Biomedical subjects

K Sugiyama

Publications and source records attributed to K Sugiyama.

At least 73 records · Page 4Linked to original sources

PubMed2001

Change of hypervariable region proteins of hepatitis C virus E2 in two infants.

Two infants vertically infected with hepatitis C virus (HCV) were followed-up from 3 or 4 months to 2.5 years of age. We analyzed five complementary DNA (cDNA) clones from each patient and compared the genetic drift of the HCV E2 gene hypervariable region (HVR) between the two infants and between the infants and their mothers within the two families. The HCV strains initially detected in infant 1 were identical to those found in her mother, while the HCV strains initially detected in infant 2 were very different from those of her mother. The mutation rate of HVR-1 proteins was higher in mother 1 than in mother 2, but was 1.6 to 2-fold higher in infant 2 than in infant 1 during the follow-up period. Serum ALT levels or serum HCV-core protein activity did not correlate with the mutation rates of HVR-1 proteins in either infant. However, the mutation rate of HVR-1 proteins significantly increased from 6 months of age in both infants, with concomitantly increased serum HCV antibody (anti-HCV) levels.

Adult↗

PubMed2001

[A case of juvenile pilocytic astrocytoma with unusual neuroimaging features].

We present a case of cerebellar juvenile pilocytic astrocytoma(JPA) with unusual neuroimaging features. The patient was a 14-year-old male who suffered from chronic headaches for a couple of weeks. Plain craniogram showed a decalcification and bulging of the occipital bone. Computed tomography(CT) scans demonstrated low density multiple components with small calcifications in the right cerebellar hemisphere extending to the left. These calcifications were found at the margin of these multi-lobular components. Magnetic resonance imaging(MRI) revealed iso or low intensity on T1 weighted image, and slightly high intensity on T2 weighted image. The lesion indicated more heterogeneous and higher intensity than brain parenchyma on FLAIR imaging, and remarkable higher intensity than brain parenchyma with some small low intensity areas on diffusion weighted imaging. He underwent the complete resection except for the cranial tissue surrounding the pons. Histologic diagnosis was juvenile pilocytic astrocytoma, because of biphasic pattern of bipolar cells and a number of Rosenthal fibers. Generally JPA has sharp and smooth demarcated cysts with well-enhanced mural nodule. It was difficult to diagnose the presented tumor as JPA before operation, since its unusual neuroimaging resembled both dermoid and high grade gliomas.

Adolescent↗

PubMed2001

Prediction of peritoneal micrometastasis by peritoneal lavaged cytology and reverse transcriptase-polymerase chain reaction for matrix metalloproteinase-7 mRNA.

PURPOSE: Peritoneal dissemination is the most common cause of death associated with gastric cancer. In this study, we report the significance of molecular diagnosis of peritoneal dissemination by means of matrix metalloproteinase-7 (MMP-7) reverse transcriptase-PCR (RT-PCR) assay using preoperative peritoneal wash fluid. EXPERIMENTAL DESIGN: Preoperative peritoneal lavage by paracentesis was performed on 152 patients with gastric cancer. The peritoneal lavaged fluid was subjected to RT-PCR analysis with primers specific for MMP-7 and conventional cytological Papanicolaou examination. RESULTS: The MMP-7 RT-PCR assay was able to detect cancer cells at densities even lower than 10 cells/sample. There was no signal of MMP-7 mRNA from mesothelial cells, fibroblasts, peripheral blood, and lavaged fluid from patients with benign disease. Cytological examination and MMP-7 RT-PCR assay results were positive for 27 (18%) and 28 (18%) samples, respectively. The sensitivity for the prediction of peritoneal dissemination by cytology and MMP-7 RT-PCR assay were 46% and 33%, but the combination analysis using both parameters improved the sensitivity rate with 62%. Logistic regression analysis revealed that the cytological examination and MMP-7 RT-PCR assay are independent predictors of peritoneal dissemination. CONCLUSION: The combination of cytological examination and RT-PCR assay of preoperative peritoneal lavaged fluid is a highly efficient and reliable method for the selection of patients for adjuvant i.p. chemotherapy.

