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Biomedical subjects

K Higashi

Publications and source records attributed to K Higashi.

At least 289 records · Page 16Linked to original sources

Surgical aspects of N-myc oncogene amplification of neuroblastoma.

The surgical aspects of N-myc oncogene amplification of neuroblastic tumors were studied in 42 patients with ganglioneuroblastoma or neuroblastoma. The cumulative survival rate of patients with fewer than 10 copies of N-myc (L group) was 73.7% 48 months after initiation of therapy, whereas the rate for those with more than 10 copies of N-myc (H group) was 0% by 20 months (P less than 0.000001). Clinical prognostic factors of neuroblastic tumors such as age, stage, histologic findings, and primary site correlated with the amplification of N-myc. N-myc amplification of more than 10 copies was evident in one of 16 (6.3%) patients less than 1 year of age and in 13 of 26 (50%) patients over 1 year of age and was detected in one of six tumors in stage II, four of 10 in stage III, seven of 16 in stage IV, and two of six in stage IV-S. The amplification occurred more frequently in patients with neuroblastoma than in those with ganglioneuroblastoma and was observed only in tumors of a suprarenal region. Preoperative chemotherapy was prescribed for 19 of the 26 patients with stage III or IV tumors and was similarly effective in both L and H groups. Ipsilateral nephrectomy or combined resection of a part of liver had to be performed in nine of 11 (82%) patients with stage III or IV tumors in the H group but in only one of 15 (6.7%) in the L group, thereby suggesting that the tumor with an amplified N-myc is more invasive. In patients in the advanced stage, total or nontotal resection of the tumor did not affect the survival in the L group, but the survival interval was prolonged significantly by the total removal of the tumor in patients in the H group. These data should aid in the surgical treatment of patients with poor-prognostic neuroblastoma and an amplified N-myc oncogene.

Child↗

Biological characteristics of N-myc amplified neuroblastoma in patients over one year of age.

1. A genomic amplification of N-myc of neuroblastoma was frequently observed in patients in the advanced stage of the disease, in those with the tumor originating from the suprarenal region, and in those with a histologically undifferentiated neuroblastoma. Thus, N-myc may be one of the most pertinent prognostic factors of neuroblastoma in patients over one year of age. 2. The neuroblastoma patient with 1-10 copies of N-myc responded to aggressive multidisciplinary therapy, even those over one year of age. 3. Rapid invasion and progression of the tumor was evident in children with more than 10 copies of N-myc. 4. N-myc amplification may correlate with immaturity of catecholamine metabolism of neuroblastoma.

Age Factors↗

Glutathione contents in rat livers after acute and chronic exposure to ethylene oxide.

Wistar rats were subjected to a 6 hr exposure to ethylene oxide once at the concentration of 500 ppm, 3 times a week for 12 weeks as a chronic experiment. Hepatic glutathione contents were determined after these treatments. The specific content of reduced form of glutathione (GSH) in the rat livers of chronic exposures was 28.9 nmoles/mg protein, which is not significantly different from that of control group. On the other hand, the hepatic content of GSH in rats subjected to a 4 hr exposure to ethylene oxide at a concentration of 2500 ppm decreased markedly to the levels of 5% of control value. The present results suggest the involvement of glutathione, at least in part, in the detoxication of ethylene oxide.

Animals↗

Genetic analysis of the cell binding domain region of the chicken fibronectin gene.

We have determined the nucleotide sequence of the cell binding domain region of the chicken fibronectin gene and analyzed it evolutionaly. We present here the complete nucleotide sequence of 4.3 kb HindIII/EcoRI segment from the clone lambda FC23 of the chicken fibronectin gene. There were five exons in this segment. When we lined up the amino acid of exons 28, 29 and 31, three alignments, known as the Type III repeat, appeared. Tetrapeptide, -RGDS-, called the cell binding domain, existed in the second repeat, coding exon 30. It was presumed that the Type III repeats were composed of two exons in the chicken gene, the same as in the rat and humans. We found repeatedly appearing amino-acid sequences such as -TIT- (three arrays in these Type III repeats) but also found one of the amino acids substituted in the tripeptide in these Type III repeats (seven arrays). We analyzed these repeats from the point of view of evolution. We used three of the nucleotide sequences (12-18 bp) coding such -TIT- repeats as a unit length for comparing the various homologies after dividing the coding region into 56 segments. The mutual homology of the divided segments to each one of three showed 53% on average. On the other hand, the mutual nucleotide homology of the Type III repeat was 44%. This suggested that the Type III repeat may have been developed by frequent duplication of small gene units.

