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PubMed1995

A new sigmoidal function describing the small field dose profile data from a linear accelerator.

Dose profile data from small circular fields have been used in treatment dose planning for stereotactic radiosurgery. Generally, a two-dimensional interpolation of the measured beam profiles from circular collimators is used to calculate the dose at any axial depth and radial distance from the central axis. Instead, the dose profile data can be transformed into a sigmoidal form. A new three parameter sigmoidal function was developed to fit the transformed (sigmoidal) dose profile data. The values of the three estimated parameters were found to follow either linearly or exponentially as a function of axial depth. Thus, instead of linear interpolation, these formulas can be used to calculate dose at any axial depth and radial distance from the central axis for circular collimators of various diameters. This new sigmoidal function provides another formula to describe dose profile data from circular collimator of small fields.

Humans↗
PubMed2004

Global gene expression analysis of the developing postnatal mouse retina.

PURPOSE: Postnatal mouse retinal development involves glial and neuronal differentiation, vascularization, and the onset of vision. In the current study, the gene expression profiles of thousands of genes in the developing postnatal mouse retina were analyzed and compared in a large-scale, unbiased microarray gene expression analysis. METHODS: For each of eight different time points during postnatal mouse retinal development, two separate sets of 30 retinas were pooled for RNA isolation, and gene expression was analyzed by hybridization to gene chips in triplicate (Mu74Av2; Affymetrix, Santa Clara, CA). Genes were sorted into clusters based on their expression profiles and intensities. Validation was accomplished by comparing the microarray expression profiles with real-time RT-PCR analysis of selected genes and by comparing selected expression profiles with predicted profiles based on previous studies. RESULTS: The Mu74Av2 chip contains more than 6000 known genes and 6500 estimated sequence tags (ESTs) from the mouse Unigene database. Of these, 2635 known gene sequences and 2794 ESTs were expressed at least threefold above background levels during retinal development. Expressed genes were clustered based on expression profiles allowing potential functions for specific genes during retinal development to be inferred by comparison to developmental events occurring at each time point. Specific data and potential functions for genes with various profiles are discussed. All data can be viewed online at http://www.scripps.edu/cb/friedlander/gene_expression/. CONCLUSIONS: Expression analysis of thousands of different genes during normal postnatal mouse retinal development as reported in this study demonstrates that such an approach can be used to correlate gene expression with known functional differentiation, presenting the opportunity to infer functional correlates between gene expression and specific postnatal developmental events.

Animals↗
PubMed1984

An improved approach to the analysis of autoradiographs containing isolated sources of simple shape: method, theoretical basis and reference data.

There are circumstances in which, by assuming that a high proportion of the radioactivity in a biological specimen is associated with certain well-dispersed structures of simple shape, a relatively simple and effective objective analysis can be carried out. The usefulness of this type of restricted analysis has previously been severely limited by the requirement that all the profiles of interest should be of roughly the same size, which is rarely the case. A procedure is proposed which, by appropriately combining image spread functions for profiles of the same shape but of various sizes, allows realistic hypothesis testing in such circumstances. Details for the practical application of the method are offered and criteria for assessing the feasibility of applying the method in particular circumstances are discussed. The necessary backup information to the method is supplied in the form of the derivation of the fundamental image spread function, the introduction of a coherent notation and reference data quantitatively describing the image spread around certain extended sources of simple shape.

Animals↗
PubMed1989

Microgravity and musculoskeletal system of mammals.

This review surveys data in the literature and our own findings concerning the effects of weightlessness on bones and muscles of white rats flown on Cosmos biosatellites and Spacelab-3. It has been shown that the magnitude and sign of functional changes in muscles depend on their biomechanical profile. Structural and metabolic foundations of functional adaptation and its dynamics have been identified: in 5-7 day flights muscle contractility changes are mainly associated with a diminished activity of excitation-contraction coupling, in longer-term flights they are produced by changes in myosin populations specific for myofibers of different functional profile. At early flight stages (up to 1 week) osteoporosis and bone demineralization are very mild; therefore decrease in bone mechanical strength may be caused by changes in physico-chemical parameters of the collagen-crystal system. In flights of up to 3 weeks noticeable osteoporosis develops which is primarily produced by osteogenesis inhibition and which is responsible for a marked decrease of bone strength. These changes may result from uncoupling of bone resorption and remodelling processes. This uncoupling is characterized as incomplete osteogenesis and may be caused by changes in the collagen composition of the organic bone matrix. The above-mentioned adaptive changes in muscle functions of specific skeletal compartments may play a role in different responses of various bones to weightlessness.

