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Polymorphisms in the human X-linked pyruvate dehydrogenase E1 alpha gene.

Pyruvate dehydrogenase E1 alpha deficiency is an X-chromosome-linked disorder, often with fatal consequences. We have searched for genetically useful polymorphisms in or near this gene. No restriction fragment length polymorphisms were detected using a battery of 36 different restriction enzymes and probing with a full-length cDNA fragment, or two single-copy genomic fragments located within intron 8, and 15 kb 3' of the coding region, respectively. The chemical cleavage method was then applied to the detection of base changes in or near the gene. One polymorphism was found in exon 8 of the coding region. However, no base changes were detected in intron 3 or in the part of intron 8 covered by fragment gB2. Three blocks of microsatellite DNA containing variable numbers of CA-repeats were isolated from the 5' end of the gene and characterized. Length polymorphisms in these microsatellite DNAs were analysed using the polymerase chain reaction. Although the three loci are tightly linked, the polymorphisms appear not to be in disequilibrium, making them useful markers in linkage studies of the pyruvate dehydrogenase E1 alpha gene. Of 31 females analysed 12(39%) were heterozygous for at least one length polymorphism of the three (CA)n alleles.

Autoradiography↗

Germ line mutations of the HMGA2 gene are rare among the general population.

Proteins encoded by the HMGA family are architectural transcription factors, which induce conformational changes in the DNA and thus influence gene expression. Despite the obvious association of the expression of high mobility group protein genes with human cancer, very little is known about the variation of the HMGA proteins within human populations. Therefore, the coding regions of HMGA2 from 87 normal healthy donors were sequenced with the aim of detecting single nucleotide polymorphisms. There was only one sequence divergence leading to an amino acid change in coding regions of HMGA2. Thus, HMGA2 is not only well conserved between species but there is also a high intra-individual conservation of HMGA2, further supporting the important role of HMGA proteins in cellular processes. This analysis clearly demonstrates that as a rule, germ line mutations of HMGA2 are not the cause for benign tumors, e.g. uterine leiomyomas, or human malignant solid tumors.

Germ-Line Mutation↗

Conservation of alternative splicing and genomic organization of the myosin alkali light-chain (Mlc1) gene among Drosophila species.

The Mlc1 gene of Drosophila melanogaster encodes two MLC1 isoforms via developmentally regulated alternative pre-mRNA splicing. In larval muscle and tubular and abdominal muscles of adults, all of the six exons are included in the spliced mRNA, whereas, in the fibrillar indirect flight muscle of adult, exon 5 is excluded from the mRNA. We show that this tissue-specific pattern of alternative splicing of the Mlc1 pre-mRNA is conserved in D. simulans, D. pseudoobscura, and D. virilis. Isolation and sequencing of the Mlc1 genes from these three other Drosophila species have revealed that the overall organization of the genes is identical and that the genes have maintained a very high level of sequence identity within the coding region. Pairwise amino acid identities are 94%-99%, and there are no charge changes among the proteins. Total nucleotide divergence within the coding region of the four genes supports the accepted genealogy of these species, but the data indicate a significantly higher rate of amino acid replacement in the branch leading to D. pseudoobscura. A comparison of nucleotide substitutions in the coding portions of exon 5 and exon 6, which encode the alternative carboxyl termini of the two MLC1 isoforms, suggests that exon 5 is subject to greater evolutionary constraints than is exon 6. In addition to the coding sequences, there is significant sequence conservation within the 5' and 3' noncoding DNA and two of the introns, including one that flanks exon 5. These regions are candidates for cis-regulatory elements. Our results suggest that evolutionary constraints are acting on both the coding and noncoding sequences of the Mlc1 gene to maintain proper expression and function of the two MLC1 polypeptides.

Alternative Splicing↗

Body mass index in elementary school children, metropolitan area food prices and food outlet density.

