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At least 613 records · Page 34Linked to original sources
PubMed2005

Comparison of experimental nerve injury caused by ultrasonically activated scalpel and electrosurgery.

BACKGROUND: Iatrogenic nerve injury caused by heat from dissection instruments is a significant problem in many areas of surgery. The aim of the present study was to compare the risk of nerve injury for three different dissection instruments: monopolar and bipolar electrosurgery (ES) and an ultrasonically activated (US) instrument. METHODS: The biceps femoris muscle was cut in a standard manner just adjacent to the sciatic nerve using monopolar ES, bipolar ES or US shears. A total of 73 functional experiments were conducted in which the nerve was isolated, divided proximally, and stimulated supramaximally in 37 anaesthetized rats. The electromyographic (EMG) potential was recorded distally before and after each experiment. Nerve dysfunction was defined as more than 10 per cent loss of the evoked EMG potential. Fifty-nine nerves were examined histologically after dissection with the different instruments. The extent of heat damage was determined in four nerves that were divided with ES bipolar scissors and five that were divided with US shears. RESULTS: Reduction in the EMG potential was significantly more frequent in the monopolar ES group than in the US group. Morphological examination also showed significantly less nerve damage in the US group. CONCLUSION: US instruments may be safer than ES for dissection close to nerves.

Animals↗
PubMed2005

Alpha1- and alpha2-adrenoreceptor antagonist profiles of 1- and 2-[omega-(4-arylpiperazin-1-yl)alkyl]-1,2,3-benzotriazoles.

A series of pharmacologically interesting 1- and 2-[omega-(4-arylpiperazin-1-yl)alkyl]-1,2,3-benzotriazoles, compounds 1-27, were synthesized (Scheme) and subjected to various biological studies to identify structure-activity relationships (SAR). The new compounds were found to exhibit good non-selective binding affinity towards the alpha1-adrenoreceptor (Table 1). In several cases, high functional antagonism was observed towards the alpha1A-, alpha1B-, and alpha1D-adrenoreceptor subtypes (Table 2). The selectivity for these three subtypes was comparable with or superior to that displayed by the standard drug prazosin. The most-common selectivity rank order was alpha1D > alpha1B > alpha1A, followed by alpha1B > alpha1D > alpha1A. In functional experiments, antagonism towards the alpha2-adrenoreceptor was generally low; however, a few compounds were endowed with significant antagonist properties (pA2 values of up to 7.87).

Adrenergic alpha-Agonists↗
PubMed2004

Nodal/activin signaling establishes oral-aboral polarity in the early sea urchin embryo.

Components of the Wnt signaling pathway are involved in patterning the sea urchin primary or animal-vegetal (AV) axis, but the molecular cues that pattern the secondary embryonic axis, the aboral/oral (AO) axis, are not known. In an analysis of signaling molecules that influence patterning along the sea urchin embryonic axes, we found that members of the activin subfamily of transforming growth factor-beta (TGF-beta) signaling molecules influence the establishment of AO polarities in the early embryo. Injection of activin mRNAs into fertilized eggs or treatment with exogenously applied recombinant activin altered the allocation of ectodermal fates and ventralized the embryo. The phenotypes observed resemble the ventralized phenotype previously reported for NiCl2, a known disrupter of AO patterning. Sensitivity to exogenous activin occurs between fertilization and the late blastula stage, which is also the time of highest NiCl2 sensitivity. These results argue that specification of fates along the embryonic AO axis involves TGF-beta signaling. To further examine TGF-beta signaling in these embryos, we cloned an endogenous TGF-beta from sea urchin embryos that is a member of the activin subfamily, SpNodal, and show through gain of function analysis that it recapitulates results obtained with exogenous activins and NiCl2. The expression pattern of SpNodal is consistent with a role for nodal signaling in the establishment of fates along the AO axis. Loss of function experiments using SpNodal antisense morpholinos also support a role for SpNodal in the establishment of the AO axis.

Amino Acid Sequence↗
PubMed2005

Retinoic acid down-regulates Tbx1 expression in vivo and in vitro.

