beta2-adrenergic receptor gene polymorphisms in myasthenia gravis (MG)

The beta2-adrenergic receptor (beta2-AR) belongs to the group of G-protein coupled receptors and is present mainly on skeletal and cardiac muscle cells and lymphocytes. The gene encoding beta2-AR (ADRB2) displays a moderate degree of heterogeneity in the human population. The distribution of polymorphisms at amino acid positions 16, 27 and 164 is changed in asthma, hypertension and obesity. We have earlier reported a decreased density of the beta2-AR on peripheral blood mononuclear cells and the presence of beta2-AR antibodies in patients with MG. Since certain polymorphisms affect the function of the beta2-AR, it was of interest to analyse these in MG. Using allele-specific polymerase chain reaction amplification, we revealed an over-representation of homozygosity for Arg16 and a lower prevalence of homozygosity for Gly16 in MG patients compared with healthy individuals. The increased frequency of homozygosity for Arg16 was due to a contribution from patients with generalized MG but not from patients with only ocular disease. Homozygosity for Glu27 was negatively associated with both the presence of beta2-AR antibodies and severity of disease. Moreover, acetylcholine receptor (AChR) antibodies were more often present in patients being homozygous for Gln27. Our results imply that homozygosity for Arg16 confers susceptibility to generalized MG, and that certain polymorphisms at amino acid position 27 are associated with subgroups of patients.     

Glial cell line-derived neurotrophic factor receptor alpha1 availability regulates glial cell line-derived neurotrophic factor signaling: evidence from mice carrying one or two mutated alleles

Glial cell line-derived neurotrophic factor receptor alpha1 (GFRalpha1, also known as GDNFR-alpha) is a glycolipid-anchored membrane protein of the GFRalpha family, which binds glial cell line-derived neurotrophic factor [Jing S. et al. (1996) Cell 85, 1113-1124; Treanor J. J. et al. (1996) Nature 382, 80-83], a survival factor for several populations of central and peripheral neurons, including midbrain dopamine neurons [Lin L. F. et al. (1993) Science 260, 1130-1132], and mediates its ligand-induced cell response via a tyrosine kinase receptor called Ret [Takahashi M. et al. (1988) Oncogene 3, 571-578; Takahashi M. and Cooper G. M. (1987) Molec. Cell Biol. 7, 1378-1385]. In this paper, we show that mice with a null mutation of the GFRalpha1 gene manifest epithelial-mesenchymal interaction deficits in kidney and severe disturbances of intestinal tract development similar to those seen with glial cell line-derived neurotrophic factor or Ret null mutations. There is a marked renal dysgenesis or agenesis and the intrinsic enteric nervous system fails completely to develop. We also show that newborn GFRalpha1-deficient mice display no or minimal changes in dorsal root and sympathetic ganglia. This is in contrast to the deficits reported in these neuronal populations in glial cell line-derived neurotrophic factor and Ret null mutations. Mesencephalic dopaminergic neurons in the substantia nigra and ventral tegmental area appear intact at the time of birth of the mutated mice. Mice homozygous for the GFRalpha1 null mutation die within 24 h of birth because of uremia. Heterozygous animals, however, live to adulthood. There is a significantly reduced neuroprotective effect of glial cell line-derived neurotrophic factor in such heterozygous animals, compared with wild-type littermates, after cerebral ischemia. Taken together with previous data on glial cell line-derived neurotrophic factor and Ret, our results strongly suggest that GFRalpha1 is the essential GFRalpha receptor for signaling in the glial cell line-derived neurotrophic factor-Ret pathway in the kidney and enteric nervous system development, and that GFRalpha2 or GFRalpha3 cannot substitute for the absence of GFRalpha1. Moreover, neuroprotective actions of exogenous glial cell line-derived neurotrophic factor also require full GFRalpha1 receptor expression.     

