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Biomedical subjects

A Sakamoto

Publications and source records attributed to A Sakamoto.

At least 37 records · Page 2Linked to original sources
PubMed2001

Conservative therapy for adenocarcinoma and atypical endometrial hyperplasia of the endometrium in young women: central pathologic review and treatment outcome.

Thirty-nine patients with endometrioid adenocarcinoma (EA) and atypical hyperplasia (AH) of the endometrium who received conservative treatment to preserve fertility were collected from member institutions of the Japan Gynecologic Oncology Study Group. Twenty-nine and ten were originally diagnosed with EA without myometrial invasion and AH, respectively. We performed a central pathological review to make definite diagnoses, and the diagnosis of EA in 29 cases was changed to AH in ten, complex hyperplasia in three and atypical polypoid adenomyoma in three, and AH in ten was changed to EA in one and simple hyperplasia in one. Nine of 12 women (75%) with EA and 15 of 18 women (83%) with AH had an initial response to medroxyprogesterone acetate (MPA) treatment. Two of nine responders with EA later developed relapse, and one of them had metastasis to the left obturator lymph node. Two became pregnant, and one delivered one full-term infant. One of the responders with AH had a relapse in the endometrium. Five became pregnant, and four delivered four normal infants. The young women with endometrial carcinoma localized in the endometrium who wish to preserve fertility may be treated as successfully with MPA as those with AH.

Adenocarcinoma↗
PubMed2001

Morphological and physiological restorations of hereditary form of dilated cardiomyopathy by somatic gene therapy.

TO-2 strain hamsters with dilated cardiomyopathy, gene deletion of delta-sarcoglycan (SG) and no expression of alpha-, beta-, gamma-, and delta-SG proteins are useful for developing the potential gene therapy of intractable heart failure. We prepared recombinant adeno-associated virus vector including normal delta-SG gene driven by CMV promoter and intramurally administered in vivo. The transfected myocardium induced robust expression of both transcript and transgene for 2/3 period of the animal's life expectancy. Immunostaining demonstrated reexpression of not only delta-SG but also other three SGs in 40% cells in the transfected region and normalization of the diameter of transduced cardiomyocytes. Hemodynamic study revealed preferential amelioration of the diastolic indices (LVEDP, the dP/dt(min) and CVP). These results provide the first evidence that supplementation of a specific gene with efficient and sustained transfection capability restores the genetic, morphological, and functional deteriorations.

Animals↗
PubMed2001

Matrilysin (MMP-7) as a significant determinant of malignant potential of early invasive colorectal carcinomas.

Matrix metalloproteinases play a crucial role in tumour invasion and metastasis. Matrilysin (MMP-7) has been shown to correlate with nodal or distant metastasis in colorectal carcinomas; however, its implication in early invasive colorectal carcinomas has not been determined. This study was undertaken to clarify the association of matrilysin expression with clinicopathologic parameters in early invasive colorectal carcinomas. 38 early invasive colorectal carcinomas treated by local excision or radical surgery were examined. Tumour budding was evaluated as the number of dedifferentiation units along the entire invasive margin. Matrilysin protein levels were determined using immunohistochemical study. Univariate analysis showed that matrilysin expression alone was significantly associated with distant metastasis (P = 0.0339), and both tumour budding and matrilysin expression were significantly associated with adverse outcome (P = 0.0005, 0.0341). Histological differentiation, vessel invasion, and depth of invasion were not significantly associated with either distant metastasis or adverse outcome. Multivariate analysis confirmed that tumour budding and matrilysin expression were independently associated with adverse outcome, although the significance of matrilysin expression was marginal (P = 0.0488). Tumour budding at the invasive margin and matrilysin expression are more useful in identifying high-risk groups for adverse outcome in patients with early invasive colorectal carcinomas.

Aged↗
PubMed2001

First total synthesis of mosin B.

[figure: see text] The first total synthesis of mosin B and a diastereomer was accomplished using asymmetric desymmetrization of the sigma-symmetric diol and the Nozaki-Hiyama-Kishi reaction as the key steps. The THF core segment was stereoselectively constructed employing a stereodivergent synthesis starting from a common intermediate, 4-cyclohexene-1,2-diol, based on a desymmetrization strategy. By virtue of these synthetic results, it is suggested that the absolute configuration is 1a.

