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Biomedical subjects

S Ozaki

Publications and source records attributed to S Ozaki.

At least 19 recordsLinked to original sources
PubMed2002

Drug-induced neutropenia associated with anti-neutrophil cytoplasmic antibodies (ANCA): possible involvement of complement in granulocyte cytotoxicity.

Although antineutrophil antibodies are thought to be involved in drug-induced neutropenia, neither the precise mechanisms nor the particular antigens on the neutrophil surface have yet been clarified. Recently, we examined a patient with Graves' disease who developed antineutrophil cytoplasmic antibodies (ANCA) after propylthiouracil treatment and exhibited neutropenia. Because several target antigens of ANCA are expressed on the surface of neutrophils, it was suggested that ANCA might contribute to neutropenia. The patient's serum bound specifically to neutrophils and HL-60 cells differentiated into granulocytes, and lysed the HL-60 cells via a complement-mediated mechanism. Furthermore, two representative ANCA antigens, proteinase 3 and myeloperoxidase, significantly inhibited both the binding and cytotoxicity of the serum. Finally, tumour necrosis factor-alpha, which is known to up-regulate cell surface expression of several ANCA antigens, enhanced both the binding and cytotoxicity of the serum. These findings suggest that ANCA induced by propylthiouracil contributed to leucopenia through a complement-mediated mechanism.

Antibodies, Antineutrophil Cytoplasmic↗
PubMed2001

Observation of the "self-healing" of an error field island in the large helical device.

It was observed that the vacuum magnetic island produced by an external error magnetic field in the large helical device shrank in the presence of plasma. This was evidenced by the disappearance of flat regions in the electron temperature profile obtained by Thomson scattering. This island behavior depended on the magnetic configuration in which the plasmas were produced.

Journal Article↗
PubMed2001

Lack of the involvement of mu1-opioid receptor subtype on motivational effects induced by the endogenous mu-opioid receptor ligands endomorphin-1 and -2 in the mouse.

The present study was designed to investigate the role of mu-opioid receptor subtypes in the motivational effect of endogenous mu-opioid receptor ligands, endomorphin-1 and -2. In C57BL/6J mice, endomorphin-1 produced a significant place preference, whereas endomorphin-2 exhibited a significant place aversion. These effects were abolished by a mu1/mu2-opioid receptor antagonist beta-funaltrexamine. Under these conditions, both endomorphin-1 and -2 produced their motivational effects in mu1-opioid receptor-deficient CXBK mice, indicating the mu2-opioid receptor involvement. Furthermore, in the lower midbrain including ventral tegmental area, both endomorphin-1 and -2 equally produced dose-related increases in guanosine-5'-o-(3-[35S] thio) triphosphate bindings in C57BL/6J and CXBK mice. These findings indicate that endomorphin-1 and -2 may produce distinct motivational effects via respective mu2-opioid receptor isoforms in the mouse. Furthermore, endomorphin-1 and -2 produced the mu1-resistant G-protein activation in the mouse lower midbtrain.

Analgesics, Opioid↗
PubMed2001

In vitro inhibitory effects of J-113397 on nociceptin/orphanin FQ-stimulated.

J-113397 (1-[(3R,4R)-1-cyclooctylmethyl-3-hydroxymethyl-4-piperidyl]-3-ethyl-1,3-dihydro-2H-benzimidazol-2-one) is a recently developed antagonist of the opioid receptor-like 1 (ORL1) receptor. We compared the in vitro functional profile J-113397 on [35S]guanosine 5'-O-(gamma-thio)triphosphate (GTPgammaS) binding to mouse brain with that of [Phe1psi(CH2-NH)Gly2]nociceptin(1-13)NH2 and naloxone benzoylhydrazone (NalBzoH). J-113397 antagonized nociceptin/orphanin FQ-stimulated [35S]GTPgammaS binding to mouse brain with an IC50 value of 7.6 nM, but had no effect on basal [35S]GTPgammaS binding by itself. [Phe1psi(CH2-NH)Gly2]nociceptin(1-13)NH2 partially antagonized nociceptin/orphanin FQ-stimulated [35S]GTPgammaS binding but showed agonistic activity on ORL1 by itself. NalBzoH showed antagonistic activity on ORL1 receptor but had significant agonistic activity on other opioid receptors at lower doses. Schild plot analysis demonstrated competitive antagonism of J-113397 on ORL1 receptor in mouse brain. A [35S]GTPgammaS binding study using ORL1 receptor-deficient mice confirmed the selective antagonism of J-113397 on ORL1 receptor. These data indicate that J-113397 is the most potent and selective antagonist of ORL1 receptor in mouse brain that has yet been reported, and therefore will be a useful tool for characterization of ORL1 receptors in the brain.

