Lowered seizure threshold as a part of the narcotic abstinence syndrome in rats.
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Biomedical subjects
Publications and source records attributed to C Lin.
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The quality of volume-localized magnetic resonance spectroscopy is affected by eddy currents caused by gradient switching. Eddy currents can be reduced with improved gradient systems; however, it has been suggested that the distortion due to eddy currents can be compensated for during postprocessing with a single-frequency reference signal. The authors propose modifying current techniques for acquiring the single-frequency reference signal by using relaxation weighting to reduce interference from components that cannot be eliminated by digital filtering alone. Additional sequences with T1 or T2 weighting for reference signal acquisition are shown to have the same eddy current characteristics as the original signal without relaxation weighting. The authors also studied a new eddy current correction method that does not require a single-frequency reference signal. This method uses two free induction decays (FIDs) collected from the same volume with two sequences with opposite gradients. Phase errors caused by eddy currents are opposite in these two FIDs and can be canceled completely by combining the FIDs. These methods were tested in a phantom. Eddy current distortions were corrected, allowing quantitative measurement of structures such as the -CH = CH- component, which is otherwise undetectable.
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A series of short AVP analogs with D- or L-arginine forming the C-terminal was synthesized, and their peripheral effects, i.e., vasoconstrictor and antidiuretic activities, and behavioral effects in enhancing retention in passive avoidance in rats were evaluated. We found that: 1) AVP(4-8) and its cysteinyl methyl ester were more potent in the behavioral response than its D-Arg homologs; 2) the methyl ester derivative was the most effective analog in this behavioral test among the peptides we synthesized, with a potency 40 times as high as AVP; 3) neither the D- nor the L-Arg short derivatives of AVP showed any peripheral effects up to a dose thousands of times greater than AVP. The results support the contention that arginine in the short analogs plays an important role in their behavioral response associated with a relatively steady peptide conformation.
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The chemical composition and microstructure of seven uroliths and four urinary sediment samples associated with the feeding of high-level cottonseed meal diet to buffalo calves were examined by chemical qualitative analyses, scanning electron microscopy (SEM), X-ray diffraction, and X-ray energy dispersive spectrometry (EDS). Struvite was a major component of kidney stones and of some bladder stones. The kidney stone sample appeared cracked under low power under SEM, aggregated into tiny balls under high power, and as a blade-like structure under even higher power. The bladder stone samples appeared finely granular or granular with various forms of prismatic crystals. The urinary sediments were prismatic crystals, with granules. The newly found prismatic crystals, which were rich in potassium and similar to struvite in crystal structure, were identified as potassium magnesium phosphate (KMgPO4.6H2O) in some bladder stones and urinary sediments. However, crystals which contained Mg and P only, which had been used for struvite identification, were not found by EDS examination in urinary sediments from fresh urine samples of buffalo calves fed the high-level cottonseed meal diet.
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Erythropoietin (Epo) autocrine stimulation has been implicated in erythroleukemia. To develop a model of Epo autocrine stimulation, we made transgenic mice using a construct that linked the human Epo gene to an erythroid-specific regulatory element, designated 5'HS-2, from the human beta-globin locus control region. We hypothesized that Epo gene expression would be targeted to erythroid cells in these mice, resulting in autocrine stimulation of erythroid progenitor cell growth in culture, and that chronic autocrine Epo stimulation would result in erythroleukemia. Transgenic mice containing intact copies of the 5'HS-2Epo construction had elevated hematocrits, reticulocyte counts and serum Epo levels and marked splenic enlargement. Analysis of RNA isolated from organs of transgenic mice revealed constitutive Epo mRNA expression primarily in spleen, blood and bone marrow. RNA samples from anemic transgenic mice revealed Epo gene induction only in the liver. Marrow derived from 5'HS-2Epo mice grew BFU-E in the absence of exogenous Epo. Despite observation of up to 2 years, no mouse developed erythroleukemia, demonstrating that Epo autocrine stimulation alone is insufficient for progression to malignancy. These studies show that 5'HS-2 can be used to target Epo gene expression to erythroid tissue. These mice could provide a model system for studying autocrine growth regulation.
