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Biomedical subjects

T Jiang

Publications and source records attributed to T Jiang.

At least 73 records · Page 4Linked to original sources

Identification of neural circuits by imaging coherent electrical activity with FRET-based dyes.

We show that neurons that underlie rhythmic patterns of electrical output may be identified by optical imaging and frequency-domain analysis. Our contrast agent is a two-component dye system in which changes in membrane potential modulate the relative emission between a pair of fluorophores. We demonstrate our methods with the circuit responsible for fictive swimming in the isolated leech nerve cord. The output of a motor neuron provides a reference signal for the phase-sensitive detection of changes in fluorescence from individual neurons in a ganglion. We identify known and possibly novel neurons that participate in the swim rhythm and determine their phases within a cycle. A variant of this approach is used to identify the postsynaptic followers of intracellularly stimulated neurons.

Animals↗

An algorithmic approach to multiple complete digest mapping.

Multiple Complete Digest (MCD) mapping is a method of determining the locations of restriction sites along a target DNA molecule. The resulting restriction map has many potential applications in DNA sequencing and genetics. In this work, we present a heuristic algorithm for fragment identification, a key step in the process of constructing an MCD map. Given measurements of the restriction fragment sizes from one or more complete digestions of each clone in a clone library covering the molecule to be mapped, the algorithm identifies groups of restriction fragments on different clones that correspond to the same region of the target DNA. Once these groups are correctly determined the desired map can be constructed by solving a system of simple linear inequalities. We demonstrate the effectiveness of our algorithm on real data provided by the Genome Center at the University of Washington.

Algorithms↗

[Lateral approaches for treatment of petroclival region tumor].

OBJECTIVE: To summarize the operation experience of resecting petroclival region tumors by lateral approaches. METHODS: (1) Ameliorate pterion approach; (2) temporal-occipital transtentorial-transpetrous approach; (3) transpetrous combined with supratentorial and infratentorial presigmoid approach; (4) far lateral transcondylar approach were applied for 61 patients with petroclival region tumor. RESULTS: Of the 61 tumors studied, 54 were completely resected, 6 were nearly complete and 1 was subtotally resected. No patient died in this group, 37 patients were followed up, and all showed satisfying results. 45% of the patients had CNs deficit, with III, VI, V, VIII, IX, X, XII nerve deficits most commonly seen. CONCLUSION: Lateral approaches are recommended for total resection of petroclival region tumors. HoVDever the operative techniques are complex and potential risks of morbidity exist.

Adolescent↗

[Transpetrosal presigmoid approach for removal of giant petroclival tumors].

OBJECTIVE: To discuss the operative technique, advantage and postoperative complications in 41 patients with giant petroclival tumors treated with the supra- and infratentorial transpetrousal presigmoid approach. METHODS: Clinical data were obtained from the review of charts and radiographic images of the 41 patients after operation with temporo-occipotal free osseous flap, partial petrosectomy and mastoidectomy were performed around the labyrinth. The semicircular canals, cochlea and tympanic cavity were protected during the operation. After the super petrous was ligated and cut off, the petroclival region in front of the sigmoid sinus was exposed. RESULTS: In the 41 patients 20 had meningiomas, 20 epidermoid cysts, and one schwannoma. Total resection was performed in 34 patients, subtotal resection in 16, and greater partial resection in one. Major postoperative complications included temporal aphasia (10 patients), cerebral edema (6), brain stem infarct (2), IIIth, VIIth, VIth and posterial group cranial nerves palsies (16, 16, 8, 6 respectively), and cerebrospinal fluid leakage (4 cases). CONCLUSIONS: This approach can expose sufficiently the petroclival region. It can also reveal the area of adjacent sella, interpeduncular and formen magnum, and homolateral III-XIIth cranial nerves. The postoperative complications may be related to operative techniues and tumorous characteristics.

Adolescent↗

Membrane-permeant esters of phosphatidylinositol 3,4,5-trisphosphate.

Phosphoinositide 3-OH kinases and their products, D-3 phosphorylated phosphoinositides, are increasingly recognized as crucial elements in many signaling cascades. A reliable means to introduce these lipids into intact cells would be of great value for showing the physiological roles of this pathway and for testing the specificity of pharmacological inhibitors of the kinases. We have stereospecifically synthesized di-C8-PIP3/AM and di-C12-PIP3/AM, the heptakis(acetoxymethyl) esters of dioctanoyl- and dilauroylphosphatidylinositol 3,4,5-trisphosphate, in 14 steps from myo-inositol. The ability of these uncharged lipophilic derivatives to deliver phosphatidylinositol 3,4,5-trisphosphate across cell membranes was demonstrated on 3T3-L1 adipocytes and T84 colon carcinoma monolayers. Insulin stimulation of hexose uptake into adipocytes was inhibited by the kinase inhibitor wortmannin and was largely restored by di-C8-PIP3/AM, which had no effect in the absence of insulin. Thus phosphatidylinositol 3,4,5-trisphosphate or a metabolite was necessary but not sufficient for stimulation of hexose transport. In T84 epithelial monolayers, di-C12-PIP3/AM mimicked epidermal growth factor in inhibiting chloride secretion and potassium efflux, suggesting that phosphatidylinositol 3,4, 5-trisphosphate was sufficient to modulate these fluxes and mediate epidermal growth factor's action.

