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Biomedical subjects

S Nishiguchi

Publications and source records attributed to S Nishiguchi.

At least 37 records · Page 2Linked to original sources

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↗

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↗

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↗

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↗

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↗

Lack of the Polycomb-group gene rae28 causes maturation arrest at the early B-cell developmental stage.

The rae28 gene (rae28) is a murine homologue of the Drosophila polyhomeotic gene, which is a member of the Polycomb-group genes. In this study, we examined the role of rae28 in lymphocyte development. Because homozygous rae28-deficient (rae28-/-) mice died in the perinatal period, we examined lymphocyte development by generating chimeric mice reconstituted with green fluorescence protein-labeled mutant fetal liver cells as well as in in vitro culture systems. We further examined RAE28 expression by reverse transcriptase polymerase chain reaction assay in human leukemic cells with B-lineage acute lymphoblastic leukemia (ALL). Severe B-cell maturation arrest was observed in rae28-/- between pro- and pre-B lymphocyte stages. B-cell development was also delayed in heterozygous neonates. Furthermore, interleukin-7-dependent colony-forming ability was impaired not only in homozygous lymphocytes but also in heterozygotes. Its human homologue, RAE28, is located on chromosome 12p13, which frequently is associated with chromosomal abnormalities and loss of heterozygosity in patients with hematologic malignancies. To determine whether a link exists between RAE28 and leukemia, we examined RAE28 expression in leukemic cells from pediatric patients with B-lineage ALL. RAE28 expression was not detected in four B-cell precursor ALL cases of a total of 43 examined, although RAE28 is normally expressed constitutively during the process of B-cell maturation as assessed in isolated cell populations. rae28 plays an important role in the early B-cell developmental stage in a gene dosage-dependent manner. Furthermore, the human RAE28 locus may provide a candidate gene causing the molecular pathogenesis of childhood B-cell precursor ALL.

Animals↗

Identification of genes differentially expressed by putrescine in HepG2 hepatoblastoma cells.

In order to identify genes differentially expressed by putrescine, a polyamine, which play important roles in the regulation of cell proliferation and the development of cancer, we performed mRNA differential display analysis using total RNA extracted from HepG2 cells (human hepatoblastoma cell line) treated with a specific inhibitor of polyamine biosynthesis, alpha-difluorometylornithine (DFMO). A total of 25 genes were up-regulated and 32 genes down-regulated by putrescine. Of the genes differentially expressed by putrescine, we chose three that were related to the respiratory chain and oxidative phosphorylation and analyzed them by Northern blot analysis. Cytochrome oxidase subunit 1, low molecular mass ubiquinone-binding protein, and NADH dehydrogenase subunit 2 were found to be down-regulated by putrescine. We examined intracellular ATP level in HepG2 cells, and found that ATP level in DFMO-treated cells was increased by exogenous putrescine.

Journal Article↗

Previous or occult hepatitis B virus infection in hepatitis C virus-associated hepatocellular carcinoma without hepatic fibrosis.

We investigated the role of hepatitis B virus infection in development of hepatocellular carcinoma in hepatitis C virus-infected patients without hepatic fibrosis. Of 253 patients, 8 lacked hepatic fibrosis (group 1); group 2 included the remaining 245 patients. Clinicopathologic findings were compared between the groups. Hepatitis B x gene was sought in cancers and adjoining noncancerous liver. Group 1 showed better liver function parameters and milder active hepatitis than group 2. The proportion of patients with anti-hepatitis B virus antibody tended to be higher in group 1 than in group 2. The proportion of patients with hepatitis B x RNA in cancers was significantly higher in group 1 than in group 2. All group 1 patients had previous or occult hepatitis B virus infection. Previous or occult hepatitis B virus infection may be critical in development of hepatocellular carcinomas in hepatitis C virus-infected patients without hepatic fibrosis.

Aged↗

Comparison of real-time quantitative polymerase chain reaction with three other assays for quantitation of hepatitis C virus.

BACKGROUND AND AIMS: Evaluation of serum levels of hepatitis C virus (HCV) is important for predicting the response to interferon treatment and monitoring its therapeutic efficacy. The aim of this study was to evaluate real-time quantitative polymerase chain reaction (PCR) as a method for the measurement of HCV-RNA. METHODS: The subjects were 50 patients with chronic hepatitis C: 36 with genotype 1b, eight with genotype 2a, and six with genotype 2b. Samples were tested for HCV-RNA by using real-time quantitative PCR with the ABI Prism 7700 sequence detection system, a branched DNA signal amplification assay, and an Amplicor monitor test; and for HCV core protein by using a fluorescent enzyme immunoassay. RESULTS: The detection range of the real-time quantitative PCR was between 10(1)-10(8) copies/mL of HCV-RNA. Hepatitis C virus RNA was detectable in all 50 samples by the use of real-time quantitative PCR, but was undetectable in 14 samples by the use of a branched DNA assay and in two samples by using the Amplicor monitor test; HCV core protein was undetectable in three samples. A significant correlation was found between the results of real-time quantitative PCR and those of the three other assays: branched DNA assay (r = 0.837, P < 0.0001), Amplicor monitor test (r = 0.853, P < 0.0001), and HCV core protein concentrations (r = 0.549, P < 0.0001). CONCLUSIONS: Our results showed that the real-time quantitative PCR was a highly sensitive assay for the measurement of HCV-RNA.

