Mouse strain variability in the expression of the hematopoietic stem cell antigen Ly-6A/E by bone marrow cells

The cell surface molecule Ly-6A/E provides a convenient marker for primitive stem cells in the hematopoietic tissues of both fetal and adult mice. However, previous studies have shown that Ly-6A/E expression by lymphocytes is variable depending on the haplotype of the Ly-6 locus. Therefore, strain-specific variation in Ly-6A/E expression by bone marrow (BM) cells was investigated. The results show that Ly-6a mice have, on average, 50% of the number of BM cells expressing Ly-6A/E relative to that for Ly-6b mice. Furthermore, among the 5% of BM cells that do not express antigens characteristic of mature T, B, myeloid, or erythroid lineages, which include the primitive hematopoietic stem cell compartment, Ly-6a mice have, on average, more than fivefold fewer Ly- 6A/E+ cells relative to that for Ly-6b mice. Isolation of Ly-6A/E- and Ly-6A/E+ cells from mice of both haplotypes showed that, whereas 99% of the marrow repopulating activity (MRA) of C57BL/Ka (Ly-6b) mice could be recovered in the Ly-6A/E+ fraction, only about 25% of the MRA of BALB/c (Ly-6a) was recoverable in the same population. On a per-cell basis, the Ly-6A/E+ cells that were isolated from BALB/c mice were essentially equivalent in MRA to those isolated from C57BL/Ka mice. Thus, whereas a large percentage of the hematopoietic stem cells of Ly- 6a mice do not express the Ly-6A/E molecule, the antigen may be used to isolate a subset of stem cells from these mice. These results show that hematopoietic stem cell phenotype can vary between mouse strains and imply that caution should be exercised in the identification of human stem cell antigens such as CD34, because a similar variability may occur between individual humans. To further explore the influence of Ly- 6 haplotype on Ly-6A/E expression by specific cell subsets, lymph-node lymphocytes from a panel of mouse strains were analyzed by multiparameter flow cytometry for correlated expression of Ly-6A/E, CD4, and CD8. All Ly-6a strains examined had less than 20% Ly-6A/E+ cells, and those cells were predominantly CD8+ T lymphocytes. In contrast, the Ly-6b strains had greater than 30% Ly-6A/E+ cells, and those cells included CD4+, CD8+, and B lymphocytes.     

Retrograde non trans‐septal balloon mitral valvotomy in mitral stenosis with interrupted inferior vena cava,left superior vena cava,and hugely dilated coronary sinus

A 22‐year‐old woman with severe mitral stenosis was referred to us for further evaluation and management. She was found to have severe mitral stenosis, severe tricuspid regurgitation with dilated right atrium and right ventricle with persistent left superior vena cava and hugely dilated coronary sinus. Valve was suitable for balloon mitral valvotomy. Cardiac catheterization showed interrupted inferior vena cava with azygos continuation to right atrium and large left superior vena cava draining to coronary sinus which was very much dilated. Right trans‐jugular approach was tried for balloon mitral valvotomy, but was unsuccessful due to a very large right atrium and coronary sinus. Retrograde non trans‐septal approach was used and balloon valvotomy was done successfully using a 24 mm × 40 mm TYSHAK balloon without any major complication. Reduction in the transmitral pressure gradient on cardiac catheterization data and transthoracic echocardiography confirmed successful procedure. Balloon mitral valvotomy can be done successfully in patients with the above unusual cardiac anatomy with no major procedural complications. © 2015 Wiley Periodicals, Inc.     

Role of copper in mitochondrial iron metabolism

Heme synthesis by copper-deficient cells was investigated to elucidate the nature of the defect in intracellular iron metabolism. Iron uptake from transferrin by copper-deficient reticulocytes was 52% of normal, and the rate of heme synthesis was 33% of normal. Hepatic mitochondria isolated from copper-deficient animals were deficient in cytochrome oxidase activity and failed to synthesize heme from ferric iron (Fe III) and protoporphyrin at the normal rate. The rate of heme synthesis correlated with the cytochrome oxidase activity. Heme synthesis from Fe(III) and protoporphyrin by normal mitochondria was enhanced by succinate and inhibited by malonate, antimycin A, azide, and cyanide. It is proposed that an intact electron transport system is required for the reduction of Fe(III), thereby providing a pool of ferrous iron (Fe II) for protoheme and heme a synthesis.     

Outcome of Complex Adult Congenital Heart Surgery in the Developing World

Background. There is scanty information on the outcome of adult congenital heart disease surgery from the developing world. Methods. This was a retrospective chart review of the surgical outcome of 153 adults with congenital heart disease over a 5‐year period. Surgical atrial septal defect closure was considered “simple” while all other surgeries were considered “complex.” Results. There were 102 patients in the “simple” group and 51 in the “complex” group. Only three (2%) patients had prior operations. The “complex” group had longer bypass time and cross clamp time. Intensive care unit stay, ventilation time, and inotrope administration were longer. Major complications were more common and there were two deaths in the “complex” group. Age more than 30 years, cyanosis, and New York Heart Association class more than II were predictors of longer stay in the intensive care unit. Surgical repair of Tetralogy of Fallot in adults tended to have a longer ventilation time and intensive care unit stay with a mortality of 4%. At follow up, all patients were in New York Heart Association class I or II. Improvement of the functional class with negligible adverse events was noted in both groups. Conclusions. A retrospective evaluation of 153 adults with congenital heart disease who underwent open heart surgery at a single center in India showed strikingly fewer reoperations compared with large European studies. There was a similar prevalence of complex lesions. Surgical mortality was low, and long‐term functional outcome was gratifying.