Non-Epstein-Barr virus-associated T-cell lymphoma following cardiac transplantation for Barth syndrome

Barth syndrome is a metabolic disease characterized by infantile cardiomyopathy, neutropenia and organic aciduria. We report disease evolution in one of the first affected boys to undergo successful cardiac transplantation. CONCLUSION: Although cardiac status stabilized, he developed disabling skeletal myopathy, protracted lymphopenia and--5 y after transplant--fatal Epstein Barr (EBV)-negative T-cell non-Hodgkin's lymphoma.     

African-American factor VII-deficient variants in Georgia (FVII variants)

We studied African-American Factor (FVII)-deficient variants and carriers in Georgia by measuring their levels of FVII antigen (FVIIAG) and FVII procoagulant (FVIIC). Factor VIIAG was determined using enzyme-linked immunoassay (ELISA), whereas FVIIC was measured in two ways: 1) by fibrin clotting methods that employed human recombinant (HRFVIIC), human placental (HPFVIIC), rabbit brain (RBFVIIC), and bovine brain (BBFVIIC) thromboplastins; and 2) by an amidolytic method (AMFVIIC). Prothrombin time tests (PT) were also performed by standard methods. These 4 FVII-deficient patients and 3 carriers demonstrated the following results: PT: 18.2 ± 6.5 sec; FVIIAG: 73.0 ± 14.9; HRFVIIC: 30.6 ± 20.3%; HPFVIIC: 30.5 ± 21.4%; RBFVIIC: 25.3 ± 21.4%; BBFVIIC: 30.6 ± 17.5%; AMFVIIC: 44.1 ± 18.3. We conclude that a group of clinically mild African-American FVII-deficient variants exists in Georgia. This group is characterized by the presence of FVIIAG and decreased FVIIC, using a variety of thromboplastins; an excellent correlation was noted for both human thromboplastins. © 1994 Wiley-Liss, Inc.     

Long‐term outcomes for different surgical strategies to treat left ventricular outflow tract obstruction in hypertrophic cardiomyopathy

Aims

Surgical intervention is used to treat dynamic left ventricular outflow tract obstruction (LVOTO) in hypertrophic cardiomyopathy. This study assesses the effect of different surgical strategies on long‐term mortality and morbidity.

Methods and results

In total, 347 patients underwent surgical intervention for LVOTO (1988–2015). Group A (n = 272) underwent septal myectomy; Group B (n = 33), septal myectomy and mitral valve (MV) repair; Group C (n = 22), myectomy and MV replacement; and Group D (n = 20), MV replacement alone. Median follow‐up was 5.2 years (interquartile range 1.9–7.9). The mean resting LVOT gradient improved post‐operatively from 71.9 ± 39.6 mmHg to 13.4 ± 18.5 mmHg (P < 0.05). Overall, 72.4% of patients improved by >1 New York Heart Association (NYHA) class; 58.9% of patients undergoing MV replacement alone did not improve their NYHA class. There were 5 perioperative deaths and 20 late deaths (>30 days). Survival rates at 1, 5 and 10 years respectively were 98.4, 96.9, 91.9% in Group A; 97.0, 92.4, 61.6% in Group B; 100.0, 100.0, 55.6% in Group C; and 94.7, 85.3, 85.3% in Group D (log‐rank, P < 0.05). Long‐term (>30 days) complications included atrial fibrillation (29.6%), transient ischaemic attack/stroke (2.4%) and heart failure hospitalisation (3.2%). There were 16 repeat surgical interventions at 3.0 years.

Conclusion

Septal myectomy is a safe procedure resulting in symptomatic improvement in the majority of patients. The annual incidence of non‐fatal disease‐related complications after surgical treatment of LVOTO is relatively high. Patients who underwent MV replacements had poorer outcomes with less symptomatic benefit in spite of a similar reduction in LVOT gradients.

