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S Fujimoto

Publications and source records attributed to S Fujimoto.

At least 55 records · Page 3Linked to original sources
PubMed2001

Radiotherapy with concurrent chemotherapy for vulvar adenocarcinoma associated with extramammary Paget's disease.

BACKGROUND: There have been no reports of the efficacy of primary radiotherapy with concurrent chemotherapy for vulvar adenocarcinoma associated with extramammary Paget's disease. In this report we discuss the differential diagnosis and efficacy of treatment for this rare tumor. CASE: The patient was diagnosed as having vulvar carcinoma stage IVb. A dose of 40 Gy in 20 fractions was administered to the vulva, including the tumor mass, and the inguinal-femoral lymph nodes with concurrent systemic chemotherapy. Outside the radiated field, bone scintigraphy showed an increase in abnormal uptake images. However, in the radiated field, the tumors disappeared macroscopically, and bone scintigraphy also showed a disappearance of the abnormal uptake images. CONCLUSION: Within the radiated field, the efficacy was brought about by either radiotherapy only or by radiotherapy together with the sensitizing effects of chemotherapy. As for the chemotherapy itself, it was not effective in this case.

Adenocarcinoma↗
PubMed2001

A study of risk factors for ovarian metastases in stage Ib-IIIb cervical carcinoma and analysis of ovarian function after a transposition.

OBJECTIVE: The objective of the present study was to examine the incidence and risk factors of ovarian metastases in cervical carcinoma. The function of transposed ovaries was also studied. METHODS: In order to analyze the risk factors of ovarian metastases, 255 slides of pathological specimens were reassessed by multivariate logistic regression analysis. Fifty-six patients were studied prospectively on the basis of the function of transposed ovaries. Basal body temperature and serum hormone levels were analyzed. RESULTS: Ovarian metastasis was identified in 2 of 485 (0.4%) patients with squamous cell carcinoma and in 12 of 146 (8.2%) patients with nonsquamous tumors of the cervix. Histologic type (P = 0.0014) and blood vessel invasion (P = 0.0433) were significant independent risk factors for ovarian metastases, as revealed by multivariate logistic regression analysis. Cumulative survival curves of preserved ovaries showed a significant (P < 0.005) decline in the group with postoperative radiotherapy. CONCLUSION: Preservation of ovarian function should be pursued in patients with squamous cell carcinoma of the cervix, provided that the patient has no other risk factor (blood vessel invasion) for ovarian metastases. Moreover, sufficient attention should be paid to the proper handling of ovarian blood vessels during surgery, in order to shield and protect them from exposure to scattered radiation administered during postoperative radiotherapy.

Adenocarcinoma↗
PubMed2001

Dominant-negative mutation of p53 tumor suppressor gene in endometrial carcinoma.

BACKGROUND: It has been suggested that mutation of the TP53 tumor suppressor gene is involved in endometrial carcinogenesis. However, the status of p53 function in endometrial cancers has not yet been investigated in detail. METHODS: We surveyed inactivating p53 mutations in endometrial carcinomas using the yeast p53 functional assay, which can evaluate the transcriptional activity of p53 in vivo in yeast. To the detected p53 mutants, we also applied a transdominance assay, which assesses the dominant-negative property of mutants. RESULTS: Of 23 endometrial carcinomas, 9 tumors (39.1%) were found to harbor p53 mutations. Only 1 of the 6 mutants in 18 endometrioid-type tumors showed dominant-negative capacity. In contrast to the endometrioid-type tumor, all 3 mutations in 5 serous-type tumors (R273H, 9-bp deletion in codons 240-243, and R248W) showed dominant-negative capacity and presented in a homozygous state in the tumors, indicating a complete functional inactivation. CONCLUSIONS: Although this study included a relatively small number of cases and therefore is a preliminary study, these results suggest that the dominant-negative mutation of the TP53 gene is related to serous adenocarcinoma. The role of the dominant-negative status of p53 mutants in endometrial carcinogenesis and progression of this disease should be further investigated.

Adult↗
PubMed2001

Expressions of endothelin-1, fibronectin, and interleukin-1alpha of human umbilical vein endothelial cells under prolonged culture.

