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Biomedical subjects

H Yamamoto

Publications and source records attributed to H Yamamoto.

At least 181 records · Page 10Linked to original sources
PubMed2001

Overexpression of CDC25B overrides radiation-induced G2-M arrest and results in increased apoptosis in esophageal cancer cells.

CDC25B phosphatase plays a key role in controlling G2-M progression by dephosphorylating two inhibitory residues of CDC2 and also has been suggested to have an oncogenic property. In this study, we investigated the effect of CDC25B overexpression on radiation-induced G2-M arrest and radiation sensitivity in esophageal cancer cells. TE8-CDC25B, in which CDC25B was overexpressed under an inducible system, was more radiosensitive than the vector control (TE8-neo) in a clonogenic survival assay. Without radiation, CDC25B overexpression had little effect on cell cycle fractions or growth rate. After 10-Gy radiation, TE8-CDC25B showed decreased G2-M arrest and increased apoptosis, whereas TE8-neo displayed prolonged G2-M arrest and less apoptosis. During this period, there were no differences in the protein amounts of CDC2 and cyclin B1 between the two cell lines. However, more CDC25B expression, which was reduced immediately by radiation, was sustained in TE8-CDC25B than in TE8-neo. Moreover, induction of tyrosine phosphorylation of CDC2 and reduction of CDC2 kinase activity after irradiation was less significant in TE8-CDC25B than in TE8-neo. These results indicate that cancer cells that overexpress CDC25B override G2-M arrest by retaining CDC2 kinase activity and undergo apoptosis after radiation. This may point to an effective approach toward improving radiotherapy outcomes of various cancers.

Apoptosis↗
PubMed2001

Measurement of the relative branching fraction of upsilon(4S) to charged and neutral B-meson pairs.

We analyze 9.7x10(6) B_B pairs recorded with the CLEO detector to determine the production ratio of charged to neutral B-meson pairs produced at the Upsilon(4S) resonance. We measure the rates for B0-->J/psiK((*)0) and B+-->J/psiK((*)+) decays and use the world-average B-meson lifetime ratio to extract the relative widths f(+-) / f(00) = gamma(Upsilon(4S)-->B+B-) / gamma(Upsilon(4S)-->B0 B-0)) = 1.04+/-0.07(stat)+/-0.04(syst). With the assumption that f(+-)+f(00) = 1, we obtain f(00) = 0.49+/-0.02(stat)+/-0.01(syst) and f(+-) = 0.51+/-0.02(stat)+/-0.01(syst). This production ratio and its uncertainty apply to all exclusive B-meson branching fractions measured at the Upsilon(4S) resonance.

Journal Article↗
PubMed2001

Mucoadhesive nanoparticulate systems for peptide drug delivery.

This chapter describes the preparation of and methods for evaluating mucoadhesive nanoparticulate systems, including liposomes and polymeric nanoparticles. Mucoadhesive ability is conferred on the particulate systems by coating their surface with mucoadhesive polymers such as chitosan and Carbopol. The feasibility of this surface modification was confirmed by measuring the zeta potential. Several methods of evaluating the mucoadhesive properties of particulate systems have been reported in the literature. We have also developed some novel evaluation procedures including a particle counting method using a Coulter counter for polymer-coated liposomes. The mucoadhesive properties of the polymer-coated liposomes and polymeric nanoparticles were confirmed by means of these mucoadhesion tests. In applying these mucoadhesive nanoparticles to the oral and pulmonary administration of peptide drugs, more effective and prolonged action was observed in comparison with non-coated systems, thereby confirming the usefulness of mucoadhesive nanoparticulate systems for the delivery of peptide drugs.

Animals↗
PubMed2001

Measurement of the lambda(+)(c) lifetime.

The Lambda+c lifetime is measured using 9.0 fb(-1) of e+e- annihilation data collected on or just below the Upsilon(4S) resonance with the CLEO II.V detector at CESR. Using an unbinned maximum likelihood fit, the Lambda+c lifetime is measured to be 179.6+/-6.9(stat)+/-4.4(syst) fs. The precision of this colliding beam measurement is comparable to other measurements, which are based on fixed-target experiments, with different systematic uncertainties.

Journal Article↗
PubMed2001

Anti-human vWF monoclonal antibody, AJvW-2 Fab, inhibits repetitive coronary artery thrombosis without bleeding time prolongation in dogs.

