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Results for “Association and function analysis”

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PubMed1991

Slow-wave activity in the spectral analysis of the electroencephalogram is associated with cortical dysfunctions in patients with Alzheimer's disease.

Cortical functions and slow-wave activity in the spectral analysis of the electroencephalogram (EEG) have been studied in 19 patients with Alzheimer's disease (AD), 18 patients with Parkinson's disease with dementia (PD), and 14 control subjects (C) to determine which functions are explained by their relationship of slow-wave activity. Multiple regression analyses revealed that a variance in visual functions, praxia of the hand, automatic speech, speech understanding, and retrieval from semantic memory were explained by their relationship with slow-wave activity in EEG in the AD group but not in the PD or C groups. The PD and AD groups exhibited equal cortical dysfunctions and mean amplitudes of delta activity in EEG. The cholinergic system, disrupted in AD, has been shown to be important in the regulation of neocortical electrical activity and may be associated with the processing of cortical functions.

Aged↗

PubMed2005

Functional genomic relationships in HIV-1 disease revealed by gene-expression profiling of primary human peripheral blood mononuclear cells.

BACKGROUND: An assessment of biomarkers from an analysis of human peripheral blood mononuclear cell gene-expression profiles was made, to acquire an understanding of transcriptional changes associated with human immunodeficiency virus type 1 (HIV-1) infection in vivo. METHODS: Supervised learning algorithms were used to create signature gene sets that could be used to distinguish seropositive from seronegative samples and delineate changes in disease status during the early stages of infection. Bioinformatic tools were used to classify persons and to functionally characterize groups of differentially expressed genes, to elucidate the impact of viral infection on host cell gene-expression patterns. RESULTS: A 10-gene signature set that could be used to accurately determine the HIV-1 serostatus was identified. A 6-gene signature set was used to distinguish seropositive persons exhibiting differential changes in CD4(+) T cell counts, with 93% accuracy. Functional classification of differentially expressed genes in HIV-1 indicated a preponderance of down-regulated genes with functions related to the immune response and apoptosis. Hierarchical cluster analysis in persons whose CD4(+) T cell counts increased, compared with that in persons whose CD4(+) T cell counts decreased, was characterized by the down-regulation of genes associated with apoptosis, mitochondrial function, protein biosynthesis, and RNA binding. CONCLUSIONS: Gene-expression profile analysis of a complex infectious virus, such as HIV-1, may be useful to elucidate the functional genomic relationships associated with viral infection.

CD4-Positive T-Lymphocytes↗

PubMed2005

Plasma homocysteine levels and the left ventricular systolic function in coronary artery disease patients.

BACKGROUND: Numerous studies have shown a relationship between hyperhomocysteinemia, atherothrombosis and cardiovascular mortality. However, an association between hyperhomocysteinemia and the extent of coronary artery disease (CAD) remains controversial whereas its relationship with left ventricular systolic function has not been established. METHODS: One hundred and fifty-seven patients with angiographically defined CAD were included. The relationships between hyperhomocysteinemia, severity of CAD and left ventricular systolic function were studied. Left ventricular systolic function was determined primarily by ventriculography. The severity of CAD was determined through coronary angiography using the Gensini score and the number of vessels with > or = 50% stenosis. RESULTS: The mean fasting plasma homocysteine level was 13.4 mumol/l+/-0.5 SE. Elevated levels of homocysteine correlated significantly with increased severity of CAD both by the Gensini scores (r-value = 0.344, P < 0.0005) and the total number of diseased vessels (r-value = 0.387, P < 0.0005). The patients with hyperhomocysteinemia were found to have significantly reduced left ventricular ejection fraction (r-value = -0.382, P < 0.0005). A multivariate regression analysis revealed homocysteine level to be an independent predictor of left ventricular systolic function. In addition, adjusted analysis revealed hyperhomocysteinemia to be associated with global left ventricular dysfunction. CONCLUSION: In patients with CAD, homocysteine levels correlate independently with left ventricular systolic function. The mechanism of this association between homocysteine and left ventricular systolic function is unknown but may be due to a direct effect of homocysteine on myocardial function separate from its effects on coronary atherosclerosis.

Aged↗

PubMed1997

Simultaneous treatment with BDNF and CNTF after peripheral nerve transection and repair enhances rate of functional recovery compared with BDNF treatment alone.

