Histologic comparison of small bowel, heart, and kidney xenografts in a rat to mouse model.
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Animals↗
Biomedical subjects
J Jiang
Publications and source records attributed to J Jiang.
Effects of head extension and tongue protrusion on voice perturbation measures.
Head extension with protruded tongue is the position for videolaryngoscopy and simultaneous glottographic recordings including photoglottographic signals. This study investigated the effect of head extension and tongue protrusion on the measures of fundamental frequency, frequency perturbation (jitter), and amplitude perturbation (shimmer). Acoustic signals recorded during sustained vowels were obtained from 49 women and 66 men with no speech or voice disorders in different head-tongue positions. Head extension was associated with increased fundamental frequency and decreased shimmer. In men, head extension did not appear to affect jitter. When the tongue was protruded, head extension tended to lower jitter. For both genders, tongue protrusion was associated with decreased fundamental frequency with head extension. In the men, tongue protrusion tended to increase shimmer when the head was in the neutral position. In the women, tongue protrusion was associated with increased jitter and increased shimmer and was most evident in the head-neutral position. These findings supported a physical linkage hypothesis of the relationship between vocal tract configuration and vocal fold vibration, suggesting that head-tongue position must be taken into account when comparing voice measures.
Adult↗
Effects of simulated source of tremor on acoustic and airflow voice measures.
To test the effects of different sources of tremor on the voice, tremor was simulated by external rhythmic perturbation of structures at the subglottal, glottal, and supraglottal levels in 10 healthy subjects. The acoustic and airflow signals simultaneously recorded during sustained phonation in the normal and the 3 simulated tremor conditions were analyzed and compared. Voice measures included: fundamental frequency, 2 short-term perturbation measures (jitter and shimmer), and 3 long-term tremor measures (prominence ratios of the spectral peaks of the acoustic frequency contour, acoustic amplitude contour, and airflow contour). Measures of fundamental frequency and percent shimmer were not significantly affected by the simulated tremors. Measures of percent jitter and the amplitudes of the long-term frequency and amplitude modulations were most prominently increased when respiratory drive was perturbed by simulated tremor. Spectral analysis of the acoustic amplitude contour was most useful in distinguishing the 3 sites of simulated tremor.
Adolescent↗
Endothelial dysfunction in atherosclerotic mice: improved relaxation by combined supplementation with L-arginine-tetrahydrobiopterin and enhanced vasoconstriction by endothelin.
1. Mice lacking the apolipoprotein E and low density lipoprotein receptor genes (E degrees xLDLR degrees ) develop atherosclerosis and endothelial dysfunction. The aim of this study was to characterize the roles of L-arginine and tetrahydrobiopterin (BH(4)) for endothelium-dependent relaxation and the changes in the vasoconstrictor response to endothelin-1 (ET-1) in thoracic aortic rings of E degrees xLDLR degrees mice. 2. Histological examination revealed severe atherosclerosis of the thoracic aorta of E degrees xLDLR degrees mice. Relaxations induced by acetylcholine (Ach), but not that to sodium nitroprusside, were significantly impaired in E degrees xLDLR degrees mice compared to control mice indicating attenuated endothelium-dependent relaxations. 3. Preincubation with the nitric oxide (NO) substrate L-arginine did not affect, whereas the co-factor for NO synthase, BH(4), slightly improved the relaxations induced by Ach. Combined preincubation with L-arginine and BH(4) induced a pronounced enhancement of Ach-induced relaxations in E degrees xLDLR degrees mice. The relaxations induced by Ach in E degrees xLDLR degrees mice in the presence of L-arginine and BH(4) were not different from those observed in control mice. 4. Preincubation with superoxide dismutase did not affect Ach-induced relaxations in aorta from E degrees xLDLR degrees mice. 5. The contractile response to ET-1 was enhanced in E degrees xLDLR degrees mouse aorta. The contractions were abolished by the ET(A) receptor antagonist LU 135252. The ET(B) receptor agonist sarafotoxin 6c did not induce contractions or relaxations. 6. It is concluded that endothelial dysfunction of E degrees xLDLR degrees mouse aorta is reversed by combined administration of L-arginine and BH(4). In addition, the ET(A) receptor-mediated vasoconstriction by ET-1 is enhanced in E degrees xLDLR degrees mice.
