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Phenylacetic acid production in dominant and non-dominant vervet monkeys.

Free and conjugated plasma phenylacetic acid concentrations were significantly higher in dominant male vervet monkeys than in non-dominant males living in stable social groups. These findings may be connected with an earlier observation that plasma from aggressive human psychopaths contains higher concentrations of phenylacetic acid than non-aggressive controls; whether they reflect an increased production of phenylethylamine is still unknown.

Animals↗

[Hemispheric dominance for speech and calculation: electrophysiologic correlates of left dominance in left handedness].

Slow brain potentials were recorded in left-handers and right-handers during: (i) processing of language and mental arithmetic tasks, without vocalization, and (ii) subsequent writing down of the answers with either the right or left hand. Left-sided laterality of negative potentials was taken as evidence of hemispheric dominance. It appeared during the processing of words and numbers in 26 of the 30 left-handers and was localized mainly in the left frontal and temporal parietal regions. Similar results were found with the right-handers. This electrophysiological evidence indicates that the left hemisphere is dominant for language and calculation in the vast majority of left-handers. Only when writing with either their left or right hand do left-handers show less left-sided laterality than right-handers.

Adolescent↗

A novel pattern of mutation in uromodulin disorders: autosomal dominant medullary cystic kidney disease type 2, familial juvenile hyperuricemic nephropathy, and autosomal dominant glomerulocystic kidney disease.

BACKGROUND: Autosomal dominant medullary cystic kidney disease type 2 (MCKD2), familial juvenile hyperuricemic nephropathy (FJHN), and autosomal dominant glomerulocystic kidney disease (GCKD) constitute a hereditary renal disease group that may lead to end-stage renal failure caused by mutations of the UMOD gene and its product, uromodulin or Tamm-Horsfall protein. Of 34 different UMOD mutations described to date, 28 were located in exon 4. Based on such mutation clustering, some investigators have proposed that the sequencing of UMOD exon 4 might become a preliminary diagnostic test for patients with this phenotype. METHODS: We performed linkage analysis and sequencing of the entire codifying region of the UMOD gene in 4 Spanish families with MCKD/FJHN/GCKD. RESULTS: All families were shown to present mutations in the UMOD gene. In 3 families, the detected mutations were located in exon 5. Although 1 novel mutation (Gln316Pro) was observed in 2 of these families, a previously reported mutation (Cys300Gly) was found in the other kindred. The Cys300Gly mutation was found in the family presenting with a GCKD phenotype. CONCLUSION: Our data show a novel mutation pattern in UMOD , suggesting that exon 5 mutations can be more frequent in some populations. Our results support that every exon of the UMOD gene must be included in molecular testing and provide additional evidence for the existence of a fourth calcium-binding epidermal growth factor-like domain in the structure of Tamm-Horsfall protein. A second family reported to date is described, confirming that the GCKD phenotype may be caused by a UMOD mutation.

Adult↗

A missense mutation in the desmin rod domain is associated with autosomal dominant distal myopathy, and exerts a dominant negative effect on filament formation.

In some myopathies of distal onset, the intermediate filament desmin is abnormally accumulated in skeletal and cardiac muscle. We report the first point mutation in desmin cosegregating with an autosomal dominant form of desmin-related myopathy. The L345P desmin missense mutation occurs in a large, six generation Ashkenazi Jewish family. The mutation is located in an evolutionarily highly conserved position of the desmin coiled-coil rod domain important for dimer formation. L345P desmin is incapable of forming filamentous networks in transfected HeLa and SW13 cells. We conclude that the L345P desmin missense mutation causes myopathy by interfering in a dominant-negative manner with the dimerization-polymerization process of intermediate filament assembly.

Amino Acid Sequence↗

Chinese white Rongchang pig does not have the dominant white allele of KIT but has the dominant black allele of MC1R.

