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Biomedical subjects

Y Monden

Publications and source records attributed to Y Monden.

At least 73 records · Page 4Linked to original sources
PubMed1997

Estimation of free calcium levels after thyroidectomy.

Total calcium is routinely measured after thyroidectomy in a clinical setting, while the measurement or calculation of the free calcium level is not generally performed. We reviewed total and free calcium levels in patients who underwent lobectomy (n = 15), subtotal thyroidectomy (n = 15) and total thyroidectomy (n = 15). Postoperative total calcium levels decreased significantly in comparison to preoperative levels in all thyroidectomies (p < 0.01), and this fall was significantly related to the extent of surgery (p < 0.01). In contrast, there was no significant difference between preoperative and postoperative free calcium levels in patients undergoing lobectomy, although we found a decrease in free calcium levels after both subtotal and total thyroidectomy. Total protein levels decreased regardless of the type of operation. Serum total calcium levels were thought to be altered by serum protein levels through the change of protein-bound calcium levels. When examined for free calcium levels, some patients were administered unnecessary calcium supplementation because hypocalcemia had been judged from the total calcium level. Since the wrong diagnosis may be given with regard to hypoparathyroidism by measurement of total calcium levels alone, we propose that free calcium levels should be routinely measured or calculated after thyroidectomy.

Biomarkers↗
PubMed1997

The expression of the CD44 variant exon 6 is associated with lymph node metastasis in non-small cell lung cancer.

Recently, it was suggested that splice variants of the surface glycoprotein CD44 (CD44v) were associated with tumor metastasis in some cancers. We examined the expression of variant forms of CD44 in 31 non-small cell lung carcinomas (NSCLCs) and in 8 normal lung tissue samples by reverse transcription-PCR (RT-PCR). CD44v3, CD44v5, CD44v6, and CD44v7 were not expressed or were weakly expressed in normal lung tissue (0 of 8). In contrast, CD44v3, CD44v5, CD44v6, or CD44v7 was expressed in 28 of 31 (90.3%) NSCLCs. Additionally, we examined the expression of CD44v6, which has been shown to be related to metastasis, in 5 normal lungs and 30 NSCLCs by RT-PCR and immunohistochemical analysis to clarify which cells express CD44v6 in NSCLC specimens. Thirty-six of 61 (59%) NSCLCs variably expressed CD44v6 by RT-PCR, and cancer cells were selectively immunostained by anti-CD44v6 antibodies in 23 of 30 (76.7%) NSCLCs. The results of immunohistochemical analysis almost correlated with those of RT-PCR. NSCLCs with lymph node metastasis expressed significantly more v6 exon than did those without lymph node metastasis [23 of 29 (79.3%) versus 13 of 32 (40.6%); P < 0.01]. There was a significant association between the intensity of v6 expression by RT-PCR and the frequency of cases showing lymph node metastasis (Cochran-Armitage's test, P < 0.002). In conclusion, this study demonstrated that in NSCLC, a number of variant forms of CD44 are frequently expressed, although these variants are infrequently expressed in normal lung tissue, and that the expression of CD44v6 is particularly associated with lymph node metastasis in NSCLC.

Adult↗
PubMed1996

Molecular epidemiology of breast cancers in northern and southern Japan: the frequency, clustering, and patterns of p53 gene mutations differ among these two low-risk populations.

Comparison of acquired mutations in the p53 tumor suppressor gene can illuminate factors contributing to carcinogenesis among cancer cohorts. Japan has an ethnically homogeneous population with a low incidence of breast cancer. Previously we reported an unusual frequency, allelic status, and clustering of mutations in breast cancers from the northern part of the main Japanese island. To extend these findings, exons 2-11 and adjacent intronic sequences were analysed in tumors of women from northern (Hokkaido) and southern (Tokushima) Japan. The frequency of breast cancers with p53 gene mutations in the Hokkaido group is the highest reported (81%) while that in Tokushima (28%) is similar to most other populations. Thirteen of the 19 mutations (68.4%) in the Hokkaido cohort were heterozygous, an unusually high frequency for p53 mutations in any tumor type. There were three missense mutations at codon 175, a known hotspot for alterations in the p53 gene, and three missense mutations at codon 179, a rare site for p53 changes. In addition, the patterns of p53 gene mutation differed between the two Japanese cohorts (P=0.04). The multiple differences in acquired p53 mutations suggest unsuspected biological differences among breast cancers in northern and southern Japan. In addition, the high frequency of p53 mutations in breast cancers from Hokkaido predicted a poorer prognosis for this population which was confirmed on examination of mortality data.

