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Biomedical subjects

A Kato

Publications and source records attributed to A Kato.

At least 127 records · Page 7Linked to original sources
PubMed2000

Reduced hepatic ischemia/reperfusion injury by IL-4: potential anti-inflammatory role of STAT6.

OBJECTIVE AND DESIGN: The ability of interleukin-4 (IL-4) to modulate activation of the transcription factors, NF-kappaB and STAT6, reduce proinflammatory cytokine expression and protect against liver injury induced by ischemia/reperfusion was assessed. MATERIALS AND SUBJECTS: C57BL/6 mice underwent 90 minutes of partial hepatic ischemia followed by 1 or 8 h of reperfusion with or without intravenous administration of 1 microg (0.5 microg just prior to ischemia, 0.5 microg at reperfusion) recombinant murine IL-4. Liver expression of TNFalpha mRNA was determined by RT-PCR. Activation of NF-kappaB and STAT6 in liver nuclear extracts was assessed by mobility shift assay. RESULTS: Hepatic ischemia/reperfusion increased hepatic expression of tumor necrosis factor-alpha (TNFalpha), induced significant neutrophil accumulation and liver injury. Treatment with IL-4 greatly suppressed liver TNFalpha mRNA expression, neutrophil accumulation and liver injury. IL-4 had no effect on liver NF-kappaB activation, but greatly increased the activation of STAT6. CONCLUSIONS: The data suggest that STAT6 activation by IL-4 may be responsible for the protective effects of this cytokine.

Animals↗
PubMed2000

Persistent trigeminal artery variants detected by MR angiography.

Persistent trigeminal artery (PTA) variants are cerebellar arteries that originate directly from the precavernous portion of the internal carotid artery (ICA). The goal of our study was to determine the incidence and MR angiographic features of PTA variants. Between April 1996 and September 1999, 523 cranial MR angiographies were performed at our institution. Most of the patients examined had or were suspected of having cerebrovascular disease. We retrospectively reviewed these 523 MR angiograms. A 1.5-T scanner was used in all studies, and maximum intensity projection (MIP) images obtained using the three-dimensional time-of-flight (3D TOF) technique were displayed stereoscopically. Four PTA variants were detected on MR angiograms, at a rate of 0.76%. At least three of the four PTA variants were anterior inferior cerebellar arteries (AICAs), small tortuous arteries arising from the precavernous portions of the ICAs and taking a posterior course. Although the clinical significance is not great, we found a relatively high incidence of PTA variants on MR angiograms. We stress that knowledge and recognition of these anomalous cerebellar arteries are useful and important in the interpretation of cranial MR angiograms.

Arteries↗
PubMed2000

Middle cerebral artery variations detected by magnetic resonance angiography.

Middle cerebral artery (MCA) variations are found incidentally on cranial magnetic resonance angiography (MRA). Our goal was to examine the incidence and types of MCA variations detected by MRA. Between April 1996 and March 1999, cranial MRA was performed in 432 cases at our institution. Most of the patients examined had or were suspected to have cerebrovascular disease. After excluding 7 patients with moyamoya disease, we retrospectively reviewed 425 MRA results. A 1.5-T scanner was used in all studies, and maximum-intensity projection images obtained using the three-dimensional time-of-flight technique were displayed stereoscopically. In the 425 patients MRA revealed 16 anomalous MCAs, including 9 duplicated MCAs, 5 accessory MCAs, and 2 fenestrated MCAs, which is a rate of 3.8%. Thus, although the clinical significance is not great, we found a relatively high incidence of anomalous MCAs on MRA. We stress that knowledge and recognition of these variations are useful and important during the interpretation of cranial MRA.

Adolescent↗
PubMed2000

Lack of disease-specific amino acid changes in the viral proteins of JC virus isolates from the brain with progressive multifocal leukoencephalopathy.