In Snell (dw) and Jackson (dwJ) dwarf mice, mutations in the gene encoding Pit-1, a tissue-specific POU-domain transcription factor, lead to the absence of somatotroph, lactotroph and thyrotroph cells. Pre-somatotroph proliferation is stimulated by increased intracellular levels of cyclic AMP, normally induced by growth hormone releasing factor (GRF; refs 7-17). Here we report the cloning of mouse and rat complementary DNAs encoding a new member of the seven-transmembrane-helix, G-protein-coupled receptor family restricted to the pituitary gland, which mediates increases in intracellular cAMP and cAMP-dependent gene transcription in response to GRF. The receptor is expressed in a spatial and temporal pattern corresponding precisely to growth hormone gene expression, and neither is expressed in dw/dw mice. The pituitary hypoplasia in these mice thus appears to be due, at least in part, to the absence of GRF receptor, which is in turn due to the absence of functional Pit-1.
High-quality biomarkers for disease progression, drug efficacy and toxicity liability are essential for improving the efficiency of drug discovery and development. The identification of drug-activity biomarkers is often limited by access to and the quantity of target tissue. Peripheral blood has increasingly become an attractive alternative to tissue samples from organs as source for biomarker discovery, especially during early clinical studies. However, given the heterogeneous blood cell population, possible artifacts from ex vivo activations, and technical difficulties associated with overall performance of the assay, it is challenging to profile peripheral blood cells directly for biomarker discovery. In the present study, Applied BioSystems' blood collection system was evaluated for its ability to isolate RNA suitable for use on the Affymetrix microarray platform. Blood was collected in a TEMPUS tube and RNA extracted using an ABI-6100 semi-automated workstation. Using human and rat whole blood samples, it was demonstrated that the RNA isolated using this approach was stable, of high quality and was suitable for Affymetrix microarray applications. The microarray data were statistically analysed and compared with other blood protocols. Minimal haemoglobin interference with RNA labelling efficiency and chip hybridization was found using the TEMPUS tube and extraction method. The RNA quality, stability and ease of handling requirement make the TEMPUS tube protocol an attractive approach for expression profiling of whole blood to support target and biomarker discovery.
Histogenesis and mechanisms of catechol-induced rat glandular stomach carcinogenesis were investigated in male F344 rats. Groups of 5 or 6 rats were treated with dietary catechol at doses of 1, 0.5, 0.1, and 0.01% for 12 hr or for 1, 2, 3, or 7 days or at a dose of 0.8% for 1, 2, 4, 12, and 24 wk; rats were then euthanatized. The initial morphological changes were edema of the gastric wall, inflammatory-cell infiltration, erosion in the pyloric region close to the duodenum, and considerable increase in apoptosis at 12 hr; later, changes included augmented DNA synthesis and cell proliferation, as evaluated by bromodeoxyuridine labeling index and thickness of mucosa, respectively, on day 1. Downward hyperplasia due to excess regeneration appeared at edges of ulceration at week 2. This lesion disappeared, and then submucosal hyperplasia appeared in the course of adenoma development. Only slight expression of c-myc or c-fos was apparent after 30-min oral administration or 1-, 3-, and 6-hr oral administration of catechol. No increase in lipid peroxide levels was evident in gastric epithelium fed catechol for 1 wk. The amount of catechol distributed in the glandular stomach and forestomach epithelium, which is not a target for carcinogenesis, did not differ 1, 3, 6, and 24 hr after a single intragastric dose of 75 mg/kg body weight. Amounts of catechol bound to tissue protein were also not specifically high in the glandular stomach. These results indicate that regenerative cell proliferation due to toxicity plays an important role in catechol-induced glandular stomach carcinogenesis. Protein binding and free radicals may not be largely responsible for the toxicity.