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Biomedical subjects

S Sakaguchi

Publications and source records attributed to S Sakaguchi.

At least 19 recordsLinked to original sources
PubMed2003

Development and disintegration of phragmoplasts in living cultured cells of a GFP::TUA6 transgenic Arabidopsis thaliana plant.

Cultured suspension cells of Arabidopsis thaliana that stably express a green-fluorescent protein-alpha-tubulin 6 fusion protein were used to follow the development and disintegration of phragmoplasts. The development and disintegration of phragmoplasts in the living cultured cells could be successively observed by detecting the green-fluorescent protein fluorescence of the microtubules. In the early telophase spindle, where two kinetochore groups and two daughter chromosome groups had completely separated from one another, fluorescence appeared in the interzone between the two chromosome groups. The fluorescent region was gradually condensed at the previous equator and increased in fluorescence intensity, and finally it formed the initial phragmoplast. The initial phragmoplast moved from the cell center towards the cell periphery, and it lost fluorescence at its center and became double rings in shape. The expansion orientation of the phragmoplast was not always the same as that of the future new cell wall before it came in contact with the cell wall. The phragmoplast did not usually come in contact with the cell wall simultaneously with its entire length. A portion of the phragmoplast which was earlier in contact with the cell wall disappeared earlier than other portions of the phragmoplast. The duration of contact between any portions of the phragmoplast and the plasma membrane of the cell wall was 15-30 min. The fluorescence intensity of the cytoplasm did not seem to be elevated by the disintegration of the strongly fluorescent phragmoplast.

Arabidopsis↗
PubMed2003

Catecholamine response during haemodynamically stable upright posture in individuals with and without tilt-table induced vasovagal syncope.

AIM: Changes in circulating catecholamine concentrations during vasovagal faints have been the subject of considerable study. However, whether catecholamines are part of the triggering mechanism, or principally reflect attempted compensation for an evolving circulatory crisis is unknown. To address this issue, we determined whether the circulating catecholamine response to upright posture differs among patients with and without inducible vasovagal faints at a time when there is no detectable haemodynamic compromise. METHODS AND RESULTS: Blood samples for measurement of adrenaline and noradrenaline (Norepi) concentrations were obtained in the baseline state, and at both 2-3 min and 4-6 min of upright posture in 22 patients undergoing head-up tilt-table testing for evaluation of syncope of unknown cause. In 11 individuals tilt-testing induced syncope at >5 min head-up posture (Group 1). In 11 other individuals tilt testing did not result in syncope (Group 2). Supine arterial catecholamine levels were comparable in the two groups. However, adrenaline concentrations during upright posture tended to be greater at 2-3 min and were significantly greater at 4-6 min in Group 1 than in Group 2 (P< 0.01). These differences occurred in the absence of significant intergroup differences in mean arterial pressure or cardiac cycle lengths. Norepi concentrations also increased in both groups, but without significant differences. CONCLUSION: Circulating adrenaline concentrations in posturally induced vasovagal faints rise more rapidly in vasovagal fainters than in comparably posturally stressed non-fainters, and were significantly greater in fainters prior to either detectable haemodynamic compromise or diminution of circulating Norepi levels. These findings suggest that a premonitory rise in adrenaline concentrations occurs in vasovagal fainters unassociated with an evolving circulatory crisis.

Adolescent↗
PubMed2002

Accelerated reendothelialization with suppressed thrombogenic property and neointimal hyperplasia of rabbit jugular vein grafts by adenovirus-mediated gene transfer of C-type natriuretic peptide.

BACKGROUND: Vein graft disease limits the late results of coronary revascularization. C-type natriuretic peptide (CNP) inhibits the growth of vascular smooth muscle cells. Given the effects of CNP on cGMP cascade, we hypothesized that transfected CNP genes modulate endothelial repair and thrombogenicity in the vein graft. METHODS AND RESULTS: Autologous rabbit jugular vein grafts were incubated ex vivo in a solution of adenovirus vectors containing CNP gene (Ad.CNP) or Escherichia coli lac Z gene (Ad.LacZ) and then interposed in the carotid artery. Reendothelialization, mural thrombi formation, and intima/media ratio were evaluated on the 14th and 28th postoperative days. More reendothelialization was seen in Ad.CNP-infected grafts than in Ad.LacZ-infected grafts both at 14 days (0.81+/-0.05 versus 0.30+/-0.14, P<0.01) and at 28 days (0.96+/-0.01 versus 0.45+/-0.08, P<0.001). The mural thrombus area was smaller in Ad.CNP-infected grafts than in Ad.LacZ-infected grafts. Neointimal thickening was significantly suppressed in the Ad.CNP group. The in vitro wound assay with human coronary artery endothelial cells revealed significant potentiation of the wound repair process by CNP and atrial natriuretic peptide administration. CONCLUSIONS: Infected Ad.CNP accelerated reendothelialization and suppressed thrombosis and neointimal hyperplasia. The method may potentially prevent vein graft disease in patients undergoing coronary artery revascularization.

