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PubMed1990

Postnatal development of striatal dopamine function. II. Effects of neonatal 6-hydroxydopamine treatments on D1 and D2 receptors, adenylate cyclase activity and presynaptic dopamine function.

To evaluate the influence of patch and matrix ingrowth of DA terminals upon striatal DA (dopamine) receptor function, we performed bilateral intrastriatal (i.s.) or single intracisternal (i.c.) injections of 6-hydroxydopamine (6-OHDA) into rat pups at various postnatal ages and determined D1 and D2 receptor binding, adenylate cyclase activities and markers for presynaptic DA terminal density and turnover as the animals matured. All injection schedules yielded: (a) variable and partial loss of DA, (b) increased DA turnover, (c) small (15-40%) increases in D1 receptor number but no change in affinity for antagonist ([3H]SCH 23390), (d) 2-3-fold increases in affinity of D1 receptors for agonist (SKF 38393) with preserved regulation of agonist affinity by guanine nucleotide, (e) no significant changes in DA-, guanine-nucleotide-, manganese- and forskolin-stimulated AC (adenylate cyclase) activity. D2 receptor binding was evaluated between 1 and 7 weeks of age in animals with i.s. treatment and 7 and 10 weeks of age in animals with i.c. treatment and was reduced by 40-50% with both treatment regimens. [3H]mazindol binding, a marker for presynaptic terminal DA transport sites, was reduced 30-40% by multiple i.s. or i.c. treatment regimens. In animals treated with one i.s. injection, [3H]mazindol binding was reduced 70% at 1 week of age, equal to control by 2 weeks and 14-46% greater than control between 3 and 7 weeks. We conclude that striatal D1 receptor sites maintain their density and second messenger function independently of postsynaptic DA terminal ingrowth, whereas the development of D2 receptor sites is sensitive to disruptions of DA terminal ingrowth.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗

PubMed1995

Functional aspects of the involvement of the hippocampus in behavior and memory functions.

In order to outline the involvement of the hippocampus in behavior and memory functions the results of grafting experiments in the hippocampal formation are presented in addition to former lesion and stimulation studies. Grafts of fetal hippocampal tissue were found to induce short-term beneficial effects on learning and memory. Functional efficiency of the grafts could be substantially improved by additional subcutaneous administration of carbachol over a period of 6 months. As carbachol does not cross the blood-brain barrier (BBB) due to its polar structure the data support the view that grafts of fetal neuronal tissue may induce a prolonged permeability of the BBB over a long period of time which could also be shown by HRP-histochemistry.

Animals↗

PubMedDate not supplied

The Functional Autonomy Measurement System (SMAF): a measure of functional change with rehabilitation.

The Functional Autonomy Measurement System (SMAF) is an instrument developed for the measurement of needs of the elderly and the handicapped. As this study shows, it can be used to demonstrate progress during rehabilitation. Of the 94 patients admitted and discharged from a 22 bed acute/rehabilitation ward for the elderly, 78 were discharged home or to their original accommodation, 7 died in hospital and 9 were transferred to a continuing care ward or a nursing home. The mean total score (admission vs. discharge: 18.06 vs. 9.18, P < 0.0001) as well as the score for subsections of Activities of Daily Living (ADL) (admission vs. discharge: 15.69 vs. 8.15, P < 0.0001), Communication (admission vs. discharge: 1.01 vs. 0.5, P < 0.0001) and Mental Function (admission vs. discharge: 1.29 vs. 0.64, P < 0.0001) showed significant improvement in the 78 patients who were discharged back to their original accommodation. Patients who died or required placement into a continuing care bed or nursing home showed no change in mean scores with treatment. The inter-observer agreement between two nurses and a doctor showed that the minor modifications to SMAF did not significantly affect the instrument.

Journal Article↗

PubMed1985

Precise calculation of the cumulative distribution function and its inverse function for Fisher's F and Student's t tests.

A computer program to calculate precise solutions (exact to the limit of computer accuracy) for the cumulative distribution function of the statistical t and F distributions is detailed. A routine that makes iterative calls of this algorithm to calculate precisely the inverse function of these distributions by successive approximation is also provided. The program provided yields precise levels of probability confidence for both Fisher's F and Student's t tests, and the inverse calculation of critical values given p. It is written in a subset of BASIC which should run on any small computer, requiring only 1538 bytes on the Commodore 64.

