Biomedical subjects

Y Imamura

Publications and source records attributed to Y Imamura.

At least 91 records · Page 5Linked to original sources

PubMed1999

Factors that predict intrahepatic recurrence of hepatocellular carcinoma in 81 patients initially treated by percutaneous ethanol injection.

BACKGROUND: In Japan, where liver transplantation has not been used to treat patients with hepatocellular carcinoma (HCC), percutaneous ethanol injection (PEI) has been employed for those with small HCCs that are not amenable to surgical resection. In the current study, the authors evaluated PEI as a treatment for HCC patients by studying recurrence rates and survival after treatment. They then examined the clinicopathologic factors that predicted patterns of local and distant intrahepatic recurrence. METHODS: For 81 patients who underwent PEI as initial therapy between 1990 and 1997, the cumulative recurrence and survival rates and their correlations with 16 clinicopathologic factors were studied using the Kaplan-Meier method. RESULTS: The 3-year overall cumulative rates of intrahepatic recurrence and survival were 81% and 84%, respectively. At the end of the observation period, intrahepatic recurrence was detected in 56 patients (69%). In 21 (38%) of 56 patients, local recurrences were significantly associated with earlier stages of underlying cirrhosis, decreased indocyanine green retention at 15 minutes (ICG R15), larger tumor size, and histologically advanced tumor grade. Distant intrahepatic recurrence was also significantly associated with liver function and ICG R15. CONCLUSIONS: PEI is most effective as the initial treatment for patients with well-differentiated HCC when the tumor is less than 15 mm in greatest dimension. However, local recurrence depends predominantly on the biologic characteristics of the tumor, regardless of the efficacy of PEI. Surgical resection of HCC should be considered, especially for patients with mild liver dysfunction.

Aged↗

PubMed1999

A cyclophilin B gene encodes antigenic epitopes recognized by HLA-A24-restricted and tumor-specific CTLs.

We have studied Ags recognized by HLA class I-restricted CTLs established from tumor site to better understand the molecular basis of tumor immunology. HLA-A24-restricted and tumor-specific CTLs established from T cells infiltrating into lung adenocarcinoma recognized the two antigenic peptides encoded by a cyclophilin B gene, a family of genes for cyclophilins involved in T cell activation. These two cyclophilin B peptides at positions 84-92 and 91-99 induced HLA-A24-restricted CTL activity against tumor cells in PBMCs of leukemia patients, but not in epithelial cancer patients or in healthy donors. In contrast, the modified peptides at position 2 from phenylalanine to tyrosine, which had more than 10 times higher binding affinities to HLA-A24 molecules, could induce HLA-A24-restricted CTL activity against tumor cells in PBMCs from leukemia patients, epithelial cancer patients, or healthy donors. PHA-activated normal T cells were resistant to lysis by the CTL line or by these peptide-induced CTLs. These results indicate that a cyclophilin B gene encodes antigenic epitopes recognized by CTLs at the tumor site, although T cells in peripheral blood (except for those from leukemia patients) are immunologically tolerant to the cyclophilin B. These peptides might be applicable for use in specific immunotherapy of leukemia patients or that of epithelial cancer patients.

Adenocarcinoma↗

PubMed1999

Mammalian BMP-1/Tolloid-related metalloproteinases, including novel family member mammalian Tolloid-like 2, have differential enzymatic activities and distributions of expression relevant to patterning and skeletogenesis.

