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Biomedical subjects

S Fujii

Publications and source records attributed to S Fujii.

At least 271 records · Page 15Linked to original sources
PubMed1998

Reducing multiple pregnancies by restricting the number of embryos transferred to two at the first embryo transfer attempt.

Though the multiple pregnancy rate in in-vitro fertilization-embryo transfer must be reduced, strict and uniform regulation of the number of embryos transferred may make it impossible for women with little natural fecundity to carry children. We therefore restricted the number of embryos per transfer. In the first half of the observation period (n = 100), we limited the number of embryos transferred to three regardless of the number of previous transfers. In the second half (n = 137), we strictly regulated the number of embryos transferred to two at the first attempt and three in the second and later attempts. The multiple pregnancy rate per pregnancy was significantly lower (P < 0.005) in the second period (20.4%) than in the first period (52.9%), while the clinical pregnancy rate and the implantation rate per transfer were similar in both observation periods. 60.7% (17/28) of the multiple pregnancies arose from the first embryo transfer attempt, and 17.9% (5/28) of them arose from a second attempt. The 18 multiple pregnancies in the first period involved six sets of triplets, while the 10 multiple pregnancies that arose in the second period all involved twins. The implantation rate per transfer at the first attempt was significantly higher than that at the second or later attempts. The criterion for determining the number of embryos transferred should be simple to minimize errors of judgement. We believe that our method of restricting the numbers of embryos transferred may be one method of reducing multiple pregnancies without eliminating the possibility of having children for women with low fecundity.

Adult↗
PubMed1998

Localization of apoptotic cells within the human endometrium and correlation between apoptosis and p21 expression.

The aim of the present study was to gain a better understanding of the localization of apoptotic cells within the human endometrium during the menstrual cycle and to elucidate the relationships among the following for the human endometrium: apoptosis, p21 expression, and cell proliferation. Apoptosis and p21 expression were identified mainly in the glandular cells of the basal layer in the late secretory phase. In contrast, cells positive for Ki-67 were observed predominantly in the functional layer (in the proliferative phase in glandular cells and in the secretory phase in stromal cells). A very strong positive correlation (r = 0.81; P < 0.001) was demonstrated between the number of apoptotic cells and the number of p21-positive cells present among the glandular cells but, topographically, individual apoptotic cells were not coincident with p21-positive cells in serial sections. The results of this study suggest that the proliferation of the glandular cells of the basal layer is regulated by both apoptosis and p21 expression, particularly in the late secretory phase. Such regulation may be necessary to maintain a healthy population of glandular cells in the basal layer of the endometrium.

Adult↗
PubMed1998

Human large luteal cells in the menstrual cycle and early pregnancy express leukotriene A4 hydrolase.

Leukotriene (LT) A4 hydrolase (EC3.3.2.6) converts LTA4 to LTB4 which shows a chemotactic activity to leukocytes. To investigate the involvement of LTB4 in human corpus luteum (CL) function, the localization of LTA4 hydrolase in human ovarian tissues was examined by immunohistochemistry with a rabbit polyclonal antibody against LTA4 hydrolase. The enzyme was weakly expressed on granulosa cells of the follicles. After ovulation, the intensity of LTA4 hydrolase on large luteal cells increased and was highest in the midluteal phase. High expression was also observed in the CL of early pregnancy. In theca interna and small luteal cells, LTA4 hydrolase was weakly detected in all developmental stages. Immunoblot analysis demonstrated that the molecular mass of LTA4 hydrolase expressed in CL was 62 kDa, and confirmed that LTA4 hydrolase expression increased during CL formation and remained high in early pregnancy. The sequence encoding mRNA of LTA4 hydrolase, which was isolated from CL and amplified by polymerase chain reaction, was shown to be identical to the previously reported one. Immunocytochemistry showed that LTA4 hydrolase expression in cultured granulosa cells increased over 4 days in vitro and was enhanced by human chorionic gonadotrophin treatment. These expression profiles of LTA4 hydrolase suggest the involvement of LTB4 in luteal cell function during CL formation and early pregnancy.

