GIGYF2 Asn56Ser and Asn457Thr mutations in Parkinson disease patients

Parkinson disease (PD) is one of the most common neurodegenerative disorders with major clinical features of bradykinesia, rigidity, resting tremor, and postural instability. At least thirteen gene loci responsible for PD or parkinsonism have been found and nine causative genes have been identified. Recently, Asn56Ser or Asn457Thr mutations in the Grb10-Interacting GYF Protein-2 gene (GIGYF2) were found to occur in about 2.4% familial PD Italian and French patients. We conducted genetic examination of Asn56Ser or Asn457Thr mutations, but none was found in 310 PD patients from North America. We did identify a non-disease-associated polymorphism Pro460Thr. Our results suggest that the GIGYF2 Asn56Ser and Asn457Thr mutations are a rare cause of PD in North American Caucasian population.     

糖尿病大鼠肾组织中miR-21和SnoN表达的变化

目的探讨糖尿病(DM)大鼠肾组织中微小核糖核酸-21(miR-21)和核转录共抑制因子(SnoN)在肾纤维化过程中的表达变化及其可能机制。方法用链脲佐菌素复制DM大鼠模型,并设对照组(NC),每组n=8。10周后处死大鼠,观察肾组织形态变化;免疫组织化学染色、Western blot及RT-q PCR检测miR-21、SnoN、转化生长因子-β1(TGF-β1)、Smad3、p-Smad3(Ser423/425)、E钙黏蛋白(E-cadherin)、α-平滑肌肌动蛋白(α-SMA)、纤维连接蛋白(FN)、胶原蛋白Ⅰ(collagenⅠ)和胶原蛋白Ⅲ(collagenⅢ)的表达。结果与对照组相比,DM组肾组织p-Smad3(Ser423/425)、TGF-β1和α-SMA蛋白表达增加(P0.05),SnoN、E-cadherin蛋白表达减少(P0.05),但SnoN mRNA和miR-21表达明显上调(P0.05),并伴有collagenⅠ、collagenⅢ和FN在间质沉积增多。结论 TGF-β1可能上调miR-21表达,抑制SnoN翻译水平的表达,促进DN的纤维化病变。     

Familial amyloidotic polyneuropathy (ATTR Ser50Ile): the first autopsy case report

We report an autopsy case of a pedigree of familial amyloidotic polyneuropathy (FAP) with a mutation of isoleucine-50 transthyretin (ATTR Ser50Ile). A 47-year-old man started developing severe diarrhea and weight loss at age 41 years, followed by urinary incontinence, autonomic-nervous-system abnormalities and serious heart failure; the diagnosis of FAP (ATTR Ser50Ile) was made on the basis of genetic, histochemical and immunohistochemical analysis. Six years after the initial symptoms, he died of septic shock. Autopsy revealed suppurative peritonitis, perforation of the sigmoid colon and marked systemic amyloid deposition. The total amount of amyloid deposited in the heart was greatly increased and was much lower in the thyroid gland and kidneys compared with amyloid deposits in ordinary FAP (ATTR Val30Met). Amyloid deposition in peripheral vessel walls was prominent, particularly in lymphatics and veins. His elder sister, 54 years old, started to develop orthostatic hypotension at age 49 years, followed by dysesthesia, diarrhea and severe congestive heart failure. Endomyocardial biopsy revealed severe TTR–amyloid deposition; ultrastructural examination demonstrated that amyloid fibrils were deposited disproportionately and extended radially around microvessels. These characteristic patterns of systemic amyloid deposition and distinct clinical manifestations, especially in the cardiovascular system, are considered to be a characteristic feature of ATTR Ser50Ile amyloidosis. Received: 31 August 1999 / Accepted: 19 October 1999     

Ser/Thr蛋白激酶信号转导系统——抗结核药物筛选的新靶点

最近的研究表明,Ser/Thr蛋白激酶不只存在于真核生物中,而且也存在于结核分枝杆菌体内.它们构成结核分枝杆菌的信号转导系统,与结核分枝杆菌在宿主体内和体外的生存密切相关.因此,这一信号转导系统可能成为研制新型抗结核药物的靶点.本文就Ser/Thr蛋白激酶信号转导系统及相关蛋白激酶的特征与功能进行了综述.     

