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Biomedical subjects

H Yoshikawa

Publications and source records attributed to H Yoshikawa.

At least 91 records · Page 5Linked to original sources
PubMed2001

Loss of the SEDL gene product (Sedlin) causes X-linked spondyloepiphyseal dysplasia tarda: Identification of a molecular defect in a Japanese family.

A 23-year-old man was diagnosed as having X-linked spondyloepiphyseal dysplasia tarda (SEDT; MIM 313400) based on his disproportionately short trunk, short stature, characteristic radiological features of the spine (posterior hump, end plate sclerosis, and disc space narrowing) and the hips (short and thick femoral necks), and positive family history. This Japanese family was found to have an intragenic deletion flanking intron 2 and exon 3 of the SEDL gene that not only included the 5' untranslated region but also the coding sequence for the first methionine through the 25th alanine. This mutation was present in the proband and his unaffected mother (a heterozygote), but not in an unaffected sister and an unaffected uncle. The nature of the mutation predicted that the SEDL protein (Sedlin) was not produced in the proband, indicating that loss of Sedlin caused SEDT.

Adult↗
PubMed2001

A subfamily of RNA-binding DEAD-box proteins acts as an estrogen receptor alpha coactivator through the N-terminal activation domain (AF-1) with an RNA coactivator, SRA.

One class of the nuclear receptor AF-2 coactivator complexes contains the SRC-1/TIF2 family, CBP/p300 and an RNA coactivator, SRA. We identified a subfamily of RNA-binding DEAD-box proteins (p72/p68) as a human estrogen receptor alpha (hER alpha) coactivator in the complex containing these factors. p72/p68 interacted with both the AD2 of any SRC-1/TIF2 family protein and the hER alpha A/B domain, but not with any other nuclear receptor tested. p72/p68, TIF2 (SRC-1) and SRA were co-immunoprecipitated with estrogen-bound hER alpha in MCF7 cells and in partially purified complexes associated with hER alpha from HeLa nuclear extracts. Estrogen induced co-localization of p72 with hER alpha and TIF2 in the nucleus. The presence of p72/p68 potentiated the estrogen-induced expression of the endogenous pS2 gene in MCF7 cells. In a transient expression assay, a combination of p72/p68 with SRA and one TIF2 brought an ultimate synergism to the estrogen-induced transactivation of hER alpha. These findings indicate that p72/p68 acts as an ER subtype-selective coactivator through ER alpha AF-1 by associating with the coactivator complex to bind its AF-2 through direct binding with SRA and the SRC-1/TIF2 family proteins.

Amino Acid Motifs↗
PubMed2001

Mutation frequencies of EXT1 and EXT2 in 43 Japanese families with hereditary multiple exostoses.

Hereditary multiple exostoses (EXT) is an autosomal dominant bone disease characterized by the formation of cartilage-capped prominences. EXT is genetically heterogeneous with at least four chromosomal loci. Among the four loci, the exostosis type 1 gene (EXT1) and type 2 gene (EXT2) have been cloned. Previous studies have shown that disease-type-specific frequency of mutations is different among various ethnic populations. To determine those frequencies in the Japanese, we conducted a large-scale mutation screening on both genes. In 23 of 43 Japanese families examined, we found 21 different mutations, of which 18 are novel. Seventeen (40%) of the 23 families had a mutation in EXT1 and six (14%) had a mutation in EXT2, suggesting that the former mutations are more frequent than the latter in Japanese EXT families. Of the 17 families with EXT1 mutations, 13 had those causing premature termination of the EXT1 protein and four showed missense mutations, whereas five of the six families with EXT2 mutations had those causing premature termination and one showed missense mutation. Interestingly, all four EXT1 missense mutations occurred in an arginine residue at codon 340 (R340) that is known as a critical site for expression of heparan sulfate glycosaminoglycans, suggesting that the region encompassing the arginine residue may play an important role in the function of the EXT1 protein. These results expand our knowledge of the ethnic difference of EXT and the structure-function relationship of the EXT genes.

DNA↗
PubMed2001

Down-regulation of Pim-1 and Bcl-2 is accompanied with apoptosis of interleukin-6-depleted mouse B-cell hybridoma 7TD1 cells.

