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Biomedical subjects

K Mukai

Publications and source records attributed to K Mukai.

At least 91 records · Page 5Linked to original sources

[Changes in cytoskeletal proteins in childhood cataract lenses].

PURPOSE: Approximately 50% of congenital and childhood cataract seen in the clinic is of undetermined origin. Biochemical analysis of the cataracts is rare. This study analyzes lens proteins to determine the mechanism of congenital and childhood cataracts. METHOD: We analyzed the lens proteins from 10 young patients after cataract operations, using sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), densitometry analysis, and western immunoblotting. RESULTS: Densitometry of separated proteins showed a decrease in the high molecular protein bands of posterior subcapsular cataract (PSC). Specifically, spectrin (235 kDa), filensin (100 kDa), and vimentin (57 kDa) were absent from the SDS-PAGE of PSC. Increases in filensin and vimentin were observed in a Christmas tree cataract and lamellar cataracts. Western immunoblots confirmed the densitometry of SDS-PAGE. CONCLUSION: These results suggest that changes in cytoskeletal proteins may contribute to congenital and childhood cataract.

Adolescent↗

Infrequent somatic mutation of the adenomatous polyposis coli gene in aberrant crypt foci of human colon tissue.

BACKGROUND: The authors examined somatic mutations of the adenomatous polyposis coli (APC) gene in 84 human aberrant crypt foci (ACF) to determine whether APC gene mutations were involved in the histologic progression of ACF. METHODS: Mutation cluster regions of the APC gene were subjected to polymerase chain reaction single-strand conformation polymorphism analysis and direct sequencing. RESULTS: Four kinds of deletion were detected in the mutation cluster regions of APC gene in five ACF. APC mutation was detected in 1 of 18 ACF with Stage I abnormalities (6%). Four of 10 adenomatous ACF (40%) harbored the mutation. There were no mutations in 56 hyperplastic ACF. CONCLUSIONS: These results suggest that APC mutations may be involved initially in only a limited number of adenomas in ACF.

Adenomatous Polyposis Coli↗

Loss of heterozygosity in the tuberous sclerosis gene associated regions in adenocarcinoma of the lung accompanied by multiple atypical adenomatous hyperplasia.

To investigate the potential allelic loss of tumor suppressor gene loci in the tuberous sclerosis complex (TSC)-associated regions located on the long arm of chromosome 9 (9q) and on the short arm of chromosome 16 (16p) in human lung carcinoma, we analyzed 21 paired normal and tumor DNAs with 11 polymorphic markers on the chromosomes. All tumors were adenocarcinoma of the lung, which included 9 adenocarcinomas with associated multiple atypical adenomatous hyperplasia (AAH). A precise microdissection technique followed by polymerase chain reaction (PCR) amplification to prevent under-evaluation of loss of heterozygosity (LOH) was used. Twelve of the 21 (57%) adenocarcinomas displayed LOH on 9q. Five of the 21 adenocarcinomas (24%) showed LOH at all informative loci on 9q, whereas 7 (33%) demonstrated partial LOH on 9q34. Among these 21, 5 (24%) showed partial LOH between D9S149 and D9S150, where TSC1 is located. The incidence of associated AAH was significantly higher in adenocarcinoma harboring a partial LOH in the TSC1-associated region (p = 0.0048). Twelve of the 21 (57%) adenocarcinomas displayed LOH on 16p. No significant differences in the clinico-pathological characteristics could be discerned between adenocarcinomas with and without LOH on 16p. When combining these data, a partial LOH at TSC1- and/or TSC2-associated loci was observed more frequently in cases with well-differentiated adenocarcinoma (p = 0.086) and associated AAH (p = 0.081). In conclusion, our results suggest that the TSC-associated regions are new candidate loci for tumor suppressor genes in lung adenocarcinoma, especially when it is accompanied by multiple AAH.

Adenocarcinoma↗

Adrenocorticotropic hormone stimulates CYP11B1 gene transcription through a mechanism involving AP-1 factors.

