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Biomedical subjects

S Noguchi

Publications and source records attributed to S Noguchi.

At least 199 records · Page 11Linked to original sources
PubMed1998

Allelic imbalance of insulin-like growth factor II gene expression in cancerous and precancerous lesions of the liver.

Allelic imbalance of the insulin-like growth factor II (IGF II) gene expression is often seen in hepatocellular carcinoma (HCC). To investigate the role of allelic imbalance in hepatocarcinogenesis, we have studied allelic expression status of the IGF II gene in dysplastic nodules, which are precancerous lesions of HCC, as well as in HCCs of different histological grade, and the influence of the allelic imbalance on IGF II gene expression has also been examined. Allelic imbalance was observed in 3 of 7 dysplastic nodules, in 7 of 9 well-differentiated HCCs, and in 8 of 9 moderately differentiated HCCs. IGF II gene expression level, which was studied by a semiquantitative reverse-transcriptase polymerase chain reaction (RT-PCR), was significantly higher (3.6-fold) in the dysplastic nodules than the control livers, but a significant increase in the IGF II gene expression was not observed in well- and moderately differentiated HCCs as compared with the control livers. These results demonstrate that the allelic imbalance of the IGF II gene expression is seen in the early stage (precancerous lesions) of hepatocarcinogenesis. Association of the allelic imbalance with an increased expression of the IGF II gene in the precancerous lesions might suggest a possible involvement of an IGF II autocrine loop in the pathogenesis of these lesions.

Alleles↗
PubMed1998

Sero-epidemiologic study of hepatitis C virus infection in Fukuoka, Japan.

We conducted an epidemiological study of 509 residents of H town, Fukuoka, Japan, to investigate the high mortality rate from liver disease. Antibodies to hepatitis C virus (HCV) (anti-HCV) were detected in 120 residents (23.6%); HCV RNA in 91 (17.9%), and hepatitis B surface antigen (HBsAg) in 13 (2.6%). Multivariate logistic regression analyses showed that presence of anti-HCV, male gender, and history of liver disease were associated with the presence of liver dysfunction, and that age of more than 40 years and a particular district were associated with the presence of anti-HCV. HCV RNA was more frequently detected in anti-HCV-positive men than women (41, or 85.4% versus 50, or 69.4%) (P < 0.05). The incidence of liver dysfunction was significantly higher in HCV RNA-positive men than women (32, or 66.7% versus 22, or 30.6%) (P < 0.05). These findings suggest that: (1) HCV was correlated with the high mortality rate from liver diseases, (2) there were district-related differences in the incidence of HCV, and (3) the lower frequency of elimination of HCV from men may explain why they showed a high mortality from liver disease.

Adult↗
PubMed1998

Cyclin D1 protein overexpression is related to tumor differentiation, but not to tumor progression or proliferative activity, in transitional cell carcinoma of the bladder.

PURPOSE: We attempted to clarify the significance of cyclin D1 in the development and progression of transitional cell carcinoma of the bladder in humans. MATERIALS AND METHODS: Immunohistochemical staining of archival tissue specimens of transitional cell bladder carcinoma obtained from 163 patients was performed by the labeled streptavidin-biotin-peroxidase method. RESULTS: Cyclin D1 protein overexpression was observed in 51 of the 163 specimens (31.3%). Cyclin D1 protein overexpression was showed a highly significant inverse correlation with the histological grade of malignancy (p < 0.01). Grade 3 tumors showed a highly significant low incidence of cyclin D1 protein overexpression as compared with grade 2 tumors (p < 0.01). There was no significant correlation between the overexpression of cyclin D1 protein and tumor stage or the Ki-67 labeling index. CONCLUSION: Cyclin D1 in transitional cell bladder carcinoma was closely related to tumor differentiation but not to tumor progression. Transitional cell carcinoma of the bladder may utilize another pathway for proliferation that is independent of cyclin D1.

Carcinoma, Transitional Cell↗
PubMed1998

Type I interferons are essential mediators of apoptotic death in virally infected cells.

