Biomedical subjects

B Tian

Publications and source records attributed to B Tian.

At least 19 recordsLinked to original sources

PubMed1999

A PET study of human auditory spatial processing.

To learn more about human auditory spatial processing, we used positron emission tomography (PET) to measure regional cerebral blood flow in human volunteers engaged in sound localization tasks. Spectral and binaural cues of localized sound were reproduced by a sound system and delivered via headphones. During localization tasks, subjects activated inferior parietal lobules (IPL) bilaterally. In a second experiment, matched in design to the first, subjects made non-spatial auditory discriminations based on frequency, activating the IPL bilaterally with left hemispheric predominance. A between-study comparison revealed that the right IPL was significantly more activated during the sound localization task compared with the feature discrimination task, suggesting a preferential role for the right IPL in auditory spatial processing.

Adult↗

PubMed1999

Tumor necrosis factor alpha stimulates lipolysis in adipocytes by decreasing Gi protein concentrations.

Prolonged treatment (12-24 h) of adipocytes with tumor necrosis factor alpha (TNFalpha) stimulates lipolysis. We have investigated the hypothesis that TNFalpha stimulates lipolysis by blocking the action of endogenous adenosine. Adipocytes were incubated for 48 h with TNFalpha, and lipolysis was measured in the absence or presence of adenosine deaminase. Without adenosine deaminase, the rate of glycerol release was 2-3-fold higher in the TNFalpha-treated cells, but with adenosine deaminase lipolysis increased in the controls to approximately that in the TNFalpha-treated cells. This suggests that TNFalpha blocks adenosine release or prevents its antilipolytic effect. Both N6-phenylisopropyl adenosine and nicotinic acid were less potent and efficacious inhibitors of lipolysis in treated cells. A decrease in the concentration of alpha-subunits of all three Gi subtypes was detected by Western blotting without a change in Gs proteins or beta-subunits. Gi2alpha was about 50% of control, whereas Gi1alpha and Gi3alpha were about 20 and 40% of control values, respectively. The time course of Gi down-regulation correlated with the stimulation of lipolysis. Furthermore, down-regulation of Gi by an alternative approach (prolonged incubation with N6-phenylisopropyl adenosine) stimulated lipolysis. These findings indicate that TNFalpha stimulates lipolysis by blunting endogenous inhibition of lipolysis. The mechanism appears to be a Gi protein down-regulation.

Adipocytes↗

PubMed1999

Combined effects of H-7 and cytochalasin B on outflow facility in monkeys.

The serine-threonine protein kinase inhibitor H-7 and the fungal metabolite cytochalasin B (CB) disrupt the actin microfilament network by different mechanisms, and increase outflow facility similarly in live monkeys. Their combined effect has therefore determined on total outflow facility in cynomolgus monkeys by 2-level constant pressure perfusion. (1) After unilateral anterior chamber (AC) bolus injection of H-7 [10 micrometers, 100 micrometers (subthreshold for increasing facility when given alone) or 500 micrometers (just-threshold)] followed by bilateral AC bolus injection of CB [2 micrograms (strong but submaximal for increasing facility when given alone)], no significant difference between eyes was observed. (2) After bilateral AC exchange with a subthreshold dose of H-7 (10 micrometers) followed by unilateral AC bolus injection of a subthreshold dose of CB (0.02, 0.05, 0.1 or 0.5 microgram), 10 micrometers H-7 plus 0.1 or 0.5 microgram CB increased facility by approximately 40 or 80% compared to 10 micrometers H-7 alone. (3) After bilateral AC exchange with a maximal dose of H-7 (300 micrometers), followed by unilateral AC bolus injection of a subthreshold dose of CB (0.1 or 0.5 microgram), 300 micrometers H-7 plus 0.5 microgram CB increased outflow facility by 47% compared to 300 micrometers H-7 alone. (4) After unilateral AC exchange with a maximal dose of H-7 (300 micrometers) followed by bilateral AC bolus injection of a near-maximal dose of CB (2 micrograms), 300 micrometers H-7 plus 2 micrograms CB increased the facility by 67% compared to 2 micrograms CB alone. The significant effect of combined subthreshold doses of H-7 and CB on outflow facility, the potentiation of the facility-increasing effect of a maximal H-7 dose by both subthreshold and near-maximal CB doses, and the known cytoskeletal effects of both compounds, may suggest that both increase facility by disrupting actin filaments in the trabecular meshwork.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

PubMed1999

Localization of changes in beta-actin expression in remodeled canine myocardium.