The mast/stem cell growth factor receptor (KIT) and melanocortin receptor 1 (MC1R) mutations are responsible for coat color phenotypes in domestic pigs. Rongchang is a Chinese indigenous pig breed with a white coat color phenotype. To investigate the genetic variability of the KIT and MC1R genes and their possible association with the coat color phenotype in this breed, a gene duplication and splice mutation of KIT were diagnosed in a sample of 93 unrelated Rongchang animals. The results show that Rongchang pigs have a single copy of KIT without the splice mutation at the first nucleotide of intron 17, indicating that the dominant white I allele of KIT is not responsible for their white phenotype. The KIT mRNA and MC1R coding sequences were also determined in this breed. Three putative amino acid substitutions were found in the KIT gene between Rongchang and Western white pigs, their association with the Rongchang white phenotype remains unknown. For the MC1R gene, Rongchang pigs were demonstrated to have the same dominant black allele (E(D1)) as other Chinese breeds, supporting the previous conclusion that Chinese and Western pigs have independent domestication origin. We also clarified that the Rongchang white phenotype was recessive to nonwhite color phenotypes. Our results provide a good starting point for the identification of the mutations underlying the white coat color in Rongchang pigs.

Alleles↗

Electromyogram and force during stimulated fatigue tests of muscles in dominant and non-dominant hands.

Mechanical and electrical properties were studied for the first dorsal interosseous muscle of the dominant (d-FDI) and non-dominant hand (nd-FDI). Observations were made before, during and after a fatigue test, fatigue being evoked by percutaneous electrical stimulation of the ulnar nerve. The test consisted of 30 Hz bursts of ten supramaximal 0.1 ms pulses, repeated once a second for 5 min. The measurements included the amplitude of the first and fifth compound muscle action potentials (M-waves) within bursts, the peak burst force and the amplitude and time course of single twitches. At the end of the fatigue test, burst force had decreased to about the same extent in the FDI of both hands. The final decline in first M-wave amplitude was, however, significantly more pronounced for the nd-FDI than for the d-FDI. There were no longer any significant discrepancies between the two muscles after a subsequent recovery-period of 15 min. Comparisons among nd-FDI of various individuals demonstrated the presence of significant inter-individual differences in fatigue-related force-drop without any associated differences in M-wave decline. Intra-individual variability was similar for fatigue-related force-drop and M-wave decline.

Adolescent↗

The dual task paradigm: speech dominance or manual dominance?

Two hundred and sixty monolinguals divided into subgroups based on gender, handedness, and familial left-handedness, were given a concurrent task, verbal-manual interference paradigm. The primary purpose of the study was to test whether the dual task interference effects were more related to hemispheric speech or manual dominance factors. The dominant hand, regardless of handedness, underwent relatively more tapping interference than the nondominant hand. The obtained results seriously question the basic assumptions underlying the interpretation of the dual task paradigm as an assessment index for hemispheric language lateralization. A possible explanation of this result that is in keeping with known hemispheric language representation proportions in left-handers is offered based on left hemisphere ipsilateral control of the left hand.

Female↗

A subchronic, teratologic, and dominant lethal study of 2-methylresorcinol in rats. II. Teratologic and dominant lethal study.

2-Methylresorcinol (2-MR) was administered to groups of 40 male and 35 female Sprague-Dawley rats by admixture with the diets at levels of 0.1, 0.4, and 1.5% (see Part I; T.H. Re, R.F. Loehr, S.C. Rodriguez, C.E. Gilmore, and C.M. Burnett, 1986, Fundam. Appl. Toxicol. 7, 287-292). Following 90 days of exposure, 25 randomly selected females in each group were mated to untreated males in a teratology study in which exposure to 2-MR continued throughout the gestation period. After 20 weeks of exposure to 2-MR, 20 males per group were removed from the test diets containing 2-MR and were mated to untreated females in a dominant lethal study. Feeding 2-MR at levels of 0.4 and 1.5% in the diet was associated with a significant reduction in body weight gain. 2-MR was not teratogenic nor did it induce a dominant lethal effect under the conditions of this study.

Animals↗

Dominant CTL-inducing epitopes on GAD65 are adjacent to or overlap with dominant Th-inducing epitopes.

Immune responses to GAD65 are associated with progression to T1D in NOD mice and humans. Our previous data suggested that dominant CTL-inducing and Th-inducing determinants might preferentially occur in proximal GAD65 sequences. Using a panel of 192 GAD65 peptides we discovered that four of the eight CTL-inducing peptides, including those most biologically relevant, were proximal to previously described I-A(g7)-restricted determinants that characterize natural islet autoimmunity in NOD mice. The CTL determinants 546-554 and 88-98 were presented by GAD65-expressing cells and were displayed on pancreatic LNC, along with 268-278, following beta cell damage. p546-554-specific CTL were detectable in young naive mice and transferred significant islet inflammation into NOD.scid mice. These findings demonstrate that unique regions of GAD65 may be favored during antigen processing, such that diverse dominant epitopes are produced from overlapping sequences, which can engage distinct T cell subsets. Additionally, cross-presentation may enhance GAD65-specific CTL responses in T1D.

