Biomedical subjects

S Noguchi

Publications and source records attributed to S Noguchi.

At least 37 records · Page 2Linked to original sources

PubMed2004

POMT1 mutation results in defective glycosylation and loss of laminin-binding activity in alpha-DG.

Walker-Warburg syndrome (WWS) is a congenital muscular dystrophy associated with neuronal migration disorder and structural eye abnormalities. The mutations in the O-mannosyltransferase 1 gene (POMT1) were identified recently in 20% of patients with WWS. The authors report on a patient with WWS and a novel POMT1 mutation. Their patient expressed alpha-dystroglycan (alpha-DG) core protein, but fully glycosylated alpha-DG antibody epitopes were absent, associated with the loss of laminin-binding activity.

Abnormalities, Multiple↗

PubMed2004

Ullrich disease due to deficiency of collagen VI in the sarcolemma.

The authors identified eight patients with Ullrich disease in whom collagen VI was present in the interstitium but was absent from the sarcolemma. By electron microscopy, collagen VI in the interstitium was never linked to the basal lamina. These findings suggest that in these patients it is not the total absence of collagen VI from the muscle but the failure of collagen VI to anchor the basal lamina to the interstitium that is the cause of Ullrich disease. Only one of the patients had a mutation in the collagen VI gene, suggesting that the primary abnormality in most of the patients involved some other molecules.

Child↗

PubMed2003

Overexpression of leucocyte common antigen (LAR) P-subunit in thyroid carcinomas.

Protein tyrosine phosphatase (PTPase) dephosphorylation and protein tyrosine kinase (PTKs) phosphorylation of key signal transduction proteins may be regulated by extracellular signals, making PTPases important in the regulation of cell proliferation. Leucocyte common antigen (LAR), a receptor-like PTPase, consists of E-subunit, containing the cell adhesion molecule-like receptor region, and P-subunit specific for a short segment of the extracellular region, the transmembrane peptide, and two cytoplasmic PTPase domains. We produced a monoclonal antibody against the LAR P-subunit for immunohistochemical screening of LAR expression in normal and tumourous tissues. Gliomas and gastric, colorectal, lung, breast and prostate cancers showed weak and relatively infrequent expression. Intense and diffuse expression, however, was detected in 95% (227 out of 239) of thyroid carcinomas, but only 12% (22 out of 128) of adenomas and no cases of benign thyroid disease were immunopositive. In contrast to broad staining in carcinomas, LAR expression in thyroid adenomas was often found in small focal or locally invasive areas. Western blot analysis similarly detected LAR P-subunit protein in thyroid carcinomas, but not in normal tissues. We believe this to be the first demonstration of LAR overexpression in thyroid carcinoma and may help to elucidate the role of PTPases in the development of malignancy.

Antigens, CD↗

PubMed2003

Fukutin-related protein gene mutated in the original kindred limb-girdle MD 2I.

The authors mapped an autosomal recessive form of limb-girdle MD on chromosome 19q13.3 (LGMD2I), further narrowed down the candidate region to 1.1 Mb, and identified one new homozygous mutation in the fukutin-related protein (FKRP) gene on patients of the original Tunisian family. Immunohistochemical and immunoblot analysis showed abnormal expression of alpha-dystroglycan and laminin-alpha2 supporting the hypothesis that FKRP has a role in the interaction between the extracellular matrix components.

Amino Acid Substitution↗

PubMed2003

Intraoperative angiography in the surgical treatment of cerebral arteriovenous malformations and fistulas.

BACKGROUND: The role of intraoperative angiography in the surgical treatment of cerebrovascular malformations remains controversial. The authors report on their experiences with intraoperative angiography in a series of 20 cases with cerebrovascular malformation to determine whether the use of intraoperative angiography has a favorable impact on the surgical treatment of cerebrovascular malformations. METHODS: Intraoperative angiography was performed in the surgical resection of arteriovenous malformation in 18 patients and in the surgical obliteration of arteriovenous fistula in 2 patients. The incidence of unexpected findings, such as residual nidus, demonstrated by intraoperative angiography was determined. FINDINGS: High-quality subtraction images were obtained by intraoperative angiography in every case and the findings prompted an additional procedure in 1 case that displayed an unexpected residual nidus (5.6%). There were no complications from the intraoperative angiography procedure. INTERPRETATION: Intraoperative assessment of technical results prior to wound closure offers the neurosurgeon the opportunity to resect or obliterate a vascular malformation completely, obviating a second operation.

