Biomedical subjects

S Noguchi

Publications and source records attributed to S Noguchi.

At least 109 records · Page 6Linked to original sources

PubMed2000

Breast cancer risk associated with polymorphism in CYP19 in Japanese women.

Screening of the entire coding and major promoter regions of the CYP19 gene identified two novel polymorphisms at codon 39 (Trp to Arg) and codon 408 (silent) in addition to those reported previously at codon 264 (Arg to Cys) and intron 4 [tetranucleotide (TTTA) simple tandem repeat]. A case-control study was conducted in order to see whether or not these polymorphisms were associated with breast cancer risk in Japanese women. Homozygous and heterozygous carriers of the variant allele Arg at codon 39 showed a significantly decreased risk of breast cancer (OR=0.39, 95%C.I.=0. 17-0.89). On the other hand, homozygous carriers of the allele with 10 or more TTTA repeats at intron 4 showed a trend toward an increase (OR=1.80, 95%C.I.=0.97-3.36) in breast cancer risk. Other polymorphisms were found not to be associated with breast cancer risk. These results suggest that the CYP19 polymorphisms at exon 39 and intron 4 would be useful for selecting Japanese women at a high risk of breast cancer.

Adult↗

PubMed2000

The mouse ZFH-4 protein contains four homeodomains and twenty-two zinc fingers.

We isolated the mouse zfh-4 cDNA which is 12 kb long and capable of encoding a 3,550-amino acid protein containing four homeodomains and 22 zinc fingers including two pseudo zinc finger motifs. The mouse ZFH-4 is 51% homologous to the mouse ATBF1 and 23% to the Drosophila ZFH-2. The homeodomain and zinc finger regions are highly conserved between ZFH-4 and ATBF1 except that one zinc finger is missing in ZFH-4. Analysis of partial genomic sequences showed that the mouse zfh-4 and ATBF1 genes are similar in exon-intron organization. RT-PCR analysis of zfh-4 transcripts in adult mouse tissues showed that zfh-4 expression was low but reproducibly detectable in brain, heart, lung and muscle. In these mouse tissues, ATBF1 transcripts were poorly amplified by PCR under the conditions where zfh-4 transcripts were amplified, suggesting that the expression of zfh-4 mRNA is higher than that of ATBF1 mRNA. Other comparative analysis suggests functional similarities and dissimilarities between ZFH-4 and ATBF1.

Amino Acid Motifs↗

PubMed2000

Cross talk between interferon-gamma and -alpha/beta signaling components in caveolar membrane domains.

Definition of cellular responses to cytokines often involves cross-communication through their respective receptors. Here, signaling by interferon-gamma (IFN-gamma) is shown to depend on the IFN-alpha/beta receptor components. Although these IFNs transmit signals through distinct receptor complexes, the IFN-alpha/beta receptor component, IFNAR1, facilitates efficient assembly of IFN-gamma-activated transcription factors. This cross talk is contingent on a constitutive subthreshold IFN-alpha/beta signaling and the association between the two nonligand-binding receptor components, IFNAR1 and IFNGR2, in the caveolar membrane domains. This aspect of signaling cross talk by IFNs may apply to other cytokines.

Animals↗

PubMed2000

Hox C cluster genes are dispensable for overall body plan of mouse embryonic development.

Hox genes encode transcription factors which provide positional information during morphogenesis along the body axis; genetic interaction among Hox genes is thought to be necessary for correct pattern formation. One of the most curious features of the 39 vertebrate Hox genes is that they form four clusters each composed of several genes paralogous between clusters. This raises the question are all four clusters necessary for the development of vertebrates and, if so, what is the function of each cluster? To provide an answer to this question, we prepared Hox C cluster null mice utilizing the Cre-loxP system. Hox C cluster null mice, lacking all nine Hox C genes, die at the time of birth; however, the mutant pups develop to this stage with minor transformations. This development shows that the Hox C genes are dispensable for the overall body plan of mouse embryogenesis. Furthermore, transformations observed in the skeletal system of the Hox C cluster null mice are milder than those observed in the Hoxc-9 null mice, providing further evidence that at least some genes within a cluster exhibit interaction functions with each other.

Animals↗

PubMed2000

Cyclin E overexpression in transitional cell carcinoma of the bladder.

We attempted to clarify the relationship between cyclin E to p27(Kip1), Ki-67 and clinicopathologic features in transitional cell bladder carcinoma. Immunohistochemical staining of archival tissue specimens of transitional cell bladder carcinoma obtained from 94 patients was performed by the labeled streptavidin-biotin-peroxidase method. Overexpression of cyclin E protein was observed in 38 of the 94 (40.4%) specimens, and was positively correlated with histological grade, Ki-67 LI and p27(Kip1) labeling index (LI). These data suggest that cyclin E may be associated with aggressive tumor growth, and may have a relationship with p27(Kip1) for the regulation of cell cycle progression in transitional cell bladder carcinoma.

