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Biomedical subjects

D Lagunoff

Publications and source records attributed to D Lagunoff.

At least 73 records · Page 4Linked to original sources
PubMed1979

Inhibition of mast cell histamine secretion by N-substituteed derivatives of phosphatidylserine.

The structural basis for the highly specific action of phosphatidylserine in enhancing mast cell histamine secretion induced by concanavalin A was investigated by studying the activities of three N-substituted derivatives: N-acetyl phosphatidylserine, N-1-dimethylaminonaphthalene-5-sulfonly phosphatidylserine, and N-4-nitrobenzo-2-oxa-1,3-diazole phosphatidylserine. None of the derivatives was capable of activating concanavalin A-induced histamine secretion at concentrations two to three times that required for maximal activation by phosphatidylserine. Instead, the derivatives were found to inhibit the secretory response of mast cells to the calcium ionophore A23187 as well as to concanavalin A. The inhibition was noncytotoxic, partially reversible by washing, and associated with binding of N-substituted phosphatidylserine to the mast cell.

Animals↗
PubMed1978

Neurological manifestations of Fabry disease in female carriers.

A family is described in which a 33-year-old man has classic X-linked recessive Fabry disease. His 2 sisters were discovered to be heterozygous carriers of the Fabry gene and to have both episodic and permanent neurological deficits including vertigo, tinnitus, long tract motor signs, and bladder incontinence. The most concise explanation for these findings is that the sisters manifest central nervous system complications of the Fabry carrier state. This family provides additional evidence that female carriers of rare X-linked recessive disorders may exhibit serious consequences of the disease, presumably related to tissue variability in expression of mutant enzyme activity.

Adult↗
PubMed1978

Interaction of phosphatidylserine with mast cells.

Phosphatidylserine (PtdSer) potentiates histamine secretion from mast cells exposed to concanavalin A and Ca2+. In order to identify the form of PtdSer that is responsible for its effect on mast cell secretion, PtdSer containing a tritium-labeled serine moiety (3H-PtdSer) was synthesized from egg yolk phosphatidylcholine. The critical micelle concentration (CMC) of 3H-PtdSer and the binding isotherm for 3H-PtdSer interaction with mast cells were determined. The midpoints of the binding isotherm and the dose-response curve for potentiation of secretion coincide and are 2 orders of magnitude greater than the CMC. The shape of the binding curve is explicable either in terms of simple binding of preformed PtdSer micelles or of cooperative binding of monomeric PtdSer in which the number of molecules cooperatively associating with a mast cell binding site is equal to the number of monomers in a PtdSer micelle. In either case, at equilibrium, PtdSer micelles are bound to the mast cells. The number of PtdSer molecules bound to a single mast cell at equilibrium was estimated to be 3.7 X 10(9).

Animals↗
PubMed1978

A major serine protease in rat skeletal muscle: evidence for its mast cell origin.

The physical, chemical, and immunologic properties of a protease from rat skeletal muscle, proposed to function in the degradation of certain intracellular enzymes, are identical to those of a chymotrypsin-like serine protease isolated from peritoneal mast cells. The results of polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate and 8 M urea indicate that the two rat proteases have identical mobilities corresponding to a molecular weight of 26,000. The relative amino acid compositions of the proteases are nearly identical. Immunodiffusion tests for crossreaction between the muscle protease and antisera directed toward mast cell protease indicate that the former is immunologically identical to mast cell protease. The first 35 amino-terminal residues of the two enzymes are identical and indicate homology of these proteins to other mammalian serine proteases. The sequence analysis of the protease from muscle was extended for an additional 16 positions, and comparison of this amino-terminal sequence with that of a similar enzyme from small intestine showed approximately 75% sequence identity. In contrast, only 40% of the residues in this region of bovine chymotrypsin A were found at corresponding loci in rat muscle protease. It is concluded that the protease from muscle or mast cells is closely related to the enzyme from small intestine which recently was localized in the "atypical" mast cells of gut mucosa [Woodbury, R. G., Gruzenski, G. M. & Lagunoff, D. (1978) Proc. Natl. Acad. Sci. USA 75, 2785-2789].

Amino Acid Sequence↗
PubMed1978

Linear arrays of intramembranous particles in pulmonary tubular myelin.

Freeze-fracture preparations of tubular myelin in edematous rat lungs reveal the presence of linear arrays of intramembranous particles. The lines of particles are approximately 50 nm apart and appear to correspond to the intersections of sheets of bilayer membranes. Particles are not seen in lamellar bodies but become evident first in membranes transitional between lamellar bodies and tubular myelin. It is proposed that the particles represent a hydrophobic protein that plays a significant role in the organization of tubular myelin.

Animals↗
PubMed1978

Immunofluorescent localization of a serine protease in rat small intestine.

An intracellular serine protease, which is believed to initiate the degradation of several intracellular pyridoxal phosphate-dependent enzymes, was localized by immunofluorescence in atypical mast cells of the lamina propria and in intraepithelial cells of the rat small intestine. Some mucus-secreting goblet cells also contained the protease antigen. Atypical mast cells containing the enzyme were present in large numbers beneath the epithelium of bronchioles. All atypical mast cells also contained low levels of the chymotrypsin-like protease of normal mast cells. Both enzymes were consistently present in normal connective tissue mast cells. Amino acid content, molecular weight, and lack of immunologic crossreactivity indicate that the two enzymes are similar but not identical. The cell-specific localization of the intestinal serine protease makes it unlikely that the enzyme has any general role in the degradation of pyridoxal phosphate-dependent enzymes. The function of the enzyme in mast cells, atypical mast cells, and intestinal goblet cells is not known.

