Biomedical subjects

Shunji Suzuki

Publications and source records attributed to Shunji Suzuki.

At least 37 records · Page 2Linked to original sources

PubMed2004

Maternal plasma hypoxanthine levels in nonpreeclamptic twin pregnancies.

We have observed that the elevated plasma adenosine levels are associated with hyperuricemia in nonpreeclamptic twin pregnancies. In animal models, extracellular adenosine is taken up by cells to form adenine nucleotides or is degraded to other purine metabolites such as hypoxanthine, which is further metabolized to xanthine and uric acid. In this study, we measured plasma hypoxanthine levels to evaluate the role of adenosine in hyperuricemia among women with twin pregnancies. Maternal blood samples were taken in 13 twin and 20 singleton pregnancies at 35-36 weeks' gestation. The average maternal plasma hypoxanthine level in twin pregnancies was significantly higher than that in singleton pregnancies. In addition, the plasma hypoxanthine levels have positive correlations both with plasma adenosine and serum uric acid levels. Our results support that an increased adenosine is the main factor contributing to hyperuricemia in twin pregnancies.

Adenosine↗

PubMed2003

Comparison between spontaneous ovarian hyperstimulation syndrome and hyperreactio luteinalis.

CASE REPORT: We present here two patients with bilateral ovarian enlargement during the first trimester of pregnancy. We clinically diagnosed one case as spontaneous ovarian hyperstimulation syndrome and the other case as hyperreactio luteinalis. CONCLUSION: It may be difficult to discriminate severe hyperreactio luteinalis in the first trimester from spontaneous ovarian hyperstimulation.

Adult↗

PubMed2003

Identification of opioid-regulated genes in human lymphocytic cells by differential display: upregulation of Krüppel-like factor 7 by morphine.

Morphine was previously found to compromise the chemotactic mobility of leukocytic cells toward inflammatory sites as well as induce the expression of chemokine receptor CCR5, a coreceptor for HIV entry, on lymphocytes. Both effects increase the host's susceptibility for HIV infection. In this report, we used a reverse transcription-polymerase chain reaction-based differential display (RT-PCR DD), an RNA finger printing procedure, coupled with Northern slot blot hybridization, in identifying gene or genes regulated by morphine in human lymphocytic cells. Ten positive gene segments, including two morphine downregulated genes and eight morphine upregulated genes, were identified. Analysis of the DNA sequences of these gene segments showed high homologies to known DNA and protein sequences on databases, of which two apoptosis/cell growth-related genes (PNAS-133 and Krüppel-like factor 7) were revealed. PNAS-133 gene was downregulated by morphine whereas the Krüppel-like factor 7 (KLF7), a zinc finger transcription factor, was upregulated by morphine. The upregulation of KLF7 by morphine was further studied and found to be at both the transcriptional and the translational levels in a naloxone-reversible manner. Cell growth was promoted by morphine up to day 4 (72 h) post treatment. These findings suggest a unique role for morphine in regulating cell proliferation and differentiation of immune cells.

Cell Differentiation↗

PubMed2003

Maternal peripheral T helper 1-type and T helper 2-type immunity in women during the first trimester of twin pregnancy.

INTRODUCTION: This study investigated the T helper Th1:Th2 balance in twin pregnancies compared with singleton pregnancies during the first trimester. METHODS: Blood samples were taken from 24 women with a singleton pregnancy and 14 women with twin pregnancy at 8-9 weeks' gestation to examine the ratios of Th1:Th2 and serum human chorionic gonadotropin (hCG) and progesterone levels. RESULTS: The average ratio of Th1:Th2 in the twin pregnancies was significantly lower than that in singleton pregnancies (7.3+/-2.3 vs. 10.5+/-2.2, p<0.05). There were negative correlations between the Th1:Th2 ratio and serum hCG levels (mIU/ml) (Th1:Th2 ratio = 14.5-4.52 x 10(-5)xhCG, r(2)=0.41, p<0.05) and between the Th1:Th2 ratio and serum progesterone levels (ng/dl; Th1:Th2 ratio = 23.0-0.63 x progesterone, r(2)=0.36, p<0.05). CONCLUSION: Our findings show marked predominance of Th2 type cytokines occurring in twin pregnancies is related to the increase in trophoblasts during the first trimester.

Blood Cell Count↗

PubMed2003

Morphine suppresses lymphocyte apoptosis by blocking p53-mediated death signaling.

