Lars Osterberg, MD, MPH

All Publications

• Back to the Future: What Learning Communities Offer to Medical Education Journal of Medical Education and Curricular Development Osterberg, L., Goldstein, E., Hatem, D. S., Moynahan, K., Shochet, R. 2016: 67-70

  View details for DOI 10.4137/JMECD.S39420

• The highly influential teacher: recognising our unsung heroes MEDICAL EDUCATION Osterberg, L., Swigris, R., Weil, A., Branch, W. T. 2015; 49 (11): 1117-1123

  View details for DOI 10.1111/medu.12808

  View details for Web of Science ID 000363514600009

• Screen of Drug Use Diagnostic Accuracy of a New Brief Tool for Primary Care JAMA INTERNAL MEDICINE Tiet, Q. Q., Leyva, Y. E., Moos, R. H., Frayne, S. M., Osterberg, L., Smith, B. 2015; 175 (8): 1371-1377

  Abstract

  Illicit drug use is prevalent, and primary care provides an ideal setting in which to screen for drug use disorders (DUDs) and negative consequences of drug use (NCDU). Comprehensive reviews have concluded that existing drug use screening instruments are not appropriate for routine use in primary care.To develop and validate a screening instrument for drug use.We revised items drawn from existing screening instruments and conducted signal detection analyses to develop the new instrument. We approached 3173 patients at 2 primary care clinics in a US Department of Veterans Affairs health care system from February 1, 2012, through April 30, 2014. A total of 1300 (41.0%) patients consented to the study, of whom 1283 adults were eligible (mean [SD] age, 62.2 [12.6] years). In the last 12 months, 241 (18.8%) participants reported using illicit drugs or prescription medication for a nonmedical purpose, and 189 (14.7%) reported 1 or more NCDU. A total of 133 (10.4%) patients met DSM-IV criteria for a DUD. The sample was randomly divided first to develop the measure and then to validate it.The Mini-International Diagnostic Interview was used as the criterion for DUDs, and the Inventory of Drug Use Consequences was used as the criterion for NCDU.The screening instrument has 2 questions. The first is, "How many days in the past 12 months have you used drugs other than alcohol?" Patients meet that criterion with a response of 7 or more days. The second question asks, "How many days in the past 12 months have you used drugs more than you meant to?" A response of 2 or more days meets that criterion. The screening instrument was 100% sensitive and 93.73% specific for DUDs (643 patients); when replicated in the second half of the sample (640 patients), it was 92.31% sensitive and 92.87% specific. The screening instrument was 93.18% sensitive and 96.03% specific for NCDU (643 patients); when replicated in the second half of the sample (640 patients), it was 83.17% sensitive and 96.85% specific.The 2-item screen of drug use has excellent statistical properties and is a brief screening instrument for DUDs and problems suitable for busy US Department of Veterans Affairs primary care clinics.

  View details for DOI 10.1001/jamainternmed.2015.2438

  View details for Web of Science ID 000361057700025

  View details for PubMedID 26075352

• Antiretroviral therapy adherence and predictors to adherence in Albania: a cross-sectional study JOURNAL OF INFECTION IN DEVELOPING COUNTRIES Morrison, S. D., Rashidi, V., Sarnquist, C., Banushi, V. H., Hole, M. K., Barbhaiya, N. J., Gashi, V. H., Osterberg, L., Maldonado, Y., Harxhi, A. 2014; 8 (7): 853-862

