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Biomedical subjects

S Inoue

Publications and source records attributed to S Inoue.

At least 901 records · Page 50Linked to original sources

[Surgical treatment of thymomas].

Forty-eight patients were evaluated. These cases were classified to stage I in 17, stage II in 11, stage III in 13, and stage IV in 7 by Masaoka staging. In 43, a complete resection was performed and in 5, an incomplete resection was carried out. Twelve patients between stage III and IV received postoperative radiotherapy because of incomplete resection and advanced invasive case (defined as high-risk group). Survival at 10 years was 55% for patients who were in high-risk group. This result was disappointed because survival was low in spite of surgical resection combined with postoperative radiation. From that reason, more concentrated therapy might be necessary with not only enlargement of radiation field but also chemotherapy for vascular invasive thymoma in addition to resection.

Adolescent↗

[Enterovirus infections].

Non-polio enteroviruses are currently the most common agents of the central nervous system viral infection, and are the major causes especially in patients with aseptic meningitis. The practical problems with enterovirus meningitis revealed from the investigation of our patients are as follows. (1) The triad of symptoms of meningitis (fever, headache, vomiting) were seen only in 50% of the older children affected. The only manifestation of neonates with aseptic meningitis was fever. (2) In more than half of the patients, the cerebrospinal fluid showed polymorphonuclear predominance within 3 days from the onset. (3) The causal viruses were isolated frequently (70%) from the cerebrospinal fluid of the children with aseptic meningitis. (4) The patients more than 1 year of age had no sequela clinically. Among neonates and early infants, transient abnormalities of brain CT findings were seen in 40% and delayed speech in 30%. Their prognosis should be investigated more precisely.

Enterovirus Infections↗

[Lipid metabolism in daunomycin-induced nephrotic rats (Part 6)].

Lipid metabolism in tissues and HDL were examined in daunomycin-induced nephrotic rats. 1) Daunomycin-induced nephrotic rats showed the decreased phospholipids, the increased cholesterol content in heart. Phospholipids, triglycerides and cholesterol content in brain, lung and spleen were similar in daunomycin-induced nephrotic rats and control rats. 2) Triglycerides content in hepatocytes was decreased in daunomycin-induced nephrotic rats. But, cholesterol esters content in hepatocytes was higher in daunomycin-induced nephrotic rats than control rats. 3) LCAT activity in serum was increased in daunomycin-induced nephrotic rats. 4) Apolipoproteins composition of HDL in daunomycin-induced nephrotic rats showed the increased apoA-I and the decreased apo E. These results show that the increased cholesterol esters in liver tissue are due to hepatocytes in daunomycin-induced nephrotic rats. The increased HDL cholesterol content may contribute to the increase of LCAT activity in daunomycin-induced nephrotic rats. The increase of LCAT activity in serum results in the increased apo A-I content in daunomycin-induced nephrotic rats. No direct evidence about the incorporation of HDL into liver is obtained from the present experiments and further study will be necessary to clarify this evidence.

Animals↗

Purification and amino-acid sequence of a nerve growth factor from the venom of Vipera russelli russelli.

Nerve growth factor (NGF) was purified from the venom of Vipera russelli russelli by Sephadex G-50 gel filtration, S-Sepharose column chromatography and Blue-Sepharose CL-6B column chromatography. The purified NGF was found to be a glycoprotein, whose apparent molecular mass was estimated to be about 17.5 kDa by SDS-PAGE. The amino-acid sequence was determined by a combination of conventional methods. The V. r. russelli NGF was composed of 117 amino-acid residues with one residue, Asn-21, being N-linked glycosylated and the molecular mass of its protein portion was calculated to be 13,280 Da.

Amino Acid Sequence↗

Fish egg glycophosphoproteins have species-specific N-linked glycan units previously found in a storage pool of free glycan chains.