The objective was to investigate the effects of brain-derived neurotropic factor (BDNF) and ciliary neurotropic factor (CNTF) on peripheral nerve regeneration. Thirty Sprague-Dawley rats underwent left sciatic nerve transection and repair according to three experimental groups: epineurial coaptation (EC), EC with BDNF delivered by an osmotic pump (EC-BDNF), and EC with BDNF and CNTF delivered similarly (EC-BDNF/CNTF). Nerve regeneration was assessed using sciatic functional indices, quantitative histomorphology, and molecular analysis for proteins associated with nerve regeneration. Analysis of variance (ANOVA) comparing all groups at each time point demonstrated significant differences between groups on days 20, 30, 40, 50, 60, and 80. A paired, two-tailed Student's t-test with the Bonferroni correction for multiple comparisons demonstrated that at 40 days postoperatively, animals in the EC-BDNF/CNTF group (n = 7) manifested superior functional recovery compared with those in the EC group (n = 9) and those in the EC-BDNF group (n = 9) (P < 0.001 and P < 0.05, respectively). At 80 days, the animals in both the EC-BDNF (P < 0.01) and EC-BDNF/CNTF (P < 0.05) groups demonstrated greater functional recovery compared with those in the EC group, with no significant difference between the two factor groups at the endpoint. Morphometric analysis demonstrated that nerves from animals in the EC-BDNF/CNTF group had the largest mean axon diameters as compared with those from the EC (proximal: P < 0.001, distal: P < 0.05) and EC-BDNF (proximal: P < 0.01) groups. No significant differences were seen in nerve cross-sectional area. In distal nerve segments, Western blot analysis revealed that expression of myelin-associated glycoprotein was higher than control for the EC group and lower than control for both the EC-BDNF and EC-BDNF/CNTF groups. We conclude that BDNF/CNTF combined treatment increases the early rate of functional sciatic nerve regeneration over treatment with BDNF alone, although the degree of maximal recovery was similar at the conclusion of the experiment.

Analysis of Variance↗

PubMed1995

Tricuspid valve replacement: postoperative and long-term results.

A series of 146 consecutive patients who underwent tricuspid valve replacement at the University Brugmann Hospital between 1967 and 1987 was reviewed. Mean age at operation was 51.4 years (+/- 12.1 years). Different types of prostheses were implanted including porcine and bovine pericardial bioprostheses and older and bileaflet mechanical valves. Most patients were severely disabled by their cardiac disease before operation, with 30.1% in New York Heart Association functional class III and 69.9% in class IV. Operative mortality and hospital mortality rates (30 days) were high (16.4%). Incremental risk factors for hospital death included icterus (p < 0.005), preoperative hepatomegaly (p = 0.012), and New York Heart Association functional class IV (p = 0.013). Multivariate analysis only selected preoperative icterus (p < 0.01) as being independently significantly related to hospital mortality. The hospital survivors were followed up for a median of 94 months. A complete follow-up was available for all patients except two for 30 months or more. At 30 months the only two significant parameters were the type of myocardial protection (p = 0.024) and the year of operation (before 1977 or after [precardioplegia era or after], p = 0.011). There were 70 late deaths during the entire follow-up period. The univariate (log-rank statistics) incremental risk factor for late death was the type of tricuspid prosthesis (Smeloff-Cutter and Kay-Shiley versus St. Jude Medical versus bioprosthesis) (p = 0.04). A trend was observed for the type of operative myocardial protection (normothermia and coronary perfusion) (p = 0.06) and preoperative New York Heart Association functional class IV (p = 0.055). Actuarial survival was 74% at 60 months and 23.4% at 180 months. Cumulative follow-up added up to 1015 patient-years. In a more detailed analysis of the effect on survival of the type of tricuspid prosthesis, a significant difference was observed between the bioprostheses and some older mechanical prostheses (Smeloff-Cutter and Kay-Shiley) (p = 0.04) but not between the bioprostheses and the bileaflet valves (p = 0.15). When the follow-up period was stratified according to less than 7 years and more than 7 years of follow-up, no difference was observed for the first period, but for the late follow-up the new mechanical prostheses did better than the bioprostheses (p = 0.05), suggesting a degradation of the bioprostheses after 7 years and favoring mechanical prostheses for those patients with a good long-term prognosis.

