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At least 1,117 records · Page 62Linked to original sources

PubMed2006

Bone marrow-derived cells require a functional glucose 6-phosphate transporter for normal myeloid functions.

Glycogen storage disease type Ib (GSD-Ib) is caused by a deficiency in the ubiquitously expressed glucose 6-phosphate transporter (Glc-6-PT). Glc-6-PT activity has been shown to be critical in the liver and kidney where a deficiency disrupts glucose homeostasis. GSD-Ib patients also have defects in the neutrophil respiratory burst, chemotaxis, and calcium flux. They also manifest neutropenia, but whether Glc-6-PT deficiency in the bone marrow underlies myeloid dysfunctions in GSD-Ib remains controversial. To address this, we transferred bone marrow from Glc-6-PT-deficient (Glc-6-PT(-/-)) mice to wild-type mice to generate chimeric mice (BM-Glc-6-PT(-/-)). As a control, we also transferred bone marrow between wild-type mice (BM-Glc-6-PT(+/+)). While BM-Glc-6-PT(+/+) mice have normal myeloid functions, BM-Glc-6-PT(-/-) mice manifest myeloid abnormalities characteristic of Glc-6-PT(-/-) mice. Both have impairments in their neutrophil respiratory burst, chemotaxis response, and calcium flux activities and exhibit neutropenia. In the bone marrow of BM-Glc-6-PT(-/-) and Glc-6-PT(-/-) mice, the numbers of myeloid progenitor cells are increased, while in the serum there is an increase in granulocyte colony-stimulating factor and chemokine KC levels. Moreover, in an experimental model of peritoneal inflammation, local production of KC and the related chemokine macrophage inflammatory protein-2 is decreased in both BM-Glc-6-PT(-/-) and Glc-6-PT(-/-) mice along with depressed peritoneal neutrophil accumulation. The neutrophil recruitment defect was less severe in BM-Glc-6-PT(-/-) mice than in Glc-6-PT(-/-) mice. These findings demonstrate that Glc-6-PT expression in bone marrow and neutrophils is required for normal myeloid functions and that non-marrow Glc-6-PT activity also influences some myeloid functions.

Animals↗

PubMed2003

Functional interaction trap: a strategy for validating the functional consequences of tyrosine phosphorylation of specific substrates in vivo.

Protein tyrosine phosphorylation controls diverse signaling pathways, and disregulated tyrosine kinase activity plays a direct role in human diseases such as cancer. Because activated kinases exert their effects by phosphorylating multiple substrate proteins, it is difficult or impossible to assess experimentally the contribution of a particular substrate to a cellular response or activity. To overcome this problem, we have developed a novel approach termed the "functional interaction trap," in which two proteins are induced to interact in a pairwise fashion through an engineered, highly specific binding interface. We show that the functional interaction trap can be used to direct a modified tyrosine kinase to specifically phosphorylate a single substrate of choice in vivo, permitting analysis of the resulting biological output. This strategy provides a powerful tool for validating the functional significance of tyrosine phosphorylation and other post-translational modifications identified by proteomic discovery efforts.

Animals↗

PubMed2001

Neuropsychological functioning and social functioning of survivors of pediatric brain tumors: evidence of nonverbal learning disability.

The purpose of the study was to examine if survivors of pediatric brain tumors exhibit a pattern of performance consistent with nonverbal learning disability (NVLD) and to explore the relationship between neuropsychological and social functioning in these children. A comprehensive neuropsychological battery and objective measures of psychosocial function designed to assess NVLD were administered to 15 survivors of brain tumors, ages 8-12 years. Despite the small sample size, a trend for better verbal skills compared to nonverbal skills was found using composite scores. Parents reported significant social deficits and a tendency for greater internalizing behavior problems as expected in NVLD. Additionally, there was a trend for a positive association between nonverbal scores and social function. Further research is needed to determine if the NVLD pattern observed is attributable to white matter damage of the right hemisphere. Routine neuropsychological and psychosocial assessment and intervention are indicated.

Brain Damage, Chronic↗

PubMed2003

The role of dichotic listening performance and tasks of executive functions in reading impairment: a discriminant function analysis.

