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Biomedical subjects

S Nishiguchi

Publications and source records attributed to S Nishiguchi.

At least 19 recordsLinked to original sources
PubMed2003

Cytokeratin-19 fragments in serum (CYFRA 21-1) as a marker in primary liver cancer.

Using an electrochemiluminescence immunoassay, CYFRA 21-1 concentrations were measured in sera from 187 patients with primary liver cancer (164 with hepatocellular carcinoma (HCC) and 23 with intrahepatic cholangiocarcinoma (ICC)) and 87 patients with benign liver diseases. Concentrations of CYFRA 21-1 were significantly higher in patients with ICC (5.0; interquartile range 3.1-10.7 ng ml(-1)) than in those with benign liver disease (1.4; 1.0-1.9; Mann-Whitney U-test, P<0.0001) or HCC (1.7; 1.1-2.7; Mann-Whitney U-test, P<0.0001). Using cutoff values selected for 95% specificity in the benign group (3.0 ng ml(-1)), CYFRA 21-1 showed higher sensitivity for ICC (87.0%) than three commonly used markers including alpha-fetoprotein (17.4%), carcinoembryonic antigen (34.8%), and carbohydrate antigen 19-9 (60.9%). Serum CYFRA 21-1 increased in ICC from stages I/II to IV (Kruskal-Wallis test, P=0.0102). CYFRA 21-1 concentration increased with extent of local invasion, but not nodal status. Serum CYFRA 21-1 represents a useful diagnostic test for ICC that offers high sensitivity. CYFRA 21-1 reflected differences in tumour burden, suggesting applicability to staging and follow-up.

Adult↗
PubMed2003

Sox1-deficient mice suffer from epilepsy associated with abnormal ventral forebrain development and olfactory cortex hyperexcitability.

Mutations in several classes of embryonically-expressed transcription factor genes are associated with behavioral disorders and epilepsies. However, there is little known about how such genetic and neurodevelopmental defects lead to brain dysfunction. Here we present the characterization of an epilepsy syndrome caused by the absence of the transcription factor SOX1 in mice. In vivo electroencephalographic recordings from SOX1 mutants established a correlation between behavioral changes and cortical output that was consistent with a seizure origin in the limbic forebrain. In vitro intracellular recordings from three major forebrain regions, neocortex, hippocampus and olfactory (piriform) cortex (OC) showed that only the OC exhibits abnormal enhanced synaptic excitability and spontaneous epileptiform discharges. Furthermore, the hyperexcitability of the OC neurons was present in mutants prior to the onset of seizures but was completely absent from both the hippocampus and neocortex of the same animals. The local inhibitory GABAergic neurotransmission remained normal in the OC of SOX1-deficient brains, but there was a severe developmental deficit of OC postsynaptic target neurons, mainly GABAergic projection neurons within the olfactory tubercle and the nucleus accumbens shell. Our data show that SOX1 is essential for ventral telencephalic development and suggest that the neurodevelopmental defect disrupts local neuronal circuits leading to epilepsy in the SOX1-deficient mice.

Animals↗
PubMed2002

Randomized clinical trial of long-term outcome after resection of hepatitis C virus-related hepatocellular carcinoma by postoperative interferon therapy.

BACKGROUND: Interferon therapy seems to decrease the incidence of recurrence after resection of hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC). Effects of postoperative interferon therapy on the survival rate after resection of such HCC are still unclear. METHODS: A prospective randomized clinical trial of postoperative interferon therapy was performed. Thirty men were allocated randomly after liver resection to an interferon-alpha group (15 patients) or a control group. Patients in the interferon group received interferon-alpha 6 MIU intramuscularly every day for 2 weeks, then three times a week for 14 weeks and finally twice a week for 88 weeks. RESULTS: The response to interferon was complete in two patients, there was a biochemical response in six patients and no response in seven patients. Interferon administration was not completed in three patients because of adverse events. Liver function did not change or worsened after operation in the control group, and did not change or improved in the interferon group. The cumulative survival rate was higher in the interferon group than in the control group (P = 0.041). CONCLUSION: Postoperative interferon therapy seems to improve the outcome after resection of HCV-related HCC.

