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41.
Debelenko LV; Brambilla E; Agarwal SK; Swalwell JI; Kester MB; Lubensky IA; Zhuang Z; Guru SC; Manickam P; Olufemi SE; Chandrasekharappa SC; Crabtree JS; Kim YS; Heppner C; Burns AL; Spiegel AM; Marx SJ; Liotta LA; Collins FS; Travis WD; Emmert-Buck MR 《Human molecular genetics》1997,6(13):2285-2290
Lung carcinoids occur sporadically and rarely in association with multiple
endocrine neoplasia type 1 (MEN1). There are no well defined genetic
abnormalities known to occur in these tumors. We studied 11 sporadic lung
carcinoids for loss of heterozygosity (LOH) at the locus of the MEN1 gene
on chromosome 11q13, and for mutations of the MEN1 gene using dideoxy
fingerprinting. Additionally, a lung carcinoid from a MEN1 patient was
studied. In four of 11 (36%) sporadic tumors, both copies of the MEN1 gene
were inactivated. All four tumors showed the presence of a MEN1 gene
mutation and loss of the other allele. Observed mutations included a 1 bp
insertion, a 1 bp deletion, a 13 bp deletion and a single nucleotide
substitution affecting a donor splice site. Each mutation predicts
truncation or potentially complete loss of menin. The remaining seven
tumors showed neither the presence of a MEN1 gene mutation nor 11q13 LOH.
The tumor from the MEN1 patient showed LOH at chromosome 11q13 and a
complex germline MEN1 gene mutation. The data implicate the MEN1 gene in
the pathogenesis of sporadic lung carcinoids, representing the first
defined genetic alteration in these tumors.
相似文献
42.
Identification of the multiple endocrine neoplasia type 1 (MEN1) gene. The European Consortium on MEN1 总被引:10,自引:0,他引:10
Lemmens I; Van de Ven WJ; Kas K; Zhang CX; Giraud S; Wautot V; Buisson N; De Witte K; Salandre J; Lenoir G; Pugeat M; Calender A; Parente F; Quincey D; Gaudray P; De Wit MJ; Lips CJ; Hoppener JW; Khodaei S; Grant AL; Weber G; Kytola S; Teh BT; Farnebo F; Thakker RV 《Human molecular genetics》1997,6(7):1177-1183
43.
Gamma-carboxylated isoforms of recombinant human protein S with different biologic properties 总被引:3,自引:0,他引:3
Grinnell BW; Walls JD; Marks C; Glasebrook AL; Berg DT; Yan SB; Bang NU 《Blood》1990,76(12):2546-2554
Human protein S (HPS), a regulator of hemostasis, is a vitamin K- dependent plasma protein with potential clinical utility. We have obtained high-level expression of the cDNA for HPS in two mammalian cell lines. Both cell lines secreted single chain recombinant HPS (rHPS) in serum-free medium as determined by Western blot analysis. The ability of the rHPS from both cell lines to act as a cofactor for human protein C (HPC) was determined; the rHPS secreted from the human 293 cell line had an activity six times that of the rHPS from the AV12-664 Syrian hamster cell line. Furthermore, the relative specific cofactor activity of rHPS from the 293 cell line was actually 2.5-fold higher than that of single-chain human plasma-derived HPS. Essentially all of the rHPS secreted from the 293 cell line exhibited a calcium-dependent elution profile on anion exchange chromatography, whereas only 25% to 35% of the hamster cell-derived rHPS exhibited this profile. However, the calcium-eluted rHPS from the AV12 cell line had a high specific cofactor activity, equivalent to that of the 293-derived rHPS. A NaCl- elutable rHPS fraction (calcium nondependent) was isolated from the recombinant AV12-664 cell line, further purified, and found to have reduced activity, only 40% that of the calcium-dependent rHPS. The only observable difference in the calcium-dependent and nondependent rHPS molecules was in the content of gamma-carboxyglutamic acid (Gla); the calcium-dependent material contained approximately 10 mol Gla/mol protein whereas the calcium-nondependent material contained only approximately 8 mol Gla/mol of protein. In addition, the calcium- nondependent rHPS had reduced ability to interact with phospholipid vesicles as evidenced by an eightfold increase in the apparent kd. Our data demonstrate the isolation of rHPS with high specific activity, and show that a reduction in as few as two Gla residues dramatically decreases its functional cofactor activity for HPC, due to a reduction in ability to interact with the phospholipid bilayer. 相似文献
44.
