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Biomedical subjects

M Sakai

Publications and source records attributed to M Sakai.

At least 127 records · Page 7Linked to original sources

Triple marker screening for trisomy 21, trisomy 18 and open neural tube defects in singleton pregnancies of native Japanese pregnant women.

OBJECTIVE: To report the results of prenatal triple marker screening on a population of Japanese pregnant women. METHODS: From April 1994 through March 1999, a total of 32,925 native Japanese women with singleton pregnancies requested a triple marker-screening test. Multiples of the median values for 3 markers and individual risks for each patient were calculated following adjustment for the Japanese weight correction factor. The risk cut-off values used for Down syndrome (T21), open spina bifida (OSB) and trisomy 18 (T18) were 1: 295, 1: 290, and 1: 100, respectively. Follow-up information was collected postpartum and statistically analyzed. RESULTS: Detection rates (DR) of T21 for women less than 35 years, over 35 years and overall were 58, 94, and 83%, respectively. DR of T18 for women less than 35 years, over 35 years and overall were 75, 79, and 79%, respectively. DR of open neural tube defects (ONTD) was 100%. CONCLUSIONS: The first cumulative data of an intervention program and prospective follow-up studies in Japan have proven to be similar to other published reports. Individual risk values were calculated for each pregnancy for T21, T18 and ONTD. This screening program is more effective than age-dependent screening for detecting T21, T18 and ONTD pregnancies.

Adult↗

Interleukin-8 levels and granulocyte counts in cervical mucus during pregnancy.

PROBLEM: We measured interleukin-8 (IL-8) and granulocyte counts in cervical mucus to assess local immunity and parturition. METHOD OF STUDY: We detected IL-8 by enzyme linked immunosorbent assay (ELISA) and Western blotting. Granulocytes were counted on a slide glass containing mucus from the external cervical os. RESULTS: ELISA and Western blotting revealed IL-8 in cervical mucus from both nonpregnant and pregnant women. There were no significant differences in cervical mucus IL-8 levels or granulocyte counts between follicular, ovulatory, and luteal phases. However, IL-8 and granulocyte counts were significantly decreased after menopause. IL-8 and granulocyte counts were increased significantly during pregnancy, and were further increased after 38 weeks of gestation and at labor. IL-8 levels were significantly correlated with granulocyte counts, based on the study of 678 samples (P <0.0001). CONCLUSION: IL-8 is involved in the increase of cervical granulocytes and in the process of parturition.

Adolescent↗

Molecular analysis of external genitalia formation: the role of fibroblast growth factor (Fgf) genes during genital tubercle formation.

The molecular mechanisms underlying the development of the external genitalia in mammals have been very little examined. Recent gene knockout studies have suggested that the developmental processes of its anlage, the genital tubercle (GT), have much in common with those of limb buds. The Fgf genes have been postulated as regulating several downstream genes during organogenesis. Fgf8 was expressed in the distal urethral plate epithelium of the genital tubercle (GT) together with other markers such as the Msx1, Fgf10, Hoxd13 and Bmp4 expressed in the mesenchyme. To analyze the role of the FGF system during GT formation, an in vitro organ culture system was utilized. It is suggested that the distal urethral plate epithelium of GT, the Fgf8-expressing region, regulates the outgrowth of GT. Ectopic application of FGF8 beads to the murine GT induced mesenchymal gene expression, and also promoted the outgrowth of the GT. Experiments utilizing anti-FGF neutralizing antibody suggested a growth-promoting role for FGF protein(s) in GT outgrowth. In contrast, despite its vital role during limb-bud formation, Fgf10 appears not to be primarily essential for initial outgrowth of GT, as extrapolated from Fgf10(-/-) GTs. However, the abnormal external genitalia development of Fgf10(-/-) perinatal mice suggested the importance of Fgf10 in the development of the glans penis and the glans clitoridis. These results suggest that the FGF system is a key element in orchestrating GT development.

Animals↗

Analysis of promoter activity of 5'-upstream regions of zebrafish olfactory receptor genes.

The vertebrate olfactory system receives and discriminates a great variety of odorants. Many lines of evidence suggest that individual olfactory neuron expresses a single type or limited types of the olfactory receptor genes. However, the mechanism of selection of a single gene in the olfactory receptor family remains unclear. In the present study, we utilized zebrafish to identify the promoter element of the olfactory receptor genes in their 5'-upstream regions. First, we isolated a number of zebrafish olfactory receptor genes. These olfactory receptor genes were specifically expressed in the olfactory tissue as visualized by whole mount in situ hybridization analysis. Time of onset of the expression of each receptor clone varied from 24 h to 48 h postfertilization. Then, we injected various constructs containing the 5'-upstream regions of the olfactory receptor genes connected to beta-galactosidase reporter gene into fertilized zebrafish embryos. Constructs from two independent olfactory receptor genes exerted beta-galactosidase (promoter) activity that is specifically upregulated in the olfactory tissue. Use of either longer or deleted constructs of these two genes diminished the promoter activity in the olfactory tissue. From these results we discuss the mechanism of the transcription of the olfactory receptor genes in the olfactory neurons.

Amino Acid Sequence↗

The effects of soybean transphosphatidylated phosphatidylserine on cholinergic synaptic functions of mice.