Beta-actin is a cytoskeletal protein that has been implicated as a potentially important mediator of the growth, signaling, migration, and remodeling of cells. Beta-actin is upregulated in remodeling myocardium in response to either pressure or volume overload. The cellular localization of this response has, however, not been determined and is a necessary first step to begin to clarify the role of beta-actin in myocardial remodeling. Here we demonstrate that beta -actin protein was confined primarily to the cardiac interstitium using immunofluorescent and immunohistochemical staining. Furthermore, both staining and immunoblotting showed markedly increased beta-actin protein in myocardium within 24 h of either regional left ventricular damage or chronic volume overload. More importantly, this increase persisted up to 90 days in both models. Double staining showed co-localization of beta-actin protein and von Willebrand factor, a specific endothelial cell marker. These results suggest that increased beta-actin expression predominantly localized in cardiac interstitial cells, including endothelial cells. The increased beta-actin could be due to either proliferation of the interstitial cells or upregulation of the beta-actin gene.

Actins↗

PubMed1999

Modality-specific frontal and parietal areas for auditory and visual spatial localization in humans.

Although the importance of the posterior parietal and prefrontal regions in spatial localization of visual stimuli is well established, their role in auditory space perception is less clear. Using positron emission tomography (PET) during auditory and visual spatial localization in the same subjects, modality-specific areas were identified in the superior parietal lobule, middle temporal and lateral prefrontal cortices. These findings suggest that, similar to the visual system, the hierarchical organization of the auditory system extends beyond the temporal lobe to include areas in the posterior parietal and prefrontal regions specialized in auditory spatial processing. Our results may explain the dissociation of visual and auditory spatial localization deficits following lesions involving these regions.

Adult↗

PubMed1999

Latrunculin-A causes mydriasis and cycloplegia in the cynomolgus monkey.

PURPOSE: To determine the effect of latrunculin (LAT)-A, which binds to G-actin and disassembles actin filaments, on the pupil, accommodation, and isolated ciliary muscle (CM) contraction in monkeys. METHODS: Pupil diameter (vernier calipers) and refraction (coincidence refractometry) were measured every 15 minutes from 0.75 to 3.5 hours after topical LAT-A 42 microg (approximately 10 microM in the anterior chamber [AC]). Refraction was measured every 5 minutes from 0.5 to 1.5 hours after intracameral injection of 10 microl of 50 microM LAT-A (approximately 5 microM in AC), with intramuscular infusion of 1.5 mg/kg pilocarpine HCl (PILO) during the first 15 minutes of measurements. Pupil diameter was measured at 1 and 2 hours, and refraction was measured every 5 minutes from 1 to 2 hours, after intravitreal injection of 20 microl of 1.25 mM LAT-A (approximately 10 microM in vitreous), with intramuscular infusion of 1.5 mg/kg PILO during the first 15 minutes of measurements (all after topical 2.5% phenylephrine), and contractile response of isolated CM strips, obtained <1 hour postmortem and mounted in a perfusion apparatus, to 10 microM PILO +/- LAT-A was measured at various concentrations. RESULTS: Topical LAT-A of 42 microg dilated the pupil without affecting refraction. Intracameral LAT-A of 5 microM inhibited miotic and accommodative responses to intramuscular PILO. Intravitreal LAT-A of 10 microM had no effect on accommodative or miotic responses to intramuscular PILO. LAT-A dose-dependently relaxed the PILO-contracted CM by up to 50% at 3 microM in both the longitudinal and circular vectors. CONCLUSIONS: In monkeys, LAT-A causes mydriasis and cycloplegia, perhaps related to its known ability to disrupt the actin microfilament network and consequently to affect cell contractility and adhesion. Effects of LAT-A on the iris and CM may have significant physiological and clinical implications.

