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Biomedical subjects

S Nishiguchi

Publications and source records attributed to S Nishiguchi.

At least 55 records · Page 3Linked to original sources
PubMed2001

Tumor-suppressor effect of interferon regulatory factor-1 in human hepatocellular carcinoma.

IFN regulatory factor-1 (IRF-1) regulates the IFN system, inhibits cell growth, and has tumor-suppressor activities. p21 is a universal cyclin-dependent kinase inhibitor, the induction of which depends on both p53 and IRF-1 in mouse embryonic fibroblasts. The expression of p21 in hepatocellular carcinomas (HCCs) is regulated by wild-type p53. We examined the expressions of IRF-1 and p21 in 32 HCCs by quantitative reverse transcription-PCR and the mutation p53 gene in 32 HCCs by single-strand conformation polymorphism and direct sequencing. The expression of IRF-1 mRNA in 15 of 32 HCCs was lower than that in adjacent noncancerous tissue. IRF-1 mRNA expression was reduced in 0 of 3 specimens of well-differentiated HCC, 9 of 21 (42%) specimens of moderately differentiated HCC, and 6 of 8 (75%) specimens of poorly differentiated HCC. IRF-1 mRNA expression was significantly lower in tumors with portal thrombus than in those without portal thrombus (P = 0.003). p53 mutations were detected in 7 of 32 HCCS: p21 expression was reduced in 6 of the 7 (86%) HCCs with p53 mutations. In contrast, p21 expression was reduced in 13 of 25 (52%) HCCs with wild-type p53. IRF-1 expression was reduced in 7 of 13 (53%) HCCs with both wild-type p53 and reduced expression of p21. These results suggest that IRF-1 may be a tumor-suppressor gene for HCC and that IRF-1 is related to p21 expression in HCC with wild-type p53.

Aged↗
PubMed2001

[Clinical significance of interferon therapy in treatments for hepatitis C virus-related hepatocellular carcinoma].

The results of liver resection for hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC) are affected by persistent active hepatitis and/or hepatic fibrosis including cirrhosis. In patients infected with HCV, interferon therapy prevents the development of HCC by eradication of HCV and/or the remission of active hepatitis. Although HCCs are found even in some patients treated with interferon, the results of liver resection for such HCCs were satisfactory, especially in patients successfully treated with interferon. Postoperative interferon-alpha therapy decreased recurrence after resection of HCV-related HCC in a randomized controlled trial. Strategies for viral infection as well as the carcinoma can improve the outcome after treatment of HCV-related HCC. Interferon therapy is useful to improve the outcome after treatments for HCV-related HCC.

Antineoplastic Agents↗
PubMed2000

The effect of alkali- and heat-treated titanium and apatite-formed titanium on osteoblastic differentiation of bone marrow cells.

This study was based on the hypothesis that osteogenesis is enhanced by growth of osteogenic cells on an apatitic surface. To test this hypothesis, the behavior of rat bone marrow cells on these surfaces was examined: commercially pure titanium (Cp Ti), alkali- and heat-treated titanium (AH Ti), and AH Ti incubated in a simulated body fluid to deposit crystalline hydroxyapatite on the surface (Ap Ti). The alkaline phosphatase (ALP) activity of the cells cultured on Ap Ti was significantly higher at day 7 and day 14 than the ALP activity observed for the other titanium surfaces. At day 14, the ALP activity on AH Ti was significantly increased compared with the ALP activity on Cp Ti. The amount of DNA per well increased nearly in parallel for each titanium. However, northern blot analysis at day 14 revealed that expression of osteocalcin and alpha1(I) collagen mRNA was higher in the cells cultured on Ap Ti than the cells cultured on AH Ti. The cells cultured on Cp Ti showed the lowest mRNA levels. After 7 days of cell-free culture in medium supplemented with 15% serum, X-ray photoelectron spectroscopy (XPS), and thin-film X-ray diffraction (TF-XRD) analysis showed that calcium phosphate had been deposited on the AH Ti (resulting in an increase in thickness with time). No phosphate was detected on the Cp Ti, even after day 14. This study indicates that Ap Ti provides the most favorable conditions for differentiation of bone marrow cells, and, at a later stage, AH Ti also provides favorable conditions, perhaps because of the formation of a surface layer of calcium phosphate. This potential for apatite formation may play an important role in osteoblastic differentiation.