3T3 Cells↗

Differential regulation of astrocytic mRNAs in the rat striatum after lesions of the cortex or substantia nigra.

This study evaluates the time course of expression of three astrocytic mRNAs, glial fibrillary acidic protein (GFAP), apolipoprotein E (ApoE), and clusterin, in the rat striatum (ST) following a unilateral lesion of either the cortex (CX) or the substantia nigra (SN), using Northern blot and in situ hybridization analyses. We found that while there was a time-dependent increase in astrocytic GFAP mRNA in the deafferented ST following both the CX and the SN lesions, the time course of the response was different between the two lesion paradigms. Specifically, the increase in GFAP mRNA in striatal astrocytes after the SN lesion was rapid and transient returning to control levels by 10 days postlesion, while the response was long lasting and remained increased until at least 27 days after the CX lesion. In addition, the mRNA response for both ApoE and clusterin was differentially regulated in response to the two lesions. Specifically, both clusterin and ApoE mRNAs were rapidly increased in the ST following the CX lesion while both mRNAs remained unchanged following the SN lesion. Data from this study extend information derived from previous investigations on the multifunctional role of astrocytes in the response to brain injury. Specifically, our data support the notion that while the time course of the GFAP response in striatal astrocytes may vary between lesion paradigms, the upregulation of GFAP is part of a generalized response of reactive astrocytes to diverse brain injuries. By comparison, upregulation of the mRNAs for the lipoproteins clusterin and ApoE are lesion specific and may play a role in the transport of recycled myelin lipids from dying axons to actively growing axons and dendrites in reactive synaptogenesis.

Animals↗

The thrombin receptor elevates intracellular calcium in adult rat ventricular myocytes.

While there is evidence that thrombin receptor activation leads to contractile dysfunction and induces arrhythmias in ischemic/reperfused cardiac tissue, thrombin is variably reported to modulate intracellular calcium in cardiomyocytes. The present study demonstrates that thrombin receptor activation leads to a rise in intracellular calcium in adult ventricular myocytes and serves to reconcile previous discrepant findings. The thrombin receptor-derived agonist peptide (SFLLRN, a portion of the tethered ligand created by thrombin's proteolytic actions) increases cytosolic calcium and twitch amplitude in cardiomyocytes isolated from adult ventricles. The truncated control peptide FLLRN has no effect, establishing that the response to SFLLRN results from a specific agonist peptide-receptor interaction. However, the response to SFLLRN occurs only at high agonist peptide concentrations and thrombin itself is inactive. This result is not compatible with an action of SFLLRN at a distinct protease-activated receptor (PAR-2; which is activated by SFLLRN, but not by thrombin), since SLIGRL (a ligand which is selective for PAR-2, but not the thrombin receptor) has no effect. Rather, the enzyme-based cell isolation procedure may partially cleave the thrombin receptor and influence cell responses, since concentrations of SFLLRN which are sub-threshold in enzymatically disaggregated myocytes significantly increase the force of isometric contraction of intact rat papillary muscles. These studies provide the first evidence that thrombin receptor activation leads to a change in intracellular calcium and a positive inotropic response in adult ventricular myocardium.

Animals↗

[Correlation study of high-resolution CT with pathologic finding of solitary small lung nodules].

OBJECTIVE: To correlate high resolution CT(HRCT) with pathologic findings and to evaluate the capability of HRCT versus conventional CT(CCT) to provide informations for accurate diagnosis of solitary small lung nodules. METHODS: Seventy-three cases (75 nodules) of solitary lesions in the lung less than 3 cm in diameter were examined with HRCT (64 cases had CCT) before surgery and correlated with histo-pathologic findings. RESULTS: In the 37 proven carcinoma, on HRCT, the lesions were round and oval in shape (34), deeply lobulated(28), with serrated margin(33), thin spiculation(37), air alveologram(19), and air bronchogram (10). Histologically, the tumor showed irregular growth pattern with interstitial fibrous proliferation and intra-tumoral residual air-containing spaces in alveoli and bronchioles. Intratumoral fat or calcification, satellate lesions, thick or long spicules, moderate or marked pleural adhesions, scallop-shaped contour were the common findings of benign lesions. HRCT was significantly superior to CCT in the assessment of the intra-structure, contour and margin of the lesion. CONCLUSION: HRCT is recommended routinely for the evaluation of solitary small pulmonary nodules.

