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A new approach to defining functional ability in ankylosing spondylitis: the development of the Bath Ankylosing Spondylitis Functional Index.

OBJECTIVE: After pain and stiffness, one of the most important complaints of patients with ankylosing spondylitis (AS) is disability. The main aims of treatment are to control pain but also to improve function. Various methods of assessing function exist but are either not specific for the disease or have not been adequately validated. As a result of this deficiency we developed the Bath Ankylosing Spondylitis Functional Index (BASFI) as a new approach to defining and monitoring functional ability in patients with AS. METHODS: This self-assessment instrument was designed by a team of medical professionals in conjunction with patients, and consists of 8 specific questions regarding function in AS and 2 questions reflecting the patient's ability to cope with everyday life. Each question is answered on a 10 cm horizontal visual analog scale, the mean of which gives the BASFI score (0-10). The questionnaire was completed 257 times in total: once by 116 outpatients and by 47 inpatients on 3 occasions over a 3-week intensive physiotherapy course. In addition, the instrument was compared with the Dougados functional index. RESULTS: Patients scores covered 95% of the BASFI range, giving a normal distribution of results. In contrast only 65% of the Dougados functional index scale was used. Furthermore, over the 3 week period of inpatient treatment, the BASFI revealed a significant improvement in function (20%, p = 0.004) while there was a less impressive change in the Dougados functional index (6%, p = 0.03). This demonstrates the superior sensitivity of the BASFI: Consistency was good for both indices (p < 0.001), as was the relationship between patient perception of function and function as assessed by an external observer (p < 0.001). CONCLUSION: The BASFI satisfies the criteria required of a functional index: it is quick and easy to complete, is reliable and is sensitive to change across the whole spectrum of disease.

Activities of Daily Living↗

Does parallel item content on WOMAC's pain and function subscales limit its ability to detect change in functional status?

BACKGROUND: Although the Western Ontario and McMaster University Osteoarthritis Index (WOMAC) is considered the leading outcome measure for patients with osteoarthritis of the lower extremity, recent work has challenged its factorial validity and the physical function subscale's ability to detect valid change when pain and function display different profiles of change. This study examined the etiology of the WOMAC's physical function subscale's limited ability to detect change in the presence of discordant changes for pain and function. We hypothesized that the duplication of some items on the WOMAC's pain and function subscales contributed to this shortcoming. METHODS: Two eight-item physical function scales were abstracted from the WOMAC's 17-item physical function subscale: one contained activities and themes that were duplicated on the pain subscale (SIMILAR-8); the other version avoided overlapping activities (DISSIMILAR-8). Factorial validity of the shortened measures was assessed on 310 patients awaiting hip or knee arthroplasty. The shortened measures' abilities to detect change were examined on a sample of 104 patients following primary hip or knee arthroplasty. The WOMAC and three performance measures that included activity specific pain assessments--40 m walk test, stair test, and timed-up-and-go test--were administered preoperatively, within 16 days of hip or knee arthroplasty, and at an interval of greater than 20 days following the first post-surgical assessment. Standardized response means were used to quantify change. RESULTS: The SIMILAR-8 did not demonstrate factorial validity; however, the factorial structure of the DISSIMILAR-8 was supported. The time to complete the performance measures more than doubled between the preoperative and first postoperative assessments supporting the theory that lower extremity functional status diminished over this interval. The DISSIMILAR-8 detected this deterioration in functional status; however, no significant change was noted for the SIMILAR-8. The WOMAC pain scale demonstrated a slight reduction in pain and the performance specific pain measures did not reflect a change in pain. All measures showed substantial improvement over the second assessment interval. CONCLUSIONS: These findings support the hypothesis that activity overlap on the pain and function subscales plays a causal role in limiting the WOMAC physical function subscale's ability to detect change.

Activities of Daily Living↗

[CT pulmonary functional imaging in emphysema: a correlative study of CT technique and pulmonary function test].