Carcinoma, Transitional Cell↗

PubMed2000

Biochemical evidence for association of dystrobrevin with the sarcoglycan-sarcospan complex as a basis for understanding sarcoglycanopathy.

The sarcoglycan complex is composed of four membrane-spanning dystrophin-associated proteins (DAPs) and is essential for skeletal muscle survival, since the absence or markedly reduced expression of this complex due to mutation of any one of the sarcoglycan genes causes a group of muscular dystrophies, collectively termed sarcoglycanopathy. Although one of the putative functions of the sarcoglycan complex is its participation in signaling processes, detailed studies have been scarce. Very recently, it was shown that gene knockout mice for a DAP, alpha-dystrobrevin, exhibit a dystrophic phenotype, possibly due to defects in muscle cell signaling. To clarify the putative function of the sarcoglycan complex, it is essential to determine whether or not there is a link between it and the intracellular signaling molecules. To elucidate this, we developed new methods for preparing various DAP complexes containing the sarcoglycan complex from the purified dystrophin-DAP complex. It was suggested from one of the complexes prepared that the sarco-glycan-sarcospan complex (the sarcoglycan complex associated with sarcospan) is associated with syntrophin and/or dystrobrevin. Further analysis of this complex revealed that the N-terminal half of dystrobrevin participates in this association. It is thus considered that the sarcoglycan-sarcospan complex is linked to the signaling protein neuronal nitric oxide synthase via alpha-syntrophin associated with dystrobrevin.

Animals↗

PubMed2000

Cyclin-dependent kinase inhibitor p27(Kip1) expression in transitional cell carcinoma of renal pelvis and ureter.

We examined the expression and significance of p27(Kip1) protein in 79 patients with transitional cell carcinoma of the renal pelvis and ureter. Immunohistochemical staining of archival tissue specimens was done using a labeled streptavidin-biotin-peroxidase method. There was no significant association between p27(Kip1) labeling index and histologic grade or pathologic stage. Patients with p27(Kip1) labeling indices of 27 or greater had more favorable prognoses in comparison to those with p27(kip1) labeling indices less than 27 (P<0.01). Multivariate analysis indicated that p27(Kip1) had an independent predictive prognostic value (P<0.05). The p27(Kip1) may be a novel prognostic marker for transitional cell carcinoma of the renal pelvis and ureter.

Adult↗

PubMed2000

Two Sox9 messenger RNA isoforms: isolation of cDNAs and their expression during gonadal development in the frog Rana rugosa.

Sox is a family of SRY-related testis-determining genes. We have isolated two different mRNA isoforms of the frog Sox9 gene from adult frog testis cDNAs. One form (Sox9 alpha) encodes a 482 amino acid protein containing the HMG box, whereas the other form (Sox9 beta), which completely lacks the HMG box, is a truncated 265 amino acid protein of Sox9 alpha. Sox9 alpha is 82% similar to mouse, 86% to chicken, and 77% to trout Sox9 at the amino acid level. Sox9 expression was upregulated in embryos after stage 16, and was seen in both developing testes and ovaries. The size of Sox9 transcripts was determined to be 7.8 knt by Northern blot analysis. In addition, Sox9 alpha expression was found prominently in the testis and brain among various tissues of adult frogs examined, and was considerably higher than Sox9 beta. The fact that Sox9 is expressed in both sexes suggests that this gene is involved in gonadal development of male and female frogs. This is dissimilar to the pattern in birds and mammals, in which Sox9 expression is male-specific.

Animals↗

PubMed2000

Guanabenz-mediated inactivation and enhanced proteolytic degradation of neuronal nitric-oxide synthase.