Biometry↗

PubMed1987

Beta-lactam antibiotics and human lymphocyte function: the in vitro effect on blastogenesis, lymphokine production and suppressor cell functions.

The effects of penicillin, cephalothin and cefoxitin on lymphokine production and mitogen stimulation of human peripheral blood lymphocytes and suppressor cell functions in man were studied with concentrations achievable in serum. Penicillin (50 and 100 micrograms/ml) and cephalosporins (50 and 100 micrograms/ml) directly stimulated production of the lymphokine leukocyte aggregating factor (LAgF) by unstimulated lymphocytes and enhanced mitogen-stimulated production of this lymphokine. Neither beta-lactam derivative interfered directly with neutrophil aggregation. Using the same concentration, penicillin did not suppress but had either no effect on or slightly increased the unstimulated and mitogen-stimulated lymphocyte transformation responses, whereas cephalosporins significantly suppressed both responses. Suppression of blastogenesis by the latter could be mediated through suppressor cell enhancement as indicated by the significant suppressed lymphocyte transformation observed while using the supernatant of cephalosporin-stimulated and cultured lymphocytes. This suppressive activity was more pronounced with cephalothin than with cefoxitin while it was not observed with penicillin which rather stimulated thymidine uptake. These findings suggest that enhancement of lymphokine production and suppression of lymphocyte transformation by cephalosporins are not contradictory and reflect a stimulating effect on two different lymphocyte subsets. The enhancement of suppressor function might account for the lower incidence of late hypersensitivity reactions observed in patients treated with the cephalosporins compared with those treated with penicillins.

Cefoxitin↗

PubMed1990

Interactions between non-symmetric mechanical vector forces in the body and the autonomic nervous system: basic requirements for any mechanical technique to engender long-term improvements in autonomic function as well as in the functional efficiency of the respiratory, cardiovascular, and brain systems.

There are known anatomical asymmetries in the respiratory, cardiovascular, and nervous system. The coupling mechanisms between each of these systems--lungs-heart, heart-brain, and lungs-brain--are also asymmetrical. There is a growing body of literature indicating that mechanical pressure asymmetrically applied to certain areas of the human body produces changes in the balance of autonomic parameters. These findings implicitly indicate that not only magnitude but also the direction and point of application of the force play a role in its influence upon the autonomic nervous system. Therefore, we suggest that asymmetrical vector forces resulting from the mechanical activity of the lungs, heart and blood moving throughout the circulatory system, will also produce a lateralization effect in autonomic balance. We postulate the existence of negative feedback loops between brain autonomic control and mechanical functions in the body as a fundamental part of the body's homeostatic mechanisms. It follows that any mechanical assist to the respiratory or cardiovascular system will be significantly reduced or even eliminated if these homeostatic mechanisms are not taken into account. Our hypothesis predicts that a long-term improvement in autonomic balance as well as in respiratory, cardiovascular, and brain function can be achieved if mechanical forces are applied to the body with the aim of reducing existing imbalances of mechanical force vectors. This technique implies continually controlling for precise timings resulting from physiological periodical forces as well as factors derived from anatomical and coupling asymmetries in the respiratory, cardiovascular, and nervous systems.

Autonomic Nervous System↗

PubMed1979

Cell-free synthesis of proteins coding for mobilisation functions of ColE1 and transposition functions of Tn3.

A hybrid plasmid, pJC74, carrying the large (3.35 Md) EcoRI-PstI fragment of ColE1, the 1.3 and 1.8 Md PstI fragments of plasmid R1 drd19 (containing a part of Tn3 and known to specify transpostion functions), and a part of gamma bacteriophage DNA carrying the fused cohesive ends of gamma (cos) was constructed. Supercoiled DNA of pJC74 and a series of deletions (series pJC75) were used in a cell-free coupled transcription-translation system. Analysis of the proteins produced allowed the identification of a 28 to 30 kd protein and/or a 3 kd protein responsible for mobilisation of the plasmids in sex-factor-promoted conjugation. Furthermore, three protein bands of 12, 12.5 and 13 kd were correlated with the presence of a portion of the Tn3 transposon previously shown to code for transposition functions which can complement in trans. These latter and the 30 kd beta-lactamase were the only proteins identified as Tn3-specific by comparison of ColE1 with RSF2124.

Cell-Free System↗

PubMed1994

Neuropsychological correlates of central monoamine function in chronic schizophrenia: relationship between CSF metabolites and cognitive function.