Aged↗
PubMed2001

Highly efficient oligosaccharide synthesis on water-soluble polymeric primers by recombinant glycosyltransferases immobilised on solid supports.

Recombinant beta-1,4-galactosyltranferase (beta 1,4-GalT) and alpha-2,6-sialytransferase (alpha 2,6-SiaT) immobilised covalently with activated Sepharose beads were employed for the practical synthesis of a trisaccharide derivative, Neu-5Ac alpha(2-->6)Gal beta(1-->4)GlcNAc beta-O-(CH2)6-NH2, on a water-soluble primer having GlcNAc residues through a alpha-chymotrypsin-sensitive linker.

Chymotrypsin↗
PubMed2001

Bioactive titanium: effect of sodium removal on the bone-bonding ability of bioactive titanium prepared by alkali and heat treatment.

As reported previously, bioactive titanium is prepared by simple alkali and heat treatment, and can bond to living bone directly. The purpose of this study was to accelerate the bioactivity of bioactive titanium in vivo. In in vitro study, sodium removal by hot water immersion enhanced the apatite-forming ability of bioactive titanium in simulated body fluid dramatically. The specific anatase structure of titania gel was effective for apatite formation in vitro. In the current study, we investigated the in vivo effect of sodium removal on the bone-bonding strength of bioactive titanium. Sodium-free bioactive titanium plates were prepared by immersion in an aqueous solution of 5 M NaOH at 60 degrees C for 24 h, followed by immersion in distilled water at 40 degrees C for 48 h before heating them at 600 degrees C for 1 h. Three kinds of titanium plates were inserted into rabbit tibiae, including untreated cp-Ti, conventional alkali- and heat-treated Ti, and sodium-free alkali- and heat-treated Ti. In vivo bioactive performance was examined mechanically and histologically after 4, 8, 16, and 24 weeks. Sodium removal enhanced the bone-bonding strength of bioactive titanium at 4 and 8 weeks postoperatively; however, its bone-bonding strength was inferior to that of conventional alkali- and heat-treated titanium at 16 and 24 weeks. Histological examinations after the detaching test revealed breakage of the treated layer in the sodium-free alkali- and heat-treated titanium group. In conclusion, sodium removal accelerated the in vivo bioactivity of bioactive titanium and achieved faster bone-bonding because of its anatase surface structure, but the loss of the surface's graded structure due to the complete removal of sodium decreased the adhesive strength of the treated layer to the titanium substrate. Further investigations are required to determine the optimum conditions for preparation of bioactive titanium.

Alkalies↗
PubMed2001

Effects of long-term postoperative interferon-alpha therapy on intrahepatic recurrence after resection of hepatitis C virus-related hepatocellular carcinoma. A randomized, controlled trial.

BACKGROUND: Interferon therapy decreases the incidence of hepatocellular carcinoma in patients with chronic hepatitis C. OBJECTIVE: To evaluate effects of interferon-alpha on recurrence after resection of hepatitis C virus-related hepatocellular carcinoma. DESIGN: Randomized, controlled trial. SETTING: University hospital, medical center, and affiliated hospital in Osaka, Japan. PATIENTS: 30 men were randomly allocated after resection to the interferon-alpha group (n = 15) or the control group (n = 15). INTERVENTION: Patients in the interferon-alpha group received interferon-alpha, 6 MIU intramuscularly daily for 2 weeks, then three times weekly for 14 weeks, and finally twice weekly for 88 weeks. MEASUREMENTS: Recurrence rates after resection. RESULTS: Recurrent tumors were detected in 5 patients in the interferon-alpha group and in 12 control patients. The recurrence rate was significantly lower in the interferon-alpha group than in the control group (P = 0.037). CONCLUSION: Postoperative interferon-alpha therapy appears to decrease recurrence after resection of hepatitis C virus-related hepatocellular carcinoma.

Antineoplastic Agents↗
PubMed2001

Bone bonding in sintered hydroxyapatite combined with a new synthesized agent, TAK-778.

