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Michael L Johnson

Publications and source records attributed to Michael L Johnson.

At least 19 recordsLinked to original sources
PubMed2006

Dehydroepiandrosterone secretion in healthy older men and women: effects of testosterone and growth hormone administration in older men.

CONTEXT: Aging is associated with diminished gonadal steroid and GH/IGF-I axis activity; whether these changes contribute to the parallel declines of dehydroepiandrosterone (DHEA) and DHEA sulfate (DHEAS) production is unknown, as are the effects of sex steroid and/or GH administration on DHEA and DHEAS production. OBJECTIVE: Our objective was to evaluate morning DHEAS concentrations and nocturnal DHEA secretory dynamics in healthy older men and women, before and after chronic administration of sex steroid(s) alone, GH alone, sex steroid(s) combined with GH, or placebo alone. DESIGN: We compared nocturnal DHEA secretory dynamics (2000 h to 0800 h, sampling every 20 min, analyzed by multiparameter deconvolution and approximate entropy algorithms) in healthy older (65-88 yr) men (n = 68) and women (n = 36), both before and after 26 wk of administration of sex steroid(s) alone [testosterone (T) in men or estrogen/progesterone in women], GH alone, sex steroid(s) combined with GH, or placebo alone. RESULTS: Morning concentrations of DHEAS were lower; nocturnal DHEA pulsatile production rate, burst frequency, and amplitude were higher; and half-life was shorter in women (P < 0.05). Nocturnal integrated DHEA concentrations, total production rate, and approximate entropy did not differ significantly by sex. Because of small treatment group sizes in women, only hormone intervention results in men are presented. In men, T and T plus GH administration significantly decreased nocturnal integrated DHEA but not morning DHEAS concentrations. GH alone exerted no significant effects on nocturnal DHEA secretion or morning DHEAS. CONCLUSIONS: Spontaneous nocturnal DHEA secretion is sexually dimorphic in healthy older individuals, and T administration decreases nocturnal DHEA secretion in older men. The clinical significance of sex steroid modulation of DHEA secretion in older persons remains to be elucidated.

Aged↗
PubMed2006

Cognitive function and behavior of children with adenotonsillar hypertrophy suspected of having obstructive sleep-disordered breathing.

OBJECTIVE: The purpose of this study was to determine whether risks of impaired cognitive function could be predicted for children or groups of children with adenotonsillar hypertrophy who were suspected of having obstructive sleep-disordered breathing, from historical and polysomnographic variables used separately or in combination. METHODS: We studied 114 consecutive 6- to 12-year-old children with adenotonsillar hypertrophy, who were referred because of suspected obstructive sleep-disordered breathing, with questionnaires, assessment of tonsil size, general and memory cognitive tests, and attended polysomnography with the use of nasal pressure recording to detect flow. RESULTS: There were important significant relationships between snore group (snored every night versus less often), sleep efficiency, and race and 2 of 3 general cognitive tests (vocabulary and similarities). Significant but weaker relationships were observed between sleep latency and 2 memory indices (verbal memory and general memory) and between sleep efficiency and 2 behavior indices (attention-deficit/hyperactivity disorder summary and hyperactive-impulsive summary). The number of episodes of apnea and hypopnea per 1 hour of sleep predicted the vocabulary score as well as did the snore group, but it did not predict other tests as well as other variables. Tonsil size did not predict any cognitive or behavior score. Confidence intervals for group means were small, whereas prediction intervals for individual children were large. CONCLUSIONS: Risk of impaired cognitive function and behavior can be predicted from snoring history, sleep efficiency, sleep latency, and race but not tonsil size. The combination of snoring history and polysomnographic variables predicted impaired cognitive scores better than did either alone. The snoring history predicted more test scores than the number of episodes of apnea and hypopnea per 1 hour of sleep.

Adenoids↗
PubMed2006

Propensity score analysis in observational studies: outcomes after abdominal aortic aneurysm repair.