Adenocarcinoma↗

[Microsurgical anatomy of far-lateral transcondylar approach].

OBJECTIVE: To supply the far-lateral transcondylar approach with some basic microsurgical anatomy and to protect vital structure. METHOD: We examined 10 cadveric adult heads and 10 dry skulls. RESULTS: Mastoid process, jugular fossa, and occipital condyle were important signs. Inferior occipital triangle was formed by muscle rectus capitis posterior major, muscle oblique capitis superior, and muscle oblique capitus inferior, the important mark for distinguishing vertebral artery. Abdundant venous plexus around vertebral artery was the important bleeding source during operation. CONCLUSION: The aforementioned anatomic landmarks assist in localization, protection of vital structures.

Adult↗

D-myo-Inositol 1,4,5,6-tetrakisphosphate produced in human intestinal epithelial cells in response to Salmonella invasion inhibits phosphoinositide 3-kinase signaling pathways.

Several inositol-containing compounds play key roles in receptor-mediated cell signaling events. Here, we describe a function for a specific inositol polyphosphate, D-myo-inositol 1,4,5,6-tetrakisphosphate [Ins(1,4,5,6)P4], that is produced acutely in response to a receptor-independent process. Thus, infection of intestinal epithelial cells with the enteric pathogen Salmonella, but not with other invasive bacteria, induced a multifold increase in Ins(1,4,5,6)P4 levels. To define a specific function of Ins(1,4,5,6)P4, a membrane-permeant, hydrolyzable ester was used to deliver it to the intracellular compartment, where it antagonized epidermal growth factor (EGF)-induced inhibition of calcium-mediated chloride (Cl-) secretion (CaMCS) in intestinal epithelia. This EGF function is likely mediated through a phosphoinositide 3-kinase (PtdIns3K)-dependent mechanism because the EGF effects are abolished by wortmannin, and three different membrane-permeant esters of the PtdIns3K product phosphatidylinositol 3,4,5-trisphosphate mimicked the EGF effect on CaMCS. We further demonstrate that Ins(1,4,5,6)P4 antagonized EGF signaling downstream of PtdIns3K because Ins(1,4,5, 6)P4 interfered with the PtdInsP3 effect on CaMCS without affecting PtdIns3K activity. Thus, elevation of Ins(1,4,5,6)P4 in Salmonella-infected epithelia may promote Cl- flux by antagonizing EGF inhibition mediated through PtdIns3K and PtdInsP3.

Epidermal Growth Factor↗

Upregulation of stathmin (p19) gene expression in adult rat brain during injury-induced synapse formation.

Stathmin (p19) is developmentally regulated as a neural-enriched phosphoprotein associated with neurite outgrowth and synaptic formation during cell proliferation and differentiation, and remains highly abundant in adult rat brain. Whether stathmin is involved in injury-induced reactive synaptogenesis in adult rat was examined in this study. Following unilateral cortical lesion, a significant increase in stathmin mRNA expression was found in the cells of contralateral homotypic cortex and in the subventricular zone of the lateral ventricle. This increase coincided in time with the corticostriatal axon sprouting and synaptic remodeling previously found in denervated striatum. Our data suggest that stathmin plays an important role in regulation of reactive synaptogenesis in adult brain.

Animals↗

Expression of protein kinase C beta in the heart causes hypertrophy in adult mice and sudden death in neonates.

Protein kinase C (PKC) activation in the heart has been linked to a hypertrophic phenotype and to processes that influence contractile function. To establish whether PKC activation is sufficient to induce an abnormal phenotype, PKCbeta was conditionally expressed in cardiomyocytes of transgenic mice. Transgene expression in adults caused mild and progressive ventricular hypertrophy associated with impaired diastolic relaxation, whereas expression in newborns caused sudden death associated with marked abnormalities in the regulation of intracellular calcium. Thus, the PKC signaling pathway in cardiocytes has different effects depending on the timing of expression and, in the adult, is sufficient to induce pathologic hypertrophy.

Age Factors↗

Functional consequences of acute collagen degradation studied in crystalloid perfused rat hearts.