Opiates such as morphine or heroin may promote cell apoptosis and cause dysfunction of immune cells. In simian immunodeficiency virus (SIV)-infected lymphocytic cells, however, morphine may protect the cells from apoptotic lysis and allow the virus to continue to replicate. To further explore this apparently antithetical effect of opiates, we evaluated in the present study the effects of morphine on human lymphocytic CEM x174 cells induced to undergo apoptosis in the presence of actinomycin D. It was found that induction of apoptosis (characterized by DNA laddering) by actinomycin D was accompanied by a stimulation of the expression of active (phosphorylated) form of p53. Pretreatment of the cells with 10nM morphine caused a transient, naloxone-reversible suppression of the appearance of activated p53 and the generation of DNA laddering. Parallel evaluation of the growth of CEM x174 indicated that morphine treatment delays the inception of cell death triggered by actinomycin D. Inasmuch as Bcl-2 suppresses while Bax accelerates apoptosis, treatment of cells with morphine reduced the expression of Bax and enhanced the expression of Bcl-2. Taken together, morphine, through binding at the opioid receptor, may protect lymphocytic cells from apoptotic lysis if cell death is initiated by apoptosis-inducing agents such as human immunodeficiency virus (HIV), SIV or actinomycin D.

Analgesics, Opioid↗

PubMed2003

Feto-maternal interface in T helper 1-type and T helper 2-type immunity in labor.

AIM: The aim of this study was to examine the relationship between Th (T helper) cells in maternal and umbilical cord blood in normal delivery. METHODS: The percentage of Th1 and Th2 cells and the Th1:Th2 cell ratios in maternal peripheral and umbilical venous blood from 61 normal singleton pregnancies at delivery at 37-41 weeks' gestation were calculated using flow cytometry. RESULTS: The proportion of Th cells and the Th1:Th2 ratio in the maternal blood were not correlated with those in the cord blood. CONCLUSION: Our results indicate that the proportion of Th cells in cord blood does not depend on that of maternal Th cells at labor.

Adult↗

PubMed2003

Basal metabolic rate in hyperemesis gravidarum: comparison to normal pregnancy and response to treatment.

OBJECTIVE: The aim of the study was to measure resting minute ventilation and oxygen consumption in patients with hyperemesis gravidarum before and after treatment and to compare the results with those of normal pregnant women. STUDY DESIGN: Baseline evaluation was performed with the use of an open-circuit ventilatory system in 17 hospitalized patients with hyperemesis gravidarum and was repeated 1 week after treatment. Thirty-seven normal pregnant women served as control subjects. RESULTS: Resting minute ventilation and oxygen consumption were decreased by 20% and 15% (P <.001), respectively, in patients with hyperemesis compared with control subjects. The decrease occurred despite a measurable increase of free thyroxine compared with normal pregnancy. Treatment resulted in a 10% increase in oxygen consumption in those patients with increased thyroid stimulation, but not otherwise. CONCLUSION: Resting oxygen consumption is reduced significantly in patients with hyperemesis gravidarum that is consistent with a state of partial starvation rather than increased in parallel with increases of thyroid axis activity.

Basal Metabolism↗

PubMed2003

Acute myocardial infarction caused by delayed heparin-induced thrombocytopenia and acute immunoreaction due to re-exposure to heparin in a systemic lupus erythematosus patient with HIT antibodies.

A patient with systemic lupus erythematosus and anticardiolipin antibodies and antibodies to platelet factor 4/heparin complexes suffered an acute myocardial infarction caused by delayed heparin-induced thrombocytopenia after heparin administration given to treat pulmonary hypertension. Furthermore, additional heparin administration for emergency coronary angiography appeared to have led to an acute immunoreaction, which might have resulted in acute coronary occlusion during coronary angiography and to a decreased platelet count. The present findings suggest that one must suspect delayed-type HIT in rare cases of induction of thrombosis after the cessation of heparin treatment, and avoid re-exposure to heparin in such cases.

Autoantibodies↗

PubMed2003

A case of maternal reaction due to fetomaternal transfusion.

We present here a case of maternal reaction to fetomaternal transfusion complicated by subchorionic hemorrhage. A 40-year-old woman, gravida 2, para 0, was admitted to our hospital at 25 weeks' gestation because of high blood pressure. On the morning of 32 weeks and 2 days' gestation, she developed sudden onset nausea, dyspnea and regular uterine contractions. Blood pressure was 80/50 mmHg and pulse was 110 beats/minute. At this time, her WBC, hemoglobin and platelets were decreased significantly. Two hours after onset, the patient's condition improved spontaneously. Increased serum alpha-fetoprotein level (3.0 multiple of median) was observed. She was suggested to be a case of acute fetomaternal transfusion.

Adult↗

PubMed2003

Uterine perforation following manual removal of the placenta.

We present here a case of uterine perforation following manual removal of the placenta during the third stage of normal labor. Total abdominal hysterectomy was performed, and the 4x3-cm perforation of the uterus and placenta accreta were confirmed. In this case, the round ligament covering the hematoma prevented bleeding into the peritoneal cavity and peritonitis. Manual removal of the placenta should be performed carefully following ultrasonographic assessment for placental abnormalities such as placenta accreta.

