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PubMed1983

(--)-alpha-Acetylmethadol effects on alcohol and diazepam use, sexual function and cardiac function.

Selected behavioral and physiological effects of maintenance on (--)-alpha-acetylmethadol (LAAM) were examined for 67 men beginning LAAM maintenance. Thirty-four began LAAM maintenance after 1 month or more on methadone; 33 others were using street heroin immediately before beginning LAAM. Subjects were followed for 20 weeks on LAAM; assessment focused on changes in alcohol and diazepam use, sexual behavior and testicular function, and cardiovascular function. There was a trend toward increased alcoholism-related behaviors, but not consumption of alcohol, when on LAAM. Use of diazepam remained low. Subjects reported slightly enhanced sexual activity: reported number of ejaculations tended to increase, although interest in sexual activity remained constant. Semen volume values remained in the low normal range. In contrast to an earlier published report of reduced sperm motility in methadone and heroin users, normal motility was noted in this sample. The incidence of abnormal sperm morphology decreased from baseline to the end of the study. Cardiovascular function, as assessed by response to standard exercise, was unchanged during LAAM maintenance. Electrocardiograms revealed minor abnormalities prior to beginning LAAM maintenance; but these abnormalities did not consistently change during treatment. There is little evidence that the effects of LAAM maintenance differ from the effects of methadone maintenance on these behavioral and physiological functions.

Adult↗

PubMed1994

Sertoli cell function declines earlier than Leydig cell function in aging Japanese men.

In order to evaluate the age-related changes in Leydig cell and Sertoli cell function, we measured serum levels of total testosterone (TT), free testosterone (FT), inhibin, LH and FSH in 116 healthy Japanese men, aged 24-92 years. Serum TT remained constant up to the age of 80 years and decreased thereafter. Serum FT declined linearly with aging and was significantly lower in men in their forties than in younger men (24-39 years old). Serum inhibin levels also declined with aging, with serum concentrations significantly lower in men older than 40 and markedly lower in men over 80 years old. LH and FSH were elevated in men over 60 and 40 years old, respectively. We also examined relationships between gonadotropins and gonadal hormones in these men divided into three age groups, young (24-39 years old), middle aged (40-59 years old) and aged (60-92 years old) men. Although there was a significant inverse correlation between LH and TT or FT for the entire population, subset analysis demonstrated that this inverse correlation was confined to men over 60 years old. In fact, in young men, TT and FT were positively correlated with LH. Overall, there was also an inverse correlation between FSH and inhibin. In subset analysis this relationship was present in both middle aged and aged men. These findings suggest that in Japanese men testicular endocrine functions decline after the fourth decade of life, and that Sertoli cell function declines earlier than Leydig cell function.

Adult↗

PubMed2026

Divergent PXR function in seals: Endocrine adaptation or functional loss?

Seals accumulate xenobiotics through dietary biomagnification and exposure to polluted marine environments, with contaminants concentrating in their blubber. Biotransformation mitigates xenobiotic toxicity by converting lipophilic compounds into excretable hydrophilic metabolites, a process coordinated by nuclear receptors including the Pregnane X Receptor (PXR), whose plastic ligand-binding domain enables broad xenobiotic sensing. By examining PXR in pinnipeds, we investigated the evolutionary conservation and functional characterization of PXR using genomic sequence analysis, protein structural prediction, and transactivation assays, revealing broadly conserved structural features alongside species-specific functional divergence in receptor responsiveness to environmental stressors. Specifically, the obtained results highlight divergent gene and functional landscapes with ORF-disrupting mutations identified in Monachus monachus and Neomonachus schauinslandi that abolish receptor activation toward known PXR ligands. In contrast, Leptonychotes weddelli retained an intact PXR ORF but showed reduced receptor activity, revealing functional divergence in PXR among pinnipeds.

Biotransformation↗

PubMed1988

A transcription-translation activation feedback circuit as a function of protein degradation, with the quality of protein mass adaptation related to the average functional load.

The balance between protein synthesis and degradation, and between active skeletal muscle cell hypertrophy and atrophy can be described as a function of protein degradation rate by a transcription-translation activation control loop. Transcription activity is presumed to be determined by the concentration of protein-specific fragments (PSF) occurring as intermediate products of protein degradation. If PSF acts as an apoinducer at the gene or operon enhancer region, formation and dissociation of PSF-enhancer complex, as a function of PSF concentration, determines the gene or operon transcription activity. The assumed regulation can be converted to a mathematical model that allows simulation of steady-state protein balance and active adaptation, according to the level of functional activity. The relationship between steady-state transcription activity and PSF concentration can be described by Michaelis-Menten or weak sigmoidicity kinetics. Similar dependency is presumed in translation activity as a function of mRNA concentration. The relationship of protein to mRNA, PSF and ribosome content, and their formation and degradation, are determined by first-order differential equations. The assumed regulation scheme may also contribute to the theory of transcription activation, and can be used to explain the mechanism determining active adaptation in living systems.