To elucidate the mechanism(s) by which adrenocorticotropic hormone (corticotropin) stimulates transcription of the steroid 11beta-monooxygenase gene (CYP11B1) in adrenocortical cells, the 5'-flanking region of rat CYP11B1 was analyzed using transient transfection and protein-binding assays with mouse adrenocortical Y1 cells. The results indicated that both basal and corticotropin-induced transcriptional activation of CYP11B1 required a common regulatory element containing a binding site for activator protein-1 (AP-1) transcription factors (dimers of the Jun and Fos family proteins) in the 5'-flanking region. Other DNA-binding protein(s) such as transcription factor Ad4BP was not required for either basal or corticotropin-induced transcriptional activation. Corticotropin stimuli were found to induce expression of a subset of the jun and fos family gene products in Y1 cells significantly, while total amounts of AP-1 factors capable of binding to its site in the CYP11B1 promoter did not change greatly. Treatment of rats with corticotropin had similar effects on mRNA levels of the jun and fos family genes in the adrenocortical zona fasciculata cells together with an enhancing effect on the level of CYP11B1 mRNA in the tissue. The effects of corticotropin on mRNA levels of the jun and fos family genes as well as transcription of CYP11B1 in Y1 cells were mimicked by treatment of the cells with dibutyryl cAMP. Furthermore, when components of AP-1 factors were overexpressed by transfecting Y1 cells with their expression vectors, a paired expression of AP-1 components such as c-Jun and c-Fos, which were inducible by corticotropin, transactivated the CYP11B1 promoter more strongly in the absence of corticotropin than other combinations such as JunD and Fra-2 expressed constitutively. These results suggest that corticotropin regulates transcription of the CYP11B1 gene by causing compositional changes in AP-1 transcription factors in the adrenocortical cells via a cAMP-dependent pathway.

Adrenal Cortex↗

Tumor thickness predicts cervical metastasis in patients with stage I/II carcinoma of the tongue.

BACKGROUND: The incidence of cervical metastases after surgery for Stages I/II carcinoma of the tongue is 30-40%. Postoperative cervical metastases are an adverse prognostic factor for patients with this malignancy. The purpose of this study was to evaluate the clinicopathologic factors associated with late cervical metastases in patients with carcinoma of the tongue. METHODS: The clinicopathologic features of 44 patients with previously untreated Stage I/II carcinoma of the tongue were reviewed. All patients were treated with partial glossectomy only. RESULTS: Cervical metastases developed in 21 of 44 patients within 5 years. Factors significantly associated with the development of cervical metastases were invasive growth, differentiation, nuclear polymorphism in the deep portion, tumor border, nest formation, infiltrative growth ratio, depth, and thickness. No statistical correlations between cervical metastases and age, gender, tumor location, clinical stage, Brinkman index, alcohol index, mitosis, connective tissue, lymphocytic infiltration, or perineural invasion were found. Multivariate analysis demonstrated that only tumor thickness > 4 mm had a predictive value for cervical metastasis (risk ratio 9.4; 95% confidence interval, 1.5-57.7). CONCLUSIONS: The current study data indicate that patients with Stage I/II carcinoma of the tongue > 4 mm in thickness are at increased risk for subsequent cervical metastasis. Thus, conservative supraomohyoid neck dissection is indicated in patients with Stage I/II carcinoma of the tongue > 4 mm in thickness.

Adult↗

Helical computed tomography in the diagnosis of portal vein invasion by pancreatic head carcinoma: usefulness for selecting surgical procedures and predicting the outcome.

OBJECTIVE: To evaluate the use of helical computed tomography (CT) in diagnosing portal vein (PV) invasion by pancreatic head carcinoma and its usefulness in predicting outcome. DESIGN: Validation cohort study. SETTING: Tertiary care public hospital. PATIENTS: Twenty-seven patients with carcinoma involving the pancreatic head were preoperatively studied with helical CT. All patients underwent resection. MAIN OUTCOME MEASURE: By quantifying the contact between the tumor and PV on helical CT, the relationship between them was classified into 1 of 4 types: type 1, visible fat layer between PV and the tumor; type 2, with the total PV circumference defined as 360 degrees, contact between the tumor and PV was considered to be 90 degrees or less; type 3, contact ranged between 91 degrees and 180 degrees; and type 4, contact greater than 180 degrees. Helical CT results were compared with intraoperative observation, histological findings of the resected specimen, and postoperative course. RESULTS: When helical CT showed type 3 or 4, the case was diagnosed as positive for PV invasion. Sensitivity, specificity, and overall accuracy were 83%, 100%, and 89% when compared with the intraoperative assessment, and 92%, 79%, and 85% with the histological assessment, respectively. One- and 2-year survival rates were 86% and 69% for type 1, 100% and 75% for type 2, and 33% and 12% for type 3, respectively. The survival rates of patients with types 1 and 2 were significantly higher than that of those with type 3 (P<.05). All 3 patients with type 4 died within 9 months. CONCLUSIONS: Helical CT facilitates detection of PV invasion by pancreatic head carcinoma. The extent of PV involvement reflected the outcome after pancreatectomy.

