SEARCH · PubMed Health

Results for “Integrated functions”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 991 records · Page 55Linked to original sources

PubMed2007

Interspecific analysis of covariance structure in the masticatory apparatus of galagos.

The primate masticatory apparatus (MA) is a functionally integrated set of features, each of which performs important functions in biting, ingestive, and chewing behaviors. A comparison of morphological covariance structure among species for these MA features will help us to further understand the evolutionary history of this region. In this exploratory analysis, the covariance structure of the MA is compared across seven galago species to investigate 1) whether there are differences in covariance structure in this region, and 2) if so, how has this covariation changed with respect to size, MA form, diet, and/or phylogeny? Ten measurements of the MA functionally related to bite force production and load resistance were obtained from 218 adults of seven galago species. Correlation matrices were generated for these 10 dimensions and compared among species via matrix correlations and Mantel tests. Subsequently, pairwise covariance disparity in the MA was estimated as a measure of difference in covariance structure between species. Covariance disparity estimates were correlated with pairwise distances related to differences in body size, MA size and shape, genetic distance (based on cytochrome-b sequences) and percentage of dietary foods to determine whether one or more of these factors is linked to differences in covariance structure. Galagos differ in MA covariance structure. Body size appears to be a major factor correlated with differences in covariance structure among galagos. The largest galago species, Otolemur crassicaudatus, exhibits large differences in body mass and covariance structure relative to other galagos, and thus plays a primary role in creating this association. MA size and shape do not correlate with covariance structure when body mass is held constant. Diet also shows no association. Genetic distance is significantly negatively correlated with covariance disparity when body mass is held constant, but this correlation appears to be a function of the small body size and large genetic distance for Galagoides demidoff. These exploratory results indicate that changing body size may have been a key factor in the evolution of the galago MA.

Animals↗

PubMed1995

Potassium currents in motoneurones.

The measurements of intrinsic unitary and macroscopic properties of potassium channels in motoneurones constitutes an important step in the characterization of cellular function. A number of potassium currents contribute to the integrated function of motoneurones and this review considers the properties of the inward rectifier (Ih-type), calcium-dependent (BK- and SK-types), delayed rectifier, transient outward, and leak currents. The modification of channel properties by agents such as serotonin and thyrotropin-releasing hormone is likely relevant to modulation of motoneurone function. Indeed, even during the course of normal cell development, the expression and properties of particular potassium channels can undergo considerable changes, which would be manifested as altered firing patterns and excitability of motoneurones. Brainstem and spinal cord slices have considerable utility for electrophysiological studies and have been used in recordings from spinal, hypoglossal and facial motoneurones. New procedures have also been developed which would enhance the purification of cultured motoneurones for patch-clamp experiments.

Animals↗

PubMed2004

Functional portal flow competition after auxiliary partial orthotopic living donor liver transplantation in noncirrhotic metabolic liver disease.

Auxilliary partial orthotopic liver transplantation (APOLT) was introduced initially as a tentative or permanent support for patients with potentially reversible fulminant hepatic failure and has extended its indication to congenital metabolic disorder of the liver that has otherwise normal functional integrity. Postoperative management of APOLT is complicated because of functional portal flow competition between the native and graft liver. The native portal vein diversion to the graft is sometimes indicated to prevent functional competition; however, it is still an open question whether this technique can be theoretically indicated for APOLT patients. The authors report a on patient with ornithine transcarbamylase deficiency who received APOLT from a living donor without native portal vein diversion. Because of functional portal vein competition between the native and graft liver, the patient had to have portal vein diversion, portal vein embolization, and finally native hepatectomy to induce the graft regeneration after APOLT. After the experience of the current case, primary portal vein diversion for APOLT with noncirrhotic metabolic liver disease patients to prevent functional portal flow competition is recommended.

Anastomosis, Surgical↗

PubMed2004

Biomarker discovery and validation: technologies and integrative approaches.

The emerging field of biomarkers has applications in the diagnosis, staging, prognosis and monitoring of disease progression, as well as in the monitoring of clinical responses to a therapeutic intervention and the development and delivery of personalized treatments to reduce attrition in clinical trials. Moreover, biomarkers have a positive impact on health economics. The word "biomarker" has been used extensively across therapeutic areas and many disciplines, and its nature takes into consideration clinical, physiological, biochemical, developmental, morphological and molecular measures. In drug trials, biomarkers have been proposed for use in efficacy determination and patient population stratification, in deducing pharmacokinetic-pharmacodynamic relationships and in safety monitoring. The interfacing and integration of different technologies for data collection and analysis are pivotal to biomarker identification, characterization, validation and application. "Integrative functional informatics" represents a novel direction in such technology integration.