Adult↗

Hepatitis C virus core protein enhances the activation of the transcription factor, Elk1, in response to mitogenic stimuli.

Mitogen-activated protein kinase (MAPK) pathways play key roles in cell proliferation, transformation of mammalian cells, and the stress response. We and other investigators showed that hepatitis C virus (HCV) core protein has an oncogenic potential, but its mechanism has remained unknown. We previously demonstrated that the MAPK-extra-cellular signal-regulated kinase (ERK) kinase (MEK)-ERK pathway and its downstream target, the serum response element (SRE), is activated in BALB/3T3 cells producing HCV core protein. To elucidate the precise mechanism by which HCV core protein activates the MEK-ERK pathway, we transiently expressed HCV core protein in several cell lines and studied the signal transduction of the pathway, using Gal4-Elk1 luciferase assay, in vitro kinas assay of MAPK, and Western blotting analysis. We discovered that, in the presence of mitogenic signal, HCV core protein enhanced Elk1 activation working downstream of MEK without affecting ERK activity and Elk1 phosphorylation. Our data suggest that HCV core protein may activate Elk1 through a pathway alternative to the typical phosphorylation cascade. These findings might give new insights into the role of HCV in hepatocarcinogenesis.

3T3 Cells↗

Method to detect substitutions in the interferon-sensitivity-determining region of hepatitis C virus 1b for prediction of response to interferon therapy.

Substitutions deduced by direct sequencing in the interferon-sensitivity-determining region (ISDR) of hepatitis C virus (HCV) are related to patients' responses to interferon (IFN), but sequencing is time consuming and results are only for the dominant virus. We developed a rapid method to detect such changes. With serum from 50 patients with chronic hepatitis C (genotype 1b) given IFN-alpha, a way to detect changes in ISDR by hybridization with oligonucleotide probes that had a prototype nucleotide sequence of HCV-J was established. Hybridization intensity was expressed as optical density (OD(NS5A)). The method was checked with serum from 100 more patients. In the study of 50 patients, all 21 with the prototype sequences had a high OD(NS5A) (> or = 0.4), and all 8 patients with a mutant-type sequence had low values (< or = 0.2). Twelve (95% confidence interval, 36-81%) of 20 patients with OD(NS5A) of <0.4 and 2 (1%-22%) of 30 patients with OD(NS5A) > or = 0.4 had complete responses (CR). All nine (66%-100%) patients with OD(NS5A) <0.4 and little HCV RNA (<100 kIU/mL) had CR, but none (0%-14%) of the 24 patients with high values from both predictors had CR. In the study of 100 patients, OD(NS5A) and the HCV RNA level were independent predictors of the effects of IFN. By multivariate analysis, the odds ratio for a CR in patients with OD(NS5A) of > or = 0.4 was 0.015 (0. 001-0.190) compared with the other patients (P =.001). In conclusion, our method should be useful in identification of prototype strains, which generally resist IFN therapy.

Amino Acid Substitution↗

Reactivation of viral replication after liver resection in patients infected with hepatitis B virus.

OBJECTIVE: To investigate the mechanisms and risk factors underlying postoperative reactivation of hepatitis after liver resection for hepatitis B virus-related hepatocellular carcinoma. SUMMARY BACKGROUND DATA: Although risk factors for acute hepatic failure after liver resection have been reported in patients with chronic liver disease, the issue of reactivation of hepatitis B virus replication after liver resection is unresolved. METHODS: Fifty-five patients with hepatocellular carcinoma and hepatitis B surface antigen underwent liver resection. In 25 of these 55 patients, serum levels of hepatitis B virus DNA and the type of hepatitis B virus were determined before and after surgery. RESULTS: Postoperative hepatitis occurred in 13 of the 55 patients (24%). Reactivation of viral replication occurred after liver resection in 7 of the 25 patients tested, and alanine aminotransferase activity increased in 6 of these 7 patients. High preoperative alanine aminotransferase activity, high levels of hepatitis B virus DNA, presence of wild-type DNA, and detection of hepatitis B core antigen in hepatocytes, all features of the immune clearance phase in the natural course of hepatitis B virus infection with no surgery, were more likely to be found in patients with reactivation than in patients without reactivation. CONCLUSIONS: During the immune clearance phase of hepatitis B virus infection, especially the period of acute exacerbation, changes in serum hepatitis B virus DNA level should be monitored for early warnings of reactivation of viral replication, likely to cause severe postoperative hepatitis and acute hepatic failure.