We examined human umbilical vein endothelial cells (HUVECs) under prolonged culture by electron microscopy and by light and electron immunocytochemistry including double immunolabeling. Based on the cell area of HUVECs through multiple passages, we divided the cells into first, second, and third stages, which exhibited distinct morphological and immunocytochemical characteristics. During the first stage, HUVECs were polygonal in shape and had already formed the monolayer confluence. During the second stage, they were characterized by an increased number of Weibel-Palade (WP) bodies, which were actively segregated from Golgi cisterns. Endothelin (ET)-1 and von Willebrand factor, an endothelial cell marker, were occasionally colocalized in WP bodies. The increase in WP bodies correlated with high ET-1 concentration in the cultured medium, suggesting that these inclusions are involved in storage and release of ET-1 in a manner indicating a regulatory pathway. During the third stage, fibronectin and interleukin (IL)-1alpha were expressed in HUVECs as well as in multinucleated giant cells, which originated from HUVECs, but WP bodies decreased in number in association with a decrease in ET-1 immunoreactivity and concentration. The foregoing changes in immunoreactivities for ET-1, fibronectin, and IL-1alpha affecting HUVECs under prolonged culture may reflect a senescent process of these cells.

Apoptosis↗
PubMed2001

Alpha-fetoprotein microheterogeneity: a potential biochemical marker for Down's syndrome.

Our purpose was to examine the utility of analyzing alpha-fetoprotein (AFP) microheterogeneity assessed by lectin affinity in Down's syndrome (DS) screening. Maternal sera and amniotic fluids were collected from 18 women who were carrying DS fetuses and 70 unaffected pregnancies around 16 weeks of gestation. The percentages of AFP which reacted with Lens culinaris agglutinin (AFP-L2,3) were determined by lectin affinity electrophoresis. AFP-L2,3 levels were significantly increased (P<0.0001) in both maternal serum and amniotic fluid from DS-affected versus unaffected pregnancies. The fractional areas under the receiver operating characteristic curves were 0.835 and 0.700 (P=0.106) for AFP-L3 and AFP MoM (multiples of the median) in maternal serum. No correlation was found between AFP-L3 and AFP MoM in maternal serum (r=0.006). Our data suggest that the measurement of AFP-L3 in maternal serum is a potential biochemical marker for DS.

Amniotic Fluid↗
PubMed2001

Distinct effect of diazoxide on insulin secretion stimulated by protein kinase A and protein kinase C in rat pancreatic islets.

Protein kinase activation is known to stimulate glucose-induced insulin secretion in the presence of diazoxide. Diazoxide opens the ATP-sensitive K(+) channel and inhibits FAD-linked glycerophosphate dehydrogenase activity in a concentration-dependent manner. In the present study, we examined the effect of lower (100 microM) and higher (250 microM) concentrations of diazoxide on insulin release by protein kinase A (PKA) and protein kinase C (PKC) activation. Forced depolarization by a high potassium concentration, augmented the intracellular Ca(2+) concentration ([Ca(2+)](i)) similarly in the presence of both concentrations of diazoxide. Under this condition, 250 microM diazoxide inhibited insulin release enhanced by PKA activation but not that by PKC. Under a basal concentration of [Ca(2+)](i), PKC activation elicited glucose-induced insulin secretion at 100 and 250 microM diazoxide, while PKA activation did so only at 100 microM. These augmentations were completely inhibited by mannoheptulose, a glucokinase inhibitor. Glyceraldehyde, in place of glucose, enhanced insulin secretion by PKC activation under both concentrations of diazoxide. On the other hand, it did not affect PKA-stimulated insulin release under either conditions, but in the case of 100 microM, glucose augmented the insulin secretion in the presence of glyceraldehyde and db-cAMP concentration-dependently. These data suggest that insulin release stimulated by PKA and PKC activation under diazoxide is dependent on glucose metabolism, and that a signal derived from proximal steps in glycolysis may be necessary for the secretion by PKA activation.

Animals↗
PubMed2001

Massive intravenous immunoglobulin treatment in pregnancy complicated by Guillain-Barré Syndrome.

A pregnant woman developed acute demyelinating poly-neuropathy (Guillain-Barré syndrome (GBS)) in the 28th week of gestation (GW) after flu-like infection. Hypertension, liver dysfunction, and a decrease in consciousness level developed at 29GW. Blood chemical analysis revealed increased levels of liver enzymes GOT 247 IU/l and GPT 624 IU/l. Viral serological study showed a positive test for Epstein-Barr virus IgM. Weakness of bilateral facial muscles and limbs, a loss of tendon reflexes, and generalized paresthesia were detected by neurologic examinations. Over the course of 5 days, a massive dose (100g) of intravenous immunoglobulin (MIVIg) was infused in 30GW. An average manual muscle testing score by the Medical Research Council method and peak flow value began to be significantly restored during and after MIVIg infusions. Values of the liver enzymes gradually decreased, and improvement of the muscle weakness and dysbasia was observed. Her pregnancy normally ended in spontaneous vaginal delivery of a healthy infant in 37GW. This is the first report confirming the efficacy of MIVIg, without plasmapheresis, in GBS-complicated pregnancy.