BACKGROUND: The interferons (IFNs) have been extensively studied in the context of host defence against viral infection. In the established model of IFN action, virally infected cells secrete type I IFNs (IFN-alpha/beta) which induce an antiviral state in uninfected cells. However, it is not clear how IFNs function on the infected cells. It has been reported that cells infected by some viruses die by apoptosis. RESULTS: In the present study, we found that three types of viruses commonly induce apoptosis in primary cell cultures. Importantly, we observed that virus-induced apoptosis was inhibited by anti-IFN-alpha/beta antibodies, and in cells lacking either the type I IFN receptor 1 (IFNAR1) or its downstream mediator, Stat1 (Signal transducer and activator of transcription 1). IFN-alpha treatment by itself did not induce apoptosis unless it was combined with transfection by double-stranded RNA (dsRNA), which is normally generated during the course of viral infection. CONCLUSION: These results indicate a novel antiviral function of the type I IFNs, i.e. the selective induction of apoptosis in virally infected cells. In effect, these IFNs have a bifunctional role in limiting the spread of virus; eliciting an antiviral state in uninfected cells while promoting apoptosis in infected cells. Our results may help explain why IFNs are sometimes useful in the treatment of viral diseases and will provide further insight into the mechanisms of virus-induced pathogenesis.

Animals↗
PubMed1998

Sequence and expression of a novel mouse gene PRDC (protein related to DAN and cerberus) identified by a gene trap approach.

Gene trapping in embryonic stem (ES) cells was used to identify a novel gene involved in mouse development. In order to screen trapped ES cell lines for the presence of developmentally regulated genes, an in vitro differentiation test was used. One of the G418 resistant cell lines, in conjunction with the lacZ reporter gene, showed differential expression patterns under differentiated and undifferentiated conditions. The gene trap insertion in this cell line was germ-line transmitted and X-gal staining was used to assess the expression pattern of lacZ in embryos heterozygous for the trapped allele. The reporter gene's expression was detected in commissural neurons in the developing spinal cord, suggesting functions for the trapped gene in mouse neural development. Structural analysis of the cDNA revealed that this trapped gene, named PRDC (protein related to DAN and cerberus), is a novel gene that encodes a putative secretory protein consisting of 168 amino acid residues. PRDC gene product shows limited similarities to the products of DAN (differential screening-selected gene aberrative in neuroblastoma) and cerberus. (DAN is a possible tumor-suppressor for neuroblastoma in human. Cerberus can induce an ectopic head in Xenopus embryos when ectopically expressed.) These three gene products may form a novel family of signaling molecules.

Alleles↗
PubMed1998

Production of immunoreactive 2',5'-oligoadenylate synthetase in p48-deficient mice.

2',5'-Oligoadenylate synthetase (2'5'OAS), an enzyme induced by interferon (IFN), is physiologically produced in IFN-untreated normal healthy mice. The enzyme is localized mainly in the epithelium of the digestive tract, reproductive organs, and the choroid plexus in the brain. 2'5'OAS is also detected in oocytes in the ovary and in neurons and glial cells of both the telencephalon and cerebellum. Here, we examined the role of p48 (ISGF3gamma), a component of IFN-stimulated gene factor 3 (ISGF3), in the physiologic production of 2'5'OAS using p48-deficient mice generated by gene targeting. In the p48-deficient mice, the physiologic production of 2'5'OAS localized in the following cells was severely impaired: hepatocytes, Kupffer cells, splenocytes, epithelium of the large intestine, oviduct, and uterus, and neurons and glial cells in both the telencephalon and cerebellum. The results show that 2'5'OAS in these cells is induced physiologically through a pathway including p48. However, the production of 2'5'OAS in oocytes was not affected in the p48-deficient mice, indicating that oocyte 2'5'OAS is produced through a p48-independent pathway. A possible function of the GAS sequence found in the promoter region of the 2'5'OAS gene to which Stat6 may bind also is discussed.

2',5'-Oligoadenylate Synthetase↗
PubMed1998

Chronic thyroiditis as a favorable prognostic factor in papillary thyroid carcinoma.

