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Biomedical subjects

D Hu

Publications and source records attributed to D Hu.

At least 19 recordsLinked to original sources

Phase relationships support a role for coordinated activity in the indirect pathway in organizing slow oscillations in basal ganglia output after loss of dopamine.

The goal of the present study was to determine the phase relationships of the slow oscillatory activity that emerges in basal ganglia nuclei in anesthetized rats after dopamine cell lesion in order to gain insight into the passage of this oscillatory activity through the basal ganglia network. Spike train recordings from striatum, subthalamic nucleus (STN), globus pallidus (GP), and substantia nigra pars reticulata (SNpr) were paired with simultaneous local field potential (LFP) recordings from SNpr or motor cortex ipsilateral to a unilateral lesion of substantia nigra dopamine neurons in urethane-anesthetized rats. Dopamine cell lesion induced a striking increase in incidence of slow oscillations (0.3-2.5 Hz) in firing rate in all nuclei. Phase relationships assessed through paired recordings using SNpr LFP as a temporal reference showed that slow oscillatory activity in GP spike trains is predominantly antiphase with oscillations in striatum, and slow oscillatory activity in STN spike trains is in-phase with oscillatory activity in cortex but predominantly antiphase with GP oscillatory activity. Taken together, these results imply that after dopamine cell lesion in urethane-anesthetized rats, increased oscillatory activity in GP spike trains is shaped more by increased phasic inhibitory input from the striatum than by phasic excitatory input from STN. In addition, results show that oscillatory activity in SNpr spike trains is typically antiphase with GP oscillatory activity and in-phase with STN oscillatory activity. While these observations do not rule out additional mechanisms contributing to the emergence of slow oscillations in the basal ganglia after dopamine cell lesion in the anesthetized preparation, they are compatible with 1) increased oscillatory activity in the GP facilitated by an effect of dopamine loss on striatal 'filtering' of slow components of oscillatory cortical input, 2) increased oscillatory activity in STN spike trains supported by convergent antiphase inhibitory and excitatory oscillatory input from GP and cortex, respectively, and 3) increased oscillatory activity in SNpr spike trains organized by convergent antiphase inhibitory and excitatory oscillatory input from GP and STN, respectively.

Action Potentials↗

Evidence for superior parietal impairment in Williams syndrome.

Parietal lobe impairment is hypothesized to contribute to the dramatic visual-spatial deficits in Williams syndrome (WS). The authors examined the superior and inferior parietal lobule in 17 patients with WS and 17 control female adults (CNLs). The right and left superior parietal lobule gray matter volumes were significantly smaller in patients with WS than in CNLs, even after controlling for total cerebral gray matter. Impaired superior parietal function could explain WS visual-spatial and visual-motor problems.

Adult↗

Nematic solvation of segmented polymer chains.

We examine the effect of polymer chain segmentation on the recently discovered ability of nematic solvents to elongate and align polymer chain solutes. Coordinated single molecule spectroscopy and beads-on-a-chain simulations are used to study the orientational and conformational order of a series of segmented conjugated polymers, dissolved in the nematic liquid crystal 5CB. The order parameters for alignment and elongation are both observed to decrease with increasing segmentation, reflecting an interplay among conformational entropy, solvation anisotropy, and bending energy of the chain.

Journal Article↗

How echographic image analysis of venous oedema reveals the benefits of leg elevation.