OBJECTIVE: To compare the effectiveness of high resolution CT, CT pulmonary functional imaging, and pulmonary function test (PFT) in the quantitative evaluation of emphysema and obstructive pulmonary disease. METHODS: The study included 37 patients with obstructive ventilatory defect and 20 normal controls. CT and pulmonary function test were performed in all subjects in one week. Correlation between and differences among HRCT visual scoring, parameters of CT pulmonary functional imaging and the result of pulmonary function test were compared. RESULTS: (1) Emphysema was detected by CT in 23 of the 37 patients with obstructive ventilatory defect. (2) HRCT visual scoring was correlated only with D(L)CO% (r = -0.731, P < 0.001) among other pulmonary function parameters. (3) HRCT visual scoring in patients with enrphysema was correlated with pixel indices (PI) at full inspiration and expiration. Visual scoring showed the best correlation with PI(-910in) (r = 0.506, P < 0.001) and PI(-910ex) (r = 0.610, P < 0.001). (4) The grading of pulmonary function based on PI(-910in) and PI(-910ex) showed no difference from the grading by pulmonary function tests (chi(2) = 0.527, P = 0.913; chi(2) = 3.645, P = 0.302). The grading of emphysema based on PI(-910in) accorded with the grading by pulmonary function tests (chi(2) = 2.59, P = 0.459). CONCLUSIONS: HRCT is more sensitive than conventional CT in diagnosing emphysema. However, in terms of slice thickness and radiation dose, it cannot be used in the evaluation of both lungs. CT functional imaging is easily performed, and the results are objective and correlated with the result of HRCT visual scoring and PFTs. It may be, therefore, more useful in diagnosing early emphysema and evaluating lung function.

Adult↗

Automated structure-based prediction of functional sites in proteins: applications to assessing the validity of inheriting protein function from homology in genome annotation and to protein docking.

A major problem in genome annotation is whether it is valid to transfer the function from a characterised protein to a homologue of unknown activity. Here, we show that one can employ a strategy that uses a structure-based prediction of protein functional sites to assess the reliability of functional inheritance. We have automated and benchmarked a method based on the evolutionary trace approach. Using a multiple sequence alignment, we identified invariant polar residues, which were then mapped onto the protein structure. Spatial clusters of these invariant residues formed the predicted functional site. For 68 of 86 proteins examined, the method yielded information about the observed functional site. This algorithm for functional site prediction was then used to assess the validity of transferring the function between homologues. This procedure was tested on 18 pairs of homologous proteins with unrelated function and 70 pairs of proteins with related function, and was shown to be 94 % accurate. This automated method could be linked to schemes for genome annotation. Finally, we examined the use of functional site prediction in protein-protein and protein-DNA docking. The use of predicted functional sites was shown to filter putative docked complexes with a discrimination similar to that obtained by manually including biological information about active sites or DNA-binding residues.

Algorithms↗

The longitudinal impact of psychological functioning, medical severity, and family functioning in pediatric heart transplantation.

BACKGROUND: Few data are available on the longitudinal psychological functioning of patients after pediatric heart transplantation. The objective of this study was to determine whether pre-transplant psychological functioning, post-transplant medical severity, and family functioning relate to the psychological functioning of pediatric patients after heart transplantation. METHODS: The study included 23 patients who underwent heart transplantation between ages 3 and 20 years, survived at least 1 year after transplantation, and had been assessed previously after transplantation between 1993 and 1995. This study reports a second post-transplant assessment between 1999 and 2000. We assessed psychological functioning using the Children's Global Assessment Scale before and after heart transplantation. We assessed medical severity using the number of outpatient visits, hospitalizations, and biopsies and using the Side Effect Severity Scale. We used the Global Assessment of Family Relational Functioning Scale to rate family functioning. RESULTS: The majority of patients (15/23) were alive at the second follow-up. They had survived a median of 9.6 (6.1-12.9) years after transplantation. Similar to their first follow-up assessments, 73% demonstrated good psychological functioning after heart transplantation. Although we found no correlation between medical severity and post-transplant psychological functioning, we did find a significant correlation between family functioning during the first 2 years of transplantation and post-transplant emotional adjustment. CONCLUSIONS: The majority of children and adolescents have the capacity for healthy psychological functioning after heart transplantation. Nevertheless, ongoing psychological assessment and intervention is necessary for patients and their families who face pediatric heart transplantation because >25% probably will have emotional adjustment difficulties.