Feedback↗

PubMed2003

Visualization of the eloquent motor system by integration of MEG, functional, and anisotropic diffusion-weighted MRI in functional neuronavigation.

BACKGROUND: In this study, we visualized the eloquent motor system including the somatosensory-motor cortex and corticospinal tract on a neuronavigation system, integrating magnetoencephalography (MEG), functional magnetic resonance imaging (fMRI), and anisotropic diffusion-weighted MRI (ADWI). METHODS: Four patients with brain lesions adjacent to the eloquent motor system were studied. Motor-evoked responses (MER) by finger-tapping paradigm were acquired with a 1.5-Tesla MR scanner, and somatosensory-evoked magnetic fields (SEF) by median nerve stimulation were measured with a 204-channel MEG system. In the same fMRI examination, ADWI and anatomic three-dimensional T1-weighted imaging (3-D MRI) were obtained. Activated areas of MER, estimated SEF dipoles, and the corticospinal tract on ADWI were coregistered to 3-D MRI, and the combined MR data were transferred to a neuronavigation system (functional neuronavigation). Intraoperative recording of cortical somatosensory-evoked potentials was performed for confirmation of the central sulcus. RESULTS: Combination of fMRI and MEG enabled firm identification of the central sulcus. Functional neuronavigation facilitated extensive tumor resection, having the advantage of sparing the motor cortex and corticospinal tract in all cases. CONCLUSIONS: The proposed functional neuronavigation allows neurosurgeons to perform effective and maximal resection of brain lesions, identifying and sparing eloquent cortical components and their subcortical connections. Potential clinical application of this technique is discussed.

Adolescent↗

PubMed2003

Novel functional imaging technique from brain surface with optical coherence tomography enabling visualization of depth resolved functional structure in vivo.

Mapping of the activity of brain by optical intrinsic signal imaging (OISI) provides a two-dimensional activation pattern of visual cortical areas at a resolution of a few hundred microns. However, integration of the intrinsic signal over depth results in loss of finer information about functional organization across the depth. Here, we report the first successful implementation of optical coherence tomography (OCT) at around 30 microm depth resolution to investigate cortical functions of a cat brain in vivo. This technique, named functional OCT (fOCT) provided visually evoked changes in the OCT signal. The fOCT signal shows stimulus specificity that correlates well with that of the intrinsic signals and provides depth resolved layer specific functional information.

Animals↗

PubMed2002

The Life Functioning Questionnaire (LFQ): a brief, gender-neutral scale assessing functional outcome.

The Life Functioning Questionnaire (LFQ) is a 5-min, 14-item, gender-neutral self-report questionnaire designed to assess role function over the preceding month in four domains: workplace, duties at home, leisure time with family and leisure time with friends. To validate the LFQ for use as an instrument assessing functional outcome in patients with a mood disorder, the LFQ was administered to three different samples of patients (N=87). Fifty-nine concurrently completed the self-report version of the Social Adjustment Scale (SAS-SR) and 32 concurrently had a Clinical Global Impression Scale for Bipolar Disorder (CGI-BP) assessment. The LFQ proved to have high internal consistency reliability, high test-retest reliability, excellent concurrent validity with the SAS-SR, and high validity as a measurement of severity of illness when compared with the CGI-BP. The LFQ provides a reliable, consistent and valid assessment of function at work and home in both male and female patients with a mood disorder.

Activities of Daily Living↗

PubMed2002

Urinary continence and erectile function: a prospective evaluation of functional results after radical laparoscopic prostatectomy.