Adult↗

Influence of previous interferon therapy on recurrence after resection of hepatitis c virus-related hepatocellular carcinoma.

Interferon (IFN) therapy decreases the incidence of hepatocellular carcinoma (HCC) in patients with hepatitis C virus (HCV). One hundred and fifty-nine consecutive patients who underwent liver resection for HCV-related HCC were studied. In 17 (group 1) of the 159 patients, HCC was detected during or after IFN therapy. The incidences of recurrence after surgery in the group 1 patients and the other 142 patients (group 2) were compared. Eight patients had a complete response to IFN, 4 had a partial response, and 5 had no response. The proportion of patients without HCV viremia was significantly higher in the group 1 patients (P < 0.0001). The tumor-free survival rate was significantly higher in the group 1 patients (P = 0.0010). By multivariate analysis of various risk factors for recurrence, no previous IFN was a significant independent risk factor for recurrence (risk ratio = 6.336; 95%CI, 1.512 - 26.50). The patients with HCC who underwent IFN therapy previously are good candidates for liver resection because recurrence after the operation was rarely observed.

Aged↗

Usefulness of positron emission tomography with fluorine-18-fluorodeoxyglucose for predicting outcome in patients with hepatocellular carcinoma.

OBJECTIVES: The present study was designed to assess the usefulness of positron emission tomography with fluorine-18-fluorodeoxyglucose (FDG-PET) for predicting outcome in patients with hepatocellular carcinoma. METHODS: FDG-PET was performed in 48 patients with hepatocellular carcinoma. For quantitative evaluation, a region of interest (ROI) was placed over the area of maximum activity within the lesion. A background ROI was then placed over the nontumor 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-nontumor ratio of the SUV. RESULTS: The tumor-volume doubling time, as index of the growth rate of hepatocellular carcinoma, correlated significantly with SUV ratio but did not correlate with SUV. On the basis of the SUV ratio, the patients were divided into two groups of similar size: group A, SUV ratio of < or = 1.5; and group B, SUV ratio > 1.5. The cumulative survival rate was significantly lower in group B than in group A. On the basis of the SUV, the patients were divided into two groups of roughly equal size: group C, < or = SUV 2.6; and group D, > SUV 2.6. The cumulative survival rate was similar in these groups. On regression analysis with the Cox proportional hazards model, the SUV ratio and tumor number were significantly related to survival. CONCLUSIONS: These results suggest that FDG-PET is useful not only for the evaluation of the malignancy of hepatocellular carcinoma but also for the prediction of outcome in patients with hepatocellular carcinoma.

Adult↗

Virologic and biochemical changes and prognosis after liver resection for hepatitis B virus-related hepatocellular carcinoma.

BACKGROUND/AIMS: During the natural course of hepatitis B virus (HBV) infection, clearance of HB e antigen (HBeAg) and HB surface antigen (HBsAg) occurs with remission of liver disease. We investigated the effects of postoperative changes in virologic and biochemical parameters on the prognosis after liver resection for HBV-related hepatocellular carcinoma (HCC). METHODS: We investigated the relationship between postoperative changes in virologic and biochemical parameters and the incidence of intrahepatic recurrence and the outcome during a 3-year period following surgery in 30 HCC patients with HBsAg. RESULTS: The incidence of intrahepatic recurrence of HCC was significantly higher in patients with acute postoperative exacerbation of hepatitis (p = 0.0084), a sustained high serum concentration of HBV DNA (> or = 5.0 mEq/ml, p = 0.001), and sustained expression of HBsAg after surgery (p = 0.0421). A high serum concentration of HBV DNA was significantly associated with a shorter survival time (p = 0.0447) and the cause of death was recurrence of HCC. CONCLUSION: Patients with acute postoperative exacerbation of hepatitis, sustained HBsAg expression, and sustained high serum concentrations of HBV DNA after surgery may require more intensive postoperative monitoring for HCC recurrence.

Adult↗

Production and characterization of active soluble human beta1,4-galactosyltransferase in Escherichia coli as a useful catalyst in synthesis of the Gal beta1-->4 GlcNAc linkage.

An active and soluble human beta1,4-galactosyltransferase (beta-GT) was produced in Escherichia coli using a maltose-binding protein fusion system. The purified recombinant beta-GT has a K(m) value of 0.035 mM for UDP-galactose and a V(max) of 643 x 10(3) nmol/mg/h. The enzyme catalyzes the transfer of galactose from UDP-galactose to N-linked oligosaccharides. The properties of the purified enzyme were identical to those of bovine milk beta-GT.

Journal Article↗