     

Differences in the morphology and duration between premature P waves and the preceding sinus complexes in patients with a history of paroxysmal atrial fibrillation

BACKGROUND: Atrial fibrillation (AF) is the most common arrhythmia encountered in clinical practice. Experimental and human mapping studies have demonstrated that perpetuation of AF is due to the presence of multiple reentrant wavelets with various sizes in the right and left atria. HYPOTHESIS: Atrial fibrillation may be induced by atrial ectopic beats originating in the pulmonary veins, and premature P-wave (PPW) patterns may help to identify the source of firing. METHODS: To evaluate the morphology and duration of PPWs, 12-lead digital electrocardiogram (ECG) strips containing clearly definable PPWs not merging with the preceding T waves were obtained in 25 patients with AF history (9 men, mean age 59.5 +/- 2.2 years) and 25 subjects without any previous AF history (11 men, mean age 53.6 +/- 25 years). The polarity of PPWs was evaluated in all 12 ECG leads. Previously described indices, such as P maximum, P dispersion (= P maximum-P minimum), P mean, and P standard deviation were also calculated. RESULTS: Premature P-wave patterns were characterized by more positive P waves in lead V1. All P-wave analysis indices were significantly higher in patients with AF than in controls when calculated in the sinus beat, whereas they did not differ between the two groups when calculated in the PPW. P-wave indices did not differ between the PPW and the sinus either patients with AF or controls, except for P mean, which was significantly higher in the sinus (110.1 +/- 1.7 ms) than in the PPW (100 +/- 2 ms) only in patients with AF (p = 0.001). CONCLUSION: The evaluation of PPW patterns is only feasible in a small percentage of short-lasting digital 12-lead ECG recordings containing ectopic atrial beats. Premature P wave patterns characterized by more positive P waves in lead V1, which indicates a left atrial origin in the ectopic foci. The observed differences in P-wave analysis indices between patients with AF and controls and between sinus beats and PPWs may be attributed to the presence of electrophysiologic changes in the atrial substrate.     

Activation and increased expression of adhesion molecules on peripheral blood lymphocytes is a mechanism for the immediate lymphocytopenia after administration of OKT3

We investigated the mechanism by which antihuman CD3 monoclonal antibodies of the isotypes IgG2a (eg, OKT3) and IgA (eg, IXA) can induce the rapid disappearance of virtually all circulating T lymphocytes. We hypothesize that upregulation of adhesion molecules on the lymphocyte membrane contributes to this effect. However, this hypothesis is difficult to test, because of the inherent lymphocytopenia and/or shifts in lymphocyte populations between intra and extra-vascular compartments. Therefore, studies in vitro were performed, as well. Analysis of peripheral blood lymphocytes isolated at several times after addition of OKT3 or IXA to whole blood of healthy individuals showed an immediate increase in the proportion of T cells expressing NKI-L16, an activation epitope on CD11a/CD18. Likewise, an increase in CD11b/CD18 expression occurred. In parallel experiments, a transiently increased adhesion of T cells to endothelial cell monolayers was observed. This adhesion could be completely blocked by anti-CD18 or anti-CD11a monoclonal antibodies and only partly by an anti-CD11b antibody. Our data indicate that upregulation of activation epitopes of CD11a/CD18, as well as increased expression of CD11b/CD18 on T lymphocytes, may result in increased adhesion of these cells to intercellular adhesion molecule-1 (ICAM-1) and ICAM-2 on vascular endothelium. This phenomenon may, at least, partly explain the rapidly occurring peripheral lymphocytopenia observed in vivo.     

B lymphoblastoid cell lines with normal and defective O-glycosylation established from an individual with blood group Tn

Individuals with the Tn blood group contain terminal serine/threonine- linked N-acetylgalactosamine residues in their blood cells. This is due to lack of UDP-D-galactose: D-N-acetyl galactosamine beta-D-galactosyl transferase from part of their red cells and probably from their leukocytes. We have established B lymphoblastoid cell lines from such an individual by in vitro infection of his lymphocytes with Epstein- Barr virus. The original line contained a mixture of cells reactive and nonreactive with Helix pomatia lectin (Hp). These cells were subcloned after staining with fluorescent Hp by a fluorescence-activated cell sorter (FACS) into homogeneous, phenotypically stable lines of Hp- positive (Hp+) and Hp-negative (Hp-) cells. The molecular differences between the membrane glycoproteins were characterized by carbohydrate- specific surface labeling techniques, Hp affinity chromatography, polyacrylamide slab gel electrophoresis and glycopeptide/oligosaccharide analysis. The major O-glycosidic membrane glycoprotein (GP105) was retained on Hp-Sepharose columns only from Hp+ cells, whereas the common leukocyte antigen (GP160-200) was partially retained on Hp columns from both lines. These proteins were isolated by immune precipitation with monoclonal antibodies and characterized. The results show that the GP105 glycoprotein from Hp+ cells contains terminal N-acetylgalactosamine residues but also more complex oligosaccharides. The common leukocyte antigen showed different electrophoretic mobilities in Hp+ and Hp- cells. UDP-galactose D-N- acetyl galactosamine beta-galactosyl transferase was almost absent in the Hp+ cells. These cell lines are useful for studies on the functional role and regulation of the biosynthesis of O-glycosidic carbohydrates.     