  Abstract

  The possibility of an HIV/AIDS epidemic in southeastern Europe (SEE) is not improbable. Thus, an understanding of the current issues surrounding HIV/AIDS care, specifically antiretroviral therapy (ART) adherence, in countries within SEE is critical. This study was conducted to determine the ART adherence characteristics of Albania's HIV-positive population.This cross-sectional study reports initial demographic and adherence characteristics of patients receiving HIV/AIDS treatment in Albania. Retrospective review of pharmacy medications dispensed supplemented reported adherence behavior. Further, an adherence index was utilized to explore adherence more thoroughly.Patient-reported adherence and pharmacy review showed adherence levels of 98.9±4.4% and 97.7±4.7%, respectively. Assessment by adherence index revealed an index level of 91.7±6.7. Factors associated with a score of < 95 on the adherence index were: being partnered (OR = 0.29, 95% CI = 0.09 - 0.98), history of depression (OR = 0.24, 95% CI = 0.08 - 0.76), increased number of barriers to care (OR = 0.80, 95% CI = 0.66 - 0.97), and increased number of current social and medical needs (OR = 0.72, 95% CI = 0.58 - 0.91).Interventions aimed at reducing barriers to care, addressing current medical and social needs, and treating mental health issues may help improve adherence to ART in patients with HIV/AIDS in Albania. With little known about HIV/AIDS in SEE, this study provides guidance on how SEE countries can help prevent a possible rise in the prevalence of HIV given the close link of ART adherence and spread of HIV.

  View details for DOI 10.3855/jidc.3563

  View details for Web of Science ID 000343790800008

  View details for PubMedID 25022295

• Strategies to Predict, Measure, and Improve Psychosocial Treatment Adherence HARVARD REVIEW OF PSYCHIATRY Gearing, R. E., Townsend, L., Elkins, J., El-Bassel, N., Osterberg, L. 2014; 22 (1): 31-45

  Abstract

  Nonadherence to psychosocial and behavioral treatment is a significant public health problem that presents a barrier to recovery and effective treatment. An estimated 20% to 70% of individuals who initiate psychosocial mental health services discontinue treatment prior to clinicians' recommendations. Empirically supported, evidence-based, stand-alone or adjunctive psychosocial interventions treat an increasingly wide range of mental health conditions. A core assumption of most, if not all, interventions is that clients will fully and actively engage in the treatment protocol. Adherence to psychosocial treatment has received much less scientific attention, however, than adherence to medical treatment. Drawing extensively from existing research, this comprehensive review conceptualizes several types of psychosocial and behavioral treatment adherence, examines predictors of adherence to psychosocial treatment, summarizes measures of adherence, and describes existing interventions to enhance psychosocial treatment adherence.

  View details for DOI 10.1097/HRP.0000000000000005

  View details for Web of Science ID 000329612100003

  View details for PubMedID 24394220

• From High School to Medical School: The Importance of Community in Education Med Sci Educ Osterberg, L. G., Gilbert, J., Lotan, R. 2014; 24:253-256
• Revolutionizing volunteer interpreter services: an evaluation of an innovative medical interpreter education program. Journal of general internal medicine Hasbún Avalos, O., Pennington, K., Osterberg, L. 2013; 28 (12): 1589-1595

  Abstract

  In our ever-increasingly multicultural, multilingual society, medical interpreters serve an important role in the provision of care. Though it is known that using untrained interpreters leads to decreased quality of care for limited English proficiency patients, because of a short supply of professionals and a lack of formalized, feasible education programs for volunteers, community health centers and internal medicine practices continue to rely on untrained interpreters.To develop and formally evaluate a novel medical interpreter education program that encompasses major tenets of interpretation, tailored to the needs of volunteer medical interpreters.One-armed, quasi-experimental retro-pre-post study using survey ratings and feedback correlated by assessment scores to determine educational intervention effects.Thirty-eight students; 24 Spanish, nine Mandarin, and five Vietnamese. The majority had prior interpreting experience but no formal medical interpreter training.Students completed retrospective pre-test and post-test surveys measuring confidence in and perceived knowledge of key skills of interpretation. Primary outcome measures were a 10-point Likert scale for survey questions of knowledge, skills, and confidence, written and oral assessments of interpreter skills, and qualitative evidence of newfound knowledge in written reflections.Analyses showed a statistically significant (P <0.001) change of about two points in mean self-ratings on knowledge, skills, and confidence, with large effect sizes (d > 0.8). The second half of the program was also quantitatively and qualitatively shown to be a vital learning experience, resulting in 18 % more students passing the oral assessments; a 19 % increase in mean scores for written assessments; and a newfound understanding of interpreter roles and ways to navigate them.This innovative program was successful in increasing volunteer interpreters' skills and knowledge of interpretation, as well as confidence in own abilities. Additionally, the program effectively taught how to navigate the roles of the interpreter to maintain clear communication.

