新的高强度高选择性阿片μ受体激动剂[11C]-羟甲芬太尼的合成

羟甲芬太尼(I)是一个新的高强度高选择性阿片μ受体激动剂。本文用cis-A-N-[1-(2-羟基-2-苯乙基)-3-甲基-4-哌啶基]-苯胺(II)或cis-N-[1-(苯甲酰甲基)-3-甲基-4-哌啶基]-苯胺(III)作为前体合成了[¹¹C]-羟甲芬太尼,以便用正电子发射断层扫描(PET)来观察μ受体。通过水解cis-A-羟甲芬太尼(I)和cis-N-[1-(苯甲酰甲基)-3-甲基-4-哌啶]-N-苯基丙酰胺(cis-IV)的4-N-丙酰基分别获得II和III。溴乙烷的格氏试剂与回旋加速器产生的[¹¹C]-二氧化碳反应后继而直接加入邻苯二甲酸二酰氯和2,6-二叔丁基吡啶生成同位素标记中间体[¹¹C]-丙酰氯。[¹¹C]-丙酰氯与OH-前体(II)反应后再经HPLC分离纯化直接得[¹¹C]-羟甲芬太尼;[¹¹C]-丙酰氯与酮-前体(III)反应后,再用硼氢化钠甲醇溶液处理,然后进行HPLC分离纯化得[¹¹C]-羟甲芬太尼。两种方法均可获得ll.1～14.8GBq/μmol的特异性放射化学纯[¹¹C]-羟甲芬太尼。总共耗时为40～50min(EOB)。     

Neonatal alloimmune thrombocytopenia due to HLA-A2 antibody.

A male, full-term baby with thrombocytopenia was born by a G3P2A1 mother who was not associated with autoimmune disease. Platelet antibody screening was positive by using lymphocytotoxicity test, platelet suspension immunofluorescence test and solid-phase red cell adherence test. The identified HLA antibody was of A2 specificity. It was confirmed by testing the mother's and the baby's sera against the lymphocytes and platelets of 10 HLA-A2-positive donors. The possibility of platelet-specific antibody as the cause of neonatal alloimmune thrombocytopenia was ruled out by testing against platelets of 10 HLA-A2-negative donors and the known platelet-specific antigens utilizing immobilized, purified platelet glycoprotein as targets. The mother's serum reacted strongly with both the father's and the baby's platelets and lymphocytes. This neonatal thrombocytopenia was most likely due to the maternal HLA antibody, which was induced by her antecedent gestations.     

HPLC和1HNMR分析确定cis-A-和cis-B-羟甲芬太尼的组成和构型

羟甲芬太尼(1)是一个强效的镇痛剂和高亲和、高选择性的阿片μ受体激动剂。通过HPLC和¹HNMR分析,cis-A-l被确定为由等量的cis-(+)-(3R,4S,2'S)-l和:cis-(—)-(3S,4R,2'R)-1组成的外消旋体,cis-B-l被确定为由等量的cis-(—)-(3R,4S,2'R)-1和cis-(+)-(3S/,4R,2'S)-1组成的外消旋体。     

Comparison of airway diameter measurements from an anthropomorphic airway tree phantom using hyperpolarized 3He MRI and high-resolution computed tomography.

An anthropomorphic airway tree phantom was imaged with both hyperpolarized (HP) 3He MRI using a dynamic projection scan and computed tomography (CT). Airway diameter measurements from the HP 3He MR images obtained using a newly developed model-based algorithm were compared against their corresponding CT values quantified with a well-established method. Of the 45 airway segments that could be evaluated with CT, only 14 airway segments (31%) could be evaluated using HP 3He MRI. No airway segments smaller than approximately 4 mm in diameter and distal to the fourth generation were adequate for analysis in MRI. For the 14 airway segments measured, only two airway segments yielded a non-equivalent comparison between the two imaging modalities, while eight more had inconclusive comparison results, leaving only four airway segments (29%) that satisfied the designed equivalence criteria. Some of the potential problems in airway diameter quantification described in the formulation of the model-based algorithm were observed in this study. These results suggest that dynamic projection HP 3He MRI may have limited utility for measuring airway segment diameters, particularly those of the central airways.     

Segmental intestinal muscular thinning: a possible cause of intestinal obstruction in the newborn

Intestinal obstruction proximal to a transition zone without an interposed physical barrier usually indicates Hirschsprung disease. The authors report one case of focal small bowel muscular thinning just distal to a transition zone that produced clinical and radiographic findings that simulated long-segment Hirschsprung disease in a 2-day-old infant.     

