Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “pathway analysis”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

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

At least 883 records · Page 49Linked to original sources
PubMed1993

Network analysis of functional auditory pathways mapped with fluorodeoxyglucose: associative effects of a tone conditioned as a Pavlovian excitor or inhibitor.

The purpose of this study was to examine how opposite learned associative properties of the same auditory stimulus are represented by the pattern of network interactions between auditory system structures. [14C(U)]2-fluoro-2-deoxyglucose (FDG) autoradiography was used to compare mean auditory system activity and interregional correlations resulting from the presentation of a tone trained as either a Pavlovian conditioned excitor or inhibitor. Rats were trained with reinforced trials of the conditioned excitor (A+) intermixed with non-reinforced trials of a tone-light compound (AX-). For the Conditioned Excitor group, the tone was the excitor (A+), while for the Conditioned Inhibitor group the tone was the inhibitor (X-). After conditioning, both groups were injected with FDG and presented with the same tone. Structural equation models, constructed from the anatomical connections between auditory regions and their interregional correlations in FDG uptake, were used to calculate path coefficients representing the network interactions. The opposite associative significance of the tone was reflected as functional changes in the interactions between parallel auditory pathways. Direct covariance effects through lemniscal pathways from the ventral cochlear nucleus were similar in absolute magnitude but differed in sign between the Excitor and Inhibitor network models. Extra-auditory influences on the dorsal cochlear nucleus were greater for the tone-inhibitor, reflecting possible interactions of this nucleus with extra-auditory regions. The different associative effects of the tone suggest that central auditory pathways can code not only the physical qualities, but also the associative significance of auditory stimuli. These findings demonstrate that neural network interactions differentiate the associative effects of tones in the brain. It is proposed that associative learning is a distributed property of neural networks and that such a property can be understood by considering the interactions between component parts of the network.

Acoustic Stimulation↗
PubMed1995

Quantitative analysis of the olfactory pathway for drug delivery to the brain.

Following intranasal administration to rats, wheat germ agglutinin-horseradish peroxidase (WGA-HRP) concentrated in the olfactory nerve and glomerular layers of the olfactory bulb resulting in a mean olfactory bulb concentration of 140 nM. A negligible amount of label was detected in the olfactory bulb following intravenous administration of WGA-HRP or intranasal administration of unconjugated HRP. This is the first quantitative assessment of intraneuronal transport of a protein into the brain using the olfactory route.

Administration, Intranasal↗
PubMed1992

Guanosine metabolism in adult rat cardiac myocytes: inhibition by acyclovir and analysis of a metabolic pathway.

The metabolic fate of transported guanosine was examined in adult rat cardiac myocytes. Freshly isolated cells were incubated with 50 microM 8-[3H]-guanosine and the purine nucleoside phosphorylase (PNP) inhibitor acyclovir, and the nucleotide products extracted and examined for radiolabel distribution. Acyclovir inhibited guanosine incorporation into the 5'-nucleotide pool up to 66%. The drug did not inhibit guanosine transport. Other experiments using 5'-[3H]-guanosine and 8-[14C]-guanosine in concert as metabolic tracers showed both tritium and radiocarbon in the guanine nucleotide products. We concluded from this study that both a kinase (probably adenosine kinase) and the enzyme pair purine nucleoside phosphorylase/hypoxanthine-guanine phosphoribosyltransferase are responsible for guanosine salvage in heart cells.

Acyclovir↗
PubMed1984

High efficiency capillary column-gas chromatography mass spectrometry: analysis of the lipoxygenase pathway in eukaryot cells.

Lipoxygenases are ubiquitous enzymes able to oxygenate polyunsaturated fatty acids. This metabolic pathway leads to hydroperoxides, hydroxyepoxyene compounds and leukotrienes. Using high performance gas chromatography prior to mass spectrometry, we studied the activity of the lipoxygenases from mouse peritoneal macrophages. Further studies on mechanism of biosynthesis of hydroxyepoxyene compounds were successfully carried out using 18O2 labelled precursors.

Animals↗
PubMed1991

The effect of griseofulvin on the heme pathway--II. An exhaustive analysis during short and long-term challenge.

