Search PubMed⌕ Search

Biomedical subjects

J Hata

Publications and source records attributed to J Hata.

At least 19 recordsLinked to original sources
PubMed2000

Imprinting of human GRB10 and its mutations in two patients with Russell-Silver syndrome.

Documentation of maternal uniparental disomy of chromosome 7 in 10% of patients with Russell-Silver syndrome (RSS), characterized by prenatal and postnatal growth retardation and dysmorphic features, has suggested the presence of an imprinted gene on chromosome 7 whose mutation is responsible for the RSS phenotype. Human GRB10 on chromosome 7, a homologue of the mouse imprinted gene Grb10, is a candidate, because GRB10 has a suppressive effect on growth, through its interaction with either the IGF-I receptor or the GH receptor, and two patients with RSS were shown to have a maternally derived duplication of 7p11-p13, encompassing GRB10. In the present study, we first demonstrated that the GRB10 gene is also monoallelically expressed in human fetal brain tissues and is transcribed from the maternally derived allele in somatic-cell hybrids. Hence, human GRB10 is imprinted. A mutation analysis of GRB10 in 58 unrelated patients with RSS identified, within the N-terminal domain of the protein, a P95S substitution in two patients with RSS. In these two cases, the mutant allele was inherited from the mother. The fact that monoallelic GRB10 expression was observed from the maternal allele in this study suggests but does not prove that these maternally transmitted mutant alleles contribute to the RSS phenotype.

Abnormalities, Multiple↗
PubMed2000

Diabetes and pancreatic tumours in transgenic mice expressing Pa x 6.

AIMS/HYPOTHESIS: Both endocrine and exocrine cells of the pancreas differentiate from epithelial cells of primitive pancreatic ducts, and four types of pancreatic islet cells (alpha, beta, delta, and PP cells) are derived from the common pluripotent precursor cells. Although Pa x 6 is expressed in all islet cells, Pa x 4 is detected only in beta cells. In homozygous Pa x 4-null mice, beta cells are absent, whereas the number of alpha cells is increased. Therefore, we hypothesized that the balance of Pa x 4 and 6 is one of the determinants by which the common progenitor cells differentiate into alpha or beta cells. METHODS: To change this balance, we generated transgenic mice overexpressing Pa x 6 driven by the insulin promoter or the PDX1 promoter. RESULTS: In both types of transgenic mice, normal development of beta cells was disturbed, resulting in apoptosis of beta cells and diabetes. In Insulin/Pa x 6-Tg mice, beta cells were specifically affected, whereas in PDX/Pa x 6-Tg mice, developmental abnormalities involved the whole pancreas including hypoplasia of the exocrine pancreas. Furthermore, PDX/Pa x 6-Tg mice experienced proliferation of both ductal epithelia and islet cells and subsequent cystic adenoma of the pancreas. CONCLUSION/INTERPRETATION: These findings suggest that Pa x 6 promotes the growth of ductal epithelia and endocrine progenitor cells and that the suppression of Pa x 6 is necessary for the normal development of beta cells and the exocrine pancreas.

Animals↗
PubMed2000

Acute myeloid leukemia possessing jumping translocation is related to highly elevated levels of EAT/mcl-1, a Bcl-2 related gene with anti-apoptotic functions.

Jumping translocations (JTs) are unbalanced chromosomal translocations in which an identical chromosomal region is translocated to the telomeric region of different chromosomes. JTs are rare in hematological malignancies where they are second translocations and may be an indicator of poor prognosis. We report a case of acute myeloid leukemia with t(16;21) and a JT in which the long arm of chromosome 1 distal to q21 is translocated to the terminal region of chromosome 10. The leukemic cells exhibit high expression of EAT/mcl1, an anti-apoptotic Bcl-2 related gene. Since EAT/mcl1 is mapped to 1q21 near the breakpoint in the JTs, high level expression of EAT/mcl1 may be associated with the poor prognosis of leukemia with JTs.

