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PubMedDate not supplied

Basic strategies of the immune system in the regulation of antibody response.

Three major regulatory mechanisms operating in the control of antibody response have been examined: 1. antibody feedback; 2. T cell regulation (I. regulatory interactions among T cell subsets, II. H-2 linked Ir gene control of T cell function, III. regulatory role of antigenic epitopes in T cell subsets induction); 3. idiotypic network. Analysis of the results of obtained in the lysozyme system together with available data in the literature have permitted the delineation of a model of antigen-triggered events involved in the regulation of antibody response. The basic feature of the proposed model is the integration of two major specific communication systems among lymphocytes engaged in the antibody response: antigen bridge and idiotypic complementarity.

Animals↗

PubMed2003

Enhancing accuracy of magnetic resonance image fusion by defining a volume of interest.

We compared the registration accuracy for corresponding anatomical landmarks in two MR images after fusing the complete volume (CV) and a defined volume of interest (VOI) of both MRI data sets. We carried out contrast-enhanced T1-weighted gradient-echo and T2-weighted fast spin-echo MRI (matrix 256 x 256) in 39 cases. The CV and a defined VOI data set were each fused using prototype software. We measured and analysed the distance between 25 anatomical landmarks in predefined areas identified at levels L(1)-L(5) corresponding to defined axial sections. Fusion technique, landmark areas and level of fusion were further processed using a feed-forward neural network to calculate the difference which can be expected based on the measurements. We identified 975 landmarks for both T1- and T2-weighted images and found a significant difference in registration accuracy ( P<0.01) for all landmarks between CV (1.6+/-1.2 mm) and VOI (0.7+/-1.0 mm). From cranial (L(1)) to caudal (L(5)), mean deviations were: L(1) CV 1.5 mm, VOI 0.5 mm; L(2) CV 1.8 mm, VOI 0.4 mm; L(3) CV 1.7 mm, VOI 0.4 mm; L(4) CV 1.6 mm, VOI 0.6 mm; and L(5) CV 1.6 mm, VOI 1.6 mm. Neural network analysis predicted a higher accuracy for VOI (0.05-0.15 mm) than for CV fusion (0.9-1.6 mm). Deviations due to magnetic susceptibility changes between air and tissue seen on gradient-echo images can decrease fusion accuracy. Our VOI fusion technique improves image fusion accuracy to <0.5 mm by excluding areas with marked susceptibility changes.

Algorithms↗

PubMed2001

Ancient mitochondrial DNA reveals the origin of Sus scrofa from Rebun Island, Japan.

The Kabukai A site (5 to 8C A.D.) of the Okhotsk cultural area is on Rebun Island, a small island near the coast, north-northwest of Hokkaido, Japan. Specimens of Sus scrofa, called the Sakhalin pig, were discovered in five cultural layers at the Kabukai A site. Ancient DNA was extracted from the remains of 42 Sakhalin pig bones. Thirty-nine nucleotide sequences of the 574-bp mitochondrial DNA control region, estimated to have originated from at least 21 individuals, were amplified and analyzed phylogenetically. Nine distinct haplotypes (A1, A2, A3, B1, B2, C1, C2, D1, and D2) from this site were classified into four haplotype groups (A, B, C, and D) by parsimonious network analysis. Phylogenetic analysis of 9 ancient and 55 modern haplotypes indicated that the population of Sakhalin pigs at the Kabukai A site belonged to two distinct clusters; haplotype groups A and B formed a cluster comprised only of themselves, and haplotype groups C and D belonged to the cluster of one of the two genetic groups of Japanese wild boars uniquely distributed in the western part of Japan, including one northeast Mongolian wild boar. Analysis of the haplotype distribution among three archaeological sites and their historical transitions among the five layers reflecting the cultural periods at the Kabukai A site suggests that the Sakhalin pig populations were introduced from Sakhalin island and the Amur River basin in the northeastern Eurasian continent together with some cultural influences.