Both Tbx1 and retinoic acid (RA) are key players in embryonic pharyngeal development; loss of Tbx1 produces DiGeorge syndrome-like phenotypes in mouse models as does disruption of retinoic acid homeostasis. We have demonstrated that perturbation of retinoic acid levels in the avian embryo produces altered Tbx1 expression. In vitamin A-deficient quails, which lack endogenous retinoic acid, Tbx1 expression patterns were disrupted early in development and expression was subsequently lost in all tissues. "Gain-of-function" experiments where RA-soaked beads were grafted into the pharyngeal region produced localized down-regulation of Tbx1 expression. In these embryos, analysis of Shh and Foxa2, upstream control factors for Tbx1, suggested that the effect of RA was independent of this regulatory pathway. Real-time polymerase chain reaction analysis of retinoic acid-treated P19 cells showed a dose-dependent repression of Tbx1 by retinoic acid. Repression of Tbx1 transcript levels was first evident after 8-12 hr in culture in the presence of retinoic acid, and to achieve the highest levels of repression, de novo protein synthesis was required.

Animals↗
PubMed2005

Sef is synexpressed with FGFs during chick embryogenesis and its expression is differentially regulated by FGFs in the developing limb.

The signaling pathways leading to growth and patterning of various organs are tightly controlled during the development of any organism. These control mechanisms usually involve the utilization of feedback- and pathway-specific antagonists where the pathway induces the expression of its own antagonist. Sef is a feedback antagonist of fibroblast growth factor (FGF) signaling, which has been identified recently in zebrafish and mammals. Here, we report the isolation of chicken Sef (cSef) and demonstrate the conserved nature of the regulatory relationship with FGF signaling. In chick embryos, Sef is expressed in a pattern that coincides with many known sites of FGF signaling. In the developing limb, cSef is expressed in the mesoderm underlying the apical ectodermal ridge (AER) in the region known as the progress zone. cSef message first appeared after limb budding and AER formation. Expression was intense at stages of rapid limb outgrowth, and gradually decreased to almost undetectable levels when differentiation was clearly apparent. Gain- and loss-of-function experiments showed that FGFs differentially regulate the expression of cSef in various tissues. Thus, removal of the AER down-regulated cSef expression, and FGF2 but not FGF4 or FGF8 beads substituted for the AER in maintaining cSef expression. At sites where cSef is not normally expressed, FGF4 and FGF2, but not FGF8 beads, induced cSef expression. Our results demonstrate the complexity of cSef regulation by FGFs and point to FGF2 as a prime candidate in regulating cSef expression during normal limb development. The spatiotemporal pattern of cSef expression during limb development suggests a role for cSef in regulating limb outgrowth but not limb initiation.

Amino Acid Sequence↗
PubMed2006

Role of X-Delta-2 in the early neural development of Xenopus laevis.

The Drosophila Delta gene and its vertebrate homologues are ligands for the Notch receptor and are involved in a variety of developmental processes, including neurogenesis, boundary formation, and axon guidance. This study deals with the ectodermal expression and function of X-Delta-2 during early Xenopus laevis development. X-Delta-2 is expressed, from early neurula stages on, throughout the central nervous system (CNS; forebrain, eyes, midbrain, hindbrain, and spinal cord) and in the majority of the cranial placodes. Loss of function experiments using a morpholino knockdown approach revealed that X-Delta-2 is necessary for hindbrain segmentation and the correct specification of the anterior CNS. X-Delta-2 also seems to be important in the determination of the size of the eyes. Furthermore, our results suggest that X-Delta-2 is involved in the migration of the cranial placodes cells, as well the migration of the cranial neural crest cells.

Animals↗
PubMed1981

Induction and regulation of silent idiotype clones.

In order to study whether allotype linkage of idiotype expression is related to the total absence of structural gene(s) or to regulatory mechanisms acting on its phenotype expression, the M460 clone expression was followed in b cells from various inbred and recombinant strains of mice cultured at low density in the presence of lipopolysaccharide. Under these conditions, all cultures were found to contain anti-trinitrophenyl (TNP) antibody plaque-forming cells, some of which inhibitable by anti-M460 immunoglobulins. In the course of these studies, it also became apparent that, even in the absence of T cells, B lymphocytes are able to exert regulatory functions. Experiments carried out using anti-M460 hybrid cells F6(%!), and affinity-purified anti-(anti-M460) antibodies revealed that clonotype regulation by B cells is mediated by idiotype-auto-antiidiotype interactions.

