辅酶Q10对兔膈肌疲劳的作用

实验以膈肌肌电图（ＥＭＧｄｉ）及膈肌诱发电位为指标，观察辅助酶Ｑ１０对兔膈肌作用，发现：（１）复制膈肌疲劳（ＤＩＦ）后静脉注射ＣｏＱ１０ｍｇ／ｋｇ，对ＤＩＦ有治疗作用，（２）提前１静脉注射ＣｏＱ１０１０ｍｇ／ｋｇ预处理，对电致作膈肌有保护作用。     

支气管哮喘患者血清IL-10与IgE水平变化的研究

分别用ELISA、IRMA法对50例支气管哮喘急性发作患者和48名对照者血清IL-10、IgE进行测定.结果是: 支气管哮喘患者IL-10含量明显低于对照组(P＜0.01), 而IgE含量则明显高于对照组(P＜0.01), 两者之间呈明显负相关(r=-0.18,P＜0.01).结论是: 支气管哮喘患者IL-10不足、IgE水平增高可能成为其发病的重要原因之一.     

Immune modulation with interleukin-4 and interleukin-10 prevents crescent formation and glomerular injury in experimental glomerulonephritis

Crescentic glomerulonephritis (GN) demonstrates immunopathological features of a T helper (Th)1-directed delayed-type hypersensitivity (DTH) response. The capacity of Th2 cytokines to attenuate crescentic glomerular injury in this disease was examined by administering interleukin (IL)-4 and IL-10, singly and in combination. GN was induced by i.v. administration of sheep anti-mouse glomerular basement membrane (GBM) globulin to mice sensitized to sheep globulin 10 days earlier. Treatment (2.5 μg, i.p.) with IL-4, IL-10, or both IL-4 and IL-10 (IL-4+10), was started 1 h before sensitization and continued daily until the end of the study (10 days after administration of anti-GBM globulin). Control mice treated with PBS developed GN with glomerular accumulation of T cells and macrophages, crescents in 42.5 ± 4.5 % of glomeruli (normal 0 %), proteinuria (8.3 ± 0.9 mg/24 h, normal 0.74 ± 0.08 mg/24 h, p < 0.001) and renal impairment (creatinine clearance [cr/cl]: 93 ± 12 μ1/min, normal 193 ± 10 μ1/min, p<0.001). 1reatment with either IL-4, IL-10, or IL-4+10 prevented crescent formation (crescentic glomeruli: 0.8 ± 0.5, 1.2 ± 0.9, and 1.4 ± 1.0 %, respectively, all p<0.01 compared to control) and attenuated proteinuria (3.6 ± 1.0, 2.2 ± 0.5, and 2.9 ± 0.5 mg/24 h, respectively, all p<0.01 compared to control). IL-4+10 prevented development of renal impairment (cr/cl: 183 ± 22 μ1/min); IL-10 given alone limited the decline in renal function (cr/cl: 150 ± 20 μ1/min), but IL-4 alone did not provide any significant protection (cr/cl: 121 ± 17 μ1/min). All treatments markedly diminished glomerular T cell and macrophage accumulation, reduced interferon-γ production by splenic T cells, prevented cutaneous DTH to the disease-initiating antigen and reduced antigen-specific immunoglobulin of the IgG2a and IgG3 isotypes. These data demonstrate that crescentic GN and renal impairment can be prevented by administration of Th2 cytokines and that this effect is associated with attenuation of the Th1 response to the disease-initiating antigen.     

Clinical consequences of heterozygosity for autosomal-recessive diseases*,**

Heterozygotes of autosomal-recessive diseases can often be recognized by special heterozygote tests, since enzyme activities are normally reduced in comparison with the normal homozygote state. In Drosophila, the majority of recessive lethal mutations shows a reduction of fitness in heterozygotes, whereas in a strong minority fitness of heterozygotes is increased. This review will be devoted to a consideration of the extent to which heterozygotes for a wide variety of nominally recessive diseases are subject either to an increased liability for common diseases or slight shifts of behavioral characteristics. The available evidence has been collected and will be discussed in three steps: Most studies are available for phenylketonuria. For this group of diseases, a slight reduction of average--especially verbal--I.Q. in heterozygotes has been reported together with signs of a slightly increased cerebral irritability, a possible slight increase of risk for mental disease, and an increase of blood phenylalanine levels in stress situations. The PKU example is used to discuss methodological problems involved in such studies. Other conditions for which relevant deviations in heterozygotes are possible or even likely include among others lipid storage diseases, microcephaly, myoclonus epilepsy, Wilson's disease, galaktokinase deficiency, homocystinuria, recessive myotonia and ataxia- teleangiectasia (increased cancer risk). Since heterozygotes for autosomal recessive diseases are common, it is possible that an appreciable fraction of "multifactorial" genetic liabilities for common, "constitutional" or mental disease might simply be due to heterozygosity for genes whose homozygous affects are already well known. By the same token, much of the "normal" genetic variability influencing cognitive performance (I.Q.)--especially in the lower range--and personality characteristics could also be caused by recessive genes in the heterozygous state.     

