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This study demonstrates that autoantibodies from drug-induced pemphigus patients have the same antigenic specificity, on a molecular level, as do autoantibodies from other pemphigus patients, because side effects of.
Table 7. Outcomes Evidence for the Entity -Adrenergic Blocking Agents Study Study Design Efficacy Variables Comparative Clinical Trials with Other Antihypertensive Classes of Drugs: Randomized, double- Primary: combined ALLHAT3, 18, 19 occurrence of fatal blind, activecontrolled study coronary heart disease Diuretic [chlorthalidone CHD ; or nonfatal 12.5-25 milligrams mg ; myocardial infarction MI ; N 24, 335 once daily qd ; ] or 1blocker [doxazosin 2-8 mg 3.3 years Secondary: all-cause qd] in subjects 55 years mortality, stroke, combined of age with hypertension cardiovascular disease and had at least one CVD ; cardiac risk factor.
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1 MacMahon S, Rodgers A. The effects of antihypertensive treatment on vascular disease: reappraisal of the evidence in 1994. J Vasc Biol Med 1993; 4: 265271. Julius S, Kjeldsen SE, Weber M, Brunner HR, Ekman S, Hansson L, et al. Outcomes in hypertensive patients at high cardiovascular risk treated with regimens based on valsartan or amlodipine: the VALUE randomised trial. Lancet 2004; 363: 20222031. Weber MA, Julius S, Kjeldsen SE, Brunner HR, Ekman S, Hansson L, et al. Blood pressure dependent and independent effects of antihypertensive treatment in the VALUE trial. Lancet 2004; 363: 20492051. Guidelines Committee. 2003 European Society of Hypertension European Society of Cardiology guidelines for the management of arterial hypertension. J Hypertens 2003; 21: 10111053. Nissen SE, Tuzcu EM, Libby P, Thompson PD, Ghali M, Garza D, et al. Effect of antihypertensive agents on cardiovascular events in patients with coronary disease and normal blood pressure. The CAMELOT Study: a randomized controlled trial. JAMA 2004; 292: 22162226. The ALLHAT Officers and Coordinators for the ALLHAT Collaborative Research Group. Major outcomes in high-risk hypertensive patients randomized to angiotensin-converting enzyme inhibitor or calcium channel blocker or diuretic. The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial ALLHAT ; . JAMA 2002; 288: 29812997. Wright JT Jr, Dunn JK, Cutler JA, Davis BR, Cushman WC, Ford CE, et al. Outcomes in hypertensive black and nonblack patients treated with chlorthalidone, amlodipine, and lisinopril. JAMA 2005; 293: 15951608. Preston RA, Materson BJ, Reda DJ, Williams DW, Hamburger RJ, Cushman WC, et al. Agerace subgroup compared with renin profile as predictors of blood pressure response to antihypertensive therapy. Department of Veterans Affairs Cooperative Study Group on Antihypertensive Agents. JAMA 1998; 280: 11681172.
Drogendijk, Annelieke, MSc ; Van Der Velden, Peter, PhD1; Gersons, Berthold, PhD2; Roskam, Albert-Jan, MSc1; Grievink, Linda, PhD3; Olff, Miranda, PhD4; Meewisse, Mariel, MSc4; Kleber, Rolf, PhD5 1 Institute for Psychotrauma, Zaltbommel, Netherlands 2 University of Amsterdam, Academic Medical Center De Meren, UVA Department of Psychiatry, Netherlands 3 National Institute for Public Health and the Environment RIVM ; , Bilthoven, Netherlands 4 AMC De Meren, Netherlands 5 Utrecht University, Netherlands To analyse these effects we used both quantitative as qualitative research methods. In a longitudinal study the characteristics of the stressor and posttraumatic distress as well as overall psychological distress were assessed among a representative sample of Turkish migrants affected by a technological disaster a large firework explosion in an urban environment ; . To analyse the background of these problems we used qualitative in-depth interviews with Turkish affected migrants. Significantly more migrants had psychological problems e.g. depression, anxiety ; compared with the control group. Furthermore, large differences were found for psychological problems between Turkish victims and the Turkish control group compared with indigenous victims and an indigenous control group. The psychological problems they expressed, in particular anger, rage, anxiety and depressive feelings and intrusions, were attributed to the disaster and in particular the social and societal effects of the disaster. By attributing their problems.
