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Biomedical subjects

Shunji Suzuki

Publications and source records attributed to Shunji Suzuki.

At least 19 recordsLinked to original sources

Mapping a nucleolar targeting sequence of an RNA binding nucleolar protein, Nop25.

Nop25 is a putative RNA binding nucleolar protein associated with rRNA transcription. The present study was undertaken to determine the mechanism of Nop25 localization in the nucleolus. Deletion experiments of Nop25 amino acid sequence showed Nop25 to contain a nuclear targeting sequence in the N-terminal and a nucleolar targeting sequence in the C-terminal. By expressing derivative peptides from the C-terminal as GFP-fusion proteins in the cells, a lysine and arginine residue-enriched peptide (KRKHPRRAQDSTKKPPSATRTSKTQRRRR) allowed a GFP-fusion protein to be transported and fully retained in the nucleolus. When the peptide was fused with cMyc epitope and expressed in the cells, a cMyc epitope was then detected in the nucleolus. Nop25 did not localize in the nucleolus by deletion of the peptide from Nop25. Furthermore, deletion of a subdomain (KRKHPRRAQ) in the peptide or amino acid substitution of lysine and arginine residues in the subdomain resulted in the loss of Nop25 nucleolar localization. These results suggest that the lysine and arginine residue-enriched peptide is the most prominent nucleolar targeting sequence of Nop25 and that the long stretch of basic residues might play an important role in the nucleolar localization of Nop25. Although Nop25 contained putative SUMOylation, phosphorylation and glycosylation sites, the amino acid substitution in these sites had no effect on the nucleolar localization, thus suggesting that these post-translational modifications did not contribute to the localization of Nop25 in the nucleolus. The treatment of the cells, which expressed a GFP-fusion protein with a nucleolar targeting sequence of Nop25, with RNase A resulted in a complete dislocation of the protein from the nucleolus. These data suggested that the nucleolar targeting sequence might therefore play an important role in the binding of Nop25 to RNA molecules and that the RNA binding of Nop25 might be essential for the nucleolar localization of Nop25.

Amino Acid Sequence↗

Molecular cloning and characterization of Nop25, a novel nucleolar RNA binding protein, highly conserved in vertebrate species.

We report here the identification and characterization of a novel nucleolar RNA binding protein, referred to as Nop25 as based on its predicted molecular size and subcellular location. Nop25 homologues were widely discovered in diverse vertebrate species as hypothetical proteins, but not found in yeasts, plants and prokaryotic organisms. Nop25 was ubiquitously expressed in adult mouse organs and constitutively during mouse embryogenesis. Indirect immunofluorescence analysis with an anti-Nop25 antibody, as well as an experiment using a GFP-fused protein, demonstrated that Nop25 was localized in the nucleolus. Treatment of the cells with a low doses of actinomycin D caused Nop25 to translocate to the periphery of the nucleolus, suggesting that nucleolar localization of Nop25 is associated with rRNA transcription. Treatment of COS7 cells with RNase A resulted in a complete dissociation of Nop25 from the nucleolus, while in vitro binding assay demonstrated that Nop25 could bind directly to single-stranded nucleic acids. Further characterization of associated RNA molecules with Nop25 using immunoprecipitation experiment showed that Nop25 might bind to 28S rRNA. Studies on this novel nucleolar RNA binding protein may provide new information on the intricate nucleolar machinery as related to the transcription and processing of rRNA molecules and/or the subsequent assembly and maturation of ribosomes.

Amino Acid Sequence↗

Influence of parity on second-trimester uterine artery Doppler waveforms in twin pregnancy.

We performed uterine artery Doppler velocimetry in 16 nulliparous and 16 parous women with non-preeclamptic singleton gestations and 16 nulliparous and 16 parous women with dichorionic twin gestations at 17-18 and 26-27 weeks of gestation. In both singleton and twin pregnancies, the average pulsatility index (PI) in nulliparous women was significantly higher than that in parous women at 17-18 weeks of gestation. At 26-27 weeks of gestation, however, there were no significant differences in PI between nulliparous and parous women with either singleton or twin pregnancies. During the early second-trimester of non-preeclamptic singleton and twin pregnancies, parity has a significant effect on uterine artery blood flow.

Arteries↗

Influence of placental position on outcome in patients with placental abruption.

We retrospectively analyzed the clinical significance of placental position in patients with placental abruption by comparing cases in which the placenta was implanted on the anterior wall of the uterus (n=17) and those in which the placenta was on the posterior wall (n=12). There were no significant differences in clinical features of patients or pregnancy outcomes between the two groups. In this study, all patients with an anterior-wall placenta received a diagnosis of placental abruption prenatally, whereas only 8 patients (67%, p=0.01) with posterior-wall placenta received a diagnosis of placental abruption prenatally. Serious consideration should be given to the diagnosis of placental abruption in patients with a posterior-wall placenta.