The antithrombotic and antihaemostatic effects of the monoclonal antibody against human vWF (AJvW-2 Fab) were investigated in comparison with those of the monoclonal antibody against platelet GPIIb/IIIa (abciximab) in dogs. The ex vivo platelet aggregation and template bleeding time were measured before, 5, 90, 210 min and 24 h after injection of either AJvW-2 Fab or abciximab in anesthetized beagle dogs. Plasma concentration, vWF occupancy and plasma vWF antigen level were also measured by ELISA. In addition, the antithrombotic effect was evaluated in a canine model of repetitive coronary thrombosis (Folts model). AJvW-2 Fab significantly inhibited the ex vivo botrocetin-induced platelet aggregation at 0.18 mg/kg (53% plasma vWF occupancy) and also inhibited cyclic flow reductions (CFRs) at 0.06 mg/kg (31% occupancy). A significant prolongation of the bleeding time was observed at 1.8 mg/kg (95% occupancy), which was 30 times as high as the antithrombotic effective dose. Whereas, abciximab significantly inhibited both the ex vivo ADP-induced platelet aggregation and CFRs at 0.8 mg/kg, which was the minimally effective dose, also resulting in a significant prolongation of the bleeding time. These results suggest that blockade of the GPIb-vWF axis with AJvW-2 Fab leads to the inhibition of thrombus formation in the stenosed coronary arteries without less bleeding time prolongation than the GPIIb/IIIa blockade with abciximab.

Animals↗
PubMed2001

In vivo evidence for accelerated generation of hydroxyl radicals in liver of Long-Evans Cinnamon (LEC) rats with acute hepatitis.

The Long-Evans Cinnamon (LEC) rats accumulate excess copper (Cu) in the liver in a manner similar to patients with Wilson's disease (WD) and spontaneously develop acute hepatitis with severe jaundice. Although hydroxyl radicals (*OH) have been proposed to be a cause of hepatitis by the accumulation of Cu, it is not clear whether or not *OH can be produced in the liver of hepatitic LEC rats in vivo and also can be involved in the onset of hepatitis. In the present study, *OH production in plasma and liver of hepatitic LEC rats was quantified by trapping *OH with salicylic acid (SA) as 2, 3-dihydroxybenzoic acid (2, 3-DHBA). The ratios of 2, 3-DHBA/SA were significantly higher in plasma and liver of hepatitic LEC rats than those of Wistar rats and LEC rats showing no signs of hepatitis. Furthermore, the ratios of 2, 3-DHBA/SA in plasma and liver of hepatitic LEC rats were almost the same as those of Wistar rats treated orally with CuSO(4) (0.5 mmol/kg) 2 h before acetylsalicylic acid (ASA) injection. We also evaluated the protective effects of D-mannitol (a *OH scavenger) treatment against acute hepatitis in LEC rats. D-mannitol (500 mg/kg) was administered intraperitoneally to 10-week-old LEC rats for 3 weeks. D-mannitol treatment suppressed the increases in serum aspartate aminotransferase activity and total bilirubin concentration. In addition, D-mannitol treatment significantly reduced hepatic mitochondrial lipid peroxidation, which is thought to be important in the pathogenesis of Cu-induced hepatotoxicity. These observations suggest that accelerated generation of *OH catalyzed by free Cu in the liver may, at least in part, play a role in the pathogenesis of acute hepatitis in LEC rats.

Acute Disease↗
PubMed2001

Expression of matrix metalloproteinases and tissue inhibitors of metalloproteinases in human pancreatic adenocarcinomas: clinicopathologic and prognostic significance of matrilysin expression.