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DHEA's effects on mood and behaviour in men and women with mood disorders related to mid-life. They will specifically ask whether increasing DHEA levels will reduce any or all of the neurasthenic nervous system ; symptoms characteristic of these disorders. Jon D. Kaiser, MD, has been prescribing DHEA to hundreds of HIV-positive patients. In his book, Healing HIV, he explains that the majority of his patients have remained stable for long periods of time by bringing DHEA levels into their optimal range, in conjunction with healthful nutrition, vitamin therapy, and aggressive antiviral strategies. Wasting syndrome and dementia are virtually unknown in his practice. He feels DHEA supplementation is safe, beneficial, and non-toxic, as long as patients monitor their blood levels regularly. His book outlines several research studies related to DHEA and HIV disease. Data from an observational study published in the American Journal of Medical Science in 1993 showed a positive relationship between the immune status of people with HIV-related illness and DHEA-S levels. They hypothesized that a deficiency of the hormone DHEA may contribute to a declining immune status. A cohort study at the University of Amsterdam showed that DHEA levels in progressors were consistently lower than in the non-progressors. The authors concluded that low DHEA levels were.
Generally, the answer to this question depends on the level of involvement the person has with the drug. Levels of involvement are described in Chapter 3, page 16 ; . It possible for people who are experiencing some problems associated with their drug to reduce but not give up their use. However, professionals in the addictions field generally agree that for someone who is dependently involved, abstinence is preferred as the goal of rehabilitation. Dependent involvement is characterized by ongoing harmful use despite negative consequences, plus some combination of the following experiences: progression, withdrawal, loss of control and preoccupation and atomoxetine, for example, generic name.
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Abstract The recent identification of pluripotent adult stem cells self-renewal and capable of differenciating in a variety of cell types is opening a new area of research, the regenerative medicine. Through the application of stem cells, it is already possible to repair a damaged tissue or organ such as the heart after an infarct. Scientists hope that in a near future the organ transplants will be replaced by auto-transplants of stem cells or therapies using cellular hormones to increase or accelerate the repairment. The potential use of these therapies is discussed, along with ethical issues about the use of stem cells in medicine. The Authors MILENA BOTELHO PEREIRA SOARES is a researcher and a coordinator in Gonalo Muniz Research Center Oswaldo Cruz Foundation, in Bahia ; . She finished her doctorate in Immunology in Carlos Chagas Filho Biophysics Institute UFRJ ; and was a visiting researcher in Harvard University USA ; . RICARDO RIBEIRO DOS SANTOS is a researcher in Gonalo Muniz Research Center Oswaldo Cruz Foundation, in Bahia ; and coordinator of the Millennium Institute of Tissue Bioengineering IMBT ; . He finished his doctorate in Medical Clinic transmissible diseases ; in the State University of Campinas Unicamp ; and was a professor of Immunology in the Faculty of Medicine of Ribeiro Preto USP and strattera.
And automating them you would think this would have led to much higher productivity, more targets fired on successfully per unit time and per dollar spent better outcomes really selecting better molecules. the numbers have not born that out . we don't work on a smooth upward slope like Moore's Law we work on these paradigm shifts that come about on kind of an unpredictable time frame no one is ever sure when new technology hits. Genomics has been a mixed blessing companies spent billions of dollars investing in genomics and to date it has not had much of a return on investment.