Adult↗

PubMed2001

[Anterior cerebral artery dissecting aneurysm associated with fibromuscular dysplasia (FMD): a case report].

We have recently encountered a rare case of anterior cerebral artery dissecting aneurysm, presenting cerebral infarction and subarachnoid hemorrhage, associated with fibromuscular dysplasia (FMD). A 50-year-old woman was admitted to our hospital with complaints of headache and hemiparesis. A right carotid angiogram obtained 9 hours after the onset revealed stenosis and slight dilatation in the A1 portion of the anterior cerebral artery. At 12 hours after the onset, the patient fell into a coma. CT scan showed diffuse subarachnoid hemorrhage. An angiogram had revealed aneurysmal dilatation and double lumen in the A1 portion, but, 34 days after the onset, angiogram showed growth of the aneurysm in the A1 portion and stenosis in the A2 and A3 portions. At 38 days after the onset, the trapping of the dilated aneurysm to prevent rerupture was performed. Pathological diagnosis was concluded to be FMD. We concluded that FMD caused stenosis as well as the formation and rupture of the dissecting aneurysm in the anterior cerebral artery.

Aortic Dissection↗

PubMed2001

[The efficacy of combination chemotherapy of 5'-deoxy-5-fluorouridine (5'-DFUR), cyclophosphamide (CPA) and medroxyprogesterone acetate (MPA) for bone metastasis in breast cancer patients].

5'-DFUR is a pro drug of 5-FU, which is known to be converted by thymidine phosphorylase (dThdPase). A recent pre-clinical study revealed that CPA upregulates dThdPase activity specifically in tumor cells. Furthermore, clinical trials have shown significant response rates in breast cancer patients, when using the chemotherapy combination of 5'-DFUR, CPA and MPA. The purpose of this study was to examine the efficacy of this regimen as a pain reduction therapy for breast cancer patients with bone metastasis. Ten patients who had bone metastasis with restricted ADL were included in the study. All of the patients had had previous exposure to such standard chemotherapy as CAF, CMF, taxol and oral 5-FU administration. The patients were administered daily oral doses of 5'-DFUR at 800-1,200 mg, CPA at 200 mg and MPA at 400-800 mg for two weeks as induction therapy, followed by two weeks rest (one to two cycles). Daily dose of 800 mg of 5'-DFUR, 100 mg of CPA, 400-800 mg of MPA was continuously administered thereafter. The main findings included a significant decrease in pain in eight patients, which continued for more than 6 months. In five patients, the effect lasted more than one year. As the pain decreased, the patients' QOL was improved. Hematological toxicity of more than grade 3 was observed in three patients but only during the induction therapy. One patient had pulmonary thrombosis and required hospitalization. In conclusion, oral administration of 5'-DFUR/CPA/MPA is well tolerated and useful in reducing pain.

Adult↗

PubMed2001

Inhibition of peritoneal dissemination in human gastric cancer by MMP-7-specific antisense oligonucleotide.

MMP-7 is a matrix-degrading enzyme that is mainly produced from cancer cells, and has a great role in the invasion and metastasis of cancer. We have established a highly metastatic cell line (MKN-45-P) on the peritoneum of nude mice from MKN-45 by repeated intraperitoneal inoculation of intraperitoneal free cancer cells. By the precise screening of metastasis-related genes using reverse transcriptase-polymerase chain reaction (RT-PCR), MKN-45-P characteristically expressed more MMP-7 than the original cell line of MKN-45. In this study, we studied the effects of antisense oligonucleotides complementary to exon 3 of MMP-7 mRNA on the expression of MMP-7 and metastatic potential of MKN-45-P by using in vitro and in vivo experiments. RT-PCR and western blot analysis demonstrated that 10 microM antisense oligonucleotides suppressed MMP-7 expression at both the mRNA level (84%) and protein level (56%). Antisense oligonucleotides, specific for MMP-7 suppressed invasion by MKN-45-P cells without influencing proliferation. On the other hand, scrambling sequence control oligonucleotides did not show any inhibitory effects. In addition, survival of MKN-45-P bearing mice, which had been treated for 48 hrs with antisense oligonucleotides before intraperitoneal injection, was significantly better than that of control mice. In contrast, control oligonucleotides did not influence the survival of mice with the peritoneal dissemination model. These results strongly suggest that MMP-7 may have a great role in the formation of peritoneal dissemination in gastric cancer, and the molecular control of MMP-7 using antisense oligonucleotides may be a hopeful treatment modality for peritoneal dissemination.