Adenocarcinoma↗

Small polypoid lesions of the gallbladder: differential diagnosis and surgical indications by helical computed tomography.

OBJECTIVES: To demonstrate the helical computed tomographic (CT) features of small polypoid lesions of the gallbladder and to establish a clinical strategy based on CT findings for the treatment of such lesions. DESIGN: Validation cohort study. SETTING: Tertiary care public hospital. PATIENTS: Thirty-one patients with polypoid lesions of the gallbladder (< or = 3 cm) underwent CT followed by resection. MAIN OUTCOME MEASURE: The detectability of the lesions on both unenhanced and enhanced CT and the configuration of the lesions on enhanced CT were prospectively evaluated in comparison with the histopathological findings. RESULTS: Unenhanced CT detected 14 (45%) of the 31 lesions, whereas enhanced CT detected all of the lesions. The detection rates of the neoplastic lesions (adenoma, adenocarcinoma, and metastatic tumor) and cholesterol polyps were 81% (13/16) and 7% (1/15), respectively (P<.001). Among the 20 lesions demonstrated as pedunculated, 6 (30%) were neoplastic, whereas 10 (91%) of the 11 lesions demonstrated as sessile were neoplastic (P<.001). When a lesion was demonstrated on unenhanced CT or its shape was sessile on enhanced CT, the case was diagnosed as a neoplastic lesion. The sensitivity, specificity, positive predictive value, negative predictive value, and overall accuracy of the CT diagnosis of the neoplastic lesions were 88% (14/16), 87% (13/15), 88% (14/16), 87% (13/15), and 87% (27/31), respectively. CONCLUSION: Computed tomography can differentiate neoplastic and nonneoplastic small polypoid lesions of the gallbladder and reliably identify the presence of neoplastic lesions that should be resected.

Adult↗

Malignant phyllodes tumour with a noninvasive ductal carcinoma component.

A malignant phyllodes tumour with a noninvasive ductal carcinoma component is reported. The patient was an 80-year-old Japanese woman with a breast tumour detected by routine physical examination. A simple mastectomy was performed. The excised tumour was 10.5 x 9.4 x 5.4 cm in size and bulged into the skin with ulceration. The macroscopic appearance was that of a phyllodes tumour. Histologically the tumour consisted mainly of stromal components with a leaf-like structure lined by atypical ductal epithelium. The epithelial component showed gradual evolution to intraductal papillary carcinoma in a few areas. The stromal component was composed mainly of fibrosarcoma with areas of osteosarcoma and rhabdomyosarcoma. Neither stromal invasion of intraductal carcinoma nor transition between the stromal and epithelial elements was seen. Three months after the operation, death occurred, with multiple pulmonary and subcutaneous metastases. This case probably represents malignant change in both the stromal and the epithelial components of a phyllodes tumour. Since the two elements were independent, the possibility that a phyllodes tumour may be one of the origins of true carcinosarcoma is raised.

Aged↗

The fibrotic focus in advanced colorectal carcinoma: a hitherto unrecognized histological predictor for liver metastasis.

A fibrotic focus (FF) is a clearly defined area consisting of fibroblasts and/or collagen fibres arranged in irregular or storiform patterns within tumours. We looked to see whether FF in advanced colorectal carcinoma was associated with distant organ metastasis especially to the liver. The correlation between FF and the presence of synchronous or total (synchronous and/or metachronous) liver metastasis and tumour recurrence was assessed in 77 patients with Dukes B and C advanced colorectal carcinoma treated by resection. The median follow-up period was 21 months. In multivariate analysis, FF significantly increased the relative risk (RR) of synchronous liver metastasis (RR=4.9, P<0.05) and total liver metastasis (RR=4.6, P<0.05). FF also increased the RR of tumour recurrence (RR=2.4), but the increase was not statistically significant. FF is a newly recognized histological indicator of liver metastasis in advanced colorectal carcinoma.