PURPOSE: A disruption in the balance between the matrix metalloproteinases (MMPs) and their natural inhibitors, tissue inhibitors of metalloproteinases (TIMPs), has been implicated in the progression of many types of cancer. The aim of this study was to determine whether a specific MMP or TIMP has clinicopathologic and prognostic significance in pancreatic carcinoma. PATIENTS AND METHODS: Using immunohistochemistry, we analyzed 70 pancreatic ductal adenocarcinoma tissues for expression of MMP-1, MMP-2, MMP-3, MMP-7 (matrilysin), MMP-9, MT1-MMP, TIMP-1, and TIMP-2. The results were matched with clinicopathologic characteristics and patients' survival. The effects of the suppression of a specific MMP on in vitro invasiveness of pancreatic carcinoma cells were also examined. RESULTS: Expression of MMP-1, MMP-2, MMP-3, matrilysin, MMP-9, MT1-MMP, TIMP-1, and TIMP-2 was detected in either tumor cells or tumor stromal cells, or in both components, at varying frequencies. Among MMPs, matrilysin showed a unique distribution in the tumor nests; its expression was usually most pronounced at the invasive front of the tumors. Sections with immunostaining signals in more than 30% of carcinoma cells at the invasive front, which were observed in 40 cases (57%), were judged to be positive for matrilysin. Matrilysin positivity was significantly correlated with pT, pN, and pM categories and with more advanced pathologic tumor-node-metastasis stages. Patients with matrilysin-positive carcinoma had a significantly shorter overall survival time than did those with matrilysin-negative carcinoma. Matrilysin was a significant independent prognostic factor for overall survival in multivariate analysis. In contrast, there was no correlation between the presence of other MMPs or TIMPs and clinicopathologic characteristics, nor was the presence of individual MMPs or TIMPs related to survival. Antisense matrilysin-transfected CFPAC-1 cells expressed reduced levels of matrilysin and demonstrated a similar growth potential but were less invasive in vitro compared with neotransfected CFPAC-1 cells. CONCLUSION: Our results suggest that matrilysin may play a key role in progression of pancreatic carcinoma and thereby contribute to a poor prognosis. Because different synthetic MMP inhibitors affect different types of MMPs to a different degree, examination of the expression of MMPs, especially that of matrilysin, may serve as an indicator for selecting the most effective MMP inhibitor.

Adenocarcinoma↗
PubMed2001

Effects of high ELF magnetic fields on enzyme-catalyzed DNA and RNA synthesis in vitro and on a cell-free DNA mismatch repair.

Environmental electromagnetic fields have been implicated in human cancers. We examined whether high extremely low frequency (ELF) AC magnetic fields could affect DNA synthesis, transcription or repair, using in vitro model systems with defined sequences. The rate and fidelity of DNA polymerase catalyzed DNA synthesis, as well as of RNA polymerase catalyzed RNA synthesis, were not statistically significantly affected by 60 Hz 0.25-0.5 Tesla magnetic fields. The efficiency of mutS dependent mismatch repair with human cell extracts was also not affected by the magnetic field exposure. The results suggest that the core processes related to the transmission of genetic information are stable under high ELF magnetic fields.

Animals↗
PubMed2001

Exposure of Caenorhabditis elegans to extremely low frequency high magnetic fields induces stress responses.

Responses of the small heat shock protein gene, hsp-16, were examined in transgenic Caenorhabditis elegans exposed to electromagnetic fields. Expression of the hsp-16-lacZ gene was enhanced when transgenic animals were exposed to magnetic fields up to 0.5 T at 60 Hz. The hsp-16 promoter was more efficiently expressed at the embryonic than at the post-embryonic stage irrespective of exposure. Promoter activity was more sensitive to the stimulus in the intestine at the post-embryonic stage. Evidence is presented that the induction occurs at the transcriptional step of hsp-16.

Animals↗
PubMed2001

Surgical management of multidrug-resistant tuberculosis.

We report surgical resections in 3 patients with active multidrug-resistant tuberculosis. All cases involved strains of Mycobacterium tuberculosis resistant to at least isoniazid and rifampin and patients who were poor candidates for medical therapy alone. We conducted pulmonary resections (partial resection in case 1, lobectomy in case 2, and segmentectomy in case 3). The optimum multiple-drug regimen, based on drug susceptibility studies, was used preoperatively and postoperatively. In all cases, sputum smears and cultures yielded negative results postoperatively, and continue to be negative for Mycobacterium tuberculosis to date. It is recommended that, if localized disease is present and medical treatment is likely to fail, pulmonary resection be conducted for multidrug-resistant Mycobacterium tuberculosis.

Adult↗
PubMed2001

A case of basal cell carcinoma of the nipple and areola with intraductal spread.