Amino Acid Sequence↗

Kinetics of anaerobic metabolism in human skeletal muscle: influence of repetitive high-intensity exercise on sedentary dominant and non-dominant forearm. A 31P NMR study.

Potential differences were assessed between the dominant (D) and non-dominant (ND) forearms of sedentary subjects during anaerobic exercise. Subjects performed voluntary concentric contractions of D and ND forearm muscle during a series of three high-intensity (60% of the maximal voluntary contraction force (MVC)) exercise bouts. The time-dependent changes in intracellular pH (pH(i)), Pi, and PCr concentrations, and their relation to muscular work were examined using 31P magnetic resonance spectroscopy (MRS) techniques, and revealed that D forearm metabolic kinetics in sedentary individuals are improved during repetitive high-intensity exercise compared to their respective ND forearm muscle. We postulate that the more regular and preferential utilization of the D limb leads to a "trained-like" condition.

Adult↗

Regulation of interleukin-2 transcription by inducible stable expression of dominant negative and dominant active mitogen-activated protein kinase kinase kinase in jurkat T cells. Evidence for the importance of Ras in a pathway that is controlled by dual receptor stimulation.

Engagement of the T cell receptor induces the activation of several mitogen-activated protein kinase modules, including the extracellular signal-regulated kinase and c-Jun N-terminal kinase (JNK) cascades. Whereas extracellular signal-regulated kinase is activated by T cell receptor/CD3 ligation alone, activation of JNK requires co-stimulation by the CD28 receptor. Activation of MEKK-1, which acts as a mitogen-activated protein kinase kinase kinase in the JNK pathway, was also induced by CD3 plus CD28 (CD3/CD28) ligation in Jurkat cells. To study the significance of the JNK cascade in T lymphocytes, we established stable Jurkat cell lines that inducibly express dominant active (DA) or dominant negative (DN) MEKK-1. Whereas expression of DA-MEKK-1 resulted in the constitutive activation of JNK along with the transcriptional activation of the minimal interleukin-2 (IL-2) promoter, DN-MEKK-1 inhibited JNK responsiveness during CD3/CD28 co-stimulation. In addition to inhibiting CD3/CD28-induced IL-2 mRNA expression, DN-MEKK-1 abrogated the transcriptional activation of the IL-2 promoter and the distal nuclear factor of activated T cells (NFAT)-activating protein 1 (AP-1) response element in that promoter. A c-Jun mutant lacking activation sites for JNK also interfered with the activation of the distal NFAT/AP-1 complex, suggesting that the JNK pathway functions by controlling AP-1 response elements in the IL-2 promoter. Using inducible stable expression of DA- and DN-Ras in Jurkat cells, we found that Ras regulates JNK activation in these cells. Our results suggest that the dual ligation of CD3 and CD28 in T cells triggers a cascade of events that involve Ras, the JNK cascade, and one or more AP-1 response elements in the IL-2 promoter.

Base Sequence↗

A pregnancy following PGD for X-linked dominant [correction of X-linked autosomal dominant] incontinentia pigmenti (Bloch-Sulzberger syndrome): case report.

Incontinentia Pigmenti (Bloch-Sulzberger syndrome) is a rare multisystem, ectodermal disorder associated with dermatological, dental and ocular features, and in <10% of cases, severe neurological deficit. Pedigree review suggests X-linked dominance with lethality in affected males. Presentation in female carriers is variable. Following genetic counselling, a mildly affected female carrier diagnosed in infancy with a de novo mutation was referred for preimplantation sexing, unusually selecting for male gender, with an acceptance of either normality or early miscarriage in an affected male. Following standard in-vitro fertilization and embryo biopsy, fluorescence in situ hybridization (FISH) unambiguously identified two male and two female embryos. A single 8-cell, grade 4 male embryo was replaced. A positive pregnancy test was reported 2 weeks after embryo transfer, although ultrasonography failed to demonstrate a viable pregnancy. Post abortive fetal tissue karyotyping diagnosed a male fetus with trisomy 16. This is an unusual report of preimplantation genetic diagnosis (PGD) being used for selection of males in an X-linked autosomal dominant disorder and demonstrates the value of PGD where amniocentesis or chorion villus sampling followed by abortion is not acceptable to the patient. This case also demonstrates the importance of follow-up prenatal diagnosis.