Animals↗
PubMed1978

Mast cell secretion: membrane events.

Stimulation of secretion with A23187 circumvents the usual mechanism of stimulation of secretion by direct mediation of an increase in cytoplasmic Ca++ and thereby permits study of the terminal components of the secretory process in which granules are externalized by membrane fusion events. Two alterations in the plasma membrane precede fusion: the formation of bulges and the aggregation of intramembranous particles. These changes require a permissive level of ATP and are sensitive to reagents that bind to intracellular protein sulfhydryl groups. They seem not to be attributable to a direct effect of Ca++ on membrane phospholipids. The cell components responsive to Ca++ and responsible for the alterations in the membrane are not known; neither microtubules nor actin filaments seem to qualify.

Adenosine Triphosphate↗
PubMed1978

Mast cell granule formation in the beige mouse.

The formation of mast cell granules was studied in the beige mouse utilizing histochemistry and electron microscopy. The time and sequence of appearance of heparin, histamine and the chymotrypsin-like protease were normal. By electron microscopy, the initial formation of progranules and subsequent aggregation was normal, but the granules from early stages were abnormally large. Reorganization of intermediate granule forms to homogeneous mature granules was delayed. Late fusions of intermediate and/or mature granules were not observed. Our findings indicate that the defect lies in the excessive initial fusion of progranules rather than in continued formation of new progranules or in fusion of mature granules with one another.

Animals↗
PubMed1978

Pulmonary surface-active materials in the Chediak-Higashi syndrome.

Beige mice express the Chediak-Higashi syndrome. Large inclusions, identified as abnormal lysosomes, are found in many cells. The inclusions in type II alveolar epithelial cells are enlarged lamellar bodies and they are associated with an increase in total lung surface-active material and phospholipid. Comparison of recovery of phospholipid in surface-active materials from beige and black (normal) mice indicates that in the beige mice there is an increase in total phospholipid and disaturated phosphatidylcholines in whole lung and in surface-active materials in residual lung after lavage. Hosphatidycholine and phosphatidylglycerol are increased as percentages of total lung phospholipid. Calculated alveolar surface coverage of surface-active materials isolated from residual beige lungs is greater than three times that of normal lungs. Surface-active materials recovered from beige mice are qualitatively similar in phospholipid composition and in surface activity to materials recovered from normal mice. The quantity of surface-active material phospholipid recovered in the lavage of beige mouse lungs was normal. The basis for the abnormal accumulation of lamellar body lipids is not known.

Animals↗
PubMed1977

Effects of the number of DNP groups on dinitrophenylated human serum albumin upon the induction of immunological memory for the dinitrophenyl determinant.

Immunological memory to the DNP determinant is shown to be a positive correlate of the primary anti-DNP response and of the extent of DNP substitution in the priming antigen. Antigen dose-response curves for immunological memory first increase with antigen dose to reach a maximum and then decrease in the high dose region. Increasing the extent of DNP substitution in the priming antigen shifts the dose-response curves to lower antigen doses and promotes the antigen's ability to induce immunological memory to a level greater than that expected by its ability to induce a primary response. The findings are interpreted in terms of postulated effects of degree of DNP substitution on the binding of antigen to cell receptors.

Antibody Formation↗
PubMed1976

Mouse amyloid protein AA: Homology with nonimmunoglobulin protein of human and monkey amyloid substance.

The major protein extracted from anyloid deposits induced in mice by injection of either Candida albicans cells or sodium caseinate was found to have chromatographic and electrophoretic properties and an amino-acid compostiion characteristic of the AA class of amyloid proteins. The homology of the mouse protein with protein AA from man and monkey was established by determination of the sequence of the first 28 amino-acid residues.

Amino Acid Sequence↗
PubMed1976

Freeze-fracture study of mast cell secretion.

Within seconds after exposure of rat peritoneal mast cells to polymyxin B, bulges appear on the surface of the cells. Freeze-fracture electron microscopy reveals that each bulge overlies a mast cell granule. In contrast to the even distribution of intramembranous particles in the plasma membrane of unstimulated cells, the intramembranous particles in the stimulated cells are unevenly distributed in the membrane of the bulges with large patches of membrane lacking intramembranous particles. The membranes over the most prominent bulges are entirely free of intramembranous particles, and in some instances there is an increased concentration of intramembranous particles at the margins of the bulges. Perigranule membranes exhibit the same changes in distribution of intramembranous particles. Electron microscopy of thin sections of rapidly fixed, stimulated mast cells shows a peculiar structure of the membrane overlying some bulges; instead of the pentalaminar membranes previously demonstrated, the membrane at these sites of presumptive fusion of perigranule and plasma membrane assumes the form of a single dense lamina with a fine fuzzy coating on either side. It seems possible that membrane fusion and subsequent pore formation proceed in the stimulated mast cell through a stage of flight of intramembranous particles and molecular rearrangement of the other membrane components.

Animals↗