Accommodation, Ocular↗

PubMed1999

Latrunculin-A increases outflow facility in the monkey.

PURPOSE: To determine the effect of Latrunculin (LAT)-A, a macrolide that binds to G-actin, which leads to the disassembly of actin filaments, on shape, junctions, and the cytoskeleton of cultured bovine aortic endothelial cells (BAECs) and on outflow facility in living monkeys. METHODS: Latrunculin-A dose-time-response relationships in BAECs were determined by immunofluorescence and phase contrast light microscopy, facility by two-level constant pressure anterior chamber perfusion. RESULTS: In BAECs, LAT-A caused dose- and incubation time- dependent destruction of actin bundles, cell separation, and cell loss. Cell-cell adhesions were more sensitive than focal contacts. Recovery was also dose- and time-dependent. In monkeys, exchange intracameral infusion and topical application of LAT-A induced dose- and time-dependent several-fold facility increases. The facility increase was completely reversed within several hours after drug removal. However, for at least 24 hours after a single topical LAT-A dose, perfusion with drug-free solution caused an accelerated increase in facility beyond that attributed to normal resistance washout. CONCLUSIONS: Pharmacological disorganization of the actin cytoskeleton in the trabecular meshwork by specific actin inhibitors like LAT-A may be a useful antiglaucoma strategy.

Actins↗

PubMed1999

Effect of staurosporine on outflow facility in monkeys.

PURPOSE: To determine the effect of the serine-threonine kinase inhibitor staurosporine on outflow facility in living monkeys. METHODS: Total outflow facility was determined by two-level constant pressure perfusion of the anterior chamber bilaterally before and after intracameral infusion of staurosporine or vehicle in opposite eyes. RESULTS: Intracameral staurosporine dose-dependently doubled outflow facility, with 0.1 microM, 1 microM, and 10 microM being subthreshold, effective, and maximal doses, respectively. At 50 microM, intracameral staurosporine was less effective than 10 microM on facility and induced corneal toxicity. CONCLUSIONS: The broad-spectrum protein kinase inhibitor staurosporine increases outflow facility in living monkeys, perhaps by affecting the trabecular meshwork cytoskeleton.

Animals↗

PubMed1999

H-7 increases trabecular facility and facility after ciliary muscle disinsertion in monkeys.

PURPOSE: To determine the effects of the serine-threonine kinase inhibitor H-7 on total outflow facility in iridectomized + ciliary muscle (CM)- disinserted, and on trabecular facility in normal, monkey eyes. METHODS: Total outflow facility was determined by two-level constant pressure perfusion of the anterior chamber. Trabecular outflow facility was determined from accumulation in blood of intracamerally infused radioiodinated albumin at two intraocular pressure levels. RESULTS: Three-hundred micromoles of intracameral H-7 doubled facility in iridectomized + CM- disinserted monkey eyes and contralateral iridectomized-only eyes. Four 5-microl drops of 400 mM H-7 applied topically followed 2 hours later by anterior chamber exchange for 10 minutes and intracameral infusion for 90 minutes with 100 microM H-7 increased trabecular and total outflow facility by 135%+/-29% and 105%+/-35% (n 5, P < 0.01, P < 0.05), respectively, compared with contralateral vehicle-treated eyes. CONCLUSIONS: H-7 increases trabecular outflow facility in monkeys by a mechanism independent of the CM, presumably acting directly on the trabecular meshwork.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

PubMed1998

Thick-film electrochemical immunosensor based on stripping potentiometric detection of a metal ion label.

A disposable electrochemical immunosensor based on potentiometric stripping analysis (PSA) of a metal tracer and using an entirely on-chip assay format is demonstrated. Challenges associated with the adaptation of earlier stripping voltammetric immunoassays to an on-chip operation, and with meeting the demands of decentralized testing, have been addressed. These include the surface immobilization of the antibody, the replacement of mercury drop electrodes, elimination of the separation and oxygen-removal steps, and the use of quiescent 30-microL sample droplets. Human serum albumin (HSA) and anti-HSA antibody were used as a model system, while bismuth ion served as the metal label. The anti-HSA was immobilized onto the surface of a thick-film electrode, followed by a competition between the Bi-labeled analyte-tracer and the analyte (HSA) for the antibody binding sites. Upon removal of the unbound tracer, Bi3+ was released and detected by PSA. The dynamic concentration range for HSA (0.3-30 micrograms/mL) and the detection limit (0.2 microgram/mL, i.e., 90 fmol in the 30-microL sample) indicate that the greatly simplified protocol does not compromise the performance characteristics of stripping immunoassays. Consequently, this on-chip operation offers great promise for decentralized (clinical and environmental) applications.