Schizophrenia is associated with multiple cognitive deficits which in turn may be related to abnormal dopamine (DA) function. To examine possible associations between cognitive dysfunction and central DA activity in schizophrenia, neuropsychological measures (visuospatial and verbal recall; performance on the Wisconsin Card Sort Test (WCST); visuospatial perception) were examined in 17 drug-free male schizophrenic patients and related to cerebrospinal fluid concentrations of the metabolites of dopamine (homovanillic acid (HVA)), serotonin, and norepinephrine. CSF HVA concentrations were correlated with the ability to recall visuospatial information, with attention to verbal tasks, and with WCST performance (low CSF HVA concentrations predicting poor performance on these tests) but not with the ability to recall verbally presented material and visuospatial perception. These data are consistent with earlier results suggesting that (cortical) DA function is associated with recall and retrieval of visuospatial information and with WCST performance.

Adult↗

PubMed2004

A prehabilitation program for the prevention of functional decline: effect on higher-level physical function.

OBJECTIVE: To determine whether a home-based physical therapy (PT) program prevented decline in several higher-level measures of physical function among physically frail, community-living older persons. DESIGN: Randomized controlled trial. SETTING: General community. PARTICIPANTS: Persons (N=188) who were physically frail and aged 75 years or older. INTERVENTION: A home-based PT program (ie, prehabilitation) that focused primarily on improving underlying impairments in physical capabilities. MAIN OUTCOME MEASURES: Self-reported instrumental activities of daily living (IADLs); mobility, as determined by a modified version of the Performance Oriented Mobility Assessment; timed rapid gait and timed chair stands; and integrated physical performance, as determined by a modified version of the Physical Performance Test, were assessed at baseline, 7 months, and 12 months. RESULTS: As compared with participants in the educational control group, participants in the intervention group had reductions in IADL disability of 17.7% at 7 months (P=.036) and 12.0% at 12 months (P=.143) and had gains, ranging from 7.2% to 15.6%, in mobility and integrated physical performance at 7 and 12 months. CONCLUSIONS: Our home-based prehabilitation program offered modest but consistent benefits for the prevention of decline in several higher-level measures of physical function.

Activities of Daily Living↗

PubMed2005

Modification of the functional reach test: analysis of lateral and anterior functional reach in community-dwelling older people.

The purpose of this study was to evaluate the validity and reproducibility of the modified lateral functional reach (FR), and to examine the associations between a variety of functional variables and the FR in community-dwelling older people (>65 years of age). A total of 383 aged Japanese participated in this study at the rural district Kahoku, Kochi, Japan, in 2002. The average age of the subjects was 78.6 years. The activity of daily living (ADL) and mental status were measured as outcomes. FR (anterior and lateral) and timed up and go (TUG) were measured as predictors. The test-retest reliability of lateral FR between the first and second measurement was very consistent. Subjects with greater lateral FR had higher basic and instrumental ADL (IADL) scores than did those with shorter lateral FR. However, there was no significant relationship between anterior FR and ADLs. The lateral FR of participants with depression was shorter than in those without depression, while the anterior FR did not correlate with the participants' scores on the geriatric depression scale (GDS). Lateral FR should be considered as a new, alternative means of assessing geriatric social activity and mental status in the elderly.

Activities of Daily Living↗

PubMed2006

Preoperative function and gender predict pattern of functional recovery after hip and knee arthroplasty.

Gender, preoperative function, and other variables were explored as predictors of recovery after total hip and knee arthroplasty. One hundred fifty-two subjects (63.8 +/- 10.2 years) were repeatedly assessed in the first 4 postoperative months. Average recovery curves for the Western Ontario and McMaster Universities Osteoarthritis Index, 6-minute walk test, and timed up and go test were characterized using hierarchical linear modeling. Recovery predictors were sequentially modeled after validation of the basic developmental models. Gender was a significant predictor (P < or= .003) of physical performance measure scores 1 week after surgery. Thereafter, men and women had similar rates of improvement. Preoperative score was a significant predictor (P < or= .001) in all models. Patients' and surgeons' expectations of outcome need to take preoperative function into account.

Aged↗

PubMed2004

Alcohol and HIV decrease proteasome and immunoproteasome function in macrophages: implications for impaired immune function during disease.

