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At least 217 records · Page 12Linked to original sources
PubMed2000

Integrins alpha5beta1, alphavbeta1, and alphavbeta6 collaborate in squamous carcinoma cell spreading and migration on fibronectin.

The expression of alphavbeta6 fibronectin/tenascin receptor integrin is induced in malignant transformation of oral epithelium. In this study, we demonstrate the contribution of alphavbeta6 as well as other fibronectin receptor integrins in squamous cell carcinoma (SCC) cell adhesion and migration. Of 11 SCC cell lines isolated from the head and neck area, 8 (73%) expressed alphavbeta6 integrin on the cell surface. Three cell lines were chosen for further functional experiments: 1 with relatively high, 1 with moderate, and 1 with minimal surface expression of alphavbeta6 integrin. In addition to alphavbeta6, all 3 cell lines expressed alpha5beta1 and alphavbeta1 fibronectin receptor integrins. Function-blocking experiments with inhibitory anti-integrin antibodies showed that all these three integrins were functional in SCC cell spreading on fibronectin. Integrin alphavbeta6, however, was not used as a primary but as an alternative fibronectin receptor by SCC cells, as the inhibitory anti-beta6 integrin antibody alone had no effect on spreading. In migration, however, alphavbeta6, alpha5beta1, and alphavbeta1 integrins were all used in cooperation. The presence of alphavbeta1 integrin in SCC cells is a novel finding as is its contribution to SCC cell migration. When one or two of these three receptors were blocked, the cells demonstrated an adaptive ability to remain migratory using integrins that were not targeted by antibodies. Utilization of a combination of receptors of different affinities may be beneficial for SCC cell migration versatility.

Antibodies, Monoclonal↗
PubMed1999

NASDA aquatic animal experiment facilities for Space Shuttle.

National Space Development Agency of Japan (NASDA) has been developed aquatic animal experiment facilities for space experiments using NASA Space Shuttle. Vestibular Function Experiment Unit (VFEU) has been firstly designed and developed for Spacelab-J mission (STS-47), and 8 days space experiment with carp has been performed. Following, the VFEU, Aquatic Animal Experiment Unit (AAEU) has been developed to accommodate small aquatic animals second International Microgravity Laboratory mission (IML-2, STS-65). Four kinds of space experiments with goldfish, medaka, newt, and newt eggs have been performed for 15 days mission duration. Then, VFEU has been improved to accommodate marine fish under low temperature condition for Neurolab (STS-90) and STS-95 missions. 17 days (STS-90) and 9 days (STS-95) experiments with oyster toadfish have been performed by using the VFEU. This report summarizes the outline of these aquatic animal experiment facilities.

Animals↗
PubMed1996

The ileal neobladder in women: 9 years of experience with 18 patients.

PURPOSE: We present our surgical and functional experience with orthotopic bladder replacement in women. MATERIALS AND METHODS: Since 1986, 18 women have undergone lower urinary tract reconstruction with an ileal neobladder. A nerve sparing cystectomy is done, and reservoirs are connected to the proximal urethra or urethrovesical junction. A total of 13 patients was available for complete followup as of March 1995. RESULTS: There were no perioperative deaths and few early complications. The only 2 failures were a neobladder vaginal fistula and these cases, which were converted to a conduit, are excluded from this study. Late complications requiring rehospitalization or reoperation in 2 patients included urethroileal stenosis that had to be dilated without further sequelae and bilateral ureteroileal stenosis that was treated endoscopically. At 3 months postoperatively excellent continence was achieved in 8 patients, while 2 had grade 1 stress incontinence and 3 were hypercontinent. As of March 1995 only 4 patients voided to completion while 9 required intermittent catheterization (continuously in 5 and twice daily for residual urine in 4). We were unable to demonstrate a functional difference of the various resection lines located at the proximal urethra or urethrovesical junction. CONCLUSIONS: Urethral support and nerve sparing cystectomy plus the ileal neobladder as a reservoir guarantee excellent continence in all patients. Despite our efforts, we have been unable to demonstrate any advantage of the nerve and urethral support sparing cystectomy technique as far as micturition is concerned. The development of hypercontinence in 70% of the patients with time demonstrates that our current understanding of the functional and anatomical basics of the voiding process is too limited to allow bladder replacement with a perfect functional result in all female patients. Our long-term experience, which is different from initial reports, justifies creation of an ileal neobladder in select female patients as long as they accept a 70% risk of clean intermittent catheterization in the long term. Overall patient satisfaction, including sexual life, is exceptional. However, disappointment is considerable when clean intermittent catheterization is required after periods of successful voiding per urethram.