  View details for DOI 10.1007/s11606-013-2502-5

  View details for PubMedID 23739810

• Adherence to Medications: Insights Arising from Studies on the Unreliable Link Between Prescribed and Actual Drug Dosing Histories ANNUAL REVIEW OF PHARMACOLOGY AND TOXICOLOGY, VOL 52 Blaschke, T. F., Osterberg, L., Vrijens, B., Urquhart, J. 2012; 52: 275-?

  Abstract

  Satisfactory adherence to aptly prescribed medications is essential for good outcomes of patient care and reliable evaluation of competing modes of drug treatment. The measure of satisfactory adherence is a dosing history that includes timely initiation of dosing plus punctual and persistent execution of the dosing regimen throughout the specified duration of treatment. Standardized terminology for initiation, execution, and persistence of drug dosing is essential for clarity of communication and scientific progress. Electronic methods for compiling drug dosing histories are now the recognized standard for quantifying adherence, the parameters of which support model-based, continuous projections of drug actions and concentrations in plasma that are confirmable by intermittent, direct measurements at single time points. The frequency of inadequate adherence is usually underestimated by pre-electronic methods and thus is clinically unrecognized as a frequent cause of failed treatment or underestimated effectiveness. Intermittent lapses in dosing are potential sources of toxicity through hazardous rebound effects or recurrent first-dose effects.

  View details for DOI 10.1146/annurev-pharmtox-011711-113247

  View details for Web of Science ID 000301839600014

  View details for PubMedID 21942628

• Levels of self-reported depression and anxiety among HIV-positive patients in Albania: a cross-sectional study CROATIAN MEDICAL JOURNAL Morrison, S. D., Banushi, V. H., Sarnquist, C., Gashi, V. H., Osterberg, L., Maldonado, Y., Harxhi, A. 2011; 52 (5): 622-628

  Abstract

  To gain an initial perspective of mental health issues facing the Human Immunodeficiency Virus (HIV)-positive population at the University Hospital Center of Tirana (UHCT) HIV/AIDS Ambulatory Clinic.From June-August 2009, we conducted semi-structured interviews with 79 patients (93% response rate) at the UHCT HIV/AIDS Ambulatory Clinic. The interviews assessed patient-reported histories of mental health diagnoses, patients' demographics, and current emotional health status.The percentage of patients who reported a history of diagnosis of depression or anxiety was high - 62.3% and 82.3%, respectively. Factors associated with a history of depression included having been diagnosed with anxiety (P<0.001), having a higher number of barriers to care (P<0.001), having a higher number of current medical and social needs (P<0.001), or having not obtained antiretroviral therapy (ART) abroad (P=0.004). Factors associated with a history of anxiety included having been on first-line ART (P=0.008), having been diagnosed with HIV for shorter periods of time (P=0.043), having been diagnosed with depression (P<0.001), having a higher number of current medical and social needs (P=0.035), or having not obtained ART abroad (P=0.003).Mental health problems are widespread among the known HIV-positive patient population in Albania. The high prevalences of anxiety and depression and of dual diagnoses of these conditions suggest the need for more mental health care for HIV-positive patients in Albania.

