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Biomedical subjects

T Fukushige

Publications and source records attributed to T Fukushige.

At least 55 records · Page 3Linked to original sources

Extrarenal Wilms' tumour.

Extrarenal Wilms' tumour is rare and its imaging has received scant mention in the literature. We describe a 2-year-old boy with a firm mass in the right flank. CT, MRI and ultrasonography showed an inhomogeneous solid mass located in the retroperitoneum, which was separate from the right kidney. Angiography showed an enlarged right gonadal artery and irregularly tortuous vessels in the tumour similar to intrarenal Wilms' tumour ("spider leg" or "creeping vine" appearance). Histopathological examination confirmed an extrarenal Wilms' tumour.

Child, Preschool↗

C. elegans osm-3 gene mediating osmotic avoidance behaviour encodes a kinesin-like protein.

In the nematode Caenorhabditis elegans, mutants in osm-3 gene are known to be defective in osmotic avoidance, chemotaxis and dauer formation behaviours. To study the molecular basis of these pleiotropic defects we have cloned the osm-3 gene by germline transformation of osm-3 (p802) mutants through microinjection of the wild type genomic DNA. Northern analysis reveals a 3.0 kb transcript corresponding to osm-3. DNA sequencing of the transforming 4.3 kb fragment revealed a kinesin heavy chain-like protein, which contains conserved ATPase and microtubule binding domains. Our results are consistent with the previous EM data on osm-3 (p802) mutants that show an accumulation of dense matrix material in the amphid sheath cytoplasm and a shortened distal segment of the amphid channel cilium. These data suggest a kinesin-like role of the osm-3 product in axonal transport.

Amino Acid Sequence↗

[Changes in epidural pressure during epidural injection].

To evaluate the change of epidural pressure when local anesthetic was injected into epidural space, we inserted three epidural catheters in 13 patients. Epidural catheters were inserted at Th8/9, Th10/11 and L3/4 intervertebral spaces, and 2% mepivacaine 10 ml was injected through Th10/11 or L3/4 catheter. The change of epidural pressure was recorded from three catheters. The elevation of pressure was largest in the injected catheter, but the pattern of elevation was similar in all three catheters. The results suggest that the elevation of epidural pressure occurs at the same time all over the epidural space when local anesthetic is injected.

Aged↗

Serum calcium-decreasing factor (caldecrin) from porcine pancreas has proteolytic activity which has no clear connection with the calcium decrease.

We purified a serum calcium-decreasing factor, which showed chymotrypsin-like protease activity, from porcine pancreas to homogeneity. The factor administered to mice intravenously at a dose of 20 micrograms/kg b.w. decreased serum calcium by 15%. Treatment of the factor with the serine protease inhibitor, PMSF, caused a leftward shift in the dose-response curve, showing strengthened activity. It also caused a decrease in serum calcium and hydroxyproline levels in rats. At a dose of 10 ng/ml, the factor inhibited 45Ca release from cultured fetal long bone stimulated by parathyroid hormone (PTH) and PTH-related protein, but not by interleukin-1 alpha, prostaglandin E1 and 1,25-dihydroxy vitamin D3. No other well-known pancreatic proteases had these effects. In view of the results of experiments using protease inhibitor and pancreatic proteases, and in view of the specificity of this factor in vitro, we propose that the factor exerts its serum calcium-decreasing activity most probably not through proteolytic degradation of PTH, but through an inhibition of PTH action on bones by a yet undefined mechanism.

Animals↗

Undifferentiated (embryonal) sarcoma of the liver: report of three cases.

Undifferentiated (embryonal) sarcoma is a rare malignant tumor of the liver. It typically presents in late childhood and its prognosis is poor. We experienced three cases of such a tumor during the period of 1976-1989; two of these patients are still alive without disease. Each case was independently treated with a combination of surgery and pre- and/or postoperative chemotherapy, which was found to be effective. In one surviving patient, cyclophosphamide and vincristine were found to be effective, while in the other a combination of cisplatin, Adriamycin (ADM), vincristine and cyclophosphamide was observed to induce a rapid reduction in the size of the recurrent tumor. Thus, an adequate combination of surgery and chemotherapy may improve the prognosis of this tumor.

