Bone marrow transplantation for patients with Philadelphia chromosome- positive acute lymphoblastic leukemia

We report the treatment outcome of allogeneic bone marrow transplantation in ten patients with Philadelphia chromosome-positive acute lymphoblastic leukemia. Six patients are alive and well for 6 to 30 months (median 19 months) after transplantation. Four patients died with transplant related complications. In view of the poor prognosis associated with this disease, marrow ablation followed by allogeneic or syngeneic marrow grafting may be the preferred treatment modality if a suitable marrow donor is available.     

Elucidation of the thromboregulatory role of CD39/ectoapyrase in the ischemic brain

Endothelial CD39 metabolizes ADP released from activated platelets. Recombinant soluble human CD39 (solCD39) potently inhibited ex vivo platelet aggregation in response to ADP and reduced cerebral infarct volumes in mice following transient middle cerebral artery occlusion, even when given 3 hours after stroke. Postischemic platelet and fibrin deposition were decreased and perfusion increased without increasing intracerebral hemorrhage. In contrast, aspirin did not increase postischemic blood flow or reduce infarction volume, but did increase intracerebral hemorrhage. Mice lacking the enzymatically active extracellular portion of the CD39 molecule were generated by replacement of exons 4-6 (apyrase-conserved regions 2-4) with a PGKneo cassette. Although CD39 mRNA 3' of the neomycin cassette insertion site was detected, brains from these mice lacked both apyrase activity and CD39 immunoreactivity. Although their baseline phenotype, hematological profiles, and bleeding times were normal, cd39(-/-) mice exhibited increased cerebral infarct volumes and reduced postischemic perfusion. solCD39 reconstituted these mice, restoring postischemic cerebral perfusion and rescuing them from cerebral injury. These data demonstrate that CD39 exerts a protective thromboregulatory function in stroke.     

Predictors of advanced proximal neoplasia in persons with abnormal screening flexible sigmoidoscopy.

BACKGROUND & AIMS: The relationship between distal and proximal colonic findings is uncertain. Thus, there is no consensus on which findings on screening flexible sigmoidoscopy should trigger colonoscopy. METHODS: We analyzed data from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial to assess the relationship between distal and proximal colonic findings. RESULTS: A total of 8802 subjects had an abnormal baseline sigmoidoscopy and colonoscopy follow-up. Subjects with <10-mm single or multiple tubular adenomas had similar risks for advanced proximal neoplasia as subjects with hyperplastic polyps or other benign lesions (3%-5%). Subjects with large (>or=10 mm), villous, or severely dysplastic distal adenomas had similarly elevated risks for advanced proximal neoplasia (11%-12%). Multivariate logistic modeling showed a significantly increased risk for advanced proximal neoplasia associated with the presence of a large tubular (odds ratio [OR], 2.6; 95% confidence interval [CI], 2.0-3.4) or villous distal adenoma (OR, 2.7; 95% CI, 2.1-3.5) but not with the presence of one (OR, 1.05; 95% CI, 0.8-1.3) or multiple (OR, 0.8; 95% CI, 0.5-1.2) <10-mm tubular distal adenomas. CONCLUSIONS: Among subjects with a polypoid lesion on screening flexible sigmoidoscopy, those with small tubular distal adenomas are at similar risk for advanced proximal neoplasia as those without distal adenomas. Subjects with a large, villous, or dysplastic distal adenoma are at increased risk. A strategy that encourages individuals with small tubular adenomas on sigmoidoscopy to undergo follow-up colonoscopy and excludes those with nonadenomatous lesions is of questionable validity, because both groups are at similar risk for advanced proximal neoplasia.     

