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Biomedical subjects

L Carter

Publications and source records attributed to L Carter.

At least 37 records · Page 2Linked to original sources
PubMed1996

Understanding balloon mitral valvuloplasty: the Inoue technique.

Severe mitral stenosis has traditionally been treated with surgical splitting or replacement of the mitral valve. A less invasive option is available, in which the value is stretched by an inflated balloon inserted via the femoral vein (percutaneous balloon mitral valvuloplasty). The most widely used method of mitral valvuloplasty, the inoue technique, is described in detail. Pertinent aspects of patient management and nursing care are also described.

Catheterization↗
PubMed1995

Lysine residues at positions 234 and 236 in yeast porin are involved in its assembly into the mitochondrial outer membrane.

Various point mutations of lysyl residues in yeast mitochondrial porin (283 residues) were tested for their ability to assemble in vitro into the outer membranes of intact yeast mitochondria. Assembly was evaluated by protection from proteinases. The extent of assembly of two of the mutants, K234E and K236E porins, was much less than for wild-type in either post-translational or co-translational assembly assays. Lysine to glutamate mutants at other positions and K234R porin assembled as well as wild-type, but K234Q porin was poorly inserted. When both Lys-234 and Lys-236 were mutated, K234R/K236R porin was inserted better than K234Q/K236Q porin, which was inserted better than K234E/K236E; however, none of these mutants assembled as well as wild-type porin. It was concluded that optimal assembly of yeast porin depended on the presence of positively charged residues at both positions 234 and 236 and a lysine at one of these positions. After undergoing the assembly reaction, mutants that were vulnerable to proteinase K (i.e. K234E, K234Q, and K236E porins) seemed to be incompletely digested and were, to varying degrees, resistant to extraction by Na2CO3 (pH 11.5). These experiments suggested that these mutants were incompletely inserted into the outer membrane. Both Lys-234 and Lys-236 are included in an internal pentapeptide, VKAKV, that is conserved in porins from protists, plants, and animals, and it is possible that, at least, the lysines in this tract are one of the signals for the membrane assembly of these proteins.

Amino Acid Sequence↗
PubMed1995

A phylogenetic analysis of monocotyledons based on the chloroplast gene rps4, using parsimony and a new numerical phenetics method.

We have sequenced the chloroplast gene rps4 of 72 species; the sequence of 6 more species was found in the databanks. The 78 species were chosen so as to be representative of two taxonomic levels: the family, with 39 Poaceae, and the class, with 28 additional monocot species. Eleven dicots and other land plants were used as outgroups to the monocots. The 78 sequences were aligned by eye. Phylogenetic reconstruction was performed using the Wagner parsimony method: our first results were in contradiction with classical systematics, due to a local minimum. We then used the results obtained with the new distance method Anataxis to redraw a new tree and carry on further the parsimony calculations starting from this Anataxis tree. Up to 20,000 most parsimonious trees were thus obtained. The robustness of our results was checked by the bootstrap test and decay analyses. The Anataxis and the strict consensus tree fitted the general features of land plant evolution. Some of our results concerning relationships within the monocots corroborated those obtained with the chloroplast gene rbcL. Both genes raise questions concerning the monocot superorders as defined in a previous classification. This study proves the rps4 gene to be a useful phylogenetic tool within the Poaceae family and the Monocotyledonae order.

Base Sequence↗
PubMed1995

Alterations in rat peripheral blood neutrophil function as a consequence of colitis.

Altered peripheral neutrophil function is a feature of IBD that may contribute to the chronicity and extragastrointestinal manifestations of this disease, but clinical evidence for such alterations is confounded by variations in patient characteristics, disease onset, and use of therapeutics that can influence neutrophil function. The use of a rat model of colitis has permitted us to characterize, in a controlled manner, the causal relationship between colitis and altered peripheral neutrophil function. At various times after induction of colitis with trinitrobenzene sulfonic acid (TNBS), peripheral neutrophils were isolated and assays of phagocytosis, chemotaxis, leukotriene B4 (LTB4) synthesis, and superoxide production were performed using a variety of stimuli. Circulating neutrophil numbers increased about fourfold within 12 hr of TNBS administration and returned to normal levels over the following two weeks. LTB4 synthesis in response to calcium ionophore decreased at 12 hr after induction of colitis, then returned to control levels. The chemotactic responses of peripheral neutrophils to LTB4 and FMLP in vitro and to LTB4 and IL-8 in vivo were profoundly suppressed through the two-week study period. Phagocytosis of nitroblue tetrazolium was significantly enhanced (ca. threefold) at 12 hr after induction of colitis and remained elevated throughout the study period. Superoxide production was also significantly elevated in the early phase of colitis (by ca. fourfold), but was not different from control levels at seven and 14 days. These results demonstrate that colonic inflammation profoundly influences peripheral blood neutrophil function, although the direction and magnitude of the alteration varied among the various functions assessed. The prolonged depression of chemotactic activity may represent a physiological reaction to limit the inflammatory response.