Alkaline Phosphatase↗
PubMed2000

Bioactive macroporous titanium surface layer on titanium substrate.

A macroporous titanium surface layer is often formed on titanium and titanium alloy implants for morphological fixation of the implants to bone via bony ingrowth into the porous structure. The surface of titanium metal was recently shown to become highly bioactive by being subjected to 5.0 M-NaOH treatment at 60 degrees C for 24 h and subsequent heat treatment at 600 degrees C for 1 h. In the present study, the NaOH and heat treatments were applied to a macroporous titanium surface layer formed on titanium substrate by a plasma spraying method. The NaOH and heat treatments produced an uniform amorphous sodium titanate layer on the surface of the porous titanium. The sodium titanate induced a bonelike apatite formation in simulated body fluid at an early soaking period, whereby the apatite layer grew uniformly along the surface and cross-sectional macrotextures of the porous titanium. This indicates that the NaOH and heat treatments lead to a bioactive macroporous titanium surface layer on titanium substrate. Such a bioactive macroporous layer on an implant is expected not only to enhance bony ingrowth into the porous structure, but also to provide a chemical integration with bone via apatite formation on its surface in the body.

Apatites↗
PubMed2000

Histologic improvement of fibrosis in patients with hepatitis C who have sustained response to interferon therapy.

BACKGROUND: Short-term histologic improvement in hepatitis C-related hepatic fibrosis has been noted in studies with more than 2 years of follow-up, but the long-term effects of interferon therapy on hepatic fibrosis remain unclear. OBJECTIVE: To assess changes in hepatic fibrosis after interferon therapy in patients with chronic hepatitis C. DESIGN: Retrospective cohort study. SETTING: 7 university hospitals and 1 national hospital in Japan. PATIENTS: 593 patients with chronic hepatitis C who underwent a paired liver biopsy from 1987 to 1997. Of these, 487 patients received interferon therapy and 106 patients were untreated. INTERVENTION: Patients in the treatment group received a 2- to 6-month course of interferon within 6 months after the initial biopsy. MEASUREMENTS: Fibrosis and inflammatory activity in paired biopsy samples obtained a median of 3.7 years apart (range, 1 to 10 years) were graded by using the criteria of Desmet and colleagues (F0 to F4) and those of the French METAVIR Cooperative Study Group (A0 to A3), respectively. Changes in fibrosis staging and activity scores and yearly rates of fibrosis progression and regression were calculated. RESULTS: 183 of the 487 interferon-treated patients showed a sustained virologic response. Activity grade was unchanged in most of the untreated patients and improved in 89% (CI, 83% to 93%) of patients with a sustained virologic response. A sustained response to interferon was associated with a mean (+/-SE) reduction in fibrosis score of -0.60+/-0.07 at less than 3 years of follow-up and -0.88+/-0.08 at 3 years or more of follow-up. The rate of fibrosis progression was -0.28+/-0.03 unit/y (regression) in patients with sustained response, 0.02+/-0.02 unit/y in patients with nonsustained response (P< 0.001), and 0.10+/-0.02 unit/y in untreated patients. CONCLUSION: Although the time between biopsies partly affected the patient's clinical course, the differences observed here suggest that in patients with chronic hepatitis C, regression of fibrosis is associated with sustained virologic response to interferon therapy.

Adult↗
PubMed2000

Effect of viral status on recurrence after liver resection for patients with hepatitis B virus-related hepatocellular carcinoma.

