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Biomedical subjects

T Okazaki

Publications and source records attributed to T Okazaki.

At least 55 records · Page 3Linked to original sources
PubMed2001

Urinary trypsin inhibitor and biliary atresia--providing protection for the liver?

Urinary Tyrosine Inhibitor (UTI) is produced in the liver and excreted in urine hepatic inflammation, infection or malignancy. We assess the possible implications of UTI in biliary atresia (BA). Liver function was used to divide 34 postoperative BA patients into 2 groups: Group 1 (n=25), anicteric (total bilirubin [T-Bil] <2.0 mg/dl); and Group 2 (n = 9), icteric (total bilirubin >2.0 mg/dl) with abnormal liver function test results, and repeated episodes of cholangitis. 26 age-matched subjects with no history of liver disease acted as controls

Adolescent↗
PubMed2001

Antigen-specific T(h)1 cells as direct effectors of Propionibacterium acnes-primed lipopolysaccharide-induced hepatic injury.

T(h)1 cells are cytotoxic effector cells that utilize Fas ligand (FasL) and tumor necrosis factor. The physiological roles of cytotoxic T(h)1 cells are considered to be immunoregulation by eliminating autoreactive lymphocytes or hyper-activated foreign antigen-specific lymphocytes. Their pathological roles, however, remain to be clarified. To investigate whether T(h)1 cells can destroy organs, we generated a Propionibacterium acnes-specific T(h)1 clone from C57BL/6 mice and tested whether the clone could serve as an effector in a P. acnes-primed lipopolysaccharide (LPS)-induced hepatic injury system, one of the septic shock models. B6SMN:C3H-FasL(gld) (B6-gld) mice, which were deficient in functional FasL, were resistant to P. acnes/LPS-induced hepatic shock. The T(h)1 clone rendered B6-gld mice sensitive to the hepatic shock after the i.v. transfer. The hepatic injury in the clone-transferred B6-gld mice, which was evaluated by both biochemical and histological examination, was inhibited by an anti-FasL mAb that we developed. These results suggested that bacterial antigen-specific T(h)1 cells like this clone can participate in organ destruction in vivo as one of the cytotoxic effectors and play a critical role in endotoxin-induced hepatic injury.

Adoptive Transfer↗
PubMed2001

Extent of intestinal damage in the developing chick embryo after repetitive hypoxia under normoxic or hyperoxic conditions.

BACKGROUND: Episodes of hypoxia and reperfusion play an important role in the development of intestinal damage during perinatal development. The aim of this study was to investigate the histopathology of the intestine in the developing chick embryo after exposure to repetitive hypoxia and recovery under two different conditions: normoxic and hyperoxic (60% O2). METHODS: Chick embryos were exposed to 5 minutes of hypoxia. This was repeated six times with a recovery period of 15 minutes under normoxic conditions (21% O2) for chick embryos in test group 1 (TG1) and under hyperoxic conditions (100% O2) for chick embryos in test group 2 (TG2), from day 11 until day 20. Chick embryos that recovered under hyperoxic conditions (100% O2) were previously incubated under hyperoxic conditions (60% O2 for 24 hours). Histologic evaluation of the ileum was performed at different times after the interventions (2, 4, 8, 16, and 24 hours). RESULTS: In both test groups, only chick embryos older than 19 days showed intestinal damage. Intestinal histology on day 19 showed vasodilation of villus capillaries (10% in TG1 and 15% in TG2), necrosis in the top of the villi (29% in TG1 and 30% in TG2), and necrosis with preservation of base of the crypts (2% in TG1) and transmucosal necrosis (2% in TG2). CONCLUSIONS: Significant histologic changes, compared with the control group, were only found in chick embryos that were studied 2 hours after the interventions. Furthermore, recovery under hyperoxic conditions did not cause more intestinal damage compared with recovery under normoxic conditions.

Age Factors↗
PubMed2001

Role of osteopontin in the pathogenesis of bleomycin-induced pulmonary fibrosis.