This study focused on the role of dichotic listening performance for the identification of reading impaired subtypes. Dichotic listening (DL), using verbal stimuli, has shown to be a valid measure of language lateralization. Usually, lateralization is estimated from the proportion of right ear over left ear accuracy during a free recall test procedure. However, it has been suggested that a more accurate estimate of laterality can be obtained by using a directed attention procedure. A sample of 43 reading disabled children of whom 18 showed signs of impaired language comprehension skills and 25 without language comprehension impairments, were compared to 20 age, and gender, matched controls on dichotic listening performance in both an unbiased free recall task and in a directed attention task using consonant-vowel syllables as dichotic stimuli. A laterality index was calculated for left and right ear stimuli reported during both the free recall condition and the attended ear-scores for the two directed attention conditions. Although both DL procedures yielded significant group differences, with a lower laterality score for the reading disabled compared to the controls, there was no main effect of DL-procedure or group x procedure interaction. Taken alone, DL performance could correctly classify 42% of the reading impaired samples, but together with other measures of executive functions, discriminant function analyses yielded 90.74% accuracy in classifying reading impaired children. The result indicates that DL together with tests of executive functions are valuable tools for assessment of reading impaired subjects.

Child↗

PubMed2001

Advances in functional neuroimaging methodology for the study of brain systems underlying human neuropsychological function and dysfunction.

Functional neuroimaging allows the non-invasive identification of distributed patterns of human brain activity associated with perceptual, congnitive, emotional and behavioral processes, in health and disease. Work in this field is methodologically intensive, requiring an interdisciplinary team of scientists to develop and apply rapidly advancing techniques. Here we focus upon the principles and methods of functional imaging, from hypothesis generation and study design, to subject recruitment and clinical characterization, neuropsychological paradigm development, image acquisition, image processing and statistical analysis, and data interpretation. The strengths and limitations of the various techniques are discussed, with an emphasis on positron emission tomography (PET) and functional magnetic resonance imaging (fMRI), which have proven to be powerful tools for human brain mapping. The integration of these techniques with electroencephalography (EEG) and magnetoencephalography (MEG), which provide greater temporal information, is outlined. An understanding of such methodological issues is a necessary prerequisite to the development of new imaging methods with improved capabilities, to the careful application of existing methods to neuropsychological problems, and to the critical examination of planned or published studies.

Brain↗

PubMed2002

Functional roles of nasal nitric oxide in nasal patency and mucociliary function.

The purpose of this study was twofold: (i) to clarify whether it is possible to change the amount of nasal nitric oxide (NO) artificially; and (ii) to confirm that the artificially altered nasal NO has biological properties such as vasodilatation and mucociliary function. We measured nasal NO and nasal airway resistance (NAR) in healthy subjects before and after topical administration of sodium nitroprusside (SNP), an NO donor. We also measured nasal NO and saccharin transport time after administration of SNP or L-N(G)-nitroarginine methylester (L-NAME), a NO synthase inhibitor. In addition, we examined the effect of SNP and L-NAME on nasal NO and saccharin transport time after pretreatment with flutropium bromide (FB), an anticholinergic agent. Administration of SNP elicited increases in nasal NO and NAR in a dose-dependent manner. Nasal NO decreased significantly after topical administration of L-NAME. Saccharin transport time, an indicator of mucociliary function, was shortened after topical administration of SNP and prolonged after administration of L-NAME. Moreover, these phenomena were observed even after pretreatment with FB. These results suggest that artificially altered nasal NO may affect NAR and mucociliary function.

Administration, Topical↗

PubMed1998

Effect of mental stress and cisapride on autonomic nerve functions in functional dyspepsia.

BACKGROUND: Disordered autonomic nerve function is frequently present in patients with functional dyspepsia (FD). In this study we investigated whether the prokinetic cisapride, which acts via acetylcholine receptors, and stress may modulate these abnormalities. METHODS: Nineteen patients (6 men, 13 women) with FD and 10 healthy subjects (3 men, 7 women) were studied after 3 days' treatment with 10 mg cisapride three times daily and placebo in a crossover design. Mental stress was induced with a videogame. Sympathetic and vagal nerve functions were assessed noninvasively by skin conductance and respiratory sinus arrhythmia, respectively. RESULTS: Vagal tone was significantly lower in FD patients than in controls both before and after mental stress (P < 0.001). Sympathetic tone was higher in patients with FD than in controls (P < 0.03). Generally, stress scores were increased by mental stress in both groups (P < 0.001). In FD patients, but not in controls, cisapride significantly increased the sympathetic tone both before (P < 0.05) and after stress (P < 0.05). CONCLUSIONS: Patients with FD have lower vagal tone and higher sympathetic tone than healthy controls. Treatment with cisapride increased sympathetic tone in the patient group but had no effect on vagal tone.