Biosensing Techniques↗

PubMed1998

H-7 disrupts the actin cytoskeleton and increases outflow facility.

OBJECTIVES: To determine the effects of the serine-threonine kinase inhibitor H-7 on (1) cell junctions and the attached actin-based cytoskeleton in cultured bovine aortic endothelial cells, and (2) outflow facility in living monkeys. METHODS: Bovine aortic endothelial cells were cultured by standard techniques. The architecture and distribution of actin filaments, vinculin, and beta-catenin in bovine aortic endothelial cells were studied by immunolabeling before and after exposure to H-7 at various concentrations and durations. Outflow facility (perfusion) and intraocular pressure (Goldmann tonometer) were determined before and after the intracameral or topical administration of H-7 or a vehicle. RESULTS: In bovine aortic endothelial cells, exposure to H-7 produced a reversible time- and concentration-dependent disruption of actin microfilaments and an alteration in the organization of cell-cell and cell-matrix adhesions. In monkeys, intracameral and topical administration of H-7 dose dependently and reversibly doubled facility, and topical H-7 reduced intraocular pressures. CONCLUSION: H-7 increases outflow facility in monkeys, probably by inhibiting cell contractility, cytoskeletal support, and cell-cell adhesions in the trabecular meshwork.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

PubMed1998

Effects of H-7 on the iris and ciliary muscle in monkeys.

OBJECTIVES: To determine the effects of H-7 on (1) iris and ciliary muscles (CMs) in living monkeys; (2) isolated monkey CM strips; (3) actomyosin contractility in cultured Swiss 3T3 cells. METHODS: (1) Pupillary diameter (calipers) and accommodation (refractometer) in living monkeys were measured after topical, intracameral, or intravitreal administration of H-7 followed by systemic pilocarpine hydrochloride. (2) Pilocarpine-induced contraction of isolated monkey CM strips following administration of H-7 was measured in a perfusion chamber. (3) Actomyosin contractility in Swiss 3T3 cells cultured on thin silicone rubber film was determined by measuring cell-induced film wrinkles before and after administration of H-7. RESULTS: Topical H-7 prevented anesthesia-induced miosis but did not affect resting refraction. Intracameral or intravitreal H-7 dilated the pupil and inhibited miotic but not accommodative responses to pilocarpine. H-7 inhibited pilocarpine-induced contraction of isolated monkey CM strips and reduced Swiss 3T3 cell contraction. CONCLUSIONS: H-7 inhibits actin-based contractility in non-muscle cells and in monkey iris sphincter and CM. Under our in vivo experimental conditions, the effect on the iris predominates over that on the CM.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

PubMed1998

Measurements of the neutron yields from 7Li(p,n)7Be reaction (thick target) with incident energies from 1.885 to 2.0 MeV.

Accelerator-based neutron source have been considered to be practical for boron neutron capture therapy (BNCT). Based on experience with a parameters of the Brookhaven National Laboratory BMRR reactor neutron source, which has been used in treatment experiments, the future accelerator-based neutron source for BNCT should have the properties of low energy distribution (< 100 keV) and high flux (about 10(9) neutrons per second per square centimeter) in the patient zone. Using protons to bombard thick 7Li targets, generating neutrons via the 7Li(p,n)7Be reaction, is one of the optimal choices for this kind of neutron source. Neutron yield data versus incident energy are necessary in order to select the proper incident energy and for estimating how high the incident proton current should be. The required proton beam current intensity is one of the key parameters for an accelerator useful for BNCT. In the present work, neutron yields of the 7Li(p,n)7Be reaction with a thick lithium target and incident energies of 1.885 and 1.9 MeV were measured at 0 degree with respect to the incident beam direction. The results are (3.08 +/- 0.17) x 10(12) and (5.71 +/- 0.32) x 10(12) neutrons/C sr, respectively. Neutron yield angular distribution measurements at 2 MeV incident energy were also performed. The proton beams were generated by the Peking University 4.5 MV electrostatic accelerator. The emitted neutrons from these reactions have the advantages of low energy distribution and forward angular distribution, which are requirements for a BNCT neutron source. The data obtained in this work can be used as a reference to study the accelerator-based neutron sources for BNCT.

