Molecular epidemiologic studies of polycyclic aromatic hydrocarbon-DNA adducts and breast cancer

We review our studies on the role of polycyclic aromatic hydrocarbon (PAH)-DNA adducts in breast cancer. Additionally we report on analyses of the reliability of the scoring procedures used with immunohistochemical assay for PAH-DNA adducts and of potential bias arising from the use of benign breast disease (BBD) controls. We conducted a case-control study utilizing two control groups: BBD controls who donated tissue and blood samples, and healthy controls who donated blood samples. In comparisons of tumor tissue from cases and benign tissue from BBD controls, increasing adduct levels were significantly associated with case-control status [odds ratio (OR) = 2.40, 95% confidence interval (CI) 1.18-4.92], whereas in comparisons of nontumor tissue from cases and benign tissue from BBD controls the association was nonsignificant (OR = 1.97, 95% CI 0.94-4.17). We also show among cases, but not among BBD controls, that the GSTM1 null genotype is associated with increased adduct levels in breast tissue. Our reliability study found the scoring procedures used with the immunohistochemical assay to have high reliability, 0.93 in nontumor, 0.82 in tumor, and 0.74 in benign tissues. However, we found that the technician significantly contributed to the total variability of a series of data. Finally, we did not find a consistent bias to the null associated with the use of BBD controls; however, BBD controls may overestimate the prevalence of family history of breast cancer compared to that of healthy controls (18% vs.14%). We hypothesize that the higher prevalence results from a referral bias and discuss how this may influence our results.     

Impaired recognition of fear in a Chinese man with bilateral cingulate and unilateral amygdala damage

LJM, a 41-year-old schizophrenic Chinese man with bilateral anterior cingulate gyrus (Brodmann's area 24) lesions and also a small lesion in right amygdala after an operation, was compared with normal as well as brain-damaged and schizophrenic controls in identification of morphed facial expressions of six basic emotions. In repeated administrations of the test for recognition of facial emotions, over a 1- year period, LJM performed significantly worse for expressions of fear compared with the three groups of controls. Recognition of other emotions was not significantly different from that of the controls, except that his recognition of disgust during the first session (but not in two subsequent sessions) was worse than normal and brain-damaged controls but not worse than schizophrenic controls. The dissociation between recognition of fear and other emotions supported the view that the brain has separable networks for processing different emotions, and that the right amygdala as well as the anterior part of bilateral cingulate gyrus are possible substrates involved in the special network for perception of fear. The results from the various groups of Chinese subjects indicate that they perceive emotions in a categorical manner, and that the six basic emotions are likely to be cross-cultural universals.     

Deletion spanning the 5′ ends of both the COL4A5 and COL4A6 genes in a patient with Alport's syndrome and leiomyomatosis

Alport's syndrome is characterized clinically by a nonimmune glomerulopathy, often accompanied by sensorineural hearing loss and lens abnormalities, frequently due to mutations in the COL4A5 gene. The association of AS with diffuse leiomyomatosis, a benign proliferation of smooth muscle that occurs most often in the esophagus, trachea, and female genitalia, has been reported. Recently, a deletion involving both the COL4A5 and COL4A6 genes has been reported in four unrelated families. We report an additional case with Alport's syndrome associated with leiomyomatosis carrying a deletion of both COL4A5 and COL4A6 genes. A detailed characterization of the genomic region involved in the deletion event has been performed. Our results demonstrate that the deletion removed exon l of COL4A5 and exons l and 2 of COL4A6. © 1994 Wiley-Liss, Inc.     

脐带血清对骨髓粒—巨噬细胞集落形成的影响

在骨髓细胞半固体琼脂培养体系中，研究脐带血清（ＣＢｓ）对骨髓粒—巨噬细胞集落形成单位（ＣＦＵ－ＧＭ）的影响，单纯应用ＣＢｓ培养可使骨髓ＣＦＵ－ＧＭ（ｘ±ｓ为２６．０３７５±１０．２３２７）显著的高于正常成人外周血清（ＰＢｓ）组（ｘ±ｓ为１１．５９１７±３．６０４７；Ｐ＜０．００１）。ＣＢｓ加粒－巨噬细胞刺激因子，ＧＭ－ＣＳＦ组ＣＦＵ－ＧＭ（ｘ±ｓ为１１９．０７９２±３５．０９９１）是单纯ＣＢｓ组的４．５７倍；而ＰＢｓ加ＧＭＣ－ＳＦ组（ｘ±ｓ为９７．１２５±２６．７５５９）是单纯ＰＢｓ组的８．３８倍。有白细胞介素－６（ＩＬ－６）存在的ＣＢｓ组，ＣＦＵ－ＧＭ（ｘ±ｓ为３１．９３３３±１０．９１４４）明显的高于单纯ＣＢｓ组（Ｐ＜０．０２）。提示ＣＢｓ中含有较高水平的内源性ＧＭ－ＣＳＦ。     

gp49B1 suppresses stem cell factor-induced mast cell activation-secretion and attendant inflammation in vivo

