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Biomedical subjects

E Hiyama

Publications and source records attributed to E Hiyama.

At least 73 records · Page 4Linked to original sources

Correlating telomerase activity levels with human neuroblastoma outcomes.

Telomerase activity was analysed in 100 neuroblastoma cases. Although telomerase activity was not detected in normal adrenal tissues or benign ganglioneuromas, almost all neuroblastomas (94%) did express it, suggesting an important role for telomerase in neuroblastoma development. Neuroblastomas with high telomerase activity had other genetic changes (for example, N-myc amplification) and an unfavourable prognosis, whereas tumours with low telomerase activity were devoid of such genetic alterations and were associated with a favourable prognosis. Three neuroblastomas lacking telomerase activity regressed (stage IVS). Thus telomerase expression may be required as a critical step in the multigenetic process of tumorigenesis, and two different pathways may exist for the development of neuroblastoma.

Adrenal Gland Neoplasms↗

Mac-1 expression and superoxide generation of the peripheral polymorphonuclear leukocyte following gastrectomy and esophagectomy.

The aim of this study was to evaluate the characteristics of the polymorphonuclear leukocyte (PMN) function after surgical stress. We investigated Mac-1 expression and superoxide generation by peripheral PMNs and serum granulocyte-colony stimulating factor (G-CSF) concentrations in 15 patients who underwent either gastrectomy (n = 8) or esophagectomy (n = 7). The serum G-CSF rapidly increased within 24 hours after operation. The maximum levels of serum G-CSF in the cases of esophagectomy were about 5-8 fold those of gastrectomy, although the increases in PMN counts within 24 hours of esophagectomy were lower than those after gastrectomy. Mac-1 expression and superoxide generation by PMN counts and serum G-CSF. After esophagectomy, Mac-1 expression on peripheral PMNs remained elevated through the 7th day after operation, while superoxide generation by PMNs in response to PMA declined to below preoperative levels after the 3rd day. These results suggest that, after major surgery such as esophagectomy, there is a discrepancy between Mac-1 expression and superoxide generation by the peripheral PMN despite a high level of serum G-CSF.

Aged↗

Poor outcome in patients with advanced stage neuroblastoma and coincident opsomyoclonus syndrome.

BACKGROUND: Most patients with neuroblastoma who present with opsomyoclonus have a good prognosis. Neuroblastomas from such patients have been reported to contain a single copy of the N-myc gene. The authors describe three cases of patients with advanced neuroblastoma with opsomyoclonus, which had poor outcomes despite multimodal therapy. METHODS: Amplification and expression of the N-myc gene were examined in these three primary tumors using Southern and Northern blot analyses. Then, flow cytometric analysis of the cellular DNA contents of these tumors was performed. RESULTS: N-myc amplification was observed in two tumors and N-myc RNA overexpression was observed in all three. Analysis of the cellular DNA contents of the tissue specimens revealed hyperdiploidy in all three tumors; one had a triploid index and the other two had hypotetraploid indexes. CONCLUSIONS: These findings suggest that a poor outcome for patients with opsomyoclonus may be associated with N-myc gene activation (amplification and/or overexpression) and that a hyperdiploid tumor is not always associated with a good prognosis.

Adrenal Gland Neoplasms↗

Alteration in length of telomeric repeats in lung cancer.

We investigated the relationship between telomere length and various characteristics of tumor cells in 46 lung cancer specimens (40 primary lesions and six metastatic lesions). Three variant patterns of telomere length were observed in 16 cases (34.8%): reduction in 13 cases, elongation in two cases, and convergence in one case. These variant patterns were frequently observed in small cell carcinomas, in metastatic lesions, and in cases which possessed the S-type allele of the L-myc gene. All three cases with telomere elongation or convergence were associated with a poor prognosis. This is compatible with the previous report suggesting that telomerase activity may be an indicator of immortality in vitro. In adenocarcinoma, telomere reduction or elongation was also observed in the early stages with a low percentage of cells in the S-phase, while in cases with other histologic types, these changes were observed only in late stage, in metastatic lesions, or in cancerous tissues with a high percentage of cells in the S-phase. Although the reduction of telomere length in these tissues may be a result of many cell divisions, it may represent another stage of carcinogenesis in early-stage adenocarcinoma.

