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Biomedical subjects

T Fukuda

Publications and source records attributed to T Fukuda.

At least 163 records · Page 9Linked to original sources
PubMed2000

Clinical and morphologic features of perimembranous ventricular septal defect with overriding of the aorta--the so-called Eisenmenger ventricular septal defect. A study making comparisons with tetralogy of Fallot and perimembranous ventricular defect without aortic overriding.

The aim of our study was to elucidate the clinical and morphologic features of those perimembranous ventricular septal defects which extend between the ventricular outlets, particularly when found in association with anterior deviation of the muscular outlet septum and overriding of the aorta--the so called Eisenmenger ventricular septal defect. From 1990 through 1998, we have undertaken surgical correction in 203 patients with perimembranous ventricular septal defect. Of these, 15 patients had the Eisenmenger ventricular septal defect. We conducted retrospective analyses of the clinical records, catheterization data, and angiocardiographic and echocardiographic finding of these patients. Comparative studies were then made with the patients having tetralogy of Fallot, and those with simple perimembranous ventricular septal defects without overriding of the aorta. In the patients with the Eisenmenger ventricular septal defect, the extent of anterior deviation of the outlet septum was comparable with that seen in tetralogy of Fallot, but there was less rightward displacement of the aortic valvar orifice. In contrast to earlier investigators, however, we found evidence of progressive narrowing of the subpulmonary infundibulum in those with the Eisenmenger defect. These morphological features were reflected in the clinical features, since all patients showed evidence of increased pulmonary flow and congestive heart failure in early infancy, but with two-thirds of them subsequently developing right-to-left shunting. We conclude, therefore, that the Eisenmenger ventricular septal defect is a discrete cardiac abnormality in which the morphologic substrate of anterior deviation of the outlet septum gives rise to a potential for progressive narrowing of the subpulmonary infundibulum. Surgical management, therefore, needs to take account of such narrowing as an additional cardinal morphologic feature.

Angiocardiography↗
PubMed2000

Novel mutations in two Japanese cases of glycogen storage disease type IIIa and a review of the literature of the molecular basis of glycogen storage disease type III.

We report two novel mutations in two Japanese patients with glycogen storage disease type IIIa (GSD IIIa). In addition, we review the literature on mutations in GSD III to understand better the molecular basis of GSD III. In our first case, the homozygous A-to-C mutation at the acceptor site of intron 5 (IVS5-2A > C) was identified. This leads to the skipping of exon 6 and the predicted mutant protein was found to be 68 amino acids shorter than normal. This is the first report of skipping exon 6, which encodes one of the putative active sites, resulting in a profoundly deleterious effect on debrancher activity. In our second case, the homozygous deletion of an A at position 4234 (4234delA) was identified; this induces a frameshift resulting in the appearance of a stop codon at amino acid position 1276 (1276X). In patients with GSD IIIa, several mutations of the debrancher gene located in the C-terminal region containing putative glycogen binding domains have been identified as well as 4234delA in our second case. On the other hand, specific localization of the mutations within exon 3 was proposed in patients with GSD IIIb.

Adult↗
PubMed2000

Distribution of Tsc1 protein detected by immunohistochemistry in various normal rat tissues and the renal carcinomas of Eker rat: detection of limited colocalization with Tsc1 and Tsc2 gene products in vivo.

We and others previously demonstrated that hereditary mutation and a subsequent second hit in the rat homolog of tuberous sclerosis gene (Tsc2) are responsible for Eker renal carcinomas (RC). In humans, alteration in the TSC2 gene is known to cause the tuberous sclerosis complex (TSC) that results in hamartomatous lesions in multiple organs, but the function of TSC2 is not fully understood. In recent years, a second gene (TSC1) responsible for human TSC has been cloned, and binding between TSC1 and TSC2 proteins was reported. In this study, to clarify associations between Tsc proteins in vivo, the expression of Tsc1 protein was detected by immunohistochemistry, and compared with Tsc2 expression. Tsc1 protein was expressed in the nervous system and in many endocrine tissues, including pancreatic islets, the parathyroids, testis, and ovary. Tsc1 was also detected in the many epithelial tissues of organs, such as kidney, uterus, small and large intestine, and liver. Our results indicate overlapping, but not identical, organ distributions of Tsc1 and Tsc2 proteins. At the intracellular distribution, double fluorescent immunolabeling allowed the determination that only a partial portion of Tsc1 signals overlapped with Tsc2 in some organs. These results suggest the existence of co-localizing and independent forms of Tsc proteins in endogenous expressions. Additionally, relatively high expression of Tsc1 protein was detected in RC in the Tsc2 mutant (Eker) rat.