Adaptation, Physiological↗
PubMed2004

An in vitro interval before transplantation of mesencephalic reaggregates does not compromise survival or functionality.

Grafts of primary ventral mesencephalic tissue and cell suspensions to the denervated striatum are currently utilized as a treatment strategy for Parkinson's disease. Survival rates of grafted dopamine (DA) neurons are extremely poor (5-20%) and is even poorer in grafts to the aged striatum. Short pretreatment of grafted cells with various survival-promoting agents has elicited 2- to 3-fold improvements in these survival rates. However, the duration of pretreatment is limited by the necessity of implanting the embryonic cells within a critical period after tissue harvest, potentially limiting the beneficial effects of these interventions. This study details the use of a modified mesencephalic reaggregate culture system combined with striatal-derived trophic factor support to provide an extended ex vivo cell culture interval before grafting. Mesencephalic cell suspension grafts implanted immediately following dissociation were compared to grafts of an equivalent number of cells reaggregated in the presence of striatal oligodendrocyte-type-2 astrocyte (SO2A) conditioned medium for 3 or 7 days. All grafts were placed in the denervated striatum of young adult male Fischer 344 rats. Rotational assessment of amphetamine-induced rotations indicates that aggregates maintained for 3 days in culture present statistically similar functional recovery profiles as compared to cell suspension grafts. Grafts of mesencephalic reaggregates maintained in vitro for 7 days did not display significant improvements in functional recovery. Immunohistochemical analysis for tyrosine hydroxylase immunoreactive (THir) neurons conducted at 10 weeks post-grafting revealed equivalent survival rates of THir neurons in grafts of fresh cell suspensions and aggregates held in culture for 3 days. Grafts of reaggregates held in culture for 7 days possessed significantly fewer THir neurons, about 25% of the cell suspension or 3-day aggregate grafts. This ex vivo reaggregate system allows for extended pretreatment (3 days) of mesencephalic cells with survival-promoting agents and immunological screening of tissue before transplantation.

Amphetamine↗
PubMed2006

Assessing a new nonempirical density functional: difficulties in treating pi-conjugation effects.

The reliability of the Tao-Perdew-Staroverov-Scuseria (TPSS) exchange-correlation functional for the description of conjugation effects in model pi-conjugated systems has been thoroughly assessed through the calculation of torsion energy profiles. The functional reproduces qualitatively the shape of torsional potentials but, interestingly, the mixing of TPSS and exact exchange governs the quantitative results: thus, well-defined hybrid extensions of the functional are consistently employed to improve the results. The hybrid approaches led to more accurate descriptions of conjugation effects but, however, the finest performance along the whole range of dihedral angles was obtained by a customized mixing of pure or hybrid TPSS functionals and wave function methods in a multicoefficient fashion. Despite the successful construction of this nonempirical functional, higher rungs of the ladder of methods in which TPSS is based are hoped to reduce the errors with respect to reference data for pi-conjugated systems.

Journal Article↗
PubMed2006

Peroneal nerve stimulation versus an ankle foot orthosis for correction of footdrop in stroke: impact on functional ambulation.

OBJECTIVE: To compare the efficacy of the Odstock Dropped-Foot Stimulator (ODFS), a transcutaneous peroneal nerve stimulation device, versus an ankle foot orthosis (AFO) in improving functional ambulation of chronic stroke survivors. INTERVENTION: Fourteen chronic stroke survivors with foot-drop participated in the study. Participants received ambulation training under 3 test conditions: 1) ODFS, 2) customized AFO, and 3) no device. Each participant was evaluated using the modified Emory Functional Ambulation Profile under the 3 test conditions. All participants were evaluated with a post-evaluation survey to solicit device feedback and preferences. RESULTS: Functional ambulation with the AFO was significantly improved, relative to no device, on the floor (P = 0.000), carpet (P = 0.013), and "up and go" test (P = 0.042). There was a trend toward significance on the obstacle (P = 0.092) and stair (P = 0.067) trials. Functional ambulation with the ODFS was significantly improved, relative to no device, on the carpet(P = 0.004). A trend toward significance on floor (P = 0.081), obstacle (P = 0.092), and stair (P = 0.079) trials was observed. The difference in functional ambulation between the AFO and ODFS showed a trend toward statistical significance on floor (P = 0.065) and up and go (P = 0.082) trials only. Given a choice between the ODFS and AFO for long-term correction of footdrop, participants indicated a preference for the ODFS. CONCLUSION: The AFO and the ODFS may be comparable in their effect on improving functional ambulation as compared to no device. Specific characteristics of the ODFS may make it a preferred intervention by stroke survivors. More rigorously controlled trials are needed to confirm these findings.

