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Biomedical subjects

K Inoue

Publications and source records attributed to K Inoue.

At least 181 records · Page 10Linked to original sources
PubMed2000

Intrahepatic inflow areas of the drainage vein of the gallbladder: analysis by angio-CT.

BACKGROUND: The drainage veins of the gallbladder (cystic veins) are important hepatic metastatic routes of gallbladder cancer. We studied the cystic vein inflow portions of the intrahepatic vessels by computed tomography during angiography (angio-CT). METHODS: The subjects were 27 unoperated pancreatic-biliary patients. After superselective catheterization of the cystic artery, angio-CT was performed, and cystic veins and sinusoidal filling were visualized. We identified the cystic vein inflow routes and the vessels they fed. RESULTS: We found 72 cystic veins in 26 patients. All cystic veins flowed into the intrahepatic portal branches or sinusoids. The cystic veins took either of two routes: one into the liver through the hepatic hilum (17 patients, 21 veins), taken mainly by the portal branch for subsegment 4a (P4a), the anterior portal branch, and the umbilical portion of the portal branch; and the other through the hepatic bed (23 patients, 51 veins), taken mainly by S4a sinusoid, S5 sinusoid, P4a, and P5. CONCLUSIONS: Angio-CT is useful for detecting the cystic vein inflow portions of the intrahepatic vessels. It makes possible identification of areas where there is a possibility for micrometastasis of the gallbladder cancer.

Adult↗
PubMed2000

Expression of nuclear factor-kappaB in Helicobacter pylori-infected gastric mucosa detected with southwestern histochemistry.

BACKGROUND: The transcription factor nuclear factor-kappaB (NF-kappaB) plays a pivotal role in inflammatory responses by upregulating mRNA expression of, for example, proinflammatory cytokines and chemokines. Although in vitro studies have shown that Helicobacter pylori can induce NF-kappaB activation in gastric cancer cell lines, there is little information on cellular localization of NF-kappaB in H. pylori-infected gastric mucosa. METHODS: H. pylori-infected and -negative patients with various endoscopic findings were examined. NF-kappaB expression was studied by means of Southwestern histochemistry, a new method of localizing transcription factors. Labeled double-stranded oligo-DNA with specific consensus sequence for the NF-kappaB binding site was reacted with frozen sections from gastric biopsy specimens. We compared mucosal interleukin-8 (IL-8) and IL-1beta levels as measured with enzyme-linked immunosorbent assay with the degree of NF-kappaB expression. RESULTS: NF-kappaB expression was often evident in nuclei of epithelial cells in H. pylori-infected gastric mucosa. The degree of NF-kappaB expression on the epithelium was significantly more severe in H. pylori-infected than in -negative mucosa. The degree of NF-kappaB expression also correlated with mucosal IL-8 levels but not with IL-8. CONCLUSIONS: H. pylori infection increases the expression of NF-kappaB in gastric mucosa, suggesting that NF-kappaB is involved in inflammatory responses to H. pylori.

Enzyme-Linked Immunosorbent Assay↗
PubMed2000

Focal ductal branch dilatation on magnetic resonance cholangiopancreatography: a hint for early diagnosis of pancreatic carcinoma.

A 63-year-old man with a combination of early pancreatic carcinoma and an intraductal papillary adenoma was reported. A pancreatic cyst was detected by chance at the head of the pancreas by computed tomography for a follow-up study of early rectal carcinoma previously operated. Detailed studies by endoscopic retrograde pancreatography (ERP) showed irregular narrowing of the main pancreatic duct at the pancreatic body and magnetic resonance cholangiopancreatography (MRCP) revealed dilatation of ductal branches draining there. Brushing cytology of the pancreatic duct demonstrated cancer cells and total pancreatectomy was performed. Stepwise histo-pathological examinations of the specimen showed two foci of invasive carcinoma in the neck and body and multiple foci of severe dysplasia, some of which contained carcinoma in situ, in the body of the pancreas. The cystic tumor in the head of the pancreas was an intraductal papillary adenoma. In this case, the scrutiny of a pancreatic cyst including MRCP and ERP led to an early diagnosis of pancreatic cancer. Dilatation of ductal branches depicted by MRCP might be a new hint for early diagnosis of pancreatic carcinoma.