Acetylcholine↗
Fusagene vectors: a novel strategy for the expression of multiple genes from a single cistron.
Transduction of cells with multiple genes, allowing their stable and co-ordinated expression, is difficult with the available methodologies. A method has been developed for expression of multiple gene products, as fusion proteins, from a single cistron. The encoded proteins are post-synthetically cleaved and processed into each of their constituent proteins as individual, biologically active factors. Specifically, linkers encoding cleavage sites for the Golgi expressed endoprotease, furin, have been incorporated between in-frame cDNA sequences encoding different secreted or membrane bound proteins. With this strategy we have developed expression vectors encoding multiple proteins (IL-2 and B7.1, IL-4 and B7.1, IL-4 and IL-2, IL-12 p40 and p35, and IL-12 p40, p35 and IL-2 ). Transduction and analysis of over 100 individual clones, derived from murine and human tumour cell lines, demonstrate the efficient expression and biological activity of each of the encoded proteins. Fusagene vectors enable the co-ordinated expression of multiple gene products from a single, monocistronic, expression cassette.
Animals↗
Acoustic and airflow spectral analysis of voice tremor.
Acoustic spectral analysis has been used to describe voice tremor with some success, but no feature distinguishing pathological from normal tremor has been clearly identified. To assist in monitoring voice tremor associated with neurological diseases, objective and quantifiable measures that can distinguish between normal and pathological tremor are desired. This study explored the plausibility of using airflow and acoustic signals to quantify the frequency and amplitude of voice tremor and potentially to distinguish pathological from normal tremor. Subjects were 10 individuals with pathological tremor, most of them individuals with Parkinson's disease, and 10 gender and age-matched individuals with no voice disorder. Simultaneous acoustic and airflow signals were recorded during sustained vowel phonation. The acoustic intensity contours and the airflow signals were submitted to spectral analysis. A peak prominence ratio, defined as the ratio of the spectral peak energy to the overall signal energy, was calculated for each spectral peak below 30 Hz. For each subject, the 6 spectral peaks with the highest peak prominence ratios were selected. Frequency values of the 6 selected acoustic or airflow spectral peaks failed to distinguish tremor group from control group. Peak prominence ratios of the 6 selected acoustic spectral peaks were significantly higher for tremor group than for control group. Although spectral analysis of airflow signals was not useful in differentiating tremor group from control group, acoustic intensity contours and airflow time waveforms were highly and positively correlated in more tremor subjects (90%) than control subjects (40%). This finding suggests that the relationship between acoustic intensity contours and airflow time waveforms may reflect the presence and the source of voice tremor.
Adult↗
Correlation between glottal area and photoglottographic signal in normal subjects.
Photoglottography (PGG) is an established technique for depicting the vibratory patterns of the vocal folds. The present study investigates the correlation between the glottal area and the corresponding PGG signal. Six normal (five male, one female) subjects who did not use their voices professionally were investigated during constantly sustained phonation at spontaneous pitches. Laryngostroboscopy was performed in combination with PGG. The simultaneously recorded laryngostroboscopic images and PGG signals were directly digitized and stored on a computer. The correlation between the glottal area and the corresponding PGG amplitudes across each vibratory cycle of the vocal folds was calculated and they were found to be highly and positively correlated (r = 0.973, p < 0.001). The PGG signal reflects changes in the glottal area during the vibration cycle of the vocal folds. The proposed simultaneous laryngostroboscopic and PGG technique has proved to be useful for facilitating the interpretation of changes in glottal area.