Adult↗
PubMed2001

Clinical and pedigree study on familial cases of West syndrome in Japan.

Nationwide survey on familial cases of West syndrome (WS) in first- and second-degree relatives was conducted by mailing a questionnaire to 64 major university hospitals, children's hospitals, and epilepsy centers in Japan, and by review of the Japanese cases in the literatures. Thirty-four familial cases, 20 males and 14 females, were obtained in 15 families including one with five affected members in two generations and another with three affected male siblings including a half brother by a different father (X-linked WS). A mother and the child or children were involved in three families. Nine families had 21 cryptogenic cases and six families had 13 symptomatic cases, and the etiologies were same among the affected members in each family. Familial cases of WS have characteristic clinical features and genetic mechanisms. Age of onset, seizure types, electroencephalographic abnormalities, early seizure outcome, effective treatment, long-term seizure prognosis, and long-term developmental prognosis were concordant among the affected members in each family. Long-term seizure and developmental prognoses were far better than those in WS in general, with seizure-free rate of 82% and normal mental development rate of 44%. Poor prognosis was limited to specific symptomatic cases. Adrenocorticotropic hormone (ACTH) was a treatment of choice, and even in relapse of WS after ACTH therapy, the patients well responded to antiepileptic drugs. Specific inheritance pattern was difficult to imagine in the majority of the present cases, except for one family with X-linked WS and another family with five patients of maternal inheritance. These results are helpful for the treatment choice and prognostication of clinical course for familial cases of WS.

Adrenocorticotropic Hormone↗
PubMed2001

The effect of the arylhydrocarbon receptor on the human steroidogenic acute regulatory gene promoter activity.

The steroidogenic acute regulatory (StAR) protein is a rate-limiting factor in steroid hormone production. The StAR protein plays a role in the movement of cholesterol from the outer membrane to the inner membrane, where cholesterol side chain cleavage enzyme exists. Dioxins, which may act as 'endocrine disruptors', mimic and antagonize endogenous hormone actions in vivo. Although the mechanism of endocrine disruption is not clear, the actions of dioxins are known to be mediated by binding to the arylhydrocarbon receptor (AhR), and it is known that dioxins act as transcription factors to endocrine-associated gene expression. In the present study, we examined the effect of the AhR on the human StAR gene promoter, and we clarified the action mechanisms of environmental endocrine disruptors. We transfected constructs containing the human StAR gene promoter sequences pGL(2) 1.3-kb StAR (nt -1293 to +39) into mouse Y-1 adrenal tumor cells and measured the promoter activity of the StAR gene. With the addition of beta-napthoflavone (betaNF), which is a ligand of AhR, to the culture medium, the activity of the StAR gene promoter increased significantly (P<0.05), and with the addition of 1 microM of betaNF, it became maximum (3.1+/-0.6-fold higher than the control value). When the AhR and ARNT were co-transfected together in Y-1 cells or human adrenocortical carcinoma H295R cells, the promoter activity of the StAR gene significantly (P<0.05) increased, to a level 1.4+/-0.01-fold higher in Y-1 cells and to a level 1.6+/-0.04-fold higher in H295R cells than the control level, when 1 microM of betaNF was added. We examined the effect of induction of cAMP with transfection with AhR or ARNT. With the addition of 1 mM 8-Br-cAMP, there were no differences between the StAR gene promoter activities in the group in which AhR and ARNT was introduced and in the group in which they were not introduced. The results suggest that AhR plays a role in the promoter activity of the human StAR gene and that the effect of AhR on StAR gene expression may cause a disturbance to the human endocrine system.

Animals↗
PubMed2001

A new dysferlin gene mutation in two Japanese families with limb-girdle muscular dystrophy 2B and Miyoshi myopathy.

We found a new dysferlin gene mutation in two Japanese families, one with limb-girdle muscular dystrophy 2B and the other with Miyoshi myopathy. All patients in the limb-girdle muscular dystrophy 2B family showed apparent proximal dominant muscle atrophy and weakness, whereas a patient with Miyoshi myopathy in the second family showed distal muscle involvement at an early stage. The common clinical feature of all patients in both families was preferential involvement of calf muscles rather than the tibialis anterior muscle, which was confirmed by muscle computed tomography scan. All patients in both families shared the same homozygous alleles for chromosome 2p13 markers, and dysferlin gene analysis revealed a novel missense mutation, a G to A transition at nt 5882, which changed aspartic acid to asparagine at codon 1837. Allele-specific polymerase chain reaction analysis was used for confirmation of the mutation and for genotype analysis of the family members.