Female↗
PubMed1991

[Late results of mitral valve replacement with ball-type and low-profile prostheses].

The discussion covers long-term results of mitral valve replacement with Soviet-made prostheses. Two hundred and sixty-three patients have been under observation, the follow-up periods lasting from six months to five years. A ball-valve prosthesis (MK4-25) was implanted to 125 patients; 138 patients received a low-profile (,) prosthesis. Functional parameters were improved in 86 (69.9 percent) patients with ball-valve implants and in 118 (89 percent) patients with low-profile implants. Ten ball valve implanted patients (8 percent) and 6 (4.3 percent) patients with low-profile prostheses died in the long-term period. The five-year survival of rotation-disc artificial valve recipients was 90 percent, and that of the ball valve-implanted patients, 83 percent.

Adolescent↗
PubMed1990

Bile acid profile as early indicator of allograft function during orthotopic liver transplantation.

Orthotopic liver transplantation was performed in 20 pigs. Serum total bile acids (STBA) were determined and their profile compared with standard early function parameters: total bilirubin, aspartate aminotransferase (AST), alanine aminotransferase (ALT) and lactic acid. In phase I, the STBA level was 32.89 +/- 1.29 mumol/l. In phase II, STBA accumulated to 84.46 +/- 15.25 mumol/l (p less than 0.01), followed by hepatic clearance in phase III (63.61 +/- 9.71 mumol/1; NS). Between phase III and 6- and 12-hour samples, STBA decreased progressively, reaching values of 33.63 +/- 7.05 mumol/l at 24 h. AST was elevated in phases I, II, III, and at 6, 12 and 24 h (p less than 0.001), as was ALT (but with insignificant differences). Thus, STBA and their profile appear to be earlier and more specific indicators of early graft function than conventional parameters.

Alanine Transaminase↗
PubMed2005

Profiling of early gene expression induced by erythropoietin receptor structural variants.

The development of erythroid progenitor cells is triggered via the expression of the erythropoietin receptor (EPOR) and its activation by erythropoietin. The function of the resulting receptor complex depends critically on the presence of activated JAK2, and the complex contains a large number of signaling molecules recruited to eight phosphorylated tyrosine residues. Studies using mutant receptor forms have demonstrated that truncated receptors lacking all tyrosines are able to support red blood cell development with low efficiency, whereas add-back mutants containing either Tyr343 or Tyr479 reconstitute EPOR signaling and erythropoiesis in vivo. To study the contribution of tyrosines to receptor function, we analyzed the activation of essential signaling pathways and early gene induction promoted by different receptor structural variants using human epidermal growth factor receptor/murine EPOR hybrids. In our experiments, receptors lacking all tyrosine residues or the JAK2-binding site did not induce mitogenic and anti-apoptotic signaling, whereas add-back mutant receptors containing single tyrosine residues (Try343 and Tyr479) supported the activation of these functions efficiently. Profiling of early gene expression using cDNA array hybridization revealed that (i) the high redundancy in the activation of signaling pathways is continued at the level of transcription; (ii) the expression of many genes targeted by the wild-type receptor is not supported by add-back mutants; and (iii) a small set of genes are exclusively induced by add-back receptors. We report the identification of several early genes that have not been implicated in the EPOR-dependent response so far.

Animals↗
PubMed1996

Pulmonary blood flow profiles with reduced right ventricular function in lambs.