Adenoma↗
PubMed2000

Ethnic-related differences in the frequency distribution of genetic polymorphisms in the CYP1A1 and CYP1B1 genes in Japanese and Caucasian populations.

1. Race-related differences in the frequency distribution of genetic polymorphisms in the CYP1A1 and CYP1B1 genes were studied in 39 Japanese and 45 Caucasians. 2. Four types of CYP1A1 polymorphism, namely m1 (a nucleotide change at T6235C in the 3'-flanking region), m2 (A4889G at exon 7), m3 (T5639C in the 3'-flanking region) and m4 (C4887A at exon 7), and three types of CYP1B1 genetic polymorphism, namely m1 (C488G and G701T leading to Arg48Gly and Ala119Ser exchanges respectively), m2 (C1294G leading to a Leu432Val exchange) and m3 (A1358G leading to an Asn453Ser exchange) were studied. 3. The distribution of the m1-, m2-, m3-, and m4-types of CYP1A1 polymorphism in the Japanese population was 30.8, 17.9, 0 and 0% respectively; those in Caucasians were 3.3, 6.7, 0 and 2.2% respectively. Two types (m1, and m2) of CYP1B1 polymorphism were expressed at 14.1 and 21.8% respectively in the Japanese, and by 28.9 and 37.5% respectively in the Caucasian. Ethnic differences were also noted in the m3-type CYP1B1 polymorphism in which the incidence in Caucasians was 23.9%, whereas no cases in the 39 Japanese subjects were observed. 4. No apparent association was found in the incidence in each of the genetic polymorphisms of CYP1A1 and CYP1B1 genes, nor in methylenetetrahydrofolate reductase gene, except that the occurrence of the m2-type of CYP1A1 genetic polymorphism was related to that of the m1-type CYP1A1 polymorphism in the Japanese population. 5. These results suggest that there are race-related differences in the occurrence of genetic polymorphisms in both CYP1A1 and CYP1B1 genes in Japanese and Caucasian populations and that these differences in P450 genetic polymorphisms may, in part, cause differences in the occurrence of lung and breast cancers in these ethnic groups.

Alleles↗
PubMed2000

Long-term prospective study on the natural history of Wolff-Parkinson-White syndrome detected during a heart screening program at school.

UNLABELLED: In the period 1985 to 1993, a total of 802 school-aged children (284 first-graders and 518 seventh-graders) were referred to our hospital for further evaluation of electrocardiographic abnormalities. Among them, 57 (male 24 and female 33) children were confirmed as having Wolff-Parkinson-White (WPW) syndrome based on the findings of 12-lead surface electrocardiograms (ECG). According to Lindsay's criteria, the locations of the accessory pathways were as follows: Left-lateral in 10 (18%), left-posterior in 2 (4%), right-free-wall in 28 (49%), anterior-septum in 13 (23%) and posterior-septum in 3 (5%). One 12-y-old girl had multiple accessory pathways. Six patients had associated diseases: Ebstein's anomaly in 4, epilepsy in 1 and mental retardation with scoliosis in 1. Follow-up periods ranged from 2.0 to 13.0 y (mean +/- SD: 8.0 +/- 3.3 y) for 23 first-graders with WPW syndrome, and from 2.0 to 13.0y (mean +/- SD: 7.3 +/- 4.2y) for 34 seventh-graders, respectively. Initially, 5 children had at least one episode of supraventricular tachycardia (SVT) by history and 6 children developed SVT during the follow-up. One girl with multiple accessory pathways and recurrent SVT required long-term drug therapy. CONCLUSIONS: The outcome of children with WPW syndrome detected by a heart screening program at school was favorable. Our 8 y follow-up of 57 children with WPW syndrome will serve as additional information concerning the indication of radio-frequency catheter ablation therapy for WPW syndrome in children.

Adolescent↗
PubMed2000

Interleukin-6 and interleukin-8 levels in serum and synovial fluid of patients with osteoarthritis.

