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J Hata

Publications and source records attributed to J Hata.

At least 109 records · Page 6Linked to original sources
PubMed1998

EAT/mcl-1, a member of the bcl-2 related genes, confers resistance to apoptosis induced by cis-diammine dichloroplatinum (II) via a p53-independent pathway.

EAT/mcl-1 showed increased expression during the differentiation of a multipotent human embryonic carcinoma cell line, NCR-G3, and of myeloblastic cells "ML-1," and has sequence similarity to Bcl-2. In this present study, we determined whether the apoptotic cell death induced by chemotherapeutic agents could be inhibited by EAT/mcl-1, as has been found with Bcl-2. Cells transfected with EAT/mcl-1 showed higher resistance to cis-diammine dichloroplatinum (II) (CDDP) and carboplatin compared with the parental line (10)1 and neomycin-resistance gene-transfected clone, (10)1/neo. There was, however, no difference in sensitivity to etoposide, N,N-bis-(2-chloroethyl)-N'-(3-hydroxypropyl) phosphordiamidic acid cyclic ester monohydrate, adriamycin or other chemotherapeutic agents tested. DNA fragmentation of the parental cells following treatment with CDDP and carboplatin was observed in a concentration-dependent manner. In contrast, cells transfected with EAT/mcl-1 did not show DNA fragmentation following treatment with the same concentration of these drugs. EAT/mcl-1 was capable of delaying the onset of p53-independent apoptosis, although it could not inhibit apoptosis completely. Since CDDP and carboplatin damage DNA and then activate c-abl and the JNK/SAPK pathway, EAT/mcl-1 may inhibit p53-independent apoptosis through a c-abl/JNK (SAPK)-dependent mechanism. EAT/mcl-1 has functional homology to Bcl-2 in that it can enhance cell viability under conditions which otherwise cause apoptosis and increase resistance to chemotherapeutic agents.

Animals↗
PubMed1998

Molecular analysis of Ewing's sarcoma: another fusion gene, EWS-E1AF, available for diagnosis.

Ewing's sarcoma, one of the most malignant tumors of children and young adults, expresses specific chimeric genes, e.g. EWS-FLI-1, EWS-ERG, EWS-ETV1 and EWS-FEV. In this paper, we extensively characterized a new fusion gene, EWS-EIAF by means of whole cDNA sequencing, RNA blot analysis, DNA blot analysis and chromosomal analysis, and showed it to be available for the diagnosis of Ewing's sarcoma and to participate in the oncogenesis of Ewing's sarcoma. Furthermore, we conducted a genetic analysis of Ewing family tumors in conjunction with immunohistochemical analysis and ultrastructural analysis. Our results demonstrate some limitations of both genetic analysis and histopathological analysis, and establish the relationship between neurogenic phenotypes and chimera genes.

Adenovirus E1A Proteins↗
PubMed1998

Secretory carcinoma of the breast in a 51-year-old male.

Approximately 100 female secretory carcinoma cases have been reported. Although this tumor was initially termed juvenile carcinoma as the patients were all children and adolescent females, subsequent reports demonstrated that it occurs in females of all ages. Moreover, to date, only five males with this tumor have been reported. As with the initial female secretory carcinoma cases, all five were children or young adults. A very rare case of non-invasive secretory carcinoma of the breast arising in a 51-year-old Japanese male is described. He presented with a lump in his left breast. The surgically resected tumor was a typical secretory carcinoma histologically, except that there was no infiltration of the surrounding stroma, and was composed of tumor cells with vacuolated cytoplasm that contained secretory materials. This case, the first recorded secretory carcinoma of the breast in a middle-aged male, demonstrates that this tumor may also arise in mature males, as is the case in females. Physicians should not rule out the possibility of a secretory carcinoma of the breast regardless of patient age and gender.

Breast Neoplasms, Male↗
PubMed1998

Do intronic mutations affecting splicing of WT1 exon 9 cause Frasier syndrome?