OBJECTIVES: The impact of acute collagen disruption by the disulfide donor, 5,5'-dithio-2-nitrobenzoic acid (DTNB) on ventricular properties was tested in rat hearts. METHODS: Collagen was degraded acutely in 13 isolated, isovolumically contracting rat hearts by perfusion with 1 mM DTNB added to Krebs-Henseleit solution for 1 hour followed by 2-hour perfusion with normal solution. Another 13 hearts were perfused with normal solution for 3 hours (Control). RESULTS: Collagen content was 3.5 +/- 0.5% of ventricular dry weight in control group compared with 2.1 +/- 0.4% in DTNB group (decrease by 40%, p < 0.01). Scanning electron micrographs revealed loss of the delicate collagen network surrounding muscle fibers in DTNB treated hearts. Developed pressure at a fixed volume decreased to 86 +/- 17% of the baseline value after 3-hour perfusion in the control group, whereas in DTNB treated hearts developed pressure fell to 68 +/- 13% (p < 0.01). End-diastolic pressure was set at 5 mmHg at the beginning of the experiment and rose to 15 +/- 8 mmHg in control and 30 +/- 13 mmHg (p < 0.01) in the treated hearts. Concomitantly, wet-to-dry weight ratio increased from 5.63 +/- 0.26 in control to 6.07 +/- 0.11 (p < 0.05) in the DTNB treated hearts. A separate set of experiments on isolated myocytes excluded the possibility of a direct effect of DTNB on myocyte contractile function. CONCLUSIONS: These data suggested that with 40% collagen disruption by DTNB there is a significant increase in tissue edema that results in a decrease in chamber capacitance; in addition, there is a significant decrease in systolic performance which reflects the combined effect of edema and loss of collagen.

Animals↗

Facial and autonomic responses to biological and artificial olfactory stimuli in human neonates: re-examining early hedonic discrimination of odors.

Responses of awake and asleep 3-day-old human neonates were recorded to the presentation of artificial (vanillin, butyric acid, formula milks) and biological (breast milk, amniotic fluid) odorants matched on subjective intensity and trigeminal dimensions. The responses included behavioral (facial and oral movements) and autonomic (respiration, differential skin temperature) measures. The neonates reacted with significant facial and respiratory changes to low concentrations of olfactory stimuli during the various behavioral states. The analysis of olfacto-facial configurations revealed that behavioral markers of disgust (nose wrinkling, upper lip raising) discriminated between some odors judged as being pleasant and unpleasant by adult raters (vanillin vs. butyric acid). However, although some early predisposition to process the affective significance of stimuli may be suggested, no convincing evidence was obtained that neonates discriminated the hedonic valence of odors within the same perceptual space as adults. Finally, neonates evinced a differential pattern of respiratory responding to the presentation of milk odors according to the mode of feeding (breast vs. bottle feeding), suggesting that early olfactory discrimination may be mediated by stimuli with high ecological salience.

Autonomic Nervous System↗

Synergies and coincidence requirements between NO, cGMP, and Ca2+ in the induction of cerebellar long-term depression.

Parallel fiber synapses onto Purkinje neurons in acute cerebellar slices undergo long-term depression (LTD) when presynaptic activity coincides with postsynaptic depolarization. These electrical inputs can be respectively replaced by nitric oxide (NO) and Ca2+ photolytically released inside the Purkinje neuron, showing that these two messengers are sufficient for LTD induction. NO acts via cGMP production because inhibitors of guanylate cyclase prevent LTD but can be circumvented by photoreleased cGMP combined with Ca2+ elevation. Three inhibitors of cGMP-dependent protein kinase, Rp-8Br-PET-cGMPS, KT5823, and a novel pseudosubstrate peptide, all block LTD. LTD induction permits <10 ms gap between NO release and Ca2+ elevation, whereas 200-300 ms is allowed between uncaged cGMP and Ca2+ increase. This surprising difference in timing precision can be explained either by tighter localization and faster decay of cGMP when generated by NO rather than uncaging, or by two independent coincidence detectors in series.

Animals↗

Modification of colonic fermentation by bifidobacteria and pH in vitro. Impact on lactose metabolism, short-chain fatty acid, and lactate production.

Colonic fermentation plays an important role in the prevention of lactose intolerance and intestinal disorders. The objectives of this study were to evaluate whether supplementation with bifidobacteria modify colonic fermentation of lactose and short-chain fatty acid production and to assess influence of the pH in an in vitro continuous culture system. There was a significantly greater reduction in lactose concentrations at pH 6.7 than that at either pH 6.2 or pH 5.7, accompanied by the highest beta-galactosidase activity and D-lactate production. Bifidus supplementation reduced lactose and D-lactate concentrations and increased acetate production at pH 6.7. The study demonstrates that lactose is rapidly metabolized by colonic bacteria and lactose fermentation in vitro is pH dependent with a maximum rate at pH 6.7. Bifidobacteria supplementation may have the potential to improve lactose fermentation and to manipulate SCFA and lactate production.

Adult↗