Actuarial Analysis↗

PubMed2004

A Bayesian morphometry algorithm.

Most methods for structure-function analysis of the brain in medical images are usually based on voxel-wise statistical tests performed on registered magnetic resonance (MR) images across subjects. A major drawback of such methods is the inability to accurately locate regions that manifest nonlinear associations with clinical variables. In this paper, we propose Bayesian morphological analysis methods, based on a Bayesian-network representation, for the analysis of MR brain images. First, we describe how Bayesian networks (BNs) can represent probabilistic associations among voxels and clinical (function) variables. Second, we present a model-selection framework, which generates a BN that captures structure-function relationships from MR brain images and function variables. We demonstrate our methods in the context of determining associations between regional brain atrophy (as demonstrated on MR images of the brain), and functional deficits. We employ two data sets for this evaluation: the first contains MR images of 11 subjects, where associations between regional atrophy and a functional deficit are almost linear; the second data set contains MR images of the ventricles of 84 subjects, where the structure-function association is nonlinear. Our methods successfully identify voxel-wise morphological changes that are associated with functional deficits in both data sets, whereas standard statistical analysis (i.e., t-test and paired t-test) fails in the nonlinear-association case.

Aged↗

PubMed1997

Piezoelectric immunosensors for urine specimens of Chlamydia trachomatis employing quartz crystal microbalance microgravimetric analyses.

The assembly of a biosensor for Chlamydia trachomatis based on the microgravimetric quartz crystal microbalance (QCM) analysis of the bacteria association to an antibody-functionalized electrode is described. The sensing interfaces consist of a primary cystamine monolayer assembled onto Au electrodes associated with the quartz crystal. The monolayer is further modified with sulfosuccinylimidyl 4-(p-maleimidophenyl)butyrate (sulfo-SMPB) and the goat IgG-anti-mouse IgG Fc-specific Ab or the fragmented F(ab')2 anti-mouse IgG Ab that act as sublayers for the association of the sensor-active anti-C. trachomatis LPS-Ab. Bacteria in the concentration range from 260 ng.mL-1 to 7.8 micrograms.mL-1 are sensed by the functionalized crystals. The association of C. trachomatis to the sensing interface can be confirmed and amplified via interaction of the crystal with various anti-C. trachomatis antibodies. Urine-pretreated functionalized quartz crystals are applied in the analysis of C. trachomatis in urine samples. The sensitivity limits of the electrodes for sensing the bacteria in urine samples corresponds to approximately 260 ng.mL-1. The functionalized crystals assembled via association of anti-C. trachomatis LPS-Ab to the fragmented F(ab')2 anti-mouse IgG Ab reveal long-term stability upon storage at 4 degrees C.

Antibodies, Bacterial↗

PubMed2000

The Turner syndrome-associated neurocognitive phenotype maps to distal Xp.

Turner syndrome (TS) is associated with a characteristic neurocognitive profile that includes impaired visuospatial/perceptual abilities. We used a molecular approach to identify a critical region of the X chromosome for neurocognitive aspects of TS. Partial deletions of Xp in 34 females were mapped by FISH or by loss of heterozygosity of polymorphic markers. Discriminant function analysis optimally identified the TS-associated neurocognitive phenotype. Only subjects missing approximately 10 Mb of distal Xp manifested the specified neurocognitive profile. The phenotype was seen with either paternally or maternally inherited deletions and with either complete or incomplete skewing of X inactivation. Fine mapping of informative deletions implicated a critical region of <2 Mb within the pseudoautosomal region (PAR1). We conclude that haploinsufficiency of PAR1 gene(s) is the basis for susceptibility to the TS neurocognitive phenotype.

Adolescent↗

PubMed1996

Functional analysis of the MAP2 repeat domain.

