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PubMed2005

Assessment of left ventricular function by breath-hold cine MR imaging: Comparison of different steady-state free precession sequences.

PURPOSE: To compare steady-state free precession (SSFP) sequence protocols with different acquisition times (TA) and temporal resolutions (tRes) due to the implementation of a view sharing technique called shared phases for the assessment of left ventricular (LV) function by breath-hold cine magnetic resonance (MR) imaging. MATERIALS AND METHODS: End-diastolic and end-systolic volumes (EDV, ESV) were measured in contiguous short-axis slices with a thickness of 8 mm acquired in 10 healthy male volunteers. The following true fast imaging with steady-state precession (TrueFISP) sequence protocols were compared: protocol A) internal standard of reference, segmented: tRes 34.5 msec, TA 18 beats per slice; protocol B) segmented, shared phases: tRes 34.1 msec, TA 10 beats per slice; and protocol C) real-time, shared phases, parallel acquisition technique: tRes 47.3 msec, TA 24 beats for 12 slices covering the entire left ventricle. RESULTS: Phase sharing leads to a significant decrease in EDV, stroke volume (SV), and ejection fraction (EF) (median difference -7.0 mL [*], -9.6 mL, and -3.4%, respectively, for protocol B; -15.3 mL, -13.3 mL, and -2.4% for protocol C; P = 0.002, *P = 0.021). The observed median difference of real-time EDV and SV estimates is of clinical relevance. Real-time cine MR imaging shows a greater variability of EDV and SV. No relevant differences in ESV were observed. CONCLUSION: The true cine frame duration of both shared phases sequence protocols exceeds the period of isovolumetric contraction (IVCT) of the left ventricle resulting in a systematic and significant underestimation of EDV and consequently SV and EF. SSFP sequence protocol parameters, particularly tRes and use of view sharing techniques, should therefore be known at follow-up examinations in order to be able to assess LV remodeling in patients with heart failure.

Adult↗

PubMed2006

Three-class ROC analysis--a decision theoretic approach under the ideal observer framework.

Receiver operating characteristic (ROC) analysis is well established in the evaluation of systems involving binary classification tasks. However, medical tests often require distinguishing among more than two diagnostic alternatives. The goal of this work was to develop an ROC analysis method for three-class classification tasks. Based on decision theory, we developed a method for three-class ROC analysis. In this method, the objects were classified by making the decision that provided the maximal utility relative to the other two. By making assumptions about the magnitudes of the relative utilities of incorrect decisions, we found a decision model that maximized the expected utility of the decisions when using log-likelihood ratios as decision variables. This decision model consists of a two-dimensional decision plane with log likelihood ratios as the axes and a decision structure that separates the plane into three regions. Moving the decision structure over the decision plane, which corresponds to moving the decision threshold in two-class ROC analysis, and computing the true class 1, 2, and 3 fractions defined a three-class ROC surface. We have shown that the resulting three-class ROC surface shares many features with the two-class ROC curve; i.e., using the log likelihood ratios as the decision variables results in maximal expected utility of the decisions, and the optimal operating point for a given diagnostic setting (set of relative utilities and disease prevalences) lies on the surface. The volume under the three-class surface (VUS) serves as a figure-of-merit to evaluate different data acquisition systems or image processing and reconstruction methods when the assumed utility constraints are relevant.

Algorithms↗

PubMed1994

Impaired TCR signal transduction, but normal antigen presentation, in a patient with common variable immunodeficiency.

We describe a 27-year-old white man with common variable immunodeficiency (CVID) who has two healthy histoidentical brothers and one IgA-deficient sister who shares one HLA haplotype with the patient. T cells from the patient with CVID showed an impaired response to recall antigens (tetanus toxoid, E. coli), whereas his IgA-deficient sister and his two healthy histoidentical brothers responded normally. Cross-mixing experiments using isolated monocytes and T cells from the CVID patient and one histoidentical brother revealed that the patient's monocytes were fully functional in processing and presenting antigen to resting T cells of his brother, and provided normal accessory cell function for superantigen-induced activation of his brother's resting T cells. In contrast, the patient's T cells were unable to respond to antigen presented by the brother's monocytes and failed to respond with an increase in intracellular free Ca++ to stimulation with superantigen, which is known to bind to the TCR V beta-chain outside the antigen-binding groove. However, stimulation with a combination of PMA and IM, directly activating protein kinase C and increasing intracellular free Ca++ by bypassing membrane receptors, induced normal Ca++ flux. These data indicate that the patient with CVID has a defect in TCR-mediated signalling at the level of the T cells which is not present in his histoidentical healthy brothers or in his haploidentical IgA-deficient sister.

