An 86-year-old man presented with acute hepatic failure, worsening thrombocytopenia, and anemia having been diagnosed and managed expectantly with cytogenetically normal RAEB-1. After 20 months a diagnosis of disease transformation to acute monocytic leukemia (M5b) was made. Conventional G-banded analysis of unstimulated bone marrow cultures demonstrated a jumping translocation (JT) involving proximal and distal breakpoints on donor chromosome 3 at bands 3q1?2 and 3q21, respectively. Recipient chromosomes included the long-arm telomeric regions of chromosomes 5, 10, 14, 16, and 19. A low-level trisomy 8 clone was also found in association with both proximal and distal JT clones. Conventional G-banded analysis of unstimulated peripheral blood cultures detected the proximal 3q1?2 JT clone involving recipient chromosome 10 several weeks after transformation to acute monocytic leukemia. Interestingly, JTs involving recipient chromosomes 5, 14, 16, and 19 were not detected in this peripheral blood sample. Palliative care was administered until his demise 2.2 months after disease transformation. There have been fewer than 70 cases of acquired JTs reported in the literature, including one myeloproliferative neoplasm and five acute myeloid leukemias involving a single breakpoint site on donor chromosome 3. Our case is unique as it is the first acquired case to demonstrate a JT involving alternative pericentromeric breakpoint sites on a single donor chromosome consisting of a proximal breakpoint at 3q1?2 and a more distal breakpoint at 3q21.

Differences in insulin binding affinity and in concentrations of insulin receptor, were found in a variety of tissues taken, at slaughter, from mature steers (701 (s.d. 23) kg) and growing lambs (47 (s.d. 2·1) kg). In both species, liver had lower insulin binding affinity than skeletal muscles m. pectineus m. longissimus dorsi and m. rectus capitis (all P < 0·001) and subcutaneous, omental and perirenal adipose depots (all P < 0·001). Site-specific differences in affinity for insulin existed between adipose depots (subcutaneous < omental, P < 0·05; subcutaneous < perirenal, P < 0·001) and between tissue-types (subcutaneous fat < m. pectineus skeletal muscle, P < 0·05; m. rectus capitis < perirenal fat, P < 0·05) in steers. In lambs also, receptor affinity for insulin differed between tissue-type (m. longissimus dorsi < perirenal fat, P < 0·05; m. rectus capitis < subcutaneous fat, P < 0·05 and m. rectus capitis < perirenal fat, P < 0·001) but lambs did not show the adipose depot-specific differences in insulin affinity observed in steers. Insulin receptor concentration differed between adipose depots (subcutaneous < omental, P < 0·05; subcutaneous < perirenal, P < 0·01) and between tissue-type (m. pectineus < perirenal fat P < 0·05) in steers and perirenal and subcutaneous adipose depots of lambs had higher receptor concentrations than m. longissimus dorsi and m. pectineusP < 0·001). This is the first study to demonstrate, in any species, differences in insulin receptor binding affinity and receptor concentration in a wide range of tissues (liver, skeletal muscles and adipose depots) from the same individual. Such differences in meat-producing animals could, through effects on tissue sensitivity and/or responsiveness to insulin, influence nutrient partitioning to tissues and affect overall rates of lipid storage and net protein synthesis.

The advantages and disadvantages of using G-banding, CGH and i-FISH as either stand-alone or integrated screening methods for the detection and characterisation of genomic imbalances in acute leukaemia are clearly demonstrated. Abnormality detection rate significantly increased when an integrated screening approach was employed which could potentially provide valuable information for risk stratification in patients with acute leukaemia.

Insulin is as integral and important to the management of metabolism in ruminants as it is in non-ruminants. The suggestion of a lowered ruminant sensitivity and/or responsivity to insulin may relate more to the insulin receptor than to the hormone itself. We screened an ovine cDNA library using degenerate primers and polymerase chain reaction (PCR) to detect and sequence a cDNA portion corresponding to exons 10, 11 and 12 of the human insulin receptor gene in which a 36 base pair (bp) segment (exon 11) is alternatively spliced to produce two distinct receptor isoforms differing in functional characteristics including binding affinity for insulin. The ovine cDNA segment (nucleotides 671 to 770) displayed 84, 84, and 78% nucleotide homology to equivalent segments from the human, rhesus monkey and rat respectively. Reverse transcription PCR (RT-PCR) of selected tissues (liver, m. longissimus dorsi, m. rectus capitis and omental, perirenal and subcutaneous fats) taken at slaughter from three male, pure Dutch Texel lambs (experiment 1) and five male Texel-Greyface crossbred lambs (experiment 2) revealed two mRNA products in each tissue (including spleen; experiment 2 only) corresponding to cDNAs of molecular sizes 161 and 197 bp -a difference of 36 bp. Sequence alignment showed the 36 bp segment to be homologous to the alternatively spliced exon 11 region of the human insulin receptor gene and to be highly conserved with that from other species. The abundance of the exon 11 + isoform in the purebred Texel genotype was significantly higher in liver than in perirenal fat and rectus capitis and longissimus dorsi skeletal muscles (P<0·05) and higher also than in subcutaneous and omental fats (P<0·01). There was, however, no difference in the abundance of the exon 11 + isoform between the individual muscle and fat depots in this sheep genotype. The abundance of the exon 11 + isoform in the crossbred Texel genotype was significantly higher in liver (P<0·05) than in the muscles (rectus capitis, P<0·05; longissimus dorsi, P<0·001), all three fats (P<0·001) and spleen (P<0·001). In the crossbred genotype, the abundance of the exon 11 + isoform was higher in skeletal muscle than in all three fat depots (P<0·001), in which the isoform abundance was similar. Altered ratios of expression of the two products of this alternative splicing event could determine tissue sensitivity and/or responsivity to insulin and provide a mechanism for the management of nutrient partitioning and nutrient utilisation between tissues which is fundamental to the growth of tissues and manipulation of carcass characteristics in meat-producing animals.