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Biomedical subjects

S Shimada

Publications and source records attributed to S Shimada.

At least 91 records · Page 5Linked to original sources
PubMed2000

Serum itraconazole and hydroxyitraconazole concentrations and interaction with digoxin in a case of chronic hypertrophic pachymenigitis caused by Aspergillus flavus.

A patient treated with itraconazole (ITCZ) under the diagnosis of Aspergillus flavus-induced chronic hypertrophic pachymeningitis is presented. The reason for the successful cure of this patient was investigated by the pharmacokinetic analysis of serum levels of ITCZ. Concurrently administered digoxin was also investigated for its drug-drug interaction. The patient (a 75-year-old male) developed ophthalmopathy, and was diagnosed as having A. flavus hypertrophic pachymeningitis by pachymeninx biopsy. After admission, he was treated with FLCZ, AMPH, 5-FC and MCZ. The infection tended to subside with the AMPH administration. Since renal insufficiency was induced by AMPH and the other antifungal drugs were ineffective, daily administration of 200 mg of ITCZ was initiated, and the inflammatory signs and symptoms gradually subsided. The symptoms did not recur during the 36 months of itraconazole treatment after discharge, and it was concluded that ITCZ was effective for A. flavus hypertrophic pachymeningitis. Pharmacokinetic parameters of ITCZ and OH-ITCZ as follows: ITCZ: Cmax 93.2 ng/ml, T1/2 beta 11 hours, AUC0-24 999 ng.h/ml, OH-ITCZ: Cmax 159.4 ng/ml, T1/2 beta 16. 2 hours, AUC0-24 of 1391 ng.h/ml. Both ITCZ and OH-ITCZ reached steady states seven days after administration began. The ITCZ and OH-ITCZ levels in serum collected 36 months after the initiation of administration were 452.9 ng/ml and 1233.6 ng/ml, respectively. Cmax and AUC0-24 of ITCZ and OH-ITCZ on the second day were markedly lower than those in healthy adults reported by Oguchi et al., and hypoalbuminemia observed at administration on that day was considered the most probable cause. It was assumed that the most plausible reason for a successful cure even at a low dose of ITCZ was the increase of distribution to tissue by the increase of the unbound form. Digoxin was concurrently given to this patient at 0. 125 mg/day, but the blood digoxin level was not elevated. Consideration of the blood level of albumin is believed to be important for evaluating the blood concentration of ITCZ.

Aged↗
PubMed2000

Apoptosis is associated with formation and persistence of the embryonic fissure.

PURPOSE: The role of apoptosis in the transitory ocular embryonic structures has not been clarified yet, therefore, in the present study we focused on one of the transitory ocular structures, the embryonic fissure. To elucidate the developmental mechanism of the embryonic fissure, we observed cell death by apoptosis in the optic cup during early development in mice. METHODS: Pairs of C57BL6N/Jcl mice, each comprising an estrous female and a potent male, were caged together overnight. Females that had vaginal plugs the next morning were considered at day 0 of pregnancy. The embryos or fetuses were removed by laparotomy on days 9, 10, 11, 12, 13, 14, 16, and 18 of gestation. Tissue blocks of the eyes were fixed and embedded in paraffin wax. Serial frontal sections of the eye were cut and stained with the TUNEL method and then counterstained by hematoxylin or methyl green solution. We examined TUNEL-positive cells in the optic cup by light microscopy. RESULTS: TUNEL-positive cells were seen at the lower nasal side of the optic cup, corresponding to the presumed embryonic fissure area, on day 9 of gestation before the formation of the embryonic fissure. Many TUNEL-positive cells were present at the lips of the embryonic fissure on days 10, 11, and 12. In contrast, TUNEL-positive cells were not detectable in the corresponding area on day 13 after the complete closure of the embryonic fissure. CONCLUSIONS: Apoptosis is anatomically closely associated, and appears to be essential for the formation and persistence of the embryonic fissure.

Animals↗
PubMed2000

[Pharmacokinetics of panipenem in neonates and dosage recommendation].