Adaptation, Psychological↗

Comparison of density functionals for energy and structural differences between the high- [5T2g:(t2g)4(eg)2] and low- [1A1g:(t2g)6(eg)0] spin states of iron(II) coordination compounds. II. More functionals and the hexaminoferrous cation, [Fe(NH3)6]2+.

The ability of different density functionals to describe the structural and energy differences between the high- [(5)T(2g):(t(2g))(4)(e(g))(2)] and low- [(1)A(1g):(t(2g))(6)(e(g))(0)] spin states of small octahedral ferrous compounds is studied. This work is an extension of our previous study of the hexaquoferrous cation, [Fe(H(2)O)(6)](2+), [J. Chem. Phys. 120, 9473 (2004)] to include a second compound-namely, the hexaminoferrous cation, [Fe(NH(3))(6)](2+)-and several additional functionals. In particular, the present study includes the highly parametrized generalized gradient approximations (GGAs) known as HCTH and the meta-GGA VSXC [which together we refer to as highly parametrized density functionals (HPDFs)], now readily available in the GAUSSIAN03 program, as well as the hybrid functional PBE0. Since there are very few experimental results for these molecules with which to compare, comparison is made with best estimates obtained from second-order perturbation theory-corrected complete active space self-consistent field (CASPT2) calculations, with spectroscopy oriented configuration interaction (SORCI) calculations, and with ligand field theory (LFT) estimations. While CASPT2 and SORCI are among the most reliable ab initio methods available for this type of problem, LFT embodies many decades of empirical experience. These three methods are found to give coherent results and provide best estimates of the adiabatic low-spin-high-spin energy difference, DeltaE(LH) (adia), of 12 000-13 000 cm(-1) for [Fe(H(2)O)(6)](2+) and 9 000-11 000 cm(-1) for [Fe(NH(3))(6)](2+). All functionals beyond the purely local approximation produce reasonably good geometries, so long as adequate basis sets are used. In contrast, the energy splitting, DeltaE(LH) (adia), is much more sensitive to the choice of functional. The local density approximation severely over stabilizes the low-spin state with respect to the high-spin state. This "density functional theory (DFT) spin pairing-energy problem" persists, but is reduced, for traditional GGAs. In contrast the hybrid functional B3LYP underestimates DeltaE(LH) (adia) by a few thousands of wave numbers. The RPBE GGA of Hammer, Hansen, and Norskov gives good results for DeltaE(LH) (adia) as do the HPDFs, especially the VSXC functional. Surprisingly the HCTH functionals actually over correct the DFT spin pairing-energy problem, destabilizing the low-spin state relative to the high-spin state. Best agreement is found for the hybrid functional PBE0.

Journal Article↗

Visualizing bacterial tRNA identity determinants and antideterminants using function logos and inverse function logos.

Sequence logos are stacked bar graphs that generalize the notion of consensus sequence. They employ entropy statistics very effectively to display variation in a structural alignment of sequences of a common function, while emphasizing its over-represented features. Yet sequence logos cannot display features that distinguish functional subclasses within a structurally related superfamily nor do they display under-represented features. We introduce two extensions to address these needs: function logos and inverse logos. Function logos display subfunctions that are over-represented among sequences carrying a specific feature. Inverse logos generalize both sequence logos and function logos by displaying under-represented, rather than over-represented, features or functions in structural alignments. To make inverse logos, a compositional inverse is applied to the feature or function frequency distributions before logo construction, where a compositional inverse is a mathematical transform that makes common features or functions rare and vice versa. We applied these methods to a database of structurally aligned bacterial tDNAs to create highly condensed, birds-eye views of potentially all so-called identity determinants and antideterminants that confer specific amino acid charging or initiator function on tRNAs in bacteria. We recovered both known and a few potentially novel identity elements. Function logos and inverse logos are useful tools for exploratory bioinformatic analysis of structure-function relationships in sequence families and superfamilies.

Base Sequence↗

[Importance and limitations of the validation of functional MRI of motor function and language using preoperative cortical stimulation].