Concentrations of interleukin (IL)-6 and IL-8 in serum and synovial fluid obtained from patients with osteoarthritis (OA) of the knee were determined by the chemiluminescence-ELISA (CL-ELISA) method, the sensitivity of which is 100-1,000 times greater than that of the conventional ELISA method. The results were compared with those obtained from patients with rheumatoid arthritis (RA) and from healthy subjects. The mean IL-6 and IL-8 levels in synovial fluid indicated higher concentrations in RA than in OA. The IL-6 and IL-8 levels in serum were significantly higher in RA and OA relative to controls. Among OA patients in whom remarkable improvement was noted in hydrarthrosis, the synovial fluid IL-6 and IL-8 levels at the initial examination were relatively higher, and were markedly decreased after treatment with sodium hyaluronate (NaHA). Among those in whom no improvement was noted in hydrarthrosis, the synovial fluid IL-6 and IL-8 levels at the time of initial examination were relatively lower, and hydrarthrosis was not significantly improved even after treatment with NaHA. In addition, there was a tendency for the synovial fluid IL-6 and IL-8 levels to decrease as HA levels increased. Evaluation of X-ray findings revealed that the IL-6 levels in synovial fluid at the initial examination in low-grade cases tended to be significantly higher than in high-grade cases. In low-grade cases, as determined by X-ray findings, there was a significant decrease in IL-6 levels in synovial fluid after treatment with NaHA.

Adjuvants, Immunologic↗
PubMed2000

The skin permeation mechanism of ketotifen: evaluation of permeation pathways and barrier components in the stratum corneum.

To evaluate the pathways and barrier components in the stratum corneum (SC) for the permeation of ketotifen, the effect of delipidization on the permeation and partition was examined under several donor pHs. Assuming that ionized ketotifen (KTH+) and un-ionized ketotifen (KT) contribute independently in both permeation and partition, the intrinsic permeability coefficients and SC/water partition coefficients of both species were estimated. Delipidization enlarged the permeability of KTH+ 100 times. This suggested that the lipid phase functions as the barrier against KTH+. KT has an intrinsic permeability 100 times larger than that of KTH+. Delipidization did not result in a significant change in permeability of KT. This suggested that the permeability of KT through the lipid phase is comparable to that through the aqueous phase in delipidized SC; that is, the lipid phase functions as a highly permeable pathway for KT. On the other hand, the permeability coefficient of KT through delipidized SC was 1/34 of that through the pure aqueous layer, which had a thickness equivalent to SC. Since this suggests that the permeability of KT through the proteinaceous phase is much lower than that through the aqueous phase, the proteinaceous phase can be assumed to function as a barrier against the permeation of KT. From these results, it is concluded that the predominant permeation pathway for KT is through the lipid phase. The SC/water partition coefficient of KT was cut in half by delipidization, but the value was still more than 100. These results show that the proteinaceous phase functions not only as the barrier, but also as the depot for KT. The knowledge obtained here will be useful for formulation design and for the selection of enhancers in a transdermal therapeutic system of ketotifen.

Algorithms↗
PubMed2000

Suppression of S-methylglutathione-induced tentacle ball formation by peptides and nullification of the suppression by TGF-beta in Hydra.

Tentacle ball formation (TBF) in Hydra elicited by S-methylglutathione (GSM) was modulated by a number of biologically active peptides. Hydra fed on Artemia, which had been hatched in a common salt solution supplemented with LiCl and ZnCl(2), easily induced TBF in response to GSM after pretreatment with trypsin. After Hydra were treated with 100 pg/ml trypsin for 10 min, the response to GSM (TBF) was sensitively suppressed by acidic fibroblast growth factor and other biologically active peptides for >10 h. Various peptides, but not transforming growth factor beta (TGF-beta), suppressed GSM-induced TBF in a specific pattern for each peptide. However, TGF-beta was unique in that it did not suppress the response to GSM, but nullified the suppressive effect of other peptides. Only active TGF-beta nullified the suppressive effect of the peptides, and the latent form of TGF-beta neither suppressed GSM-induced TBF nor nullified the suppressive effect of other peptides. Members of the TGF-beta family suppressed GSM-induced TBF. These results indicate that all peptides examined, except for TGF-beta suppressed the response to GSM in a manner specific to each peptide. This assay system would be useful in identification of biologically active peptides.