Animals↗

PubMed2000

Structure prediction of the dimeric neu/ErbB-2 transmembrane domain from multi-nanosecond molecular dynamics simulations.

Dimerization of the neu/ErbB-2 receptor tyrosine kinase is a necessary but not a sufficient step for signaling. Despite the efforts expended to identify the molecular interactions responsible for receptor-receptor contacts and particularly those involving the transmembrane domain, structural details are still unknown. In this work, molecular dynamics simulations of the helical transmembrane domain (TM) of neu and ErbB-2 receptors are used to predict their dimer structure both in the wild and oncogenic forms. A global conformational search method, applied to define the best orientations of parallel helices, showed an energetically favorable configuration with the specific mutation site within the interface, common for both the nontransforming and the transforming neu/ErbB-2 TM dimers. Starting from this configuration, a total of 10 simulations, about 1.4 ns each, performed in vacuum, without any constraints, show that the two helices preferentially wrap in left-handed interactions with a packing angle at about 20 degrees. The resulting structures are nonsymmetric and the hydrogen bond network analysis shows that helices experience pi local distortions that facilitate inter-helix hydrogen bond interactions and may result in a change in the helix packing, leading to a symmetric interface. For the mutated sequences, we show that the Glu side chain interacts directly with its cognate or with carbonyl groups of the facing backbone. We show that the connectivity between interfacial residues conforms to the knobs-into-holes packing mode of transmembrane helices. The dimeric interface described in our models is discussed with respect to mutagenesis studies.

Amino Acid Sequence↗

PubMed2002

Retinal nerve fiber layer measurements using laser scanning polarimetry in different stages of glaucomatous optic nerve damage.

PURPOSE: To evaluate the diagnostic value of polarimetric measurements of the retinal nerve fiber layer (RNFL) thickness in different stages of glaucomatous optic nerve damage. METHODS: The study included 92 eyes of 46 controls (age 41.0+/-13.7 years) and a heterogeneous group of 232 eyes of 135 patients with different stages of glaucomatous optic nerve damage (age 54.0+/-10.2 years; 68 patients with primary open-angle glaucoma, 56 with normal-pressure glaucoma and 11 patients with secondary glaucoma due to primary dispersion syndrome or pseudoexfoliation syndrome). All control subjects and patients underwent complete ophthalmological examinations including scanning laser polarimetry of the RNFL using the GDx (Laser Diagnostic Technologies, San Diego, Calif.) and 15 degrees color stereo optic disc photographs. Only subjects and patients with disc area less than 3.4 mm(2) were included in the study. The total glaucoma group were divided into four subgroups according to the morphological criteria of the neuroretinal rim. RESULTS: The stage of morphological glaucomatous optic nerve damage was classified as follows: stage 0: n=92, stage 1: n=103, stage 2: n=65, stage 3: n=40, and stage 4: n=19. Differences in mean polarimetric retardation between controls and eyes with glaucoma were significant for all parameters except the variable symmetry. The most significant differences between controls and eyes with glaucomatous optic nerve damage were found with the "number" variable assigned by the neural network analysis ( P<0.001). With increasing stage of glaucomatous optic nerve damage, separation of the variable "the number" increased significantly. At a predetermined specificity of 90% the sensitivity of the groups with different stages of morphological glaucomatous optic nerve damage increased from 32% for stage 1 to 90% for stage 4. CONCLUSION: Polarimetric measurement of the RNFL thickness is significantly associated with morphological glaucomatous optic nerve damage. The fast performance, easy handling, and low cost of RNFL polarimetry mean that it can be included in the routine examination of glaucoma patients. Further study and refinement of this technique are indicated to improve its usefulness in both clinical diagnosis and in population-based case identification.

Adult↗

PubMed2006

Does the mitochondrial genome play a role in the etiology of Alzheimer's disease?