Adult↗

PubMedDate not supplied

Assessing sexual function and dyspareunia with the Female Sexual Function Index (FSFI) in women with vulvodynia.

Using the Female Sexual Function Index (FSFI; Rosen et al., 2000), we assessed forty-two women with vulvodynia. Internal consistency was high (Cronbach's alphas = 0.90-0.97) for all scales. We compared scale scores to published healthy and patient sample data and found very large effect sizes (1.15-2.83), which indicated that women with vulvodynia reported significantly worse overall sexual function than women without sexual dysfunction and greater pain with sexual intercourse than women with female sexual arousal disorder. Results highlight difficulties experienced across all domains of sexual function, particularly with regard to dyspareunia, for women with vulvodynia. Findings also support the internal consistency and discriminant validity of the FSFI.

Adolescent↗

PubMedDate not supplied

Cognitive functioning in the last year of life as a function of age, gender, and race.

Research has shown that many factors affect cognitive functioning. In this study cognitive functioning was analyzed using proxy reports concerning 17,135 decedents included in the 1993 National Followback Mortality Study conducted for the National Center for Health Statistics. These responses form a representative sample of all U.S. residents over age 15 who died in 1993 (except for those in South Dakota, which did not participate). Decedents had more difficulty understanding where they were than remembering what year it was or in recognizing family members. Logistic regression models found that age, gender, and race were the most important predictors of these basic cognitive functions. Although increasing age was associated with more cognitive difficulties, men had fewer deficits than women and Black Americans tended to have fewer deficits than White Americans. Possible reasons for these findings are discussed as well as some general implications for health service provision.

Black or African American↗

PubMed2006

Assessment of symptom severity and functional status in patients with carpal tunnel syndrome: reliability and functionality of the Turkish version of the Boston Questionnaire.

OBJECTIVES: The aim of this study was to develop a Turkish version of the Boston Questionnaire and assess its reliability and validity. METHODS: Sixty-seven patients with idiopathic carpal tunnel syndrome were included in the study. The Turkish version of Boston Questionnaire was obtained after translation process, and was then administered to subjects twice within seven days. Reliability was assessed by internal consistency (Cronbach's alpha and item-total correlation), and reproducibility. Validity was examined by correlating the Boston Questionnaire scores to general health status (Short Form-36), pain severity (Visual Analogue Scale) and pinch and grip strength measures. RESULTS: Reliability of the Turkish version was very good, with high internal consistency (Cronbach's alpha 0.82 for symptom severity scale, and 0.88 for functional status scale), and reproducibility (Pearson correlation coefficient 0.60 for symptom severity scale, and 0.77 for functional status scale). The Boston Questionnaire scores were correlated with Visual Analogue Scale, physical functioning, physical role, bodily pain and emotional role subscales of Short Form-36, pinch and grip strength scores to obtain coefficients for external construct validity. CONCLUSION: Adaptation of the Boston Questionnaire for use in Turkey was successful. Our results seem to support previous finding of the English version, indicating that it is valid and reliable.

Adult↗

PubMed1996

A study of recovery of memory function in a case of witnessed functional retrograde amnesia.

We describe a case of transient functional retrograde amnesia that had features of a fugue state, and that was accompanied by loss of personal identity and significant autobiographical amnesia. Uniquely, we were able to gather information from witnesses who observed the episode from its onset, and we were also able to monitor the acute stages of recovery of memory function over the subsequent four-week period. The profile of memory loss was characterised by impaired performance on both autobiographical and public events memory tasks, in the context of normal anterograde memory test scores. Shrinkage of retrograde amnesia took place over a four-week period, with autobiographical and public events components of retrograde memory recovering at the same rate. We discuss the possible role of unconscious processes underlying the episode, as compared to conscious simulation. We argue that most cases of functional retrograde amnesia may represent a combination of conscious simulation and unconscious processes.