Progressive multifocal leukoencephalopathy (PML) is a fatal demyelinating disease of the central nervous system caused by a ubiquitous human polyomavirus designated as JC virus (JCV). JCVs in the brain of PML patients (PML-type JCVs) contain various regulatory regions generated from the archetypal regulatory region during persistence in the patients. We determined the complete DNA sequences of 2 PML-type isolates and 5 archetype isolates. Amino acid sequences of individual viral proteins were deduced from complete DNA sequences, and were compared among 16 isolates (6 PML types and 10 archetypes). From the data obtained, we concluded that PML-associated amino acid changes did not occur in the viral proteins of PML-type JCVs.

Amino Acid Sequence↗
PubMed2000

Regulation of liver inflammatory injury by signal transducer and activator of transcription-6.

Liver injury induced by hepatic ischemia/reperfusion is characterized by activation of the transcription factor NF-kappaB, increased production of tumor necrosis factor-alpha (TNFalpha), liver neutrophil accumulation, and hepatocellular damage. Exogenous administration of interleukin-4 (IL-4) or IL-13 was recently shown to regulate this inflammatory injury in association with activation of signal transducer and activator of transcription-6 (STAT6). The objective of the present study was to determine whether STAT6 was required for the regulation of liver inflammation by IL-4 and IL-13. Wild-type and STAT6 knockout mice underwent 90 minutes of hepatic ischemia followed by 8 hours of reperfusion. Hepatic ischemia/reperfusion in wild-type and STAT6 knockout mice significantly increased (P < 0.05) NF-kappaB activation, serum levels of TNFalpha, liver accumulation of neutrophils [measured by myeloperoxidase (MPO) content], and hepatocellular damage [measured by serum alanine aminotransferase (ALT)] compared to sham controls. In wild-type mice, activation of STAT6 was not observed after ischemia/reperfusion. Administration of 1 microg of IL-4 or IL-13 at reperfusion reduced serum TNFalpha, liver neutrophil accumulation, and hepatocellular injury in wild-type mice. Treatment with IL-4 or IL-13 had no effect on liver NF-kappaB activation but significantly increased activation of STAT6. In STAT6 knockout mice, neither IL-4 nor IL-13 had any effect on TNFalpha, MPO, or ALT values, the regulatory effects of these cytokines being completely abolished. The data suggest that activation of STAT6 may regulate liver inflammatory injury.

Animals↗
PubMed2000

Syringe needle located deep in the brain: image-guided removal.

BACKGROUND: Removal of a thin but long foreign body lodged in the deep brain tissue may need special technique to remove it without causing major injury. We report a special technique for the safe, elective removal of such objects. CASE DESCRIPTION: A 5-year-old boy presented following mild head trauma; he was asymptomatic and physical examination revealed an intact scalp and no neurological deficit. The incidental presence of a 3.4 cm-long syringe needle in the right frontal region was noted on the skull radiographs. Cranial computed tomography (CT) scan showed the deeper end of the needle in the right caudate head and the superficial end at a depth of 3.5 cm from the cortical surface. Burr hole surgery was performed under general anesthesia employing a Fisher stereotactic frame and continuous biplanar guidance from the image intensifiers. The superficial end of the needle was clasped with an endoscopy biopsy forceps, allowing removal of the needle via the least traumatic route. The child had an uneventful recovery. Follow-up magnetic resonance imaging at 6 months did not reveal any abnormality. CONCLUSIONS: The two-dimensional biplanar image-guided stereotactic technique allowed safe removal of a long foreign body from a deep brain location with minimal trauma to the brain.

Brain↗
PubMed2000

Identification of RALDH-3, a novel retinaldehyde dehydrogenase, expressed in the ventral region of the retina.

In the developing retina, a retinoic acid (RA) gradient along the dorso-ventral axis is believed to be a prerequisite for the establishment of dorso-ventral asymmetry. This RA gradient is thought to result from the asymmetrical distribution of RA-generating aldehyde dehydrogenases along the dorso-ventral axis. Here, we identified a novel aldehyde dehydrogenase specifically expressed in the chick ventral retina, using restriction landmark cDNA scanning (RLCS). Since this molecule showed enzymatic activity to produce RA from retinaldehyde, we designated it retinaldehyde dehydrogenase 3 (RALDH-3). Structural similarity suggested that RALDH-3 is the orthologue of human aldehyde dehydrogenase 6. We also isolated RALDH-1 which is expressed in the chick dorsal retina and implicated in RA formation. Raldh-3 was preferentially expressed first in the surface ectoderm overlying the ventral portion of the prospective eye region and then in the ventral retina, earlier than Raldh-1 in chick and mouse embryos. High level expression of Raldh-3 was also observed in the nasal region. In addition, we found that Pax6 mutants are devoid of Raldh-3 expression. These results suggested that Raldh-3 is the key enzyme in the formation of an RA gradient along the dorso-ventral axis during the early eye development, and also in the development of the olfactory system.