Molecular basis of altered red blood cell membrane properties in Southeast Asian ovalocytosis: role of the mutant band 3 protein in band 3 oligomerization and retention by the membrane skeleton

Southeast Asian ovalocytosis (SAO) is an asymptomatic trait characterized by rigid, poorly deformable red cells that resist invasion by several strains of malaria parasites. The underlying molecular genetic defect involves simple heterozygous state for a mutant band 3 protein, which contains a deletion of amino acids 400 through 408, linked with a Lys 56-to-Glu substitution (band 3-Memphis polymorphism). To elucidate the contribution of the mutant SAO band 3 protein to increased SAO red blood cell (RBC) rigidity, we examined the participation of the mutant SAO band 3 protein in increased band 3 attachment to the skeleton and band 3 oligomerization. We found first that SAO RBC skeletons retained more band 3 than normal cells and that this increased retention preferentially involved the mutant SAO band 3 protein. Second, SAO RBCs contained a higher percentage of band 3 oligomer-ankyrin complexes than normal cells, and these oligomers were preferentially enriched by the mutant SAO protein. At the ultrastructural level, the increased oligomer formation of SAO RBCs was reflected by stacking of band 3-containing intramembrane particles (IMP) into longitudinal strands. The IMP stacking was not reversed by treating SAO RBCs in alkaline pH (pH 11), which is known to weaken ankyrin-band 3 interactions, or by removing the cytoplasmic domain of band 3 from SAO membranes with trypsin. Finally, we found that band 3 protein in intact SAO RBCs exhibited a markedly decreased rotational mobility, presumably reflecting the increased oligomerization and the membrane skeletal association of the SAO band 3 protein. We propose that the mutant SAO band 3 has an increased propensity to form oligomers, which appear as longitudinal strands of IMP and exhibit increased association with membrane skeleton. This band 3 oligomerization underlies the increase in membrane rigidity by precluding membrane skeletal extension, which is necessary for membrane deformation.     

Failure to express the P-selectin gene or P-selectin blockade confers early pulmonary protection after lung ischemia or transplantation

Endothelial P-selectin expression contributes to the first wave of neutrophil (polymorphonuclear leukocyte; PMN) influx in several inflammatory conditions. Although remote tissue ischemia, such as a crush injury to the hindlimb, may result in P-selectin-mediated pulmonary leukosequestration, it is not known whether the lungs exhibit a similar response after hypothermic preservation or when subjected to a direct ischemic insult. To determine if P-selectin may mediate early primary graft failure, left lungs harvested from male Lewis rats were preserved for 6 hr at 4°C and transplanted orthotopically into isogeneic recipients. Recipients immunodepleted of PMNs before transplantation demonstrated improved graft function; pulmonary vascular resistance was reduced ≈6-fold, arterial oxygenation was increased ≈3-fold, and recipient survival was increased ≈4-fold (P < 0.05, 0.05, and 0.005, respectively). Administration of a blocking anti-P-selectin IgG 10 min before reperfusion diminished graft PMN infiltration and resulted in improved graft function and recipient survival compared with controls. To establish the role of P-selectin in normothermic pulmonary ischemia, mice were subjected to temporary left pulmonary artery ligation. After functional removal of the nonischemic right lung, mice deletionally mutant for the P-selectin gene (P-selectin −/−) exhibited reduced PMN infiltration (≈2-fold), improved arterial oxygenation (≈2-fold), and improved survival (≈3-fold) compared with P-selectin +/+ control mice (P < 0.05, 0.01, and 0.05, respectively). These studies isolate and identify the central role of a single gene product (P-selectin) in early PMN recruitment and tissue injury after frank pulmonary ischemia and in the setting of lung transplantation after hypothermic preservation.     

Deletion of the long arm of the Y chromosome and review of Y chromosome abnormalities

We report on a patient whose karyotype is 45,X/46,X,del(Y) (pter----q11.212). We also present a review of literature on the Y chromosome in which evidence is presented that there are genes on the Y chromosome that prevent Ullrich-Turner syndrome manifestations; aid in testes maturation and spermatogenesis; and affect height, tooth size, and bone maturation.     

Leishmania infantum DNA detection in Phlebotomus tobbi in a new northern focus of visceral leishmaniasis in Iran

Objective

To identify the vector(s), the parasite and the species composition of sand flies in the district during May-October 2012.

Methods

For reaching our objectives we used polymerase chain reaction of kDNA, ITS1-rDNA, followed by restriction fragment length polymorphism.