Adolescent↗

PubMed1980

Sharing of an idiotypic marker by monoclonal antibodies specific for distinct regions of hen lysozyme.

Idiotypes have been defined serologically as variable-region markers present on unique subsets of antibody molecules. Most studies involving myeloma proteins and antibody responses in inbred mice have indicated that idiotypy is closely related to antigenic specificity. However, indirect evidence suggests that idiotypy can sometimes be dissociated from specificity. In the response to the small monomeric protein, hen egg-white lysozyme (HEL), previous results demonstrated that 70--95% of the anti-HEL antibody found in sera of primed and boosted mice is specific for a particular region of HEL and bears a predominant idiotype (IdX-HEL). In this report, hybridoma anti-HEL antibodies tested with well-characterized peptide fragments of HEL show that the IdX-HEL marker can be found on antibodies of completely distinct antigen specificities. Thus, a mode of recognition other than antigenic recognition probably plays a major role in the immune response to HEL.

Animals↗

PubMed1988

Study of the epitope structure of purified Dac G I and Lol p I, the major allergens of Dactylis glomerata and Lolium perenne pollens, using monoclonal antibodies.

The use of mAb allowed us to further analyze the cross-reactivity between purified Dac g I and Lol p I, the major allergens of Dactylis glomerata (cocksfoot) and Lolium perenne (Rye grass), respectively. It was first shown, using IEF, followed by immunoprinting, that serum IgE antibodies from most grass-sensitive patients recognize both Dac g I and Lol p I. Second, three different anti-Lol p I mAb, 290A-167, 348A-6, and 539A-6, and one anti-Dac g I mAb, P3B2 were all shown to react with Dac g I and Lol p I, indicating that the two molecules share common epitopes. Epitope specificity of the mAb was determined by competitive binding inhibition of a given labeled mAb to solid phase fixed Dac g I or Lol p I by the mAb. The results indicated that the four mAb are directed against four different and non-overlapping epitopes present on both allergens. Using double-binding RIA, our data strongly suggest that the common epitopes are not repetitive on both molecules. In addition to their similar physicochemical characteristics, such as isolectric points and m.w., Dac g I and Lol p I share four identical epitopes. Binding inhibition of human IgE to Lol p I and Dac g I by the mAb was also assessed. The results indicated that each mAb was able to inhibit such reactions to variable degree but no additive inhibition was observed when two mAb of different specificities were used in combination, suggesting that the human IgE binding site is partially shared by each epitope recognized by the four mAb.

Allergens↗

PubMed1993

HIV risk among women injecting drug users who are in jail.

Female offender populations and females in jail include large proportions of injecting drug users (IDUs), who are at high risk of contracting or transmitting HIV. Women IDUs (n = 165) were recruited and interviewed at New York City's central jail facility for women. The study examined these women's patterns of HIV risk behaviors related to drugs and sex and identified behavioral and attitudinal correlates of HIV serostatus. The women typically used both injectable and non-injectable drugs prior to arrest, primarily heroin, cocaine powder, crack, and illicit methadone. Self-reported HIV seropositivity was 43%. Variables correlated with HIV serostatus in the bivariate analysis were: cocaine injection frequency; lifetime injection risk behavior; providing oral sex during male crack use; Hispanic ethnicity; sharing of needles/syringes; sharing of cookers; sharing injection equipment with friends; heroin smoking (negative); injection risk acceptance; peer norms and behavior; lifetime sexual risk behavior; frequency of sex with men; provision of sex for money or drugs; and knowing people with AIDS. The first four variables listed retained statistical significance in a multiple logistic regression analysis. The paper considers the need to tailor AIDS prevention interventions for woman IDUs in jail, including taking into account risk behaviors that occur within frequently reported same-sex partnerships.

