[Pruritus sine materia: a pharmacological approach].
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Cholestasis↗
Biomedical subjects
L Michel
Publications and source records attributed to L Michel.
Photolabeling of the phosphate binding site of chloroplast coupling factor 1 with [32P]azidonitrophenyl phosphate.
Chloroplast F1-ATPase (CF1) was photolabeled by a radiolabeled photoactivatable derivative of Pi, 4-azido-2-nitrophenyl [32P]phosphate (ANPP). The radioactivity was localized in the beta subunit of CF1. Upon cleavage of the beta subunit by cyanogen bromide, the predominantly labeled peptide was recovered, which was subsequently subjected to tryptic digestion. A tryptic peptide (spanning Ile312-Arg354), was found to contain nearly all the covalently bound radioactivity. By Edman degradation, the labeled amino acid residues were identified as Tyr328, Val329 and Pro330. The labeled beta-Tyr328 of CF1 is the equivalent of beta-Tyr311 of F1 from beef heart mitochondria, which was previously found to be photolabeled by ANPP [J. Garin et al. (1989) Biochemistry 28, 1442-1448].
Affinity Labels↗
The ATP synthase (F0-F1) complex in oxidative phosphorylation.
The transmembrane electrochemical proton gradient generated by the redox systems of the respiratory chain in mitochondria and aerobic bacteria is utilized by proton translocating ATP synthases to catalyze the synthesis of ATP from ADP and P(i). The bacterial and mitochondrial H(+)-ATP synthases both consist of a membranous sector, F0, which forms a H(+)-channel, and an extramembranous sector, F1, which is responsible for catalysis. When detached from the membrane, the purified F1 sector functions mainly as an ATPase. In chloroplasts, the synthesis of ATP is also driven by a proton motive force, and the enzyme complex responsible for this synthesis is similar to the mitochondrial and bacterial ATP synthases. The synthesis of ATP by H(+)-ATP synthases proceeds without the formation of a phosphorylated enzyme intermediate, and involves co-operative interactions between the catalytic subunits.
Amino Acid Sequence↗
Leukotriene B4 and platelet-activating factor in human skin.
Acute inflammatory reactions are characterized by leukocyte infiltration associated with increases in vascular permeability and in local blood flow. Leukocyte infiltration can be induced by chemotactic factors such as leukotriene B4 (LTB4) and paf-acether (formerly known as platelet-activating factor) that can be generated within inflammatory lesions. Vascular permeability and increase in blood flow are also affected by LTB4 and paf-acether, as well as by several other substances, including histamine and prostaglandins. Derived from arachidonic acid via the 5 lipo-oxygenase pathway, LTB4 is one of the most potent leukocyte chemotactic substances known. Intradermal injections of LTB4 induce dermal neutrophil infiltration in animal models and in humans. Topical application of LTB4 to human skin induces intraepidermal micro-abscesses containing numerous intact neutrophils. LTB4 has been found to be increased in psoriatic lesions, but its synthesis by epidermal cells remains undecided. Like other leukotrienes, LTB4 can stimulate DNA synthesis in cultured human epidermal keratinocytes. However, receptors for LTC4 but not for LTB4 have been found on human keratinocytes in culture. Paf-acether is an ether-linked phospholipid identified as 1-O-alkyl-2-O-acetyl-sn-glycero-3-phosphocholine and is considered to be one of the most potent mediators of acute allergic and inflammatory reactions. For instance, intradermal injection of paf-acether induces inflammatory events such as neutrophil infiltration and increase in vascular permeability. Recent data suggest that cutaneous cells, such as fibroblasts and keratinocytes, are capable of producing paf and that paf is released during the development of allergic cutaneous reactions.(ABSTRACT TRUNCATED AT 250 WORDS)
Dermatitis↗
[Extracorporeal gallbladder lithotripsy: technology, practical methods, results and current value].
Extracorporeal shock wave lithotripsy of gallstones is a safe and well-tolerated procedure. Patients are now treated without general anesthesia and, increasingly, on an outpatient basis. Skin petechiae and transient hematuria are the most common side effects. Episodes of biliary colic are common in the follow-up period, but more serious adverse side effects such as cholecystitis and pancreatitis are distinctly uncommon. It is estimated that only 15% to 20% of all patients with symptomatic cholelithiasis are suitable lithotripsy candidates. As our knowledge of the procedure grows, it seems clear that the best results are obtained in patients with solitary radiolucent stones less than or equal to 20 mm, with stone-free rates at 12 months above 80%, for this selected group of patients. Adjuvant oral bile-acid dissolution therapy should be used in conjunction with gallstone lithotripsy. Gallstone recurrence remains to be established by clinical studies. Therapy for gallstones in 1991 has to be reevaluated by an interdisciplinary approach, taking into account not only open cholecystectomy, but also other modalities such as medical dissolution, laparoscopic surgery, percutaneous cholecystolithotomy and extra-corporeal shock wave lithotripsy. The appeal of the laparoscopic approach will substantially reduce the pool of patients for lithotripsy. Nevertheless, lithotripsy will continue to be a viable treatment option for patients with a single radiolucent stone. It is an outpatient procedure and doesn't require any incision or general anesthesia.