Biomarkers↗

PubMed2003

Regulation of Fyn through translocation of activated Lck into lipid rafts.

Whether or how the activation of Lck and Fyn during T cell receptor (TCR) signaling is coordinated, and their delivery of function integrated, is unknown. Here we show that lipid rafts function to segregate Lck and Fyn in T cells before activation. Coaggregation of TCR and CD4 leads to Lck activation within seconds outside lipid rafts, followed by its translocation into lipid rafts and the activation of colocalized Fyn. Genetic evidence demonstrates that Fyn activation is strictly dependent on receptor-induced translocation of Lck. These results characterize the interdependence of Lck and Fyn function and establish the spatial and temporal distinctions of their roles in the cellular activation process.

Animals↗

PubMed2000

Development of an in situ mouse brain perfusion model and its application to mdr1a P-glycoprotein-deficient mice.

An in situ mouse brain perfusion model predictive of passive and carrier-mediated transport across the blood-brain barrier (BBB) was developed and applied to mdr1a P-glycoprotein (Pgp)-deficient mice [mdr1a(-/-)]. Cerebral flow was estimated from diazepam uptake. Physical integrity of the BBB was assessed with sucrose/inulin spaces; functional integrity was assessed with glucose uptake, which was saturable with a Km of approximately 17 mmol/L and Vmax of 310 mmol x 100 g(-1) x min(-1). Brain uptake of a Pgp substrate (colchicine) was significantly enhanced (two- to fourfold) in mdr1a(-/-) mice. These data suggest that the model is applicable to elucidating the effects of efflux transporters, including Pgp, on brain uptake.

ATP Binding Cassette Transporter, Subfamily B↗

PubMed1992

Lower eyelid blepharoplasty.

BACKGROUND: Lower eyelid blepharoplasty is a frequently performed procedure to reverse partially gravitational aging effects on eyelid tissues. Careful planning, proper execution, and appropriate management of potential postoperative complications will generally result in a happy and satisfied patient. However, in any surgical procedure that is primarily aesthetic in nature, the surgeon needs to be constantly aware of factors that may compromise the functional integrity of the eyelid. A patient with altered visual function or ocular discomfort is no longer primarily concerned about the final aesthetic appearance of even the most perfectly executed, technically correct blepharoplasty procedure. OBJECTIVE: To describe the preoperative evaluation, surgical technique, and postoperative complications of lower eyelid blepharoplasty. Specific attention will be given to lower eyelid retraction and ectropion following blepharoplasty. CONCLUSION: Successful lower eyelid blepharoplasty surgery can be a source of both patient and physician satisfaction. As long as patient expectations are consistent with realistic surgical goals, lower eyelid blepharoplasty is an important aspect of overall facial aesthetic surgery.

Eyelid Diseases↗

PubMed1995

Duck hepatitis B virus integrations in LMH chicken hepatoma cells: identification and characterization of new episomally derived integrations.

While the cytoplasmic phase of the hepadnavirus replication cycle is well understood, very little is known about the nuclear phase. In contrast to retroviruses, proviral integration is not required for hepadnavirus replication; however, some of the viral DNAs in the nucleus are diverted into an integration pathway. Under certain conditions these integrations function as carcinogenic agents. In order to study the integration process, we have utilized LMH-D2 cells, which replicate wild-type duck hepatitis B virus (DHBV), to develop the first protocol to detect and characterize integrations of DHBV originating from episomal viral DNAs. Contrary to expectations, our results showed that stable new integrations are readily detectable in subclones of LMH-D2 cells. Complete characterization of one integration revealed a single-genome-length integrant with the structure of double-stranded linear (DSL) DHBV DNAs which are produced by in situ priming during viral replication. The integration contained a terminal redundancy of 6 bp from the r region of the virus DNA minus strand as well as a direct repeat of 70 bp of cellular DNA. On the basis of the structure of the integrant and the cellular DNA target site, we propose a molecular model for the integration mechanism that has some similarities to that of retroviruses. Identification of DSL hepadnavirus DNA integration suggests the possibility that modified DSL viral DNAs may be the precursors to a class of simple, unrearranged hepadnavirus integrations.

Animals↗

PubMed2001

Dynamic diaschisis: anatomically remote and context-sensitive human brain lesions.

