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Results for “Functional Laterality”

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PubMed2005

Familial nonmedullary thyroid cancer.

Familial nonmedullary thyroid cancer (FNMTC) is a syndrome of familial clustering of thyroid cancers of follicular cell origin. It is characterized by multifocality, early onset, more recurrences, and a higher degree of aggressiveness than nonfamilial thyroid cancers of follicular cell origin. An autosomal dominant inheritance pattern with reduced penetrance appears likely in most pedigrees. Although several candidate genes responsible for isolated clinical variants of FNMTC have been identified in single families, the gene(s) responsible for the vast majority of FNMTC cases has yet to be identified. Members of FNMTC cohorts should be followed longitudinally with physical examination and ultrasonography, and aggressively treated when cancer is diagnosed. When cancer is diagnosed, total thyroidectomy should be performed, and most patients should have a prophylactic central neck dissection and a therapeutic lateral functional neck dissection, postoperative radioiodine ablation and thyroid-stimulating hormone (TSH) suppressive therapy. Close follow-up with stimulated thyroglobulin levels, neck ultrasounds, and radioiodine scans are also central to the management strategy.

Humans↗

PubMed1996

Cell cycle control by Xenopus p28Kix1, a developmentally regulated inhibitor of cyclin-dependent kinases.

We have isolated Xenopus p28Kix1, a member of the p21CIP1/p27KIP1/p57KIP2 family of cyclin-dependent kinase (Cdk) inhibitors. Members of this family negatively regulate cell cycle progression in mammalian cells by inhibiting the activities of Cdks. p28 shows significant sequence homology with p21, p27, and p57 in its N-terminal region, where the Cdk inhibition domain is known to reside. In contrast, the C-terminal domain of p28 is distinct from that of p21, p27, and p57. In co-immunoprecipitation experiments, p28 was found to be associated with Cdk2, cyclin E, and cyclin A, but not the Cdc2/cyclin B complex in Xenopus egg extracts. Xenopus p28 associates with the proliferating cell nuclear antigen, but with a substantially lower affinity than human p21. In kinase assays with recombinant Cdks, p28 inhibits pre-activated Cdk2/cyclin E and Cdk2/cyclin A, but not Cdc2/cyclin B. However, at high concentrations, p28 does prevent the activation of Cdc2/cyclin B by the Cdk-activating kinase. Consistent with the role of p28 as a Cdk inhibitor, recombinant p28 elicits an inhibition of both DNA replication and mitosis upon addition to egg extracts, indicating that it can regulate multiple cell cycle transitions. The level of p28 protein shows a dramatic developmental profile: it is low in Xenopus oocytes, eggs, and embryos up to stage 11, but increases approximately 100-fold between stages 12 and 13, and remains high thereafter. The induction of p28 expression temporally coincides with late gastrulation. Thus, although p28 may play only a limited role during the early embryonic cleavages, it may function later in development to establish a somatic type of cell cycle. Taken together, our results indicate that Xenopus p28 is a new member of the p21/p27/p57 class of Cdk inhibitors, and that it may play a role in developmental processes.

Amino Acid Sequence↗

PubMed1983

Neuropsychological deficits associated with small unilateral thalamic lesions.

Neuropsychological deficits resulting from small, well demarcated, unilateral thalamic lesions were investigated in 13 right-handed patients. Fourteen patients with deep white matter lesions and 12 normal subjects served as controls. The performance of thalamic patients was generally worse than that of normals and patients with white matter lesions, although the lesions in the latter were significantly larger. There was no clear indication of a dichotomous lateralization of function at the level of the thalamus, although patients with left-sided lesions performed less well in almost all tests. There was some evidence of a rostrocaudal dichotomy, rostral thalamic lesions leading to memory deficits and caudal lesions to impairments of 'abstraction' and 'categorization'.

Adult↗

PubMed2006

A role for proneural genes in the maturation of cortical progenitor cells.

We showed previously that the proneural genes Neurogenin1 (Ngn1) and Ngn2 are required to specify the phenotypes of early- and not late-born neurons in the neocortex, acting in part through repression of Mash1, a third cortically expressed proneural gene. The precise timing of Ngn1/2 specification activity was unexpected given these genes are expressed throughout cortical development, prompting us to search for a later function. Here we reveal that Ngn2 and Mash1 are expressed in a dynamic fashion, acquiring a cell cycle-biased, nonoverlapping distribution, with preferential expression in prospective basal progenitors, during mid corticogenesis. We also identified a new function for Ngn2 during this latter period, demonstrating that it is required to regulate the transit of cortical progenitors from the ventricular zone (VZ) to the subventricular zone. Notably, Ngn2 regulates progenitor maturation at least in part through repression of Mash1 as misexpression of Mash1 strongly enhanced progenitor cell exit from the VZ. Significantly, the ability of Mash1 to promote progenitor cell maturation occurred independently of its ability to respecify cortical cells and is thus a novel function for Mash1. Taken together, these data support a model whereby Ngn2 and Mash1 function together to regulate the zonal distribution of progenitors in the developing neocortex.