Animals↗
PubMed1995

Hapten-induced chronic colitis in the rat: alternatives to trinitrobenzene sulfonic acid.

Hapten-induced colitis is a widely used model for the study of the intestinal inflammation and for the testing of novel therapies. However, the hapten utilized in this model, trinitrobenzene sulfonic acid, is difficult to obtain in some countries. We therefore compared this hapten to two structurally related haptens to determine if they could be substituted for trinitrobenzene sulfonic acid in terms of inducing chronic colitis in the rat. Rats received one of the three haptens intracolonically, and the severity of colonic inflammation was assessed 3 and 14 days later. Dinitrobenzene sulfonic acid produced colonic inflammation and ulceration that was indistinguishable from that induced by trinitrobenzene sulfonic acid at both time points. On the other hand, dinitrochlorobenzene produced acute colitis (3 days postadministration), but by Day 14 this inflammation had subsided. Dinitrobenzene sulfonic acid and trinitrobenzene sulfonic acid produced comparable levels of granulocyte infiltration into the colon (as measured by tissue myeloperoxidase activity and histology) at both time points. These studies suggest that for studies of up to at least 2 weeks in duration, dinitrobenzene sulfonic acid and trinitrobenzene sulfonic acid produce comparable levels of colonic inflammation. Dinitrobenzene sulfonic acid therefore offers a useful and less expensive alternative to trinitrobenzene sulfonic acid.

Animals↗
PubMed1995

Defective interleukin-1-induced ACTH release in cholestatic rats: impaired hypothalamic PGE2 release.

A complete regulatory loop exists between the immune and neuroendocrine systems. Proinflammatory mediators such as endotoxin (lipopolysaccharide) and interleukin-1 (IL-1) are capable of activating the hypothalamic-pituitary-adrenal (HPA) axis at the hypothalamic level, presumably by inducing the synthesis of prostaglandins. We have recently identified abnormalities in the stress-induced activation of the HPA axis in cholestatic rats. Therefore, in rats with cholestasis due to bile duct resection and sham-resected controls, we studied alterations in proinflammatory mediator-induced activation of the HPA axis and documented the role of alterations in hypothalamic prostaglandin synthesis in these abnormalities. Systemic administration of endotoxin and IL-1 resulted in a significant attenuation of adrenocorticotropic hormone (ACTH) release into plasma in bile duct-resected compared with sham-resected animals. This suppression of endotoxin- or IL-1-induced ACTH release in bile duct-resected rats was associated with a complete absence of IL-1-induced hypothalamic release of prostaglandin E2 (PGE2) in vitro in these animals. In contrast, sham-resected rats exhibited a 70% increase in hypothalamic PGE2 secretion in vitro in response to IL-1. However, bile duct-resected rats exhibited HPA axis activation similar to that of sham-resected animals in response to intracerebroventricularly infused PGE2. Therefore, cholestasis in the rat is associated with an attenuation of central activation of the HPA axis by proinflammatory mediators that appears to be mediated, at least in part, by defective IL-1-induced hypothalamic prostaglandin production.

Adrenocorticotropic Hormone↗
PubMed1994

ML 3000 reduces gastric prostaglandin synthesis without causing mucosal injury.

In this study we characterized the effects of a novel anti-inflammatory drug, ML 3000 ([2,2-dimethyl-6-(4-chlorophenyl)-7-phenyl-2,3-dihydro-1H-pyrrolizine- 5-yl]-acetic acid), on the gastric mucosa and attempted to determine the mechanism responsible for its apparent stomach-sparing properties. Acute gastric damaging properties of ML 3000 versus indomethacin were examined in the rat, while chronic-type gastric ulcer was examined in the rabbit. At doses of up to 100 mg/kg p.o., ML 3000 did not produce significant acute gastric injury, while indomethacin at 5-20 mg/kg p.o. caused mucosal necrosis and bleeding. ML 3000 significantly inhibited gastric and blood prostaglandin E2 synthesis, with the higher doses tested (30 and 100 mg/kg) producing comparable effects to that seen with indomethacin at 10 or 20 mg/kg. Gastric and blood leukotriene B4 synthesis were not significantly affected by either drug. While indomethacin caused a significant increase in leukocyte adherence to mesenteric venules, ML 3000 did not. When administered repeatedly to rabbits, diclofenac caused penetrating ulcer formation in the gastric antrum of the majority of the animals. ML 3000 did not produce any detectable damage at doses of 10 or 30 mg/kg, but an ulcer was observed in one of five rabbits given the 100 mg/kg dose. Prior administration of ML 3000 (10-100 mg/kg) did not significantly affect the extent of gastric damage induced by subsequent oral administration of ethanol. These studies demonstrate that ML 3000 spares the gastric mucosa despite significantly suppressing gastric prostaglandin synthesis.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetates↗
PubMed1994