OBJECTIVES: To evaluate prospectively functional results (urinary continence and erectile function) after laparoscopic radical prostatectomy. METHODS: From 1998 to 2001, 235 patients underwent laparoscopic radical prostatectomy for localized prostate cancer. All of them completed a confidential, self-administered questionnaire regarding urinary continence and erectile function before, and 1, 3, 6, and 12 months after surgery. Results were analyzed separately for day and night for urinary continence and status of neurovascular bundles as well as age for erectile function. RESULTS: To date, 100 consecutive patients have completed all questionnaires. Diurnal and nocturnal urinary continence have increased to 90% and 97% one year after surgery. Overall, 49.3% of the 77 patients, who were potent preoperatively, and did not receive any form of adjuvant therapy, had erections sufficient for intercourse one year after surgery. Potency rates were 38.4%, 53.8% and 58.8% after no, unilateral, and bilateral nerve bundle preservation, respectively. For younger patients (<60 years) with unilateral and bilateral neurovascular bundle preservation, potency rates were 75% and 83.3%, respectively. CONCLUSION: One year after laparoscopic radical prostatectomy, urinary continence rate is 90% during the day and 97% during the night. Overall potency rates after bilateral preservation of neurovascular bundles are 58.8% and 83.8% for the subgroup of younger patients (<60 years).

Aged↗

PubMed2000

An investigation of the impulse functions for the nonlinear BOLD response in functional MRI.

Functional MRI (fMRI) based on blood oxygenation level dependent (BOLD) contrast can be used to detect hemodynamic responses to a broad range of stimuli. It however remains unclear in what fashion the BOLD response is a linear system, and how the impulse function differs with stimulation of varying duration. To address this question, fMRI using visual stimulation with a wide range of duration (0.5-12 s) was performed in six human volunteers. A strong linear correlation was shown on the full width at half maximum (r = 0.998) of the BOLD response curves and the area under the curves (r = 0.999) to the duration of stimulation. However, comparing the errors of the measured and predicted response curves, our results showed a poorer linearity at stimuli of shorter duration. By examining the impulse functions derived from different stimuli, based on the assumption that a linear convolution relationship existed, a higher differentiation was shown in the experiments with shorter stimuli (<3 s). Compared to the area under the impulse function derived from 12 s stimulation, with that obtained from 0.5, 1, 2, 3, 4, 8 s stimuli resulted in differences of 66.2, 33.5, 15.1, 5.4, 0.9, 7.9%, respectively. This study suggests a higher degree of nonlinearity in the BOLD signal changes due to stimuli of shorter duration, in agreement with earlier work.

Brain↗

PubMed2000

Analysis of input functions from different arterial branches with gamma variate functions and cluster analysis for quantitative blood volume measurements.

Regional cerebral blood volume (rCBV) provides valuable information about the nature and progress of diseases of the central nervous system. While relative rCBV maps can be derived directly from dynamic susceptibility contrast data, the arterial input function (AIF) has to be measured for absolute rCBV quantification. For determination of the AIF pixels located completely within a feeding artery must be selected. However, by using a region-of-interest (ROI) based selection some confounding effects can occur, especially if single shot echo planar imaging (EPI) with low spatial resolution is used. In this study we analyzed the influence of partial volume effects and spatial misregistration due to frequency shifts induced by paramagnetic contrast agents. We analyzed AIFs from the internal carotid artery (ICA), the vertebral artery (VA) and the middle cerebral artery (MCA) using gamma variate function based parameterization. The concentration time curves (CTC) of several pixels which were selected on the basis of strong signal drop appeared distorted during the bolus passage. Moreover, the amplitudes of input functions derived from the MCA were smaller by a factor of three as compared to those of the ICA and VA. Simulations revealed that these effects can be attributed to a spatial shift of the vessel along phase-encoding direction during the passage of the bolus. We therefore developed a procedure for a pixel selection based on cluster analysis which classifies pixels according to the parameters of the fitted gamma variate functions. This approach accounted for misregistration of the vessel and yielded very consistent results for a group of normal subjects.

Brain↗

PubMed2000

The use of subcutaneous erythropoietin and intravenous iron for the treatment of the anemia of severe, resistant congestive heart failure improves cardiac and renal function and functional cardiac class, and markedly reduces hospitalizations.

OBJECTIVES: This study evaluated the prevalence and severity of anemia in patients with congestive heart failure (CHF) and the effect of its correction on cardiac and renal function and hospitalization. BACKGROUND: The prevalence and significance of mild anemia in patients with CHF is uncertain, and the role of erythropoietin with intravenous iron supplementation in treating this anemia is unknown. METHODS: In a retrospective study, the records of the 142 patients in our CHF clinic were reviewed to find the prevalence and severity of anemia (hemoglobin [Hb] <12 g). In an intervention study, 26 of these patients, despite maximally tolerated therapy of CHF for at least six months, still had had severe CHF and were also anemic. They were treated with subcutaneous erythropoietin and intravenous iron sufficient to increase the Hb to 12 g%. The doses of the CHF medications, except for diuretics, were not changed during the intervention period. RESULTS: The prevalence of anemia in the 142 patients increased with the severity of CHF, reaching 79.1% in those with New York Heart Association class IV. In the intervention study, the anemia of the 26 patients was treated for a mean of 7.2 +/- 5.5 months. The mean Hb level and mean left ventricular ejection fraction increased significantly. The mean number of hospitalizations fell by 91.9% compared with a similar period before the study. The New York Heart Association class fell significantly, as did the doses of oral and intravenous furosemide. The rate of fall of the glomerular filtration rate slowed with the treatment. CONCLUSIONS: Anemia is very common in CHF and its successful treatment is associated with a significant improvement in cardiac function, functional class, renal function and in a marked fall in the need for diuretics and hospitalization.