We studied the stimulatory effects of TAK-778, a new synthetic 3-benzothiepin derivative that promotes osteoblast differentiation, in bone bonding to sintered hydroxyapatite implants in rabbit tibiae. Smooth-surfaced rectangular plates (15 x 10 x 2 mm) made of sintered hydroxyapatite were implanted into the proximal metaphyses of bilateral rabbit tibiae, with TAK-778-containing sustained-release microcapsules packed into the medullary cavity in one limb and untreated microcapsules packed in the contralateral limb to serve as a paired control. At 4, 8, and 16 weeks after implantation, bone bonding at the bone-implant interfaces was evaluated by a detaching test and undecalcified histological examination. The tensile failure load increased from 4 to 16 weeks for both groups; however, the tensile failure load of the TAK-778-treated group was significantly greater than that of the control group at each interval after implantation. Histologically, the TAK-778-treated specimens showed greater active new bone formation mainly in the medullary cavity and more extensive bonding between the implant and bone than the untreated specimens. The results of this study suggest that adding osteoinductive TAK-778 to hydroxyapatite implants may significantly accelerate bone apposition to the implants and improve the bonding process at the interface. This would help to establish an earlier and stronger bonding of orthopedic ceramic implants between the surrounding bone tissue.

Absorbable Implants↗
PubMed2001

Somatic mutation of mitochondrial DNA in cancerous and noncancerous liver tissue in individuals with hepatocellular carcinoma.

Unlike other types of cancer, hepatocellular carcinoma (HCC) is usually preceded by chronic inflammation caused by viral infection. The mutation of mitochondrial DNA (mtDNA) in hepatocarcinogenesis associated with viral infection was investigated. Compared with control liver tissue, the frequency of mtDNA mutations was markedly increased in both noncancerous and cancerous liver specimens from individuals with HCC. The accumulation of mtDNA mutations in HCC tissue reflected the degree of malignancy. The frequency of mtDNA mutations in HCC tissue was also greater than that described previously for other types of tumors. These observations suggest that the repeated destruction and regeneration of liver tissue associated with chronic viral hepatitis lead to the accumulation of mtDNA mutations. The genetic instability that results in the high rate of mtDNA mutation in cancerous liver tissue is also consistent with the multicentric hepatocarcinogenesis detected clinically.

Carcinoma, Hepatocellular↗
PubMed2001

Severely reduced production of klotho in human chronic renal failure kidney.

We recently identified a novel gene, termed klotho (kl) that is involved in the development of a syndrome in mice resembling human aging. A defect of the kl gene expression in mice leads to multiple disorders including arteriosclerosis, osteoporosis, ectopic calcification, and skin atrophy together with short life-span and infertility. Patients with chronic renal failure (CRF), develop multiple complications that are reminiscent of phenotypes observed in kl mutant mice. Furthermore, the kl gene is mainly expressed in kidney and brain. These evidences above suggest the possible involvement of Klotho function in the complications arising in CRF patients. To investigate the above possibility, we examined the kidneys of 10 clinically or histologically diagnosed CRF cases. The level of kl gene expression was measured by utilizing RNase protection assay. The expression of Klotho protein was assayed by utilizing Western blot analysis and by immunohistochemistry. The levels of kl mRNA expression were greatly reduced in all CRF kidneys. Moreover, the production of Klotho protein was also severely reduced in all CRF kidneys. These results suggest that the decrease in kl gene expression in CRF patients may underlie the deteriorating process of multiple complications in the CRF patients.

Adult↗
PubMed2001

Prevention of hepatocellular carcinoma in patients with chronic active hepatitis C and cirrhosis.

In a prospective randomised controlled study, 90 patients with chronic active hepatitis C and compensated cirrhosis were assigned symptomatic treatment or interferon alfa (IFN-alpha). We report data on decompensation, detection of hepatocellular carcinoma, and mortality rates. IFN-alpha gave a sustained response in only a small proportion of patients, but worsening of compensated cirrhosis was prevented and development of hepatocellular carcinoma was inhibited, increasing the survival rate. The risk ratio of IFN-alpha versus symptomatic treatment decreased by 0.250 for progression to Child-Pugh grade B, 0.256 for detection of hepatocellular carcinoma, and 0.135 for a fatal outcome.

