Satish Kalhan

Summary

Affiliation: Case Western Reserve University
Country: USA

Publications

  1. pmc Resurgence of serine: an often neglected but indispensable amino Acid
    Satish C Kalhan
    Department of Molecular Medicine, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, Ohio 44195, USA
    J Biol Chem 287:19786-91. 2012
  2. doi request reprint Methionine, homocysteine, one carbon metabolism and fetal growth
    Satish C Kalhan
    Department of Molecular Medicine, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, 9500 Euclid Avenue, Cleveland, OH 44195, USA
    Rev Endocr Metab Disord 13:109-19. 2012
  3. pmc Effect of intravenous amino acids on protein kinetics in preterm infants
    Satish C Kalhan
    Department of Gastroenterology, Cleveland Clinic Foundation, Lerner Research Institute, Cleveland, Ohio 44195, USA
    Curr Opin Clin Nutr Metab Care 10:69-74. 2007
  4. doi request reprint Protein and amino acid metabolism in the human newborn
    Satish C Kalhan
    Department of Medicine, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, Ohio 44195, USA
    Annu Rev Nutr 28:389-410. 2008
  5. ncbi request reprint Transamination of leucine and nitrogen accretion in human pregnancy and the newborn infant
    Satish C Kalhan
    Schwartz Center for Metabolism and Nutrition, Department of Pediatrics, Case Western Reserve University at MetroHealth Medical Center, Cleveland, OH, USA
    J Nutr 136:281S-7S. 2006
  6. pmc Plasma metabolomic profile in nonalcoholic fatty liver disease
    Satish C Kalhan
    Department of Pathobiology, Cleveland Clinic, Cleveland, OH 44195, USA
    Metabolism 60:404-13. 2011
  7. pmc Estimates of hepatic glyceroneogenesis in type 2 diabetes mellitus in humans
    Satish C Kalhan
    Schwartz Center for Nutrition and Metabolism, MetroHealth Center, Cleveland, OH 44109, USA
    Metabolism 57:305-12. 2008
  8. pmc Metabolic and genomic response to dietary isocaloric protein restriction in the rat
    Satish C Kalhan
    Department of Pathobiology, Cleveland Clinic, Cleveland, Ohio 44195, USA
    J Biol Chem 286:5266-77. 2011
  9. pmc Methionine and protein metabolism in non-alcoholic steatohepatitis: evidence for lower rate of transmethylation of methionine
    Satish C Kalhan
    Department of Pathobiology, Cleveland Clinic, Cleveland, OH 44195, USA
    Clin Sci (Lond) 121:179-89. 2011
  10. ncbi request reprint Altered expression of genes regulating skeletal muscle mass in the portacaval anastomosis rat
    Srinivasan Dasarathy
    Department of Gastroenterology, Cleveland Clinic, Lerner Research Institute and the Cleveland Clinic Lerner College of Medicine, NE40, 9500 Euclid Ave, Cleveland, OH 44195, USA
    Am J Physiol Gastrointest Liver Physiol 292:G1105-13. 2007

Research Grants

  1. Glutamine Metabolism in the Human Newborn
    Satish Kalhan; Fiscal Year: 2003
  2. Glutamine Metabolism in the Human Newborn
    Satish Kalhan; Fiscal Year: 2007
  3. Glutamine Metabolism in the Human Newborn
    Satish Kalhan; Fiscal Year: 2006
  4. Sulfur Amino Acid Metabolism in NAFLD
    Satish C Kalhan; Fiscal Year: 2010