OBJECTIVE: The aim of this study was to examine the association between food prices and food outlet density and changes in the body mass index (BMI) among elementary school children in the USA. METHODS: The Early Childhood Longitudinal Study followed a nationally representative sample of kindergarten children over 4 years. We merged individual-level data to (a) metropolitan data on food prices and (b) per capita number of restaurants, grocery stores and convenience stores in the child's home and school zip code. The dependent variables were BMI changes over 1 and 3 years. We analysed mean changes with least-squares regression, and median changes and 85th percentile changes with quantile regression. We controlled for baseline BMI, age, real family income and sociodemographic characteristics. RESULTS: Lower real prices for vegetables and fruits were found to predict a significantly lower gain in BMI between kindergarten and third grade; half of that effect was found between kindergarten and first grade. Lower meat prices had the opposite effect, although this effect was generally smaller in magnitude and was insignificant for BMI gain over 3 years. Differences across subgroups were not statistically significant due to smaller sample sizes in subgroup analyses, but the estimated effects were meaningfully larger for children in poverty, children already at risk for overweight or overweight in kindergarten, and Asian and Hispanic children. There were no significant effects for dairy or fast-food prices, nor for outlet density, once we had controlled for individual characteristics and random intercepts to adjust standard errors for the sampling design. DISCUSSION: The geographic variation in fruit and vegetable prices is large enough to explain a meaningful amount of the differential gain in BMI among elementary school children across metropolitan areas. However, as consumption information was not available, we cannot confirm that this is the actual pathway. We found no effects of food outlet density at the neighbourhood level, possibly because availability is not an issue in metropolitan areas.

Body Mass Index↗

Isolation of a mutant TOL plasmid with increased activity and transmissibility from Pseudomonas putida (arvilla) mt-2.

Strains with greater ability to dissimilate m-toluate were obtained from the wild-type Pseudomonas putida (arvilla) mt-2 that harbors the TOL plasmid. Increased growth of a mutant strain on aromatic substrates was coupled with simultaneous increase in the activity of metapyrocatechase, an enzyme coded by the TOL plasmid, without changing its catalytic properties. In the mutant and the wild-type strains, the inducer specificity and the induction kinetics of metapyrocatechase synthesis were the same, and a half-maximal effect of m-toluate on the enzyme synthesis was observed at 0.25 mM. Thus, the increased utilizability seen in a mutant strain appeared to be due to an increased quantity of the enzymes coded by the TOL plasmid. The properties of the mutant strain were dependent upon the mutation on the TOL plasmid but not on the chromosome mutation. Transfer experiments with a strain carrying the mutant TOL (TOL-H) or the wild-type TOL plasmid revealed that the TOL-H transfer was 1,000 times greater than that of the wild type.

Benzoates↗

Activity patterns assessed throughout 24-hour recordings in preterm and near term infants.

The motility of 10 low-risk infants, aged between 34 and 40 weeks of postmenstrual age, has been continuously recorded for 24 h. Four codes were distinguished: code 1 (absence of motility or occasional occurrence of startles), code 2 (presence of small general or isolated body movements, startles, smiles, grimaces, and other facial activity), code 3 (forceful and prolonged general movements, startles, and stretches), code 4 (vigorous and abrupt general body movements accompanied by crying). Changes with age concern mainly the increase of the duration of code 1 (quiescence) episodes. Confrontation between day and night showed higher levels of motility during the night than during the day. The last weeks before term represent a time for increase in the ability to sustain a quiet behavior and to reorganize day-night motility distribution.

Circadian Rhythm↗

Reduced antigenicity of the hepatitis B virus HBsAg protein arising as a consequence of sequence changes in the overlapping polymerase gene that are selected by lamivudine therapy.

The prevalence of hepatitis B virus vaccine escape mutants has increased as a consequence of the introduction of global vaccination programs. Furthermore and as a consequence of the organization of the genome of hepatitis B virus (HBV) into overlapping reading frames, the selection of polymerase mutants during long-term lamivudine therapy can select viruses with changes in the overlapping S gene coding for the hepatitis B small antigen (HBsAg). We have investigated the role of lamivudine in selecting HBV mutants with antigenically altered HBsAg protein using pooled human vaccine sera in enzyme immunosorbent assays and radioimmunoassays. HBsAg proteins containing the vaccine escape mutations G145R and D144E/G145R demonstrated markedly reduced binding to anti-HBs antibody. HBsAg mutants including E164D, W196S, I195M, M198I, and E164D/I195M (corresponding to the polymerase protein changes of V519L, M550I, L526M/M550V V553I, and V519L/L526M/M550V) selected during lamivudine treatment also demonstrated reduced binding to anti-HBs antibody. These findings raise the possibility of lamivudine-resistant mutants arising that possess antigenically distinct HBsAg proteins.

DNA-Directed DNA Polymerase↗

Understanding global transition assessments.

