Committing embryonic stem cells to early endocrine pancreas in vitro

A panel of genetic markers was used to assess the in vitro commitment of murine embryonic stem (ES) cells toward the endoderm-derived pancreas and to distinguish insulin-expressing cells of this lineage from other lineages such as neuron, liver, and yolk sac. There are two nonallelic insulin genes in mice. Neuronal cells express only insulin II, whereas the pancreas expresses both insulin I and II. Yolk sac and fetal liver express predominately insulin II, small amounts of insulin I, and no glucagon. We found that ES-derived embryoid bodies cultured in the presence of stage-specific concentrations of monothio-glycerol and 15% fetal calf serum, followed by serum-free conditions, give rise to a population that expresses insulin I, insulin II, pdx-1 (a pancreas marker), and Sox17 (an endoderm marker). Immunohistochemical staining shows intracellular insulin particles, and its de novo production was confirmed by staining for C-peptide. Most, but not all, of the insulin+ or C-peptide+ cells coexpress glucagon, demonstrating a differentiation pathway to pancreas rather than yolk sac or fetal liver. Addition of beta-cell specification and differentiation factors activin beta B, nicotinamide, and exendin-4 to later-stage culture increased insulin-positive cells to 2.73% of the total population, compared with the control culture, which gave rise to less than 1% insulin-staining cells. These findings suggest that stepwise culture manipulations can direct ES cells to become early endocrine pancreas.     

幼师生自尊与心理健康的相关研究

目的 检验幼师女生自尊水平与心理健康的关系。方法 使用自尊量表和SCL-90量表对196名幼师女生进行测量。结果 幼师女生的心理健康总体水平不高，幼师女生自尊水平与心理健康之间存在的显著的负相关。结论 一方面幼师女生的自尊受心理健康水平的影响，特别是抑郁、强迫和人际敏感等方面；另一方面幼师女生的自尊也会影响她们的心理健康水平。     

Genetic control of serum IgE levels: a study of low molecular weight protein tyrosine phosphatase

Protein tyrosine phosphatases (PTPases) have recently been recognized as important modulators of various signal transduction pathways in immune cells. Genetic polymorphisms have been described in genes codifying for members of this family of enzymes, and the genetics of PTPases is predicted to play an important role in the etiology of immune diseases and of their clinical variability. The low molecular weight protein tyrosine phosphatase (ACP1 or LMPTP) is one of the few PTPases with a known genetic polymorphism, and has been proposed to be associated with atopic dermatitis in a small sample from an Italian population. In this paper we describe the association of the ACP1 polymorphism with total IgE levels in two independent samples from English and Italian populations. In both the samples the mean value of serum IgE is lower among subjects carrying the BC genotype than in other ACP1 genotypes. The BC genotype is associated with the highest total ACP1 enzymatic activity. Our data suggest that one or both of the ACP1 isoforms exert an inhibitory role on some signal transduction pathway relevant for IgE hyperproduction.     

High density of immobilized galactose ligand enhances hepatocyte attachment and function

Galactosylated surface is an attractive substrate for hepatocyte culture because of the specific interaction between the galactose ligand and the asialoglycoprotein receptor on hepatocytes. In this study, we described a scheme to achieve high density of immobilized galactose ligands on polyethylene terephthalate (PET) surface by first surface-grafting polyacrylic acid on plasma-pretreated PET film under UV irradiation, followed by conjugation of a galactose derivative (1-O-(6'-aminohexyl)-D-galactopyranoside) to the grafted polyacrylic acid chains. A high galactose density of 513 nmol/cm(2) on the PET surface was used in this study to investigate the behavior of cultured hepatocyte. This engineered substrate showed high affinity to fluorescein isothiocyanate-lectin binding. Primary rat hepatocytes, when seeded at a density of 2 x 10(5) cells/cm(2), attached to the galactosylated PET substrate at a similar efficiency compared with collagen-coated substrate. The hepatocytes spontaneously formed aggregates 1 day after cell seeding and showed better maintenance of albumin secretion and urea synthesis functions than those cultured on collagen-coated surface.     