  View details for DOI 10.3325/cmj.2011.52.622

  View details for Web of Science ID 000297080000006

  View details for PubMedID 21990080

• BARRIERS TO CARE AND CURRENT MEDICAL AND SOCIAL NEEDS OF HIV-POSITIVE PATIENTS IN ALBANIA CENTRAL EUROPEAN JOURNAL OF PUBLIC HEALTH Morrison, S. D., Banushi, V. H., Sarnquist, C., Gashi, V. H., Osterberg, L., Maldonado, Y., Harxhi, A. 2011; 19 (2): 91-97

  Abstract

  As HIV/AIDS prevalence rises in Eastern Europe, assessment of local epidemics in the bordering Central European region, especially South Eastern Europe, is vital in order to meet treatment and prevention needs. Understanding current medical and social needs and barriers to care experienced by HIV-positive patients in these regions may provide insight into how to best respond to the local epidemics, increase patients' access to treatment, and reduce loss to follow-up.This study assesses the patient characteristics, barriers to care, and current medical and social needs of HIV-positive patients in Albania. Semi-structured interviews were used in this cross-sectional study.We interviewed 79 of 85 patients (93% response rate) followed at the University Hospital Center of Tirana (UHCT) HIV/AIDS Ambulatory Clinic, which represented the majority of patients under HIV care in Albania during 2009.The local HIV epidemic seems to be comprised mainly of heterosexual men who have spent an average of 3.6 years abroad. The vast majority of patients under care at UHCT HIV/AIDS Ambulatory Clinic had experienced barriers to care associated with social stigma (97.4%), lack of knowledge of HIV medical care (76.6%), and medical provider's lack of knowledge of HIV (70.9%). Social needs of the patients were also overwhelmingly unmet (90.0-95.7%).In addressing HIV/AIDS in Albania, it will be crucial to educate the healthcare sector in ways to identify and address barriers to care and current medical and social needs of HIV-positive patients.

  View details for Web of Science ID 000291919600008

  View details for PubMedID 21739899

• Medical Student Wellness: An Essential Role for Mentors. Med Sci Educ 2011; Adams, P. J., Osterberg, L. G., Basaviah, P. 2011; 21(4):382-384
• Understanding Forgiveness: Minding and Mining the Gaps Between Pharmacokinetics and Therapeutics CLINICAL PHARMACOLOGY & THERAPEUTICS Osterberg, L. G., Urquhart, J., Blaschke, T. F. 2010; 88 (4): 457-459

  Abstract

  The usual objective during long-term pharmacotherapy is, in large part, to maintain continuity of action of the prescribed drug(s). Continuity of action arises from the continuity of execution of a prescribed dosing regimen that is pharmacologically sound in dose quantity and interval between successive doses. Interruptions in dosing can interrupt drug action, but the consequences vary according to length of interruption, drug, drug formulation, length of the patient's prior exposure to the drug, and the disease being treated.

  View details for DOI 10.1038/clpt.2010.171

  View details for Web of Science ID 000282064000013

  View details for PubMedID 20856243

• Electronic monitoring of patient adherence to oral antihypertensive medical treatment: a systematic review JOURNAL OF HYPERTENSION Christensen, A., Osterberg, L. G., Hansen, E. H. 2009; 27 (8): 1540-1551

  Abstract

  Poor patient adherence is often the reason for suboptimal blood pressure control. Electronic monitoring is one method of assessing adherence. The aim was to systematically review the literature on electronic monitoring of patient adherence to self-administered oral antihypertensive medications. We searched the Pubmed, Embase, Cinahl and Psychinfo databases and websites of suppliers of electronic monitoring devices. The quality of the studies was assessed according to the quality criteria proposed by Haynes et al. Sixty-two articles were included; three met the criteria proposed by Haynes et al. and nine reported the use of electronic adherence monitoring for feedback interventions. Adherence rates were generally high, whereas average study quality was low with a recent tendency towards improved quality. One study detected investigator fraud based on electronic monitoring data. Use of electronic monitoring of patient adherence according to the quality criteria proposed by Haynes et al. has been rather limited during the past two decades. Electronic monitoring has mainly been used as a measurement tool, but it seems to have the potential to significantly improve blood pressure control as well and should be used more widely.