Acquired Immunodeficiency Syndrome↗

PubMed1989

Expression of a public idiotype by human monoclonal IgM directed to myelin-associated glycoprotein and characterization of the variability subgroup of their heavy and light chains.

Most studies using rabbit or mouse antisera failed to detect CRI between human IgM directed to MAG. We show here that 9 of 10 such IgM express a public CRI as defined by a nonhuman primate antiserum. Shared idiotype is likely involved in (or close to) the combining site of those IgM since antiidiotypic serum inhibited the binding of IgM to MAG and reacted with IgM having different variable regions of light and heavy chains. Partial aminoterminal sequence of heavy and light chains showed that anti-MAG IgM use either lambda chains (one IgM) or kappa light chains (six IgM) of different variability subgroups (V kappa IV in three instances, V kappa I in two, and V kappa II in one), whereas heavy chains belong to the VHIII (six IgM) or to the VHII (1 IgM) subgroup. These features distinguish these IgM from other human monoclonal IgM with a defined antibody activity, such as rheumatoid factors or cold agglutinins.

Amino Acid Sequence↗

PubMed2003

An investigation of semantic errors in unimpaired and Alzheimer's speakers of Italian.

Semantic errors are a common type of slip of the tongue for normal speakers; they are also considered to be the hallmark of progressive diseases that affect semantic memory such as Alzheimer's Disease (AD) and semantic dementia. In unimpaired speakers, semantic errors have been shown to be affected by syntactic variables. For example, Marx (1999) has shown that speakers of a gendered language such as German tend to substitute a target with another word that shares the same grammatical gender with the target more often than chance would predict. This finding suggests that errors occur at a level at which lexical information about the target is activated and retrieved. Here, we assess whether such an effect of syntactic variables (gender) also holds in experimental tasks designed to induce errors in unimpaired speakers of Italian (another gendered language) and whether this effect can also be observed in the semantic errors produced in the same task by AD patients. We found that for the unimpaired speakers, the gender of the target word constrained the error committed, while this was not the case for the AD patients. We take this finding to suggest a different locus for the errors in the two populations: while the semantic errors by the unimpaired speakers occur because of mis-selection of a lexical entry due to lexical competition among semantically similar words, the errors by the AD patients occur because of insufficient activation of lexical representations.

Adult↗

PubMed2005

The goose reovirus genome segment encoding the minor outer capsid protein, sigma1/sigmaC, is bicistronic and shares structural similarities with its counterpart in Muscovy duck reovirus.

Reoviruses have recently been shown to be associated with disease in young geese and to be involved in epizooties of severe outcome in Hungary. To assess the genetic variability among these pathogenic goose reoviruses (GRVs), we sequenced the S4 genome segment of five GRV strains isolated from different diseased flocks. We found that the GRV S4 genome segment, consisting of two partially overlapping open reading frames (ORFs), shares substantial structural similarity with its counterpart in muscovy duck reoviruses (DRVs). ORF1 is predicted to encode a polypeptide highly similar to the p10 polypeptide of DRV, and ORF2 supposedly encodes the minor outer capsid protein, sigma1/sigmaC. In one of the five GRV strains examined, we identified a single uracil base insertion close to the middle of ORF2. This insertion resulted in a frameshift and in concomitant acquisition of a termination codon (UAA) a few codons downstream, apparently causing truncation of the C-terminal part of the protein. The functional consequences of this assumed mutation, which would result in loss of more than a half of the protein, have yet to be determined. Nonetheless, the sequence and structural similarities between the genome segment encoding sigmal/sigmaC in GRVs and DRVs suggest that these viruses belong to a species distinct from other established species within subgroup 2 of orthoreoviruses.

Amino Acid Sequence↗

PubMedDate not supplied

Variability in physician referral decisions.