Beryllium↗

PubMed1998

Processing of frequency-modulated sounds in the cat's posterior auditory field.

Single-neuron activity was recorded from the posterior auditory field (PAF) in the cortex of gas-anesthetized cats. Tone bursts and broadband complex sounds were used for auditory stimulation. Responses to frequency-modulated (FM) sounds, in particular, were studied systematically. Linear FM sweeps were centered around the best frequency (BF) of a neuron and had an excursion large enough to cover its whole frequency tuning range. Rate and direction of change of the FM sweeps were varied. In the majority of PAF neurons (75%) the FM response seemed not to be linear, i.e., their best instantaneous frequency (BIF) varied by more than one octave at different FM rates (FMR). When the difference between BIF and BF at each FMR was used as a measure of linearity, it was within one-third octave only at five or fewer FMR in most PAF neurons (74%). The majority of PAF neurons (70%) preferred moderate FM rates (<200 Hz/ms). Fifty-four percent of all neurons in this area showed band-pass behavior with a clear preference in the middle range of FM rates in at least one direction. Overall, neurons with high-pass behavior in both directions made up only a minor portion (22%) of PAF neurons. When both directions of an FM sweep (low-to-high and high-to-low frequency) were tested, 50% of the neurons were clearly selective for one direction, i.e., the response to one FM direction was at least twice as large as that to the other direction. This selectivity was not necessarily present at the preferred FM rate. In general, FM direction selectivity was equally distributed over FM rates tested. The selectivity of PAF neurons for the rate and direction of FM sounds makes these neurons suitable for the detection and analysis of communication sounds, which often contain FM components with a moderate sweep rate in a particular direction.

Acoustic Stimulation↗

PubMed1997

Serial and parallel processing in rhesus monkey auditory cortex.

Auditory cortex on the exposed supratemporal plane in four anesthetized rhesus monkeys was mapped electrophysiologically with both pure-tone (PT) and broad-band complex sounds. The mapping confirmed the existence of at least three tonotopic areas. Primary auditory cortex, AI, was then aspirated, and the remainder of the cortex on the supratemporal plane was remapped. PT-responses in the caudomedial area, CM, were abolished in all animals but one, in which they were restricted to the high-frequency range. Some CM sites were still responsive to complex stimuli. In contrast to the effects on CM, no significant changes were detectable in the rostral area, R. After mapping cortex in four additional monkeys, injections were made with different tracers into matched best-frequency regions of AI, R, and CM. Injections in AI and R led to retrograde labeling of neurons in all three subdivisions of the medial geniculate (MG) nucleus (MGv, MGd, and MGm), as well as nuclei outside MG, whereas CM injections led to only sparse labeling of neurons in a restricted zone of the lateral MGd and, possibly, MGm, in addition to labeling in non-MG sites. The combined results suggest that MGv sends direct projections in parallel to areas AI and R, which drive PT-responses in both areas. PT-responses in area CM, however, appear to be driven by input relayed serially from AI. The direct input to CM from MGd and other thalamic nuclei may thus be capable of mediating responses only to broad-band sounds.

Acoustic Stimulation↗

PubMed1997

Effects of adenosine agonists on intraocular pressure and aqueous humor dynamics in cynomolgus monkeys.