Guanabenz, a metabolism-based irreversible inactivator of neuronal nitric-oxide synthase (nNOS) in vitro, causes the loss of immunodetectable nNOS in vivo. This process is selective in that the slowly reversible inhibitor N(G)-nitro-L-arginine did not decrease the levels of nNOS in vivo. To better understand the mechanism for the loss of nNOS protein in vivo, we have investigated the effects of guanabenz and N(G)-nitro-L-arginine in HEK 293 cells stably transfected with the enzyme. We show here that guanabenz, but not N(G)-nitro-L-arginine, caused the inactivation and loss of nNOS protein in the HEK 293 cells. In studies with cycloheximide or in pulse-chase experiments with [(35)S]methionine, we demonstrate that the loss of nNOS was due in large part to enhanced proteolysis of the protein with the half-life decreasing by one-half from 20 to 10 h. Other metabolism-based irreversible inactivators to nNOS, N(G)-methyl-L-arginine, and N(5)-(1-iminoethyl)-L-ornithine, but not the reversible inhibitor 7-nitroindazole (7-NI), caused a similar decrease in the half-life of nNOS. Proteasomal inhibitors, lactacystin, Cbz-leucine-leucine-leucinal, and N-acetyl-leucine-leucine-norleucinal, but not the lysosomal protease inhibitor leupeptin, were found to effectively inhibit the proteolytic degradation of nNOS. Thus we have shown for the first time that the irreversible inactivators of nNOS, perhaps through covalent alteration of the enzyme, enhance the proteolytic turnover of the enzyme by a mechanism involving the proteasome.

Animals↗

PubMed2000

Over-expression of cbaAB genes of Bacillus stearothermophilus produces a two-subunit SoxB-type cytochrome c oxidase with proton pumping activity.

We constructed expression plasmids containing cbaAB, the structural genes for the two-subunit cytochrome bo(3)-type cytochrome c oxidase (SoxB type) recently isolated from a Gram-positive thermophile Bacillus stearothermophilus. B. stearothermophilus cells transformed with the plasmids over-expressed an enzymatically active bo(3)-type cytochrome c oxidase protein composed of the two subunits, while the transformed Escherichia coli cells produced an inactive protein composed of subunit I without subunit II. The oxidase over-expressed in B. stearothermophilus was solubilized and purified. The oxidase contained protoheme IX and heme O, as the main low-spin heme and the high-spin heme, respectively. Analysis of the substrate specificity indicated that the high-affinity site is very specific for cytochrome c-551, a cytochrome c that is a membrane-bound lipoprotein of thermophilic Bacillus. The purified enzyme reconstituted into liposomal vesicles with cytochrome c-551 showed H(+) pumping activity, although the efficiency was lower than those of cytochrome aa(3)-type oxidases belonging to the SoxM-type.

Bacterial Proteins↗

PubMed2000

Indications for bilateral modified radical neck dissection in patients with papillary carcinoma of the thyroid.

HYPOTHESES: After subtotal thyroidectomy with modified radical neck dissection of the affected side, nodal recurrence at the contralateral cervical side indicates a poor prognosis for patients with papillary thyroid cancer. Bilateral modified radical neck dissection is beneficial for patients at high risk for contralateral nodal recurrence. DESIGN AND SETTING: Retrospective study of patients with papillary cancer who were treated surgically from January 1, 1970, through December 31, 1995, at the Noguchi Thyroid Clinic and Hospital Foundation, Beppu, Japan. PATIENTS: Patients (N = 1776) had primary tumors greater than 10 mm in maximum diameter and underwent thyroidectomy and ipsilateral modified radical neck dissection with curative intent. RESULTS: Thirty-two patients (1.8%) developed contralateral lymph node metastases during the mean follow-up period of 12.1 years. The risk factors for contralateral nodal recurrence were male sex, large primary tumor, tumor extension over the isthmus, extracapsular adhesion or invasion to surrounding tissues, and the presence of gross nodal metastasis at initial surgery. These patients had a greater number of distant metastases (31.1% vs 0.7%; P<.001) and a lower 10-year survival rate (83.7% vs 99.3%; P<.001) than patients without nodal recurrence. CONCLUSION: Bilateral modified radical neck dissection should be considered for patients with papillary carcinoma who show risk factors for contralateral nodal recurrence, as it could prevent a second operation and may improve their outcome.

Adult↗

PubMed2000

High dose chemotherapy as adjuvant treatment in operable breast cancer with 10 or more involved axillary lymph nodes.