Adult↗
Acrylonitrile-induced morphological transformation in Syrian hamster embryo cells.
Acrylonitrile (ACN) is a monomer used in the synthesis of rubber, fibers and plastics. Previous studies demonstrated that ACN induces brain neoplasms (predominately astrocytomas) in rats following chronic treatment. While the mechanisms of ACN-induced glial cell carcinogenicity have not been completely elucidated, investigations by our group and others have suggested a role for the induction of oxidative stress and the resultant oxidative damage in this process. In vitro cell transformation models are useful for detecting and studying the mechanisms of chemical carcinogenesis. Cell transformation by chemical carcinogens in Syrian hamster embryo (SHE) cells exhibits a multistage process similar to that observed in vivo, for both non-genotoxic and genotoxic carcinogens. In the present study, the ability of ACN to induce morphological transformation and oxidative damage was examined in SHE cells. ACN induced an increase in morphological transformation at doses of 50, 62.5 and 75 microg/ml (maximum sub-toxic dose tested) following 7 days of continuous treatment. SHE cells exposed to ACN for 24 h failed to increase morphological transformation. Morphological transformation by ACN was inhibited by co-treatment with the antioxidants alpha-tocopherol and (-)-epigallocathechin-3 gallate (EGCG) for 7 days. Treatment of SHE cells with 75 microg/ml ACN produced a significant increase in 8-hydroxy-2'-deoxyguanosine that was also inhibited by co-treatment with alpha-tocopherol or EGCG. These results support the proposal that oxidative stress and the resulting oxidative damage is involved in ACN-induced carcinogenicity.
8-Hydroxy-2'-Deoxyguanosine↗
Comparative fluorescence in situ hybridization mapping of a 431-kb Arabidopsis thaliana bacterial artificial chromosome contig reveals the role of chromosomal duplications in the expansion of the Brassica rapa genome.
Comparative genome studies are important contributors to our understanding of genome evolution. Most comparative genome studies in plants have been based on genetic mapping of homologous DNA loci in different genomes. Large-scale comparative physical mapping has been hindered by the lack of efficient and affordable techniques. We report here the adaptation of fluorescence in situ hybridization (FISH) techniques for comparative physical mapping between Arabidopsis thaliana and Brassica rapa. A set of six bacterial artificial chromosomes (BACs) representing a 431-kb contiguous region of chromosome 2 of A. thaliana was mapped on both chromosomes and DNA fibers of B. rapa. This DNA fragment has a single location in the A. thaliana genome, but hybridized to four to six B. rapa chromosomes, indicating multiple duplications in the B. rapa genome. The sizes of the fiber-FISH signals from the same BACs were not longer in B. rapa than those in A. thaliana, suggesting that this genomic region is duplicated but not expanded in the B. rapa genome. The comparative fiber-FISH mapping results support that chromosomal duplications, rather than regional expansion due to accumulation of repetitive sequences in the intergenic regions, played the major role in the evolution of the B. rapa genome.
Arabidopsis↗
AutoDep: a web-based system for deposition and validation of macromolecular structural -information.
This paper describes the design and full implementation of a new concept in data deposition and validation: AutoDep (copyright Brookhaven Science Associates LLC). AutoDep changes the traditional procedure for data acceptance and validation of the primary databases into an interactive depositor-driven operation which almost eliminates the delay between the acceptance of the data and its public release. The system takes full advantage of the knowledge and expertise of the experimenters, rather than relying on the database curators for the complete and accurate description of the structural experiment and its results. AutoDep, developed by the Protein Data Bank at Brookhaven National Laboratory (BNL) as a flexible and portable system, has already been adopted by other primary databases and implemented on different platforms/operating systems. AutoDep was introduced at BNL in 1996 [see Manning (1996), Protein Data Bank Quart. Newslett. 77, 2 (ftp://ftp.rcsb. org/pub/pdb/doc/newsletters/bnl/newsletter96jul/newslttr+ ++.txt); Manning (1996), Protein Data Bank Quart. Newslett. 78, 2 (ftp://ftp. rcsb.org/pub/pdb/doc/newsletters/bnl/newsletter96oct/+ ++newslttr.txt)].