Pulmonary fibrosis is initiated by migration, adhesion, and proliferation of fibroblasts. Osteopontin (OPN) is one of the cytokines produced by activated macrophages and mediates various functions, including cell attachment and migration, by interacting with alphav integrin. In this study, we have investigated the role of OPN in the pathogenesis of pulmonary fibrosis. We developed a mouse model for pulmonary fibrosis by intratracheal instillation of bleomycin (BLM). OPN was strongly expressed in alveolar macrophages accumulating in the fibrotic area of the lung. OPN messenger RNA (mRNA) in the lung was notably induced by BLM instillation, and the development of the fibrotic process was associated with an increase in the expression of OPN mRNA and protein. In vitro, recombinant OPN enhanced migration, adhesion, and platelet-derived growth factor (PDGF)-mediated DNA synthesis of murine fibroblast cell line NIH3T3. These effects of OPN on fibroblasts were significantly suppressed by addition of antimouse alphav integrin monoclonal antibody (RMV-7). Furthermore, treatment of mice with RMV-7 repressed the extent of pulmonary fibrosis in this model. Conclusively, these data suggest that OPN produced by alveolar macrophages functions as a fibrogenic cytokine that promotes migration, adhesion, and proliferation of fibroblasts in the development of BLM-induced pulmonary fibrosis.

Animals↗
PubMed2001

GH inhibits interferon-gamma-induced signal transducer and activator of transcription-1 activation and expression of the inducible isoform of nitric oxide synthase in INS-1 cells.

Interferon-gamma and TNFalpha synergistically induce the inducible isoform of nitric oxide synthase and elicit severe cytotoxicity in pancreatic beta-cells. We demonstrate here that GH, the well known beta-cell mitogen, inhibits nitric oxide production by reducing inducible nitric oxide synthase gene induction by the two cytokines and counteracts their cytotoxic effect in insulin-secreting INS-1 cells. To elucidate the underlying mechanism, we examined activation of the transcription factors implicated in the induction of inducible nitric oxide synthase, signal transducer and activator of transcription-1, and nuclear factor-kappa B. GH inhibited tyrosine phosphorylation and DNA binding of signal transducer and activator of transcription-1 promoted by interferon-gamma, whereas nuclear factor-kappa B activation by TNFalpha was not affected by GH. GH was found to induce suppressor of cytokine signaling-1 and -3, both of which are able to inhibit interferon-gamma activation of signal transducer and activator of transcription-1, suggesting that they are likely to mediate the inhibitory action of GH. Finally, exposure of INS-1 cells to interferon-gamma resulted in the impairment of insulin secretion in response to glucose, which was restored by the addition of GH. These results indicate that GH counteracts the effect of interferon-gamma through the inhibition of signal transducer and activator of transcription-1. This action of GH may be sufficient to suppress the synergistic induction of inducible nitric oxide synthase by interferon-gamma and TNFalpha, thereby preventing the cytotoxicity to beta-cells.

Animals↗
PubMed2001

Effects of a community-based lifestyle-modification program on cardiovascular risk factors in middle-aged women.

We investigate the effectiveness of a community-based lifestyle-modification program for reducing blood pressure and other cardiovascular risk factors in sedentary Japanese middle-aged women. Among an initial cohort of 210 middle-aged sedentary women, 195 subjects completed a community-based 12-week lifestyle-modification program for reducing cardiovascular risk factors. Blood pressure, body weight and the serum lipid profile were measured both at baseline and at the end of the 12-week lifestyle-modification program. The program consisted of mild aerobic exercise and a mild hypocaloric diet. After the 12-week program, both systolic and diastolic blood pressure were significantly reduced, especially in subjects who were hypertensive at baseline. Desirable changes in body weight and the serum lipid profile were also found after the 12-week program. Multiple linear regression analysis revealed that, in obese subjects, the decrease in systolic blood pressure was correlated with both the initial systolic blood pressure and the change in estimated maximum oxygen consumption. In addition, the decrease in diastolic blood pressure was correlated with the initial diastolic blood pressure and the change in body weight. On the other hand, in non-obese subjects, the decrease in blood pressure was correlated with the initial blood pressure and the change in salt intake. A community-based lifestyle-modification program that consisted of mild aerobic exercise and a mild hypocaloric diet was considered to be practically effective for reducing multiple cardiovascular risk factors. Individuals who already have one or more mild cardiovascular risk factors still could be good candidates for a community-based lifestyle-modification program.