The WT1 gene, one of the genes responsible for Wilms tumour, is thought to play a crucial role in the development of the kidneys and gonads. This gene encodes four protein isoforms resulting from two alternative splicing sites, one of which involves inclusion or exclusion of lysine, threonine, and serine (KTS) between the third and fourth zinc finger domains. WT1 is virtually always mutationally inactivated in patients with Denys-Drash syndrome. We analysed WT1 in eight patients who had been diagnosed as having this syndrome, and identified five previously unknown mutations affecting splicing donor sites of intron 9. These mutations affect alternative splicing. The isoforms retaining KTS are not produced. The clinical features of the patients with these intronic mutations were consistent with those of Frasier syndrome, characterised by a more slowly progressive nephropathy than Denys-Drash syndrome, associated streak gonads, and no Wilms tumour development. Our results indicate that WT1 isoforms, including/excluding KTS, have different functions in tumorigenesis and organogenesis of the kidneys and gonads.

Adolescent↗
PubMed1998

Small solid renal lesions: usefulness of power Doppler US.

PURPOSE: To evaluate whether the vascular pattern at power Doppler ultrasonography (US) improves diagnostic accuracy in small solid renal lesions over that at gray-scale US. MATERIALS AND METHODS: Gray-scale and power Doppler US were performed prospectively in 64 small (1.5-3.0-cm-diameter) solid renal lesions (26 renal cell carcinomas [RCCs], 34 angiomyolipomas, two oncocytomas, two pseudotumors). At gray-scale US, echogenicity and homogeneity of the lesion, an anechoic rim, intratumoral cysts, shadowing, or a central scar were sought. At power Doppler US, the vascular distribution was divided into four patterns. RESULTS: Findings at gray-scale US included an anechoic rim or intratumoral cysts in 20 of 26 RCCs (77%) and the two oncocytomas. Shadowing was seen in seven of 34 angiomyolipomas (21%). Echogenicity, homogeneity, and a central scar were not pathognomonic. At power Doppler US, pattern 3 (peripheral) or 4 (mixed penetrating and peripheral) was seen in all RCCs, seven of 34 angiomyolipomas, and the two oncocytomas. Pattern 1 (intratumoral focal) or 2 (penetrating) was seen in 27 angiomyolipomas. Pattern 1 or 2 was characteristic of angiomyolipoma. The rate of correct diagnosis was significantly increased with combined US (78%) as compared to that with gray-scale (42%) or power Doppler (45%) US alone. CONCLUSION: The vascular distribution at power Doppler US could add important information to gray-scale US findings for differential diagnosis of small solid renal lesions.

Adenoma, Oxyphilic↗
PubMed1998

The genomic breakpoint and chimeric transcripts in the EWSR1-ETV4/E1AF gene fusion in Ewing sarcoma.

Chromosome translocation creates a fusion between the EWSR1 gene and an ETS family gene. The fusion between these two genes is a characteristic feature of Ewing sarcoma. We previously identified a fourth translocation, t(17;22)(q12;q12), in genomic DNA isolated from cells of patients affected with Ewing sarcoma. The discovery of this translocation suggested that there might be a novel EWSR1-ETV4 fusion gene. In the present study, we determined the genomic breakpoint and characterized the chimeric transcript of the EWSR1-ETV4 fusion gene in two t(17;22) Ewing sarcomas. Reverse transcriptase-PCR assay showed an in-frame fusion between the 5'-terminal region of EWSR1 and the 3' end of ETV4 (alias E1AF, PEA3); the chimeric transcript could thus serve as a template for expression of a protein composed of the N-terminal portion of EWSR1 fused to the DNA-binding domain of ETV4. Long PCR and sequence analysis of genomic DNA revealed that either exon 8 or intron 7 of EWSR1 is fused to the same intron of ETV4 in both tumors. Several palindromic oligomer sequences were found close to the breakpoints in both genes. The 159-bp Alu-like sequence was repeated in the breakpoint region of the ETV4 gene. These observations suggest a mechanism of EWSR1-ETV4 gene fusion.

Alu Elements↗
PubMed1998

Small round-cell type of malignant peripheral nerve sheath tumor.

