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Biomedical subjects

G Wu

Publications and source records attributed to G Wu.

At least 379 records · Page 21Linked to original sources

The significance of somatosensory stimulations to the human foot in the control of postural reflexes.

The purpose of this study was to investigate the possible pathways in the somatosensory system that relate to the postural reflexes in the leg muscles during a sudden, toes-up platform rotation. The inputs to the cutaneous mechanoreceptors in the sole of the foot as well as to the joint receptors in the ankle joint were modulated by standing on different supporting surfaces and by immobilizing the ankle joints; and three leg muscle responses (characterized by short latency, medium latency, and long latency) to the platform movement were recorded in 15 healthy young subjects. It was found that: (1) the short latency was not affected by the changes in either plantar pressure or ankle joint movement; (2) the medium latency was regulated by the plantar pressures under the foot, as sensed by the cutaneous mechanoreceptors in the sole of the foot, and by the ankle joint movement, as perceived by the joint receptors in the ankle joint; (3) the long latency was also related to the ankle joint movement, but this relation seems to be modulated by the plantar pressures under the foot; and (4) both medium and long latencies were well correlated with the time derivative of the pressure difference between the forefoot and the rear foot regions (r=0.7), as well as with the static pressure in the antagonist foot region (r>0.6).

Adult↗

Waveform complexity of unit activity recorded with concentric needle electrodes from human peripheral nerves.

Using standardised concentric needle electrodes 170 single units were recorded from myelinated cutaneous afferents in the human median or ulnar nerves. The unitary waveforms were of four types: single-peaked monophasic potentials (type I), double-peaked monophasic potentials (type II), biphasic potentials (type III) and triphasic potentials (type IV). Type II and IV occurred more frequently than the other types. Units of different functional classes had similar waveforms and there was no specific type of waveform distribution in any particular unit category. In some recording situations there were changes in unitary waveforms from one type to another. There was a tendency for the complex type IV, type III and type II waveforms to change to the simple type I. Adjustment of the electrode often provoked such waveform changes. The waveform profiles and waveform changes observed during recordings with concentric needles were significantly different from those encountered with conventional tungsten electrodes, which might be due to differences in recording properties between the two electrodes. Possible neural mechanisms underlying the observed waveforms and waveform transitions are discussed. In particular, our data suggest that concentric needle electrodes record single-unit activity from myelinated fibres extracellularly.

Action Potentials↗

Effect of probenecid on the transport of methyl mercury in erythrocytes by the organic anion transport system.

The uptake of methyl mercury (MeHg) by isolated erythrocytes from rats was studied at 5 degrees and 20 degrees C. The Na+ ion was used to examine exerted effects of probenecid on the uptake of MeHg through the organic anion transport system. Different extracellular pH levels were used to examine effects on the uptake of MeHg and on probenecid induced effects on the uptake of MeHg through the organic anion transport system; the effects of three anisotonic conditions were also determined. The results showed: (1) probenecid might partially change the role of Na+ ion from inhibition to stimulation for the uptake of MeHg; (2) the organic anion transport system for the uptake of MeHg was pH-dependent within the physiological range of extracellular pH; (3) the organic transport system for the uptake of MeHg was independent of deformation of the erythrocyte membrane.

Animals↗

Using a four-compartment closed model to describe inhalation of vaporised ethanol on 1-14C-pyruvate kinetics in mice.

A four-compartment closed model was set up by means of a system of differential equations. A completely analytical solution of the four-compartment closed model was found by means of Laplace transform and Cramer's rule. 1-14C-pyruvate kinetics were studied in mice without and with inhalation of vaporised ethanol. The 1-14C-pyruvate kinetics were modelled by the four-compartment closed model, i.e. injected site, blood, 14CO2 expired in air, and 14C eliminated in urine. The kinetic parameters were estimated using the analytical solution of the four-compartment closed model to fit expired 14CO2 and 14C eliminated in urine simultaneously. Although the results showed that the inhalation of vaporised ethanol increased the expired 14CO2, the compartmental analysis revealed that the increase of expired 14CO2 is mainly attributed to increased 1-14C-pyruvate transmembrane process. The developed model is useful for toxicokinetic analysis when blood is not easy to obtain. Moreover, the developed model can also be used to model two compartments as urine and faeces when the toxin is not eliminated through air.