Skin tests and blood leukocyte histamine release of patients with allergies to laboratory animals

Skin tests and in vitro histamine-release reactions were used to evaluate 130 patients observed in an employee allergy clinic at a biomedical research facility. The allergens used included extracts from pollens (ragweed, grasses, trees, weeds), molds, mixed feathers, house dust, cat, dog, mouse, rat, rabbit, guinea pig, and hamster. Of all patients, 66% complained of allergic symptoms on laboratory animal exposure, although only 52% worked directly with animals. Among patients with symptoms, 91% were positive by skin test to at least one laboratory animal, and 46% had asthma. The median length of exposure to laboratory animals before onset of symptoms was 2.8 yr with 60% of the patients developing their symptoms within 3 yr. Among patients who had allergic symptoms before exposure to laboratory animals, 79% were skin test positive to laboratory animals when they were evaluated in this study. There was a close association found between the skin test and histamine-release results with the laboratory animal allergens: 91% of the 4+ skin reactors had leukocytes positive for histamine release versus 5% of the leukocyte donors with less than 1+ skin reactions. A close relationship in positive reactions to different laboratory animal allergens was also found. For example, individuals positive to mouse were positive also to rat (95%), rabbit (79%), guinea pig (83%), and hamster (88%). Patients who reacted to laboratory animals also reacted to some extent to house dust and cat and dog allergens, and about one half of the animal-allergic individuals reacted to pollens. Although nonpollen-allergic individuals can develop sensitivity to laboratory animals, the group at higher risk are allergic individuals, especially those sensitive to house dust, cats, or dogs.     

Differentiation of endometrial stromal cells in vitro: down-regulation of suppression of the cell cycle inhibitor p57 by HOXA10?

Decidualization is a critical step during embryo implantation that is characterized by the differentiation of endometrial stromal cells (ESC) into decidua cells. However, the mechanism of differentiation remains largely unknown. Previously, it has been shown that the null function of homeo box A10 (HOXA10) causes defects in both implantation and decidualization, suggesting that the HOXA10 signalling pathway is likely to be involved in uterine decidualization. In the present study, we determined the expression and subcellular distribution of HOXA10 and its downstream molecule, p57, in ESC during in vitro decidualization induced by a combination of 8-bromo-cAMP and medroxyprogesterone acetate. We demonstrated that the HOXA10 was down-regulated while in contrast, p57 was up-regulated in the process of decidualization. Immunocytochemistry and transient expression of the HOXA10 tagged with green fluorescence protein revealed that there were no differences in the HOXA10 subcellular localization between the induced and non-induced ESC. Our results suggest that the down-regulation of HOXA10 may contribute to increased p57 and that up-regulation of p57 likely plays an important role in ESC differentiation in the process of decidualization. The progesterone receptor pathway may participate in promoting ESC to exit the cell cycle and enter differentiation.     

Involvement of interleukin 18 in Crohn's disease: evidence from in vitro analysis of human gut inflammatory cells and from experimental colitis models