小儿肝的年龄解剖学研究

分六个年龄组观察了180个(男98,女82)小儿肝的形态、度量、位置及体表投影.小儿肝相对较大,右叶大于左叶,下界位置较低并逐渐上移.在右锁骨中线的肋弓下一般均可触到.小儿肝重随其年龄(身高)的增长而增长,其增长速度相对较慢,尤以Ⅶ组小儿更明显.     

Vesicle-associated membrane protein 4, a positional candidate gene on 1q24-q25, is not associated with type 2 diabetes in the Old Order Amish

OBJECTIVE: The vesicle-associated membrane protein-4 (VAMP4) gene is an excellent type 2 diabetes (T2DM) positional candidate gene. It is located on chromosome 1q24-q25, a region of linkage to T2DM in the Amish and several other populations. VAMP4 is expressed in liver and skeletal muscle and participates in intracellular trafficking of secreted and membrane-associated proteins. DESIGN AND METHODS: We sequenced VAMP4 in 20 Amish subjects. Polymorphisms in and around VAMP4 were genotyped in 65 Amish subjects with T2DM, 64 subjects with impaired glucose homeostasis (IGH), and 126 normal glucose tolerant controls, as well as in an expanded set of 749 participants of the Amish Family Diabetes Study for whom glucose and insulin levels during an oral glucose tolerance test (OGTT) and other quantitative traits related to diabetes were available. Case-control and quantitative trait association analyses were performed. RESULTS: We found three common non-coding intragenic polymorphisms: a 23bp insertion/deletion (I/D) in the 5' untranslated region (UTR) in exon 1 at position 73127, and G35319T and C335296T single nucleotide polymorphisms (SNPs) in the 3' UTR (NCBI Accession No. Z98751). The two 3' UTR SNPs were in complete linkage disequilibrium (LD) and both were in strong LD with the exon 1 I/D polymorphism (|D'|=0.82). Similarly, three extragenic flanking SNPs (rs978985, rs203255, and rs1023479) showed moderate LD with the neighboring intragenic SNPs (|D'|=0.23-0.69). None of the SNPs individually nor any of the 2-, 3-, 4-, or 5-polymorphism haplotypes were associated with T2DM or IGH. The exon 1 I/D polymorphism was not associated with significant differences in mean fasting or stimulated glucose or insulin levels during an OGTT or other diabetes-related quantitative traits in the expanded set of 749 subjects. CONCLUSION: Variation in VAMP4 does not significantly influence risk of T2DM or IGH in the Amish.     

Effect of dosage on immunogenicity of a Vi conjugate vaccine injected twice into 2- to 5-year-old Vietnamese children

In a double-blind, randomized, and placebo-controlled previous trial, the efficacy of Vi-rEPA for typhoid fever in 2- to 5-year-olds was 89.0% for 46 months. Vi-rEPA contained 25 microg of Vi and induced a greater-than-eightfold rise in immunoglobulin G (IgG) anti-Vi in all of the vaccinees tested. In this investigation, we conducted a dosage-immunogenicity study of 5, 12.5, and 25 microg of Vi-rEPA in this age group. Two doses of Vi-rEPA were injected 6 weeks apart. Blood samples were taken before and at 10 weeks (4 weeks after the second injection) and 1 year later. All postimmunization geometric mean (GM) levels were higher than the preimmune levels (P < 0.0001). At 10 weeks, the GM IgG anti-Vi level elicited by 25 microg (102 EU/ml) was higher than those elicited by 12.5 microg (74.7 EU/ml) and 5 microg (43 EU/ml) (P < 0.004): all of the children had > or = 3.52 EU/ml (estimated minimum protective level). One year later, the levels declined about sevenfold (13.3 and 11.3 versus 6.43 EU/ml, P < 0.0001) but remained significantly higher than the preimmune levels (P < 0.0001), and >96% of the children had a greater-than-eightfold rise. This study also confirmed the safety and consistent immunogenicity of the four lots of Vi-rEPA used in this and previous trials.