Animals↗
PubMed2000

Prognostic significance of apoptosis in synovial sarcoma: correlation with clinicopathologic parameters, cell proliferative activity, and expression of apoptosis-related proteins.

bcl-2 overexpression in synovial sarcomas has been recently reported. Although it is widely known that bcl-2 suppresses apoptosis in various cells, there are no studies that have examined the significance of apoptosis in synovial sarcoma. In the present study, we visualized apoptotic tumor cells by the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate in situ nick end-labeling (TUNEL) method in 49 cases of primary synovial sarcoma. The degree of apoptosis was analyzed in relation to several clinicopathologic parameters, cell proliferative activity, and immunohistochemical expression of apoptosis-related proteins, including bcl-2, bax, bcl-x, bak, p53, p21 (WAF1/CIP1), Fas, and Fas ligand. TUNEL index (TUNEL-I) significantly correlated with the mitotic index (MI) (ñ = 0.60, P < .0001) and Ki-67 labeling index (MIB1-I) (ñ = 0.52, P = 0.0005). There was a highly significant association between high TUNEL-I value (>.8%) and poor prognosis (log-rank test; P < .0001). Many synovial sarcomas were diffusely positive for bcl-2 family proteins (bcl-2, bax, bcl-x, and bak) and were negative or only sporadically positive for Fas, Fas ligand, p53, and p21 (WAF1/CIP1) proteins. The results indicated that increased rate of apoptosis in primary synovial sarcoma was considered to be an indicator of poor prognosis. In addition, apoptosis in synovial sarcoma may be controlled by multiple apoptosis-regulating mechanisms, including the bcl-2 family.

Adolescent↗
PubMed2000

Proliferative involvement of ENX-1, a putative human polycomb group gene, in haematopoietic cells.

Homeobox genes have important roles in haematopoiesis and are regulated in an activated state by the trithorax group (trxG) of genes. In a repressed state, they are regulated by the Polycomb group (PcG) of genes. ENX-1, a putative human PcG gene product, interacts with the proto-oncogene product Vav. We report an investigation of the role of ENX-1 in human haematopoiesis. CD34+ cells mobilized to peripheral blood strongly expressed ENX-1. When stimulated to proliferate, both T and B lymphocytes rapidly up-regulated ENX-1. ENX-1 was expressed in all cell lines of the various lineages examined. When HL-60 cells were differentiated to mature granulocytes with all-trans retinoic acid, ENX-1 was down-regulated. Moreover, ENX-1 antisense oligodeoxynucleotide suppressed DNA synthesis in HL-60 cells. Our data indicate that ENX-1 is involved in the proliferation of both normal and malignant haematopoietic cells.

Antineoplastic Agents↗
PubMed2000

Clonal expansion of T cells infiltrating in the airways of non-atopic asthmatics.

CD4+ T cells are thought to play an important role in airway inflammation in both atopic and non-atopic asthma. However, the mechanism by which T cells are activated in non-atopic asthma, where there is no causative antigen identified, is unknown. To elucidate this issue, we analysed T cell receptor (TCR) Vbeta gene clonotypes of T cells in the bronchoalveolar lavage fluids (BALF) of non-atopic asthmatics using polymerase chain reaction single-strand conformation polymorphism (PCR-SSCP) analysis and a sequencing method. We found that the numbers of TCR Vbeta gene clonotypes of T cells in the BALF of non-atopic asthmatics were significantly increased compared with those of peripheral blood lymphocytes (PBL). We also found that there were several shared amino acid motifs in complementarity-determining region 3 (CDR3) of TCR Vbeta genes from those T cell clones in BALF of non-atopic asthmatics, whereas these shared motifs were not found in the same Vbeta family genes from PBL in the patients. Moreover, a conserved amino acid sequence was detected in two patients who shared a common HLA-DR allele. These results indicate that the infiltrating T cells in the airways of non-atopic asthmatics recognize relatively limited epitopes of antigens and are clonally expanded by antigen-driven stimulation.

Adult↗
PubMed2000

Expression of cyclooxygenase-1 (COX-1) in labial salivary glands of Sjögren's syndrome.

COX plays an important role in inflammatory diseases such as rheumatoid arthritis. To determine the role of COX in Sjögren's syndrome (SS), we examined COX expression in the salivary glands of SS patients. We examined 15 patients with SS and two normal subjects. Labial salivary gland tissue samples were analysed immunohistochemically using anti-COX-1 and COX-2 antibodies. All biopsy samples from 15 patients with SS were stained for COX-1. In contrast, COX-1 immunostaining was not detected in normal salivary gland tissues. Co-expression of COX-1 and CD68 was confirmed by mirror section technique and double antibody immunostaining. This finding indicated that COX-1-expressing cells in SS salivary glands were infiltrating macrophages. In contrast to COX-1 staining, only a little COX-2 immunostaining was observed in salivary gland tissues from SS patients. These data suggest that COX-1 expression on infiltrating macrophages may contribute to the inflammatory process of salivary glands in SS.