UNLABELLED: This chapter describes and discusses the value of the localization of functional areas obtained from functional MRI in brain tumor cases. Correlation method is cortical brain mapping by intraoperative stimulation. The experience reported here is focused on the study of motricity and language. METHODS: Twenty two patients with tumors of the rolandic region (n = 16) or in the temporal lobe (n = 6) underwent functional MR mapping and subsequently cortical mapping before tumor resection. The tasks chosen were a flexion and extension of the fingers or a naming task. We used 3D reconstructed images of the surface of the brain to assess intra and post operatively the functional MRI and stimulation data. RESULTS: For the motor correlation, in each case, the results of direct cortical mapping matched those obtained with functional MRI, both positively and negatively, although the extent of the functional activations was larger than the area required to elicit the corresponding movement during intraoperative brain mapping. For the language correlation and for the task chosen, only the results of the precentral areas matched those of functional MRI. CONCLUSIONS: Functional MRI can be used preoperatively to assess motor functional area in patients with rolandic tumors. More studies are needed to validate intraoperatively the language areas and the real extent of functional MRI activations. Finally, the observed discrepancy between functional MRI and cortical stimulation is likely due to the rather profound differences between both techniques, in terms of neurophysiology, practical applications and statistical analysis.

Adult↗

[Functional treatment of Colles fractures and the relation of anatomic recovery and function].

Functional treatment of Colles fractures is a recently developed approach to fracture injury. It aims to bring about faster recovery and a better functional end result by permitting early motion and function by means of a functional brace. Early motion and function, however, might jeopardize the anatomical result. Whether an inferior anatomical result jeopardizes the functional end result is not clear, as the relationship between anatomy and function has not been established. In a prospective clinical study it was concluded that in displaced Colles fractures functional treatment with a below-the-elbow functional brace offers little advantage over conventional plaster of Paris immobilisation. Minimally displaced Colles fractures (volar angle greater than or equal to 0 degrees) should be treated with a bandage after one week of plaster immobilisation. The relationship between the anatomical and functional end result is weak and probably depends on initial displacement and complications. To improve the functional result after a Colles fracture, prevention and better treatment of complications seem to be more important than improvement of the method of fracture treatment of the anatomical end result.

Adolescent↗

Impact of psychologic functioning, medical severity, and family functioning in pediatric heart transplantation.

BACKGROUND AND METHODS: This study examined (1) the psychologic functioning of children and adolescents before and after heart transplantation and (2) whether pretransplantation psychologic functioning, posttransplantation medical severity, and family functioning were related to the patients' posttransplantation psychologic functioning. The subjects were 23 patients, ages 3 to 20 years, who underwent heart transplant and survived at least 1 year after their transplantation. Psychologic functioning was assessed by the Children's Global Assessment Scale before and after heart transplantation. Medical severity was assessed by number of outpatient visits, hospitalizations, biopsies, and the Side Effect Severity Scale. Family functioning was rated on the Global Assessment of Family Relational Functioning Scale. RESULTS: The majority of the patients (78.3%) had good psychologic functioning after their heart transplantation. Patients with psychologic difficulties before and after transplantation had more hospitalizations after transplantation. CONCLUSIONS: Pretransplantation emotional functioning and family functioning were more correlated with posttransplantation psychologic functioning than medical side effect severity.

Adaptation, Psychological↗

The functional status of inner-city primary care patients. Diminished function in a family practice population and its potential determinants.