The pharmacokinetics of panipenem/batamipron (Carbenin; PAPM/BP) was studied in 17 neonates of the postconceptional age (PCA) of 25.6 to 43.1 weeks. PAPM/BP was administered at 10 mg/kg to 20 mg/kg every 12 hours over 60 minutes by intravenous infusion. Blood samples were obtained just prior to the infusion, one or two hours and six hours after the infusion. All the data for the 85 serum PAPM concentrations were analyzed by one-compartment model using a nonlinear mixed-effect model (NONMEM). The pharmacokinetic parameters in these population are given below: CLPAPM; 0.239 +/- 0.206 (L/hr), VdPAPM; 0.97 +/- 0.80 (L), Half Life; 3.1 +/- 0.5 (hr). Half life in the patients with PCA < 34 (2.66 +/- 0.44 hr) were significantly lower (p < 0.001) than that with PCA > or = 34 (3.39 +/- 0.23 hr). Our results suggest that postnatal alterations in the PAPM excretion are related to maturational changes in the renal function and that we should consider the values of PCA when determining the initial PAPM/BP dosing regimen in neonates. We conclude that the dosage of 10 mg/kg to 20 mg/kg every 12 hours are adequate treatment for neonatal infectious disease.

Bacterial Infections↗
PubMed2000

Retinal fascin: functional nature, subcellular distribution, and chromosomal localization.

PURPOSE: To investigate the functional properties, subcellular localization, and chromosomal location of retinal fascin. METHODS: Recombinant retinal fascin protein was prepared by using a baculovirus-insect expression system. Actin-binding and -bundling assays were performed with chick actin purified from skeletal muscle. Western blot analysis and immunohistochemistry were performed with a polyclonal antibody raised against bovine retinal fascin. A human retinal cDNA library was screened with an expressed sequence tag cDNA fragment. Chromosomal location was determined with fluorescent in situ hybridization. RESULTS: The actin-binding and actin-bundling activities of retinal fascin were demonstrated by high- and low-speed centrifugation assays. Formation of filamentous (F)-actin bundles by retinal fascin in vitro was also morphologically confirmed by fluorescence microscopy and electron microscopy. Immunohistochemical analysis revealed that retinal fascin protein was localized specifically in the outer and inner segments of the photoreceptor cells in the retina. Two splicing variants of human retinal fascin cDNA were also located. One clone encoded 492 amino acids, and the other encoded 516 amino acids. The gene encoding retinal fascin was localized to human chromosome 17, region q24 -25. CONCLUSIONS: These results suggest that retinal fascin may play a role in formation of unique morphologic structures of the photoreceptor cells and is a candidate gene for retinal degenerative disorders.

Actins↗
PubMed2000

Histochemical studies on glycosaminoglycans in Bruch's membrane of postnatal rat eyes.

Localization of glycosaminoglycans (GAG) in Bruch's membrane of postnatal rat eyeballs was examined histochemically. Fixed eyeballs from postnatal rats (ages 5 days and 8 weeks) were routinely processed and embedded in paraffin wax or Quetol 651 resin. Paraffin-embedded tissue sections were stained with hematoxylin and eosin or sensitized high iron diamine procedure in combination with selective methods such as GAG-degrading enzyme digestions and/or a chemical modification, and examined by light microscopy. Quetol 651-embedded ultrathin sections were stained with heavy metals and examined by electron microscopy. In rats at postnatal day 5, Bruch's membrane contained mainly chondroitin sulfate (CS) and heparan sulfate (HS). In contrast, at 8 weeks after birth the membrane included a large amount of dermatan sulfate (DS) and HS. According to electron microscopic findings, Bruch's membrane on day 5 consisted of only 3 layers without a central elastic layer. However, at 8 weeks after birth the membrane was constructed of 5 layers. These findings suggested that the difference in GAG molecular species in the membranes at 5 days and at 8 weeks after birth could be correlated with the development and maturation of the collagenous layer in Bruch's membrane. Moreover, maturation of Bruch's membrane may contributes to the architectural stabilization of the outer portions of the photoreceptor cells.

Animals↗
PubMed2000

[Exencephaly].