Animals↗
PubMed2001

Protein conformation change of myoglobin upon ligand binding probed by ultraviolet resonance Raman spectroscopy.

Conformational change of myoglobin (Mb) accompanied by binding of a ligand was investigated with 244 nm excited ultraviolet resonance Raman Spectroscopy (UVRR). The UVRR spectra of native sperm whale (sw) and horse (h) Mbs and W7F and W14F swMb mutants for the deoxy and CO-bound states enabled us to reveal the UVRR spectra of Trp7, Trp14, and Tyr151 residues, separately. The difference spectra between the deoxy and CO-bound states reflected the environmental or structural changes of Trp and Tyr residues upon CO binding. The W3 band of Trp7 near the N-terminus exhibited a change upon CO binding, while Trp14 did not. Tyr151 in the C-terminus also exhibited a definite change upon CO binding, but Tyr103 and Tyr146 did not. The spectral change of Tyr residues was characterized through solvent effects of a model compound. The corresponding spectral differences between CO- and n-butyl isocyanide-bound forms were much smaller than those between the deoxy and CO-bound forms, suggesting that the conformation change in the C- and N-terminal regions is induced by the proximal side of the heme through the movement of iron. Although the swinging up of His64 upon binding of a bulky ligand is noted by X-ray crystallographic analysis, UVRR spectra of His for the n-butyl isocyanide-bound form did not detect the exposure of His64 to solvent.

Animals↗
PubMed2001

Successful emergency endometrial ablation for intractable uterine bleeding in a postmenopausal woman complicated with liver cirrhosis and morbid obesity.

Life-threatening intractable uterine bleeding is difficult to treat when concurrent medical complications contraindicate invasive surgery. We present a case of heavy uterine bleeding in a postmenopausal woman that was complicated by liver cirrhosis and morbid obesity. The bleeding was successfully halted through emergency endometrial ablation after failure of uterine artery embolization.

Electrocoagulation↗
PubMed2001

Immature multipotent hemopoietic progenitors lacking long-term bone marrow-reconstituting activity in the aorta-gonad-mesonephros region of murine day 10 fetuses.

Previous studies indicated that multipotent progenitors exist in early fetuses that do not contain long-term reconstituting (LTR) activity. However, it remained unclear whether these multipotent progenitors are committed to the hemopoietic lineage or are immature mesodermal cells or hemangioblasts. In this study, we have succeeded in enriching the multipotent progenitors that are capable of generating myeloid, T, and B cells in the LFA-1(-) subpopulation of TER-119(-)c-kit(+)CD45(+) cells from the aorta-gonad-mesonephros (AGM) region of day 10 fetuses. We found that these day 10 AGM LFA-1(-) cells do not show the LTR activity, whereas day 11 AGM LFA-1(-) cells do have such an activity. These results strongly suggest that multipotent progenitors lacking LTR activity emerge as CD45(+) hemopoietic progenitor cells in the AGM region on the 10th day of gestation, and such p-Multi mature into hemopoietic stem cells by acquiring LTR activity.

Animals↗
PubMed2001

Molecular engineering of myoglobin: the improvement of oxidation activity by replacing Phe-43 with tryptophan.

The F43W and F43W/H64L myoglobin (Mb) mutants have been constructed to investigate effects of an electron rich oxidizable amino acid residue in the heme vicinity on oxidation activities of Mb. The Phe-43 --> Trp mutation increases the rate of one-electron oxidation of guaiacol by 3-4-fold; however, the peroxidase activity for F43W/H64L Mb is less than that of the F43W single mutant because the absence of histidine, a general acid-base catalyst, in the distal heme pocket suppresses compound I formation. More than 15-fold improvement versus wild-type Mb in the two-electron oxidation of thioanisole and styrene is observed with the Phe-43 --> Trp mutation. Our results indicate that Trp-43 in the mutants enhances both one- and two-electron oxidation activities (i.e., F43W Mb > wild-type Mb and F43W/H64L Mb > H64L Mb). The level of (18)O incorporation from H2(18)O2 into the epoxide product for the wild type is 31%; however, the values for F43W and F43W/H64L Mb are 75 and 73%, respectively. Thus, Trp-43 in the mutants does not appear to be utilized as a major protein radical site to form a peroxy protein radical in the oxygenation. The enhanced peroxygenase activity might be explained by the increase in the reactivity of compound I. However, the oxidative modification of F43W/H64L Mb in compound I formation with mCPBA prevents us from determining the actual reactivity of the catalytic species for the intact protein. The Lys-C achromobacter digestion of the modified F43W/H64L mutant followed by FPLC and mass analysis shows that the Trp-43-Lys-47 fragment gains a mass by 30 Da, which could correspond two oxygen atoms and loss of two protons.