Animals↗
PubMed1996

Phenotype and function of human B cells expressing CD70 (CD27 ligand).

CD70, the cellular ligand of the tumor necrosis factor receptor family member CD27, can be found on a limited number of germinal center (GC) B cells in some tonsils, on scattered lymphocytes residing in secondary lymphoid organs, and on a fraction of the circulating B cell population. Due to the restricted expression of CD70 in vivo, we analyzed signals that determine CD70 expression levels and characterized the phenotype and function of CD70+ B cells. Expression of CD70 on B cells activated in vitro was found to be dependent on the continuous presence of a B cell antigen receptor cross-linking agent, and induced or potentiated by CD40 ligation but was down-modulated by the Th2 cytokines interleukin (IL)-4 and IL-13. Both in peripheral blood and tonsil cell suspensions, CD70+ B cell subpopulations were found to be enriched for CD27- and IgG-expressing cells, but contained less IgD+ B cells. Additional analysis of markers which define specific differentiation stages (Bm1-5) of mature B cells within human tonsils did not place CD70-expressing B cells in one of these subsets. Functional experiments revealed that whereas both CD70- and CD70+ B cells can secrete immunoglobulin after activation with a combination of Staphylococcus aureus Cowan strain I and IL-2, only CD70+ B cells can produce large quantities of antibodies when stimulated in a T cell-dependent fashion. Our combined data imply that CD70 is a marker for mature B cells which have recently been primed by antigen in vivo.

Antibody Formation↗
PubMed2004

Mechanism of modulation of T cell responses by N-palmitoylated peptides.

Small structural changes in the antigenic peptides recognized by TCR can alter the biological properties of those peptides and convert them into weak agonists, partial agonists, or antagonists of these receptors. These altered peptide ligands (APL) are usually generated by conservative amino acid substitutions at TCR contact residues. Here, we show that APL with therapeutic properties can also be generated by attachment of palmitic acid at the N terminus of the peptide without the need to modify the peptide's primary sequence. Using N-palmitoylated pigeon cytochrome-c peptide 81-104 (PALPCC(81-104)), we were able to induce T cell hyporesponsiveness to the wild-type peptide in vitro. More importantly, administration of the PALPCC(81-104 )to mice reduced the responsiveness to the native peptide when tested ex vivo. Biochemical and functional experiments indicated that the action of N-palmitoylated peptides was due to the conversion of the native peptide into a weak agonist that could then induce T cell anergy. Our results demonstrate that N-palmitoylation of antigenic peptides is a feasible strategy to generate APL, as it avoids the need to screen multiple amino acid variants of each specific antigen to identify those with therapeutic properties.

Animals↗
PubMed2001

Pitx1 and Pitx2c are required for ectopic cement gland formation in Xenopus laevis.

The mucus secreting cement gland is the anterior-most ectodermal organ of the Xenopus embryo. The homeobox genes Pltx1 and Pitx2c are expressed in the cement gland primordium. Misexpression of both genes induced ectopic cement gland tissue in whole embryos and transcription of the marker genes Xag1 and Xag2 in animal cap explant cultures. Antisense morpholino oligonucleotides against Pitx1 and Pitx2c inhibited ectopic cement gland formation induced by otx2. Gene knock downs generated by morpholino oligonucleotides were specific and could be rescued by coinjection of Pitx mRNAs. These data demonstrate for the first time the requirement of specific genes for cement gland formation by loss-of-function experiments. genesis 30:144--148, 2001.

Animals↗
PubMed1993

p60v-src causes tyrosine phosphorylation and inactivation of the N-cadherin-catenin cell adhesion system.

Transformation of chick embryonic fibroblasts with Rous sarcoma virus strongly suppresses N-cadherin-mediated cell-cell adhesion, without inhibiting its expression. This suppression is correlated with tyrosine phosphorylation of N-cadherin and catenins, the cadherin-associated proteins, which are known to regulate cadherin function. Experiments with non-myristylation and temperature-sensitive mutants of RSV and with herbimycin A, a potent inhibitor of tyrosine kinases, suggest that both the suppression of cell adhesion and tyrosine phosphorylation of catenins are highly transformation-specific.