Recent findings (Ishii, K., Iwasaki, M., Inoue, S., Kenny, P. T. M., Komura, H., and Inoue, Y. (1989) J. Biol. Chem. 264, 1623-1630; Inoue, S., Iwasaki, M., Ishii, K., Kitajima, K., and Inoue, Y. (1989) J. Biol. Chem. 264, 18520-18526) of a relatively large quantity of complex-type free sialo-oligosaccharides in the unfertilized eggs of freshwater fish, Plecoglossus altivelis and Tribolodon hakonensis, prompted us to search for their progenitor glycoproteins. First we demonstrated a third occurrence of free sialoglycans in the unfertilized eggs of Medaka fish (Oryzias latipes). Next, in all three species studied, a uniformly high level of glycophosphoproteins (GPP) was identified and found to possess N-linked glycan units. The carbohydrate structures of the GPP were determined to be identical with those of the free glycans isolated from the unfertilized eggs of the respective fish species. Thus, the most likely candidate for the progenitor of free sialoglycans appeared to be the oocyte GPPs. This implies that the liberation of the free glycans by a putative peptide-N4-(N-acetyl-beta-glucosaminyl)asparagine amidase may represent a necessary biochemical event during vitellogenesis or oogenesis. The present results may provide insight into a new concept of a "protein N-glycosylation/de-N-glycosylation system" recently proposed by us (Seko, A., Kitajima, K., Inoue, Y., and Inoue, S. (1991) J. Biol. Chem. 266, 22110-22114).

Amino Acids↗

Stimulation of glucose transport by guanine nucleotides in permeabilized rat adipocytes.

Effects of guanine nucleotides on glucose transport were studied in permeabilized rat epididymal fat cells. GTP gamma S and Gpp(NH)p, but not App(NH)p, stimulated 3-O-methylglucose transport. Effect of GTP gamma S was dose-dependent, being detectable at 0.1 mM, and 1.0 mM GTP gamma S stimulated glucose transport to the same extent as insulin. GTP gamma S (0.3 mM) enhanced insulin-stimulated glucose transport while 1 mM GTP gamma S did not affect insulin-mediated transport. GDP beta S had no effect on glucose transport by itself but rather enhanced insulin action. NaF, which is known to activate trimeric G proteins, increased glucose transport to the same extent as insulin. Likewise, mastoparan augmented glucose transport. These results indicate that a certain type of trimeric G protein(s) is involved in the regulation of glucose transport.

3-O-Methylglucose↗

Acute myeloid leukemia (AML) in Down's syndrome is highly responsive to chemotherapy: experience on Pediatric Oncology Group AML Study 8498.

The treatment of acute myeloid leukemia (AML) in children with Down's syndrome (DS) has engendered considerable controversy. Because of the concerns for toxicity and increased rate of infections, treatment approaches varied considerably in the past with mixed results. However, experience on the recently completed Pediatric Oncology Group (POG) 8498 AML study suggests that DS children with AML constitute a distinct subgroup that responds well to therapy. Twelve of 285 children on POG 8498 (protocol for newly diagnosed AML) had DS. Children with DS and AML were predominantly male (9 of 12) and were quite younger at diagnosis (< 24 months in 10). The white blood cell count was less than 50 x 10(3)/microL in all 12 and French-American-British types M6 and M7 were frequent (5 of 12). An abnormal cytogenetic marker, in addition to constitutional trisomy 21, was present in 9 of 12 and involved chromosome 8 in 4 of 9. All cases studied (n = 5) were positive for myeloid cell surface markers (CD33, CD13, or CD11b) and, interestingly, were also positive for the CD7 antigen. Chemotherapy included daunorubicin, cytarabine (Ara-C), and 6-thioguanine for remission induction and featured high-dose Ara-C (3 g/m2 per dose) with or without L-asparaginase early in remission. Compared with children without DS, children with DS had a superior event-free survival (EFS at 4 years 100% v 28% +/- 6.2%; P = .003). The EFS remained superior even when compared with non-DS children less than 2 years of age with a white blood cell count less than 10 x 100,000/microL (100% v 48% +/- 17.3%; P = .01).

Acute Disease↗

Vitamin K2 modulates proliferation and function of osteoblastic cells in vitro.