OBJECTIVE: Large databases composed of well-designed prospectively collected cohort data provide an opportunity to examine and compare healthcare treatments in actual clinical practice settings. Because the analysis of these data often leads to a retrospective cohort design, it is essential to adequately adjust for lack of balance in patient characteristics when making treatment comparisons. We used matched propensity scoring in a cohort of patients undergoing elective aneurysm repair as an illustrative example of this important statistical method that adjusts for baseline characteristics and selection bias by matching covariables. METHODS: By using prospectively collected clinical data from the National Surgical Quality Improvement Program of the Department of Veterans Affairs, we studied 30-day mortality, 1-year survival, and postoperative complications in 1904 patients who underwent elective AAA repair (endovascular aneurysm repair [EVAR], n=717 (37.7%); open aneurysm repair, n=1187 [62.3%]) at 123 Veterans Health Administration's hospitals between May 1, 2001, and September 30, 2003. In bivariate analysis, patient characteristics and operative and hospital variables were associated with both type of surgery and outcomes of surgery. Therefore, the predicted probability of receiving EVAR was tabulated for all patients by using multiple logistic regression to control for 32 independent demographic and clinical characteristics and then stratified into 5 groups. Patients were matched within strata based on similar levels of the independent measures (a propensity score technique), creating a pseudo-randomized control design. The proportion of patients with the morbidity and mortality outcomes was then compared between the EVAR and open procedures within strata to control for selection. RESULTS: Patients undergoing EVAR had significantly lower unadjusted 30-day (3.1% versus 5.6%, P=.01) and 1-year mortality (8.7% versus 12.1%, P=.018) than patients undergoing open repair. By using propensity scoring, the proportions of EVAR patients experiencing 30-day mortality were equal or less than patients undergoing open procedures for all levels of probability and decreased as the probability of EVAR increased. Furthermore, propensity scoring also showed that patients having EVAR had lower 1-year mortality and experienced fewer perioperative complications. CONCLUSIONS: We used a propensity score approach to examine outcomes after elective AAA repair to statistically control for many factors affecting both treatment selection and outcome. Patients who underwent elective EVAR had substantially lower perioperative mortality and morbidity rates compared with patients having open repair, which was not explained solely by patient selection in an observational dataset.

Aged↗
PubMed2006

Open versus endovascular abdominal aortic aneurysm repair in VA hospitals.

BACKGROUND: Endovascular abdominal aortic aneurysm repair (EVAR), when compared with conventional open surgical repair, has been shown to reduce perioperative morbidity and mortality. We performed a retrospective cohort study with prospectively collected data from the Department of Veterans Affairs to examine outcomes after elective aneurysm repair. STUDY DESIGN: We studied 30-day mortality, 1-year survival, and postoperative complications in 1,904 patients who underwent elective abdominal aortic aneurysm repair (EVAR n=717 [37.7%]; open n=1,187 [62.3%]) at 123 Department of Veterans Affairs hospitals between May 1, 2001 and September 30, 2003. We investigated the influence of patient, operative, and hospital variables on outcomes. RESULTS: Patients undergoing EVAR had significantly lower 30-day (3.1% versus 5.6%, p=0.01) and 1- year mortality rates (8.7% versus 12.1%, p=0.018) than patients having open repair. EVAR was associated with a decrease in 30-day postoperative mortality (adjusted odds ratio[OR]=0.59; 95% CI=0.36, 0.99; p=0.04). The risk of perioperative complications was much less after EVAR (15.5% versus 27.7%; p<0.001; unadjusted OR 0.48; 95% CI=0.38, 0.61; p<0.001). Patients operated on at low volume hospitals (25% of entire cohort) were more likely to have had open repair (31.3% compared with 15.9% EVAR; p<0.001) and a nearly two-fold increase in adjusted 30-day mortality risk (OR=1.9; 95% CI=1.19, 2.98; p=0.006). CONCLUSIONS: In routine daily practice, veterans who undergo elective EVAR have substantially lower perioperative mortality and morbidity rates compared with patients having open repair. The benefits of a minimally invasive approach were readily apparent in this cohort, but we recommend using caution in choosing EVAR for all elective abdominal aortic aneurysm repairs until longer-term data on device durability are available.

