Human milk as a carrier of biochemical messages

Not only does breast milk provides an ideal nutrient composition for the newborn, but it also contains a variety of substances that may actively influence growth and development of the infant and stimulate neonatal protection against gastrointestinal diseases. Hormones, growth factors, cytokines and even whole cells are present in breast milk and act to establish biochemical and immunological communication between mother and child. In addition, milk nutrients such as nucleotides, glutamine and lactoferrin have been shown to influence gastrointestinal development and host defense. The unique properties of milk as a mediator of biochemical messages will be presented and the clinical significance of breastfeeding in the prevention of neonatal gastrointestinal diseases will be discussed.     

Stimulation of β-adrenoceptors inhibits store-operated channel currents via a cAMP-dependent protein kinase mechanism in rabbit portal vein myocytes

Previously we have described the properties of store-operated channel currents (SOCs) in freshly dispersed rabbit portal vein smooth muscle cells. In addition to Ca²⁺ store depletion these SOCs could also be activated by α-adrenoceptor stimulation and diacylglycerol (DAG) via a protein kinase C (PKC)-dependent mechanism. In the present study we have investigated the effect of β-adrenoceptor stimulation on SOCs in rabbit portal vein myocytes. With whole-cell recording the selective β-adrenoceptor agonist isoprenaline reduced the current evoked by cyclopiazonic acid (CPA, sarcoplasmic/endoplasmic reticulum ATPase inhibitor) by over 85%. With cell-attached patch recording, bath application of isoprenaline produced a pronounced inhibition of SOC activity evoked by either CPA or the acetoxymethyl ester form of BAPTA (BAPTA-AM). SOC activity evoked by CPA, the DAG analogue, 1-oleoyl-acetyl- sn -glycerol (OAG) or the phorbol ester, phorbol-12,13-dibutyrate (PDBu) was also markedly inhibited by the adenylate cyclase activator, forskolin, and the cell-permeable non-hydrolysable analogue of cyclic adenosine monophosphate (cAMP), 8-Br-cAMP. With inside-out patches, bath application of PDBu evoked channel currents with similar properties to SOCs which were inhibited by over 90% by a catalytic subunit of protein kinase A (PKA) and by 8-Br-cAMP. Moreover bath application of PKA inhibitors, H-89, KT5720 and an inhibitory peptide to quiescent cell-attached or inside-out patches, activated channel currents with similar properties to SOCs. These data suggest that in rabbit portal vein myocytes, stimulation of β-adrenoceptors inhibits SOC activity via a cAMP-dependent protein kinase signal transduction cascade. In addition it is concluded that constitutive PKA activity has a profound inhibitory effect on SOC activity in this vascular preparation.     

慢性低氧时小鼠肺组织低氧诱导因子-1α的表达

目的：研究低氧时小鼠肺组织中低氧诱导因子-1α(HIF-k)表达的变化。方法：实验用雄性小鼠,低氧仓浓度分别为10％、7％、5％。用免疫荧光组织化学技术及共聚焦显微术,检测小鼠在低氧条件下肺组织中HIF-1α表达的变化。结果：正常组小鼠肺组织HIF-1α无表达,低氧组HIF-1α表达增加,且随低氧时间的延长及低氧强度的增加而增强。结论：低氧可诱导小鼠肺组织中HIF-1α的表达增强,(HIF-k)可能参与肺组织细胞凋亡的发生。     

Proteases, extracellular matrix, and cancer: a workshop of the path B study section

The role of the extracellular matrix (ECM) in the tumor microenvironment is not limited to being a barrier against tumor invasion. The ECM is a reservoir of cell binding proteins and growth factors that affect tumor cell behavior. It is also substantially modified by proteases produced by tumor cells or stroma cells. As a result of the activity of these proteases, cell-cell and cell-ECM interactions are altered, new biologically active ECM molecules are generated, and the bioavailability and activity of many growth factors, growth factor receptors, and cytokines are modified. ECM-degrading proteases also play a critical role in angiogenesis, where they can act as positive as well as negative regulators of endothelial cell proliferation and vascular morphogenesis. This review article summarizes some of the most relevant findings made over the recent years that were discussed at a workshop organized by the Path B Study Section of the National Institutes of Health in October 2002.     