Abruptio Placentae↗

Relation between plasma adenosine and serum TSH levels in women with hyperemesis gravidarum.

INTRODUCTION: This study investigated the relation between adenosine and thyroid function associated with hyperemesis gravidarum. METHODS: We examined 84 Japanese singleton pregnant women with an average age of 33.0+/-5.8 years at 9-12 weeks gestation being managed at our hospital. The patients were divided into three groups according to the severity of emesis: (1) those with hyperemesis gravidarum (nausea and vomiting with weight loss >5%, n=13), (2) those with emesis (nausea and vomiting with weight loss <5%, n=31), and (3) those with no symptoms as a control (n=40). RESULTS: The average serum TSH levels in the emesis and hyperemesis groups were significantly higher than that in the control group (P<0.05). The average plasma adenosine level in the hyperemesis group was significantly higher than those in the control pregnant and emesis groups (P<0.05). There were no significant differences in plasma adenosine levels between the control pregnant and emesis groups. The serum TSH level showed significant correlations with weight loss (%) and plasma adenosine levels (P<0.05). CONCLUSIONS: Our findings support the possible role of adenosine in counteracting the further progression of hyperemesis gravidarum associated with gestational thyrotoxicosis.

Adenosine↗

HbA1C levels in Japanese women during early pregnancy.

INTRODUCTION: The maternal glycosylated hemoglobin (HbA1C) level in early pregnancy has been observed to be lower than the prepregnant value. In Japan, the average body mass index (BMI) shows a very slight change during early pregnancy, which has been thought to be associated with the incidence of hyperemesis gravidarum. METHODS: We examined the relation between HbA1C and changes in BMI levels of 274 pregnant Japanese women managed at our hospital during early pregnancy. RESULTS: The average HbA1C in early pregnancy was 5.1 +/- 0.4%, which did not differ markedly from that of nonpregnancy (5.0 +/- 0.5%). The HbA1C level showed a negative correlation with the increasing value of BMI during early pregnancy (r2 = 0.26, p < 0.05). CONCLUSIONS: In this study, we could not identify a significant decrease in HbA1C in Japanese women during early pregnancy. This finding may be associated with the incidence of hyperemesis gravidarum in Japanese women.

Adult↗

Maternal basal metabolic rate in twin pregnancy.

OBJECTIVE: This study examined the basal metabolic rate in patients with twin pregnancies and compared the results with those of singleton pregnancies and non-pregnant women. METHODS: In 15 non-pregnant women, 14 patients with twin and 25 patients with singleton pregnancies, the resting energy expenditure was measured using an open-circuit ventilatory system during the third trimester of pregnancy. RESULTS: The averaged resting energy expenditure in patients with twin pregnancy was 1,636 +/- 174 kcal/day, significantly higher than that in patients with singleton pregnancy (1,456 +/- 158 kcal/day; p < 0.05). Both of these levels are significantly higher than those in non-pregnant women (1,228 +/- 132 kcal/day; p < 0.05). CONCLUSION: Our results indicate that the estimated increased metabolic demands in patients during the third trimester of twin pregnancy are about 10% higher than those in women with singleton pregnancy. A prospective clinical study concerning nutrition counseling is needed.

Adult↗

Opioids and the progression of simian AIDS.

This review is a concise description of the study undertaken to examine the modulation by opioids of simian acquired immunodeficiency syndrome (SAIDS) induced by inoculation of rhesus monkeys with simian AIDS virus SIVmac239. The study showed that the replication rate of the virus was several times greater in monkeys made dependent on morphine than in those of non-morphine treated monkeys. Further, a significant change in the mutation rate of the infecting virus in morphine-treated monkeys resulted in the production of mutants that were silent to conventional serological screening tests as well as resistant to AZT. In addition, opioid and chemokine receptors involved were identified in immune cells and a full comparative spectrum of the compromise of the immune system was examined allowing subsequent studies to evaluate wherein the modulation of the development of the syndrome could be better characterized. The data gathered to date are unique and germane to furthering our understanding of AIDS in humans and its subsequent treatment thereof.

Animals↗

Resting oxygen consumption in patients with twin pregnancy.

OBJECTIVE: This study examined the resting oxygen consumption in patients with a twin pregnancy and compared the results with those of singleton pregnancies. METHODS: In 15 patients with a twin and 26 patients with a singleton pregnancy, the resting oxygen consumption was measured using an open-circuit ventilatory system during the third trimester of pregnancy. RESULTS: The average resting oxygen consumption in patients with a twin pregnancy was 231+/-25 ml/min, significantly higher than that in patients with a singleton pregnancy (209+/-24 ml/min, P<0.05). CONCLUSION: Our results indicate an estimated increase in metabolic rate in patients during the third trimester of a twin pregnancy compared with those with a singleton pregnancy.

