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Doppler spectra were recorded at different cyclosporin A (CSA) levels (trough and peak) in 30 stable renal-transplanted outpatients: 15 with unimpaired renal function (plasma creatinine < 150 mumol/l) and 15 with renal impairment (plasma creatinine 150-350 mumol/l). Pulsatility (PI) and resistive indexes (RI) have been measured in the renal artery at the hilum and in the renal cortex. RI and PI were markedly increased (p < 0.0001) in the cortex at peak time while in the renal artery no significant changes were observed. These variations were statistically related with CSA blood levels (PI = p < 0.02; r = 0.54, RI = p < 0.05; r = 0.45). These effects were also found in the presence of renal damage. CSA dose-dependently reduces cortical blood flow, causing a persistent arteriolar vasoconstriction and a reduction in diastolic flow. This effect can be measured in man in a noninvasive and repeatable way using color Doppler sonograms.

A new case of IgE myeloma is described. A 77-year-old woman presented with bone pain and fatigue. Serum protein analysis revealed a paraprotein of the IgE kappa type; bone marrow aspirate and immunofluorescence confirmed the diagnosis; ultrastructural examination showed immature plasma cells. Treatment with prednisone, melphalan, cyclophosphamide and interferon alfa did not produce any improvement and the patient died 5 months after diagnosis. The patient's clinical and laboratory data are compared with those of IgE myeloma cases reported in the literature.

Circulating immune complexes were detected in the sera of 7 patients with hypergammaglobulinemic purpura of Waldenström by the following methods: KgB-SP, mRF-LIA, Cc test, ClqBA. Analytical ultracentrifugation showed intermediate complexes between 7S and 19S (16S-19S); simple immunodiffusion of the complexes, purified by 2.5% PEG precipitation, revealed the presence of IgG3, IgA, IgM, Clq, C3 and C4. Constant high titers of rheumatoid activity in the sera in toto and after purification, and normal serum complement levels were also detected.

Human one-way mixed lymphocyte culture induces a significant increase of EA(7S) rosette-forming cells. Using fractionation procedures, an increased number of Fc receptor-bearing cells in the T high-enriched populations was found from alloactivated lymphocytes compared with similar fractions obtained after autologous control cultures. Additional experiments showed a parallel increase of E-rosette-forming cells in the Fc receptor-enriched alloactivated fractions. The results indicate that an increase of T.G lymphocytes occurs during in vitro alloactivation in man.

In a case series of 56 patients with essential cryoglobulinemia, 35 were followed-up for 4-13 years (mean 7 years). A membranous proliferative glomerulonephritis, which in about half the cases showed a progression to renal insufficiency, was the commonest complication, observed in more than one third of the patients. In 2 patients hepatic cirrhosis became manifest after a completely asymptomatic period and in 2 others a lymphoproliferative disease appeared 2 and 8 years after the onset of purpura. In 51% of patients the intial clinical pattern did not change. In searching for a correlation between the development of nephropathy and cryoglobulin characteristics, none was demonstrated studying the cryoglobulin level, the presence of autoantibody and the complement components.

Basophil releasability was studied in 24 cord blood samples from normal-term deliveries. The histamine content in cord blood basophils was similar to that of adult blood basophils. The response to IgE-independent degranulating stimuli such as calcium ionophore A23187 and zymosan-activated human serum was overlapping with that of normal adults. Conversely, a reduced releasability was observed after challenge with anti-IgE, even after sensitization with an IgE-rich serum. The IgE-dependent degranulation seems to be hampered by the low concentrations of circulating and cell-bound IgE antibodies. The number of IgE molecules bound to the specific receptors in cord blood basophils is significantly lower than in adult blood basophils.

This study was performed to evaluate mediator (histamine and leukotriene C4) release from cord blood and adult blood basophils, challenged with IgE-independent (calcium ionophore A23187) and IgE-mediated (anti-IgE) stimuli. IgE-independent mediator release was similar in adult blood and umbilical blood basophils. Conversely, the anti-IgE-induced histamine and immunoreactive leukotriene C4 (iLTC4) release was significantly reduced in cord blood basophils. Passive sensitization with an IgE-rich serum was followed by a significant increase in the number of eluted IgE molecules from cord blood basophils and by an increase in IgE-mediated histamine release. iLTC4 production was not affected by passive sensitization of umbilical blood basophils. The IgE-dependent mediator release from cord blood basophils was not correlated with the number of cell-bound IgE. In addition, histamine secretion and leukotriene C4 production from cord blood basophils seem to be independent events.

The clinical and immunochemical classification of 166 patients with cryoglobulinemia are presented. 52% of the cryoglobulins were detected in patients hospitalized because of various causes. The most frequent association was with liver and lymphoproliferative diseases (in particular with Waldenström's macroglobulinemia); two thirds of the patients with liver diseases presented with a purpura-arthralgia syndrome, and the hepatic involvement was only brought to evidence by subsequent laboratory investigation. The presence of cryoglobulins did not usually interfere with the clinical course of the basic condition. In 79 patients the cryoglobulinemia was considered idiopathic. In order to study the natural course of the disease in the idiopathic cases, a group of 35 patients had been followed up for 8-17 years: 37% developed a membranous proliferative glomerulonephritis, and more than half died of renal insufficiency; in 11% cirrhosis was diagnosed after a period of 4-9 years; another 11% developed a lymphoproliferative disease; of the remaining 40%, 2 are still asymptomatic, and the others are affected by purpura-arthralgia syndrome.