| PPL Corp.: Equal-weight as Stock Nears Target Price on Rate Rulings Kit Konolige Electric Utilities: Watt's News - The Weekly Update Kit Konolige Natural Gas & Electric Utilities: Winter 2004 Sector Overview Kit Konolige FirstEnergy: Failed OH Auction Indicates High Market Prices Kit Konolige Kit Konolige Kit Konolige Kit Konolige Scott Soler Electric Utilities: Watt's News - The Weekly Update Electric Utilities: Capex Study - FCF Peaks in 2004, A Contrarian View Electric Utilities: Watt's News - The Weekly Update Electric Utilities: Watt's News - The Weekly Update Natural Gas & Electric Utilities: Winter 2004 Sector Overview Entravision: TV Station Robust, Despite UVN Scatter Weakness Pharmaceuticals, Specialty: 3Q04 Preview; No Reason to Get Bullish Yet Weekly Technical Perspective: Extra Innings and azathioprine.
Glucagon expression shift in a syngeneic single-donor intrahepatic rat Gunther L., Liu X., Neeff H., et al.; Transplant. Proc. 37 8 islet transplantation model 3487-3489 ; , 2005 [Dr. L. G nther, Department of General and u Visceral Surgery, Freiburg University Hospital, Hugstetter Str 55, 79106 Freiburg, Germany] Beneficial effects of nerve growth factor on islet transplantation Miao G., Mace J., Kirby M., et al.; Transplant. Proc. 37 8 3490-3492 ; , 2005 [Dr. E. Hathout, Islet Transplant Lab., Department of Pediatrics, Loma Linda University, 11175 Campus St., Loma Linda, CA 92354, United States] Koblas T., Girman P., Berkova Z., et al.; Transplant. Proc. 37 8 3493-3495 ; , 2005 [F. Saudek, Department of Diabetes, Diabetes Center, Institute for Clinical and Experimental Medicine, Videnska 1958 9, 140 Prague, Czech Republic] Elliott R.B., Escobar L., Tan P.L.J., et al.; Transplant. Proc. 37 8 3505-3508 ; , 2005 [R.B. Elliott, Living Cell Technologies New Zealand, Ltd., P.O. Box 23- 566 Hunters Corner, Papatoetoe, Auckland, New Zealand] Tashiro H., Iwata H., Warnock G.L., et al.; Transplant. Proc. 37 8 3512-3513 ; , 2005 [H. Tashiro, Institute for Frontier Medical Sciences, Kyoto University, 53 Shogoin- kawara- cho, Sakyo- ku, Kyoto, 606- 8507, Japan] Rood P.P.M., Hara H., Ezzelarab M., et al.; Transplant. Proc. 37 8 3514-3515 ; , 2005 [Dr. D.K.C. Cooper, Thomas E. Starzl Transplantation Institute, University of Pittsburgh Medical Center, Biomedical Science Tower E1550A, 200 Lothrop St., Pittsburgh, PA 15261, United States] Brandhorst H., Duan Y., Iken M., et al.; Transplant. Proc. 37 8 3519-3520 ; , 2005 [Dr. H. Brandhorst, Third Medical Department, University Hospital, Rodthohl 6, 35385 Giessen, Germany].
Despite the fact marijuana was first cultivated almost 10, 000 years ago, modern medicine has yet to find a pharmaceutical equal and imuran.
No specific information on tenoretic is available, but common symptoms of overdose with the drug's atenolol component are: congestive heart failure, constricted airways, low blood pressure, low blood sugar, slow heartbeat, sluggishness, wheezing symptoms of overdose with the chlorthalidone component include: dizziness, nausea, weakness user comments: be the first to write a comment about tenoretic all services a-z drug list drugs & medications diseases & conditions news & articles pill identifier interactions checker drug side effects drug image search new drug approvals new drug applications fda drug alerts clinical trial results patient care notes medical encyclopedia medical dictionary medical videos - community forums for professionals drug imprint codes medical abbreviations veterinary drugs contact us news feeds advertise here recent searches arimidex ziac allegra-d 24 hour nasacort vitamin e bontril creatine norco januvia levoxyl alli viagra propecia xenical botox levitra imodium nepafenac zantac cyanokit emsam dacogen endometrin claritin risperdal recently approved totect acam2000 somatuline depot evithrom zingo selzentry evamist calomist privigen atralin gel more.
