Yaacov Matzner

Expression and function of serum amyloid A, a major acute-phase protein, in normal and disease states.

Serum amyloid A (SAA), the precursor protein in inflammation-associated reactive amyloidosis (AA-type), is an acute phase reactant whose level in the blood increases in response to various insults. It is expressed in the liver, but its physiological role is not well understood. Recently, a broader view of SAA expression and function has been emerging. Expression studies show local production of SAA proteins in histologically normal, atherosclerotic, Alzheimer, inflammatory, and tumor tissues. Binding sites in the SAA protein for high density lipoproteins, calcium, laminin, and heparin/heparan-sulfate were described. Adhesion motifs were identified and new functions, affecting cell adhesion, migration, proliferation and aggregation have been described. These findings emphasize the importance of SAA in various physiological and pathological processes, including inflammation, atherosclerosis, thrombosis, AA-amyloidosis, rheumatoid arthritis, and neoplasia. In addition, recent experiments suggest that SAA may play a “housekeeping” role in normal human tissues.

Suppressive Effect of Ferritin on in Vitro Lymphocyte Function

Summary. This study describes the effect of ferritin on lymphocyte function in vitro. Peripheral blood lymphocytes isolated from normal donors were incubated with purified human splenic ferritin, and the mitogenic effect of phytohaemagglutinin (PHA), concanavalin A (Con A), pokeweed mitogen (PWM) and mixed lymphocyte reaction (MLR) were assessed by the uptake of 3H‐thymidine (3H‐TdR). Ferritin (0·25–5·0 μg/ml culture) caused a marked suppression of PHA and Con A blastogenesis but had no suppressive effect on PWM‐induced transformation. Maximal suppression was obtained at a ferritin concentration of 1 μg/ml and this was not enhanced by increasing ferritin concentrations. Ferritin also reduced the Con A capping phenomenon in normal lymphocytes from 22% to 6%, suppressed the MLR reaction but had no effect on the ability of normal lymphocytes to form E, EA and EAC rosettes or on in vitro lymphocyte cytoxicity against the K‐562 cell line. Visual proof of the suppressive effect of ferritin on mitogen induced blastogenesis was provided by scanning electron microscopy, and direct evidence for the ability of lymphocytes to bind ferritin was obtained from studies with radioiodine labelled ferritin. The above findings indicate that ferritin suppresses certain parameters of T‐lymphocyte function in vitro. The relation of the present findings to recognized abnormalities of T‐cell function encountered in certain neoplastic disorders associated with high serum ferritin levels is at present unknown.

Systemic leishmaniasis mimicking malignant histiocytosis

A 22‐year‐old man with fever, hepato‐splenomegaly and severe pancytopenia is described in whom the histologic features of the spleen, liver and lymph nodes were consistent with malignant histiocytosis. Characteristic Leishman‐Donovan bodies were demonstrated on a bone marrow aspirate, and the diagnosis of visceral leishmaniasis was confirmed by culturing the flagellated forms of the pathogen, and by an excellent response to sodium stibogluconate. In view of the similarity in clinical and histologic appearance, visceral leishmaniasis must be considered in the differential diagnosis of malignant histiocytosis in geographic areas where leishmaniasis is still endemic.

Differential effect of isolated placental isoferritins on in vitro T‐lymphocyte function

Summary The effect of isoferritins isolated from human term placenta on certain T‐lymphocyte parameters was studied in vitro using normal human lymphocytes. These isoferritins differed in ion exchange affinity, isoelectric point, and subunit composition. Only the acidic isoferritins caused a marked suppression of phytohaem‐agglutinin (PHA) blastogenesis and the most acidic isoferritin (‘Acid I’) was suppressive at a concentration as low as 0.25 μg/ml. All four isoferritins suppressed concanavalin A (Con A) blastogenesis in a similar concentration dependent manner, with maximum effect at an isoferritin concentration of 1 μg/ml.

The Familial Mediterranean Fever Gene — Cloned at Last

Familial Mediterranean fever is an inherited condition prevalent among people of the Near East — Arabs, Turks, Armenians, and Sephardic Jews.1 Transmitted as an autosomal recessive trait, familial ...