Amino Acid Sequence↗

Analysis of N-myc amplification in relation to disease stage and histologic types in human neuroblastomas.

Both untreated and treated primary neuroblastomas from 52 patients were analyzed to determine the correlation between the amplification of N-myc oncogene and various prognostic factors. Amplification of N-myc was observed in eight of 28 untreated cases and in 12 of 24 treated cases. As a whole, 12 of 18 tumors (67%) in Stage IV had N-myc amplification, but there were fewer cases in the unadvanced disease stage, as reported previously by others. Furthermore, the authors detected N-myc amplification in three of nine tumors in Stage IV-S, although the amplification was less than 50 copies. Analysis of progression-free survival at 24 months revealed that amplification of N-myc was associated with the worst prognosis (P less than 0.001). In the untreated group, no amplification of N-myc was detected in any of two ganglioneuromas and four ganglioneuroblastomas, whereas amplification of N-myc was observed in all two round-cell and six of 20 rosette fibrillary neuroblastomas. On the other hand, the authors detected amplification of N-myc in three of eight less differentiated ganglioneuroblastomas in the treated group and observed the worst prognosis in these three patients. The total percentage of the cases from both untreated and treated groups suggest that amplification of N-myc may occur more frequently in undifferentiated types of neuroblastomas than in less malignant types. In conclusion, the amplification of N-myc in neuroblastomas was closely associated with the worst prognosis, which was suggested by both disease stage and histologic characteristics.

Child↗

Inhibition of single and double-stranded DNA-dependent ATPase of RecA protein by ATP ribose-modified analogs.

The single-stranded (SS) DNA-dependent ATP hydrolysis at pH 7.5 and 6.2 and the double-stranded (DS) DNA-dependent ATP hydrolysis at pH 6.2 by recA protein (no reaction was detectable at pH 7.5) were found to be inhibited competitively by ribose-modified analogs of ATP, 3'-0-anthraniloyl-ATP (Ant-ATP) and 3'-0-(N-methylanthraniloyl)- ATP (Mant-ATP). The Ki values for Ant-ATP and Mant-ATP is SS DNA-dependent hydrolysis were about 8 and 5 microns at pH 7.5 and 12 and 10 microns at pH 6.2. For the DS DNA-dependent hydrolysis, the Ki values for Ant-ATP and Mant-ATP were about 7 and 6 microns. All these Ki values were much smaller than those of ADP which is also a competitive inhibitor for the ATPase activity of the recA protein. Ant-ATP and Mant-ATP caused a reduction in the Hill coefficients for ATP in SS DNA-dependent ATP hydrolysis at pH 7.5 and DS DNA-dependent hydrolysis. These observations showed that the ATP analogs which have a bulky substituent in the ribose moiety of ATP had strong hydrophobic interactions with the ATP binding site on the recA protein and also contributed to the cooperative effect of ATP.

Adenosine Triphosphatases↗

Familial ossicular malformations: case report and review of literature.

Familial middle ear ossicular anomalies are rare. We report on a daughter and her mother with congenital conductive hearing loss. Tympanotomy disclosed hypoplasia of long crus of incus whose tip had been replaced with a fibrous strand. A review suggests that middle ear ossicular anomalies may be inherited as autosomal dominant traits. Most individuals were bilaterally affected. Most isolated cases were affected unilaterally.

Adult↗

Amplification of N-myc oncogene in stage II and IVS neuroblastomas may be a prognostic indicator.