Adult↗

Plasma adenosine concentrations increase in women with hyperemesis gravidarum.

BACKGROUND: Adenosine is an important metabolic modulator and its concentrations are affected by sympathetic nerve stimulation and cytokine production. Since hyperemesis gravidarum is characterized by overactivation of sympathetic nerves and enhanced production of tumor necrosis factor (TNF)-alpha, plasma adenosine concentrations may be altered. The present study evaluated plasma adenosine concentrations and their relation with norepinephrine and TNF-alpha concentrations in hyperemesis gravidarum. METHODS: Plasma concentrations of adenosine, norepinephrine, and TNF-alpha were measured in 34 healthy nonpregnant women, and 34 women with hyperemesis gravidarum and normal pregnancies, matched for age, parity and gestational week. The relationships between plasma adenosine, and norepinephrine and TNF-alpha concentrations in hyperemesis gravidarum were evaluated. RESULTS: Mean plasma adenosine, norepinephrine, and TNF-alpha concentrations were significantly increased in women with hyperemesis gravidarum compared to those in nonpregnant and normal pregnant women (p<0.05). The increase in plasma adenosine concentrations correlated with the increase of norepinephrine and TNF-alpha in hyperemesis gravidarum (r=0.50, p<0.05 and r=0.43, p<0.05, respectively). CONCLUSIONS: Adenosine is an established suppressor of excessive sympathetic nerves activation and cytokine production, so the increase in plasma adenosine in hyperemesis gravidarum might serve to counteract further progression of hyperemesis gravidarum.

Adenosine↗

Functional expression of CCL6 by rat microglia: a possible role of CCL6 in cell-cell communication.

There is growing evidence that chemokines play important roles in the immune surveillance of central nervous system (CNS). In the CNS, microglia are primary immune effector cells and secrete various chemokines in response to their microenvironment. Using the RT-PCR procedure and indirect immunofluorescence analysis, we found that CCL6 (known as C10/MRP-1 in mouse) was expressed in rat primary microglia without any stimulation, but not in primary astrocytes, although both cell types expressed CCR1 mRNA, which is a receptor for CCL6. Furthermore, immunohistochemical analysis demonstrated that microglia produced CCL6 protein in a normal brain, suggesting that microglia may be the primary source of CCL6 in a normal brain. Recombinant rat CCL6 mediated the migration of microglia and astrocytes in vitro. The CCL6-mediated cell migration was blocked by treating the cells with LY294002, a PI3-kinase inhibitor and Western blot analysis showed that the phosphorylation of Akt could be induced by treating microglia with a recombinant CCL6, suggesting that CCL6 functions by activating the PI3-kinase/Akt pathway. A proinflammatory cytokine, interferon-gamma enhanced the expression of both CCL6 mRNA and protein in microglia, while other proinflammatory cytokines, interleukin-6 and tumor necrosis factor-alpha and an anti-inflammatory cytokine, transforming growth factor-beta exerted no effect on CCL6 expression in microglia. These findings suggest that CCL6 may be a mediator released by microglia for cell-cell communication under physiological as well as pathological conditions of CNS.

Analysis of Variance↗

Preexisting antibodies to platelet factor 4-heparin complexes in patients with acute coronary syndrome who have no history of heparin exposure.

Preexisting heparin-induced thrombocytopenia (HIT) antibodies are detected in some patients who have not previously been exposed to any kind of heparin. However, the role of preexisting HIT antibodies in acute coronary syndrome (ACS) is still unknown. This study was carried out to clarify the role of preexisting HIT antibodies in patients with ACS. Forty patients with ACS who had not been exposed to any kind of heparin via the venous or subcutaneous route or heparin-coated materials and had undergone percutaneous coronary intervention (PCI) under heparin anticoagulation within 6 h from the onset of ACS were chosen from the medical records in the cardiac emergency department. As a control of the ACS patients, 51 patients with angina pectoris who underwent elective PCI under heparin anticoagulation were chosen in the same manner as the ACS patients. Preexisting HIT antibodies were detected by ELISA in 6 patients. Two of the 6 patients developed HIT and 1 patient experienced thrombosis requiring intracoronary thrombolytic therapy. Thrombotic complications during and immediately after PCI in the very early stage after heparin administration were found in 4 of 6 patients with preexisting HIT antibodies. The frequency of preexisting HIT antibodies in ACS patients was significantly increased in comparison with that in non-ACS patients. The odds ratio of the risk of thrombotic complication between ACS and non-ACS patients was estimated at 8.82 (95% CI: 1.3-63). Also, preexisting HIT antibodies in ACS patients significantly increased the risk of thrombotic complications compared with ACS without preexisting HIT antibodies. In conclusion, ACS patients with positive HIT antibodies have an increased risk of thrombotic complications during PCI performed under anticoagulation with heparin.