In addition, the Supreme Court of Ohio has ruled that a claimant who cannot perform a full range of sedentary jobs but can nevertheless perform some sedentary jobs is therefore capable of sustained remunerative employment. State ex rel. Wood v. Indus. Comm. 1997 ; , 78 Ohio St.3d 414. In the present case, relator has no restrictions on sitting, standing and walking, but has limitations with regard to the use of his left arm. The record indicates that relator is right-handed and that his arm limitations only come into play above table top level. As such, based upon the record, relator would be capable of performing work for eight hours per day. Relator contends, however, that the specific job of "school crossing guard" is a job which would only last a couple of hours per day and, as such, that job does not constitute "some remunerative employment." However, the argument is not whether or not a specific job, in and of itself, would provide a claimant with eight hours of employment; the question is whether or not the claimant would be capable of working part-time or full time. There is no reason why relator could not work as a "school crossing guard" and also perform other work as well. Furthermore, the commission listed several other jobs which relator could perform from a physical standpoint, and the fact that the job of "school crossing guard" would only provide employment for a limited number of hours per day does not invalidate the commission's order. Because the magistrate finds that the commission's order is supported by some evidence and meets the requirements of Noll, it would be inappropriate to grant relator's request for Gay relief and co-trimoxazole.
Review and meta-analysis of data from 13 studies generated a firestorm response, generally focused on the heavy reliance on the results of the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial ALLHAT ; .4 Casas and coauthors pointed out in rebuttal to the letters that the ALLHAT results did contribute about half of the available evidence on renal outcomes, but ALLHAT included renal disease as a prespecified outcome, and ALLHAT is the only study with a population size near the size necessary 57, 000 ; to demonstrate a 10% relative risk reduction in ESRD.5 Aside from the specific question regarding the potential value of ACE inhibitors or ARBs in renoprotection beyond blood pressure reduction, the results of key clinical trials suggested that there might be some effect of ACE inhibitors on glucose metabolism and a potential role in diabetes prevention. Two studies in particular, neither of which was designed to assess specifically the outcome of a new diagnosis of diabetes, suggested that ACE inhibitors might be associated with a side effect in preventing diabetes. Ingelfinger and Solomon in an editorial published earlier this month6 inform us that the Captopril Prevention Project CAPPP ; found a 14% lower incidence of diabetes in the captopril group compared with diuretics or betablockers in hypertensive patients, 7 and results of the Heart Outcomes Prevention Evaluation HOPE ; Study in patients at high risk for cardiovascular events found a 34% reduction in risk of newly diagnosed diabetes in patients who received ramipril 10 mg per day compared with placebo.8 However, the absolute rates of a new diagnosis of diabetes were small. For the 5 years of follow-up in the HOPE Study, 102 3.6% ; patients in the ramipril arm developed a new diagnosis for diabetes versus 155 5.4% ; for placebo. In a study designed specifically to assess the development of a new diagnosis of diabetes in patients with either impaired glucose tolerance or impaired fasting glucose levels, the Diabetes Reduction Assessment with Ramipril and Rosiglitazone Medication DREAM ; results showed no difference in new diagnosis of diabetes for an average 3 years of therapy with ramipril up to 15 mg per day ; , 17.1% versus 18.5% for placebo, hazard ratio [HR], 0.91; 95% CI, 0.80-1.03 ; .9 The choice of a preferred antihypertensive agent in a particular patient involves consideration of multiple factors.10 ALLHAT results showed that compared with the diuretic chlorthalidone, the ACE inhibitor lisinopril was associated with a higher risk of stroke P 0.02 ; and a higher risk of cardiovascular disease P 0.001 ; , including a higher risk of heart failure and higher risk of coronary revascularization.11 The Valsartan Antihypertensive Long-term Use Evaluation VALUE ; trial involving 15, 245 patients at high risk for cardiac events, including 31.7% with diabetes, found no difference in the primary composite outcome of sudden cardiac death, fatal myocardial infarction MI ; , cardiovascular death, or cardiovascular morbidity including heart failure ; between the ARB valsartan and amlodipine. However, valsartan had a smaller effect compared with amlo.