An imbalance of immunoregulatory factors and/or cells contributes to uncontrolled mucosal T cell activation and inflammation in Crohn's disease (CD). Bioactive interleukin (IL)-18 has been shown to be produced by macrophages in CD lesions. We report here that T cells freshly isolated from inflamed tissue of CD patients (and not T cells from control intestinal tissue) were responsive to IL-18. In the presence of IL-18, these T cells produced more interferon (IFN)-gamma and less IL-10. To analyse further the role of IL-18 in this disease, an acute and a chronic model of murine colitis were used. IL-18 mRNA was significantly enhanced in trinitrobenzene sulphonic acid (TNBS) induced colitis, and treatment with IL-18 binding protein (IL-18BPa), which neutralizes IL-18 bioactivity, significantly reduced the severity of colitis. However, IL-18BPa did not affect the course of chronic colitis in CD45RBhighCD4+ T cell reconstituted SCID mice. Production of IFN-gamma in lamina propria mononuclear cell cultures from IL-18BPa-treated SCID mice was decreased, but at the same time fewer lamina propria CD4+ T cells harvested from IL-18BPa-treated mice compared to non-treated mice were in apoptosis. We conclude that IL-18 clearly has a modulatory role in the inflammatory cascade of CD and experimental colitis by affecting IFN-gamma and IL-10 production, and apoptosis. In view of the divergent effects of IL-18 neutralization in the two different murine colitis models, it is unlikely that IL-18 is at the top of this cascade.     

Pericentric inversions of chromosome 4: report of a new family and review of the literature

A family was cytogenetically studied because of the birth of a male child with a multiple congenital anomaly pattern, in whom a dup (4q) recombinant was found. His phenotypically normal mother's karyotype showed an apparently balanced pericentric inversion in a chromosome 4. So as to analyze the occurrence of recombinants, the cytogenetic data from this family are compared with those of the 18 previously reported familial cases of pericentric inversions (PIs) of chromosome 4. The congenital anomalies observed in the child strongly suggest Wolf-Hirschhorn syndrome but some of his clinical features seem to be pathogenetically related to the presence of lymphedema during the intrauterine period. In the multiple congenital anomaly pattern observed in this patient, the lymphedema could be the consequence of the large 4q duplication. The review of chromosome 4 PIs with 4q duplication suggests that the q3 region should be examined when edema is detected prenatally.     

Familial translocation t(10;14) (q26.1;q32.3): report of three offspring with 10q deletion and 14q duplication

We describe two brothers and a cousin with common clinical features, including mild mental retardation, motor delays, hypotonia with truncal ataxia, esotropia, and mild facial and hand dysmorphia. The initial routine chromosome study failed to detect any abnormality in the proband. Based on a high index of clinical suspicion, high-resolution chromosome studies were performed on the proband's parents. A small reciprocal translocation t(10;14) (q26.1;q32.3) was detected in the father. The breakpoint on the derivative chromosome 14 was further placed telomeric to the immunoglobulin heavy-chain gene cluster at the band q32.33 by fluorescence in situ hybridization. Studies of the proband and two affected paternal cousins revealed that each had inherited the same derivative chromosome 10 from their carrier parents. This unbalanced karyotype resulted from an adjacent-1 segregation of the 10;14 translocation.     

谷氨酸脱羧酶65片段与IL－10双基因真核表达载体的构建与鉴定

 目的 优化以往构建的以预防 1 型糖尿病为目的的全长谷氨酸脱羧酶（GAD）65 DNA疫苗，尝试构建GAD 65片段与IL-10双基因真核表达载体。方法 从GAD65质粒中扩增出GAD190-315片段和GAD490-570片段的cDNA，以overlap PCR法将之分别与hIL-2信号肽cDNA拼接，得到SGAD190-315、SGAD490-570融合基因。以p43.2-mIL-10质粒为模板，用PCR方法扩增出IL-10基因。将SGAD190-315、SGAD490-570融合基因分别与IL-10基因依次克隆入双启动子真核表达载体pBudCE4.1中，构建出2种双基因重组真核表达载体pBud-SGAD190-315/IL-10和pBud-SGAD490-570/IL-10。2种重组真核表达载体经测序鉴定正确后，用脂质体介导的方法转染COS-7细胞，转染后48和72 h以蛋白质印迹法检测细胞裂解产物及上清液中SGAD190-315和SGAD490-570融合基因的表达，ELISA方法检测细胞上清液中IL-10的表达。结果　核酸序列测定表明克隆的SGAD190-315、SGAD490-570融合基因和IL-10基因序列与报告序列一致。蛋白质印迹法和ELISA方法均检测到SGAD190-315/IL-10和SGAD490-570/IL-10重组真核表达载体在COS-7细胞中的表达。结论　成功构建了2种GAD65片段与IL-10双基因真核表达载体，为1型糖尿病的基因疫苗预防研究提供了实验基础。