We report here the analyses of complete mtDNA coding region sequences from more than 270 Alzheimer's disease (AD) patients and normal controls to determine if inherited mtDNA mutations contribute to the etiology of AD. The AD patients and normal individuals were carefully screened and drawn from two populations of European descent in an effort to avoid spurious effects due to local population anomalies. Overall, there were no significant haplogroup associations in the combined AD and normal control sequence sets. Reduced median network analysis revealed that the AD mtDNA sequences contained a higher number of substitutions in tRNA genes, and that there was an elevated frequency of replacement substitutions in the complex I genes of the control sequences. Analysis of the replacement substitutions indicated that those arising in the AD mtDNAs were no more deleterious, on average, than those in the control mtDNAs. The only evidence for the synergistic action of mutations was the presence of both a rare non-conservative replacement substitution and a tRNA mutation in 2 AD mtDNAs, from a total of 145, whereas such a combination of mutations was not observed in the control sequences. Overall, the results reported here indicate that pathogenic inherited mtDNA mutations do not constitute a major etiological factor in sporadic AD. At most, a small proportion of AD patients carry a pathogenic mtDNA mutation and a small proportion of cognitively normal aged individuals carry a mtDNA mutation that reduces the risk of AD.

Aged, 80 and over↗

PubMed2005

Getting the big picture in community science: methods that capture context.

Community science has a rich tradition of using theories and research designs that are consistent with its core value of contextualism. However, a survey of empirical articles published in the American Journal of Community Psychology shows that community scientists utilize a narrow range of statistical tools that are not well suited to assess contextual data. Multilevel modeling, geographic information systems (GIS), social network analysis, and cluster analysis are recommended as useful tools to address contextual questions in community science. An argument for increased methodological consilience is presented, where community scientists are encouraged to adopt statistical methodology that is capable of modeling a greater proportion of the data than is typical with traditional methods.

Cluster Analysis↗

PubMed2026

APOM-associated inflammation and apoptosis in stroke-exacerbated myocardial infarction: implications for brain-heart interactions.

Brain-heart syndrome (BHS) describes cardiac dysfunction secondary to central nervous system injury, with acute ischemic stroke (AIS) serving as a critical driver that exacerbates myocardial infarction (MI). This study aimed to elucidate the role of Apolipoprotein M (APOM) in stroke-aggravated MI and to explore its underlying systemic and molecular mechanisms. Clinical data were analyzed to evaluate the correlation between stroke and MI. A combined mouse model of middle cerebral artery occlusion (MCAO) and MI was established to assess neurological and cardiac injury. Quantitative proteomics and Weighted Gene Co-expression Network Analysis (WGCNA) were employed to screen key differentially expressed proteins. The role of APOM in myocardial injury was validated using APOM-knockout (KO) mice. Furthermore, nuclear-cytoplasmic fractionation, immunofluorescence, and Western blot were performed to investigate its effects on the Saa1 and NF-κB signaling, NLRP3-related inflammatory signaling pathway, and lipid metabolism pathways. Clinical analysis indicated that stroke is a significant risk factor for MI (OR = 4.5). In the mouse model, MCAO significantly exacerbated post-MI electrocardiographic abnormalities, myocardial inflammatory response, while elevating circulating levels of cTnT and IL-1β. Proteomics identified a significant downregulation of APOM in the heart, brain, and serum post-stroke, a trend consistent with observations in AIS patients. Further experiments revealed that APOM deficiency markedly worsened cardiac conduction disturbances, histological damage, and inflammatory responses in MI mice. Mechanistically, the loss of APOM upregulates the acute-phase protein Saa1, triggers NF-κB phosphorylation and nuclear translocation, and enhances inflammatory signaling related to inflammasomes, while simultaneously mediating cytokine release from cardiomyocytes. Concurrently, APOM deficiency led to a significant decrease in sphingosine-1-phosphate (S1P) and also caused myocardial lipid droplet accumulation and metabolite changes. Additionally, the loss of APOM increased the expression of D-dimer and fibrinogen family proteins. Our findings suggest that APOM is a potential cardioprotective agent post-AIS. Downregulation of APOM may exacerbate myocardial injury after MI by elevating Saa1 expression, activating the NF-κB pathway and the inflammasome-mediated signaling, and inducing lipid metabolic disorders and coagulation-associated alterations. APOM may represent a potential therapeutic target for the intervention of brain-heart syndrome.