Journal Article↗

PubMedDate not supplied

The locus of age x health-related physical fitness interactions in serial choice responding as a function of task complexity: central processing or motor function?

The extent to which health-related physical fitness (HRF) attenuates age differences in psychomotor speed as a function of task complexity was examined in a sample of 48 men. Physiological measures were used to assign participants to fitness group (n1-4- = 12): young less fit (mean age = 25.83 years), young fitter (mean age = 25.08 years), old less fit (mean age = 71.83 years), old fitter (mean age = 66.75 years). A serial choice reaction time (RT) task was used in which three conditions of two, four, or eight choices were administered. RTs for the choice and motor components of the task were recorded separately. A significant Age x HRF interaction was found in relation to choice RT but not motor time; older less fit individuals underperformed older fitter participants, and younger adults regardless of fitness level. This interaction remained significant having statistically controlled for motor function, suggesting benefits to central processing. The strength of this interaction did not increase as a function of task complexity. The findings suggest an association between HRF and psychomotor speed, and support the view that physically active lifestyles should be encouraged among older adults.

Adult↗

PubMed1998

A functional GTPase domain, but not its transmembrane domain, is required for function of the SRP receptor beta-subunit.

The signal recognition particle and its receptor (SR) target nascent secretory proteins to the ER. SR is a heterodimeric ER membrane protein whose subunits, SRalpha and SRbeta, are both members of the GTPase superfamily. Here we characterize a 27-kD protein in Saccharomyces cerevisiae (encoded by SRP102) as a homologue of mammalian SRbeta. This notion is supported (a) by Srp102p's sequence similarity to SRbeta; (b) by its disposition as an ER membrane protein; (c) by its interaction with Srp101p, the yeast SRalpha homologue; and (d) by its role in SRP-dependent protein targeting in vivo. The GTP-binding site in Srp102p is surprisingly insensitive to single amino acid substitutions that inactivate other GTPases. Multiple mutations in the GTP-binding site, however, inactivate Srp102p. Loss of activity parallels a loss of affinity between Srp102p and Srp101p, indicating that the interaction between SR subunits is important for function. Deleting the transmembrane domain of Srp102p, the only known membrane anchor in SR, renders SR soluble in the cytosol, which unexpectedly does not significantly impair SR function. This result suggests that SR functions as a regulatory switch that needs to associate with the ER membrane only transiently through interactions with other components.

Amino Acid Sequence↗

PubMed2005

The offloading model for dynein function: differential function of motor subunits.

During mitosis in budding yeast, dynein moves the mitotic spindle into the mother-bud neck. We have proposed an offloading model to explain how dynein works. Dynein is targeted to the dynamic plus end of a cytoplasmic microtubule, offloads to the cortex, becomes anchored and activated, and then pulls on the microtubule. Here, we perform functional studies of dynein intermediate chain (IC) and light intermediate chain (LIC). IC/Pac11 and LIC/Dyn3 are both essential for dynein function, similar to the heavy chain (HC/Dyn1). IC and LIC are targeted to the distal plus ends of dynamic cytoplasmic microtubules, as is HC, and their targeting depends on HC. Targeting of HC to the plus end depends on IC, but not LIC. IC also localizes as stationary dots at the cell cortex, the presumed result of offloading in our model, as does HC, but not LIC. Localization of HC to cortical dots depends on both IC and LIC. Thus, the IC and LIC accessory chains have different but essential roles in dynein function, providing new insight into the offloading model.

Blotting, Western↗

PubMed1979

Augmentation of macrophage complement receptor function in vitro. I. Characterization of the cellular interactions required for the generation of a T-lymphocyte product that enhances macrophage complement receptor function.

The function of complement receptors of mouse peritoneal macrophages was converted in vitro from mediating only attachment of macrophage complement receptor function was achieved by treating freshly explanted macrophages with supernates from cultures containing T lymphocytes and appropriately triggered macrophages. Fc receptor-mediated phagocyctosis by macrophages was required for the production of active supernates, for neither ingestion via the cells' complement receptors nor ingestion via nonimmunologic means was a sufficient stimulus for the macrophages' participation in the generation of supernatant activity. Fc receptor-triggered macrophages interacted by a contact dependent, but histocompatibility independent, mechanism with T lymphocytes, thereby signalling the lymphocytes to elaborate the active product. The possible significance of enhanced macrophage complement receptor function in inflammation, host defense against microbial pathogens, immune complex disease, and neoplasia is discussed.

