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At least 973 records · Page 54Linked to original sources

PubMed2006

Development of a pharmacokinetic/pharmacodynamic model for carvedilol to predict beta1-blockade in patients with congestive heart failure.

To determine whether the controlled-release (CR) formulation of carvedilol given once daily provides 24-hour beta1-receptor blockade similar to the currently marketed immediate-release (IR) formulation given twice daily, changes in exercise-induced heart rate after bicycle ergometry were measured. The pharmacokinetic (PK)/pharmacodynamic (PD) relation between S(-)-carvedilol concentration-the enantiomer with beta-blocking activity-and change in exercise-induced heart rate was defined in healthy subjects and was best described using a direct effect inhibitory E(max) model (with E(max) being the maximum effect). The population estimates for E(max) and concentration at 50% of the maximum effect (EC50) were 19.2 beats per minute (an approximately 13% maximum decrease in exercise-induced heart rate) and 7.7 ng/mL, respectively. The PK/PD model was used to predict PD effects in patients with mild-to-severe heart failure and in patients after myocardial infarction with left ventricular dysfunction who had received both the IR and CR formulations of carvedilol. In these patients, carvedilol CR had equivalent predicted overall PD (area under the effect curve) and trough (PD(min)) effects compared with carvedilol IR, indicating 24-hour beta-blocking coverage for the new CR formulation of carvedilol given once daily.

Administration, Oral↗

PubMed1997

Estimated benefits of glycemic control in microvascular complications in type 2 diabetes.

BACKGROUND: The benefits of intensive glycemic control in patients with type 2 diabetes are not well quantified. It is therefore not clear which patients will benefit most from aggressive glycemic control. OBJECTIVE: To evaluate the efficacy of glycemic control in type 2 diabetes. DESIGN: Markov decision model. PATIENTS: Diabetic patients at a health maintenance organization. MAIN OUTCOME MEASURES: Risks for developing blindness and end-stage renal disease; number of patients and patient-years needed to treat to prevent complications. RESULTS: For a patient in whom diabetes developed before 50 years of age, reducing hemoglobin A1c levels from 9% to 7% results in an estimated 2.3-percentage point decrease (from 2.6% to 0.3%) in lifetime risk for blindness due to retinopathy. The same change in a patient with diabetes onset at 65 years of age would be expected to decrease the risk for blindness by 0.5 percentage points (from 0.5% to < 0.1%). However, the Markov model predicts substantially greater benefit when moving from poor to moderate glycemic control than when moving from moderate to almost-normal glycemic control. Targeting less than 20% of the patients at one health maintenance organization for intensified therapy may prevent more than 80% of the preventable patient-time spent blind. The risks for end-stage renal disease and the risk reduction provided by improved glycemic control are lower than those for blindness. CONCLUSIONS: This probability model, based on extrapolation from the experience with type 1 diabetes, suggests that patients with early onset of type 2 diabetes will accrue substantial benefit from almost-normal glycemic control. In patients with later onset, moderate glycemic control prevents most end-stage complications caused by microvascular disease. These results have important implications for informing patients and allocating health care resources.

Adult↗

PubMed2002

Comparison of striatal dopamine D2 receptors in Parkinson's disease and progressive supranuclear palsy patients using [123I] iodobenzofuran single-photon emission computed tomography.

BACKGROUND AND PURPOSE: To investigate the clinical applicability and validity of [123I] iodobenzofuran (IBF) single-photon emission computed tomography (SPECT), the authors analyzed the changes in striatal dopamine D2 receptor binding among 7 patients with Parkinson's disease (PD), 6 patients with progressive supranuclear palsy (PSP) (Hoehn and Yahr stage II to IV), and 8 normal controls. METHODS: SPECT data were acquired every 1 minute for 60 minutes postinjection of 167 MBq [123I] IBF. The binding potential (BP) of the striatum was evaluated by 2 methods: region-of-interest (ROI) analysis by the nonlinear least squares method using blood sampling and time-series brain radioactivities in normal controls and a voxel-by-voxel method based on a region model that provided parametric images of BP without blood sampling. RESULTS: Statistical parametric mapping indicated that BP in the striatum of PSP patients was significantly lower than that of PD patients and normal controls (P < .005, uncorrected), and there was no significant difference between PD patients and normal controls, even in patients with PD at an advanced stage. Data derived from the ROI method and a simplified reference region model showed good correlations in normal controls, indicating the validity of the latter model. CONCLUSIONS: The results predict that [123I] IBF SPECT, especially voxel-by-voxel BP parametric imaging, can discriminate among extrapyramidal diseases such as PD and PSP and may be applicable for clinical use.