OBJECTIVE: Venous insufficiency, leading to venous oedema, is a key pathogenic factor for the non-healing of venous leg ulcers. This study aimed to evaluate the effects of leg elevation on venous oedema. METHOD: Ten patients aged 44-89 years (median: 61) with leg oedema had high-frequency B-mode ultrasound scanning and digital image analysis before and after three to four hours of leg elevation. The echographic image analysis system was used, where oedema is represented by the hypoechogenic part of the image--that is, the total number or density of low echogenic pixels (LEPs) in a particular area. RESULTS: Compared with pre-elevation, the volume of the lower leg decreased by 2.9% +/- 0.6 (138 cm3 +/- 39) after three to four hours' elevation (p < 0.05). After elevation, the LEPs in the upper, middle and lower sites of the limb decreased by 8.8%, 15.6% and 17.3% respectively, reaching statistical significance (p < 0.05) in the lower site. The ratio of LEPs in the upper and lower dermis in the upper, middle and lower sites decreased by 30.3%, 45.8% and 22.5% respectively. This was significant in both the middle and lower sites (p < 0.01). After elevation dermal thickness increased by 0.047 mm, 0.194 mm and 0.232 mm respectively. This change was statistically significant in the middle (p < 0.05) and lower sites of the limb (p < 0.01). CONCLUSION: LEPs are a sensitive marker of dermal oedema and its effects. Leg elevation is extremely effective in reducing oedema, even if only for three to four hours.

Adult↗

Bioavailability and pharmacokinetics of florfenicol in broiler chickens.

The bioavailability and pharmacokinetic disposition of florfenicol in broiler chickens were investigated after intravenous (i.v.), intramuscular (i.m.) and oral administrations of 15 and 30 mg/kg body weight (b.w.). Plasma concentrations of florfenicol were determined by a high performance liquid chromatographic method in which plasma samples were spiked with chloramphenicol as internal standard. Plasma concentration-time data after i.v. administration were best described by a two-compartment open model. The elimination half-lives were 168 +/- 43 and 181 +/- 71 min, total body clearance 1.02 +/- 0.17 and 1.02 +/- 0.16 L x kg/h, the volume of distribution at steady-state 4.99 +/- 1.11 and 3.50 +/- 1.01 L/kg after i.v. injections of 15 and 30 mg/kg b.w., respectively. Plasma concentration-time data after i.m. and oral administrations were adequately described by a one-compartment model. The i.m. bioavailability and the oral bioavailability of florfenicol were 95, 98 and 96, 94%, respectively, indicating that florfenicol was almost absorbed completely after i.m. and oral administrations of 15 and 30 mg/kg b.w.

Administration, Oral↗

Shifts in striatal responsivity evoked by chronic stimulation of dopamine and glutamate systems.

Dopamine and glutamate are key neurotransmitters in cortico-basal ganglia loops affecting motor and cognitive function. To examine functional convergence of dopamine and glutamate neurotransmitter systems in the basal ganglia, we evaluated the long-term effects of chronic stimulation of each of these systems on striatal responses to stimulation of the other. First we exposed rats to chronic intermittent cocaine and used early-gene assays to test the responsivity of the striatum to subsequent acute motor cortex stimulation by application of the GABA(A) (gamma-aminobutyric acid alpha subunit) receptor antagonist, picrotoxin. Reciprocally, we studied the effects of chronic intermittent motor cortex stimulation on the capacity for subsequent acute dopaminergic treatments to induce early-gene activation in the striatum. Prior treatment with chronic intermittent cocaine induced motor sensitization and significantly potentiated the striatal expression of Fos-family early genes in response to stimulation of the motor cortex. Contrary to this, chronic intermittent stimulation of the motor cortex down-regulated cocaine-induced gene expression in the striatum, but enhanced striatal gene expression induced by a full D1 receptor agonist (SKF 81297) and did not change the early-gene response elicited by a D2 receptor antagonist (haloperidol). These findings suggests that repeated dopaminergic stimulation produces long-term enhancement of corticostriatal signalling from the motor cortex, amplifying cortically evoked modulation of the basal ganglia. By contrast, persistent stimulation of the motor cortex inhibits cocaine-stimulated signalling in the striatum, but not signalling mediated by individual dopamine receptor sites, suggesting that chronic cortical hyperexcitability produces long-term impairment of dopaminergic activity and compensation at the receptor level. These findings prompt a model of the basal ganglia function as being regulated by opposing homeostatic dopamine-glutamate neurotransmitter interactions. The model provides a framework for analysing the neurological alterations associated with disorders of the basal ganglia and their treatment with pharmacotherapies affecting dopamine and glutamate neurotransmitter systems.