1. A clear biphasic response of the enzyme activities as a function of intoxication time due to the topical cutaneous griseofulvin treatment was observed. 2. The initial acute induction of ALA-S activity would be due to depletion of free heme in the regulatory pool caused by cytochrome P 450 destruction. 3. The second induction peak, would be due to less heme formation, secondary to the ferrochelatase inhibition, as expected for the erythropoietic protoporphyria model. 4. The biphasic response of hepatic ALA-D and PBGase activities would be related to ALA-S activity changes and the subsequent augmented available substrates. 5. Endogenous liver porphyrin distribution in cytosolic, mitochondrial and nuclear fractions was investigated. 6. The in vitro biosynthesis of porphyrins confirmed both the biphasic model and the hepatic porphyrins subcellular distribution. 7. Two mechanisms to explain the action of griseofulvin at shorter and longer times of intoxication are proposed.

5-Aminolevulinate Synthetase↗
PubMed1982

A 14C-2-deoxyglucose analysis of the neural pathways of the limbic forebrain in the rat: II. The hypothalamus.

An attempt was made to characterize the nature of the functional organization of the hypothalamus by observing the patterns of uptake of 14C-2-deoxyglucose (2DG) following electrical stimulation of different regions within the preoptico-hypothalamus in the rat. The experimental paradigm consisted of electrical brain stimulation delivered continuously for periods of 30 sec on and 30 sec off for 45 minutes following injection of 2DG. Brains were removed and processed for autoradiography. Activation of the medial forebrain bundle was noted following stimulation of the nucleus accumbens and lateral preoptico-hypothalamus. Activated fibers could be followed only in a caudal direction through the medial forebrain bundle and into the ventral tegmental area as a result of nucleus accumbens stimulation. Stimulation of the lateral preoptic region or of the anterior half of lateral hypothalamus produced activation of the lateral septal nucleus, lateral habenular nucleus, perifornical region, midline thalamus and ventral tegmental area. Since stimulation of the perifornical hypothalamus significantly activated the rostro-caudal extent of the midbrain cental gray, it is suggested that impulses from the lateral hypothalamus reach the lower brainstem via its connections with the perifornical hypothalamus. Ventromedial hypothalamic stimulation activated only the lateral septal nucleus, cortico-medial amygdala and medial preoptico-hypothalamus, while medial preoptico-hypothalamic stimulation resulted in increased 2DG uptake in the midbrain central gray, thus suggesting that medial hypothalamic impulses reach the brainstem by first ascending to the level of the preoptico-hypothalamus. Mammillary body stimulation orthodromically activated fibers in the mammillothalamic and mammillotegmental tracts and antidromically fibers in the fornix for a short distance.

Amygdala↗
PubMed1993

Analysis of DNA repair pathways of Schizosaccharomyces pombe by means of swi-rad double mutants.

In Schizosaccharomyces pombe 11 different switching genes (swi1 to swi10 and rad22) are known which are involved in mating-type (MT) switching. Mutations in swi5, swi9, swi10 and rad22 also cause an increased radiation sensitivity. We tested whether the survival of these mutants after UV irradiation is influenced by caffeine. We included rad1 and rad13 mutants in our experiments which do not affect MT switching. Several double and triple mutants were constructed. We were able to assign the switching genes to different repair pathways: swi9 and swi10 are involved in excision repair, rad22 has a function in recombination repair, while swi5 appears to be involved in a hitherto unknown pathway. This 'swi5 pathway' is stimulated (!) by caffeine. Previously it was found that the swi5 mutation also reduces meiotic recombination. As to rad genes, we found a few inconsistencies with previous reports in the literature.

Alleles↗
PubMed2006

Quantitative proteomics analysis of the secretory pathway.

We report more than 1400 proteins of the secretory-pathway proteome and provide spatial information on the relative presence of each protein in the rough and smooth ER Golgi cisternae and Golgi-derived COPI vesicles. The data support a role for COPI vesicles in recycling and cisternal maturation, showing that Golgi-resident proteins are present at a higher concentration than secretory cargo. Of the 1400 proteins, 345 were identified as previously uncharacterized. Of these, 230 had their subcellular location deduced by proteomics. This study provides a comprehensive catalog of the ER and Golgi proteomes with insight into their identity and function.

