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Biomedical subjects

D Wallach

Publications and source records attributed to D Wallach.

At least 271 records · Page 15Linked to original sources

Stimulation of guanylate cyclase of fibroblasts by free fatty acids.

The membranous guanylate cyclase of Balb 3T3 fibroblasts was stimulated by a fraction of calf serum extracted by ether. Stimulation was observed with Mg2+ as the only bivalent cation in the presence of Lubrol PX. The activator co-chromatographed with free fatty acids, and several of these were found to stimulate guanylate cyclase. Among the saturated fatty acids, myristic acid had the highest activity. Stimulating activity diminished as the hydrocarbon chain of the fatty acid was lengthened or shortened. Introduction of an unsaturated bond enhanced the activation by the longer fatty acids. This pattern of specificity is similar to that observed for the effect of fatty acids on many other membranous functions. Under appropriate conditions fatty acids were found to stimulate guanylate cyclase activity in the absence of Lubrol PX. The relationship among the effects of Mg2+, Mn2+, Lubrol PX, and fatty acids on enzyme activity was examined. On the basis of these studies, it appears that fatty acids stimulate the enzyme by a mechanism different from nonionic detergents or Mn2+.

Adenylyl Cyclases↗

[Mast-cell rosettes in the immunized rat].

After stimulation by ovalbumin + Bordetella pertussis, rat peritoneal mast cells can form rosettes with antigen-coated erythrocytes. This phenomenon is inhibited by previous incubation of mast cells with antigen; it is attributed to apparition of membrane-bound anaphylactic antibody. The variations of percentage of rosette forming mast cells during the course of immunization are reported and compared with P.C.A. titers.

Animals↗

The proteins of the content of the secretory granules of the rat parotid gland.

The proteins of the secretory granules of the rat parotid gland were characterized by sodium dodecylsulfate gel electrophoresis, by chromatography of [3-H]proline-labeled proteins on DEAE-cellulose and by amino acid analysis. Sodium dodecylsulfate gel electrophoresis of the secretory granule content showed five principal proteins and a limited number of minor components. Only two of the principal bands could be identified as known secretory enzymes of the parotid gland. One was identified as the alpha-amylase and one as deoxyribonuclease. Peroxidase and ribonuclease form minor portions of the secretory proteins. The other three major proteins constitute, together, about 60% by weight, of the secretory granule content proteins. Of these, one which represents more than 30% of the total granule protein was found to contain uniquely high amounts of leucine residues (21 mole%). Another one of these principal proteins was relatively rich in cysteine residues (7 mole%). The fifth principal protein was found to contain high amounts of proline (28 mole%) glutamic acid (17 mole%) and glycine (18 mole%) residues. Its amino acid composition was very similar to that of the proline-se granules. This protein, however, differed from the "membranous" proline-rich proteins by several criteria. Two minor glycoproteins of the secretory granule content were also found to be rich in proline residues (37 mole%). As with the other proline-rich proteins of the granule, they contained no sulphur-containing amino acids, stained faintly pink with Coomassie Blue and were underestimated by the Lowry method. They differ however, from all the other proline-rich proteins of the granule by having a significantly higher content of threonine, less glycine (9 mole%) and much less glutamic acid (3 mole%). Of the principal proteins, only the deoxyribonuclease and the half-cystine-rich proteins were positively stained by periodic acid Schiff staining. The possible functions of the leucine-rich, the half cystine-rich and the various proline-rich proteins are discussed.

Amino Acids↗

Non-parallel transport of membrane proteins and content proteins during assembly of the secretory granule in rat parotid gland.

The insertion of newly synthesized protein molecules into the membrane of the secretory granule of the rat parotid gland was studied by in vivo labeling with [3-H]-proline and [3-H]leucine. 2 h after the injection of the amino acid into the rat, the membrane fraction isolated from the secretory granules was found to be highly labeled with proline but only slightly labeled with leucine. The ratio of proline label in the granule membrane to that in the granule's secretory content was roughly equivalent to the ratio of total proline in the proteins of these two fractions. In contrast the ratio of leucine label in the membrane to that in the secretory content was much less than would be expected from the relative amount of leucine in both fractions. Separation of the proteins of the granule membrane by gel electrophoresis in presence of sodium dodecylsulfate showed that a considerable amount of these proteins was unlabeled. The labeled proteins could be selectively extracted from the membrane by 0.15 M Nacl solution or by dilute buffer at pH 4.5. These extracted proteins were found to contain a high proportion of proline residues and a negligible amount of leucine residues. In the extract proline constituted 36 mole % of the total amino acids. Proline plus glycine plus glutamic acid constituted more than 80 mole % and leucine constituted about 1 mole% of the total amino acids. Further analyses by gel electrophoresis in presence of sodium dodecylsulfate showed that the fractions of secretory granule membrane and secretory granule content are relatively free of contamination by proteins from other subcellular structures. It is suggested that the proteins which will constitute the mature secretory granule are transported to the site of final assembly by two pathways. The proline-rich proteins are transported to the site of assembly in close coordination with all the exportable proteins. The other membrane proteins arrive by a different pathway. Two alternative mechanisms are suggested to explain the finding that a considerable part of the membrane proteins are not labeled. I. The pathway of the intracellular transport of the unlabeled membrane proteins is similar to that of the secretory proteins but the newly synthesized membrane protein molecules are diluted in a large intermediate pool--the GOLgi complex. II. The proteins that did not get labeled are derived by a process of reutilization, from membranes of granules which have previously discharged their content in the process of secretion.

Amino Acids↗

Mycobacterium leprae-reactive T-cell clones isolated from polar lepromatous and tuberculoid leprosy patients.