Adolescent↗
PubMed1998

Involvement of cyclin-dependent kinase inhibitor p27Kip1 in growth inhibition of endometrium in the secretory phase and of hyperplastic endometrium treated with progesterone.

A cyclin-dependent kinase (cdk) inhibitor, p27Kip1 (p27), binds to the cyclin E-cdk2 complex and functions as a suppressor of cell cycle promotion. Here, the involvement of p27 in the growth of normal human endometrium was immunohistochemically studied, and the findings were compared with those of Ki-67, cyclin E and cdk2. In addition, to elucidate the effect of progesterone on the expression of p27, tissues from patients with endometrial hyperplasia were examined before and after the administration of medroxyprogesterone acetate (MPA) for the treatment of this disease. In the glandular cells of the normal endometrium, p27 was negligible during the proliferative phase, whereas it was markedly increased in the secretory phase. The staining pattern of Ki-67 was the reverse. Cyclin E/cdk2-positive cells were observed throughout the menstrual cycle. In the secretory phase, the cyclin E/cdk2-positive cells were also positive for p27, suggesting an interaction between these molecules. Stromal cells, especially in the basalis, showed a consistent expression of p27 throughout the menstrual cycle. The expression of p27 in hyperplastic epithelia before the MPA treatment was negligible, whereas it was greatly increased after the treatment. The Ki-67 positivity decreased after the treatment. These findings suggest that p27 is involved in the progesterone-induced growth suppression of normal and hyperplastic endometria.

Adult↗
PubMed1998

Immunohistochemical analysis of cell cycle regulatory gene products in normal trophoblast and placental site trophoblastic tumor.

Intermediate trophoblast (IT) rarely gives rise to a placental site trophoblastic tumor (PSTT) To examine the different growth mechanisms present in normal and neoplastic IT, the expression of cell cycle regulatory molecules was compared at normal implantation sites and in PSTTs. Normal implantation sites in early gestation (19 patients) and PSTTs (6 patients) were immunohistochemically studied using antibodies against cytokeratin, human chorionic gonadotropin, and human placental lactogen to identify IT, and antibodies against Ki-67, cyclins (A, B, D1, and E), cyclin-dependent kinases (cdks), and p53 to investigate the proliferative activity of the trophoblast. Marked proliferative activity was observed in the trophoblast of the cell columns. Normal IT exhibited a very low labeling index for Ki-67, with negative expression for cdks and cyclins, except for cyclins B and E. The tumor cells of PSTT exhibited a high labeling index for Ki-67 with positive expression for all the cyclins and cdks examined. Expression of p53 was identified in tumor cells of PSTTs and the distribution of p53-positive cells correlated topographically with that of the cyclin A-positive cells. The transformed IT of PSTT has high proliferative activity with an abnormal expression of cell cycle regulatory molecules, which is not observed in normal IT.

Adult↗
PubMed1998

Mast cells in smooth muscle tumors of the uterus.

Mast cells (MCs) have been reported in the myometrium and uterine smooth muscle tumors. We examined the number of MCs in various uterine smooth muscle tumors (including leiomyosarcomas) and assessed whether this feature might be of value in their pathologic diagnosis. The number of MCs in 95 uterine smooth muscle tumors, including 55 ordinary leiomyomas, 17 cellular leiomyomas, 8 bizarre leiomyomas, and 15 leiomyosarcomas, was counted using toluidine blue and immunohistochemical staining. The number of MCs that stained for tryptase was lowest in leiomyosarcoma and next lowest in ordinary leiomyoma; the number in each of these two groups was significantly lower than in the myometrium (p < 0.001). In cellular and bizarre leiomyomas, the number of MCs was significantly higher than in ordinary leiomyoma (p < 0.001 and p < 0.001, respectively) and leiomyosarcoma (p < 0.001 and p < 0.005, respectively). Statistical analysis revealed that counting the number of MCs and using a cut-off value of 16 MCs per high-power-field is useful for the differential diagnosis of leiomyosarcomas from cellular leiomyoma and bizarre leiomyoma, yielding 100% sensitivity and 96% specificity. The number of MCs was significantly lower in leiomyosarcomas at TNM stages III and IV than in those at stages I and II (p < 0.05), but there was no significant correlation between the number of MCs and patient survival. These results suggest that the number of MCs might be useful as part of a multivariate approach to the differential diagnosis of leiomyosarcoma from bizarre or cellular leiomyoma.