Aging↗

PubMed1986

A female-specific lethal lesion in an X-linked positive regulator of the Drosophila sex determination gene, Sex-lethal.

Characterization of a partial-loss-of-function, female-specific lethal mutation has identified an X-linked genetic element (1-34.3; 10B4) that functions as a positive regulator of Sxl, a central gene controlling sex determination in Drosophila melanogaster. The name, sisterless-a, was chosen both to suggest functional similarities that exist between this gene and another positive regulator of Sxl, the maternally acting gene daughterless (da), and also to highlight an important difference; namely, that in contrast to da, it is the zygotic rather than maternal functioning of sis-a that is involved in its interaction with Sxl. As with da, the female-specific lethal phenotype of sis-a is suppressed both by SxlM#1, a gain-of-function mutant allele of the target gene, and, to a lesser extent, by a duplication of Sxl+. Mutations at sis-a, da and Sxl display female-specific dominant synergism, each enhancing the others' lethal effects. The allele specificity with respect to Sxl of these dominant interactions indicates that sis-a and da affect the same aspect of Sxl regulation. As with previous studies of da and Sxl, the masculinizing effects of loss of sis-a function are generally obscured by lethal effects, presumably related to upsets in dosage compensation. The masculinizing effects can be dissociated from lethal effects by analysis of triploid intersexes (XX AAA) or by analysis of diploid females who are also mutant for autosomal genes known to be required for the transcriptional hyperactivation associated with dosage compensation in males. Analysis of foreleg development shows that intersexuality generated by sis-a is of the mosaic type: At the level of individual cells, only male or female development is observed, never an intermediate sexual phenotype characteristic of true intersexes. Sexual development of diplo-X germline and somatic clones of sis-a tissue generated by mitotic recombination during larval stages is normal, as is the sexual phenotype of homozygous sis-a escapers. Considered in their totality, these results indicate that sis-a functions early in development to help establish the activity state of Sxl and thereby initiate the sexual pathway commitment, rather than functioning later in the processes by which Sxl maintains and expresses the sex determination decision.

Animals↗

PubMed1995

Proliferation-dependent differential regulation of the dolichol pathway genes in Saccharomyces cerevisiae.

The dolichol pathway serves in the synthesis of the dolichol-linked oligosaccharide precursor for protein N-glycosylation. Recently, we reported that mRNAs of genes that function at the early steps in the dolichol pathway in yeast, ALG7, ALG1 and ALG2, were co-ordinately induced following growth stimulation of G0-arrested cells in a manner similar to that of the transcripts of the early growth response genes (Kukuruzinska, M.A. and Lennon, K. Glycobiology, 4, 437-443, 1994). To determine whether the entire dolichol pathway was co-ordinately regulated with growth, we examined the expression of genes functioning late in the pathway, including two genes encoding oligosaccharyltransferase subunits, at two critical control points in the G1 phase of cell cycle: G0/G1 and START. We show that early in G1, at the G0/G1 transition point, the late ALG genes and the two oligosaccharyltransferase-encoding genes examined were regulated co-ordinately with the early ALG genes: they were downregulated upon exit from the mitotic cell cycle into G0, and they were induced following growth stimulation in the absence of de novo protein synthesis. All the dolichol pathway genes produced transcripts with short half-lives that were rapidly stabilized in the presence of cycloheximide. In contrast, cell division arrest late in G1, at START, was accompanied by a selective downregulation of only the first dolichol pathway gene, ALG7, and not of the genes functioning later in the pathway. These results indicate that, depending on their position in G1, cells either co-ordinately or differentially regulate the dolichol pathway genes.

Base Sequence↗

PubMed1997

Multiple isoforms of GAGA factor, a critical component of chromatin structure.