Antineoplastic Agents, Phytogenic↗
PubMed2001

Temperature dependence of near-IR excited Raman spectra of crystalline hen egg-white lysozyme.

Near-IR excited Raman spectroscopy was applied to examine the structural change of hen egg-white lysozyme in tetragonal crystals at low temperatures. There was little difference found in the amide I and amide III regions between the spectra observed at 77 and 298 K, suggesting that the secondary structures of lysozyme were conserved in the temperature range from 77 to 298 K. Several bands arising from the protein side chains, particularly the methylene and phenylalanyl groups, showed significant changes in either intensity or bandwidth (or in both of them) on going from 77 to 298 K. Some of the spectral changes occurred gradually over the wide temperature range, and others occurred abruptly at around 200-240 K. The implications of these findings are discussed.

Animals↗
PubMed2001

Primary leiomyosarcoma of the patella.

We report on a case of primary leiomyosarcoma of the patella in a 59-year-old woman. To our knowledge, this is the first report of this rare tumor in a bone where malignant lesions rarely occur.

Bone Neoplasms↗
PubMed2001

Glomangiopericytoma causing oncogenic osteomalacia. A case report with immunohistochemical analysis.

A 47-year-old woman suffered from gait disturbance due to back pain and muscle weakness. Laboratory data showed serum hypophosphatemia, elevated alkaline phosphatase, and a normal level of ionized calcium. Radiological examinations revealed multiple pathologic fractures in the ribs and pubic rami. She had had no episode of familial or any other notable disorder, and so she was initially treated with medication for adult-onset osteomalacia. However, 19 years later (when she was 66 years old), she noticed a soft-tissue tumor in her buttock. The tumor was excised. The histological features were those of glomangiopericytoma characterized by both glomus tumor-like and hemangiopericytoma-like structures. After removal of the tumor, her symptoms disappeared immediately. Laboratory data normalized 8 months later. To our knowledge, this is the first report of oncogenic osteomalacia caused by glomangiopericytoma.

Aged↗
PubMed2001

E-cadherin gene mutations frequently occur in synovial sarcoma as a determinant of histological features.

Synovial sarcoma is a mesenchymal tumor that has an epithelial character and two major histological subtypes, the biphasic type and the monophasic fibrous type. However, the mechanisms involved in its epithelial differentiation are unknown, and furthermore, the determinants for histological subtype in synovial sarcoma remain unclear. In this study, we immunohistochemically examined E-cadherin expression and screened for genetic alterations in the E-cadherin gene from exon 4 to exon 9 in 49 cases of synovial sarcoma. In addition, we also examined the mRNA expressions of E-cadherin and Snail, a direct repressor of E-cadherin gene expression, by reverse transcriptase-polymerase chain reaction in 20 samples of frozen material. Immunohistochemical E-cadherin membranous expression was observed in 12 cases (24.5%), and was predominant in biphasic tumors. Single-strand conformation polymorphism analysis followed by DNA direct sequencing revealed 15 missense E-cadherin mutations in 12 cases (24.5%: monophasic, 11 of 42; biphasic, 1 of 6; poorly, 0 of 1) and 7 silent mutations (14.3%) in 7 cases. Ten of the 12 cases with E-cadherin missense mutations did not show E-cadherin membranous expression. Reverse transcriptase-polymerase chain reaction demonstrated E-cadherin and Snail mRNA expressions in 14 cases (70%) and in all cases, respectively. E-cadherin gene expression was inactivated by missense mutations in three of the eight cases (37.5%) of monophasic fibrous tumors that showed E-cadherin mRNA expressions. The E-cadherin gene was potentially inactivated in a significant number of synovial sarcomas. E-cadherin dysfunction because of its mutation in the central region of the molecule was associated with its decreased immunohistochemical expression and histological fibroblastic and spindle-shaped features of monophasic tumors. Thus, E-cadherin gene mutation may be one of the determinants of histological subtype in synovial sarcoma.

