Biomedical subjects

M Noguchi

Publications and source records attributed to M Noguchi.

At least 361 records · Page 20Linked to original sources

PubMed1993

p53 mutation in gastric cancer: a genetic model for carcinogenesis is common to gastric and colorectal cancer.

Mutation of the p53 tumour-suppressor gene in exons 5 through 8 was examined in 118 cases of gastric cancer (59 early gastric cancers and 59 advanced gastric cancers) using PCR-SSCP (polymerase-chain-reaction-single-strand-conformation polymorphism) analysis and direct sequencing. In early gastric cancer, mutations were found in 15 of 41 (37%) cases of the cohesive type, i.e., papillary adenocarcinoma, well to moderately differentiated tubular adenocarcinoma, and poorly differentiated adenocarcinoma with solid nests or focal tubular structures, but were not detected in 18 cases of the non-cohesive type, i.e., signet-ring-cell carcinoma and poorly differentiated adenocarcinoma growing in a scattered manner. In advanced gastric cancer, 25 of 59 (42%) cases of the cohesive type had p53 mutation. No significant association was found between p53 mutation and other histopathological parameters such as macroscopic classification, lymph-node involvement and depth of tumour invasion. Fifteen of 25 (60%) mutations in the advanced gastric-cancer group were accompanied by allele loss at the p53 gene locus. Eighty-three percent of mutations in early gastric cancer and 52% of mutations in advanced gastric cancer showed G:C-to-A:T transition, almost exclusively at CpG dinucleotide mutational hot spots, indicating that the spectrum of p53 mutation was similar to that of colorectal cancer. These data suggest that the p53 mutation occurs selectively in gastric cancer of the cohesive type from the intramucosal cancer stage.

Adenocarcinoma↗

PubMed1993

Characterization of the human interleukin-2 receptor gamma chain gene.

The interleukin-2 (IL-2) receptor gamma chain is an essential component of high and intermediate affinity IL-2 receptors (IL-2Rs), playing critical roles for ligand binding and internalization. We report here the isolation and characterization of the genomic locus for human IL-2R gamma, which, like IL-2R beta, is a member of the cytokine receptor superfamily. The IL-2R gamma gene is composed of eight exons and seven introns and spans approximately 4.2 kilobases. Analogous to the IL-2R beta gene, the two pairs of conserved cysteines typical of cytokine receptor superfamily proteins are located in adjacent exons, and the conserved WSXWS motif is located in the exon preceding the one that encodes the transmembrane domain and a small part of the cytoplasmic domain. In each gene, the remainder of the cytoplasmic domain is encoded by the final two exons. Southern blot analysis suggests that IL-2R gamma is encoded by a single copy gene. Cross-hybridizing sequences were detected in DNA derived from a number of other mammalian species but not from yeast. Primer extension analysis and ribonuclease protection assays revealed that there are three principal transcription initiation sites located 32-38 nucleotides 5' to the translation initiation AUG codon. These sites are upstream of the 5' end of the published IL-2R gamma cDNA sequence. The region 5' to the transcription initiation sites exhibited promoter activity when cloned upstream of the luciferase reporter gene. With this study, the organization of the genes encoding all three chains (alpha, beta, and gamma) of the IL-2 receptor has been determined and promoters for each identified.

Amino Acid Sequence↗

PubMed1993

Biological consequences of overexpression of a transfected c-erbB-2 gene in immortalized human bronchial epithelial cells.

In order to examine the effects of the overexpression of c-erbB-2 (HER-2, neu) on human bronchial epithelial cells, a human c-erbB-2 expression vector was introduced into the simian virus 40 large T-antigen-immortalized human bronchial epithelial cell line BEAS-2B. Isolation of multiple clonal cell lines after selection revealed a wide range of expression of the gene product gp185erbB-2. While three of six clones tested expressed gp185erbB-2 at levels detectable by immunocytochemistry, only one, B2BE6, induced adenocarcinoma-like tumors in athymic nude mice. Both a nontumorigenic clone, B2BE2, and a tumorigenic clone, B2BE6, expressed comparable amounts of gp185erbB-2, which became phosphorylated on tyrosine in response to treatment with the c-erbB-2 ligands gp30 and p75. These data suggest that overexpression of c-erbB-2 in human bronchial epithelial cells can contribute to, but is not sufficient for, induction of tumorigenicity in this human model system.