消咳汤治疗感冒后干咳症81例

咳嗽是冬春季节的常见病、多因感冒而引起,常用止咳药与抗生素治疗,虽有一定效果,但有些患者外感症状解除后,咳嗽持久不愈,且多为干咳,伴有少量的粘痰,咽红干痒或痛而不适,舌苔薄白或薄黄,或稍厚或欠润,脉象正常.     

泌尿排石汤的药理作用实验研究

目的；研究泌尿排石汤的药理作用。为临床应用提供依据。方法：采用热板法、足肿用法、漏斗法、玻片法。结果：泌尿排石汤与排石颗粒相比其止痛、利尿作用无显著性差异，但其抗炎、止血作用差异显著。结论：泌尿排石汤具有镇痛、抗炎、利尿、止血作用。     

Residual Right-to-Left Shunt Following Repair of Atrial Septal Defect

Information about 5 patients with residual right-to-left shunts following repair of an atrial septal defect is presented. In each patient the defect was located low in the atrial septum adjacent to the inferior vena cava. During operation, either the eustachian valve of the inferior vena cava had been mistaken for the lower margin of the defect or the lower portion of the defect was not closed; blood flow was then diverted from the inferior vena cava into the left atrium. To prevent this occurrence, the inferior margin of the atrial septal defect should be closed first.     

Dejerine-Sottas' neuropathy caused by the missense mutation PMP22 Ser72Leu

OBJECTIVE: To describe a patient with the Dejerine-Sottas' syndrome due to a de novo Ser72Leu amino acid substitution in the PMP22 protein and summarize the phenotype associated with this frequent mutation. CASE REPORT: The proband has a medical history of early onset, severe, and progressive demyelinating neuropathy, accompanied by mild ptosis and limitations of eye movements. Ulnar nerve motor conduction velocities were extremely reduced (2.6 and 2.2 m/s), and the sural nerve biopsy showed onion bulbs and thinly myelinated axons. Duplication of chromosome 17p11.2 was ruled out, and the Ser72Leu substitution was found upon sequencing the PMP22 gene. CONCLUSION: The Ser72Leu substitution is being confirmed as the most frequent point mutation in the PMP22 gene. This 'hot spot' should be considered in the strategy of looking for point mutations in the hereditary demyelinating neuropathies.     

First demonstration of a lack of viral sequence evolution in a nonprogressor,defining replication-incompetent HIV-1 infection

It is universally acknowledged that genetic diversity is a hallmark of HIV-1 infection, and it is one of the traits that has considerably hampered the development of an effective vaccine. In a study of full-length HIV-1 genomic sequences (>9 kb), we show unique evidence for complete absence of viral evolution in an individual with truly nonprogressive infection. Gross gene defects were not detected, but the state of replication incompetence was attributed to the presence of stop codons in the structural genes gag p17 and p24 and in pol RT, which emerged as a consequence of G-A hypermutation. These inactivating mutations may have occurred early, soon after infection, during the clonal stage of primary viral replication, since these are the sole archival strains present today. This genetic homogeneity, with <1% variation between strains over an 8-year period, suggests that only limited proviral integration events occurred in this patient. Further study on the antigenic properties of this strain may assist in the development of HIV vaccines and therapeutics.     

Role of follicle-stimulating hormone receptor Ser680Asn polymorphism in the efficacy of follicle-stimulating hormone

OBJECTIVE: To evaluate the association between FSH efficacy and FSHR alleles. DESIGN: Retrospective study. SETTING: University-based fertility unit and a private center for biomedical research. PATIENT(S): One hundred two women with ovarian function who were undergoing controlled ovarian stimulation (COS). Women were categorized as poor responders (< or =3 ovarian follicles at the end of the cycle) or normal responders (>3 follicles). INTERVENTION(S): Daily administration of exogenous FSH. MAIN OUTCOME MEASURE(S): Number of good or poor responders. RESULT(S): The allele frequency and genotype distribution of the Ser680Asn marker differed significantly between groups. Cycle cancellations were increased (21%) among women who were homozygous for Ser680 compared with Ser/Asn and Asn/Asn patients, and 36% of poor-responders were homozygous for Ser680. CONCLUSION(S): The results support a role for FSHR gene in COS outcome. However, the weight of this factor is probably low. The Ser680 allele may act in concert with other environmental and genetic factors that contribute to FSH efficacy.