Bile Acids and Salts↗
[Comparative study of ambulatory clients in private and public psychiatry].
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Adult↗
[Studying the mast cell. Recent data].
In the light of recently published data, the mast cell can now be viewed as a key cell, not only in allergic reactions such as immediate hypersensitivity responses, but also in a broad spectrum of other biologic responses including host-parasite interactions, nonspecific inflammatory reactions, fibrosis, angiogenesis, tissue reconstruction, and wound healing. Nevertheless the molecular basis for the intervention of mast cells in many of these biologic responses is still unclear. Very recent studies have demonstrated that mast cells are capable of producing a wide range of cytokines, a property which may influence various physiologic, immunologic and disease processes. Furthermore, although substantial differences have been reported between mast cells located in different tissues, the reasons and mechanisms underlying this heterogeneity long remained obscure. The recent development of two original experimental approaches, i.e., in vitro culture of mast cells, mainly derived from mouse bone marrow precursors, and replenishment of mast cell-deficient mice, has provided new insight into the mechanisms by which tissue microenvironment influence of regulation mast cell phenotype. Extrapolation to humans of data obtained in rodents is, however, hazardous. In the review presented here, the most recent data from the literature provide the basis for outlining avenues of research which can be expected, in the near or remote future, to solve what mast cell experts term "the riddle of the mast cells".
Animals↗
Paf-acether in human skin.
Paf is a phospholipid mediator present in human skin which induces inflammatory events, such as neutrophil infiltration and increased vascular permeability. Recent data suggest that cutaneous cells, such as fibroblasts and keratinocytes, produce paf and that paf is released during allergic cutaneous reactions. It is tempting to speculate that paf may contribute to the development of various skin disorders with acute and chronic skin inflammation. Paf antagonists may help in bringing answers to this hypothesis and may offer new prospects for the treatment of cutaneous inflammatory diseases.
Humans↗
Cyclosporin A inhibits the antigen-presenting functions of freshly isolated human Langerhans cells in vitro.
Cyclosporin A (CsA) is a strong inhibitor of skin allograft rejection. It has been also reported to act, not only on helper T cells, but also on the antigen-presenting functions of mouse epidermal cells (EC) enriched in Langerhans cells (LC). We tested the effects of CsA on the human allogeneic mixed epidermal cell-lymphocyte reaction (MECLR) using whole EC and freshly isolated LC as stimulator cells. Results were as follows. 1) CsA inhibited the lymphocyte proliferative response in a dose-dependent fashion, by about 80% for a CsA concentration of 10(-7) M. To evaluate the effects of the drug on the two cell populations involved in MECLR, stimulator EC and responder PBMC were separately pulsed for 2 h with CsA, washed, and combined to form MECLR. Inhibition by CsA of the alloantigen-dependent lymphocyte proliferation appeared to be multifactorial, because CsA-pulsed EC and CsA-pulsed effector PBMC led to identical reductions of 40% each in proliferation. 2) The nature of EC sensitivity to CsA during MECLR was then analyzed after freshly separating highly purified CD1-positive LC (greater than 95%) and LC-depleted EC (mainly keratinocytes), using an immunomagnetic particle technique. When responder PBMC were cultured with CsA-pulsed LC, a highly significant reduction of lymphocyte proliferation was observed, indicating that CsA has direct effects on LC. 3) Some of the possible mechanisms by which CsA might act on LC were studied. Substantial IL-1 activity and PGE2 amounts were induced during MECLR by LC and keratinocytes, but CsA did not act via these factors. Neither did it significantly modify HLA-DR, DQ, or DP antigen expressions on EC. In conclusion, CsA directly inhibits antigen presentation by human LC. This inhibition may partly explain the beneficial effects of CsA on skin allografts and certain cutaneous immune reactions.
Adolescent↗
Soluble CD23 increases IL-3 induction of histamine synthesis by human bone marrow cells.