Antineoplastic Agents↗
PubMed2001

Alkali- and heat-treated porous titanium for orthopedic implants.

This study was carried out to investigate the effects of the alkali and heat treatments on the bone-bonding behavior of porous titanium implants. Porous titanium implants had a 4.6 mm solid core and a 0.7 mm thick porous outer layer using pure titanium plasma-spray technique. Three types of porous implants were prepared from these pieces: 1.control implant (CL implant) as manufactured 2.AW-glass ceramic bottom-coated implant (AW implant) in which AW-glass ceramic was coated on only the bottom of the pore of the implant 3.alkali- and heat-treated implant (AH implant), where implants were immersed in 5 mol/L NaOH solution at 60 degrees C for 24 h and subsequently heated at 600 degrees C for 1 h. The implants were inserted into bilateral femora of six dogs hemi-transcortically in a randomized manner. At 4 weeks, push-out tests revealed that the mean shear strengths of the CL, AW, and AH implants were about 10.8, 12.7, and 15.0 MPa, respectively. At 12 weeks there was no significant difference between the bonding strengths of the three types of the porous implants (16.0-16.7 MPa). Histologically and histomorphologically, direct bone contact with the implant surface was significantly higher in the AH implants than the CL and AW implants both at 4 and 12 weeks. Thus, the higher bonding strength between bone and alkali- and heat-treated titanium implants was attributed to the direct bonding between bone and titanium surface. In conclusion, alkali and heat treatments can provide porous titanium implants with earlier stable fixation.

Animals↗
PubMed2001

A case of tuberculous peritonitis monitored by gallium-67 scintigraphy.

An 18-year-old man was admitted to our hospital for further examination of fever of unknown origin and ascites. Ga-67 scintigraphy revealed diffuse increased uptake throughout the abdomen. He was diagnosed with tuberculous peritonitis and began the treatment for tuberculosis (rifampicin, 450 mg/day orally and isoniazid, 300 mg/day orally, and 0.75 g of streptomycin by intramuscular injection 2 times a week). One year after starting the treatment, Ga-67 scintigraphy revealed accumulation of radioactivity in the upper abdomen, but the diffuse accumulation in the abdomen decreased. A specimen obtained by tumor biopsy under ultrasonic guidance revealed a tuberculous granuloma. Percutaneous injection was performed in the tumor with 1.0 g of streptomycin. On Ga-67 scintigraphy performed 2 weeks after the injection of streptomycin, the accumulation of radioactivity in the upper abdomen had disappeared. These findings suggest that Ga-67 scintigraphy is useful for diagnosis and observation during treatment of tuberculous peritonitis.

Adolescent↗
PubMed2001

Mesenteric desmoid with uptake on gallium-67 citrate scintigraphy.

A 72-year-old man was hospitalized for further evaluation of a space-occupying lesion in the abdomen. Magnetic resonance imaging revealed a tumor 40 mm in diameter in the abdomen. Anterior Ga-67 citrate scintigraphy revealed a region of accumulation of radioactivity in the abdomen corresponding to the tumor. Mesenteric desmoid was diagnosed on the basis of histological findings for the excised tumor. These finding suggested that mesenteric desmoid may be one of the tumors which show high uptake of Ga-67.

Abdominal Pain↗
PubMed2001

A case of glucagonoma with high uptake on F-18 fluorodeoxyglucose positron emission tomography.

Glucagonomas are relatively rare, and can be difficult to differentiate from other pancreatic tumors. A 62-year-old woman who had suffered from diabetes mellitus was hospitalized for further evaluation of a space-occupying lesion in the head of the pancreas and tumors in the liver. F-18 fluorodeoxyglucose positron emission tomography revealed accumulation of isotope corresponding to a tumor of the pancreas with a standardized uptake value of 4.3, and tumors in the liver with standardized uptake values of 2.4 and 2.8. The serum glucagon level was high (1,170 pg/ml) and the secretin tolerance test was negative. She was diagnosed with glucagonoma with a high serum glucagon level and clinical findings. It is suggested that glucagonoma may be one of the tumors which show high uptake of F-18 fluorodeoxyglucose.