Amino Acid Substitution↗
PubMed2001

Frequent molecular identification of Campylobacter but not Helicobacter genus in bile and biliary epithelium in hepatolithiasis.

Bacterial infection of the biliary tree and bile stasis may be causally related to hepatolithiasis, but which bacterial species are involved and their roles in the pathogenesis of hepatolithiasis have not been ascertained. Recently, the Helicobacter genus was detected in human bile and biliary mucosal samples by molecular techniques, and its association with several biliary diseases has been suggested. The Campylobacter genus, which is closely related to the Helicobacter genus, has also recently been identified as causative of human gastrointestinal diseases. This study attempted to elucidate whether Helicobacter and/or Campylobacter bacteria are present in bile samples and biliary mucosal specimens from hepatolithiasis patients and whether they are involved in the pathogenesis of hepatolithiasis. The 16S rRNA gene of the Helicobacter and of the Campylobacter genus was examined by polymerase chain reaction in DNA samples extracted from bile and/or microdissected biliary epithelium from 69 patients with hepatolithiasis and control patients with choledocholithiasis, cholecystolithiasis, and normal gall bladders. The Helicobacter genus was detected in 1 of 8 (13%) biliary epithelial samples in hepatolithiasis and 1 of 10 (10%) bile samples in choledocholithiasis. The Campylobacter genus was detected in 3 of 14 (21%) bile samples and 5 of 8 (63%) epithelial samples in hepatolithiasis, and in 2 of 15 (13%) bile samples and 1 of 8 (13%) epithelial samples in cholecystolithiasis. The detection rate for Campylobacter in biliary epithelium of hepatolithiasis was significantly higher than in the bile or biliary epithelium of control groups (p<0.05). By a phylogenetic analysis based on nucleotide sequences, the Campylobacter genuses detected in hepatolithiasis were clustered with C. rectus or C. showae. The frequent detection of the Campylobacter 16S rRNA gene in bile, and especially in biliary epithelium of hepatolithiasis, suggests a pathogenetic relationship with Campylobacter infection.

Aged↗
PubMed2001

PCR and in situ hybridization studies of telomerase subunits in human non-neoplastic livers.

Telomerase, a ribonucleoprotein enzyme associated with cellular immortality, consists of human telomerase RNA component (hTERC), human telomerase protein 1 (hTEP1), and human telomerase reverse transcriptase (hTERT). In this study, the expression of these subunits was examined in non-neoplastic livers [13 cases of chronic viral hepatitis (CVH), 16 of primary biliary cirrhosis (PBC), two of primary sclerosing cholangitis, and six normal livers], using the reverse transcription-polymerase chain reaction (RT-PCR), nested PCR, and in situ hybridization (ISH). Six hepatocellular carcinoma (HCC) cases and one colonic cancer were used as positive controls. Telomeric repeat amplification protocol (TRAP) assay disclosed distinct telomerase activity in all positive controls and weak telomerase activity in non-neoplastic livers in 4 of 13 CVH cases and 5 of 16 PBC cases. By RT- and nested PCR, both hTERC and hTEP1 mRNA were detectable in all non-neoplastic liver tissues; ISH revealed hTERC and hTEP1 mRNA in the periportal and periseptal hepatocytes and inflammatory mononuclear cells in those cases examined. ISH revealed hTERT mRNA only in a few infiltrating mononuclear cells in 3 of 13 CVH and 2 of 16 PBC livers and these five cases were also positive by TRAP assay. In four of these five cases, hTERT mRNA was also detectable by nested PCR, suggesting that hTERT mRNA in the non-neoplastic liver is expressed by infiltrating mononuclear cells. Biliary epithelial cells were totally negative for these human telomerase subunits. Three subunits were constantly detected in all positive controls by ISH as well as by RT- and nested PCR. The finding that hTERC and hTEP1 mRNA, but not hTERT mRNA, were detectable in the non-neoplastic hepatocytes suggests that telomerase is present but not activated and that additional factor(s) are necessary for the expression of hTERT mRNA in the hepatocytes, along with immortalization and neoplastic transformation.

Adult↗
PubMed2001

Local cellular sources of apolipoprotein E in the human retina and retinal pigmented epithelium: implications for the process of drusen formation.