Vertebrate bone morphogenetic protein 1 (BMP-1) and Drosophila Tolloid (TLD) are prototypes of a family of metalloproteases with important roles in various developmental events. BMP-1 affects morphogenesis, at least partly, via biosynthetic processing of fibrillar collagens, while TLD affects dorsal-ventral patterning by releasing TGFbeta-like ligands from latent complexes with the secreted protein Short Gastrulation (SOG). Here, in a screen for additional mammalian members of this family of developmental proteases, we identify novel family member mammalian Tolloid-like 2 (mTLL-2) and compare enzymatic activities and expression domains of all four known mammalian BMP-1/TLD-like proteases [BMP-1, mammalian Tolloid (mTLD), mammalian Tolloid-like 1 (mTLL-1), and mTLL-2]. Despite high sequence similarities, distinct differences are shown in ability to process fibrillar collagen precursors and to cleave Chordin, the vertebrate orthologue of SOG. As previously demonstrated for BMP-1 and mTLD, mTLL-1 is shown to specifically process procollagen C-propeptides at the physiologically relevant site, while mTLL-2 is shown to lack this activity. BMP-1 and mTLL-1 are shown to cleave Chordin, at sites similar to procollagen C-propeptide cleavage sites, and to counteract dorsalizing effects of Chordin upon overexpression in Xenopus embryos. Proteases mTLD and mTLL-2 do not cleave Chordin. Differences in enzymatic activities and expression domains of the four proteases suggest BMP-1 as the major Chordin antagonist in early mammalian embryogenesis and in pre- and postnatal skeletogenesis.

Amino Acid Sequence↗

PubMed1999

Efficacy of tympanostomy tube insertion for otitis media with effusion in children with Down syndrome.

OBJECTIVE: Although the insertion of tympanostomy tubes is regarded as an effective treatment for otitis media with effusion in the general population, it remains to be determined whether tympanostomy tube insertion is also effective for otitis media with effusion in children with Down syndrome. The present study was carried out to determine the efficacy of tympanostomy tube insertion in children with Down syndrome. PATIENTS AND METHODS: We studied 28 children (18 males and ten females) with Down syndrome and 28 age-matched control children who underwent tympanostomy tube insertion and were followed up for more than 2 years, up to 7 years of age or older. The children were followed up every month for 6 months after the operation and every 2 months thereafter. The tympanostomy tubes were not removed unless granulation tissue appeared around the ventilation tubes. RESULTS: The cure rate for otitis media with effusion was lower in the children with Down syndrome than in the age-matched control children. Sequelae of otitis media with effusion (atelectatic eardrum, permanent perforation of the eardrum and middle ear cholesteatoma) were significantly often encountered in the former group. The children with Down syndrome had more frequent episodes of otorrhea from the tympanostomy tubes than the control children and antibiotic-resistant-bacteria were frequently isolated. Moreover, improvement in hearing acuity after the placement of tympanostomy tubes was not always achieved in children with Down syndrome. CONCLUSION: The efficacy of the tympanostomy tube insertion for children with Down syndrome was much lower than in control children. We propose that in children with Down syndrome conservative management should be the treatment of first choice and that the insertion of tympanostomy tubes should be indicated only when hearing loss due to middle ear effusion is in a severe degree and when pathological changes of the eardrum, such as adhesion and deep retraction pocket formation, are going to occur.

Adolescent↗

PubMed1999

Functional domains of alpha-catenin required for the strong state of cadherin-based cell adhesion.

The interaction of cadherin-catenin complex with the actin-based cytoskeleton through alpha-catenin is indispensable for cadherin-based cell adhesion activity. We reported previously that E-cadherin-alpha-catenin fusion molecules showed cell adhesion and cytoskeleton binding activities when expressed in nonepithelial L cells. Here, we constructed deletion mutants of E-cadherin-alpha-catenin fusion molecules lacking various domains of alpha-catenin and introduced them into L cells. Detailed analysis identified three distinct functional domains of alpha-catenin: a vinculin/alpha-actinin-binding domain, a ZO-1-binding domain, and an adhesion-modulation domain. Furthermore, cell dissociation assay revealed that the fusion molecules containing the ZO-1-binding domain in addition to the adhesion-modulation domain conferred the strong state of cell adhesion activity on transfectants, although those lacking the ZO-1-binding domain conferred only the weak state. The disorganization of actin-based cytoskeleton by cytochalasin D treatment shifted the cadherin-based cell adhesion from the strong to the weak state. In the epithelial cells, where alpha-catenin was not precisely colocalized with ZO-1, the ZO-1-binding domain did not completely support the strong state of cell adhesion activity. Our studies showed that the interaction of alpha-catenin with the actin-based cytoskeleton through the ZO-1-binding domain is required for the strong state of E-cadherin-based cell adhesion activity.

