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Biomedical subjects

S Nakatsu

Publications and source records attributed to S Nakatsu.

At least 19 recordsLinked to original sources
PubMed2006

Cross-species function of the pig C1 esterase inhibitor.

BACKGROUND: The use of a bioartificial liver with pig cells for the treatment of fulminant hepatic failure will require research on the plasma complement regulatory proteins of the pig, because the liver produces most of the complement components and plasma complement regulatory proteins. In our previous study, the pig C1 esterase inhibitor (C1-INH), which functions as an inhibitor of the complement reaction in the first step of the classical pathway in the fluid phase, was cloned and some relevant features of the molecule were characterized, especially its cross-species regulation, in comparison with human C1-INH. In a further analysis, the species specificity of C1-INH was examined, using pig endothelial cells (PEC) and several types of sera. MATERIALS AND METHODS: The cDNA of pig C1-INH was used to produce the membrane type pC1-INH, pC1-INH-PI, and inserted into the cloning site of pCXN2 (chicken beta actin promoter). The pCX/pCl-INH-PI plasmid was then transfected into PEC to establish stable PEC with pCl-INH-PI. The expression of the pCl-INH-PI was evaluated by a FACS analysis, and complement-dependent cell lysis with human, dog, rabbit, and mouse sera was then assessed. RESULTS: The transfectant with pig Cl-INH-PI showed a high level of expression on PEC. The PEC transfectants showed an inhibitory effect on complement-dependent PEC lysis. Pig Cl-INH did not show the same suppressive effect for each serum. However, considering the alternative pathway activation of each serum on the pig cell membrane, it can be concluded that pCl-INH has a relatively small species restriction. CONCLUSION: Pig Cl-INH, having a similar structure to human Cl-INH, shows a strong complement regulatory function on other species sera.

Actins↗
PubMed2000

["Adenoid" glioblastoma].

A surgical case of glioblastoma which showed a pronounced "adenoid" (or "epithelioid") appearance was reported. The patient was an 81-year-old woman, who presented with unsteady gait. Neuroradiological examination revealed three discrete mass lesions located in the 1-frontal, 1-parieto-occipital, and r-occipito-temporal lobes. Despite the subtotal removal of two of the three lesions and postoperative chemotherapy and radiotherapy, the patient died 21 months after the onset of illness. Histopathological examination of the resected tumors revealed typical features of glioblastoma in the peripheral region of the tumor. In the central region, the tumor cells were arranged in a papillary fashion or formed solid, sheet-like cell nests and were surrounded by fibrous connective tissue septa. Although the histopathological appearance of the tumor closely resembled metastasis of adenocarcinoma, the immunohistochemical and ultrastructural studies of the tumor failed to detect evidence of a definite differentiation towards epithelial cells.

Aged↗
PubMed1997

Induction of apoptosis in multi-drug resistant (MDR) human glioblastoma cells by SN-38, a metabolite of the camptothecin derivative CPT-11.

The overexpression of the multidrug resistance (mdr1) gene and its product, P-glycoprotein (P-gp), is thought to limit the successful chemotherapy of human tumors. Recent studies demonstrate that SN-38, a metabolite of the camptothecin (CPT) derivative CPT-11, has antitumor effects on several tumors, but the mechanisms responsible for its cytotoxicity remain unclear. We therefore determined whether SN-38 has cytotoxic effects on MDR human glioblastoma GB-1 cells and non-MDR human glioblastoma U87-MG cells. Furthermore, we determined what role SN-38 plays in the induction of cytotoxicity in these tumor cells. In this study, we demonstrated that SN-38 had significantly stronger antitumor effects on GB-1 and U-87MG cells than did CPT (P < 0.01 and P < 0.05, respectively). In addition, findings obtained using a DNA fragmentation assay, Hoechst 33258 staining, in situ end-labeling and cell cycle analysis demonstrated that SN-38 induced apoptosis in these tumors. Our results suggest that SN-38 has a stronger antitumor effect on malignant glioma cells regardless of MDR expression than does CPT, and therefore can be considered a new chemotherapeutic agent potentially effective in the treatment of human primary or recurrent malignant gliomas resistant to chemotherapy.

Antineoplastic Agents, Phytogenic↗
PubMed1997

Emergent treatment of iatrogenic dissection of the internal carotid artery with the Palmaz-Schatz stent--case report.

A 67-year-old male presented with sudden onset of aphasia and right hemiparesis on January 27, 1995. Iatrogenic dissection of the left internal carotid artery occurred during attempted local thrombolytic therapy for embolic occlusion of the middle cerebral artery. His neurological condition worsened. Following an unsuccessful angioplasty for the dissection, a Palmaz-Schatz stent was deployed over the dissection. Local thrombolytic therapy was then successfully completed. Anticoagulation and antiplatelet medications were given to prevent further embolic stroke. Follow-up angiography at 2 weeks and 8 months showed good patency of the stented segment. He has experienced no cerebral ischemic events since the treatment.

