Fat‐water separated delayed hyperenhanced myocardial infarct imaging

Fat deposition associated with myocardial infarction (MI) has been reported as a commonly occurring phenomenon. Magnetic resonance imaging (MRI) has the ability to efficiently detect MI using T₁‐sensitive contrast‐enhanced sequences and fat via its resonant frequency shift. In this work, the feasibility of fat‐water separation applied to the conventional delayed hyperenhanced (DHE) MI imaging technique is demonstrated. A three‐point Dixon acquisition and reconstruction was combined with an inversion recovery gradient‐echo pulse sequence. This allowed fat‐water separation along with T₁ sensitive imaging after injection of a gadolinium contrast agent. The technique is demonstrated in phantom experiments and three subjects with chronic MI. Areas of infarction were well defined as conventional hyperenhancement in water images. In two cases, fatty deposition was detected in fat images and confirmed by precontrast opposed‐phase imaging. Magn Reson Med 60:503–509, 2008. © 2008 Wiley‐Liss, Inc.     

Homology modelling of CYP2A6 based on the CYP2C5 crystallographic template: enzyme-substrate interactions and QSARs for binding affinity and inhibition.

The results of homology modelling of the human P450 enzyme CYP2A6, based on the CYP2C5 crystallographic template structure are reported. A substantial number of selective substrates of the CYP2A6 enzyme fit the putative active site in a manner that is consistent with their known metabolites. Moreover, the evidence from site-directed mutagenesis experiments is in accordance with the current model, particularly in relation to complementary amino acid contacts within the haem environment. The binding of substrates is rationalized in terms of QSAR analyses and from a consideration of the contributory factors affecting the binding affinity. The latter approach appears to represent a highly correlated (R=0.99) method for estimating the relative strength of enzyme-substrate binding within CYP2A6-selective compounds, albeit within a fairly limited dataset of substrates.     

阿苯达唑治疗前后泡状棘球蚴病患者淋巴细胞亚群变化及临床意义

目的　探讨泡球蚴病患者经阿苯达唑治疗后 ,机体免疫应答的状态和对病程转归的影响。　方法　 7例未治疗泡球蚴病患者 ,6例经阿苯达唑治疗 12个月泡球蚴病患者 ,6例经阿苯达唑治疗 2 4个月泡球蚴病患者和 18例非流行区健康人群 ,用 FCM分析了 CD3+ 、CD4 + 、CD8+ 、CD1 9+ 、CD38+ 、CD1 6 + 56 + 和 HL A- DR+ 细胞的数量。　结果　治疗 12个月后 ,患者 CD8+细胞数继续上升 (P<0 .0 1) ,CD4 + / CD8+比值进一步倒置 ;治疗 2 4个月后 ,CD4 +细胞数开始升高 (P<0 .0 5 ) ,CD8+ 细胞数下降 ,CD4 + / CD8+ 比值升高 (P<0 .0 5 ) ;CD1 9+ 细胞在治疗 2 4个月后显著性升高 (P<0 .0 5 ) ;CD38+ 和 HL A-DR+ 细胞在治疗 2 4个月后呈显著性下降 (P<0 .0 1)。　结论　泡球蚴病患者治疗后 ,CD8+ 细胞引起的免疫抑制状态有所减轻 ,机体的保护性免疫应答有所恢复。     

Transmissible familial Creutzfeldt-Jakob disease associated with five, seven, and eight extra octapeptide coding repeats in the PRNP gene.

The PRNP gene, encoding the amyloid precursor protein that is centrally involved in Creutzfeldt-Jakob disease (CJD), has an unstable region of five variant tandem octapeptide coding repeats between codons 51 and 91. We screened a total of 535 individuals for the presence of extra repeats in this region, including patients with sporadic and familial forms of spongiform encephalopathy, members of their families, other neurological and non-neurological patients, and normal controls. We identified three CJD families (in each of which the proband's disease was neuropathologically confirmed and experimentally transmitted to primates) that were heterozygous for alleles with 10, 12, or 13 repeats, some of which had "wobble" nucleotide substitutions. We also found one individual with 9 repeats and no nucleotide substitutions who had no evidence of neurological disease. These observations, together with data on published British patients with 11 and 14 repeats, strongly suggest that the occurrence of 10 or more octapeptide repeats in the encoded amyloid precursor protein predisposes to CJD.     

N-myc can cooperate with ras to transform normal cells in culture.

