Showing papers by "National Institutes of Health published in 1996"
TL;DR: The short variant of the polymorphism reduces the transcriptional efficiency of the 5-HTT gene promoter, resulting in decreased 5HTT expression and 5HT uptake in lymphoblasts as discussed by the authors, which is the site of action of widely used uptake-inhibiting antidepressant and antianxiety drugs.
Abstract: Transporter-facilitated uptake of serotonin (5-hydroxytryptamine or 5-HT) has been implicated in anxiety in humans and animal models and is the site of action of widely used uptake-inhibiting antidepressant and antianxiety drugs. Human 5-HT transporter (5-HTT) gene transcription is modulated by a common polymorphism in its upstream regulatory region. The short variant of the polymorphism reduces the transcriptional efficiency of the 5-HTT gene promoter, resulting in decreased 5-HTT expression and 5-HT uptake in lymphoblasts. Association studies in two independent samples totaling 505 individuals revealed that the 5-HTT polymorphism accounts for 3 to 4 percent of total variation and 7 to 9 percent of inherited variance in anxiety-related personality traits in individuals as well as sibships.
5,072 citations
TL;DR: The existence of subsets of CD4+ helper T lymphocytes that differ in their cytokine secretion patterns and effector functions provides a framework for understanding the heterogeneity of normal and pathological immune responses.
Abstract: The existence of subsets of CD4+ helper T lymphocytes that differ in their cytokine secretion patterns and effector functions provides a framework for understanding the heterogeneity of normal and pathological immune responses. Defining the cellular and molecular mechanisms of helper-T-cell differentiation should lead to rational strategies for manipulating immune responses for prophylaxis and therapy.
4,578 citations
TL;DR: A cofactor for HIV-1 (human immunodeficiency virus-type 1) fusion and entry was identified with the use of a novel functional complementary DNA (cDNA) cloning strategy that is a putative G protein-coupled receptor with seven transmembrane segments.
Abstract: A cofactor for HIV-1 (human immunodeficiency virus-type 1) fusion and entry was identified with the use of a novel functional complementary DNA (cDNA) cloning strategy. This protein, designated “fusin,” is a putative G protein-coupled receptor with seven transmembrane segments. Recombinant fusin enabled CD4-expressing nonhuman cell types to support HIV-1 Env-mediated cell fusion and HIV-1 infection. Antibodies to fusin blocked cell fusion and infection with normal CD4-positive human target cells. Fusin messenger RNA levels correlated with HIV-1 permissiveness in diverse human cell types. Fusin acted preferentially for T cell line-tropic isolates, in comparison to its activity with macrophage-tropic HIV-1 isolates.
4,231 citations
TL;DR: It is demonstrated that p300/CBP acetylates nucleosomes in concert with PCAF, a novel class of acetyltransferases in that it does not have the conserved motif found among various other acetyl transferases.
2,863 citations
TL;DR: Recombinant CC CKR5, a G protein-coupled receptor for these chemokines, rendered CD4-expressing nonhuman cells fusion-competent preferentially with macrophage-tropic Envs, and is thus a fusion cofactor for HIV-1 strains.
Abstract: Human immunodeficiency virus-type 1 (HIV-1) entry requires fusion cofactors on the CD4 + target cell. Fusin, a heterotrimeric GTP-binding protein (G protein)-coupled receptor, serves as a cofactor for T cell line-tropic isolates. The chemokines RANTES, MIP-1α, and MIP-1β, which suppress infection by macrophage-tropic isolates, selectively inhibited cell fusion mediated by the corresponding envelope glycoproteins (Envs). Recombinant CC CKR5, a G protein-coupled receptor for these chemokines, rendered CD4-expressing nonhuman cells fusion-competent preferentially with macrophage-tropic Envs. CC CKR5 messenger RNA was detected selectively in cell types susceptible to macrophage-tropic isolates. CC CKR5 is thus a fusion cofactor for macrophage-tropic HIV-1 strains.
2,767 citations
TL;DR: New indices calculated from the entire diffusion tensor are rotationally invariant (RI) and show that anisotropy is highly variable in different white matter regions depending on the degree of coherence of fiber tract directions.