BACKGROUND: Research on health care quality and effectiveness often relies on global health status measures, such as functional status, but little is known about the functional status of patients in the primary care setting (without limitation to specific diseases) and even less about the function of the poor or ethnic minorities. In preparation for a planned practice-based research network, we administered a functional-status survey to patients visiting an inner-city family practice center. METHODS: Over 9 weeks, 555 established patients older than 18 years, as well as adolescents accompanied by a parent or guardian, completed a survey that included the SF-36 Health Survey and questions about demographic variables and cigarette use. The survey was self-administered in the waiting area and examination room, and patients received no assistance from staff. RESULTS: Functional-status scores reported by this primary care cohort were significantly lower than those of the general population (P < .001) and comparable with those reported nationally for patients with chronic diseases (e.g., congestive heart failure, diabetes). Functional-status scores were associated with age, sex, and, most strikingly, socioeconomic status. For example, patients with a yearly income of less than $15,000 had lower mean physical function scores than those reported nationally for patients with hypertension, diabetes, depression, recent myocardial infarction, or hypertension (P < .05). Patients who currently smoked reported lower physical function (P = .004) and strikingly lower mental function (P < .001) than nonsmokers. CONCLUSIONS: Although patients completing the survey included healthy persons seeking preventive care and sick patients with acute and chronic illnesses, their overall functional status resembled that reported nationally for patients with chronic disease, perhaps reflecting the influence of poverty. Few studies have reported the association we observed between smoking and lower functional status. Further longitudinal studies in the primary care setting are necessary to fully interpret these associations and to evaluate the true impact of interventions on outcomes.

Adolescent↗

One-year posttransplant renal function is a strong predictor of long-term kidney function: results from the Neoral-MOST Observational Study.

BACKGROUND: Peritransplant risk factors influence short-term and long-term graft survival, and 1-year serum creatinine is known to predict long-term graft survival. To examine interrelationships between risk factors, renal function at 1 year, and long-term graft function in patients maintained on cyclosporine, we analyzed data collected from 10,692 de novo or maintenance renal transplant recipients in an ongoing international, prospective, observational study--Neoral-MOST (Multinational Observational Study in renal Transplantation). The effect of donor age, delayed graft function, acute rejection, donor type, panel-reactive antibodies, and previous graft on 1- and 5-year renal function and their relationship to 1-year serum creatinine was assessed. RESULTS: Donor age, delayed graft function, acute rejection, and donor type significantly increased the risk for serum creatinine > 130 micromol/L at 1 year posttransplant, and 1-year serum creatinine was the strongest predictor of 5-year renal function. After adjustment for 1-year serum creatinine, an ongoing influence was observed for donor age, donor type, and previous graft. Delayed graft function and acute rejection had a significant effect on serum creatinine at year 1 but no additional impact on long-term graft function. CONCLUSIONS: Serum creatinine at 1 year is influenced by risk factors known to affect overall graft survival and is predictive of 5-year renal graft function. The effects of delayed graft function and acute rejection appear to be limited to their influence on serum creatinine at 1 year, whereas donor type and previous graft predominantly affect later stages of graft life.

Creatinine↗

Prediction of global left ventricular function after bypass surgery in patients with severe left ventricular dysfunction. Impact of pre-operative myocardial function, perfusion, and metabolism.

AIMS: Previous studies have compared the accuracy of various tests of viability for the prediction of recovery of regional left ventricular function; global left ventricular recovery has been less well studied, although it has important prognostic and functional ramifications. We sought to identify the relative contribution of ischaemia, regional and global contractile reserve, perfusion and metabolic function to changes in left ventricular volumes and global function after coronary artery bypass surgery in patients with severe left ventricular dysfunction. METHODS AND RESULTS: Dipyridamole stress Rb-82, fluorodeoxyglucose positron emission tomography and low and high-dose dobutamine-atropine stress echocardiography were obtained in 66 patients with left ventricular impairment. Myocardial segments were considered viable if ischaemia or either metabolic or contractile reserve were present, on positron emission tomography or dobutamine echocardiography. Resting left ventricular function was reassessed after surgery (mean 10+/-3 weeks) in the 59 patients who had not suffered a major peri-operative event; functional improvement was defined by a 5% increment of ejection fraction. Myocardial viability was found in 37 (63%) patients using positron emission tomography and in 42 (71%) patients using dobutamine echocardiography; post-operative functional improvement was noted in 28 (47%) patients. In univariate analyses, predictors of global post-operative functional recovery included: the extent of viability according to positron emission tomography [OR (odds ratio): 2.08 for each additional viable segment, 95% CI (confidence interval): 1.33-3. 25, P=0.001] or dobutamine echocardiography (OR: 2.06 for each additional viable segment, 95% CI: 1.28-3.30, P=0.003) and the increase in ejection fraction with low-dose dobutamine (OR: 1.9 for each 1% increase in ejection fraction with low dose dobutamine, 95% CI 1.39-2.61, P<0.0001). In a multivariate model which included evidence of viability by either technique, and change in ejection fraction with low-dose dobutamine echocardiography, only change in ejection fraction with low-dose dobutamine echocardiography was predictive of post-operative left ventricular functional recovery (adjusted OR: 1.81, 95% CI: 1.30-2.52, P=0.0005). CONCLUSION: Among patients with severe left ventricular dysfunction who are referred for surgical revascularization, the overall accuracies of positron emission tomography and dobutamine echocardiography for the prediction of post-operative myocardial recovery are comparable. However, the strongest predictor of overall improvement of post-operative left ventricular function is an increase of ejection fraction with a low-dose dobutamine infusion.

