On the genetic involvement of apoptosis-related genes in Crohn's disease as revealed by an extended association screen using 245 markers: no evidence for new predisposing factors

Crohn's disease (CD) presents as an inflammatory barrier disease with characteristic destructive processes in the intestinal wall. Although the pathomechanisms of CD are still not exactly understood, there is evidence that, in addition to e.g. bacterial colonisation, genetic predisposition contributes to the development of CD. In order to search for predisposing genetic factors we scrutinised 245 microsatellite markers in a population-based linkage mapping study. These microsatellites cover gene loci the encoded protein of which take part in the regulation of apoptosis and (innate) immune processes. Respective loci contribute to the activation/suppression of apoptosis, are involved in signal transduction and cell cycle regulators or they belong to the tumor necrosis factor superfamily, caspase related genes or the BCL2 family. Furthermore, several cytokines as well as chemokines were included. The approach is based on three steps: analyzing pooled DNAs of patients and controls, verification of significantly differing microsatellite markers by genotyping individual DNA samples and, finally, additional reinvestigation of the respective gene in the region covered by the associated microsatellite by analysing single-nucleotide polymorphisms (SNPs). Using this step-wise process we were unable to demonstrate evidence for genetic predisposition of the chosen apoptosis- and immunity-related genes with respect to susceptibility for CD.     

Prostaglandin E2 in basal gastric secretion and during stimulation of muscarinic receptors in man

The physiological importance of prostaglandin E₂ (PGE₂) biosynthesis in the gastric mucosa is unknown. A role of endogenous prostaglandins in protecting the gastrointestinal epithelia has been suggested, but the evidence is unsufficient and rarely supported by concomitant measurement of PG production. Amounts of PGE₂ in luminal gastric contents which can be sampled atraumatically may reflect PGE₂ synthesis in the gastric mucosa in vivo. To confirm earlier reported measurements made with radioimmunoassay we have measured by gas chromatography - mass spectrometry (GC-MS) PGE₂ in gastric juice of five healthy men under basal conditions and during stimulation of muscarinic receptors with iv. bethanechol which in dog is reported to enhance PGE₂ output. PGE₂ was detected in all basal samples. The output was in median 32.1 pmol/15 min (range 17.0–105.4, 1 pmol=0.352 ng), which is similar to results from earlier studies. Bethanechol infusion (60 μg x kg^-1 x h^-1) did not affect PGE₂ outputs systematically in spite of a significant increase in outputs of acid and chlorides. Stimulation of muscarinic receptors does not seem to influence PGE₂ synthesis in gastric mucosa in vivo. Alternatively changes in PGE₂ synthesis may be masked by rapid chemical or enzymatical degradation or reabsorption of PGE₂.Studies are under way to explore those phenomena.     

Strong Suppression by Mononuclear Leukocytes From Cord Blood of Human Newborns on Maternal Leukocytes Associated With Differences in Sensitivity to Prostaglandin E2*

ABSTRACT: We have tested peripheral mononuclear leukocytes (PML) from the cord blood of newborns, from sera of their mothers, and from sera of nonrelated nonpregnant adult women for sensitivity to suppressive exogenous prostaglandin E₂ (PGE₂). Endogenous PG production was simultaneously inhibited by indomethacin 2.8 μM. The phytohemagglutinin-stimulated (PHA-stimulated) uptake of tritiated thymidine (³H-TdR) by PML from the mothers and the nonpregnant women was suppressed by the exogenous PGE₂ at a concentration of 1.4 × 10^?8 M, 100 times less than the one required to suppress the PML from newborns (1.4 × 10^?6 M). In addition, 1.4 × 10^?7 M or less of PGE₂ reversed the suppression of neonatal PML to stimulation. The maternal PML were reversed into stimulation at 1.4 × 10^?9 of exogenous PGE₂. The amount of endogenous PGE₂ synthesized by 1 × 10⁶ fresh, nonstimulated neonatal PML according to gas chromatography-mass spectrometry assay was 5 ng (1.4 × 10^?8 M). The synthesis increased to 27 ng/10⁶ cells after 18 hours' incubation. These concentrations are similar to the ones of exogenous PGE₂ at which neonatal PML were slightly stimulated but the maternal cells were still suppressed. Preincubation for 18 h at 37°C decreased the PGE₂-induced suppression of the adult PML but did not change the response of the neonatal PML.     