Explore the source record for details and available documents.

Female↗
PubMed2000

Factors influencing the expression of Fas and Fas ligand on newborn murine keratinocytes and fibroblasts.

OBJECTIVE: To investigate the expression of Fas, FasL mRNA and proteins on keratinocytes and fibroblasts, and the influence by retinoid acid (RA) and dexamethasone (Dex). METHODS: RNase protection assay and flow cytometry were used. RESULTS: Fas mRNA was expressed on neonatal murine keratinocytes and was up-regulated by all-trans retinoid acid and down-regulated by Dex. RA and Dex also increased the Fas protein expression on keratinocytes. Newborn murine keratinocytes express FasL mRNA, which was up-regulated by RA and Dex, while its protein expression was moderately induced by RA. Newborn murine fibroblasts also expressed Fas and FasL mRNA, which were up-regulated by the RA and Dex. CONCLUSIONS: The results indicated that RA and Dex might regulate apoptosis of keratinocytes and fibroblasts via the Fas-FasL system.

Animals↗
PubMed1999

Generation of polymeric immunoglobulin receptor-deficient mouse with marked reduction of secretory IgA.

We generated mouse lacking exon 2 of polymeric Ig receptor (pIgR) gene by a gene-targeting strategy (pIgR-deficient mouse; pIgR-/- mouse) to define the physiological role of pIgR in the transcytosis of Igs. pIgR-/- mice were born at the expected ratio from a cross between pIgR+/- mice, indicating that disruption of the pIgR gene in mice is not lethal. pIgR and secretory component proteins were not detected in pIgR-/- mice by Western blot analysis. Moreover, immunohistochemical analysis showed that pIgR protein is not expressed in jejunal and colonic epithelial cells of pIgR-/- mice, whereas IgA+ cells are present in the intestinal mucosa of pIgR-/- mice as well as wild-type littermates. Disruption of the pIgR gene caused a remarkable increase in serum IgA concentration and a slight increment of serum IgG and IgE levels, leaving serum IgM level unaltered. In contrast, IgA was much reduced but not negligible in the bile, feces, and intestinal contents of pIgR-/- mice. Additionally, IgA with a molecular mass of 280 kDa preferentially accumulated in the serum of pIgR-/- mice, suggesting that transepithelial transport of dIgA is severely blocked in pIgR-/- mice. These results demonstrate that dIgA is mainly transported by pIgR on the epithelial cells of intestine and hepatocytes, but a small quantity of IgA may be secreted via other pathways.

Animals↗
PubMed1999

Imaging magma transport during the 1997 seismic swarm off the izu peninsula, japan

The spatio-temporal evolution of a propagating magma-filled crack was estimated from inversion of Global Positioning System (GPS) data, tiltmeters, and leveling. The dike opened at a maximum rate of 50 millimeters per day and had a peak magma flux of 2 x 10(6) cubic meters per day. Although the spatial resolution was limited, slow upward propagation was resolved during the 9-day-long intrusion. In contrast, the earthquakes migrated rapidly upward during the first 12 hours of the swarm, and nearly all of the seismic energy was released in the first 2 days. Comparison of inversion results with accurate hypocenter locations will lead to improved understanding of magma transport through the brittle crust and of the causes of volcanic seismicity.

Journal Article↗
PubMed1999

Effects of pressure stress on the fission yeast Schizosaccharomyces pombe cold-sensitive mutant nda3.

To investigate the influence of pressure stress on the cell cycle of Schizosaccharomyces pombe, we used a cold-sensitive nda3-KM311 mutant which arrests cell division at a step similar to the mitotic prophase, proposed by Hiraoka and colleagues (Cell 39 (1984) 349-358), under the restrictive temperature, 20 degrees C. The nda3-KM311 cells were first aerobically grown at 30 degrees C, transferred to 20 degrees C for 4 h and shifted to a permissive temperature of 36 degrees C for 15 min. The cells were treated with 100-200 MPa pressure and studied by electron and fluorescence microscopy. At 100 MPa, the nuclear membrane was damaged and the matrix of mitochondria had an electron-dense area. At 150 MPa, the nuclear membrane was broken over broad areas; numerous small vacuoles had fused into large pieces. Actin patches were concentrated in the central region and actin rings were seen in the 20 degrees C-grown cells. Even at 100 MPa, specific actin distribution was lost. Although at 100 MPa, long and fine actin cables were seen all over the cells, large actin patches and the actin rings remained in the center of the cell. They changed into thick and short cables at 150 MPa and above 200 MPa they decomposed but the actin ring was visible even with faint fluorescence. Immunoelectron microscopic observation confirmed this phenomenon.