Aged↗

Surgical management of tracheal agenesis.

Tracheal agenesis is a rare congenital malformation that usually is fatal. This report describes our experience in two such cases. In both cases, the diagnosis was suspected at birth, because the patients had respiratory distress without an audible cry and were difficult to intubate. A gastrostomy and banding of the abdominal esophagus provided effective initial stabilization, in conjugation with respiratory management. The first patient also had complex cardiac malformations, and the infant died of cardiac failure 1 week after birth. The second infant, who had tracheal agenesis with a proximal tracheoesophageal fistula and a bronchoesophageal fistula, was managed successfully. At 9 months of age, a tracheotomy was performed, a long T tube was inserted to maintain the airway patency beyond the proximal tracheoesophageal fistula, and the patient was discharged. At 3 years of age, esophageal reconstruction was performed with a colonic interposition graft. The patient is thriving and developing normally at 4 years of age. Diagnosis at birth and maintenance of airway patency are essential for successful management of tracheal agenesis. Initial surgical interventions are palliative but lifesaving. Subsequent management focuses on improving the quality of life and allowing swallowing and speech.

Fatal Outcome↗

Prognostic prediction in neuroblastomas: clinical significance of combined analysis for Ha-ras p21 expression and N-myc gene amplification.

Ha-ras p21 expression and N-myc gene amplification were examined in 69 neuroblastomas and their clinical significance was analyzed retrospectively. Thirty-nine (89%) of forty-four patients who survived for more than 2 years after diagnosis showed high Ha-ras p21 expression, whereas 19 (76%) of 25 patients who died of progressive disease showed low Ha-ras p21 expression in their tumors. Although all 14 patients whose tumors exhibited N-myc gene amplification died of the disease, 11 other patients (56%) who died did not exhibit N-myc gene amplification. When we considered both low Ha-ras p21 expression and N-myc gene amplification as risk factors, 23 (92%) of the 25 patients who died had at least one of the two and thus could have been predicted to be high-risk patients at diagnosis. The combined analysis of the two factors should provide more accurate information pertinent to patient care.

Child, Preschool↗

Length of telomeric repeats in neuroblastoma: correlation with prognosis and other biological characteristics.

Telomeres are the physical ends of eukaryotic chromosomes. In view of reports of the reduction of telomeric repeats in human malignant tumors, we measured the lengths of telomeric repeats in 55 primary neuroblastomas. The average lengths of telomeric repeats in these tumors fell in a wide range (from 1.1 kb to more than 23 kb) relative to those in ganglioneuromas and normal peripheral mononuclear cells. The reduction of telomeric repeats was significantly correlated with advanced stages of tumor development, poor prognosis, and increased S-phase fractions in tumor cells. On the other hand, three cases of Stage IV-S tumors showed the reduction of telomeric repeats and low percentage of S-phase fractions. These Stage IV-S patients had a good prognosis with spontaneous regression of metastatic tumors.

Adolescent↗

Neuroblastoma with DNA amplification and rearrangement in the N-myc gene region.

We detected a rearrangement in the N-myc gene region in a neuroblastoma from a 9-month-old girl. In this case, the N-myc gene was amplified 50-fold in the primary tumor, the lymph node metastasis, and the hepatic metastasis. The rearrangement was detected only in the primary tumor and the lymph node metastasis, whereas N-myc RNA and protein expression were detected only in the primary tumor and the hepatic metastasis. Both the rearranged N-myc gene and the normal N-myc gene were amplified 25-fold, and the rearrangement occurred 723 nucleotides downstream from the 3' end of exon 3. The cell line (NH-6) derived from the primary tumor showed N-myc gene amplification without this rearrangement. These results suggest the following: (a) the primary tumor had a least two clones; (b) the rearrangement interrupted N-myc gene expression; and (c) oncogenesis preceded N-myc gene amplification.

Adrenal Gland Neoplasms↗

Immunohistochemical analysis of N-myc protein expression in neuroblastoma: correlation with prognosis of patients.