Abstract: Indices of diffusion anisotropy calculated from diffusion coefficients acquired in two or three perpendicular directions are rotationally variant. In living monkey brain, these indices severely underestimate the degree of diffusion anisotropy. New indices calculated from the entire diffusion tensor are rotationally invariant (RI). They show that anisotropy is highly variable in different white matter regions depending on the degree of coherence of fiber tract directions. In structures with a regular, parallel fiber arrangement, water diffusivity in the direction parallel to the fibers (Dparallel approximately 1400-1800 x 10(-6) mm2/s) is almost 10 times higher than the average diffusivity in directions perpendicular to them (D + D)/2 [corrected] approximately 150-300 x 10(-6) mm2/s), and is almost three times higher than previously reported. In structures where the fiber pattern is less coherent (e.g., where fiber bundles merge), diffusion anisotropy is significantly reduced. However, RI anisotropy indices are still susceptible to noise contamination. Monte Carlo simulations show that these indices are statistically biased, particularly those requiring sorting of the eigenvalues of the diffusion tensor based on their magnitude. A new intervoxel anisotropy index is proposed that locally averages inner products between diffusion tensors in neighboring voxels. This "lattice" RI index has an acceptably low error variance and is less susceptible to bias than any other RI anisotropy index proposed to date.
2,504 citations
TL;DR: Criteria that support the diagnosis of progressive supranuclear palsy, and that exclude diseases often confused with PSP, are presented.
Abstract: To improve the specificity and sensitivity of the clinical diagnosis of progressive supranuclear palsy (PSP, Steele-Richardson-Olszewski syndrome), the National Institute of Neurological Disorders and Stroke (NINDS) and the Society for PSP, Inc. (SPSP) sponsored an international workshop to develop an accurate and universally accepted set of criteria for this disorder. The NINDS-SPSP criteria, which were formulated from an extensive review of the literature, comparison with other previously published sets of criteria, and the consensus of experts, were validated on a clinical data set from autopsy-confirmed cases of PSP. The criteria specify three degrees of diagnostic certainty: possible PSP, probable PSP, and definite PSP. Possible PSP requires the presence of a gradually progressive disorder with onset at age 40 or later, either vertical supranuclear gaze palsy or both slowing of vertical saccades and prominent postural instability with falls in the first year of onset, as well as no evidence of other diseases that could explain these features. Probable PSP requires vertical supranuclear gaze palsy, prominent postural instability, and falls in the first year of onset, as well as the other features of possible PSP. Definite PSP requires a history of probable or possible PSP and histopathologic evidence of typical PSP. Criteria that support the diagnosis of PSP, and that exclude diseases often confused with PSP, are presented. The criteria for probable PSP are highly specific, making them suitable for therapeutic, analytic epidemiologic, and biologic studies, but not very sensitive. The criteria for possible PSP are substantially sensitive, making them suitable for descriptive epidemiologic studies, but less specific. An appendix provides guidelines for diagnosing and monitoring clinical disability in PSP.
2,382 citations
TL;DR: In this paper, the intrinsic properties of water diffusion in normal human brain were assessed by using quantitative parameters derived from the diffusion tensor, D, which are insensitive to patient orientation and showed that diffusion appeared cylindrically symmetric.
Abstract: PURPOSE: To assess intrinsic properties of water diffusion in normal human brain by using quantitative parameters derived from the diffusion tensor, D, which are insensitive to patient orientation. MATERIALS AND METHODS: Maps of the principal diffusivities of D, of Trace(D), and of diffusion anisotropy indices were calculated in eight healthy adults from 31 multisection, interleaved echo-planar diffusion-weighted images acquired in about 25 minutes. RESULTS: No statistically significant differences in Trace(D) (approximately 2,100 x 10(-6) mm2/sec) were found within normal brain parenchyma, except in the cortex, where Trace(D) was higher. Diffusion anisotropy varied widely among different white matter regions, reflecting differences in fiber-tract architecture. In the corpus callosum and pyramidal tracts, the ratio of parallel to perpendicular diffusivities was approximately threefold higher than previously reported, and diffusion appeared cylindrically symmetric. However, in other white matter regions, p...
2,374 citations
TL;DR: The phosphorylation of MLC by Rho-kinase resulted in the facilitation of the actin activation of myosin ATPase, which may partly account for the mechanism by which Rho regulates cytokinesis, cell motility, or smooth muscle contraction.
2,017 citations
TL;DR: These revisions evolved as the guidelines were used in a systematic fashion in large clinical trials and with the experience following the use of newer, more effective agents, such as fludarabine.
1,940 citations
TL;DR: Whole-genome scanning by spectral karyotyping allowed instantaneous visualization of defined emission spectra for each human chromosome after fluorescence in situ hybridization, and all human chromosomes were simultaneously identified.