The determinants of right ventricular (RV) performance with damaged RV free wall, such as occurs with RV infarction, are still unclear. Using 20-MHz Doppler ultrasound equipment, we investigated the changes in pulmonary blood flow velocity profiles before and after ligation of the right coronary artery. RV dp/dt, stroke volume, RV stroke work, aortic pressure and cardiac output decreased and central venous pressure rose after the ligation. The RV stroke work-end-diastolic pressure relationship indicated impaired RV function following ligation. We observed shortened acceleration time (65.0 +/- 15.1 vs 54.4 +/- 6.2 ms, P < 0.05) and reduced maximum velocity of forward flow (59.0 +/- 5.9 vs 52.5 +/- 7.6 cm/s, P < 0.05) after the ligation. Acceleration was interrupted earlier after ligation than before ligation. These alterations in flow are thought to be a consequence of the altered movement of the RV free wall and ventricular septum induced by RV infarction.

Animals↗
PubMed1985

Serum melatonin profiles and endocrine responses of ewes exposed to a pulse of light late in the dark phase.

To determine whether effects of light pulses on the photoperiodic time measuring system involve changes in pineal gland function, melatonin profiles were determined in groups of ewes maintained under 10-h light, 14-h dark (10L:14D) or 10L:10D:1L:3D. Ewes exposed to 10L:14D had a significantly (P less than 0.01) longer duration of melatonin secretion (15.0 +/- 0.4 h, mean +/- SE) than ewes under 10L:10D:1L:3D (9.0 +/- 0.4 h). The 1-h pulse of light therefore acted as a dawn signal in the latter group. During a period of extended darkness imposed to study endogenous control of melatonin release, there was no change in the duration of elevated melatonin in control ewes (16.1 +/- 0.5 h), but a significant (P less than 0.05) lengthening occurred in pulsed ewes (13.2 +/- 1.4 h). PRL responses to a bolus iv injection of TRH (50 ng/kg BW) were significantly (P less than 0.01) smaller in control ewes (478 +/- 134 ng/ml) compared with pulsed ewes (1578 +/- 175 ng/ml), with responses in the latter group resembling those observed in ewes on long days. A 1-h pulse of light late in the dark phase, therefore, resulted in a melatonin pattern normally observed under long days in ewes, and this was associated with other endocrine functions also characteristic of sheep on long days. It is concluded that pulses of light modify activity of the pineal gland which in turn interacts with the photoperiodic time-measuring system via melatonin. The increase in duration of melatonin secretion observed in pulsed ewes under extended darkness suggests that the melatonin rhythm is under the control of two oscillators coupled to dusk and dawn, and that these oscillators interact more strongly when compressed by an interrupted dark phase.

Animals↗
PubMed1992

Synaptic interactions between GABA-immunoreactive profiles and the terminals of functionally defined myelinated nociceptors in the monkey and cat spinal cord.

This study analyzes the synaptic interactions between the central terminals of A delta high threshold mechanoreceptors (A delta HTMs) and GABA-immunoreactive profiles. A delta HTM primary afferents from three monkeys and one cat were electrophysiologically identified and intracellularly labeled with HRP, and their terminal arborizations in laminae I and II of the sacrocaudal spinal cord were studied at the ultrastructural level. GABA-immunoreactive profiles in relation to A delta HTM terminals were demonstrated using postembedding colloidal gold techniques. Monkey A delta HTM terminals (n = 131) usually constituted the central element of synaptic glomeruli; they established large asymmetric synaptic contacts with 1-13 dendrites (modal value 2-4) and were surrounded by 0-6 peripheral axon terminals (modal value 2-3). The large majority (around 85%) of the peripheral axon terminals were GABA immunoreactive. They were found presynaptic to the A delta HTM terminal and/or to dendrites postsynaptic to the primary afferent terminal. Furthermore, all peripheral axon terminals found presynaptic to the A delta HTM terminals showed GABA immunoreactivity. Within a single A delta HTM fiber, this synaptic arrangement was found in 20-60% of its boutons. In addition, 28% of the postsynaptic dendritic profiles displayed weak GABA immunoreactivity. Some of them contained vesicles; however, only in a few cases did we observe synapses between a GABA-immunoreactive vesicle-containing dendrite and a dendritic profile postsynaptic to an A delta HTM terminal. Similar synaptology and interactions with GABA-immunoreactive profiles were displayed by the terminals of the single cat A delta HTM fiber studied. Our data support the hypothesis that GABA-containing neurons use both presynaptic and/or postsynaptic mechanisms to exert a powerful control, presumably inhibitory, over the transmission of nociceptive information between A delta HTM afferents and second-order neurons in monkey and cat spinal cord. Our results also imply that GABA may be released within the synaptic glomeruli formed by A delta HTM terminals either by local dendrites or by axon terminals. We discuss the possibility that these GABAergic synapses can be driven by inputs from both primary afferents and/or descending systems to modulate the transmission of nociceptive sensory information.