OBJECTIVE: Several methods currently used for determining meaningful or important change in health-related quality of life (HRQoL) measures are anchored by global transition items. It can be empirically demonstrated that patients' responses to these gold standards for change do not adequately incorporate the prior condition, yet these transition items play an influential role in patient-clinician communications and cannot be disregarded. This follow-up study queried patients to better understand how they ascertained their transition assessments. DATA SOURCE: Prior to their qualitative interviews, the 41 participants in this study had completed 1 year of enrollment in a clinical study with bi-monthly HRQoL telephone interviews that included the SF-36 and a disease-specific HRQoL instrument (asthma, COPD, or heart disease), as well as global transition assessments for each instruments domains. STUDY DESIGN: We used face-to-face cognitive interview and the think aloud approaches to obtain qualitative clues for understanding patient reports of HRQoL changes over time. Interview transcripts were coded using the four components of the Rapkin-Schwarz Appraisal Model: frame of reference; sampling strategy; standards of comparison; and combinatory algorithm. PRINCIPAL FINDINGS: Patients' explanations for determining global transition item responses often focused on current mobility and fatigue patterns, physicians' statements about their conditions, comparisons of their current states with the prior health conditions, and strong personal convictions that reflected a resistance to voicing any emotional changes. Patients also expressed primary health concerns, like back pain, that were not related to the chronic conditions (asthma, COPD or heart disease) under investigation. CONCLUSIONS: HRQoL studies and patient-clinician communications that incorporate global transition assessments to anchor the interpretations of HRQoL changes should also consider additional relevant questions to understand the process patients uses to appraise and report changes in HRQoL.

Aged↗

[Doppler sonographic monitoring control of perfusion of hepatocellular carcinoma after arterial chemoembolization].

INTRODUCTION: 22 patients with hepato-cellular carcinomas were examined sonographically before and after intra-arterial chemo-embolisation. The aim was to evaluate different techniques for judging tumour morphology and for assessing changes in perfusion. MATERIAL AND METHODS: The morphological appearances and perfusion changes were analysed by means of colour coded duplex sonography and power Doppler sonography before and after intravenous contrast medium. Pulsatility (Pl) and resistance index (RI) were used as quantitative parameters for judging changes in perfusion. RESULTS: In 13 patients intra-tumoral arteries were identified by duplex sonography and in four patients only by the power Doppler procedure. In three patients arterial vessels could only be identified after intravenous contrast. In 9 patients it was possible to document a reduction in arterial perfusion following embolisation. The indices calculated from these findings gave no prognostic indication. DISCUSSION: The methods described give information concerning changes in perfusion of a tumour following chemo-embolisation and, in conjunction with CT and clinical findings, provide indications for further tumour embolisation.

Antineoplastic Combined Chemotherapy Protocols↗

Estimating the influence of selection on the variable amino acid sites of the cytochrome B protein functional domains.

We evaluated the effects of selection on the molecular evolution of the functional domains of the mammalian cytochrome b gene as it relates to physicochemical properties shown to correlate with rates of amino acid replacement. Two groups of mammals were considered: pocket gophers of the rodent family Geomyidae, and cetaceans and ungulates of the monophyletic taxon Cetartopdactyla. Several characteristics of cytochrome b evolution were common to both mammal groups. The evolution of the matrix domain reflected the region's relative lack of function. Goodness of fit to neutral expectations indicated that external influences have had very little effect on the evolution of the matrix, although in some cases conservative and moderate changes have been favored. Although rates of synonymous nucleotide substitution have been relatively high, the transmembrane domain exhibited poor goodness of fit to neutral expectations. However, the evolution of the transmembrane domain has been constrained by negative selection, allowing a preponderance of conservative and moderate amino acid replacements. We hypothesize that a high rate of substitution is maintained in spite of negative selection because the codons of the transmembrane coding region are predisposed to conservative changes in all amino acid properties. The evolutionary patterns of the intermembrane domain in pocket gophers and cetartiodactyls, however, were very different. Changes inferred from the pocket gopher phylogenetic tree exhibited a significant fit to neutral expectations for each of the amino acid properties. Changes inferred from the cetartiodactyl tree exhibited significant fit to neutral expectations for polarity and isoelectric point, but not for composition, molecular volume, polar requirement, or hydropathy. In each case, lack of fit was due to selection that promoted conservative or moderate change, with the noteworthy exception of polar requirement. We detected an unexpectedly large change in polar requirement (from aspartic acid to threonine) in two separate lineages (Camelus bactrianus and all cetaceans) at amino acid position 159. This inferred change occurred in a region of the cyt-b protein that directly interacts with external surface proteins of the cytochrome bc(1) complex and resulted in a reversion to a more common character state in vertebrates.

