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Biomedical subjects

J Denburg

Publications and source records attributed to J Denburg.

34 records · Page 2Linked to original sources
PubMed1987

Neuropeptides and immunity.

Our studies have clearly shown that neuropeptides have a profound effect on immunoglobulin synthesis both in vivo and in vitro. The effects varied according to the neuropeptide added or the tissue from which the lymphocytes were obtained. Substance P caused the most pronounced enhancement of both functions, especially in Peyer's patch cells, where it selectively increased IgA synthesis. Somatostatin was inhibitory, and the effect of vasoactive intestinal peptide varied according to the source of the cells. We have previously shown that neuropeptides also cause mast cell secretion and that only substance P was effective in this regard on intestinal mucosal mast cells. Therefore, we looked for microanatomic relationships between peptidergic nerves and immune effector cells. Mast cells appear to have structural associations with neuropeptides-containing nerves in the intestine. Nerve growth factor, known to promote the growth of sensory afferent and sympathetic nerves, has significant direct effects on mast cells. In vitro, this substance caused enhanced antigen mediated histamine release and, in vivo, extensive mast cell hyperplasia. Also, in humans, we were able to produce increased numbers of mast cell/basophil colonies from peripheral blood in the presence of nerve growth factor.

Animals↗
PubMed1987

Mast cell involvement in various inflammatory processes.

Mast cells from different tissue sites may have different histochemical, chemical, and functional properties. Whatever the basis for these differences, they must be important in terms of their biologic significance. Through their mediators, mast cells are involved in many different acute and chronic inflammatory processes. They act in delayed hypersensitivity, immediate hypersensitivity, and in granulomatous reactions. They can influence phagocytosis, chemokinesis, and many aspects of immune activity in several different T and B cell pathways, to mention only a few effects. Mast cells are involved in repair processes including fibroblast function and fibrosis. Their growth may be influenced by T cell-derived factors as well as factors derived from the epithelium. They appear to be intimately involved with nerves and can form apparent communications with neurones, especially those containing Substance P, which causes all types of mast cells to degranulate. Mast cells may therefore act as central switchboards between the central nervous system and migrating and sessile cell types in inflammatory processes.

Animals↗
PubMed1986

In vitro appearance of large human histamine-containing basophilic cells.

The appearance of large human basophilic cells containing histamine was followed to reflect cell maturation in cultures of peripheral blood leukocytes. Aliquots were taken on day 0 and after 7, 9-10 and 14 days in culture, and the basophilic cell numbers were determined in 200 microliter cytospin specimens stained with Wright's stain. The number of small basophils initially present declined during the culture period. The number of spontaneously appearing large basophilic cells varied among the cultures from different individuals and was slightly, though not significantly, higher in atopic individuals than in normals. In cultures of cells from atopic individuals, the number of large basophilic cells was reproducibly increased by the addition of appropriate allergen to the cultures. In cultures of cells from normal individuals, the number was increased two- to six-fold by adding conditioned medium (CM), either from 3-day cultures of cells from atopic individuals stimulated with allergen or with CM from the Mo T cell leukemic line. The addition of mitomycin C decreased the number of large basophilic cells and cycloheximide abrogated their appearance.

Allergens↗
PubMed1986

Peripheral blood basophils, basophil progenitors, and nasal metachromatic cells in allergic rhinitis.

Relationships among mature blood basophils, blood basophil colony-forming units in culture (CFU-c), and nasal metachromatic cells (NMC) were investigated using hemopoietic and histochemical techniques in 29 patients with allergic rhinitis and in 7 nonatopic control subjects. Total blood granulocyte and basophil CFU-c were significantly elevated in atopy; the highest levels of basophil CFU-c were found in patients with low total NMC counts in nasal scrapings (Group I), compared with those with intermediate (Group II) or high (Group III) counts: 10 +/- 3 basophil CFU-c per 10(6) cells in 10 Group I patients, 4 +/- 2 in 10 Group II patients, 3 +/- 1 in 9 Group III patients, and 0.1 +/- 0.1 in nonatopic control subjects (p less than 0.05). Mean histamine content and frequency of histamine-positive granulocyte colonies correlated with counts of basophils in colonies (r = 0.864, p less than 0.001). Peripheral blood basophils, which stained metachromatically with toluidine blue at pH 0.5 after Mota's lead acetate but not after formalin fixation, were highest in atopic Group III and lowest in Group I; a similar relationship was observed only for NMC, which also failed to stain after formalin fixation. Metachromatic cells in colonies were similar to formalin-sensitive NMC and to peripheral blood basophils in their sensitivity to different fixatives. Nasal symptoms correlated inversely with the number of basophil CFU and directly with the number of either formalin-sensitive NMC or peripheral blood basophils. These findings confirm and extend evidence for increased nasal metachromatic cells, basophilia, and alterations in basophilopoiesis in atopy.

Adolescent↗
PubMed1986

Stimulation of maturation of large immature histamine-containing basophilic cells from human peripheral blood, cord blood and bone marrow.