Adenoviridae↗
PubMed2001

Catalytic oxyalkylation of alkenes with alkanes and molecular oxygen via a radical process using N-hydroxyphthalimide.

A novel catalytic method for the radical addition of alkanes and molecular oxygen to electron-deficient alkenes was achieved by the use of N-hydroxyphthalimide (NHPI) combined with a Co species as the catalyst. This reaction is referred to as oxyalkylation of alkenes with alkanes and O(2). For instance, the reaction of 1,3-dimethyladamantane with methyl acrylate under molecular oxygen in the presence of catalytic amounts of NHPI and Co(acac)(3) at 70 degrees C for 16 h gave oxyalkylated products in 91% yield. Other alkenes such as fumarate and acrylonitrile also serve as good acceptors of alkyl radicals and O(2) to afford the corresponding adducts in high yields. The generality of the present reaction was examined between various alkanes and alkenes under dioxygen. The behavior of Co ions during the reaction course was discussed. The present reaction involves (i) an alkyl radical generation via hydrogen abstraction of alkane by phthalimide N-oxyl generated in situ from NHPI and O(2) assisted by Co(II), (ii) the addition of the resulting alkyl radical to an electron-deficient alkene to form an adduct radical, (iii) trapping of the adduct radical by O(2) yielding a hydroperoxide, and (iv) the decomposition of the hydroperoxide by Co ions to form an adduct in which a hydroxy or a carbonyl function is incorporated.

Journal Article↗
PubMed2001

Iridium-catalyzed transfer hydrogenation of alpha,beta-unsaturated and saturated carbonyl compounds with 2-propanol.

The selective transfer hydrogenation of alpha,beta-unsaturated carbonyl compounds to saturated ones was achieved by the use of 2-propanol as a hydrogen donor under the influence of catalytic amounts of [Ir(cod)Cl](2), 1,3-bis(diphenylphosphino)propane (dppp), and Cs(2)CO(3). Thus, a variety of conjugated enones were allowed to react with 2-propanol in the presence of the [Ir(cod)Cl](2)/dppp/Cs(2)CO(3) system to give the corresponding saturated carbonyl compounds in good to excellent yields without formation of allylic alcohols. Both dppp and Cs(2)CO(3) were essential components to achieve the reduction satisfactorily. Additionally, the reduction of carbonyl compounds to alcohols was also promoted by the same catalytic system. When the reaction of a 1:1 mixture of a conjugated ketone and a saturated ketone with 2-propanol was carried out in the presence of [Ir(cod)Cl](2) combined with dppp and Cs(2)CO(3), the reduction of the alpha,beta-unsaturated ketone was found to take place in preference to that of the saturated ketone.

2-Propanol↗
PubMed2001

Effects of N(G)-nitro-L-arginine methyl ester on endotoxin-induced leakage of lactate dehydrogenase and cytotoxicity in J774A.1 cells.

In the present study, we investigated the effects of the nitric oxide (NO) synthase inhibitor N(G)-nitro-L-arginine-methyl ester (L-NAME) on tissue injury or cytotoxicity caused by endotoxin challenge by assaying lactate dehydrogenase (LDH) isozymes and cell viability in J774A.1 cells. In mice treated with L-NAME (10 mg kg(-1), i.v.), the activity of LDH in serum 18 h after endotoxin (6 mg kg(-1), i.p.) injection was not significantly different from that in mice treated with endotoxin alone. Mice injected with endotoxin exhibited leakage of LDH isozymes 3 and 5, but L-NAME did not protect against endotoxin-induced acute leakage of LDH isozymes. Treatment with L-NAME (10-1000 microM) significantly inhibited NO generation by endotoxin (1 microg ml(-1))-activated J774A.1 cells. However, L-NAME (10-1000 microM) did not affect endotoxin-induced cytotoxicity in J774A.1 cells. These findings suggested that endotoxin-induced NO formation may not contribute to tissue injury or cytotoxicity caused by endotoxin.

Animals↗
PubMed2001

cGMP-dependent protein kinase phosphorylates and inactivates RhoA.

