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Biomedical subjects

S Noguchi

Publications and source records attributed to S Noguchi.

At least 253 records · Page 14Linked to original sources
PubMed1997

Thymidine phosphorylase activity in human bladder cancer: difference between superficial and invasive cancer.

The activity of thymidine phosphorylase (TdR-Pase), which is identical to platelet-derived endothelial cell growth factor (a potent angiogenic factor), was analyzed in primary human bladder cancer tissues. TdR-Pase activity in tissues was determined from the conversion rate of 5'-deoxy-5-fluorouridine to 5-fluorouracil. The mean activity in 37 bladder cancers and in 8 samples of normal bladder epithelial tissue was 108.5 and 19.2 microgram 5-fluorouracil/mg protein/h, respectively, showing a statistically significant difference. Among the cancer tissues, differences in activity were seen according to the stage and grade of tumors. Low-grade (grade 1) tumors had significantly lower activities than high-grade tumors, and high-grade invasive tumors showed significantly higher activities than low-grade superficial tumors. These results demonstrate that a high TdR-Pase activity in bladder cancer is associated with the tumor characteristics of invasion and malignant potential. Our conclusions support the hypothesis that angiogenesis that is mediated by this molecule may be involved in the development of invasive human bladder cancer, as suggested by T. O'Brien et al. (Cancer Res., 55: 510-513, 1995), and also suggest that TdR-Pase is a potential therapeutic target in human bladder cancer.

Epithelial Cells↗
PubMed1996

Recent Progress in Breast Conserving Therapy: From Experiences in Japan.

Breast conserving therapy (BCT) was conducted in 22.1% of breast cancer patients in 1994 in Japan and is being performed with increasing frequency. According to the data already published, 10-27% of patients treated with BCT had a positive surgical margin. The recurrence rate in the breast is 1-2% annually, The 5-year overall survival in patients mostly consisting of stage I is 90% or higher at the present time. A case-control analysis of a multicenter study revealed that significant risk factors for breast recurrence were a positive surgical margin and absence of radiation therapy. Progress in basic research and diagnosis has also been instrumental in improving treatment results.

Journal Article↗
PubMed1996

Histologic characteristics of breast cancers with occult lymph node metastases detected by keratin 19 mRNA reverse transcriptase-polymerase chain reaction.

BACKGROUND: Amplification of keratin 19 mRNA (K19) by reverse transcriptase-polymerase chain reaction (RT-PCR) has been shown to be a sensitive method to detect occult breast cancer metastases in lymph nodes. METHODS: Axillary lymph nodes were obtained from 126 patients with breast cancer, and metastases in these lymph nodes were studied by both histologic examination and K19 RT-PCR. The patients were categorized into 3 groups according to the results of these 2 examinations, i.e., patients with 1) both histologically and K19 RT-PCR negative lymph nodes (metastases negative group [n = 91]); 2) histologically negative but K19 RT-PCR positive lymph nodes (occult metastases positive group [ n = 15]); and 3) histologically positive lymph nodes (metastases positive group [n = 20]). RESULTS: Various histologic parameters such as tumor size, histologic type, histologic grade, lymphatic invasion, vascular invasion, and estrogen receptor status were compared among these three groups. There were no significant differences among any of these histologic parameters between the metastases positive and occult metastases positive groups. Conversely, tumor size of the metastases positive (2.5 +/- 0.2 cm) and occult metastases positive (2.5 +/- 0.2 cm) groups was significantly (P < 0.05) greater than that of the metastases negative group (1.9 +/- 0.1 cm), and positivity of lymphatic vessel invasion in the former 2 groups (70% and 53%, respectively) was also significantly (P < 0.01) greater than that in the latter group (18%). CONCLUSIONS: These results demonstrate that histologic characteristics of breast cancers with occult metastases are similar to those of breast cancers with histologically detectable metastases.

Actins↗
PubMed1996

Structural characterization of the N-linked carbohydrate chains of the zona pellucida glycoproteins from bovine ovarian and fertilized eggs.