Adult↗
PubMed2000

Oesophageal cavernous haemangioma diagnosed histologically, not by endoscopic procedures.

Haemangioma of the oesophagus is uncommon in patients with benign oesophageal tumours. We present a patient with an oesophageal haemangioma detected during mass screening of the upper gastrointestinal tract. The patient, a 59-year-old man, had neither abdominal complaints nor a history of gastrointestinal diseases. Endoscopic examination revealed a blue-coloured submucosal tumour (approximately 3 cm in diameter) at the middle portion of oesophagus. Endoscopic Doppler ultrasonography showed an homogeneous and hypoechoic mass without blood flow in the submucosal layer of the oesophagus. However, a magnetic resonance imaging scan did not give a typical image for oesophageal haemangioma. Therefore, partial resection of the tumour was performed to obtain a differential diagnosis using the procedures of endoscopic ligation and polypectomy. Histological examination of the resected tissue showed a cavernous haemangioma in the oesophagus. This endoscopic technique may be useful for the differential diagnosis of oesophageal haemangioma.

Diagnostic Imaging↗
PubMed2000

Abnormal pigmentation of schwannoma attributed to excess production of neuromelanin-like pigment.

Five cases of non-melanotic pigmented schwannoma with excess accumulation of neuromelanin are presented. The tumors were composed basically of spindle or fusiform tumor cells, compatible with those of classical schwannoma, together with varying numbers of tumor cells containing various amounts of light brown or grayish pigment. Fontana-Masson stain demonstrated argentaffin granules in some tumor cells of each tumor and bleaching with potassium permanganate abolished argentaffin reaction. Ultrastructural examination demonstrated the granules contained fine particles with heterogeneous density, occasionally together with coarse granular materials or amorphous high-density areas, indicating lysosome or autophagosome. Neither typical melanosomes nor neurosecretory granules were detected. In immunohistochemistry, neurogenic markers as well as CD68 were expressed in most tumor cells in each case and various numbers of tumor cells were positive for Leu7 and CD34. Lysozyme was also frequently positive in tumor cells, especially in granular cells. HMB45 was not expressed in any of the cases. These findings indicate that these cases are schwannomas with abnormal accumulation of neuromelanin-like pigment.

Aged↗
PubMed2000

Clear cell sarcoma arising in the transverse colon.

A case of clear cell sarcoma (CCS) arising in the transverse colon is presented. The tumor consisted of sheets or small nests of epithelioid malignant cells possessing pleomorphic nuclei with one or more prominent nucleoli and ample clear or slightly eosinophilic cytoplasm. Some of the tumor cells contained various amounts of melanin pigments that were confirmed by histochemical and ultrastructural examinations. Immunohistochemical examination showed a positive immunoreactivity for HMB45 and S-100 protein. A metastatic nodule, which was found 9 months after surgery, showed similar histological findings to those of the primary one but lacked melanin pigments. Reverse transcriptase- polymerase chain reaction using total ribonucleic acid obtained from metastatic nodule demonstrated the presence of EWS-ATF-1 fusion gene. Based on these findings, the present case tumor is a CCS of the colon.

Aged↗
PubMed2000

Three-dimensional hysterosalpingo-contrast sonography (3D-HyCoSy) as an outpatient procedure to assess infertile women: a pilot study.

OBJECTIVES: This study aimed to assess the use of three-dimensional hysterosalpingo-contrast sonography (3D-HyCoSy) as a routine outpatient procedure for evaluating infertile women. METHODS: In 25 unselected infertile patients, tubal patency and uterine cavity were investigated by 3D-HyCoSy with saline as a contrast medium. The efficacy of the procedure was evaluated with X-ray hysterosalpingography (XHSG) as reference. RESULTS: The positive predictive value, negative predictive value, sensitivity, and specificity of predicting tubal patency by 3D-HyCoSy were 100, 33.3, 84.4, and 100%, respectively. The full contour of the uterine cavity was depicted in 96% of cases by 3D-HyCoSy and 64% by XHSG (P < 0.005). The uterine cavity area measured on 3D-HyCoSy correlated well with the volume of contrast medium required on XHSG (r2 = 0.8166). CONCLUSIONS: 3D-HyCoSy provided advantages of better assessment of uterine cavity over XHSG. Compared with conventional XHSG, the efficacy of 3D-HyCoSy to assess tubal patency was acceptable. In addition, the procedure of 3D-HyCoSy appears to be better tolerated, requiring no sedation or anesthesia and a reduced examination time. Thus, 3D-HyCoSy with saline as a contrast medium is feasible and could comprise a routine outpatient procedure in the initial evaluation of infertile women.

