Histamine release from human leukocytes: modulation by a cytochalasin B-sensitive barrier

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Abstract

Cytochalasin B, a metabolic product of several fungi, enhances up to 10-fold the sensitivity and reactivity of human leukocytes to antigen E or anti-IgE-mediated histamine release. The effect of cytochalasin B is a result of its action on the second, antigen-independent, stage of histamine release. These data suggest that normally, antigen-triggered histamine release is modulated by a cytochalasin-sensitive barrier (CSB). This CSB modulation of histamine release can be separated from the modulating effect of cyclic adenosine monophosphate (AMP).

Authors

Harvey R. Colten, Kenneth H. Gabbay

Predominance of histocompatibility antigen HL-A8 in patients with gluten-sensitive enteropathy

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Abstract

HL-A phenotypes were determined in 24 unrelated patients with gluten-sensitive enteropathy (GSE) using a lymphocyte microcytotoxicity test. 21 of the 24 patients had HL-A8 in the second segregant series, a frequency of 0.875. In contrast, the HL-A8 frequency in 200 normal individuals was 0.215 (difference significant at P < 0.002), and in 6 patients with villous atrophy due to tropical sprue or hypogammaglobulinemia the HL-A8 frequency was 0.17 (difference from normal not significant). The HL-A types in the families of three HL-A8 positive patients with GSE indicated that the HL-A8 antigen was inherited as an autosomal dominant. Frequencies of the other HL-A antigens in the GSE group did not differ significantly from that of the normal group. These findings are compatible with the hypothesis that GSE is due to the presence of an abnormal “immune response (Ir) gene,” leading to the production of pathogenic antigluten antibody or, alternatively, to the presence of a particular membrane configuration leading to the binding of gluten to epithelial cells with subsequent tissue damage.

Authors

Z. Myron Falchuk, G. Nicholas Rogentine, Warren Strober

Biologic effects of 1,25-dihydroxycholecalciferol (a highly active vitamin D metabolite) in acutely uremic rats

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Abstract

The development of a vitamin D-resistant state in the course of renal failure may be responsible for reduced intestinal absorption of calcium and an impaired response of skeletal tissue. Moreover, the kidney has been shown to carry out the conversion of 25-hydroxycholecalciferol (25-OH-CC) to a highly biologically active metabolite, 1,25-dihydroxycholecalciferol (1,25-diOH-CC). In the present studies, vitamin D-deficient rats, made acutely uremic by either bilateral nephrectomy or urethral ligation, received physiological doses of cholecalciferol (vitamin D3) (CC), 25-OH-CC or 1,25-diOH-CC; 24 hr later intestinal calcium transport, in vitro, and bone calcium mobilization, in vivo, were assessed. Whereas CC and 25-OH-CC stimulated calcium transport in sham-operated controls, they were without effect in the uremic animals. In contrast, administration of 1,25-diOH-CC stimulated calcium transport in both groups of uremic animals. Administration of 1,25-diOH-CC also stimulated calcium mobilization from bone in each group of animals. However, CC and 25-OH-CC were only effective in the sham controls and the uremic group produced by urethral ligation and had little or no effect in animals without kidneys. These results indicate that renal conversion of calciferol to a more biologically active form is necessary for the stimulation of intestinal calcium absorption and calcium mobilization from bone, and that 1,25-diOH-CC may bypass a possible defect in vitamin D metabolism in uremia. From these studies it is likely that uremia, per se, may also impair intestinal calcium transport.

Authors

Richard G. Wong, Anthony W. Norman, Chilumula R. Reddy, Jack W. Coburn

Cholesterol distribution in the bulk tissues of man: variation with age

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Abstract

Lacking reliable data on cholesterol concentrations in muscle, adipose tissue, skin, and connective tissues (i.e., the “bulk tissues”) in “normal” man, we have completed these analyses in 21 men and 8 women who died suddenly and unexpectedly; their ages ranged from 23 to 78 yr.

Authors

J. R. Crouse, S. M. Grundy, E. H. Ahrens Jr.

Failure to demonstrate a humoral mechanism in the antinatriuresis of acute caval constriction

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Abstract

Previous studies reported from this laboratory provided support for the hypothesis that the natriuresis of volume expansion is mediated in part by a humoral mechanism. In the present study we examined whether suppression of this factor participates in the antinatriuresis of acute constriction of the thoracic inferior vena cava. An isolated kidney was perfused by a second dog pretreated with deoxycorticosterone acetate. Expansion of the perfusion dog with equilibrated blood from a reservoir resulted in an increase in sodium excretion from 102±30 to 259±65 μEq/min, P < 0.001. Fractional sodium excretion increased from 2.3±0.6 to 6.2±1.2%, P < 0.01. Inulin clearance, plasma protein concentration, and packed cell volume remained constant; renal perfusion pressure and renal blood flow decreased. After the natriuresis was established, the thoracic inferior vena cava was constricted to decrease systemic arterial pressure in the perfusion dog 50 mm Hg. This maneuver suppressed urine output in the dog but did not significantly alter sodium excretion in the isolated kidney. During the period of caval constriction absolute sodium excretion in the isolated kidney measured 198±42 μEq/min and fractional sodium excretion measured 5.7±1.1%. Neither value is significantly different from that measured during volume expansion alone. The data suggest that the antinatriuresis of acute caval constriction probably does not require suppression of a humoral natriuretic factor and that other more rapidly acting mechanisms, presumably hemodynamic and neural, may be involved.