Cell Count↗
PubMed1998

Pathogenetic implications of hyaluronan-induced modification of vascular smooth muscle cell fibrinolysis in diabetes.

BACKGROUND: Proteolysis, modulated in part by intramural fibrinolytic system proteins and their inhibitors, appears to influence vascular smooth muscle cell (SMC) migration and proliferation and remodeling of extracellular matrix (ECM). Alterations of fibrinolysis in circulating blood and of proteolysis within vessel walls in experimental animals and patients with diabetes have been associated with accelerated vascular disease. Hyaluronan, a prominent component of ECM in normal vessels, is increased in the tunica media of macroscopically normal arterial vessels from patients with type 2 diabetes. OBJECTIVE: To determine whether hyaluronan alters the expression of the fibrinolytic system protein, plasminogen activator inhibitor type-1 (PAI-1), in human vascular SMCs, thereby potentially accelerating vascular disease in patients with type 2 diabetes. METHODS: Urokinase-type and tissue-type plasminogen activators (uPA and tPA) and PAI-1 were assayed in vascular SMC conditioned media and in cell lysates, using enzyme-linked immunosorbent assay and western blotting. RESULTS: Hyaluronan increased the 24-h release of PAI-1 into conditioned media in a concentration-dependent and time-dependent manner (1.8-fold compared with control with 1 mg/ml hyaluronan; n = 9, P < 0.01). Although the accumulation of uPA in conditioned media tended to increase also, uPA content was reduced in cell lysates (64% of control with 0.1 mg/ml hyaluronan at 24 h; n = 9, P < 0.01) without any change in PAI-1. Concentrations of tPA in conditioned media and cell lysates were unchanged. Digestion of hyaluronan with hyaluronidase (50 turbidity reducing units (TRU)/ml) or exposure of the smooth muscle cells to antihuman CD44 antibody (1 microgram/ml) that binds to the hyaluronan cell surface receptor obviated the effects of hyaluronan. CONCLUSION: Our results indicate that increases in hyaluronan increase vascular SMC expression of PAI-1, a phenomenon that may alter the balance between proteolysis and its inhibition in vessels of patients with type 2 diabetes, thereby contributing to the acceleration of macroangiopathy.

Antibodies↗
PubMed1998

A comparative study of pre-operative procedures to assess cervical invasion by endometrial carcinoma.

OBJECTIVE: To compare the accuracy of different diagnostic procedures currently used to assess cervical involvement in endometrial carcinoma. DESIGN: Retrospective observational study. SETTING: Department of Obstetrics and Gynecology, Shinshu University Hospital, Matsumoto, Japan. PARTICIPANTS: Sixty-four patients with endometrial carcinoma were evaluated pre-operatively for cervical involvement by six different diagnostic procedures: cervical cytology, endocervical curettage, transvaginal ultrasonography, hysteroscopy, magnetic resonance imaging, and serum levels of CA125. The number of positive and negative diagnoses of cervical invasion by each of these procedures were correlated with the actual invasion determined by histological examination. RESULTS: Cervical invasion was confirmed in 12 (18.8%). Endocervical curettage showed high sensitivity (91%), the highest negative predictive value (96%), and the lowest negative likelihood ratio (0.14). Hysteroscopy showed high positive likelihood ratio (8.2) and low negative likelihood ratio (0.20). Magnetic resonance imaging showed the highest positive predictive value (75%) and the highest positive likelihood ratio (12.5). Magnetic resonance imaging was excellent for predicting stromal invasion, whereas hysteroscopy was superior for assessing mucosal involvement to magnetic resonance imaging. CONCLUSION: Endocervical curettage is a good test for excluding cervical involvement by endometrial carcinoma. Hysteroscopy is a good test in making both positive and negative diagnoses for cervical involvement. Magnetic resonance imaging is an excellent test for detecting cervical involvement, especially when the stroma is invaded.