Adenocarcinoma↗

Modification of enzyme sulfhydryl groups suppresses UV-induced mutagenesis depending on the nucleotide excision repair system in Escherichia coli B/r WP2.

S-Methyl methanethiosulfonate (MMTS), which was isolated from cauliflower (Brassica oleracea var. botrytis) homogenate as a potent bio-antimutagen, has been used as an enzyme-sulfhydryl (SH) temporary blocking agent in modification studies of enzyme activities. We examined whether 23 kinds of MMTS-related compounds have a suppressing effect on UV mutagenesis in Escherichia coli B/r WP2. Disulfide derivatives of diphenyl, 2.2'-dipyridine and 4.4'-dipyridine, and N-ethyl maleimide (NEM), which temporarily or tightly block sulfhydryl (SH)-groups, showed similar suppressing effect in E. coli B/r WP2, but not in WP2s hcr- (uvrA-) in the range of nanomolar/plate as MMTS previously did. Cystamine sulfate, methyl methylsulfinylmethyl sulfide and S-methyl-L-cysteinesulfoxide moderately suppressed, and diallyl disulfide and glutathione (oxidized form) weakly suppressed UV mutagenesis in E. coli B/r WP2 in the range of micromolar/plate. MMTS and phorone, a glutathione (GSH)-depleting agent, lowered the intracellular GSH level in E. coli B/r WP2, but phorone did not inhibit UV-induced mutation. These results indicate that the target for SH-modification is enzyme-SHs but not GSH, and that the direct or indirect modification of enzyme-activity by SH-blocking might be involved in the antimutagenesis through a pathway associated with the DNA-excision repair system.

Antimutagenic Agents↗

Fibrotic focus in infiltrating ductal carcinoma of the breast: a significant histopathological prognostic parameter for predicting the long-term survival of the patients.

The presence of fibratic fows (FF) in infiltrating ductal carcinoma (IDC) has been shown to be an important histological factor associated with high tumor aggressiveness, or early tumor recurrence or death. However, the clinicopathological significance of FF for predicting the long-term survival of the patients with IDC has not been fully investigated. In order to elucidate this aspect, we divided 140 IDCs with at least 10 years of follow up into tumors with FF and those without. IDC with FF showed significantly higher histologic grade (P=0.02), higher frequency of tumor necrosis (P=0.02), higher frequency of cases with more than three positive lymph node metastases (P=0.04), higher T classification (P=0.009), and higher pathological stage (P=0.0002) than those without FF. Relative risk (RR) of tumor recurrence and death was significantly higher in tumors with FF than in those without (RR=4.5, P < 0.00001 and RR=5.6, P < 0.00001, respectively). In cases of early stage cancer (stages I, IIA, and IIB), or in those with less than four lymph node metastases, IDCs with FF demonstrated a significantly higher risk than those without. Multivariate adjustments for other pathological factors did not change the RRs significantly. These results indicate that in long-term follow up the presence of FF is a significant prognostic parameter for IDC, and therefore strongly suggest that IDCs must be divided into those with and without FF.

Adult↗

Microsatellite instability in female non-small-cell lung cancer patients with familial clustering of malignancy.

There is accumulating evidence of an increased risk of familial clustering of cancer in the first-degree relatives of lung cancer probands. However, no explanation has been proposed for these epidemiological data. We reviewed 379 female non-small-cell lung cancer (NSCLC) patients to obtain their family histories of malignancy. Among them, nine female NSCLC patients with three or more relatives diagnosed with malignancy and 28 control patients without a family history of malignancy were selected to be analysed for instability at six different microsatellite loci. We observed microsatellite instability (MSI) more frequently in the patients with three or more family histories of malignancy (six out of nine, 67%) than the control patients (5 out of 28, 18%). The incidence of MSI in the former was significantly higher than that in the control (P=0.011: Fisher's exact test). We detected no significant difference in clinicopathological characteristics between the cases with MSI and those without MSI, except for their family histories of cancer. Our results show that a significantly higher rate of MSI is associated with familial clustering of malignancy. MSI could be one of the underlying mechanisms for familial clustering of malignancy in female NSCLC patients.

Adenocarcinoma↗

Infective endocarditis-induced crescentic glomerulonephritis dramatically improved by plasmapheresis.