Collaborators

Detail Information

Publications46

  1. pmc Resurgence of serine: an often neglected but indispensable amino Acid
    Satish C Kalhan
    Department of Molecular Medicine, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, Ohio 44195, USA
    J Biol Chem 287:19786-91. 2012
    ..Here, we review recent information regarding the synthesis of serine and the regulation of its metabolism and discuss the role played by phosphoenolpyruvate carboxykinase in this process...
  2. doi request reprint Methionine, homocysteine, one carbon metabolism and fetal growth
    Satish C Kalhan
    Department of Molecular Medicine, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, 9500 Euclid Avenue, Cleveland, OH 44195, USA
    Rev Endocr Metab Disord 13:109-19. 2012
    ..These unique changes in methionine and one carbon metabolism in response to physiological, nutritional and hormonal influences make these processes critical for cellular and organ function and growth...
  3. pmc Effect of intravenous amino acids on protein kinetics in preterm infants
    Satish C Kalhan
    Department of Gastroenterology, Cleveland Clinic Foundation, Lerner Research Institute, Cleveland, Ohio 44195, USA
    Curr Opin Clin Nutr Metab Care 10:69-74. 2007
    ..To summarize recent findings of the effects of intravenous amino acids on protein kinetics in low-birth-weight infants and to describe the potential cellular mechanism for these observations...
  4. doi request reprint Protein and amino acid metabolism in the human newborn
    Satish C Kalhan
    Department of Medicine, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, Ohio 44195, USA
    Annu Rev Nutr 28:389-410. 2008
    ..Finally, the physiological rationale and the impact of nutrient (amino acids) interventions on the dynamics of protein metabolism are discussed...
  5. ncbi request reprint Transamination of leucine and nitrogen accretion in human pregnancy and the newborn infant
    Satish C Kalhan
    Schwartz Center for Metabolism and Nutrition, Department of Pediatrics, Case Western Reserve University at MetroHealth Medical Center, Cleveland, OH, USA
    J Nutr 136:281S-7S. 2006
    ..The regulatory mechanism involved in this redirection of nitrogen from irreversible loss to accretion remains under investigation...
  6. pmc Plasma metabolomic profile in nonalcoholic fatty liver disease
    Satish C Kalhan
    Department of Pathobiology, Cleveland Clinic, Cleveland, OH 44195, USA
    Metabolism 60:404-13. 2011
    ..Statistical analysis identified a panel of biomarkers that could effectively separate healthy controls from NAFLD and healthy controls from NASH. These biomarkers can potentially be used to follow response to therapeutic interventions...
  7. pmc Estimates of hepatic glyceroneogenesis in type 2 diabetes mellitus in humans
    Satish C Kalhan
    Schwartz Center for Nutrition and Metabolism, MetroHealth Center, Cleveland, OH 44109, USA
    Metabolism 57:305-12. 2008
    ..The contribution of glyceroneogenesis to triglyceride-glycerol is not affected by short (4 hours) infusion of insulin in type 2 diabetes mellitus...
  8. pmc Metabolic and genomic response to dietary isocaloric protein restriction in the rat
    Satish C Kalhan
    Department of Pathobiology, Cleveland Clinic, Cleveland, Ohio 44195, USA
    J Biol Chem 286:5266-77. 2011
    ..These may be related to high methylation demands placed on the organism and caused by possible changes in cellular osmolarity as a result of the efflux of the intracellular taurine...
  9. pmc Methionine and protein metabolism in non-alcoholic steatohepatitis: evidence for lower rate of transmethylation of methionine
    Satish C Kalhan
    Department of Pathobiology, Cleveland Clinic, Cleveland, OH 44195, USA
    Clin Sci (Lond) 121:179-89. 2011
    ..These results are the first evidence for perturbed metabolism of methionine in NASH in humans and provide a rationale for the development of targeted intervention strategies...
  10. ncbi request reprint Altered expression of genes regulating skeletal muscle mass in the portacaval anastomosis rat
    Srinivasan Dasarathy
    Department of Gastroenterology, Cleveland Clinic, Lerner Research Institute and the Cleveland Clinic Lerner College of Medicine, NE40, 9500 Euclid Ave, Cleveland, OH 44195, USA