Adolescent↗
PubMed2001

Plasma total glutathione concentrations in healthy pediatric and adult subjects.

Glutathione, as a free radical scavenger, plays an important role in protecting cells against oxidative damage. Since aging is associated with decreased plasma glutathione levels, we investigated plasma concentrations of total glutathione (including the reduced and oxidized forms, tGSH=GSH+GSSG) and total cysteine in 129 healthy pediatric and adult subjects. Plasma tGSH concentrations were significantly lower in infants than in adults. There were no significant differences in plasma tGSH concentrations between the children and adult group. No significant differences in plasma total cysteine concentrations were found between any pediatric and adult group. We conclude that lower plasma tGSH levels in pediatric subjects may reflect greater oxidative stress during the neonatal and infant period.

Adolescent↗
PubMed2001

H-ras oncogene mutation in dedifferentiated chondrosarcoma: polymerase chain reaction-restriction fragment length polymorphism analysis.

Dedifferentiated chondrosarcomas, which are known for their poor prognosis, are characterized by conventional chondrosarcoma with high-grade anaplastic components. Activating mutations in ras genes are a common genetic abnormality in human malignancies. The presence of point mutations at codons 12 and 13 of the H-ras gene was studied in 20 formalin-fixed paraffin-embedded chondrosarcomas, comprising 11 cases of conventional chondrosarcoma (six Grade 1 cases and five Grade 2 cases) and nine cases of dedifferentiated chondrosarcoma, using polymerase chain reaction-restriction fragment length polymorphism and direct sequencing analysis. H-ras mutations were only seen in two out of the nine cases of dedifferentiated chondrosarcoma (2/9, 22%) and they were not seen in any of the cases of conventional chondrosarcoma (0/11, 0%). Dedifferentiated chondrosarcomas had a worse prognosis than conventional chondrosarcomas (P < .01); among the patients with dedifferentiated chondrosarcomas, those with H-ras mutation (n = 2) tended to have a worse prognosis than those without (n = 7), although the difference was not statistically significant (P = 0.068). Our results would seem to suggest that H-ras mutation may occur during the course of dedifferentiation and may also have some effect on malignant potential.

Adult↗
PubMed2001

Immunoexpression of ultraviolet photoproducts and p53 mutation analysis in atypical fibroxanthoma and superficial malignant fibrous histiocytoma.

p53 mutation is one of the major results of ultraviolet (UV) radiation. UV photoproducts of cyclobutane pyrimidine dimers (CPDs) and pyrimidine-pyrimidone (6-4) photoproducts (64PPs) also play an important role in skin cancer development. Atypical fibroxanthoma (AFX), which mimics malignant fibrous histiocytoma (MFH) histologically, occurs in the sun-exposed skin of the elderly, and therefore, an association with UV has long been suspected. Eighteen fibrohistiocytic skin lesions comprising AFX (n = 7), storiform-pleomorphic type MFH centered in the subcutis (superficial MFH; S-MFH; n = 4) and benign fibrous histiocytoma (BFH; n = 7) were used for immunohistochemical and molecular analysis. Eight cases of deep MFH (D-MFH) were also analyzed for UV photoproduct expression for the purposes of comparison. Immunohistochemically, the CPD scores of AFX (3.6 +/- 0.4) were significantly higher than those of S-MFH (1.3 +/- 0.8), D-MFH (0.8 +/- 0.5), or BHF (1.4 +/- 0.7); however, the 64PP scores were extremely low in all these tumors (AFX, 0.1 +/- 0.1; S-MFH, 0.0 +/- 0.0; D-MFH, 0.0 +/- 0.0; and BHF, 0.0 +/- 0.0). AFX, S-MFH, and BFH showed immunoexpression for p53 (2/7, 2/4, and 0/7), respectively. p53 mutations were detected in AFX (4/6; 67%) and S-MFH (1/4; 25%), but not in BFH (0/5; 0%) using polymerase chain reaction-single-strand conformation polymorphism, and all of the mutations in AFX were either C-T transitions or at dipyrimidine sites. In conclusion, AFX and S-MFH are both similar fibrohistocytic lesions; however, AFX has high immunoreactivity for CPDs compared with S-MFH, D-MFH, or BFH. These data suggest that CPDs may play an important role in the pathogenesis of AFX.