Adult↗
PubMed1996

Cloning of the RhoB gene from the mouse genome and characterization of its promoter region.

Rho proteins have been implicated in a variety of cytoskeletal functions, but it is unclear how Rho proteins regulate these cellular functions and how Rho proteins are regulated. In this study, we cloned the rhoB gene from the mouse genome and characterized its promoter region. The predicted amino acid sequence was identical to that encoded by the human rhoB gene. A site for initiation of transcription was found at position -376 relative to the site for initiation of translation. Deletion analysis of the 5'-flanking region of the rhoB gene revealed that the minimum region of the promoter was located between positions -507 and -376. Northern blotting analysis showed that the expression of the mouse rhoB gene was induced by serum, suggesting that expression of the rhoB gene might be controlled by some signal-responsive element(s).

3T3 Cells↗
PubMed1996

A dose-response relationship between the frequency of p53 mutations and tobacco consumption in lung cancer patients.

Mutations of the p53 tumor suppressor gene are frequent in lung cancers. It is suggested that p53 mutations are associated with smoking-induced lung carcinogenesis. We examined p53 mutations in 53 lung cancers by analyzing reverse transcription-polymerase chain reaction-single strand conformation polymorphism (RT-PCR-SSCP) to ascertain the association between p53 mutations and smoking. Twenty-five (47%) of 53 lung cancers carried p53 mutations. A discriminant analysis showed that the Brinkman index (0.156) and gender (0.140) significantly influenced p53 mutations. Furthermore, there was a dose-response relationship between the quantity of cigarettes consumed and the frequency of p53 mutations in lung cancer patients (P < 0.001). In patients with adenocarcinoma, the frequency of p53 mutations correlated with the amount of the tobacco smoked (P < 0.05). We suggest that the p53 gene is a target of particular carcinogen in tobacco smoke.

Adenocarcinoma↗
PubMed1996

Difference in cytokine production in acute and chronic rejection of rat lung allografts.

In Brown Norway to Lewis rat lung transplantation, short-term administration of cyclosporine produces permanent adoption of allografts; however, the adopted grafts show symptoms of chronic rejection. To clarify the difference in cytokine production in acute an chronic rejection of the allografts, an immunohistochemical study was performed. In acute rejection, positive cells for respective cytokines were observed in infiltrating cells, increasing in number as the days after transplantation passed, and reaching a maximum on the fifth day. The strongest reactivity was observed perivenously. In chronic rejection, TNF-alpha positive cells were observed in the perivascular and peribronchial regions, especially around class II positive epithelia. The number of positive cells was, however, less than that in the vascular phase of acute rejection. Few cells were positive for IL-1 beta, IFN-gamma and, unexpectedly, for IL-4. These facts indicate the functional difference of infiltrating cells between acute and chronic rejection.

Animals↗
PubMed1996

Myasthenia gravis induces the activation and maturation of lymphocytes in thymoma.