Effect of ellagic acid and hydroxylated flavonoids on the tumorigenicity of benzo[a]pyrene and ({+/-})-7{beta}, 8{alpha}-dihydroxy-9{alpha}, 10{alpha}-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene on mouse skin and in the newborn mouse

Ellagic acid, quercetin and robinetin were tested for theirability to antagonize the tumor-initiating activity of benzo[a]pyrene(B[a]P) and (±)-7ß, 8-dihydroxy-9, 10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene(B[a]P 7,8-diol-9,10-epoxide-2), the ultimate carcinogenic metaboliteof benzo[a]pyrene. Ellagic acid, robinetin or quercetin (2500nmol) had no tumor-initiating activity on mouse skin, but thetopical application of 2500 nmol of ellagic acid 5 min beforea tumor-initiating dose of 200 nmol of B[a]P 7,8-diol-9,10-epoxide-2caused a 59–66% inhibition in the number of skin tumorsper mouse that were observed after 15–20 weeks of promotionwith 12-O-tetradecanoylphorbol-13-acetate. Similar treatmentwith 2500 nmol of robinetin or quercetin caused a statisticallyinsignificant 16–24% inhibition in the tumor-initiatingactivity of 200 nmol of B[a]P 7,8-diol-9,10-epoxide-2 applied5 min later. Treatment of mice with 2500 nmol of ellagic acid5 min before the application of 50 nmol of B[a]P inhibited themean number of skin tumors per mouse by 28–33% after 15–20weeks of promotion, but these decreases were not statisticallysignificant. Robinetin and quercetin had little or no effecton the tumor-initiating activity of B[a]P on mouse skin. Treatmentof preweanling mice with 1/7, 2/7 and 4/7 of the total doseof ellagic acid (300 nmol), robinetin (1400 nmol), myricetin(1400 nmol) or quercetin (1400 nmol) i.p. on their first, eighthand fifteenth day of life, respectively, did not cause the formationof tumors in animals that were killed 9–11 months later.Similar treatment of preweanling mice with the above doses ofthe phenolic compounds 10 min before the i.p. injection of atotal dose of 30 nmol of B[a]P 7,8-diol-9,10-epoxide-2 duringthe animal's first 15 days of life caused a 44–75% inhibitionin the number of diol-epoxide-induced pulmonary tumors per mouse.Similar treatment with these plant phenols had little or noeffect on B[a]P-induced pulmonary tumors.     

Radiographic findings in cotton textile workers and the relationship to cigarette smoking

A group of 140 cotton textile workers from Shanghai, Shandong, Guangxi, and Beijing have had their chest radiographs taken using similar requirements. Most had come from the preparatory departments of cotton mills and had a history of exposure to cotton dust for at least 20 years. As controls, 140 healthy individuals with no dust exposure were matched with respect to sex, age, and smoking history. All the radiographs were read according to the ILO International Pneumoconiosis Classification, and the manifestations belonging to categories 0/0 and 0/1 were grouped as "normal," whereas categories 1/0, 1/1, and 1/2 and above as "abnormal." There was no significant difference in X-ray abnormalities between cotton textile workers and controls (P greater than 0.05). But when the data on the cotton textile workers and controls were combined, an appreciable difference in the incidence of radiographic abnormalities was found between smokers and non-smokers (P less than 0.001). Cotton dust exposure may induce nonspecific interstitial pulmonary changes, but these changes were exaggerated by cigarette smoking. These two factors appeared to have an additive effect on the pulmonary X-ray findings.     

Disposition of the naturally occurring antimutagenic plant phenol, ellagic acid, and its synthetic derivatives, 3-O-decylellagic acid and 3, 3'-di-O-methylellagic acid in mice