Generation of polarized antigen-specific CD8 effector populations: reciprocal action of interleukin (IL)-4 and IL-12 in promoting type 2 versus type 1 cytokine profiles.

We have generated primary effector populations from naive CD8 T cells in response to antigen and determined their patterns of cytokine secretion upon restimulation. The effect of exogenous factors on the effector generation was examined and compared with responses of antigen-specific CD4 effectors generated under comparable conditions. CD8 cells from bm1 mice were stimulated with C57BL/6 (B6) antigen presenting cells (APCs) bearing allogeneic class I and CD8 cells from female severe combined immunodeficiency (SCID) B6 mice, transgenic for a T cell receptor alpha/beta (TCR-alpha/beta) that recognizes H-Y on Db, were stimulated with APCs from male mice. In parallel, CD4 cells from bm12 mice were stimulated with alloantigen and CD4 cells from V beta 3/V alpha 11 TCR transgenics were stimulated with a peptide of pigeon cytochrome c on IEk. T cells from both transgenic mice were of naive phenotype whereas normal mice contained 10-20% memory cells. Effector CD8 populations generated were L-selectin low, CD45RB high, and CD44 high. Naive CD8 cells from SCID anti-H-Y mice made little or no cytokine immediately upon stimulation in contrast to naive CD4 which produced large amounts of interleukin 2 (IL-2). Both populations, however, generated primary effectors over 4-5 d that made substantial quantities of many cytokines upon restimulation. Both CD8 and CD4 effectors produced similar patterns of cytokines with alloantigen or specific antigen. Cytokines present during naive CD8 stimulation influenced the cytokine secretion profile of the effectors, as previously shown for CD4 cells, although secretion by CD8 effectors was generally lower than that of CD4 effectors. CD8 cells cultured with IL-2 alone made predominantly interferon gamma (IFN-gamma) and no IL-4 or IL-5, similar to CD4 cells. Priming with IFN-gamma increased IFN-gamma secretion from CD4 effectors, but had little if any effect on CD8 cells. In contrast, priming with IL-12 generated CD8 effectors, as well as CD4 effectors, producing elevated quantities of IFN-gamma, with similar levels from both the CD4 and CD8 populations. The presence of IL-4 during effector cell generation promoted synthesis of IL-4 and IL-5 from both CD8 and CD4 cells while downregulating IFN-gamma secretion. CD8 cells made only small amounts of IL-4, more than 100-fold less than CD4 cells, whereas significant levels of IL-5 were induced, only 3-10-fold lower than from CD4.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1994

Interleukin 1 beta and corticotropin-releasing factor inhibit pain by releasing opioids from immune cells in inflamed tissue.

Local analgesic effects of exogenous opioid agonists are particularly prominent in painful inflammatory conditions and are mediated by opioid receptors on peripheral sensory nerves. The endogenous ligands of these receptors, opioid peptides, have been demonstrated in resident immune cells within inflamed tissue of animals and humans. Here we examine in vivo and in vitro whether interleukin 1 beta (IL-1) or corticotropin-releasing factor (CRF) is capable of releasing these endogenous opioids and inhibiting pain. When injected into inflamed rat paws (but not intravenously), IL-1 and CRF produce antinociception, which is reversible by IL-1 receptor antagonist and alpha-helical CRF, respectively, and by the immunosuppressant cyclosporine A. In vivo administration of antibodies against opioid peptides indicates that the effects of IL-1 and CRF are mediated by beta-endorphin and, in addition, by dynorphin A and [Met]enkephalin, respectively. Correspondingly, IL-1 effects are inhibited by mu-, delta-, and kappa-opioid antagonists, whereas CRF effects are attenuated by all except a kappa-antagonist. Finally, IL-1 and CRF produce acute release of immunoreactive beta-endorphin in cell suspensions freshly prepared from inflamed lymph nodes. This effect is reversible by IL-1 receptor antagonist and alpha-helical CRF, respectively. These findings suggest that IL-1 and CRF activate their receptors on immune cells to release opioids that subsequently occupy multiple opioid receptors on sensory nerves and result in antinociception. beta-Endorphin, mu- and delta-opioid receptors play a major role, but IL-1 and CRF appear to differentially release additional opioid peptides.

