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Biomedical subjects

Takehiko Ohzeki

Publications and source records attributed to Takehiko Ohzeki.

At least 19 recordsLinked to original sources

Pilot study of ifosfamide/carboplatin/etoposide (ICE) for peripheral blood stem cell mobilization in patients with high-risk or relapsed medulloblastoma.

OBJECTIVES: The purpose of this study is to evaluate the stem cell mobilization capacity, anti-tumor effect, and feasibility of ifosfamide/carboplatin/etoposide (ICE) for transplant-eligible patients with medulloblastoma. MATERIALS AND METHODS: Six patients (23 months to 18 years old) with high-risk or relapsed medulloblastoma received one cycle of ICE, which consisted of ifosfamide at 1.8 g/m(2) for 5 days, carboplatin 400 mg/m(2) for 2 days, and etoposide 100 mg/m(2) for 5 days. Stem cells were mobilized with ICE followed by granulocyte colony-stimulating factor at 10 microg kg(-1) day(-1). RESULTS: After one cycle of ICE, the median number of harvested CD34+ cells per apheresis session was 11.85 x 10(6) cells/kg (range, 0.2 to 71.2 x 10(6) cells/kg). Two patients obtained a complete response and three patients a partial response. All patients experienced severe myelosuppression, and three infectious toxicities were observed. CONCLUSIONS: These results suggest that ICE is optimal for mobilizing stem cells, effective for high-risk or relapsed medulloblastoma, and tolerable with limited non-hematological toxicity.

Adolescent↗

Differential effect of DHEA on mitogen-induced proliferation of T and B lymphocytes.

Dehydroepiandrosterone (DHEA) is the predominant steroid hormone secreted by adrenal gland, and it has been proposed in recent years that DHEA has significant effects on immune function. We investigated the effect of DHEA (1 x 10(-5) - 1 x 10(-8)M) on proliferation of human T cells and B cells and on immunoglobulin production, a representative function of B cells. High doses of DHEA (1 x 10(-5)) significantly inhibited proliferation of peripheral blood mononuclear cells (PBMCs) and T cells induced by T cell mitogens hemagglutinin (PHA) and concanavalin A (Con A). Proliferation of PBMCs induced by B cell mitogens pokeweed mitogen (PWM) was increased by 1 x 10(-7) - 1 x 10(-6)M DHEA. Proliferation of PBMCs and B cells induced by Staphylococcus aureus Cowan strain I (SAC) was not significantly changed at any concentrations of DHEA. However, a concentration of 1 x 10(-7)M DHEA tended to potentiate their proliferation. This study suggested that DHEA acted on T and B lymphocytes differentially in immune system.

Adult↗

Prevalence of antibodies against Simkania negevensis in a healthy Japanese population determined by the microimmunofluorescence test.

Simkania negevensis has been associated with bronchiolitis in infants and community-acquired pneumonia in adults. Reports of exposure to this microorganism are only available from Israel, North America and Western Europe. Currently, no standard method for diagnosis of S. negevensis infection has been established nor have prevalence rates been shown in Japan. For the first time we demonstrated the ability of the microimmunofluorescence (MIF) test to detect S. negevensis-specific immunoglobulin G and exposure to S. negevensis in Japan. The positive rate in healthy volunteers was 4.3% (25/588), with rates increasing with age. Results indicate the usefulness of the MIF test as a serological method for detecting S. negevensis-specific antibodies. A standard serological test for infection with S. negevensis is needed.

Adult↗

Clinical efficacy of fluvoxamine and functional polymorphism in a serotonin transporter gene on childhood autism.

We studied the correlation between response to fluvoxamine and serotonin transporter gene promoter region polymorphism (5-HTTLPR). Eighteen children with autistic disorder completed a 12-week double-blind, placebo-controlled, randomized crossover study of fluvoxamine. Behavioral assessments were obtained before and at 12 weeks of treatment. 5-HTTLPR (long (l) or short(s)), was analyzed by the PCR method. Ten out of 18 patients responded to fluvoxamine treatment; allele type analysis revealed that clinical global effectiveness was noted significantly more in the l allele than in the s allele. However, with respect to language use, a significant effectiveness was noted in the s allele. 5-HTTLPR may influence the individual responses to fluvoxamine administration.

Alleles↗

A case report of an extremely low birthweight infant with circulatory collapse accompanied by cerebral infarction after the acute period.