Interleukin 3 (IL-3) and soluble CD23 (sCD23/IgERII) have similar capacities to induce basophil development from human bone marrow (BM) precursors. IL-3 also has the capacity to induce de novo histamine synthesis from human BM cells. In the present study, we examined the effect of sCD23 on histamine synthesis by human BM cells and its relationship with IL-3. Our data showed that recombinant 25 KDa sCD23, although on its own failed to induce histamine release, significantly enhanced IL-3-stimulated histamine synthesis by BM cells. These data provide further support for the cytokine-like role of sCD23 on hematopoietic cells.
Antigens, Differentiation, B-Lymphocyte↗
Recurrent pleuro-pericarditis due to gastrodiaphragmatic fistula.
A 61-year-old woman presented with recurrent pleuro-pericarditis following Nissen fundoplication. A diagnosis of anterior gastrodiaphragmatic fistula was made. The suspected etiology of the fistula was local ischemia. This kind of fistula, although exceptional, should always be considered in the presence of unexplained recurrent pleuro-pericarditis after fundoplication.
Diaphragm↗
Production of paf-acether by human epidermal cells.
The production of the inflammatory mediator paf-acether (paf) from human epidermal cells was investigated in vitro. Human epidermal cells, freshly isolated from normal skin or in culture, were incubated in Tyrode's buffer containing 0.25% lipid-free bovine serum albumin in the presence of 2 microM calcium ionophore A23187, at 37 degrees C, for 1 to 60 min. Paf production slightly began at the first min of stimulation, was significant after 10 min, reached a maximum at 20 min (251 +/- 25 pg/l X 10(6) cells, mean +/- 1 SD), and decreased thereafter. About 50% of the paf amount produced by epidermal cells was recovered in supernatants. Addition of the non-acetylated paf precursor 1-O-octadecyl-sn-glycero-3-phosphocholine, i.e., lyso-paf, at 0.1 microM to epidermal cells during A23187-stimulation did not alter this production. In contrast, addition of acetyl-coenzyme A at 0.1 mM enhanced paf production by 5 times. The material produced by epidermal cells was identical to synthetic paf because: 1) the aggregation of aspirin-treated and ADP-insensitive washed rabbit platelets it induced was inhibited by BN 52021, an antagonist of the paf putative receptor; 2) the factor was inactivated by phospholipase A2 but was insensitive to lipase from Rhizopus arrhizus; 3) it exhibited the same retention time as synthetic paf during standard and reverse-phase (RP) high-pressure liquid chromatography (HPLC) elution. The paf precursors, i.e., lyso-paf and 1-O-alkyl-2-acyl-sn-glycero-3-phosphocholine, were also detected in epidermal cells, stimulated with A23187 or not. As determined by RP-HPLC analysis and confirmed by gas chromatography analysis, these precursors and the paf produced by epidermal cells exhibited more than 90% of a hexadecyl chain at the sn-1 position of the molecule. The present results demonstrate the synthesis and release of paf by normal human epidermal cells. Paf production within the epidermis might account for the development of cutaneous inflammation and the pathogenesis of many skin disorders.
Acetyl Coenzyme A↗
Cetirizine effects on the cutaneous allergic reaction in humans.
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Adult↗
Synthesis and properties of azidonitrophenyl pyrophosphate, a photoaffinity probe of the nucleotide binding sites of mitochondrial F1-ATPase.
4-Azido-2-nitrophenyl pyrophosphate (azido-PPi) labeled with 32P in the alpha position was prepared and used to photolabel beef heart mitochondrial F1. Azido-PPi was hydrolyzed by yeast inorganic pyrophosphatase, but not by mitochondrial F1-ATPase. Incubation of F1 with [alpha-32P]azido-PPi in the dark under conditions of saturation resulted in the binding of the photoprobe to three sites, two of which exhibited a high affinity (Kd = 2 microM), the third one having a lower affinity (Kd = 300 microM). Mg2+ was required for binding. As with PPi [Issartel et al. (1987) J. Biol. Chem. 262, 13538-13544], the binding of 3 mol of azido-PPi/mol of F1 resulted in the release of one tightly bound nucleotide. ADP, AMP-PNP, and PPi competed with azido-PPi for binding to F1, but Pi and the phosphate analogue azidonitrophenyl phosphate did not. The binding of [32P]Pi to F1 was enhanced at low concentrations of azido-PPi, as it was in the presence of low concentrations of PPi. Sulfite, which is thought to bind to an anion-binding site on F1, inhibited competitively the binding of both ADP and azido-PPi, suggesting that the postulated anion-binding site of F1 is related to the exchangeable nucleotide-binding sites. Upon photoirradiation of F1 in the presence of [alpha-32P]azido-PPi, the photoprobe became covalently bound with concomitant inactivation of F1. The plots relating the inactivation of F1 to the covalent binding of the probe were rectilinear up to 50% inactivation.(ABSTRACT TRUNCATED AT 250 WORDS)
Adenosine Diphosphate↗
Photolabeling of the phosphate binding site of mitochondrial F1-ATPase by [32P]azidonitrophenyl phosphate. Identification of the photolabeled amino acid residues.