Adolescent↗

PubMed2003

Association of genetic polymorphisms in CYP19 and CYP1A1 with the oestrogen receptor-positive breast cancer risk.

Since tamoxifen has been shown to reduce the risk of oestrogen receptor (ER)-positive, but not ER-negative, breast cancers in a chemoprevention trial (P-1), it is important to develop assays to assess risk factors for ER-positive breast cancer in order to appropriately select candidates for chemoprevention with tamoxifen. Thus, the significance of genetic polymorphisms of genes involved in oestrogen biosynthesis (CYP19) and metabolism (CYP1A1) as a risk factor for ER-positive breast cancers was evaluated. A case-control study was conducted with 257 breast cancer patients and 191 healthy female controls. Two polymorphisms, CYP19 (TTTA repeats) in intron 4 and CYP1A1 6235C/T in the 3' non-coding region, and their association with the breast cancer risk after adjustment for the other epidemiological risk factors were examined. CYP19 (TTTA)7(-3bp) allele carriers showed a significantly (P<0.05) increased risk of ER-positive breast cancers (Odds Ratio (OR)=1.72, 95% Confidence Interval (CI) 1.10-2.69), but not ER-negative breast cancers. CYP1A1 6235C allele carriers showed a non-significant (P=0.06) trend towards a decreased risk of ER-positive breast cancers (OR=0.65, 95% CI 0.42-1.02), but not ER-negative breast cancers. The combination of these two polymorphisms was found to be more useful in the assessment of the ER-positive breast cancer risk (OR=3.00, 95% CI=1.56-5.74) than the CYP19 (TTTA)7(-3bp) polymorphism alone. The combination of CYP19 (TTTA)7(-3bp) and CYP1A1 6235C/T polymorphisms is associated with an ER-positive, but not ER-negative, breast cancer risk, and, thus, would be useful in the selection of candidates for chemoprevention with tamoxifen.

Adult↗

PubMed2003

Parathyroid scintigraphy with 99mTc-MIBI and 123I subtraction: a comparison with magnetic resonance imaging and ultrasonography.

The aim of this study was to evaluate the efficacy of 99mTc-MIBI and 123I subtraction scintigraphy for the detection of abnormal parathyroid glands to be referred for surgical treatment. Thirty-nine consecutive patients, including 35 primary and four secondary cases of hyperparathyroidism, were evaluated. 99mTc-MIBI/123I subtraction scintigraphy (MIBI/I) was performed on all patients, and the results were compared with delayed images of 99mTc-MIBI (D-MIBI), magnetic resonance imaging (MRI) and ultrasonography (US). The overall sensitivity of MIBI/I, MRI, US and D-MIBI was 55.9%, 43.4%, 50.8% and 39.0%, respectively. In cases of single-gland disease, the sensitivity of MIBI/I, MRI, US and D-MIBI was 62.1%, 48.3%, 55.2% and 44.8%, respectively. In cases of multi-gland disease, the sensitivity of MIBI/I, MRI, US and D-MIBI was 50.0%, 37.5%, 46.7% and 36.7%, respectively. In cases of parathyroid adenoma, the sensitivity of MIBI/I, MRI, US and D-MIBI was 71.4%, 50.0%, 71.4% and 50.0%, respectively. In cases of parathyroid hyperplasia, the sensitivity of MIBI/I, MRI, US and D-MIBI was 55.2%, 42.3%, 50.0% and 39.7%, respectively. It is concluded that 99mTc-MIBI/123I subtraction is more useful than the delayed imaging of 99mTc-MIBI, MRI and US.

Adolescent↗

PubMed2002

Distal myopathy with rimmed vacuoles is allelic to hereditary inclusion body myopathy.