We report an 82-year-old Japanese woman with basal cell carcinoma of the left nipple and areola extending into the lactiferous duct. The patient developed a small papular lesion of the left areola about 1 year before admission. The lesion, which had slowly progressed to involve the nipple, had become symptomatic showing weeping and bleeding. Mammography revealed microcalcification in the nipple. Although Paget's disease was suspected from these clinical features, histologically basal cell carcinoma was diagnosed. There was no axillary lymphadenopathy, and no evidence of distant metastasis. The lesion of the nipple and areola was resected with a 2 cm free margin along with the underlying mammary tissue. The patient has remained well without signs of recurrence for 2 years after surgery. We reviewed cases of basal cell carcinoma of the nipple or areola and discuss considerations and problems of this rare tumor.

Aged↗
PubMed2001

The usefulness of brain perfusion SPECT in an infant with focal convulsions associated with hemophilus influenzae central nervous system infection.

Left hemiconvulsions occurred in a 13-month-old girl with Hemophilus influenzae (H. influenzae) central nervous system (CNS) infection. Tc-99m HMPAO brain SPECT showed a focal hyperperfusion area in the right frontal lobe. The patient recovered without complications, and follow-up SPECT revealed markedly improved findings. Tc-99m HMPAO brain SPECT is useful for evaluating focal convulsions associated with H. influenzae CNS infection.

Brain↗
PubMed2001

Use of digirad 2020tc Imager, a multi-crystal scintillation camera with solid-state detectors in one case for the imaging of autografts of parathyroid glands.

99mTc-methoxy-isobutyl-isonitrile (99mTc-MIBI) scintigraphy with Digirad 2020tc ImagerTM (2020tc), which was a multi-crystal scintillation camera with solid-state detectors was performed for patients with secondary hyperparathyroidism having autografts of parathyroid glands in the right arm. With the 2020tc camera, three abnormal accumulations were found in the right arm. The images obtained with this camera were superior in resolution to those obtained with a conventional NaI crystal gamma camera (ZLC7500, Siemens, Germany). The next day, resection of autografts of parathyroid glands was done. Four hyperplastic parathyroid glands were resected and all were hyperplastic in pathological findings.

Cesium↗
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

Use of vascularized pedicle iliac bone graft in the treatment of avascular necrosis of the femoral head.

A vascularized pedicle iliac bone graft was performed in patients with extensive necrosis in whom the necrotic area occupied more than two-thirds of the femoral head. The purpose of this procedure is to supply vascularity and mechanical strength to the avascular femoral head. Our series consisted of 18 hips. The patients' age at surgery ranged from 21 to 55 years. Fourteen hips were identified as stage II and 4 hips as stage III. Iliac bone graft alone was performed in 4 stage II joints. Transtrochanteric anterior rotational osteotomy of the femoral head was done additionally in 10 stage II joints and 4 stage III joints. In the group who underwent iliac bone graft alone, the mean Japanese Orthopedic Association (JOA) score improved from 58.5 to 63.8 (mean follow-up 52 months). In the group who underwent combination procedure with osteotomy, the mean JOA score improved from 71.7 to 85.0 (mean follow-up 43 months). Stage progression was noted in 3 of 4 joints in the group who underwent iliac bone graft alone. In the group who underwent the combined procedure, stage progression was noted in 2 of 10 joints at more than 1 year after operation. A vascularized pedicle iliac bone graft to treat avascular necrosis of the femoral head is considered promising for joint preservation.

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

Extreme discrepancy between macroscopic diagnosis and pathological findings of gallbladder cancer treated by hepatopancreatoduodenectomy.

Diagnosis of gallbladder cancer in terms of invasion depth and spread is an important factor in determining cumulative survival after surgical treatment. However, diagnostic methods available at present occasionally fail to judge staging correctly. We report a case of gallbladder cancer which showed extreme discrepancy between the preoperative macroscopic and imaging diagnosis (positive direct invasion to the liver and invasion to the bile duct and duodenum through the serosal layer; S3, Hinf3, Binf2, and stage IV by the Japanese Society of Biliary Surgery classification) and the pathological findings (limited in vasion within the subserosal layer; ss, hinf0. binf0, and stage II). This discrepancy allowed us to perform curative treatment by hepatopancreatoduodenectomy, including extended right lobectomy of the liver, external bile duct resection, resection of the mesocolon, and lymph node dissection. Surgeons should aim for curability of advanced gallbladder cancer by radical resection until accurate methods for the preoperative diagnosis of cancer spread are available, because the clinical picture may be modified by inflammatory changes.

Cholangiopancreatography, Endoscopic Retrograde↗