Animals↗

PubMed1999

The human mucus protease inhibitor and its mutants are novel defensive compounds against infection with influenza A and Sendai viruses.

Tryptase Clara, a trypsin-like protease localized exclusively in and secreted by Clara cells of the bronchial epithelium, is a prime host factor that processes viral envelope glycoproteins and determines the infectivity of influenza A and Sendai viruses (H. Kido, Y. Yokogoshi, K. Sakai, M. Tashiro, Y. Kishino, A. Fukutomi, and N. Katunuma, The Journal of Biological Chemistry, 1992, Vol. 267, pp. 13573-13579). We report here that human mucus protease inhibitor (MPI), a major inhibitor of granulocyte elastase in the lining fluid of the human respiratory tract, significantly inhibited induction of the infectivity of influenza A and Sendai viruses by tryptase Clara in vitro and multicycles of mouse-adapted influenza A virus replication in rat lungs in vivo. Recombinant MPI and the C- but not the N-terminal domain of MPI inhibited both the activity of tryptase Clara and the induction of virus infection by tryptase Clara. The 50% inhibitory concentrations of MPI and the C-terminal domain peptide (Pro50-Ala107) of MPI for tryptase Clara were 7.4 and 61.6 nM, respectively, with Sendai virus envelope glycoproteins as the substrate. Studies on deletion mutants of the C-terminal domain of MPI revealed that the minimal size of MPI required for the inhibition of tryptase Clara is the peptide Lys60-Ala107. Studies involving site-directed mutagenesis of the C-terminal domain of MPI indicated that the Leu72-Met73 site of MPI is the inhibitory site for tryptase Clara. Substitution of residue Leu72 with a basic amino acid significantly increased in the inhibitory activity of the C-terminal domain of MPI, but further substitution of residue Met73 with various amino acids in these mutants reduced the inhibitory activity. Since there is evidence suggesting that the concentration of MPI in respiratory fluid is insufficient for prevention of virus infection, the administration of MPI, the recombinant C-terminal domain of MPI, and their mutants, with residue Leu72 substituted with residues Arg72 and Lys72, may be useful for treatment of such pneumotropic virus infections.

Animals↗

PubMed1999

Pancreatoscopy for the next generation: development of the peroral electronic pancreatoscope system.

BACKGROUND: To improve visualization of the pancreatic duct with a pancreatoscope, we have developed the smallest known electronic endoscope, that is, the peroral electronic pancreatoscope. METHODS: This instrument (2.1 mm, external diameter) was developed with a 50k-pixel interline charge coupled device. A peroral fiberoptic pancreatoscope was used as control, connected to a video converter. The visibility of both systems was studied with a test chart. The model pancreatic duct, the oral mucosa, and the pancreatic ducts of a healthy control subject and patients with chronic pancreatitis were examined with both systems. RESULTS: The smallest visible interval (with a 5 mm distance between the object and the distal end of the endoscope) was 0.07 mm with the peroral electronic pancreatoscope and 0.2 mm with the peroral fiberoptic pancreatoscope. The electronic instrument produced better images of the model pancreatic duct than the fiberoptic endoscope. A clear image of the small vessels of the oral mucosa was obtained with the electronic but not with the fiberoptic instrument. The fine vessel network of the pancreatic duct was visualized only with the electronic instrument; pancreatic duct stones and rough-surfaced pancreatic duct were shown more precisely with the electronic endoscope. CONCLUSIONS: The peroral electronic pancreatoscope provides images of the fine detail of the pancreatic duct and will contribute to the diagnosis of pancreatic diseases.

Calculi↗

PubMed1999

Studies of bovine enterovirus structure by ultraviolet resonance Raman spectroscopy.

