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Biomedical subjects

S Izumi

Publications and source records attributed to S Izumi.

At least 19 recordsLinked to original sources

Regulation of dally, an integral membrane proteoglycan, and its function during adult sensory organ formation of Drosophila.

In Drosophila, imaginal wing discs, Wg and Dpp, play important roles in the development of sensory organs. These secreted growth factors govern the positions of sensory bristles by regulating the expression of achaete-scute (ac-sc), genes affecting neuronal precursor cell identity. Earlier studies have shown that Dally, an integral membrane, heparan sulfate-modified proteoglycan, affects both Wg and Dpp signaling in a tissue-specific manner. Here, we show that dally is required for the development of specific chemosensory and mechanosensory organs in the wing and notum. dally enhancer trap is expressed at the anteroposterior and dorsoventral boundaries of the wing pouch, under the control of hh and wg, respectively. dally affects the specification of proneural clusters for dally-sensitive bristles and shows genetic interactions with either wg or dpp signaling components for distinct sensory bristles. These findings suggest that dally can differentially regulate Wg- or Dpp-directed patterning during sensory organ assembly. We have also determined that, for pSA, a bristle on the lateral notum, dally shows genetic interactions with iroquois complex (IRO-C), a gene complex affecting ac-sc expression. Consistent with this interaction, dally mutants show markedly reduced expression of an iro::lacZ reporter. These findings establish dally as an important regulator of sensory organ formation via Wg- and Dpp-mediated specification of proneural clusters.

Animals↗

Evaluation of a floating dosage form of nicardipine hydrochloride and hydroxypropylmethylcellulose acetate succinate prepared using a twin-screw extruder.

A floating dosage form composed of nicardipine hydrochloride (NH) and hydroxypropylmethylcellulose acetate succinate (enteric polymer) was prepared using a twin-screw extruder. By adjusting the position of the high-pressure screw elements in the immediate vicinity of die outlet, and by controlling the barrel temperature, we were able to prepare a puffed dosage form with very small and uniform pores. It was found that the porosity and pore diameter could be controlled by the varying amount of calcium phosphate dihydrate. In the shaking test, the puffed dosage form was found to have excellent floating ability and mechanical strength in acid solution (JP First Fluid, pH 1.2). The dissolution profile of NH was controlled by the amount of wheat starch. In the dissolution test using JP Second Fluid (pH 6.8), rapid dissolution of NH and loss of buoyancy were observed. It was shown that the puffed dosage form, consisting of enteric polymer prepared using the twin-screw extruder, was very useful as a floating dosage form that was retained for a long period in the stomach.

Administration, Oral↗

Structural analysis of gene encoding cuticle protein BMCP18, and characterization of its putative transcription factor in the silkworm, Bombyx mori.

BMCP18(2) is one of the major cuticle proteins identified in the larval cuticle of the silkworm, Bombyx mori. A genomic clone coding for BMCP18 was isolated from a B. mori genomic library, and its structure was analyzed. The BMCP18 gene consists of three exons interspersed by two introns. Bm1 element-like sequences were identified around this gene, suggesting possible involvement of this retroposon in the duplication of B. mori cuticle protein genes during evolution. A structural comparison of the BMCP18 gene and related cuticle protein genes of other lepidopteran species (MSCP14.6 and HCCP12) showed that the 5' upstream region of the BMCP18, MSCP14.6, and HCCP12 genes has a 12-bp identical sequence matching the recognition sequence for transcription factors COUP-TF and HNF-4. This implies that molecular mechanisms regulating expression of these cuticle protein genes are also conserved. mRNAs coding for Bmsvp, the B. mori homolog of Drosophila Seven-up, which is known as a homolog of vertebrate COUP-TF, and BmHNF-4, a homolog of vertebrate HNF-4, were detected in the larval epidermis. Bmsvp bound to the 12-bp sequence in vitro, suggesting that Bmsvp regulates the BMCP18 gene expression.

Amino Acid Sequence↗

Transcriptional and posttranscriptional regulation of the gene for Dally, a Drosophila integral membrane proteoglycan.