A human osteosarcoma cell line, HOS TE85 cells, and a mouse osteoblastic cell line, MC3T3-E1 cells, were cultured for 3 days in a medium containing various concentrations of menaquinone-4 (vitamin K2). As a result, the proliferation of HOS cells was suppressed by vitamin K2 in a dose dependent manner up to 56% of control by 10(-7)M of vitamin K2 and that of MC3T3-E1 cells was suppressed to 84% of control by 10(-6)M of vitamin K2. Vitamin K2 increased alkaline phosphatase activity in both kinds of cells. Warfarin counteracted the effect of vitamin K2 on osteoblastic cell proliferation. Our results show that vitamin K2 modulates proliferation and function of osteoblastic cells by some mechanisms including gamma-carboxylation system.

Animals↗

3-Hydroxy-3-methylglutaryl-coenzyme A reductase and T cell receptor alpha subunit are differentially degraded in the endoplasmic reticulum.

3-Hydroxy-3-methylglutaryl-coenzyme A reductase (HMG-CoA reductase) is located in the endoplasmic reticulum (ER) and responds to rapid degradation which is regulated by mevalonate or sterols. T cell antigen receptor alpha chain (TCR alpha) is also known to be rapidly degraded within the ER. In both cases, the membrane domains of the proteins have a crucial role in their rapid degradation. In order to investigate protein degradation in the ER, we compared the degradation of HMG-CoA reductase and TCR alpha in the same Chinese hamster ovary cells. Among the protease inhibitors tested, N-acetyl-leucyl-leucyl-methioninal blocks the degradation of HMG-CoA reductase and also inhibits the degradation of TCR alpha. On the other hand, N-tosyl-L-phenylalanine chloromethyl ketone and N-carbobenzoxy-L-phenylalanine chloromethyl ketone inhibit the degradation of TCR alpha but have no effect on the degradation of HMG-CoA reductase. Diamide, a thiol-oxidizing agent, blocks the degradation of both HMG-CoA reductase and TCR alpha. Perturbation of cellular Ca2+ attenuates the rapid degradation of HMG-CoA reductase but does not affect the degradation of TCR alpha. Furthermore, thapsigargin, a selective ER Ca(2+)-ATPase inhibitor, and Co2+, a potent Ca2+ antagonist, increase the half-life of HMG-CoA reductase but not that of TCR alpha. Energy inhibitors diminish the rapid degradation of HMG-CoA reductase but not that of TCR alpha. These results suggest that although HMG-CoA reductase and TCR alpha appear to be degraded in the same subcellular compartment, the mechanisms responsible for degradation differ.

1-Deoxynojirimycin↗

Follistatin is a developmentally regulated cytokine in neural differentiation.

Activin acts mitogenically on P19 cells as well as being inhibitory of the differentiation of retinoic acid-treated P19 cells and some neuroblastoma cell lines. Here, we show some lines of evidence that follistatin, an activin-binding protein, is also involved in neural differentiation. Counteracting the activity of activin, addition of follistatin suppresses the anchorage-independent growth of P19 cells in soft agar and stimulates neurite outgrowth of a neuroblastoma cell line, IMR-32 cells. While activin does not seem to be expressed significantly, follistatin is demonstrated in the conditioned medium of these cells. Furthermore, the expression of follistatin in P19 cells is subject to dynamic fluctuations in response to retinoic acid treatment. These neural cells may produce follistatin in a cell stage-specific manner in order to interact with exogenously derived activin.

Activin Receptors↗

Peptide transport by the multidrug resistance pump.

The membrane P-glycoprotein (P170) is an ATP-hydrolyzing transmembrane pump, and elevated levels of P170, due to higher expression with or without amplification of the multidrug resistance gene (mdr1), result in resistance to a variety of chemotherapeutic agents in mammalian cells. The function of the P170 pump has been proposed as a protection against toxic substances present in animal diets. Here we describe a Chinese hamster ovary cell line that was selected for resistance to a synthetic tripeptide, N-acetyl-leucyl-leucyl-norleucinal (ALLN). This ALLN-resistant variant shows the classical multidrug resistance (MDR) phenotype, including overexpression and amplification of the mdr1 gene. Additionally, a mouse embryo cell line overexpressing the transfected mdr1 gene is likewise resistant to ALLN. Our results demonstrate that P170 is capable of transporting peptides and raise the possibility that the mdr1 gene product or other MDR-like genes, present in the genome of mammalian cells, may be involved in secretion of peptides or cellular proteins as is the case with the structurally similar hylB and ste6 gene products of Escherichia coli and yeast, respectively.

