Search PubMed⌕ Search

Biomedical subjects

S Kawaguchi

Publications and source records attributed to S Kawaguchi.

At least 73 records · Page 4Linked to original sources
PubMed2000

Induction of apoptosis in glioma cells by recombinant human Fas ligand.

OBJECTIVE: Fas ligand (FasL) belongs to the tumor necrosis factor family and has the ability to induce apoptosis in susceptible target cells by binding to its receptor, Fas. It has been demonstrated recently that the FasL/Fas system plays a pivotal role in the cytocidal activity of T lymphocytes in the immune system. FasL may act as a cytotoxic effector molecule to Fas-expressing malignant tumor cells. We reported previously that Fas is commonly expressed in human brain tumor cells. In this study, we examine the possible application of FasL to therapy for malignant brain tumors. METHODS: To develop an expression system yielding large amounts of FasL, we constructed a baculovirus vector containing complementary deoxyribonucleic acid of human FasL under the control of a polyhedrin promoter. We produced human FasL in Spodoptera frugiperda (Sf9) insect cells infected by the recombinant baculovirus carrying FasL complementary deoxyribonucleic acid and studied the cytocidal activity of FasL against the T98G human glioblastoma cell line. RESULTS: FasL expression in Sf9 cells was confirmed immunocytochemically with rabbit antibody raised against the cytoplasmic domain of human FasL. The FasL released into the supernatant of cultured Sf9 cells was also verified by Western blotting, and it specifically induced apoptosis in T98G cells. The induced apoptosis by recombinant human FasL was confirmed by annexin V-fluorescein isothiocyanate staining. CONCLUSION: The present results suggest that the induction of apoptosis by the Fas/FasL system could be a new strategy for the treatment of malignant brain tumors, which are resistant to conventional therapies.

Animals↗
PubMed2000

Effect of direct arterial bypass on the prevention of future stroke in patients with the hemorrhagic variety of moyamoya disease.

OBJECT: The authors evaluated the effects of superficial temporal artery-middle cerebral artery (STA-MCA) bypass in the prevention of future stroke, including rebleeding or an ischemic event, in patients suffering from hemorrhagic moyamoya disease by comparing this method with indirect bypass and conservative treatment. METHODS: Twenty-two patients who had hemorrhagic moyamoya disease but no aneurysm comprised the study group. These patients' clinical charts were examined with respect to their treatment and clinical course after an initial hemorrhagic episode. The mean age of the patients was 43 years and the follow-up period ranged from 0.8 to 15.1 years, with a mean of 8 years. Eleven patients (50%) were conservatively treated. Among the 11 patients who were surgically treated, STA-MCA bypass was performed in six patients (27%) and encephaloduroarteriosynangiosis (EDAS) in the other five patients (23%). Nine patients (41%) presented with an ischemic or rebleeding event during the follow-up period. The incidence of future stroke events in patients who had undergone an STA-MCA bypass was significantly lower (p<0.05) than that in patients who had been treated conservatively or with EDAS. Kaplan-Meier plots comparing stroke-free times in patients treated with direct bypass and those in patients who conservatively or with indirect bypass showed a significant difference (p<0.05) in favor of direct bypass. CONCLUSIONS: The effect of STA-MCA bypass on the prevention of recurrent hemorrhage or an ischemic event in patients with hemorrhagic moyamoya disease has been statistically confirmed in this study.

Adult↗
PubMed2000

Vascular endothelial growth factor expression in untreated osteosarcoma is predictive of pulmonary metastasis and poor prognosis.

To investigate the clinical significance of vascular endothelial growth factor (VEGF) in osteosarcoma, we immunohistochemically stained biopsy specimens of 27 primary osteosarcomas using an antibody against VEGF and evaluated the correlation between the expression of VEGF and local density of CD34-positive microvessels, clinicopathological variables, and survival of patients. VEGF staining was positive in 17 tumors (63.0%) in which the density of CD34-positive microvessels was significantly higher than that in VEGF-negative 10 tumors (P < 0.05). In terms of clinicopathological variables, there was no correlation between the expression of VEGF and histological subtype, stage, or response to neoadjuvant chemotherapy, or, strikingly, to the development of pulmonary metastasis (89% of VEGF-positive tumors versus 10% of VEGF-negative tumors; P < 0.0003). Moreover, patients with a VEGF-positive tumor were poorer in both disease-free survival (P < 0.001) and overall survival (P < 0.03) compared to those with a VEGF-negative tumor. These findings strongly suggest that VEGF expression in untreated osteosarcoma is predictive of pulmonary metastasis and poor prognosis in patients who underwent aggressive therapy and also provide the basis for a therapeutic strategy targeting angiogeneic property of osteosarcoma.