The amplification of N-myc oncogene is frequently observed in tumors of patients with advanced, poor prognostic stages of neuroblastoma (unfavorable stage group). However, there has been little documentation of the N-myc amplification in tumors of patients with stages II and IVS neuroblastoma (favorable stage group). In this communication, we present data on one patient in stage II and two in stage IVS. In these children, the primary tumors had an amplified N-myc and the clinical course was poor. In addition, from an analysis of the N-myc oncogene of 26 neuroblastomas, genomic amplification of more than three copies was observed in 4 of 11 (36%) in the favorable stage group, and in 9 of 15 (60%) in the unfavorable stage group. Death occurred only in those with an amplified N-myc, in both groups. The smaller copy number of N-myc amplification of stage IVS tumors as compared with those of stages III and IV, appeared to be characteristic. These findings suggest that N-myc amplification may be a reliable prognostic indicator even in the favorable stage group of neuroblastomas, and may be clinically useful as a guide for treating those with a poor prognosis in stages II and IVS.

Adrenal Gland Neoplasms↗

N-myc oncogene amplification and prognostic factors of neuroblastoma in children.

The N-myc oncogene of 28 neuroblastic tumors obtained from 16 untreated and 12 pretreated children was clinically evaluated and compared with known prognostic factors. Significant amplification of the N-myc (more than ten copies) was observed in 0 of 2 tumors in stage I, 1 of 5 in stage II, 2 of 6 in stage III, 6 of 9 in stage IV, and 2 of 6 in stage IVS. In stages II, III, IV, and IVS, all 15 patients with low N-myc amplification (under ten copies) are alive without disease, while among 11 patients with the amplification, seven died with progressive disease and two have a recurrence (P less than .01). All tumors with N-myc amplification originated from the suprarenal region and the amplification appeared in 55% of those from that origin. The amplification also correlated with the age factor. These results suggest that the genomic amplification of N-myc seems to be correlated with known prognostic factors of neuroblastoma, and may be a reliable factor even in the case of preoperatively treated tumors.

Age Factors↗

Low serum reverse T3 levels in patients with primary hyperparathyroidism.

Although patients with primary hyperparathyroidism (1 degree HPT) were euthyroid, we measured serum thyroid hormone levels in 16 patients with 1 degree HPT together with 17 patients with hypercalcemia due to malignant diseases (HCM). In patients with 1 degree HPT, serum levels of T3, T4 and T3U were within normal range, but serum rT3 (reverse T3) levels (205 +/- 37 pg/ml, mean +/- SD) were significantly decreased as compared with those in normal controls (276 +/- 44 pg/ml, P less than 0.01). A significant inverse correlation was observed between the serum levels of rT3 and parathyroid hormone (PTH) (r = 0.54, P less than 0.05). After parathyroidectomy, serum rT3 levels were significantly elevated (240 +/- 56 pg/ml) compared to preoperative levels (P less than 0.01). Low levels of serum rT3 seemed to be attributed to the high levels of serum PTH. On the other hand, serum levels of T3 and T4 were low and serum rT3 levels were high in patients with HCM. Low serum rT3 allows for the differentiation of patients with 1 degree HPT from those with HCM.

Adolescent↗

Preparation and some properties of giant liposomes and proteoliposomes.

Optimal conditions for formation of giant liposomes and proteoliposomes were investigated. A suspension of small unilamellar vesicles made of various phospholipids in a buffer of 0-3 M KCl, 0.1 mM EDTA, and 20 mM MOPS (pH 7.0) was subjected to a freeze-thaw treatment. Giant multilamellar liposomes of diameter ranging from 10 to 60 microns were found to form from phospholipid mixtures containing phosphatidylethanolamine as a major component and phosphatidylserine as a minor component. The concentration of KCl optimal for the giant vesicle formation was 30-500 mM. By applying a patch-pipette to a giant liposome, suitable conditions for obtaining a high-resistance (giga-ohm) seal were sought. It was found that use of a patch-pipette of relatively small tip diameter (less than 1 micron), the presence of divalent metal cations in the suspension medium and inflation of vesicles in a hypotonic solution facilitated giga-seal formation. In a suspension of asolectin (soybean phospholipid) vesicles which had been subjected to the freeze-thaw treatment, giant unilamellar vesicles were found. They could be held on the tip of a suction pipette and impaled with a microelectrode filled with an EGTA solution. Small unilamellar proteoliposomes were prepared by the cholate-dialysis method from asolectin and sarcoplasmic reticulum vesicles, and were subjected to a freeze-thaw cycle. When the ratio of exogenous phospholipid to protein was larger than 10, giant multilamellar vesicles were formed.(ABSTRACT TRUNCATED AT 250 WORDS)

Electrochemistry↗