Animals↗

PubMed1993

Interleukin-2 receptor gamma chain mutation results in X-linked severe combined immunodeficiency in humans.

The interleukin-2 (IL-2) receptor gamma chain (IL-2R gamma) is a component of high and intermediate affinity IL-2 receptors that is required to achieve full ligand binding affinity and internalization. We have localized the IL-2R gamma gene to human chromosome Xq13. Genetic linkage analysis indicates that the IL-2R gamma gene and the locus for X-linked severe combined immunodeficiency (XSCID) appear to be at the same position. Moreover, we demonstrate that each of three unrelated patients with XSCID has a different mutation in his IL-2R gamma gene resulting in a different premature stop codon and predicted C-terminal truncation. These data establish that XSCID is associated with mutations of the IL-2R gamma gene product. Since XSCID is characterized by absent or markedly reduced numbers of T cells, our findings imply that IL-2R gamma plays a vital role in thymic maturation of T cells. These results also have important implications for prenatal and postnatal diagnosis, carrier female detection, and gene therapy for XSCID.

Base Sequence↗

PubMed1993

Characterization of 5-HT receptors in simian isolated gastroepiploic artery.

The vascular responses of simian gastroepiploic arteries to 5-hydroxytryptamine (5-HT), 5-carboxamidotryptamine (5-CT, a selective 5-HT1-like receptor agonist), 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT, a selective 5-HT1A receptor agonist), m-trifluoromethylphenylpiperazine (TFMPP, a selective 5-HT1B receptor agonist), noradrenaline and KCl were examined in isolated, cannulated and perfused preparations. 5-HT induced dose-dependent vasoconstrictions more potently than noradrenaline did. The rank order of potency was 5-HT > noradrenaline > 5-CT >> 8-OH-DPAT = TFMPP. 5-HT- and 5-CT-induced vasoconstrictions were not significantly changed by endothelial denudation, although acetylcholine-induced vasodilatations were abolished. 5-HT-induced vasoconstrictions were depressed by phentolamine (an alpha-adrenoceptor antagonist), diltiazem (a calcium ion channel inhibitor), methysergide (a 5HT1- and 5HT2-receptor antagonist) and ketanserin (a selective 5-HT2 receptor antagonist). Noradrenaline-induced vasoconstrictions were readily inhibited by phentolamine and ketanserin. 5-CT-, 8-OH-DPAT- and TFMPP-induced vasoconstrictions were inhibited by both methysergide and ketanserin. KCl-induced vasoconstrictions were blocked by diltiazem. From these results, we conclude that (1) the simian gastroepiploic artery contains 5-HT receptors, (2) 5-HT1-like and 5-HT2 receptors are involved in the vasoconstriction of the simian gastroepiploic artery, and (3) the vasoconstriction is at least partially related to the activation of calcium ion channels.

Animals↗

PubMed1993

Internal mammary nodal status is a more reliable prognostic factor than DNA ploidy and c-erb B-2 expression in patients with breast cancer.

We evaluated the relationship among DNA ploidy, c-erb B-2 oncoprotein expression, and clinicopathologic prognostic factors, especially axillary and internal mammary node metastases, and their value in estimating the prognosis in 128 patients with operable breast cancer. There were significant correlations between DNA ploidy and clinical stage, tumor size, or axillary or internal mammary lymph node metastases, and between c-erb B-2 expression and clinical stage or axillary lymph node metastases. In a univariate study, overall or disease-free survival was significantly correlated to clinical stage, tumor size, DNA ploidy, c-erb B-2 expression, and axillary and internal mammary node metastases. In a multivariate study, however, only axillary and internal mammary node metastases were recognized as independent factors on overall survival, whereas on disease-free survival, only axillary lymph node metastases were identified as an independent indicator. Since the DNA ploidy status and c-erb B-2 expression were closely correlated with the axillary and/or internal mammary lymph node metastases, they did not appear as independent prognostic factors in this small series.