PURPOSE: The inheritance of specific apolipoprotein E allelles has been linked to atherosclerosis, Alzheimer disease, and, most recently, to the incidence of age-related macular degeneration. Apolipoprotein E is a common component of the extracellular plaques and deposits characteristic of these disorders, including drusen, which are a hallmark of age-related macular degeneration. Accordingly, we assessed the potential biosynthetic contribution of local ocular cell types to the apolipoprotein E found in drusen. METHODS: We measured apolipoprotein E mRNA levels in human donor tissues using a quantitative assay of apolipoprotein E transcription, and we localized apolipoprotein E protein to specific cell types and compartments in the neural retina, retinal pigmented epithelium, and choroid using laser scanning confocal immunofluorescence microscopy. RESULTS: Apolipoprotein E immunoreactivity is associated with photoreceptor outer segments, the retinal ganglion cell layer, the retinal pigmented epithelium basal cytoplasm and basal lamina, and with both collagenous layers of Bruch membrane. Apolipoprotein E appears to be a ubiquitous component of drusen, irrespective of clinical phenotype. It also accumulates in the cytoplasm of a subpopulation of retinal pigmented epithelial cells, many of which overlie or flank drusen. Mean levels of apolipoprotein E mRNA in the adult human retina are 45% and 150% of the levels measured in liver and adult brain, the two most abundant biosynthetic sources of apolipoprotein E. Apolipoprotein E mRNA levels are highest in the inner retina, and lowest in the outer retina where photoreceptors predominate. Significant levels of apolipoprotein E mRNA are also present in the retinal pigmented epithelium/choroid complex and in cultured human retinal pigmented epithelial cells. CONCLUSIONS: Apolipoprotein E protein is strategically located at the same anatomic locus where drusen are situated, and the retinal pigmented epithelium is the most likely local biosynthetic source of apolipoprotein E at that location. Age-related alteration of lipoprotein biosynthesis and/or processing at the level of the retinal pigmented epithelium and/or Bruch membrane may be a significant contributing factor in drusen formation and age-related macular degeneration pathogenesis.

Adult↗
PubMed2001

Calcification characteristics of porcine stented valves in a juvenile sheep model.

BACKGROUND: Different antimineralization treatments of stented porcine bioprostheses were evaluated: ethanol (Epic), alpha-amino-oleic acid (AOA) (Mosaic), and sodium dodecyl sulfate (SDS) (Hancock II). A nontreated, glutaraldehyde-fixed valve (Labcor) served as control. METHODS: For each treatment, six valves were implanted in juvenile sheep in the pulmonary position. Valves were explanted after 3 and 6 months and examined macroscopically, by roentgenogram and light and transmission electron microscopy. Calcium content (microg/mg) was determined by atomic absorption spectrometry. RESULTS: The Labcor valves revealed small calcium deposits in the cusps, although calcium content remained low (median value 0.4+/-0.8 microg/mg). SDS did not prevent cusp calcification as assessed by histology and calcium content measurement, which was higher than in all other valves: 1.9+/-4.6 microg/mg (p < 0.05). Cusp retraction and rupture were occasionally found in the Hancock. The Mosaic and Epic valves showed no cusp calcification and had low calcium contents (0.3+/-2.4 microg/mg and 0.7+/-0.6 microg/mg, respectively). Epic showed less pannus formation, but had hematoma or iron staining in the cusps. CONCLUSIONS: SDS is inefficient as an antimineralization treatment, in contrast to ethanol or AOA. Cusp hematoma after ethanol treatment needs further investigation.

Animals↗
PubMed2001

Increased expression of WAF1 in intrahepatic bile ducts in primary biliary cirrhosis relates to apoptosis.

BACKGROUND/AIMS: In primary biliary cirrhosis (PBC), the intrahepatic small bile ducts are selectively damaged by immune attacks, followed by progressive loss mainly due to apoptosis. Compared to the intercellular signaling such as the CD95/CD95 ligand interaction, little is known about alterations in intracellular cell cycle regulatory proteins and genotoxic damage in this apoptotic process. WAF1 is a potent and reversible inhibitor of cell cycle progression at both the G1 and G2 checkpoint and upregulated WAF1 induces irreversible G1 arrest and apoptosis. Transcriptional activation of the WAF1 gene is induced by the upregulated p53 in response to DNA damage. In this study, the cell cycle regulatory process of apoptosis in PBC was examined with respect to expression of WAF1. METHODS: Immunostaining for WAF1 and p53 was performed using 11 liver sections of PBC and 26 control livers. In addition, Ki67, apoptosis (TUNEL-positive), and human telomerase RNA (hTR) were also detected. RESULTS: WAF1 was expressed in the nuclei of several epithelial cells in most damaged bile ducts in PBC but infrequently or rarely in controls. Some of these cells were also positive for p53, while the remainder were not. Ki67 immunostaining and TUNEL disclosed that the bile ducts in PBC showed increased cell division as well as enhanced apoptosis. Immunostaining of Ki67 and TUNEL staining showed that WAF1-positive cells were not proliferating, while some WAF1-positive cells were undergoing apoptosis. Moreover, the bile ducts lacked hTR expression, implying progressive shortening of telomeres during increased cell divisions. CONCLUSIONS: It seems possible that in PBC, expression of WAF1 on biliary epithelial cells relates to the apoptosis. p53 may be involved in this upregulation. This may be due to physiological upregulation of WAF1 and p53 in response to genotoxic damage such as oxidative stress associated with cholangitis, suggesting other processes than CD95/CD95 ligand interaction in biliary epithelial apoptosis in PBC.