Adult↗
PubMed2000

Apheresis treatment in Lambert-Eaton myasthenic syndrome.

The Lambert-Eaton myasthenic syndrome (LEMS) is an autoimmune disorder of peripheral cholinergic transmission in which autoantibodies decrease the presynaptic release of acetylcholine at the neuromuscular junction and autonomic system. Recent results suggest that the antibodies to P/Q-type calcium channels are the principal pathogenic factors in LEMS. Here, we present our experience with cases of LEMS who are noncarcinomatous. We studied the efficacy of plasmapheresis, analyzing the clinical score, electrophysiological finding, and the titer of anti-P/Q-type voltage-gated calcium channel (P/Q-VGCC) antibody. The first case, a 72-year-old female presenting with leg weakness, was treated by plasma exchange (PE). However, clinical improvement was transient; intravenous immunoglobulin (IVIg) therapy was followed by additional PE. She had a clinical and electromyologic improvement, and her P/Q-VGCC antibody titers decreased. Her clinical status and CMAP amplitude correlated closely with the anti-P/Q-VGCC antibody titers. The second case, a 73-year-old male presenting with leg weakness, was treated by PE and double-filtration plasmapheresis. The P/Q-VGCC antibody titres decreased immediately after these aphereses, but recovered to the pretreatment levels 1 week after them. After the immunosuppressive drugs prednisolone and azathioprine were started, his clinical symptoms improved. His antibody titers decreased gradually after immunosuppressive therapy. It is speculated that no sufficient efficacious improvement could be obtained by apheresis alone because of a high rate of P/Q-VGCC antibody production. Considering our experiences and other literature, we discuss the indication of apheresis treatment of LEMS.

Aged↗
PubMed2000

Changes in E-cadherin associated with cytoplasmic molecules in well and poorly differentiated endometrial cancer.

E-cadherin function is thought to be impaired in epithelial cancer. To investigate the alterations in E-cadherin associated with cytoplasmic molecules including alpha-catenin, beta-catenin, gamma-catenin, p120CAS, and IQGAP1 in various endometrial cancers with different degree of differentiation, we examined the localization and expression of E-cadherin and cytoplasmic molecules in 30 cases of both well and poorly differentiated endometrioid adenocarcinomas, using immunofluorescence and immunoblotting techniques. E-cadherin and cytoplasmic molecules demonstrated linear staining at the cell boundaries in normal endometrium. In all 20 cases with well differentiated adenocarcinomas, alpha-catenin and IQGAP1 disappeared from the cell adhesive sites, but other cytoplasmic molecules were co-localized with E-cadherin along the cell boundaries. In all 10 cases with poorly differentiated adenocarcinomas, E-cadherin and cytoplasmic molecules accumulated as large aggregates along cell adhesive sites, and the localization of IQGAP1 differed from those of other cytoplasmic molecules. The expression of these molecules in all 20 cases with well differentiated adenocarcinomas decreased or was lost in Triton-insoluble fraction, in comparison with the findings for all cases with normal endometrium or poorly differentiated adenocarcinomas. These results suggested that each alteration in E-cadherin associated with cytoplasmic molecules may play a different role in E-cadherin dysfunction between well and poorly differentiated adenocarcinomas.

Adenocarcinoma↗
PubMed2000

Glycogen storage disease type Ib without neutropenia.

We report 2 patients with atypical glycogen storage disease type Ib without neutropenia or infectious complications. Neither patient was deficient in hepatic glucose-6-phosphatase activities in microsome-disrupted homogenates; both had mutations in the glucose-6-phosphate transporter gene, suggesting an allelic variant of glycogen storage disease type Ib.

Adult↗
PubMed2000

Production of serine protease of Aeromonas sobria is controlled by the protein encoded by the gene lying adjacent to the 3' end of the protease gene.

We cloned a protease gene of Aeromonas sobria and determined its nucleotide sequence. The protease is composed of 624 amino acid residues and its calculated molecular weight is 66,737.7. The amino acid sequence showed the characteristic features of a bacterial serine protease. We expressed the protease gene in Vibrio parahaemolyticus from which the synthesized protease is secreted into the culture medium as the mature form, and purified the mature protease by successive column chromatographies. The size of the mature protease is 65,000 daltons and the amino acid sequence analysis revealed that a 24-amino acid peptide at the amino terminal of the precursor is removed from the mature protease. This peptide might function as a signal peptide in translocation across the inner membrane. Subsequently, we found that the protein, designated ORF2 protein, encoded by the gene lying adjacent to the 3' end of the protease gene plays an important role in production of the protease. Mutation of the ORF2 gene did not affect transcription of the protease gene, but resulted in degradation of the protease in the cell. This shows that ORF2 protein is required for the successful production of the serine protease by cell.

Aeromonas↗