Here we report, interleukin-6 (IL-6) dependent mouse B-cell hybridoma, 7TD1 cells underwent apoptotic cell death with the starvation of IL-6. First, 7TD1 cells cultured without IL-6 arrested at G0/G1 phase (maximum accumulation at 24 h ) of the cell cycle. After that, the parameters of apoptosis namely, decreased mitochondrial transmembrane potential (DeltaPsi(m)), activation of caspases, DNA fragmentation and morphological changes (condensed nucleus and formation of apoptotic bodies) were observed. As evidents by reverse transcription-polymerase chain reaction (RT-PCR) and Western blot analyses, down-regulation of Pim-1 (a serine/threonine kinase) and Bcl-2 was observed in the IL-6-depleted 7TD1 cells. There was no change in the expression of c-Myc, Bcl-xL and Mcl-1, even at 48 h of IL-6-depletion. Taken together, these results indicate that IL-6 withdrawn from the 7TD1 cells resulted in G0/G1 arrest and then caspase-dependent apoptosis via mitochondrial pathway by down-regulation of Pim-1 and Bcl-2, which may be essential for anti-apoptotic signals of IL-6.

Animals↗
PubMed2001

Nasal immunization of mice with peptide having a cross-neutralization epitope on minor capsid protein L2 of human papillomavirus type 16 elicit systemic and mucosal antibodies.

A common cross-neutralization epitope for human papillomavirus types 6 and 16 (HPV 6 and 16) is present in the region of amino acids (aa) 108-120 of HPV-16 minor capsid protein, L2. We nasally immunized Balb/c mice with a synthetic peptide with the 13 aa HPV 16 L2 sequence, and examined the antibodies elicited. ELISA showed that the immunization induced predominantly IgG and IgA antibodies cross-binding to L1/L2-capsids of HPVs 6, 16, and 18 in sera and in vaginal secretions, respectively. The serum containing the IgG antibody and the vaginal wash containing the IgA antibody neutralized HPV 16 pseudovirions and HPV 11 authentic virions, as shown by surrogate infectivity assays. From their cross-binding activity for HPV 16 and 18, the peptide-induced antibodies can probably cross-neutralize most of the genital HPVs. The peptide-induced neutralizing activity in vaginal wash was comparable to that induced by nasally immunization with HPV 16 L1-capsids. Unlike Balb/c, C57BL/10, which has different MHC class II, did not respond to the peptide immunization, but aa substitutions in the peptide to fulfill the requirement for the C57BL/10 agretope rendered the modified peptides immunogenic. The results provide a basis for development of a peptide vaccine against broad-spectrum of genital HPVs for humans.

Administration, Intranasal↗
PubMed2001

The der(17)t(X;17)(p11;q25) of human alveolar soft part sarcoma fuses the TFE3 transcription factor gene to ASPL, a novel gene at 17q25.

Alveolar soft part sarcoma (ASPS) is an unusual tumor with highly characteristic histopathology and ultrastructure, controversial histogenesis, and enigmatic clinical behavior. Recent cytogenetic studies have identified a recurrent der(17) due to a non-reciprocal t(X;17)(p11.2;q25) in this sarcoma. To define the interval containing the Xp11.2 break, we first performed FISH on ASPS cases using YAC probes for OATL1 (Xp11.23) and OATL2 (Xp11.21), and cosmid probes from the intervening genomic region. This localized the breakpoint to a 160 kb interval. The prime candidate within this previously fully sequenced region was TFE3, a transcription factor gene known to be fused to translocation partners on 1 and X in some papillary renal cell carcinomas. Southern blotting using a TFE3 genomic probe identified non-germline bands in several ASPS cases, consistent with rearrangement and possible fusion of TFE3 with a gene on 17q25. Amplification of the 5' portion of cDNAs containing the 3' portion of TFE3 in two different ASPS cases identified a novel sequence, designated ASPL, fused in-frame to TFE3 exon 4 (type 1 fusion) or exon 3 (type 2 fusion). Reverse transcriptase PCR using a forward primer from ASPL and a TFE3 exon 4 reverse primer detected an ASPL-TFE3 fusion transcript in all ASPS cases (12/12: 9 type 1, 3 type 2), establishing the utility of this assay in the diagnosis of ASPS. Using appropriate primers, the reciprocal fusion transcript, TFE3-ASPL, was detected in only one of 12 cases, consistent with the non-reciprocal nature of the translocation in most cases, and supporting ASPL-TFE3 as its oncogenically significant fusion product. ASPL maps to chromosome 17, is ubiquitously expressed, and matches numerous ESTs (Unigene cluster Hs.84128) but no named genes. The ASPL cDNA open reading frame encodes a predicted protein of 476 amino acids that contains within its carboxy-terminal portion of a UBX-like domain that shows significant similarity to predicted proteins of unknown function in several model organisms. The ASPL-TFE3 fusion replaces the N-terminal portion of TFE3 by the fused ASPL sequences, while retaining the TFE3 DNA-binding domain, implicating transcriptional deregulation in the pathogenesis of this tumor, consistent with the biology of several other translocation-associated sarcomas. Oncogene (2001) 20, 48 - 57.