BACKGROUND: Risk factors for recurrence after resection of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) require more precise definition. METHODS: Forty patients who underwent liver resection for HBV-related HCC were studied. Their clinical findings, laboratory data (including viral status), pathologic findings, and operative methods were evaluated for recurrence risk in univariate and multivariate analyses. RESULTS: The HB envelope (HBe) antigen, wild-type HBV, intrahepatic metastases, elevated serum activities of aspartate aminotransferase and alanine aminotransferase, and moderately or severely active hepatitis were more likely to be found in patients with a high viral load than in patients with a low viral load. Precore mutant-type HBV was more likely to be found in patients with a low viral load than in patients with a high viral load. The platelet count was significantly lower in the patients with a high viral load. A high viral load, the presence of wild-type HBV, the absence of anti-HBe, the absence of precore mutant-type HBV, Child score B, a low platelet count, and a positive surgical margin were risk factors for recurrence in univariate analysis. A nonanatomic resection tended to be a risk factor. A high viral load and positive surgical margin were independent risk factors for recurrence. CONCLUSIONS: The measurement of viral load and detection of anti-HBe, wild-type HBV, and precore mutant-type HBV are useful for estimating a patient's prognosis after resection of HBV-related HCC.

Adult↗
PubMed2000

Bonding of alkali- and heat-treated tantalum implants to bone.

Alkali- and heat-treated tantalum (Ta) has been shown to bond to bone. The purpose of this study was to investigate the effects of chemical treatments on the bone-bonding ability of tantalum implants in rabbit tibiae. Miyazaki et al. reported in vitro that alkali- and heat-treated tantalum had an apatite forming ability in an acellular simulated body fluid (SBF). In this study, smooth-surfaced rectangular plates (15 x 10 x 2 mm) of pure tantalum and treated tantalum were prepared. The plates were implanted transcortically into the proximal metaphyses of bilateral rabbit tibiae, alkali- and heat-treated plates for one limb and untreated plates for the contralateral limb, which served as a paired control. Bone bonding at the bone/implant interface was evaluated by tensile testing and undecalcified histological examination, at 8 and 16 weeks after implantation. The treated implants showed weak bonding to bone at 8 weeks, and exhibited significantly higher tensile failure loads compared with untreated tantalum implants at 16 weeks. The untreated implants showed almost no bonding, even at 16 weeks. Histological examination by Giemsa surface staining, contact microradiography (CMR), and scanning electron microscopy (SEM) revealed that treated tantalum implants bonded directly to bone tissue. In contrast, the untreated tantalum implants had a intervening fibrous tissue layer between the bone and the plate and did not bond to bone at 8 and 16 weeks. It is clear from these results that alkali and heat treatment induce the bone-bonding ability of tantalum. This new bioactive tantalum should be an effective material for weight-bearing and bone-bonding orthopedic devices.

Alkalies↗
PubMed2000

TT virus infection in patients with chronic liver disease of unknown etiology.

The role of a novel virus, designated as TT virus (TTV), as a cause of chronic liver disease has not been well defined. We investigated the prevalence of TTV among 69 patients with chronic liver disease of unknown etiology and 50 volunteer blood donors with normal transaminase levels. TTV DNA was amplified by polymerase chain reaction (PCR) by using two different sets of primers: one based on the sequence of the original N22 clone within the open reading frame 1 (set A) and the other derived from the untranslated region (set B). The prevalence of TTV detected by PCR primers set A only, set B only, and in total (by either set A or B) was 11 (31%), 31 (86%), and 31 (86%) of 36 patients with chronic hepatitis; 2 (40%), 4 (80%), and 4 (80%) of 5 with cirrhosis; 11 (39%), 17 (61%), and 22 (79%) of 28 with hepatocellular carcinoma; and 9 (18%), 39 (78%), and 40 (80%) of 50 volunteer blood donors, respectively. Of the interpretable 25 PCR products amplified with primers set A, 9 were classified as genotype 1a, 10 as genotype 1b, 4 as genotype 2, 1 as genotype 3, and 1 as genotype 4. Molecular evolutionary analysis did not suggest any particular strains of TTV that might be associated with chronic liver disease. The nucleotide sequences of the untranslated region on which PCR primers set B were designed were highly conserved, and the interpretable 22 PCR products amplified with primers set B were not clearly divisible into distinct genotypes. Our findings provided no evidence that TTV is a causative agent of chronic liver disease.

Chronic Disease↗
PubMed2000

Sublobular veins as the main site of lymphocyte adhesion/transmigration and adhesion molecule expression in the porto-sinusoidal-hepatic venous system during concanavalin A-induced hepatitis in mice.