Adult↗

PubMed1993

In vitro biomechanical analysis of suture methods for flexor tendon repair.

This study was designed to compare five different suture methods that are used clinically for tendon repair. The flexor digitorum profundus tendons from the digits of adult mongrel dogs and adult human cadavers were used as models. The tendons in zone II of the hand, defined as the region from the distal palmar crease to the insertion of the flexor digitorum superficialis tendon at the middle phalanx, were transected and then were repaired by one of the suture methods developed by Kessler, Tsuge, Tajima, Savage, or Lee. The gliding function and tensile properties of the repaired tendons were evaluated biomechanically at time zero. The Tajima and Savage methods produced better gliding function than the other techniques. In the canine specimens that had been repaired by one of these two methods, the rotation of the distal interphalangeal joint was more than 60% of the rotation of the canine control specimens; only the Savage technique produced a rotation 124% that of the human control specimens. After the Tajima repair, the rotation of the proximal interphalangeal joint was 113% that of the canine control specimens and 157% that of the human controls. In the canine specimens that had had the Tajima or Savage repair, excursion of the tendon was greater than 55% that of the controls. The tendons repaired by the Savage method tolerated a significantly higher ultimate load to failure (14 and 25% that of the canine and human control specimens, respectively) than the other methods.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1993

Risk of internal mammary lymph node metastases and its prognostic value in breast cancer patients.

The risk of an internal mammary lymph node (IMN) metastasis and its prognostic value for patients with invasive breast cancer were assessed by evaluating 142 patients who had either a mastectomy with lymph node dissection or a biopsy of the IMN. By univariate analysis, overall survival significantly correlated with the patient's age, clinical axillary node status, tumor size, and DNA ploidy, as well as histologically confirmed axillary and IMN metastases. By multivariate analysis, however, only the presence of axillary and IMN metastases appeared to be an important independent factor affecting survival. However, the incidence of IMN metastases was associated significantly with age, clinical tumor and axillary node status, tumor size, axillary lymph node metastases, and DNA ploidy. Accordingly, the patient's age, tumor size, DNA ploidy, and axillary lymph node metastases proved to be effective variable for discrimination. Consequently, in predicting the presence of IMN metastases, a diagnostic accuracy of 82%, a sensitivity of 84%, and a specificity of 82% can be achieved by a discriminant function. We conclude that the discriminant function with these four variables is effective in assessing the risk of IMN metastases.

Aneuploidy↗

PubMed1993

Risk of bilateral cervical lymph node metastases in papillary thyroid cancer.

We evaluated the risk of bilateral or contralateral cervical lymph node metastases in 135 patients with papillary thyroid cancer who underwent bilateral neck dissection. We confirmed that bilateral jugular lymph node metastases were frequent in patients with obvious carcinoma in both lobes of the gland, in those with cancers arising in the isthmus, in those with clinically detectable bilateral lymphadenopathy, and in those with recurrent thyroid cancer. However, only 24% of the patients who had cancer clinically confined to one lobe with no bilateral or contralateral lymphadenopathy had histologically detected bilateral or contralateral jugular lymph node metastases. But the occurrence of contralateral jugular lymph node metastases was significantly correlated with both clinical lymphadenopathy in the ipsilateral neck and contralateral paratracheal lymph node metastases. Bilateral lymph dissection might be beneficial for these patients.

Adolescent↗

PubMed1993

Psychologic and cosmetic self-assessments of breast conserving therapy compared with mastectomy and immediate breast reconstruction.