The biological differences between lymphocytes separated from thymoma patients with myasthenia gravis (MG) and those separated from thymoma patients without MG was examined. We investigated whether lymphocytes in thymoma (Th-L) of patients with and without MG could react to interleukin-2 (IL-2) to develop cytolytic activity against K562 and lympho kine-activated killer (LAK) activity, and their phenotypic changes during incubation with IL-2. Sixteen thymoma patients who consisted of eight patients with MG and eight patients without MG were investigated. Th-L of all MG patients could react to IL-2 to develop LAK activity. Th-L of all of MG patients also developed cytolytic activity against K562 target cells. Cytolytic activity against K562 and LAK activity from Th-L of the MG patients were significantly higher than those from Th-L of the patients without MG (P < 0.01, P < 0.01). The proportions of CD3+ and CD4-/CD8+ cells of Th-L of MG patients increased significantly during the incubation period with IL-2 (P < 0.05, P < 0.05). The proportion of CD4+/CD8+ cells of Th-L of patients with MG decreased significantly (P < 0.05) during incubation with IL-2. On the other hand, there was no significant phenotypic change in Th-L of the patients without MG. These results indicate that MG induces the functional and phenotypic activation and functional and phenotypic maturation of Th-L.

Adult↗
PubMed1996

Postoperative adjuvant randomised trial comparing chemoendocrine therapy, chemotherapy and immunotherapy for patients with stage II breast cancer: 5-year results from the Nishinihon Cooperative Study Group of Adjuvant Chemoendocrine Therapy for Breast Cancer (ACETBC) of Japan.

Between 1985 and 1988, the effect of using ftorafur (FT) or PSK (an immunotherapy agent) in combination with the conventional postoperative adjuvant therapy using mitomycin (MMC) plus tamoxifen (TAM) was assessed in stage II, oestrogen receptor-positive (ER+) breast cancer patients. Furthermore, in ER- breast cancer stage II patients, the effects of postoperative adjuvant therapy using MMC plus FT were compared with the effects of postoperative adjuvant therapy using MMC plus PSK. Patients had primary stage II breast cancer and had undergone total mastectomy plus axillary dissection or more radical surgery. On the day of surgery, MMC (13 mg/m2) was administered intravenously. Then, ER+ patients received one of three regimens of drug therapy, starting 2 weeks after surgery: regimen A (daily oral treatment with 30 mg of TAM), regimen B (daily oral treatment with 30 mg of TAM and 600 mg of FT) or regimen C (daily oral treatment with 30 mg of TAM and 3 g of PSK) [corrected]. ER- patients received either regimen D (daily oral treatment with 600 mg of FT) or regimen E (daily oral treatment with 3 g of PSK), starting 2 weeks after surgery. Of the 540 ER+ patients registered, 525 were evaluated. The 5-year overall survival rate for ER+ patients was higher for patients who received regimen B (94.2%) than for those who received regimen A (86.9%) or regimen C (89.9%) (P = 0.063). The 5-year relapse-free survival rate was higher for regimen B (88.9%) than for regimen A (78.6%) and regimen C (77.2%) (P = 0.010). Stratified analysis revealed better results with the FT-combined therapy in patients positive for lymph node metastasis and premenopausal patients. These results indicate the effectiveness of using FT in combination with TAM. Of the 376 ER- patients registered, 364 were evaluated. The 5-year overall and relapse-free survival rate for ER- patients did not differ significantly between patients who received regimen D and those who received regimen E.

Adult↗
PubMed1996

Extended thymectomy for myasthenia gravis patients: a 20-year review.

BACKGROUND: Since 1973 we have performed extended thymectomy for myasthenia gravis because of the presence of thymic tissue in the anterior mediastinal fatty tissue. Follow-up results were reviewed and influencing factors were investigated. METHODS: Three hundred seventy-five patients with myasthenia gravis (286 nonthymomatous and 89 thymomatous) who have undergone extended thymectomies were reviewed. The status of the patients was evaluated as follows: A (remission), B (improvement), C (no change), D (deterioration), E (death due to myasthenia gravis). Evaluation was performed at 3 and 6 months, and at 1, 3, 5, 10, 15, and 20 years. The effectiveness of the operation was estimated by the remission rate (RR = A/Total number of patients evaluated) and the palliation rate (PR = A + B/Total number of patients evaluated) at each point. RESULTS: Remission rates of the nonthymomatous patients were 15.2% (3 months), 15.9% (6 months), 22.4% (1 year), 36.9% (3 years), 45.8% (5 years), 55.7% (10 years), 67.2% (15 years), and 50.0% (20 years). Remission rates in the thymomatous patients were 13.6% (3 months), 17.5% (6 months), 27.5% (1 year), 32.4% (3 years), 23.0% (5 years), 30.0% (10 years), 31.8% (15 years), and 37.5% (20 years). Absence of thymoma, younger age, and short duration of the disease were favorable prognostic factors. Thymectomy was effective also in patients with ocular myasthenia gravis. Preoperative steroid administration did not improve the outcome. CONCLUSIONS: Extended thymectomy is an excellent operative procedure for myasthenia gravis in both nonthymomatous and thymomatous patients.