Cystectomy↗
PubMed1997

Comparison of simulation and experiments of different closed-loop strategies for functional electrical stimulation: experiments in paraplegics.

Open-loop and closed-loop stimulation of the knee extensors for the control of the knee joint angle and torque were tested as a potential basis for more complex functional electrical stimulation (FES) systems to be used in human locomotion. The output of the biomechanical simulation model described previously was compared with stimulation experiments in patients with complete thoracic spinal cord injury. Good correspondence between simulation and experiments was obtained under both isometric conditions and conditions with a freely swinging shank. For closed-loop control, a simple proportional integral derivative (PID) controller yielded sufficient performance only under isometric conditions, especially if combined with (linear) feedforward. Because of additional nonlinearities of musculotendon and body segmental dynamics, more complex strategies have to be applied to the control of unconstrained movements. To compensate for these nonlinearities, an inverse model was derived from the direct biomechanical model. This inverse model had satisfactory agreement between the measured knee angle and the desired trajectory already under open-loop conditions. A combination of the inverse model in the feedforward part of the control loop and a PID controller provided robust and precise control of the knee angle. Further improvement may be achieved by including elements of spasticity into the simulation model and by controlling both agonistic and antagonistic muscles.

Biomechanical Phenomena↗
PubMed2002

Single-shot interleaved z-shim EPI with optimized compensation for signal losses due to susceptibility-induced field inhomogeneity at 3 T.

A new single-shot echo-planar imaging (EPI) sequence with interleaved z-shim and optimized compensation for susceptibility-induced signal loss is proposed in this paper. Experiments on human brain demonstrated that the new method is able to regain signal dropout in brain areas with severe susceptibility-induced local gradients, while its image acquisition speed is comparable to that of conventional single-shot EPI techniques. Significant signal-to-noise ratio improvements were demonstrated in the ventral prefrontal and lateral temporal lobes with the new technique compared to a conventional EPI. Brain activation experiments with a bilateral finger-tapping task were performed with intentionally introduced local gradients near the left sensorimotor cortex, by a small gadolinium (Gd)-doped bottle placed on the left side of the head. The results of the functional experiments showed that the interleaved z-shim EPI sequence effectively recovered the signal loss caused by the Gd-doped bottle and reliably detected activation signals in bilateral sensorimotor regions, while the activation signals on the left side diminished considerably in a conventional EPI technique. The new technique, with the capability of reducing susceptibility artifacts and rapid scanning speed, may be particularly useful for event-related functional MRI experiments in the base of the brain, which are of great importance in neuropsychiatric studies.

Adult↗
PubMed2001

Functional asymmetry in schizophrenic patients during auditory speech processing.

In two experiments, functional laterality and interhemispheric transfer was investigated in schizophrenic patients (n=14) and healthy controls (n=17). In Experiment 1, words and pseudowords were presented either to the left or right ear (monaural condition) or simultaneously to both ears (binaural condition). In Experiment 2, subjects had to discriminate two tones differing in frequency during monaural and binaural stimulation. Healthy controls showed a right ear advantage (REA) for word stimuli, indicating left-hemispheric superiority for word processing. The same lateralization pattern was found in schizophrenic patients, indicating unimpaired functional lateralization of auditory language processing. In both groups, no REA was found for pseudowords resulting in significant WordnessxEar interactions. When presented binaurally, auditory processing of words and pseudowords did not differ significantly from any of the two monaural conditions. Tone discrimination did not lead to any ear asymmetry. The results show normal patterns of functional asymmetry during auditory language processing and tone discrimination in schizophrenic patients.