Lymphocyte infiltration is a manifest feature of hepatitis. To reveal the main site and mechanism of lymphocyte adhesion/extravasation in the hepatic vasculature during inflammation, we morphometrically and histologically analyzed these events in relation to adhesion molecule expression using a murine model of T-cell mediated hepatitis induced by concanavalin A (Con A). Although lymphocyte adhesion was restricted to the sinusoids in untreated mice, it increased in all the segments of porto-sinusoidal-hepatic venous system 8 hours after Con A injection; the number of adhering lymphocytes per unit vascular circumference was the largest in the sublobular veins, relatively large in the central veins and small hepatic veins, and relatively small in the sinusoids and negligible in the portal veins. At 20 hours, extravascular lymphocytes showed similar distribution to lymphocyte adhesion at 8 hours except in the portal veins, around which they were possibly accumulated by the translocation of extrasinusoidal lymphocytes. E-selectin and vascular cell adhesion molecule-1 (VCAM-1) were transiently expressed at 4 to 6 hours, whereas P-selectin and intercellular adhesion molecule-1 were not changed between 0 and 48 hours. In particular, E-selectin expression coincided with that of lymphocyte adhesion in distribution. Lymphocyte attachment was inhibited by pretreatment with anti-E-selectin monoclonal antibody (MAb) or anti-VCAM-1 MAb, and expression of E-selectin and VCAM-1 was suppressed by pretreatment with anti-tumor necrosis factor-alpha (TNF-alpha) MAb. Electron microscopically, lymphocytes were trapped by endothelial lamellipodia and traversed the endothelium by diapedesis. These results indicate that lymphocyte adhesion/transmigration preferentially takes place in the sublobular veins in association with TNF-alpha-induced endothelial activation, i.e., E-selectin and VCAM-1 expression and lamellipodia formation.

Animals↗
PubMed2000

Course before and after percutaneous transhepatic portal vein embolization of a patient with cholangiocarcinoma monitored by scintigraphy with Tc-99m galactosyl human serum albumin.

Percutaneous transhepatic portal vein embolization (PTPE) causes atrophy of the embolized lobe and compensatory hypertrophy of the nonembolized lobe, and improves the safety of hepatectomy. We report a patient with cholangiocarcinoma who underwent embolization of both anterior and posterior branches of the right portal vein before hepatectomy. Scintigraphy with Tc-99m galactosyl human serum albumin was performed before and 4 weeks after PTPE. After PTPE, the right lobe of the liver was atrophied and the left lobe of the liver was enlarged, compared with before PTPE. The receptor index of the entire liver was almost unchanged before and after PTPE, but the right lobe receptor index after PTPE was 23% less than the pre-PTPE value, whereas the left lobe receptor index had increased 37%. Scintigraphy with Tc-99m galactosyl human serum albumin is useful for evaluating segmental functional reserve before and after PTPE.

Aged↗
PubMed2000

Clinical usefulness of positron emission tomography with fluorine-18-fluorodeoxyglucose in the diagnosis of liver tumors.

We studied various liver tumors by positron emission tomography with fluorine-18 fluorodeoxyglucose (FDG-PET) to examine the diagnostic usefulness of this technique. We also examined the relation between findings on FDG-PET and the characteristics of hepatocellular carcinoma. FDG-PET was performed in 78 patients with liver tumors, including 53 with primary liver cancer [48 hepatocellular carcinomas (HCC) and 5 cholangiocellular carcinomas (CCC)], 20 with metastatic liver cancer, 2 with liver hemangioma, and 3 with focal nodular hyperplasia. For quantitative evaluation, a region of interest (ROI) was placed over the entire tumor region, at the level of the maximum diameter of the tumor. A background ROI was then placed over the non-tumor region of the liver. The average activity within each ROI was subsequently corrected for radioactive decay, and the standardized uptake value (SUV) was calculated by dividing the tissue activity by the injected dose of radioactivity per unit body weight. SUV ratio was expressed as the tumor-to-non-tumor ratio of the SUV. The median SUV was significantly lower in HCC than in metastatic live cancer or CCC, and the median SUV ratio was significantly lower in HCC than in metastatic liver cancer or CCC. The median SUV was not higher in multiple HCC than in single HCC, but the median SUV ratio was significantly higher in multiple HCC than in single HCC. The median SUV and the median SUV ratio were significantly higher in the presence of portal vein thrombosis than in the absence of such thrombosis. The Cancer of the Liver Italian Program score and the alpha-fetoprotein value correlated significantly with both the SUV and SUV ratio. These results suggest that FDG-PET is clinically useful not only for the differential diagnosis of liver tumors but also for evaluation of the clinical characteristics of HCC.