Animals↗

Pediatric motor vehicle related injuries in the Navajo Nation: the impact of the 1988 child occupant restraint laws.

BACKGROUND: Navajo motor vehicle mortality is the highest among the 12 Indian Health Service (IHS) administrative areas. In July 1988, the Navajo Nation enacted a primary enforcement safety belt use and a child restraint law. OBJECTIVE: Assess the impact of the laws on the rate and severity of pediatric (0-19 years) motor vehicle injury resulting in hospitalizations in the Navajo Nation. METHODS: Hospitalizations associated with motor vehicle related injury discharges were identified by International Classification of Diseases, 9th revision, CM E codes, 810-825 (.0,.1) from the Navajo IHS hospital discharge database. Age specific rates for the period before the law, 1983-88, were compared with those after enactment and enforcement, 1991-95. Severity of injury, measured by the abbreviated injury scale (AIS) score and new injury severity score (NISS), was determined with ICDMAP-90 software. Wilcoxon rank sum and chi(2) tests were used for analysis. RESULTS: Discharge rates (SE) for motor vehicle injury (per 100 000) decreased significantly in all age groups: 0-4 years (62 (7) to 28 (4)), 5-11 years (55.3 (6) to 26 (4)), and 15-19 years (139 (14) to 68 (7)); p=0.0001. In children 0-4 years, the median AIS score decreased from 1.5 (1,3) (25th, 75th centile) to 1 (1,2), p=0.06, and the median NISS decreased from 3.5 (1,9) to 2 (1,5), p=0.07. The proportion of children with NISS scores >4 decreased significantly for the 0-4 year age group (p=0.03). CONCLUSIONS: Concurrent with enactment of the Navajo Nation occupant and child restraint laws there was a reduction in the rate of motor vehicle related hospital discharges for children. Severity of injury declined in very young Navajo children. The effect of enactment and enforcement of this Native American child occupant restraint law may serve as an example of an effective injury control effort directed at Native American children.

Abbreviated Injury Scale↗

Refolding of beta-lactoglobulin studied by stopped-flow circular dichroism at subzero temperatures.

Refolding of bovine beta-lactoglobulin was studied by stopped-flow circular dichroism at subzero temperatures. In ethylene glycol 45%-buffer 55% at -15 degrees C, the isomerization rate from the kinetic intermediate rich in alpha-helix to the native state is approximately 300-fold slower than that at 4 degrees C in the absence of ethylene glycol, whereas the initial folding is completed within the dead time of the stopped-flow apparatus (10 ms). At -28 degrees C, we observed at least three phases; the fastest process, accompanied by an increase of alpha-helix content, is completed within the dead time of the stopped-flow apparatus (10 ms), the second phase, accompanied by an increase of alpha-helix content with the rate of 2 s(-1), and the third phase, accompanied by a decrease of alpha-helix content. This last phase, corresponding to the isomerization process at -15 degrees C described above, was so slow that we could not monitor any changes within 4 h. Based on the findings above, we propose that rapid alpha-helix formation and their concurrent collapse are common even in proteins rich in beta-structure in their native forms.

Circular Dichroism↗

Insulin receptor-mediated p62dok tyrosine phosphorylation at residues 362 and 398 plays distinct roles for binding GTPase-activating protein and Nck and is essential for inhibiting insulin-stimulated activation of Ras and Akt.