Adult↗
PubMed1997

Activation and activation-induced death of human tonsillar B cells and Burkitt lymphoma cells: lack of CD95 (Fas/APO-1) ligand expression and function.

Activation of T cells was shown to up-regulate the Fas ligand (FasL) which binds to the CD95 (APO-1/Fas) antigen and mediates activation-induced cell death (AICD) of activated T cells and T lymphoma cells. A recent report showed that mouse B cells express the FasL upon activation with lipopolysaccharide (LPS). We therefore asked whether activation of human B cells induces expression of FasL and whether AICD is mediated, as in T cells, through autocrine production of the FasL. We used human tonsillar B cells and Burkitt lymphoma cell lines which were activated by CD40 ligand, surface (s)IgM cross-linking, or LPS. Northern and Western blot analysis failed to detect FasL during B cell activation or AICD of both normal and malignant B cells. Low-level expression of FasL was detected by reverse transcriptase-polymerase chain reaction. Functional experiments, however, showed that FasL is not functionally expressed upon activation. IgM-mediated AICD in the tonsillar or Burkitt lymphoma B cells could not be inhibited by FasL blocking. Thus, our data show that, in contrast to T cells, activation of normal or malignant human B cells does not lead to functional FasL expression.

Apoptosis↗
PubMed1991

Angiotensin II-induced increase in slowly exchanging 45Ca2+ in relation to contractile responses of rat and guinea-pig aorta.

To gain more information about sources of activator Ca2+ involved in the contraction of rat and guinea-pig aorta evoked by angiotensin II and their sensitivity to Ca2+ entry blockers, measurement of slowly exchanging 45Ca2+ was established. A more physiological procedure was used, replacing La(3+)- and EGTA-containing solutions by a normal Ca(2+)-containing buffer. It was demonstrated that the angiotensin II-induced increase in slowly exchanging 45Ca2+ in rat aorta was incompletely (by approximately 60%-70%) inhibited by the organic Ca2+ entry blockers nifedipine, verapamil and diltiazem and by other Ca2+ entry blocking compounds like CoCl2 and chlorpromazine. 8-(N,N-diethylamino)octyl 3,4,5-trimethoxybenzoate hydrochloride (TMB-8) was able to inhibit the angiotensin II-induced increase in 45Ca2+ content completely, but this may be an intracellular storage effects. By contrast, the organic Ca2+ entry blockers completely inhibited that part of the angiotensin II-induced contraction of rat aorta which was dependent upon extracellular Ca2+. In guinea-pig aorta, the increase in 45Ca2+ content elicited by angiotensin II could be completely suppressed by all compounds under study. The results of these experiments correlated well with data from the functional experiments in guinea-pig aorta. In both preparations the release of Ca2+ from a rapidly as well as a slowly exchanging intracellular pool appears to contribute to the contractile response elicited by angiotensin II.

Angiotensin II↗
PubMed2026

Integrative analysis identifies a glycosylation-related lncRNA signature associated with prognosis in kidney renal clear cell carcinoma.