Aldehyde Oxidoreductases↗
PubMed2000

Regional differences in cerebral glucose metabolism in cirrhotic patients with subclinical hepatic encephalopathy using positron emission tomography.

Although it is recognized that abnormalities of glucose metabolism occur substantially throughout the brain in cirrhotic patients with subclinical hepatic encephalopathy (SHE), little attention has been paid to these abnormalities in situ due to technical difficulties. The aim of this study is to clarify the regional differences of cerebral glucose metabolism (CMRglu) in patients with or without SHE using positron emission tomography (PET). Fifteen patients with posthepatitic cirrhosis and 13 control subjects underwent PET imaging of the brain using 2-[18F]fluoro-2-deoxy-D-glucose. Neurological tests included the digit symbol and block design subtests from the Wechsler Adult Intelligence Scale. Auditory brain stem reaction and electroencephalogram were also used in diagnosis of SHE. Regions were defined as frontal, parietal, occipital, basal ganglia, and the white matter. The CMRglu value in the grey matter of SHE is lower than that of control, particularly in the frontal and temporal regions and basal ganglia (P<0.05, respectively). The CMRglu values in the grey matter of non-SHE and control are almost the same, excepting the basal ganglia. The CMRglu value in the basal ganglia of non-SHE is higher than that of control and SHE. The CMRglu value in the grey matter of SHE is depressed as compared to both non-SHE and control. These data suggest that the abnormalities of cerebral glucose metabolism may be a contributing factor in SHE.

Journal Article↗
PubMed2000

Immunological characterization of recombinant soy protein allergen produced by Escherichia coli expression system.

To elucidate the molecular mechanism of the allergenicity of soybean P34 protein recognized as the most allergenic protein in soybean, the protein was expressed in Escherichia coli transformed with a plasmid carrying P34 cDNA. SDS-PAGE pattern showed that the molecular weight of the recombinant P34 was approximately 2 kDa less than that of the native soybean P34. The difference in the molecular mass between these two proteins could be due to the native P34 in soybean being glycosylated at position Asn(170), whereas the recombinant protein generated in E. coli lacks this post-translational modification. Immunoblot analysis showed that both soybean and recombinant P34 proteins cross-reacted not only with polyclonal and monoclonal antibodies produced against P34 and crude soybean protein but also with patients' sera. The results suggest that the recombinant P34 is immunologically reactive, indicating that both proteins have similar epitope structures. Thus, the recombinant P34 produced by the E. coli expression system can be used as a standard allergen for molecular design to reduce the allergenic structure.

Allergens↗
PubMed2000

Lipophilization of lysozyme by short and middle chain fatty acids.

Hen egg white lysozyme was lipophilized with short and middle chain saturated fatty acids (caproic, capric, or myristic acid). The yield, bactericidal properties, and structural properties of lipophilized lysozymes were investigated. The yield of lipophilization of lysozyme greatly increased with the decrease in the chain length of fatty acid. Lipophilization broadened the bactericidal action of lysozyme to Gram-negative bacteria with little loss of enzymatic activity. The bactericidal activity increased in proportion to the number of bound short chain fatty acids. The thermal stability of lipophilized lysozyme decreased in proportion to the chain length and number of bound fatty acids.

Animals↗
PubMed2000

Bactericidal action of egg yolk phosvitin against Escherichia coliunder thermal stress.