Aged↗
PubMed2001

Protein purification, cDNA cloning and gene expression of lysozyme from eri-silkworm, Samia cynthia ricini.

Lysozyme was isolated from immunized hemolymph of Samia cynthia ricini larvae by heat treatment, cation exchange and reverse-phase chromatography. A cDNA encoding lysozyme was cloned by screening the cDNA library from immunized fat body using, as a probe, a DNA fragment obtained by PCR-based differential display method. The deduced amino acid sequence showed high homology with other chicken-type lysozymes. The calculated molecular mass of the mature peptide was 13785, which agreed precisely with that obtained by MALDI-TOF mass spectrometry of the isolated protein. The lysozyme transcripts were detected at a significant level in naïve fat body, and the level increased 5-10-fold upon injection of the larvae with UV-killed bacteria or peptidoglycan.

Animals↗
PubMed2001

Identification of genes differentially expressed by putrescine in HepG2 hepatoblastoma cells.

In order to identify genes differentially expressed by putrescine, a polyamine, which play important roles in the regulation of cell proliferation and the development of cancer, we performed mRNA differential display analysis using total RNA extracted from HepG2 cells (human hepatoblastoma cell line) treated with a specific inhibitor of polyamine biosynthesis, alpha-difluorometylornithine (DFMO). A total of 25 genes were up-regulated and 32 genes down-regulated by putrescine. Of the genes differentially expressed by putrescine, we chose three that were related to the respiratory chain and oxidative phosphorylation and analyzed them by Northern blot analysis. Cytochrome oxidase subunit 1, low molecular mass ubiquinone-binding protein, and NADH dehydrogenase subunit 2 were found to be down-regulated by putrescine. We examined intracellular ATP level in HepG2 cells, and found that ATP level in DFMO-treated cells was increased by exogenous putrescine.

Journal Article↗
PubMed2001

Histopathological prognostic factors of adult granulosa cell tumors of the ovary.

BACKGROUND: The prognostic factors of adult granulosa cell tumor (AGCT) have not been well defined. METHODS: In 27 AGCT patients, we examined clinical stage, microscopic patterns, mitotic index (MI), and lymph-vascular space invasion (LVSI) to determine whether these factors were related to disease-free survival (DFS) of patients with AGCT. We also performed immunohistochemical examination for p53. RESULTS: Seventeen cases represented stage I tumors, four stage II, five stage III, and one stage IV. Patients with stage I disease had more favorable prognosis than those with stage II to IV disease (p=0.034). There was no relation between the microscopic patterns and the DFS. The MI, which was categorized into < or =3/10 high power field (HPF) and > or =4/10 HPF, was significantly related to patients DFS (p<0.0005). The DFS time for patients with moderate or prominent LVSI was significantly shorter than that for patients with no or minimal LVSI (p<0.0001). By multivariate analysis, MI and LVSI were shown to be independent prognostic factors. Five of seven patients with recurrent tumor had extrapelvic spread; two in the abdominal cavity and three in the liver. CONCLUSION: The results of this study suggest that prognosis for patients with AGCT depends on the MI and LVSI. During the follow-up period of patients, they need to be examined for distant metastasis including liver.

Adolescent↗
PubMed2001

Massive intravenous immunoglobulin treatment in women with four or more recurrent spontaneous abortions of unexplained etiology: down-regulation of NK cell activity and subsets.

PROBLEM: The aims of this study were to investigate the efficacy of massive intravenous immunoglobulin (MIVIg) treatment for women with recurrent spontaneous abortion (RSA) of unexplained etiology, and to investigate changes in peripheral natural killer (NK) cell activity and subsets. METHOD OF STUDY: MIVIg treatment was performed in 18 pregnancies from 15 women with 4 or more consecutive RSA of unexplained etiology. NK cell activity and subsets were assessed in 8 of the pregnancies. RESULTS: 14 pregnancies resulted in live births and 4 resulted in abortions with chromosome abnormality. The pre-infusion NK cell activity (mean + SD. 40.9 + 17.0%) at 4.4 +/- 0.5 weeks of gestation (GW) decreased to 15.0 +/- 7.90% at post-infusion status (5.4 +/- 0.5 GW). Pre-infusion percentages of CD56+ CD16- cells (3.5 +/- 2.1%) and CD56+ CD16- cells (16.8 +/- 8.8%) decreased to 3.0 +/- 2.2% and 11.1 +/- 6.9%, respectively, after MIVIg treatment. CONCLUSIONS: MIVIg treatment was effective in all 14 pregnancies from RSA women of unexplained etiology, excluding 4 abortions with chromosome abnormality. Peripheral NK cell activity and subsets were suppressed by MIVIg treatment.