Adolescent↗
PubMed2000

Augmentation of human leukemic cell invasion by activation of a small GTP-binding protein Rho.

OBJECTIVE: The functions of a small GTP-binding protein, Rho, in human leukemic cell invasion was investigated in vivo and in vitro. MATERIALS AND METHODS: Human leukemic KM3 and Reh cells (derived from B-cell-type common acute lymphoid leukemias) were inoculated into severe combined immundeficiency (SCID) mice. Alteration of invasion in SCID mice inoculated with KM3 cells that were introduced with the expression vector for Rho Val14 (Rho V14), an activated mutant form of Rho, was observed. RESULTS: SCID mice inoculated with KM3 and Reh cells developed paraplegia 21 days after inoculation. All died by day 26-27. The leukemic cells were localized to bone marrow and around the spinal cord, with no infiltration into peripheral blood, spleen, liver, thymus, or lymph nodes. SCID mice inoculated with Rho V14-transfected KM3 cells showed a 5-day reduction in the time to paraplegia and death compared with SCID mice inoculated with hygromycin-resistance gene-transfected KM3 (hyg(r)) cells. In addition, the mice inoculated with Rho V14 cells showed leukemic cell infiltration, not only into bone marrow and around the spinal cord but also into peripheral blood, liver, and spleen. There were no in vitro or in vivo differences in growth rates of Rho V14 and hyg(r) cells. However, the Rho V14 cells showed markedly increased cell adhesion compared to the hyg(r) cells. CONCLUSION: Results suggest that Rho activation accelerates human leukemic cell invasion via augmentation of cell adhesion.

Animals↗
PubMed2000

Metastatic carcinoma in follicular adenoma of the thyroid gland.

We report here two autopsy cases of carcinoma that metastasized to a thyroid follicular adenoma. The first was an 82-year-old man with sigmoid colon adenocarcinoma. Three years after a colectomy he died of multiple metastases. Autopsy revealed that the metastatic colonic carcinoma was located in a thyroid follicular adenoma. The second case was a 51-year-old man with primary lung adenocarcinoma. At the time of admission, he was inoperable because of multiple organ metastasis. He died 14 months after admission due to the carcinoma. Autopsy revealed a metastatic lung adenocarcinoma also located in a follicular adenoma, as in the first case. The phenomenon of tumor-to-tumor metastasis is rare. The mechanism is still unknown, and to our knowledge, only five cases of carcinoma metastatic to thyroid follicular adenoma have been documented in the literature.

Adenocarcinoma↗
PubMed2000

Arsenic trioxide (As2O3)-induced apoptosis and differentiation in retinoic acid-resistant acute promyelocytic leukemia model in hGM-CSF-producing transgenic SCID mice.

Recent clinical studies in China and USA showed that arsenic trioxide (As2O3) is an effective treatment of acute promyelocytic leukemia (APL) patients refractory to all-trans retinoic acid (RA). We here investigate the effects of As2O3 on RA-resistant APL in vivo and in vitro using our RA-resistant APL model system. As2O3 can induce inhibition of cellular growth of both RA-sensitive NB4 and RA-resistant UF-1 APL cells via induction of apoptosis in vitro. The expression of BCL-2 protein decreased in a dose- and time-dependent manner in NB4 cells. Interestingly, the levels of BCL-2 protein were not modulated by As2O3, but it did upregulate BAX protein in UF-1 cells. UF-1 cells (1x10(7)) were transplanted into hGM-CSF-producing transgenic SCID mice and successfully formed subcutaneous tumors. After 40 days of implantation, mice were treated with As2O3, all-trans RA and PBS for 21 days. In all-trans RA- and PBS-treated mice, tumors grew rapidly, with a 4.5-fold increase in volume at day 21 compared to the initial size. In marked contrast, tumor size was decreased to half of the initial size by the treatment of As2O3, which resulted in cells with the typical appearance of apoptosis. Interestingly, one of the As2O3-treated mice showed mature granulocytes in the diminished tumor, suggesting that As2O3 had dual effects on RA-resistant APL cells in vivo: both inducing apoptosis and differentiation of the leukemic cells. We conclude that our RA-resistant APL model will be useful for evaluating novel therapeutic approaches to patients with RA-resistant APL, and for further investigation of the metabolism of As2O3 in vivo.