The neuronal microtubule-associated protein MAP2 binds to microtubules via a domain near its C terminus containing a set of 3 or 4 imperfect repeats of a 31 amino acid motif. Using naturally occurring and mutated forms of the molecule containing between 1 and 4 repeats we have examined the contribution that these repeats make to MAP2 function and explored the significance of their repetition. The experiments utilised the short 3- and 4-repeat splice variants MAP2c and MAP2d that are expressed in developing neurons and in glia respectively, and mutant 1- and 2-repeat versions that were produced by using in vitro mutagenesis to remove further 31 amino acid units while leaving the rest of the molecule unaltered. The properties of these MAP2 variants were compared both with respect to their influence on microtubules in transfected non-neuronal cells and their ability to promote microtubule assembly in vitro. We found that each of the known effects of MAP2, including the bundling of microtubules and induction of process formation in living cells, are expressed by the 1-repeat form MAP2c3, which contains only the third repeat (R3). A second 1-repeat form, MAP2c4, which contains only R4, interacts more weakly with tubulin in vitro and does not bind to microtubules in transfected cells. The microtubule-related properties of MAP2 thus arise mainly from a single predominant repeat unit, R3. In vitro assembly experiments showed that the primary effect of all the repeats is to lower the critical concentration of tubulin required for microtubule assembly but that they differ greatly in potency. The results did not reveal a separate function related to the repetition of the repeat motifs, but instead suggest that its purpose is to tailor the efficiency of MAP2 to the cellular environment in which it has to function.

Amino Acid Sequence↗

PubMed2026

Proteomic and Phosphoproteomic Signatures Link Molecular Remodeling to Behavioral Outcomes Following Elderberry and DHA Supplementation in Aging Mice.

Background: Aging is a risk factor for Alzheimer's disease and related dementias, which are associated with synaptic dysfunction and cognitive decline. Elderberry (Sambucus spp.) is rich in anthocyanins with antioxidant and anti-inflammatory properties. Docosahexaenoic acid (DHA), an essential fatty acid, plays a key role in neuronal membrane integrity during brain aging. However, it remains unclear whether elderberry and DHA exert overlapping or distinct effects on brain aging and how these relate to molecular signaling. This study aimed to characterize molecular signatures induced by dietary supplementation and to determine their relationships with behavioral outcomes. Methods: 44-week-old male C57BL/6J mice were randomly assigned to control, elderberry, DHA, or combined diets for 12 weeks. Behavioral testing assessed anxiety-like behavior, spatial learning and memory. Brain tissues underwent proteomic and phosphoproteomic profiling and fatty-acid analysis. Data were analyzed using Ingenuity Pathway Analysis to identify enriched pathways, upstream regulators, and functional associations. Results: Elderberry as well as DHA supplementation induced targeted remodeling of the proteome and phosphoproteome, with pathway enrichment involving synaptogenesis, glutamatergic signaling, and long-term potentiation. Upstream-regulator analysis predicted elderberry-associated CDK5 signaling, accompanied by reduced MAPT/Tau phosphorylation at selected sites, whereas DHA supplementation was associated with CAMK-related signaling. DHA supplementation altered fatty-acid composition, increasing the n-3/n-6 ratio. Elderberry reduced anxiety-like behavior and improved target-directed search during the Barnes maze probe test. Molecular signatures were examined in relation to the measured behavioral outcomes. Conclusions: Elderberry and DHA are associated with distinct molecular networks related to synaptic function and behavioral outcomes in the aging male mouse brain. These findings support further investigation of elderberry and DHA as dietary interventions targeting molecular and behavioral features of brain aging.

Animals↗

PubMedDate not supplied

Reading and language in 9- to 12-year olds prenatally exposed to cigarettes and marijuana.

Facets of reading and language were examined in 131 9- to 12-year-old children for whom prenatal exposure to marijuana and cigarettes had been ascertained. The subjects were from a low-risk, predominantly middle class sample who are participants in an ongoing longitudinal study. Discriminant Function Analysis revealed a dose-dependent association that remained after controlling for potential confounds, between prenatal cigarette exposure and lower language and lower reading scores, particularly on auditory-related aspects of this latter measure. The findings are interpreted as consistent with earlier observations of an association between cigarette smoking during pregnancy and altered auditory functioning in the offspring. Similarities and differences between the reading observations and dyslexia are discussed. Maternal prenatal passive smoke exposure did not appear to contribute to either the language or reading outcomes at this age but postnatal secondhand smoke exposure by the child was associated with poorer language scores. Prenatal marijuana exposure was not significantly related to either the reading or language outcomes.

Child↗

PubMed1999

Molecular cloning and functional analysis of the murine bax gene promoter.