Computer Security↗
Apotheosis, not apocalypse: methods in protein crystallography.
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Crystallography↗
Glottographic phase difference in recurrent nerve paralysis.
Phase measures with simultaneously recorded electroglottography (EGG) and photoglottography (PGG) signals have been studied in canine models and found to be sensitive to the effect of recurrent laryngeal nerve (RLN) paralysis on vocal fold vibration. This study examined the usefulness of this type of measure in clinical application. The combined glottographic signals were obtained from 5 men with a diagnosis of unilateral RLN paralysis and 5 age-matched controls. In the patient group, EGG waveforms were found to have a consistent phase delay in relation to PGG. A measure of the overall glottographic phase difference (GPD) was found to significantly distinguish the control group (mean GPD = 0.2371 ms) from the patient group (mean GPD = -0.2765 ms). A validity analysis performed on 19 subjects with or without unilateral RLN paralysis confirmed that the GPD test had a relatively high efficiency (91.7%) in detecting unilateral RLN paralysis in the male population.
Adult↗
Effects of dehydration on phonation in excised canine larynges.
The effects of exposure to dry air on phonation were measured in an ex vivo model of vocal fold vibration. Excised canine larynges were mounted on an apparatus and made to phonate at a constant subglottal pressure by means of unhumidified airflow. The phonation threshold pressure (PTP), glottal airflow, sound intensity of the acoustic output, and effects on vocal efficiency were also assessed. Student's t-test was performed on the results. In 17 larynges, the average PTP increased from 10.0 cm H2O to 15.0 cm H2O after exposure to dry airflow (p < .001). In addition, the average flow increased from 585 mL/s to 801 mL/s at a constant suprathreshold subglottal pressure (p < .001), and from 323 mL/s to 610 mL/s at the PTP (p < .001). The average acoustic output levels, measured during stable phonation segments, markedly decreased with exposure to the dry airflow, from 91.5 dB to 88.5 dB (p < .001). The average vocal efficiency decreased from 3.63 x 10(-4) to 7.00 x 10(-5) (p < .001). No such changes were seen in control larynges phonated with 100% humidified air used for driving the airflow. The results support previously reported modeling and experimental findings that dehydration of the vocal fold generally degrades laryngeal performance.
Animals↗
Role of esophageal pH recording in management of chronic laryngitis: an overview.
Chronic laryngitis typically produces symptoms of frequent throat-clearing, soreness, decreased voice quality with use, nonproductive cough, globus sensation, and odynophagia. The endoscopic laryngeal examination usually demonstrates posterior glottic edema, erythema, and increased vascularity and nodularity. There is increasing support for the hypothesis that reflux of acidic gastric contents is often responsible for the symptoms and findings of chronic laryngitis. Prospective trials of acid suppression therapy demonstrate not only efficacy in symptom reduction, but also objective improvement in measurements of voice quality and mucosal erythema. Although traditionally considered the "gold standard" for diagnosis of reflux causing laryngitis, routine esophageal pH recording may result in false negatives in up to 50% of patients. This may confound the diagnosis of chronic laryngitis and delay treatment. Conversely, a positive study during comprehensive therapy may help identify patients who need additional treatment. A single distal probe is probably insufficient for evaluation of a supraesophageal disorder. Current recommendations for double-probe pH study in the evaluation of chronic laryngitis fall into 2 categories: 1) a double-probe pH study is indicated if there is ongoing moderate-to-severe laryngitis despite antireflux precautions and proton pump inhibitor treatment for at least 6 to 12 weeks; and 2) a double-probe pH study is indicated as a baseline measurement before Nissen or Toupet fundoplication. The pH study would also be indicated in patients who have symptoms after fundoplication. There is clearly much more work to be done on the technical issues of obtaining accurate objective data related to laryngeal acidification. In addition, although acid reflux appears to be causative in many cases of chronic laryngitis, further work is indicated to identify reliable testing methods that will predict treatment success.