    Am J Physiol Gastrointest Liver Physiol 292:G1105-13. 2007
    ....
  11. pmc Effect of intravenous amino acids on glutamine and protein kinetics in low-birth-weight preterm infants during the immediate neonatal period
    Mark M Kadrofske
    Schwartz Center for Metabolism and Nutrition, MetroHealth Medical Center Department of Pediatrics, Case Western Reserve University, Cleveland, Ohio 44109 1998, USA
    Am J Physiol Endocrinol Metab 290:E622-30. 2006
    ..The mechanisms of this transient effect on whole body protein/nitrogen metabolism remain unknown...
  12. ncbi request reprint Intraoperative glucose control in diabetic and nondiabetic patients during cardiac surgery
    Charles E Smith
    Department of Anesthesiology, MetroHealth Medical Center, Case Western Reserve University, Cleveland, OH 44109, USA
    J Cardiothorac Vasc Anesth 19:201-8. 2005
    ..The purpose of this study was to evaluate intraoperative glucose control...
  13. ncbi request reprint Longitudinal changes in energy expenditure and body composition in obese women with normal and impaired glucose tolerance
    Ndubueze C Okereke
    Department of Reproductive Biology, Case Western Reserve University at MetroHealth Medical Center, Cleveland, Ohio 44109, USA
    Am J Physiol Endocrinol Metab 287:E472-9. 2004
    ..The increased reliance on fat metabolism is accompanied by a concomitant decrease in carbohydrate metabolism during hyperinsulinemia. The increase in fat oxidation may be related to increased maternal serum leptin...
  14. ncbi request reprint Effects of moderate weight loss and orlistat on insulin resistance, regional adiposity, and fatty acids in type 2 diabetes
    David E Kelley
    Department of Medicine, Division of Endocrinology and Metabolism, University of Pittsburgh, Pittsburgh, Pennsylvania 15213, USA
    Diabetes Care 27:33-40. 2004
    ....
  15. pmc Parenteral amino acid and metabolic acidosis in premature infants
    Pushkaraj Jadhav
    Schwartz Center for Metabolism and Nutrition and Department of Pediatrics, Case Western Reserve University, MetroHealth Medical Center, Cleveland, Ohio, USA
    JPEN J Parenter Enteral Nutr 31:278-83. 2007
    ..Aggressive parenteral nutrition (PN) including amino acids is recommended for low-birth-weight infants to prevent energy and protein deficit. Their impact on acid-base homeostasis has not been examined...
  16. ncbi request reprint TNF-alpha is a predictor of insulin resistance in human pregnancy
    John P Kirwan
    Department of Reproductive Biology, Case Western Reserve University School of Medicine at MetroHealth Medical Center, Bell Greve Building Rm G 232E, 2500 MetroHealth Drive, Cleveland, OH 44109 1998, USA
    Diabetes 51:2207-13. 2002
    ....
  17. ncbi request reprint Glutamine supplementation in the newborn infant
    Prabhu S Parimi
    Department of Pediatrics, Case Western Reserve University at MetroHealth Medical Center, 2500 MetroHealth Drive, Cleveland, OH 44109 1998, USA
    Semin Fetal Neonatal Med 12:19-25. 2007
    ..The reasons for these differences are discussed...
  18. ncbi request reprint Skeletal muscle atrophy is associated with an increased expression of myostatin and impaired satellite cell function in the portacaval anastamosis rat
    Srinivasan Dasarathy
    Schwartz Center for Metabolism and Nutrition, Department of Medicine, Division of Gastroenterology, Case Western Reserve University, MetroHealth Medical Center, Cleveland OH 44109, USA
    Am J Physiol Gastrointest Liver Physiol 287:G1124-30. 2004
    ..05). These data suggest that skeletal muscle atrophy seen in the portacaval shunted rats is a consequence of impaired satellite cell proliferation and differentiation mediated, in part, by higher myostatin and lower IGF1 expression...
  19. ncbi request reprint Glutamine and leucine nitrogen kinetics and their relation to urea nitrogen in newborn infants
    Prabhu S Parimi
    Department of Pediatrics, Robert Schwartz M D Center for Metabolism and Nutrition, MetroHealth Medical Center, Case Western Reserve University School of Medicine, Cleveland, Ohio 44109 1998, USA
    Am J Physiol Endocrinol Metab 282:E618-25. 2002