The structural comparison of bovine enterovirus MZ468 strain before and after the heat treatment was studied by ultraviolet resonance Raman (UVRR) spectra excited at both 235 and 251 nm. The difference between full, heated full and purified empty particles, which were expected as an in vitro model of uncoating, were demonstrated. At 235 nm excitation, the Raman bands of the capsid protein dominated in all the UVRR spectra. The UVRR spectra of the empty particles exhibited non-homogenious broadening for tryptophan W3 band and W7 Fermi doublet bands, which were characteristics of hydrophobic environment, when compared with those of the full particles. The results indicates that some Trp indole rings of the full particles were packaged inside the viral capsids and not strained by virion assembly. On the other hand, the Raman bands assigned to guanine residues of the single stranded-RNA genome were enhanced strongly in the 251-nm excited UVRR spectrum. The spectral differences between the packaged (full particles) and the unpackaged virions (heated full particles) indicates that some guanine residues had strong hydrogen bonds in the full particles.

Animals↗

PubMed1999

Increase in the threshold of pain and touch sensation in the human face with clonidine plus 30% nitrous oxide.

OBJECTIVE: This study was undertaken to assess the effects of clonidine combined with 30% nitrous oxide on tactile and pain sensations in the human face. STUDY DESIGN: Thirty-three subjects were involved in the study. The subjects were divided into 4 groups: 100% oxygen with placebo; 30% N2O with placebo; 100% oxygen with clonidine (0.075 mg), and 30% N2O with clonidine. Three tests for the threshold of pain sensation and tactile sensation were made at 60 minutes before and 0, 15, and 30 minutes during N2O or O2 inhalation. RESULTS: (1) The N2O with clonidine significantly increased the threshold of pain and tactile sensation in comparison with the other 3 treatments. (2) In terms of pain sensation, both N2O and clonidine showed significant increases in threshold of pain in comparison with the control values. CONCLUSIONS: These results indicate that the analgesic effects of 30% nitrous oxide are enhanced when use of the gas is combined with prior clonidine administration.

Adult↗

PubMed1999

Modulation of formalin-evoked hyperalgesia by intrathecal N-type Ca channel and protein kinase C inhibitor in the rat.

1. omega-CgTx attenuated formalin-evoked biphasic flinches, while PKC inhibitor (STU) attenuated phase 2 and was reversed by PDBu. 2. omega-CgTx and STU suppressed the increase in CSF-glutamate after formalin injection. 3. Morphine completely suppressed both increased flinching and CSF glutamate release. 4. Thus, omega-CgTx (N-type Ca channels) may regulate neurotransmitter release evoked by C fiber activation and the formalin-evoked hyperalgesia may possibly be provoked as a result of PKC activation elicited by both presynaptic neurotransmitter release and activation of NMDA receptors in the spinal neurons.

Analgesics, Opioid↗

PubMed1999

A novel cytokine-inducing glycolipid isolated from the lipoteichoic acid fraction of Enterococcus hirae ATCC 9790: a fundamental structure of the hydrophilic part.

Previously, we showed that quantitatively minor several glycolipids totaling only less than 5% of the lipoteichoic acid (LTA) fraction from Enterococcus hirae ATCC 9790 possessed cytokine-inducing activity, whereas the major component (over 90%) did not [Suda et al. (1995) FEMS Immun Med Microbiol 12:97-112]. The major inactive component was shown to have the chemical structure as was proposed for the LTA by Fischer [Hashimoto et al. (1997) J Biochem 121:779-86], suggesting that so-called LTA is not a cytokine-inducing component in the Gram-positive bacteria. In the present paper, the structure of the hydrophilic part of one of the cytokine-inducing glycolipid tentatively named GL4 is elucidated. GL4 was first subjected to hydrolysis with aqueous HF to give a polysaccharide and a mixture of low molecular weight products. The polysaccharide was composed mainly of highly branching mannan as concluded from NMR and MS analyses of its acetolysis products. The low molecular weight products consisted of phosphate and glycerol, suggesting the presence of a poly(glycerophosphate) structure in the original GL4. From these observations, the hydrophilic part of GL4 was shown to consist of mannose-rich polysaccharide and poly(glycerophosphate), the latter being bound to the former by a phosphodiester linkage.

Carbohydrate Sequence↗

PubMed1999

Surface phenotype analysis of CD16+ monocytes from leukapheresis collections for peripheral blood progenitors.

