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At least 145 records · Page 8Linked to original sources
PubMed2003

Lack of association of mutations in optineurin with disease in patients with adult-onset primary open-angle glaucoma.

OBJECTIVE: To determine whether mutations in the optineurin gene contribute to susceptibility to adult-onset primary open-angle glaucoma. METHODS: The optineurin gene was screened in 86 probands with adult-onset primary open-angle glaucoma and in 80 age-matched control subjects. Exons 4 and 5, containing the recurrent mutations identified in patients with normal-tension glaucoma, were sequenced in all individuals studied, while the remaining exons were screened for DNA sequence variants with denaturing high-performance liquid chromatography. RESULTS: The recurrent mutation, Met98Lys, previously found to be associated with an increased risk of disease was found in 8 (9%) of 86 probands. We also found the Met98Lys mutation in 10% of individuals from a control population of similar age, sex, and ethnicity. Consistent segregation of the mutation with the disease was not demonstrated in any of the 8 families. No other DNA changes altering the amino acid structure of the protein were found. CONCLUSION: The mutations in the optineurin gene associated with normal-tension glaucoma are not associated with adult-onset primary open-angle glaucoma in this patient population. Clinical Relevance Genetic abnormalities that render the optic nerve susceptible to degeneration are excellent candidates for genetic factors that could contribute to adult-onset primary open-angle glaucoma. Mutations in optineurin have been associated with normal-tension glaucoma, but are not associated with disease in patients with adult-onset primary open-angle glaucoma. This result may indicate that normal-tension glaucoma is not necessarily part of the phenotypic spectrum of adult open-angle glaucoma.

Aged↗
PubMed2005

Deficient fear conditioning in psychopathy: a functional magnetic resonance imaging study.

CONTEXT: Psychopaths belong to a larger group of persons with antisocial personality disorder and are characterized by an inability to have emotional involvement and by the repeated violation of the rights of others. It was hypothesized that this behavior might be the consequence of deficient fear conditioning. OBJECTIVE: To study the cerebral, peripheral, and subjective correlates of fear conditioning in criminal psychopaths and healthy control subjects. DESIGN: An aversive differential pavlovian delay conditioning paradigm with slides of neutral faces serving as conditioned and painful pressure as unconditioned stimuli. SETTING: The Department of Medical Psychology at the University of Tübingen, Tübingen, Germany. PARTICIPANTS: Ten male psychopaths as defined by the Hare Psychopathy Checklist-Revised and 10 age- and education-matched healthy male controls. The psychopaths were criminal offenders on bail and waiting for their trial or were on parole. The healthy controls were recruited from the community. MAIN OUTCOME MEASURES: Brain activation based on functional magnetic resonance imaging, electrodermal responses, emotional valence, arousal, and contingency ratings. RESULTS: The healthy controls showed enhanced differential activation in the limbic-prefrontal circuit (amygdala, orbitofrontal cortex, insula, and anterior cingulate) during the acquisition of fear and successful verbal and autonomic conditioning. The psychopaths displayed no significant activity in this circuit and failed to show conditioned skin conductance and emotional valence ratings, although contingency and arousal ratings were normal. CONCLUSION: This dissociation of emotional and cognitive processing may be the neural basis of the lack of anticipation of aversive events in criminal psychopaths.

Adult↗
PubMed1981

Endoscopic tissue diagnosis of gastric involvement in the staging of non-Hodgkin's lymphoma.

The results of radiologic and endoscopic examinations and endoscopic biopsies of the stomach and duodenum in the staging of non-Hodgkin's lymphoma (NHL) were assessed in 147 patients. Radiologic results were positive for non-Hodgkin's lymphoma in 36 of 147 patients, with diagnosis of NHL from biopsy specimens of 16 of these 36 patients. Results of endoscopic studies were abnormal in 35 of 147 patients and 20 of these 35 patients also had biopsy specimens positive for NHL. Twenty-four patients (16.3%) had NHL involvement of the gastric and/or duodenal mucosa demonstrated by biopsy material. More than 15% of the patients whose primary tumors were nodal, and 19% of those patients with extranodal involvement also had lymphoma involvement of the stomach and/or duodenum. According to the results of the endoscopic biopsies, 15.1% (10 of 66 patients) had Stages I and II, and 17.2% (14 of 81 patients) had Stages II and IV of non-Hodgkin's lymphoma.

Adolescent↗
PubMed2001

Low-resolution electrical tomography of the brain during psychometrically matched verbal and spatial cognitive tasks.