Aged↗

PubMedDate not supplied

Questions about behavioral function (QABF): a behavioral checklist for functional assessment of aberrant behavior.

Functional assessment is a method to identify the relationships between a behavior of interest and an individual's environment. Traditional methods for functional assessment have relied on experimental techniques in which analog sessions are designed to replicate conditions in the individual's environment. However, these techniques can be time-consuming, require advanced training, and rely on the availability of extensive resources in the individual's setting. Development of a brief functional assessment checklist would circumvent these difficulties and meet clinical needs for efficient assessment methods. The current study provides psychometric data for the Questions About Behavioral Function. These data include test-retest, inter-rater, and internal consistency.

Activities of Daily Living↗

PubMed2003

T-cell function in anti-GAD65(+)diabetes with residual beta-cell function.

We have recently reported that in patients with anti-glutamic acid decarboxylase (GAD) 65(+)diabetes with residual beta-cell function, most with a 'high-titer' (>10U/ml) required insulin within 5 years, whereas most with a 'low-titer' (1.3-9.9U/ml) did not need insulin for over 15-20 years after the onset. We therefore examined T-cell function to evaluate the difference between the high-titer and low-titer groups. Interleukin (IL)-10 production upon polyclonal activation was significantly lower in the high-titer group than in the low-titer group. The serum level of interferon-inducible protein-10 (IP-10) was higher in the high-titer than the low-titer group. Although GAD65-reactive CD4(+)cells in the periphery were detected in both groups, a significant positive correlation between serum IP-10 level and the number of GAD65-reactive CD4(+)cells was observed only in the high-titer group. Therefore, it has been speculated that the co-existence of GAD65-reactive IFN-gamma-producing CD4(+)cells and a high serum IP-10 level may be important for rapid disease progression as seen in the high-titer group. Based upon these results, T-cell function is considered to be different between the high-titer and low-titer groups in anti-GAD65(+)diabetes with residual beta-cell function, supporting our previous findings regarding the clinical outcome of insulin-dependence in the two groups.

Adult↗

PubMed1987

Condylar position following ramus osteotomy and functional osteosynthesis. A clinical function-analytic and computer tomographic study.

Opponents of the application of a stable fixation of the fragments with compression screws in osteotomies of the mandibular ramus quite often claim that there is the possibility of a postoperative dislocation of the proximal fragment with consequent functional disturbances of the temporo-mandibular joint. For determination of the frequency and the extent of such possible displacements of the condyle, a total of 174 patients, in whom ramus osteotomies were performed, were clinically examined. In 9 of them, a functional analysis and in 10 other patients, a CT scan investigation of the position of the TM joint, was carried out. Only in 1 case could a considerable dislocation of the proximal fragment be observed, which was due to a strong unilateral deviation of the ascending ramus. For correction of the functional disturbance the bone screws had to be removed in this particular case. In those cases where a functional analysis and CT study were undertaken, only slight changes of the pre- and post-operative position of the condyles were observed: it did not lead to clinical disturbances and complaints.

Bone Screws↗

PubMed1998

Multimodal imaging of residual function and compensatory resource allocation in cortical atrophy: a case study of parietal lobe function in a patient with Huntington's disease.

In a case of Huntington's disease (HD) with dementia and pronounced parieto-frontal atrophy, the functional state of the affected regions was investigated using functional magnetic resonance imaging (fMRI) and fluorodeoxyglucose-positron emission tomography (FDG-PET). It was observed that although parietal areas showed extensive atrophy and reduced resting glucose metabolism, the patient performed with similar accuracy but with longer response time in a visuospatial task compared with healthy control subjects. At the same time, the blood oxygen level-dependent (BOLD) fMRI signal in these areas, which are involved in visuospatial processing, showed a similar task-dependent modulation as in control subjects. The signal amplitude (signal percent change) of the task-dependent activation was even higher for the HD patient than in the control group. This residual functionality of parietal areas involved in visuospatial processing could account for the patient's performance in the task concerned, which contrasted with his poor performance in other cognitive tasks. The increased percent-signal change suggests that a higher neuronal effort was necessary to reach a similar degree of accuracy as in control subjects, fitting well with the longer reaction time. We propose that fMRI should be considered as a tool for the assessment of functionality of morphologically abnormal cortex and for the investigation of compensatory resource allocation in neurodegenerative disorders.