A subgroup of patients with papillary thyroid carcinoma (PTC) also has chronic thyroiditis (CT) as an associated disease of the thyroid. To assess the prognostic value of CT in patients with PTC, we reviewed the histological slides of 2225 patients with PTC who had undergone surgery between 1971 and 1992. Of the 2225 patients, 692 were excluded from the analysis because regional lymph nodes and/or nonneoplastic thyroid tissues were unavailable for histological assessment. The series included 281 patients with CT in nonneoplastic thyroid tissue and 1252 without CT. We performed statistical analyzes by the log-rank test and Cox's proportional-hazard method. Sixty-two (5.0%) of the 1252 patients without CT died of metastatic disease during the follow-up period and the relapse-free 10-year survival rate was 85%. By contrast, only 2 (<1.0%) of the 281 patients with CT died, and their relapse-free 10-year survival rate was 95%. The difference between patients with CT and those without CT in terms of relapse-free and overall survival was statistically significant (p < 0.0001). Risk factors for unfavorable outcome were age 45 years or more, absence of psammoma bodies, and absence of CT (p < 0.0001), followed by vascular invasion (p = 0.0007), male sex (p = 0.0013), and metastasis to regional lymph nodes (p = 0.047). Multivariate analysis indicated that all of these factors with the exception of gender were independent factors in the final model for overall survival. Chronic thyroiditis in the nonneoplastic thyroid of patients with PTC is a powerful prognostic factor for both relapse-free and overall survival.

Adult↗
PubMed1998

Novel point mutations and allele loss at the RET locus in sporadic medullary thyroid carcinomas.

Germline mutations in the RET proto-oncogene have been shown to be the underlying cause of multiple endocrine neoplasia type 2 (MEN 2A and 2B) and familial medullary thyroid carcinoma (FMTC). Some cases of sporadic medullary thyroid carcinoma (sporadic MTC) are reported to have specific codon 918, 883 and 768 mutations of the RET gene in tumor tissues. We examined RET gene mutations in 40 Japanese cases who had previously undergone surgery for sporadic MTC. DNA extracted from formalin-fixed tumor tissues and corresponding normal thyroid tissues or peripheral blood leukocytes was analyzed for mutations of exon 10, 11, 13, 14 and 16 of the RET gene by DNA sequencing and by mutation-specific restriction enzyme analysis. Germline RET point mutations were found in six of 40 cases (15%), cysteine residues at codon 618 in two, codon 634 in three and valine residue at codon 804 in one, and were newly identified as heritable MTC. Of the remaining 34 sporadic MTC cases, four (12%) had tumor-specific RET point mutations. Two were found in exon 16; one case showed an ATG to ACG (Met to Thr) mutation at codon 918, and the other showed two point mutations, ATG to ACG (Met to Thr) at codon 918 and GCA to GTA (Ala to Val) at codon 919 with loss of the wild-type allele, suggesting that both alleles at the RET locus were altered. The other two were found in exon 13; one case showed a CCG to TCG (Pro to Ser) mutation at codon 766 and the other showed a silent mutation, GTC to GTT (Val) at codon 778 with loss of the wild-type allele. There was no association of sporadic mutations with recurrence or prognosis in patients with sporadic MTC. The low rate of somatic RET mutation at codon 918 in our sporadic MTC suggests that as yet unknown factors may be involved. Genetic alterations in both alleles may have an important role in small fraction of sporadic MTCs.

Adult↗
PubMed1998

Prognostic significance of Ki-67, p53, and Bcl-2 expression in prostate cancer patients with lymph node metastases: a retrospective immunohistochemical analysis.

The prognostic significance of Ki-67, p53, and Bcl-2 expression was evaluated in prostate cancer patients with lymph node metastases. Immunohistochemical staining of archived material obtained from 56 patients was performed by the streptavidin-biotin method. Univariate survival analysis showed that a Ki-67 labeling index (Ki-67 LI) of > or = 8.4 in the primary tumor identified a group of patients with a significantly poorer prognosis (P < 0.001). furthermore, a Ki-67 LI of > or = 8.7 in the nodal metastatic tumor was also associated with a poorer prognosis (P < 0.01). Multivariate analysis showed that the Ki-67 LI of primary tumors (P < 0.01) and lymph node metastases (P < 0.01) had independent prognostic value. p53 and Bcl-2 expression had no prognostic value in patients with prostate cancer and lymph node involvement. The Ki-67 LI has more prognostic value than p53 and Bcl-2 expression for patients with prostate cancer that has spread to the lymph nodes.