EEGs were recorded from 75 normal, young, female subjects during psychometrically matched verbal (WF) and spatial (DL) cognitive tasks to elicit the differences in the electrical source distribution inside the brain. Recordings were obtained using 43 EEG and 3 guard electrodes then visually edited and spatially filtered to remove extracerebral artifacts. Twenty 1-sec artifact-free epochs were obtained and analyzed from 42 and 60 subjects during WF and DL respectively. Of these subjects, 20 were placed in a training set and the remainder into a test set. The baseline for the comparison of the two tasks was established by factoring the average cross-spectral matrices of the training-set EEGs, computed in the theta, alpha, and beta frequency bands into spatial patterns common to the two tasks. Only those spatial patterns that contributed to the correct classification of subjects in the test set were included in the source analysis. The source-current density distributions were obtained using the LORETA-KEY algorithm. The results show that the source-current density distribution is related to the putative functional activity in the brain in all three frequency bands. The electrical effects of the tasks are both most highly localized and lateralized in the theta band. The effects in the alpha and beta bands are much more generalized and are strongly lateralized only during one and the other of the tasks respectively. The conclusion is that WF is mainly a left central and bilateral frontal cerebral process while DL is mainly a right central and bilateral posterior cerebral process.

Adult↗
PubMed1993

Long-term high-level expression of human beta-globin occurs following transplantation of transgenic marrow into irradiated mice.

When the human beta-globin gene is transferred into the bone marrow cells of live mice, its expression is very low. To investigate the reason for this, we transferred the bone marrow of transgenic mice containing and expressing the human beta-globin into irradiated recipients. We demonstrate that long-term high level expression of the human beta-globin gene can be maintained in the marrow and blood of irradiated recipients following transplantation. Although expression decreased over time in most animals because of host marrow reconstitution, the ratio of human beta-globin transgene expression to endogenous mouse beta-globin gene expression in donor-derived erythroid cells remained constant over time. We conclude that there is no inherent limitation to efficient expression of an exogenous human beta-globin gene in mouse bone marrow cells following marrow transplantation.

Animals↗
PubMed2002

Significance of penetration, excretion, and transovarial uptake to toxicity of three insect growth regulators in predatory lacewing adults.

Topical treatment of the predatory lacewing adults, Chrysoperla carnea (Stephens) (Neuroptera: Chrysopidae) before and after the onset of oviposition with diflubenzuron (DFB) at doses based on the maximum field recommended concentration resulted in a total inhibition of egg hatch due to death of the embryo. In contrast, pyriproxyfen (PYR) and tebufenozide (TEB) did not affect fecundity and egg fertility. To explain these differences in toxicity, the patterns of penetration through the cuticle, distribution inside the insect body, and excretion were studied using [(14)C]-labeled isotopes of each insect growth regulator (IGR). Penetration of DFB and TEB reached about 16 and 26% in 7 days, whereas 88% of PYR had penetrated in 24 h. However, the rate of excretion for PYR was very high, compared to that of DFB and TEB. Low amounts of absorbed radioactivity were recovered from the female body with the exception of DFB, the ovaries and the eggs deposited during a week. DFB and PYR concentration reached a peak in the eggs deposited at the fourth and second day after treatment, respectively. The current data indicate the importance of penetration through the insect cuticle. However, other mechanisms are likely to be involved in the selectivity of the current IGRs towards this beneficial insect.

Animals↗
PubMed2003

Operant behavioral treatment of fibromyalgia: a controlled study.

OBJECTIVE: To evaluate the efficacy of operant pain treatment for fibromyalgia syndrome (FMS) in an inpatient setting. METHODS: Sixty-one patients who fulfilled the American College of Rheumatology criteria for FMS were randomly assigned to the operant pain treatment group (OTG; n = 40) or a standardized medical program with an emphasis on physical therapy (PTG; n = 21). Pain assessments were performed before, immediately after, 6 months after, and 15 months after treatment. RESULTS: The OTG patients reported a significant and stable reduction in pain intensity, interference, solicitous behavior of the spouse, medication, pain behaviors, number of doctor visits, and days at a hospital as well as an increase in sleeping time. Sixty-five percent of the OTG compared with none of the patients in the PTG showed clinically significant improvement. CONCLUSION: These results suggest that operant pain treatment provided in an inpatient setting is an effective treatment for FMS, whereas a purely somatically oriented program may lead to a deterioration of the pain problem.

Behavior↗
PubMed2005

Predictors of pain behaviors in fibromyalgia syndrome.