Adolescent↗
PubMed2001

Lymphoid chemokine B cell-attracting chemokine-1 (CXCL13) is expressed in germinal center of ectopic lymphoid follicles within the synovium of chronic arthritis patients.

A unique feature in inflammatory tissue of rheumatoid arthritis (RA) is the formation of ectopic lymphoid aggregates with germinal center (GC)-like structures that can be considered to contribute to the pathogenesis of RA, because local production of the autoantibody, rheumatoid factor, is thought to be a causative factor in tissue damage. However, the factors governing the formation of GC in RA are presently unknown. To begin to address this, the expression of B cell attracting chemokine (BCA-1) (CXCL13), a potent chemoattractant of B cells, was examined in the synovium of patients with RA or with osteoarthritis (OA). Expression of BCA-1 mRNA was detected in all RA samples, but in only one of five OA samples. Lymphoid follicles were observed in four of seven RA samples and in two of eight OA samples, and in most of them BCA-1 protein was detected in GC. BCA-1 was not detected in tissues lacking lymphoid follicles. Notably, BCA-1 was detected predominantly in follicular dendritic cells in GC. CD20-positive B cells were aggregated in regions of BCA-1 expression, but not T cells or macrophages. These data suggest that BCA-1 produced by follicular dendritic cells may attract B cells and contribute to the formation of GC-like structures in chronic arthritis.

Adult↗
PubMed2001

The cloning and characterization of the CDC50 gene family in Saccharomyces cerevisiae.

We have cloned a gene that complements the cold-sensitive growth of cdc50-1 mutant strain of Saccharomyces cerevisiae at 14 degrees C. The CDC50 gene was found to be identical to YCR094w on chromosome III and contains 1173 nucleotides encoding 391 amino acids. We found a missense mutation at the first initiation codon of cdc50-1. The disruption of the CDC50 gene revealed that it is not essential for growth, but the disruptant caused the same cold-sensitive phenotype as cdc50-1, suggesting that the cdc50-1 is a null mutation resulted from the mutation in the first codon. The cdc50-1 mutant arrests at START in G1 phase at the non-permissive temperature. The CDC50 gene product has strong structural similarity to two other proteins in Saccharomyces cerevisiae encoded by YNR048w and YNL323w. The over-expression of either YNR048w or YNL323w suppressed the cdc50-1 mutant and the double disruption of either CDC50 and YNR048w or CDC50 and YNL323w resulted in a severe slow-growth phenotype. We conclude that these three genes constitute a family with redundant function. We also found that the CDC39 gene was a multicopy suppressor of cdc50-1 mutation, suggesting that the CDC50 family is involved in regulation of transcription via CDC39.

Amino Acid Sequence↗
PubMed2001

Identification of seven novel mutations including the first two genomic rearrangements in SLC26A3 mutated in congenital chloride diarrhea.

Congenital chloride diarrhea (CLD) is an autosomal recessive disorder characterized by defective intestinal electrolyte absorption, resulting in voluminous osmotic diarrhea with high chloride content. A variety of mutations in the solute carrier family 26, member 3 gene (SLC26A3, previously known as CLD or DRA) are responsible for the disease. Since the identification of the SLC26A3 gene and the determination of its genomic structure, altogether three founder and 17 private mutations have been characterized within miscellaneous ethnic groups. We screened for mutations in seven unrelated families with CLD. The diagnoses were confirmed by fecal chloride measurements. The combined PCR-SSCP and sequencing analyses revealed altogether seven novel mutations including two missense mutations (S206P, D468V), two splicing defects (IVS12-1G>C, IVS13-2delA), one nonsense mutation (Q436X), one insertion/deletion mutation (2104-2105delGGins29-bp), and an intragenic deletion of SLC26A3 exons 7 and 8. Two previously identified mutations were also found. This is the first report of rearrangement mutations in SLC26A3. Molecular features predisposing SLC26A3 for the two rearrangements may include repetitive elements and palindromic-like sequences. The increasingly wide diversity of SLC26A3 mutations suggests that mutations in the SLC26A3 gene may not be rare events.

Antiporters↗
PubMed2001

Comparison of fit and fill between anatomic stem and straight tapered stem using virtual implantation on the ORTHODOC workstation.