The effect of ellagic acid and some of its more lipophilk derivativeson the mutagenicity of (? )-7ß, 8-di-hydroxy-9 10-epoxy-7,8, 910-etrahydrobenz[a]pyrene was examined in Salmonella typhimuriumTA100. Ellagic acid, 3, 3' -di-O-methylellagic add, 4, 4' -di-O-methylellagicacid and 3-O-decyiellagic acid were found to have approximatelyequal antimutagenic activity. The tissue distribution and eliminationof ellagic add, 3, 3' -di-O-methyleCagic add and 3-O-decylellagicacid were examined in CD-I mice. Little or no ellagic acid (<1 nmol/g) was found in blood, lung or liver after the oral administrationby gavage of 300 µunol of ellagic acid per kg body weightor after feeding 1% of ellagic acid in the diet for 1 week.Following the i.p. administration of 120 µmol/kg of ellagicacid, the blood and lung levels of ellagic acid were 15–20nmol/g at 30 min after the dose, and the concentrations of ellagicacid decreased to 1–3 nmol/g at 6–8 h after thedose. A portion of the administered i.p. dose precipitated inthe abdominal cavity. After i.v. administration, ellagic acidwas eliminated very rapidly from blood, lung and liver, and 70% of the administered dose was recovered in the urine andfeces as free ellagic acid and its conjugates. At 2 h afteran i.v. injection of 60 µ/kg of ellagic add, 46% of thedose was recovered in the urine as ellagic acid and its conjugates.Of this amount, about half was excreted as free ellagic acidand half was excreted as conjugates. An additional 25% of thedose was recovered in the feces (mostly as free ellagic acid)after 7 h. The disposition of 3, 3' -di-O-methylelIagic acidor 3–O-decyIellagic acid after i.v. administration (32µmol;sol;kg) was examined and compared to the dispositionof the same i.v. dose of ellagic acid. The concentrations ofellagic acid, 3,3' -di-O-methylellagic acid and 3-O-decytellagicadd decreased rapidly in the blood, liver and lung, but theconcentrations of 3-O-decylellagic add in the lung throughoutthe experimental period (2–360 min) was on average 20-to 40-fold higher than the corresponding average concentrationsof ellagic acid or 3, 3' -di-O-methylellagic acid.     

842例工人、农民和战士最大呼气流量-容积曲线的测定

作者用“点值法”对成都市内和郊区842例从事轻、中、重劳动的健康工人、农民和战士作了MEFV曲线和常规肺功能测定,发现工人和农民在低肺容积时流量增加,在高、中肺容积时流量下降,并以农民最明显,重劳动工人次之,轻、中劳动工人较不明显,战士则相反。揭示不同的体力活动方式及生活条件可导致不同肺容积时的流量改变,以适应其代谢增强时的耗氧需求。     

Hepatic elimination of drugs with concentration-dependent serum protein binding

For a drug with concentration-dependent serum protein binding, the unbound fraction of drug decreases during the drug elimination process. The clearance of the drug at a given blood flow rate is lower than would be expected from the observed unbound fraction in venous blood from a noneliminating organ. Based on both the well-stirred and parallel tube models, simulations demonstrated that consideration of concentration-dependent binding during drug elimination is important when the intrinsic clearance is higher than the blood flow and when the unbound drug concentration is much greater than the dissociation equilibrium constant of the binding complex.Supported in part by Grant GM 28423 from the National Institutes of General Medical Sciences, NIH.     

The study of tuberculosis outbreak in a high school—Shanghai,China, 2017–2018

Journal of Public Health - To investigate the attack rate of active tuberculosis (TB) cases and detection rate of latent tuberculosis infection (LTBI) cases, and to identify possible factors...     

新增工伤康复服务项目遴选及支付标准探索*

通过梳理工伤康复服务项目规范与支付标准制定等相关政策,阐述“国家版”和“广东省版”工伤康复服务项目和支付标准制定情况,分析新增工伤康复服务项目管理现状。选择广东省40家协议医院为样本,基于专家咨询法,计算专家采纳率,建立新增工伤康复服务项目目录,并通过基准项目赋值定价,为新增工伤康复服务项目遴选及支付标准提出管理措施。文章建议进一步细化新增工伤康复服务价格项目立项审批流程,建立新增工伤康复服务项目管理办法,规范管理制度。探索新增工伤康复服务项目纳入工伤保险目录管理机制,同时,充分发挥行业学会或协会的作用,加强卫生技术评估准入评审与价格制定管理决策中的广泛应用。