Myocardial infarction and 5,10-methylenetetrahydro-folate reductase mutation

A 40-year-old woman with previous venous thrombosis in the lower limbs had recurrent myocardial infarction in the early puerperium. The only documented risk factor was an elevated level of plasma homocysteine, associated to a heterozygotic anomaly in the enzyme responsible for its metabolism, 5,10-methylenetetrahydrofolate reductase. The case and approaches to treatment are discussed.     

Extensive in vivo self-renewal, long-term reconstitution capacity, and hematopoietic multipotency of Pax5-deficient precursor B-cell clones

Self-renewal, pluripotency, and long-term reconstitution are defining characteristics of single hematopoietic stem cells. Pax5(-/-) precursor B cells apparently possess similar characteristics. Here, using serial transplantations, with in vitro recloning and growth of the bone marrow-homed donor cells occurring after all transplantations, we analyzed the extent of self-renewal and hematopoietic multipotency of Pax5(-/-) precursor B-cell clones. Moreover, telomere length and telomerase activity in these clones was analyzed at various time points. Thus far, 5 successive transplantations have been performed. Clones transplanted for the fifth time, which have proliferated for more than 150 cell divisions in vitro, still repopulate the bone marrow with precursor B cells and reconstitute these recipients with lymphoid and myeloid cells. During this extensive proliferation, Pax5(-/-) precursor B cells shorten their telomeres at 70 to 90 base pairs per division. Their telomerase activity remains at 3% of that of HEK293 cancer cells during all serial in vivo transplantations/in vitro expansions. Together, these data show that Pax5(-/-) precursor B-cell clones possess extensive in vivo self-renewal capacity, long-term reconstitution capacity, and hematopoietic multipotency, with their telomeres shortening at the normal rate.     

Simultaneous double-isotope autoradiographic measurement of local cerebral glucose metabolic rate and acid-base status in rat brain

We developed a double-isotope autoradiographic method for the simultaneous measurement of the local cerebral metabolic rate for glucose (1CMRG) and index of regional acid-base status (rABI) in single brain slices using [2-¹⁴C]deoxy-D-glucose (DG) and 5,5-dimethyl-[2-¹⁴C]oxazolidine-2,4, dione (DMO). After iv isotope administration, paper chromatography separates plasma DMO from DG activity using a methanol-methylene chloride solvent system. Initial tissue autoradiograms depict regional DMO plus DG and DG metabolite distribution. After 14 days in a well-ventilated hood, 97.5 ±0.5% of all DMO is lost from tissue sections by sublimation, and a second autoradiogram depicts DG plus DG metabolite distribution. Retention of brain lipids does not alter beta-particle self-absorption, avoiding problems associated with isotope extraction with solvents. Autoradiograms are digitized and converted to isotope-content images. The second autoradiogram is used for lCMRG computation. After subtracting the second regional isotope-content value from the first, the DMO content is obtained and used to compute rABI. Application of this method to normal animals yields expected values for lCMRG and rABI. This method is amenable to whole-slice digitization and creation of functional images of lCMRG and ABI followed by pixel-by-pixel correlations of the two variables, making this a potentially valuable tool for the investigation of the relationships between glucose metabolism and brain acid-base balance.     

Social reasoning in Tourette syndrome

Introduction. Tourette syndrome (TS) is thought to be associated with striatal dysfunction. Changes within frontostriatal pathways in TS could lead to changes in abilities reliant on the frontal cortex. Such abilities include executive functions and aspects of social reasoning.

Methods. This study aimed to investigate executive functioning and Theory of Mind (ToM; the ability to reason about mental states, e.g., beliefs and emotions), in 18 patients with TS and 20 controls. A range of tasks involving ToM were used. These required participants to make judgements about mental states based on pictures of whole faces or the eyes alone, reason about humour in cartoons that featured sarcasm, irony or “slapstick” style humour, and make economic decisions. The executive measures assessed inhibition and verbal fluency.

Results. Patients with TS exhibited significantly poorer performance than controls on all four tasks involving ToM, even when patients with comorbid obsessive-compulsive disorder were excluded. These difficulties were despite no inhibitory deficits. Patients with TS exhibited impairment on the verbal fluency task but their performance on executive and ToM tasks was not related.

Conclusions. We propose that TS is associated with changes in ToM. The observed deficits could reflect dysfunction in frontostriatal pathways involving ventromedial prefrontal cortex.     

Chromosomal location of the co-expressed human skeletal and cardiac actin genes.

We have examined the relationship between chromosomal location and regulation of the two human genes encoding the sarcomeric muscle actins. The human genes encoding skeletal alpha-actin and cardiac alpha-actin are co-expressed in both human skeletal muscle and heart. We have subcloned a single-copy DNA fragment from an intervening sequence in the human cardiac alpha-actin gene and a single-copy DNA sequence from the 3' untranslated region of a human skeletal alpha-actin cDNA. Using these two gene-specific probes, we examined DNA isolated from human-mouse somatic cell hybrid lines segregating human chromosomes. We observed the segregation of restriction endonuclease-generated DNA cleavage fragments that hybridize to the two probes. The two striated muscle genes do not co-segregate and are on different autosomes. The human cardiac alpha-actin gene (ACTC) is on chromosome 15 in the q11----qter region whereas the skeletal alpha-actin gene (ACTSK) is on chromosome 1 in the p21----qter region. The co-expression of these two genes is not a function of chromosomal linkage. Neither of these muscle genes can be the primary target resulting in X-linked muscular dystrophies.     

Screening for colorectal cancer in a high-risk population. Results of a mathematical model

A mathematical model was used to estimate the cost-effectiveness of colorectal cancer screening strategies for people who are at high risk because of a first-degree relative with colorectal cancer. The model uses indirect evidence about such factors as cancer incidence, sensitivity and specificity of different tests, and treatment effectiveness. The analysis indicates that for screening people over 40 yr old an annual fecal occult blood test may reduce colorectal cancer mortality by about one-third, either colonoscopy or barium enema may reduce mortality by approximately 85%, a 3-5-yr frequency for endoscopies or barium enemas preserves 70%-90% of the effectiveness of an annual frequency, and beginning screening at age 50 reduces effectiveness by 5%-10%. Although both barium enemas and colonoscopies appear to be effective in reducing mortality, the lower cost of the barium enema makes it a more cost-effective strategy. All of these estimates depend on the baseline estimates of each of the factors incorporated in the model; the conclusions are most sensitive to assumptions about the natural history of adenomatous polyps, the bleeding of adenomas and presymptomatic cancers, and the sensitivity of the fecal occult blood test. Recommendations about colorectal cancer screening must also consider factors such as discomfort, inconvenience, and the availability of various technologies.