"division abnormally delayed"(dally), a Drosophila member of the glypican family, has been implicated in Dpp and Wg signaling. Here, we report the genomic structure and regulation of the dally gene. The dally gene is composed of nine exons, and its expression is controlled by a TATA-less promoter. Analysis of transgenic flies bearing the dally promoter fused to the lacZ reporter gene showed that a 371 bp sequence of the dally 5' flanking region was capable of mimicking the patterns of dally enhancer trap expression in developing tissues, including embryonic epidermis and imaginal discs. The tissue-specific enhancers that drive marker gene expression in embryo and the wing disc are mapped in the 5' upstream region of dally gene. We propose that dally gene expression is also regulated posttranscriptionally by controlling the translation efficiency and stability of its mRNA.

Amino Acid Sequence↗

Drosophila heparan sulfate 6-O-sulfotransferase (dHS6ST) gene. Structure, expression, and function in the formation of the tracheal system.

Heparan sulfate, one of the most abundant components of the cell surface and the extracellular matrix, is involved in a variety of biological processes such as growth factor signaling, cell adhesion, and enzymatic catalysis. The heparan sulfate chains have markedly heterogeneous structures in which distinct sequences of sulfate groups determine specific binding properties. Sulfation at each different position of heparan sulfate is catalyzed by distinct enzymes, sulfotransferases. In this study, we identified and characterized Drosophila heparan sulfate 6-O-sulfotransferase (dHS6ST). The deduced primary structure of dHS6ST exhibited several common features found in those of mammalian HS6STs. We confirmed that, when the protein encoded by the cDNA was expressed in COS-7 cells, it showed HS6ST activity. Whole mount in situ hybridization revealed highly specific expression of dHS6ST mRNA in embryonic tracheal cells. The spatial and temporal pattern of dHS6ST expression in these cells clearly resembles that of the Drosophila fibroblast growth factor (FGF) receptor, breathless (btl). RNA interference experiments demonstrated that reduced dHS6ST activity caused embryonic lethality and disruption of the primary branching of the tracheal system. These phenotypes were reminiscent of the defects observed in mutants of FGF signaling components. We also show that FGF-dependent mitogen-activated protein kinase activation is significantly reduced in dHS6ST double-stranded RNA-injected embryos. These findings indicate that dHS6ST is required for tracheal development in Drosophila and suggest the evolutionally conserved roles of 6-O-sulfated heparan sulfate in FGF signaling.

Amino Acid Sequence↗

A case of multiple sclerosis with granulomatous uveitis in Japan--use of the antilipoarabinomannan (LAM)-B test in differential diagnosis.

PURPOSE: To report a patient with multiple sclerosis and associated with granulomatous uveitis, and how anti-lipoarabinomannan (LAM)-B antibody can play a key role in differential diagnosis. METHODS: Case report. RESULTS: A 35-year-old Japanese woman with multiple sclerosis, diagnosed 3 years ago, presented with blurred vision in her left eye. Ophthalmological examinations revealed granulomatous iridocyclitis in her left eye and retinal periphlebitis in both eyes. The diagnosis of tuberculosis was suspected because of a positive tuberculin skin test. However, a further examination by an anti-LAM-B antibody test excluded active tuberculosis. Her clinical findings were thought most likely to be caused by multiple sclerosis and treated with corticosteroids. CONCLUSION: We should consider the possibility of multiple sclerosis as the underlying origin in patients with granulomatous uveitis. A measurement of anti-LAM-B antibody titer may be useful in the differential diagnosis of granulomatous uveitis.

Administration, Topical↗

Anti-annexin V antibodies in patients with early pregnancy loss or implantation failures.