Abstract: The simultaneous and unequivocal discernment of all human chromosomes in different colors would be of significant clinical and biologic importance. Whole-genome scanning by spectral karyotyping allowed instantaneous visualization of defined emission spectra for each human chromosome after fluorescence in situ hybridization. By means of computer separation (classification) of spectra, spectrally overlapping chromosome-specific DNA probes could be resolved, and all human chromosomes were simultaneously identified.
TL;DR: These studies provide compelling support for the view that one mechanism by which these mutant PS1 cause AD is by increasing the extracellular concentration of Abeta peptides terminating at 42(43), species that foster Abeta deposition.
TL;DR: These findings define a single cell-surface receptor that regulates both matrix degradation and motility, thereby facilitating directed cellular invasion.
TL;DR: In this paper, a prospective multicenter study of pregnant women was conducted to measure the length of the cervix and documented the incidence of spontaneous preterm delivery before 35 weeks' gestation.
Abstract: Background The role of the cervix in the pathogenesis of premature delivery is controversial. In a prospective, multicenter study of pregnant women, we used vaginal ultrasonography to measure the length of the cervix; we also documented the incidence of spontaneous delivery before 35 weeks' gestation. Methods At 10 university-affiliated prenatal clinics, we performed vaginal ultrasonography at approximately 24 and 28 weeks of gestation in women with singleton pregnancies. We then assessed the relation between the length of the cervix and the risk of spontaneous preterm delivery. Results We examined 2915 women at approximately 24 weeks of gestation and 2531 of these women again at approximately 28 weeks. Spontaneous preterm delivery (at less than 35 weeks) occurred in 126 of the women (4.3 percent) examined at 24 weeks. The length of the cervix was normally distributed at 24 and 28 weeks (mean [+/- SD], 35.2 +/- 8.3 mm and 33.7 +/- 8.5 mm, respectively). The relative risk of preterm delivery increased as the length of the cervix decreased. When women with shorter cervixes at 24 weeks were compared with women with values above the 75th percentile, the relative risks of preterm delivery among the women with shorter cervixes were as follows: 1.98 for cervical lengths at or below the 75th percentile (40 mm), 2.35 for lengths at or below the 50th percentile (35 mm), 3.79 for lengths at or below the 25th percentile (30 mm), 6.19 for lengths at or below the 10th percentile (26 mm), 9.49 for lengths at or below the 5th percentile (22 mm), and 13.99 for lengths at or below the 1st percentile (13 mm) (P Conclusions The risk of spontaneous preterm delivery is increased in women who are found to have a short cervix by vaginal ultrasonography during pregnancy.
TL;DR: The DISC-2 is a reliable and economical tool for assessing child psychopathology and the 2.3 version of the instrument provides a significant improvement over earlier versions.
Abstract: Objective To describe the NIMH Diagnostic Interview Schedule for Children (DISC) Version 2.3 and to provide data on its performance characteristics in the Methods for the Epidemiology of Child and Adolescent Mental Disorders (MECA) Study. Method Data were collected on the DISC-2.3 at four sites on 1,285 randomly selected children, aged 9 through 17 years, and their parents. Two hundred forty-seven of these child–parent pairs were reassessed on the DISC-2.3 by a clinician interviewer, 1 to 3 weeks later. Results Administration time was approximately 1 hour and the interview was acceptable to more than 90% of subjects. The reliability of questions to parents assessing impairment and age of onset was generally good to acceptable for most diagnoses but was less satisfactory for the child interview. Using information from parent and child, the prevalence for any diagnosis ranged from 50.6 If no impairment criteria were required to 5.4 if a Global Assessment Scale score of 50 or less was necessary. The prevalence of anxiety disorders and enuresis was markedly reduced by requiring attributable impairment. Conclusions The DISC-2 is a reliable and economical tool for assessing child psychopathology. Reliability of the DISC-P-2.3 is superior to that of the child DISC for most diagnoses but is least good for anxiety disorders. The 2.3 version of the instrument provides a significant improvement over earlier versions.
TL;DR: A new cellular p300/CBP-associated factor (P/CAF) having intrinsic histone acetylase activity has been identified that competes with E1A, a new adenoviral oncoprotein that induces progression through the cell cycle by binding to the products of the p300 and retinoblastoma gene families.