Aged↗
PubMed2006

Therapeutic goal attainment in patients with hypertension and dyslipidemia.

BACKGROUND: Recent guidelines emphasize the need to assess and treat overall risk for cardiovascular disease through the concomitant management of multiple risk factors. We sought to ascertain treatment patterns and attainment of therapeutic goals in patients with isolated and concomitant hypertension and dyslipidemia, both with and without diabetes mellitus (DM) and symptomatic cardiovascular disease. METHODS: Inception cohorts of more than 41,000 newly diagnosed hypertension and dyslipidemia patients from 6 medical centers of the south-central Veterans Affairs health care system were evaluated. Treatment patterns and goal attainment for low-density lipoprotein cholesterol (LDL-C; Third Report of the National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults guidelines: <160, <130, or <or=100 mg/dL depending on risk factors) and blood pressure (BP; Joint National Committee 6: <140/90 or <130/85 mm Hg depending on risk factors) were measured at 1 year. Separate analyses were conducted in patients with and without DM and symptomatic cardiovascular disease. RESULTS: Treatment rates in patients with and without DM and symptomatic disease ranged from 46.6% to 71.3% in patients with hypertension only, from 31.5% to 64.1% in patients with dyslipidemia only, and from 64.3% to 91.3% in patients with both conditions. Among asymptomatic patients, 40.6% of nondiabetics and 20.6% of patients with DM with isolated hypertension reached BP targets. Attainment of LDL-C goals was slightly higher and reached 52.8% among patients with DM with concomitant hypertension. Among symptomatic patients, attainment of all goals was <40% for all groups. The proportion of asymptomatic patients with concomitant disease reaching goal for both BP and LDL-C was 24.4% among nondiabetics and 15.4% among patients with DM; these proportions decreased to 13.6% and 13.4% respectively, among patients with symptomatic cardiovascular disease. CONCLUSIONS: The majority of patients were receiving pharmacological treatment of hypertension and dyslipidemia, yet attainment of therapeutic goals was generally <50%. Further work is needed to determine factors related to improvement in management and outcomes of patients with multiple cardiovascular risk factors.

Adult↗
PubMed2006

Adapting the Rx-Risk-V for mortality prediction in outpatient populations.

OBJECTIVES: We sought to operationalize, test, and validate an outpatient pharmacy-based case-mix adjuster. METHODS: Outpatients from the Department of Veterans Affairs (VA) prescribed a nonsteroidal anti-inflammatory drug (NSAID) or cyclooxygenase-2 selective drug during 2002 were identified. We updated and extended the Rx-Risk-V by adding 26 additional disease categories and mapping them to VA drug-class codes; derived empirical weights for each from a logistic model of 1-year mortality; adjusted for age, race and sex; and scored the weights into 1 measure of comorbidity. We compared the weighted score to the Deyo diagnosis-based comorbidity index and validated it in a national cohort of 260,321 outpatients with chronic heart failure (CHF). RESULTS: One-year mortality among the 724,270-outpatient NSAID cohort was 1.6% (n = 11,766). Using a baseline model of age, race, and gender (c-index = 0.716), we found that the Deyo measure improved the prediction of mortality (c-index = 0.765), and the pharmacy comorbidity score further improved the prediction (c-index = 0.782), an increase of 25.8%. Using both, we found further improvement (c-index = 0.792). Among the CHF cohort, 9.7% (n = 25,251) died within 1 year. Performance of the baseline model controlling for age, race, and gender (c index = 0.620) improved with addition of the pharmacy comorbidity score (c index = 0.689), compared with the addition of the Deyo measure (c index = 0.651), an increase of 55.1%. Together, they slightly improved prediction in CHF patients (c index = 0.695). CONCLUSIONS: The updated and extended Rx-Risk-V is useful for case-mix adjustment of mortality in an outpatient population.