Abortion, Habitual↗
PubMed2001

Anti-phosphatidylserine/prothrombin antibodies are not frequently found in patients with unexplained recurrent miscarriages.

OBJECTIVE: To determine whether the presence of anti-phosphatidylserine/ prothrombin antibodies (anti-PS/PT) can be a major factor in otherwise unexplained recurrent miscarriages. PATIENTS AND METHODS: Eighty-one consecutive patients with history of 2 or more recurrent miscarriages were studied. Patients with history of overt thrombotic events were not included. Patients were examined for plausible causes of miscarriages, and titer of IgG, IgM and IgA anti-PS/PT were measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: Thirty-five patients had one or more plausible causes of recurrent miscarriages, including 12 positive for well-established anti-phospholipid antibodies, such as anti-beta2-glycoprotein I. None of the patients included in this study was found to be positive for anti-PS/PT. CONCLUSION: Detection of anti-PS/PT in addition to other anti-phospholipid antibodies does not seem to aid in the evaluation of patients with unexplained recurrent miscarriages.

Abortion, Habitual↗
PubMed2001

Clarification of the active gelatinolytic sites in human ovarian neoplasms using in situ zymography.

Tissues from 26 human ovarian common epithelial tumors were examined to determine where and how gelatinolytic activity was present, in relation to tumor-stromal interaction and histologic types. For this purpose, we used in situ zymography, a newly developed technique using gelatin-coated film. Gelatinolytic activity was evident in ovarian carcinomas and in borderline tumors. Benign tumors had no or only weak activity. Four tissue localization patterns of gelatinolysis were identified: pattern A, tumor cytoplasm; pattern B, tumor-stromal junction; pattern C, stroma; and pattern D, cystic fluid. Mucinous cystadenocarcinomas showed A and/or D patterns. One mucinous and one serous adenocarcinoma and one mucinous borderline tumor had a B pattern. Most serous and all clear cell adenocarcinomas showed strong gelatinolysis of C pattern, especially in the desmoplastic stroma, an area where the tumor cells were dispersed. Immunohistochemically in 12 adenocarcinomas and 3 borderline tumors, the tumor cytoplasm was positive for matrix metalloproteinases (MMP-2) (5 cases), MMP-7 (9 cases), and MMP-9 (6 cases). Stromal components were positive for MMP-2 in 5 cases and for MMP-9 in 3 cases, but they were not positive for MMP-7. MMP antigens were mostly distributed in an almost identical pattern consistent with that seen with in situ zymography. In situ zymography clarified the cellular localization of active gelatinolysis in human ovarian neoplasms, a finding which supports the view that interaction between tumor and stroma is critical for tumor growth. This newly developed method contributes to a better understanding of biologic features of ovarian malignancies.

Adenoma↗
PubMed2001

Recurrent pregnancy loss: etiology of thrombophilia.

Congenital and acquired thrombophilia are associated with an increased risk of pregnancy-associated venous thrombosis and fetal loss. Two hundred eighty-nine patients with a history of recurrent spontaneous abortion were subjected to screening examinations for the etiology of these abortions. Endocrine abnormality (28.0%), uterine abnormality (10.4%), autoimmune diseases (1.4%), antiphospholipid antibody syndrome (4.5%), and balanced type chromosome translocation (4.2%) were found as underlying causes of recurrent abortions, and the remaining 55.0% of the 289 patients were classified as having an unexplained etiology. Congenital thrombophilia such as protein C (PC) deficiency, protein S (PS) deficiency, antithrombin deficiency, and factor V Leiden mutation was not frequently detected; only one patient had PS deficiency. A reduced factor XII activity was found at a frequency of 4.2%. The frequency of methylene tetrahydrofolate reductase gene C677T mutation in recurrent aborters (0.38) was the same as that found in a fertile control group. Although the prevalence of anti-beta2-glycoprotein I antibody (abeta2-GPI) syndrome was very low (1.7%), patients with a high titer of immunoglobulin G (IgG) class abeta2-GPI, despite anticoagulation therapy, experienced severe fetomaternal complications in subsequent pregnancies. The rate (13.8%) of positive tests for serum IgA class abeta2-GPI in patients with unexplained etiology was higher than that in the controls (0%) (P < .05). We conclude that congenital thrombophilia is rare in Japanese patients who had experienced consecutive spontaneous abortions.

Abortion, Habitual↗