抗肿瘤药物的研究Ⅲ. 数种锑胺羧螯合物对实验肿瘤的作用

1.锑胺羧螯合物是一种新型的抗肿瘤药物,应用Sb-26(EDTA-SbNa)、Sb-57(PDTA-SbNa)、Sb-66(HEDT-Sb)和Sb-71(ATA-Sb)分别为15—20、30—50、25—30和20—40毫克/公斤剂量时,均能显著地抑制小白鼠Ehrlich 腹水瘤的生长,平均延长生存时间4—22天,延长率36—147%.上述剂量对大白鼠Guerin 氏癌也有抑制作用,抑制率为58—70%.后3个药物,还能使小白鼠梭形细胞肉瘤腹水型的生存时间延长5—16天,延长率50—160%,其中以Sb-71的疗效最著.Sb-26、Sb-57、Sb-71、Sb-66对肉瘤180和AK 肉瘤及前3者对Ehrlich 固体瘤和淋巴白血病固体型的实验结果,除Sb-71对肉瘤180有抑制作用外,其他均无疗效.2.4 类锑化合物:3个(月弟)酸化合物(Sb-8,Sb-11和Sb-42)及1个酒石酸锑(Sb-15),与螯合的间苯二酚锑(Sb-64)和8羟基喹啉锑(Sb-85)各1个,对Ehrlich 腹水瘤的实验结果,均无明显疗效.3.小白鼠的急性半数致死量,Sb-57和Sb-71分别为131和62毫克/公斤,亚急性半数致死量分别为75和58毫克/公斤.     

Assessment of neutrophil chemotaxis and random migration in childhood. Comparison between leading-front and lower surface count methods

Neutrophil chemotaxis and random migration were studied in 65 healthy children and 18 normal adults. The method used, the leading-front technique, was more accurate and reproducible than the lower surface count method. Chemotaxis in children under 15 years differed from that in adults. This age effect was most pronounced in those less than 6 years, and particularly in those less than 2 years. When investigating chemotaxis in childhood, comparisons with age-matched controls should be made.     

Distinct prevalence of the CYP19 Delta3(TTTA)(7) allele in premenopausal versus postmenopausal breast cancer patients,but not in control individuals

The CYP19 gene encodes the enzyme aromatase, which plays a key role in the conversion of androgens to oestrogens. A polymorphism in CYP19 in intron 4 (TTTA)n has been reported to be associated with breast cancer (BC) risk, although conflicting evidence has also been published. Here, we employ a non-traditional, highly demonstrative design of a molecular epidemiological study, where the comparison of BC cases and healthy middle-aged female donors was supplemented by an analysis of groups with extreme characteristics of either BC risk (bilateral breast cancer (biBC) patients) or cancer tolerance (tumour-free elderly women aged >or=75 years). None of the (TTTA)n polymorphic variants was significantly overrepresented among the affected women compared with any of the control groups. However, a 3-bp deletion/insertion CYP19 polymorphism, which is located in the same intron approximately 50 bp upstream to the (TTTA)n repeat, was evidently associated with the menopausal status in both the BC and biBC cohorts. In particular, the Delta3(TTTA)(7) allele occurred significantly more frequently in premenopausal than in postmenopausal BC patients (65/172 (38%) versus 67/310 (22%); P=0.0001; Odds Ratio (OR)=2.20 (95% Confidence Interval (CI) 1.46-3.32)), while the perimenopausal cases demonstrated an intermediate value (9/34 (26%)). In the biBC cohort, women who developed both tumours during their premenopausal period had a significantly higher prevalence of the Delta3(TTTA)(7) allele than patients with a postmenopausal onset of bilateral disease (16/46 (35%) versus 8/50 (16%); P=0.035; OR=2.80 (1.08-7.23)); those biBC patients, whose tumours were diagnosed before and after the cessation of menses, displayed an intermediate occurrence of the Delta3(TTTA)(7) allele (7/32 (22%)). Similar tendencies in the Delta3(TTTA)(7) allele distribution in BC and biBC patients suggest that its association with the menopausal status of the patients is truly non-random and thus this observation deserves further detailed investigation.     

同时测定乌梅中8种有机酸含量

目的：建立RP-HPLC同时测定乌梅中8种有机酸成分：草酸、酒石酸、苹果酸、抗坏血酸、乳酸、醋酸、柠檬酸和琥珀酸。方法：在C₁₈柱上,用（NH₄）H₂PO₄-H₃PO₄水溶液(pH 2.8)作流动相,紫外检测器检测（214 nm）,流动相流速为0.5 mL·min^-1。结果：分别建立了8种有机酸成分的回归方程。草酸、酒石酸、苹果酸、抗坏血酸、乳酸、醋酸、柠檬酸和琥珀酸的含量分别为1.29%,0.36%,1.82%,1.82%,2.09%,1.65%,16.0%,3.09%。结论：该方法操作简便,准确,快速,一次测定不超过10 min；不但可以作为中药乌梅有机酸成分的质量分析,也可用作为其他植物中有机酸的定量分析。