Aged↗

Candesartan cilexetil improves left ventricular function, left ventricular hypertrophy, and endothelial function in patients with hypertensive heart disease.

Patients with hypertension often develop left ventricular (LV) hypertrophy and deterioration of the cardiac and endothelial functions. Recent clinical trials have shown the added benefits of angiotensin II receptor blockers in hypertensive patients. Twenty-nine patients with hypertensive heart disease (HHD) underwent echocardiography, radionuclide ventriculography and the measurement of endothelial function before and after administration of candesartan (8 mg/day). The subjects were divided into poorly controlled blood pressure (BP) (group P, n=6) and well controlled BP (group C, n=23). Endothelial function was evaluated from flow-dependent dilation, which was calculated as the percent change of the radial artery diameter during reactive hyperemia after upper arm occlusion, measured with a high-resolution ultrasound system. In group C, LV diastolic function and endothelial function were significantly (p<0.05) improved at 3 months after administration, LV systolic function and hypertrophy were significantly (p<0.05) improved after 6 months and these effects were maintained at 12 months. Even in group P, LV function, LV hypertrophy, endothelial function and brain natriuretic peptide were significantly (p<0.05) improved at 6 months after administration. In patients with HHD, candesartan improves LV systolic and diastolic function, LV hypertrophy and endothelial function within 6 months of administration, regardless of the control of BP.

Adult↗

[Maximal functional capacity, ejection fraction, and functional class in Chagas cardiomyopathy. Are these indices related?].

OBJECTIVE: Left ventricular ejection fraction (LVEF) and maximal functional capacity (VO2max) have both been shown to be related to a poor long-term survival in Chagas' disease patients. The aim of this study was to estimate the potential association of VO2max, LVEF, and NYHA functional class in patients with Chagas' disease cardiomyopathy. METHODS: One hundred four male patients, aged 40.3+/-9.0 years (range, 18 to 65), with a definite diagnosis of Chagas disease cardiomyopathy were studied. LVEF and VO2max were both classified into 3 degrees: LVEF 0.50 and VO2max < or = 10, 10 < VO2max < or = 20, and VO2max > 20 ml.kg(-1).min(-1), respectively. RESULTS: Thirty-one patients (29.8%) were in NYHA functional class II, 41 (39.4%) in functional class III, and 32 (30.8%) in functional class IV. The corresponding values of VO2max and LVEF for functional classes II, III, and IV were 21.5+/-4.0 ml.kg(-1).min(-1), 18.3+/-5.8 ml.kg(-1).min(-1), and 14.7+/-4.9 ml.kg(-1).min(-1) and 0.50+/-0.6, 0.35+/- 0.9, and 0.29+/-0.7, respectively. LVEF = < or = 0.30 and VO2max = < or = 10 ml.kg(-1).min(-1) were found in the majority of patients in NYHA functional class IV. Conversely, patients in functional class II were mostly those with LVEF > 0.50 as well as VO2max > 20 ml.kg(-1).min(-1). CONCLUSION: A convincingly good association exists between NYHA functional class, functional capacity and LVEF in patients with Chagas' disease cardiomyopathy. These data may be helpful in the management of heart failure in Chagas' disease patients.