Amino Acids↗

Mediating the gap between the white coat ceremony and the ethics and professionalism curriculum.

OBJECTIVE: Like many other medical schools, the University of California, Irvine annually conducts a White Coat ceremony in which incoming students take a professional oath of ethical conduct.(1) We report a new educational activity to connect the values expressed in the oath taken to the Ethics and Professionalism (EP) curriculum for first-year medical students(2) and its potential impact on physician training. DESCRIPTION: Following the White Coat ceremony, students participated in the Patient Doctor Society course that integrates diverse curricular topics centered on physician-patient communication. During this course, the students were introduced to EP content through a collaborative peer exercise. With the assistance of background readings on professional values and ethics concepts, small groups of students were asked to construct their own codes of ethics. The process of working in a group became part of the learning. After developing a code of ethics, each group was asked to identify primary values embodied in its code; primary obligations to patients and their families, other members of the health care team, and the community; key factors influencing code development; and likely effects of the code on the conduct of medical students and physicians. The goals of the session were to recognize formally both individual values and the values to which students commit themselves during the White Coat ceremony, to facilitate understanding of those values, and to begin to reconcile differences between personal and professional values. The small groups convened to report their findings in a three-hour session. Common values expressed by the students included patient autonomy, respect, beneficence, and professionalism. The delivery of quality health care, communication, education, and the equitable distribution of health care were among the most often listed obligations. The students reported that culture, societal values, family, experience, religion, education, and assigned readings were the key sources of the values in their codes. Most of the students enjoyed and learned from the exercise, believing that a code of ethics will serve as a helpful educational guide while they are students and as an action guide in their future practices. Student evaluations, narrative feedback, and faculty observation indicated that the students appreciated the opportunity to work in teams and to explore professional values. The students' most common suggestion for improvement involved incorporating analysis of clinical cases in which questions about professional values arise. DISCUSSION: Medical educators suggest that students' values and professional behaviors change throughout medical school, but such change is difficult to assess. The code-development exercise established a baseline of values at entry to medical school. We plan to track this cohort of students by reintroducing this exercise in their fourth year and will compare the codes developed in their first and fourth years to identify changes in values and to suggest what the students have learned about values during medical school. The comparison will be used to inform further development of the EP curriculum toward the goal of shaping and supporting the positive professional growth of our student-physicians.

California↗

Oligonucleotide microarray based detection of repetitive sequence changes.

Prior studies of oligonucleotide microarray-based mutational analysis have demonstrated excellent sensitivity and specificity except in circumstances where a frameshift mutation occurs in the context of a short repeated sequence. To further evaluate this circumstance, a series of nucleic acid samples having heterozygous mutations within repetitive BRCA1 sequence tracts was prepared and evaluated. These mutations included single nucleotide insertions and deletions in homopolymer runs, insertions and deletions of trinucleotide repeats, and duplications. Two-color comparative hybridization experiments were used wherein wild type reference and test targets are co-hybridized to microarrays designed to screen the entire BRCA1 coding sequence for all possible sequence changes. Mutations in simulated heterozygote samples were detected by observing relative losses of test target hybridization signal to select perfect match oligonucleotide probes. While heterozygous mutations could be readily distinguished above background noise in 9/19 cases, it was not possible to detect alterations in a poly dA/dT tract, small triplet repeat expansions, and a 10 bp direct repeat. Unexpectedly, samples containing (GAT)(3) triplet repeat expansions showed significantly higher affinity toward specific perfect match probes relative to their wild type counterparts. Therefore, markedly increased as well as decreased test sample hybridization to perfect match probes should be used to raise a suspicion of repetitive sequence changes.

Algorithms↗

Discrimination of vibrotactile frequencies in a delayed pair comparison task.

This study quantified human short-term-memory decay functions for delayed vibrotactile frequency discriminations. Subjects indicated which of two successive intervals contained the higher or lower frequency of a pair separated by delay periods of 0.5-30 sec. Performance decreased as a function of length of delay and was higher when delays were unfilled than when they were filled with a backwards-counting task. This interpolated task may have interfered with rehearsal of a coded representation of the remembered vibrotactile frequency. A change in decay rate after 5-sec delays suggests a switch from reliance on sensory memory to the coded frequency representation. Performance and decay rate depended on presentation order of higher or lower frequency within pairs. Reciprocal performance asymmetries seen in high-versus low-frequency ranges did not result from simple response bias.