Five cases of primitive, small, round-cell tumor that are a type of hitherto unclassified neurogenic sarcoma are described. The tumors were located deep within the soft tissue of the trunks and limbs without association with major nerves. The histologic features consisted mainly of uniform, small, round, tumor cells with scanty cytoplasm. Foci of uniform, short, spindle-shaped tumor cells arranged in whorl-like patterns were observed in some areas. Although the immunoreactivity for the neural markers, Leu-7 and MIC-2, was not marked, cell processes and fragmentous basal laminae, which are ultrastructural neural features, were found in both spindle-shaped and round tumor cells. In four cases, EWS chimeric transcripts were analyzed by reverse-transcription polymerase chain reaction. EWS chimeric mRNA (EWS-FLI-1, EWS-ERG, EWS-E1AF, EWS-ETV1, EWS-FEV) was not detected in any cases. The tumors were not consistent with peripheral primitive neuroectodermal tumor. We propose them as a small round-cell type of MPNST that might differentiate toward the immature neural cells.

Adolescent↗
PubMed1997

A neuroblastoma cell line derived from a case detected through a mass screening system in Japan: a case report including the biologic and phenotypic characteristics of the cell line.

BACKGROUND: A mass screening system in Japan, which involves measuring urinary catecholamine metabolites, has resulted in an increasing number of cases of neuroblastoma, most of which have favorable biologic properties and some of which are associated with tumor regression or involution. At the time this study was begun, the characteristics and biologic nature of the neuroblastomas had not been fully defined, because a cell line had not yet been established with tumor tissue taken from a neuroblastoma detected in the mass screening. METHODS: The authors established a cell line by tissue culture for over 50 generations from a neuroblastoma found during mass screening, which was characterized by favorable histology, with a triploid DNA stemline and without N-myc gene amplification. The morphologic and biologic characteristics of the new cell line were investigated in vitro. RESULTS: The cell line, designated MASS-NB-SCH-1, has neuronal properties, such as neurite-like processes and neurofilaments, as well as the expression of vimentin and fibronectin in studies of the cell morphology and immunohistochemistry. Karyotype analysis detected the presence of 42-46 chromosomes, with a deletion of the short arm of 1 of the 3 copies of chromosome 1. DNA ploidy was near-diploid in association with 20-fold amplification of N-myc genes. CONCLUSIONS: The cell line has a nature distinct from the original tumor tissue. It may be characterized by phenotypic change caused by clonal selection or evolution of aggressive, proliferative properties in vitro. This cell line will be a useful model to investigate the properties of the neuroblastoma in relation to the N-myc amplification mechanism.

Biology↗
PubMed1997

Neurogenic potential of Ewing's sarcoma cells.

We investigated the capacity of eight well-characterized Ewing's sarcoma cell lines to differentiate towards a neural phenotype. Ewing's sarcoma cells expressed the neuroectoderm-associated antigens such as nerve growth factor (NGF) receptor, N-CAM (6H7 and Leu-19) and Leu-7. Ewing's sarcoma cells also exhibited the potential for neural differentiation at the mRNA level; neuron-specific medium- and low-sized filament (NF-M and NF-L) expression was induced by dibutyryladenosine cyclic monophosphate. The pattern of expression of NF-L obtained by using alternative polyadenylation sites in Ewing's sarcoma cells differed from that in peripheral primitive neuroectodermal tumour (PNET) cells, and was similar to that in undifferentiated neural tissues. Furthermore, the NGF receptors detected by immunohistochemistry were found to be non-functional as assayed by c-fos induction with NGF treatment. The results indicate that Ewing's sarcoma cells maintain a primitive phenotype and have the potential to differentiate into a neural phenotype, indicating that Ewing's sarcoma is distinct from PNET.

Bone Neoplasms↗
PubMed1997

Effects of octreotide, a somatostatin analogue, on gastric function evaluated by real-time ultrasonography.

