomy with thrombectomy through a choledochotomy appears to be as effective as a resection procedure.

Bile Duct Neoplasms↗

PubMed2001

X-ray crystal structure of a monoclonal antibody that binds to a major autoantigenic epitope on thyroid peroxidase.

Thyroid peroxidase (TPO) catalyzes the production of thyroid hormones and is a major autoantigen in autoimmune thyroid disease (AITD). It is believed that the majority of TPO autoantibodies bind to an immunodominant region consisting of two overlapping domains. Precise location of these domains would help our understanding of the interaction between TPO and TPO autoantibodies. 4F5 is a mouse monoclonal antibody (IgG1, kappa) that reacts with high affinity (2.6 x 10(10) mol/L(-1)) with one of the major autoantigenic regions on TPO. Heavy chain genes of 4F5 were from the VH1 germline gene family, germline genes for the D region could not be assigned and the J region was from the JH2 germline. Light chain genes were from Vkappa4/5 and Jkappa2, germline gene families. The Fab fragment of 4F5 was prepared by papain digestion, purified, crystallized, and the structure solved to 1.9 A using molecular replacement. The refined structure had an R factor of 19.5% and a free R factor of 23.9%. Deduced amino acid sequence and amino acid sequence obtained from diffraction analysis were compared and used to finalize the 4F5 Fab model. Structural analysis indicated that the structure of 4F5 is that of a standard Fab and its combining site is flat and is rich in tyrosine residues. Comparison of the structure of 4F5 with that of a TPO autoantibody Fab, TR1.9 suggests that the two antibodies are unlikely to recognise the same structures on TPO.

Adaptor Proteins, Signal Transducing↗