Bcl-2-associated X protein (Bax) is a proapoptotic protein and is suggested to have an important role in carcinogenesis. To investigate the mechanism of bax gene transcriptional regulation, we isolated and sequenced the genomic DNA fragment of the 5' flanking region of the murine bax gene, and subcloned its promoter region into a luciferase reporter construction. The murine bax promoter is TATA-less, and the sequence is only partially homologous to that of the human bax promoter. Transient transfection into NIH 3T3 cells using unidirectionally deleted promoters and mutants of Sp1 sites revealed that two Sp1 sites were partially responsible for the basal activity. The murine bax promoter was not responsive to exogenous p53, suggesting that the p53-responsive element may not exist in the region used in our current experiments.

3T3 Cells↗

PubMed2025

Identification and external validation of a prognostic signature based on myeloid-derived suppressor cells-related LncRNAs to evaluate survival prognosis and treatment efficacy in invasive breast carcinoma.

BACKGROUND: Originating in the hematopoietic tissue, myeloid-derived suppressor cells (MDSCs) significantly contribute to tumor-related immunological processes. However, their relationship with long noncoding RNAs (lncRNAs) and breast cancer remains incompletely understood. In this study, we introduced MDSCs-associated lncRNAs as novel prognostic biomarkers to assess outcomes in patients with invasive breast carcinoma (BRCA). METHODS: Information regarding BRCA cases, including clinical and genomic details, was obtained from the TCGA repository. Predictive indicators were discovered, and their reliability underwent thorough verification. A clinically useful nomogram was developed following application-based validation. Additional investigations encompassed functional analysis, TMB assessment, TME profiling, immunotherapy efficacy forecasting, and drug sensitivity testing along with target identification. Long non-coding RNA expression was measured using reverse transcription quantitative PCR. RESULTS: A risk stratification model incorporating eight MDSCs-related lncRNAs effectively predicted patient outcomes. Kaplan-Meier (K-M) survival analysis clearly indicated a much worse prognosis among patients classified as high-risk (p < 0.001). The nomogram accurately forecasted overall survival (OS). Analysis of functional enrichment revealed that pathways associated with epithelial cells showed activity among patients at higher risk. Characterization of the tumor microenvironment showed increased immune cell presence in those classified as low-risk. Conversely, individuals with greater risk displayed higher tumor mutational burden. TIDE and IPS analyses indicated superior immunotherapy responsiveness in the low-risk BRCA subgroup. Among 47 drugs with notable IC50 variations, Ribociclib, PD173074, KU-55933, NU7441, and nutlin-3a exhibited lower IC50 values within the low-risk group, whereas Lapatinib demonstrated greater efficacy among the high-risk group. Moreover, 10 potential therapeutic agents and their targets were predicted for high-risk patients. RT-qPCR validation confirmed the robustness of the model. CONCLUSIONS: We successfully verified a new model of molecular markers of MDSCs-related lncRNAs, offering critical insights for predicting outcomes and guiding therapeutic decisions in BRCA cases.

Bioinformatics↗

PubMed2005

Association between intellectual functioning and age in children and young adults with Duchenne muscular dystrophy: further results from a meta-analysis.

This study used meta-analytical techniques to explore the association between intelligence and age in children with Duchenne muscular dystrophy (DMD). The sample comprised 1224 children and young adults with DMD (mean age 12 y 3 mo, SD 4 y; range 2 y to 27 y). Standardized measures including the Wechsler Intelligence Scales (WIS) and the Stanford-Binet Intelligence Scales were used to estimate intelligence. No age-related difference was noted for Full-scale and Performance intelligence quotients (IQ). However, Verbal IQ increased significantly with age. Age-related increases were noted for the WIS Information, Similarities, Arithmetic, Comprehension, Digit Span, Picture Arrangement, Block Design, and Coding subscales. These results support the notion that younger children with DMD have deficits in verbal reasoning and verbal processing. Older children with DMD, particularly those of 14 years and older, were less likely to present with these problems. Implications of these findings and possible future research directions are discussed.

Adolescent↗

PubMed2005

Comparative analysis of autogenous infrainguinal bypass grafts in African Americans and Caucasians: the association of race with graft function and limb salvage.