Animals↗

PubMed2005

Social networks and community prevention coalitions.

This study investigates the links between community readiness and the social networks among participants in Communities That Care (CTC), community-based prevention coalitions. The coalitions targeted adolescent behavior problems through community risk factor assessments, prioritization of risk factors, and selection/implementation of corresponding evidence-based family, school, and community programs. Key leaders (n = 219) in 23 new CTC sites completed questionnaires focusing on community readiness to implement CTC and the respondents' personal, work, and social organization links to other key leaders in the community. Outside technical assistants also completed ratings of each community's readiness and early CTC functioning. Measures of network cohesion/integration were positively associated with readiness, while centralization was negatively associated. These results suggest that non-centralized networks in which ties between members are close and direct may be an indicator of community readiness. In addition, we found different associations between readiness and different domains of social relations. EDITORS' STRATEGIC IMPLICATIONS: The authors present the promising practice of using social network analysis to characterize the functioning of local prevention coalitions and their readiness to implement a community-based prevention initiative. Researchers and community planners will benefit from the lessons in this article, which capitalizes on a large sample and multiple informants. This work raises interesting questions about how to combine the promotion of coalition functioning while simultaneously encouraging diversity of coalition membership.

Adolescent↗

PubMed2026

MYBL2 promotes malignant phenotypes and M2-like macrophage polarization through CCL2 in non-small cell lung cancer.

Hub genes associated with non-small cell lung cancer (NSCLC) were identified through bioinformatics screening. In vitro experiments analyzed the potential mechanisms by which these genes regulate tumor malignant phenotypes and macrophage polarization. Differentially expressed genes were identified from The Cancer Genome Atlas (TCGA)-NSCLC and GSE32175 datasets, followed by protein-protein interaction (PPI) network analysis to screen hub genes. The effects of MYB Proto-Oncogene Like 2 (MYBL2) on NSCLC progression and macrophage polarization were evaluated using in vitro models. The regulatory relationship between MYBL2 and C-C motif chemokine ligand 2 (CCL2) was investigated by Chromatin immunoprecipitation (ChIP) and dual-luciferase reporter assays, and rescue experiments were performed to validate the role of the MYBL2-CCL2 axis. Bioinformatics screening identified BUB1B, CDCA2 and MYBL2 as key hub genes with high expression in NSCLC, among which MYBL2 was significantly upregulated in NSCLC cells. Functional experiments confirmed that MYBL2 silencing markedly inhibited the malignant proliferation, migration and invasion of NSCLC cells. Tumor cell MYBL2 knockdown effectively reversed M2-like polarization and promoted M1-like polarization in the co-culture system. Mechanistically, MYBL2 directly bound to the CCL2 promoter region to enhance CCL2 transcriptional activity and upregulate CCL2 expression in NSCLC cells. Exogenous CCL2 supplementation significantly rescued the inhibitory effect of MYBL2 knockdown on macrophage M2-like polarization, verifying the mediating role of CCL2 in this regulatory axis. MYBL2 is strongly expressed in NSCLC cells and is associated with enhanced malignant phenotypes. It may affect macrophage M2-like polarization by upregulating CCL2, thus participating in NSCLC immune microenvironment remodeling.

CCL2↗

PubMed1984

A phenomenological interpretation of the frequency-dependent impedance behaviour of bovine dental enamel.