T-cell clones capable of mounting a proliferative response to Mycobacterium leprae were obtained in three leprosy patients (two polar lepromatous and one polar tuberculoid) either from M. leprae-activated or from protein-purified derivative-activated polyclonal T lymphoblasts. All these clones expressed the CD4 surface marker. Some of them proliferated to the antigen only in the presence of interleukin-2. A majority expressed cross-reactive responses to other mycobacteria. Clones obtained from the lepromatous patients did not differ in any of these features from those obtained from the tuberculoid patient. M. leprae-reactive clones obtained from one lepromatous patient displayed strong antigen-specific cytotoxicity toward autologous antigen-coated target cells. This phenomenon was not observed for any clone of the other lepromatous patient and was seen only for one clone in the tuberculoid patient.

Antigens, Bacterial↗

Generalized lymphangiomatosis with chylothorax and skin lymphangiomas in a neonate.

Generalized lymphangiomatosis is an extremely rare condition with clinical features depending on the extent of involvement. We report a newborn infant with chylothorax and cutaneous lymphangiomas of unique clinical presentation. The baby required artificial ventilation, pleural drainage, low triglyceride infusions, and diet. The course was favorable, with a complete regression of the cutaneous lymphangiomas.

Biopsy↗

Development of the acetabulum and hip: computed tomography analysis of the axial plane.

Acetabular growth and development in the axial plane was evaluated by computed tomography (CT) scan. One hundred seventy normal hips of children ranging in age from 6 months to 17 years were evaluated for axial acetabular index, anterior and posterior center-edge angles (CEA), and acetabular anteversion. The acetabulum deepens and becomes increasingly spherical with time until the age of 13 years. Little further change in acetabular shape occurs once the triradiate cartilage closes. Closure ensues between the ages of 11 and 13 years, occurring slightly earlier in girls. Posterior bony coverage of the femoral head is greater than anterior coverage at all times. Acetabular anteversion showed little change as the acetabulum developed. Establishing normal values for axial development of the hip and acetabulum allows a better three-dimensional concept of the different pathologic conditions and aids in treatment planning.

Acetabulum↗

Pharmacokinetics and tissue distribution of human urinary tumor necrosis factor binding protein in mice.

Iodinated natural human urinary tumor necrosis factor binding protein I (125I-uTBP) was iv injected into BALB/c mice, and its pharmacokinetics and tissue distribution were assessed during a short-term (0-1 hr) and for a long-term (0-24 hr) period. The blood 125I-uTBP concentration displayed a biphasic pattern that was adequately described by a biexponential function with estimated half-lives of 0.1 and 3.8 hr. The apparent volume of distribution (Vc) of the central compartment was 3 ml, which approximated the mouse blood volume. The clearance (CL) derived either from a model-dependent or a model-independent method of analysis was 2.5 and 2.9 ml/hr, respectively. One hr after the iv administration of 125I-uTBP, the radioactivity accumulated in the major organs and tissues. The highest concentrations in terms of pg per organ were seen in the skin and in the liver. When expressed as pg 125I-uTBP per mg organ, the distribution was the highest in the gallbladder, bladder, kidneys, and lungs. At 24 hr, the distribution of 125I-uTBP represented about 10% of the amount measured at 1 hr. The rank order of accumulation of the radiolabeled uTBP in the major organs, expressed as pg per organ at 24 hr was skin greater than liver greater than kidneys greater than lungs greater than gut greater than spleen greater than gallbladder.

Animals↗

[1801-2001: two centuries of dermatology and venereology in the Assistance Publique-Hôpitaux de Paris].

The specialization "Dermatology" was born at the Saint-Louis hospital in France in 1801, in the light of the revolutionary reforms that led to fundamental changes in the functioning of the hospitals in Paris. Hence, the Saint-Louis hospital occupies an eminent position in the history of dermatology in France, reinforced by the role of Jean-Louis Alibert, who founded the French school of Dermatology. Despite the place occupied by the physicians of the Saint-Louis Hospital in the creation and development of the French school of dermatology, other physicians in other hospitals contributed to the expansion of the dermatology school. The work of Pierre Rayer, in the nineteenth century, at the Saint-Antoine and subsequently the Charité hospitals, are within this scope. More recently, the re-organization of the Faculty of Medicine into University Hospital Centers has permitted the creation of various treatment, teaching and research centers within the structure of the public hospitals in Paris. From the start, syphilis was part of the Dermatology teaching and practice. In Paris, several so-called "specialized" hospitals were created to house patients presenting with syphilis. Later on, the existence of these hospitals was questioned notably because of the constraints that their functioning imposed on the patients. Anti-venereal care centers were developed in response to the request of the practitioners to facilitate the access to treatment.

Dermatology↗

Inhibition of tumor necrosis factor-induced cell killing by tryptophan and indole.

Cells sensitive to the cytocidal effect of tumor necrosis factor (TNF) were protected against this effect when growth in the presence of elevated concentrations of tryptophan. Several other indole derivatives also provided protection against TNF cytotoxicity. Most effective were indole itself and its monomethyl derivatives, providing a degree of protection greatly exceeding that observed with tryptophan. Protection was also observed against the cytocidal effect of TNF applied in the presence of a protein synthesis inhibitor. The protective effect of tryptophan was largely dependent on preexposure of the cells, for several hours, to a high concentration of this amino acid. On the other hand, indole was protective also when applied to cells together with TNF, or even two hours after TNF application. The inhibition of the cytotoxicity of TNF by tryptophan and other indole derivatives may serve as a useful experimental tool in exploring the mechanisms and the physiological implications of TNF cytotoxicity.

Animals↗