Functional neuroimaging was used to investigate how lesions to the Broca's area impair neuronal responses in remote undamaged cortical regions. Four patients with speech output problems, but relatively preserved comprehension, were scanned while viewing words relative to consonant letter strings. In normal subjects, this results in left lateralized activation in the posterior inferior frontal, middle temporal, and posterior inferior temporal cortices. Each patient activated normally in the middle temporal region but abnormally in the damaged posterior inferior frontal cortex and the undamaged posterior inferior temporal cortex. In the damaged frontal region, activity was insensitive to the presence of words but in the undamaged posterior inferior temporal region, activity decreased in the presence of words rather than increasing as it did in the normal individuals. The reversal of responses in the left posterior inferior temporal region illustrate the context-sensitive nature of the abnormality and that failure to activate the left posterior temporal region could not simply be accounted for by insufficient demands on the underlying function. We propose that, in normal individuals, visual word presentation changes the effective connectivity among reading areas and, in patients, posterior temporal responses are abnormal when they depend upon inputs from the damaged inferior frontal cortex. Our results serve to introduce the concept of dynamic diaschisis; the anatomically remote and context-sensitive effects of focal brain lesions. Dynamic diaschisis reveals abnormalities of functional integration that may have profound implications for neuropsychological inference, functional anatomy and, vicariously, cognitive rehabilitation.

Aphasia, Broca↗

PubMed1988

Effect of rapid normalization of plasma glucose levels on microvascular dysfunction and polyol metabolism in diabetic rats.

Effects of rapid normalization of plasma glucose levels (by insulin infused via Alzet pumps implanted intraperitoneally) on plasma insulin-like growth factor I (IGF-I) levels, granulation tissue polyol levels, and vascular permeation by 125I-labeled albumin were examined in male Sprague-Dawley rats with streptozocin-induced (60-65 mg/kg) diabetes. Two days after implantation of pumps, plasma insulin levels were twice normal levels and remained elevated (1.4-2.5 times normal) throughout the remainder of the study. Plasma glucose levels and granulation tissue polyol levels were normalized within 2 days after initiation of insulin treatment. Plasma IGF-I levels were significantly increased (2 times) by 2 days, but were not normalized until 7 days. In contrast, 125I-albumin permeation normalized at a much slower relatively linear rate and was still not completely normal after 14 days of insulin treatment. In view of 1) previous studies demonstrating that diabetes-induced increases in 125I-albumin permeation in this tissue are linked to increased metabolism of glucose to sorbitol and 2) the rapid normalization of tissue polyol levels in this study, the relatively linear rate of normalization of vascular permeability over 14 days in these studies suggests that impaired vascular barrier functional integrity in this model is mediated by structural and/or functional vascular alterations associated with sustained increased polyol metabolism rather than by increased polyol levels per se and/or by readily reversible functional and metabolic alterations associated with acute increases in polyol metabolism.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMedDate not supplied

First metatarsocuneiform joint arthrodesis: a five-year retrospective analysis.

Historically, first metatarsocuneiform joint arthrodesis has been advocated for severe metatarsus primus adductus deformity and as a salvage procedure in reconstructive forefoot surgery. At the Podiatry Hospital of Pittsburgh, the authors have expanded the use of this procedure to include elimination of excessive motion at the first metatarsocuneiform joint and to restore functional integrity to the first ray in an otherwise poorly functioning foot. First metatarsocuneiform arthrodesis has had poor acceptance by podiatric surgeons. Common reasons for this poor acceptance are technical difficulty associated with the procedure and often-cited complications such as shortening of the first ray, with symptomatic transfer lesions, as well as nonunion of the arthrodesis site. The authors evaluated 54 procedures. Results of first metatarsocuneiform joint arthrodesis for long-term reduction of the intermetatarsal angle and for limiting abnormal motion at this joint have been very good. Few complications were encountered. Shortening of the first metatarsal with secondary transfer lesions was not found to be a common problem. Several radiographic nonunions occurred, none of which were symptomatic. The surgical procedure, as it is performed at the Podiatry Hospital of Pittsburgh, is described. Results from a 5-year retrospective analysis of first metatarsocuneiform arthrodesis are presented.

Adolescent↗

PubMedDate not supplied

Stability examination of the knee: a simple anatomic approach.