Adolescent↗
PubMed1999

Conformation of poly(methacrylic acid) in acidic aqueous solution studied by small angle X-ray scattering.

The nature of the contracted form of poly(methacrylic acid) PMA chain in salt-free acidic aqueous solution was studied by analyzing scattering curves registered by small-angle X-ray scattering, comparing it with those of PMA in methanol at 26 degrees C and of partially neutralized PMA in aqueous solution containing added salt (the concentration of added salt, Cs=0.1 M NaF). It is shown that the distribution of segments in the contracted form as well as that of PMA in methanol is that of a random-coil in a theta medium and that this distribution of segments is stable over a fair range of degrees of ionization alpha for Cs below 0.1 M. Moreover, the persistence length of PMA at Cs=0.1 M (4+/-0.5 A) is substantially constant throughout the entire range of alpha, indicating that the contracted form of PMA changes to an expanded random-coil in a higher pH region without a significant change in the chain flexibility.

Journal Article↗
PubMed1999

Multiple chondromatous hamartomas of the lung: a case report and review of the literature with special reference to Carney syndrome.

BACKGROUND: Multiple chondromatous hamartomas of the lung, which are very rare, are a feature of Carney syndrome. The relation between the two entities is not clear. METHODS: A patient with multiple chondromatous hamartomas of the lung is described in this article. The literature was reviewed with special reference to the relation between multiple chondromatous hamartomas of the lung and Carney syndrome as well as the triad of gastric epithelioid leiomyosarcoma, functioning extra-adrenal paraganglioma, and pulmonary chondroma. RESULTS: A total of 15 cases of multiple chondromatous hamartomas of the lung have been published worldwide. Two cases exhibited two other features of Carney syndrome, namely, gastric leiomyogenic neoplasms and extra-adrenal paragangliomas, and three other cases demonstrated only gastric leiomyomatous neoplasms. These five patients were all young females. CONCLUSIONS: Some patients with multiple chondromatous hamartomas of the lung have a history of Carney syndrome. Patients with multiple chondromatous hamartomas require further examination of other sites, particularly the stomach and nervous system.

Chondromatosis↗
PubMed1999

Structure of Thermus thermophilus HB8 aspartate aminotransferase and its complex with maleate.

The three-dimensional structures of pyridoxal 5'-phosphate-type aspartate aminotransferase (AspAT) from Thermus thermophilus HB8 and pyridoxamine 5'-phosphate type one in complex with maleate have been determined by X-ray crystallography at 1.8 and 2.6 A resolution, respectively. The enzyme is a homodimer, and the polypeptide chain of the subunit is folded into one arm, one small domain, and one large domain. AspATs from many species were classified into aminotransferase subgroups Ia and Ib. The enzyme belongs to subgroup Ib, its sequence being less than 16% identical to the primary sequences of Escherichia coli, pig cytosolic, and chicken mitochondrial AspATs, which belong to subgroup Ia whose sequences are more than 40% identical and whose three-dimensional structures are quite similar with the active site residues almost completely conserved. The first X-ray analysis of AspAT subgroup Ib indicated that the overall and the active site structures are essentially conserved between the AspATs of subgroup Ia and the enzyme of subgroup Ib, but there are two distinct differences between them. (1) In AspAT subgroup Ia, substrate (or inhibitor) binding induces a large movement of the small domain as a whole to close the active site. However, in the enzyme of subgroup Ib, only the N-terminal region (Lys13-Val30) of the small domain approaches the active site to interact with the maleate. (2) In AspAT subgroup Ia, Arg292 recognizes the side chain carboxylate of the substrate; however, residue 292 of the enzyme in subgroup Ib is not Arg, and in place of Arg292, Lys109 forms a salt bridge with the side chain carboxylate. The thermostability of the enzyme is attained at least in part by the high content of Pro residues in the beta-turns and the marked increase in the number of salt bridges on the molecular surface compared with the mesophilic AspAT.

Amino Acid Sequence↗
PubMed1999

Regeneration of the lateral vestibulospinal tract in adult rats by transplants of embryonic brain tissue.

We transected the lateral vestibulospinal tract in the spinal cord of adult rats. In one group we performed simple transection, and in other group we transplanted the lesion with embryonic tissue. In rats receiving simple transection, there was no regeneration, but in 22% of the rats receiving transplants of embryonic tissue, the axon regrew beyond the transected site, regenerated on the denervated side, terminating in the normal targets. The present findings are contrary to the widely held view that the adult mammalian central vestibular system cannot be restored following damage.