Adult↗

Immunization with live versus killed Salmonella typhimurium leads to the generation of an IFN-gamma-dominant versus an IL-4-dominant immune response.

The mechanisms responsible for differential commitment of effector T cells to the production of either the IL-4/5/10 group or to the IL-2/IFN-gamma group of lymphokines during an immune response have not yet been clearly elucidated. We have used Salmonella typhimurium as a model murine bacterial parasite in BALB/c mice for live-cell versus killed-cell immunization and looked at the immune response in terms of delayed type hypersensitivity (DTH), IgG subclass distribution in the serum antibody response, and antigen-specific T cell proliferation and lymphokine secretion. The results indicate that the two forms of immunogen induce qualitatively different immune responses. Intraperitoneal immunization with live bacteria induces an IFN-gamma-dominant immune response associated with a strong DTH reaction and relatively higher levels of specific antibodies belonging to the IFN-gamma-dependent IgG2a isotype rather than the IL-4-dependent IgG1 isotype. Immunization with heat-killed bacteria gives rise to an IL-4-dominated response that shows excellent proliferative capacities in vitro, with lower levels of DTH responses and comparatively high levels of specific antibodies of the IgG1 isotype. IL-2 production in the responses generated by the two modes of immunization, however, is not preferentially associated with IFN-gamma production, unlike the reported profiles of long-lived murine T cell clones in vitro.

Animals↗

Hepatic metastases from breast carcinoma: comparison of noncontrast, arterial-dominant, and portal-dominant phase spiral CT.

PURPOSE: The purpose of this work was to determine the relative value of noncontrast (NC), arterial-dominant (AD), and portal-dominant (PD) phase images in spiral CT of the liver for breast cancer metastases. METHOD: Forty-four spiral CT scans in 18 patients with hepatic metastases from breast cancer were retrospectively reviewed by three radiologists. Subjective evaluations of overall lesion conspicuity and margination were graded on a 5 point scale for NC, AD, and PD phase images, and the three phases were also ranked for demonstration of overall tumor volume. Those scans with hypervascular lesions were separately analyzed, resulting in three groups (all, hypervascular, hypovascular). RESULTS: For lesion conspicuity and margination for the entire study group, AD phase images showed the lowest grades (1.97 and 1.83), whereas the PD phase showed the highest grade (3.34 and 3.14; p < 0.0001) followed by NC (2.36 and 2.42; p < 0.0001). For the hypervascular subgroup, the AD phase also showed the lowest grades (2.39 and 2.24). In no case did the AD phase show more lesions than the combination of NC and PD phases. For depiction of overall tumor volume, the AD phase had the lowest ranking (2.51) compared with the NC and PD phases (1.71 and 1.78; p < 0.001). For the hypervascular subgroup, the AD phase had the lowest ranking (2.33) compared with the NC and PD phases (1.39 and 2.27; p < 0.0001). CONCLUSION: The AD phase is not required for lesion detection in spiral CT for hepatic metastases from breast carcinoma. The NC phase depicts the maximal tumor volume.

Adult↗

Liquid flow through aqueous foams: from the plateau border-dominated regime to the node-dominated regime.

The velocity of gravity-driven flow through aqueous foams (forced drainage) has been determined by using electrical conductivity measurements in foams made with solutions of different surfactants. There is always a scaling behavior (power law) between the drainage velocity V and the imposed flow rate Q: V approximately Q(alpha), but the alpha coefficient varies between the different surfactant solutions and increases with surface viscosity. An explanation of this behavior will be given in terms of a transition between a node-dominated and a Plateau border-dominated viscous dissipation, for which theory predicts respectively alpha=1/3 and alpha=1/2.

Journal Article↗

Thyroid autoantibody profiles in ophthalmic dominant and thyroid dominant Graves' disease differ and suggest ophthalmopathy is a multiantigenic disease.

