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81.
Schizophrenic patients are extremely heavy tobacco smokers. However, a lower incidence of lung cancer in schizophrenic patients has been observed in comparison to other heavy smokers. Nicotine increases the proliferation of pulmonary neuroendocrine tissue, causing the release of a bombesin-like peptide. Thus, bombesin-like peptide levels in urine may be an indicator of precancerous, cigarette-induced lung damage. Bombesin-like peptide levels of 10 schizophrenic smokers and 11 schizophrenic nonsmokers were compared to those of nonschizophrenic subjects matched for age and pack-years of smoking. The nonschizophrenic smokers showed the expected increase in urinary bombesin-like peptide levels, as compared to nonschizophrenic nonsmokers. Schizophrenic patients had lower bombesin-like peptide levels independent of smoking effects. The mechanism of the difference in bombesin-like peptide levels between schizophrenic patients and nonschizophrenic subjects is unknown, but one possibility involves alteration in the alpha 7-nicotinic acetylcholine receptor, which mediates the growth of some neuroendocrine cell lines in vitro. 相似文献
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JF Watchko MJ Daood GC Sieck JJ LaBella BT Ameredes AP Koretsky B Wieringa 《Canadian Metallurgical Quarterly》1997,82(5):1416-1423
Creatine kinase (CK) is an enzyme central to cellular high-energy phosphate metabolism in muscle. To characterize the physiological role of CK in respiratory muscle during dynamic contractions, we compared the force-velocity relationships, power, and work output characteristics of the diaphragm (Dia) from mice with combined myofibrillar and sarcomeric mitochondrial CK deficiency (CK[-/-]) with CK-sufficient controls (Ctl). Maximum velocity of shortening was significantly lower in CK[-/-] Dia (14.1 +/- 0.9 Lo/s, where Lo is optimal fiber length) compared with Ctl Dia (17.5 +/- 1.1 Lo/s) (P < 0.01). Maximum power was obtained at 0.4-0.5 tetanic force in both groups; absolute maximum power (2,293 +/- 138 W/m2) and work (201 +/- 9 J/m2) were lower in CK[-/-] Dia compared with Ctl Dia (2,744 +/- 146 W/m2 and 284 +/- 26 J/m2, respectively) (P < 0.05). The ability of CK[-/-] Dia to sustain shortening during repetitive isotonic activation (75 Hz, 330-ms duration repeated each second at 0.4 tetanic force load) was markedly impaired, with CK[-/-] Dia power and work declining to zero by 37 +/- 4 s, compared with 61 +/- 5 s in Ctl Dia. We conclude that combined myofibrillar and sarcomeric mitochondrial CK deficiency profoundly impairs Dia power and work output, underscoring the functional importance of CK during dynamic contractions in skeletal muscle. 相似文献
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MH Skiadopoulos S Surman JM Tatem M Paschalis SL Wu SA Udem AP Durbin PL Collins BR Murphy 《Canadian Metallurgical Quarterly》1999,73(2):1374-1381
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O Eickelberg CO Sommerfeld C Wyser M Tamm F Reichenberger PG Bardin M Solèr M Roth AP Perruchoud 《Canadian Metallurgical Quarterly》1997,156(6):1987-1992
The matrix metalloproteinases (MMP) are proteolytic enzymes that are essentially involved in the turnover of the extracellular matrix (ECM). Their activity is counterbalanced by specific antagonists, the tissue inhibitors of metalloproteinases (TIMP). In this study, we sought to analyze the expression of MMP and TIMP isoforms in pleural effusions from 88 patients. We compared MMP and TIMP isoform expression in transudates (n = 21) and exudates (n = 67), the latter divided into exudates of paraneoplastic (n = 46) or parainfectious (n = 21) origin. Zymographic and Western blot analyses revealed constant expression of interstitial collagenase (MMP-1), gelatinase-A (MMP-2), and TIMP-1 in all 88 samples. In contrast, analyses of gelatinase-B (MMP-9) demonstrated a specific expression pattern, with high expression in exudates and lack of expression in transudates. Neutrophil collagenase (MMP-8) was detected in trace amounts, and correlated with the number of neutrophils in the effusion. Low levels of TIMP-2 were detected only in exudates and not in transudates. Quantitative analysis of the expression ratio of gelatinase-B to gelatinase-A revealed statistically significant differences between effusions of different origin. The ratio was highest in exudates of paraneoplastic origin and lowest in transudates. Our data thus suggest that interstitial collagenase, gelatinase-A, and TIMP-1 play a role in homeostasis of the pleural space in vivo as constitutively expressed proteins, whereas gelatinase-B and TIMP-2 expression are induced in specific disease states. These observations contribute to the understanding of the pathophysiology of pleural effusions, and may help to characterize and possibly distinguish effusions of different origin. 相似文献
88.
We developed a novel approach for the high-level production of a microbial transglutaminase (TGase) from Streptoverticillium in E. coli. The direct expression of the TGase gene in E. coli cells did not cause overproduction, probably due to the harmful influence of TGase activity, which introduces covalent crosslinks between proteins. Therefore, we fused the chemically synthesized TGase gene coding for the entire 331 amino acid residues at the amino terminus to a bacteriophage T7 gene 10 leader peptide (260 amino acids) using an inducible expression vector. The TGase gene was expressed as inclusion bodies in the E. coli cytoplasm. Restoring 15 amino acid residues upstream of the amino terminus of the mature TGase by a two-step deletion of the fusion sequence facilitated solubilization and subsequent proteolytic cleavage, thus releasing mature TGase. Although the mature form had less TGase activity than native TGase, because of the poor refolding rate, these results suggest that this system is suitable for the efficient production of TGase. 相似文献
89.
AD Marais JC Firth ME Bateman P Byrnes C Martens J Mountney 《Canadian Metallurgical Quarterly》1997,17(8):1527-1531
Hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase inhibitors are the drugs of choice in heterozygous familial hypercholesterolemia (FH), which has a high risk of ischemic heart disease. An open-label study was conducted to test the efficacy and safety of atorvastatin, a new synthetic HMG-CoA reductase inhibitor in proven FH. After a 4-week placebo phase, 22 subjects were randomized to either 80 mg atorvastatin at night (n = 11) or 40 mg twice a day for 6 weeks. The two dosage groups were well matched and had no difference in lipoprotein responses. After 6 weeks, the LDL cholesterol concentration was reduced by 57%, from 8.16 +/- 1.15 to 3.53 +/- 0.99 mmol/L (P < .001). The total cholesterol concentration decreased from 9.90 +/- 1.32 to 5.43 mmol/L (P < .001). HDL cholesterol concentration increased from 1.19 +/- 0.31 to 1.49 +/- 0.43 mmol/L (P < .001). Triglyceride concentrations decreased from 1.34 +/- 0.66 to 0.88 +/- 0.36 mmol/L (P < .01). Three subjects had single, transient increases of serum transaminase of up to twice the upper limit of normal. Apolipoprotein B concentration decreased significantly by 42%. Changes in apolipoproteins AI and (a) were not statistically significant. Nondenaturing gradient gel electrophoresis revealed increases in the size of smaller LDL particles in four subjects. Plasma fibrinogen concentration increased by 44%. The drug was well tolerated. One subject withdrew for personal reasons. Atorvastatin is a powerful and safe lipid-modifying agent for LDL cholesterol; it also modifies HDL cholesterol and triglyceride concentrations, and may suffice as a single agent for many subjects with heterozygous FH. 相似文献
90.