Aged↗
PubMed2006

Interictal and postictal circadian and ultradian luteinizing hormone secretion in men with temporal lobe epilepsy.

PURPOSE: Hypothalamic regulation of the reproductive axis in temporal lobe epilepsy (TLE), represented by the ultradian pulsatile secretion of luteinizing hormone (LH), has been shown to be altered interictally and postictally. Our objective is to determine if epilepsy or seizures disrupt normal circadian fluctuations of LH as well as circadian organization of ultradian bursts of LH. METHODS: We characterized LH secretion in 10 men with TLE during two 24-h blocks: an interictal epoch and a postictal epoch initiated by a seizure. Serum LH was measured every 10 min and characterized by circadian and ultradian patterns with cosinor and deconvolution analysis. RESULTS: Mean peak serum concentrations of LH occurred at approximately 0400 in controls, were significantly delayed approximately 5 h interictally, and were randomly distributed postictally. Burst amplitudes differed significantly by phase among controls, with the largest amplitudes between 0101 and 0700 and the smallest between 1301 and 1900. No phase differences were present in interictal or postictal epochs. Burst frequency weakly but significantly was slowest between 0101 and 0700 in controls, but did not differ significantly by phase in either interictal or postictal epochs. Postictal LH burst frequencies, but not amplitudes, were significantly decreased immediately postictally. CONCLUSION: The pulsatile secretion of LH in TLE is abnormal both in the circadian as well as the ultradian domain. Interictal effects consist mainly in loss of circadian fluctuations in LH burst amplitude, whereas postictal effects consist of altered burst timing. Altered daily patterns of neuroendocrine signals may underlie other disorders of homeostasis in TLE.

Activity Cycles↗
PubMed2005

An immunogenetic basis for the high prevalence of urogenital cancer in a free-ranging population of California sea lions (Zalophus californianus).

In response to an unprecedented prevalence of cancer recently identified in free-ranging populations of California sea lions [(CSL) (Zalophus californianus], we examined the role of the immunologically important major histocompatibility (MHC) genes in this disease epidemic. Associations between MHC genes and cancer have been well established in humans, but have never before been investigated in wildlife. Using a previously developed technique employing sequence-specific primer-based PCR with intercalating dye technology, MHC genotypes were examined from 27 cancer-positive and 22 cancer-negative CSL stranded along the California coastline. Analyses elucidated an underlying immunogenetic component to the high prevalence of urogenital cancer in sea lions. Furthermore, these results demonstrate the functional relevance of CSL class II MHC by revealing a non-random nature of cancer susceptibility associated with the presence of specific genes.

Animals↗
PubMed2005

National adherence to evidence-based guidelines for the prescription of nonsteroidal anti-inflammatory drugs.