Animals↗
PubMed2000

Diazepam-binding inhibitor-like activity in rat cerebrospinal fluid after stimulation by an aversive quinine taste.

Cerebrospinal fluid (CSF) taken from rats after stimulation by an aversive quinine taste (hereafter called quinine CSF) administered into the fourth ventricle of mice suppressed their intake of 5% sucrose solution. We examined the effects of CSF on glutathione-induced tentacle ball formation (TBF) of hydra to determine the change in CSF components associated with aversive taste stimuli. The suppressive activity of quinine CSF on TBF in the presence of 3 microM S:-methyl-glutathione (GSM) was markedly lower than that of CSF obtained from control rats (control CSF). Pronase-treated quinine CSF had suppressive activity similar to that of control CSF. The active principle passed through an ultrafiltration membrane, with a molecular weight cut-off of 30 kDa, but not through one with a cut-off of 3 kDa. A peptide fragment of diazepam-binding inhibitor (DBI) nullified the suppression of TBF at 3 microM GSM by control CSF. The nullifying activity of quinine CSF was not observed after treatment with a benzodiazepine receptor preparation that was able to bind DBI. When flumazenil, a benzodiazepine receptor antagonist, was given to mice, the suppression of the intake of 5% sucrose solution by quinine CSF was partially reversed. It is suggested that quinine CSF contains a DBI-like substance.

Animals↗
PubMed2000

Selective and continuous elimination of mitochondria microinjected into mouse eggs from spermatids, but not from liver cells, occurs throughout embryogenesis.

Exclusion of paternal mitochondria in fertilized mammalian eggs is very stringent and ensures strictly maternal mtDNA inheritance. In this study, to examine whether elimination was specific to sperm mitochondria, we microinjected spermatid or liver mitochondria into mouse embryos. Congenic B6-mt(spr) strain mice, which are different from C57BL/6J (B6) strain mice (Mus musculus domesticus) only in possessing M. spretus mtDNA, were used as mitochondrial donors. B6-mt(spr) mice and a quantitative PCR method enabled selective estimation of the amount of M. spretus mtDNA introduced even in the presence of host M. m. domesticus mtDNA and monitoring subsequent changes of its amount during embryogenesis. Results showed that M. spretus mtDNA in spermatid mitochondria was not eliminated by the blastocyst stage, probably due to the introduction of a larger amount of spermatid mtDNA than of sperm mtDNA into embryos on fertilization. However, spermatid-derived M. spretus mtDNA was eliminated by the time of birth, whereas liver-derived M. spretus mtDNA was still present in most newborn mice, even though its amount introduced was significantly less than that of spermatid mtDNA. These observations suggest that mitochondria from spermatids but not from liver have specific factors that ensure their selective elimination and resultant elimination of mtDNA in them, and that the occurrence of elimination is not limited to early stage embryos, but continues throughout embryogenesis.

Animals↗
PubMed2000

Membrane structure of the hepatitis B virus surface antigen particle.

Expression of S protein, an envelope protein of hepatitis B virus, in the absence of other viral proteins, leads to the secretion of hepatitis B virus surface antigen (HBsAg) particles that are formed by budding from the endoplasmic reticulum membranes. The HBsAg particles produced by mouse fibroblast cells show a unique lipid composition, with 1,2-diacyl glycerophosphocholine being the dominant component. The lipid organization of the HBsAg particles was studied by measuring electron spin resonance (ESR) using various spin-labeled fatty acids, and the results were compared with a parallel study on HVJ (Sendai virus) and vesicles reconstituted with total lipids of the HBsAg particles (HBs-lipid vesicles). HVJ and the HBs-lipid vesicles showed typical ESR spectra of lipids arranged in a lipid bilayer structure. In contrast, the ESR spectra obtained with the HBsAg particles showed that the movement of lipids in the particle is severely restricted and a typical immobilized signal characteristic of tight lipid-protein interactions was also evident. Phosphatidylcholine (PC) in the HBsAg particles was not exchangeable by a PC-specific exchange protein purified from bovine liver, while phospholipase A(2) from Naja naja vemon was able to hydrolyze all the PC in the particles. These analyses suggest that the lipids in the HBsAg particles are not organized in a typical lipid bilayer structure, but are located at the surface of the particles and are in a highly immobilized state. Based on these observations we propose a unique lipid assembly and membrane structure model for HBsAg particles.