Adult↗

PubMed1991

Follicular size at the time of human chorionic gonadotropin administration predicts ovulation outcome in human menopausal gonadotropin-stimulated cycles.

OBJECTIVE: The objectives of this study were: (1) to correlate follicle size by transvaginal sonography with ovulation outcome in cycles of controlled ovarian hyperstimulation with human menopausal gonadotropins; (2) to determine if follicular size on the day of human chorionic gonadotropin (hCG) administration predicts the incidence of ovulation; and, if so, (3) to derive a mathematical model that predicts the number of expected ovulations in any given cycle of controlled ovarian hyperstimulation. DESIGN: A retrospective analysis. PARTICIPANTS: Forty-nine consecutive patients undergoing 122 cycles of controlled ovarian hyperstimulation were studied in a tertiary care setting. MAIN OUTCOME MEASURES: Follicular size and evidence of ovulation were determined sonographically. The main outcome measure was the rate of ovulation per follicle size. RESULTS: The percentages of follicles measuring less than or equal to 14 mm, 15 to 16 mm, 17 to 18 mm, 19 to 20 mm, and greater than 20 mm on the day of hCG administration that subsequently ovulated were 0.5%, 37.4%, 72.5%, 81.2%, and 95.5%, respectively. CONCLUSIONS: (1) Follicular size on the day of hCG administration correlates with the incidence of ovulation. (2) The expected number of ovulations in any given controlled ovarian hyperstimulation cycle can be predicted with 95% confidence using the accompanying equation.

Chorionic Gonadotropin↗

PubMed2006

Radiation-induced leukemia at doses relevant to radiation therapy: modeling mechanisms and estimating risks.

BACKGROUND: Because many cancer patients are diagnosed earlier and live longer than in the past, second cancers induced by radiation therapy have become a clinically significant issue. An earlier biologically based model that was designed to estimate risks of high-dose radiation-induced solid cancers included initiation of stem cells to a premalignant state, inactivation of stem cells at high radiation doses, and proliferation of stem cells during cellular repopulation after inactivation. This earlier model predicted the risks of solid tumors induced by radiation therapy but overestimated the corresponding leukemia risks. METHODS: To extend the model to radiation-induced leukemias, we analyzed--in addition to cellular initiation, inactivation, and proliferation--a repopulation mechanism specific to the hematopoietic system: long-range migration through the blood stream of hematopoietic stem cells (HSCs) from distant locations. Parameters for the model were derived from HSC biologic data in the literature and from leukemia risks among atomic bomb survivors who were subjected to much lower radiation doses. RESULTS: Proliferating HSCs that migrate from sites distant from the high-dose region include few preleukemic HSCs, thus decreasing the high-dose leukemia risk. The extended model for leukemia provides risk estimates that are consistent with epidemiologic data for leukemia risk associated with radiation therapy over a wide dose range. For example, when applied to an earlier case-control study of 110,000 women undergoing radiotherapy for uterine cancer, the model predicted an excess relative risk (ERR) of 1.9 for leukemia among women who received a large inhomogeneous fractionated external beam dose to the bone marrow (mean = 14.9 Gy), consistent with the measured ERR (2.0, 95% confidence interval [CI] = 0.2 to 6.4; from 3.6 cases expected and 11 cases observed). As a corresponding example for brachytherapy, the predicted ERR of 0.80 among women who received an inhomogeneous low-dose-rate dose to the bone marrow (mean = 2.5 Gy) was consistent with the measured ERR (0.62, 95% CI = -0.2 to 1.9). CONCLUSIONS: An extended, biologically based model for leukemia that includes HSC initiation, inactivation, proliferation, and, uniquely for leukemia, long-range HSC migration predicts, with reasonable accuracy, risks for radiation-induced leukemia associated with exposure to therapeutic doses of radiation.

Adult↗

PubMed2001

Personal models of diabetes in relation to self-care, well-being, and glycemic control. A prospective study in adolescence.