Adult↗
PubMed2000

A case of cavernous hemangioma of the small intestine diagnosed by scintigraphy with Tc-99m-labeled red blood cells.

Hemangioma of the small intestine is rare, and the preoperative diagnosis of it is difficult. We report a patient with gastrointestinal bleeding for whom Tc-99m-labeled red blood cell scintigraphy was useful in diagnosing cavernous hemangioma of the small intestine. A 25-year-old man was referred to our hospital for recurrent iron deficiency anemia. Because of the patient's severe anemia, imaging was performed to locate the bleeding lesion in the gastrointestinal tract. Scintigraphy with Tc-99m-labeled red blood cells revealed pooling indicating a tumor and extravasation of blood from the tumor. Scintigraphy with Tc-99m pertechnetate revealed no abnormal accumulation. Partial resection of the small intestine was done, and cavernous hemangioma of the small intestine was diagnosed by using the specimen of resected tissue.

Adult↗
PubMed2000

A case of recurrent cholangitis after bile duct injury during laparoscopic cholecystectomy: value of scintigraphy with Tc-99m GSA and hepatobiliary scintigraphy for indication of lobectomy.

A 39-year-old woman with acute cholecystitis and gallstones underwent laparoscopic cholecystectomy. She suffered from recurrent episodes of cholangitis due to injury of the major bile ducts during laparoscopic cholecystectomy. Hepatobiliary scintigraphy with Tc-99m Sn-N-pyridoxyl-5-methyltryptophan was performed. Although normal bile excretion was found from the left hepatic duct to the percutaneous transhepatic biliary drainage (PTBD) tube, excretion from the right hepatic lobe was prolonged. Scintigraphy with Tc-99m diethylenetriaminepentaacetic acid-galactosyl human serum albumin demonstrated atrophy of the right hepatic lobe and enlargement of the left hepatic lobe. Cholangiography via the PTBD tube revealed complete obstruction of the left hepatico-jejunal anastomosis and could not enhance the right intrahepatic bile duct. A right hepatic lobectomy was performed because of the atrophy, glissonitis and the absence of an appropriate bile duct for reconstruction. Postoperatively she was active and exhibited no evidence of recurrent cholangitis.

Adult↗
PubMed2000

Risk factors for recurrence after resection of hepatitis C virus-related hepatocellular carcinoma.

Although there have been many studies of the risk factors for recurrence after resection of hepatocellular carcinoma (HCC), the subjects were patients with various viral status in the previous studies, and hepatitis C viremia has not been evaluated. We investigated risk factors, including hepatic C viremia and histologic findings of noncancerous hepatic tissue, for recurrence after resection of hepatitis C virus (HCV)-related HCC. A total of 223 patients who underwent liver resection for HCV-related HCC were studied. HCV viremia, laboratory data, degree of HCC malignancy, histologic findings in noncancerous hepatic tissue, preoperative interferon therapy, and operative methods were evaluated for recurrence risk by univariate and multivariate analyses. Serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and total bilirubin, and the proportion of patients with a high histologic activity score (mild to severe active hepatitis) were significantly higher in patients with HCV viremia than in those without viremia. Serum albumin was significantly lower in patients with HCV viremia. By univariate analysis, older age (> 65 years old), HCV viremia, elevated AST (> 40 IU/L) and ALT (> 45 IU/L), large tumors (> 40 mm), multiple HCCs, moderately or poorly differentiated HCC, portal invasion, mild to severe active hepatitis, and lack of preoperative interferon therapy were risk factors for recurrence. Multivariate analysis showed that older age, HCV viremia, high AST, multiple HCCs, and portal invasion were independent risk factors. For HCV-related HCCs, not only the degree of malignancy of the HCC but also HCV viremia and active hepatitis are risk factors for recurrence.