Chicken egg yolk phosvitin showed a remarkable antibacterial effect against Escherichia coli under thermal stress at 50 degrees C. E. coli cells (10(6)/mL) completely disappeared in 1 mL of L-broth coexisting with 0.l mg/mL phosvitin when incubated at 50 degrees C for 20 min, whereas a considerable amount of cells (10(5)/mL) survived at the same thermal stress without phosvitin. Blocking of the chelating effect of phosvitin by the addition of Ca(2+) ion displayed a protective effect against the bactericidal activity at 50 degrees C. In addition, the antibacterial activity of phosvitin was dramatically reduced by treatment with alpha-chymotrypsin, although the chelating effect remained. The surface properties, such as interfacial tension and emulsifying properties of phosvitin, which are an index of the affinity with the outer membrane, were greatly reduced by the alpha-chymotrypsin digestion. This indicates that the alpha-chymotrypsin-digested membrane-penetrating hydrophobic domains at the N- and C-terminal regions play an important role in antibacterial activity. These results suggest that a significant part of the bactericidal activity of phosvitin against E. coli resides in the synergistic effect of the high metal-chelating ability and the high surface activity under the influence of thermal stress.

Anti-Bacterial Agents↗
PubMed2000

Ultrastructural changes of the vascular endothelium after intra-arterial administration of tumor necrosis factor-alpha (TNFalpha) in rat gliomas.

The ensuing ultrastructural changes in tumor vascular endothelial cells following intra-arterial administration of tumor necrosis factor-alpha (TNFalpha) were studied in an experimental rat glioma model. C6 glioma cells were implanted in Wistar rats and then after 14 days, 5 x 10(3) U of human natural-type TNFalpha (1.7 x 10(5) U/m2) was administered through the carotid artery. The animals were sacrificed at 3 or 24 h after TNFalpha treatment. A detailed examination with transmission electron microscope revealed swelling of the tumor vascular endothelial cell nuclei and mitochondria with matrix densities at 3 h. At 24 h, these cells demonstrated the presence of high amplitude mitochondrial swelling or the violent blebbing characteristic of damaged mitochondria; the cytoplasm was swollen enormously and there were dissolution of cytoplasmic organelles and rupture of the plasma membrane. The observed findings were typical of cell necrosis and confirms yet another mechanism by which TNFalpha exerts its anti-tumor effects, that is, necrotizing effects on tumor vascular endothelium. The information appears to be important in the context of clinical application of intra-arterial TNFalpha in the treatment of malignant gliomas.

Animals↗
PubMed2000

Efficient gene transfer to airway epithelium using recombinant Sendai virus.

Clinical studies of gene therapy for cystic fibrosis (CF) suggest that the key problem is the efficiency of gene transfer to the airway epithelium. The availability of relevant vector receptors, the transient contact time between vector and epithelium, and the barrier function of airway mucus contribute significantly to this problem. We have recently developed recombinant Sendai virus (SeV) as a new gene transfer agent. Here we show that SeV produces efficient transfection throughout the respiratory tract of both mice and ferrets in vivo, as well as in freshly obtained human nasal epithelial cells in vitro. Gene transfer efficiency was several log orders greater than with cationic liposomes or adenovirus. Even very brief contact time was sufficient to produce this effect, and levels of expression were not significantly reduced by airway mucus. Our investigations suggest that SeV may provide a useful new vector for airway gene transfer.

Adenoviridae↗
PubMed2000

In vitro inhibition and intracellular enhancement of lysosomal alpha-galactosidase A activity in Fabry lymphoblasts by 1-deoxygalactonojirimycin and its derivatives.