The N-linked oligosaccharides that were released by hydrazinolysis from glycoproteins of zonae pellucidae of bovine ovarian eggs, were composed of neutral (23%) and acidic (77%) carbohydrate chains; almost all the acidic chains were neutralized by sialidase digestion. Sugar mapping analysis of pyridylaminated N-linked chains by reverse-phase and normal-phase HPLC and 500-MHz 1H-NMR spectroscopy revealed that the major neutral chain is a high-mannose-type oligosaccharide and the acidic chains are di-, tri-, and tetra-antennary, fucosylated complex-type chains that have N-acetyllactosamine repeats in the non-reducing regions. The structures of the neutral chain and the core regions of the acidic chains of N-linked oligosaccharides from the zona proteins of fertilized eggs, which were obtained by the in vitro fertilization method, were essentially the same as those of the ovarian egg zonae. The amount, however, of the acidic chains decreased to 32 mol/100 mol in the fertilized egg zonae, which suggests that a sialidase released from the oocyte during fertilization operates on the zona glycoproteins.

Animals↗
PubMed1996

Phyllodes Tumor of the Breast: Pathology, Histogenesis, Diagnosis, and Treatment.

Phyllodes tumor of the breast is histologically unique in that it is composed of epithelial and stromal components. The histogenesis of this disease has remained largely unknown but recently we have obtained interesting information through clonal analysis, and have been able to show a difference in the histogenesis between phyllodes tumor and fibroadenoma. Elucidation of histogenesis would difinitely improve our understanding of the biological behavior of this disease and also help to establish the most appropriate treatment strategy. The pathology, histogenesis, diagnosis, and treatment of phyllodes tumor are reviewed in this paper. Our hypothesis on the histogenesis of this disease is also presented.

Journal Article↗
PubMed1996

Bacillus stearothermophilus qcr operon encoding rieske FeS protein, cytochrome b6, and a novel-type cytochrome c1 of quinol-cytochrome c reductase.

The gcr of Bacillus stearothermophilus K1041 encoding three subunits of the quinol-cytochrome c oxidoreductase (cytochrome reductase, b6c1 complex) was cloned and sequenced. The gene (qcrA) for a Rieske FeS protein of 19,144 Da with 169 amino acid residues, and the gene (qcrC) for cytochrome c1 of 27,342 Da with 250 amino acid residues were found at adjacent upstream and downstream sides of the previously reported qcrB (petB) for cytochrome b6 of subunit 25,425 Da with 224 residues (Sone, N., Sawa, G., Sone, T., and Noguchi, S. (1995) J. Biol. Chem. 270, 10612-10617). The three structural genes for thermophilic Bacillus cytochrome reductase form a transcriptional unit. In the deduced amino acid sequence for the FeS protein, the domain including four cysteines and two histidines binding the 2Fe-2S cluster was conserved. Its N-terminal part more closely resembled the cyanobacteria-plastid type than the proteobacteria-mitochondria type when their sequences were compared. The amino acid sequence of cytochrome c1 was not similar to either type; the thermophilic Bacillus cytochrome c1 is composed of an N-terminal part corresponding to subunit IV with three membrane-spanning segments, and a C-terminal part of cytochrome c reminiscent of cytochrome c-551 of thermophilic Bacillus. The subunit IV in the enzyme of cyanobacteria and plastids is the counterpart of C-terminal part of cytochrome b of proteobacteria and mitochondria. These characteristics indicate that Bacillus cytochrome b6c1 complex is unique.

Amino Acid Sequence↗
PubMed1996

Targeted disruption in the mouse Hoxc-4 locus results in axial skeleton homeosis and malformation of the xiphoid process.

Hoxc-4 is a mouse homeobox gene located at the 3' end of the HoxC cluster. Of the HoxC genes, Hoxc-4 is expressed in the most anterior regions of the central nervous system and prevertebral column. To investigate its role in mouse development, we have generated Hoxc-4 mutant mice by gene targeting. Mice homozygous for the Hoxc-4 mutation are viable and fertile. Analysis of the skeletal system of homozygous mutants revealed various abnormalities in the cervical and thoracic regions. The most frequent abnormality was a partial posterior homeotic transformation of the seventh cervical vertebra. Less frequently, anterior transformations of the third and eighth thoracic vertebrae were observed. Furthermore, the xiphoid process of the sternum was malformed such that it had an aperture or a fissure. Although Hoxc-4 is expressed abundantly in the central nervous system, no obvious defects were observed. These results suggest that Hoxc-4 is required for specifying cervical and thoracic vertebral identity.