Biological Transport↗
PubMed2001

Accessory spleen in the pelvis diagnosed by Tc-99m phytate scintigraphy.

We report a 58-year-old woman with an accessory spleen in the left side of the pelvis. She visited our outpatient clinic complaining of lower abdominal discomfort. Abdominal ultrasonography revealed a tumor 4 cm in diameter in the left side of the pelvis. Color Doppler ultrasonography demonstrated plentiful pulsating blood flow. Magnetic resonance angiography revealed that the blood supply for the tumor was from a branch of the splenic artery. Scintigraphy with Tc-99m phytate revealed accumulation of radioactivity concordant with a mass in the left side of the pelvis, and the spleen was normally visualized. These findings suggested that this tumor was an accessory spleen, and the patient underwent no further invasive procedures.

Female↗
PubMed2001

Does ascorbic acid prevent retinopathy during interferon therapy in patients with chronic hepatitis C?

PURPOSE: Ascorbic acid was administered to patients with chronic hepatitis C to elucidate the mechanism of onset of retinopathy during interferon (IFN) therapy, and its prevention. METHODS: The subjects were 62 patients with chronic hepatitis C who had been admitted to our hospital. For the IFN therapy, 6 MIU of natural IFN-alpha, or 10 MIU of recombinant human IFN-alpha 2b was administered every day for the first 2 weeks, followed by administration three times a week for 22 weeks. The patients were randomly assigned to a group receiving 600 mg/day of ascorbic acid or a group not receiving ascorbic acid (control group). The optic fundi were examined by ophthalmologists before the IFN therapy began and subsequently at weeks 2 and 4 and then every 4 weeks during the IFN therapy. RESULTS: Retinopathy was found in 9 of the 31 patients (29%) in the ascorbic acid-treated group and in 11 of the 31 patients (35%) in the control group. The cumulative incidence of hemorrhage in the ascorbic acid-treated group was lower than that in the control group during the IFN therapy, but the difference between the two groups was not significant (P = 0.186). The cumulative incidence of cotton-wool spots in the ascorbic acid-treated group was almost same as that in the control group during the IFN therapy. The median platelet counts before the therapy was begun were 11.8 x 10(4)/mm2 in the group with hemorrhage and 16.6 x 10(4)/mm2 in the group without, and the lowest platelet counts during IFN therapy were 7.3 x 10(4)/mm3 in the group with hemorrhage and 9.5 x 10(4)/mm3 in the group without, indicating significantly lower values in the group with hemorrhage (P = 0.018 and P = 0.020, respectively). The lowest platelet counts during IFN therapy were 7.4 x 10(4)/mm3 in the group with cotton-wool spots and 9.7 x 10(4)/mm3 in the group without, indicating a significantly lower value in the group with cotton-wool spots (P = 0.036). CONCLUSIONS: Ascorbic acid was not considered to be useful for the prevention of the retinopathy associated with IFN therapy in patients with chronic hepatitis C.

Adult↗
PubMed2001

Titanium metals form direct bonding to bone after alkali and heat treatments.

In this article we evaluated the bone-bonding strengths of titanium and titanium alloy implants with and without alkali and heat treatments using the conventional canine femur push-out model. Four kinds of smooth cylindrical implants, made of pure titanium or three titanium alloys, were prepared with and without alkali and heat treatments. The implants were inserted hemitranscortically into canine femora. The bone-bonding shear strengths of the implants were measured using push-out test. At 4 weeks all types of the alkali- and heat-treated implants showed significantly higher bonding strength (2.4-4.5 MPa) than their untreated counterparts (0.3-0.6 MPa). At 12 weeks the bonding strengths of the treated implants showed no further increase, while those of the untreated implants had increased to 0.6-1.2MPa. Histologically, alkali- and heat-treated implants showed direct bonding to bony tissue without intervening fibrous tissue. On the other hand, untreated implants usually had intervening fibrous tissue at the interface between bone and the implant. The early and strong bonding to bone of alkali- and heat-treated titanium and its alloys without intervening fibrous tissue may be useful in establishing cementless stable fixation of orthopedic implants.

Alkalies↗