HLA phenotype distribution was investigated in 91 affective patients. Significant increases over those of the control population were found in HLA-A 29 and in Bw 22 frequencies, while A 10 and A 30 were decreased. No significant difference was shown between the two clinical subgroups (41 unipolar patients and 50 bipolar ones). On comparing our data with those from other authors, Bw 16 was significantly increased. However, a high degree of heterogeneity was also shown for this antigen. Of some interest is the finding that relapsed and non-relapsed patients during long-term lithium therapy display diverging HLA phenotype distributions, with B 5 increased among the non-relapsed subjects.

Local antigen challenge in patients with respiratory allergy is associated with histamine and arachidonic acid metabolites release, both in upper and in lower respiratory airways. Raised histamine levels can be detected in nasal secretions 5 min after allergen stimulation. Increased leukotriene C4 and prostaglandin D2 concentrations persist for a longer period (respectively 20 and 30 min). Endobronchial antigen stimulation is also followed by release of histamine, leukotriene C4 and prostaglandin D2, which can be detected in bronchial lavage fluid. Elevated concentrations of these mediators can be found 5 and 15 min after challenge. Moreover, endobronchial antigen stimulation is associated with an increase in the number of bronchial epithelial cells recovered in bronchial lavage fluids.

In 20 patients with nephrotic syndrome (10 minimal change glomerulonephritis, MCN; 10 focal glomerulosclerosis, FGS) the peripheral blood lymphocytes showed a statistically significant increase in IgG-bearing cells (SIgG-C) in comparison with 30 patients with other histological types of primary glomerulonephritis with and without nephrotic syndrome (14 and 16, respectively). In the same MCN and FGS patients the serum IgG levels were slightly decreased. Furthermore, 5 cases of MCN in sustained remission for 1 year after steroid therapy showed normalization of the SIgG-C and the serum IgG levels. The possible significance of these phenomena in the pathogenesis of the hypo-IgG-globulinemia in MCN and FGS is discussed.

Anti-gamma-globulin activity, free DNA, and DNA binding were studied in 19 cryoglobulinemias: 8 patients with Waldenström's disease (WD), 9 patients with essential cryoglobulinemia (EC), and 2 with chronic aggressive hepatitis (CAH). Antihuman gamma-globulin activity was detected in all sera and dissolved cryoprecipitates but two from EC and one from the CAH group. By diphenylamine assay we found DNA in two sera from WD and in one serum and cryoprecipitate from EC. An antibody to denaturated DNA was shown only in sera from the two patients with CAH and from one patient with EC. Nonspecific binding was more frequent.

Transmembrane calcium flux is a critical step in basophil and mast cell activation and subsequent histamine release. This calcium flux is likely to take place through specialized membrane ion channels. Two types of calcium channels have been described so far: the first type is voltage operated and the second type is receptor operated. Depolarization of cell membrane by K+-rich solutions is followed by voltage-operated channel opening in excitable cells, such as smooth muscle cells. We evaluated whether high K+ extracellular concentrations can trigger basophil activation and histamine release. We found that human basophil leucocytes, showing a normal response to activating signals, such as anti-IgE antiserum and formylmethionine peptide, release no histamine when exposed to K+-rich media, alone or in combination with the K+ carrier valinomycin. These results are consistent with there being receptor-operated, but not voltage-operated, calcium channels in the basophil leucocyte plasma membrane.

Basophil activation, observed in patients with idiopathic mixed cryoglobulinemia, has been related to the complement anaphylatoxins C4a, C3a and C5a. In the present study the plasma levels of the complement anaphylatoxins have been evaluated in 21 patients affected with idiopathic mixed cryoglobulinemia. The plasma concentration of C3a desArg was significantly higher in the patients than in the healthy controls; conversely the plasma values of C4a desArg were significantly lower. C5a desArg was not detectable in plasma from any subject. The high plasma level of C3a desArg in our patients may suggest a role for C3a anaphylatoxin in 'in vivo' basophil activation. No correlation was found between the plasma concentrations of C3a desArg or C4a desArg, the amount of cryoprecipitate and the clinical activity of the disease.

In 5 patients with mixed cryoglobulinemia, 3 with Waldenström's disease and 2 with essential cryoglobulinemia, a C1-inhibitor (C1-INH) deficiency was discovered. The complement profile was characteristic of the acquired type: the total hemolytic activity and the early components were reduced, C3 was diminished in 1 patient only, C5 and C9 were normal or elevated. 1 atient with Waldenström's disease and 1 with essential cryoglobulinemia experienced episodes of angioedema. Circulating immune complexes were found in all patients' sera by the 125I-radiolabelled C1q binding activity (C1q BA) test. The values of the C1q binding activity were correlated with the depletion of the early complement components and that of C1-inh. 4 patients showed circulating 7S IgM. Our data support the hypothesis of a complement activation by the cryoprecipitating immune complexes; the C1-INH depletion is secondary to its consumption following C1 activation.