OBJECTIVE: African Americans (AAs) are at risk for developing diabetes mellitus and atherosclerosis. Whether race influences the results of infrainguinal arterial reconstruction is unclear. The purpose of this study was to compare the results of autogenous infrainguinal bypasses in AAs and Caucasians to determine the association of race with graft function and limb salvage. METHODS: This was a retrospective, comparative cohort study of AA and Caucasian patients who had undergone autogenous infrainguinal bypass surgery. Only single-limb bypasses in each patient cohort were considered in this analysis. In patients who had undergone bilateral lower limb bypasses, the first limb bypass was chosen as the index bypass procedure. RESULTS: From January 1985 to December 2003, 1459 autogenous infrainguinal bypasses were performed in 1459 patients for lower limb ischemia. Within this group, 89 AA patients/vein grafts formed the study cohort. The control group comprised 1370 Caucasian patients/vein grafts. Compared with the Caucasian cohort, AA patients were significantly younger (median age, 65 vs 70 years, respectively; P = .001) and predominantly female (57% vs 41%, respectively; P = .002). AA patients also had a higher prevalence of diabetes mellitus, hypertension, cerebrovascular disease, congestive heart failure, and dialysis-dependent renal failure. More AA than Caucasian patients presented with gangrene (34% vs 16%, respectively; P = .001), and more underwent bypass surgery for limb salvage indications (91% vs 81%, respectively; P = .01). The venous conduit used was predominantly the greater saphenous vein (AA, 83%; Caucasian, 85%), and the site of distal anastomosis was at the tibial/pedal level in 67% of AA and 61% of Caucasian patients. Overall morbidity (AA, 28%; Caucasian, 23%) and 30-day mortality (AA, 3%; Caucasian, 3%) were similar. Thirty-day graft failure was significantly greater in AAs than Caucasians (12% vs 5%, respectively; P = .003). The overall 5-year primary graft patency (+/-SE) was significantly worse in AA patients (AA, 52% +/- 6%; Caucasian, 67% +/- 2%; P = .009). The 5-year limb salvage rate (+/-SE) was also significantly worse in AA patients (AA, 81% +/- 5%; Caucasian, 90% +/- 1%; P = .04). With the Cox proportional hazard model, significant risk factors associated with primary graft failure were AA race, age younger than 65 years, female sex, secondary reconstructions, tibial bypasses, and critical limb ischemia. Significant risk factors associated with limb loss were age younger than 65 years, female sex, absence of coronary disease, presence of critical limb ischemia, and secondary reconstructions. CONCLUSIONS: Autogenous infrainguinal bypass surgery in AAs is associated with poorer primary graft patency and limb salvage rates compared with those of Caucasians. This may partially account for the higher rate of limb loss in AA patients with peripheral arterial occlusive disease.

Black or African American↗

PubMed2006

Closed transventricular aortic valvotomy for critical aortic stenosis in neonates: outcomes, risk factors, and reoperations.

BACKGROUND: Critical aortic stenosis (AS) in neonates necessitates urgent intervention for patient survival. The optimal treatment, however, continues to be controversial and still has high morbidity and mortality in many centers. This study examined our late outcome, risks, and reoperations after the treatment of critical AS in neonates. METHODS: Sixty-six neonates (47 boys and 19 girls) underwent closed transventricular aortic valvotomy for critical AS between 1978 and 2000. The mean age at the first intervention was 15.1 +/- 19.6 days (range, 1 to 78). Their weight ranged from 1.4 to 6.2 kg (mean, 3.5 +/- 0.9 kg). Sixteen patients (23%) had isolated critical AS and normal or dilated left ventricles, and 50 neonates (77%) had associated cardiovascular anomalies (ie, aortic annular hypoplasia, hypoplasia of the left ventricle, mitral valve abnormalities, and endocardial fibroelastosis, coarctation, or interruption of aorta). RESULTS: The hospital mortality was 29% (19 of 66). Kaplan-Meier 5- and 15-year survival was 61% and 58%, respectively. The operative mortality rates were 6% in neonates with isolated AS and 36% in patients with complex AS. The five risk factors significant for mortality on univariate analysis were (1) presence of endocardial fibroelastosis (p = 0.05), (2) presence of hypoplastic left ventricle (p = 0.003), (3) presence of associated cardiovascular anomalies (p = 0.04), (4) aortic valve annulus of less than 5.0 mm (p = 0.01), and (5) surgery before 1985 (p = 0.003). Of these five factors, only the presence of hypoplastic left ventricle (p = 0.001) and surgery before 1985 (p = 0.001) remain significant for mortality by multivariate analysis. At last follow-up (mean, 8.2 +/- 6.2 years), 36 of 47 of the long-term survivors were in New York Heart Association functional class I and II. Kaplan-Meier analysis showed 5- and 15-year freedom from aortic valve reoperation to be 83% and 60%, respectively. Univariate and multivariate analysis showed the presence of multilevel stenosis (p = 0.04) as the best preoperative predictor for the need for late reoperation in survivors. CONCLUSIONS: We conclude that critical AS in neonates continues to be associated with significant mortality. Reintervention such as surgical and balloon valvotomy are usually required within 10 years of initial surgery.