BACKGROUND: it is well known that breast cancer patients with more than 10 axillary lymph nodes involved have poor prognosis even with extensive adjuvant chemotherapy. To improve this poor outcome, high-dose adjuvant chemotherapy has been applied to the these patients. This study was intended to clarify the efficacy and usefulness of high dose adjuvant chemotherapy (HDC) for high-risk breast cancer patients and its efficacy was compared with conventional adjuvant chemotherapy (non-HDC group). PATIENTS AND METHODS: Twelve patients with breast cancer involving more than 10 axillary nodes received high-dose chemotherapy with peripheral progenitor-stem cell transplantation (PBSCT). This regimen consists of BCNU (carmustine) 130 mg/m(2) x 3, CBDCA (carboplantin) 500 mg/m(2) x 3 and CPA (chyclophosphamide) 50 mg/kgx 2 after induction chemotherapy with 3 cycles of CE (chyclophosphamide 600 mg/m(2), epirubicin 60 mg/m(2)). RESULTS: Twelve patients completed the high-dose chemotherapy regimen as planned, no patient died of chemotherapy related toxicity. After a median follow-up period of 44 months, disease-free and overall survival at 48 months after the operation for 12 patients determined by Kaplan-Meier methods was 63 % and 83 %, respectively. Disease-free survival was superior in the high-dose chemotherapy group compared with the control group but a statistical difference was not observed. CONCLUSION: High-dose chemotherapy seems to be an effective and feasible treatment for high-risk breast cancer patients. However, the usefulness of high-dose adjuvant chemotherapy for high-risk breast cancer patients should be confirmed by a large-scale randomized trial.

Adult↗

PubMed2000

Nafamostat mesilate, a serine protease inhibitor, suppresses lipopolysaccharide-induced nitric oxide synthesis and apoptosis in cultured human trophoblasts.

We investigated the effects of nafamostat mesilate, a synthetic protease inhibitor clinically used for patients with pancreatitis or disseminated intravascular coagulopathy, on NO synthesis and apoptosis in lipopolysaccharide (LPS)-treated human trophoblasts. Nafamostat mesilate or aminoguanidine, an inhibitor of NO synthase, suppressed NO synthesis and apoptosis in trophoblasts induced by LPS. Both agents also suppressed matrix metalloproteinase-2 activity induced by LPS. LPS also stimulated secretion of IL-6 and IL-8 in cultured trophoblasts, which was suppressed by nafamostat mesilate. Protease inhibitors including nafamostat mesilate may be therapeutic agents for chorioamnionitis and various diseases including septic shock, ischemia-reperfusion injury in brain and heart, graft rejection, and acute phase inflammatory diseases, in which overproduction of NO or peroxynitrite is involved in tissue injury.

Anti-Inflammatory Agents, Non-Steroidal↗

PubMed2000

Diagnostic pitfalls in osteomyelitis of the odontoid process: case report.

BACKGROUND: Pyogenic osteomyelitis of the odontoid process is a very rare disease associated with a variety of clinical symptoms, and previous reports have stressed the difficulties inherent in making the diagnosis. The authors present a case of osteomyelitis of the odontoid process with epidural abscess in which magnetic resonance imaging (MRI) was used in the diagnosis, assessment of the extent of concomitant epidural abscess, treatment effect, and long-term follow-up. CASE DESCRIPTION: A 68-year-old male was admitted to our hospital with cervical pain, neck stiffness, and fever. Although the diagnosis was missed at the beginning, the patient was diagnosed with osteomyelitis of the odontoid process with a paravertebral epidural abscess by MRI. The patient became asymptomatic after 3 months of antibiotic therapy. CONCLUSION: Pyogenic osteomyelitis of the odontoid process is a rare condition requiring a high index of suspicion for diagnosis. MRI examination should be considered in the diagnosis in patients with neck pain combined with fever. Serial MRI during and after antibiotic therapy provided an objective assessment of the healing rate of the lesions.

Aged↗

PubMed2000

C-ERBB-2 gene amplification as a prognostic marker in human bladder cancer.

OBJECTIVES: To evaluate c-erbB-2 gene amplification and its prognostic significance in transitional cell carcinoma of the bladder. METHODS: Alterations in the gene copy number of c-erbB-2 were detected in 57 bladder tumor samples using a method based on the polymerase chain reaction. RESULTS: Eighteen tumors (32%) showed gene amplification of c-erbB-2, which correlated with tumor grade and stage. A strong association of c-erbB-2 amplification with patient survival was also found. The amplification resulted in a significantly poorer prognosis among the patients with high-grade and/or invasive tumors. Multivariate analysis revealed that c-erbB-2 amplification and tumor grade were independent prognostic factors. CONCLUSIONS: Our data indicate a possible role of the c-erbB-2 gene in the development of aggressive behavior in bladder tumors. Moreover, the use of c-erbB-2 gene amplification, together with tumor grade and stage, could provide an accurate basis for determining the prognosis of bladder cancer.

Adult↗

PubMed2000

Absence of somatic RET gene mutation in sporadic parathyroid tumors and hyperplasia secondary to uremia, and absence of somatic Men1 gene mutation in MEN2A-associated hyperplasia.