Animals↗
PubMed2000

Evaluation of lower oesophageal sphincter pressure using endoscopic manometric sleeve assembly.

BACKGROUND: The purpose of this study was to establish a method to determine lower oesophageal sphincter (LOS) pressure using an endoscopic manometric sleeve assembly. METHODS: We used a 250-cm, three-lumen, 2.2-mm external diameter silicon catheter with a 3-cm sleeve sensor that was passed easily through the biopsy channel (2.8 mm diameter) of the gastroscope. Each lumen was perfused with distilled water using a low-compliance, pneumohydraulic capillary infusion system. Forty-seven healthy subjects and 35 patients with oesophageal disorders underwent study during routine diagnostic endoscopy. In 27 of the subjects, standard transnasal manometry with a three-lumen, 4.5-mm diameter polyvinyl catheter with a 5-cm sleeve sensor was also performed. RESULTS: Lower oesophageal sphincter pressure (LOS) was evaluated in all subjects (median pressure 16 mmHg, range 0-55 mmHg) for 6 min during routine endoscopic examination. The LOS pressure readings between standard and endoscopic manometry correlated well. The LOS pressure was significantly lower in healthy subjects with hiatal hernia than in those without hernia and was also significantly lower in patients with reflux oesophagitis than in healthy subjects. CONCLUSIONS: Endoscopic manometric sleeve assembly was used during routine endoscopic examination and was useful for easily determining LOS pressure. It could be used for evaluation of oesophageal motility disorders, thus avoiding the use of a more invasive and time-consuming method.

Case-Control Studies↗
PubMed2000

Variations on the "baby-sitter" procedure for reconstruction of facial paralysis.

Four cases of fresh facial paralysis were treated using the "baby-sitter" procedure, with fairly satisfactory results obtained. This procedure involves a combination of cross-face nerve grafting and a nerve cross-over technique such as using a hypoglossal-facial nerve or accessory-facial nerve anastomosis. Two stages are required. Nerve cross-over and cross-face nerve grafting using the sural nerve are performed in the first stage. After 1 year nerve anastomosis between the stump of the cross-face nerve graft and that of a buccal branch in the paralyzed cheek is performed during the second stage. The recovery of facial animation through this method is good, with patients able to create a near-natural smile. Electromyography demonstrates double innervation in the paralyzed cheek area.

Accessory Nerve↗
PubMed2000

Function of 90-kDa heat shock protein in cellular differentiation of human embryonal carcinoma cells.

Heat shock proteins (HSPs) have been recognized as molecules that maintain cellular homeostasis during changes in the environment. Here we report that HSP90 functions not only in stress responses but also in certain aspects of cellular differentiation. We found that HSP90 showed remarkably high expression in undifferentiated human embryonal carcinoma (EC) cells, which were subsequently dramatically down-regulated during in vitro cellular differentiation, following retinoic acid (RA) treatment, at the protein level. Surprisingly, heat shock treatment also triggered the down-regulation of HSP90 within 48 h at the protein level. Furthermore, the heat treatment induced cellular differentiation into neural cells. This down-regulation of HSP90 by heat treatment was shifted to an up-regulation pattern after cellular differentiation in response to RA treatment. In order to clarify the functions of HSP90 in cellular differentiation, we conducted various experiments, including overexpression of HSP90 via gene transfer. We showed that the RA-induced differentiation of EC cells into a neural cell lineage was inhibited by overexpression of the HSP90alpha or -beta isoform via the gene transfer method. On the other hand, the overexpression of HSP90beta alone impaired cellular differentiation into trophoectoderm. These results show that down-regulation of HSP90 is a physiologically critical event in the differentiation of human EC cells and that specific HSP90 isoforms may be involved in differentiation into specific cell lineages.