A 50-year-old woman was referred to our hospital because of skin purpura, anemia, high fever, and acute renal insufficiency. Five years ago, she had been diagnosed as having ventricular septal defect without any complications. A blood culture drawn during the hospitalization grew Streptococcus viridans. She was diagnosed as having infective endocarditis-induced crescentic glomerulonephritis (GN) according to echocardiography and renal biopsy results. Although antibiotic treatment alone showed no apparent efficacy, after the initiation of plasmapheresis, the high fever and acute renal insufficiency were dramatically improved. After clinical stability was achieved, closure of the ventricular septal defect was performed. This result suggests that plasmapheresis may be beneficial in the treatment of infective endocarditis-induced crescentic GN. The possible mechanisms of this therapy are discussed.

Acute Kidney Injury↗

Recurrence of a germ cell tumor 12 years after initial treatment: a case report.

Patients with testicular germ cell tumors who have disease-free remission for more than 2 years are usually considered to be cured of their disease. This report describes a case of a germ cell tumor recurring 12 years after initial diagnosis and its treatment in a 35-year-old man who developed a retroperitoneal mass adhering to the abdominal aorta with a bout of severe colic in the left flank. Although tumor markers were not elevated and histology of the biopsy specimen was initially diagnosed as adenocarcinoma, we finally concluded that the retroperitoneal tumor was teratoma developing as a recurrence of the germ cell tumor for the following reasons: (1) the histology of the specimen was similar to an epithelial component of teratoma found in the tissue resected 12 years before; (2) systemic survey failed to detect any other primary site; (3) the young age of this patient was consistent with germ cell tumor rather than adenocarcinoma; and (4) the retroperitoneum is the most frequent site of late recurrences of testicular cancer. He was treated successfully with combination chemotherapy of cisplatin, etoposide and bleomycin followed by surgery. It is important to differentiate this treatable disease from metastasis from an unknown primary, because the latter responds poorly to therapy and survival is usually short.

Adult↗

Acute myelogenous leukemia with monosomy 7, inv(3) (q21q26), involving activated EVI 1 gene occurring after a complete remission of lymphoblastic lymphoma: a case report.

A 42-year-old female with a mediastinal tumor and massive pleural effusion ws admitted to our hospital in June 1993. Biopsy revealed lymphoblastic lymphoma. She had no evidence of distant metastasis except pleural effusion. Bone marrow examination revealed a normal karyotype (46, XY). The patient had been progression-free for more than 1 year after achieving complete remission by induction, consolidation and maintenance therapy according to the standard chemotherapy and involved-field radiation for lymphoblastic lymphoma. From May 1996 progressive leukopenia and thrombocytopenia developed. The diagnosis of refractory anemia with excess of blasts (RAEB) was made. Subsequently, in November 1996, she developed acute myelogenous leukemia (AML), M4 type by FAB classification. The karyotype of MDS and AML clones involved inversion (3) (q21q26) and monosomy 7. The EVI 1 gene was examined and was proved to be rearranged and activated. This may be the first case among the therapy-related cases of MDS/AML reported whose karyotypes were followed and in which the mRNA expression of EVI 1 gene involved was directly proved in the leukemogenesis process of chemotherapy-induced secondary MDS and AML.

Chromosome Inversion↗

Determination of cytosol c-erbB-2 protein in breast cancer by sandwich enzyme immunoassay.

We determined cytosol c-erbB-2 protein levels using a sandwich enzyme immunoassay in benign breast disease and primary and recurrent breast cancer and analyzed the relationship between c-erbB-2 protein levels and clinicopathological factors. Overexpression of c-erbB-2 protein, the cut-off value being set at 18 ng/mg protein, was observed in 26 of the 139 cases of stages I-IIIB breast cancer (18.7%), four of the 12 cases of stage IV breast cancer (33.3%) and seven of the 13 recurrent breast cancer cases (53.8%). The levels of c-erbB-2 protein were significantly different between the stages. Overexpression of c-erbB-2 protein in stages I-IIIB breast cancer was associated with histological grade and serum CEA level, but not with other clinicopathological factors. In addition, there was an inverse correlation in the group of stages I-III plus IV breast cancer between c-erbB-2 protein expression and estrogen receptor status. Overexpression of c-erbB-2 protein can be easily determined in the cytosol fraction together with hormonal receptor by this method. The prognostic importance will be evaluated in ongoing adjuvant trials for operable breast cancer patients.

Breast Diseases↗