OBJECTIVE: To evaluate the contributions of physical, pain-related, cognitive, stress-related, affective, and spouse-related variables to differences in pain behaviors in subgroups of patients with fibromyalgia syndrome (FMS). METHODS: One hundred forty FMS patients underwent medical, physical, and psychological evaluation. Patients and 30 pain-free controls performed a routine physical activity (window-washing task) to elicit pain behaviors with or without the presence of their spouses. The behaviors and spouses' responses during this task were videotaped and subsequently rated. Patients were classified as dysfunctional (DYS), interpersonally distressed (ID), or adaptive copers (AC) based on responses to the Multidimensional Pain Inventory. Hierarchical regression analyses were used to identify predictors of pain behaviors for the total group and subgroups of patients. RESULTS: Patients classified as DYS demonstrated the highest number of pain behaviors compared with those classified as ID or AC. This difference was observable when the spouse was present. Spouse responses and physical variables were significantly related to pain behaviors in the DYS and ID groups with the model accounting for 77.1% and 41.9% of the variance, respectively. In contrast, for the AC group, stress factors were the most significant predictor of pain behaviors, accounting for 22.8% of the variance. CONCLUSION: The results indicate that different variables account for the presence of pain behaviors in different subgroups of patients. The data provide support for the heterogeneity of the diagnosis of FMS and have implications for treatment of subgroups of patients.

Behavior↗
PubMed1990

A sensitive high performance liquid chromatography microassay for bemoradan, a novel cardiotonic agent, in plasma/serum using a semi-automatic liquid/solid extraction sample preparation system--AASP.

A high performance liquid chromatographic method for the measurement of bemoradan levels in plasma/serum is described. This method uses Varian's AASP (Varian Associates, Sunnyvale, CA, USA), a semi-automatic liquid/solid extraction sample preparation system. It requires only small volumes of plasma/serum samples (0.2-1 mL) and needs no organic solvent for sample preparation. The mean recovery of bemoradan at plasma or serum concentrations of 0.5-100 ng/mL is 82%. The assay has a detection limit of 0.5 ng/mL (when 1 mL of plasma/serum is used) and is linear in the concentration range 0.5-500 ng/mL.

Animals↗
PubMed2006

Simultaneous determination of natural and synthetic estrogens by EKC using a novel microemulsion.

A novel microemulsion based on sodium bis(2-ethylhexyl) sulfosuccinate (AOT) was developed for the simultaneous determination of natural and synthetic estrogens by microemulsion EKC (MEEKC). The microemulsion system consisted of 1.4% w/w AOT, 1.0% w/w octane, 7.0% w/w 1-butanol and 90.6% w/w 20 mM sodium salt of 3-(cyclohexylamino)-2-hydroxy-1-propanesulfonic acid (CAPSO) and 10 mM phosphate buffer at pH 12.5. A baseline resolution in the separation of estrone, 17beta-estradiol, estriol, estradiol 17-hemisuccinate, etinilestradiol, estradiol 3-benzoate, and estradiol 17-valerate was achieved in comparison to the traditional MEEKC system with SDS in less than 15 min. The optimized electrophoretic conditions included the use of an uncoated-silica capillary of 60 cm of total length and 75 microm id, an applied voltage of 25 kV, a temperature of 25 degrees C and 214 UV-detection. Parameters of validation such as specificity, linearity, accuracy, LOD, LOQ and robustness were evaluated according to international guidelines. Due to its simplicity, accuracy, and reliability, the proposed method can be an advantageous alternative to the traditional methodologies for the analysis of natural and synthetic estrogens in different pharmaceutical forms.

Buffers↗
PubMed2005

Laboratory variability does not preclude identification of biological functions impacted by hydroxyurea.

The multi-lab International Life Sciences Institute (ILSI) project on the application of genomics to risk assessment offered the unique opportunity to investigate the influence of variability within and between laboratories on identifying biologically relevant gene expression changes. We assessed the gene expression profiles of mouse lymphoma L5178Y cells treated with hydroxyurea (HU) in three independent studies from two different laboratories, Sanofi Aventis and Procter and Gamble. Cells were dosed for 4 hr and harvested immediately at the end of the treatment or after a 20-hr recovery period. Cytotoxicity and genotoxicity were evaluated by standard assays. Statistical analysis of these data revealed that, while gene expression responses to HU treatment were markedly different at 4 hr vs. 24 hr, there was otherwise a consistent pattern of dose-response across the three studies. Therefore, the studies were merged and each time point was evaluated separately. At 4 hr, we identified 173 (P < 0.0001) dose-responsive genes with a common trend in all three studies. These were mainly associated with the cell cycle, DNA repair and DNA metabolism, and in particular, the intra-S and G2/M phase checkpoints. At 24 hr, we identified 434 dose-responsive genes common across studies. These genes were involved in lymphocyte-specific activities and the activation of apoptosis via the caspase cascade. Our results show that despite inter-laboratory variability, combining the three studies in a single statistical analysis identifies more significantly-modulated genes than in any of the individual studies, due to improved statistical sensitivity. The genes identified in our study provide information that is relevant to HU biology.