Animals↗
PubMed1996

Nucleotide and amino acid sequences for cytochrome caa3-type oxidase of Bacillus stearothermophilus K1041 and non-Michaelis-type kinetics with cytochrome c.

A pseudo-sigmoidal cytochrome c-dependence curve of oxidase activity was observed with cytochrome oxidase from the Bacillus stearothermophilus strain K1041, while the other thermophilic Bacillus PS3 which has been extensively studied possessed normal Michaelis-Menten type kinetics. The genes coding for four subunits of cytochrome caa3-type oxidase and for heme O synthase were isolated from a genomic DNA library of K1041 by using a PS3 DNA fragment containing the highly-conserved region of the largest subunit as a probe, and sequenced. Most residues in subunits I (COI/caaB product), III (COIII/caaC product), and IV (COIV/caaD product) of K1041 were highly conserved when compared with those of PS3. However, the sequence of K1041 subunit II (COII/caaA product) was distinctly different from that of the PS3 subunit II. These Bacillus COIIs have an additional sequence for cytochrome c after the CuA binding protein portion with two transmembrane segments which is homologous to the mitochondrial counterpart, and represents the site of electron ingress. Several charged residues in the vicinity of cytochrome c moiety are replaced by oppositely charged residues. It is likely that these amino acid replacements in subunit II are the cause of the abnormal sigmoidal saturation curve for extrinsic cytochromes c of the K1041 enzyme.

Amino Acid Sequence↗
PubMed1996

Demonstration of monoclonal origin of human parotid gland pleomorphic adenoma.

BACKGROUND: Parotid gland pleomorphic adenoma is histologically comprised of epithelial and mesenchymal elements. It remains to be established whether this neoplasm arises from epithelial and mesenchymal elements, or solely from the epithelial element. METHODS: In an attempt to resolve this issue, we have conducted clonal analysis on five pleomorphic adenomas. The method for clonal analysis was based on the trinucleotide repeat polymorphism of the x-chromosome-linked androgen receptor gene and on random inactivation of this gene by methylation. The epithelial and mesenchymal elements were obtained separately from the paraffin sections of the pleomorphic adenomas using a microdissection technique and then subjected to clonal analysis. RESULTS: Clonal analysis revealed that both epithelial and mesenchymal elements were monoclonal. In addition, the same allele of the androgen receptor gene was inactivated in both elements in every case. CONCLUSIONS: It is unlikely that the epithelial and mesenchymal elements of different origin happen to inactivate the same allele of the androgen receptor gene in all five tumors. Rather, it is more reasonable to consider that these two elements have a common single cell origin.

Adenoma, Pleomorphic↗
PubMed1996

Small carcinomas of the thyroid. A long-term follow-up of 867 patients.

OBJECTIVE: To determine the adequate extent of surgery for small carcinomas of the thyroid. DESIGN: Retrospective cohort study of 867 consecutive patients with small carcinomas of the thyroid (lesions < 10 mm in diameter) who were operated on at the Noguchi Thyroid Clinic, Oita, Japan, between 1965 and 1987. Mean follow-up was 12.8 years. SETTINGS: A center for treatment of thyroid disease, where about 1400 thyroid operations are performed per year. PATIENTS: Thyroidectomy was performed in patients with a preoperative diagnosis of Graves' disease, Graves' disease with nodules, solitary thyroid nodules, multinodular goiters, cysts, chronic thyroiditis and small carcinomas of the thyroid, in 394, 22, 136, 193, 18, 28, and 76 patients, respectively. RESULTS: Operations were conservative. Three patients who had adenomatous nodular goiters underwent total thyroidectomy. Modified radical neck dissection was performed in 66 patients. Of these 66 patients, 30 had grossly noticeable nodal metastases and 17 had microscopic metastases. Another 50 patients underwent selective lymph node excision, and 28 patients had nodal metastases. Recurrence from remnants of thyroid was seen in five patients. They were treated by surgery. Recurrence in lymph nodes was observed in five patients, and four of them were successfully treated. Recurrence in bone was observed in two patients; one with recurrence in the femur was successfully treated. Two patients died with recurrent cancer. CONCLUSIONS: Small carcinomas of the thyroid can be fatal. Total thyroidectomy is unnecessary. Modified radical neck dissection is unnecessary unless gross nodal metastases are present. Long-term follow-up is mandatory. A

Adolescent↗
PubMed1996

Immunohistochemical loss of thyroid peroxidase in papillary thyroid carcinoma: strong suppression of peroxidase gene expression.