Animals↗
PubMed2005

Restoring function in exhausted CD8 T cells during chronic viral infection.

Functional impairment of antigen-specific T cells is a defining characteristic of many chronic infections, but the underlying mechanisms of T-cell dysfunction are not well understood. To address this question, we analysed genes expressed in functionally impaired virus-specific CD8 T cells present in mice chronically infected with lymphocytic choriomeningitis virus (LCMV), and compared these with the gene profile of functional memory CD8 T cells. Here we report that PD-1 (programmed death 1; also known as Pdcd1) was selectively upregulated by the exhausted T cells, and that in vivo administration of antibodies that blocked the interaction of this inhibitory receptor with its ligand, PD-L1 (also known as B7-H1), enhanced T-cell responses. Notably, we found that even in persistently infected mice that were lacking CD4 T-cell help, blockade of the PD-1/PD-L1 inhibitory pathway had a beneficial effect on the 'helpless' CD8 T cells, restoring their ability to undergo proliferation, secrete cytokines, kill infected cells and decrease viral load. Blockade of the CTLA-4 (cytotoxic T-lymphocyte-associated protein 4) inhibitory pathway had no effect on either T-cell function or viral control. These studies identify a specific mechanism of T-cell exhaustion and define a potentially effective immunological strategy for the treatment of chronic viral infections.

Animals↗
PubMed1988

Intracerebral neuronal grafting in experimental animal models of age-related motor dysfunction.

The combined morphological, biochemical, electrophysiological, and behavioral data summarized above show that implanted embryonic nerve cells in some cases can substitute quite well for a lost intrinsic neuronal system in mammals. The intracerebral implants probably exert their effects in several ways. The functional effects seen with grafts placed into one of the cerebral ventricles (such as those described in the studies of Perlow et al., Freed et al., and Gash et al.) are thus probably explained on the basis of a diffuse release of an active amine or peptide into the host CSF and adjacent brain tissue. In other instances, as in animals with DA-rich grafts reinnervating the neostriatum, we believe that the available data provide quite substantial evidence that the behavioral recovery is caused by the ability of the grafted neurons to reinnervate relevant parts of the host brain. This is illustrated by the studies mentioned above that show that the degree of functional recovery in 6-OHDA-lesioned rats with nigral transplants is directly correlated with the extent of striatal DA reinnervation and that the "profile" of functional recovery is dependent on that area of the striatal complex that is reinnervated by the graft. This point is particularly well illustrated in a further study in which rats with electrodes implanted into the center of intracortical nigral grafts were allowed to "self-stimulate" via the graft. The results show that the graft can indeed sustain self-stimulation behavior and that the rate of lever-pressing is related to the proximity between the electrode tip and the DA-containing neurons in the graft. This strongly supports the notion that the implanted DA neurons can transmit behaviorally meaningful and temporally organized information to the host brain via their efferent connections. To what extent the intracerebral implants can be functionally integrated with the host brain is still poorly known, though, and it therefore remains an interesting question for further investigation. The chances for extensive integration may be greatest for neuronal suspension grafts implanted as deposits directly into the depth of the brain, but even solid grafts inserted as whole pieces into the brain have, in several cases, been seen to become reinnervated from the host brain in adult and developing recipients. Nevertheless, a recent HRP study failed to detect any host afferents to intracortical solid nigral grafts, despite the fact that these grafts had themselves formed extensive DA connections in the host striatum and had produced behavioral recovery.(ABSTRACT TRUNCATED AT 400 WORDS)

Aging↗
PubMedDate not supplied

Psychological stress measure in type 2 diabetes.