Antineoplastic Combined Chemotherapy Protocols↗

Establishment and characterization of a cell line of congenital primitive neuroectodermal tumor of soft tissue.

A new human cell line, termed Muraoka, has been established from the recurrent tumor of a case of congenital primitive neuroectodermal tumor (PNET) arising at the temporofacial region of a male infant. The microscopic findings of this cell line were epithelioid, and the xenografted tumor in a nude mouse consisted of the malignant epithelioid cells. Immunohistochemically, the cells were positive for neuron-specific enolase, S-100 protein, carcinoembryonic antigen, cytokeratin, epithelial membrane antigen, and glial fibrillary acidic protein. These findings were quite similar to those of the epithelioid cells in the original tumor and of the xenografted tumor cells. Neither chromosomal abnormalities nor N-myc amplification were observed. Morphological differentiation after treatment with N6-2'-O-dibutyryladenosine 3':5'-cyclic monophosphate (Bt2-cAMP), all-trans-retinoic acid (RA), prostaglandin E1 (PGE1), and 5-bromo-2'-deoxyuridine (BrdU) showed two different results. Bt2-cAMP and PGE1 induced neuronal differentiation with the extension of neurites, whereas RA and BrdU predominantly induced Schwannian differentiation (flat cells). In these respects, the cell line Muraoka seems to be useful for studying characteristics of PNET as well as for developing the new treatments against such tumors.

Animals↗

Combined effects of vitamin E (alpha-tocopherol) and cisplatin on the growth of murine neuroblastoma in vivo.

Combined effects of vitamin E (alpha-tocopherol) and cisplatin on the growth of two murine neuroblastomas (C1300, NS-20) was investigated in vivo. Five groups of mice were prepared; group 1 were fed the control diet, group 2 were fed a vitamin E-deficient diet, group 3 were fed a vitamin E-supplemented diet, group 4 were fed the control diet and plus vitamin E solution given intraperitoneally during the treatment (solvent i.p. group), and group 5 were given vitamin E in the same manner (20 mg/kg/day; vitamin E i.p. group). Cisplatin (6 mg/kg) was injected intraperitoneally into the mice of each group during the treatment. In case of the C1300 neuroblastoma, the antitumor activity of cisplatin was most enhanced in the mice receiving vitamin E i.p., and the intra-tumor vitamin E and platinum levels were significantly higher in this group than in the other groups (P less than 0.01, and P less than 0.05 respectively). In contrast, in animals transplanted with the NS-20 murine neuroblastoma, which proved to be a cisplatin-tolerant tumor in separate experiments, no combined effect of those drugs was observed, although the intra-tumor level of platinum was elevated. The possibility was that vitamin E increases the influx of cisplatin into the tumor cells and acts after incorporation of cisplatin through the plasma membrane. Vitamin E did not accentuate the cisplatin-induced renal impairment in vitamin E-loaded groups. Those results suggested that vitamin E should be considered as a co-agent of cisplatin for the treatment of neuroblastoma.

Animals↗

Different clonal drug sensitivity of murine neuroblastoma cells in vivo.

Four cloned murine neuroblastomas were implanted intramuscularly into the left thigh of adult A/Jax mice. Cyclophosphamide, cisplatin, adriamycin, imidazole carboxamide, and vincristine were administered intraperitoneally, in a dose of one third to one fourth of a median lethal dose, every week after the implantation until all the mice died. The effects of continuous long-term chemotherapy, particularly on clonal differences, were then assessed. Cyclophosphamide was most effective for four murine neuroblastomas, and cisplatin was the next most effective drug. Cisplatin was not effective in the NS-20 cell line, a cholinergic cloned neuroblastoma. The C 1300 cell line (wild type) was tolerant to adriamycin, imidazole carboxamide, and vincristine. The N-18 cell line (an inactive clone) exhibited tolerance of adriamycin and imidazole carboxamide. In the N1E-115 cell line, an adrenergic clone, tumor growth was inhibited by all the drugs given. We conclude from this study that drug sensitivity differs with the clone, and that there are clones resistant to each drug.