Authors

George J. Kaloyanides, Maher Azer

Thyrotropin Increases Prostaglandin Levels in Isolated Thyroid Cells

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Abstract

We have shown that two unrelated prostaglandin antagonists block both thyrotropin (TSH) and prostaglandins E (PGE1, PGE2) stimulation of thyroidal adenyl cyclase activation and cyclic 3′,5′-adenosine monophosphate (cAMP) formation, suggesting that prostaglandins play an important role in regulating thyroid function. To further explore this postulate, we measured prostaglandin content by radioimmunoassay in homogeneous bovine thyroid cell preparations in the presence and absence of TSH. Antibodies to albumin-conjugated PGE1 and PGF2α showed specificity for prostaglandins E and F, respectively, but reacted, albeit far less effectively, with heterologous prostaglandins. A double antibody system was used to separate free from antibody-bound PGE1-3H and PGF2α-3H. Thyroid cells were extracted with ethanol/ethyl acetate and the various prostaglandins separated on silicic acid columns. Recoveries of added PGE1-3H and PGF2α-3H through the extraction and separation procedures ranged from 50-80%. The sensitivity of the method was 10-50 pg. Basal thyroid cell content of PGE1 and PGF2α “equivalents” varied between cell preparations (range = 2-6 ng/0.2 ml cell suspension) but, in each instance, remained constant during 5-30-min incubations at 37°C. TSH, 10-100 mU/ml, increased the levels of cell PGE1 and PGF2α “equivalents” 30-80% above basal during 5-15-min incubations. The stimulatory effect was specific for TSH, no increase in PGE1 or PGF2α “equivalent” levels being seen with luteinizing hormone (LH), human growth hormone (HGH), adrenocorticotropic hormone (ACTH), or glucagon. These data support the thesis that prostaglandins may mediate TSH effects on thyroid.

Authors

S.-C. Yu, L. Chang, G. Burke

Immunoglobulins on the Surface of Lymphoid Cells in Waldenström's Macroglobulinemia

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Abstract

Immunofluorescence study of viable and fixed cells was performed on marrow and blood samples from 25 patients with Waldenström's macroglobulinemia. Whereas intracytoplasmic staining for IgM was restricted to the plasma cells and to a limited number of lymphocytic cells, the vast majority of the pleomorphic “lymphoid” proliferating cells in the marrow were shown to bear the monoclonal IgM on their surface. All IgM-secreting plasma cells displayed membrane positivity. Most lymphocytic proliferating cells carried the monoclonal IgM on their surface in the absence of detectable amounts of intracytoplasmic IgM. Despite the usual absence of increase in blood lymphocyte counts, a large number of circulating lymphocytes were shown to bear membrane-bound monoclonal IgM in patients with active disease. The number of fluorescent spots, their size and brightness varied greatly from cell to cell in marrow and blood samples of a given patient, and this finding is in contrast to the homogeneous fluorescent pattern observed in chronic lymphocytic leukemia. The data suggest that macroglobulinemia represents the proliferation of a clone of B cells which continues to mature and differentiate.

Authors

Jean-Louis Preud'homme, Maxime Seligmann

Functional Evaluation of Prolactin Secretion: a Guide to Therapy

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Abstract

Stimulation and inhibition tests are proposed for evaluating prolactin secretion. Thyrotropin-releasing hormone (TRH) stimulates the release of prolactin from the pituitary. Chlorpromazine acts presumably at the hypothalamic level to increase prolactin secretion. L-Dopa (D,L-α-hydrazino-α-methyl-β-[3,4-di-hydroxyphenyl]) has the opposite effect; it inhibits prolactin secretion and may be effective in suppressing galactorrhea.

Authors

H. Friesen, H. Guyda, P. Hwang, J. E. Tyson, A. Barbeau

Erythrocytosis in Spontaneously Hypertensive Rats

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Abstract

During the study of an inbred strain of Wistar rats which spontaneously develop hypertension when they reach a weight of approximately 150 g, it was found that these animals also develop an erythrocytosis. A significant increase in red cell count was observed in spontaneously hypertensive (SH) rats (8-11 × 106 RBC/mm3) when compared with normotensive rats (6-7 × 106 RBC/mm3) of the same strain. This increase in red cell count paralleled the increase in body weight and the rise in blood pressure.

Authors

Subha Sen, George C. Hoffman, Nicholas T. Stowe, Robert R. Smeby, F. Merlin Bumpus

Prostaglandins and Their Effects on Human Placental Adenyl Cyclase

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Abstract

Prostaglandins increased adenyl cyclase activity in human term placental homogenates in a dose-dependent manner during 10-min incubation periods. The potency of the prostaglandins examined was demonstrated to be in the ascending order, prostaglandin F1α < A2, F2α, B2 < A1 < E2 < E1. Although no specific trophic or regulating factors for placental function have been described as yet, it is possible that prostaglandins which are synthesized in decidual tissue could play such a physiological role.

Authors

Kazuo Satoh, Kenneth J. Ryan