BACKGROUND: Distal myopathy with rimmed vacuoles (DMRV) is an autosomal-recessive disorder with preferential involvement of the tibialis anterior muscle that starts in young adulthood and spares quadriceps muscles. The disease locus has been mapped to chromosome 9p1-q1, the same region as the hereditary inclusion body myopathy (HIBM) locus. HIBM was originally described as rimmed vacuole myopathy sparing the quadriceps; therefore, the two diseases have been suspected to be allelic. Recently, HIBM was shown to be associated with the mutations in the gene encoding the bifunctional enzyme, UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase (GNE). OBJECTIVE: To determine whether DMRV and HIBM are allelic. METHODS: The GNE gene was sequenced in 34 patients with DMRV. The epimerase activity in lymphocytes from eight DMRV patients was also measured. RESULTS: The authors identified 27 unrelated DMRV patients with homozygous or compound-heterozygous mutations in the GNE gene. DMRV patients had markedly decreased epimerase activity. CONCLUSIONS: DMRV is allelic to HIBM. Various mutations are associated with DMRV in Japan. The loss-of-function mutations in the GNE gene appear to cause DMRV/HIBM.

Alleles↗

PubMed2002

Identification of DNA markers of tobacco linked to bacterial wilt resistance.

Bacterial wilt caused by Ralstonia solanacearum is one of the most destructive soil-borne diseases in the world. Breeding resistant commercial varieties of tobacco is difficult because most donor candidates' resistance is controlled by polygenes. In this paper, we demonstrate the identification of useful DNA markers for bacterial wilt-resistant tobacco breeding. One hundred and seventeen markers were identified by the amplified fragment length polymorphism (AFLP) method between W6, a burley variety with resistance originating from a Japanese domestic variety, Hatano, and Michinoku 1, a commercial burley wilt-susceptible variety, using 3,072 primer combinations. These markers were analyzed in 125 doubled haploid lines, derived from F(1) hybrids between W6 and Michinoku 1, and a linkage map consisting of ten linkage groups was drawn. The resistance phenotype of each of these lines was investigated on the basis of the average of disease severity obtained from field trials over two growing cycles. Quantitative trait loci (QTL) analysis was performed on the marker phenotypes and the resistance phenotype of each line. One QTL for the bacterial wilt resistance of W6 and DNA markers associated with this QTL were identified on a linkage group consisting of 15 markers, 32 cM in length. This QTL explained more than 30% of the variance in resistance among these lines.

Burkholderia↗

PubMed2002

Total endoscopic and video-assisted thyroidectomy: cervical approach.

Several procedures have been proposed for surgical treatment of the thyroid nodule; they have not gained wide acceptance, however, because of the expertise required, the relatively long operation times, the wide dissection needed to create a working space, and the extra cost of specialized instruments, especially when port sites are created in the remote area. These barriers have led some surgeons to perform video-assisted thyroidectomy via the neck. We describe the indications for, procedures related to, and results of both total endoscopic thyroidectomy and video-assisted thyroidectomy via the neck. Excellent cosmetic results were obtained by both procedures; however, video-assisted procedures required less time and a smaller dissection area.

Adolescent↗

PubMed2002

Multiple sectioning and immunohistochemical staining of sentinel nodes in patients with breast cancer.

BACKGROUND: The aim of the present study was to investigate whether focused analysis of sentinel nodes is more useful than routine haematoxylin and eosin examination of axillary lymph nodes obtained by axillary lymph node dissection. METHODS: One hundred and fifty-two patients with breast cancer with clinically negative axillary nodes underwent successful sentinel node biopsy using a combination of dye and radioisotope, followed immediately by standard level I and II axillary lymph node dissection. Multiple sectioning, with haematoxylin and eosin and immunohistochemical analysis of sentinel nodes using cytokeratin antibody, was compared with single section and haematoxylin and eosin analysis of sentinel and non-sentinel nodes (routine examination). RESULTS: A mean of 1.9 (range 1-12) sentinel nodes and 11.2 (range 4-24) non-sentinel nodes were excised per patient. Metastases were detected in 44 patients (29 per cent) by single section and haematoxylin and eosin analysis of sentinel and non-sentinel nodes. An additional five patients (3 per cent) with metastases were detected by multiple sectioning and haematoxylin and eosin analysis of sentinel nodes. A further 20 patients (13 per cent) with metastases were identified by multiple sectioning and immunohistochemical analysis of sentinel nodes. Both haematoxylin and eosin and immunohistochemical analysis of sentinel nodes missed one patient with node metastases, which led to a false-negative rate of 1 per cent. CONCLUSION: Multiple sectioning and immunohistochemical staining of sentinel nodes identified 16 per cent more patients with positive axillary lymph nodes than routine haematoxylin and eosin examination.