Results

Two species of Phlebotomus sergenti and Phlebotomus tobbi were the most prevalent among 8 species identified comprising 51.1% and 32.9% respectively. Among the 160 specimens of female sand flies tested by polymerase chain reaction of kDNA, ITS1-rDNA, followed by restriction fragment length polymorphisms, only 1 out of 80 Phlebotomus tobbi (1.25%) were positive to Leishmania infantum parasites.

Conclusions

Our finding showed that Phlebotomus tobbi may play as a vector to circulate the parasite of Leishmania infantum among reservoir(s) and human.     

In-hospital and mid-term adverse clinical outcomes of a direct stenting strategy versus stenting after predilatation for the treatment of coronary artery lesions

Background

Direct stenting without balloon dilatation may reduce procedural costs and duration, and hypothetically, the restenosis rate. This study was designed to compare the in-hospital and long-term outcomes of direct stenting (DS) versus stenting after pre-dilatation (PS) in our routine clinical practice.

Methods

The 1 603 patients treated with stenting for single coronary lesions were enrolled into a prospective registry. Patients with acute myocardial infarction (MI) within the preceding 48 hours, and those with highly calcified lesions, total occlusions, or a lesion in a saphenous graft were excluded. The baseline, angiographic and procedural data, inhospital outcomes and follow-up data were recorded in our database and analysed with appropriate statistical methods.

Results

Eight hundred and fifty-seven patients (53.5%) were treated with DS and 746 (46.5%) underwent PS. In the DS group, lesions were shorter in length, larger in diameter and had lower pre-procedural diameter stenosis. Type C and diffuse lesions and drug-eluting stents were found less often (p < 0.001). With univariate analysis, dissection and non-Q-wave MI occurred less frequently in this group (0.2 and 0.6% vs 3.9 and 2.1%, p < 0.001 and p = 0.01, respectively). However, the cumulative major adverse cardiac events (MACE) did not differ significantly (4.9 vs 4.6%, p = 0.79). With multivariate analysis, direct stenting reduced the risk of dissection (OR = 0.07, 95% CI: 0.01–0.33, but neither the cumulative endpoint of MACE (OR = 1.1, 95% CI = 0.58–2.11, p = 0.7) nor its constructing components were different between the groups.

Conclusions

Direct stenting in the real world has at least similar long-term outcomes in patients treated with stenting after pre-dilatation, and is associated with lower dissection rates.     

Unexpected patterns of fisheries collapse in the world's oceans

Understanding which species are most vulnerable to human impacts is a prerequisite for designing effective conservation strategies. Surveys of terrestrial species have suggested that large-bodied species and top predators are the most at risk, and it is commonly assumed that such patterns also apply in the ocean. However, there has been no global test of this hypothesis in the sea. We analyzed two fisheries datasets (stock assessments and landings) to determine the life-history traits of species that have suffered dramatic population collapses. Contrary to expectations, our data suggest that up to twice as many fisheries for small, low trophic-level species have collapsed compared with those for large predators. These patterns contrast with those on land, suggesting fundamental differences in the ways that industrial fisheries and land conversion affect natural communities. Even temporary collapses of small, low trophic-level fishes can have ecosystem-wide impacts by reducing food supply to larger fish, seabirds, and marine mammals.     

An outbreak of cat-associated Q fever in the United States

Q fever is usually acquired by contact with aerosols generated during parturition of domestic ungulates (e.g., sheep, cows, goats). In the maritime provinces of Canada, parturient cats have also been implicated in its transmission. A 66-year-old woman from eastern Maine developed high fever, rigors, headache, myalgias, pulmonary infiltrates, and elevated hepatocellular enzymes, and the diagnosis of acute Q fever was confirmed serologically. She and 14 other family members had attended a family reunion in Maine 2 weeks earlier, when they were exposed to a parturient cat. All 11 adults and older children attending the reunion developed symptoms consistent with acute Q fever. Serum samples were obtained from 10 who attended the reunion and 8 who did not attend. Titers greater than or equal to 1:64 to Coxiella burnetii were present in all who attended the reunion but in none of those who did not. Cat-associated Q fever should be considered when sporadic cases of the disease occur in the United States.