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Diuretics Chlorthalidone, 12.5 to 25 mg once daily Hydrochlorothiazide HCTZ ; , 12.5 to 50 mg once daily Triamterene HCTZ, 37.5 to 75 mg 25 to 50 mg once daily Aldosterone blockers Spironolactone, 25 to 50 mg once daily Angiotensin-converting enzyme inhibitors Lisinopril, 10 to 40 mg once daily Enalapril, 2.5 to 40 mg daily, divided doses once to twice daily Beta blockers Metoprolol, 50 to 100 mg once to twice daily Atenolol, 25 to 100 mg once daily!
Conclusion Rates of suicide and attempted suicide did not differ significantly among placeboand drug-treated groups. Studies evaluated for safety included various indications and Phase 1-3 protocols. Based on patient exposure years, similar suicide rates were seen among SSRI, placebo, or other antidepressant recipients. Studies included Phase 1-3 protocols and bentyl and chlorthalidone, for instance, what is chlorthalidone!
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Lowe A.P.J. Mol eds. ; , European Integration and Environmental Policy. London and New York: Belhaven Press, 241. Jasanoff, Sheila, 1986: Neutral Expertise. In: Sheila Jasanoff ed. ; Risk Management and Political Culture. A Comparative Study of Science in the Policy Context. New York: Russell Sage Foundation, 69-77. Joerges, Christian, 1999: "Good Governance" Through Comitology? In: Christian Joerges Ellen Vos eds. ; , EU Committees: Social Regulation, Law and Politics. Oxford and Portland: Hart Publishing, 311-338. Kaufer, Erich, 1990: The Regulation of New Product Development in the Drug Industry. In: Giandomenico Majone ed. ; Deregulation or Re-regulation? Regulatory Reform in Europe and the United States. London: Pinter Publishers, 153175. Kaufmann, Franz-Xaver G. Majone Vincent Ostrom, 1986: Guidance, Control, and Evaluation in the Public Sector. The Bielefeld Interdisciplinary Project. Berlin New York: de Gruyter. Kirk, Beate, 1999: Der Contergan-Fall: Eine unvermeidbare Katastrophe? Zur Geschichte des Arzneistoffs Thalidomid, Greifswalder Schriften zur Geschichte der Pharmazie und Sozialpharmazie. Vol. 1. Stuttgart: Wissenschaftliche Verlagsgesellschaft mbH Stuttgart. Krapohl, Sebastian, 2002: A New Mode of Single Market Regulation: The European Agency for the Regulation of Pharmaceuticals. Conference paper, Bamberg. Krapohl, Sebastian, 2004: Single Market Regulation between Technocratic Independence and Political Control: The European Agency for the Evaluation of Medicinal Products and the Authorization of Pharmaceuticals. Paper presented at conference on 'Good Governance' in Supranational Market Regulation: How Do Regulatory Institutions Matter?, University of Bamberg, 16. 17.01.2004. Lane, Jan-Erik, 2000: New Public Management. London, New York: Routledge. Liikanen, Eric, Member of the European Commission, responsible for Enterprise and the Information Society, 2002: Pharmaceuticals in Europe. Getting the Future Legal Framework Right. Paper presented at the 8th Annual Pharmaceuticals Conference, London, 14 February 2002. : europa .int Lindblom, Charles E., 1977: Politics and Markets. The World's Political-Economic Systems. New York: Basic Books. Luhmann, Hans-Jochen, 2000: Die Contergan-Katastrophe revisited - Ein Lehrstck vom Beitrag der Wissenschaft zur gesellschaftlichen Blindheit. In: Umweltmed Forsch Prax 5, 295-300. MacInnes, Rona Cynthia E. Lumley Stuart R. Walker, 1994: New chemical entity output of the international pharmaceutical industry from 1970 to 1992. In: Clinical Pharmacology & Therapeutics 56, 339-349. Majone, Giandomenico, 1996: Redistributive und sozialregulative Politik. In: Markus Jachtenfuchs Beate Kohler-Koch eds. ; , Europische Integration. Opladen: Leske + Budrich, 225-247. Majone, Giandomenico, 1997: The new European agencies: regulation by information. In: Journal of European Public Policy 4, 262-275, for instance, neurontin.