Adult↗

Evolution of a simian immunodeficiency virus pathogen.

Analysis of disease induction by simian immunodeficiency viruses (SIV) in macaques was initially hampered by a lack of molecularly defined pathogenic strains. The first molecularly cloned SIV strains inoculated into macaques, SIVmacBK28 and SIVmacBK44 (hereafter designated BK28 and BK44, respectively), were cases in point, since they failed to induce disease within 1 year postinoculation in any inoculated animal. Here we report the natural history of infection with BK28 and BK44 in inoculated rhesus macaques and efforts to increase the pathogenicity of BK28 through genetic manipulation and in vivo passage. BK44 infection resulted in no disease in four animals infected for more than 7 years, whereas BK28 induced disease in less than half of animals monitored for up to 7 years. Elongation of the BK28 transmembrane protein (TM) coding sequence truncated by prior passage in human cells marginally increased pathogenicity, with two of four animals dying in the third year and one dying in the seventh year of infection. Modification of the BK28 long terminal repeat to include four consensus nuclear factor SP1 and two consensus NF-kappaB binding sites enhanced early virus replication without augmenting pathogenicity. In contrast, in vivo passage of BK28 from the first animal to die from immunodeficiency disease (1.5 years after infection) resulted in a consistently pathogenic strain and a 50% survival time of about 1.3 years, thus corresponding to one of the most pathogenic SIV strains identified to date. To determine whether the diverse viral quasispecies that evolved during in vivo passage was required for pathogenicity or whether a more virulent virus variant had evolved, we generated a molecular clone composed of the 3' half of the viral genome derived from the in vivo-passaged virus (H824) fused with the 5' half of the BK28 genome. Kinetics of disease induction with this cloned virus (BK28/H824) were similar to those with the in vivo-passaged virus, with four of five animals surviving less than 1.7 years. Thus, evolution of variants with enhanced pathogenicity can account for the increased pathogenicity of this SIV strain. The genetic changes responsible for this virulent transformation included at most 59 point mutations and 3 length-change mutations. The critical mutations were likely to have been multiple and dispersed, including elongation of the TM and Nef coding sequences; changes in RNA splice donor and acceptor sites, TATA box sites, and Sp1 sites; multiple changes in the V2 region of SU, including a consensus neutralization epitope; and five new N-linked glycosylation sites in SU.

Amino Acid Sequence↗

Nucleotide deletion and P addition in V(D)J recombination: a determinant role of the coding-end sequence.

During V(D)J recombination, the coding ends to be joined are extensively modified. Those modifications, termed coding-end processing, consist of removal and addition of various numbers of nucleotides. We previously showed in vivo that coding-end processing is specific for each coding end, suggesting that specific motifs in a coding-end sequence influence nucleotide deletion and P-region formation. In this study, we created a panel of recombination substrates containing actual immunoglobulin and T-cell receptor coding-end sequences and dissected the role of each motif by comparing its processing pattern with those of variants containing minimal nucleotide changes from the original sequence. Our results demonstrate the determinant role of specific sequence motifs on coding-end processing and also the importance of the context in which they are found. We show that minimal nucleotide changes in key positions of a coding-end sequence can result in dramatic changes in the processing pattern. We propose that each coding-end sequence dictates a unique hairpin structure, the result of a particular energy conformation between nucleotides organizing the loop and the stem, and that the interplay between this structure and specific sequence motifs influences the frequency and location of nicks which open the coding-end hairpin. These findings indicate that the sequences of the coding ends determine their own processing and have a profound impact on the development of the primary B- and T-cell repertoires.

Animals↗

Cell cycle-related proteins and flow cytometry.