The knee is a complex joint and its stability depends upon many factors, but static stablizing structures are the most critical. The anatomic integrity of these structures correlates well with both their functional integrity and the instability observed during manual stress-testing of the knee. This makes accurate diagnosis possible. Stability of the knee is most easily defined in terms of straight planes, varus, valgus, anterior and posterior displacement. Rotory instabilities are syndromes which represent combinations of straight-plane instabilities. The stability in each plane is supplied by a primary static stabilizer and secondary and at times tertiary reinforcing structures. The information required to accurately interpret the pattern of injury is readily obtained by stressing the knee in the planes described.

Biomechanical Phenomena↗

PubMed2000

Investigation of functional and morphological integrity of freshly isolated and cryopreserved human hepatocytes.

There is a pressing need for alternative therapeutic methods effective in the treatment of patients with liver insufficiency. Isolated human hepatocytes may be a viable alternative or adjunct to orthotopic liver transplantation in such patients. The purpose of this study was to evaluate the viability and functional integrity of freshly isolated and cryopreserved human hepatocytes, in preparation for a multi-center human hepatocyte transplantation trial. We are currently processing transplant-grade human parenchymal liver cells from nondiseased human livers that are obtained through a network of organ procurement organizations (OPOs). Thus far, sixteen hepatocyte transplants have been performed using hepatocytes processed by our methods. At the time of referral all specimens were deemed unsuitable for transplantation due to anatomical anomalies, high fat content, medical history, etc. Hepatocytes were isolated from encapsulated liver sections by a modified two-step perfusion technique. Isolated cells were cryopreserved and stored in liquid nitrogen for one to twelve months. The total yield of freshly isolated hepatocytes averaged 3.7x10(7) cells per gram of wet tissue. Based on trypan blue exclusion, fresh preparations contained an average of 85% viable hepatocytes vs. 70% in cryopreserved samples. The plating efficiencies of cells seeded immediately after isolation ranged from 87% to 98%, while those of cryopreserved/thawed cells were markedly lower. Flow cytometry analysis of cells labeled with 5,6-carboxyfluorescein diacetate succinimidyl ester (CFSE) showed that there was no significant difference in viability compared with trypan blue staining. Both freshly isolated hepatocytes and those recovered from cryopreservation showed typical and intact morphology as demonstrated by light and electron microscopy. The product of the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) reaction was always expressed more intensely in cultures of freshly isolated hepatocytes. Measurements of lactate dehydrogenase (LDH) leakage were inversely correlated with trypan blue exclusion and CFSE labeling. Energy status, evaluated by the intracellular ATP concentration measurements, and various liver-specific functions such as urea synthesis and metabolism of 7-ethoxycoumarin were maintained both in fresh and cryopreserved/thawed hepatocytes. However, the activities were expressed at different levels in thawed cells. These data illustrate the importance and feasibility of human hepatocyte banking. In addition, it is clear that further refinements in the methods of hepatocyte isolation and cryopreservation are needed to utilize more fully these valuable cells in the clinic.

Journal Article↗

PubMed1983

Morphological and functional characteristics of isolated acini used for in vitro studies of prostatic secretion.

Acini of the rat ventral prostate were isolated by interstitial injection of a collagenase-containing medium, subsequent incubation in the same medium and repeated aspiration through pipette tips with decreasing gauge of the tip opening. Functional integrity of the isolated acini was assessed by morphological studies, including transmission and scanning electron microscopy, freeze-fracturing, and immunocytochemistry. Incubation studies with different incubation media were performed monitoring O2-consumption as a parameter of functional activity, in addition to the incorporation rate of radioactively labeled amino acids into newly synthesized proteins. Optimal incubation conditions (shaking water bath, 20 strokes/min, 37 degrees C, gassing with carbogen at 15 min intervals) were found with M 199 medium supplemented with dihydrotestosterone. Stimulation of prostatic secretion was maximal with 10(-7) M of pilocarpin, which was more effective than carbamylcholine. Incorporation of precursors into prostatic proteins proceeded for about 2 h at a linear rate. Thereafter a rapid loss of functional and morphological integrity of the isolated acini was observed including disintegration, vacuolation and lysis of individual cells. The system of isolated prostatic epithelium developed is a useful tool in the study of prostatic secretion in vitro in short term experiments.

Acid Phosphatase↗

PubMedDate not supplied

REALISIS: a medicinal chemistry-oriented reagent selection, library design, and profiling platform.