Animals↗
PubMed1999

Establishment and characterization of human pancreatic carcinoma lines with a high metastatic potential in the liver of nude mice.

To investigate of human pancreatic cancer metastasis to the liver, a pancreatic carcinoma line, HPC-3, was injected into the spleens of nude mice. The cells from a few liver metastatic foci of the mice injected with HPC-3 were expanded in vitro and subsequently injected into the spleens of nude mice. By repeating these procedures, we were able to obtain a cell line, designated HPC-3H4. The mice were observed to have liver metastasis in 6 of 6 (100%) cases injected with HPC-3H4, whereas the rate was 0% at 3 weeks after the intrasplenic injection of HPC-3. The tumorigenicity of HPC-3H4 was more rapid than that of HPC-3. The motile activity of HPC-3H4 was also stronger than that of HPC-3, and the adhesion to the extracellular matrix of HPC-3H4 was stronger than that of HPC-3. We also analyzed the cell surface expression of the metastasis-related adhesion molecules. As a result, no substantial changes were observed in the expression level of adhesion molecules. These results suggest that HPC-3H4 is useful for studies aimed at the prevention of liver metastasis.

Animals↗
PubMed1999

Regeneration of the mammalian central vestibular pathway using the rat as animal model.

Regeneration of the mammalian central vestibular system was examined in rat. The lateral vestibulospinal tract (LVST) of infant rat was transected unilaterally at the level of C1-3. After a postoperative interval of several weeks, the LVST was examined by injecting an anterograde tracer (wheat germ agglutinin-conjugated horseradish peroxidase) into the lateral vestibular nucleus (LVN) and a retrograde tracer (Fast Blue) into the lumbar enlargement. More than half of the rats showed successful regeneration, indicating definite plasticity in the mammalian central vestibular system.

Animals↗
PubMed1999

Effects of bypass on CO2 cerebrovascular reactivity in ischaemic cerebrovascular diseases--based on the intra-operative LCBF and CO2 cerebrovascular reactivity studies.

The authors evaluated the effects of superficial temporal to middle cerebral artery (STA-MCA) bypass on CO2 cerebrovascular reactivity (CVR) in ischaemic cerebrovascular diseases (CVDs). Local cerebral blood flow (LCBF) and CO2 CVR in 19 patients with ischaemic CVD subjected to standard STA-MCA bypasses were examined during surgery. Single photon emission computed tomography (SPECT) with acetazolamide (ACZ) activation was also performed before and at 1 month after surgery. The results are as follows. 1) Before bypass, the average CO2 CVR value was -1.50 +/- 2.30%/mmHg (mean +/- SD). SPECT showed disturbed response to ACZ in all cases. Fifteen cases showed the steal phenomenon. After bypass, the mean CO2 CVR value significantly (p < 0.05) increased, and four cases resolved their steal phenomenon. 2) Before bypass, the mean LCBF was significantly (p < 0.05) lower than the control level. After bypass, the mean LCBF significantly (p < 0.05) increased. 3) In the postoperative SPECT findings, 13 cases showed a disturbed response to ACZ. The CO2 CVR value in these 13 cases was -1.21 +/- 1.19%/mmHg, which was significantly (p < 0.05) low compared to the values for the 6 cases showing normal postoperative ACZ responses. In ischaemic CVDs before bypass, the CO2 CVR values were extremely low. After bypass, however, CO2 CVR and LCBF values significantly improved. SPECT findings, including ACZ challenge, correlated well to the LCBF and CO2 CVR values. STA-MCA by pass exerted a favourable effect on the CO2 CVR and LCBF values immediately after bypass in the cases showing a reduced pre-operative response to CO2.

Acetazolamide↗
PubMed1999

Endovascular stent graft repair of aortopulmonary fistula.

Two patients who had aortopulmonary fistula of postoperative origin with hemoptysis underwent successful repair by means of an endovascular stent graft procedure. One patient had undergone repeated thoracotomies two times, and the other one time to repair anastomotic aneurysms of the descending aorta after surgery for Takayasu's arteritis. A self-expanding stainless steel stent covered with a Dacron graft was inserted into the lesion through the external iliac or femoral artery. The patients recovered well, with no signs of infection or recurrent hemoptysis 8 months after the procedure. Endovascular stent grafting may be a therapeutic option for treating patients with aortopulmonary fistula.

Anastomosis, Surgical↗
PubMed1999

Regeneration of the central auditory pathway in adult rats.