3T3 Cells↗

Functional regulation of osteoblastic cells by the interaction of activin-A with follistatin.

A high number of 125I-activin-A binding sites (an apparent Kd of 260 pM and 5,600 sites/cell) were observed on MC3T3-E1 cells, a well characterized osteoblastic cell line. Activin-A has a mitogenic effect on these cells, with the greatest influence being observed on cells in an undifferentiated state, as well as a suppressive effect on the alkaline phosphatase activity. Northern and ligand blotting analyses revealed that these osteoblastic cells produce follistatin, which was down-regulated by retinoic acid treatment. Because follistatin is an activin-A-binding protein, we suggest that activin-A modulates the function of osteoblastic cells by being regulated by follistatin during differentiation.

Activins↗

Epidermal cell differentiation inhibitor ADP-ribosylates small GTP-binding proteins and induces hyperplasia of epidermis.

Epidermal cell differentiation inhibitor (EDIN) is a recently discovered protein which inhibits terminal differentiation of cultured keratinocytes (Sugai, M., Enomoto, T., Hashimoto, K., Matsumoto, K., Matsuo, Y., Ohgai, H., Hong, Y.-M., Inoue, S., Yoshikawa, K., and Suginaka, H. (1990) Biochem. Biophys. Res. Commun. 173, 92-98). The amino acid sequenced deduced from the EDIN gene has revealed that EDIN shares high amino acid sequence homology with the exoenzyme C3 of Clostridium botulinum (Inoue, S., Sugai, M., Murooka, Y., Paik, S.-Y., Hong, Y.-M., Ohgai, H., and Suginaka, H. (1991) Biochem. Biophys. Res. Commun. 174, 459-464), which has been shown to ADP-ribosylate the rho/rac proteins (members of the small GTP-binding protein family). We show here that EDIN ADP-ribosylates rhoB p21 in time- and dose-dependent manners in a cell-free system. Kinetic studies of the ADP-ribosylation and peptide mapping of the reaction products of rhoB p21 by EDIN and C3 suggest that the mode of action of the ADP-ribosylation by EDIN is quite similar to that by C3 and that the ADP-ribosylation site of rhoB p21 by EDIN is presumably the same as that by C3. Proteins in epidermal membranes and keratinocyte homogenate with Mr values of about 22,000 are ADP-ribosylated by EDIN or C3. Treatment of cultured human keratinocytes by EDIN or C3 results in an inhibition of terminal differentiation and a stimulation of growth of the cells. Moreover, EDIN and C3 injected into adult mouse skin induce hyperplasia of epidermis. These results suggest that EDIN and C3 affect growth and differentiation of keratinocytes by ADP-ribosylation of protein(s) with a Mr of about 22,000, which may be the rho/rac proteins or related proteins.

Adenosine Diphosphate Ribose↗

Morphology of the kidney of the platypus (Ornithorhynchus anatinus: Monotremata).

The platypus kidney shows morphological similarities to those of other mammals. Macroscopically, the cortex is easily distinguishable from the fairly wide medulla. Within the medulla, no clear border is observed between the inner and outer zones. Light and transmission electron microscopically, the glomeruli show quite similar architecture to those of other mammals; however, the glomerular lobulation is very clear. The glomerular tufts are rather simple, but capillary lumen varies widely in size, which is one of the unique features of the platypus kidney. The urinary tubule is generally similar to that of human and other mammals in shape and segmentation; however, the staining specificities of histochemical reactions and the shape of epithelial cells of the Henle's loop differ from those of other mammals. The most conspicuous features are: 1) although no protein casts are found in the tubular lumina, epithelial cells of the proximal convoluted tubule (PCT) have numerous electron-dense vesicles as in human nephrotic kidneys; and 2) the platypus Henle's loop consists of the thick epithelial cells similar to the mammalian type nephron of birds. As compared to those of other mammals such as humans and rats, our observations suggest that the platypus kidney is less developed, in terms of evolution.