OBJECTIVE: Personal models of diabetes have been shown to be proximal determinants of self-care behavior in adults with diabetes, both cross-sectionally and prospectively. This study set out to test the predictive utility of this approach in adolescents with diabetes. RESEARCH DESIGN AND METHODS: Participants were recruited from four regional hospitals in southern England (n = 54). They completed questionnaires assessing diabetes self-care, well-being, and personal models of diabetes (perceived impact, perceived seriousness, and short- and long-term treatment effectiveness) at baseline and 1-year follow-up. GHb assays performed as part of the patients' usual diabetes care were used to assess glycemic control. RESULTS: After controlling for baseline anxiety, change in perceived impact of diabetes prospectively predicted adolescents' anxiety (beta = -0.21; t = -2.65; P < 0.01). After controlling for baseline dietary self-care, change in perceived effectiveness of the diabetes treatment regimen to control diabetes predicted dietary self-care (beta = -0.39; t = -3.28; P < 0.0005). Poorer dietary self-care and being female were predictive of poorer glycemic control (r2 = 0.29; F = 2.74; P < 0.005). CONCLUSIONS: This study provides further support for the role of personal models of illness in determining responses to illness. As adolescents take responsibility for the management of their diabetes, parents, clinicians, educators, and interventionists should consider these adolescents' beliefs about their diabetes and its treatment as key factors influencing self-care, emotional well-being. and glycemic control.

Adolescent↗

PubMed1993

A role for computer simulation in solving the riddles of autoreceptor-mediated regulation of GABA release.

The autoreceptor-mediated control of GABA release was simulated on a personal computer using commercially available software (STELLA/ITHINK). The experimental data to be matched were taken from previous publications. A basic model was able to fairly accurately reproduce frequency dependencies of GABA release in the presence and absence of uptake inhibition as well as concentration-response curves for changes in release produced by the agonist, (-)-baclofen, or by relatively low concentrations of the antagonists, phaclofen and CGP 35348. Obvious mismatch was observed at high concentrations of a potent antagonist, at a stimulation frequency of 2 Hz. Whereas the experimental data indicate a 3-fold increase in release as compared to controls, simulation predicts a 7-fold increase. By adaptation of the model, simulation data were obtained indicating that this mismatch was not due to (a) the autoreceptor occurring as two subtypes with different affinities for antagonists, (b) the occurrence of an agonist and antagonist state of the autoreceptor, with the latter prevailing at low synaptic concentrations of endogenous GABA, and (c) overruling of uptake inhibition by markedly elevated synaptic GABA concentrations. On the other hand, a simple restriction of the amount of transmitter able to be released per time unit produced much better matching data. A refined model assuming a restricted replacement capacity for exocytotically emptied synaptic vesicles at their docking sites gave similar results. As a consequence, we shall attempt to address this possibility experimentally. Simulation can never prove a case in the positive sense. It can, however, help to exclude ill-matching solutions of a problem and to prioritize among possible ones, which then must be experimentally addressed. We found simulation with this user-friendly software extraordinarily useful, also and not least because it necessitates and stimulates very intense dealing with a subject.

Animals↗

PubMed2001

The foot-and-mouth epidemic in Great Britain: pattern of spread and impact of interventions.

We present an analysis of the current foot-and-mouth disease epidemic in Great Britain over the first 2 months of the spread of the virus. The net transmission potential of the pathogen and the increasing impact of control measures are estimated over the course of the epidemic to date. These results are used to parameterize a mathematical model of disease transmission that captures the differing spatial contact patterns between farms before and after the imposition of movement restrictions. The model is used to make predictions of future incidence and to simulate the impact of additional control strategies. Hastening the slaughter of animals with suspected infection is predicted to slow the epidemic, but more drastic action, such as "ring" culling or vaccination around infection foci, is necessary for more rapid control. Culling is predicted to be more effective than vaccination.

Animals↗

PubMed2004

A tracer kinetic model for 18F-FHBG for quantitating herpes simplex virus type 1 thymidine kinase reporter gene expression in living animals using PET.