Adderall Amphetamine with Dextroamphetamine Salt Combination ; Aldactone Spironolactone ; Amaryl Glimepiride ; Anaprox Naproxen ; Arava QL Leflunomide QL ; Ativan Lorazepam ; Augmentin, Augmentin ES Amoxicillin with Potassium Clavulanate ; Buspar Buspirone ; Calan, Calan SR Verapamil ; Capoten Captopril ; Cardizem CD except for 360mg strength Diltiazem Sustained Release 24 Hour Capsule ; Cardura Doxazosin ; Ceftin Cefuroxime ; Celexa QL Citalopram QL ; Ciloxan Eye Drops Ciprofloxacin ; Cipro Ciprofloxacin ; Cleocin T Clindamycin Gel, Lotion, Solution, Swabs ; Copegus QL, N RibavirinQL, N ; Darvocet-N Propoxyphene with Acetaminophen ; DDAVP Desmopressin ; Dexedrine SR Dextroamphetamine Sustained Release Capsule ; DiaBeta, Micronase, Glynase Glyburide ; Didronel Etidronate Disodium ; Diflucan 50, 100, 200mg Tablet N Fluconazole N ; Diflucan 150mg QL Fluconazole QL ; Diprolene AF Betamethasone Dipropionate Augmented Cream ; Duricef Cefadroxil ; Dyazide Triamterene with Hydrochlorothiazide ; Dynacirc Isradipine ; Elocon Cream, Ointment Mometasone ; Eskalith CR Lithium Carbonate Controlled-Release ; Fioricet Butalbital with Acetaminophen and Caffeine ; Flexeril Cyclobenzaprine ; Glucophage, XR Metformin ; Glucotrol, XL Glipizide ; Hytrin Terazosin ; Inderal Propranolol ; Keflex Cephalexin ; Klonopin Clonazepam ; Lasix Furosemide ; Lithobid Lithium Carbonate Extended-Release ; Lopid Gemfibrozil ; Lopressor Metoprolol ; Lotensin Benazepril ; Lotensin HCT Benazepril with Hydrochlorothiazide ; Lotrisone Betamethasone with Clotrimazole ; Macrobid Nitrofurantoin Nitrofurantoin Macrocrystal ; Medrol Dosepak Methylprednisolone ; Metrocream Metronidazole Cream ; Mevacor QL QD Lovastatin QL QD ; Motrin Ibuprofen ; - Prescription strengths only Mycelex Troche Clotrimazole Troche ; Naprosyn Naproxen ; - Prescription strengths only Neurontin Capsule, Tablet Gabapentin ; Nizoral Ketoconozole ; Ocuflox Eye Drops Ofloxacin ; Percocet 5-325, 7.5-500, 10-650 Oxycodone with Acetaminophen ; Plendil Felodipine ; Pletal Cilostazol ; Prinivil, Zestril Lisinopril ; Prinzide, Zestoretic Lisinopril with Hydrochlorothiazide ; Procardia XL Nifedipine Extended-Release ; Proventil Inhaler QL, Ventolin Inhaler QL Albuterol Inhaler QL ; Provera Medroxyprogesterone ; Prozac QL Fluoxetine QL ; Rebetol QL, N Ribavirin QL, N ; Remeron QL Mirtazapine QL ; Remeron SolTab QL Mirtazapine Dispersible Tablet QL ; Restoril 15, 30mg Temazepam ; Ritalin Methylphenidate ; Ritalin SR Methylphenidate Extended-Release ; Sporanox QL, N Itraconazole QL, N ; Tenormin Atenolol ; Tenoretic Atenolol with Chlorthalidonf ; Terazol 3 Cream Terconazole ; Tylenol #3 Acetaminophen with Codeine ; Ultracet QL Tramadol with Acetaminophen QL ; Ultram QL Tramadol QL ; Ultravate Cream, Ointment Halobetasol Propionate ; Valium Diazepam ; Vaseretic Enalapril with Hydrochlorothiazide ; Vasotec Enalapril ; Vicodin Acetaminophen with Hydrocodone ; Vicoprofen Ibuprofen with Hydrocodone ; Videx EC 200, 250, 400mg Didanosine Capsule Delayed Release ; Voltaren Tablet Diclofenac ; Wellbutrin QL Bupropion QL ; Wellbutrin SR QL, N Bupropion Sustained Release QL, N ; Xanax, Xanax XR Alprazolam ; Ziac Bisoprolol with Hydrochlorothiazide ; Zonegran Zonisamide ; Zovirax Tablet, Capsule, Suspension Acyclovir and tenoretic.