Regeneration of the auditory pathway in the central nervous system, which has not been reported previously, was investigated in adult rats. The ventral cochlear tract (VCT) in the medulla oblongata of adult rats was completely transected unilaterally by a ventral approach through an opening in the basioccipital bone. After postoperative intervals of 1 day to 3 months, the cochlear tract was examined by an anterograde tracing method using wheat germ aggulutinin-conjugated horseradish peroxidase (WGA-HRP) injected unilaterally in the ventral cochlear nucleus (VCN) ipsilateral to the lesion. In this simple transection experiment no regeneration was observed. However, when embryo brainstem tissue was transplanted on the transected site, regeneration occurred in about 30% of the rats examined. These results indicate the occurrence of obvious regeneration in the central auditory pathway, which was previously thought not to be restored once damaged, and they raise hope for future treatment of humans.

Animals↗
PubMed1999

Cervical myelopathy due to dynamic compression by the laminectomy membrane: dynamic MR imaging study.

Dynamic magnetic resonance (MR) imaging is useful in assessing delayed neurologic deterioration after multilevel cervical laminectomy. The authors report a case of a 75-year-old woman who deteriorated 24 years after a C4-C7 laminectomy. When the extension MR demonstrated marked spinal cord compression attributable to a laminectomy membrane, the patient had an anterior diskectomy and fusion performed, after which she demonstrated significant neurologic improvement. In this and other cases, the dynamic MR may be a useful tool in discerning the etiology of the delayed neurologic changes occurring in postoperative patients.

Aged↗
PubMed1999

[Endodermal cyst of the cerebellopontine angle cistern: case report].

We report a case of a 55-year-old man with endodermal cyst located in the cerebellopontine angle cistern. The patient presented with dizziness. Magnetic resonance imaging (MRI) revealed multilocular cystic lesion at the right cerebellopontine angle. T1-weighted image showed a mass with a low signal intensity, but higher intensity than CSF. Gd-DTPA T1-weighted image showed no enhancement in the mass. Diffusion-weighted image showed a mass with no signal lesion. After successful surgical removal, it was found to be an endodermal cyst. These cysts have usually been found in the spinal canal, and their intracranial occurrence is exceptional. The unusual location of the cyst and its histological features and radiological findings are discussed.

Cerebellar Diseases↗
PubMed1998

Regeneration of the auditory pathway in adult rats by transplants of fetal brain tissue.

The ventral cochlear tract in the brain stem to pons was transected on one side in two groups of adult rats. In one group simple transection was performed, while in the other group tissue from embryos (E14-E16) was used to cover the lesion site. While rats receiving simple transection without transplantation showed no evidence of regeneration, in 30% of the rats receiving transplants of embryonic tissue the axons regrew beyond the transected site and regenerated into the denervated side and terminated at the normal targets. The present findings contradict the widely held view that the adult mammalian central auditory system cannot be restored following damage.

Animals↗
PubMed1998

The novel substrate recognition mechanism utilized by aspartate aminotransferase of the extreme thermophile Thermus thermophilus HB8.

Aspartate aminotransferase (AspAT) is a unique enzyme that can react with two types of substrate with quite different properties, acidic substrates, such as aspartate and glutamate, and neutral substrates, although the catalytic group Lys-258 acts on both types of substrate. The dynamic properties of the substrate-binding site are indispensable to the interaction with hydrophobic substrates (Kawaguchi, S., Nobe, Y., Yasuoka, J., Wakamiya, T., Kusumoto, S., and Kuramitsu, S. (1997) J. Biochem. (Tokyo) 122, 55-63). AspATs from various organisms are classified into two subgroups, Ia and Ib. The former includes AspATs from Escherichia coli and higher eukaryotes, whereas the latter includes those from Thermus thermophilus and many prokaryotes. The AspATs belonging to subgroup Ia each have an Arg-292 residue, which interacts with the distal carboxyl groups of dicarboxylic (acidic) substrates, but the functionally similar residue of subgroup Ib AspATs has not been identified. In view of the x-ray crystallographic structure of T. thermophilus AspAT, we expected Lys-109 to be this residue in the subgroup Ib AspATs and constructed K109V and K109S mutants. Replacing Lys-109 with Val or Ser resulted in loss of activity toward acidic substrates but increased that toward the neutral substrate, alanine, considerably. These results indicate that Lys-109 is a major determinant of the acidic substrate specificity of subgroup Ib AspATs. Kinetic analysis of the interactions with neutral substrates indicated that T. thermophilus AspAT is subject to less steric hindrance and its substrate-binding pocket has a more flexible conformation than E. coli AspAT. A flexible active site in the rigid T. thermophilus AspAT molecule may explain its high activity even at room temperature.

Amino Acid Sequence↗