  View details for DOI 10.1097/HJH.0b013e32832d50ef

  View details for Web of Science ID 000268803900008

  View details for PubMedID 19474761

• Planning services for the homeless in the San Francisco Peninsula JOURNAL OF HEALTH CARE FOR THE POOR AND UNDERSERVED Osterberg, L. G., Barr, D. A. 2007; 18 (4): 749-756

  Abstract

  A survey of clients seeking homeless services at agencies in the SF Peninsula, indicates that a disproportionate percentage are minority group members (African American and Hispanic) and veterans, and points to the need for integrated housing, social services, and health care for this vulnerable population.

  View details for Web of Science ID 000252211100005

  View details for PubMedID 17982204

• Adherence to medication - Reply NEW ENGLAND JOURNAL OF MEDICINE Osterberg, L., Blaschke, T. 2005; 353 (18): 1973-1974

  View details for Web of Science ID 000232972800024

• Drug therapy - Adherence to medication NEW ENGLAND JOURNAL OF MEDICINE Osterberg, L., Blaschke, T. 2005; 353 (5): 487-497

  View details for Web of Science ID 000230939000008

• Missed opportunities for patient education and social worker consultation at the arbor free clinic JOURNAL OF HEALTH CARE FOR THE POOR AND UNDERSERVED Soller, M., Osterberg, L. 2004; 15 (4): 538-546

  Abstract

  We conducted a cross-sectional survey of 210 patients who came to a free medical clinic for health care over an 8-month period. We (1) measured their satisfaction with care, (2) determined the frequency of missed opportunities for providing health education and social work consultation, and (3) assessed whether patient-specific factors drive the frequency of these missed opportunities. Of the 210 patients surveyed, a total of 168 (80.0%) completed the entire survey. The mean satisfaction rating was high (4.6 on a scale of 1 to 5). A significant number of missed opportunities occurred, with only 28% of patients receiving patient education material, and 32% of patients visiting the social worker. No particular patient groups emerged as most susceptible to these missed opportunities. This study shows both the high degree of patient satisfaction at this free clinic and the many opportunities for improving patient education and social services. Adding health education and social work consultation to the patient encounter could improve the health of these patients.

  View details for Web of Science ID 000225119700006

  View details for PubMedID 15531813

• A Web Based Course in Clinical Pharmacology Academic Exchange Quarterly Osterberg LG, Stiller C-O, Tornqvist E, Ayers M, Youngblood P, Bastholm P, Gardner P, Gustafsson LG 2003; 7 (Spring): 29-33
• Comparison of treadmill scores with physician estimates of diagnosis and prognosis in patients with coronary artery disease AMERICAN HEART JOURNAL Lipinski, M., Froelicher, V., Atwood, E., Tseitlin, A., Franklin, B., Osterberg, L., Do, D., Myers, J. 2002; 143 (4): 650-658

  Abstract

  Our purpose was to compare exercise test scores and ST measurements with a physician's estimation of the probability of the presence and severity of angiographic disease and the risk of death. The American College of Cardiology/American Heart Association exercise testing guidelines provide equations to calculate treadmill scores and recommend their use to improve the predictive accuracy of the standard exercise test. However, if physicians can estimate the probability of coronary artery disease and prognosis as well as the scores, there is no reason to add this complexity to test interpretation.A clinical exercise test was performed and an angiographic database was used to print patient summaries and treadmill reports. The clinical/treadmill test reports were sent to expert cardiologists and to 2 other groups, including randomly selected cardiologists and internists. They classified the patients summarized in the reports as having a high, low, or intermediate probability for the presence of any severe angiographic disease and estimated a numerical probability from 0% to 100%. The Social Security Death Index was used to determine survival status of the patients.Twenty-six percent of the patients had severe angiographic disease, and the annual mortality rate for the population was 2%. Forty-five expert cardiologists returned estimates on 473 patients, 37 randomly chosen practicing cardiologists returned estimates on 202 patients, 29 randomly chosen practicing internists returned estimates on 162 patients, 13 academic cardiologists returned estimates on 145 patients, and 27 academic internists returned estimates on 272 patients. When probability estimates for presence and severity of angiographic disease were compared, in general, the treadmill scores were superior to physicians' and ST analysis at predicting severe angiographic disease. When prognosis was estimated, treadmill prognostic scores did as well as expert cardiologists and better than most other physician groups.Estimates of the presence of clinically significant and severe angiographic coronary artery disease provided by scores were superior to physician estimates and ST analysis alone. Estimates of prognosis provided by scores were similar to the estimates made by expert cardiologists and more accurate than the estimates made by most other physician groups.