Acetamides↗
PubMed2000

[A case of metanephric adenoma treated with partial nephrectomy].

A 32-year-old female presented with a right renal mass detected by abdominal ultrasound examination at a routine medical check up. Computed tomography scans and magnetic resonance images revealed a solid tumor in the upper pole of the right kidney measuring 1.5 cm in diameter. Partial nephrectomy was performed on suspicion of the renal cell carcinoma. Histologically, the tumor is composed of small, uniform, epithelial cells with scant cytoplasm and hyperchromatic round nuclei that formed a tubular or glomerular-like structure. The histological diagnosis was metanephric adenoma.

Adenoma↗
PubMed2000

Ultrasonography improves diagnostic accuracy of acute appendicitis and provides cost savings to hospitals in Japan.

A cost analysis based on changes in patient care was used to evaluate the utility of abdominal ultrasonography in both the clinical management of patients clinically suspected of having acute appendicitis and in reducing expenditure of hospital resources. Among the 200 patients suspected of having acute appendicitis, 57 actually had acute appendicitis. Interpretation of appendiceal ultrasonographic results was 98.5% accurate. The ultrasonographic result led to changes in the treatment of 103 patients. Moreover, ultrasonography led to the prevention of unnecessary appendectomy in 25 patients, providing a savings to the hospital of about Yen 8,013,450 ($65,150), and prevented unnecessary hospital admission for 78 patient-days, thus saving the hospital approximately Yen 1,199,250 ($9750). The cost of performing the 200 ultrasonographic examinations was about Yen 1,096,176 ($8912), and thus the overall savings to the hospital was approximately Yen 40,590 ($330) per patient. Ultrasonography performed in patients with suspected acute appendicitis improves patient diagnostic accuracy, thus leading to more appropriate selection of patient treatment and reduced hospital expenditure.

Acute Disease↗
PubMed2000

A case of aortoduodenal fistula occurring after surgery and radiation for pancreatic cancer.

The patient was a 58-year-old woman given curative treatment (pancreatectomy (body and tail) + intraoperative irradiation (25 Gy)) on the basis of a diagnosis of pancreatic carcinoma. Having a favorable postoperative course, she was discharged 24 days after surgery. A week after discharge, she was readmitted for a hemorrhagic gastric ulcer. She was later discharged again on conservative treatment, and followed up at the outpatient clinic, but nine months postoperatively, was readmitted complaining of loss of appetite and abdominal pain. Subsequent tests revealed stricture of the horizontal portion of the duodenum with distension oral to the stricture. Around the celiac artery, the paraaortic lymph nodes were swollen, and a diagnosis of stricture due to recurrent pancreatic carcinoma was made. On the day before bypass surgery was scheduled, the patient vomited blood, so the operation was postponed, conservative treatment such as blood transfusion was administered, and emergency angiography was performed simultaneously. The findings were an aortic pseudoaneurym 1 cm in diameter immediately below the origin of the superior mesenteric artery and between the left and right renal arteries, and a hemorrhage, caused by an aortoduodenal fistula, issuing from the horizontal portion of the duodenum. Hemostasis via a laparotomy was judged difficult, and so an indwelling stent-graft in the aorta was tried to stanch the blood, but without success. Another stent then had to be inserted within the first, thus stopping the flow, but the blood supply to the celiac artery, the superior mesenteric arteries and the renal arteries was impaired, and the patient died about six hours later. Postmortem examination revealed aortoduodenal fistula without recurrence of the carcinoma. The duodenal wall around the fistulous tract showed delayed radiation changes with deep ulceration. The intraoperative radiation may have played an important part in the formation of the fistula.

