A COMPARATIVE STUDY OF THE SAFETY AND EFFICACY OF DYSPROSIUM-165 HYDROXIDE MACRO-AGGREGATE AND YTTRIUM-90 SILICATE COLLOID IN RADIATION SYNOVECTOMY--A MULTICENTRE DOUBLE BLIND CLINICAL TRIAL

The aim of our study was to compare the safety and efficacyof a new preparation, Dysprosium-165 Hydroxide Macro-aggregate(¹⁶⁵Dy) with Yttrium-90 Silicate (⁹⁰Y) for radiation synovectomyof the knee in patients with RA and OA. A multicentre doubleblind clinical trial with subjects randomized to receive ¹⁶⁵Dyor ⁹⁰Y was undertaken in Sydney, Melbourne and Perth. Seventyknees of 59 patients were studied, using as clinical end pointmeasurements pain in the knee on walking, pain in the knee atrest and stiffness in the knee after rest. Cytogenetic damage,knee retention and extra-articular spread of the radionuclideto regional lymph nodes, liver, urine and blood were evaluated.There was no significant difference in clinical response inthe two treatment groups for either RA or OA. Chromosomal changesoccurred with equal frequency and the knee retention and extra-articularleakage of radiocolloids to regional lymph nodes and liver werecomparable in the two groups. For radiation synovectomy of theknee, ¹⁶⁵Dy is at least as safe and as effective as ⁹⁰Y andhas the advantage of a short half-life (2.334 h) and hence requiresa shorter period of post-injection immobilization and hospitalization. KEY WORDS: Radiation synovectomy, Dysprosium-165, Yttrium-90, Rheumatoid synovitis, Osteoarthritis     

Immunological properties of recombinant proteins of the transmission blocking vaccine candidate, Pfs48/45, of the human malaria parasite Plasmodium falciparum produced in Escherichia coli

A precondition for the development of a transmission blocking vaccine based on the sexual stage-specific surface antigen Pfs48/45 of Plasmodium falciparum is its heterologous synthesis in a native state. Here we describe the production of recombinant Pfs48/45 in Escherichia coli . Two recombinant proteins, of which one is a glutathione-S-transferase fusion protein, were produced. Enzyme-linked immunosorbent assays showed that at least a subfraction of the recombinant proteins had a conformation capable of binding transmission blocking monoclonal antibodies. However, despite the fact that both proteins were very immunogenic, they did not induce transmission blocking immunity in mice or rabbits. Immunological studies with congenic mouse strains demonstrated that immune responses could be boosted with gametocyte extracts and were not restricted to a particular class II major histocompatibility complex haplotype .     

E-SELECTIN EXPRESSION IN EXPERIMENTAL MODELS OF INFLAMMATION IN MICE

E-selectin (CD62E, formerly termed ELAM-1) is a cytokine-inducible adhesion molecule which mediates the binding of neutrophils, monocytes, and skin homing T-cells. The murine homologue of E-selectin has been cloned. A monoclonal antibody (21KC10) was used here to study immunohistochemically the expression and regulation of murine E-selectin in vitro and in vivo . As described for the human system, there was no staining of normal endothelium in skin and other tissues. LPS and tumour necrosis factor-alpha (TNF-α ), but not interleukin-4 (IL-4) or interferon-gamma (IFN- γ), induced a transient expression of E-selectin, both when injected in vivo and when added to endothelial cell lines in vitro. To analyse temporal expression of E-selectin under pathophysiological conditions in vivo, we chose two murine models of inflammation: allergic (ACD) and irritant contact dermatitis (ICD). Expression of E-selectin was found to be induced on vascular endothelium of post-capillary venules in both ACD and ICD. In ICD, maximal staining of endothelial cells occurred earlier than in ACD. Expression of E-selectin during ICD and ACD was then compared between strains of mice which differ with regard to the intensity of their inflammatory reaction. BALB/c mice, which in contrast to C57BI/6 mice show a denser infiltrate and prolonged influx of granulocytes and monocytes, revealed a more pronounced and more prolonged expression of E-selectin than C57BI/6 mice. This held true for both ACD and ICD, and in each case, peak expression of E-selectin was associated with the highest density of the leukocytic infiltrate. This study thus reveals regulatory mechanisms involved in the expression of murine E-selectin in vivo and in vitro . It also demonstrates a correlation between endothelial expression of E-selectin and the genetically determined intensity of the inflammatory response.     

Familial Hemolytic Anemia with Erythrocyte Inclusion Bodies and a Defect in Pigment Metabolism

1. Two patients, a father and his only son, suffered from a severe congenitalhemolytic syndrome, which was characterized by the presence of spontaneousinclusion bodies in erythrocytes and by the excretion of dark-brown pigmentsin the urine.

2. The inclusion bodies present in approximately one-third of the erythrocytes, were indistinguishable from Heinz-Ehrlich bodies. They occurred inreticulocytes and occasionally in normoblasts. In addition to these bodies,many erythrocytes contained basophilic stippling, siderocytic granules androd-like structures. These morphologic abnormalities are believed to be theresult of an inherited metabolic abnormality of the red cells.

3. The urinary pigments were found to have properties which were similarto mesobilifuscin. It is believed that these pigments possessed a dipyrrolicstructure and were derived from erythrocyte catabolism.

4. Transfusion of the patient’s erythrocytes into a normal recipient resultedin rapid removal of the heterologous cells from the circulation and in excretion of similar dark pigments in the urine.

Submitted on November 4, 1958 Accepted on November 30, 1958     

MEASUREMENT OF 1,25-DIHYDROXYCHOLECALCIFEROL IN MAN BY RADIOIMMUNOASSAY

1 alpha, 25-Dihydroxycholecalciferol (1,25-(OH)2D3) has been measured in human serum by radioimmunoassay. The assay uses a high titre antiserum raised in sheep against 1,25-(OH)2D3-25-hemisuccinate, conjugated to bovine serum albumin. The sensitivity of the assay is 10 pg/tube. Other hydroxylated forms of vitamin D3 cross react with the antiserum and are therefore removed from serum extracts by chromatography on Sephadex LH 20 followed by high pressure liquid chromatography. The mean (+/- SEM) serum 1,25-(OH)2D3 concentration for a group of healthy adult subjects was 41 +/- 2.5 pg/ml. None was detected in anephric patients and the concentration was low or undetectable in patients with chronic renal failure.     

Total serum haemolytic complement activity, erythrocyte sedimentation rate and plasma fibrinogen as indicators of the stage in Hodgkin''s disease

Total serum haemolytic complement activity, plasma fibrinogen, erythrocyte sedimentation rate and other biological values in forty-three patients with Hodgkin's disease were correlated with results of staging. A highly significant increase (P=10(-5)) of the mean total serum haemolytic complement activity was found in stages IIIA and IVA and in all stages with systemic symptoms. The complement activity in patients with less extensive disease without systemic symptoms (stages IA and IIA) did not show a significant increase over the controls. The best initial parameters correlating well with disease activity were complement activity, ESR and fibrinogen level. It is concluded that total serum haemolytic complement activity gives additional information and can be helpful in differentiating between favourable and unfavourable forms of Hodgkin's disease.