Acid-Base Equilibrium↗
Tumor necrosis factor-alpha converting enzyme (TACE) is a growth hormone binding protein (GHBP) sheddase: the metalloprotease TACE/ADAM-17 is critical for (PMA-induced) GH receptor proteolysis and GHBP generation.
The GH binding protein (GHBP), which exists in many vertebrates, is a circulating high affinity binding protein corresponding to the extracellular domain of the GH receptor (GHR). In humans, rabbits, and several other species, the GHBP is generated by proteolysis of the GHR and shedding of its extracellular domain. We previously showed that GHBP shedding is inducible by the phorbol ester phorbol 12-myristate,13-acetate (PMA) and inhibited by the metalloprotease inhibitor, Immunex Corp. Compound 3 (IC3). The metzincin metalloprotease, tumor necrosis factor-alpha (TNF-alpha)-converting enzyme (TACE), catalyzes the shedding of TNF-alpha from its transmembrane precursor, a process that is also inhibitable by IC3. TACE may hence be a candidate for GHBP sheddase. In this study, we reconstitute fibroblasts derived from a TACE knockout mouse (Null cells) with either the rabbit (rb) GHR alone (Null/R) or rbGHR plus murine TACE (Null/R+T). Although GHR in both cells was expressed at similar abundance, dimerized normally and caused JAK2 activation in response to GH independent of TACE expression, PMA was unable to generate GHBP from Null/R cells. In contrast, PMA caused ample GHBP generation from TACE reconstituted (Null/R + T) cells, and this GHBP shedding was substantially inhibited by IC3 pretreatment. Corresponding to the induced shedding of GHBP from Null/R + T cells, PMA treatment caused a significant loss of immunoblottable GHR in Null/R+T, but not in Null/R cells. We conclude that TACE is an enzyme required for PMA-induced GHBP shedding and that PMA-induced down-regulation of GHR abundance may in significant measure be attributable to TACE-mediated GHR proteolysis.
ADAM Proteins↗
Insulin receptor substrate-1-mediated enhancement of growth hormone-induced mitogen-activated protein kinase activation.
Interaction of GH with the cell-surface GH receptor (GHR) causes activation of the GHR-associated tyrosine kinase, JAK2, and consequent triggering of signaling cascades including the STAT, Ras/Raf/MEK1/MAP kinase, and insulin receptor substrate-1(IRS-1)/PI3kinase pathways. We previously showed that IRS- and GHR-deficient 32D cells that stably express the rabbit GHR and rat IRS-1 (32D-rbGHR-IRS-1) exhibited markedly enhanced GH-induced proliferation and MAP kinase (ERK1 and ERK2) activation compared with cells expressing only the GHR (32D-rbGHR). We now examine biochemical mechanism(s) by which IRS-1 augments GH-induced MAP kinase activation. Time-course experiments revealed a similarly transient (maximal at 15 min) GH-induced ERK1 and ERK2 activation in both 32D-rbGHR and 32D-rbGHR-IRS-1 cells, but, consistent with our prior findings, substantially greater activation was seen in the IRS-1-containing cells. In both cells, GH-induced MAP kinase activation was markedly blunted by the MEK1 inhibitor, PD98059, but not by the PKC inhibitor, GF109203X. Interestingly, pretreatment with the PI3K inhibitor, wortmannin (EC50 approximately 10 nM), significantly reduced GH-induced MAP kinase activation in both 32D-rbGHR and 32D-rbGHR-IRS-1 cells. This same pattern in both cells of IRS-1-dependent augmentation and IRS-1-independent wortmannin sensitivity was also observed for GH-induced activation of Akt and MEK1 (using state-specific antibody blotting for both), despite the lack of difference in GHR, JAK2, SHP-2, p85, Akt, Ras, Raf-1, MEK1, ERK1, or ERK2 abundance between the two cells. A different PI3K inhibitor, LY294002 (50 microM), substantially inhibited (roughly 72%) GH-induced MAP kinase activation in 