Adolescent↗
PubMed2001

Secondary malignant giant-cell tumour of bone: molecular abnormalities of p53 and H-ras gene correlated with malignant transformation.

AIMS: We report two cases of secondary malignant giant-cell tumour occurring without irradiation therapy. To elucidate the mechanism of malignant transformation in this tumour, we searched for the molecular abnormalities of p53, MDM2 and the H-ras genes. METHODS AND RESULTS: These cases were retrieved after a review of 103 cases of primary giant-cell tumour of bone, registered in our institute. One case occurred in the distal femur of a 42-year-old female after surgical curettage, while the other arose in the acetabulum of a 25-year-old male after en bloc resection. Microscopically, the malignant tumour in the distal femur was composed of a proliferation of ovoid or fusiform cells arranged in fascicles with high mitotic activities. The malignant transformed tumour in the acetabulum was made up of pleomorphic tumour cells with atypical mitoses. In the tumour of the distal femur, both p53 and H-ras mutations were detected. Abnormal nuclear accumulation of p53 protein and c-myc expression were also revealed by immunohistochemistry. In both cases, the recurrent malignant tumour over-expressed MMP-9 and revealed a higher MIB-1-labelling index compared with the primary conventional giant-cell tumour. CONCLUSIONS: Our results suggest that multiple oncogene or tumour suppressor gene mutations may play an important role during malignant transformation in conventional giant-cell tumours.

Adult↗
PubMed2001

Betaine and homocysteine concentrations in infant formulae and breast milk.

BACKGROUND: Early diagnosis and treatment of homocystinuria with methionine-free or low methionine formulae significantly improve prognosis in children found by newborn screening and treated soon after birth. Betaine (Bet) supplementation is also an effective strategy for dietary treatment of homocystinuria. However, previous reports on diet therapy have only examined methionine and cysteine concentrations but not those of Bet and homocysteine (Hcy) in infant diets. METHODS: We measured Bet and Hcy concentrations in three methionine-free formulae, five infant starter formulae, and 33 samples of human breast milk from 10 mothers. RESULTS: In methionine-free formulae, Hcy but not Bet was isolated. However, in human breast milk and infant starter formulae, both Bet and Hcy were detected. However, the Bet concentration was not sufficient for the treatment. CONCLUSIONS: Our study suggests that methionine-free formulae should have Hcy eliminated and be fortified with Bet to the concentration of 150 mg/dL for the treatment of homocystinuria.

Animals↗
PubMed2001

H-, K-, and N-ras gene mutation in atypical fibroxanthoma and malignant fibrous histiocytoma.

Atypical fibroxanthoma (AFX) which is histologically similar to malignant fibrous histiocytoma (MFH), occurs in the sun-exposed skin. The presence of mutations at codons 12 and 13 of the H- and K-ras genes and in exons 1 and 2, which include codons 12, 13, and 61, of the N-ras gene was studied in 8 cases of AFX and 8 cases of storiform-pleomorphic-type MFH using polymerase chain reaction (PCR)-restriction fragment length polymorphism and PCR-single-conformation polymorphism. Two of the 8 cases of MFH showed ras mutations in the H-ras gene at codon 12 (GGC-AGC) and in the K-ras gene at codon 13 (GGC-GAC). H- and K-ras gene mutations were not seen in any of the cases of AFX (0 of 8). N-ras gene mutation was not detected in either the AFX (0 of 8) or MFH (0 of 8) cases. In conclusion, although the number of cases in this study was small, H- and K-ras genes were present in some of the MFH cases and accordingly may play an important role in the pathogenesis of MFH. In addition, the finding that H-, K-, and N-ras gene mutations are not present in AFX may indicate why AFX has a more favorable behavior than MFH.

Adult↗
PubMed2001

Immunoexpression of neurofibromin, S-100 protein, and leu-7 and mutation analysis of the NF1 gene at codon 1423 in osteofibrous dysplasia.