OBJECTIVE: To describe the prevalence of annexin V antibodies (aANX) in women with early recurrent pregnancy losses (RPLs) or recurrent IVF-ET failure. DESIGN: Retrospective data analysis. SETTING: Tokai University Hospital, Kanagawa, Japan. PATIENT(S): Two hundred thirty-eight patients with RPLs, 48 patients with recurrent IVF-ET failure and 179 nonpregnant and 120 pregnant control group women. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): ELISA was used to measure autoantibodies to annexin V. RESULT(S): An ELISA system developed for aANX revealed a dose-dependent relationship between annexin V and aANX. The positive/negative cutoff was set at 7 multiples of the median based on the 99th percentile of normal nonpregnant control group patients. Patients with RPLs (5.5%) or recurrent IVF-ET failure (8.3%) had a significantly increased incidence of aANX (IgG) compared with normal nonpregnant (1.1%) or pregnant control group women (0), whereas the prevalence of aANX between both patient groups or between both control groups was not statistically different. Specificity was confirmed by absorption studies using annexin V and by immunoblots. CONCLUSION(S): Our data show that aANX are associated with both RPLs and IVF-ET failure. We propose that anti-annexin V antibodies should be considered a risk factor for these reproductive failures.

Abortion, Habitual↗

Increased natural killer-cell activity is associated with infertile women.

PROBLEM: An increase in natural killer (NK)-cell activity has been observed in women with unexplained recurrent miscarriages. Because of the many similarities between infertility and early pregnancy loss patients, we investigated whether infertile women had raised NK-cell activity. METHOD OF STUDY: We tested 94 infertile women who, in spite of treatment, were unable to conceive for 6 or more months. NK-cell activity was measured by using a chromium-51 release cytotoxicity assay. with K562 human myeloid leukemia cells as targets. RESULTS: NK-cell activity of the infertile group (mean +/- SD; 40.2%+/-14.7) was significantly higher than the control group (31.5%+/-11.9, P < 0.0001). The increased NK-cell activity was not associated with age, infertile duration, depression scores, treated hyperprolactinemia, or treated endometriosis. CONCLUSIONS: In certain patients, elevated NK-cell activity may be considered an independent risk factor for infertility.

Abortion, Spontaneous↗

Different antiphospholipid antibody specificities are found in association with early repeated pregnancy loss versus recurrent IVF-failure patients.

PROBLEM: Patients having in vitro fertilization and embryo transfer (IVF-ET) failures show an increased incidence of antiphospholipid (aPL) antibodies; but controversy exists whether aPL can induce IVF-failure. This study was designed to compare aPL specificities between recurrent IVF-failure patients versus repeated early pregnancy loss (RPL) patients. METHOD OF STUDY: Anticardiolipin (aCL), lupus anticoagulant (LA), antiphosphatidylserine (aPS), antiphosphatidylethanolamine (aPE), and antinuclear antibodies (ANA) were measured in 74 recurrent IVF-ET failure patients and compared with 273 early RPL patients ( < 10 weeks). RESULTS: An increased incidence of IgG-aPE and ANA was observed for both groups in comparison with controls. Patients with recurrent IVF-ET failure showed a significantly higher prevalence of IgG-aPS (P = 0.02) and IgG-aCL (P = 0.02) when compared with early RPL patients or controls. CONCLUSIONS: IgG-aPS and IgG-aCL may be responsible for some IVF-failures. Additional studies are needed to clarify the pathogenic role of IgG-aPS and IgG-aCL on IVF-ET failure.

Abortion, Habitual↗

Chemokine receptor expression profile of eosinophils at inflamed tissue sites: Decreased CCR3 and increased CXCR4 expression by lung eosinophils.