Actins↗
PubMed1999

Cytolytic and IFN-gamma-producing activities of gamma delta T cells in the mouse intestinal epithelium are T cell receptor-beta-chain dependent.

We analyzed the cytolytic activity of intraepithelial T cells (IEL) isolated from the small intestines of 2- to 3-month-old mutant mice rendered deficient in different gene(s) in which the number of IEL expressing either T cell receptor (TCR)-alpha beta (alpha beta-IEL) or TCR-gamma delta (gamma delta-IEL) were absent or markedly diminished. When compared with wild-type littermates, cytolytic activity of gamma delta-IEL was sharply attenuated in TCR-beta mutant mice but remained unaltered in TCR-alpha mutant mice in which a minor population of dull TCR-beta+ (betadim)-IEL was also present. Cytolytic activity of gamma delta-IEL was maintained in mice doubly homozygous for beta2-microglobulin and transporter associated with antigen processing 1 gene mutations in which a conspicuous decrease was noted in absolute numbers of alpha beta-IEL. In contrast, both TCR-delta and IL-7 receptor-alpha gene mutations that lead to lack of gamma delta-IEL generation did not affect the development or cytolytic activity of the remaining alpha beta-IEL. The anti-CD3 and anti-TCR-gamma delta mAb-induced IFN-gamma production of gamma delta-IEL showed the same TCR-alpha and TCR-beta mutation-dependent variability. These results indicate that cytolytic and IFN-gamma-producing activities of gamma delta T cells in mouse intestinal epithelium are TCR-beta-chain-dependent.

Animals↗
PubMed1999

Expression of norepinephrine and serotonin transporter mRNAs in the rat superior cervical ganglion.

We investigated the gene expression of three monoamine transporters (norepinephrine transporter, NET; serotonin transporter, SERT; and dopamine transporter, DAT) in the rat superior cervical ganglion (SCG). Most of principal ganglion neurons abundantly expressed NET mRNA. In addition, about 30% of principal ganglion neurons also expressed SERT mRNA. However, DAT mRNA expression was not observed there. These results suggest that serotonin as well as norepinephrine works as a neurotransmitter in a subset of principal ganglion neurons.

Animals↗
PubMed1999

Comparison between the decrease of dopamine transporter and that of L-DOPA uptake for detection of early to advanced stage of Parkinson's disease in animal models.

Early diagnosis of Parkinson's disease (PD) is important for the potential application of neuroprotective therapies. The purpose of this study was to assess the detection of the early changes of PD by either imaging the dopamine transporter (DAT) or uptake of L-3,4-dihydroxyphenylalanine (L-DOPA). An early to advanced stage model of PD was induced in rats by stereotaxic injection of 1-10 microg 6-hydroxydopamine (6-OHDA) into the substantia nigra pars compacta. Using adjacent sections of the same animals, the binding of [I-125]beta-CIT, which labels DAT and the uptake of [C-14]L-DOPA, were evaluated 4 weeks after induction of the lesion. Any decrease in dopaminergic neurons was evaluated by in situ hybridization histochemistry (ISH) by detection of DAT mRNA-positive neurons. In addition, the expression levels of DAT, dopa decarboxylase (DDC), and vesicular monoamine transporter (VMAT2) in each neuron were studied with ISH. Our results show a decrease in both [I-125]beta-CIT binding and [C-14]L-DOPA uptake in parallel with a decrease in DA neurons from early to advanced stage models of PD. The decrease in [C-14]L-DOPA uptake was smaller than that in [I-125]beta-CIT binding in the same animal (P < 0.0001). Expression levels of DAT, DDC, and VMAT2 mRNAs were also decreased with the progression of the disease. Although ISH failed to detect the origin of the discrepancy between [I-125]beta-CIT and [C-14]L-DOPA levels, it was concluded that [C-14]L-DOPA levels underestimated the decrease of dopaminergic neurons and that [I-125]beta-CIT levels more precisely reflected the decrease.