Small GTPase Rho and cGMP/cGMP-dependent protein kinase (cGK) pathways exert opposing effects in specific systems such as vascular contraction and growth. However, the direct interaction between these pathways has remained elusive. We demonstrate that cGK phosphorylates RhoA in vitro at Ser188, the same residue phosphorylated by cAMP-dependent protein kinase. In HeLa cells transfected with constitutively active cGK (C-cGK), stress fiber formation induced by lysophosphatidic acid or V14RhoA was blocked. By contrast, C-cGK failed to inhibit stress fiber formation in cells transfected with mutant RhoA with substitution of Ser188 to Ala. C-cGK did not affect actin reorganization induced by Rac1 or Rho-associated kinase, one of the effectors for RhoA. Furthermore, C-cGK expression inhibited the membrane translocation of RhoA. Collectively, our findings suggest that cGK phosphorylates RhoA at Ser188 and inactivates RhoA signaling. The physiological relevance of the direct interaction between RhoA and cGK awaits further investigation.

Actins↗
PubMed2001

Increased T cell autoreactivity in the absence of CD40-CD40 ligand interactions: a role of CD40 in regulatory T cell development.

Mutations in the CD40 ligand (CD40L) gene lead to X-linked immunodeficiency with hyper-IgM, which is often associated with autoimmune diseases. To determine the contribution of defective CD40-CD40L interactions to T cell autoreactivity, we reconstituted CD40-CD40L interactions by transferring T cells from CD40-deficient mice to syngenic athymic nude mice and assessed autoimmunity. T cells from CD40-deficient mice triggered autoimmune diseases accompanied with elevations of various autoantibodies, while those from wild-type mice did not. In CD40-deficient mice, the CD25(+) CD45RB(low) CD4(+) subpopulation which regulates T cell autoreactivity was markedly reduced. CD40-deficient APCs failed to induce T regulatory cells 1 producing high levels of an inhibitory cytokine, IL-10 in vitro. Furthermore, autoimmune development was inhibited when T cells from CD40-deficient mice were cotransferred with CD45RB(low) CD4(+) T cells from wild-type mice or with T regulatory cells 1 induced on CD40-expressing APCs. Collectively, our results indicate that CD40-CD40L interactions contribute to negative regulation of T cell autoreactivity and that defective interactions can lead to autoimmunity.

Animals↗
PubMed2001

Clinical features and management of hepatic portal venous gas: four case reports and cumulative review of the literature.

HYPOTHESIS: Hepatic portal venous gas (HPVG) has been considered a rare entity associated with a grave prognosis. Since 1978, when Liebman et al reviewed 64 cases of HPVG and reported a mortality of 75%, the number of reported cases has been increasing. DESIGN: Case series. PATIENTS AND METHODS: We reviewed the literature on 182 cases of HPVG in adults, including 4 of our patients, (transplantation and abdominal trauma cases were excluded) and analyzed the cause, pathogenesis, and clinical features. RESULTS: In this series, the underlying clinical events associated with HPVG were bowel necrosis (43%), digestive tract dilatation (12%), intraperitoneal abscess (11%), ulcerative colitis (4%), gastric ulcer (4%), Crohn disease (4%), complications of endoscopic procedures (4%), intraperitoneal tumor (3%), and other (15%). The overall mortality was 39% but varied depending on the underlying disease. CONCLUSIONS: Hepatic portal venous gas is a lethal or curable entity caused by various diseases. The underlying disease associated with HPVG determines the clinical features and prognosis of the patients. The treatment of patients with HPVG should be directed to the underlying disease.

Aged↗
PubMed2001

Mannose 6-phosphate/insulin-like growth factor 2 receptor (M6P/IGF2R) variants in American and Japanese populations.

M6P/IGF2R encodes a multifunctional protein involved in lysosomal enzyme trafficking, fetal organogenesis, tumor suppression, and cytotoxic T cell-induced apoptosis. M6P/IGF2R is imprinted and expressed only from the maternally inherited allele in marsupials and rodents. In contrast, humans were initially reported to differ from the imprinted mammalian orders by not having an imprinted M6P/IGF2R; however, some studies now suggest M6P/IGF2R imprinting may be a human polymorphic trait. Mutational and functional evidence are consistent with M6P/IGF2R also being a tumor suppressor in human colon, liver, lung, breast, and ovarian cancers. M6P/IGF2R expression is also pathologically downregulated following mammalian in vitro embryo culture, resulting in fetal overgrowth and "large offspring syndrome." Therefore, the M6P/IGF2R imprint status in humans is an unresolved question that critically impacts upon biological issues ranging from human cancer predisposition to evolution. Attempts to further characterize the imprint status of human M6P/IGF2R and loss of heterozygosity at this locus in cancer have been hindered by a lack of readily usable polymorphisms. To facilitate these genetic analyses, we have screened American and Japanese populations for M6P/IGF2R single nucleotide polymorphisms (SNPs). We have identified nine novel SNPs intragenic to human M6P/IGF2R, and have described experimental conditions for their optimal use. Three identified amino-acid variants in the M6P/IGF2R ligand-binding domains may be under selection in humans.