Study on the relationship between interleukin-10 promoter polymorphism and the chronic severe hepatitis

The aim of this study is to investigate whether three mononucleotide polymorphisms at the locus -1082,-819 and -592 in the promoter region of the IL-10 gene are associated with chronic severe hepatitis. The IL-10-592 and IL-10-1082 polymorphisms were genotyped by polymerase chain reactionrestriction fragment length polymorphism analysis （PCR-RFLP） while polymerase chain reaction-sequence specific primer （PCR-SSP） assay was used to test the IL-10-819 polymorphism. The polymorphisms of IL-10-1082, -819 and -592 genes were detected in 98 patients with chronic severe hepatitis （CSH）, 478 patients with chronic hepatitis B （CHB）, 223 asymptomatic （chronic） HBV carriers （ASC） and 267 patients with self-restricted HBV. There was significant difference of the polymorphisms of IL-10-1082, IL-10-819 and IL-10-592 genes between CSH group and other groups. The frequency of AA genotype at IL-10 gene promoter -1082 locus in chronic severe hepatitis patients was higher than that in asymptomatic HBV carriers （2 = 13. 314, P = 0.001）, and self-restricted HBV patients （χ^2 = 13.545, P = 0.000）; the frequency of CC and AC genotype at IL-10 gene promoter -592 locus in chronic severe hepatitis patients was higher than that in chronic hepatitis patients（χ^2 = 15.970, P=0.000） （χ^2 =20.414, P=0.000）, asymptomatic HBV carriers （χ^2 =21.283, P= 0.000） （χ^2 = 28.309, P = 0.000） and self-restricted HBV patients（χ^2 = 17.047, P = 0.000） （χ^2 = 16.528, P = 0.000） ; the frequency of TC genotype at IL-10 gene promoter -819 locus in chronic severe hepatitis patients was higher than that in chronic hepatitis patients（χ^2 = 58.961, P = 0.000）, asymptomatic HBV carriers （ χ^2 = 53. 255, P = 0. 001 ） and self-restricted HBV patients （χ^2 = 39.616, P = 0.001）. So interleukine-10 gene polymorphism was associated with the chronic severe hepatitis.     

颅底外面枕骨基底部及周边骨性结构的测量和临床意义

目的为斜坡区肿瘤手术提供解剖资料。方法20例整颅,10例行水平切面,10例行正中矢状切面。测量切牙孔、前鼻棘、后鼻棘、枕骨大孔前端、枕髁前端、卵圆孔、破裂孔、颈动脉管外口及舌下神经管外口的内侧缘至咽结节的距离;测量卵圆孔、破裂孔、颈动脉管外口及舌下神经管外口的内侧缘至正中线的距离;测量枕骨基底部颅底外面的长径、枕骨大孔纵径(FML)、枕骨大孔前正中点与枕髁后缘连线垂直距离(AOCP)、枕髁轴径(OCA)、枕髁间距。结果切牙孔后缘、前鼻棘、后鼻棘、枕骨大孔前端、枕髁前端、卵圆孔、破裂孔、颈动脉管外口及舌下神经管外口的内侧缘至咽结节的距离分别为(mm):72.12±4.25、77.77±3.89、33.73±2.07、13.14±1.91、15.71±1.74、27.51±2.12、15.98±1.98、25.93±2.23、19.15±1.49。卵圆孔、破裂孔、颈动脉管及舌下神经管外口的内侧缘至中线的距离分别为:25.55±1.63、11.72±1.70、25.75±1.98、17.41±1.41。枕骨基底部颅底外面长径、FML、AOCP、OCA、枕髁间距分别为(mm):28.80±2.67、35.84±2.59、17.10±1.13、24.55±2.35、21.07±1.92。结论经口咽至斜坡区的手术入路中,开骨窗时安全范围是以咽结节为中心,以15mm为半径做斜坡磨除;也可以做矩形骨窗,即以咽结节为中心开一长(高)25mm×宽20mm的骨窗。     