Adult↗
PubMed1998

In vivo three-dimensional EPR imaging of nitric oxide production from isosorbide dinitrate in mice.

Recently, in vivo electron paramagnetic resonance (EPR) spectroscopy and imaging have been widely used to investigate free radical distribution and metabolism in tissues, organs, and whole body of small animals. Endogenous nitric oxide (NO) is an attractive target of this method. In the present study, NO production from a nitrovasodilator, isosorbide dinitrate (ISDN), in live mice was investigated by in vivo EPR spectroscopy and imaging combined with the spin-trapping technique. A highly water-soluble Fe complex with N-(dithiocarboxy)sarcosine (DTCS) was used as an NO-trapping agent. Mice received [14N]-ISDN, and the Fe-DTCS complex subcutaneously exhibited the characteristic triplet EPR signal of the NO adduct [14NO-Fe(DTCS)2]2-. Using [15N]ISDN instead of [14N]ISDN, we were able to observe that the doublet EPR signal stemmed from the 15NO adduct, which directly demonstrated that NO was produced from ISDN. The three-dimensional EPR images of the upper abdomen of living mice showed that the NO adducts were distributed in the liver and the kidneys. This EPR image combined with the ex vivo EPR measurements of the blood suggested that NO production from ISDN occurred in the liver in this experimental condition.

Animals↗
PubMed1998

Therapeutic effect of erythromycin on influenza virus-induced lung injury in mice.

Erythromycin (EM) is an antibiotic with potent antiinflammatory effects that is used for treating chronic lower respiratory tract infections. It has been shown that free radicals, such as the superoxide anion and nitric oxide (NO), are pathogenic molecules in viral disease. Much attention has been given to a critical role of NO in the pathologic events of various inflammatory diseases. In the present study, we evaluated the effects of EM on influenza-virus-induced pneumonia in mice infected with a lethal dose of influenza virus A/Kumamoto/Y5/67 (H2N2). The administration of EM at a dose of 3.3 mg/kg/d (intraperitoneally, from Days 1 to 6 after infection), significantly improved the survival rate of mice infected with influenza virus, and the survival rate of the virus-infected mice at Day 20 after infection increased in a dose-dependent fashion with EM administered to the animals, from 14% among controls to 42% among animals given EM at 1.0 mg/kg/d and 57% among those given EM at 3.3 mg/kg/d. The induction of interferon-gamma (IFN-gamma) in the mouse lung was inhibited by EM treatment on Day 6 after infection. Simultaneously, the number of inflammatory cells recovered in lung lavage fluid 6 d after virus infection was significantly reduced by the treatment with EM. The EM treatment resulted in a dose-dependent decrease in the level of nitrite/nitrate (metabolites of NO) in the serum and the NO synthase (NOS)-inducting potential in the lungs of the virus-infected mice. These results indicate that EM may have substantial therapeutic value for various acute inflammatory disorders such as influenza-virus-induced pneumonia, by inhibiting inflammatory-cell responses and suppressing NO overproduction in the lung.

Animals↗
PubMed1998

Augmentation of leptin synthesis and secretion through activation of protein kinases A and C in cultured human trophoblastic cells.

