The relationships between normal and leukemic stem/progenitor cells are unclear. We show that in ∼80% of primary human CD34+ acute myeloid leukemia (AML), two expanded populations with hemopoietic progenitor immunophenotype coexist in most patients. Both populations have leukemic stem cell (LSC) activity and are hierarchically ordered; one LSC population gives rise to the other. Global gene expression profiling shows the LSC populations are molecularly distinct and resemble normal progenitors but not stem cells. The more mature LSC population most closely mirrors normal granulocyte-macrophage progenitors (GMP) and the immature LSC population a previously uncharacterized progenitor functionally similar to lymphoid-primed multipotential progenitors (LMPPs). This suggests that in most cases primary CD34+ AML is a progenitor disease where LSCs acquire abnormal self-renewal potential.
Inflammatory myofibroblastic tumours (IMFT) may arise at any anatomical site, including lung, soft tissues, retroperitoneum and bladder. Although morphologically similar, these lesions encompass a spectrum of entities with differing aetiology, ranging from reactive/regenerative proliferations to low-grade neoplasms with a risk of local recurrence, but no significant metastatic potential. Vesical IMFT usually presents as a polypoid mass with a pale firm cut surface and can be of considerable size, mimicking a malignant tumour clinically and radiologically. Its good outcome, however, warrants conservative surgical excision, emphasising the importance of identification and distinction from malignant tumours of the bladder that may require more radical surgery and/or adjuvant therapy. We conducted a preliminary retrospective, comparative immunocytochemical study of 20 bladder tumours, including nine IMFTs, five spindle cell (sarcomatoid) carcinomas, two rhabdomyosarcomas, two leiomyosarcomas and two neurofibromas. The results confirmed IMFT positivity for smooth muscle actin, desmin and cytokeratin in 78-89% cases, resulting in potential confusion with sarcomatoid carcinoma or leiomyosarcoma. In contrast, cytoplasmic anaplastic lymphoma kinase (ALK 1) staining was present in eight IMFT (89%), but was not seen in any other lesion examined. The ALK 1 staining was confirmed by fluorescence in situ hybridisation, with translocation of the ALK gene present in 15-60% tumour cells in four of six IMFT examined, but not in four cases of sarcomatoid carcinoma or three of leiomyosarcoma. In conclusion, ALK 1 staining may be of value in the distinction of vesical IMFT from morphologically similar entities, and often reflects ALK gene translocations in these lesions.
~Children (227), aged 7-12 years, weighed and recorded all food and drink consumed for seven consecutive days. Each child completed tests of verbal and non-verbal intelligence, and was then randomly allocated to one of two groups after matching for age, sex, IQ and height. In a double-blind trial lasting for 28 d, one group received a vitamiwmineral supplement daily and the other group a placebo. On re-testing, there were no significant differences in performance between the two groups. Furthermore, there were no consistent correlations between test scores and micronutrient intakes based on the weighed records. Thus, we found no evidence that learning ability in a cross-section of British schoolchildren was limited by the quality of their diets. Diet: Intelligence : Vitamin-mineral supplementation : Schoolchildren Nutrient deficiencies, whether dietary or metabolic in origin, have long been known to cause learning disabilities and cognitive disorders (Passmore & Eastwood, 1986), and a number of studies have shown the benefits of dietary supplements on mental function in underfed children. It was reported, for example, that thiamin supplements improved test scores in 9-to 19-year-old children living in an orphanage in Virginia (Harrell, 1946). Pollitt ef al. (1985) presented results on the positive effect of iron supplements on cognitive performance in Egyptian children with anaemia (mean age 9-5 years), while Walter et al. (1983) showed similar effects in infants aged 15 months in whom haemoglobin levels were normal but other biochemical indicators of Fe status were low. The benefits of a supplement (energy, protein, vitamins and minerals) on the cognitive competence of infants born into poverty in Bogota, Colombia were demonstrated by Waber et al. (1981), in a prospective study lasting 3-5 years. Likewise, Barrett & Frank (1987) showed that the provision of a broad-based supplement to Guatemalan children aged 6-8 years with mild to moderate protein+nergy malnutrition resulted in improved mental test scores. In all these studies, however, evidence of undernutrition, obtained principally from anthropometric or biochemical measurements, was unequivocal. In the last two studies mentioned, the authors concluded that the effect of deprivation was to decrease motivation and arousal rather than to limit cognitive development per se, and that the benefits of supplementation diminish with increasing age.A recent paper on the effect of vitamin and mineral supplementation in British schoolchildren purported to demonstrate that in 12-to 13-year-old children with apparently normal growth and no clinical signs of nutrient deficiency, additional vitamins and minerals had a positive effect on performance in tests of non-verbal intelligence (Benton & Roberts, 1988). This is a surprising and potentially important finding. While there is a significant proportion of British schoolchildren who fail to meet the recommended daily allowance (RDA) for one or more of the micronutrients (Department of Health and Social Security, availa...
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