In peripheral blood progenitor cell (PBPC) collections from patients with solid tumour or haematological malignancy, monocytes were separated into two subpopulations. The majority of monocytes expressed CD14 at a high density without CD16 antigen (the CD14+CD16- monocytes). The remaining monocytes co-expressed CD14 and CD16 (the CD14+CD16+ monocytes). These CD14+CD16+ monocytes amounted to 20.6 +/- 15.8%, while those in peripheral blood (PB) obtained from healthy volunteers were 7.3 +/- 3.1% (P < 0.05). When subdividing the CD14+CD16+ monocytes into CD14brightCD16dim and CD14dimCD16bright cells, both populations were found to be increased in PBPC collections. Since typical CD14+CD16+ monocytes are the CD14dimCD16bright population, we compared the additional surface antigens on CD14dimCD16bright monocytes with those of CD14+CD16- monocytes. In PBPC collections, the CD14dimCD16bright monocytes exhibited lower levels of CD11b, CD15, CD33 and CD38 expression and higher levels of CD4, CD11a, CD11c and MHC class II, and also revealed a higher percentage of CD4+ cells and a lower percentage of CD15+ cells and CD38+ cells, compared with the CD14+CD16- monocytes. When compared with the CD14dimCD16bright monocytes in PB, those in PBPC collections exhibited higher expression of CD4 and lower expression of CD11b, and also showed higher percentages of CD4+ cells and CD38+ cells and a lower percentage of CD11b+ cells. These results suggest that PBPC collections may be rich in the CD14+CD16+ monocytes in which the proportion of the immature population is increased. It is likely that these monocytes participate in the haematological and immune recovery after PBPC transplantation.

Adolescent↗

PubMed1999

Purification and catalytic properties of a tetrameric carbonyl reductase from rabbit heart.

An enzyme responsible for the ketone-reduction of 4-benzoylpyridine (4BP) was purified 350-fold to homogeneity from the cytosolic fraction of rabbit heart. The purified enzyme exhibited a molecular mass of 110 kDa on gel filtration, and 27 kDa on SDS-PAGE, indicating that it is a tetrameric protein composed of four identical-size subunits. Aromatic aldehydes, ketones, and menadione were effective substrates for the enzyme. Flavonoids were potent inhibitors of the enzyme, but barbiturates or pyrazole was not. Based on this substrate specificity and inhibitor sensitivity, the enzyme was taken to be a carbonyl reductase. Kinetic studies led us to conclude that the reduction of 4BP by the enzyme follows an ordered Bi Bi mechanism. The enzyme also appeared to catalyze the redox (oxidation-reduction) cycling of menadione to produce the superoxide radical. Furthermore, we provide evidence that a hydrophobic pocket, which corresponds to a straight-chain alkyl group of five carbon atoms in length, is located in the substrate-binding site of the enzyme.

Alcohol Oxidoreductases↗

PubMed1999

Lifetime prevalence of schizophrenia among individuals prenatally exposed to atomic bomb radiation in Nagasaki City.

OBJECTIVE: The aim of this study was to examine the relationship between prenatal exposure to atomic bomb (A-bomb) radiation and the development of schizophrenia in adulthood. METHOD: We investigated the lifetime prevalence of schizophrenia among people prenatally exposed to the 1945 Nagasaki A-bomb, using the schizophrenia register and the A-bomb survivors' database. RESULTS: Among 1867 prenatally exposed individuals, 18 subjects (0.96%) had developed schizophrenia later in life. The prevalence was significantly higher in people exposed in the second trimester of pregnancy than in those exposed in the third trimester. The closer they had been to the hypocentre, the higher was the prevalence, but no statistically significant linear relationship was seen. CONCLUSION: This investigation could not clarify the nature of exposure to A-bomb radiation as a risk factor for schizophrenia in the prenatal period.

Adult↗

PubMed1999

Sex-dependent pharmacokinetics and in vitro reductive metabolism of acetohexamide in Wistar-Imamichi rats.