BACKGROUND: Because it is possible that part of the variability in frequency of interventions and even in outcomes results from the variability in referral patterns of primary care physicians, our objectives were to examine primary care physician decision making about referrals for several common adult and childhood conditions. METHODS: One hundred thirty-six family physicians in 80 office-based practices recorded reasons for referral to the most common types of specialists and the expectation of the specialist for conditions with at least seven referrals to each specialist. RESULTS: By far the most referrals were expected to be short-term (< 12 months); for more than 50%, the referrals were for consultation only (rather than direct intervention). For most of the 10 types of conditions, there were no apparent differences in reason for or expectation of the referral that would explain the choice of different types of specialists for referral. Expectations for shared care were generally more common in referrals to nonphysicians than to physicians. CONCLUSIONS: This study revealed unexplained variability among family physicians in the specialists to whom patients are referred for specific conditions. Why some patients with the same condition are referred to surgeons and others to medical specialists is unclear, at least in the context of expectations for referral as being long-term vs short-term or consultative vs referral for definitive management. The impact of this variability on costs and outcome could be considerable and deserves more intensive study.

Decision Making↗

PubMed2003

Decreased thalamic expression of the homeobox gene DLX1 in psychosis.

CONTEXT: A shared vulnerability to develop psychosis can be related to abnormalities in thalamic circuits in schizophrenia and bipolar disorder and could be a genetic link between these disorders. Homeobox genes involved in development and differentiation of the brain could play an important role in these disorders. OBJECTIVE: To determine whether patients with schizophrenia and bipolar disorder have different thalamic expression patterns of 2 homeobox genes, DLX1 and SHOX2 (alias OG12X or SHOT) compared with psychiatric and nonpsychiatric control subjects. DESIGN: Postmortem sections containing the thalamic mediodorsal nucleus were subjected to in situ hybridization with mouse Dlx1 and human SHOX2 RNA probes. The number of both DLX1- and SHOX2-positive neurons relative to Nissl-stained neurons was estimated in systematic randomly sampled volume probes. Patients Fifteen patients with schizophrenia, 15 with bipolar disorder with or without history of psychosis, 15 with major depressive disorder, and 15 nonpsychiatric controls from the Stanley Foundation Brain Bank. MAIN OUTCOME MEASURE: Relative numbers of DLX1- and SHOX2-positive neurons in patients with schizophrenia and bipolar disorder with history of psychosis compared with psychiatric and nonpsychiatric controls. RESULTS: Patients with a history of psychosis showed significantly decreased relative numbers of DLX1-positive neurons compared with patients without history of psychosis and nonpsychiatric controls (P =.02), whereas no differences could be found in relative numbers of SHOX2-positive neurons (P>.15). Results were obtained blind to diagnosis, symptoms, or any other variable except hemisphere. CONCLUSION: Decreased thalamic expression of DLX1 in schizophrenia and bipolar disorder with psychosis suggests shared genetic deficits in expression of this homeobox gene.

Adult↗

PubMed1998

Marijuana use and treatment outcome among opioid-dependent patients.

AIMS: Information concerning the association between marijuana use and opioid dependence and its treatment is needed to determine effective clinical guidelines for addressing marijuana use among opioid abusers. SETTING AND PARTICIPANTS: Marijuana use was assessed in 107 people enrolled in treatment for opioid dependence. DESIGN AND MEASUREMENT: Univariate comparisons of marijuana users and non-users and multivariate regression analyses were performed to examine associations between marijuana use and socio-demographic, psychosocial, medical and substance-use variables. The relationship between marijuana use and treatment outcome was also explored in a subset of this sample who received treatment that included buprenorphine detoxification and behavior therapy (N = 79). FINDINGS: Sixty-six per cent of participants were current marijuana users and almost all (94%) continued to use during treatment. Users were less likely to be married than non-users, and more likely to report financial difficulties, be involved in drug dealing and engage in sharing of needles (p < 0.05). A unique effect of marijuana use on drug dealing and sharing needles was retained after statistically controlling for the influence of heroin and alcohol use and other socio-demographic variables. No significant adverse relations were observed between marijuana use and treatment outcome. CONCLUSION: Pending a more comprehensive understanding of the function and consequences of marijuana use on psychosocial functioning, it appears that progress in treatment for opioid dependence can be made without mandating that patients abstain from marijuana use.