Fabry disease is a lysosomal storage disorder caused by deficient lysosomal alpha-galactosidase A (alpha-Gal A) activity. Deficiency of the enzyme activity results in progressive deposition of neutral glycosphingolipids with terminal alpha-galactosyl residue in vascular endothelial cells. We recently proposed a chemical chaperone therapy for this disease by administration of 1-deoxygalactonojirimycin, a potent inhibitor of the enzyme, at subinhibitory intracellular concentrations [Fan, J.-Q., Ishii, S., Asano, N. and Suzuki, Y. (1999) Nat. Med. 5, 112-115]. 1-Deoxygalactonojirimycin served as a specific chaperone for those mutant enzymes that failed to maintain their proper conformation to avoid excessive degradation. In order to establish a correlation between in vitro inhibitory activity and intracellular enhancement activity of the specific chemical chaperone, a series of 1-deoxygalactonojirimycin derivatives were tested for activity with both alpha-Gal A and Fabry lymphoblasts. 1-Deoxygalactonojirimycin was the most potent inhibitor of alpha-Gal A with an IC50 value of 0.04 microM. alpha-Galacto-homonojirimycin, alpha-allo-homonojirimycin and beta-1-C-butyl-deoxygalactonojirimycin were effective inhibitors with IC50 values of 0.21, 4.3 and 16 microM, respectively. N-Alkylation, deoxygenation at C-2 and epimerization at C-3 of 1-deoxygalactonojirimycin markedly lowered or abolished its inhibition toward alpha-Gal A. Inclusion of 1-deoxygalactonojirimycin, alpha-galacto-homonojirimycin, alpha-allo-homonojirimycin and beta-1-C-butyl-deoxygalactonojirimycin at 100 microM in culture medium of Fabry lymphoblasts increased the intracellular alpha-Gal A activity by 14-fold, 5.2-fold, 2.4-fold and 2.3-fold, respectively. Weaker inhibitors showed only a minimum enhancement effect. These results suggest that more potent inhibitors act as more effective specific chemical chaperones for the mutant enzyme, and the potent competitive inhibitors of alpha-Gal A are effective specific chemical chaperones for Fabry disease.

1-Deoxynojirimycin↗
PubMed2000

Cystic renal cell carcinoma diagnosed by cystofiberscopy.

A 64-year-old man suffered from hypertensive syncope and was admitted to Branch Hospital, Faculty of Medicine, The University of Tokyo. On admission he had no symptoms; however, two renal cysts of about 5 cm in diameter were found in his left kidney. Cystofiberscopy with a thin optical fiberscope was performed in addition to puncture and cystography. Cytology revealed class I, but the wall surface of the lower cyst was uneven, fluid-filled, colloid-like and white-gray compared with that seen in the upper cyst. It was diagnosed as renal cell carcinoma (RCC) and left nephrectomy was performed (5 cm in diameter, RCC, papillary tubular, common, clear cell subtype, G2>G1, INF beta, pT2, pMx, pV0, ew(-)).

Carcinoma, Renal Cell↗
PubMed2000

Morphological changes in rat lung after long-term exposure to diesel emissions.

Wistar rats were exposed for 24 mo to diesel emissions containing a low (0.2 ppm, 0.21 mg/m(3)), medium (1.04 ppm, 1.18 mg/m(3)), or high (2.96 ppm, 3.05 mg/m(3)) concentration of NO(2) and particles, or diesel emissions containing a medium (1.12 ppm, 0.01 mg/m(3)) concentration of NO(2) without particles. At 6-mo intervals during the exposure period, rats were autopsied, and their lungs were prepared for light- and electron-microscopic examination. Morphological evaluations included examination for hyperplasia of airway goblet cells, shift in the types of glycoprotein of intracellular mucus granules in goblet cells, infiltration of inflammatory cells in the airways, enlargement of the cross-sectional area of an alveolus as a parameter of air space enlargement, and development of alveolar holes, which is considered to be an early hallmark of alveolar destruction. The number of goblet cells with acid-form mucus granules increased with the exposure concentration and time; however, goblet cells did not show any hyperplastic changes. Furthermore, inflammatory cells such as alveolar macrophages, mast cells, plasma cells, neutrophils, and lymphocytes infiltrated the airways and the alveoli, and showed some cell-to-cell contact. Although no significant enlargement of the air space of the lungs was seen in any exposure group, the number of alveolar holes was significantly higher in the high-concentration group in comparison with the control group at each exposure time, and also increased in other exposure groups, even in the low-concentration group at certain exposure times. Morphological changes in the lungs were mild even in the animals exposed to the highest levels of diesel emissions for 24 mo. Elimination of particles from diesel emissions led to reduced morphological changes such as a decreased shift in the types of glycoprotein of mucus granules in goblet cells, decreased infiltration of inflammatory cells in the lungs, and reduced anthracosis.

Animals↗