Psychological stress has been implicated as a cause of several psychosomatic disorders, but also as a factor that can unfavourably influence many diseases including diabetes mellitus. Measure of psychological stress in diabetes was performed by Psychological Stress Measure (PSM), a validated instrument, designed using 49 items drawn from descriptors generated by focus groups on stress. Clinical and psychological framework was assessed in a cohort of 100 type 2 diabetic patients (30 m, 70 f), aged 66.99 +/- 13.68 years considering disease grade, complications and level of instruction. Three other questionnaires were administered concurrently to all patients: Sickness Impact Profile (SIP), Functional Living Index (FLI) and SF-36 QOL. ANOVA statistical testing and Spearman correlation matrix were used also vs socio-cultural and clinical profile. Gender, obesity, diet compliance, smoking do not affect PSM response. Hypertensive patients and those with family history of diabetes show lower PSM scores, according to a sort of moderator effect on stress of concurrent and/or previous experience with chronic disease. Neuromuscular ailments are more prevalent in women; men vs women experience severe limitations of their working capacities and relational possibilities, with severe discomfort. In the whole, higher scores of PSM (greater stress p < 0.01) and lower scores of FLI (fair well-being perception; p < 0.01) are reciprocally related inside any school instruction level. Despite the great reciprocal association of the PSM vs FLI and SIP, no significant correlation is found between PSM vs SF-36 QOL. Socio-cultural elements interfere, and particularly instruction level quantified as school grades achieved, with the manner of living their disease. Interventions on psychological distress of type 2 diabetes mellitus patients is warranted, specially in the groups with lower levels of instruction which may need an attentive strategy for achieving a satisfactory coping with this disease.

Aged↗
PubMed2002

Melanin-concentrating hormone receptor subtypes 1 and 2: species-specific gene expression.

To assess the contribution of potential central nervous system pathways implicated in the control of appetite regulation and energy metabolism, it is essential to first identify appropriate animal models. Melanin-concentrating hormone (MCH), a conserved cyclic neuropeptide implicated in the modulation of food intake, has been shown to bind and activate two G-protein-coupled receptors, called GPR24 and MCHR2, expressed in human brain and other tissues. Here we show that several non-human species (rat, mouse, hamster, guinea pig, and rabbit) do not have functional MCHR2 receptors, or encode a nonfunctional MCHR2 pseudogene while retaining GPR24 expression. We identified three species for further evaluation that express both MCH receptor subtypes. We cloned and functionally characterized dog, ferret, and rhesus GPR24 and MCHR2 in mammalian cells and studied their brain distribution patterns by in situ hybridization. The homology, expression profile, and functional similarity of the receptors in the dog, ferret, and rhesus to that of human support the potential use of these species as preclinical animal models in the development of therapeutic agents for obesity or other MCH-mediated disorders.

Amino Acid Sequence↗
PubMedDate not supplied

[Analyses of the communicative functions expressed by language therapists and patients of the autistic spectrum].

BACKGROUND: communicative functions used by language therapists and patients. AIM: to analyze the communicative functions used by language therapists and patients of the autistic spectrum. METHOD: the communicative functions expressed by six therapists in interaction with six patients each were analyzed, constituting 36 profiles of communicative functions expressed by the dyad therapist-patient. All therapists were part of a Training Program in Childhood Psychiatric Disorders and the patients were diagnosed within the autistic spectrum. Data were gathered using the transcriptions of a videotaped therapy session and these were analyzed according to the criteria suggested by Fernandes (2000). The communicative functions were divided in two different ways: interpersonal and non-interpersonal, and instrumental, regulatory, interactive, personal, heuristic and imaginative. RESULTS: the comparison between the functions used by the language therapists and the patients indicated a statistically significant difference in use of the following functions: request of social routine, request of information, request of action, comment, recognition of other, exclamation, non-focused, exploratory, exhibition, play and reactive. There was also a statistically significant difference between the use of interpersonal, non-interpersonal, regulatory, interactive, personal and heuristic communicative functions. CONCLUSION: the functional communicative profile of language therapists is different from the one presented by their patients when comparing each communicative function and when the communicative functions are grouped (interpersonal and non-interpersonal, and instrumental, regulatory, interactive, personal, heuristic and imaginative). Therapists use communicative functions to fill in the communicative space and to make requests. This finding agrees with the findings of previous studies.

Adolescent↗