32D-rbGHR-IRS-1 cells, but only marginally (and statistically insignificantly) inhibited GH-induced MAP kinase activation in 32D-rbGHR cells. Because GH-induced Akt activation was completely inhibited in both cells by the same concentration of LY294002, these findings indicate that the wortmannin sensitivity of both the IRS-1-independent and -dependent GH-induced MAP kinase activation may reflect the activity of another wortmannin-sensitive target(s) in addition to PI3K in mediation of GH-induced MAP kinase activation in these cells. Notably, GH-induced STAT5 tyrosine phosphorylation, unlike Akt or MAPK activation, did not differ between the cells. Finally, while GH promoted accumulation of activated Ras in both cells, both basal and GH-induced activated Ras levels were greater in cells expressing IRS-1 than in 32D-rbGHR cells. These data indicate that while GH induces tyrosine phosphorylation of STAT5 and activation of the Ras/Raf/MEK1/MAPK and PI3K pathways, IRS-1 expression augments the latter two more than the former.
Androstadienes↗
Effect of long-term mild hypothermia therapy in patients with severe traumatic brain injury: 1-year follow-up review of 87 cases.
OBJECT: The goal of this study was to investigate the protective effects of long-term (3-14 days) mild hypothermia therapy (33-35 degrees C) on outcome in 87 patients with severe traumatic brain injury (TBI) (Glasgow Coma Scale score < or = 8). METHODS: In 43 patients assigned to a mild hypothermia group, body temperatures were cooled to 33 to 35 degrees C a mean of 15 hours after injury and kept at 33 to 35 degrees C for 3 to 14 days. Rewarming commenced when the individual patient's intracranial pressure (ICP) returned to the normal level. Body temperatures in 44 patients assigned to a normothermia group were maintained at 37 to 38 degrees C. Each patient's outcome was evaluated 1 year later by using the Glasgow Outcome Scale. One year after TBI, the mortality rate was 25.58% (11 of 43 patients) and the rate of favorable outcome (good recovery or moderate disability) was 46.51% (20 of 43 patients) in the mild hypothermia group. In the normothermia group, the mortality rate was 45.45% (20 of 44 patients) and the rate of favorable outcome was 27.27% (12 of 44 patients) (p < 0.05). Induced mild hypothermia also markedly reduced ICP (p < 0.01) and inhibited hyperglycemia (p < 0.05). The rates of complication were not significantly different between the two groups. CONCLUSIONS: The data produced by this study demonstrate that long-term mild hypothermia therapy significantly improves outcomes in patients with severe TBI.
Adult↗
Construction of a bacterial artificial chromosome (BAC) library for potato molecular cytogenetics research.
Lack of reliable techniques for chromosome identification is the major obstacle for cytogenetics research in plant species with large numbers of small chromosomes. To promote molecular cytogenetics research of potato (Solanum tuberosum, 2n = 4x = 48) we developed a bacterial artificial chromosome (BAC) library of a diploid potato species S. bulbocastanum. The library consists of 23,808 clones with an average insert size of 155 kb, and represents approximately 3.7 equivalents to the potato genome. The majority of the clones in the BAC library generated distinct signals on specific potato chromosomes using fluorescence in situ hybridization (FISH). The hybridization signals provide excellent cytological markers to tag individual potato chromosomes. We also demonstrated that the BAC clones can be mapped to specific positions on meiotic pachytene chromosomes. The excellent resolution of pachytene FISH can be used to construct a physical map of potato by mapping molecular marker-targeted BAC clones on pachytene chromosomes.
Chromosome Mapping↗