The permeability of dental enamel can be estimated by means of diffusion measurements with radio-isotopes. Because of the low intrinsic permeability of enamel membranes, determination via this route may take two weeks. A much faster electrochemical method is presented, in which the real and imaginary part of the membrane impedance are measured at discrete intervals in the frequency-range 1 Hz-1 MHz. Using the principles of network-analysis, a phenomenological interpretation of these electrochemical data in terms of a 6-parameter model is given. The model contains R0, the intrinsic membrane resistance, R infinity, the residual membrane resistance and the four parameters, necessary to describe the postulated enamel diffusion impedance, which bears strong resemblance to the Warburg impedance. Starting from this model, optimal estimates (with standard-errors) of a membrane's R0 and vmax (the log of the frequency where the imaginary part of the membrane impedance is maximal) were derived. These parameters were predictors of the permeability of enamel.

Animals↗

PubMed1976

The growth of the dendritic trees of Purkinje cells in the cerebellum of the rat.

The growth of Purkinje cell dendritic trees in the cerebellum of the rat was studied over the first 50 days of life, using the technique of network analysis and the Golgi-Cox impregnation method. Our findings showed that a growth spurt occurred from the 10th to 30th day post partum (pp) and involved the production of a massive number of branches of fairly constant length. Growth of the tree occurred firstly in the lateral domain, so that by 15 days pp most trees were of adult width. Thereafter, increases in height occurred until 30 days pp. Associated with this change in direction of growth, from the mainly transverse to the vertical plane, was a deviation from the normal random pattern of branching of the tree, but this was reestablished when reorientation was complete, and growth in the vertical plane underway. The lengths of proximal segments increased once they had become established, but distal branches probably maintained a constant length. The above results, together with changes in segment length, trichotomy, branching probability, and growth cone morphology during development have been discussed in relation to current concepts of dendritic growth.

Age Factors↗

PubMed1976

The effects of reduced climbing and parallel fibre input on Purkinje cell dendritic growth.

The effects of afferent fibre depletion on the development of the dendritic trees of Purkinje cells in the cerbellum were investigated. Parallel fibres were reduced by postnatal administration of a schedule of low level X-irradiation. Climbing fibers were prevented from innervating the cerebellum by lesioning the olivo-cerebellar tract. Network analysis was performed on Purkinje cells in Golgi-Cox preparations of the vermis of 30-day-old animals. tin the irradiated cerebella Purkinje cells with a 'weeping willow' type morphology predominated. Purkinje cells devoid of their climbing fibre contact exhibited large spines on their main dendritic trunks. In both experimental situations the size of the dendritic tree was reduced. This diminution was the result of a decrease in the total number of dendritic segemnts. Individual segment lengths were largely unalteral. Topological type analysis revealed that the trees had arisen in a manner indistinguishable from terminal dichotomous branching and that the 'weep-willow' pattern was produced by a deviation of branching from a purely random form. The interaction of intrinsic and extrinsic factors in the formation of segments and on the nature of branching were discussed.

Animals↗

PubMed1976

The growth of the dendritic trees of Purkinje cells in irradiated agranular cerebellar cortex.

The heads of noenatal Wistar rats were irradiated with 200 rads daily from birth to the 10th day post-partum. Ten litters each containing 5 animals were killed at 30 days post-partum and their brains treated by the Golgi-Cox technique. The dendritic trees of 24 Purkinje cells were analysed using the quantitative technique of network analysis, and comparisons made between parameters obtained from 20 normal Purkinje cells. All dendritic trees in agranular irradiated cortex were markedly reduced in size (as indicated by total dendritic length and total number of segments) although mean path lengths were normal. Segment lengths were normal over proximal branches, but uniformly increased over distal branches. Abnormal appendages, called 'giant spines' were observed on many dendrites. They were often some 10 mum in length and their presence effectively reduced segment lengths, increased the frequency of trichotomy and deviated growth from the normal random terminal pattern so that long collateral branching topologies were formed. Nevertheless, trichotomy was uniformly reduced in those trees without 'giant spines' and the distribution of branching patterns suggested that growth had proceeded by random terminal dichotomy. These results demonstrate that the development of dendritic trees is retarded in the agranular irradiated cerebellum, where synaptogenesis is very greatly reduced below normal. The quantitative changes in segment lengths, size of trees, and trichotomy accord with those predicted by the filopodial synaptogenic hypothesis of dendritic growth formulated by Vaughn et al. 99, whilst the results of the topological analysis suggest that branching is established by a degree of non-random interaction between growing dendrites and their substrate. 'Claw-like' dendritic complexes within some Purkinje cell trees may have been induced by aberrent fibre bundles of few surviving granule cells.