BACKGROUND: Somatostatin exerts inhibitory effects on physiological functions in the gastrointestinal tract. The actions differ, however, depending on the test meal, dose, and other factors. AIMS: To determine by use of ultrasonography and scintigraphy the effect of a somatostatin analog, octreotide, on gastric emptying and antral contraction. SUBJECTS: Twenty healthy men; mean age 23.9 years METHODS: Subjects were studied for 7 days, once after subcutaneous injection of octreotide, 50 microg, 5 min before the ingestion of a test meal and once after subcutaneous injection of placebo. Ten subjects received a liquid meal, 10 others received a solid meal. With the liquid meal, gastric emptying was measured 15 min after its ingestion and antral contraction was measured for 15 min by ultrasonography. With the solid meal, gastric emptying was measured both by ultrasonography (n = 10) and by simultaneous scintigraphy (n = 6), with antral contraction measured by ultrasonography for 5 h after ingestion of the meal. RESULTS AND CONCLUSIONS: Octreotide given with a liquid or solid meal inhibited gastric emptying in healthy subjects. A significant suppression of antral contraction occurred only with a solid meal.

Adult↗
PubMed1997

Malignant fibrous histiocytoma of the cecum: report of a case and review of the literature.

Malignant fibrous histiocytoma (MFH) of the gastrointestinal tract is extremely rare. Here we report a case of MFH of the cecum and review other cases of large bowel MFH in the literature. A 64-year-old man had a large tumor mass in the cecum associated with multiple small peritoneal implants. Histologically, most of the lesion showed inflammatory pseudotumor-like appearance; that is, a mixed proliferation of fibroblasts and myofibroblasts loosely arranged in sweeping fascicles or whorled structures and an admixture of chronic inflammatory cell infiltrate. The myofibroblastic nature of the spindle-shaped cells was confirmed by their immunohistochemical and ultrastructural findings. In addition, there was atypical histiocytic cells infiltrate in some areas and marked lymphatic involvement and lymph node metastasis by such histiocytic cells. These features were interpreted as MFH, although it had to be distinguished from inflammatory fibrosarcoma and leiomyosarcoma. The differential diagnosis is discussed here.

Actins↗
PubMed1997

Impaired male sex development in an infant with molecularly defined partial 9p monosomy: implication for a testis forming gene(s) on 9p.

This paper describes a genetically male infant with impaired male sex development and partial 9p monosomy. The external genitalia were ambiguous with microphallus (penile length at birth 10 mm, mean age matched normal length 29 mm (SD 5)), hypospadias, and hypoplastic scrotum. The tests were undescended and severely hypoplastic (testis size at 12 months of age, right 8 x 5 x 4 mm and left 4 x 3 x 2 mm; mean age matched normal size, length 18 mm (SD 2), width 11 mm (SD 1). Cytogenetic studies showed a 46,XY,del(9)(p23) karyotype in all the 30 peripheral lymphocytes and 20 skin fibroblasts examined. Microsatellite analysis for a total of 13 loci assigned to the 9p22-24 region showed that the deleted chromosome 9 was of paternal origin and was missing a region distal to D9S168. Southern blot analysis for D9S47 also confirmed the 9p deletion. The sequence of SRY was normal. The results provide further support for the previously proposed hypothesis that a gene(s) for testis formation is present on the distal part of 9p and indicate in molecular terms that the putative testis forming gene(s) resides in the region distal to D9S168.

Blotting, Southern↗
PubMed1997

Fatal diffuse alveolar damage from bird fanciers' lung.

A 68-year-old man, who had continuing exposure to budgerigars, developed fatal acute respiratory failure following years of slowly progressive pulmonary deterioration. His lung function was characterized first by mild airflow obstruction and later by progressive loss of lung volume. Computed tomography showed progressive development of pulmonary fibrosis and honeycombing. His serum disclosed precipitins to pigeon antigen. During his final illness his chest radiograph showed widespread patchy consolidation. At autopsy, his lungs revealed left lower lobe bronchopneumonia, fibrosis and honeycombing at the bases and widespread evidence of diffuse alveolar damage with organized exudate in some alveoli. To our knowledge, this is the second reported fatality due to acute alveolar injury in bird fanciers' lung.