Animals↗

PubMed2001

Falcotentorial meningioma accompanied by temporal lobe hematoma.

We report a case of a falcotentorial meningioma accompanied by hematoma in the temporal lobe. A healthy 51 year-old-female with no history of hypertension presented with sudden onset of consciousness disturbance and right hemiparesis. Computed tomography revealed a hematoma 5.5 cm in diameter surrounded by thick edematous brain in the left temporal lobe and a tumor 3.5 cm in diameter in the pineal region. Bilateral carotid angiography detected occlusion of the Galenic vein and straight sinus. No causative abnormality of hemorrhage was apparent. However, the left basal vein of Rosenthal had disappeared, and anastomotic venous channels could be observed in the medial left temporal lobe, contiguous to the hematoma. Emergency craniotomy failed to detect any abnormality which could cause hemorrhage in the brain parenchyma surrounding the hematoma. Subtotal removal of the tumor, histologically diagnosed as fibrous meningioma, was achieved three months later employing an occipital transtentorial approach. Venous congestion caused by compression due to the tumor was considered to be one of possible causes of the hemorrhage.

Brain↗

PubMed2001

[Symptomatic subependymoma of the lateral ventricle in a young female].

We present a case of a symptomatic subependymoma (SE) in a young. The patient was a 20-year-old female who suffered from severe headache and vomiting. Precontrast CT scans revealed a large spotty-calcified isodensity mass lesion in the right anterior lateral ventricle, showing scarce contrast enhancement at the center of the mass and with marked hydrocephalus. MRI demonstrated the lesion as slightly hypo-intensity on T1-weighted image, hyper-intensity on T2-weighted image. On FLAIR imaging, the lesion indicated remarkable hyperintensity and was clearly distinguishable from surrounding brain parenchyma and the cerebrospinal fluid. After Gd-DTPA infusion central vein was revealed, but no tumor enhancement was seen. The tumor was totally extirpated through the transcortical approach. Histological diagnosis was SE, and high MIB-1 staining index (9.3%) was seen. FLAIR imaging is useful for the preoperative diagnosis and the postoperative assessment of SEs.

Adult↗

PubMed2000

Evolutionary aspects of gobioid fishes based upon a phylogenetic analysis of mitochondrial cytochrome B genes.

The Gobioidei is a large suborder in the order Perciformes and consists of more than 2000 species belonging to about 270 genera. The vast number of species and their morphological specialization adapted to diverse habits and habitats makes the classification of the gobioid fishes very difficult.A comprehensive estimation of the evolutionary scenario of all gobioid fishes using only morphological information is difficult for two major reasons: first, in addition to wide ecological diversification, there is a trend towards specialization and degeneration of morphological characters among these species; second, an appropriate outgroup of gobioid fishes has not been recognized. Based upon nucleotide sequence comparisons of gobioid mitochondrial cytochrome b genes, we established the phylogenetic relationships of their differentiation into many groups of morphological and ecological diversity. The phylogenetic trees obtained show that most species examined have diverged from each other almost simultaneously or during an extremely short period of time.

Animals↗

PubMed2000

Novel acyl-CoA synthetase in adrenoleukodystrophy target tissues.