Aged↗
PubMed1997

Possible role of neurointerventional techniques in the diagnosis of hemifacial spasm.

We used neurointerventional techniques to conduct a functional investigation of the artery responsible for hemifacial spasm in a 48-year-old woman. Insertion of a microcatheter into the posterior inferior cerebellar artery stopped the hemifacial spasm immediately and completely. The artery was verified intraoperatively as the vessel compressing the root exit zone of the facial nerve.

Arteries↗
PubMed1996

Apoptosis induced by selenium in human glioma cell lines.

Several studies have shown that selenium can inhibit tumorigenesis in tissues. However, little is known about the mechanism and the effect of selenium on DNA, especially in brain tumor cells. In this study we examined the biological effect of selenium on human glioma cell lines (A172 and T98G). Selenium exhibited an antiproliferative effect on these cell lines (and induced the typical ladder pattern of DNA fragmentation commonly found in apoptosis), which were prevented by catalase. Few effects of selenium on NT14 fibroblasts were found. These findings demonstrate that selenium may induce, by apoptosis, cell death of human glioma cell lines, which are resulting from free radical oxygen forming.

Apoptosis↗
PubMed1995

Effect of selenium on malignant tumor cells of brain.

Some reports have demonstrated that selenium can inhibit tumorigenesis in some tissues of animal. However, little is known about the inhibitory effect on malignant tumor cells of brain. The purpose of our study was to determine the biological effect of selenium on growth of rat glioma and human glioblastoma cell lines. Cell lines C6 and A172 were obtained from Japanese Cancer Research Resources Bank, Tokyo, Japan (JCRB). Cells were cultured in Dulbecco's Modified Eagle's Medium (DMEM) supplemented with 10% fetal calf serum at 37 degrees C in a humidified atmosphere of air and 5% CO2. Antiproliferative effects of selenium were evaluated using growth rate assay quantifying cell number by MTT assay. An antiproliferative effect of selenium was found in two cell lines, which was more effective on human A172 glioblastoma and less effective on rat C6 glioma.

Animals↗
PubMed1995

Combination therapy with cisplatin and nifedipine induces apoptosis in cisplatin-sensitive and cisplatin-resistant human glioblastoma cells.

We attempted to determine whether calcium channel blockers (CCBs) enhance the anti-tumour activity of cis-diamminedichloroplatinum (cisplatin) against both cisplatin-sensitive human glioblastoma U87 MG cells and cisplatin-resistant U87-MG-CR cells, the latter of which we developed for resistance to cisplatin. Nifedipine, a dihydropyridine class CCB, significantly enhanced the anti-tumour effect of cisplatin on these two cell types in vitro and in vivo. Our findings also indicated that, in the absence of normal extracellular Ca2+ nifedipine was capable of enhancing the cytotoxicity of cisplatin. In addition, this anti-tumour activity was partially inhibited by actinomycin D and cycloheximide, suggesting that it is possibly dependent upon new RNA and protein synthesis. Interestingly, ultrastructural analysis, DNA fragmentation assay and cell cycle analysis demonstrated that synergism between cisplatin and nifedipine results in apoptosis (programmed cell death) at a relatively low concentration of cisplatin, which when tested alone did not induce apoptosis. Furthermore, we demonstrated that nuclei from these cells lack a Ca(2+)-dependent endonuclease that degrade chromatin in the linker region between nucleosomes. In conclusion, our studies suggest that the non-cytotoxic agent nifedipine is able to synergistically enhance the anti-tumour effects of cisplatin on U87-MG and U87-MG-CR cells lacking a Ca(2+)-dependent endonuclease and subsequently to induce apoptosis via interaction of nifedipine with an as yet uncharacterised functional site other than a calcium channel on target cells.

Animals↗
PubMed1994

Tumour necrosis factor-alpha induces an increase in susceptibility of human glioblastoma U87-MG cells to natural killer cell-mediated lysis.

The mechanism by which tumour necrosis factor (TNF)-alpha increases the susceptibility of U87-MG human glioblastoma cells to lysis by natural killer (NK) cells was studied. Treatment with TNF-alpha (100 units ml-1) for 48 h enhanced the susceptibility of tumour cells to lysis by NK cells. Increased susceptibility to lysis was associated with enhanced expression of intercellular adhesion molecule 1 (ICAM-1) and HLA class I antigen. Antisense ICAM-1 oligonucleotide inhibited lysis by NK cells of TNF-alpha-treated tumour cells. In contrast, acid treatment following TNF-alpha treatment increased lysis by NK cells. These findings indicate that TNF-alpha treatment of glioblastoma cells increased their susceptibility to lysis by NK cells, since ICAM-1 up-regulation would have more profound effects on NK susceptibility than would HLA class I antigen up-regulation.