Prognostic Factors in Multiple Myeloma

The prognostic significance of age, sex, ethnic origin and various laboratory data was studied retrospectively in 69 patients with multiple myeloma using conventional statistical tests and the multipl

Anticardiolipin antibodies in acute myeloid leukemia: prevalence and clinical significance.

This prospective study was designed to explore the prevalence and the clinical and prognostic significance of anticardiolipin (ACL) antibodies in patients with acute myeloid leukemia (AML). The study includes 37 consecutive AML patients >15 years old without previous history of thromboembolism, recurrent fetal loss, or autoimmune disease and with no evidence of infection at the time of enrollment. ACL antibodies were found in 25 patients (68%). None of the patients had high positive titers; 8 had moderately positive while 17 had low positive ACL antibody titers. ACL antibody positivity did not predict response to chemotherapy and was not correlated with age, gender, FAB class, platelet and white blood cell counts at presentation, and the risk of thromboembolism. ACL antibody titers did correlate, however, with AML activity in the majority of patients (93%) during 4–19 months of follow up. These results demonstrate a high prevalence of ACL antibodies in AML patients and suggest that serum ACL antibodies may be a useful adjunct in predicting relapse and documenting disease activity and therapy response. Am. J. Hematol. 57:139–143, 1998.

Prevalence and causes of anemia in elderly hospitalized patients.

The prevalence and causes of anemia have been studied in 104 patients over 60 years of age admitted to a general medical ward in Jerusalem. In males and females, mean hemoglobin levels were about 1 g less than in the corresponding groups of healthy younger controls. A primary nutritional anemia could not be implicated in any of the 15 patients with hemoglobins below 11 g/dl. The most important causes of anemia were chronic renal failure, metastatic carcinoma, gastrointestinal bleeding, and infection. Conversely, in diseases with no adverse effect on erythropoiesis such as chronic ischemic heart disease, hypertension and diabetes, hemoglobin levels were equal to those of the younger controls. These findings indicate that although diminished serum iron and RBC folate levels may occasionally be found in elderly subjects, nutritional deficiency is seldom responsible for anemia in this age group in Israel- and anemia when present is often the manifestation of a chronic underlying disease.

Cerebrospinal fluid ferritin in malignant CNS involvement

Cerebrospinal fluid (CSF) ferritin was measured in patients with benign inflammatory and noninflammatory neurologic disorders and in patients with malignant disease with and without documented central nervous system (CNS) involvement. CSF ferritin levels were increased in the majority of patients with inflammatory neurologic disease and in patients with malignant involvement of the CNS. In contrast, in patients with noninflammatory neurologic disorders and in malignant disease without CNS involvement, CSF ferritin levels were normal. These findings indicate that although the specificity of CSF ferritin measurement is limited, it is a highly sensitive test that may be useful in the initial evaluation of patients with malignant CNS involvement, and in assessing their response to therapy.

Chronic lymphocytic leukemia presenting with extreme hyperleukocytosis and thrombosis of the common femoral vein

Very few case reports dealing with chronic lymphocytic leukemia (CLL) and hyperleukocytosis have been reported in the medical literature and none with venous thrombosis as a complication. Here, we describe a 73-year-old woman who presented with newly diagnosed CLL, leukostasis, and hyperleukocytosis (2000 × 10 9 /l), affecting the respiratory and nervous system. In addition, she also had deep vein thrombosis (DVT). Although hypercoagulability and thrombosis are well-described phenomena in solid tumors and in myeloproliferative neoplasms, CLL is generally not associated with an acquired coagulopathy. We hypothesize that in our patient the extreme number of circulating lymphocytes resulted in an abnormal accumulation of lymphocytes possibly causing stasis and occlusion of a larger vessel, which resolved after leukopheresis. The patient has since been successfully maintained with chemotherapy. We conclude that leukopheresis should be considered as the therapy of choice in CLL patients presenting with major complications of leukostasis.