Leptin is a fat cell-derived hormone that regulates food intake and energy expenditure. We previously demonstrated that leptin is produced by nonadipose cells, i.e. by placental trophoblasts. We also reported that a human trophoblastic cell line, BeWo cells, expresses leptin gene and secretes leptin into culture media. To elucidate the regulatory mechanisms of leptin production by human trophoblasts, we investigated synthesis and secretion of leptin in BeWo cells and in explant cultures of human placental tissue. Leptin production and gene expression in BeWo cells were increased by treatment with forskolin. The forskolin-induced increase in leptin production was completely suppressed by H89, an inhibitor of protein kinase A. Leptin production and gene expression in BeWo cells were increased by treatment with phorbol myristate acetate (PMA). The PMA-induced increase in leptin production was completely suppressed by H7 and staurosporine, both of which are inhibitors of protein kinase C. Leptin secretion from first trimester chorionic tissue was approximately 50-fold greater than that from term placental tissue. Leptin production and gene expression in explant cultures of placental tissue at both stages of pregnancy were augmented markedly by treatment with forskolin or PMA. The present study demonstrated augmentation of leptin production by protein kinase A and protein kinase C in cultured human trophoblasts, thereby leading to a better understanding of the regulatory mechanisms of leptin production in human trophoblasts in vivo.

Cell Line↗
PubMed1998

Endothelin-converting enzyme-1 is expressed on human ovarian follicles and corpora lutea of menstrual cycle and early pregnancy.

We have previously reported that membrane-bound amino- and carboxypeptidases were expressed on the human follicles and corpora lutea (CL), and we proposed that these peptidases are involved in ovarian functions, probably by regulating the extracellular peptide concentrations. In this study, we examined the expression of endothelin-converting enzyme-1 (ECE-1) on human follicles and CL, which is a membrane-bound endopeptidase and is known to convert big endothelin-1 to endothelin-1. In the preovulatory follicles, immunohistochemical study showed that ECE-1 was expressed, with moderate intensity, on the theca interna cells and weakly on the granulosa cells. In the menstrual and pregnant CL, ECE-1 was highly expressed on both large and small luteal cells, indicating that ECE-1 expression increases during luteinization. Western blotting analysis revealed that the molecular mass of the ECE-1 extracted from the menstrual CL was 130 kDa and that ECE-1 was more strongly expressed on the CL in early and midluteal phases than the CL in late luteal phases. In the isolated luteinizing granulosa cells obtained from patients undergoing in vitro fertilization, ECE-1 was immunohistochemically detected on their cell surface. The activity of ECE-1 was also detected on cultured luteinizing granulosa cells by measuring endothelin-1 production from its precursor. The activity of ECE-1 was significantly enhanced by the treatment of human CG (10 U/mL) and interleukin (IL)-1 (10 ng/mL) during 4-day culture, whereas no significant alteration was observed by IL-4 (10 ng/mL) and IL-10 (10 ng/mL) treatment. These results indicate that ECE-1 is a cell surface differentiation-related molecule of human granulosa and of theca interna cells and suggest that the expression of ECE-1 is regulated by LH/human CG and cytokines.

Adult↗
PubMed1998

Physical mapping of the linear plasmid pSLA2-L and localization of the eryAI and actI homologs.

The 200-kb linear plasmid pSLA2-L was suggested to be involved in the production of lankamycin and lankacidin in Streptomyces rochei 7434AN4. In this study, we have constructed a physical map for 23 PstI fragments of pSLA2-L, the sum of which was 206 kb. Detailed restriction maps for both ends of pSLA2-L revealed the presence of terminal inverted repeats, the size of which was found to be 2.1 kb by cloning and sequencing of the end-points. Hybridization experiments using two polyketide biosynthetic genes, eryAI and actI, located their homologous regions on PstI fragments A and I, respectively.

Anti-Bacterial Agents↗
PubMed1998

Peliosis hepatis associated with idiopathic restrictive cardiomyopathy.

A rare case of peliosis hepatis associated with idiopathic restrictive cardiomyopathy is reported. A 75-year-old man was admitted for evaluation of marked edema and jaundice. Serum total bilirubin was elevated above 20 mg/dl. The liver biopsy under laparoscopy revealed marked sinusoidal dilatation and retention of red blood cells, which was consistent with a diagnosis of peliosis hepatis. Cardiac catheterization revealed right ventricular filling disturbance without specific findings on endomyocardial biopsy, suggesting idiopathic restrictive cardiomyopathy. The level of serum total bilirubin decreased in association with improvement of edema after drip infusion of furosemide therapy.