X-linked adrenoleukodystrophy (X-ALD) is a neurodegenerative disorder characterized by demyelination of white matter. The X-ALD gene product adrenoleukodystrophy protein (ALDP) is expressed broadly among various tissues. However, deficiency of functional ALDP exclusively impairs brain, adrenal gland, and testis. Thus, loss of ALDP function is assumed to involve inactivation of a putative mediating factor that functions in a tissue-specific manner. Here we cloned a mouse cDNA encoding a novel protein, Lipidosin, that possesses long-chain acyl-CoA synthetase (LCAS) activity. Lipidosin is expressed exclusively in mouse brain, adrenal gland, and testis, which are affected by X-ALD. LCAS activity of Lipidosin was diminished by mutation of conserved amino acids within the AMP-binding domain. Mutation of the Drosophila homologue of Lipidosin has been reported to cause neuronal degeneration. Thus, Lipidosin may mediate the link between ALDP dysfunction and the impairment of fatty acid metabolism in X-ALD.

Adrenoleukodystrophy↗

PubMed2000

Role of glutathione in heat-shock-induced cell death of Saccharomyces cerevisiae.

Previously we reported that expression of GSH1 (gamma-glutamylcysteine synthetase) and GSH2 (glutathione synthetase) of the yeast Saccharomyces cerevisiae was increased by heat-shock stress in a Yap1p-dependent fashion and consequently intracellular glutathione content was increased [Sugiyama, Izawa and Inoue (2000) J. Biol. Chem. 275, 15535-15540]. In the present study, we discuss the physiological role of glutathione in the heat-shock stress response in this yeast. Both gsh1 and gsh2 mutants could acquire thermotolerance by mild heat-shock stress and induction of Hsp104p in both mutants was normal; however, mutant cells died faster by heat shock than their parental wild-type strain. After pretreatment at a sublethal temperature, the number of respiration-deficient mutants increased in a gsh1 mutant strain in the early stages of exposure to a lethal temperature, although this increase was partially suppressed by the addition of glutathione. These results lead us to suspect that an increase of glutathione synthesis during heat-shock stress is to protect mitochondrial DNA from oxidative damage. To investigate the correlation between mitochondrial DNA damage and glutathione, mitochondrial Mn-superoxide dismutase (the SOD2 gene product) was disrupted. As a result, the rate of generation of respiration-deficient mutants of a sod2 delta strain was higher than that of the isogenic wild-type strain and treatment of the sod2 delta mutant with buthionine sulphoximine, an inhibitor of glutathione synthesis, inhibited cell growth. These results suggest that glutathione synthesis is induced by heat shock to protect the mitochondrial DNA from oxidative damage that may lead to cell death.

Blotting, Western↗

PubMed2000

Transcription factor BACH1 is recruited to the nucleus by its novel alternative spliced isoform.

The transcription factor Bach1 is a member of a novel family of broad complex, tramtrack, bric-a-brac/poxvirus and zinc finger (BTB/POZ) basic region leucine zipper factors. Bach1 forms a heterodimer with MafK, a member of the small Maf protein family (MafF, MafG, and MafK), which recognizes the NF-E2/Maf recognition element, a cis-regulatory motif containing a 12-O-tetradecanoylphorbol-13-acetate-responsive element. Here we describe the gene structure of human BACH1, including a newly identified promoter and an alternatively RNA-spliced truncated form of BACH1, designated BACH1t, abundantly transcribed in human testis. The alternate splicing originated from the usage of a novel exon located 5.6 kilobase pairs downstream of the exon encoding the leucine zipper domain, and produced a protein that contained the conserved BTB/POZ, Cap'n collar, and basic region domains, but lacked the leucine zipper domain essential for NF-E2/Maf recognition element binding. Subcellular localization studies using green fluorescent protein as a reporter showed that full-length BACH1 localized to the cytoplasm, whereas BACH1t accumulated in the nucleus. Interestingly, coexpression of BACH1 and BACH1t demonstrated interaction between the molecules and the induction of nuclear import of BACH1. These results suggested that BACH1t recruits BACH1 to the nucleus through BTB domain-mediated interaction.

Alternative Splicing↗

PubMed2000

Specific ganglioside changes in extraneural tissues of adult rats with hypothyroidism.