Abstract: The adenoviral oncoprotein E1A induces progression through the cell cycle by binding to the products of the p300/CBP and retinoblastoma gene families. A new cellular p300/CBP-associated factor (P/CAF) having intrinsic histone acetylase activity has been identified that competes with E1A. Exogenous expression of P/CAF in HeLa cells inhibits cell-cycle progression and counteracts the mitogenic activity of E1A. E1A disturbs the normal cellular interaction between p300/CBP and its associated histone acetylase.
TL;DR: Atm-disrupted mice recapitulate the ataxia telangiectasia phenotype in humans, providing a mammalian model in which to study the pathophysiology of this pleiotropic disorder.
TL;DR: It is found that naming pictures of animals and tools was associated with bilateral activation of the ventral temporal lobes and Broca's area, and the brain regions active during object identification are dependent, in part, on the intrinsic properties of the object presented.
Abstract: An intriguing and puzzling consequence of damage to the human brain is selective loss of knowledge about a specific category of objects. One patient may be unable to identify or name living things, whereas another may have selective difficulty identifying man-made objects. To investigate the neural correlates of this remarkable dissociation, we used positron emission tomography to map regions of the normal brain that are associated with naming animals and tools. We found that naming pictures of animals and tools was associated with bilateral activation of the ventral temporal lobes and Broca's area. In addition, naming animals selectively activated the left medial occipital lobe--a region involved in the earliest stages of visual processing. In contrast, naming tools selectively activated a left premotor area also activated by imagined hand movements, and an area in the left middle temporal gyrus also activated by the generation of action words. Thus the brain regions active during object identification are dependent, in part, on the intrinsic properties of the object presented.
TL;DR: White matter findings were significantly associated with age, silent stroke, hypertension, FEV1, and income, and may not be considered benign because they are associated with impaired cognitive and lower extremity function.
Abstract: Background and Purpose Our aim was to identify potential risk factors for and clinical manifestations of white matter findings on cranial MRI in elderly people. Methods Medicare eligibility lists were used to obtain a representative sample of 5888 community-dwelling people aged 65 years or older. Correlates of white matter findings were sought among 3301 participants who underwent MRI scanning and denied a history of stroke or transient ischemic attack. Participants underwent extensive standardized evaluations at baseline and on follow-up, including standard questionnaires, physical examination, multiple blood tests, electrocardiogram, pulmonary function tests, carotid sonography, and M-mode echocardiography. Neuroradiologists graded white matter findings from 0 (none) to 9 (maximal) without clinical information. Results Many potential risk factors were related to the white matter grade, but in the multivariate model the factors significantly (all P<.01) and independently associated with increased grade w...
TL;DR: A significant increase in neutrophils and increased concentrations of tumor necrosis factor-alpha (TNF alpha) and interleukin-8 (IL-8) in the patients with COPD compared with the smoking and nonsmoking control subjects means that the cytokines TNF alpha and IL-8 may be involved in the inflammation in COPD.
Abstract: Asthma and chronic obstructive pulmonary disease are characterized by chronic airway inflammation. Studies using bronchoalveolar lavage (BAL) have shown an increased proportion of eosinophils in the BAL fluid from asthmatics compared with that from normal subjects, whereas studies of chronic obstructive pulmonary disease (COPD) have shown increased numbers of neutrophils. Induced sputum allows sampling of respiratory tract secretions from patients and control subjects, providing a noninvasive method of studying airway secretions and allowing characterization of cells and measurement of soluble markers. We investigated whether induced sputum was a useful method of studying airway fluid from patients with moderate to severe COPD and whether it could be used to compare inflammation in this condition with that in asthma. An initial reproducibility study was undertaken. Sputum was induced twice in 13 patients with severe COPD at a 14-d interval. Total and differential cell counts were carried out and were found to be reproducible over this period. Sputum was then induced in 14 patients with COPD, 23 patients with asthma, 12 healthy cigarette smokers, and 16 normal nonsmoking control subjects. We found a significant increase in neutrophils and increased concentrations of tumor necrosis factor-alpha (TNF alpha) and interleukin-8 (IL-8) in the patients with COPD compared with the smoking and nonsmoking control subjects. Interleukin-8, but not TNF alpha, was significantly higher in the COPD group than in the asthmatic group. We conclude that the cytokines TNF alpha and IL-8 may be involved in the inflammation in COPD.
TL;DR: An RNA virus, designated hepatitis G virus (HGV), was identified from the plasma of a patient with chronic hepatitis and extension from an immunoreactive complementary DNA clone yielded the entire genome, encoding a polyprotein of 2873 amino acids.