Blood Pressure↗
PubMed2001

[Disseminated atypical mycobacteriosis in a patient with chronic myelogenous leukemia].

A 61-year-old woman with a 6-year history of chronic myelogenous leukemia (CML) presented with recurrent fever in July 1996. Bone marrow aspiration, biopsy and chromosome analysis showed that CML was in the chronic phase. Bone marrow biopsy revealed nonspecific inflammatory lesions. Chest X-ray and computed tomography examinations demonstrated interstitial pneumonia. Cultures of gastric juice and bone marrow yielded colonies of Mycobacterium avium complex (MAC), and a diagnosis of disseminated atypical mycobacteriosis was made. Multidrug treatment including rifampicin, ethambutol, clarithromycin and ciprofloxacin was begun. The cultures subsequently became negative and the fever was resolved. However, fever eventually recurred and the patient died of multiple organ failure in October 1997. since disseminated atypical mycobacteriosis complicating hematological disorders worsens the prognosis, its early diagnosis and prompt treatment are important. Although it is often difficult to identify atypical mycobacterium as a causal agent, frequent culturing of atypical mycobacterium from various sources including bone marrow fluid can be helpful for early diagnosis whenever fever of undetermined origin occurs in patients with hematological disorders.

Female↗
PubMed2001

[Regulation of PTH gene by calcium and phosphate].

The mechanism of PTH gene regulation by extracellular calcium and phosphate is currently divided into two categories. One is through the transcriptional event in which negative calcium responsive element conserved in the 5'-flanking region of the PTH genes of various species and its binding protein play an crucial role. Another hypothesis is that regulation by calcium and phosphate, especially the effect of hypocalcemia and hypophosphatemia, is triggered by the post-transcriptional regulation of the PTH gene. Although both hypotheses are not mutually exclusive, in vivo effect of low calcium and low phosphate is likely to be exerted chiefly by the post-transcriptional mechanism. However, both studies have never linked their findings to the function of calcium sensing receptors. Here, I will review the current understanding of these molecular events regarding physiological regulation of the PTH gene.

English Abstract↗
PubMed2000

Element-selective single atom imaging.

Electron energy-loss spectroscopy (EELS) is widely used to identify elemental compositions of materials studied by microscopy. We demonstrate that the sensitivity and spatial resolution of EELS can be extended to the single-atom limit. A chemical map for gadolinium (Gd) clearly reveals the distribution of Gd atoms inside a single chain of metallofullerene molecules (Gd@C82) generated within a single-wall carbon nanotube. This characterization technique thus provides the "eyes" to see and identify individual atoms in nanostructures. It is likely to find broad application in nanoscale science and technology research.

Journal Article↗
PubMed2000

One-dimensional metallofullerene crystal generated inside single-walled carbon nanotubes.

Electron microscope imaging for gadolinium metallofullerenes encapsulating in single-wall carbon nanotubes [(Gd@C82)n@SWNTs] identifies the single Gd atom encaged in each. The intermolecular distance between Gd@C82 is extremely regular, regarding the chains of Gd@C82 as novel one-dimensional crystals. Chemical state analysis of Gd atoms suggests evidence for charge transfer from Gd to either a fullerene cage or a nanotube. The slopes of the temperature dependence of electric resistance for the mat-like films of (Gd@C82)n@SWNTs and (C60)n@SWNTs are much steeper than that for empty SWNTs, suggesting the electron scattering due to the electrostatic potential from inside fullerenes playing an important role.

Journal Article↗
PubMed2000

Genomic organization, chromosomal localization, and the complete 22 kb DNA sequence of the human GCMa/GCM1, a placenta-specific transcription factor gene.