Alleles↗
PubMed2001

Power Doppler sonography of hepatocellular carcinomas with portal-vein blood supply.

We report the power Doppler imaging (PDI) findings in 2 cases of hepatocellular carcinoma (HCC) with a portal-vein blood supply. Gray-scale sonography in both cases showed a well-circumscribed nodule, hypoechoic in case 1 and hyperechoic in case 2. PDI revealed an afferent tumor vessel with constant flow in both nodules, and CT during arterial portography demonstrated a portal-vein supply to both nodules. The nodules were diagnosed by percutaneous core biopsies as highly differentiated HCC. We also examined with PDI another 64 patients with 76 HCC nodules, and none of the nodules showed a constant-flow afferent tumor vessel. The presence of a constant-flow afferent tumor vessel indicates a supplying portal vein; but this is not diagnostic of HCC, and biopsy remains necessary to establish a final diagnosis.

Aged↗
PubMed2001

Similar target, different effects: late-onset ataxia and spatial learning in prion protein-deficient mouse lines.

Several lines of mice with targeted deletion of the prion protein gene (Prnp) have been produced, some of them appearing phenotypically normal, others developing late-onset ataxia. This has been tentatively attributed to the size of the targeted deletion in the Prnp gene. but a masking role of genetic background could not be excluded. Thus, we have crossed an ataxic mutant line with large deletion of Prnp (Ngsk Prnp0/0) with a knockout line showing only partial deletion of Prnp and no neurological deficits (Zrchl Prnp0/0). A F2 generation was then studied for up to 70 weeks for co-segregation of lesion size and behavioral phenotype, including cognitive and neurological anomalies. These mice were later crossed with a recently generated PrP-deficient line also having a large deletion and late-onset ataxia (Zrch2 Prnp0/0). They underwent similar testing for up to 90 weeks. The ataxic phenotype always co-segregates with large homozygous deletions involving either the Ngsk or the Zrch2 allele, independent of genetic background or sex. Compound heterozygous Zrchl/Ngsk mice or Zrch1/Zrch2 mice showed intermediate neurological phenotypes, suggesting a gene-dosage effect of large deletions. At 12 weeks of age, large deletions were also associated with minor non-cognitive impairments in water maze learning, and hyperactivity in open field and elevated zero maze. These impairments were not predictive for the development of ataxia. Thus, the neurological deficits are closely associated with large deletions, which entail an upregulation of the recently discovered prion Doppel protein (Dpl), while genetic background factors seem to be responsible for shifting the onset of neurological symptoms.

Age of Onset↗
PubMed2001

Epidemiological studies of tobacco smoking and dependence in Japan.

In this study, we attempted to determine the prevalence of tobacco or nicotine dependence in current smokers in Japan and to assess the relationship between alcoholism and tobacco or nicotine dependence. The subjects consisted of 246 alcohol-dependent and 1,111 non-alcohol-dependent individuals. We used a questionnaire, consisting of items obtained from the World Health Organization's The ICD-10 Classification of Mental and Behavioural Disorders: Clinical Descriptions and Diagnostic Guidelines (ICD-10) and the American Psychiatric Association's Diagnostic and Statistical Manual of Mental Disorders (4th ed.; DSM-IV) criteria for tobacco or nicotine dependence. The prevalence of tobacco dependence diagnosed according to the ICD-10 criteria was 23.9% among all subjects. The prevalence of tobacco dependence diagnosed according to the ICD-10 criteria was higher in alcohol-dependent individuals (58.1%) than in nondrinkers or social drinkers (12.8%). Alcohol-dependent subjects consumed significantly more nicotine per day than did nondrinkers or social drinkers. The prevalence of nicotine physical dependence diagnosed by using DSM-IV criteria for nicotine withdrawal was 2.4% in alcohol-dependent individuals, whereas only 0.3% of nondrinkers or social drinkers exhibited nicotine physical dependence. These results indicate to us that the potential for nicotine physical dependence is not much stronger than that reported among current smokers.

Adult↗
PubMed2001

Immunologic self tolerance maintained by T-cell-mediated control of self-reactive T cells: implications for autoimmunity and tumor immunity.

T-cell-mediated dominant control of self-reactive T cells is one mechanism for maintaining immunologic self tolerance. It also hampers the generation of immunity to autologous tumor cells. Abrogation of the control can evoke potent tumor immunity as well as autoimmunity in normal animals. This common regulatory mechanism for autoimmunity and tumor immunity can be exploited to devise a novel immunotherapy against cancer.

Animals↗