We report that gp49B1, a mast cell membrane receptor with two immunoreceptor tyrosine-based inhibitory motifs (ITIM), constitutively inhibits mast cell activation-secretion induced by stem cell factor (SCF), a tissue-derived cytokine that also regulates mast cell development. The intradermal injection of SCF into the ears of gp49B1 null (gp49B(-/-)) mice elicited approximately 4- and 2.5-fold more degranulating mast cells and tissue swelling caused by edema, respectively, than in gp49B(+/+) mice. SCF did not induce tissue swelling in mast cell-deficient mice, and the responsiveness of gp49B(-/-) mice to mast cell-associated amine and lipid mediators was unaltered. When gp49B(+/+) and gp49B(-/-) mice were pretreated with antagonists of the amines, SCF-induced tissue swelling was reduced by >90% and 60%, respectively, and it was reduced by >90% in both genotypes when a cysteinyl leukotriene receptor antagonist was also provided. Hence, the dominant contribution of secretory granule amines to SCF-induced tissue swelling is the result of gp49B1-mediated inhibition of the production of cysteinyl leukotrienes by mast cells. Our findings also provide the first example of an ITIM-bearing receptor that constitutively suppresses inflammation generated in vivo independently of the adaptive immune response by a receptor that signals through intrinsic tyrosine kinase activity rather than immunoreceptor tyrosine-based activation motifs.     

胃动素对血管灌流大鼠离体胃运动的作用

通过血管灌流大鼠离体胃,探讨胃动素对胃运动的影响。结果表明:(1)胃动素可以明显地兴奋胃窦自发的胃运动;(2)胃动素抗血清可以完全消除胃动素兴奋胃窦运动的作用;(3)阿托品可以阻断胃动素兴奋胃窦运动的作用。上述结果提示,胃动素可特异性兴奋血管灌流大鼠胃窦收缩运动,该作用通过壁内胆碱能神经介导。     

不同年龄组儿童甲状腺测量值及其变化的研究

调查了90具童尸用状腺的基本形态,可分四型。其中以甲状腺由两侧叶及峡部组成者为最多,占50.22%。测量了甲状腺各部的长、宽、厚。分年龄组进行了数据的统计学处理,并计算出儿童与成人甲状腺各部相应值的百分比。结果显示:小儿甲状腺侧叶的长度和宽度在幼儿期(1—3岁)就已发育近成人的一半。随着年龄的增长,甲状腺各部的均值逐渐增加。除各部的宽度以及锥体叶的长度外,各相邻两组间同项均数的比较,经双侧T检验发现差异具有高度显著性(P<0.01)。     

Simultaneous inhibition of caudal medullary raphe and retrotrapezoid nucleus decreases breathing and the CO2 response in conscious rats

The medullary raphe (MR) and the retrotrapezoid nucleus (RTN) in the ventral medulla are two of many central chemoreceptor sites. We examine their combined function in conscious rats by focal inhibition using microdialysis. Inhibition of RTN neurons with the GABA_A receptor agonist muscimol, with simultaneous dialysis of artificial cerebrospinal fluid (ACSF) in or near to the caudal MR, causes hypoventilation (decrease in the ratio of minute ventilation to oxygen consumption,     ) and reduces the ventilatory response to 7% CO₂ by 24%. Inhibition of caudal MR serotonergic neurons with the 5-HT_1A receptor agonist ( R )-(+)-8-hydroxy-2(di- n -propylamino)tetralin (8-OH-DPAT), with simultaneous dialysis of ACSF in or near to the RTN, causes hypoventilation but has no significant effect on the CO₂ response. Inhibition of both the RTN and the caudal MR simultaneously produces enhanced hypoventilation and a 51% decrease in the CO₂ response. The effects of treatment on the CO₂ response are similar in wakefulness and in non-rapid eye movement sleep. Comparison of the effect of 8-OH-DPAT microdialysed into a more rostral portion of the MR, where the CO₂ response is reduced by 22%, demonstrates heterogeneity within the MR of the function of serotonergic neurons in breathing. We conclude that serotonergic neurons within the caudal MR provide a non-CO₂-dependent tonic drive to breathe and potentiate the effects of RTN neurons that contribute to a resting chemical 'drive to breathe' as well as the response to added CO₂. These effects of caudal MR serotonergic neurons could be at a chemoreceptor site, e.g. the RTN, or at 'downstream' sites involved in rhythm and pattern generation.