Androgen-Binding Protein↗
PubMed2000

Dual pathways for the secretion of lysosomal cholesterol into a medium from cultured macrophages.

The removal of cholesterol from macrophages is important for reversing foam cell formation. In a previous study, we demonstrated that mouse peritoneal macrophages in culture secrete significant amounts of unesterified cholesterol from the lysosomes into the medium during endocytosis and subsequent metabolism of cholesterol-containing liposomes [Furuchi, T., Aikawa, K., Arai, H., and Inoue, K. (1993) J. Biol. Chem. 268, 27345-27348]. In this study, we found that at least two distinct mechanisms are involved in this process. The efflux of unesterified cholesterol into the medium was greatly suppressed by pregnenolone, an inhibitor of lysosomal cholesterol transport, but an appreciable proportion of the unesterified cholesterol was still released into the medium. Analysis of the medium containing the secreted cholesterol by NaBr density gradient ultracentrifugation revealed that the unesterified cholesterol was distributed in two different density peaks (bottom and d =/ approximately 1.1). The d =/ approximately 1.1 peak material formed high-density lipoprotein (HDL)-like particles that were produced and secreted by the macrophages. The lipid components of these particles were phosphatidylcholine and sphingomyelin, while the sole protein component was apolipoprotein E (apo E). Treatment with pregnenolone completely abolished the production of these HDL-like particles but had little effect on the bottom fractions. These data indicate that macrophages release lysosomal cholesterol via both pregnenolone-sensitive and -insensitive pathways, and that only the cholesterol secreted through the pregnenolone-sensitive pathway is associated with endogenously synthesized apo E-containing HDL-like particles. Moreover, we found that the pregnenolone-sensitive pathway operated independently of the presence or absence of exogenous HDL, whereas secretion via the pregnenolone-insensitive pathway was greatly stimulated by exogenously added HDL.

Animals↗
PubMed2000

The functional implications of the dimerization of the catalytic subunits of the mammalian brain platelet-activating factor acetylhydrolase (Ib).

The mammalian brain contains significant amounts of the cytosolic isoform Ib of the platelet-activating factor acetylhydrolase (PAF-AH), a unique type of PLA2. This oligomeric protein complex contains three types of subunits: two homologous (63% identity) 26 kDa catalytic subunits (alpha(1) and alpha(2)) which harbor all the PAF-AH activity, and the 45 kDa beta-subunit (LIS1), a product of the causal gene for Miller-Dieker lissencephaly. During fetal development, the preferentially expressed alpha(1)-subunit forms a homodimer, which binds to a homodimer of LIS1, whereas in adult organisms alpha(1)/alpha(2) and alpha(2)/alpha(2) dimers, also bound to dimeric LIS1, are the prevailing species. The consequences of this "switching" are not understood, but appear to be of physiological significance. The alpha(1)- and alpha(2)-subunits readily associate with very high affinity to form homodimers. The nature of the interface has been elucidated by the 1.7 A resolution crystal structure of the alpha(1)/alpha(1) homodimer (Ho et al., 1997). Here, we examined the functional consequences of the dimerization in both types of alpha-subunits. We obtained monomeric protein in the presence of high concentrations (>50 mM) of Ca2+ ions, and we show that it is catalytically inactive and less stable than the wild type. We further show that Arg29 and Arg22 in one monomer contribute to the catalytic competence of the active site across the dimer interface, and complement the catalytic triad of Ser47, Asp192 and His195, in the second monomer. These results indicate that the brain PAF-acetylhydrolase is a unique PLA2 in which dimerization is essential for both stability and catalytic activity.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗
PubMed2000

Vitamin D receptor gene polymorphisms and osteoarthritis of the hand, hip, and knee: acase-control study in Japan.