Adult↗

PubMed1981

Dissociation of smooth-pursuit and saccadic eye tracking in remitted schizophrenics. An ocular reaction time task that schizophrenic perform well.

Twenty-four schizophrenic outpatients in remission were compared with 21 medical outpatient controls on tasks designed to evaluate smooth pursuit of different frequency sinusoidal targets, saccadic eye tracking, and performance on psychomotor analogues of these tasks that require eye-hand coordination. The schizophrenics demonstrated impaired performance on all the smooth-pursuit and psychomotor tracking tasks. However, the oculomotor reaction times of schizophrenics during the saccadic eye-tracking tasks were equal to those of controls. This dissociation of smooth-pursuit and saccadic performance indicates that smooth-pursuit dysfunction cannot be attributed to a lack of motivation, simple inattention, or oculomotor control mechanisms for which the pursuit and saccadic systems share a common anatomy. The saccadic eye-tracking task is quite similar to a variable-foreperiod simple reaction-time task. That schizophrenics produce normal response latencies on this task raises important questions about the nature of the reaction-time deficit in schizophrenia.

Attention↗

PubMed1991

A myeloma M 104E private idiotope is represented predominantly among anti-dextran, peritoneal cavity Ly-1+ precursor B cells.

Public and private idiotopes (Id) had been defined in the BALB/c anti-dextran B1355 fraction S (Dex) response by means of syngeneic monoclonal anti-M 104E Id antibodies. Most of the primary anti-Dex antibodies shared the public Id-1 while the private Id-5 constituted a comparatively low, but highly variable proportion of humoral anti-Dex antibodies of individual mice. In the present work we have analyzed by limiting dilution the expression of these two Id by anti-Dex B cell precursors from the spleen and peritoneal cavity of BALB/c mice. Testing spleen cells we found about 65% of anti-Dex precursors to be Id-1+ and only a minority to be Id-5+. Treatment with anti-Ly-1 and complement was without any effect on anti-Dex precursors from spleen. Anti-Dex B cell precursors among peritoneal cavity lymphocytes differed from those found in the spleen in two ways. First, on average, 50% of them were Id-5+; second, about 80% carried the Ly-1 marker. Both markers are, therefore, expressed on at least 30% of anti-Dex B cell precursors from the peritoneal cavity but rarely on anti-Dex precursors from the spleen.

Animals↗

PubMed1995

Dementia lacking distinctive histopathology: clinicopathological evaluation of 32 cases.

We report the neuropathological findings in 32 patients, aged 46-86 years, with dementia lacking distinctive histopathology. All of the patients were classified clinically as having Pick's or atypical Pick's disease, but the routine neuropathological evaluation showed no specific histopathological changes such as Pick bodies, senile plaques, neurofibrillary tangles or Lewy bodies. In 50% of the cases the first symptoms appeared before 65 years of age. However, there were 9 patients with onset in the eighth decade. Positive family history was found only in 6 presenile cases. The retrospective evaluation of the clinical records revealed the consistent presence of "frontal" symptomatology, including loss of personal awareness, inappropriate euphoria and stereotyped behavior. Speech disorders were observed in 80% of the cases, whereas temporospatial disorientation and memory impairment were less frequent. Praxis and gnosis were strikingly preserved in most of the cases. The macroscopic neuropathological examination revealed frontal or temporopolar atrophy in 97% of the cases, while the hippocampus and subcortical structures were relatively spared in the majority of the cases. Histologically, four groups were recognized. Group A showed moderate to severe neuron loss and gliosis in the frontal and/or temporopolar cortex without subcortical involvement. In group B, the neocortical cell loss was widespread, and the striatum and substantia nigra displayed differential degrees of gliosis but no neuron loss. Group C patients showed a lesion distribution comparable to that observed in group B but with severe neuron loss in at least one subcortical region. Four cases formed group D, which was characterized by the preservation of the pyramidal neurons in the neocortex and variable subcortical changes. Despite these differences in the topography of pathological changes, all of the cases shared a similar clinical profile. These findings further demonstrate the epidemiological and neuropathological heterogeneity of dementia lacking distinctive histopathology. Furthermore, they suggest that the same clinical manifestations may correspond to several distinct pathological processes in this condition.