BACKGROUND: To date, most studies dealing with eosinophil chemokine receptors have used eosinophils isolated from peripheral blood. During the movement of eosinophils from the peripheral blood to inflamed tissue sites, microenvironmental signals might alter their expression of chemokine receptors. However, little is known about the profile of expression of chemokine receptors by eosinophils at inflamed tissue sites in human beings. OBJECTIVE: The purpose of this study was to determine whether eosinophils that have migrated into inflamed tissues exhibit a profile of chemokine receptor expression that is qualitatively and/or quantitatively different from that of eosinophils in peripheral locations. METHODS: We studied simultaneously the expression and function of chemokine receptors in eosinophils in both bronchoalveolar lavage fluid (BALF) and peripheral blood specimens of 7 patients with eosinophilic lung diseases. RESULTS: De novo expression of CCR2, CCR4, and CCR5 was not detected at either the protein or the mRNA level. However, surface expression of CCR3 was decreased and CXCR4 was conversely increased with statistical significance in BALF eosinophils. Moreover, the changes in CCR3 and CXCR4 expression were reflected in the altered migratory response to their ligands. On the other hand, the levels of CXCR1, CXCR2, CXCR3, and CCR1 were virtually unchanged in BALF eosinophils, and these receptors did not have functional significance. CONCLUSION: Eosinophils at inflamed tissue sites exhibited an expression profile qualitatively similar to that in peripheral locations, except for decreased CCR3 and increased CXCR4 expression. Our results suggest that CCR3 is primarily and CXCR4 is cooperatively involved in eosinophil accumulation at inflamed tissue sites.

Adult↗

Emotional distress of infertile women in Japan.

Although recent papers have suggested that psychological factors are implicated in the experience of infertility, few studies have assessed this relationship in a sample of Japanese infertile women. This study was carried out in order to clarify whether Japanese infertile women experience emotional distress. A cross-sectional questionnaire study was performed to assess the psychological states of 101 infertile women compared to 81 healthy pregnant women. The hospital anxiety and depression scale (HADS) and the profile of mood states (POMS) were administered. These questionnaires produced scores for depression/dejection, anxiety, aggression/hostility, lack of vigour, fatigue, tension anxiety, and confusion. The HADS and the POMS scores of infertile women were significantly higher than those of pregnant women, except for fatigue score. Infertile women with positive HADS indicating emotional disorders (39/101, 38.6%) were significantly (P = 0.0008, chi(2) test) more than those of pregnant women (13/81, 16.0%) when the threshold was set at 12/13 of total HADS scores. The HADS scores were not affected by the women's age, duration of infertility, experience of conception, routine tests, and work states. In this Japanese population, infertile women reported higher levels of emotional distress than pregnant women, suggesting psychological support is needed for infertile women.

Adult↗

Doxorubicin-induced DNA intercalation and scavenging by nuclear glutathione S-transferase pi.

Glutathione S-transferase (GST) functions in xenobiotic biotransformation and drug metabolism. Increased expression of GSTpi, an isozyme of GST, has been found in cancer cells resistant to doxorubicin hydrochloride (DOX) or cis-diamminedichloroplatinum (II) (CDDP), and this increase was believed to be correlated with drug resistance of cancer cells. GST is mainly expressed in the cytoplasm; GSTpi in the nucleus has been reported in cancer cells, but the meaning of this result is not known. Here, we studied changes in the amount of nuclear GSTpi after exposure of cancer cells to anticancer drugs, and role of the nuclear GSTpi in drug resistance. We found nuclear GSTpi in cancer cells resistant to DOX, and the amount of nuclear GSTpi was enhanced by treatment of the cancer cells with DOX or CDDP. We also found that a mushroom lectin, an inhibitor of nuclear transport, inhibited the nuclear transfer of GSTpi, suggesting the existence of a specific transport system for the nuclear transfer of GSTpi. Nuclear GSTpi protected DNA against damage by anticancer drugs. These results suggest a possible role of GSTpi in the acquisition of resistance to anticancer drugs by cancer cells.

Antineoplastic Agents↗

Chlamydia pneumoniae infects and multiplies in lymphocytes in vitro.

The obligate intracellular pathogen Chlamydia (Chlamydophila) pneumoniae is known to be associated with some chronic inflammatory diseases, such as atherosclerosis. Interaction between C. pneumoniae and immune cells is important in the development of such diseases. However, susceptibility of immune cells, particularly lymphocytes, to C. pneumoniae infection has not been reported, even though lymphocytes play a pivotal role in the development of the diseases caused by this bacterium. In this regard, we examined the susceptibility of lymphocytes to C. pneumoniae infection in vitro. The results demonstrated that human peripheral blood lymphocytes as well as mouse spleen lymphocytes could be infected with C. pneumoniae. Furthermore, purified T lymphocytes as well as established T-lymphocyte cell line cells showed an obvious susceptibility to C. pneumoniae infection, indicating that T cells could be one of the host cells for this bacterial infection. These findings reveal a new infection site for C. pneumoniae, i.e., lymphocytes.