A male infant (gestational age, 26 weeks and 1 day; birthweight, 752 g) was treated for respiratory distress syndrome and thereafter required mechanical ventilation due to chronic pulmonary insufficiency. On the 34th day after birth, urine volume suddenly decreased and hypotension, oliguria, and generalized edema developed. Laboratory studies revealed rapid progression of severe hyponatremia and hyperkalemia. Although hypovolemic shock was suspected, the patient did not respond to conventional treatment of volume expansion and inotropic support. Only treatment with glucocorticoids was effective. Two weeks later, cranial ultrasonography revealed multiple, right-sided, cystic lesions that were subsequently diagnosed as cerebral infarction by magnetic resonance imaging. Several cases of extremely low birthweight infants with circulatory collapse after the acute period have been described recently, but the cause has been unclear. There has been no previous report of a case accompanied by cerebral infarction.

Anti-Inflammatory Agents↗

Left ventricular diastolic performance in neonates.

BACKGROUND: The left ventricular (LV) diastolic performance of infants who were in a stable post-treatment condition in the neonatal intensive care unit was evaluated using echocardiography. METHODS AND RESULTS: The study group comprised 55 infants (Stable infant group, SI) and the parameters of LV performance were: LV propagation velocity (Vp) by color M-mode Doppler echocardiography (CMD), peak E wave, peak A wave, and the E/A ratio of transmitral flow. In a second set of measurements, a subset of 10 infants (patent ductus arteriosus (PDA) infant group, PI) were evaluated for LV diastolic performance during closure of PDA. The mean Vp in the SI was 27.2+/-7.3 cm/s and a positive correlation was observed between Vp and gestational age (r = 0.477, p = 0.0002). In the PI, Vp did not change significantly during closure of the PDA (from 23.3+/-8.2 cm/s to 27.5+/-8.4 cm/s); however, the E/Vp ratio decreased significantly with closure (from 3.14+/-0.83 to 2.12+/-0.68, p = 0.0051). CONCLUSION: The measurement of Vp by CMD can be considered a parameter for the evaluation of LV diastolic performance, even in the neonatal period. The LV diastolic performance of the infant is maintained from immediately after birth to spontaneous closure of the PDA.

Blood Flow Velocity↗

Streptozotocin-induced diabetes in the pregnant rat reduces 11 beta-hydroxysteroid dehydrogenase type 2 expression in placenta and fetal kidney.

Several epidemiological and animal studies have shown that the offsprings of diabetic mothers have higher incidences of glucose intolerance, obesity, insulin resistance, and hypertension in later life. It is well known that glucocorticoid metabolism plays a crucial role on several adult disease originated from fetal environment. The aim of this study was to investigate the relation between diabetic pregnancy and glucocorticoid metabolism of both mother and fetus, focusing on the 11 beta-hydroxysteroid dehydrogenase (11beta-HSD) type 2. A model of diabetic pregnancy was made by intravenous injection of streptozotocin (35 mg/kg body weight) to Sprague-Dawley rats, and blood and tissue samples were collected on day 20 of pregnancy. In the diabetic group, expression of 11 beta-hydroxysteroid dehydrogenase type 2 in placentas and fetal kidneys was decreased remarkably. Corticosterone levels of diabetic mothers were lower than those of control rats. Despite the differences in maternal corticosterone levels, fetal levels of corticosterone did not differ between the groups. Our results lend support to the concept that diabetic pregnancy imprints glucocorticoid regulation in these fetuses, which may contribute to their increased incidence of higher blood pressure as adults.

11-beta-Hydroxysteroid Dehydrogenase Type 2↗

A novel mutation in the renal V2 receptor gene in a boy with trisomy 21.

We describe for the first time an infant with Down syndrome and congenital nephrogenic diabetes insipidus (NDI). The 11-day-old Japanese boy was admitted with failure to thrive and fever. Polyuria (3,000-3,500 ml/m(2) per day), low urine specific gravity (1.001-1.002), and high plasma arginine vasopressin (AVP) (18.2 pg/ml) suggested NDI. Gene analysis confirmed the diagnosis of congenital NDI due to a novel mutation of the V2 receptor gene (L309P). He also had symptoms of Down syndrome and karyotype analysis of the peripheral lymphocytes revealed trisomy 21. The relationship between pyelectasis and a risk of Down syndrome is discussed.

Diabetes Insipidus, Nephrogenic↗

Different responsiveness in body weight and hepatic 11beta-hydroxysteroid dehydrogenase (11beta-HSD) type 1 mrna to 11beta-HSD inhibition by glycyrrhetinic acid treatment in obese and lean zucker rats.