Animals↗
PubMed1997

Mechanism and echo time dependence of the fast response in fMR.

The fast response (FR) is an early reduction in the amplitude of the fMR signal occurring shortly after the onset of stimulation. Owing to its potential advantages in terms of temporal and spatial resolution, it may be of considerable significance in functional experiments. A model for the mechanism of the FR was developed which accounts for the fMRS finding that the amplitude of the dip decreases with increasing echo time. Two computer simulations that confirmed the predictions of the model and showed that it is possible to select optimal echo times for the detection of the FR were performed.

Computer Simulation↗
PubMedDate not supplied

Prophylactic oophorectomy versus screening: psychosocial outcomes in women at increased risk of ovarian cancer.

This study investigated the psychosocial outcome of prophylactic oophorectomy versus regular screening in women at increased risk of ovarian cancer. Women who had undergone prophylactic oophorectomy (n=29) were compared with women who remained on the ovarian screening programme (n=28). Assessments were made retrospectively by postal questionnaire. The surgical group showed significantly poorer functioning on two sub-scales of the Short Form (SF)-36 Health Status Questionnaire (role-emotional (p=0.04) and social functioning (p=0.01)), and there was a trend (p=0.06) for them to report more menopausal symptoms. General Health Questionnaire (GHQ) scores were significantly higher (p=0.03) in the surgical group. There were no significant differences between the groups for cancer worry or sexual functioning. Experience of the operation was better (p=0.01) and incidence of self-reported post-operative problems was lower (p=0.02) for women who had undergone the 'keyhole' rather than an 'open' procedure. Being pre-menopausal at the time of surgery predicted higher GHQ (p=0.04) and longer subjective recovery time (p=0.04). Women who have undergone prophylactic oophorectomy may have more physical and emotional symptoms than women who remain on an ovarian cancer screening programme, and may report equivalent levels of cancer worry. Those who are pre-menopausal at the time of the operation may be particularly vulnerable to psychological distress and take longer to recover post-operatively. A larger prospective study is needed to evaluate the casual versus causal role of oophorectomy in these findings, and the extent to which it allays patients' fear of cancer.

Body Image↗
PubMed1995

Effect of chronic ethanol consumption on the energy state and structural stability of periportal and perivenous hepatocytes.

This study was implemented to evaluate whether perivenous cells experience functional alterations due to a deficit in oxygen tension resulting from ethanol oxidation in the periportal regions of the lobule. Periportal and perivenous hepatocytes were prepared from ethanol-fed and control animals (Lieber-DeCarli diet, 31 days). These cells were either incubated at various oxygen tensions by varying the composition of the gases utilized to equilibrate the incubation buffers (0, 5, 25, and 95% oxygen) or they were unincubated. They were analyzed for adenine nucleotide and inorganic phosphate concentrations and from these data phosphorylation potentials and energy charge values were determined. Under highly aerobic conditions no differences were observed in the energy states of the cells irrespective of their source (control vs ethanol-fed; periportal vs perivenous). The ATP concentrations, phosphorylation potentials, and energy charge values indicated that the energy states of cells from both ethanol-fed and control rats were maintained at relatively high levels in incubations with 5 and 25% oxygen. However, unincubated cells and those incubated at 0% oxygen demonstrated lowered energy states and the decreases were most striking in hepatocytes from ethanol-fed animals. Measurements of LDH loss and trypan blue exclusion indicate that cell leakage and viability loss occur when cells are incubated under anoxic and hypoxic conditions. At low oxygen tensions perivenous cells from ethanol-fed rats demonstrated much greater loss of structural stability than did the other cell preparations. These observations indicate that decreased energy state is one factor which contributes to cell damage in hepatocytes from ethanol-fed animals. Moreover, perivenous cells from ethanol-fed animals seem to be particularly vulnerable to damage under hypoxic conditions.