A significant sex-related difference was observed for the pharmacokinetics of acetohexamide in Wistar-Imamichi (Wistar-IM) rats. However, there was no sex difference of the in vitro reductive metabolism of acetohexamide in the liver or kidney of these rats. Testectomy was found to decrease the plasma clearance (CLp) of acetohexamide in male rats, whereas ovariectomy had no effect on the CLp of acetohexamide in female animals, suggesting that androgens regulate the pharmacokinetics of acetohexamide. The co-administration of sulfamethazine, which is known to be metabolized by a male-specific cytochrome P450 (CYP) isoform (CYP2C11), significantly decreased the CLp of acetohexamide in male Wistar-IM rats. Based on these results, it is reasonable to assume that the sex-dependent pharmacokinetics of acetohexamide observed in Wistar-IM rats is associated with the male-specific hydroxylation catalyzed by CYP2C11.

Acetohexamide↗

PubMed1999

Inhibition of rabbit heart carbonyl reductase by fatty acids.

The inhibition of rabbit heart carbonyl reductase (RHCR) by fatty acids was examined using 4-benzoylpyridine (4BP) as a substrate. The inhibitory potency of saturated fatty acids increased with elongation in the carbon chain from caprylic acid to myristic acid, but decreased with further elongation. Myristic acid with 14 carbon atoms most strongly inhibited RHCR. All of the unsaturated fatty acids tested strongly inhibited RHCR; the cis-isomers were more potent inhibitors than the corresponding trans-isomers. The methyl esters and alcohols, which lack a carboxyl group, derived from fatty acids did not exert a significant inhibitory effect on RHCR. These results indicate that the existence of a proper length of carbon chain, double bond(s), and a carboxyl group in a fatty acid molecule is important for RHCR inhibition. We also propose the possibility that myristic acid at low concentrations inhibits the reduction of 4BP by interacting with a binding site other than the coenzyme- and substrate-binding sites of RHCR.

Alcohol Oxidoreductases↗

PubMed1999

Enzymatic synthesis of (-)- and (+)-acetoxyhexamides and (-)- and (+)-hydroxyhexamides.

The enantioselective hydrolysis of (+/-)-4-(1-acetoxyethyl)-N-(cyclohexylcarbamoyl)-benzenesulfona mides 3 with lipase Amano P from Pseudomonas sp. in a water-saturated solvent gave (R)-4-(1-hydroxyethyl)-N-(cyclohexylcarbamoyl)benzenesulfonamide 2 (39%, > 99% ee) and unchanged (S)-3 (50%, 62% ee). On the other hand, enantioselective esterification of (+/-)-2 with lipase Amano P in the presence of vinyl acetate provided (R)-3 (41%, > 99% ee) and unchanged (S)-2 (46%, 78% ee).

Acetohexamide↗

PubMed1999

[Physiological, genetic and pathological factors regulating the reductive metabolism of drugs with a ketone group].

In this review, we describe the physiological, genetic and pathological factors regulating the reductive metabolism of drugs with a ketone group. Acetohexamide (AH) was chosen as a model drug with a ketone group. Species differences of AH reductase activity were observed in liver cytosol and microsomes of animals tested. AH reductase activity in liver microsomes of rats was much higher in males than females. The activity was not detectable until 4 weeks of age after birth in both sexes, but increased markedly at puberty only in males. AH reductase activity in liver microsomes of male rats was decreased by testectomy, and restored by the treatment with testosterone propionate, indicating that the sex-related difference and postnatal development of the activity are regulated by androgens. There was a strain difference of AH reductase activity in liver microsomes of male rats. Of rat strains tested, only Wistar-Imamichi strain was found to lack male-specific microsomal enzyme activity. The inheritance pattern of AH reductase activity in liver microsomes of rats was determined by mating the genetic deficiency Wistar-Imamichi strain with Fischer-344 strain. Streptozotocin-induced diabetes significantly decreased AH reductase activity in liver microsomes of male rats. Furthermore, the physiological role of AH reductase present in liver microsomes of male rats was examined. We propose the possibility that the male-specific microsomal enzyme physiologically functions as a 20 beta-hydroxysteroid dehydrogenase.

20-Hydroxysteroid Dehydrogenases↗