The objective of this article was to determine the influence of stem design on fit and fill using the preoperative planning workstation of the ROBODOC system. Anatomic ABG and straight Osteolock femoral components were virtually implanted into 50 femora (25 from patients with developmental dysplasia of the hip (DDH), 25 morphologically normal) on the workstation display. Fit and fill, and length of the proximal posterolateral femoral cortex removed by milling (LPFCR), were measured on the cross-sectional images. Lateral curvature (alpha angle) and anteversion of the femur were evaluated. The ABG components showed significantly better fit than the Osteolock components at the levels proximal to the lesser trochanter. The Osteolock components showed significantly greater LPFCR than the ABG components, especially in the patients with DDH. The patients with DDH showed significantly greater alpha angle and femoral anteversion than those with morphologically normal femora. With the Osteolock components, the alpha angle correlated significantly with femoral anteversion and LPFCR. Use of an anatomic proximal body of the stem helped to improve the proximal canal fit. Greater LPFCR was required when a straight stem was implanted in patients with a relatively high alpha angle.

Adult↗
PubMed2001

Mucinous adenocarcinoma arising in a neovagina using the sigmoid colon thirty years after operation: a case report.

BACKGROUND: Because of a relative rarity of the cases with an artificial vagina, the incidence of a case with malignant disease arising in the neovagina is extremely rare. A case of adenocarcinoma arising from a neovagina is presented with a review of the literature. CASE: A neovagina was constructed using the sigmoid colon at the age of 23 for congenital agenesis of the vagina, Rokitansky-Küster-Hauser syndrome. Subsequently, the patient had regular sexual intercourse for about 20 years. At the age of 53, she came to our outpatient clinic with a complaint of vaginal bleeding, and adenocarcinoma was found at the anterior wall of the neovagina adjoining the introitus. Total resection of the neovagina and adjuvant radiotherapy was performed. The pathological diagnosis was mucinous adenocarcinoma. CONCLUSIONS: In view of relatively low incidence of mucinous carcinoma arising in the sigmoid colon along with the ectopic localization, this case may have implications for the understanding of pathogenesis of sigmoid colon cancer.

Adenocarcinoma, Mucinous↗
PubMed2001

Prognostic factors of stage IV epithelial ovarian cancer: a multicenter retrospective study.

OBJECTIVE: In the present study, we conducted a multicenter retrospective analysis to elucidate the prognostic factors of stage IV epithelial ovarian cancer. METHODS: In November 1999, 24 Japanese institutions received questionnaires regarding stage IV epithelial ovarian cancer patients. Eligibility criteria included all patients with stage IV epithelial ovarian cancer who were surgically confirmed and initially treated in each institution between January 1990 and December 1997. Data were collected regarding age, performance status, tumor histologic subtype, site of metastasis, preoperative CA125, cytoreductive surgery, residual disease after cytoreductive surgery, and response to primary chemotherapy. Survival analysis and comparisons were performed by univariate and multivariate methods. RESULTS: Two hundred twenty-five patients with stage IV ovarian cancer were identified. The median age of the patients was 54 years. The most common site of extraperitoneal disease was malignant pleural effusion (39.6%). Of the 225 patients who underwent an attempt at surgical debulking, 70 (31.1%) were optimally cytoreduced. Most patients received platinum-based combination chemotherapy for primary chemotherapy. In multivariate analysis, performance status, histology, and residual disease after cytoreductive surgery were independent prognostic predictors of outcome. The overall median survival for optimally debulked patients was 32 months compared to 16 months for suboptimally debulked patients (P < 0.0001, hazard ratio: 0.415). CONCLUSION: Optimal surgical debulking, performance status, and histology appear to be important prognostic factors of survival in patients with stage IV epithelial ovarian cancer.

Adult↗
PubMed2001

Postradiation sarcomas of the pelvis after treatment for uterine cervical cancer: review of the CT and MR findings of five cases.

OBJECTIVE: To characterize the radiologic features of postradiation sarcomas arising in the pelvic bones following treatment for uterine cervical carcinoma. DESIGN AND PATIENTS: Five patients who developed postradiation sarcomas in the pelvic bones following radiation therapy for carcinoma of the uterine cervix within the irradiated field were evaluated. Pelvic radiographs, computed tomography (CT) and magnetic resonance (MR) imaging were undertaken in all patients. Histologic confirmation of the tumor type was obtained. RESULTS: Three patients whose tumors were characterized as an osteosarcoma, an angiosarcoma and a malignant fibrous histiocytoma (MFH) showed a large round or oval mass mainly in the sacroiliac joint which extended into the posterior gluteal soft tissues. In a fourth patient an osteosarcoma developed in the central ilium extending widely into the soft tissues both anteriorly and posteriorly, with calcified areas within the extraosseous mass. The fifth patient had a MFH which showed osteolytic destruction of the cortex of the acetabulum, and minimal soft tissue extension. There were no specific features or signal intensity changes on MR imaging to differentiate these cases from primary sarcomas. CONCLUSION: Postradiation sarcoma must be considered in patients with uterine carcinoma when a soft tissue mass is seen in the previously irradiated field, especially if the mass is posterior to the sacroiliac joint and the latent period is more than 5 years.