Aortic Diseases↗
PubMed2000

[Choriocarcinoma of the renal pelvis: a case report].

A 68-year-old male presented to our hospital complaining of gross hematuria. Intravenous pyelography subsequently demonstrated a left non-visualized kidney, and he was admitted for further evaluation. Cystoscopy revealed a bladder tumor around the left ureteral orifice and retrograde pyelography showed a filling defect in the left renal pelvis. The urinary cytology from the left renal pelvis indicated class IV, and the microscopic findings of a bladder biopsy demonstrated grade 1 transitional cell carcinoma. We performed transurethral resection of bladder tumor (TUR-BT) followed by left nephroureterectomy with bladder cuff. The pathological diagnosis was high grade transitional cell carcinoma with choriocarcinomatous component. After the operation, the serum human chorionic gonadotropin-beta (hCG-beta) level was slightly elevated, and the combination chemotherapy with methotrexate, vinblastine and cisplatin (MVC) was administered. Although the serum hCG-beta level fell to 0.1 ng/ml, after two courses of MVC chemotherapy, bilateral pulmonary metastases appeared in the chest X-ray with increasing hCG-beta levels. Salvage chemotherapy with cisplatin, etoposide and bleomycin (PEB) was performed. After two courses of PEB chemotherapy, the serum hCG-beta level fell to within the normal range and all pulmonary metastases disappeared.

Aged↗
PubMed1999

The EAT/mcl-1 gene, an inhibitor of apoptosis, is up-regulated in the early stage of acute myocardial infarction.

EAT/mcl-1 (EAT), a bcl-2-related immediate early gene, is up-regulated at an early stage of differentiation of human embryonal carcinoma cells. Recent studies have revealed that EAT inhibits apoptosis both in vitro and in vivo. In the present study, we demonstrated that the EAT gene was up-regulated in the early stage of rat myocardial infarction. This pattern of up-regulation was apparently different from that of another immediate early gene, c-fos. EAT, an anti-apoptotic molecule, was strongly up-regulated in the non-ischemic region. In contrast, the expression of c-fos was induced in both ischemic and non-ischemic regions, and was higher in the ischemic region. Apoptosis of cardiomyocytes is currently thought to significantly contribute to acute myocardial infarction. We detected cardiomyocyte apoptosis by gel electrophoresis of genomic DNA and in situ nick end labeling in the ischemic region, but not in the non-ischemic region. As an inhibitor of apoptosis, EAT may play a role in the protection of cardiomyocytes in the early stage of acute myocardial infarction.

Animals↗
PubMed1999

High frequency of inactivation of the imprinted H19 gene in "sporadic" hepatoblastoma.

Embryonal tumors such as Wilms' tumor (WT), embryonal rhabdomyosarcoma (eRMS) and hepatoblastoma have been thought to have a common pathogenetic mechanism. H19 was found to be inactivated in WT and eRMS either by loss of heterozygosity or by hypermethylation of the maternal allele. We show here that the expression of the H19 gene is inactivated by maternal allelic loss or hypermethylation in 7 out of 8 "sporadic" hepatoblastomas. Furthermore, we analyzed expression of the IGF2 gene. Loss of imprinting of the IGF2 gene was detected and linked to inactivation of the H19 gene in 2 hepatoblastomas. However, 2 sporadic cases demonstrated monoallelic expression of the IGF2 gene with inactivation of the H19 gene. Our results suggest that H19 may play a role as a common imprinted tumor suppressor gene in "sporadic" hepatoblastomas but may at times work independently of IGF2 expression.

Child↗
PubMed1999

Terminology and morphologic criteria of neuroblastic tumors: recommendations by the International Neuroblastoma Pathology Committee.