Adult↗
PubMed1996

DNA adduct formation by hormonal steroids in vitro.

We examined the binding of various steroid hormones to DNA in vitro by means of 32P-postlabeling. Seventeen steroid hormones and cholesterol (CS) were incubated with human liver DNA at 37 degrees C for 1 h under aerobic conditions in the absence of catalysis. The reaction mixtures were analyzed by the nuclease P-1 version of 32P-postlabeling. The results showed that cortexolone (CX), prednisolone (PS), cortisone (CN), cortisol (CL), tetrahydrocortisol (TC), corticosterone (CC), 11-deoxycorticosterone (DC), dexamethasone (DX), dihydrocortisol (DL), and aldosterone (AL) covalently bound with DNA. However, progesterone (PG), 17 alpha-hydroxyprogesterone (HG), estrone (E1), estradiol (E2), estriol (E3), testosterone (TS), cortol (CR) and the original compound for biosynthesis, CS, did not form adducts. In absence of DNA, the steroids themselves did not give rise to any spot on TLC under the same conditions. The dose-responses of DNA binding by DC, DL, CC, CL and CN were linear. The relative adduct labeling of reactive steroids at a concentration of 2 mM were as follows: 68.8 (CX), 53.2 (PS), 39.6 (CN), 29.9 (CL), 20.9 (TC), 12.9 (CC), 12.3 (DC), 7.5 (DX), 4.7 (DL), 1.2 (AL) adducts per 10(8) nucleotides. Reactive and nonreactive steroids were distinguishable by the presence or absence of the carbonyl group (-CO-CH2OH) at carbon seventeen (C17) of the cholesterol skeleton. This implies that the electrophilic carbonyl or a neighboring group perhaps involved in the formation of covalent bond with DNA. To investigate the nature of target base(s) of these DNA reactive steroids, mononucleotides of all four bases of DNA were reacted with CN, CL, CC and cochromatographed with the obtained spots of DNA reactions. The results of which stated that these steroids and guanine reaction gave the same spots as observed in DNA reaction, indicating guanine is the main target of these DNA reactive steroids. Hep G2 human hepatocellular carcinoma cells were used as an alternative model. Although nine steroids (CL, DL, TC, PS, DX, PG, E2, TX, CR) did not react with intracellular DNA under our experimental conditions, our findings suggested that some hormonal steroids can form covalent DNA adducts in vivo.

Carcinogens↗
PubMed1996

Failure to detect mutations in the retinoblastoma protein-binding domain of the transcription factor E2F-1 in human cancers.

The functions of the transcription factor E2F-1 are regulated by the RB protein through the RB-binding domain of E2F-1 and this factor is considered to be an important molecule that functions downstream of the RB protein. In order to determine whether E2F-1 that cannot bind to RB might be associated with various human cancers, we searched for mutations in the RB-binding domain of E2F-1 using samples of DNA from various clinical specimens obtained from 406 cancer patients (with lung, pancreatic, stomach, colon, esophageal, and hepatic cancers) by analysis of polymerase chain reaction-mediated single-strand conformational polymorphism. No mutations or deletions were detected in genes for E2F-1 from any of the tumor tissues examined. These results suggest that a mutation or deletion in E2F-1 that might affect binding of the RB protein is not involved in human cancers.

Base Sequence↗
PubMed1996

Heterogeneous distribution of thyrotrophin receptor messenger ribonucleic acid (TSH-R mRNA) in papillary thyroid carcinomas detected by in situ hybridization.