The development of FcR epsilon-bearing histamine-containing basophilic cells was studied in cultures of peripheral blood leucocytes and bone marrow leucocytes from normal individuals. The determination of basophilic cells was performed blindly. Before cultivation there were fairly similar numbers of basophilic cells in the samples from the three different sources (1.6 +/- 1.6 n = 13; 1.4 +/- 2.0 n = 21; 4.3 +/- 4.7 n = 8, respectively). During cultivation spontaneously appearing large blast-like basophilic cells were seen in good correspondence with a formation of histamine in the cultures (Spearman rank correlation coefficient = 0.9135, n = 13, P less than 0.001). This was more accentuated with bone marrow cells than with peripheral blood and cord blood cells. Conditioned medium (CM) was prepared from cells isolated from various tissues and stimulated by different means, e.g. peripheral blood from atopic individuals stimulated with allergen and unstimulated tonsil cells. Addition of the CM resulted in increased development of histamine-containing basophilic cells. Optimum stimulation was achieved with 10% CM. The basophilic stimulation by CM, as assessed as indices vs. unstimulated cultures, was more accentuated in cultures of peripheral blood cells than of bone marrow and cord blood cells (2.8 +/- 1.2; 1.8 +/- 0.5; 2.0 +/- 0.4, respectively). In contrast, the histamine formation was particularly evident in stimulated cultures of bone marrow cells, where more than four-fold increases of histamine were found. In bone marrow cells the histamine levels per basophilic cell also increased, whereas this was not the case in cord blood cells. A pronounced development of basophilic cells was achieved when using leukoagglutinin, provided the mitogen in the CM was eliminated. The formation of basophilic cells was prevented with mitomycin c and cycloheximide. In conclusion, the system described may provide important information on the development of histamine-containing basophilic cells at various maturation stages from different compartments, and mechanisms in a developing atopic disease.

Basophils↗
PubMed1985

Heterogeneity of metachromatic cells in human nose: significance of mucosal mast cells.

The distribution and abundance of histochemically and morphologically distinct subpopulations of metachromatic cells were investigated in nasal secretions and scrapings from patients with allergic rhinitis, as well as in nasal biopsy specimens from other patients. These analyses of the metachromatic cells demonstrate that basophils and two distinct mast cell populations are present in nasal specimens. One mast cell subpopulation was analogous to the atypical mucosal mast cell of the rat and human intestine, whereas the other cell population was similar to the typical connective tissue mast cell type. In nasal scrapings greater than 80% of the metachromatic cells was mast cells, almost exclusively of the atypical "mucosal" type. However, basophils were the predominant metachromatic cell type in nasal secretions, and atypical mast cells were more abundant than typical mast cells. Few basophils were observed in biopsy specimens, but mast cells were widely distributed in various anatomic compartments. Atypical mast cells outnumbered the typical type in the epithelium and lamina propria, whereas the reverse was true in the submucosa. When the number and type of metachromatic cell in scrapings were analyzed in relation to clinical findings, there was a significant correlation with severity of symptomatology and nasal swelling and pallor. Atypical "mucosal" mast cells were the major cell type in all specimens, from those with mild to those with severe clinical findings. When the distinct spectrum of responsiveness to antiallergic compounds of atypical mast cells is considered, these observations have important therapeutic implications.

Adolescent↗
PubMed1983

Serum lymphocytotoxic antibodies in neuropsychiatric lupus: a serial study.

The pathogenesis of neuropsychiatric (NP) SLE remains speculative. A relationship between circulating brain cross-reactive lymphocyte antibodies (LCA) and NP-SLE has been postulated but serial, prospective study of LCA in individual patients with SLE has rarely been performed. In the current study a group of 34 patients with SLE was analyzed using clinical, neurologic, psychiatric, and neuropsychological examinations, together with routine serological tests, to define NP-SLE. Previous history of alloimmunization was also recorded. LCA were measured by a two-stage microcytotoxicity assay against a panel of 25 normal donor B and T cells, at both 40 and 37 degrees C. LCA by this method were found in the serum of 20/34 (58%) SLE, 2/22 (9%) rheumatoid arthritis, and 3/24 (12%) antinuclear-antibody-positive chronic psychiatric patients (P less than 0.01). Analysis of LCA serially in individual SLE patients revealed: (1) No difference in B- or T-cell reactivity at either 4 or 37 degrees C, (2) no significant correlation between previous alloimmunization and the presence of LCA, (3) fluctuations in LCA associated with NP-SLE relapses or remissions, but not with therapy, in 10 patients prospectively studied. A significant positive association was found between the occurrence of single neuropsychiatric events and serial LCA determinations in 180 sera (P less than 0.000001). LCA as measured in this study appear more frequently in SLE than in controls and may indicate active NP-SLE in some patients. Further study of the pathogenic role and diagnostic value of LCA in NP-SLE, including their relationship to subtle neurocognitive changes, is proposed.