Adenosine Diphosphate↗
PubMed1995

Anti-syntaxin antibodies inhibit calcium-dependent catecholamine secretion from permeabilized chromaffin cells.

Adrenomedullary chromaffin cells release catecholamines in response to the intracellular calcium rise upon stimulation by different secretagogues. The presence of syntaxin 1, a protein presumably involved in docking of synaptic vesicles to presynaptic membranes, has been investigated in chromaffin cells. The study using two different monoclonal antibodies shows that syntaxin 1 is present in the chromaffin cell membrane fraction. Functional experiments demonstrate that anti-syntaxin antibodies inhibit calcium-dependent secretion in permeabilized cells. These results suggest that syntaxin 1 is an important component of the secretory machinery in chromaffin cells.

Adrenal Medulla↗
PubMed1997

A member of the Met/HGF-receptor family is expressed in a BMP-4-like pattern in the ectoderm of Xenopus gastrulae.

The importance and involvement of growth factors and their corresponding receptors in embryonic induction has been more and more recognized during the past decade, in particular by loss-of-function experiments using dominant negative receptors. Here, we report the isolation of XHR, a Xenopus receptor-type tyrosine kinase, with homology to members of the Met/hepatocyte growth factor (HGF)-receptor family. Sequence comparison of XHR with other members of the Met/HGF-receptor family as well as in situ expression analyses suggest that XHR represents a novel member of this family of receptor-type tyrosine kinases. As could be shown by whole-mount in situ analysis, XHR transcripts are first expressed in the entire ectoderm at the onset of gastrulation. As gastrulation proceeds, XHR-transcription is turned off in cells induced by dorsal mesoderm to form neural tissue and thus, becomes predominantly confined to prospective epidermis. The strikingly similar expression patterns of XHR and Bone Morphogenetic Protein-4 (BMP-4), an inducer of epidermis and inhibitor of neural development, suggest an involvement of XHR signalling in the early cell-fate decision of ectodermal cells to form either neural derivatives or epidermis.

Animals↗
PubMed2000

Regulated expression of endothelial cell-derived lipase.

A lipoprotein lipase-like gene was recently cloned from endothelial cells. In vitro functional experiments have suggested that this endothelial-derived lipase (EDL) has phospholipase activity, and preliminary in vivo studies have suggested a role in the regulation of high-density lipoprotein metabolism. To investigate local control of lipase activity and lipid metabolism in the blood vessel wall, we have examined the regulation of EDL expression in cultured human umbilical vein and coronary artery endothelial cells. EDL mRNA levels were upregulated in both cell types by inflammatory cytokines implicated in vascular disease etiology, including TNF-alpha and IL-1beta. In addition, both fluid shear stress and cyclic stretch were found to increase the EDL mRNA levels in these cultured cells. This highly regulated expression of EDL in vascular endothelial cells suggests that this recently identified lipase is intricately involved in modulating vessel wall lipid metabolism and may play a role in vascular diseases such as atherosclerosis.

Arteriosclerosis↗
PubMed2001

SNARE proteins are critical for regulated exocytosis of ECP from human eosinophils.

The SNARE hypothesis, describing a protein assembly-disassembly pathway, was recently proposed for the sequential steps of synaptic vesicle docking, activation and fusion. To determine if SNARE proteins are involved in regulated exocytosis in eosinophils, the presence and functional role of SNAREs was examined in human blood eosinophils. Immunoblotting, subcellular fractionation, and immunocytochemistry documented that vesicle-associated membrane protein-2 (VAMP-2), a vesicle-SNARE, was expressed in human eosinophils. Syntaxin 4 and SNAP-25 were also detected. Sequencing of cloned RT-PCR products amplified from a domain conserved among VAMP isoforms revealed identity only to VAMP-2 but not to VAMP-1 or cellubrevin. Functional experiments revealed that tetanus toxin pretreatment, which cleaved VAMP-2 in eosinophils, significantly inhibited both IgE receptor- and phorbol ester-mediated exocytosis of eosinophil cationic protein (ECP) from streptolysin-O-permeabilized eosinophils. Thus, these results strongly suggest a critical role of SNAREs in regulated exocytosis in eosinophils.

Amino Acid Sequence↗