Animals↗
PubMed2005

Extramammary Paget's disease: analysis of growth signal pathway from the human epidermal growth factor receptor 2 protein.

Paget's disease is a skin cancer characterized by characteristic (Paget) cells scattered in the epidermis. Although its prognosis is generally favorable with surgical resection, the clinical outcome turns unfavorable in cases with recurrence and metastasis. Therefore, establishment of effective therapeutic regimens is required for advanced Paget's disease. The human epidermal growth factor receptor 2 (HER2) protein, a transmembrane growth factor receptor, is frequently overexpressed in malignancies, causing activation of the phosphatidylinositol 3 kinase (PI3K) and extracellular signal-regulated kinase (ERK) signal pathways. Recently, HER2-targeting molecular therapy using trastuzumab (Herceptin; Genentech, Inc, South San Francisco, Calif) was revealed to be effective in advanced breast cancers overexpressing HER2 protein. Here, we analyzed the correlation between activation of the HER2 signal pathways and clinicopathologic parameters of 36 extramammary Paget's disease samples from 34 Japanese patients, using immunohistochemical analyses for HER2, phosphorylated HER2, phosphorylated AKT, and phosphorylated ERK proteins. We found overexpression of the HER2 protein in 19.4% (7) of the lesions, 3 of which showed HER2 amplification by chromogenic in situ hybridization. Phosphorylated HER2 protein was detected in 12 lesions (33.3%), including 2 of the 7 HER2-overexpressing lesions. Phosphorylated AKT was detected in approximately 75.0% (27/36) and phosphorylated ERK in 38.9% (14/36). Both HER2 and AKT were simultaneously phosphorylated in 9 cases (25.0%) and HER2 and ERK in 9 cases (25.0%), but all 3 molecules were phosphorylated in only 1 sample. Phosphorylated ERK correlated with the maximum diameter of the tumors (P < .025), but other immunohistochemical parameters failed to show any correlation with clinicopathologic features. These results suggest the contribution of the HER2 signaling pathway to the pathogenesis and progression of some cases of extramammary Paget's disease, for which clinical use of molecular target therapy against the HER2 pathway is warranted.

Aged↗
PubMed2006

Analysis of the endocytic pathway mediating the infectious entry of mosquito-borne flavivirus West Nile into Aedes albopictus mosquito (C6/36) cells.

The initial interaction between mosquito-borne flavivirus West Nile and mosquito cells is poorly characterized. This study analyzed the endocytic and the associated signaling pathway that mediate the infectious entry of West Nile virus (WNV) into mosquito cell line (C6/36). Pretreatment of C6/36 cells with pharmacological drugs that blocks clathrin-mediated endocytosis significantly inhibited virus entry. Furthermore, the transfection of functional blocking antibody against clathrin molecules and the overexpression of dominant-negative mutants of Eps15 in C6/36 cells caused a marked reduction in WNV internalization. WNV was shown to activate focal adhesion kinase (FAK) to facilitate the endocytosis of virus but not the mitogen-activated protein kinases (ERK1 and ERK2). Subsequent to the internalization of WNV, the virus particles are translocated along the endosomal pathway as revealed by double-immunofluorescence assays with anti-WNV envelope protein and cellular markers for early and late endosomes. Specific inhibitor for protein kinase C (PKC) was shown to be highly effective in blocking WNV entry by inhibiting endosomal sorting event. The disruption of the microtubule network using nocodazole also drastically affects the entry process of WNV but not the disruption of actin filaments by cytochalasin D. Finally, a low-pH-dependent step is required for WNV infection as revealed by the resistance of C6/36 cells to WNV infection in the presence of lysosomotropic agents.

Actin Cytoskeleton↗
PubMed1991

High-performance liquid chromatographic analysis of the unusual pathway of oxidation of L-arginine to citrulline and nitric oxide in mammalian cells.

A very unusual pathway of the oxidation of L-arginine to citrulline and nitric oxide has been discovered recently in cytotoxic macrophages. In an attempt to detect molecules generated through this metabolic pathway, a fast radio high-performance liquid chromatographic method was developed to analyse the whole set of radiolabelled L-arginine-derived metabolites produced by mammalian cells after appropriate induction. A new intermediate which might be NG-hydroxy-L-arginine was found.

Adenocarcinoma↗