BACKGROUND: Glycosylation and long non-coding RNAs (lncRNAs) play critical roles in tumor progression. However, the prognostic significance of glycosylation-related lncRNAs (GRLncs) in kidney renal clear cell carcinoma (KIRC) remains largely unclear. This study aimed to identify prognostic GRLncs and construct a predictive model for KIRC prognosis. METHODS: Transcriptomic and clinical data of KIRC patients were analyzed to identify GRLncs associated with overall survival (OS). A prognostic model was constructed based on selected GRLncs, and its predictive performance was evaluated using Kaplan-Meier (KM) survival analysis, receiver operating characteristic (ROC) curves, and univariate and multivariate Cox regression analyses. Patients were stratified into high- and low-risk groups according to the median risk score, and internal validation was performed using training and testing cohorts to assess the stability of the model. Tumor microenvironment characteristics, immune checkpoint expression, immunotherapy response, and drug sensitivity were further analyzed. In addition, the expression of three signature lncRNAs was validated by real-time quantitative polymerase chain reaction (RT-qPCR) in 10 paired KIRC tumor and adjacent normal tissues. Functional roles of selected lncRNAs were investigated using antisense oligonucleotides (ASOs)-mediated knockdown in KIRC cell lines, followed by Cell Counting Kit 8 (CCK-8), 5-ethynyl-2'-deoxyuridine (EdU) incorporation, colony formation, and migration assays. RESULTS: Five GRLncs (AC093278.2, EPB41L4A-DT, DLGAP1-AS2, AC084876.1, and AC005261.3) were identified and used to construct a prognostic model. AC093278.2 and EPB41L4A-DT were protective factors, whereas DLGAP1-AS2, AC084876.1, and AC005261.3 were risk factors. KM analysis on GRLncs-based risk score stratification revealed patients in the high-risk group had significantly poorer OS than those in the low-risk group. ROC analysis and Cox regression demonstrated that the GRLnc-based risk score served as an independent predictor of KIRC prognosis and exhibited favorable predictive performance compared with conventional clinical variables. High- and low-risk groups also exhibited distinct immune microenvironment characteristics, immune checkpoint expression patterns, and predicted drug sensitivities. RT-qPCR detected significant downregulation of protective factor-EPB41L4A-DT in KIRC tissues, while risk factors-DLGAP1-AS2 and AC084876.1 showed expression trends consistent with their predicted risk attributes. Functional experiments further revealed that knockdown of DLGAP1-AS2 and AC084876.1 suppressed proliferation and migration of KIRC cells, whereas knockdown of EPB41L4A-DT promoted these processes, supporting the biological relevance of these three signature lncRNAs. CONCLUSIONS: This study establishes a novel prognostic model based on five GRLncs that showed promising performance in The Cancer Genome Atlas (TCGA)-based analyses of KIRC. The combined clinical expression analysis and functional validation of three constituent GRLncs (DLGAP1-AS2, EPB41L4A-DT, and AC084876.1) supports the biological plausibility of the model and suggest that GRLncs may serve as potential prognostic biomarkers and therapeutic targets for KIRC.

Kidney renal clear cell carcinoma (KIRC)↗
PubMed2002

NASDA aquatic animal experiment facilities for Space Shuttle and ISS.

National Space Development Agency of Japan (NASDA) has developed aquatic animal experiment facilities for NASA Space Shuttle use. Vestibular Function Experiment Unit (VFEU) was firstly designed and developed for physiological research using carp in Spacelab-J (SL-J, STS-47) mission. It was modified as Aquatic Animal Experiment Unit (AAEU) to accommodate small aquatic animals, such as medaka and newt, for second International Microgravity Laboratory (IML-2, STS-65) mission. Then, VFEU was improved to accommodate marine fish and to perform neurobiological experiment for Neurolab (STS-90) and STS-95 missions. We have also developed and used water purification system which was adapted to each facility. Based on these experiences of Space Shuttle missions, we are studying to develop advanced aquatic animal experiment facility for both Space Shuttle and International Space Station (ISS).

Animals↗
PubMed2003

Proanthocyanidin-accumulating cells in Arabidopsis testa: regulation of differentiation and role in seed development.

Anthocyanidin reductase encoded by the BANYULS (BAN) gene is the core enzyme in proanthocyanidin (PA) biosynthesis. Here, we analyzed the developmental mechanisms that regulate the spatiotemporal expression of BAN in the developing Arabidopsis seed coat. PA-accumulating cells were localized histochemically in the inner integument (seed body and micropyle) and pigment strand (chalaza). BAN promoter activity was detected specifically in these cells. Gain-of-function experiments showed that an 86-bp promoter fragment functioned as an enhancer specific for PA-accumulating cells. Mutations in regulatory genes of PA biosynthesis abolished BAN promoter activity (transparent testa2 [tt2], tt8, and transparent testa glabra1 [ttg1]), modified its spatial pattern (tt1 and tt16), or had no influence (ttg2), thus revealing complex regulatory interactions at several developmental levels. Genetic ablation of PA-accumulating cells targeted by the BAN promoter fused to BARNASE led to the formation of normal plants that produced viable yellow seeds. Importantly, these seeds had no obvious defects in endosperm and embryo development.