Aged↗
PubMed2001

Ossification of the ligamentum flavum associated with osteoblastoma: a report of three cases.

We report three cases of spinal osteoblastoma with ossification of the ligamentum flavum (OLF) adjacent to the tumor. The patients in this report, all young adults, had no symptoms except for back pain. Computed tomography (CT) demonstrated a typical radiolucent nidus in the spinal pedicle/lamina with a dense sclerotic rim. In addition, ectopic bone formation at the insertion point of the ligamentum flavum adjacent to the tumor was clearly illustrated. Magnetic resonance imaging (MRI) revealed the tumor and surrounding inflammatory responses, but OLF was not detected clearly. Histological examination revealed endochondral ossification of the ligamentum flavum that is quite unusual for normal young adults. Immunohistochemical assays in one case demonstrated that bone morphogenetic protein (BMP)-2/4 was expressed in the osteoblastic tumor cells. This case raises the possibility that BMPs secreted from the tumor cells triggered ectopic ossification in the spinal ligament.

Adult↗
PubMed2001

Full weight-bearing after cementless total hip arthroplasty.

In a prospective study of cementless total hip arthroplasty, 19 hips in 17 patients (Group A) were allowed full weight-bearing immediately after the operation while 18 hips in 16 patients (Group B) were first allowed weight-bearing after 6 weeks. Patients were matched for sex, age at surgery, height, weight, and follow-up period and there were no significant differences in hip scores between the two groups. Rehabilitation to gain walking ability with a cane lasted 5.8 days for Group A and 44.8 days for Group B (P = 0.0001). The hospital stay after surgery was 30.1 days for Group A and 46.7 days for Group B (P = 0.006). All patients showed bone ingrowth radiographically. There were no complications in either group.

Activities of Daily Living↗
PubMed2001

Influence of polyethylene and femoral head surface quality on wear: a retrieval study.

Thirty-two polyethylene sockets and 22 femoral heads were retrieved because of aseptic loosening more than 9 years after total hip arthroplasty. The volumetric wear rates of the retrieved polyethylene sockets were significantly greater in those coupled with an alumina head (P < 0.05). The retrieved alumina heads showed significantly better surface roughness and roundness than heads of Co-Cr and of stainless steel (P < 0.05). However, no significant difference was found in polyethylene quality demonstrated as fusion defects among the three different groups. The present study suggests that maintaining better surface roughness and roundness of the femoral heads does not always result in an in vivo reduction of polyethylene wear.

Adult↗
PubMed2001

Tissue factor increases in the aqueous humor of proliferative diabetic retinopathy.

BACKGROUND: Tissue factor (TF) is a cellular initiator of the coagulation cascade and is upregulated by the major factors of diabetic angiopathy, TF might thus be one of the key molecules in diabetic retinopathy (DR). PURPOSE: To measure TF in diabetic eyes and evaluate its possible role in DR. METHODS: TF concentration in the aqueous humor of the eyes in 44 patients with diabetes and 35 age-matched control patients was evaluated by ELISA. The concentration of TF in aqueous humor (AH) was compared with the grade of DR. The concentration of TF in AH was also compared with duration of diabetes, renal function, and blood glucose control. The serum TF concentration in each group was also compared. The correlation between the serum TF and aqueous TF in each patient was analyzed. The effect of vascular endothelial growth factor (VEGF) on the TF activity of cultured bovine retinal endothelial cells was evaluated. RESULTS: The mean TF concentration in AH was higher in patients with active proliferative DR (244.5 pg/ml) than in either those with non-proliferative DR (132.4 pg/ml, P<0.05) or the control patients (114.9 pg/ml, P<0.01). The serum TF concentration in active proliferative DR patients (348.3 pg/ml) was significantly higher than in either non-proliferative DR patients, (235.9 pg/ml, P<0.01) or in the controls (223.5 pg/ml, P<0.01). However, the TF concentration of AH was not significantly correlated to that of the serum in each patient. The TF concentration in AH closely correlated with the grade of DR and protein concentration. VEGF increased the biological activity of TF in vitro. CONCLUSION: The origin of TF in AH, however, is still not clearly understood. Nonetheless, TF in AH directly reflects the severity of ocular diabetic change, and the present results indicate that TF indeed plays some role in the progression of DR.

Adult↗