Cosmetic and psychologic morbidity was evaluated by patients' self-assessment in 42 patients who underwent breast conserving therapy (BCT) and 48 patients who underwent mastectomy with immediate breast reconstruction (MIBR). Although sexual adjustment and fear of cancer recurrence were not significantly different between the two groups, body image was rated as significantly better in the BCT group. Additionally, in the MIBR group, nine patients expressed concern about abdominal or back scars and 15 related abdominal or back pain. Eighty-three percent of the BCT group indicated BCT as a future choice of treatment, whereas only 38% of the MIBR group indicated MIBR as a future choice of treatment. Therefore, body image and patients' satisfaction were thought to have been improved by BCT, but psychologic morbidity was the same in both groups.

Adult↗

PubMed1993

Bone mineral and other bone components in vertebrae evaluated by QCT and MRI.

To evaluate the usefulness of assessing bone components using magnetic resonance imaging (MRI), the contributions of bone components, including mineral, fat and collagen, to bone mineral density (BMD) and T1 relaxation time (T1) were studied using phantoms. Excised human vertebrae were also evaluated by quantitative computed tomography (QCT) and MRI. T1 was shortened with increasing quantities of fat and collagen. In water, T1 was significantly affected by bone density, while in oil, T1 became slightly longer as bone density increased. The presence of fat and collagen caused under- and overestimations of BMD, respectively. There was good correlation between T1 and BMD in osteoporotic vertebrae and the vertebrae with long T1 showed an increased content of hematopoietic marrow and/or abnormally increased bone mineral. It was concluded that the experimental data showed that MRI can contribute to the assessment of bone quality.

Adipose Tissue↗

PubMed1993

A comparison of breast cancers detected by mass screening and those found in out-patient clinics.

We evaluated the results of a mass screening study on breast cancer detection by physical examination alone conducted in Ishikawa Prefecture from 1978 to 1990. The number of cases of breast cancer detected by mass screening was then compared with that found in out-patient clinics during the same period. Breast cancer was detected in 88 of 152,969 women by mass screening, the detection rate being 0.06% for the total study: 0.08% at the initial screening and 0.04% at periodic screenings. Early stage breast cancer was more frequently detected during periodic screenings than at the initial screening or in out-patient clinics. Moreover, although the initial screenings may have identified patients with breast cancer at more advanced stages, the survival was not significantly different. The results of this series led us to conclude that mass screening by physical examination alone may have no impact on the mortality rate of breast cancer.

Adult↗

PubMed1993

A retrospective study on the clinical and biological prediction of axillary lymph node metastasis in breast cancer.

If axillary lymph node metastases were able to be accurately predicted, dissection could be avoided in some patients with breast cancer whose axillary nodes are clinically negative. In this study, we assessed the relationships between histological axillary lymph node metastases and clinical axillary nodal status, tumor size, DNA-ploidy, c-erbB-2 expression, and the score of the argyrophilic nucleolar organizer region. We then attempted to evaluate their predictive values for axillary lymph node metastasis in 173 patients with invasive breast cancer, retrospectively. The clinical and biological variables were significantly correlated with the presence and degree of axillary lymph node metastases. A metastatic index, calculated from the clinical and biological variables, proved especially useful for predicting axillary lymph node metastases in patients whose axillary nodes were clinically negative. However, the predictive abilities were still limited and thus it was concluded that as yet, only axillary dissection can provide accurate information on axillary lymph node metastases.

Adult↗

PubMed1993

The psychological and cosmetic aspects of breast conserving therapy compared with radical mastectomy.

An evaluation of the psychological and cosmetic morbidity of 31 patients who had undergone breast conserving treatment (BCT group) and 71 patients who had undergone radical mastectomy (RM group) revealed that 85% and 73%, respectively, were satisfied with their operative results. BCT appeared superior to RM in relation to body image, with 93% of the BCT group indicating BCT as a future choice of treatment, whereas only 35% of the RM group indicated RM as a future choice of treatment. For 59% of the BCT patients, the results were considered excellent or good by a physician, but fear of recurrence was frequently expressed by both groups even though an early stage of breast cancer had been significantly more common in the BCT group than the RM group. Sexual adjustment was the same in both groups. Body image was thus concluded to have been improved by BCT rather than RM, but psychological morbidity was essentially the same in both groups.