Age Distribution↗

PubMed2006

Dynamic updating of distributed neural representations using forward models.

In this paper, we present a continuous attractor network model that we hypothesize will give some suggestion of the mechanisms underlying several neural processes such as velocity tuning to visual stimulus, sensory discrimination, sensorimotor transformations, motor control, motor imagery, and imitation. All of these processes share the fundamental characteristic of having to deal with the dynamic integration of motor and sensory variables in order to achieve accurate sensory prediction and/or discrimination. Such principles have already been described in the literature by other high-level modeling studies (Decety and Sommerville in Trends Cogn Sci 7:527-533, 2003; Oztop et al. in Neural Netw 19(3):254-271, 2006; Wolpert et al. in Philos Trans R Soc 358:593-602, 2003). With respect to these studies, our work is more concerned with biologically plausible neural dynamics at a population level. Indeed, we show that a relatively simple extension of the classical neural field models can endow these networks with additional dynamic properties for updating their internal representation using external commands. Moreover, an analysis of the interactions between our model and external inputs also shows interesting properties, which we argue are relevant for a better understanding of the neural processes of the brain.

Animals↗

PubMed2001

Characterization of a new citrus viroid species tentatively termed Citrus viroid OS.

A new viroid was obtained from a viroid sample, named 'OS', collected from a citrus plant. The viroid consists of 330-331 nucleotides, contains the central conserved region (CCR) characteristic of the genus Apscaviroid, and has the highest sequence similarity (only 68%) with Citrus III viroid (CVd-III) among known viroids. This viroid, by itself, caused only mild petiole necrosis and characteristically very mild leaf bending in Arizona 861-S1 Etrog citrons (Citrus medica L.), the degree of which differed from that induced by other citrus viroids. This viroid could be a new citrus viroid species belonging to the genus Apscaviroid; for convenience, it was tentatively named Citrus viroid OS (CVd-OS) after the original sample. CVd-OS has chimeric features related to other viroids. In particular, CVd-OS has high sequence similarity with CVd-III and Apple dimple fruit viroid in the putative central and terminal left domains, including a duplicative sequence from the lower CCR of the genus Pospiviroid in the left terminus. Further, CVd-OS shares high sequence similarity with Citrus exocortis viroid (CEVd) in the lower strand of the putative variable and terminal right domains, including the sequence identical to that of the right termini of CEVd and of Citrus IV viroid.

Base Sequence↗

PubMed1979

Site-specific cleavage of DNA by E. coli DNA gyrase.

E. coli DNA gyrase, which catalyzes the supercoiling of DNA, cleaves DNA site-specifically when oxolinic acid and sodium dodecylsulfate are added to the reaction. We studied the structure of the gyrasecleaved DNA because of its implications for the reaction mechanism and biological role of gyrase. Gyrase made a staggered cut, creating DNA termini with a free 3' hydroxyl and a 5' extension that provided a template primer for DNA polymerase. The cleaved DNA was resistant to labeling with T4 polynucleotide kinase even after treatment with proteinase K. Thus the denatured enzyme that remains attached to cleaved DNA is covalently bonded to both 5' terminal extensions. The 5' extensions of many gyrase cleavage fragments from phi X174, SV40 and Col E1 DNA were partially sequenced using repair with E. coli DNA polymerase I. No unique sequence existed within the cohesive ends, but G was the predominant first base incorporated by DNA polymerase I. The cohesive and sequences of four gyrase sites were determined, and they demonstrated a four base 5' extension. The dinucleotide TG, straddling the gyrase cut on one DNA strand, provided the only common bases within a 100 bp region surrounding the cleavage sites. Analysis of other cleavage fragments showed that cutting between a TG doublet is common to most, or all, gyrase cleavages. Other bases common to some of the sequenced sites were clustered nonrandomly around the TG doublet, and may be variable components of the cleavage sequence. This diverse recognition sequence with common elements is a pattern shared with several other specific nucleic acid-protein interactions.

Base Sequence↗