BACKGROUND & AIMS: Our objective was to assess adherence to evidence-based guidelines by providers of the Department of Veterans Affairs nationwide. METHODS: This was a cross-sectional study among veterans prescribed a nonsteroidal anti-inflammatory drug (NSAID) from January 1, 2002, to December 31, 2002. Prescription data were linked to inpatient and outpatient medical records and death files. The population was characterized as high risk based on the following: age 65 years or older, concurrent corticosteroid or anticoagulant use, history of peptic ulcer, and high average daily dose of NSAIDs. Adherence was defined as the prescription of a traditional NSAID with gastroprotection or a coxib in high-risk NSAID users. Univariate and multivariate analyses assessed the potential predictors of adherence. RESULTS: Three hundred three thousand seven hundred eighty-seven met our definition of high risk. Most (97.3%) were male; 55.6% were white, 9.6% black, and 34.8% of other/unknown race. Age 65 years or older was the largest high-risk subset (87.1%). Overall, only 27.2% of high-risk veterans (n = 82,766) were prescribed an adherent strategy. Among veterans with at least 2 risk factors, adherence was 39.7%; among those with 3 risk factors, adherence was 41.8%. Predictors of adherence included history of upper gastrointestinal events, anticoagulant use, rheumatologic disease, high Deyo comorbidity index score, use of low-dose salicylates, and concurrent corticosteroid use. Predictors of nonadherence included prescriptions > or =90 days and high average daily dose of NSAIDs. CONCLUSIONS: Adherence to evidence-based guidelines for safe prescription of NSAIDs in the Department of Veterans Affairs is low (27.2%). The likelihood of adherence is further decreased if veterans are prescribed NSAIDs for > or=90 days.

Aged↗
PubMed2005

Mortality after cardiac bypass surgery: prediction from administrative versus clinical data.

BACKGROUND: Risk-adjusted outcome rates frequently are used to make inferences about hospital quality of care. We calculated risk-adjusted mortality rates in veterans undergoing isolated coronary artery bypass surgery (CABS) from administrative data and from chart-based clinical data and compared the assessment of hospital high and low outlier status for mortality that results from these 2 data sources. STUDY POPULATION: We studied veterans who underwent CABS in 43 VA hospitals between October 1, 1993, and March 30, 1996 (n=15,288). METHODS: To evaluate administrative data, we entered 6 groups of International Classification of Diseases (ICD)-9-CM codes for comorbid diagnoses from the VA Patient Treatment File (PTF) into a logistic regression model predicting postoperative mortality. We also evaluated counts of comorbid ICD-9-CM codes within each group, along with 3 common principal diagnoses, weekend admission or surgery, major procedures associated with CABS, and demographic variables. Data from the VA Continuous Improvement in Cardiac Surgery Program (CICSP) were used to create a separate clinical model predicting postoperative mortality. For each hospital, an observed-to-expected (O/E) ratio of mortality was calculated from (1) the PTF model and (2) the CICSP model. We defined outlier status as an O/E ratio outside of 1.0 (based on the hospital's 90% confidence interval). To improve the statistical and predictive power of the PTF model, selected clinical variables from CICSP were added to it and outlier status reassessed. RESULTS: Significant predictors of postoperative mortality in the PTF model included 1 group of comorbid ICD-9-CM codes, intraortic balloon pump insertion before CABS, angioplasty on the day of or before CABS, weekend surgery, and a principal diagnosis of other forms of ischemic heart disease. The model's c-index was 0.698. As expected, the CICSP model's predictive power was significantly greater than that of the administrative model (c=0.761). The addition of just 2 CICSP variables to the PTF model improved its predictive power (c=0.741). This model identified 5 of 6 high mortality outliers identified by the CICSP model. Additional CICSP variables were statistically significant predictors but did not improve the assessment of high outlier status. CONCLUSIONS: Models using administrative data to predict postoperative mortality can be improved with the addition of a very small number of clinical variables. Limited clinical improvements of administrative data may make it suitable for use in quality improvement efforts.

Cardiopulmonary Bypass↗
PubMed2005

Mortality after noncardiac surgery: prediction from administrative versus clinical data.