PB09 Improvement of Signal Sequence for Separation of Protein Y. Tsuchiya, K. Morioka, J. Shirai, K. Yoshida National Institute of Animal Health, Kodaira, Tokyo, Japan Although protein has come to be mass-produced by the low price in recent years using bioengineering technology, it is a still difficult problem to separate the purpose protein and cell ingredients. To solve this, most effective breakthrough is the secretory production of recombinant protein. Signal sequence plays an important role in the translocation of newly synthesized proteins across the membrane of the endoplasmic reticulum eukaryotic cells ; or across the cell membrane prokaryotic cells ; . These sequences are composed of three structurally and functionally distinct regions: a positively charged N-terminal region, a central core region, and a C-terminal region recognized by signal peptidase. We have a human lysozyme HLY ; secretory system in yeast Saccharomyces cerevisiae ; and insect cell by use of a synthetic fusion gene for chicken lysozyme signal peptide CLSP ; and HLY. By using this system, structural requirement of each region of CLSP have been elucidated, which show the importance of positive charge in N-terminal region, hydriphobicity in central core region, turn-formation in C-terminal region. Following on these, in present study, the N-terminal region and central core region of CLSP were altered to improve the secretion amount of HLY in yeast or insect cell. The amino acid sequence of the mutant signal peptides prepared in this study and their effects on HLY secretion are summarized in Table 1. In order to raise the amount of HLY secretion, basic residues Arg ; were introduced into the N-terminal region of CLSP and the sequence of central core region of CLSP was changed into continuation of Leu. Hybrid genes coded these signal peptides connected with HLY, were expressed in yeast S. cerevisiae ; or in insect cell BmN4 ; . Each recombinant cell was cultured for 4 days. HLY activity in culture medium was measured photometrically by the method of Mrsky. One unit corresponded to 0.33g of HLY mL of culture medium under our assay conditions. Additional positive charge in the N-terminal region raised the amount of HLY secretion in yeast, but not in insect cell. About the significance of positive charge in the N-terminal region, previous report has confirmed it in prokaryote, but denied it in eukaryote. Indeed, yeast is the eukaryote, but not the multicellular organism. For the mechanism in which signal peptide enters into membrane, there may be some differences by the unicellular yeast, or bacteria ; and the multicellular organism insecta, or mammals ; . In contrast with the Nterminal region, the increase of hydrophobicity in the central core region of CLSP, remarkably enhanced the HLY secretion, similar to previous reports. The structural requirement of this region may be common over species.
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