BACKGROUND: As part of the international cooperative effort to develop a complete set of International Neuroblastoma Risk Groups, the International Neuroblastoma Pathology Committee (INPC) initiated activities in 1994 to devise a morphologic classification of neuroblastic tumors (NTs; neuroblastoma, ganglioneuroblastoma, and ganglioneuroma). METHODS: Six member pathologists (H.S., I.M.A., L.P.D., J.H., V.V.J., and B.R.) discussed and defined morphologically based classifications (Shimada classification; risk group and modified risk group proposed by Joshi et al.) on the basis of a review of 227 cases, using various pathologic characteristics of the NTs. The classification-grading system was evaluated for prognostic significance and biologic relevance. RESULTS: The INPC has adopted a prognostic system modeled on one proposed by Shimada et al. It is an age-linked classification dependent on the differentiation grade of the neuroblasts, their cellular turnover index, and the presence or absence of Schwannian stromal development. Based on morphologic criteria defined in this article, NTs were classified into four categories and their subtypes: 1) neuroblastoma (Schwannian stroma-poor), undifferentiated, poorly differentiated, and differentiating; 2) ganglioneuroblastoma, intermixed (Schwannian stroma-rich); 3) ganglioneuroma (Schwannian stroma-dominant), maturing and mature; and 4) ganglioneuroblastoma, nodular (composite Schwannian stroma-richlstroma-dominant and stroma-poor). Specific features, such as the mitosis-karyorrhexis index, the mitotic rate, and calcification, were also included to allow the prognostic significance of the classification to be tested. Recommendations are made regarding the surgical materials to use for an optimal pathobiologic assessment and the practical handling of samples. CONCLUSIONS: The current article covers the essentials and important points regarding the histopathologic evaluation of NTs. Using the morphologic criteria described herein, the INPC is proposing the International Neuroblastoma Pathology Classification. It is reported in a companion article in this issue (Cancer 1999;86:363-71).

Biometry↗
PubMed1999

The International Neuroblastoma Pathology Classification (the Shimada system).

BACKGROUND: The International Neuroblastoma Pathology Committee, which is comprised of six member pathologists, was convened with the objective of proposing a prognostically significant and biologically relevant classification based on morphologic features of neuroblastic tumors (NTs) (i.e., neuroblastoma, ganglioneuroblastoma, and ganglioneuroma). METHODS: A total of 227 cases were reviewed. Consensus diagnoses from morphologic features (criteria described separately) based on five of six or six of six agreements by the reviewer pathologists were used for prognostic analysis. Prognostic effects of morphology, both individual and in combination, taken in conjunction with age (Shimada classification, histologic grade, and risk group), were analyzed. RESULTS: Approximately 99% of cases (224 of 227) had consensus diagnoses for categorization: neuroblastoma (Schwannian stroma-poor), 190 cases; ganglioneuroblastoma, intermixed (Schwannian stroma-rich), 5 cases; ganglioneuroma (Schwannian stroma-dominant) maturing, 1 case; ganglioneuroblastoma, nodular (composite Schwannian stroma-rich/stroma-dominant and stroma-poor), 19 cases; and NT-unclassifiable, 9 cases. For the NTs, subtype (93% consensus: undifferentiated, 6 cases; poorly differentiated, 155 cases; and differentiated, 15 cases), mitosis-karyorrhexis index (90% consensus: low, 94 cases; intermediate, 40 cases; and high, 37 cases), mitotic rate (75% consensus: low, 89 cases; high, 50 cases; and not determined, 4 cases), and calcification (100% consensus: yes, 110 cases and no, 80 cases) were recorded. Statistical analysis demonstrated that the Shimada classification system (90% consensus; 3-year event free survival: 85% for the group with favorable histology and 41% for the group with unfavorable histology; P = 0.31 x 10(-9)) had a significantly stronger prognostic effect than individual features and other combinations. CONCLUSIONS: The International Neuroblastoma Pathology Classification, a system based on a framework of the Shimada classification with minor modifications, is proposed for international use in assessing NTs.

Brain Neoplasms↗