Tissue-specific dysregulation of 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) activity in obese humans and animals may be associated with obesity and the metabolic syndrome. We investigated the effect of inhibition of 11beta-HSD with glycyrrhetinic acid (GE), an effective 11beta-HSD inhibitor, on body weight regulation in obese Zucker rats, which have a defect in the leptin receptor gene. GE (280 mg/kg/d) was administered in drinking water to 8-week-old male Zucker rats for 14 weeks. GE had no effect on food intake or weight gain, and did not affect hepatic 11beta-HSD1 and renal 11beta-HSD2 mRNA levels in obese rats. In contrast, average daily food intake and body weight on week 14 were significantly reduced by GE in lean rats (both P <.0001). Hepatic 11beta-HSD1 and renal 11beta-HSD2 mRNA levels were also significantly decreased by GE in lean rats (both P <.05). GE had no significant effect on plasma corticosterone levels in obese rats but lowered them in lean rats (P <.05). Plasma leptin levels declined in both GE-treated obese and lean rats (both P <.01). In conclusion, long-term GE treatment decreased weight gain in lean Zucker rats but not in obese Zucker rats. These findings suggest that the differing responses of 11beta-HSD1 to GE in obese and lean Zucker rats are closely associated with the different weight-gain responses. Furthermore, the weight-lowering effect of GE may require intact leptin receptors.

11-beta-Hydroxysteroid Dehydrogenases↗

Effects of leptin and dexamethasone on long and short leptin receptor mRNA.

BACKGROUND: Leptin exerts its effects by using both long (OB-Rb) and short (OB-Ra) receptors. Although leptin resistance or insensitivity is reported to be a cause of human obesity, there have not been enough studies to clarify regulation of leptin receptors. METHODS: The authors studied leptin receptor regulation by leptin and dexamethasone in the human hepatocellular carcinoma cell (HepG2). Using a quantitative RT-PCR technique, the authors demonstrate expression of OB-Ra and OB-Rb mRNA after the incubation for 24 h with leptin or dexamethasone at various concentrations (10(-9)-10(-6) M). RESULTS: Leptin (10(-7)-10(-6) M) significantly inhibited expression of OB-Rb mRNA, with maximum inhibition (43% of control) at 10(-6) M. Expression of OB-R219.1 and OB-R219.3, two short isoforms of leptin receptor, were also reduced in cells treated with leptin most remarkably at 10(-7) M for OB-R219.1 (44% of the control) and at 10(-6) M for Ob-R219.3 (49% of the control). In contrast, dexamethasone (10(-8)-10(-6) M) significantly increased OB-Rb mRNA levels, with a maximum increase (204% of the control) at 10(-7) M, and OB-R219.1 and OB-R219.3 mRNA expression was also markedly increased at 10(-9)-10(-6) M. The peak values were 254% of the control for OB-R219.1 and 246% of the control for OB-R219.3 at 10(-7) M. CONCLUSIONS: In HepG2 cells, leptin inhibits and dexamethasone increases OB-Ra and OB-Rb mRNA expression. It is suggested that glucocorticoids as well as leptin itself contribute to regulatory effects of leptin through changes in gene expression of leptin receptors.

Anti-Inflammatory Agents↗

Factors improving the propagation of Simkania negevensis strain Z in cell culture.

The purpose of the present study was to develop an optimal method for culturing Simkania negevensis. Centrifugation was effective for the propagation of S. negevensis, but sonication was not effective. The addition of cycloheximide to the culture medium significantly decreased the number of inclusions. Pretreatment of host monolayers with diethylaminoethyl-dextran or polyethylene glycol was detrimental. The most optimal conditions were centrifugation of the inocula onto untreated Vero cells, and culture in RPMI 1640 medium containing 10% fetal calf serum without cycloheximide or antimicrobial agents.

Animals↗

In vitro efficacy of l-asparaginase in childhood acute myeloid leukaemia.

To explore the potential efficacy of l-asparaginase treatment in acute myeloid leukaemia (AML) patients, we studied the in vitro resistance of French-American-British (FAB) subtypes of childhood AML to l-asparaginase using a methyl-thiazol-tetrazolium assay. We tested leukaemic cells obtained from 177 common acute lymphoblastic leukaemia (cALL) and 228 AML children at diagnosis. The median 70% lethal dose of l-asparaginase (LD70asp) (U/ml) was 0.46 in the cALL and 6.70 in the AML samples. The median LD70asp among each FAB subtype of AML was 0.76 (M0), 0.46 (M1), 10.00 (M2), 10.00 (M3), 1.18 (M4), 1.35 (M5) and 10.00 (M7). Type M3 samples had the highest LD70asp. The LD70asp of the M2 samples was significantly higher than that of the M1, M4 and M5 samples. When the LD70asp values were classified as low (0.016-0.159), intermediate (0.16-1.59) or high (1.6-10.00), the frequency of low, intermediate or high LD70asp among the M1 samples were similar to those among the cALL samples. In conclusion, cells from AML types M1, M4 and M5 were relatively sensitive to l-asparaginase, and M1 cells were as sensitive as those of cALL, suggesting that l-asparaginase treatment may be effective for these subtypes of AML.

Acute Disease↗