Aged↗
PubMed2000

Effect of ethanol on bone mineral density of rats evaluated by dual-photon X-ray absorptiometry.

Abuse of alcohol may derange bone metabolism and cause osteoporosis. Due to confounding factors associated with alcohol abuse, e.g., dietary deficiencies and liver damage, a study using an animal model is preferable to examine whether alcohol itself actually reduces bone density. We evaluated the effect of alcohol intake on bone in rats by dual-energy X-ray absorptiometry. Six-week-old male (n = 16) and female (n = 16) Wister rats were divided into two groups. Sixteen alcohol-exposed rats (8 male and 8 female) were fed Lieber's liquid diet and 16 control rats (8 male and 8 female) were fed a control liquid diet. The bone mineral density (BMD) and bone mineral content (BMC) of the right femur were measured before and after experimental feeding under anesthesia. The BMD of lumbar spine (L2-L4) of sacrificed rats was measured. For male rats, BMD and BMC decreased significantly in the alcohol group (P = 0.0132 and 0.0133, respectively) but did not decrease in control group. For female rats, BMD and BMC decreased significantly in the alcohol group (P = 0.0012 and <0.0001, respectively) but did not decrease in the control group. For male rats, the mean ratio of BMD after experimental feeding divided by BMD before experimental feeding was significantly lower in the alcohol group than in the control group (P = 0.0031). For female rats, the mean ratio of BMD after experimental feeding divided by BMD before experimental feeding was also lower in the alcohol group than in the control group (P = 0.0002). For male rats, the mean BMD of L2-L4 after experimental feeding was significantly lower in the alcohol group than in the control group (P = 0.0210). For female rats, the mean BMD of L2-L4 after experimental feeding was also significantly lower in the alcohol group than in the control group (P = 0.0006). These results indicate that alcohol intake decreased the BMD of rats in both spongy and cortical bone, and that the reduction of BMD was greater in female rats than in male rats.

Absorptiometry, Photon↗
PubMed2000

Formation of a bioactive graded surface structure on Ti-15Mo-5Zr-3Al alloy by chemical treatment.

Simple NaOH and heat treatments provided a Ti-15Mo-5Zr-3Al alloy with a bioactive graded surface structure of an amorphous sodium titanate, where the sodium titanate on the top surface gradually changed into the alloy substrate through titanium oxide. The sodium titanate was free of alloying species of Mo, Zr and Al, since almost all of them were released from the surface of alloy during the first NaOH treatment. The sodium titanate transformed into a hydrated titania via Na+ ion release to induce a bone-like apatite formation on the alloy substrate in a simulated body fluid (SBF). The alloying species neither were released into the SBF nor affected the apatite formation. In the process of apatite formation, the graded surface structure developed into one where the apatite on the top surface gradually changed into the alloy composition through hydrated titania and titanium oxide. It is expected that this graded structure will lead to a strong interfacial bonding strength between the apatite layer and the alloy substrate, thereby providing a tight integration of the alloy with living bone through the apatite layer.

Alloys↗
PubMed2000

Formation of bioactive functionally graded structure on Ti-6Al-4V alloy by chemical surface treatment.

An Al- and V-free sodium titanate hydrogel layer with a graded structure where the sodium titanate gradually decreases toward the interior, was formed on the surface of Ti-6Al-4V alloy, when the alloy was exposed to 5M NaOH solution at 60 degrees C for 24 h. This gel layer was transformed into an amorphous sodium titanate layer without giving considerable change in the graded structure, except a little increase in the depth of the oxygen distribution by a heat treatment at 600 degrees C for 1 h. The sodium titanate layer formed Ti-OH groups on its surface by exchanging its Na+ ion with H3O+ ion in simulated body fluid when soaked in the fluid, and thus formed Ti-OH groups induced the apatite nucleation. The apatite layer also formed a graded structure toward the substrate. The strong bond of the apatite layer to the substrate was attributed to this graded structure.

Journal Article↗