Acute Disease↗
PubMed1997

Establishment of three monoclonal antibodies specific for prespermatogonia and intratubular malignant germ cells in humans.

Intratubular malignant germ cells (ITMGC), as assessed by clinicopathologic or cytogenetic studies, are regarded as a preinvasive lesion of all human testicular germ cell tumors with the exception of yolk sac tumors (in infants) and spermatocytic seminomas. To characterize specific surface molecules of ITMGC, we raised three mouse monoclonal antibodies (mAb) against NCR-G3 (G3), a multipotent, human embryonal carcinoma (EC) cell line, and screened cryostat sections of human testicular tissue containing ITMGC. These three mAb (HB5, IgG1; HF2, IgG1; HE11, IgG1) reacted to the surface of ITMGC, seminomas, and EC in vivo as well as to human EC cell lines in vitro. Expression of HB5 and HF2 antigens was down-regulated during cellular differentiation of G3 cells by retinoic acid or N,N'-hexamethylene-bis-acetamide treatment, whereas that of HE11 antigen was up-regulated with cellular differentiation by retinoic acid. Furthermore, these three mAb reacted to stage-specific prespermatogonia in the human fetus but not in human adults. HB5, HF2, and HE11 antigens were shown to be glycoproteins with molecular weights of approximately 80, 80, and 70 kd, respectively, and could be immunoprecipitated after deglycosylation treatment. Peptide mapping with Staphylococcus aureus V8 protease suggested that the HB5 and HF2 antigens were identical. We concluded that HB5/HF2 and HE11 antigens are oncodevelopmental antigens in testicular germ cell tumors and human spermatogenesis that may play a significant role in tumorigenesis and the development of human germ cells.

Adult↗
PubMed1996

A method for direct DNA amplification of uncharacterized DNA viruses and for development of a viral polymerase chain reaction assay: application to the red sea bream iridovirus.

A method is described for isolating a DNA segment of a virus for which no protein or DNA sequence information is available. This segment can then be used to develop a PCR-based assay for the virus. The method is based on the widespread presence and strong conservation of the ribonucleotide reductase gene among DNA viruses. The validity of the procedure is demonstrated by development of an assay for the fish iridovirus. We report the direct isolation from infected fish of a 738-bp segment of the iridovirus ribonucleotide reductase small subunit gene without prior virus purification. Using the sequence information obtained, a PCR-based diagnostic system was developed for detecting iridovirus infection.

Amino Acid Sequence↗
PubMed1996

Somatic mutations of the APC gene in sporadic hepatoblastomas.

Hepatoblastoma is a rare hepatic malignancy that occurs in children with an average age of 2 or 3 years and is known to be one of the extracolonic manifestations of familial adenomatous polyposis. Only a single hepatoblastoma with a germ-line mutation of the adenomatous polyposis coli (APC) gene has been reported thus far. To elucidate the possible roles of APC gene alterations in sporadic hepatoblastomas, we examined loss of heterozygosity (LOH) at the APC and MCC loci and performed a sequencing analysis of a part of the APC gene, including the mutation cluster region, in 13 hepatoblastomas of non-familial adenomatous polyposis patients. LOH at the APC and/or MCC loci was observed in four of seven (57%) informative cases. Of the 13 cases, somatic mutations were detected in 8 (61.5%), with 9 (69%) cases showing genetic alterations in the APC gene as LOH or somatic mutations. Two cases demonstrated double mutations. Furthermore, the nature of the somatic mutations observed in the present study was unusual because 9 of the 10 mutations were missense, with only 1 case featuring a frame-shift mutation due to an insertion. Previous reports have described almost all (>90%) mutations of the APC gene in colorectal tumors to result in a truncated APC protein due to either frame-shift or nonsense mutations. These findings suggest that a mutation of the APC gene may play an important role in the genesis of sporadic hepatoblastomas, and the mechanisms of APC gene alteration may be different from those reported previously for colorectal tumors.

Base Sequence↗