[32P]Azidonitrophenyl phosphate [( 32P]ANPP) is a photoactivatable analogue of Pi. It competes efficiently with Pi for binding to the F1 sector of beef heart mitochondrial ATPase and photolabels the Pi binding site located in the beta subunit of F1 [Lauquin, G. J. M., Pougeois, R., & Vignais, P. V. (1980) Biochemistry 19, 4620-4626]. By cleavage of the photolabeled beta subunit of F1 with cyanogen bromide, trypsin, and chymotrypsin, bound [32P]ANPP was localized in a fragment spanning Thr 299-Phe 326. By Edman degradation of the radiolabeled tryptic peptide spanning Ile 296-Arg 337, [32P]ANPP was found to be attached covalently by its photoreactive group to Ile 304, Gln 308, and Tyr 311. These results are discussed in terms of a model in which the phosphate group of [32P]ANPP interacts with a glycine-rich sequence of the beta subunit, spanning Gly 156-Lys 162, which is spatially close to the photolabeled Ile 304-Tyr 311 segment of the same subunit.
Affinity Labels↗
Biological and cellular responses to grass pollen in sensitive patients.
Using a noninvasive skin chamber technique, we studied the in vivo development of anaphylactic reactions in 8 pollen-sensitive patients suffering from seasonal allergic rhinitis/conjunctivitis/asthma and showing positive cutaneous reactions after intradermal allergen challenge. As agonists, histamine and pollen were introduced into the skin chambers and left in contact with superficial dermis during 6 h. The release of mediators (histamine and prostaglandin [PG] D2) and the modifications in protein diffusion occurring during the immediate (30 min) and the late (6 and 24 h) cutaneous reaction phases were quantitatively analyzed. 24 h after agonist introduction, the recruitment of inflammatory cells on the superficial dermis was studied by use of Rebuck's windows. Histamine release in pollen-containing skin chambers was immediate and persisted until the 24th h despite replacement of the agonists by control medium at the 6th h. An intense PGD2 release occurred as soon as the first 30 min in chambers containing either exogenous histamine or pollen and was maintained until the 24th h. Protein diffusion induced by histamine and pollen was similar to the control one at 30 min but was intensely enhanced at the 6th h. At the 24th h, pollen-induced protein diffusion was still intense whereas that induced by histamine was analogous to the control one. 24 h after pollen challenge, numerous eosinophils were recruited on the superficial dermis but almost none were observed after control medium or histamine.(ABSTRACT TRUNCATED AT 250 WORDS)
Eosinophils↗
[Profile of a psychiatric consultation service for students].
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Adult↗
Biochemical and morphological modifications in dexamethasone-treated mouse bone marrow-derived mast cells.
Addition of 1 microM dexamethasone (DM) to bone marrow-derived mast cells (BMMC) induced a time-dependent increase in cell histamine content. The latter reached a plateau of 2.5 micrograms/1 x 10(6) cells after 11 days in culture, compared with 100 ng/1 x 10(6) for untreated BMMC. Steroids, such as beta-estradiol, androsterone, and testosterone (1 microM), did not alter the histamine content of BMMC, whereas progesterone (1 microM) induced a moderate increase. Other glucocorticosteroids also enhanced histamine content, suggesting that the observed increase was specific for glucocorticosteroid. Treatment of BMMC with 1 microM DM for 14 days inhibited the Ag-induced, IgE-mediated release of histamine, beta-hexosaminidase, platelet-activating factor-acether, LTB4, and LTC4 by 65 +/- 3%, 66 +/- 1%, 93 +/- 3%, 66 +/- 2%, and 74 +/- 10%, respectively (mean +/- 1 SD, n = 3). In contrast with untreated cells which produce less than 2 ng/1 x 10(6) cells PGD2 after Ag challenge, DM-treated BMMC generated 16.8 +/- 0.3 ng/1 x 10(6) cells PGD2. Moreover, most of DM-treated BMMC became Alcian blue+/safranin+ and by ultrastructure, exhibited numerous cytoplasmic granules filled with abundant and uniform electron-dense matrix. The present results indicate that DM-treated BMMC exhibit biochemical and functional properties different from immature untreated cells, suggesting that a maturation-like process occurred in vitro during DM treatment.
Alcian Blue↗