We have analyzed N-myc gene amplification and N-myc protein expression in 41 primary neuroblastomas. In this series, 22 patients are currently alive and disease-free, whereas 19 patients have died or are alive with progressive disease. All tumor samples were obtained at operation. N-myc gene amplification was detected by Southern blot analysis, and N-myc protein expression was detected using Bouin-fixed, paraffin-embedded tissue sections and immunohistochemical staining with anti-N-myc gene products serum. N-myc protein expression was detected in all 9 tumors with N-myc gene amplification (greater than or equal to 10 N-myc gene copies). Among 19 patients with poor prognosis, N-myc gene amplification was detected in 8 (42%) and N-myc protein expression in 18 (95%); neither was detected in 20 of the 22 patients who survived free of disease. We conclude that the immunohistochemical detection of N-myc protein expression is one of the most unfavorable prognostic factors in neuroblastoma patients.

Adrenal Gland Neoplasms↗

N-myc gene amplification and other prognosis-associated factors in neuroblastoma.

The correlation between N-myc gene amplification and heretofore known prognosis-associated factors was studied in 23 cases of neuroblastoma, comprising a total of 29 tumors (23 primary and six metastatic), examined in and after 1983. DNAs were extracted from tumor tissues preserved at -70 degrees C and digested with the restriction enzyme EcoRI. Southern blotting analysis was performed on these DNAs with the N-myc probe labelled with alpha-32P-dCTP. Prognosis-associated factors studied were age at diagnosis, stage, primary site, histological type, blood biochemistry tests, and catecholamine metabolites in urine. Amplification of N-myc gene was observed only in the cases in which primary site was the adrenal gland, but the relation to the stage, histological type, and prognosis was not as apparent as reported by other investigators. However, the amounts of catecholamine metabolites were low in the cases with amplification, and this suggests immaturity of catecholamine metabolism in the tumor with N-myc gene amplification.

Blotting, Southern↗

[Pulmonary vascular changes after portasystemic shunt operation in rats].

The prevalence of pulmonary hypertension among patients with portal hypertension, especially following a shunt operation, is significantly higher than that of primary pulmonary hypertension, suggesting the hypothesis that large portasystemic shunt plays a major role in development of pulmonary hypertension. To support this hypothesis, I studied experimentally the hemodynamic changes and the pathological findings in lung in 97 rats killed between one and 24 months after portasystemic shunt operations. The right ventricular systolic pressure (RVSP) and the right ventricular wall thickness were significantly high in the 82 rats raised over 3 months after the operations. In these rats the pathological findings in the lung revealed a thickness of pulmonary arterioles with medial hypertrophy, concentric intimal proliferation, and plexiform lesions. The values of endotoxin in central venous blood were significantly high and related with RVSP and shunt ratio. In pulmonary venous blood, thromboxane B2 increased and 6-keto PGF1a decreased. In conclusion, some of the rats developed pulmonary hypertension fter receiving a portasystemic shunt operation. It is suspected that endotoxin passing through the shunt plays a role in the development of pulmonary hypertension.

6-Ketoprostaglandin F1 alpha↗

[Studies on antibacterial activity of flomoxef and its distribution to serum and intraperitoneal exudate in surgery].

1. Bacteria detected in cases of acute abdominal ailments encountered in the first department of surgery at Hiroshima university and its related facilities during the recent 4 and a half years were reviewed and the antibacterial activities of flomoxef (FMOX, 6315-S) against these isolates were investigated. As a result, this antibiotic was found to show very high activities against Staphylococcus aureus, Staphylococcus epidermidis, Escherichia coli, Klebsiella pneumoniae and Proteus spp. 2. One gram of FMOX dissolved in 100 ml of physiological saline was administered by intravenous drip infusion during operation and its concentrations in serum and intraperitoneal exudate were determined. The intraperitoneal exudate concentration exceeded the serum concentration in 2 hours after the completion of the drip infusion and, reached high enough concentration to be effective against susceptible bacteria with MICs about 12.5 micrograms/ml. The above results suggested that the new cephem antibiotic FMOX for injection should be sufficiently effective against acute peritonitis.

Acute Disease↗