OBJECTIVE: To investigate the association between vitamin D receptor (VDR) gene polymorphisms andJapanese female patients with osteoarthritis (OA) of the hand, hip, and knee. METHODS: BsmI,ApaI, andTaqI restriction fragment length polymorphisms (RFLPs) of the VDR gene were analysed in 270Japanese female patients with radiographic OA of the hand, hip, tibiofemoral (TF) joint, andpatellofemoral (PF) joint, as well as in female controls. RESULTS: There was no significant association between the VDR gene RFLPs and OA of the hand, hip, TFjoint, PF joint, or polyarticular involvement. The previously detected preventive genotype of the VDRgene was uncommon in our test population. CONCLUSION: The relative importance of VDR gene polymorphism in the development of OA may vary betweenethnic groups.

Adult↗
PubMed2000

Polymorphic CAG repeats of the androgen receptor gene in Japanese male patients with ankylosing spondylitis.

OBJECTIVE: In view of a possible role of androgens in the pathogenesis of ankylosing spondylitis (AS), we investigated the association between Japanese male patients with AS and CAG microsatellites of the androgen receptor (AR) gene which related to the AR transactivation function. METHODS: Peripheral blood was collected from 39 men with AS and 305 male control subjects. The number of CAG repeats in exon 1 of the AR gene was determined. RESULTS: CAG repeat lengths in AS patients were significantly shorter than those in the controls (median value 22 vs 23; P = 0.03). However, there was no significant difference in CAG repeats between HLA-B27-positive and -negative patients (median value 22 vs 22; P = 0.78). CONCLUSIONS: Shorter CAG repeats of the AR gene, presenting high levels of transactivation activity, may play a role in male AS.

Adolescent↗
PubMed2000

Prevalence of hip osteoarthritis and acetabular dysplasia in french and japanese adults.

OBJECTIVE: : To determine ethnic variations of acetabular morphology, and to delineate their relationship with hip osteoarthritis (OA). METHODS: : Radiographs of 283 French men, 118 French women, 414 Japanese men and 368 Japanese women, aged 20-79 yr, who underwent intravenous urography were assessed by a single observer for morphometric measurement and hip OA scoring. RESULTS: : The standardized morbidity ratio (SMR) for hip OA was highest in French men and lowest in Japanese men, whereas the SMR for acetabular dysplasia was highest in Japanese women and lowest in French men. French men and women had the highest centre-edge angle, followed by Japanese men then Japanese women. CONCLUSION: : In a large number of subjects assessed by a single observer, this study confirms other previous reports that the relationship between acetabular dysplasia and risk of hip OA is negative.

Acetabulum↗
PubMed2000

Production of male cloned mice from fresh, cultured, and cryopreserved immature Sertoli cells.

Although it is generally accepted that relatively high efficiencies of somatic cell cloning in mammals can be achieved by using donor cells from the female reproductive system (e.g., cumulus/granulosa, oviduct, and mammary gland cells), there is little information on the possibility of using male-specific somatic cells as donor cells. In this study we injected the nucleus of immature mouse Sertoli cells isolated from the testes of newborn (Days 3-10) males into enucleated mature oocytes in order to examine the ability of their nuclei to support embryonic development. After activation of the oocytes that had received the freshly recovered immature Sertoli cells, some developed into the morula/blastocyst stage, depending on the age of the donor cells (22.0-37.4%). When transferred into pseudopregnant females, 7 (3.3%, 7 of 215) developed into normal pups at term. Nuclear transfer of immature Sertoli cells after 1 wk in culture also produced normal pups after embryo transfer (3.1%, 2 of 65). Even after cryopreservation in a conventional cryoprotectant solution, their ability as donor cells was maintained, as demonstrated by the birth of cloned young (6.7%, 7 of 105). Immature Sertoli cells transfected with green fluorescent protein gene also supported embryo development into morulae/blastocysts, which showed specific fluorescence. This study demonstrates that immature Sertoli cells, male-specific somatic cells, are potential donors for somatic cell cloning.

Animals↗