    ..The negative relationship between glutamine turnover and the irreversible oxidation of protein (urea synthesis) suggests an important role of glutamine as a nitrogen source for other synthetic processes and accretion of body proteins...
  20. ncbi request reprint Glutamine supplement with parenteral nutrition decreases whole body proteolysis in low birth weight infants
    Satish C Kalhan
    Schwartz Center for Metabolism and Nutrition, MetroHealth Medical Center, Department of Pedatrics and Biochemistry, CaseWestern Reserve University, 2500 MetroHealth Drive, Cleveland, OH 44109, USA
    J Pediatr 146:642-7. 2005
    ..To examine the effect of supplemental glutamine (0.6 g.kg -1 .d -1 ) on whole body protein/nitrogen and glutamine kinetics in low birth weight (LBW) infants receiving parenteral nutrition in the immediate neonatal period...
  21. ncbi request reprint Amino acids, glutamine, and protein metabolism in very low birth weight infants
    Prabhu S Parimi
    Department of Pediatrics, Schwartz Center for Metabolism and Nutrition, Case Western Reserve University School of Medicine, MetroHealth Medical Center, Cleveland, OH 44109, USA
    Pediatr Res 58:1259-64. 2005
    ..These data show an acute increase in parenteral amino acid-suppressed proteolysis, however, such an effect was not seen when amino acids were infused for 20 h and resulted in an increase in glutamine synthesis...
  22. ncbi request reprint The key role of anaplerosis and cataplerosis for citric acid cycle function
    Oliver E Owen
    Department of Pediatrics, Case Western Reserve University School of Medicine, Robert Schwartz M D Center for Metabolism and Nutrition, MetroHealth Medical Center, Cleveland, OH 44109, USA
    J Biol Chem 277:30409-12. 2002
  23. ncbi request reprint Metabolism of threonine in newborn infants
    Prabhu S Parimi
    Schwartz Center for Metabolism and Nutrition, Bell Greve Bldg, Room G 735, MetroHealth Medical Center, 2500 MetroHealth Drive, Cleveland, OH 44109, USA
    Am J Physiol Endocrinol Metab 289:E981-5. 2005
    ..These data suggest that threonine is exclusively degraded by the glycine-independent serine/threonine dehydratase pathway. A higher flux of threonine relative to phenylalanine indicates higher turnover of threonine enriched proteins...
  24. pmc Glycine and urea kinetics in nonalcoholic steatohepatitis in human: effect of intralipid infusion
    Srinivasan Dasarathy
    Department of Gastroenterology and Hepatology, Lerner Research Institute, Cleveland, USA
    Am J Physiol Gastrointest Liver Physiol 297:G567-75. 2009
    ..An increase in oxidative stress, induced by a higher rate of fatty acid oxidation in NASH, may have caused an increase in the contribution of serine to cystathionine to meet the higher demands for glutathione...
  25. ncbi request reprint Effect of enteral glutamine or glycine on whole-body nitrogen kinetics in very-low-birth-weight infants
    Prabhu S Parimi
    Schwartz Center for Metabolism and Nutrition, MetroHealth Medical Center, Cleveland, OH 44109 1998, USA
    Am J Clin Nutr 79:402-9. 2004
    ..Although supplementation with glutamine has been suggested for growing infants, its effect on protein metabolism has not been examined...
  26. doi request reprint Reassessing triglyceride synthesis in adipose tissue
    Colleen Nye
    Department of Biochemistry, Case Western Reserve University School of Medicine, Cleveland, OH 44106 3549, USA
    Trends Endocrinol Metab 19:356-61. 2008
    ..Here, we review recent information on triglyceride synthesis and introduce the pathway of glyceroneogenesis as an important and highly regulated source of glyceride-glycerol in adipose tissue...
  27. pmc Metabolism of methionine in the newborn infant: response to the parenteral and enteral administration of nutrients
    Biju Thomas
    Department of Pediatrics, MetroHealth Medical Center, Cleveland, Ohio 44109, USA
    Pediatr Res 64:381-6. 2008
    ....
  28. ncbi request reprint Serine metabolism in human pregnancy
    Satish C Kalhan
    Departments of Pediatrics and Reproductive Biology, Case Western Reserve University, MetroHealth Medical Center, Cleveland, Ohio 44109 1998, USA
    Am J Physiol Endocrinol Metab 284:E733-40. 2003
    ....
  29. ncbi request reprint Metabolic responses to protein restriction during pregnancy in rat and translation initiation factors in the mother and fetus
    Prabhu S Parimi