The GAGA transcription factor of Drosophila melanogaster is ubiquitous and plays multiple roles. Characterization of cDNA clones and detection by domain- specific antibodies has revealed that the 70-90 kDa major GAGA species are encoded by two open reading frames producing GAGA factor proteins of 519 amino acids (GAGA-519) and 581 amino acids (GAGA-581), which share a common N-terminal region that is linked to two different glutamine-rich C-termini. Purified recombinant GAGA-519 and GAGA-581 proteins can form homomeric complexes that bind specifically to a single GAGA sequence in vitro. The two GAGA isoforms also function similarly in transient transactivation assays in tissue culture cells and in chromatin remodeling experiments in vitro . Only GAGA-519 protein accumulates during the first 6 h of embryogenesis. Thereafter, both GAGA proteins are present in nearly equal amounts throughout development; in larval salivary gland nuclei they colocalize completely to specific regions along the euchromatic arms of the polytene chromosomes. Coimmunoprecipitation of GAGA-519 and GAGA-581 from crude nuclear extracts and from mixtures of purified recombinant proteins, indicates direct interactions. We suggest that homomeric complexes of GAGA-519 may function during early embryogenesis; both homomeric and heteromeric complexes of GAGA-519 and GAGA-581 may function later.

Amino Acid Sequence↗

PubMed1995

Gender differences in schizophrenia: hormonal effect or subtypes?

Compared with their male counterparts, females with schizophrenia, on average, show better premorbid functioning, later onset, and a more benign course of illness. They are also more likely to have a family history of schizophrenia and/or affective illness, to exhibit "atypical" and affective features, and to show a seasonal pattern of hospital admission that mimics that of patients with mania. However, there exists a paradox. Although schizophrenia in females has much in common with affective disorder, the "schizophrenogenic" effect of maternal influenza also appears to be more significant in female than in male schizophrenia. Perhaps females with a predisposition to affective psychosis who have also been subject to the effects of maternal viral infection during gestation develop some subtle neurodevelopmental damage that renders their psychosis schizophrenia-like.

Female↗

PubMed1986

A comparison between sternum and rib in osteomyocutaneous reconstruction of major mandibular defects.

Following major mandibular resection for intraoral malignancy, 6 patients underwent reconstruction using rib and 22 patients underwent reconstruction using the outer table of the sternum; the pectoralis major muscle was used as the vascular carrier for both bone and skin in all patients. Five of the 6 patients in the rib group encountered major complications. In the sternal group, loss of bone occurred in only 2 of 22 patients. Those aspects of technique considered important to the outcome are detailed. Results are discussed in terms of bone survival, intraoral features including denture placement, and the patient's appearance. The sternal transfer has consistently shown itself to be superior to rib, in terms of both early morbidity and later functional and aesthetic results. It is our present method of choice for reconstruction following major intraoral resection.

Bone Transplantation↗

PubMed1992

Intracavitary repair of ventricular aneurysm and regional dyskinesia.

Myocardial damage after infarction is a common sequela in patients with coronary occlusive disease. The extent of injury varies and may be localized or diffuse. Since March 1989, the authors have used a new surgical repair technique that employs an intracavitary patch of Dacron fabric or glutaraldehyde-treated pericardium to exclude the hypokinetic or fibrotic myocardial segment. An elliptical configuration preserves the contour and volume of the ventricular cavity. After securing the patch, the ventriculotomy is closed with a simple continuous suture. Through July 31, 1991, 136 patients underwent repair using this technique. Of these patients, 100 (group I) had neither sustained an acute myocardial infarction (within 30 days before surgery) nor had undergone previous cardiac surgery, whereas 36 (group II) had sustained an acute myocardial infarction or had undergone previous cardiac surgery. In group I, four (4%) died within 30 days of surgery, and seven died later, resulting in a 6-month survival of 90.5% and a 1-year survival of 85.3%. In group II, 11 (30.6%) died within 30 days of surgery, and three died later. Functional class improved after repair in 95.7% of patients in group I and all patients in group II. In both groups, ejection fraction improved significantly (p less than 0.0001, group I; p less than 0.0001, group II). By eliminating the need for epicardial buttresses to repair the ventriculotomy, myocardial revascularization has been possible in most patients. This method of intraventricular repair is also appropriate for patients with calcified aneurysms, acquired ventricular septal defects, and acute ventricular rupture.

Bioprosthesis↗

PubMed2000

Opposite hemispheric lateralization effects during speaking and singing at motor cortex, insula and cerebellum.