Adolescent↗

Distal radius fracture in adults: self-reported physical functioning, role functioning, and meaning of injury.

PURPOSE: To identify physical function, role function, and meaning of injury in adults with a distal radius fracture. SAMPLE: Convenience sample of 60 adults with an isolated distal radius fracture. METHOD: Repeated measures of analysis of variance were used to test the relationship of gender, age, education, hand dominance, preinjury physical health, and treatment modality to physical function, role function, and meaning of illness/injury. The independent variable is time and the dependent variables are physical function, role function, and meaning of illness/injury. FINDINGS: Although improvement occurred with time, older adults had significantly lower physical functioning than younger adults while their wrist was immobilized, and middle-age adults had significantly lower role functioning compared to younger and older adults. Physical function was influenced by age, and role function was influenced by both age and education. CONCLUSION: The identified need for additional guidance and physical and emotional support with the standard treatment of distal radius fractures highlights the need for nursing care during the early recovery period.

Activities of Daily Living↗

Sequential development of helper and suppressor functions, antibody titers and functional avidities to a streptococcal antigen in rhesus monkeys.

Sequential development of antibody titer, functional avidity, helper and suppressor activities were investigated in rhesus monkeys. These were immunized with a single dose of 0.1 microgram to 10 mg of a streptococcal protein antigen (SA) in aluminium hydroxide. The IgG antibody titers followed the classical pattern first established in mice, of high-dose and low-dose tolerance with intermediate doses of immunity. This was correlated with a similar pattern of functional avidity of IgG antibodies, as measured by a dissociation assay. Helper and suppressor functions were assayed in parallel by inducing the corresponding factors from monkey lymphocytes in Marbrook flasks and testing the factors which cross the species barrier in cooperative cultures with CBA mouse spleen B cells. A progressive modulation of helper and suppressor activities was elicited by the increasing doses of SA, during the initial 28 days after immunization. Thus, dominant suppressor with minimal helper activity, IgG antibody titer and functional avidity were elicited by 0.1 microgram SA. However, 1 or 10 micrograms SA induced dominant helper with minimal or transient suppressor activity and high IgG antibody titers and functional avidity. Somewhat intermediate responses were elicited by 100 micrograms SA, but 1 mg and especially 10 mg SA induced dominant suppressor and minimal helper activity, with low IgG antibody titers and functional avidities. When the immune response was established, about 28 days after immunization, the intermediate dose of SA elicited IgG antibodies with high titer and functional avidity, high T cell helper but low suppressor activities. In contrast, both high- and low-dose SA induced partial tolerance, with low IgG antibody titer, functional avidity and T cell helper activity. These studies suggest cyclical development of helper and suppressor functions during the 4 weeks after immunization. The emergence of a dominant helper or suppressor function is antigen dose dependent.

Animals↗

Detecting functional nodes in large-scale cortical networks with functional magnetic resonance imaging: a principal component analysis of the human visual system.

This study aimed to demonstrate how a regional variant of principal component analysis (PCA) can be used to delineate the known functional subdivisions of the human visual system. Unlike conventional eigenimage analysis, PCA was carried out as a second-level analysis subsequent to model-based General Linear Model (GLM)-type functional activation mapping. Functional homogeneity of the functional magnetic resonance imaging (fMRI) time series within and between clusters was examined on several levels of the visual network, starting from the level of individual clusters up to the network level comprising two or more distinct visual regions. On each level, the number of significant components was identified and compared with the number of clusters in the data set. Eigenimages were used to examine the regional distribution of the extracted components. It was shown that voxels within individual clusters and voxels located in bilateral homologue visual regions can be represented by a single component, constituting the characteristic functional specialization of the cluster(s). If, however, PCA was applied to time series of voxels located in functionally distinct visual regions, more than one component was observed with each component being dominated by voxels in one of the investigated regions. The model of functional connections derived by PCA was in accordance with the well-known functional anatomy and anatomical connectivity of the visual system. PCA in combination with conventional activation mapping might therefore be used to identify the number of functionally distinct nodes in an fMRI data set in order to generate a model of functional connectivity within a neuroanatomical network.

Adult↗