The effects of single or multiple topical doses of the relatively selective A1 adenosine receptor agonists (R)-phenylisopropyladenosine (R-PIA) and N6-cyclohexyladenosine (CHA) on intraocular pressure (IOP), aqueous humor flow (AHF) and outflow facility were investigated in ocular normotensive cynomolgus monkeys. IOP and AHF were determined, under ketamine anesthesia, by Goldmann applanation tonometry and fluorophotometry, respectively. Total outflow facility was determined by anterior chamber perfusion under pentobarbital anesthesia. A single unilateral topical application of R-PIA (20-250 micrograms) or CHA (20-500 micrograms) produced ocular hypertension (maximum rise = 4.9 or 3.5 mmHg) within 30 min, followed by ocular hypotension (maximum fall = 2.1 or 3.6 mmHg) from 2-6 hr. The relatively selective adenosine A2 antagonist 3,7-dimethyl-1-propargylxanthine (DMPX, 320 micrograms) inhibited the early hypertension, without influencing the hypotension. Neither 100 micrograms R-PIA nor 500 micrograms CHA clearly altered AHF. Total outflow facility was increased by 71% 3 hr after 100 micrograms R-PIA. In conclusion, the early ocular hypertension produced by topical adenosine agonists in cynomolgus monkeys is associated with the activation of adenosine A2 receptors, while the subsequent hypotension appears to be mediated by adenosine A1 receptors and results primarily from increased outflow facility.

Adenosine↗

PubMed1997

Delayed reperfusion alters matrix metalloproteinase activity and fibronectin mRNA expression in the infarct zone of the ligated rat heart.

Delayed reperfusion has a beneficial effect on prognosis, independent of infarct size. One potential mechanism to explain this observation may be an effect on infarct healing. In this study, the impact of delayed reperfusion on two aspects of the healing process was examined, the activity of matrix metalloproteinase (MMP) enzymes and the expression of fibronectin (FN) mRNA. The rat model of coronary artery ligation was used and rats were randomly assigned to delayed reperfusion (150 min following coronary ligation) or permanent ligation. Animals were subsequently killed 1, 2, 3 and 7 days following infarction. Infarct tissue was harvested for MMP activity (zymography), FN mRNA (RNase protection analysis) and protein (immunofluorescence microscopy and Western analysis), and collagen content (hydroxyproline concentration). Infarction produced marked activation of MMP-1, -2, and -9. Reperfusion significantly attenuated the activity of these enzymes (approximately 50% reduction in MMP-1, P=0.03 and ;60% reduction in MMP-2 at 7 days, P=0.001; approximately 55% reduction in MMP-9 at 24 h and 84% reduction at 48 h, P=0.01 and 0.002, respectively). Delayed reperfusion also produced a trend toward a greater increase in FN mRNA 24 h following infarction and immunofluorescent staining suggested the presence of more FN protein at this point. These data demonstrate that delayed reperfusion alters matrix metalloproteinase activity and fibronectin mRNA expression in the infarct zone. The impact of these changes on infarct healing and their association with the improved prognosis of a patent infarct vessel following infarction will require further study.

Animals↗

PubMed1997

Echolocation signals of the greater horseshoe bat (Rhinolophus ferrumequinum) in transfer flight and during landing.

Echolocation signals of horseshoe bats (Rhinolophidae) consist of a relatively long component of constant frequency (CF) which is preceded by an initial frequency-modulated (iFM) component and followed by a terminal frequency-modulated (tFM) component. To examine the role of these components in echolocation, four bats were trained to fly from a perch to a landing bar. A dual camera system allowed reconstruction of the flight paths in three dimensions. Echolocation signals were recorded, analyzed, and correlated with the flight behavior of the bats. It was confirmed that during flight the bats compensate the Doppler shifts which are produced by their own flight movement. In free flight they emit per wing beat one single signal of long duration, with little variation in the three signal components. In approach flight the bats reduce pulse duration and interval with decreasing target range. The iFM is not varied with respect to target range, suggesting that this component plays little role in the processing of echolocating a target of interest. The bandwidth of the tFM component is increased while its duration is shortened in proportion to decreasing target range, so that the signal-echo overlap of the FM component is avoided down to a target distance of 15 cm. These concurrent changes suggest that the tFM component is used for ranging. During the last 60 cm of the approach the bats compensated for the increase of echo SPL by lowering the emission level of the CF component by 6-9 dB and that of the tFM component by 9-11 dB per halving of range. The specific signal structure of horseshoe bats is discussed as an adaptation for the hunting of fluttering insects in highly cluttered environments.

Animals↗