Preferential expression of insulin-like growth factor binding proteins-1, -3, and -5 during early diabetic renal hypertrophy in rats

The renal insulin-like growth factor-I (IGF-I) system has been implicated in the pathogenesis of renal hypertrophy, altered hemodynamics, and extracellular matrix expansion associated with early diabetes. The relative abundance of IGF binding proteins (IGFBPs) in the renal microenvironment may modulate IGF-I actions. However, the precise IGFBPs expressed in the glomerular and tubulointerstitial compartments during diabetic renal growth have not been characterized. In the present study, in situ hybridization studies were performed to examine the expression of IGFBP-1 to -6 messenger RNAs (mRNAs) 3, 7, and 14 days after streptozotocin (STZ) injection in rats. In control, nondiabetic kidneys, all six IGFBP mRNAs were differentially expressed with a predominance of IGFBP-5. The onset of renal hypertrophy in STZ-induced diabetes was associated with a rapid and site-specific induction of IGFBP-1, -3, and -5 mRNAs. In contrast, basal expression of IGFBP-2, -4, and -6 mRNAs was not altered in diabetic rats. IGFBP-5 mRNA expression increased in diabetic glomeruli, cortical, and inner medullary peritubular interstitial cells at days 3, 7, and 14. Although normal glomeruli failed to express IGFBP-3, it was induced concomitantly with IGFBP-5 in diabetic glomeruli and cortical peritubular interstitial cells. IGFBP-1 mRNA levels also increased in cortical tubular cells at each time point tested. Peak induction of IGFBP-3 and -5 was observed at day 3, whereas IGFBP-1 was delayed until day 7. IGFBP-1, -3, and -5 mRNA levels declined by day 14, but remained persistently elevated above control. By immunoperoxidase staining, similar alterations in the pattern of IGFBP-3 and -5 protein expression were observed at each time point. The preferential and site-specific increase in IGFBP-1, -3, and -5 suggest that these IGFBPs may regulate the local autocrine and/or paracrine actions of IGF-I and contribute to the pathogenesis of the early manifestations of diabetic nephropathy.     

Human anti-JC virus serum reacts with native but not denatured JC virus major capsid protein VP1

The immunoreactivity of human anti-JC virus (JCV) serum against the major capsid protein VP1 of JCV was analyzed by Western blot, dot blot, and hemagglutination inhibition (HAI) assays. JCV-positive human serum reacted with native but not denatured JCV major capsid protein VP1, as demonstrated by dot blot and Western blot. Rabbit antiserum raised against native JCV capsid had immunoreactivities similar to those of human anti-JCV serum. These results indicate that the antigenecity of native and denatured JCV VP1 is different. In addition, both JCV-positive human serum and rabbit antiserum raised against native JCV capsid protein inhibited the hemagglutination activity of JCV capsid particles. In contrast, rabbit antiserum raised against denatured JCV VP1 did not inhibit hemagglutination. These findings reveal that denaturation may alter the antigenic epitopes of JCV VP1. Therefore, keeping the JCV capsid protein native appears to be essential for serological or other immunological analyses of the virus.     

Transcriptome analysis in blastocyst hatching by cDNA microarray

BACKGROUND: Hatching is an important process for early embryo development, differentiation and implantation. However, little is known about its regulatory mechanisms. By integrating the technologies of RNA amplification and cDNA microarrays, it has become possible to study the gene expression profile at this critical stage. METHODS: Pre-hatched and hatched ICR mouse embryos (25 blastocysts in each group were used in the triplicate experiments) were collected for RNA extraction, amplification, and microarray analysis (the mouse cDNA microarray, 6144 genes, including expressed sequence tags). RESULTS: According to cDNA microarray data, we have identified 85 genes that were expressed at a higher level in hatched blastocyst than in pre-hatched blastocysts. In this study, 47 hatching-related candidate genes were verified via re-sequencing. Some of these genes have been selected and confirmed by real-time quantitative RT-PCR. These hatching-specific genes were also expressed at a lower level in the delayed growth embryos (morula or blastocyst without hatching at day 6 post hCG). These genes included: cell adhesion and migration molecules [E-cadherin, neuronal cell adhesion molecule (NCAM), lectin, galactose binding, soluble 7 (Lgals7), vanin 3 and biglycan], epigenetic regulators (Dnmt1, and SIN3 yeast homolog A), stress response regulators (heme oxygenase 1) and immunoresponse regulators [interleukin (IL)-2-inducible T-cell kinase, IL-4R, interferon-gamma receptor 2, and neurotrophin]. The immunostaining of E-cadherin and NCAM showed strong and specific localization in hatched blastocyst. CONCLUSIONS: This work provides important information for studying the mechanisms of blastocyst hatching and implantation. These hatching-specific genes may have potential as new drug targets for controlling fertility.