Animals↗

Analysis of collagen type III by uninterrupted sodium dodecyl sulfate-polyacrylamide gel electrophoresis and immunoblotting: changes in collagen type III polymorphism in aging rats.

A new method of type III collagen analysis by uninterrupted sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) combined with immunoblotting was developed. The electrophoresis was carried out with gels containing 4 M urea. A negatively charged reducing agent, thioglycolic acid, was added to the running buffer of the cathodic reservoir between 15 and 20 min after Bromphenol Blue (BPB) migrated to the top of the separating gel, to reduce interchain disulfide binding of the collagen. The polymorphic type III collagens, i.e., an alpha-chain derived from a trimer [alpha 1(III)]3 with interchain disulfide bonds but without covalent cross-links, alpha 1(III), a beta-chain with covalent cross-links, beta(III), or an alpha-chain released from a trimer without reduction of the disulfide bonds, alpha*1(III), were identified by immunostaining and quantified by densitometry. Using this method, changes in collagen type III polymorphism with aging were examined in the aorta, brachial artery, and skin of rats. The total quantity of collagen type III decreased with aging in all tissues. beta(III) was the major component in the aorta and brachial artery, but alpha 1(III) was the major component in the skin. With increasing age from 3 to 60 weeks, the ratio of beta(III) to alpha 1(III), which is correlated with the extent of covalent cross-linking, showed a steep increase in the aorta but only a slight increase in the skin and it remained almost constant in the brachial artery.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗

Comparison of hepatectomy and transcatheter arterial chemoembolization for the treatment of hepatocellular carcinoma: necessity for prospective randomized trial.

Transcatheter arterial chemoembolization is now widely used in cases of surgically unresectable hepatocellular carcinoma. However, it is unclear whether patients with surgically resectable hepatocellular carcinoma should always be treated with hepatectomy as opposed to transcatheter arterial chemoembolization. Sixty-six patients with hepatocellular carcinoma underwent hepatectomy, whereas 29 patients with more advanced hepatocellular carcinoma were treated with transcatheter arterial chemoembolization at our hospital from 1984 to 1990. All cases were associated with cirrhosis of Child class A or B. All of them underwent hepatectomy or transcatheter arterial chemoembolization for the first time. Their outcomes were determined on March 31, 1991. The backgrounds and survival curves for hepatectomy and transcatheter arterial chemoembolization were compared in both Child A and Child B patients. For both Child A and B patients, no significant difference was found between hepatectomy and transcatheter arterial chemoembolization with respect to age, sex, cause of underlying cirrhosis, liver function assessed by indocyanine green test and maximum diameter of the main tumor. The incidence of multiple hepatocellular carcinoma, more advanced hepatocellular carcinoma (TNM stage III or IV) or both was significantly higher in the transcatheter arterial chemoembolization group than in the hepatectomy group for both Child A and Child B patients. The survival curves of both the hepatectomy and the transcatheter arterial chemoembolization groups showed no significant difference for both Child A and Child B patients. A prospective study is therefore warranted to elucidate whether hepatectomy or transcatheter arterial chemoembolization is more effective for treating resectable hepatocellular carcinoma associated with cirrhosis.

Adult↗

Spontaneous rupture of hepatocellular carcinoma: an approach with delayed hepatectomy.

Two cirrhotic patients with ruptured hepatocellular carcinoma (HCC), presenting with hemoperitoneum, were successfully treated by elective hepatectomy. Both of these patients, a 67-year-old female and a 76-year-old male, had first been taken to other primary hospitals by ambulance due to hypovolemic shock. They were then found to have a mass of approximately 5 cm in the cirrhotic liver. In the initial management, however, neither any direct hemostasis by surgery nor indirect measures such as transcatheter hepatic arterial embolization were performed in either case. Instead, conservative treatment consisting mainly of fresh blood and plasma transfusions were continued for more than a month until the liver function stabilized. In both hepatectomies, the use of a microwave tissue coagulator resulted in minimal intra-operative blood loss and an appreciably excellent post-operative course. These cases point to the effectiveness of a "wait and see" policy for selected patients with ruptured HCC.

Aged↗