    Schwartz Center for Metabolism and Nutrition, Department of Pediatrics, Case Western Reserve University at MetroHealth Medical Center, Cleveland, OH 44109 1998, USA
    Pediatr Res 56:423-31. 2004
    ..The data on translation initiation factors suggest a higher rate of protein synthesis in the maternal liver and a lower rate in the fetal liver in response to protein restriction...
  30. pmc A computational model of adipose tissue metabolism: evidence for intracellular compartmentation and differential activation of lipases
    Jaeyeon Kim
    Department of Biomedical Engineering, Case Western Reserve University, Cleveland, OH 44106, USA
    J Theor Biol 251:523-40. 2008
    ..3) Glyceroneogenesis contributes more to glycerol-3-phosphate synthesis during epinephrine infusion when pyruvate oxidation is inhibited by a high acetyl-CoA/free-CoA ratio...
  31. ncbi request reprint Fatty liver in type 2 diabetes mellitus: relation to regional adiposity, fatty acids, and insulin resistance
    David E Kelley
    Department of Medicine, University of Pittsburgh, 810N Montefiore University Hospital, 3459 Fifth Avenue, Pittsburgh, PA 15213, USA
    Am J Physiol Endocrinol Metab 285:E906-16. 2003
    ..34; P < 0.01). In summary, fatty liver is relatively common in overweight and obese volunteers with type 2 DM and is an aspect of body composition related to severity of insulin resistance, dyslipidemia, and inflammatory markers...
  32. ncbi request reprint Effect of reduced maternal inspired oxygen on hepatic glucose metabolism in the rat fetus
    Prabhu S Parimi
    Robert Schwartz MD Center for Metabolism and Nutrition, Departments of Pediatrics and Biochemistry, Case Western Reserve University School of Medicine, MetroHealth Medical Center, Cleveland, Ohio 44109 1998, USA
    Pediatr Res 53:325-32. 2003
    ..IUGR, as a result of decreased fractional inspired oxygen concentration may also be the consequence of pH-mediated changes in uterine blood flow. However, these remain to be examined in this experimental model...
  33. doi request reprint Obesity, hepatic metabolism and disease
    John M Edmison
    Department of Gastroenterology and Hepatology, Cleveland Clinic, Cleveland, OH, USA
    Nestle Nutr Workshop Ser Pediatr Program 63:163-72; discussion 172-6, 259-68. 2009
    ..Bariatric surgery is indicated in selected patients. A greater understanding of the pathophysiological progression of NASH in obese patients must be obtained in order to develop more focused and improved therapy...
  34. pmc Glyceroneogenesis is the dominant pathway for triglyceride glycerol synthesis in vivo in the rat
    Colleen K Nye
    Department of Biochemistry, Case Western Reserve University, Cleveland, Ohio 44106, USA
    J Biol Chem 283:27565-74. 2008
    ..Thus, glyceroneogenesis, in contrast to glucose, via glycolysis, is quantitatively the predominant source of triglyceride glycerol in adipose tissue, skeletal muscle, and liver of the rat during fasting and high sucrose feeding...
  35. pmc Simultaneous assay of isotopic enrichment and concentration of guanidinoacetate and creatine by gas chromatography-mass spectrometry
    Takhar Kasumov
    Department of Pathobiology, Lerner Research Institute, Cleveland Clinic, OH 44195, USA
    Anal Biochem 395:91-9. 2009
    ..00097), suggesting a large pool size and a slow rate of synthesis of creatine. This method can be used to estimate the rate of synthesis of creatine in vivo in human and animal studies...
  36. ncbi request reprint Overexpression of the cytosolic form of phosphoenolpyruvate carboxykinase (GTP) in skeletal muscle repatterns energy metabolism in the mouse
    Parvin Hakimi
    Department of Biochemistry, Case Western Reserve University School of Medicine, Cleveland, OH 44106 4935, USA
    J Biol Chem 282:32844-55. 2007
    ..5 years ran twice as fast as 6-12-month-old control animals. We conclude that overexpression of PEPCK-C repatterns energy metabolism and leads to greater longevity...
  37. ncbi request reprint Triacylglycerol infusion improves exercise endurance in patients with mitochondrial myopathy due to complex I deficiency
    Mark J Roef
    Department of Pediatric Gastroenterology, The University Children s Hospital, Utrecht, Netherlands
    Am J Clin Nutr 75:237-44. 2002
