Alison May

Uptake and intracellular distribution of iron from transferrin and chelators in erythroid cells.

SummaryIron chelators of different physicochemical properties were studied for their ability to donate iron in vitro to uninduced K562 cells, human bone marrow cells and purified human erythroblasts. To a large extent uptake was found to be related to lipophilicity and those chelators able to deliver iron to the cells in significant amounts were also able to deliver iron to ferritin and haem. Some differences in the distribution of iron delivered was observed but no chelator showed exclusive delivery to or rejection of a particular cellular iron compartment. Several chelators could probably substitute for transferrin and be used to probe metabolic events subsequent to iron removal from transferrin. Two chelators which were excellent iron donors were also found to cause considerable inhibition of iron incorporation into haem from transferrin. The implications of this for in vivo toxicity are briefly discussed.

Red cell dimorphism in a young man with a constitutional chromosomal translocation t(11;22)(p15.5;q11.21).

SUMMARY. A constitutional, balanced chromosomal translocation t(11;22)(p15.5;q11.21) was discovered in a tall young man during investigation of a red cell dimorphism. The red cells are predominantly normochromic and normocytic with a small population of hypochromic, microcytic cells. Contained within the regions involved in the translocation are determinants of height (IGF2:11p15.5), red cell haemoglobinization (non‐α globin gene complex: 11p15.5) and oncogenesis (cHa‐Ras‐1, Beckwith‐Wiedemann syndrome: 11p15.5; BCR, Burkitts lymphoma, Ewings sarcoma: 22q11.21). To map these regions in the patient, somatic cell hybrids were generated and cell lines that segregated the chromosomes 11, 22 and 22q‐ were obtained. All 11p15.5 sequences investigated, in particular the whole of the non‐α globin gene complex including its 5’and 3’regulatory sequences, were found to be translocated to 22q‐. All chromosome 22 sequences studied were missing from the 22q‐ cell lines, including the proximal anonymous marker D22S24, and therefore assumed to be translocated to 11p+. These results suggest that the non‐α globin gene complex has been moved close to the centromeric region of chromosome 22q‐. It is postulated that such a positioning subjects the complex to a variegated position‐effect bringing about a clonal exclusion of the complex and thus producing a β‐thalassaemia trait mosaic.

A novel model for differentiation therapy of leukaemia [Abstract]

ul vein thrombosis (PVT) is a relative rare condition affecting both children -. adults. A mutation in factor V gene was described in 20% of the patients , I inherited thrombosis, being the most common hereditary cause of venous --=nboembolism. It has also a high frequency (2 to 7%) among normal cau.ans controls and a low frequency (< 0.1) in black and asian populations. purpose of our study was to determine whether the factor V Leiden mutation xrs commonly in children with PVT. Casuistic: Patient group consisted of 20 ;.:-fen, 76 months (range 2 to 136 months). Diagnosis of PVT was performed ;Y :-%iominal ultrasound. Risk factors which could predispose to PVT were: I natal sepsis by citomegalovirus and rubeola infection at 28 days of life (01 v?), neonatal sepsis at 6 days of life (01 case), onphalocele surgery at one day i3fe (01 case), umbilical catheterization and previous citomegalovirus infection case), blastomicosis (01 case), and an antecedent of hospitalization of inAtermined cause at 3 days of life (01 case). Familial antecedent for thrombosis