  View details for DOI 10.1067/mhj.2002.120967

  View details for Web of Science ID 000175352300012

  View details for PubMedID 11923802

• Comparison of exercise test scores and physician estimation in determining disease probability Lipinski, M., Do, D., Froelicher, V., Osterberg, L., Franklin, B., West, J., Atwood, E. AMER MEDICAL ASSOC. 2001: 2239-2244

  Abstract

  The recent American College of Cardiology/American Heart Association exercise testing guidelines provided equations to calculate treadmill scores and recommended their use to improve the predictive accuracy of the standard exercise test. However, if physicians can estimate the probability of coronary artery disease as well as the scores can, there would be no reason to add this complexity to test interpretation. To compare the exercise test scores with physician's estimation of disease probability, we used clinical, exercise test, and coronary angiographic data to compute the recommended scores and print patient summaries and treadmill reports.To determine whether exercise test scores can be as effective as expert cardiologists in diagnosing coronary disease.Five hundred ninety-nine consecutive male patients without previous myocardial infarction with a mean +/- SD age of 59 +/- 11 years were considered for this analysis. With angiographic disease defined as any coronary lumen occlusion of 50% or more, 58% had disease. The clinical/treadmill test reports were sent to expert cardiologists and to 2 other groups, including randomly selected cardiologists and internists, who classified the patients as having high, low, or intermediate probability of disease and estimated a numerical probability from 0% to 100%.Forty-five expert cardiologists returned estimates on 336 patients, 37 randomly chosen practicing cardiologists returned estimates on 129 patients, 29 randomly chosen practicing internists returned estimates on 106 patients, 13 academic cardiologists returned estimates on 102 patients, and 27 academic internists returned estimates on 174 patients. When probability estimates were compared, the scores were superior to all physician groups (0.76 area under the receiver operating characteristic curve to 0.70 for experts [P=.046], 0.73 to 0.58 for cardiologists [P=.003], and 0.76 to 0.61 for internists [P=.006]). Using a probability cut point of greater than 70% for abnormal, predictive accuracy was 69% for scores compared with 64% for experts, 63% to 62% for cardiologists, and 70% to 57% for internists.Although most similar to the disease estimates of the presence of clinically significant angiographic coronary artery disease provided by the expert cardiologists, the scores outperformed the nonexpert physicians.

  View details for Web of Science ID 000171237800009

  View details for PubMedID 11575981

• Images in clinical medicine. Constrictive pericarditis. New England journal of medicine Atwood, J. E., Osterberg, L. 2000; 343 (2): 106-?

  View details for PubMedID 10891518

• Constrictive pericarditis NEW ENGLAND JOURNAL OF MEDICINE Atwood, J. E., Osterberg, L. 2000; 343 (2): 106-106

  View details for Web of Science ID 000088116500005

• Case in point - Discoloration due to "chest pen" HOSPITAL PRACTICE Osterberg, L. 1999; 34 (3): 37-37

  View details for Web of Science ID 000079058300004

  View details for PubMedID 10089925

• Case presentation and review: Constrictive pericarditis WESTERN JOURNAL OF MEDICINE Osterberg, L., Vagelos, R., Atwood, J. E. 1998; 169 (4): 232-239