Animals↗
PubMed1999

Cloning of a bovine orphan transporter and its short splicing variant.

We have isolated a cDNA (bv7-3) encoding a member of the Na+,Cl(-)-dependent transporter family and its short splicing variant (bv7-3s) by screening a bovine retina cDNA library. Sequence analysis revealed that bv7-3 encodes a protein of 729 amino acids and is a bovine homologue of the rat orphan transporter v7-3-2. bv7-3s contains 265 amino acids, sharing 252 N-terminal amino acids with bv7-3. Both mRNAs for bv7-3 and bv7-3s were detected in nervous system by Northern blot analysis. In immunofluorescence analysis in transfected HEK 293T cells, myc-tagged bv7-3 was mainly detected on the plasma membrane, whereas myc-tagged bv7-3s showed a pattern of intracellular membrane staining.

Alternative Splicing↗
PubMed1999

Molecular cloning and characterization of rat trp homologues from brain.

Identification of trp (transient receptor potential) gene from Drosophila photoreceptor and subsequent molecular cloning of the human cDNA homologues suggest its participation in capacitative calcium entry (CCE) or so called store-operated Ca2+ channel (SOC). We identified five different trp-related amplifications of reverse-transcription-polymerase chain reaction (RT-PCR) from rat brain; these corresponded to mouse trp homologues, mtrp1,3,4,5,6 and were distributed in various tissues with multiple expression levels. Two cDNAs, homologous to Drosophila trp from rat brain, designated rtrp3 and rtrp6, were isolated and characterized. By RT-PCR analysis, mRNAs of rtrp3 and rtrp6 were found to be expressed differently in brain and other tissues. In situ hybridization analysis revealed that rtrp6 mRNA was preferentially expressed in hippocampal dentate gyrus and cortical layers II and III. Expression of rat TRP3 and TRP6 in COS cells revealed an increase in CCE, as compared to that in the mock-transfected COS cells of the control. Isolation of cDNAs of rat trp gene family provides a useful model for studying mechanism of CCE.

Animals↗
PubMed1999

Overexpression of CD82 on human T cells enhances LFA-1 / ICAM-1-mediated cell-cell adhesion: functional association between CD82 and LFA-1 in T cell activation.

We previously demonstrated that CD82, expressed on both T cells and antigen-presenting cells (APC), plays an important role as a co-stimulatory molecule especially in the early phase of T cell activation. We also showed that the CD82 expression level is up-regulated on activated T cells and memory T cells. This up-regulation enhances both T cell-T cell and T cell-APC interactions. In this study, we further investigated the mechanism of CD82-mediated cell-cell adhesion. The enhanced adhesion between CD82-overexpressing Jurkat cells was completely blocked by anti-ICAM-1 / LFA-1 monoclonal antibodies. Increased interaction of LFA-1 with ICAM-1 was further confirmed by enhanced adhesion of CD82-overexpressing Jurkat cells to immobilized ICAM-1-Ig. CD82 co-immunoprecipitated with LFA-1 from Jurkat cells and CD82 and LFA-1 colocalized at an adhesion foci. These results suggest that the T cell stimulation via anti-CD3 cross-linking or phorbol myristate acetate treatment up-regulates CD82 expression, leading to the colocalization of CD82 and LFA-1, and results in enhanced interaction between LFA-1 and ICAM-1. In addition, a blocking experiment using monoclonal antibodies suggested that CD82 and LFA-1 molecules on APC are also important for the optimal activation of T cells. This is the first report that describes the enhancement of cell-cell interaction through LFA-1 and ICAM-1 by the overexpression of another cell surface molecule, CD82.

Antigens, CD↗