Analysis of Variance↗
PubMed1994

Temporal analysis of the anti-inflammatory effects of decentralization of the rat superior cervical ganglia.

Bilateral decentralization of the superior cervical ganglia (SCG) reduced the pulmonary inflammation that develops 4-8 h after induction of anaphylaxis in Nippostrongylus brasiliensis-sensitized rats. Histamine levels in peritoneal lavage fluid and rat mast cell protease type II in serum were increased to comparable levels in sham-operated and decentralized rats. In vitro stimulation of alveolar macrophages (ALM) with lipopolysaccharide (LPS) provoked tumor necrosis factor-alpha (TNF-alpha) release that was two to three times greater with unchallenged decentralized rats than with sham-operated rats. However, after allergen challenge LPS-stimulated TNF-alpha release from ALM of sham-operated rats increased threefold and lasted at least 24 h, whereas with decentralized rats release of this cytokine actually decreased at 4 and 8 h. The increase in the phagocytosis and respiratory burst of circulating neutrophils seen at 4 and 8 h after allergen challenge in sham-operated rats was reduced significantly by decentralization. These results suggest that the attenuation of anaphylaxis-induced pulmonary inflammation that occurs with decentralization of the SCG is primarily associated with downregulation of neutrophil and macrophage functions.

Anaphylaxis↗
PubMed1993

Decentralization of the superior cervical ganglia inhibits mast cell mediated TNF alpha-dependent cytotoxicity. 1. Potential role of salivary glands.

Decentralization or ganglionectomy of the superior cervical ganglia (SCG) reduces pulmonary inflammation, as well as chemotaxis and activation of circulating neutrophils. However, the protective effect of decentralization was abolished when combined with removal of the submandibular glands (sialadenectomy) in the same animals. Thus, it has been postulated that the submandibular glands (SMG) release an anti-inflammatory factor(s) that is controlled by cervical sympathetic nerves. Decentralization of SCG did not modify in vitro histamine release or in vivo levels of rat mast cell protease II, but it reduced mast cell (MC)-mediated tumor necrosis factor alpha (TNF alpha)-dependent cytotoxicity. Combined decentralization/sialadenectomy abrogated the inhibition of MC cytotoxic activity, as we have shown previously for pulmonary inflammation and neutrophil functions. However, sialadenectomy alone inhibited MC-mediated TNF alpha-dependent cytotoxicity, an observation which suggests that SMG produce a factor(s) that can potentiate MC cytotoxic activity. Studies of the effects of SMG-derived factors, such as epidermal growth factor, nerve growth factor, and transforming growth factor beta (TGF beta), showed that only pretreatment of MCs with TGF beta 10(-8) g/ml inhibited MC-mediated TNF alpha-dependent cytotoxicity. Thus, the modulation of MC-mediated TNF alpha-dependent cytotoxicity by cervical sympathetic innervation and SMG is complex and distinct from the modulation of pulmonary inflammation and neutrophil functions identified previously.

Animals↗
PubMed1993

Tissue-selective inhibition of prostaglandin synthesis in rat by tepoxalin: anti-inflammatory without gastropathy?

BACKGROUND: Inhibition of prostaglandin synthesis is likely a primary mechanism for both the anti-inflammatory and ulcerogenic effects of nonsteroidal anti-inflammatory drugs (NSAIDs). The present study examined the mechanism underlying the ability of a novel anti-inflammatory drug, tepoxalin, to suppress prostaglandin synthesis without inducing gastric mucosal injury. METHODS: The effects on prostaglandin synthesis by various tissues of tepoxalin, diclofenac, and indomethacin were examined in vivo and in vitro. These compounds were also studied in two inflammation models. The capacity of indomethacin and tepoxalin to induced antral ulceration in the rabbit was compared. RESULTS: In most tissues, tepoxalin was a weaker inhibitor of prostaglandin synthesis than the two NSAIDs. However, at a site of peripheral inflammation, tepoxalin was comparable with the NSAIDs in suppressing prostaglandin synthesis and in exerting anti-inflammatory effects. Indomethacin induced penetrating antral ulcers in rabbits whereas tepoxalin produced no detectable mucosal injury. CONCLUSIONS: The ability of tepoxalin to suppress inflammation without causing gastric mucosal injury appears to be related to its differential suppression of prostaglandin synthesis in various tissues. Compounds that selectively inhibit prostaglandin synthesis at sites of inflammation may represent a class of anti-inflammatory drugs without detrimental effects on the stomach.