Adults rats with hypothyroidism were prepared by administration of 6-propyl-2-thiouracil (PTU) or methimazole, and the tissues were examined for their gangliosides through methods including glycolipid-overlay techniques. Normal thyroid tissue contained GM3, GD3, and GD1a as the major gangliosides, with GM1, GD1b, GT1b, and GQ1b in lesser amounts. The goitrous tissue of PTU-induced hypothyroid rats had higher concentrations of GM1 and GD1a with a concomitant decrease of GM3. The amount of GT3 in thyroid tissue was increased in hypothyroid animals. While normal liver tissue had a complex ganglioside pattern with a- and b-series gangliosides, the PTU-induced hypothyroid tissue showed a simpler ganglioside profile that consisted mainly of a-series gangliosides with almost undetectable amounts of b-series gangliosides. The expression of c-series gangliosides was suppressed in the hypothyroid liver tissue. Heart tissue had higher contents of GM3 and GT3 than control. No apparent change was observed in the compositions of major and c-series gangliosides in other extraneural tissues (i.e., kidney, lung, spleen, thymus, pancreas, testis, skeletal muscle, and eye lenses), and neural tissues (i.e., cerebrum and cerebellum) from PTU-induced hypothyroid rats. The ganglioside changes of thyroid, liver, and heart tissues were reproduced in corresponding tissues of methimazole-induced hypothyroid rats. These results suggest that hypothyroid conditions affect the biosynthesis and expression of gangliosides in specific tissue and cell types.

Animals↗

PubMed2000

Recurrence of meningiomas.

BACKGROUND: Macroscopic total resection with removal of involved dura and bone does not always prevent the recurrence of meningioma of histologically benign subtype. Many causative factors have been investigated, although the mechanism of recurrence remains unclear. Vascular endothelial growth factor (VEGF) is a key factor in meningiomas neovascularization, and the authors investigated whether VEGF expression can predict the recurrence of histologically benign meningiomas after macroscopic total resection. METHODS: Fifty-four patients with supratentorial convexity meningiomas were investigated at least 3 years after surgery or until tumor recurrence to clarify risk factors for recurrence. Patients were restricted to Simpson Grade 1 resection only, and the authors excluded multiple meningiomas, neurofibromatosis, and atypical and anaplastic meningiomas. Correlation between recurrence and the following factors were statistically analyzed: age, gender, tumor volume, tumor shape, bone change, brain edema, vascular supply, histologic subtype, MIB-1 labeling index (LI), and VEGF expression. RESULTS: Of the 54 patients with meningioma, 34 were positive (24: +1; 10: +2) for VEGF, and 20 were negative. Six (11.1%) meningiomas recurred during the follow-up period. Multivariate analysis revealed that high levels of expression of VEGF constituted the most useful predictor of recurrence (P = 0.005), followed by high MIB-1 LI (P = 0.039). The other factors were not significant. The tumor recurrence, when it occurred, was within the brain and not durally based. CONCLUSIONS: The current results suggest that high levels of VEGF expression are significantly related to the recurrence of meningioma. VEGF secretion from microscopic residue remaining after surgery may induce neovascularization, which promotes the recurrence of meningioma.

Adult↗

PubMed2000

Gangliosides of rat eye lens: a severe reduction in the content of C-series gangliosides following streptozotocin treatment.

Gangliosides of eye lenses from normal and experimentally induced diabetic rats were investigated by methods including glycolipid-overlay techniques. Adult rat eye lens showed a complex ganglioside pattern that consisted of six major ganglioside components. These gangliosides were identified as GM3, GD3, GD1a, GD1b, GT1b, and GQ1b based upon their reactivity to anti-GM1 antibody after in situ sialidase treatment and mobility on thin-layer chromatography (TLC). Gangliosides in eye lens were further characterized by TLC-immunostaining with A2B5, a specific monoclonal antibody directed toward c-series gangliosides. Eye lens contained GT3 as the main c-series ganglioside component. Unexpectedly, the relative concentration of GT3 in total gangliosides of eye lens was highest among neural and extra-neural tissues examined. Administration of streptozotocin to rats caused a severe reduction in the GT3 content in eye lenses as early as day 3 without apparent changes in the composition of major gangliosides. Alloxan failed to produce such an effect despite producing similar hyperglycemic conditions. These results suggest that rat eye lens probably contains a streptozotocin-susceptible cell type(s), which is highly enriched with c-series gangliosides.