BACKGROUND: Thyroid-associated ophthalmopathy (TAO) occurs in 25-50% of patients with Graves' disease (GD) and is occasionally seen in hypothyroid Hashimoto's disease or euthyroid individuals. The link between TAO and hyperthyroidism remains unclear. We hypothesized that qualitative or quantitative differences in thyroid antibodies might determine individual predisposition to these features. METHODS: In a prospective study over 3 years, thyroid antibody levels were measured in all patients diagnosed at the Singapore National Eye Centre to have GD. These patients had no known history of thyroid disease, presented with eye complaints and diagnosis was made by an ophthalmologist. A total of 31 patients were identified. Antibody levels were compared against 71 consecutive patients referred to a thyroid clinic (TC) for thyrotoxic symptoms in whom the diagnosis of GD was confirmed by a thyroidologist. FINDINGS: Thyroid autoantibody profiles of patients diagnosed at the ophthalmology centre (OC) and TC differed markedly. OC patients had significantly higher TSI (P = 0.003) but lower TPOAb (P = 0.008) and TgAb levels (P < 0.001). In contrast, TC patients had higher free T4 (P = 0.048) and higher TBII levels (P < 0.001). Antibody levels were correlated with four parameters of ophthalmopathy--chronic lid retraction, lid swelling, proptosis and extraocular myopathy (EOM). On univariate logistic regression analysis, TSI was a positive predictor and TPOAb and TgAb negative predictors of all four features. In the absence of TgAb, the odds ratios for individual TAO features ranged from 2.8 to 7.9, with corresponding values of 3.9-10.2 when TPOAb was absent. In stepwise logistic regression analysis, TSI was the strongest independent predictor of all aspects studied: lid fullness P = 0.001, proptosis P = 0.001, lid retraction P = 0.008, EOM P = 0.009. Among smokers, TPOAb were significantly lower (P = 0.044) but no association between smoking and the other antibodies was observed. INTERPRETATION: The study demonstrates markedly different thyroid autoantibody profiles in newly diagnosed GD patients with ophthalmic dominant as opposed to thyroid dominant features. It suggests differing antibody patterns are associated with predisposition to hyperthyroidism and orbitopathy. In addition, an association between smoking and low TPOAb levels was noted.

Adult↗

Comparison of sympathetic nerve activity during handgrip exercise performed with the dominant and non-dominant arm.

To investigate whether handedness influences sympathetic nerve responses during exercise, muscle sympathetic nerve activity (MSNA), heart rate, and blood pressure during maximal voluntary handgrip exercise under ischemic conditions (MVHG) and during post-exercise ischemia (PEI) were compared between the dominant (DA) and non-dominant arm (NDA) in eight left-handed subjects. MSNA expressed as burst frequency or total activity (TSNA) and blood pressure increased significantly during MVHG and PEI. Although the heart rate rose during MVHG, it returned to resting level during PEI. The increased MSNA was less in DA exercise than the NDA, while no significant differences in heart rate and blood pressure response were observed. The results suggest that handedness seems to influence reflex sympathetic activation during muscular contraction, but has no significant effect on heart rate or blood pressure.

Adult↗

[Synergy, addition, indifference, antagonism and dominance. Dominance and antibiotic combination].

Six strains of Staphylococcus aureus have been studied using an original method which associate the chessboard's technique to that of bactericidal kinetic's. Associations of pefloxacin and rifampicin, vancomycin and fosfomycin are analysed, and result of each concentration's connection is expressed, at 1.5, 3,5 and 24 h, by a three dimensional representation, which facilitate the phenomenon's dynamic. Interpretation of these diagrams can show the classical phenomena of synergy, addition, indifference and antagonism, and also that of domination of an antibiotic in the association. This one can work, by example, by imposing its bactericidal's speed (vancomycin) or by selecting deficient surviving bacteria (rifampicin). This, the intrinsic and sometimes undesirable characteristics of some antibiotics are not masked by the others antibiotics used in the association. This mechanism must be proved in vivo, but it is sure that during physico-chemical inactivity or during diffusion's deficiency of one of antibiotics, transient relation of concentrations are favorable conditions for domination's expression.

Anti-Bacterial Agents↗