Antigens, Neoplasm↗
PubMed1994

Interferon-gamma induces a decrease in the susceptibility of human glioma cells to lysis by lymphokine-activated killer cells.

We studied the effect that treating two types of glioblastoma cell lines, U-87 MG and U-251 MG, with interferon (IFN)-gamma had on their susceptibility to lysis by lymphokine-activated killer (LAK) cells. We also examined the participation of cell-adhesion molecules and major histocompatibility complex (MHC) class I and II antigens present on the target cells in lysis by LAK cells. Treatment with IFN-gamma (1000 U/ml) for 48 hours resulted in the increased expression of both intercellular-adhesion molecule 1 and MHC class I antigens on tumor cells. In addition, untreated tumor cells expressed neural-cell-adhesion molecules and MHC class II antigens highly, but their expression was not affected by IFN-gamma treatment. These changes in expression were accompanied by a decreased susceptibility to lysis by LAK cells. Treatment with antisense-intercellular-adhesion molecule-1 oligonucleotide further inhibited LAK lysis of target cells, following treatment with IFN-gamma. In contrast, acid treatment of tumor cells after treatment with IFN-gamma increased their susceptibility to lysis by LAK cells. These findings suggest that treatment of glioblastoma cells with IFN-gamma decreased their susceptibility to lysis by LAK cells, and that this decrease in susceptibility is attributable principally to the increased expression of MHC class I antigen on target cells.

Base Sequence↗
PubMed1993

Antitumour activity of an immunoconjugate composed of anti-human astrocytoma monoclonal antibody and neocarzinostatin.

Neocarzinostatin (NCS) linked to the thiol group on the hinge region of the Fab' fragment of GA-17, a murine monoclonal antibody reacting with tyrosine-specific phosphorylated antigens, which are exclusively expressed on the cell surface of human astrocytomas, was evaluated for in vivo activity. GA-17-NCS immunoconjugates significantly suppressed the growth of human malignant glioma cell line U87-MG subcutaneous xenografts in nude mice until day 50 when administered intravenously into the tail vein. Disulphide- and thioether-linked GA-17-NCS were nearly equipotent immunoconjugates, but thioether-linked GA-17-NCS was more effective than disulphide-linked conjugates with 250 U/kg NCS content on day 50 (P < 0.05). Thioether-linked GA-17-NCS was significantly more effective on day 50 than free NCS with 500 U/kg or 250 U/kg NCS content (P < 0.05, P < 0.01, respectively). These results suggest that GA-17-NCS may prove useful in the treatment of human malignant gliomas.

Animals↗
PubMed1993

Isolation and characterization of a novel microsomal membrane-bound phenol sulfotransferase from bovine liver.

A novel phenol sulfotransferase (PST) was detected in bovine liver microsomal membrane fraction. The enzyme was found to be capable of catalyzing the sulfation of simple phenolic compounds, with 3'-phosphoadenosine-5'-phosphosulfate as the sulfate donor. Detergent extracted PST showed a pH optimum of 5.7 and, among the simple phenols tested, the PST exhibited highest activity toward alpha-naphthol. No activities were detected when tyrosine and its derivatives were used as substrates. Both 2,6-dichloro-4-nitrophenol and chlorpromazine were capable of inhibiting the activity of the PST toward p-nitrophenol with inhibition Coefficient50 values of 100 nM and 4 mM, respectively.

Animals↗
PubMed1992

Analysis of the close relationship between human astrocytoma-specific antigens detected by murine monoclonal antibodies and c-kit proto-oncogene product.

Tyrosine-specific phosphorylated proteins found exclusively on the cell surface of human astrocytomas were previously identified with murine monoclonal antibodies, designated as GA-17, GB-4 and GC-3. The purpose of this study was to further characterize the antigens and investigate the relationship between them and c-kit protooncogene product. We demonstrated that the antigens had protein kinase activity. Moreover, GA-17 reacted with c-kit protein expressed on the membrane of A172 human glioblastoma cells.

Antibodies, Monoclonal↗
PubMed1992

Post-translational modification of protein by tyrosine sulfation: active sulfate PAPS is the essential substrate for this modification.

In vitro tyrosine sulfation of recombinant proteins would be a valuable tool in converting those proteins expressed in prokaryotic vectors to their natural form. For this purpose tyrosylprotein sulfotransferase (TPST), the enzyme responsible for tyrosine sulfation of proteins, was characterized from a bovine liver Golgi preparation. TPST was active in a acidic environment with a pH optimum of 6.25, and displayed a stimulation by the Mn2+, with the optimum activity in the presence of 5mM MnCl2. TPST was able to sulfate recombinant hirudin variant 1 (rHV-1) expressed in Escherichia coli and the C-terminal hirudin fragment 54-65 but not the N-terminal hirudin fragment 1-15 by using 3'-phosphoadenosine 5'-phosphosulfate (PAPS), indicating its specificity for the naturally sulfated tyrosine 63. Comparison of the reaction kinetics on synthetic peptides showed that the bovine liver TPST has a higher affinity and reaction rates for those peptides with a aspartyl residue on the N-terminal side of the tyrosine when compared with a glutamyl residue.