Adult↗

PubMed2003

Role of adenosine in regulation of uterine blood flow during nonpreeclamptic twin gestation.

We evaluated the possible role of increased adenosine in the regulation of uteroplacental circulation during nonpreeclamptic twin gestations. We performed uterine artery Doppler velocimetry and maternal arterial blood sampling for measurement of plasma adenosine levels in 16 women with singleton gestation and 14 women with dichorionic twin gestation without preeclampsia at 11-12, 25-26 and 34-36 weeks. In singleton gestations, a negative correlation between maternal plasma adenosine levels and maternal uterine artery pulsatility index was observed. In twin gestations, there were no noticeable association between maternal plasma adenosine levels and maternal uterine artery pulsatility index. Our results suggest that the decrease in vascular resistance in twin gestations may be through the mechanisms that are independent of adenosine.

Adenosine↗

PubMed2002

Interactions of opioid and chemokine receptors: oligomerization of mu, kappa, and delta with CCR5 on immune cells.

Activation of opioid receptors by morphine was previously shown to specifically induce the expression of chemokine receptor CCR5, promoting simian AIDS virus entry and replication in immune cells. The present study was undertaken to determine whether these two structurally and functionally distinct G-protein-coupled receptors are in close proximity and form an oligomeric complex in the cell membrane so that the activation of one triggers the activity of the other. Both human CEM x174 and monkey lymphocytes were used in this study and gave similar results. Immunoprecipitation experiments showed that CCR5, but not CD4 nor Na(+)/H(+) exchanger, coprecipitates with all three subtypes (mu, delta, and kappa) of opioid receptors. A single protein band immunoreactive with antibodies against both the CCR5 and the opioid receptors was identified after electrophoresis on nondenaturing polyacrylamide gels. Chemical crosslinking experiments using glutaraldehyde or BS(3) indicate that these receptors are closely situated on the cell membrane with an intermolecular distance less than 11.4A. Functional studies revealed that a combination treatment of cells with morphine, an agonist for mu, and MIP-1beta, a ligand for CCR5, suppresses the inhibitory effect of MIP-1beta and increases the stimulatory effect of morphine on CCR5 expression. These results suggest that oligomerization of chemokine receptor CCR5 and opioid receptors on the cell membrane of human or monkey lymphocytes may modulate receptor functions.

Analgesics, Opioid↗

PubMed2002

Curcumin inhibits interleukin 8 production and enhances interleukin 8 receptor expression on the cell surface:impact on human pancreatic carcinoma cell growth by autocrine regulation.

BACKGROUND: Curcumin, the yellow pigment in turmeric, has been shown to prevent tumor progression in a variety of tissues in rodents. The authors investigated the effect of curcumin on human carcinoma cell lines to determine whether constitutive interleukin-8 (IL-8) production of tumor cells was correlated with nuclear factor kappaB (NF-kappaB) activation and cell growth activity. METHODS: A human pancreatic carcinoma cell line, SUIT-2, was incubated with various concentrations of curcumin for 2 hours. Biologic features, including IL-8 production, DNA binding activity, transactivation of NF-kappaB, cell growth activity, cell viability, and the expression of IL-8 receptors (CXCR1 and CXCR2) were analyzed. RESULTS: The constitutive production of IL-8 was inhibited by curcumin at concentrations of 10-100 microM in a dose dependent manner. NF-kappaB activity was reduced significantly by curcumin treatment. Pretreatment with curcumin inhibited the growth rate of carcinoma cells significantly. Such cell growth inhibition by curcumin was not recovered by exogenous recombinant IL-8. The investigation of expression in IL-8 receptors, CXCR1 and CXCR2, revealed that the expression of both receptors was enhanced remarkably by curcumin. Exogenous IL-8 could not recover this enhancement of IL-8 receptors. These results suggest that curcumin inhibits IL-8-induced receptor internalization. CONCLUSIONS: The authors concluded that curcumin contributed not only to the inhibition of IL-8 production but also to signal transduction through IL-8 receptors. These data suggest that curcumin reduces numerous IL-8 bioactivities that contribute to tumor growth and carcinoma cell viability. From this point of view, curcumin is a potent anticancer agent that inhibits the production of proinflammatory cytokines, including IL-8, by tumor cells.

Antineoplastic Agents↗

PubMed2002

Chemokine receptor CCR5: polymorphism at protein level.

