Transfected leukocyte integrin CD11b/CD18 (Mac-1) mediates phorbol ester-activated, homotypic cell:cell adherence in the K562 cell line

The CD11b/CD18 leukocyte integrin molecule mediates diverse neutrophil adherence-related functions, including cell:cell and cell:extracellular matrix attachments. To study the individual role of this leukocyte integrin in cell adherence in hematopoietic cells, we expressed the CD11b/CD18 complex on the surface of K562 cells, a cell line derived from an individual with chronic myelogenous leukemia in blast crisis. We used an amphotrophic retroviral vector designated LCD18SN, harboring the complete coding sequence for the CD18 subunit, to transfer the CD18 cDNA into K562 cells and select stable cell lines. The CD11b subunit in the expression plasmid pREP4 was transfected into these K562/CD18 cells by electroporation and stable cell clones were selected. These K562 cells possessed RNA and intracellular protein for each subunit, and they expressed the CD11b/CD18 heterodimer on the cell surface. When CD11b/CD18 expressing K562 cells were stimulated with phorbol myristate acetate (50 ng/mL) for 24 to 48 hours, these K562 cells formed dense cell:cell aggregates. This homotypic aggregation required both activation of the CD11b/CD18 complex and the induction of the counter- receptor for CD11b/CD18 on the conjugate cell. This cell line will (1) enable the structure-function relationships between cell activation and homotypic adherence to be assessed, (2) provide the opportunity to identify accessory molecules required for activation of the CD11b/CD18 complex, and (3) facilitate the identification of novel ligands for the CD11b/CD18 complex.     

Identification of MEN1 gene mutations in sporadic carcinoid tumors of the lung

Lung carcinoids occur sporadically and rarely in association with multiple endocrine neoplasia type 1 (MEN1). There are no well defined genetic abnormalities known to occur in these tumors. We studied 11 sporadic lung carcinoids for loss of heterozygosity (LOH) at the locus of the MEN1 gene on chromosome 11q13, and for mutations of the MEN1 gene using dideoxy fingerprinting. Additionally, a lung carcinoid from a MEN1 patient was studied. In four of 11 (36%) sporadic tumors, both copies of the MEN1 gene were inactivated. All four tumors showed the presence of a MEN1 gene mutation and loss of the other allele. Observed mutations included a 1 bp insertion, a 1 bp deletion, a 13 bp deletion and a single nucleotide substitution affecting a donor splice site. Each mutation predicts truncation or potentially complete loss of menin. The remaining seven tumors showed neither the presence of a MEN1 gene mutation nor 11q13 LOH. The tumor from the MEN1 patient showed LOH at chromosome 11q13 and a complex germline MEN1 gene mutation. The data implicate the MEN1 gene in the pathogenesis of sporadic lung carcinoids, representing the first defined genetic alteration in these tumors.      

Length polymorphism of heterochromatic segment of the Y chromosome in boys with acute leukemia

The extent of length polymorphisms of the heterochromatic and euchromatic segment of the human Y chromosome were investigated in 15 boys with acute leukemia and were compared with 15 normal controls. A greater value of the Yh/F index in relation to controls was established (P < 0.05). The length of the euchromatic segment was also shorter in the patients than the controls (P < 0.05).     

Effects on Plasma Glucose Concentration of Light-for-date Infants and Infants of Diabetic Mothers of Feeds Supplemented with a Glucose Polymer

ABSTRACT. Serial plasma glucose estimations were performed in 44 light-for-date infants and 17 infants of diabetic mothers fed 2, 3 or 4-hourly with feeds containing 10 % additional carbohydrate in the form of a glucose polymer (Caloreen). In the infants fed 2 and 3-hourly, plasma glucose was higher following the high carbohydrate feeds, particularly immediately before the next feed was due. Given 4-hourly, the high carbohydrate feed had little effect in most light-for-date infants, and in one light-for-date infant and two infants of diabetic mothers the plasma glucose was lower at the end of 4 hours than following normal formula. It is concluded that the addition of glucose polymer to feeds given 2 and 3 hourly has a potentially useful effect in neonates at risk of developing hypoglycaemia, but it cannot be used to increase the feed interval to 4 hours.