OBJECTIVE: TSH suppression therapy has been reported to be effective in some cases of papillary carcinoma of the thyroid. However, there has been little information regarding the status of expression of TSH-R mRNA in papillary carcinomas. Therefore, we examined the expression of TSH receptor (TSH-R) mRNA in thyroid tumours by in situ hybridization. DESIGN: Surgically resected thyroid tumour specimens were used. The expression level of TSH-R mRNA was detected by in situ hybridization, and the difference between tumours and their adjacent normal thyroid tissues was assessed. PATIENTS: Tumours and adjacent normal thyroid tissues were obtained from nine patients with differentiated papillary carcinomas and eight with adenomas. MEASUREMENTS: We performed in situ hybridization on frozen sections of thyroid tissues. Digoxigenin-labelled oligonucleotide was used to hybridize and to detect TSH-R mRNA. We counted positively stained cells and non-stained cells in each section, calculated the positivity of stained cells and assessed the distribution of positively stained cells. RESULTS: In normal thyroid tissue, the positivity was 95.3 +/- 2.3% (mean +/- SD) and the distribution of TSH-R mRNA was homogeneous. In adenoma, positivity was 93.5 +/- 4.4%. In most cases of adenoma, the distribution was homogeneous. In papillary carcinoma, the expression level of TSH-R mRNA was significantly lower and the positivity was 81.9 +/- 12.6%. Furthermore, in five cases of papillary carcinoma, the distribution was heterogeneous; four of these cases were stage 3, while the remaining case was stage 1. Three of the four cases with a homogeneous distribution were stage 1, while one case was stage 3. CONCLUSIONS: The heterogeneity of TSH-R mRNA distribution suggests the effect of TSH on carcinoma cells may be variable. Furthermore, papillary carcinomas of advanced clinical stage showed a tendency to low expression and heterogeneous distribution of TSH-R mRNA.

Adenoma↗
PubMed1995

Mucosa-preferential DNA adduct formation by 2-amino-3-methylimidazo-[4,5-f]quinoline in the rat colonic wall.

The mechanism of mucosa-specific formation of DNA adducts, which was found recently in human intestines, was studied in male F344 rats treated with 2-amino-3-methylimidazo[4,5-f]quinoline (IQ). There are three conceivable pathways for p.o. administered IQ to reach the target colonic mucosal cells: pathway 1, through the digestive canal which exposes from the lumenal direction; pathway 2, following enterohepatic circulation re-expose from the lumenal direction; and pathway 3, exposure via blood circulation. To investigate these possible pathways, the following surgical procedures were performed: (a) portal catheterization for IQ administration to eliminate pathway 1 and (b) choledochal catheterization for bile drainage to eliminate pathway 2. When both procedures are combined, only pathway 3 is active. Four types of IQ-DNA adducts were commonly observed in the colons of all experimental groups, with no qualitative difference between the mucosal and muscular layers. When IQ-HCl was administered by p.o. gavage at a dose of 100 mumol/kg body weight, approximately 70% of the IQ-DNA adducts in the colonic mucosa (13.1 +/- 4.3 adducts/10(7) nucleotides) was induced through pathway 1. Pathway 3 induced the remaining 30% of mucosal adducts, producing equal adduct levels in both layers. Pathway 2 did not work for adduct formation. The DNA adduct formation was unaffected in the presence of intestinal flora, indicating that detoxified IQ does not reactivate by floral enzymes. In conclusion, mucosa-specific DNA adduct formation in the colon is caused most likely by the absorption of carcinogens through the lumen.

Animals↗
PubMed1995

A Malignant Phyllodes Tumor of the Breast in a 6-Year Old Girl.