It is believed that qualitative changes in thyroid peroxidase (TPO) cause decreased enzyme activity in differentiated thyroid carcinoma. To re-evaluate TPO expression in thyroid cancer, TPO mRNA expression was compared with TPO protein expression in 38 samples of thyroid tissue obtained from patients with various thyroid diseases. In Northern blot studies, while TPO mRNA was highly expressed in tissues from all 18 benign lesions, it was strongly suppressed in 14 tumours, including 12 out of 12 papillary carcinomas, one of seven follicular carcinomas, and one medullary carcinoma. TPO mRNA was not detected in six carcinomas, of which four were papillary, one follicular, and one medullary, by the usual Northern blot method. The 14 cases with strong underexpression of TPO mRNA were very weakly stained with anti-TPO monoclonal antibody 38E, whereas all 18 benign tissues were strongly stained. Moreover, a comparative study of TPO expression by Northern blot and immunohistochemical analysis revealed a positive correlation between TPO mRNA expression and the staining intensity of TPO protein. These results suggest that strong suppression of TPO mRNA transcription causes low TPO activity in papillary carcinoma; immunohistochemical loss of TPO may be a useful diagnostic marker. TPO mRNA expression in differentiated thyroid carcinomas did not always correlate with the mRNA expression of thyroglobulin, thyroid stimulating hormone receptor, and thyroid transcription factor 1.

Biomarkers, Tumor↗
PubMed1996

Portsite and intraabdominal metastases of unsuspected gallbladder carcinoma after laparoscopic cholecystectomy: report of a case.

We herein report a rare case of portsite metastasis of gallbladder carcinoma which occurred after laparoscopic cholecystectomy. A 64-year-old man underwent laparoscopic cholecystectomy at another hospital for symptomatic cholecystolithiasis. The histological examination revealed an adenocarcinoma of the gallbladder infiltrating the entire wall. Despite the physician's advice the patient refused any additional treatment. Thirteen months after surgery he visited our hospital because of a palpable mass at the scar of the right trocar incision. The nodule was removed and histological examination confirmed metastasis from the gallbladder carcinoma.

Abdominal Neoplasms↗
PubMed1996

Differential distribution of ErbB-2 and pS2 proteins in ductal carcinoma in situ of the breast.

We examined the expression of ErbB-2 and pS2 proteins in 59 ductal carcinoma in situ (DCIS) of the breast, either pure DCIS or DCIS associated with invasive carcinoma, using immunohistochemical staining of paraffin-embedded sections. Positive staining for ErbB-2 and pS2 proteins was noted in 32% (19/59) and 46% (27/59) of DCIS, respectively. An inverse relationship between ErbB-2 and pS2 status in DCIS was observed (p < 0.01). From the viewpoint of histological subtype, the prevalence of ErbB-2 protein expression was significantly higher in the comedo subtype than the cribriform-micropapillary subtype. The prevalence of immunoreactivity for ErbB-2 in solid subtype was intermediate between those of the other two groups. In contrast, the prevalence of pS2 expression was significantly lower in the comedo subtype than in the cribriform-micropapillary subtype. Again, the prevalence of pS2 protein expression in the solid subtype was intermediate between those of the other two subtypes. Our results suggest that DCIS is biologically heterogeneous with regard to such marker substances. This has possible implications for management of these lesions.

Biomarkers, Tumor↗
PubMed1996

Essential and non-redundant roles of p48 (ISGF3 gamma) and IRF-1 in both type I and type II interferon responses, as revealed by gene targeting studies.