Aged↗
PubMed1998

Central diabetes insipidus associated with a missense mutation in the arginine vasopressin gene that replaces Ala at the carboxyterminus of the signal peptide with Thr.

We report an 18-year-old male with a history of polyuria, polydipsia, and thirst since childhood. In a hypertonic saline infusion test, the patient's plasma vasopressin rose only to 0.28 pg/ml. In a water deprivation test, his urinary osmolality rose only to 189 mosmol/kg and then rose to 538 mosmol/kg by vasopressin administration. A T1-weighted magnetic resonance imaging (MRI) scan revealed a loss of the posterior pituitary bright spot. Sequencing of the vasopressin gene showed a heterozygous point mutation that replaced Ala at the carboxyterminus of the signal peptide with Thr. His father also had similar history, and we therefore diagnosed his illness as familial central diabetes insipidus.

Adolescent↗
PubMed1998

Indication for carotid endarterectomy.

From recent randomized studies, carotid endarterectomy (CEA) is highly beneficial to the patients with a symptomatic high-grade carotid artery stenosis (70-99%), but the surgical indication for an asymptomatic carotid artery disease remains unsolved. Sixty-three atheromatous plaques (symptomatic 51, asymptomatic 12) were obtained from 57 patients who underwent CEA. The presence of an intraplaque hemorrhage was noted in 75% from symptomatic plaques, compared with 33% from asymptomatic ones. A plaque disruption occurred over protruding mounds of intraplaque hemorrhage and was noted in 76% and 42% from symptomatic and asymptomatic ones, respectively. However, asymptomatic plaques, which were angiographically demonstrated as carotid ulcer of types B and C, had a high incidence of intraplaque hemorrhage as well as plaque disruption. Three patients followed with asymptomatic contralateral carotid artery disease developed a stroke following ipsilateral revascularization and all three specimens showed the presence of plaque hemorrhage and disruption. It is concluded that before prophylactic CEA is considered, an intraplaque hemorrhage and/or plaque disruption should be detected by less invasive procedures such as ultrasonography.

Carotid Stenosis↗
PubMed1998

Glomerular charge and size selectivity assessed by changes in salt intake in type 2 diabetic patients.

OBJECTIVE: To evaluate glomerular charge selectivity in patients with type 2 diabetes, we studied changes in fractional clearance of proteins with different sizes and charges when patients were placed on two diets with different salt contents. RESEARCH DESIGN AND METHODS: Nineteen patients with type 2 diabetes and normoalbuminuria (< 20 micrograms/min, n = 8), microalbuminuria (20-100 micrograms/min, n = 7), or advanced albuminuria (> 100 micrograms/min, n = 4) were placed on a low-salt diet (85 mEq of sodium daily) or a high-salt diet (255 mEq of sodium daily) for 1 week, and then on the other diet, in random order. Fractional clearances of albumin and immunoglobulin G (IgG) were calculated on the last 3 days of each diet. RESULTS: In patients with normoalbuminuria, the high-salt diet increased the fractional clearance of IgG, which is electrically neutral, but the fractional clearance of albumin, which is anionic, was unaltered, suggesting that the pore charge of the glomerular barrier was unaffected. However, in patients with microalbuminuria, the high-salt diet increased the fractional clearances of IgG and albumin equally, indicating some neutralization of the pore charge. Fractional clearance of IgG in these first two groups was similar when salt intake was low, so pore size was the same in these groups. In patients with advanced albuminuria, fractional clearance of IgG was higher than in the other groups, indicating that size selectivity had worsened. CONCLUSIONS: In type 2 diabetic patients, charge selectivity is lost before size selectivity as diabetic nephropathy progresses.

Adult↗