Aged↗
PubMed1998

Expression of splice variants of CD44 in thyroid neoplasms derived from follicular cells.

Isoform expression of CD44 in follicular carcinoma (FC) of the thyroid was analyzed by immunohistochemical staining and compared to the isoforms in follicular adenoma (FA) and papillary carcinoma (PC) of the thyroid. Variant isoforms of CD44 (CD44v) were detected in these neoplastic cells but not in non-neoplastic cells. CD44v6 was expressed in PC with nodal metastasis and also in FC at significantly higher frequencies than those in PC without metastasis and FA. The frequency of expression of CD44v3 was significantly higher in PC with nodal metastasis than in PC without metastasis. The reverse transcription-polymerase chain reaction (RT-PCR) followed by Southern blotting analysis revealed the presence of a transcript for a variant of CD44 that contained variant exon 6 in FA, FC and PC. DNA sequencing of the products of RT-PCR yielded three species of cDNA for CD44v. One of the cDNA corresponded to a transcript that contained variant exon 6. These results suggest that immunohistochemical staining and RT-PCR with Southern blotting analysis for CD44v6 might be a useful diagnostic tool for the differentiation of FC from FA and that the expression of CD44v3 and CD44v6 might be important for the development of nodal metastasis in cases of PC.

Adenoma↗
PubMed1998

Two cases of adult varicella accompanied by hepatic dysfunction.

Varicella is a typical acute exanthematous viral infection caused by varicella-zoster virus (VZV). In recently years, as far as hepatic dysfunction caused by viruses other than the hepatitis virus is concerned, there have been a few reports on hepatic dysfunction accompanying varicella following organ transplantation of Europe and America and another report on an immunocompromized adult following treatment for Systemic lupus erythematosis (SLE) in Japan. Nonetheless, we searched the MEDLINE and J MEDICINE listing the publications between 1986 and 1996 and found one report on healthy adults with varicella accompanied by hepatic dysfunction in Europe and America and two reports in Japan. Only Noguchi et al. dealt with the findings of liver biopsy. We examined two healthy adults with varicella and mild-to-moderate hepatic dysfunction, and referred to the results of their liver biopsies. The present paper discusses this issue, citing some references.

Adult↗
PubMed1998

Prognostic significance of p53 protein overexpression in transitional cell carcinoma of the renal pelvis and ureter.

Fifty-three patients with invasive transitional cell carcinoma of the renal pelvis and ureter were studied for p53 protein overexpression by immunohistochemistry. Overexpression of p53 protein was observed in 19 patients (35.8%). There was a significant correlation between overexpression of p53 protein and histologic grade (p < 0.01). However, there was no correlation found between p53 immunoreactivity and pathologic stage. By univariate survival analysis, a significant difference in cumulative survival was observed between stage pT2 and stage pT3 or pT4 tumors (p < 0.05). The difference in survival between patients with p53-positive and negative tumors did not reach statistical significance (0.05 < p < 0.01). Multivariate analysis revealed that pathologic stage had an independent prognostic value (p < 0.05). The independent prognostic value of p53 protein overexpression did not quite reach statistical significance (p = 0.07). p53 protein nuclear overexpression appears to be a relatively weak prognostic indicator for patients with invasive transitional cell carcinoma of the renal pelvis and ureter.

Adult↗
PubMed1998

Cytotoxic actions of FTY720, a novel immunosuppressant, on thymocytes and brain neurons dissociated from the rat.

Effects of FTY720 (2-amino-2-(2-[4-octylphenyl]ethyl)-1,3-propanediol HCl), a novel immunosuppressant, were examined on neurons and thymocytes respectively dissociated from rat brains and thymus glands using a flow cytometer to see if FTY720 exerts cytotoxic actions not only on spleen cells as previously reported but also on the other cells. FTY720 at a concentration of 10 microM deteriorated almost all of the thymocytes, while it was not the case for brain neurons. FTY720 increased the intracellular concentration of Ca2+ ([Ca2+]i) of thymocytes in both the presence and absence of external Ca2+, although the [Ca2+]i increased by FTY720 in the presence of external Ca2+ was much greater than that in the absence of external Ca2+. Thus, FTY720 may increase the membrane permeability of Ca2+ and release Ca2+ from intracellular Ca2+ stores in thymocytes. Furthermore, the number of thymocytes stained with ethidium, a dye impermeant to intact membranes, time-dependently increased after drug application. Therefore, FTY720 at concentrations of 3 - 10 microM non-specifically increases the membrane permeability of thymocytes, resulting in necrotic cell death, although FTY720 at micromolar concentrations was reported to induce apoptosis of spleen cells.