  View details for Web of Science ID 000076401200015

  View details for PubMedID 9795593

• PULMONARY MELIOIDOSIS CHEST Ip, M., Osterberg, L. G., Chau, P. Y., Raffin, T. A. 1995; 108 (5): 1420-1424

  Abstract

  Melioidosis is the name given to all diseases caused by the bacterium Pseudomonas pseudomallei. Melioidosis is a tropical disease and prevails in parts of Southeast Asia, northern Australia, and Central and South America. However, in recent years, cases of melioidosis have been reported in the United States and other areas. The organism can infect any organ system, although the lung is the most common organ affected. Pulmonary melioidosis presents either as an acute fulminant pneumonia or as an indolent cavitary disease. In northeastern Thailand, the incidence of P pseudomallei infection is extremely high with significant mortality. One of the key problems with treating melioidosis is its recalcitrance to therapy and high relapse rate. In addition, this Gram-negative rod is resistant to aminoglycosides. In nonendemic regions, patients with melioidosis more typically present with reactivation disease occurring months to years after initial exposure to the organism. The pulmonary disease is mainly in the apices and resembles tuberculosis. With the increasing mobility of people throughout the world and the influx of immigrants from endemic to nonendemic areas, it is important that clinicians be aware of this disease. This article will review the epidemiology, clinical presentations, diagnosis, and treatment of pulmonary melioidosis.

  View details for Web of Science ID A1995TD70800046

  View details for PubMedID 7587451

• [Rotavirus diarrhea in a health center and a hospital of Managua, Nicaragua]. Revista cubana de medicina tropical López Cruz, S., Osterberg, L. 1992; 44 (1): 7-11

  Abstract

  Diarrhoea has been considered by WHO as a major problem of morbidity and mortality in children under 5 years. Rotavirus has been reported as one of the main causal agents, although its frequency as causal agent of diarrhoea in Nicaragua is not known. A study was carried out on 206 samples from an equal number of children under 5 years, who presented at a health center and a pediatric hospital in Managua during 9 months in 1987. In order to detect the presence of Rotavirus in faeces, the ELISA technique was used. It was proved that Rotavirus is not a significant cause of diarrhoea in children under 5 years in the places studied.

  View details for PubMedID 1344693

• PURIFICATION OF A PROTEIN HISTIDINE KINASE FROM THE YEAST SACCHAROMYCES-CEREVISIAE - THE 1ST MEMBER OF THIS CLASS OF PROTEIN-KINASES JOURNAL OF BIOLOGICAL CHEMISTRY Huang, J. M., Wei, Y. F., Kim, Y. H., Osterberg, L., Matthews, H. R. 1991; 266 (14): 9023-9031

  Abstract

  An enzyme of molecular weight 32,000 comprising a single subunit has been isolated from whole cell extracts of the yeast Saccharomyces cerevisiae. In vitro, the enzyme transfers the gamma phosphate of ATP to a protein substrate, histone H4, to produce an alkali-stable phosphorylation. Modification of the substrate histidine with diethylpyrocarbonate prevented phosphorylation. Phosphoamino acid analysis of the phosphorylated substrate showed the presence of 1-phosphohistidine. Hence, the isolated enzyme is a protein histidine kinase. A novel assay for acid-labile alkali-stable protein phosphorylation was used in the purification of the kinase activity to a final specific activity of 2,700 nmol/15 min/mg. The purified enzyme phosphorylates specifically histidine 75 in histone H4 and does not phosphorylate histidine 18 nor histidine residues in any other core histone. Steady state kinetic data are consistent with an ordered sequential reaction with Km values for Mg-ATP and histone H4 of 60 and 17 microM, respectively. The protein histidine kinase requires a divalent cation such as Mg2+, Co2+, or Mn2+ but will not use Ca2+, Zn2+, Cu2+, Fe2+, spermine, or spermidine. This is the first purification of an enzyme that catalyzes N-linked phosphorylation in proteins.

  View details for Web of Science ID A1991FM03800057

  View details for PubMedID 2026610