Abstract: An RNA virus, designated hepatitis G virus (HGV), was identified from the plasma of a patient with chronic hepatitis. Extension from an immunoreactive complementary DNA clone yielded the entire genome (9392 nucleotides) encoding a polyprotein of 2873 amino acids. The virus is closely related to GB virus C (GBV-C) and distantly related to hepatitis C virus, GBV-A, and GBV-B. HGV was associated with acute and chronic hepatitis. Persistent viremia was detected for up to 9 years in patients with hepatitis. The virus is transfusion-transmissible. It has a global distribution and is present within the volunteer blood donor population in the United States.
TL;DR: The TCP fits diagonally across the MHC peptide-binding site in a surface feature common to all class I and class II MHC molecules, providing evidence that the nature of binding is general.
Abstract: Recognition by a T-cell antigen receptor (TCR) of peptide complexed with a major histocompatibility complex (MHC) molecule occurs through variable loops in the TCR structure which bury almost all the available peptide and a much larger area of the MHC molecule. The TCR fits diagonally across the MHC peptide-binding site in a surface feature common to all class I and class II MHC molecules, providing evidence that the nature of binding is general. A broadly applicable binding mode has implications for the mechanism of repertoire selection and the magnitude of alloreactions.
TL;DR: It was clear, however, that features of the template in addition to the 3' terminal base also affect the fraction of product adenylated, and it proved difficult to identify a single sequence capable of protecting the products of all markers from non-templated addition of nucleotide.
Abstract: Taq DNA polymerase can catalyze non-templated addition of a nucleotide (principally adenosine) to the 3' end of PCR-amplified products. Recently, we showed that this activity, which is primer-specific, presents a potential source of error in genotyping studies based on the use of short tandem repeat (STR) markers. Furthermore, in reviewing our data, we found that non-templated nucleotide addition adjacent to a 3' terminal C is favored and that addition adjacent to a 3' terminal A is not. It was clear, however, that features of the template in addition to the 3' terminal base also affect the fraction of product adenylated. To define consensus sequences that promote or inhibit product adenylation, we transplanted sequences between the 5' ends of the reverse primers of markers that are adenylated and those of markers that are not adenylated. It proved difficult to identify a single sequence capable of protecting the products of all markers from non-templated addition of nucleotide. On the other hand, placing the sequence GTTTCTT on the 5' end of reverse primers resulted in nearly 100% adenylation of the 3' end of the forward strand. This modification or related ones (called "PIG-tailing") should facilitate accurate genotyping and efficient T/A cloning.
TL;DR: Because PPARα regulates the oxidative degradation of fatty acids and their derivatives, like this lipid mediator, a feedback mechanism is proposed that controls the duration of an inflammatory response and the clearance of leukotriene B4 in the liver.
Abstract: Inflammation is a local immune response to 'foreign' molecules, infection and injury. Leukotriene B4, a potent chemotactic agent that initiates, coordinates, sustains and amplifies the inflammatory response, is shown to be an activating ligand for the transcription factor PPARalpha. Because PPARalpha regulates the oxidative degradation of fatty acids and their derivatives, like this lipid mediator, a feedback mechanism is proposed that controls the duration of an inflammatory response and the clearance of leukotriene B4 in the liver. Thus PPARalpha offers a new route to the development of anti- or pro-inflammatory reagents.
TL;DR: Stat6-l- mice were deficient in IL-4-mediated functions including Th2 helper T-cell differentiation, expression of cell surface markers, and immunoglobulin class switching to IgE, indicating the lack of a non-redundant function in normal development.
Abstract: Signal transducers and activators of transcription (Stats) are activated by tyrosine phosphorylation in response to cytokines, and are thought to mediate many of their functional responses. Stat6 is activated in response to interleukin (IL)-4 and may contribute to various functions including mitogenesis, T-helper cell differentiation and immunoglobulin isotype switching. To evaluate the role of Stat6, we generated Stat6-null mice (Stat6 -/-) by gene disruption in embryonic stem cells. The mice were viable, indicating the lack of a non-redundant function in normal development. Although naive lymphoid cell development was normal, Stat6 -/- mice were deficient in IL-4-mediated functions including Th2 helper T-cell differentiation, expression of cell surface markers, and immunoglobulin class switching to IgE. In contrast, IL-4-mediated proliferation was only partly affected.