Adaptation, Psychological↗

PubMed1993

DNA ploidy and helix pomatia lectin binding as predictors of regional lymph node metastases and prognostic factors in breast cancer.

This study was designed to evaluate whether DNA ploidy and/or Helix pomatia lectin (HPA) staining would be useful for predicting regional lymph node metastases and patients' prognosis in 106 patients with invasive breast cancer. The combination of DNA ploidy and HPA staining correlated better with regional lymph node metastases than DNA aneuploidy or HPA staining alone. DNA ploidy and HPA staining in combination correlated strongly with overall and disease-free survival by univariate analysis. However, the prognostic significance of DNA ploidy and HPA staining in combination was lost in multivariate analysis when regional lymph node metastases were introduced into the models. This emphasized the relationship in survival between regional lymph node metastases and the combination of DNA ploidy and HPA staining. We therefore concluded that the combination of DNA ploidy and HPA staining might provide prognostic information for breast cancer patients in whom regional lymph node dissection has not been performed.

Adult↗

PubMed1993

Visualization of the thymus with therapeutic doses of radioiodine in patients with thyroid cancer.

Two cases of papillary carcinoma of the thyroid are presented in which whole-body scans following therapeutic doses of iodine-131 revealed intense anterior mediastinal uptake. In both cases, the mediastinal uptake was absent from scans obtained after removal of the entire thymus. Histologically, the resected thymus glands showed hyperplasia and contained neither thyroid tissue nor metastatic foci of thyroid carcinoma. We therefore concluded that anterior mediastinal uptake of radioiodine may be caused by hyperplasia of the thymus.

Adult↗

PubMed1993

Influence of hormones on tumor growth, cell kinetics, estrogen receptor and insulin-like growth factor-I-related protein of human breast cancer (MCF-7) cells transplanted in nude mice.

The influence of estrogens and tamoxifen on estrogen receptor (ER)-positive human breast cancer (MCF-7) cells transplanted into athymic nude mice was investigated. The mice were divided into the following three groups: (1) an E2 group with mice receiving 17 beta-estradiol dipropionate; (2) a TAM group with mice receiving tamoxifen; (3) a control group with mice given no hormone. (1) Tumor growth was significantly increased in the E2 group, but significantly decreased in the TAM group compared to control; (2) the tumor contents of insulin-like growth factor-I (IGF-I) and the rate of IGF-I-positive cells were significantly lower in the E2 group, but significantly higher in the TAM groups compared to control; (3) the IGF-I-positive cell rates were in significant inverse correlation with the [3H]thymidine-labeled cell rates in the E2, TAM and control groups. Thus, the tumor contents of IGF-I and the rate of IGF-I-positive cells were inversely correlated to the tumor growth and the [3H]thymidine-labeled cell rate in this in vivo study, although IGF-I is known to be a mitogen for breast cancer cells in vitro. Further studies are necessary to answer the questions as to the in vivo roles of immunoreactive IGF-I in ER-positive breast cancer.

Animals↗

PubMed1993

Clinical and biological prediction of axillary and internal mammary lymph node metastases in breast cancer.

We assessed the relationships among histological axillary (AX) or internal mammary (IM) metastases and clinical and biological variables, and then attempted to evaluate their predictive values for AX and IM metastases in 128 patients with invasive breast cancer. As the results, these clinical and biological variables were significantly correlated with AX and IM metastases. However, a metastatic index calculated from clinical and biological variables was not much better in prediction of the AX metastases than axillary nodal status, whereas it was useful to predict the IM metastases. Thus, the predictive ability was still limited. Since accurate prediction of AX and IM metastases is critical to therapeutic choice, however, further study would be required.

Adult↗