Animals↗

PubMed1982

Involvement of spectrin in the maintenance of phase-state asymmetry in the erythrocyte membrane.

The fluorescent probe merocyanine 540 does not stain the plasma membrane of normal human or murine erythrocytes, nor of genetically abnormal human spherocytic erythrocytes. It does, however, stain erythrocyte membranes in several systems in which the underlying spectrin network is altered or missing. Because of the greater affinity of merocyanine 540 for fluid--phase lipid bilayers, these results suggest that the external leaflet of erythrocyte membranes becomes more disordered upon alteration or loss of the internal spectrin network. Analysis of the transbilayer arrangement of membrane phospholipids by digestion with phospholipase A2 suggests that lipid compositional asymmetry of the erythrocyte membrane is responsible for a phase-state asymmetry between the two lipid leaflets, and that spectrin is required to maintain this asymmetry and the gel-like state of the external leaflet.

Animals↗

PubMed1992

A computer model of the kidney.

We developed a computer model of renal function that factors perfusion pressure, serum sodium, potassium, antidiuretic hormone and aldosterone concentrations to derive urine output, urinary sodium and urinary potassium excretion. The model implements Uttamsingh's (Uttamsingh, R.J., et al. Mathematical model of the human renal system. Med. Biol. Eng. Comput. 23 (1985) 525-536) analytical equations as an electrical circuit suitable for network analysis. This model is useful for studying the effects of renal blood flow and the humoral milieu on renal function in normal kidneys either as a stand-alone unit or in combination with other physiological electrical models.

Computer Simulation↗

PubMedDate not supplied

Variability in cigarette smoking within and between adolescent friendship cliques.

Research has consistently shown that adolescent smoking is related to friends' smoking, yet smoking in the context of adolescent peer groups (friendship cliques) has been little studied. Formal network analysis was used to identify 87 adolescent friendship cliques in a sample of 1,092 ninth graders at five schools. There was intraclique homogeneity and interclique heterogeneity in current cigarette smoking, confirming that smokers tend to be in cliques with smokers and nonsmokers tend to be with nonsmokers. Most cliques were comprised entirely or mostly of nonsmokers, suggesting that friendship cliques may contribute more to the maintenance of nonsmoking than to the onset and maintenance of smoking. Prevention and research implications are discussed.

Adolescent↗

PubMed1994

Current perspectives on AIDS/HIV education and counseling.

This whole issue of Patient Education and Counseling is devoted to current perspectives on AIDS/HIV education and counseling. The results of 15 completed empirical studies and empirically-based reviews are described, highlighting the central role of education and counseling in research and clinical practice in the AIDS/HIV arena in the USA, UK, Australia, The Netherlands, and Israel. The articles concern: readability of educational materials, format of informed consent, participation of drug users in HIV-testing, measurement of condom use, safe sex among the young and non-monogamous, sexual network analysis, high-risk sexual behavior among gay men, prostitution, public reactions towards people with AIDS, teachers' attitudes towards AIDS, measurement of mental adjustment to AIDS, influencing quality of life by counseling, satisfaction with HIV counseling, the influence of psychosocial factors on the course of HIV infection, and a report on the recently held 10th International Conference on AIDS.

Counseling↗