The effects of soybean transphosphatidylated phosphatidylserine (SB-tPS) on cholinergic synaptic functions were investigated using cerebral cortical synaptosomes from mice. Treatment of the synaptosomes with SB-tPS increased high K+-induced acetylcholine (ACh) release in a bell-shaped, dose-dependent manner without affecting ACh synthesis. SB-tPS (10 and 50microM) also enhanced synaptosomal synthesis of sn-glycero-3-phosphocholine, but did not affect phosphorylcholine synthesis. In contrast, the choline synthesis was significantly reduced as SB-tPS concentration increased. The present result that SB-tPS modified the cholinergic pathway can partly explain its nootropic functions.

Acetylcholine↗

Effects of valproic acid on fertility and reproductive organs in male rats.

Crj:CD(SD)IGS rats were orally administered valproic acid at doses of 250, 500 or 1000 mg/kg/day for 4, 7 or 10 weeks. At each dose, one group of male rats was euthanized after 4-week dosage (4-week dose group) and the other two were mated with untreated females after 4 (7-week dose group) or 7 (10-week dose group) weeks of treatment with valproic acid and their fertility was evaluated. Females were euthanized on day 14-17 of gestation, and numbers of corpora lutea, implantations and live and dead fetuses were recorded. After 4, 7 or 10 weeks of treatment, males were euthanized, genital organs were weighed, the number of sperm in the cauda epididymis was counted, sperm motion analyzed, and histopathological examination of testes performed. The male rats of the 1000 mg/kg dose group died or were moribund 3 or 4 days after the start of treatment. No effects on fertility of male rats were observed up to the 500 mg/kg 10-week dose group. Treatment for 4 weeks at 500 mg/kg/day decreased epididymis weight. After 7 weeks at 500 mg/kg/day, the weights of epididymis, seminal vesicles and prostate were decreased, and the number of sperm heads per cauda epididymis and percentage of motile sperm were reduced. In the 500 mg/kg 10-week dose group, the weight of testis was decreased. On histopathological examination of the testis, degeneration of seminiferous tubules and loss or exfoliation of spermatids were observed, and the ratio of retention of step 19 spermatids in stage IX-XI was increased in the 500 mg/kg 4-, 7- and 10-week dose groups. These results suggest that analysis of sperm motion and histopathological evaluation of testes are sensitive methods for assessing toxicity of valproic acid on male reproductive organs.

Animals↗

Remnant-like particle cholesterol, triglycerides, and insulin resistance in nonobese Japanese type 2 diabetic patients.

OBJECTIVE: The aim of the study was to investigate the relationships between remnant-like particle (RLP) cholesterol, triglycerides, and insulin resistance in nonobese Japanese type 2 diabetic patients. RESEARCH DESIGN AND METHODS: A total of 86 nonobese Japanese type 2 diabetic patients (72 men and 14 women, aged 40-83 years, BMI 20.1-26.6 kg/m2) were studied. BMI, HbA1c levels, and fasting concentrations of plasma glucose, serum lipids (RLP cholesterol, total cholesterol, HDL cholesterol, and triglycerides), and serum insulin were measured. Insulin resistance was estimated by the homeostasis model assessment (HOMA-IR). The subjects were divided into two groups according to the value of HOMA-IR. Values >2.5 were indicative of the insulin-resistant state, and values <2.5 were indicative of the insulin-sensitive state. RESULTS: The insulin-resistant group had significantly higher RLP cholesterol and triglyceride levels and lower HDL cholesterol levels compared with the insulin-sensitive group. Univariate regression analysis showed that insulin resistance was positively correlated with BMI (r = 0.254, P = 0.019), HbA1c levels (r = 0.278, P = 0.011), RLP cholesterol levels (r = 0.315, P = 0.004), and triglyceride levels (r = 0.332, P = 0.002) and was negatively correlated with HDL cholesterol levels (r = -0.301, P = 0.006) in our diabetic patients. Multiple regression analysis showed that insulin resistance was independently associated with serum triglyceride levels, which explained 13.5% of the variability of insulin resistance in our nonobese Japanese type 2 diabetic patients. CONCLUSIONS: These results indicate that 1) nonobese Japanese type 2 diabetic patients with insulin resistance are characterized by high RLP cholesterol and triglyceride levels, and low HDL cholesterol levels; and 2) the level of serum triglycerides is an independent predictor of insulin resistance in these patients.

Apolipoproteins↗

Granulocyte/macrophage colony-stimulating factor plays an essential role in oxidized low density lipoprotein-induced macrophage proliferation.

We and other groups have recently demonstrated that oxidized low density lipoprotein (Ox-LDL) induces proliferation of macrophages in vitro. Since previous immunohistochemical studies demonstrated that macrophages and macrophage derived foam cells proliferated in situ in atherosclerotic lesions, it seems reasonable to expect that the Ox-LDL-induced macrophage proliferation might be linked to the development of atherosclerotic lesions. Thus, clarification of the molecular cascades of Ox-LDL-induced macrophage proliferation is expected to enhance our knowledge of the pathogenesis of atherosclerosis. Recently, we demonstrated that the activation of PKC leads to release into the culture medium of granulocyte/macrophage colony-stimulating factor (GM-CSF) which plays an important role in Ox-LDL-induced macrophage proliferation. In this review article, we mainly show the role of GM-CSF in the Ox-LDL-induced macrophage proliferation. Moreover, based on our recent findings, we summarize the Ox-LDL-induced signaling pathway for macrophage proliferation.

Animals↗