BACKGROUND: Hospital profiles are increasingly constructed using risk-adjusted clinical data abstracted from patient records. OBJECTIVE: We sought to compare hospital profiles based on risk adjusted death within 30 days of surgery from administrative versus clinical data in a national cohort of surgical patients. DESIGN: This was a cohort study that included 78,546 major noncardiac operations performed between October 1, 1991 and December 31, 1993 in 44 Veterans Affairs hospitals. Administrative data were used to develop and validate multivariable logistic regression models of 30-day postoperative death for all surgery and 4 surgical specialties (general, orthopedic, thoracic, and vascular). Previously developed and validated clinical models were obtained and reproduced for matching operations using data from the VA National Surgical Quality Improvement Program. Observed-to-expected 30-day mortality ratios for administrative and clinical data were calculated and compared for each hospital. RESULTS: In multivariable logistic regression models using administrative data, characteristics such as patient age, race, marital status, admission from a nursing home, interhospital transfer, admission on the weekend, weekend surgery, and risk strata consisting of groups of principal and comorbidity diagnoses were predictive of postoperative mortality (P <0.05). Correlations of the clinical and administrative observed-to-expected ratios were 0.75, 0.83, 0.64, 0.78, and 0.86 for all surgery, general, orthopedic, thoracic, and vascular surgery, respectively. When compared with clinical models, administrative models identified outlier hospitals with sensitivity of 73%, specificity of 89%, positive predictive value of 51%, and negative predictive value of 96%. CONCLUSIONS: Our data suggest that risk adjustment of mortality using administrative data may be useful for screening hospitals for potential quality problems.

Aged↗
PubMed2005

Prescribing patterns of diuretics in multi-drug antihypertensive regimens.

Recent literature suggests that most hypertensives will require two or more drugs to achieve target blood pressure. Our objective was to estimate the proportion of patients receiving diuretics, including thiazides, for blood pressure control among those receiving two or more drugs. We studied 25,052 hypertensives in a tertiary care Veterans Affairs facility and identified individuals taking any thiazide or loop diuretic among patients receiving two, three, four, or more drugs. Rates of any diuretic use were 50%, 73%, and 89%, and decreased to 39.0%, 59.0%, and 72.5% for thiazide use, respectively. Rates of thiazide use were statistically significantly higher among African Americans compared with the general study population, but did not differ significantly in the elderly. Though overall diuretic use seems to be increasing as compared with previous studies, there is room for improvement in the use of thiazides in multi-drug hypertension regimens.

Aged↗
PubMed2005

Patterns of antihypertensive therapy among patients with diabetes.

BACKGROUND: Hypertension is extremely prevalent in patients with diabetes. Limited data exist on whether patterns of antihypertensive use in this population are consistent with evidence-based practice guidelines. OBJECTIVE: To evaluate utilization patterns of antihypertensive agents and blood pressure (BP) control among diabetic patients with hypertension. DESIGN: Retrospective cohort study. PATIENTS/PARTICIPANTS: In all, 9,975 patients with diabetes and hypertension as of March 2001 from an outpatient medical center of the Department of Veterans Affairs. MEASURES: Proportions of use of 6 different antihypertensive drug classes were compared for all patients receiving 1, 2, 3, or 4 or more drugs, and separately among patients with and without coronary artery disease (CAD). Blood pressure control (<130/85 mmHg) was compared for untreated patients, those on monotherapy, and patients on multi-drug regimens. RESULTS: Over 60% of patients were receiving angiotensin-converting enzyme inhibitors (ACEI) or angiotensin receptor blocker (ARB), followed by diuretics (38.1%), calcium channel blockers (35.3%) and beta-blockers (28.5%) with 19.1% of patients untreated. Patients on monotherapy were mostly receiving ACEI/ARB (59.5%). The majority (70.7%) of treated patients were on multidrug regimens. In patients with CAD, beta-blocker and ACEI/ARB use was higher, and 70.5% of patients on single-drug regimens received either ACEI/ARB or beta-blockers. The proportions of patients not on medications, on monotherapy, or multidrug regimens achieving BP control were 23.4%, 27.4%, and 24.9%, respectively. CONCLUSIONS: Patterns of anti-hypertensive therapy were generally consistent with evidence-based practice guidelines. Areas of improvement include increasing ACEI/ARB and diuretic use, decreasing the number of untreated patients, and increasing the proportion of patients with controlled BP in this population.