<Emphasis Type="Italic">TCF7L2</Emphasis>variant genotypes and type 2 diabetes risk in Brazil: significant association,but not a significant tool for risk stratification in the general population

Background  

Genetic polymorphisms of the TCF7L2 gene are strongly associated with large increments in type 2 diabetes risk in different populations worldwide. In this study, we aimed to confirm the effect of the TCF7L2 polymorphism rs7903146 on diabetes risk in a Brazilian population and to assess the use of this genetic marker in improving diabetes risk prediction in the general population.     

Engaging populations living with vulnerable conditions in community‐based research: A concept mapping approach to understanding positive practices

The goal of this research is to identify positive practices used when conducting community‐based research with people living with vulnerable conditions. Community‐based research practitioners who participated in the research included 37 researchers, community partners, program planners, and government employees, working in health, human services, children and youth, and education sectors. Concept mapping, a participatory stakeholder‐driven process, was used to generate a framework of how community‐based research practitioners responded to the complex environments of people living with vulnerable conditions when conducting research. Respondents generated positive practices, determined relationships among practices, and rated practices on frequency of use and perceived effectiveness. This study revealed 7 clusters of positive practices: ethical practices, participant supports, social accountability, community involvement, language competence, financial compensation, and project management.     

LONGITUDINAL AND CONCURRENT PATHWAYS TO ALCOHOLISM: THE IMPORTANCE OF PERCEPTION OF NEIGHBORHOOD DISORDER

Neighborhood‐level and individual‐level variables from childhood and adulthood were examined in relation to alcoholism in adulthood. In 1976–1978, children from working‐class neighborhood schools in Montreal, Canada participated in a study examining the outcomes of childhood behaviors. At this time, peer nominations of childhood aggression were collected. In 1999–2003, these participants were contacted during mid‐adulthood (N = 676) and asked to complete measures of perception of neighborhood disorder as well as a structured clinical interview assessing their lifetime history of alcoholism. Measures of participants’ neighborhood socioeconomic status (SES) from adolescence and adulthood were retrieved from Canadian census tract data and included in the model. Findings supported an association between neighborhood disorder and alcoholism, such that perceived disorder mediated the association between census‐based assessments of neighborhood SES and alcoholism, but not when examined within a larger model. These findings supported the importance of the individual's interpretation of their environment in relation to alcoholism.     

Induction of IL-5 expression by IL-2 is resistant to the immunosuppressive agents cyclosporin A and rapamycin

T cell cytokine expression may be induced by the cytokine IL-2 or via the TCR complex. The comparative effects of cytokine- and TCR-mediated signalling on the induction of human IL-5 mRNA were examined. Cytokine mRNA expression was analysed by RT-PCR in fresh peripheral blood mononuclear cells (PBMC) from normal individuals and in populations of activated T lymphocytes, derived from phytohaemagglutinin (PHA)- stimulated PBMC. rIL-2 induced IL-5 expression in PBMC, the kinetics of which were similar to the effects of PHA. rIL-4 induced IL-5 mRNA expression in activated T lymphocytes. IL-5 expression induced by either IL-2 or PHA was completely abolished by the protein synthesis inhibitor cycloheximide. rIL-2-induced IL-5 expression was resistant to cyclosporin A (CsA), whereas IL-5 expression elicited by PHA was inhibited by CsA, at doses as low as 10 ng/ml. Rapamycin (RAP) had no effect on rIL-2-stimulated IL-5 expression, but suppressed IL-5 expression induced by PHA. The inhibitory effect of RAP on PHA-induced IL-5 expression was more apparent at 12 and 24 h after stimulation than at earlier times. The resistance of IL-2 receptor (IL-2R) signalling to CsA and RAP indicates that the IL-2R and the TCR are associated with different pathways regulating IL-5 expression.