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Query: UMLS:C0027947 (neutropenia)
 17,527 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Three children displaying hypotonia, cardiac involvement and defects of the mitochondrial respiratory chain complexes are reported. The first case showed severe neonatal hypotonia, failure to thrive, hepatomegaly, dilation of the right cardiac cavities, profound lactic acidosis and amino aciduria. The boy died at the age of 7 weeks. In the second case hypotonia, severe cardiomyopathy, cyclic neutropenia, lactic acidosis and 3-methylglutaconic aciduria occurred. The boy died at the age of 27 months. The third case presented at the age of 16 months as an acute hypokinetic hypertrophic cardiomyopathy with transient hypotonia and mild lactic acidosis. Spontaneous clinical remission occurred. In all cases muscle biopsy was performed. Morphological studies failed to show ragged-red fibers but there was lipid storage myopathy and decreased cytochrome c oxidase activity. Biochemical studies confirmed the cytochrome c oxidase deficiency in muscle in all cases. It was associated with complex I III deficiency in case 1 and with severe deficits of all respiratory chain complexes in case 2. Post-mortem studies in case 1 indicated that complex IV was reduced in the liver but not in the heart and quantitative analysis of mtDNA revealed a depletion in muscle. Cases 1 and 2 shared some clinical features with fatal infantile myopathy associated with cytochrome c oxidase deficiency, while case 3 displayed a very unusual clinical presentation. The histochemical enzyme reaction of cytochrome c oxidase is useful for the diagnosis of mitochondrial myopathy because ragged-red fibers may be lacking. Finally, biochemical measurement of the different mitochondrial respiratory chain complexes is required because multiple defects are frequent and occasionally related to mtDNA depletion.
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PMID:Defects of the mitochondrial respiratory chain complexes in three pediatric cases with hypotonia and cardiac involvement. 132 Jun 61

Trace mineral deficiencies tend to have profound effects on the integrity of formed blood elements. Anemia and neutropenia are commonly seen in copper (Cu) deficiency. We therefore developed a serum-free medium to examine the trace mineral requirements, in particular iron and Cu, for proliferation and retinoic acid (RA)-induced differentiation of HL-60 cells. This defined medium (DFM) was composed of Iscove's Modified Dulbecco's Medium (IMDM) supplemented with insulin and human apo-transferrin (each at 5 micrograms/ml) and 1.4 microM FeSO4. The iron concentration range for optimal cellular proliferation was narrow (2-3 microM). HL-60 cells could be maintained in DFM for 15 passages with a doubling time of 38-40 hr. The Cu content of IMDM was very low. Thus, by the fourth passage in DFM, the activity of cuproenzymes (cytochrome c oxidase, CCO; and copper-zinc superoxide dismutase, CuZnSOD) began to decline. Supplementation of DFM with CuSO4 (50 nM) restored enzyme activities. Treatment of cells with a Cu chelator (tetrathiomolybdate, 1 microM) rapidly reduced the activities of both CCO and CuZnSOD. Over the Cu concentration range examined (5-350 nM), Cu supplementation had little effect on HL-60 proliferation. Cell retained the ability to differentiate along the granulocytic pathway when treated with RA, but seemed to be less sensitive to the inducing agent except at the highest concentration tested (1 microM). This decreased sensitivity to RA did not seem to be related to the Cu status of the cells but rather to the absence of a component of serum. Indeed, cells grown in DFM regained their sensitivity to RA when allowed to differentiate in IMDM with 5% serum. These data indicate that the processes of growth and terminal differentiation in HL-60 cells are not greatly influenced by Cu. Thus, it seems likely that the insult resulting in neutropenia which is associated with Cu deficiency may occur earlier than the promyelocytic stage. However, the possibility that the mechanisms contributing to neutropenia may be unrelated to primary defects in the biochemistry of neutrophil maturation cannot be ruled out.
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PMID:Iron and copper requirements for proliferation and differentiation of a human promyelocytic leukemia cell line (HL-60). 777 91