Animals↗

PubMed2000

The Yap1p-dependent induction of glutathione synthesis in heat shock response of Saccharomyces cerevisiae.

Glutathione is synthesized in two sequential reactions catalyzed by gamma-glutamylcysteine synthetase (GSH1 gene product) and glutathione synthetase (GSH2 gene product). The expression of GSH1 in Saccharomyces cerevisiae has been known to be up-regulated by Yap1p, a critical transcription factor for the oxidative stress response in yeast. The present study demonstrates that GSH2 expression is also regulated by Yap1p under oxidative stress-induced conditions. In addition to oxidative stress, expression of GSH1 and GSH2 was induced by heat shock stress in a Yap1p-dependent manner with subsequent increases in intracellular glutathione content. Oxygen respiration rate increased when cells were exposed to higher temperatures, and as a result, intracellular oxidation levels were increased. The heat shock-induced expression of GSH1 and GSH2 did not occur under anaerobic conditions. Furthermore, even under aerobic conditions, the heat shock response of these genes was not observed when cells were pretreated with KCN to block oxygen respiration. We speculate that heat shock stress enhances oxygen respiration, which in turn results in an increase in the generation of reactive oxygen species in mitochondria. This signal may be mediated by Yap1p, resulting in the elevation of intracellular glutathione levels.

Base Sequence↗

PubMed2000

A lectin from an edible mushroom Pleurotus ostreatus as a food intake-suppressing substance.

In an experiment in which rats were allowed free access to food and water, the rats did not eat the diet containing a mushroom Pleurotus ostreatus even if they were emaciated. A P. ostreatus lectin (POL) was isolated from the mushroom as the food intake-suppression principle. In hemagglutination inhibition assays, Me-alphaGalNAc was the most potent inhibitor among the monosaccharides tested. Among all the sugars tested, 2'-fucosyllactose (Fucalpha1-->2Galbeta1-->4Glc) was the strongest inhibitor and its inhibitory potency was five times greater than that of Me-alphaGalNAc. POL exhibited a binding ability to bovine submaxillary mucin (BSM) and asialo-BSM and the other glycoproteins were inert to the binding. The food intake-suppressing activity of POL was dependent on the dose. The diet containing 0.1% POL caused a 50% decrease in the food intake of rats against the control.

Amino Acids↗

PubMed2000

A distinct ganglioside composition of rat pancreatic islets.

Gangliosides in rat pancreatic tissue and isolated pancreatic islets were examined by methods including glycolipid-overlay techniques. The content of gangliosides in isolated pancreatic islets was approximately 6-fold higher than that in pancreatic tissue when compared on a protein basis. While N-glycolylneuraminic acid amounted to 7.2% of total lipid-bound sialic acids of pancreatic tissue, this molecular species was not detected in that of pancreatic islets. A remarkable difference in ganglioside composition was observed between pancreatic tissue and pancreatic islets. Pancreatic tissue showed a complex ganglioside pattern with GM3 as the largest ganglioside component, whereas isolated pancreatic islets had a simpler ganglioside profile without detectable amounts of GM3 and some other components. Pancreatic gangliosides were further examined by thin-layer chromatographic immunostaining with a monoclonal antibody A2B5 that reacts specifically with c-series gangliosides. Pancreatic tissue and pancreatic islets showed almost identical ganglioside patterns consisting of GT3, GT2, GQ1c, and GP1c. The concentration of c-series gangliosides in pancreatic islets was calculated to be more than 250-fold higher than that of pancreatic tissue. These results shows that pancreatic islet cells have a distinct ganglioside composition in rat pancreas.

Animals↗