Proteasomes (proteinase complexes, PR) and immunoproteasomes (IPR) degrade damaged proteins and affect protein processing required for antigen presentation by mononuclear phagocytes. These critical immune processes are attenuated during progressive HIV-1 infection and are affected by alcohol abuse. To investigate the mechanisms underlying these functional changes, we measured PR and CYP2E1 activities [an ethanol (EtOH) metabolizing enzyme] and reactive oxygen species (ROS) in human monocyte-derived macrophages (MDM) following HIV-1 infection and EtOH treatment. We observed progressive declines of PR activity and PR/IPR contents in HIV-1-infected MDM. PR activity and IPR expression increased after IFN-gamma stimulation but reduced after HIV-1 infection. EtOH inhibited both IFN-gamma-induced PR and IPR. Paradoxically, EtOH attenuated PR catalytic activity in infected MDM and suppressed viral replication. Elevated ROS followed EtOH exposure and paralleled decreased PR activity. The latter was restored by anti-oxidant. The data support the notion that HIV-1 infection and EtOH may work in concert to affect immune function including antigen presentation and thereby affect disease progression.

Alcoholism↗

PubMed2007

An exploration of the function of the triceps surae during normal gait using functional electrical stimulation.

Gastrocnemius and soleus have a common tendon and both are active during stance phase, where they are thought to arrest and control tibial advance. Soleus is associated with the production of an extending moment at the knee. The two-joint gastrocnemius, which crosses the knee joint, will have an additional contribution to the knee flexors. Recent work using induced acceleration analysis (IAA) has demonstrated distinct differences between the actions of gastrocnemius and soleus. This study aims to use gait analysis to provide in vivo examination of these theoretical predictions. Functional electrical stimulation (FES) was chosen to provide a perturbation in muscle force, a close physical analogue to the theoretical predictions of IAA. Five adult male subjects, with no gait problems, participated. Each had gastrocnemius and soleus stimulated at three different timings during normal gait, while 3D gait data were collected. The order of testing was randomised and unstimulated trials were randomly interspersed to act as a control. The results show very different actions for soleus (ankle plantarflexing/knee extending) and gastrocnemius (ankle dorsiflexing/knee flexing) in stance phase. The counterintuitive nature of the action of gastrocnemius suggests that further clinical and biomechanical investigation into this muscle's function is required. The actions of both muscles at the knee confirm published IAA predictions. In vivo evidence such as this gives greater confidence when using model predictions. The approach adopted in this study could eventually be extended to other muscles and patient populations.

Adult↗

PubMed2004

Hydration status and cardiovascular function: effects of hydration enhancement on cardiovascular function at rest and during psychological stress.

This study examined the effects of a 3-day enhanced hydration regimen on resting cardiac function and reactivity to acute stress. Healthy volunteers (14 male, 14 female) were assigned to one of two groups: Enhanced Hydration and Normal Hydration Group. Participants in the Enhanced Group were given six 1-l bottles of water and instructed to drink two bottles a day in addition to normal fluid intake for 3 days preceding their laboratory session; no extra water was given to the Normal Group. Heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP), cardiac output (CO), stroke volume (SV), and total peripheral resistance (TPR) were recorded during a 10-min baseline, 6-min Paced Auditory Serial Addition Test (PASAT), 5-min recovery, 5-min intermediate baseline, and 3-min Cold Pressor Test. Repeated-measures ANOVA revealed a significant Hydration GroupxTask interaction for DBP during the cold pressor (p<0.01) with the Enhanced Group exhibiting greater DBP reactivity to cold stress relative to the Normal Group. Analysis revealed significant Hydration GroupxGender interactions for SV and TPR (p<0.05) at rest and during both the PASAT and Cold Pressor Test. Females in the Enhanced Group displayed higher SV and lower TPR relative to Enhanced Group males, whereas females in the Normal Group displayed lower SV and greater TPR relative to Normal Group males. These results suggest that 3-day hydration enhancement influences blood pressure reactivity in both men and women, and that long-term hydration enhancement is related to resting gender differences in cardiac function.

Adolescent↗

PubMed2026

Spatial transcriptomics of Ciona adult brains reveals functional zonalization and insights into neural gland function.

The ascidian Ciona is a pivotal chordate model for illuminating the evolutionary origins of the vertebrate brain. Here, spatial transcriptomics of the adult Ciona neural complex, combined with image-based computational super-resolution mapping, resolved distinct tissue domains including the cerebral ganglion, neural gland, ciliated funnel, neural gland duct/dorsal strand, and body wall muscle. Within the cerebral ganglion, high-resolution mapping revealed clear molecular zonalization separating the cortex and medulla, alongside regional specialization within the cortex itself. The neural gland exhibited localized enrichment of genes associated with extracellular matrix and cell-cell interactions. These spatial features suggest that the neural gland functions as a homeostatic and signaling interface, reminiscent of primitive vertebrate meninges or choroid plexus. Overall, this spatially defined gene expression map provides a foundational framework for understanding functional regionalization in the tunicate brain and its evolutionary relationship to vertebrate nervous systems.