N-myc, a cellular gene bearing homology to the c-myc protooncogene, is frequently amplified and overexpressed in a highly restricted set of related tumors, most notably neuroblastomas and retinoblastomas. We have examined the possibility that N-myc may play a causal role in the genesis of these tumors by defining its ability to transform primary cells in tissue culture. Using an N-myc expression construct capable of producing constitutively deregulated levels of full-length murine N-myc mRNA, we demonstrate that a deregulated N-myc gene can cooperate with the activated Ha-ras oncogene to cause tumorigenic conversion of normal embryonic fibroblasts in a manner indistinguishable from the deregulated c-myc oncogene. Cell lines established from N-myc/ras-transformed foci express high levels of the N-myc gene, and such lines are similar to c-myc/ras transformants in their ability to grow in soft agar and cause tumors in syngeneic rats. These results illustrate that N-myc does encode a c-myc-like transforming activity and that this transforming activity is not specific for the very restricted set of tumors in which N-myc is normally amplified or overexpressed.     

Senescence of canine biotinylated erythrocytes: increased autologous immunoglobulin binding occurs on erythrocytes aged in vivo for 104 to 110 days

We have evaluated senescence related changes in canine red blood cells (RBCs) using the biotinylation system, where RBCs are labeled in vivo with biotin at the beginning of their life span, and retrieved from circulation on immobilized avidin at the end of their life span. This approach avoids the controversial use of density gradient centrifugation to collect presumably old RBCs. Furthermore, the dog is an appropriate model for human RBC senescence because it has a low degree of random RBC loss and a similarly long RBC life span (approximately 110 days). Two dogs had 97% to 100% of their circulating RBCs biotinylated by infusion of N-hydroxysuccinimido biotin (Clontech, Palo Alto, CA; Calbiochem, La Jolla, CA) dissolved in dimethyl sulfoxide. At postbiotinylation days 104 and 107 for one dog and day 110 for the other dog, biotinylated RBCs were isolated by magnetic cell sorting and analyzed for the presence of autologous IgG using 125I- labeled sheep-antidog IgG (SAD IgG). On all 3 days, there were at least three times more SAD IgG molecules per RBC on senescent biotinylated RBCs than on control (unfractionated) RBCs (day 104: 11,677 v 3,399; day 107: 6,710 v 2,115; day 110: 6,042 v 1,838 molecules of SAD IgG per senescent v control RBC). Furthermore, it is unlikely that an immune response to the conjugated biotin had been elicited, because fresh in vitro biotinylated RBCs that were incubated in autologous plasma (taken after exposure to circulating biotinylated RBCs for 113 days) and then exposed to the SAD IgG showed no increase in antibody binding over control (non-biotinylated) RBCs (1,431 v 1,378 cpm/10(8) biotinylated v control RBCs; P > .20). These results suggest that senescence of canine biotinylated RBCs is characterized by binding of autologous IgG and that antibiotin antibodies do not contribute to this process.     

Mutations that affect the translation efficiency of Tn9-derived cat gene in Bacillus subtilis.

We have isolated two spontaneous mutations that increase the expression of the Tn9-derived cat gene in Bacillus subtilis. These mutations, which appear to affect initiation of translation of chloramphenicol acetyltransferase (CAT; acetyl-CoA:chloramphenicol 3-O-acetyltransferase, EC 2.3.1.28) consist of a tandem duplication and triplication of a 55-base-pair sequence located at the 5' end of cat. Included in the repeated sequence are the Shine-Dalgarno site, initiation codon, and a region of dyad symmetry located within the structural portion of the cat gene. A striking feature of the mutated initiation sites is their potential to form stem-loop structures at the 5' end of the cat messenger RNA. Within the single-stranded loops of these structures are the ribosome binding site and initiation codon for the cat gene. It appears that the Gram-negative cat translation initiation site has mutated to permit efficient utilization in B. subtilis without directly affecting Shine-Dalgarno sequence homology. This report suggests that secondary structure in the vicinity of the Shine-Dalgarno site can exert a strong positive influence on the initiation of translation in B. subtilis.     

Platelet survival in patients with beta-thalassemia

Thromboembolic events associated with significant morbidity and mortality have been observed in patients with beta-thalassemia major (TM). These include arterial as well as venous thrombosis and the development of early arteriosclerosis. To elucidate the possibility that TM patients may develop a hypercoagulable state we carried out a study of platelet kinetics on ten patients with TM and four patients with thalassemia intermedia (TI). Autologous platelets were labeled with indium-111-oxine, and the platelet lifespan (PLS) was determined. A significant shortening of PLS was observed in 13 out of 14 patients examined. The mean PLS (+/- 1 SD) in ten patients (8 TM, 2 TI) who underwent splenectomy was 107 +/- 36 hr (control splenectomized 248 + 51 hr) (P less than .001) and in four nonsplenectomized patients (2 TM, 2 TI) was 102 +/- 64 hr (control 224 + 23 hr) (P less than .01). The short PLS in addition to reported findings of increased circulating platelet aggregates and the decreased response of TM platelets to aggregating agents suggests in vivo platelet activation in thalassemic patients.