Axilla↗

PubMed2002

Endoscopic ultrasonography in patients with thyroid cancer: its usefulness and limitations for evaluating esophagopharyngeal invasion.

BACKGROUND AND STUDY AIMS: Although computed tomography (CT) and magnetic resonance imaging (MRI) are useful for detecting esophagopharyngeal invasion by thyroid cancer, they cannot assess the depth of invasion, which is important for the surgical planning. In the present study, endoscopic ultrasonography (EUS) of the esophagus was used to assess esophagopharyngeal invasion by thyroid cancer, and the value of this technique was assessed prospectively. PATIENTS AND METHODS: Between 1 December 1998 and 31 December 2000, EUS examinations were carried out in 59 patients in whom esophagopharyngeal invasion by thyroid cancer was suspected due to large tumors or tumors with poor mobility. The EUS findings were evaluated in 52 patients (10 men, 42 women; mean age 62.4 years; mean tumor size 39.5mm) with complete resections, and compared with the pathological results. RESULTS: The diagnostic specificity and accuracy of EUS in assessing invasion into the muscularis propria (82.9 %, 82.7 %) were greater than those of MRI (60 %; P = 0.034, 65.4 %; P = 0.044) and esophagography (58.8 %; P = 0.034, 60 %; P = 0.028). The accuracy for detecting cancer invasion located in the upper part of the lobe was less than for invasion in the middle and/or lower parts of the lobe ( P = 0.020). Conclusions. EUS is useful for assessing esophagopharyngeal invasion by thyroid cancer, although its effectiveness may be limited in thyroid lesions located in the upper part of the lobe.

Adenocarcinoma, Follicular↗

PubMed2002

Elevated blood flow resistance in uterine arteries of women with unexplained recurrent pregnancy loss.

BACKGROUND: Uterine perfusion appears to regulate uterine receptivity. However, vascular changes in recurrent pregnancy loss (RPL) remain poorly studied. METHODS: One hundred and twenty one women were enrolled into this study: normal women with sterility caused by male factor (control group: n = 72) and women with RPL (n = 49). Women with uterine anomaly, impaired glucose tolerance, abnormal thyroid function, or anti-phospholipid antibodies were excluded from the study. In the mid-luteal phase of a non-pregnant cycle, transvaginal pulsed Doppler ultrasonography of the uterine artery was performed. Uterine arterial pulsatility index (PI), endometrial thickness, serum estradiol, progesterone, and nitrite/nitrate concentrations were determined. RESULTS: In the RPL group, the PI in the uterine artery of women with antinuclear antibodies was significantly higher than that of women without antinuclear antibodies (P < 0.05). Among women without antinuclear antibodies, the mean (+/-SD) uterine artery PI in the RPL group (2.44 +/- 0.41) was also significantly higher than in the control group (2.19 +/- 0.40; P < 0.01). The PI was inversely correlated with serum progesterone levels (r = -0.47, P < 0.01). CONCLUSIONS: Elevated uterine arterial impedance is associated with RPL. Pulsed Doppler ultrasonography is useful in identifying women with unexplained RPL who have impaired uterine circulation.

Abortion, Habitual↗

PubMed2002

Oncogenic mutations in the thyrotropin receptor of autonomously functioning thyroid nodules in the Japanese population.