UNLABELLED: Reporter probe 9-(4-18F-fluoro-3-[hydroxymethyl]butyl)guanine (18F-FHBG) and reporter gene mutant herpes simplex virus type 1 thymidine kinase (HSV1-sr39tk) have been used for imaging reporter gene expression with PET. Current methods for quantitating the images using the percentage injected dose per gram of tissue do not distinguish between the effects of probe transport and subsequent phosphorylation. We therefore investigated tracer kinetic models for 18F-FHBG dynamic microPET data and noninvasive methods for determining blood time-activity curves in an adenoviral gene delivery model in mice. METHODS: 18F-FHBG (approximately 7.4 MBq [approximately 200 microCi]) was injected into 4 mice; 18F-FHBG concentrations in plasma and whole blood were measured from mouse heart left ventricle (LV) direct sampling. Replication-incompetent adenovirus (0-2 x 10(9) plaque-forming units) with the E1 region deleted (n = 8) or replaced by HSV1-sr39tk (n = 18) was tail-vein injected into mice. Mice were dynamically scanned using microPET (approximately 7.4 MBq [approximately 200 microCi] 18F-FHBG) over 1 h; regions of interest were drawn on images of the heart and liver. Serial whole blood 18F-FHBG concentrations were measured in 6 of the mice by LV sampling, and 1 least-squares ratio of the heart image to the LV time-activity curve was calculated for all 6 mice. For 2 control mice and 9 mice expressing HSV1-sr39tk, heart image (input function) and liver image time-activity curves (tissue curves) were fit to 2- and 3-compartment models using Levenberg-Marquardt nonlinear regression. The models were compared using an F statistic. HSV1-sr39TK enzyme activity was determined from liver samples and compared with model parameter estimates. For another 3 control mice and 6 HSV1-sr39TK-positive mice, the model-predicted relative percentage of metabolites was compared with high-performance liquid chromatography analysis. RESULTS: The ratio of 18F-FHBG in plasma to whole blood was 0.84 +/- 0.05 (mean +/- SE) by 30 s after injection. The least-squares ratio of the heart image time-activity curve to the LV time-activity curve was 0.83 +/- 0.02, consistent with the recovery coefficient for the partial-volume effect (0.81) based on independent measures of heart geometry. A 3-compartment model best described 18F-FHBG kinetics in mice expressing HSV1-sr39tk in the liver; a 2-compartment model best described the kinetics in control mice. The 3-compartment model parameter, k3, correlated well with the HSV1-sr39TK enzyme activity (r2 = 0.88). CONCLUSION: 18F-FHBG equilibrates rapidly between plasma and whole blood in mice. Heart image time-activity curves corrected for partial-volume effects well approximate LV time-activity curves and can be used as input functions for 2- and 3-compartment models. The model parameter k3 from the 3-compartment model can be used as a noninvasive estimate for HSV1-sr39TK reporter protein activity and can predict the relative percentage of metabolites.

Animals↗

PubMed1988

Modeling the neurological control of human movements.

Although computer models have been extensively used in recent years to understand the way physical systems operate and interact, the enormous power of mathematical modeling and computer simulations has been difficult to implement for the benefit of neuroscientists studying the human motor control system. Nevertheless, homeomorphic models are now being used to explain and predict the neural and biomechanical aspects of different human movements. This paper argues for the importance of regarding model simulations as a supplementary approach to traditional methods of experimental investigation by drawing examples from both the experimental and the modeling literature. The discussion focuses on studies of the triphasic control signal for fast, goal-directed movements and on aspects of sampled data control for slow, tracking movements. The aim of this viewpoint article is to promote a more widespread use of modeling and simulation in the field of motor control.

Journal Article↗

PubMed2003

Sniffers, buzzers, toggles and blinkers: dynamics of regulatory and signaling pathways in the cell.

The physiological responses of cells to external and internal stimuli are governed by genes and proteins interacting in complex networks whose dynamical properties are impossible to understand by intuitive reasoning alone. Recent advances by theoretical biologists have demonstrated that molecular regulatory networks can be accurately modeled in mathematical terms. These models shed light on the design principles of biological control systems and make predictions that have been verified experimentally.

Animals↗

PubMed2002

Hysteresis drives cell-cycle transitions in Xenopus laevis egg extracts.