Animals↗

PubMed1988

Functional heterogeneity of L3T4+ T cells in MRL-lpr/lpr mice. L3T4+ T cells suppress major histocompatibility complex-self-restricted L3T4+ T helper cell function in association with autoimmunity.

The present study demonstrates in MRl-lpr/lpr autoimmune mice an age-dependent loss of MHC-self-restricted function by L3T4+ Th. This defect is not present in age-matched, congenic MRL-+/+ spleen cells and appears to be due to the presence of suppressor cells that are selective for L3T4+ Th and not for Lyt-2+ Th. Surprisingly, the suppressor cells are also L3T4+ T cells and can suppress the IL-2 production of congenic MRL/+ L3T4+ Th to MHC-self-restricted antigens. These data support the idea of functional specialization within the L3T4+ population of T cells. Because L3T4+ suppressor cells are detected late in the course of autoimmunity, we interpret their presence not as a primary initiating event in the development of autoimmunity, but rather as a compensatory mechanism. Additionally, similar suppression of L3T4+ Th function has also been reported in a murine graft-vs.-host model of autoimmunity, suggesting that the suppressor cells represent an immunoregulatory mechanism that is a common feature of autoimmunity. Since excessive class II-restricted Th activity for B cells has been reported for both models of autoimmunity, L3T4+ suppressor cells may represent an attempt to down regulate such excessive Th activity. These findings may be relevant to human autoimmune diseases, such as systemic lupus erythematosus, in which B cell hyperactivity is also associated with reduced IL-2 production by Th.

Aging↗

PubMed2005

Evidence for correlations between distant intentionality and brain function in recipients: a functional magnetic resonance imaging analysis.

This study, using functional magnetic resonance imaging (fMRI) technology, demonstrated that distant intentionality (DI), defined as sending thoughts at a distance, is correlated with an activation of certain brain functions in the recipients. Eleven healers who espoused some form for connecting or healing at a distance were recruited from the island of Hawaii. Each healer selected a person with whom they felt a special connection as a recipient for DI. The recipient was placed in the MRI scanner and isolated from all forms of sensory contact from the healer. The healers sent forms of DI that related to their own healing practices at random 2-minute intervals that were unknown to the recipient. Significant differences between experimental (send) and control (no send) procedures were found (p = 0.000127). Areas activated during the experimental procedures included the anterior and middle cingulate area, precuneus, and frontal area. It was concluded that instructions to a healer to make an intentional connection with a sensory isolated person can be correlated to changes in brain function of that individual.

Adult↗

PubMed2005

Muscle function and functional ability improves more in community-dwelling older women with a mixed-strength training programme.

BACKGROUND: Supervised training can reach a limited number of elderly people. OBJECTIVE: To determine the impact of a 1-year mixed-strength training programme on muscle function (MF), functional ability (FA) and physical activity (PA). SETTING: Twice-a-week hospital-based exercise classes and a once-a-week home session. PARTICIPANTS: twenty-eight healthy community-dwelling men and women on the training programme and 20 controls aged over 75 years. METHODS: Training with two multi-gym machines for the lower limbs at 60% of the repetition maximum (1RM). At-home subjects used elastic bands. MEASUREMENTS: Maximum isometric strength of knee extensors (KE), ankle plantar flexors (PF), leg extensor power (LEP), functional reach (FR), chair rise 1 (CR1) and 10 times (CR10), bed rise (BR), six-minute walking test (6MWT), stair climbing (SC), get-up-and-go (GU&G), one-leg standing (1LS). PA was assessed with the Paqap questionnaire. RESULTS: Women were significantly weaker than men at baseline: -47% for KE and -59% for PF. Training induced significant gains in MF and FA in the training females; males improved significantly only in FA. PA levels increased non-significantly (2%) in all of the training group. CONCLUSIONS: Long-term mixed-strength programmes can improve MF and FA in elderly females, and FA in elderly males.

Activities of Daily Living↗