An MTHFR variant, homocysteine, and cardiovascular comorbidity in renal disease.

BACKGROUND: It is unclear whether total serum homocysteine (tHcy) and the C677T mutation of methylenetetrahydrofolate reductase (MTHFR) are associated with cardiovascular disease (CVD) in patients with end-stage renal disease (ESRD). METHODS: A cross-sectional sample of 459 patients with ESRD on chronic dialysis was assessed to determine whether tHcy and the C677T mutation are associated with CVD prevalence in multiple logistic regression. As CVD mortality is high, we examined the relationship between homozygosity and duration of dialysis. RESULTS: Mean tHcy was higher in patients without a history of CVD (35.2 micromol/L vs. 30.4 micromol/L, P = 0.02). In multivariate models, CVD was negatively associated with tHcy and positively associated with TT genotype, male gender, and body mass index. Mean tHcy levels were higher among those with the TT genotype compared with those with the CC genotype when adjusted for age, folate, creatinine, and albumin (37.9 micromol/L vs. 31.9 micromol/L, P = 0.005). Among whites, the prevalence of the TT genotype was higher in those having undergone less than one year of dialysis (P = 0.002). CONCLUSIONS: The C677T genotype of MTHFR is associated with CVD in ESRD and may be a more meaningful marker than tHcy for abnormal homocysteine metabolism in ESRD. Prospective data from ongoing clinical trials are needed to improve our understanding of these findings. Screening for this polymorphism may help guide prevention measures.

Malnutrition: detection and intervention.

Malnutrition is common in patients with renal failure. Causes of malnutrition in this population are varied and sometimes specific to the method of renal replacement therapy. No single marker absolutely identifies malnutrition or tracks changes in status. Renal dietitians use a variety of parameters and techniques to identify malnutrition because many of the traditional markers can be skewed by renal disease and its comorbidities. Once malnutrition is identified, treatment is also complex and not well defined. Treatment is usually progressive in nature, ranging from intense nutritional counseling to total parenteral nutrition. Further research is needed to define optimal nutrition status, to refine techniques to maintain optimal nutrition status, to simplify the identification of malnutrition, and to improve the treatment for malnutrition.

An adult case of acute biphenotypic leukemia with characteristic mixed morphology.

A case of acute biphenotypic leukemia with mixed blast morphology and combined myeloid and T-lymphoid features is reported. The leukemic cells consisted of small lymphoid hand-mirror blasts and large blasts with cytoplasmic granules and rare Auer rods. The cells expressed myeloid and immature T-lymphoid features by cytochemistry and immunophenotyping, however T cell receptor genes were in germline configuration. Cases of biphenotypic leukemia with similar morphological and immunophenotypic findings have been described previously in children. This case represents a morphologically and phenotypically distinct subtype of acute biphenotypic leukemia.

Reconstitution of the energy-linked transhydrogenase activity in membranes from a mutant strain of Escherichia coli K12 lacking magnesium ion- or calcium ion-stimulated adenosine triphosphatase.

1. We have isolated a mutant of Escherichia coli K12 (strain AN295) that forms de-repressed amounts of Mg(2+),Ca(2+)-stimulated adenosine triphosphatase. 2. The Mg(2+),Ca(2+)-stimulated triphosphatase activity was separated from membrane preparations from strain AN295 by extraction with 5mm-Tris-HCl buffer containing EDTA and dithiothreitol, resulting in a loss of the ATP-dependent transhydrogenase activity. The non-energy-linked transhydrogenase activity remained in the membrane residue. 3. The solubilized Mg(2+),Ca(2+)-stimulated adenosine triphosphatase activity from strain AN295 was partially purified by repeated gel filtration. The addition of the purified Mg(2+),Ca(2+)-stimulated adenosine triphosphatase to the membrane residue from strain AN295 reactivated the ATP-dependent transhydrogenase activity. 4. Strain AN296, lacking Mg(2+),Ca(2+)-stimulated adenosine triphosphatase activity, was derived by transducing the mutant allele, uncA401, into strain AN295. The ATP-dependent transhydrogenase activity was lost but the non-energy linked transhydrogenase was retained. 5. The ATP-dependent transhydrogenase activity in membrane preparations from strain AN296 (uncA(-)) could not be re-activated by the purified Mg(2+),Ca(2+)-stimulated adenosine triphosphatase from strain AN295. However, after extraction by 5mm-Tris-HCl buffer containing EDTA and dithiothreitol, the ATP-dependent transhydrogenase activity could be re-activated by the addition of the purified Mg(2+),Ca(2+)-stimulated adenosine triphosphatase from strain AN295 to the membrane residue from strain AN296 (uncA(-)).

Characterization and genetic analysis of mutant strains of Escherichia coli K-12 accumulating the biquinone precursors 2-octaprenyl-6-methoxy-1,4-benzoquinone and 2-octaprenyl-3-methyl-6-methoxy-1,4-benzoquinone.

The ubiquinone precursors, 2-octaprenyl-6-methoxy-1,4-benzoquinone and 2-octaprenyl-3-methyl-6-methoxy-1,4-benzoquinone, were isolated from ubiquinone-deficient mutants of Escherichia coli and identified by nuclear magnetic resonance and mass spectrometry. Mutants accumulating 2-octaprenyl-6-methoxy-1,4-benzoquinone and 2-octaprenyl-3-methyl-6-methoxy-1,4-benzoquinone were shown to carry mutations in genes designated ubiE and ubiF, respectively. The ubiE gene was shown to be cotransducible with metE (minute 75) and close to two other genes concerned with ubiquinone biosynthesis. The ubiF gene was located close to minute 16 by cotransduction with the lip, gltA, and entA genes.

Biosynthesis of ubiquinone in Escherichia coli K-12: location of genes affecting the metabolism of 3-octaprenyl-4-hydroxybenzoic acid and 2-octaprenylphenol.

Two genes (ubiB and ubiD) concerned with two successive reactions in ubiquinone biosynthesis in Escherichia coli were mapped and found to be closely linked. Mutant strains of E. coli carrying the ubiB(-) and ubiD(-) alleles were shown to accumulate 2-octaprenylphenol and 3-octaprenyl-4-hydroxybenzoic acid, respectively. These compounds were isolated and identified by using nuclear magnetic resonance and mass and infrared spectroscopy. Cell extracts from the mutant strain carrying the ubiD(-) allele lack 3-octaprenyl-4-hydroxybenzoate decarboxylase activity.