BACKGROUND: Interferons (IFNs) are a class of cytokines which confer cellular resistance against viral infections. Type I (IFN-alpha and -beta) and type II (IFN-gamma) IFNs utilize distinct receptors, the stimulation of which results in the induction of downstream target genes. These target genes usually contain within their promoter region an IFN responsive element, termed ISRE (IFN stimulated response element) which binds a heterotrimeric transcription factor, ISGF3 (IFN-stimulated gene factor 3) consisting of p48 (ISGF3 gamma), Stat1 (Signal transducers and activators of transcription-1; alpha or beta), and Stat2. The ISRE sequence overlaps with that of IRF-E which binds another IFN-inducible factor, IRF-1 (IFN regulatory factor-1). RESULTS: We generated mice lacking p48 by gene targeting. We show that p48 plays an essential role in both type I and type II IFN responses; activation of IFN-inducible genes and establishment of the antiviral state by IFN-alpha or -gamma are both severely impaired, and ISRE-binding activities induced by both IFNs are absent in the p48-negative embryonic fibroblasts (EFs). Furthermore, we generated mice deficient for both p48 and IRF-1 and found that at least one IFN-inducible gene is dependent on both factors. CONCLUSIONS: p48 and IRF-1 do not perform redundant functions in the cell, but rather complement one another in both type I and II IFN responses.

Animals↗
PubMed1996

Regulation of IFN-alpha/beta genes: evidence for a dual function of the transcription factor complex ISGF3 in the production and action of IFN-alpha/beta.

BACKGROUND: Efficient production of interferons (IFNs) in virally infected cells is an essential aspect of the host defence. The transcription factor complex ISGF3 (IFN-stimulated gene factor 3) was originally identified as a critical mediator of the IFN signal; it is formed upon IFN receptor (IFNR) stimulation and binds to ISREs (IFN-stimulated response elements) to activate IFN-inducible genes. It has recently been shown that the DNA binding component of ISGF3, p48 (ISGF3gamma) also binds to virus-inducible elements in the IFN-alpha/beta genes, suggesting a potential new role of p48 in IFN production. RESULTS: Primary cells from mice with a targeted disruption of the p48 gene show severe defects in virus-induced IFN-alpha/beta gene expression. A similar defect was also observed in cells lacking type I IFNR or Stat1, further demonstrating the role of IFN signalling in the induction of these IFN genes. ISGF3 in fact binds to the virus-inducible elements within the IFN-alpha/beta promoters. We also provide evidence showing that these elements are additionally controlled by an unidentified factor(s) which presumably triggers the primary phase of IFN gene induction. CONCLUSIONS: Our results demonstrate that the IFN signal transducing complex ISGF3 plays a crucial role in IFN production and suggest that ISGF3 may participate directly in the activation of IFN-alpha/beta promoters. This dual function of ISGF3 may insure the efficient operation of this cytokine system in the host defence.

Animals↗
PubMed1996

Clonal analysis of precancerous lesion of hepatocellular carcinoma.

BACKGROUND & AIMS: It remains to be established whether precancerous lesion (dysplastic nodule) of hepatocellular carcinoma (HCC) is a neoplastic or hyperplastic lesion. Clonal analysis of this lesion was conducted to elucidate this important issue on histogenesis. METHODS: The method for clonal analysis was based on restriction fragment length polymorphism of the X chromosome-linked phosphoglycerokinase gene and on random inactivation of the gene by methylation. Clonal somatic mutations were also analyzed by DNA fingerprinting with two multilocus probes (33.6 and 33.15), and loss of heterozygosity was studied using five single-locus probes (MS1[1p33-p35], MS31[7p22-pter], MS43a[12q24.3-qter], MS8[5q35-qter], and g3[7q36-qter]). RESULTS: Clonal analysis by the phosphoglycerokinase gene-based method showed that all of the five dysplastic nodules and seven HCCs were monoclonal in origin. DNA fingerprinting showed clonal somatic mutations in six of 10 dysplastic nodules and in six of nine HCCs. Loss of heterozygosity was found in one dysplastic nodule (7p22-pter) and two HCCs (1p33-p35 and 12q24.3-qter). CONCLUSIONS: These results confirm monoclonality of HCC and show that hepatic precancerous lesion (dysplastic nodule) is not a hyperplastic but a neoplastic lesion, consisting of monoclonal cells with genetic alterations.

Aged↗