Germline mutations of the MEN1 gene are found in more than 85% of multiple endocrine neoplasia type 1 (MEN 1) patients, and germline mutations of the RET gene are found in more than 95% of multiple endocrine neoplasia type 2 (MEN2) patients. Parathyroid hyperplasia is seen in more than 90% of MEN 1 and about 15% of MEN2A patients. To date, somatic MEN1 mutations are reported in about 20% of sporadic parathyroid tumors. To elucidate the genetic basis of parathyroid tumor development, we examined somatic RET gene mutations in sporadic parathyroid tumors and hyperplasia secondary to uremia, and somatic MEN1 gene mutations in parathyroid hyperplasia from MEN2A patients. A total of 145 parathyroid tumors comprising 129 sporadic parathyroid tumors, 14 hyperplastic lesions secondary to uremia, and two hyperplastic lesions from MEN2A patients were examined. DNA was extracted from fresh frozen parathyroid tissue. Exons 2-10 of the MEN1 gene and exons 10 and 11 of the RET gene were sequenced. No somatic RET gene mutations were found in the 129 sporadic parathyroid tumors or 14 parathyroid hyperplastic lesions secondary to uremia. No somatic MEN1 gene mutations were found in the two parathyroid hyperplasia from MEN2A patients. These data suggest that RET gene mutation may not be involved in the development of sporadic parathyroid tumors and hyperplasia secondary to uremia and that MEN1 gene mutation may not be or is rarely associated with development of parathyroid hyperplasia in MEN2A patients.

Aged↗

PubMed2000

Usefulness of quick intraoperative measurements of intact parathyroid hormone in the surgical management of hyperparathyroidism.

We investigated the use of quick measurement of intraoperative intact parathyroid hormone (I-PTH) to predict the outcome of parathyroidectomy. We examined intraoperative monitoring of I-PTH in 34 consecutive primary hyperparathyroidism (pHPT) patients operated on between April and December 1999. The average patient age was 56 +/- 13 years, and all but one were women. Four had a history of thyroidectomy. Blood samples were drawn before excision of enlarged parathyroid gland(s) and at 2, 5, 10, and 15 minutes afterward. Plasma I-PTH was measured by a two-site immunochemiluminometric assay. Twenty-three patients were shown to have single gland disease, and ten had multiglandular disease. All patients, except one, underwent successful parathyroidectomies. The plasma I-PTH value 15 minutes after removal of enlarged gland(s) had dropped to 26 +/- 10% of pre-excision I-PTH value. In one patient with a previous history of thyroidectomy for thyroid papillary cancer, no gland enlargement was found in the area where the lesion had been suggested by both ultrasonography and 99mTc sestamibi scanning. In this case, intraoperative measurements of I-PTH in the bilateral internal jugular veins identified an ectopic parathyroid tumor, which was successfully removed. We conclude that quick measurement of intraoperative I-PTH is a valuable tool for decision-making, especially for reoperative parathyroid surgery, for patients with previous history of thyroidectomy, and for patients in whom unilateral neck exploration or a single-gland approach is scheduled based upon preoperative localization.

Female↗

PubMed2000

Laparoscopic adrenalectomy: lateral transabdominal approach vs posterior retroperitoneal approach.

Laparoscopic adrenalectomy has been used to remove a wide variety of adrenal neoplasms. Although several laparoscopic approaches to the adrenal gland have been described, the lateral transabdominal approach has several advantages when compared with other approaches for laparoscopic adrenalectomy. From October 1995 to July 1999, we performed laparoscopic adrenalectomies on 16 patients, including eight posterior retroperitoneal approaches and eight lateral transabdominal approaches. Sixteen patients, ranging in age from 23 to 69 years, were treated for the following conditions: non-functioning adenoma, four patients; aldosteronoma, seven patients; pheochromocytoma, three patients; Cushing's adenoma, two patients. The average tumor size was 2.5 +/- 0.5 cm (1.8-3.0 cm, median 2.4 cm) in the lateral transabdominal approach, 1.2 +/- 0.8 cm (0.8-3.2 cm, median 1.75 cm) in the posterior retroperitoneal approach. Average operative time of lateral transabdominal approach was significantly shorter than that of the posterior retroperitoneal approaches (mean 129 min vs 269 min, P = 0.0005). Conversion to laparotomy was required in one patient in the posterior approach. Postoperative complication occurred in one pneumothorax in the lateral transabdominal approach and two subcutaneous emphysemas in the posterior retroperitoneal approach. There was no statistical difference in blood loss during the operation in the two groups. There was no mortality in either group. The lateral transabdominal approach is a safe and efficient technique for the removal of the adrenal neoplasms. Compared with other approaches, this technique has a wider working space and also good exposure for removing the adrenal gland.

Abdomen↗