We recently encountered a 6-year-old girl with a malignant phyllodes tumor of the breast. The patient's mother noticed a tumor on the right breast of her first doughter at 8 months after from her birth. The baby was brought to the Second Depertment of Surgery, University of Tokushima, at age 20 months. We recommended removal of the 3.5 x 2.9 cm tumor in the right breast, but it was not done. Next, she visited our department at 6 years of age because the tumor had gradually enlarged, reaching a size of 4.3 &timus; 4.0 cm. She underwent excisional resection of the tumor, and the tumor was diagnosed as a malignant phyllodes tumor of the breast coexisting with a borderline phyllodes tumor. To our knowledge, this is the youngest reported case of a malignant phyllodes tumor of the breast. Moreover, the malignant lesion was positive for estrogen receptor (ER) and showed strong proliferating cell nuclear antigen (PCNA) staining. On the other hand, the borderline part was negative for ER and showed weak PCNA staining. Thus, in the present case, the expression of ER, the exposure to estrogen (for example, the mother's estrogen during gestation) and increase in the proliferation rate may have played important roles in the mechanism of the transformation of the phyllodes tumor.

Journal Article↗
PubMed1995

Trichostatin A inhibits both ras-induced neurite outgrowth of PC12 cells and morphological transformation of NIH3T3 cells.

During screening for inhibitors of ras-mediated differentiation of PC12 cells, trichostatin A (TSA) was isolated from the metabolites of Streptomyces as a potent inhibitor. TSA blocked both oncogenic ras- and NGF-induced neurite outgrowth from PC12 cells. However, addition of TSA 1 h after NGF-stimulation did not inhibit neuronal differentiation, suggesting that TSA affects an early step in the NGF-signaling pathway mediated by ras. Northern blotting analysis showed that TSA prolonged the maximum expression period of c=fos mRNA triggered by NGF and delayed its return to the basal level. TSA reduced c-jun mRNA induction by NGF but greatly enhanced c-myc mRNA induced by NGF. Yoshida et al. (J. Biol. Chem, 265, 17174-17179, 1990) showed that TSA inhibits histone deacetylation, which might influence the gene expression involved in cellular differentiation. In this study, we also found that TSA prevents histone deacetylation in PC12 cells as well as other cell lines, suggesting that inhibition of histone deacetylation by TSA might affect the expression of early-response genes. We also demonstrated that TSA induced reversion of oncogenic ras-transformed NIH3T3 cells to a normal morphology, suggesting that inhibitors of ras-mediated differentiation of PC12 cells may be effective as anticancer agents.

3T3 Cells↗
PubMed1995

Human calgizzarin; one colorectal cancer-related gene selected by a large scale random cDNA sequencing and northern blot analysis.

A cDNA library was constructed from COLO 205 and 1056 clones randomly selected from this library were partially sequenced. Two hundred and two (38.4%) out of 526 independent genes had more than 80% similarity to the genes reported in GenBank. In Northern blot analysis, 96 out of 98 genes were shown to be expressed at the same level in colon and lung carcinoma cell lines and control fibroblasts. Only two clones, including human synovial phospholipase A-2 and a homologue to rabbit calgizzarin, were expressed at different levels among these cell lines. The full sequence of human calgizzarin was determined and its expression was remarkably elevated in colorectal cancers compared with that in normal colorectal mucosa.

Amino Acid Sequence↗
PubMed1995

Difference in thymidylate synthetase activity in involved nodes compared with primary tumor in breast cancer patients.

Thymidylate synthetase (TS) is a key enzyme as a methyl donor in the methylation reaction from dUMP to dTMP. TS activity was assessed in various tissue of mammary disorders. The descending order of TS activity was as follows: cancer-positive nodes, primary cancers, cancer-negative nodes, benign lesions, and normal parenchyma. Significant differences in TS activity were found between the positive nodes and each of the other tissues (p < 0.01). In node-positive cases, a significant correlation in TS activity was found between the primary cancers and positive nodes (r = 0.616, p = 0.033). There was no correlation between the nodal status and the TS activity in primary cancers. In 11 of 12 cases, the TS activity of positive nodes was higher than the 'calculated' TS activity of the primary cancer, which was defined as the TS activity per unit weight of cancer cells. A significant correlation was found between the calculated TS activity and the mitotic frequency in primary cancers (r = 0.697, p = 0.0001). On the other hand, a significant correlation could not be found between the TS activity and the mitotic frequency in positive nodes (r = 0.364, p = 0.244).

Breast↗