Alprostadil↗

PubMed1989

Relationships between renin, aldosterone, blood pressure and renal function in hypertensive insulin-dependent diabetes mellitus.

A cross-sectional analysis of associations between total plasma renin (TPR) and aldosterone, blood pressure, renal haemodynamics, autonomic function and electrolyte balance was carried out in 35 hypertensive non-azotaemic insulin-dependent diabetics. Supine TPR was increased in 10 subjects and reduced in one, although erect TPR was increased in nine but reduced in 18 subjects. The supine to erect TPR gradient was greater than 40% in all cases. Supine and erect TPR correlated closely (r = 0.99, P less than 0.001). No correlation was found between TPR and age or blood pressure and multiple regression analysis failed to reveal independent predictors for TPR. Supine aldosterone was reduced in two subjects and increased in three, and erect aldosterone levels were reduced in three but increased in eight subjects. However, the postural aldosterone gradient was greater than 40% in only 20 cases. Supine and erect aldosterone correlated with each other (rs = 0.64, P = 0.001) but not with TPR. Aldosterone levels were most strongly related inversely to duration of diabetes, diabetic retinopathy, parasympathetic neuropathy and directly to diastolic blood pressure and glomerular filtration rate. Aldosterone levels correlated negatively with age. This was corrected for in multiple regression analysis which revealed an inverse relationship between supine aldosterone and serum potassium (P less than 0.05) and a direct one with renal plasma flow (P less than 0.007). Erect aldosterone was independently associated with duration of diabetes (P less than 0.005), systolic postural gradient (P less than 0.02), and the postural aldosterone gradient with the presence of parasympathetic neuropathy (P less than 0.004). The observation of elevated TPR in 10 subjects and the lack of relationship between TPR and other variables may reflect the overproduction of inactive relative to active renin in insulin-dependent hypertensive diabetics with autonomic dysfunction. The association between aldosterone and blood pressure, renal haemodynamics and electrolyte balance suggests that mineralocorticoids may be relevant to the natural history of hypertensive diabetic renal disease.

Adult↗

PubMed2006

Dynamic evolution of the human immunodeficiency virus type 1 pathogenic factor, Nef.

The human immunodeficiency virus type 1 (HIV-1) early gene product Nef is a multifunctional protein that alters numerous pathways of T-cell function, including endocytosis, signal transduction, vesicular trafficking, and immune modulation, and is a major determinant of pathogenesis. Individual Nef functions include PAK-2 activation, CD4 downregulation, major histocompatibility complex (MHC) class I downregulation, and enhancement of viral particle infectivity. How Nef accomplishes its multiple tasks presents a difficult problem of mechanistic analysis because of the complications associated with multiple, overlapping functional domains in the context of significant sequence variability. To address these issues we determined the conservation of each Nef residue based on 1,643 subtype B Nef sequences. Mutational analysis based on conservative substitutions and Nef sequence data allowed us to search for amino acids on the surface of Nef that are specifically required for PAK-2 activation. We found residues 85, 89, and 191 to be highly significant determinants for Nef's PAK-2 activation function but functionally unlinked to CD4 and MHC class I downregulation or enhancement of infectivity. These residues are not conserved across HIV-1 subtypes but are confined to separate sets of surface elements within a subtype. Thus, L85/H89/F191 and F85/F89/R191 are dominant in subtype B and subtype E or C, respectively. Our results provide support for developing subtype-specific interventions in HIV-1 disease.

Amino Acid Sequence↗