OBJECTIVE: Constitutively activating mutations of the thyrotropin receptor (TSHR) have been found in the majority of autonomously functioning thyroid nodules (AFTNs) in European patients. The reported frequency of these mutations varies among reports but amounts to 50-80%. To date, only one such mutation responsible for AFTNs has been identified in the Japanese population and the pathogenic role of such mutations in Japanese AFTNs has been questioned. In the present study, we evaluated the frequency of activating mutations in the TSHR and G(alpha)s in 10 Japanese AFTNs. DESIGN: Genomic DNA was extracted from fresh frozen tissue. The TSHR and the almost entire sequence of the gene coding for the alpha subunit of Gs have been amplified and sequenced. RESULTS: In sequence analysis, four mutations in the TSHR (T632A, I486M, M453T and L512R) were found. To complete our analysis, we searched mutations in the gene coding for the alpha subunit of Gs, in the samples negative for TSHR mutations. In one case a mutation (R201H) affecting GTPase activity was found. CONCLUSIONS: If we focus on the solitary nodules, we obtain the same mutation proportion as in European patients (70%). The absence of TSHR and G(alpha)s mutations in a significant proportion of autonomous adenomas in multinodular goiters suggests that other causes may also play a role in the genesis of these lesions.

DNA↗

PubMed2001

Involvement of up-regulation of 17beta-hydroxysteroid dehydrogenase type 1 in maintenance of intratumoral high estradiol levels in postmenopausal breast cancers.

Estradiol (E2) and estrone (E1) levels as well as mRNA expression levels of aromatase, sulfatase and 17beta-hydroxysteroid dehydrogenase type 1 (17beta-HSD1) in breast cancer tissues were studied to elucidate the mechanism involved in the maintenance of the intratumoral high E2 levels in postmenopausal patients with very low serum E2 levels. Intratumoral E2 levels of postmenopausal patients (127.2 +/- 17.5 pg/g) (mean +/- SE) were not significantly different from those of premenopausal patients (110.1 +/- 10.1 pg/g) (p = 0.36). The mRNA expression levels of aromatase and sulfatase, determined by a quantitative real-time PCR, were not significantly different between premenopausal and postmenopausal breast cancers, but 17beta-HSD1 mRNA expression levels were significantly higher in postmenopausal than premenopausal breast cancers (p < 0.05). Intratumoral E2/E1 ratios were significantly higher in postmenopausal than premenopausal breast cancers (p < 0.01). These results demonstrate that the increased conversion from E1 to E2 catalyzed by 17beta-HSD1 may play an important role in the maintenance of the intratumoral high E2 levels in postmenopausal patients.

17-Hydroxysteroid Dehydrogenases↗

PubMed2001

Technetium-99m tetrofosmin for parathyroid scintigraphy: a direct comparison with (99m)Tc-MIBI, (201)Tl, MRI and US.

The aim of this study was to evaluate the efficacy and role of technetium-99m tetrofosmin for the detection of abnormal parathyroid glands to be referred for surgical treatment. Twenty-eight consecutive patients, including 25 primary and 3 secondary cases of hyperparathyroidism, were evaluated. (99m)Tc-tetrofosmin/(99m)Tc-pertechnetate subtraction scintigraphy (TF/Tc) was performed on all patients, and the results were directly compared with those of (99m)Tc-methoxyisobutylisonitrile (MIBI)/(99m)Tc-pertechnetate subtraction scintigraphy (MIBI/Tc), (201)Tl/(99m)Tc-pertechnetate subtraction scintigraphy (Tl/Tc), magnetic resonance imaging (MRI) and ultrasonography (US). In cases of single-gland disease, the sensitivities of TF/Tc, MIBI/Tc, Tl/Tc, MRI and US were 63.2%, 68.4%, 57.9%, 55.6% and 63.2%, respectively. In cases of multi-gland disease, the sensitivities of TF/Tc, MIBI/Tc, Tl/Tc, MRI and US were 41.7%, 41.7%, 37.5%, 58.3% and 54.2%, respectively. In cases of parathyroid adenoma, the sensitivities of TF/Tc, MIBI/Tc, Tl/Tc, MRI and US were 68.8%, 75.0%, 68.8%, 62.5% and 75.0%, respectively. In cases of parathyroid hyperplasia, the sensitivities of TF/Tc, MIBI/Tc, Tl/Tc, MRI and US were 40.7%, 40.7%, 33.3%, 53.8% and 48.1%, respectively. It is concluded that, for the detection of abnormal parathyroid glands, (99m)Tc-tetrofosmin is as useful as (99m)Tc-MIBI and is more useful than (201)Tl.