The genomic sequence of the human GCMa/GCM1 gene, a mammalian homologue of Drosophila melanogaster GCM, was determined. Drosophila GCM is a neural transcription factor that regulates glial cell fate. The mammalian homolog however, is a placenta-specific transcription factor that is necessary for placental development. The 22 kb DNA sequence spanning the GCMa gene contains six exons and five introns, encoding a 2.8 kb cDNA. Overall genomic organization is similar for the human and mouse. Several potential binding sites for transcription factors like GATA, Oct-1, and bHLH proteins were found in the 5'-flanking region of the human gene. A DNA motif for GCM protein binding exists in the 5'-flanking region that is highly homologous with that of the mouse gene. The location of this gene was mapped to chromosome 6 using fluorescence in situ hybridization.

Animals↗
PubMed2000

Persistent carbocations from bay region methoxy-substituted cyclopenta[a]phenanthrene and its derivatives. A structure/reactivity study.

Using 500 MHz NMR, we have carried out a stable ion protonation and model nitration study of the methoxy-substituted hydrocarbon 6, its 15-ol 7, and the dimer 10, in order to evaluate OMe substituent effects on directing electrophilic attack and on charge delocalization mode/conformational aspects in the resulting carbocations. It is found that the C-11 methoxy group directs the electrophilic attack to C-12 and C-14. Thus protonation of 6 with FSO(3)H/SO(2)ClF gives a 4:1 mixture of monoarenium ions 6H(+)()/6aH(+)(). Prolonged reaction times and increased temperature induced fluorosulfonylation at C-14 (6(+)-SO(2)()F), whereas ambient nitration with NO(2)(+)BF(4)(-) occurred at C-12. The 15-ol derivative 7 is cleanly ionized to 11(+)(), providing the first example of an alpha-phenanthrene-substituted carbocation from phenanthrene C-1 position. Contrasting behavior of the D-ring methyl-substituted 9 and the C-11 methoxy-substituted 10 dimers is remarkable in that unlike 9 which is readily cleaved to produce the monomeric arenium ion 3H(+)(), 10 is diprotonated at the two C-12 sites and at C-12/C-14 in each unit. The latter dication-dimer exists as a mixture of diastereomers. Reactivity of 7 underscores the importance of 11(+)(). Attack at the C-14 ring junction is in concert with the proposal that electrophilic oxygen would attack at C-14/C-15 (epoxidation) followed by ring opening to give the biologically active 15-ol as a major metabolite.

Cations↗
PubMed2000

Engagement of the PD-1 immunoinhibitory receptor by a novel B7 family member leads to negative regulation of lymphocyte activation.

PD-1 is an immunoinhibitory receptor expressed by activated T cells, B cells, and myeloid cells. Mice deficient in PD-1 exhibit a breakdown of peripheral tolerance and demonstrate multiple autoimmune features. We report here that the ligand of PD-1 (PD-L1) is a member of the B7 gene family. Engagement of PD-1 by PD-L1 leads to the inhibition of T cell receptor-mediated lymphocyte proliferation and cytokine secretion. In addition, PD-1 signaling can inhibit at least suboptimal levels of CD28-mediated costimulation. PD-L1 is expressed by antigen-presenting cells, including human peripheral blood monocytes stimulated with interferon gamma, and activated human and murine dendritic cells. In addition, PD-L1 is expressed in nonlymphoid tissues such as heart and lung. The relative levels of inhibitory PD-L1 and costimulatory B7-1/B7-2 signals on antigen-presenting cells may determine the extent of T cell activation and consequently the threshold between tolerance and autoimmunity. PD-L1 expression on nonlymphoid tissues and its potential interaction with PD-1 may subsequently determine the extent of immune responses at sites of inflammation.