Aside from spoken language, singing represents a second mode of acoustic (auditory-vocal) communication in humans. As a new aspect of brain lateralization, functional magnetic resonance imaging (fMRI) revealed two complementary cerebral networks subserving singing and speaking. Reproduction of a non-lyrical tune elicited activation predominantly in the right motor cortex, the right anterior insula, and the left cerebellum whereas the opposite response pattern emerged during a speech task. In contrast to the hemodynamic responses within motor cortex and cerebellum, activation of the intrasylvian cortex turned out to be bound to overt task performance. These findings corroborate the assumption that the left insula supports the coordination of speech articulation. Similarly, the right insula might mediate temporo-spatial control of vocal tract musculature during overt singing. Both speech and melody production require the integration of sound structure or tonal patterns, respectively, with a speaker's emotions and attitudes. Considering the widespread interconnections with premotor cortex and limbic structures, the insula is especially suited for this task.

Adult↗

PubMed1997

Five years after child sexual abuse: persisting dysfunction and problems of prediction.

OBJECTIVE: To assess change in behavior, depression, and self-esteem in sexually abused children after 5 years and to determine which factors predict later functioning. METHOD: Sixty-eight of 84 children and their nonoffending parents were reassessed after 5 years for depression, self-esteem, and behavior problems in the children; parental mental health; and family functioning. RESULTS: There were no significant changes in depression, self-esteem, or behavior over 5 years. Forty-three percent of the children were now sad or depressed, 43% had low self-esteem, and 46% had behavioral dysfunction. While some children improved, a nearly equal number deteriorated, with no clear pattern of change. The only abuse-related variables associated with 5-year functioning were further contact with the abuser, which was significantly associated with depression and self-esteem, and sexual abuse prior to intake, which was related to an increased incidence of behavior problems. Older children showed more depression and lower self-esteem but less behavioral dysfunction. Poor family functioning at 5 years was associated with low self-esteem and behavior problems. Treatment had no effect on depression, self-esteem, or behavior. Multivariate analysis showed that depression and self-esteem at intake were prognostic indicators of 5-year outcome. CONCLUSION: Many sexually abused children have continuing problems with behavior, self-esteem, and depression. Family and abuse-related variables do not appear to be good predictors of outcome, although sexually abused children who are sad or depressed and have low self-esteem at intake are likely to have continuing problems in these areas.

Adolescent↗

PubMed1987

Borderline personality disorder and unipolar affective disorder. Long-term effects of comorbidity.

This study tracks the baseline clinical presentation and long-term course (average 15 years) of three patient groups defined largely by DSM-III from the Chestnut Lodge follow-up study: unipolar affective disorder (UNI, N = 22), borderline personality disorder (BPD, N = 55), and a comorbid cohort (UNI/BPD, N = 21). Comorbid BPD effects on UNI include earlier onset and absence of psychotic symptoms at baseline and more substance abuse and use of psychiatric treatment at follow-up. Comorbid UNI effects on BPD include better premorbid instrumental functioning, later onset at baseline, and a higher risk for suicide over the long term. Other noteworthy findings are a low rate of suicide (2%) among the noncomorbid BPD patients and a high rate of diagnostic instability (68%) among the noncomorbid UNI patients. Findings demonstrate a lack of syndromal stability within and among all three study groups and highlight the shortcomings of DSM-III for the investigation of comorbidity.

Borderline Personality Disorder↗

PubMed1993

A biomechanical definition of spinal segmental instability taking personal and disc level differences into account.

The biomechanical definition of spinal segmental instability has not been clarified sufficiently, because of the great personal and level differences in intervertebral disc deformation. This article proposes a new method of judging spinal segmental instability regardless of these differences, using lateral functional radiographs. The linear relationship between the disc geometry and the disc deformation was confirmed in the normal intervertebral discs. The degree of spinal segmental instability could be evaluated statistically by calculating a regression residual from the regression line of the normal discs. Strain distributions of an intervertebral disc in the sagittal plane also were investigated to make sure of the differences in the deformation behaviors between normal spines and unstable lumbar spines. Although normal lumbar spines showed the consistent deformation pattern, the patterns of the unstable lumbar spines were different.

Adult↗

PubMed1999

Cells of the monocyte-macrophage lineage and pathogenesis of HIV-1 infection.

It is thought that monocyte-macrophages and probably dendritic cells play a central role in HIV-1 primary infection, as well as in its evolution, given that they are among the first cells infected and later function as important reservoirs for the virus. These cells may participate in the selection of certain viral strains instead of others. Levels of CCR5 coreceptor expression on the surface of monocytes and macrophages determine their susceptibility to infection by HIV-1 strains using this coreceptor and may explain, in part, the differences in the infectivity of these cells through the maturation process. However, selection for certain strains is not only determined by the level of coreceptor expression, but by the biochemical properties of the different coreceptors and their relationship with other surface molecules and the chemokine and cytokine networks, which also influence the selective viral infection and replication in these cells. Any current or newly designed therapies need to be evaluated, including careful analysis of the levels of HIV-1 infection of the cells of the monocyte-macrophage lineage, because these cells are both significant viral reservoirs and a center of virus production at all stages of the disease.