Polymorphisms in chemokine receptor CCR5 genes have been implicated in HIV disease progression, resistance, or non-progressive infection. Multiple CCR5 transcripts and mRNA diversity have also been identified. This study presents evidence to show that two distinct forms of CCR5 protein, 62 and 42k Da, are present in human lymphocytic cells and monkey peripheral blood mononuclear cells. The ratio of these two forms of CCR5 changes with cell growth. The 62k Da CCR5 predominates if the electrophoresis sample buffer does not contain reducing agent. However, the 62 and the 42 kDa CCR5 are not interconvertible. Morphine sulfate induces the formation and expression of both forms of CCR5 whereas RANTES, MIP-1alpha or MIP-1beta inhibits them. Localization studies indicate that the 62 kDa CCR5 resides mainly on the cell membrane and the 42 kDa CCR5 is present solely in the cytoplasm of the cells.

Analgesics, Opioid↗

PubMed2002

Relation between plasma endothelin-1 levels and T helper-1:T helper-2 immunity in women with twin pregnancies.

The aim of this study was to investigate the relationship between plasma ET-1 levels and T helper-1 (Th1):Th2 immunity in women with twin pregnancies. The percentage of Th1 and Th2 cells and the Th1:Th2 cell ratios in peripheral blood from 13 normal singleton pregnant women and 13 patients with twin pregnancies at 29-34 weeks' gestation were calculated using flow cytometry. The plasma ET-1 was also determined using a modified radioimmunoassay. The plasma ET-1 concentrations and the cell ratios of Th1:Th2 in twin pregnancies were significantly lower than those in singleton pregnancies. A positive correlation was found between plasma ET-1 levels and the ratios of Th1:Th2 cells in the whole subjects. Our results indicate that decreased ET-1 levels are associated with Th1:Th2 immunity in twin pregnancies.

Adult↗

PubMed2002

Methadone induces CCR5 and promotes AIDS virus infection.

Methadone, a regimen for the treatment of opioid dependency, was found to induce the expression of CCR5, a co-receptor for human immunodeficiency virus (HIV)/simian form of HIV (SIV) entry, on human CEM x174 lymphocytes. Both CCR5 mRNA and protein were elevated in methadone-treated cells. A concomitant increase of mu opioid receptors was also observed. Upon methadone exposure, SIVmac239-infected CEM x174 cells released greater amounts of virus particles as revealed by both the number of syncytia formation and reverse transcriptase activities. Similar methadone effect was not observed on CEM x174 cells infected with other simian retroviruses that do not depend on CCR5 for cellular entry. These studies raise concerns considering methadone as an innocuous morphine substitute.

Cell Line↗

PubMed2002

Morphine promotes simian acquired immunodeficiency syndrome virus replication in monkey peripheral mononuclear cells: induction of CC chemokine receptor 5 expression for virus entry.

Rhesus monkeys (Macaca mulatta) chronically administered opioids were more susceptible to simian immunodeficiency virus (SIV) strain mac239 (SIVmac239) infection than those without prior exposure to opioids. Increased plasma viremia in morphine-dependent monkeys allowed SIV to be detected in the animals' peripheral blood mononuclear cells (PBMC) without cocultivation with a tissue culture cell line. In contrast, virus titers from the PBMC of morphine-naive SIVmac239-infected animals were undetectable in the absence of cocultivation. PBMC isolated from noninfected animals and treated with morphine sulfate in vitro produced an increase in the expression of beta-chemokine receptor 5 (CCR5). Because both SIVmac239 and human immunodeficiency virus (HIV) require CCR5 for cell entry, the unique role of morphine in promoting SIV infection may provide a mechanism to account for the high incidence of HIV disease among drug-using populations.

Animals↗

PubMed2002

Relationship between plasma malondialdehyde levels and adenosine deaminase activities in preeclampsia.

BACKGROUND: Preeclampsia is characterized by endothelial cell dysfunction, and lipid peroxidation and alterations of immune responses may be involved in the pathogenesis of this disease. The aim of the present study was to examine changes in plasma malondialdehyde (MDA) level, an indicator of lipid peroxidation, and adenosine deaminase (ADA) activity, as a marker of T-cell activation in preeclampsia, and evaluated the possible relationship between those parameters in the pathogenesis of preeclampsia. METHODS: Plasma levels of MDA, an end product of lipid peroxidation induced by reactive oxygen species, and ADA activities were measured in 26 women with preeclampsia and 26 normal pregnancies. RESULTS: In preeclampsia, plasma MDA level and ADA activity averaged 0.43 +/- 0.03 micromol/l and 15.8 +/- 0.8 U/l, respectively, which were significantly higher than those of normal pregnancy (0.31 +/- 0.02 micromol/l and 9.5 +/ -0.6 U/l, respectively) (P<0.05). In addition, plasma MDA level was positively correlated to ADA activity in preeclampsia (r=0.52, P<0.05). CONCLUSIONS: These results suggest that enhanced lipid peroxidation and T-cell activation, and the presence of possible interrelationship and cross talk between those parameters may be related at least partly to the pathogenesis of preeclampsia.

Adenosine Deaminase↗