Cells progressing through the cell cycle must commit irreversibly to mitosis without slipping back to interphase before properly segregating their chromosomes. A mathematical model of cell-cycle progression in cell-free egg extracts from frog predicts that irreversible transitions into and out of mitosis are driven by hysteresis in the molecular control system. Hysteresis refers to toggle-like switching behavior in a dynamical system. In the mathematical model, the toggle switch is created by positive feedback in the phosphorylation reactions controlling the activity of Cdc2, a protein kinase bound to its regulatory subunit, cyclin B. To determine whether hysteresis underlies entry into and exit from mitosis in cell-free egg extracts, we tested three predictions of the Novak-Tyson model. (i) The minimal concentration of cyclin B necessary to drive an interphase extract into mitosis is distinctly higher than the minimal concentration necessary to hold a mitotic extract in mitosis, evidence for hysteresis. (ii) Unreplicated DNA elevates the cyclin threshold for Cdc2 activation, indication that checkpoints operate by enlarging the hysteresis loop. (iii) A dramatic "slowing down" in the rate of Cdc2 activation is detected at concentrations of cyclin B marginally above the activation threshold. All three predictions were validated. These observations confirm hysteresis as the driving force for cell-cycle transitions into and out of mitosis.

Animals↗

PubMed2002

A case study of logistic QSAR modeling methods and robustness tests.

Acute toxicity (15-min EC(50)) determination of 16 substituted naphthalene compounds to Photobacterium phosphoreum was undertaken according to the standard procedures, while the effects of molecular structures of selected compounds on their toxicity to test microorganisms were logistically conducted using the quantitative structure-activity relationship (QSAR) technique. The relationship was developed as -log EC(50)=5.5916 (+/-0.1189)-7.4893(+/-0.4900)qH(+)+0.7771(+/-0.0619E(lumo)+0.0088(+/-0.0009)alpha(N=16, R(2)(adj)=0.9698, SE=0.0892, P=0.0000). The cluster analyses of individual structure descriptors as well as the quality control chart and Monte Carlo simulation test indicated that the prediction model was reasonable and robust even if tested with several different methods. Furthermore, the quantum chemical parameters entering into the QSAR model were used to discuss the possible toxicity pathways, and the results revealed that the selected compounds were reactive and their toxicity behaviors were complex processes containing physical partition stages as well as biochemical reaction stages.

Lethal Dose 50↗

PubMed2001

Development of a real-time control strategy with artificial neural network for automatic control of a continuous-flow sequencing batch reactor.

The purpose of this study is to develop a reliable and effective real-time control strategy by integrating artificial neural network (ANN) process models to perform automatic operation of a dynamic continuous-flow SBR system. The ANN process models, including ORP/pH simulation models and water quality ([NH4(+)-N] and [NOx(-)-N]) prediction models, can assist in real-time searching the ORP and pH control points and evaluating the operation performances of aerobic nitrification and anoxic denitrification operation phases. Since the major biological nitrogen removal mechanisms were controlled at nitrification (NH4(+)-N-->NO2(-)-N) and denitritification (NO2(-)-N-->N2) stages, as well as the phosphorus uptake and release could be completely controlled during aerobic and anoxic operation phases, the system operation performances under this ANN real-time control system revealed that both the aeration time and overall hydraulic retention time could be shortened to about 1.9-2.5 and 4.8-6.2 hrs/cycle respectively. The removal efficiencies of COD, ammonia nitrogen, total nitrogen, and phosphate were 98%, 98%, 97%, and 84% respectively, which were more effective and efficient than under conventional fixed-time control approach.

Ammonia↗

PubMed2003

Quantifying generalization from trial-by-trial behavior of adaptive systems that learn with basis functions: theory and experiments in human motor control.

During reaching movements, the brain's internal models map desired limb motion into predicted forces. When the forces in the task change, these models adapt. Adaptation is guided by generalization: errors in one movement influence prediction in other types of movement. If the mapping is accomplished with population coding, combining basis elements that encode different regions of movement space, then generalization can reveal the encoding of the basis elements. We present a theory that relates encoding to generalization using trial-by-trial changes in behavior during adaptation. We consider adaptation during reaching movements in various velocity-dependent force fields and quantify how errors generalize across direction. We find that the measurement of error is critical to the theory. A typical assumption in motor control is that error is the difference between a current trajectory and a desired trajectory (DJ) that does not change during adaptation. Under this assumption, in all force fields that we examined, including one in which force randomly changes from trial to trial, we found a bimodal generalization pattern, perhaps reflecting basis elements that encode direction bimodally. If the DJ was allowed to vary, bimodality was reduced or eliminated, but the generalization function accounted for nearly twice as much variance. We suggest, therefore, that basis elements representing the internal model of dynamics are sensitive to limb velocity with bimodal tuning; however, it is also possible that during adaptation the error metric itself adapts, which affects the implied shape of the basis elements.