A GTPase-activating protein (GAP)-associated 60-kDa protein has been found to undergo rapid tyrosine phosphorylation in response to insulin stimulation. However, whether this protein is a direct in vivo substrate for the insulin receptor (IR) tyrosine kinase and whether the tyrosine phosphorylation plays a role in insulin signaling remain to be established. Here we show that the insulin-stimulated tyrosine phosphorylation of the GAP-associated protein, now identified as p62(dok), is inhibited by Grb10, an adaptor protein that binds directly to the kinase domain of the IR, both in vitro and in cells. Replacing Tyr(362) and Tyr(398) with phenylalanine greatly decreased the IR-catalyzed p62(dok) tyrosine phosphorylation in vitro, suggesting that these two residues are the major IR-mediated phosphorylation sites. However, mutations at Tyr(362) and Tyr(398) only partially blocked insulin-stimulated p62(dok) tyrosine phosphorylation in cells, indicating that p62(dok) is also a target for other cellular tyrosine kinase(s) in addition to the IR. Replacing Tyr(362) with phenylalanine abolished the interaction between p62(dok) and Nck. Mutations at Tyr(362/398) of p62(dok) disrupted the interaction between p62(dok) and GAP and decreased the inhibitory effect of p62(dok) on the insulin-stimulated activation of Ras and Akt, but not mitogen-activated protein kinase. Furthermore, the inhibitory effect of p62(dok) on Akt phosphorylation could be blocked by coexpression of a constitutively active Ras. Taken together, our findings indicate that p62(dok) is a direct substrate for the IR tyrosine kinase and that phosphorylation at Tyr(362) and Tyr(398) plays an essential role for p62(dok) to interact with its effectors and negatively regulate the insulin signaling pathway.

Adaptor Proteins, Signal Transducing↗

[Percutaneous radiofrequency ablation treatment of hepatocellular cancer].

OBJECTIVE: To evaluate the safety, efficacy and complication of radiofrequency ablation (RFA) in treatment of hepatocellular cancer (HCC). METHODS: 78 HCC patients (58 of Child class A, 14 of Child class B, 6 Child class C) with 110 tumors (with the median diameter of 6.1 cm +/- 2.9 cm and the range of 1.9 to 13.7 cm) were treated by electrodes inserted to the foci percutaneously under ultrasound guidance using RF 2000 generator for 105 times in total (on average for 1.3 times and with 6.3 ablated sessions per patient). After the treatment the patients were followed up for 9.2 months on average (1-16 months). RESULTS: The serum ALT and TBIL were transiently elevated one day after RFA in all patients, and returned to baseline values in 2 weeks. The common response after RFA was mild fever. 6 patients (7.7%) had complications; however, no treatment-related death took place. 43 patients (55.1%) had tumor recurrence 6.1 months after RFA on average. Multivariate analysis demonstrated that the tumor diameter were related significantly to local recurrence (P = 0.0001). There was a significant linear correlation between the number of overlapping ablation sessions and tumor diameter (r = 0.772 16, P = 0.0001) among patients without local recurrence. From further liner regression analysis, a mathematical model: y = -1.794 + 1.733x (P = 0.0001, R-square = 0.5303, y: ablation sessions, x: tumor diameter) was got. CONCLUSION: RFA is a safe and effective nonoperative treatment for HCC.

Adult↗

Metachromatic leukodystrophy in the Navajo: fallout of the American-Indian wars of the nineteenth century.

Our aim was to determine if the high frequency of metachromatic leukodystrophy (MLD) in Navajo Indians of the Southwestern United States is the result of a "genetic bottleneck" that occurred in the mid 19th century. Navajo Nation, Indian Health Service, and other national databases were queried for Native American patients with MLD. Pedigrees, including birth location, were established by interviewing relatives. We found that cases of MLD and their ancestors are clustered in a portion of the western Navajo Nation to which a small number of Navajo fled after armed conflict with the United States Army in the 1860s. The observed incidence of MLD on the western Navajo Nation is 1/2,520 live births, with an estimated carrier frequency of 1/25 to 1/50. No cases were observed in the eastern part of the Navajo Nation over a period of 18 years (60,000 births). The high incidence of MLD in the western Navajo Nation appears to be the result of a genetic bottleneck and probable founder effect from the mid 19th century: This mechanism may also explain the high incidence of a number of other unique, heritable disorders among the Navajo. The history of the Navajo may also be relevant to other American Indian and Alaskan Native groups that have undergone severe population reduction since the arrival of Europeans in North America.