Domain communication in the dynamical structure of human immunodeficiency virus 1 protease. 总被引:4,自引:4,他引:4 下载免费PDF全文
W E Harte Jr S Swaminathan M M Mansuri J C Martin I E Rosenberg D L Beveridge 《Proceedings of the National Academy of Sciences of the United States of America》1990,87(22):8864-8868
A dynamical model for the structure of the human immunodeficiency virus 1 (HIV-1) protease dimer in aqueous solution has been developed on the basis of molecular dynamics simulation. The model provides an accurate account of the crystal geometry and also a prediction of the structural reorganization expected to occur in the protein in aqueous solution compared to the crystalline environment. Analysis of the results by means of dynamical cross-correlation coefficients for atomic displacements indicates that domain-domain communication is present in the protein in the form of a molecular "cantilever" and is likely to be involved in enzyme function at the molecular level. The dynamical structure also suggests information that may ultimately be useful in understanding and further development of specific inhibitors of HIV-1 protease. 相似文献
45.
Daniels DL; Czervionke LF; Millen SJ; Haberkamp TJ; Meyer GA; Hendrix LE; Mark LP; Williams AL; Haughton VM 《Radiology》1989,171(3):807-809
The authors evaluated magnetic resonance (MR) images obtained with intravenously administered gadolinium in ten patients who had facial paralysis and no facial nerve tumor. In patients with either Bell palsy (four patients) or facial paralysis after temporal bone surgery (six patients), intratemporal facial nerve enhancement was seen. Facial nerve enhancement on MR images proved to be a nonspecific finding. 相似文献
46.
Christopher B. Harte Ph.D. Gabrielle I. Liverant Ph.D. Denise M. Sloan Ph.D. Barbara W. Kamholz Ph.D. Laina E. Rosebrock B.A. Maurizio Fava M.D. Gary B. Kaplan M.D. 《Annals of behavioral medicine》2013,46(1):73-80
Background
Both depression and smoking have been independently associated with lower heart rate variability (HRV), suggesting dysregulation of cardiac autonomic function. However, no studies have systematically explored the effects of smoking on HRV among depressed patients.Purpose
This study examined differences in HRV based on smoking status among depressed individuals.Methods
Electrophysiological data were examined among 77 adult outpatients without a history of myocardial infarction, who met criteria for major depressive disorder or dysthymia. Frequency domain [low frequency (LF), high frequency (HF), LF/HF ratio, respiratory sinus arrhythmia (RSA)] parameters of HRV, and heart rate and inter-beat interval (IBI) data were compared between depressed smokers (n?=?34) and depressed nonsmokers (n?=?44).Results
After controlling for covariates, depressed smokers, compared to depressed nonsmokers, displayed significantly lower LF, HF, and RSA.Conclusions
Among depressed patients, smoking is associated with significantly lower HRV, indicating dysregulated autonomic modulation of the heart. 相似文献47.
Oyen RH; Gielen JL; Van Poppel HP; Verbeken EK; Van Damme BJ; Baert LV; Baert AL 《Radiology》1988,169(3):705-707
Abdominal radiography, excretory urography, retrograde pyelography, and computed tomography were performed in two patients who had undergone retrograde pyelography with thorium dioxide (Thorotrast) approximately 40 years ago. Both patients developed a transitional cell carcinoma due to suburothelial thorium deposition. Typical thorium densities were demonstrated at CT in the peripelvicalyceal area as well as in retroperitoneal lymph nodes. Elderly patients in whom radiographic examination reveals retained Thorotrast in the kidney should be followed up because of the high risk of renal carcinoma. 相似文献
48.
49.
Aims Glucagon‐like peptide‐1 (GLP‐1) is an insulinotropic hormone and major component of the enteroinsular axis. Its therapeutic potential in human diabetes is limited by rapid degradation and inactivation by the enzyme dipeptidylpeptidase‐4 (DPP‐4). We investigated the acute effects of metformin with and without food on DPP‐4 activity in Type 2 diabetes. Methods Ten subjects with Type 2 diabetes (6 male/4 female, age 65.8 ± 2.6 years, body mass index 30.0 ± 1.2 kg/m2, glycated haemoglobin (HbA1c) 6.3 ± 0.2%, mean ± sem ) received metformin 1 g orally or placebo together with a standard mixed meal (SMM) in a random crossover design. Six subjects re‐attended fasting and received metformin 1 g without a SMM. Results Following SMM (n = 10), DPP‐4 activity was not suppressed by metformin compared with placebo [area under curve (AUC)0–4 h 1574 ± 4 vs. 1581 ± 8 μmol/ml/min, respectively]. Plasma glucose, insulin and active GLP‐1 were not different. However, DPP‐4 activity was suppressed with metformin following fasting compared with a SMM (n = 6) (AUC0–4 h 1578 ± 4 vs. 1494 ± 9 μmol/min, P < 0.02). Metformin serum levels were significantly lower (P < 0.001) after SMM than fasting (AUC0–4 h 350 ± 66 vs. 457 ± 55 mg/ml/min). Conclusion Metformin inhibits DPP‐4 activity in Type 2 diabetic patients in the fasting state but not when taken with a standard mixed meal. Metformin serum concentrations are lower if the drug is taken with food. These findings should be taken into account in establishing how to maximize efficacy of the drug. 相似文献
50.