Adult↗

PubMed2001

Quantitative analysis of estrogen receptor-alpha and -beta messenger RNA expression in human pancreatic cancers by real-time polymerase chain reaction.

Recent studies have disclosed the presence of a second estrogen receptor (ER; ER-beta) in addition to a classical ER-alpha. ER-beta mRNA expression has yet to be studied in pancreatic cancers. Thus, we studied the expression of ER-alpha and ER-beta mRNA in pancreatic cancers (n=29) by real-time quantitative reverse transcriptase-polymerase chain reaction, and compared the expression levels in pancreatic cancers with those in breast cancers (n=116) which are typical estrogen-dependent tumors. Breast cancers were divided into two groups, ER-positive and ER-negative, according to the ER status determined by enzyme immunoassay. ER-alpha mRNA levels were significantly (P<0.01) higher in ER-positive (679.4+/-74.7 fmol/microg RNA) than ER-negative (159.7+/-33.4) breast cancers, and pancreatic cancers showed significantly (P<0.01) lower ER-alpha mRNA levels (17.5+/-10.0) than ER-negative breast cancers. On the other hand, ER-beta mRNA levels were significantly (P<0.01) higher in ER-negative (14.1+/-1.6) than ER-positive breast cancers (7.9+/-1.0), and pancreatic cancers showed significantly (P<0.01) higher ER-beta mRNA levels (28.1+/-5.1) than ER-negative breast cancers. Accordingly, ER-alpha/ER-beta mRNA ratios were significantly (P<0.01) lower in pancreatic cancers (0.94+/-053) than in ER-positive (203.9+/-34.5) and ER-negative (21.9+/-5.2) breast cancers. ER-beta2 mRNA variant expression was significantly (P<0.05) higher in pancreatic cancers than in ER-positive and ER-negative breast cancers, and, on the contrary, ER-beta1 mRNA variant expression was significantly (P<0.01) lower in pancreatic cancers than in ER-positive and ER-negative breast cancers. These results suggest a possibility that ER-beta (ER-beta2) plays a more important role than ER-alpha in pancreatic cancers.

Adult↗

PubMed2001

Decreased expression of BRCA2 mRNA predicts favorable response to docetaxel in breast cancer.

The clinical usefulness of BRCA1 and BRCA2 mRNA levels in tumor tissues in the prediction of response to docetaxel (DOC) treatment has been studied in breast-cancer patients. Twenty-five patients with locally advanced breast tumors (n = 13) or locally recurrent tumors (n = 12) underwent tumor biopsy and were treated with DOC (60 mg/m2 every 3 weeks). BRCA1 and BRCA2 mRNA levels in the tumors were determined by real-time PCR, and the expression of 6 biological markers (P-glycoprotein, p53, erbB2, BCL2, MIB1, estrogen receptor-alpha) in the tumors was determined by immunohistochemistry. BRCA2 mRNA levels (0.547 +/- 0.200, mean +/- SE) of responders to DOC treatment were significantly (p < 0.05) lower than those of non-responders (1.538 +/- 0.358), but there was no significant difference in BRCA1 mRNA levels between responders (0.389 +/- 0.081) and non-responders (0.779 +/- 0.172). Tumors were dichotomized into groups with high or low BRCA2 mRNA levels according to the cut-off value of 0.13. The response rate (25%) of tumors with high BRCA2 mRNA levels was significantly (p < 0.01) lower than that (100%) of tumors with low BRCA2 mRNA levels. Positive predictive value, negative predictive value and diagnostic accuracy of the BRCA2 mRNA assay in the prediction of response to DOC were 100%, 75% and 80%, respectively. No significant difference was found between responders and non-responders in the expression status of any of the other 6 biological markers. These results suggest that BRCA2 mRNA levels in tumor tissues might be clinically useful in the prediction of response to DOC treatment in breast-cancer patients.

Adult↗