Eugenia E. Calle1, Clark W. Heath1, H. L. Miracle-McMahill1, R. J. Coates2 +185 more•Institutions (41)
TL;DR: Breast cancer and hormonal contraceptives: Collaborative reanalysis of individual data on 53297 women with breast cancer and 100239 women without breast cancer from 54 epidemiological studies as mentioned in this paper.
TL;DR: Insight is provided into mechanisms of MAPK regulation by H2O2 and ERK plays a critical role in cell survival following oxidant injury and is suggested to have a role for growth factor receptors in this activation.
Journal Article•
TL;DR: These studies provide strong evidence that the immunopathologic process characteristic of the two major forms of IBD is associated with very different cytokine secretion patterns, which may determine the type of inflammatory process present.
Abstract: In this study, we investigate whether human inflammatory bowel disease (IBD) (ulcerative colitis and Crohn's disease) is associated with altered lymphokine secretion profiles, as recently found in various animal models of chronic intestinal inflammation. In initial studies, we determined the proliferative responses of purified lamina propria (LP) CD4+ T cells from patients with IBD under defined conditions of T cell stimulation. We found that IBD LP CD4+ T cells in comparison with control LP CD4+ T cells have diminished TCR/CD3 pathway proliferative responses, whereas CD2/CD28 accessory pathway proliferative responses are relatively preserved. In further studies centering on lymphokine production, we showed that LP T cells from inflamed Crohn's disease mucosa manifest increased IFN-gamma secretion compared with control LP T cells, particularly when stimulated via the CD2/CD28 pathway. Subsequent ELISPOT analysis indicated that this was due to an increased number of IFN-gamma-secreting CD4+ T cells. In contrast, IL-4 and IL-5 production by Crohn's disease LP T cells was decreased compared with that of control LP T cells. Of interest, IL-2 production by Crohn's disease LP T cells was also reduced, as was IL-2 production by peripheral blood T cells. In parallel studies, LP T cells from inflamed ulcerative colitis mucosa stimulated via either the TCR/CD3/CD28 or CD2/CD28 produced increased amounts of IL-5, again when measured either as secreted IL-5 or by ELISPOT analysis. Such increased IL-5 production was not associated with increased IL-4 secretion and, in contrast to Crohn's disease, ulcerative colitis LP T cell production of IL-2 and IFN-gamma was normal. Taken together, these studies provide strong evidence that the immunopathologic process characteristic of the two major forms of IBD is associated with very different cytokine secretion patterns. These different patterns may determine the type of inflammatory process present.
TL;DR: This first comprehensive morphometric analysis is consistent with hypothesized dysfunction of right-sided prefrontal-striatal systems in ADHD.
Abstract: Background: Anatomic magnetic resonance imaging (MRI) studies of attention-deficit hyperactivity disorder (ADHD) have been limited by small samples or measurement of single brain regions. Since the neuropsychological deficits in ADHD implicate a network linking basal ganglia and frontal regions, 12 subcortical and cortical regions and their symmetries were measured to determine if these structures best distinguished ADHD. Method: Anatomic brain MRIs for 57 boys with ADHD and 55 healthy matched controls, aged 5 to 18 years, were obtained using a 1.5-T scanner with contiguous 2-mm sections. Volumetric measures of the cerebrum, caudate nucleus, putamen, globus pallidus, amygdala, hippocampus, temporal lobe, cerebellum; a measure of prefrontal cortex; and related right-left asymmetries were examined along with midsagittal area measures of the cerebellum and corpus callosum. Interrater reliabilities were.82 or greater for all MRI measures. Results: Subjects with ADHD had a 4.7% smaller total cerebral volume ( P =.02). Analysis of covariance for total cerebral volume demonstrated a significant loss of normal right>left asymmetry in the caudate ( P =.006), smaller right globus pallidus ( P =.005), smaller right anterior frontal region ( P =.02), smaller cerebellum ( P =.05), and reversal of normal lateral ventricular asymmetry ( P =.03) in the ADHD group. The normal age-related decrease in caudate volume was not seen, and increases in lateral ventricular volumes were significantly diminished in ADHD. Conclusion: This first comprehensive morphometric analysis is consistent with hypothesized dysfunction of right-sided prefrontal-striatal systems in ADHD.
TL;DR: Attractive inter-residue contact energies for proteins have been re-evaluated with the same assumptions and approximations used originally by us in 1985, but with a significantly larger set of protein crystal structures.