Aminoimidazole Carboxamide↗

Different effects of vitamin E on the growth and morphological differentiation of 4 murine neuroblastoma cell lines in vitro.

The effects of vitamin E (vit.E, d-alpha-tocopherol acid succinate) on the growth and the morphological differentiation of 4 representative murine neuroblastoma cell lines: C1300 (wild type), NS-20 (cholinergic type), N-18 (inactive type), N1E-115 (adrenergic type), and the combined effects of vit.E and cis-diamminedichloroplatinum(II)(cisplatin, CDDP) were studied in culture. Vitamin E inhibited the growth of all clonal cells in a dose-dependent manner, especially that of NS-20 cells, and it caused significant morphological differentiation only in NS-20 cells. In addition, vit.E enhanced the growth inhibition of C1300 cells by cisplatin in an additive manner, but not that of NS-20 cells. These suggested that both phenomena induced by vit.E may not always occur in parallel in each clonal neuroblastoma, and both mechanisms might be different.

Animals↗

Characterization of human wild-type and mutant argininosuccinate synthetase proteins expressed in bacterial cells.

Argininosuccinate synthetase (ASS) is a urea cycle enzyme with a tetrameric structure composed of identical subunits. Citrullinemia is an autosomal recessive disease caused by a deficiency of ASS. We have previously identified 20 mutations in ASS mRNA of human classical citrullinemia. However, it is difficult to evaluate the effects of each mutation on the enzyme structure and function, since most of the patients are compound heterozygotes. In the present study, wild-type ASS and 12 mutant ASSs were expressed with a bacterial expression system and analyzed enzymologically and immunochemically. The properties of the purified recombinant protein with wild-type human ASS showed good agreement with native enzyme purified from human liver. Mutant ASS proteins with an expected molecular mass, except for delta 7b/Ex16, were highly expressed in the bacterial cells. It was difficult to extract ASS proteins with some mutations (A118T, delta Ex7, R157H, R363W, R363L, G390R and ins37b/Ex15&16) from cells by freezing and thawing. Extractable mutant proteins were as follows: G280R mutant was extracted with an amount of ASS protein similar to wild-type but with no ASS activity, and A192V, R272C and R304W mutants detected various amounts of ASS protein (13, 110 and 33% of wild-type, respectively) with a low ASS activity and abnormal kinetics. Higher Km values for citrulline were obtained in mutant ASSs with A192V (15 mmol/1), R272C (4.2 mmol/l) and R304W. (190 mmol/l) than in wild-type ASS (0.056 mmol/l). The results confirm that these mutations are responsible for ASS deficiency and also indicate that these amino acid residues are important for the function and structure of ASS protein.

Amino Acid Sequence↗

The expression of cadherins in human neuroblastoma cell lines and clinical tumors.

Cadherins are Ca(2+)-dependent cell-cell adhesion molecules which play crucial roles in the cell-cell interactions during development, tumorigenesis and metastasis. The absence of N (neural)-cadherin is correlated with the onset of neural crest migration and its reappearance is correlated with the cessation of migration and precedes gangliogenesis. We investigated the expression of cadherins including N-cadherin in five cell lines and eleven clinical specimens of human neuroblastomas, which originated from neural crest cells. We found that three of the neuroblastoma cell lines and all the clinical specimens were positive for the expression of the N-cadherin protein. The other two neuroblastoma cell lines were negative for the expression suggesting they originated from migrating neural crest cells. All these cell lines and clinical samples expressed either cadherin-6, cadherin-11 or both, i.e. cadherins expressed on neural crest cells, supporting their neural crest origin.

Adolescent↗