Ammonia binding to the oxygen-evolving complex of photosystem II identifies the solvent-exchangeable oxygen bridge (μ-oxo) of the manganese tetramer

The assignment of the two substrate water sites of the tetra-manganese penta-oxygen calcium (Mn₄O₅Ca) cluster of photosystem II is essential for the elucidation of the mechanism of biological O-O bond formation and the subsequent design of bio-inspired water-splitting catalysts. We recently demonstrated using pulsed EPR spectroscopy that one of the five oxygen bridges (μ-oxo) exchanges unusually rapidly with bulk water and is thus a likely candidate for one of the substrates. Ammonia, a water analog, was previously shown to bind to the Mn₄O₅Ca cluster, potentially displacing a water/substrate ligand [Britt RD, et al. (1989) J Am Chem Soc 111(10):3522–3532]. Here we show by a combination of EPR and time-resolved membrane inlet mass spectrometry that the binding of ammonia perturbs the exchangeable μ-oxo bridge without drastically altering the binding/exchange kinetics of the two substrates. In combination with broken-symmetry density functional theory, our results show that (i) the exchangable μ-oxo bridge is O5 {using the labeling of the current crystal structure [Umena Y, et al. (2011) Nature 473(7345):55–60]}; (ii) ammonia displaces a water ligand to the outer manganese (Mn_A4-W1); and (iii) as W1 is trans to O5, ammonia binding elongates the Mn_A4-O5 bond, leading to the perturbation of the μ-oxo bridge resonance and to a small change in the water exchange rates. These experimental results support O-O bond formation between O5 and possibly an oxyl radical as proposed by Siegbahn and exclude W1 as the second substrate water.     

Pet ownership and survival of European older adults

With pet ownership on the rise, millions of individuals are exposed to this environmental exposure. Although the subject has been largely studied, more evidence is needed to clarify the potential association of pet ownership with human health. The aim of this research is to study the potential association of pet exposure (any pet, cat, dog, bird, fish) with all-cause, cardiovascular and cancer mortality of older (≥ 50 years) European residents. To this end, a total of 23,274 participants from the Survey of Health Ageing and Retirement in Europe (SHARE) were employed (median follow-up 119 months). All-cause mortality (5163 events), as well as cardiovascular (CVD) (1832 events), and cancer mortality (1346 events) were examined using Cox Proportional Hazards models for their relation with pet exposure at baseline. Stratified analyses were also performed by gender and for single or multi-person households. No significant association was observed for any of the pets with all-cause mortality on the whole sample and the fully adjusted models. In stratified analyses, bird exposure significantly increased the risk of all-cause mortality in women [Hazard Ratio (HR)=1.23; 95% CI 1.04–1.44] as well as women living alone (HR=1.38; 95% CI 1.02–1.85). Cause-specific models revealed an increased risk of death for women bird owners for causes other than cancer and CVD (HR=1.40; 95% CI 1.05–1.99). In conclusion, bird ownership may be negatively associated with survival of older women in Europe.     

The vacuolated glycogen-laden leukemic lymphocytes of a T-cell lymphoproliferative disorder

In this report, we present a case of peripheral T-cell leukemia/lymphoma having mostly small- to medium-sized cells with abundant clear cytoplasmic vacuoles. The presentation at the time of diagnosis was one of leukemia/lymphoma. The phenotype of the leukemic cells of the peripheral blood was T1+, T11+, TQ1+, interleukin-2+, T3-, T4-, and T8-. The cells in the peripheral blood as well as those obtained from lymph node biopsy were strongly periodic acid-Schiff positive; the positivity was diastase sensitive. Electron microscopy confirmed the presence of glycogen in the cytoplasmic vacuoles. Serologic tests were negative for human T-cell lymphotropic virus type 1 antibody. The data presented in this article support the existence of a vacuolated variant of peripheral T-cell leukemia/lymphoma and further expand the morphological spectrum of T-cell lymphoproliferative disorders.