Female↗

Definition of a novel binding site on CD8 cells for a conserved region of the MHC class Ib molecule Qa-1 that regulates IFN-gamma expression.

Natural killer (NK) cells and activated CD8 cells both express cytotoxic activity and produce substantial levels of IFN-gamma in response to viral and bacterial infections. In the case of NK cells, cellular activation and IFN-gamma expression are regulated by an interaction between NK receptors and MHC class Ib molecules, including HLA-E/Qa-1. We have used soluble tetrameric complexes of the murine class Ib molecule Qa-1 to define the significance of this interaction for CD8 cells. We find that all CD8 cells express a receptor for Qa-1 and that ligation of this receptor by Qa-1 results in up-regulation of IFN-gamma production.

Animals↗

Organ culture of craniofacial primordia.

Organ culture systems have proven extremely useful techniques in studies that investigate the process of normal and abnormal development. The explant of tissues into an organ culture system is one of the few techniques that maintains three-dimensional cellular interactions under conditions that simultaneously permit controlled experimental manipulation in vitro. In this article we outline a procedure for growing "faces" in culture. In this system, the facial primordia prepared from embryonic mice or chicks can be maintained in culture for up to 7--8 days. During this time, the facial primordia continue to grow, differentiate, fuse and develop into organized structures that closely resemble those observed in situ. The procedure is relatively simple, requiring only a stable substratum, culture medium, sufficient oxygenation and incubation of the organ system at 37 degrees C. The advantages and disadvantages of the procedure are presented, along with detailed methods to help troubleshoot some of the common pitfalls of organ culture systems.

Animals↗

A comparative study of the effects of magnetic stimulation and electric stimulation on peripheral nerve injury in rat.

The influence of pulsed magnetic stimulation (MS) on the sciatic nerve injury was investigated. Thirty rats were divided into three groups equally: MS group (A), electric stimulation (ES) group (B) and the control group (C). The MS and ES were applied immediately after the first 10 min of the sciatic nerve crush. Sciatic function index (SFI), toe spreading reflex (TSR), muscular weight and volume were measured after the experiment. The TSR of in the groups A and B occurred at 4th day while in the control group it occurs at 10th day. There was statistically significant difference in SFI between groups A and B (P < 0.01). The weight and volume of the gastrocnemius muscle were statistically greater in the groups A and B than in the control group (P < 0.01). The effect of MS was similar to that of ES. It was suggested that the application of MS immediately after the nerve injury might have an important clinical value as it can accelerate functional recovery and prevent or minimize muscle atrophy. The technique is easily to operate, non-invasion, painless and permits tolerance of high intensity output to be used.

Animals↗

Experimental laser-assisted in situ keratomileusis induces the reactivation of latent herpes simplex virus.

PURPOSE: We determined whether laser-assisted in situ keratomileusis acts as a trigger for the reactivation and ocular shedding of herpes simplex virus type-1 in a rabbit latency model. METHODS: Herpes simplex virus type-1 latently infected rabbits were divided into three treatment groups: Group I received surface excimer laser ablation in both eyes (positive control), Group II received laser-assisted in situ keratomileusis in both eyes, and Group III received no treatment (negative control). Eyes were cultured daily for 10 days to determine herpes simplex virus type-1 reactivation. RESULTS: The number of herpes simplex virus type-1 positive eye cultures and total herpes simplex virus type-1 shedding days were significantly greater after surface excimer laser ablation and laser-assisted in situ keratomileusis compared with the untreated control group (P < 0.002 and P < 0.000001, respectively). CONCLUSION: Laser-assisted in situ keratomileusis as well as surface excimer laser ablation act as a trigger for the reactivation of herpes simplex virus type-1 in the rabbit latency model.

Animals↗