Animals↗

Serial assessment of left and right ventricular filling in patients with congestive heart failure.

Serial changes in the diastolic filling of both ventricles were studied using Doppler echocardiography in 19 patients with congestive heart failure from the acute to the convalescent stage. During the acute stage, left ventricular early filling velocity (E) was high (88 +/- 17 cm/s) and atrial filling velocity (A) was low (44 +/- 23 cm/s), whereas the right ventricular E was depressed (17 +/- 8 cm/s) and A was enhanced (40 +/- 9 cm/s). As the condition improved, left ventricular E decreased (43 +/- 11 cm/s, p < 0.01) and A increased (59 +/- 24 cm/s, p < 0.01) along with a decrease in the left ventricular and atrial dimensions. In contrast to the changes in left ventricular filling, right ventricular E increased (31 +/- 10 cm/s, p < 0.01) and A decreased (32 +/- 5 cm/s, p < 0.05). There are opposite directional changes in left and right ventricular filling with clinical improvement from the acute to the convalescent stage of congestive heart failure, which suggest that the changes are related to improvement of the hemodynamic conditions of both ventricles. The changes in the right ventricular filling pattern was likely to be related to changes in right ventricular afterload, ventricular interaction and external constraint rather than a change in right ventricular filling pressure.

Adult↗

Sex difference in platelet aggregation detected by new aggregometry using light scattering.

Earlier studies in platelet aggregation have shown that females seemed to have greater aggregability than males as detected by conventional aggregometry which used light transmission (LT), but controversy still remains. This study was performed to determine whether sex difference exists in platelet aggregation by using the recently developed laser light scattering (LS) method, which can detect small aggregates (i.e., two or three platelets). Blood was drawn from healthy volunteers (10 male and 10 female in follicular phase after menstruation), and platelet aggregation was detected by either LT or LS method in platelet rich plasma. Platelet aggregation was stimulated by increasing concentration of adenosine 5'-diphosphate (ADP, 0, 0.5, 1 and 2 microM). To detect the effect of sex hormones, platelets were incubated with estradiol (10 nM) or testosterone (40 nM) for 30 min, then platelet aggregation studies were performed. LT method revealed that female had greater aggregability than male. With weak stimuli (< or = 1 microM ADP), LS method showed that females had more medium aggregates than males, and that testosterone decreased small aggregates, and that estradiol decreased all sizes of aggregates. These data suggest that the female is more conductive to platelet aggregation than the male at a physiologic concentration of ADP (< or = 1 microM), but that both estradiol (10 nM) and testosterone (40 nM) have countereffects on platelet aggregation at the same condition. Therefore, the reason why females have greater aggregability than males may partly be explained by their lack of testosterone, but the mechanism still remains to be elucidated.

Adenosine Diphosphate↗

[Prognostic factors of eating function in tube-fed infants and young children].

To investigate prognostic factors for eating function of dysphagic infants and young children and to propose a guideline for more reasonable future treatment, we retrospectively evaluated clinical findings at the initial examination of 51 tube-fed infants and young children who visited our center, and correlated them to the grade of improvement of their eating function after treatment. The patients were divided into good and poor groups according to the abilities of swallowing, and a multiple survival time analysis was performed in the former. The rate of successful tube-extraction during treatment was adopted as indices of improvement. We found that in the poor group the following factors are significantly associated with higher rate of tube-extraction: shorter period of dysphagia prior to the treatment, younger age to start treatment for eating, onset of feeding impairment after 8 months old, and the grade of the severity scores up to 2. In the good group, the children who received treatment by 36 months old had a high rate of tube-extraction. Based on these findings, we proposed a guideline for future treatment.

Child, Preschool↗