Amino Acid Sequence↗
PubMed2000

Structural factors for the formation of propellane-type products in the solvolysis of bicyclic bridgehead compounds

Methanolyses of 2-oxobicyclo[3.3.1]non-1-yl triflate, 3, 3-dimethyl-2-oxobicyclo[3.3.1]non-1-yl triflate, and 2-oxobicyclo[4. 3.1]dec-1-yl mesylate gave the corresponding propellanone in 12%, 20%, or 3.2% yield, respectively, beside substitution or rearranged products under typical conditions. No propellane-type product was obtained in the solvolyses of 1-bromobicyclo[3.3.1]nonane, 2-methylidenebicyclo[3.3.1]non-1-yl heptafluorobutyrate, and 3, 3-dimethyl-2-thioxobicyclo[3.3.1]non-1-yl tosylate. The factors that permit the formation of the propellane-type product from the intermediate bridgehead cations are examined with the aid of theoretical calculations at PM3 and B3LYP/6-31G.

Journal Article↗
PubMed2000

Human centromere protein A (CENP-A) can replace histone H3 in nucleosome reconstitution in vitro.

Centromere protein A (CENP-A) is a variant of histone H3 with more than 60% sequence identity at the C-terminal histone fold domain. CENP-A specifically locates to active centromeres of animal chromosomes and therefore is believed to be a component of the specialized centromeric nucleosomes on which the kinetochores are assembled. Here we report that CENP-A, highly purified from HeLa cells, can indeed replace histone H3 in a nucleosome reconstitution system mediated by nucleosome assembly protein-1 (NAP-1). The structure of the nucleosomes reconstituted with recombinant CENP-A, histones H2A, H2B, and H4, and closed circular DNAs had the following properties. By atomic force microscopy, "beads on a string" images were obtained that were similar to those obtained with nucleosomes reconstituted with four standard histones. DNA ladders with repeats of approximately 10 bp were produced by DNase I digestion, indicating that the DNA was wrapped round the protein complex. Mononucleosomes isolated by glycerol gradient sedimentation had a relative molecular mass of approximately 200 kDa and were composed of 120-150 bp of DNA and equimolar amounts of CENP-A, and histones H4, H2A, and H2B. Thus, we conclude that CENP-A forms an octameric complex with histones H4, H2A, and H2B in the presence of DNA.

Autoantigens↗
PubMed2000

Stable ion study of regioisomeric carboxonium-substituted pyrenium ions: directive effects, charge delocalization mode, and conformational aspects.

Regioisomeric monoacyl- and monobenzoyl-substituted pyrenes are diprotonated in FSO(3)H.SbF(5) (4:1)/SO(2)ClF to give persistent carboxonium-pyrenium dications, whereas diacetyl- and dibenzoylpyrenes are diprotonated to give dicarboxonium dications. The resulting dications were studied by low-temperature NMR at 500 MHz. Conformational aspects of the carboxonium group in various regioisomers are addressed by a combination of NOED spectra and 2D-NMR and AM1 calculations. Charge delocalization pathways are gauged and compared on the basis of the magnitude of Deltadelta (13)C values.

Acetylation↗
PubMed2000

Ipsilateral hemiparesis after putaminal hemorrhage due to uncrossed pyramidal tract.

OBJECTIVE: Previous case reports supported the presence of the uncrossed pyramidal tract in exceptional patients. However, most of these case reports have not fully discussed involvement of the motor cortex controlling the ipsilateral limbs. DESIGN AND METHOD: The authors investigated a 62-year-old man who developed right hemiparesis after right putaminal hemorrhage by using MRI, transcranial magnetic stimulation, functional MRI (fMRI), and sensory evoked potentials. He had moderate weakness including the face, spasticity with brisk deep tendon reflexes and Babinski sign, and impaired vibration and position sense, all on the right side. RESULT: A MRI study showed hemorrhage in the right putamen and the wedge-shaped medulla. A fMRI study during a sequential finger opposition task showed activation in the motor cortex ipsilateral to the finger movements, but not on the contralateral side. Sensory evoked potentials showed cortical response ipsilateral to the side of stimulation. CONCLUSION: The pyramidal tract and the dorsal column-medial lemniscus pathway did not cross in the medulla in this patient. In view of the presence of the abnormal shape in the medulla and congenital scoliosis, a congenital factor might be responsible for the uncrossed pyramidal tract and dorsal column-medial lemniscus in this patient.

Brain Mapping↗