A study of the cellular and humoral immune response in patients with myelofibrosis

There was evidence of impaired cellular immunity in 10 patients with myelofibrosis. In-vitro lymphocyte transformation with phytohaemagglutin, concanavalin A, and dinitrochlorobenzene skin reaction were diminished. Signs of impaired humoral activity were also found, the primary response to a-Helix pomatia haemocyanin being impaired, particularly in the immunoglobulin-A class. Moreover three patients had a benign paraproteinaemia. Immune-complexes (1C) could be demonstrated with various test systems. The indirect granulocyte phagocytosis test was positive in 50%, the Clq-binding in 70% and the polyethylene glycol precipitation test in 50%. In most patients complement levels were normal, although the patient with the most advanced disease had low C3A, C3 and C4 levels accompanied by high levels of IC. No correlation could be shown between impaired immune response or levels of IC when they were related to spleen diameter or degree of anaemia. Some relation however existed between disturbed immune response and IC when they were related to time elapsed since diagnosis. It is suggested that the impaired immune response is the result of primary bone marrow disease and that the presence of IC may reflect the extent of fibrosis.     

Allergen challenge primes for IL-5 mRNA production and abrogates β-adrenergic function in peripheral blood T lymphocytes from asthmatics

BACKGROUND: In previous studies, we have found a dysfunctional adenylyl cyclase (AC) system in patients with asthma after allergen provocation, which resulted in a 40-50% decreased generation of intracellular cAMP. In addition, in activated T helper lymphocyte clones, it has been demonstrated that IFN-gamma (TH1-like cytokine) and IL-5 (TH2-like cytokine) are differentially regulated by the AC system. Therefore, we postulate that an increased IL-5/IFN-gamma ratio as observed in asthmatics might be due to a dysfunctional AC system. OBJECTIVE: To assess whether a dysfunctional AC system as observed in asthmatics after allergen provocation, is responsible for an increased IL-5/IFN-gamma cytokine ratio. METHODS: Peripheral blood T lymphocytes of seven asthma patients were stimulated with anti-CD3 plus anti-CD28 MoAbs in the absence and presence of isoproterenol (ISO) and prostaglandin E2 (PGE2) to activate the AC system. Before, 3 h and 24 h after allergen provocation, IFN-gamma and IL-5 mRNAs were detected by semiquantitative RT-PCR. RESULTS: Before allergen provocation, ISO (10-5 mol/L) significantly downregulated IFN-gamma mRNA (P < 0.03, n = 6), and showed a trend to upregulate IL-5 mRNA (P = 0.138, n = 5). Three and 24 h after allergen provocation, ISO was not longer able to modulate IFN-gamma and IL-5. In contrast with the observations with ISO, PGE2 still dose-dependently inhibited IFN-gamma mRNA, both before, 3 h and 24 h after allergen provocation (n = 7). IL-5 mRNA, but not IFN-gamma mRNA, was significantly upregulated in anti-CD3 plus anti-CD28-activated T cells (P < 0.05, n = 5) 24 h after allergen provocation, compared with before allergen provocation. CONCLUSION: Twenty-four hours after allergen provocation, a significant reduction of beta-adrenergic control on IFN-gamma and IL-5 mRNA expression was observed in peripheral blood T lymphocytes, which coincides with a selective priming of IL-5 mRNA production.     

A syndrome of liver damage and intravascular coagulation in the last trimester of normotensive pregnancy. A clinical and histopathological study

Summary. Six women without hypertension or proteinuria, admitted for severe upper abdominal pain in the third trimester of pregnancy had elevated serum liver enzymes (SGOT, SGPT), markedly increased serum LDH levels, thrombocytopenia and abnormal blood coagulation tests, in particular low antithrombin III levels, indicating disseminated intravascular coagulation (DIC). Liver biopsies showed periportal and/or focal parenchymal lesions with large fibrin deposits, comparable to the liver lesions in eclampsia. Immunofluorescence (IF) showed microthrombi and large fibrin deposits. Three of the six women recovered spontaneously before delivery; in the remaining three all signs and symptoms rapidly disappeared after delivery. Perinatal outcome was poor. Seven women with pregnancy-induced hypertension and elevated serum liver enzymes constituted a reference series. Histopathological examination of liver biopsies in the reference group revealed periportal and/or focal parenchymal lesions in three whereas IF showed fibrin deposition in all seven, but less extensive than in the study group. The present findings indicate that upper abdominal pain in the last trimester of pregnancy can be caused by a syndrome of (pre) eclamptic liver damage and DIC, even when hypertension and proteinuria are lacking.     

Relation Between Signs and Symptoms in Paget's Disease of Bone

The relation between signs and symptoms of Paget's disease ofbone was studied in 180 patients consecutively submitted fortreatment. In these patients 826 lesions were identified byscintigraphy. The intensity of scintigraphic uptake was correlatedwith long-term calcium uptake in bone. The frequency distributionof lesions over the patients was compatible with a 65 per centchance of local disease once the patient had been exposed toan extraneous agent. The spatial distribution within a skeletonwas related to the local density of the osteoclast population.The particular frequency distribution resulted in a log-normaldistribution diagram for anatomical spread. Within lesions,increases in numbers of osteoclasts and osteoblasts were proportionaland these too had a log-normal distribution. Increases of alkalinephosphatase levels and hydroxyproline excretion were closelyrelated and reflected anatomical spread on the one hand andlocal activity on the other. They were also closely correlatedwith overall calcium fluxes. It was shown that alkaline phosphataseis the more sensitive and hydroxyproline the more accurate ofthe biochemical signs. Maximum values, corresponding to totalskeletal disease, were aproximately 25 times the upper limitof normal. Equilibrium between bone formation and resorptionwas not always maintained. There were, indeed, wide variationsof urinary calcium, which were significantly related to thedifference between bone formation and resorption, but the extracellularcalcium homeostasis was generally maintained. This may explainthe frequent occurrence of normocalcaemic and hypercalcaemichyperparathyroidism. The hypercalciuria constitutes an additionalrisk for urolithiasis in men. The most frequent complaint waspain (86 per cent). Extent of lesions was important, but a majordecisive factor was the specific nature of the bone affected.The findings allowed assessment of the relative importance ofthe various signs, symptoms and locations as criteria of diseaseseverity and as indications for treatment.