Adaptation, Physiological↗

PubMed1998

Adaptive pole placement control algorithm for DO-control in beta-lactamase production.

The dissolved oxygen (DO) is an important variable in aerobic fermentations and affects the cell growth and product formation. Dissolved oxygen control is difficult in batch fermentations because of the time-varying conditions, time delays, and the probe dynamics. Modeling of the various patterns of biological activity in fermentations and their impact on the DO process dynamics is essential to both achieve a satisfactory control and to track the aforementioned patterns. An adaptive pole placement algorithm with time-delay compensation was used for controlling the DO, coupled with system identification using recursively estimated autoregressive models with exogeneous inputs (ARX). The flow rate of O2 in a constant flow rate gas inlet mixture is used as the manipulated variable. Supervision and coordination techniques are applied to improve the control performance. The control performance is affected by the accuracy of the model prediction and the selected time delay. The effect of DO level on the productivity of beta-lactamase using Bacillus subtilis under oxygen-limited conditions is investigated. Beta-lactamase stability is improved under prolonged growth conditions with low DO levels.

Aerobiosis↗

PubMed2000

Experimental observation, theoretical models, and biomechanical inference in the study of mandibular form.

Experimental studies and mathematical models are disparate approaches for inferring the stress and strain environment in mammalian jaws. Experimental designs offer accurate, although limited, characterization of biomechanical behavior, while mathematical approaches (finite element modeling in particular) offer unparalleled precision in depiction of strain magnitudes, directions, and gradients throughout the mandible. Because the empirical (experimental) and theoretical (mathematical) perspectives differ in their initial assumptions and their proximate goals, the two methods can yield divergent conclusions about how masticatory stresses are distributed in the dentary. These different sources of inference may, therefore, tangibly influence subsequent biological interpretation. In vitro observation of bone strain in primate mandibles under controlled loading conditions offers a test of finite element model predictions. Two issues which have been addressed by both finite element models and experimental approaches are: (1) the distribution of torsional shear strains in anthropoid jaws and (2) the dissipation of bite forces in the human alveolar process. Not surprisingly, the experimental data and mathematical models agree on some issues, but on others exhibit discordance. Achieving congruence between these methods is critical if the nature of the relationship of masticatory stress to mandibular form is to be intelligently assessed. A case study of functional/mechanical significance of gnathic morphology in the hominid genus Paranthropus offers insight into the potential benefit of combining theoretical and experimental approaches. Certain finite element analyses claim to have identified a biomechanical problem unrecognized in previous comparative work, which, in essence, is that the enlarged transverse dimensions of the postcanine corpus may have a less important role in resisting torsional stresses than previously thought. Experimental data have identified subperiosteal cortical thinning as a culprit in diminishing the role of cross-sectional geometry in conditioning the strain environment. These observations raise questions concerning the biomechanical significance of mandibular form in early hominids, fueling persistent arguments over whether gnathic morphology can be related to dietary specialization in the "robust" australopithecines. Nonmechanical explanations (e.g., tooth size or body size) for Paranthropus mandibular dimensions, however, are not compelling as competing hypotheses. Both theoretical and experimental models are in need of refinement before it is possible to conclude that the jaws of the "robust" australopithecines are not functionally linked to elevated masticatory loads.

Animals↗

PubMed1999

No support for HLA-DQ encoded susceptibility in rheumatoid arthritis.

OBJECTIVE: To test predictions based on data from immunogenetic and peptide-binding studies of collagen-induced arthritis in mice, in which it has been suggested that susceptibility to rheumatoid arthritis (RA) might be determined by the interaction between susceptibility alleles at the HLA-DQ locus and protective alleles at the HLA-DRB1 locus (including susceptibility effects for HLA-DQ7 and DQ8). METHODS: Predictions based on these models were tested in 166 healthy controls and 167 patients with RA, all of whom were typed for HLA-DRB1 and HLA-DQ alleles. RESULTS: In this population, HLA-DQ7 did not encode an increased risk for RA. This lack of susceptibility effect of HLA-DQ7 could not be attributed to competing HLA-DQ susceptibility alleles, protective HLA-DRB1 alleles, or the absence of DQA1*0301. CONCLUSION: These observations do not support the DR/DQ hypothesis in its present form.

Alleles↗