The NF1 (neurofibromatosis type 1, or von Recklinghausen disease) gene, is a tumor-suppressor gene, and its product, neurofibromin, down-regulates ras protein by its guanosine triphosphatase-activating protein (GAP)-related domain. Osteofibrous dysplasia (OFD) is characterized by fibroblast-like spindle cells and osseous tissue and is generally seen in the tibia or fibula during childhood. The precise nature of OFD remains controversial. Cosegregations of OFD and NF1 have been reported, and it has been surmised that OFD is associated with the NF1 gene. We studied the expressions of NF1 gene product (neurofibromin) and so-called Schwann cell markers (S-100 protein, Leu-7) in 17 cases of OFD immunohistochemically. Ten cases of fibrous dysplasia (FD) were also used for the purpose of comparison. Five OFD and 7 FD cases were analyzed for NF1 gene mutation at codon 1423, which is a GAP-related domain, by single-strand conformation polymorphism. Fibroblast-like cells of OFD showed the expression of neurofibromin (5 of 17), S-100 protein (9 of 17), and Leu-7 (5 of 17), and those of FD did not show these expressions, with the exception of 1 case that showed Leu-7 expression. Regarding the OFD cases, significant correspondence was found between cases showing expression of neurofibromin and S-100 protein, between cases showing expression of neurofibromin and Leu-7, and between cases showing expression of S-100 protein and Leu-7 (P < .01). NF1 gene mutation at codon 1423 was not detected in either the OFD (0 of 5) or FD (0 of 7) cases. These results seem to suggest the possible involvement of neurofibromin in the development of OFD, which is associated with the expression of Schwann cell markers (S-100 protein and Leu-7). Furthermore, NF1 gene mutation at codon 1423 did not seem to be related to OFD.

Adolescent↗
PubMed2001

An immunohistochemical analysis of cyclin D1, p53, and p21waf1/cip1 proteins in tumors originating from the follicular epithelium of the thyroid gland.

This study aimed at clarifying the factors closely related to the tumor progression of thyroid neoplasms. We examined the immunoreactivity of cyclin D1, p53, and p21waf1/cip1 proteins in 179 thyroid tumors originating from the follicular epithelium using an immunohistochemical technique. Cyclin D1 positivity was frequent in well-differentiated thyroid carcinomas (39/122 cases), but it was rarely seen in follicular adenomas (1/33 cases), (p < 0.05). Positivity for p53 was more frequent in poorly differentiated carcinomas (7/19 cases) and undifferentiated carcinomas (4/5 cases) than in well-differentiated carcinomas (14/122 cases) (p < 0,05, respectively). P21waf1/cip1 positivity was more frequent in well-differentiated thyroid carcinomas (43/122 cases) than in follicular adenomas (4/33 cases) (p < 0.05). Regarding the relationships of these proteins, co-positivity for cyclin D1 and p53 was observed more often in poorly differentiated carcinomas (5/7 cases) than in well-differentiated carcinomas (7/39 cases) (p < 0.05). Most cases with cyclin D1 positivity did not show p21waf1/cip1 expression in poorly differentiated carcinomas (6/7 cases). Three cases examined showed co-positivity of p53 and p21waf1/cip1. Our results suggest that cyclin D1 is invoved in thyroid oncogenesis. Moreover, p53 might be closely related to the development of poorly differentiated carcinomas and undifferentiated carcinomas originating from well-differentiated carcinomas.

Adenoma↗
PubMed2001

Optical study of cytochrome cM formation in Synechocystis.

The expression of the cytM gene, which encodes cytochrome cM in Synechocystis sp. PCC 6803, is induced under stress conditions such as low temperature. Results of spectrophotometric studies revealed that cytochrome cM was oxidized by light absorbed by photosystem I in cells that had acclimatized to a low temperature. However, no similar light-induced oxidation of cytochrome cM was observed in delta cytM mutant cells. The kinetics of the oxidation and reduction of P700 before and after acclimation of Synechocystis cells to low temperature suggested that cytochrome cM might donate electrons to photooxidized P700. Our observations indicate that cytochrome cM is synthesized under low-temperature stress and that it might carry electrons directly to P700+ in photosystem I.

Bacterial Proteins↗