Animals↗
PubMed2004

HLA class II genotype influences the type of liver injury in drug-induced idiosyncratic liver disease.

Drug-induced idiosyncratic liver disease (DIILD) depends largely on host susceptibility factors. Small studies support the genetic influence of human leukocyte antigen (HLA) class II molecules on the predisposition to DIILD. We sought associations between HLA-DRB and -DQB alleles and DIILD considered collectively or according to the biochemical expression of liver damage. We studied a total of 140 patients with a definitive or probable diagnosis of DIILD, as assessed with the Council for International Organizations of Medical Sciences scale, with 635 volunteer bone marrow and blood donors serving as controls. HLA-DRB1* and -DQB1* genotyping was performed by hybridization with sequence-specific oligonucleotides after genomic amplification. The group with DIILD did not differ from control subjects with regard to the distribution of HLA-DRB and -DQB antigens. The frequencies of alleles DRB1*15 (35.4% vs. 18.6% of controls; P =.002; odds ratio [OR] 2.31) and DQB1*06 (61.5% vs. 40.8%; P =.001; OR 2.32) were significantly increased in patients with the cholestatic/mixed type of liver damage in comparison to healthy subjects. By contrast, frequencies of alleles DRB1*07 (16.9% vs. 35.4%; P =.003; OR 0.37) and DQB1*02 (32.3% vs. 55.8%; P =.0003; OR 0.39) were significantly decreased. In conclusion, there is no association between any specific HLA allele and the propensity to develop DIILD. However, the genetic influence associated with HLA class II alleles appears to play a role in the biochemical expression of liver injury in cholestatic/mixed hepatotoxicity and may explain why a given drug may cause different patterns of liver damage.

Adolescent↗
PubMed1989

A conserved base pair within helix P4 of the Tetrahymena ribozyme helps to form the tertiary structure required for self-splicing.

Site-specific mutagenesis of the self-splicing Tetrahymena intron has been used to investigate the function of C109-G212, a conserved base pair in the P4 stem of group I introns. Mutation of C109 to G affects splicing only slightly, whereas mutation of G212 to A or C reduces the rate of splicing substantially (500-fold reduction in kcat/Km under standard in vitro splicing conditions for the G212C mutant). Splicing activity of the compensatory double mutant (C109G:G212C) is intermediate between those of the two single mutants. Thus, the stability of the P4 stem as well as the identity of the base at position 212 are important for self-splicing. Single and double mutants containing the G212C substitution have a decreased temperature optimum for self-splicing and are partially Mg2+ suppressible, both indicative of structural destabilization. Chemical structure mapping indicates that the mutations do not redirect the global folding of the RNA, but affect the structure locally and at one other site (A183) that is distant in the secondary structure. We propose that, in addition to its pairing in P4, G212 is involved in a base triplet or an alternate base pair that contributes to the catalytically active tertiary structure of the ribozyme.

Animals↗
PubMed1992

Characterization of the Antirrhinum floral homeotic MADS-box gene deficiens: evidence for DNA binding and autoregulation of its persistent expression throughout flower development.

We have determined the structure of the floral homeotic deficiens (defA) gene whose mutants display sepaloid petals and carpelloid stamens, and have analysed its spatial and temporal expression pattern. In addition, several mutant alleles (morphoalleles) were studied. The results of these analyses define three functional domains of the DEF A protein and identify in the deficiens promoter a possible cis-acting binding site for a transcription factor which specifically upregulates expression of deficiens in petals and stamens. In vitro DNA binding studies show that DEF A binds to specific DNA motifs as a heterodimer, together with the protein product of the floral homeotic globosa gene, thus demonstrating that the protein encoded by deficiens is a DNA binding protein. Furthermore, Northern analysis of a temperature sensitive allele at permissive and non-permissive temperatures provides evidence for autoregulation of the persistent expression of deficiens throughout flower development. A possible mechanism of autoregulation is discussed.

Alleles↗