Arabidopsis↗
PubMed2002

Does performance on theory of mind tasks decline in old age?

In the first reported study of theory of mind (ToM; the ability to attribute mental states) in old age, Happe, Winner, and Brownell (1998) observed better performance on ToM tasks in older participants (mean age 73 years) than in young participants (mean age 21 years). We present two experiments exploring the generality of this finding. Experiment 1 compared young, young-old, and old-old age groups (mean ages 19, 67, and 81 years, respectively) on their understanding of ToM stories both with and without the need to remember the information, and control studies that did not require the ability to attribute mental states. For ToM stories with a memory load, the young group performed significantly better than both the young-old and old-old groups; without a memory load, the young and young-old groups performed significantly better than the old-old group. In Experiment 2, young and old-old age groups (mean ages 21 and 81 years, respectively) were compared on their understanding of ToM and control stories without the need to remember the information. Again, the young group performed significantly better than the old-old group on ToM stories. There were no significant age differences in performance on the control stories in either experiment. The age deficit on ToM stories remained significant after taking account of measures of vocabulary and processing speed (Experiments 1 and 2), and measures of executive functioning (Experiment 2).

Adolescent↗
PubMed1993

Psychosocial functioning and subjective experience in schizophrenia.

This study examines the relationship between psychosocial functioning and subjective experience in 193 individuals diagnosed with schizophrenia or schizoaffective disorder according to Research Diagnostic Criteria. Psychosocial functioning was measured as work functioning, social functioning, living situation, symptomatology, and intrapsychic aspects of the deficit syndrome. Subjective experience consisted of measures of self-esteem, satisfaction with life, and subjective distress. Multivariate analyses resulted in two major findings. The first finding is a model of psychosocial functioning that consists of two factors: disorder-related variables (symptomatology and intrapsychic deficits) and functional status variables (work, social, and living situation). The second major finding is a two-tiered model of the relationship between psychosocial functioning and subjective experience. The model suggests a primary and pervasive relationship between the disorder-related variables and subjective experience and a secondary and less pronounced relationship between functional status variables and subjective experience. The implications of these findings for treatment and rehabilitation and for the study of subjective experience in schizophrenia are discussed.

Activities of Daily Living↗
PubMed1994

Pharmacological profile of selective muscarinic receptor antagonists on guinea-pig ileal smooth muscle.

The present study examined the effects of a series of tricyclic muscarinic receptor antagonists on muscarinic receptors present in the guinea-pig ileum, both in vitro and in vivo. The selectivity profiles of these antagonists and that of atropine were determined by their affinity for cortical muscarinic M1, cardiac M2 and submandibular M3 receptors and for m4 receptors expressed in CHO cells. The compounds pirenzepine, UH-AH 37, AQ-RA 391 and AQ-RA 618 possessed high affinity (pKi 7.94-8.22) for muscarinic M1 receptors. Pirenzepine exhibited the most pronounced muscarinic M1 selectivity. AF-DX 384 and AQ-RA 741 possessed an approximately 10-fold higher affinity for the cardiac muscarinic M2 receptor than AF-DX 116. However, both compounds also exhibited high affinity for muscarinic m4 receptors. High affinity for muscarinic M3 and m4 receptors was observed for UH-AH 37, AQ-RA 391 and AQ-RA 681. The antagonists were then tested for their interaction with the muscarinic receptors which are responsible for the methacholine-induced contraction of longitudinal muscle in vitro, circular muscle in vivo and muscarinic receptors which mediate the distension-evoked ascending reflex contraction of circular muscle in vitro. Compounds showing high affinity for muscarinic M3 receptors (e.g. AQ-RA 618) were the most potent antagonists in the functional experiments. Comparison of the binding displacement data with the functional results indicates that the effects of methacholine on the longitudinal and circular muscle of the guinea-pig ileum were predominantly mediated by muscarinic M3-type receptors. In contrast, the correlation between muscarinic M2 receptor affinity and antagonism of muscarinic receptors in the ileum was very weak.

Animals↗
PubMed1996

Expression of a dominant-negative Wnt blocks induction of MyoD in Xenopus embryos.