Adolescent↗
PubMed1983

Association of chronic urticaria and angioedema with thyroid autoimmunity.

Seventeen patients, constituting 12.1% of 140 consecutively seen cases of chronic urticaria, demonstrated thyroid autoimmunity with thyroid microsomal antibodies (TMAs) in serum titers greater than or equal to 1:1,600. Eight of these 17 patients had goiter or thyroid dysfunction. In a control group of 477 consecutively seen patients, only 27 (5.6%) had similar TMA titers. Routine and special immunologic test results in this group of 17 patients did not differ from those found in other patients with chronic urticaria and angioedema (CUA), and the only notable clinical feature was that all 17 had angioedema. The age and sex distribution and thyroid features of these 17 patients were similar to those described in autoimmune thyroiditis. Patients (especially women) with CUA should be tested for the presence of TMAs. In this subgroup, CUA may have an autoimmune basis.

Adolescent↗
PubMed1981

Hypersensitivity to tobacco glycoprotein in human peripheral vascular disease.

One hundred and sixty-four patients with peripheral vascular disease (PVD) were skin tested with a purified tobacco glycoprotein (TGP). A basophil degranulation test (BDT) was also performed to assess in vitro reactivity to TGP. Immediate skin test hypersensitivity to TGP was found in 18 of 164 (11%) patients with radiologically demonstrable PVD. BDT was positive in 25/42 (60%) smokers as opposed to 6/23 (24%) nonsmokers (p less than 0.01). Twenty-one of 49 (43%) skin test-negative and 10/11 (91%) skin test-positive patients wih PVD had a positive BDT (p less than 0.02). Only 1/34 (3%) patients with negative BDT had a positive skin test. Skin test-positive patients had significantly higher BDT at 0.01 and 0.001 microgram/ml TGP in vitro compared to skin test-negative patients (p less than 0.01). When PVD was graded by arteriography, one of 11 patients with "mild," 11/87 with "moderate" and 4/20 with "severe" PVD were skin test-positive to TGP (p less than 0.01 "mild" vs "moderate"; p less than 0.05 "mild" vs. "severe"). These differences could not be attributed to age, sex, atopy or smoking status. Reactivity to TGP exists in a proportion of patients with PVD and may be causally related in such cases to the development of atherosclerotic vascular disease.

Adult↗
PubMed1977

Megaloblastic anemia in patients receiving total parenteral nutrition without folic acid or vitamin B12 supplementation.

Pancytopenia developed in four patients receiving postoperatively total parenteral nutrition (TPN). Symptoms and signs were related mainly to underlying bowel disease. Hematologic abnormalities, first noted from 4 to 7 weeks following institution of TPN, consisted of normocytic anemia (mean decrease in hemoglobin value, 2.2 g/dL), occasional macrocytes being noted, leukopenia (range of leukocyte counts, 1.2 to 3.6 X 10(9) L), some hypersegmented neutrophils being detected, and clinically significant thrombocytopenia (range of platelet counts, 25 to 52 X 10(9)/L). In all patients the bone marrow showed megaloblastic changes, with ring sideroblasts, although pyridoxine was included in the TPN regimens. Serum vitamin B12 values were normal in one patient and at the lower limit of normal in the other two patients in whom it was measured, while serum or erythrocyte folate values, or both, were reduced in three patients. Full hematologic response was observed in the four patients after folic acid replacement therapy; leukocytosis and thrombocytosis were noted in three. Thus, folic acid and possibly vitamin B12 should be added routinely to TPN regimens to prevent deficiency of either substance.

Anemia, Macrocytic↗
PubMed1976

Thrombotic thrombocytopenic purpura: a syndrome of intravascular platelet consumption.

In four of five patients with thrombotic thrombocytopenic purpura (TTP) in whom serial tests of hemostatic function were performed, severe thrombocytopenia, normal plasma fibrinogen concentrations and mildly increased concentrations of fibrinogen/fibrin degradation products were observed. Widespread platelet thrombi were found in arterioles and capillaries. Fibrin could be seen around some of the platelet clumps and was the main component in a small number of the thrombi in two patients. The observations show that TTP is a disorder in which intravascular platelet consumption results in disseminated platelet thrombosis. The coagulation system is apparently activated secondarily to platelet aggregation and variable quantities of fibrin are incorporated into the thrombi. Clinical improvement resulted from combined therapy with corticosteroids, heparin and drugs that suppress platelet function.

Adult↗
PubMed1970

Purification of a specific tRNA by Sepharose-bound enzyme.

A new procedure for measuring binding of tRNA to aminoacyl-tRNA synthetases is described. The purified isoleucyl-tRNA synthetase from Escherichia coli can be covalently bound to activated Sepharose with retention of approximately 40% of the original enzymatic activity. If crude tRNA is passed through a small column of enzyme-Sepharose, isoleucyl-tRNA is preferentially retained. The procedure can be used as a means of purifying specific tRNA molecules.

Carbon Isotopes↗