Ciona↗

PubMed2004

Biogenesis and function of mouse mammary epithelium depends on the presence of functional alpha-catenin.

Alpha-catenin is a structural molecule and essential to the function of epithelial adherens junctions. Its role in the morphogenesis of mammary epithelium was explored using experimental mouse genetics. Since loss of alpha-catenin in mice leads to embryonic lethality, the alpha-catenin gene was flanked by loxP sites and inactivated in mammary epithelium using the WAP-Cre and MMTV-Cre transgenes. Loss of alpha-catenin arrested alveolar epithelial expansion. These cells lacked proper polarity and markers of functional differentiation, which resulted in impaired milk protein gene expression. Without alpha-catenin, increased epithelial cell death was observed at parturition and the tissue resembled an involuted gland that is normally observed after weaning. Lastly, no tumors were detected in mammary tissue lacking alpha-catenin.

Animals↗

PubMed2006

Different role for mouse and human CD3delta/epsilon heterodimer in preT cell receptor (preTCR) function: human CD3delta/epsilon heterodimer restores the defective preTCR function in CD3gamma- and CD3gammadelta-deficient mice.

The majority of T cell receptor (TCR) complexes in mice and humans consist of a heterodimer of polymorphic TCRalpha and beta chains along with invariant CD3gamma, delta, epsilon, and zeta chains. CD3 chains are present as CD3gammaepsilon, deltaepsilon, and zetazeta dimers in the receptor complex and play critical roles in the antigen receptor assembly, transport to the cell surface, and the receptor-mediated signal transduction. That CD3 chains play critical roles in thymocyte development is apparent from the analyses of CD3 deficient mice. PreT cell receptor (preTCR)-mediated CD4(-)CD8(-) (double negative or DN) to CD4(+)CD8(+) (double positive or DP) transition is severely impaired in mice deficient in either CD3gamma, or epsilon, or zeta chain. In contrast, CD3delta deficiency impairs thymocyte maturation at the CD4(+)CD8(+) double positive (DP) stage suggesting that CD3delta is not required for the preTCR-mediated DN to DP transition. However, recent data suggest that a defect in human CD3delta results in impaired development at the DN stage indicating a role for hCD3delta in preTCR-mediated DN to DP transition. To determine if human CD3delta/epsilon (hCD3delta/epsilon) could mediate preTCR-mediated DN to DP transition, we employed a human CD3 transgene that encodes full length CD3delta and a truncated but functional form of CD3epsilon. Surprisingly, the transgene restored the defective preTCR function in not only CD3epsilon- but CD3gamma- and CD3gammadelta-deficient mice as well. A possible role for human CD3delta/epsilon heterodimer in the preTCR-mediated DN to DP transition is discussed.

Animals↗

PubMed2005

Functional magnetic resonance imaging based on SEEP contrast: response function and anatomical specificity.

Functional magnetic resonance imaging based on a non-BOLD-contrast mechanism, which we have termed "SEEP" (Signal Enhancement by Extravascular water Protons), has previously been demonstrated. Here the reproducibility of areas of activity identified with both SEEP and BOLD contrast is assessed in duplicate experiments in healthy volunteers, with relatively high resolution (1.6 mm) image data at 1.5 T. These areas of activity are equally well localized to voxels containing primarily gray matter with the two contrast mechanisms. As in previous studies, areas of SEEP activity are observed to be immediately adjacent to areas of BOLD activity, with very little overlap. The response functions were estimated for both SEEP and BOLD contrast, and are observed to be distinct. The peak SEEP response is observed to lag the BOLD response by approximately 1 s and to decay more slowly with no poststimulus undershoot. Average BOLD signal changes (GE-EPI, TE=50 ms) were observed to be 3.4+/-1.2% (mean+/-S.D.), whereas SEEP signal changes (SE-EPI, TE=23 ms) were 1.9+/-0.5%, consistent with previous studies carried out at 0.2 and 3 T. These observations provide further support for the existence of a non-BOLD-contrast mechanism for fMRI, based on changes in extravascular spin density.

Brain↗