During gastrulation of Xenopus embryos the prospective mesoderm is induced initially with domains of dorsal and ventral fate, then further patterned to generate somitic mesoderm by signals from the gastrula organizer. Although Xwnt-8 is expressed in future ventrolateral mesoderm and induces prospective epidermis to differentiate in vitro as ventral mesoderm, no loss-of-function studies have demonstrated a requirement for Wnt signaling for the normal expression of mesodermal genes in the gastrula. We report development of a dominant-negative Wnt (dnXwnt-8) that inhibits embryonic responses to Wnt signaling in a cell-nonautonomous fashion. By expressing dnXwnt-8 in Xenopus embryos, we uncover a requirement of Wnt signaling for localized expression in prospective mesoderm of XMyoDa and Xenopus-posterior (Xpo). Because ectopic expression of functional Xwnt-8 in the dorsal marginal zone of the gastrula induces ectopic XMyoDa and Xpo, both gain-of-function and loss-of-function experiments support a model in which endogenous Xwnt-8 functions to induce expression of genes involved in specification of ventral and somitic mesoderm.

Amino Acid Sequence↗
PubMed1996

Inhibitory effects of (+/-)-tetrahydropalmatine on thyrotropin-stimulating hormone concentration in hyperthyroid rats.

The effects of (+/-)-tetrahydropalmatine ((+/-)-THP) on the hypothalamus-pituitary-thyroid system in rats were investigated. Thyroid function experiments indicated that (+/-)-THP produces significant decreases in thyroid function in hyperthyroid rats after 14 days of treatment. These effects were the same as those of propylthiouracil. However, propylthiouracil also decreased thyroid function in normal rats. Measurements of thyrotropin-stimulating hormone (TSH) demonstrated that (+/-)-THP decreased TSH in hyperthyroid rats after 14 days of treatment; however, propylthiouracil increased TSH in hyperthyroid rats. (+/-)-THP had no influence on TSH, or thyroid and pituitary weight in normal and hyperthyroid rats. We conclude that (+/-)-THP has an antithyroid function and the mechanism of action may be related to the inhibition of TSH in the pituitary.

Animals↗
PubMed1991

Central auditory skills in blind and sighted subjects.

Three different central auditory skills were compared and evaluated in 56 blind and 40 sighted subjects. The study consisted of three experiments conducted in three subgroups. Experiment A was performed in order to evaluate the localization function; experiment B for the temporal auditory resolution ability of the blind adult, and experiment C to test the ability of the blind person to discriminate speech material in noise. In all three experiments the blind subjects obtained significantly better results than the sighted subjects. From these results it was concluded that there is supporting evidence of a certain superiority of the blind individual with regard to central auditory function.

Adolescent↗
PubMed1996

Interaction of elicitor-induced DNA-binding proteins with elicitor response elements in the promoters of parsley PR1 genes.

PR1 is a pathogenesis-related protein encoded in the parsley genome by a family of three genes (PR1-1, PR1-2 and PR1-3). Loss- and gain-of-function experiments in a transient expression system demonstrated the presence of two fungal elicitor responsive elements in each of the PR1-1 and PR1-2 promoters. These elements, W1, W2 and W3, contain the sequence (T)TGAC(C) and mutations that disrupt this sequence abolish function. Gel shift experiments demonstrated that W1, W2 and W3 are bound specifically by similar nuclear proteins. Three cDNA clones encoding sequence-specific DNA-binding proteins were isolated by South-Western screening and these proteins, designated WRKY1, 2 and 3, also bind specifically to W1, W2 and W3. WRKY1, 2 and 3 are members of the family of sequence-specific DNA-binding proteins, which we call the WRKY family. Treatment of parsley cells with the specific oligopeptide elicitor Pep25 induced a transient and extremely rapid increase in mRNA levels of WRKY1 and 3. WRKY2 mRNA levels in contrast showed a concomitant transient decrease. These rapid changes in WRKY mRNA levels in response to a defined signal molecule suggest that WRKY1, 2 and 3 play a key role in a signal transduction pathway that leads from elicitor perception to PR1 gene activation.

Amino Acid Sequence↗