Aged↗
PubMed2001

Involvement of protein kinase Cgamma isoform in morphine-induced reinforcing effects.

The present study was designed to investigate the role of protein kinase C (PKC) isoform in the morphine-induced reinforcing effect in mice. An intracerebroventricular injection of calphostin C, a specific PKC inhibitor, produced a dose-dependent reduction in the morphine-induced place preference. The protein level of PKCgamma was significantly up-regulated in membrane preparations of the limbic forebrain obtained from the morphine-conditioned mice compared to that from the saline-conditioned mice. However, the protein levels of PKCalpha, betaI, betaII and epsilon were not affected in the same preparation. By contrast, there were no changes in the protein level of all five PKC isoforms in the lower midbrain. Furthermore, we investigated the rewarding properties of morphine in mice lacking PKCgamma gene. A significant place preference was observed following treatment with morphine in wild-type mice, whereas such an effect of morphine was not found in PKCgamma knockout mice. These findings suggest that activated PKCgamma in the limbic forebrain following the treatment with morphine may be critical for the development and/or maintenance of reinforcing effects induced by morphine in mice.

Analgesics, Opioid↗
PubMed2001

Different motivational effects induced by the endogenous mu-opioid receptor ligands endomorphin-1 and -2 in the mouse.

The present study was designed to investigate the motivational effects of the newly discovered endogenous mu-opioid receptor ligands, endomorphin-1 and endomorphin-2, using the conditioned place preference paradigm in mice. The binding properties of these peptides were first examined using an opioid binding assay. In membranes obtained from the mouse whole brain, the binding of [3H][D-Ala2, NMePhe4, Gly(ol)5]enkephalin (DAMGO; mu), but not of [3H][D-Phe2, D-Phe5]enkephalin (DPDPE; delta) or [3H]U69593 (kappa) selectively and concentration-dependently competed with that of endomorphin-1 and endomorphin-2, indicating that both endomorphin-1 and endomorphin-2 are specific ligands for mu-opioid receptors in the brain. Endomorphin-1 (1-30 nmol/mouse) given i.c.v. produced a dose-related place preference. This effect was abolished by pre-treatment with the mu-opioid receptor antagonist beta-funaltrexamine but not the delta-opioid receptor antagonist naltrindole or the kappa-opioid receptor antagonist nor-binaltorphimine. In contrast, endomorphin-2 (5.6 nmol/mouse) produced place aversion. This aversive effect was inhibited by nor-binaltorphimine as well as beta-funaltrexamine, but not by naltrindole. The place aversion produced by endomorphin-2 was also attenuated by pre-treatment with antiserum against the endogenous kappa-opioid receptor ligand dynorphin A (1-17). These findings indicate that endomorphin-1 may produce its rewarding effect via mu-opioid receptors. On the other hand, the aversive effect induced by endomorphin-2 may be associated with the stimulation of endomorphin-1-insensitive mu-opioid receptors and the activation of dynorphinergic systems in the mouse brain.

Animals↗
PubMed2001

Characteristics of patients with hypnotic-related psychiatric disorders in the nationwide mental hospital survey.

We investigated the characteristics of patients with hypnotic-related psychiatric disorders. Subjects were 90 patients reported in the nationwide Mental Hospital Survey in 1998, who were divided into three groups according to their history of substances use. Group A (patients without history of any illicit substance use) was estimated to be the most common and core group with iatrogenic characteristics. Hypnotic use in Group B (patients with history of any illicit substance use) was recognized as one of behavioral disorders in the psychosocial context. Patients in Group C (patients with multiple-substance use and without history of any illicit substance use) showed the most serious disorders in the context of addiction. More specified treatment programs would be required considering patients' characteristics.

Adult↗