Acute Disease↗

Plasma adenosine levels in peri-menopausal women having frequent hot flushes.

BACKGROUND: The effect of hormone replacement therapy (HRT) on plasma adenosine levels was investigated in climacteric women experiencing hot flushes. METHODS AND RESULTS: Plasma adenosine levels were measured in 13 peri-menopausal women with frequent hot flushes (>5 per day) before and 3-4 months after initiating HRT. Thirteen healthy pre-menopausal, 9 peri-menopausal women with few hot flushes (<1 or 2 per day) and 10 healthy postmenopausal women were enrolled as controls. The average plasma adenosine level in the peri-menopausal women was 0.20+/-0.09 micromol/L, which was significantly higher than in the pre-menopausal (0.12+/-0.07 micromol/L, p<0.05), peri-menopausal with few hot flushes (0.10+/-0.09 micromol/L, p<0.05) and postmenopausal women (0.13+/-0.06 micromol/L, p<0.05). Both the increased adenosine level and the hot flushes were decreased by HRT (plasma adenosine: 0.13+/-0.06 micromol/L). CONCLUSIONS: Increased plasma adenosine in peri-menopausal women may be associated with frequent hot flushes.

Adenosine↗

Influence of spinal hypotension on fetal oxidative status during elective cesarean section in uncomplicated pregnancies.

METHODS: We examined the relation between spinal hypotension (systolic blood pressure: <100 mmHg or <80% of the baseline value) and fetoplacental oxygen free radicals during elective cesarean section. Plasma xanthine, serum uric acid and plasma malondialdehyde levels in umbilical venous blood and blood gases in the umbilical artery were measured in patients receiving spinal anesthesia for elective cesarean section complicated with (n=26) and without (n=26) spinal hypotension. Patients with spinal hypotension were divided to two groups on the duration of the hypotension: those with the duration of <2 min (n=19) and those with the duration of > or =2 min (n=7). RESULTS: There were no measurable differences in these variables between the control and the hypotension with the duration of <2 min groups. While, the plasma xanthine, serum uric acid and plasma malondialdehyde levels in the hypotension group with the duration of > or =2 min were significantly higher than those in the control group without the significant differences in blood gases and pH-levels.

Adult↗

Plasma adenosine concentrations increase in women with hyperemesis gravidarum.

BACKGROUND: Adenosine is an important metabolic modulator and adenosine concentrations are affected by sympathetic nerve stimulation and cytokine production. Since hyperemesis gravidarum is characterized by overactivation of sympathetic nerves and enhanced production of tumor necrosis factor (TNF)-alpha, plasma adenosine concentrations may be altered. The present study evaluated plasma adenosine concentrations and their relation with norepinephrine and TNF-alpha concentrations in hyperemesis gravidarum. METHODS: Plasma concentrations of adenosine, norepinephrine, and TNF-alpha were measured in 34 healthy nonpregnant women, and 34 women with hyperemesis gravidarum and normal pregnancies, matched for age, parity and gestational week. The relationships between plasma adenosine, and norepinephrine and TNF-alpha concentrations in hyperemesis gravidarum were evaluated. RESULTS: Mean plasma adenosine, norepinephrine, and TNF-alpha concentrations were significantly increased in women with hyperemesis gravidarum compared to those in nonpregnant and normal pregnant women (p<0.05). The increase in plasma adenosine concentrations correlated with the increase of norepinephrine and TNF-alpha in hyperemesis gravidarum (r=0.50, p<0.05 and r=0.43, p<0.05, respectively). CONCLUSIONS: Adenosine is an established suppressor of excessive sympathetic nerves activation and cytokine production, so the increase in plasma adenosine in hyperemesis gravidarum might serve to counteract further progression of hyperemesis gravidarum.

Adenosine↗

Thrombotic complications in three hemodialysis patients with heparin-induced thrombocytopenia type I.

Although unfractionated heparin is the most commonly used anticoagulant for hemodialysis and has been associated with bleeding episodes, a more devastating complication that can occur is heparin-induced thrombocytopenia (HIT). It is believed that HIT type II is much more dangerous than type I, because HIT type II is associated with thromboembolic complications whereas there are no such complications in HIT type I. However, increased clot formation in the extracorporeal circuit during hemodialysis with unfractionated heparin is sometimes experienced by not only patients with HIT type II but also those with HIT type I. Three patients with HIT type I are presented who suffered from clot formation during hemodialysis, and in whom 81 mg of aspirin and/or cessation of heparin was prescribed. All three patients had received recombinant human erythropoietin (rHuEpo). Both heparin and rHuEpo induce enhanced platelet aggregation; therefore, it is possible that even HIT type I patients may suffer clot formation in the extracorporeal circuit due to platelet activation via the synergistic effects of unfractionated heparin and rHuEpo.

Aged↗