Aged↗
PubMed2004

Nocturnal ghrelin pulsatility and response to growth hormone secretagogues in healthy men.

The physiological importance of endogenous ghrelin in the regulation of growth hormone (GH) secretion is still unknown. To investigate the regulation of ghrelin secretion and pulsatility, we performed overnight ghrelin and GH sampling every 20 min for 12 h in eight healthy male subjects [age 37 +/- 5 (SD) years old, body mass index 27.2 +/- 2.9 kg/m2]. Simultaneous GH and ghrelin levels were assessed to determine the relatedness and synchronicity between these two hormones in the fasted state during the overnight period of maximal endogenous GH secretion. Pulsatility analyses were performed to determine simultaneous hormonal dynamics and investigate the relationship between GH and ghrelin by use of cross-approximate entropy (X-ApEn) analyses. Subjects demonstrated 3.0 +/- 2.1 ghrelin pulses/12 h and 3.3 +/- 0.9 GH pulses/12 h. The mean normalized ghrelin entropy (ApEn) was 0.93 +/- 0.09, indicating regularity in ghrelin hormone secretion. The mean normalized X-ApEn was significant between ghrelin and GH (0.89 +/- 0.12), demonstrating regularity in cosecretion. In addition, we investigated the ghrelin response to standard GH secretagogues [GH-releasing hormone (GHRH) alone and combined GHRH-arginine] in separate testing sequences separated by 1 wk. Our data demonstrate that, in contrast to GHRH alone, which had little effect on ghrelin, combined GHRH and arginine significantly stimulated ghrelin with a maximal peak at 120 min, representing a change of 66 +/- 14 pg/ml (P = 0.001 by repeated-measures ANOVA and P = 0.02 for GHRH vs. combined GHRH-arginine by MANOVA). We demonstrate relatedness between ghrelin and GH pulsatility, suggesting either that ghrelin participates in the pulsatile regulation of GH or that the two hormones are simultaneously coregulated, e.g., by somatostatin or other stimuli. Furthermore, the differential effects of GHRH alone vs. GHRH-arginine suggest that inhibition of somatostatin tone may increase ghrelin. These data provide further evidence of the physiological regulation of ghrelin in relationship to GH.

Adult↗
PubMed2004

Class II multiformity generated by variable MHC- DRB region configurations in the California sea lion ( Zalophus californianus).

In light of the immunological importance of molecules encoded within the major histocompatibility complex ( MHC), there are numerous studies examining the variability of these genes in wildlife populations. An underlying assumption in many of these studies is that MHC diversity invariably arises from a high level of allelic variation at a single gene locus, leading to widespread descriptions of thriving species with apparently limited MHC polymorphism. Indeed, in a previous study we failed to find sequence features compatible with traditionally diverse peptide-binding functions in MHC class II ( DQA and DQB) genes in California sea lions and therefore expanded the search for polymorphism to the DRA and DRB genes. Our results show that, in contrast to Zaca-DQA, -DQB, and - DRA, Zaca-DRB has sequence features compatible with antigen binding and presentation. In fact Zaca-DRB constitutes a gene family, comprising at least seven loci, each of which exhibits limited variability, and which are present in variable configurations between individuals. This unusual mechanism for generating MHC DRB diversity is similar to that observed in the rhesus macaque, but has not been reported in any other species. The identification of a novel system of class II MHC variability in the California sea lion justifies new studies into the organizational basis of immunogenetic diversity in other marine species, and its role in infectious disease susceptibility.

Animals↗
PubMed2004

Spinning with Dave: David Yphantis's contributions to ultracentrifugation.

For nearly 50 years David Yphantis has helped advance analytical ultracentrifugation, promoted rigor in the thermodynamic analysis of biochemical data and encouraged students and colleagues to look for the deepest possible understanding of science. This article, written by five of Dave's students, presents some of the impressions he has made over the years.

Biochemistry↗