REALISIS is a software system for reagent selection, library design, and profiling, developed to fit the workflow of bench chemists and medicinal chemists. Designed to be portable, the software offers a comprehensive graphical user interface and rapid, integrated functionalities required for reagent retrieval and filtering, product enumeration, and library profiling. REALISIS is component-based, consisting of four main modules: reagent searching; reagent filtering; library enumeration; and library profiling. Each module allows the chemist to access specific functionalities and diverse filtering and profiling mechanisms. By implementing the entire process of reagent selection, library design, and profiling and by integrating all the necessary functionalities for this process, REALISIS cuts the time required to design combinatorial and noncombinatorial libraries from several days to a few hours.

Journal Article↗

PubMed1995

Integration of hippocampal suspension grafts with host neocortex.

The possibility of histological and functional integration of nervous tissue heterotopically grafted into the adult host brain was investigated. Suspensions of embryonic (E17-18) rat hippocampus with dentate fascia were placed into acute cavities in the barrel field of young adult rats (n = 25). Golgi-Cox silver impregnation and Cresyl Violet stain were used for histological analysis 3-4 months postgrafting. The surviving grafts were present in 80% of the grafted animals. Only three out of 20 surviving grafts were completely isolated from the surrounding host brain; other grafts had areas of direct confluence with the host neuropil. Extracellular recording of neuronal activity revealed normal spontaneous activity typical of the hippocampus in the majority of the grafts. Electrical stimulation of the posterior nucleus of the thalamus, homolateral motor neocortex, contralateral barrel field, and sensory stimulation of the host evoked responses in 50-60% of the grafted neurons. This did not differ significantly from the responsiveness of the similarly tested neurons of homotopic neocortical suspension grafts. The latencies of the responses in the hippocampal grafts were consistently longer (by about 10 ms) than in the neocortical ones. Comparison of the hippocampal suspension grafts with other types of hippocampal and neocortical grafts suggests that under certain conditions heterotopic tissue can be successfully integrated into the host brain. Development of the host-graft interconnections depends on topical proximity, the presence of denervated synaptic loci in both tissues, elimination of the intragraft neuronal targets and disruption of the intrinsic connections between them.

Animals↗

PubMed2006

MLH1-deficient tumor cells are resistant to lipoplatin, but retain sensitivity to lipoxal.

Lipoplatin, currently under phase III evaluation, is a novel liposomal cisplatin formulation highly effective against cancers. Lipoplatin has eliminated or reduced the systemic toxicity frequently seen for cisplatin. The objective of the present study was to determine whether the cytotoxic effect of lipoplatin is dependent on the functional integrity of DNA mismatch repair (MMR), a post-replicative DNA repair machinery implicated in cell cycle control and apoptosis. Clonogenic data revealed a significant (P<0.05) 2-fold resistance to lipoplatin of HCT116 human colorectal adenocarcinoma cells lacking MLH1, one of five proteins crucial to MMR function, as compared to MLH1-expressing HCT116 cells. In addition, MLH1-deficient cells were at least 3-fold less susceptible to apoptosis (DNA fragmentation) than MLH1-proficient cells. However, proteolytic processing of caspase-3, caspase-7 and poly(ADP-ribose)polymerase-1 following lipoplatin treatment was comparable in MLH1-deficient cells and -proficient cells. Furthermore, MLH1-deficient cells retained the ability to attenuate cell cycle progression past the G2/M checkpoint following lipoplatin treatment. In conclusion, our results indicate that the lipoplatin-sensitive phenotype of MLH1-proficient cells correlated with increased apoptosis which may occur via caspase-independent pathways. They also suggest that the integrity of MMR function is a relevant determinant accounting for the cytotoxicity of lipoplatin. However, this does not seem to apply to lipoxal, a novel liposomal formulation of oxaliplatin, because MLH1-deficient cells were as sensitive to lipoxal as MLH1-proficient cells.

Adaptor Proteins, Signal Transducing↗

PubMed1997

Activation of duration-sensitive auditory cortical fields in humans.

The influence of stimulus duration on auditory evoked potentials (AEPs) was examined for tones varying randomly in duration, location, and frequency in an auditory selective attention task. Stimulus duration effects were isolated as duration difference waves by subtracting AEPs to short duration tones from AEPs to longer duration tones of identical location, frequency and rise time. This analysis revealed that AEP components generally increased in amplitude and decreased in latency with increments in signal duration, with evidence of longer temporal integration times for lower frequency tones. Different temporal integration functions were seen for different N1 subcomponents. The results suggest that different auditory cortical areas have different temporal integration times, and that these functions vary as a function of tone frequency.

Adolescent↗