Animals↗
PubMed1992

Inhibition of neutrophil chemotaxis and activation following decentralization of the superior cervical ganglia.

Recent studies have shown that bilateral decentralization (sympathectomy) of the superior cervical ganglia (SCG) of rats sensitized to the parasite Nippostrongylus brasiliensis attenuated the development of pulmonary inflammation following allergen challenge. Sympathectomy inhibited total leukocyte infiltration into lung lavage fluids, particularly neutrophil infiltration. To define the effects of decentralization of the SCG on neutrophil responses, peripheral blood neutrophils of rats were isolated and tested in in vitro chemotaxis and phagocytosis assays. Neutrophils from rats that were sympathectomized 7 days previously displayed a marked reduction in chemotaxis to N-formyl-methionyl-leucyl-phenylalanine and leukotriene B4 compared to neutrophils from sham-operated or unoperated groups. Although the degree of chemotaxis was greater in blood neutrophils from parasite-infected rats than from uninfected rats, sympathectomy markedly reduced the chemotactic responses of both groups. In addition, neutrophils of sympathectomized rats were unresponsive to lipopolysaccharide-induced metabolic activation as assessed by in vitro phagocytosis and oxidative reduction of nitroblue tetrazolium. Thus, decentralization of the SCG of rats affects the chemotactic responses and functions of neutrophils. Understanding the role of the sympathetic nervous system in modulating the behavior of neutrophils will shed light on the interactions between the nervous and immune systems.

Animals↗
PubMed1992

Hemoprotein-dependent production of a neutrophil-activating factor from arachidonic acid.

Hemoproteins have been suggested to contribute to various forms of tissue injury by catalyzing the peroxidation of lipids. In this study, the ability of hemoglobin to catalyze the production of a neutrophil-activating factor from arachidonic acid was examined. Incubation of arachidonic acid, hydrogen peroxide, and hemoglobin at 37 degrees C for 30 min resulted in the production of a lipid-extractable substance that was chemotactic for neutrophils in vitro and could stimulate leukocyte adherence in vivo. These actions could be inhibited by two leukotriene B4 (LTB4) receptor antagonists. The peroxidation product cross-reacted significantly with an antibody directed against LTB4, but not with an antibody directed against LTC4. The production of this factor was hemoprotein dependent. Immunoreactive LTB4 and biological activity were produced only when hemoglobin, or another hemoprotein, cytochrome c, was present in the reaction mixture. The amount of the factor produced could be increased in a concentration-dependent manner by increasing the amounts of arachidonic acid or hydrogen peroxide in the reaction mixture. The production of this factor could be inhibited by 5-aminosalicylic acid, catalase, or deferoxamine. Separation of the lipid-extractable products of the peroxidation of arachidonic acid on high-performance liquid chromatography revealed that the immunoreactive (with anti-LTB4) and chemotactic substance had a retention time distinct from that of LTB4 and the hydroxyeicosatetraenoic acids. A lipid-extractable substance with significant cross-reactivity to anti-LTB4 could also be produced if plasma was substituted for arachidonic acid in the reaction mixture.(ABSTRACT TRUNCATED AT 250 WORDS)

Aminosalicylic Acids↗
PubMed1990

Marked antiinflammatory effects of decentralization of the superior cervical ganglia.

Intravenous challenge with parasite antigens in Nippostrongylus brasiliensis-sensitized rats resulted in anaphylactic shock and, in some animals, death. Surviving animals showed significant drop in mean arterial blood pressure, cardiac output, and blood flow to the trachea, bronchioles, and mesentery. After anaphylaxis, changes in the cellular and protein composition in bronchoalveolar lavage fluids (BALF) were assessed. 8 h after antigen challenge, there was significant influx of inflammatory cells and an increase in the levels of histamine and serum-derived immunoglobulins (IgG and IgM) in BALF. Chemotactic activity for neutrophils was also present in BALF. Once we established this anaphylaxis-induced model of pulmonary inflammation, we sought to determine whether or not the superior cervical ganglia (SCG) modulate this inflammation. We performed bilateral superior cervical ganglionectomy or decentralization of the SCG. Our results show that decentralization significantly reduced mortality (by 68%) after anaphylaxis. Furthermore, the increases in levels of serum-derived proteins, histamine, and influx of cells (especially neutrophils) observed in BALF after anaphylaxis were attenuated by both decentralization and ganglionectomy. By contrast, hemodynamic parameters in the respiratory tract and the presence of neutrophil chemotactic activity in BALF were not influenced by decentralization. Thus, the severity of pulmonary inflammation initiated by systemic anaphylaxis is depressed by bilateral ganglionectomy or decentralization of SCG.

Animals↗