Animals↗
PubMed1998

Post-operative thyroid status of patients with Graves' disease is determined by the responsiveness of thyrocyte to TSH under the present thyroid gland remnant.

In order to determine whether thyrocyte responsiveness to TSH is correlated with post-operative thyroid status, thyrocytes obtained from 51 patients with Graves' disease were cultured for 3 days. This was followed by culture with 10 mU/mL of TSH (TSH group) or without TSH (control group) for 3 additional days. On the 8th culture day, the amount of thyroglobulin (Tg) secreted into the culture medium was assayed and the Tg ratio (amount of Tg from the stimulated group/amount of TG from the control group) was calculated. Log10 (the Tg ratio) was used for the statistic study. The post-operative status of the patient was determined based mainly on the serum concentration values of free T3 and T4 obtained between 5 and 16 months after surgery. Multivariate analysis revealed that among age, gender, TSH-binding inhibitory immunoglobulin (TBII) obtained before the surgery, estimated weight of the thyroid gland remnant, and Log10 (Tg ratio), only Log10 (Tg ratio) was statistically significant (P=0.008). When the Log10 (Tg ratio) value was small, most patients showed signs of as post-operative hypothyroidism, and as the value became larger as the number of euthyroid and/or hyperthyroid patients increased.

Adult↗
PubMed1998

Mutations of glucocorticoid responsive element of HBV DNA.

The mutation of glucocorticoid responsive element (GRE) of HBV DNA obtained from a patient with chronic hepatitis B was evaluated. This patient showed fatal course by glucocorticoid administration. The HBV DNA from this patient (GRE-M) and two patients with HBeAg positive chronic hepatitis B (GRE-W1,2) whose HBV DNA have few mutations, were examined. The 212 bp region from nt.274 to nt.485 (GRE region) was amplified by PCR and the nucleotide sequence was determined. A base mismatched sequence of the latter half of the GRE consensus sequence was confirmed at nt.296-301 (G1), nt.347-352 (G2), nt.359-364 (G3), and nt.473-478 (G4). Also one base mismatched sequence of the AP-1 response element was detected at nt.331-337 (A1). The nucleotide substitutions in GRE-M generate three putative loop formation sites, four bases in length, from nt.22 to nt.31 (L1), nt.35 to nt.42 (L2), and nt.74 to nt.83 (L3). The L1 was located just upstream of the G1. The L2 was located between the A1 and the G2. These mutations followed by three-dimensional form change may affect the responses to glucocorticoid.

Base Sequence↗
PubMed1998

Negative-strand HCV RNA was not detected in bone marrow cells of patients with HCV infection.

To determine whether hepatitis C virus (HCV) replicates in bone marrow, we investigated positive- and negative-strand HCV RNA in bone marrow cells and fluids, and sera from patients with HCV infection. The study population consisted of 15 patients positive for antibodies to HCV (anti-HCV). Positive- and negative-strands HCV RNA were detected using highly strand-specific rTth reverse transcription-polymerase chain reaction (rTth RT-PCR) followed by Southern blotting analysis. Positive-strand HCV RNA was detected in 12 (80%) serum samples, in 13 (86.7%) bone marrow fluid specimens, and in 6 (40.0%) bone marrow cell samples. Negative-strand HCV RNA was detected in 9 (60.0%) serum samples, 11 (91.7%) fluid specimens, while it was not detected in bone marrow cells. The absence of negative-strand HCV RNA in bone marrow cells suggested that HCV does not replicate in these cells. Negative-strand HCV RNA detected in serum and bone marrow fluid samples may have been due to contamination with circulating HCV RNA from hepatocytes.

Adult↗