Amino Acid Sequence↗
PubMed1991

Malignant meningioma with repeated multiple recurrence. A case report.

A case of malignant meningioma with repeated multiple recurrence was reported. A 22 year-old male first underwent the total removal of left parieto-occipital convexity meningioma in 1965. Although he had lived an uneventful life after the operation, he recognized motor weakness of the left lower limb in April 1985 when he was 41 years old and CT revealed a large tumor in the parieto-occipital parasagittal region. He underwent the total removal of the tumor and cranioplasty on May 23, 1985. After the second operation, repeated recurrence of multiple tumors was seen, which were in the frontal, parietal and occipital convexities, parasagittal regions and falx. He underwent further operations on January 23, 1986, December 11, 1986, March 30, 1987 and July 20, 1987 in addition to the first and second ones. Histological study on every operation indicated malignant meningioma with mitosis, hypercellularity and necrosis. Though radiotherapy (56 Gy whole brain irradiation) was conducted after the sixth operation, multiple tumors recurred and clinical symptoms and signs deteriorated gradually and he finally died September 9, 1989. In malignant meningioma such as our case, early aggressive radiotherapy and chemotherapy should be considered besides radical operations.

Adult↗
PubMed1991

[A case of pregnancy-induced lymphocytic adenohypophysitis complicated by postpartum painless thyroiditis].

We report a patient with pregnancy-induced lymphocytic adenohypophysitis complicated by postpartum painless thyroiditis. A 27-year-old female noticed visual field defect in the 36th week of pregnancy. After delivery in the 39th week by cesarean section, she was admitted for close examination. Goiter was not palpable, and postpartum galactorrhea was not observed. Routine examination revealed no abnormal findings. On October 8, 1989, magnetic resonance imaging (MRI) revealed a tumor image (height 22.4mm) from the sella turcia to suprasellar cistern with a lower signal intensity than that of the white matter on T1 weighted images and a high signal intensity on T2 weighted images. Gd-DTPA contrast images showed a symmetrical and homogeneous tumor image at the same site. However, the posterior lobe of the pituitary gland appeared normal. These findings suggested lymphocytic adenohypophysitis. The LH was less than 0.3mIU/ml. The FSH (7.8mIU/ml), PRL (12ng/ml), GH (1.6ng/ml) and cortisol (10 micrograms/dl) levels were normal. T4 was 5.3 micrograms/dl, T3 67ng/dl, fT4 0.53ng/dl, which indicated mild hypothyroidism, but the TSH was normal. TRH test showed a slight increase in TSH and no response of PRL. Insulin tolerance test showed delayed response of GH and normal response of cortisol. LHRH test revealed no response of LH and delayed response of FSH. Anti-GH3 cell antibody and anti-thyroglobulin antibody were positive, but the anti-AtT20 cell antibody was negative. Since visual disturbance improved, and slight reduction in the mass (height 20.1mm) was confirmed by MRI after delivery on October 21, her course was observed without treatment. After 1 month, the LH became detectable, but the PRL and cortisol decreased to 2.5ng/ml and 6.0 micrograms/dl, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

Study on cases with posterior fossa epidural hematoma--clinical features and indications for operation.

In this retrospective study, 11 cases of posterior fossa epidural hematoma were analyzed in terms of clinical and radiological features, treatment, and outcome. Posterior fossa epidural hematomas accounted for 11.8% of all epidural hematomas encountered during the 7-year period studied. There were eight males and three females ranging in age from 2 to 53 years (mean, 20.7 years). Glasgow Coma Scale scores on admission were relatively good in many cases. Headache and/or vomiting were common symptoms on admission, whereas cerebellar signs were rare. As all 11 cases involved trauma, occipital fractures were present in eight (72.7%). Six patients underwent surgery. The indications for surgery, in terms of computed tomography findings, were: 1) the maximum thickness of the epidural hematoma was more than 15 mm; 2) the posterior fossa cisterns (e.g., the quadrigeminal and ambient cisterns) were poorly visualized; 3) there was marked deformity and/or displacement of the fourth ventricle; and 4) the hematoma extended to the supratentorial region and severely compressed the brain. At discharge, eight patients showed good recovery and one was moderately disabled. Two patients died. The prognosis for posterior fossa epidural hematoma appears relatively good, if it is not accompanied by severe primary brainstem injury and is diagnosed early, and appropriately and promptly treated.

Adolescent↗