    ..A high-fat diet has been recommended for the treatment of patients with mitochondrial myopathy due to complex I (NADH dehydrogenase) deficiency (CID)...
  38. ncbi request reprint Lactate disposal via gluconeogenesis is increased during exercise in patients with mitochondrial myopathy due to complex I deficiency
    Mark J Roef
    Department of Pediatric Gastroenterology, University Children s Hospital, Utrecht, The Netherlands
    Pediatr Res 51:592-7. 2002
    ..GNG(PYR) is a significant mechanism of lactate disposal in exercising CID patients, but triglyceride infusion does not enhance their lactate disposal through this mechanism...
  39. ncbi request reprint Triacylglycerol infusion does not improve hyperlactemia in resting patients with mitochondrial myopathy due to complex I deficiency
    Mark J Roef
    Department of Pediatric Gastroenterology, The University Children s Hospital, Utrecht, Netherlands
    Am J Clin Nutr 75:228-36. 2002
    ..A high-fat diet has been recommended for correction of biochemical abnormalities and muscle energy state in patients with complex I (NADH dehydrogenase) deficiency (CID)...
  40. ncbi request reprint Gluconeogenesis in humans with induced hyperlactatemia during low-intensity exercise
    Mark J Roef
    Department of Pediatric Gastroenterology, VU University Medical Center, 1007 MB Amsterdam, The Netherlands
    Am J Physiol Endocrinol Metab 284:E1162-71. 2003
    ....
  41. ncbi request reprint Gender differences in the regulation of amino acid metabolism
    Linda S Lamont
    Exercise Science Program, University of Rhode Island, Kingston, RI 02881, USA
    J Appl Physiol 95:1259-65. 2003
    ..Gender-specific fuel preferences during exercise are regulated by beta-adrenergic-receptor activity. Substrate availability during exercise appears to modulate the amino acid oxidation differences between genders...
  42. ncbi request reprint Glyceroneogenesis and the triglyceride/fatty acid cycle
    Lea Reshef
    Department of Biochemistry, Hebrew University Hadassah Medical School, Jerusalem 91120, Israel
    J Biol Chem 278:30413-6. 2003
  43. ncbi request reprint Maternal nutrition and optimal infant feeding practices: executive summary
    Daniel J Raiten
    Office of Prevention Research and International Programs, Endocrinology, Nutrition and Growth Branch, Center for Research on Mothers and Children, DHHS NIH NICHD, Bethesda, MD 20892, USA
    Am J Clin Nutr 85:577S-583S. 2007
    ..These proceedings contain presentations about the effect of maternal nutrition and the placental environment on fetal growth and birth outcomes, as well as issues pertaining to feeding preterm and full-term infants...
  44. ncbi request reprint Nutrition
    Satish C Kalhan
    Semin Fetal Neonatal Med 12:1. 2007
  45. ncbi request reprint Docosahexaenoic acid and arachidonic acid enhance growth with no adverse effects in preterm infants fed formula
    Sheila M Innis
    Department of Pediatrics, University of British Columbia, Vancouver, Canada
    J Pediatr 140:547-54. 2002
    ..To determine if docosahexaenoic acid (DHA) and arachidonic acid (ARA) supplementation influences growth or visual acuity of formula-fed premature infants...
  46. pmc Re: "alternative equations for whole-body protein synthesis and for fractional synthetic rates of proteins" by Ramakrishnan (Metabolism 2007;56:1550-60)
    Satish C Kalhan
    Metabolism 57:871; author reply 871-2. 2008

Research Grants8

  1. Glutamine Metabolism in the Human Newborn
    Satish Kalhan; Fiscal Year: 2003
    ..abstract_text> ..
  2. Glutamine Metabolism in the Human Newborn
    Satish Kalhan; Fiscal Year: 2007
    ..RESEARCH GRANT TABLE OF CONTENTS Page Numbers Face Page .............................................................................................................................................. 1 Description, ..
  3. Glutamine Metabolism in the Human Newborn
    Satish Kalhan; Fiscal Year: 2006
    ..abstract_text> ..
  4. Sulfur Amino Acid Metabolism in NAFLD
    Satish C Kalhan; Fiscal Year: 2010
    ..The proposed studies are aimed at examining the metabolic mechanisms involved in the progression of this disease, so that specific targeted intervention strategies related to the stage of the disease can be identified and evaluated. ..