Cell Lineage↗

PubMed2003

Cyclosporin A administration during pregnancy induces a permanent nephron deficit in young rabbits.

Cyclosporin A (CsA) is an immunosuppressive agent used to prevent graft rejection and to treat autoimmune disorders. Successful pregnancies can be achieved among CsA-treated women, although it is known that CsA is nephrotoxic and crosses the human placenta. The aim of this study was to evaluate the harmlessness of CsA toward the embryonic kidney. Twenty-one pregnant rabbits were divided into four groups. Groups of six and four female animals were subjected to daily injections of 10 mg/kg per d CsA (administered subcutaneously) for 5 d, from day 14 to day 18 of gestation or from day 20 to day 24 of gestation, respectively. In the third group, five female animals received the CsA diluent (Cremophor) from day 14 to day 18 of gestation. The fourth group consisted of six untreated female animals. Pregnancy outcomes among CsA-treated does demonstrated a reduced number of living pups, which were also growth-retarded, with exposure to CsA from day 20 to day 24 of gestation. However, pups exposed to CsA from day 14 to day 18 of gestation exhibited normal fetal growth, and blood concentrations of CsA matched human data. Examinations of kidneys at birth demonstrated vacuolation of proximal and collecting tubules and ureteric bud ends. Increased glomerular volumes and decreased nephron densities suggested nephron mass reduction, which was quantitatively evaluated in 1-mo-old animals. The nephron numbers were reduced by 25 and 33% in day 14 to 18 CsA-treated and day 20 to 24 CsA-treated animals, respectively, which displayed compensatory adaptation of the existing nephrons. However, foci of segmental glomerular sclerosis were already present, which would possibly jeopardize renal function later in life.

Age Factors↗

PubMed2005

Dysfunctional elimination symptoms in childhood and adulthood.

PURPOSE: The dysfunctional elimination syndrome (DES) is rare in adulthood. We evaluate the natural history of DES to identify aspects of the disorder that may be carried into adulthood. MATERIALS AND METHODS: A 2-part questionnaire was devised and self-administered to 191 consecutive women attending a urogynecological clinic (UG) and to 251 normal women. The first section asked for recall of childhood symptoms known to be associated with DES, while the lat-ter section explored current bladder and bowel problems. Data sets from the normal cohort (55) reporting current bladder problems were excluded. Descriptive statistics, chi-square and Mann-Whitney-U tests were used to compare variables. RESULTS: UG patients had significantly higher childhood DES scores than normal women. Overall 41.7% of UG patients could be labeled as having dysfunctional elimination as an adult. Symptoms reported significantly more often in childhood by UG patients than by control women were frequent urinary tract infection, vesicoureteral reflux, frequency, urge incontinence, slow and intermittent urine flow, small volume high urge voids, hospitalization for constipation, frequent fecal soiling and nocturnal enuresis. Higher DES scores correlated significantly with current adult urgency, urge leak, stress incontinence, incomplete emptying, post-void leak, hesitancy, nocturia and nocturnal enuresis. Constipation and fecal incontinence in adulthood also showed a significant association with high DES scores. Logistic regression revealed childhood urgency to be associated with adult DES. CONCLUSIONS: Childhood lower urinary tract dysfunction may have a negative impact on bladder and bowel function later life.

Adolescent↗

PubMed2000

Human-like, population-level specialization in the manufacture of pandanus tools by New Caledonian crows Corvus moneduloides.

The main way of gaining insight into the behaviour and neurological faculties of our early ancestors is to study artefactual evidence for the making and use of tools, but this places severe constraints on what knowledge can be obtained. New Caledonian crows, however, offer a potential analogous model system for learning about these difficult-to-establish aspects of prehistoric humans. I found new evidence of human-like specialization in crows' manufacture of hook tools from pandanus leaves: functional lateralization or 'handedness' and the shaping of these tools to a rule system. These population-level features are unprecedented in the tool behaviour of free-living non-humans and provide the first demonstration that a population bias for handedness in tool-making and the shaping of tools to rule systems are not concomitant with symbolic thought and language. It is unknown how crows obtain their tool behaviour. Nevertheless, at the least they can be studied in order to learn about the neuropsychology associated with early specialized and/or advanced population features in tool-making such as hook use, handedness and the shaping of tools to rule systems.

Animals↗