Several nuclear and surface proteins are expressed in varying amounts in the different phases of the cell cycle. For some of them the coding gene is not known and changes in their expression could simply be secondary to changes in the proliferative activity of the population. Other proteins are oncogene products, probably having a direct regulatory function in cell proliferation, differentiation and malignant transformation. Studying these proteins may both permit a better understanding of the mechanisms regulating proliferation and differentiation and provide kinetic parameters for describing the cell cycle. Based on antibodies against these proteins, bivariate flow cytometry (FCM) is able to quantitate their expression simultaneously with DNA distribution. This allows protein expression to be related precisely with each cell cycle phase in populations having different proliferative activity. Further advantages of bivariate FCM are that few cells are required for the analysis and the percentage of cells expressing the (onco) gene product can be determined. Several cellular proteins have been investigated with bivariate FCM, and the data are reviewed. Some proteins not coded by oncogenes (such as cyclin, the Ki-67 reactive antigen and DNA polymerase alpha) are expressed in cycling, but not in G0 cells and are of special interest for the kineticist, since they could identify cells which are able to initiate DNA synthesis, i.e. those representing the "growth fraction" of the population. Statin, on the contrary, is apparently expressed only in G0 cells. The expression of some proteins coded by oncogenes, such as p53 and the c-myc product is high in proliferating G1 cells and decreases with differentiation. The expression of the c-ras product is not strictly related to cell cycle phases and increases with differentiation. Technical improvements (allowing, for example, the monitoring of the changes in protein expression following the microinjection of a protein-blocking substance into the cells and the inclusion of phenotype markers into the analysis) will expand the role of bivariate FCM for these research works.

Animals↗

Neural cell adhesion molecule (NCAM) and N-cadherin mRNA during development and aging: selective reduction in the 7.4-kb and 6.7-kb NCAM mRNA levels in the hippocampus of adult and old rats.

By examining the time course, from E15 to 720 days of age, for changes in the prevalence of mRNAs coding for neural cell adhesion molecule (NCAM), N-cadherin and alpha-tubulin in rat hippocampus and forebrain, it was concluded that (i) the NCAM 7.4-, 6.7-, 5.2-, 4.3- and 2.9-kb mRNAs are differentially regulated during development and aging; (ii) the 7.4- and 6.7-kb mRNA are drastically reduced starting from day 21 onward; (iii) the E15- and day-1-specific mRNA of 4.3 kb is replaced with the 5.2-kb mRNA starting with 21 days, thereafter the 5.2-kb message remained relatively constant over the entire life-span studied. Likewise, the 2.9-kb mRNA, which was very abundantly expressed at E15 and early postnatal stages, remained relatively constant between 180 days and 720 days; (iv) postnatal rat brains showed both qualitative and quantitative changes in N-cadherin 4.3- and 4.0-kb transcripts. The 4.3-kb mRNA was relatively abundant at 1 and 21 days postnatal stages, thereafter the signal remained very low over the entire life-span studied. The 4.0-kb message, which was specific for the E15 stage, was replaced with the 4.3-kb message; (v) as expected, the 1.8-kb mRNA coding for embryonic alpha-tubulin decreased dramatically after 1 day, but became stabilized at moderate levels during the subsequent developmental stages. At least for the NCAM gene, the regulation seems to occur post-transcriptionally, possibly at the level of RNA processing while the N-cadherin mRNA expression seems to be transcriptionally regulated.

Aging↗

Changes in cerebral and ocular hemodynamics in Behçet's disease assessed by color-coded duplex sonography.

AIM: To quantify the cerebral and retrobulbar hemodynamics in Behçet's disease with and without ocular involvement and compared with that of healthy controls. MATERIALS AND METHODS: Of 51 people studied, 17 had Behçet's disease with ocular involvement, 17 had Behçet's disease without ocular involvement, and 17 were healthy controls. A single eye was examined in each patient. Peak systolic velocity (PSV), end-diastolic velocity (EDV), time-averaged maximum velocity (Tamax), and resistance index (RI) were evaluated in the ophthalmic (OA), posterior ciliary (PCA), central retinal (CRA) and middle cerebral artery (MCA). Additionally, the average blood flow velocities in the central retinal vein (CRV), and acceleration time (AT) and pulsatility index (PI) in the MCA were calculated. RESULTS: The mean EDV in the PCA was 25% lower and RI was higher in patients with ocular involvement of BD than in patients without involvement (p = 0.006 and p = 0.005, respectively) and in healthy controls (p = 0.003 and p = 0.004, respectively). Differences were smaller in comparisons of the CRA and absent on comparisons of the OA and MCA. The acceleration time of the MCA was significantly higher in patients with Behçet's disease than in healthy controls (p = 0.03). CONCLUSION: This study suggests that the flow hemodynamics in retrobulbar circulation has more altered Behçet's disease with ocular involvement than without ocular involvement and healthy control. Additionally, the cerebral hemodynamic might be affected in patients with Behçet's disease compared with healthy controls.

Adult↗