Adult↗

PubMed1999

Functional analysis of SNF, the Drosophila U1A/U2B" homolog: identification of dispensable and indispensable motifs for both snRNP assembly and function in vivo.

In Drosophila, the spliceosomal protein SNF fulfills the functions of two vertebrate proteins, U1 snRNP-UlA and U2 snRNP-U2B". The structure and sequence of SNF, U1A, and U2B" are nearly identical with two RNA recognition motifs (RRM) separated by a short linker region, yet they have different RNA-binding properties: U1A binds U1 snRNA, U2B" binds U2 snRNA, and SNF binds both snRNAs. Structure/function studies on the human proteins have identified motifs in the N-terminal RRM that are critical for RNA-binding specificity but have failed to identify a function for the C-terminal RRM. Interestingly, SNF is chimeric in these motifs, suggesting a basis for its dual specificity. Here, we test the importance of these motifs by introducing site-directed mutations in the snf coding region and examining the effects of these mutations on assembly into the snRNP and on snf function in vivo. We found that an N-terminal RRM mutant protein predicted to eliminate RNA binding still assembles into snRNPs and is capable of rescuing snf's lethal phenotype only if the normally dispensable C-terminal RRM is present. We also found that the mixed motif in the "RNA-specificity" domain is necessary for SNF's dual function whereas the mixed motif in the U2A'-protein-binding region is not. Finally, we demonstrate that animals carrying a snf mutation that converts SNF from a bifunctional protein to a U1 snRNP-specific protein are viable. This unexpected result suggests that SNF's presence within the U2 snRNP is not essential for splicing.

Amino Acid Sequence↗

PubMed1995

Functionally selective M1 muscarinic agonists. 3. Side chains and azacycles contributing to functional muscarinic selectivity among pyrazinylazacycles.

In an attempt to improve upon the M1 agonist activity of the selective M1 agonist xanomeline and related compounds, the M1 muscarinic efficacies and potencies of 3- and 6-substituted pyrazinylazacycles were varied by changing both the 3- and 6-substituents as well as the azacycle. Significant improvements in efficacy and potency over the previously prepared [3-(hexyloxy)pyrazinyl]tetrahydropyridine 19 were obtained with the [3-(hexyloxy)pyrazinyl]-quinuclidine 5i. The M1 activity of 5i showed some enantioselectivity with (S)-5i being ca. 4-fold more potent than (R)-5i. Like 19 and xanomeline, 5i was a functionally selective M1 agonist that showed greater functional selectivity than widely studied pyrazinylquinuclidine 5n (L-689,660). The improved functional selectivity of 5i over 5n could be attributed to the additional binding interactions between the hexyloxy side chain of 5i and the M1 receptor that are not available to 5n. Although 5i may show M1 functional selectivity comparable to xanomeliine, 5i is a less efficacious and potent M1 agonist than xanomeline.

Animals↗

PubMed1998

Functional ability among elderly people in three service settings: the discriminatory power of a new functional ability scale.

The purpose is to assess the discriminatory power of the Avlund scales: (1) by assessing the ability of the scales to discriminate between three different populations of elderly people, and (2) by studying groups with a poor fit between use of formal home care and functional ability. The study included (A) all residents in new sheltered housing facilities (response rate 68%, n = 102), (B) a random sample of users of home care (response rate 67%, n = 435), and (C) a random sample of individuals not using home care (response rate 74%, n = 501). All participants were 60+ years old. Data were collected by personal interviews (group A) and by postal questionnaires (group B and C). Functional ability was measured by The Avlund Mob-T scale about tiredness related to mobility and the Mob-H scale about need of help to mobility. Both scales were able to distinguish the three sub-populations. The whole range of the Mob-T scale was used in all three subpopulations, and the whole range of the Mob-H scale was used among the oldest residents and the oldest users of home care. A small group of well-functioning users of home care (n = 52) was characterized by good self-rated health, good hearing, vision and memory abilities; they gave more help to others, had higher social participation, and lived alone (only the women). A somewhat lager group of poor functioning non-users of home care (n = 266) had the opposite characteristics. In addition, they were older, had a poor social network and poor social support.

Activities of Daily Living↗