Administration, Inhalation↗

Ventilation inhomogeneities and mixed venous blood N2 in multibreath N2 washout.

The single path model of airway gas transport, with and without a distributed blood source term, was used to simulate multiple-breath N2 washout by breathing pure O2 in two lung models: a single-region lung model (SRLM) which produces series inhomogeneity, and a seven-region lung model (7RLM) incorporating both series and parallel inhomogeneities. Normalized phase III slopes (Sn) from N2 expirograms were computed for each breath and compared with published human experimental data obtained under similar conditions. The 7RLM predicts well the trend of experimental Sn N2 changes and is superior to the SRLM in the first part (the unsteady state), implying that this part of the curve is mostly due to convective mixing of the seven parallel flow streams. In the quasi-steady state, the 7RLM is not obviously superior to the SRLM. Functional residual capacity and pulmonary perfusion are shown to strongly affect the number of breaths required to reach the quasi-steady state. The anatomical dimensions that appear to be critical in SRLM are not as important in the 7RLM.

Computer Simulation↗

Interaction of the delta-opioid receptor with GM1 ganglioside: conversion from inhibitory to excitatory mode.

Previous studies have shown GM1 ganglioside to play a crucial role in regulating excitatory opioid receptor function, which may underlie some aspects of opioid dependence, tolerance, and supersensitivity. To study the mechanism of this receptor modulation we have employed CHO cells containing a single, transfected opioid receptor of the delta-type. When forskolin was employed to elevate cAMP the reduction affected by 10 microM DADLE was counteracted by preincubation of the cells with GM1. No effect was observed with GD1a, GD1b, GT1b GM3, or the GM1 derivative, GM1-OH. In pertussis toxin-treated cells 10 nM DADLE increased basal levels of cAMP after preincubation with as little as 10 nM GM1. The results suggest conformational alteration of the opioid receptor from a form coupled primarily to G(i)/G(o) to one also capable of interacting with G(s).

Adenylyl Cyclases↗

Effects of tetramethylpyrazine on the release of PGI2 and TXA2 in the hypoxic isolated rat heart.

We examined the effect on 6-Keto-PGF1a and TXB2 (the stable metabolites of PGI2 and TXA2) outflow of pretreatment with tetramethylpyrazine in the hypoxic isolated rat heart. In control hearts, 6-Keto-PGF1a was increased from 185 +/- 46 pg/ml of baseline value to 335 +/- 76 pg/ml after 2 min of hypoxia and TXB2 increased from 136 +/- 28 pg/ml of baseline value to 230 +/- 43 pg/ml at 20 min of hypoxia and 252 +/- 32 pg/ml after 5 min of reoxygenation. Pretreatment with tetramethylpyrazine increased the 6-Keto-PGF1a concentration to 266 +/- 51 pg/ml (143% of control heart), 471 +/- 89 pg/ml (150% of control heart) and 332 +/- 47 pg/ml (195% of control heart) at 15 min of normoxia, 2 min of hypoxia and 5 min of reoxygenation, respectively (p < 0.05 vs control). On the other hand, tetramethylpyrazine diminished the release of TXB2 to 78 +/- 21 pg/ml (174% of control heart), 160 +/- 30 pg/ml (144% of control heart), and 196 +/- 23 pg/ml (128% of control heart) at 15 min of normoxia, 20 min of hypoxia and 5 min of reoxygenation, respectively (p < 0.05 vs control). These data show that pretreatment with tetramethylpyrazine enhances PGI2 outflow and attenuates release of TXA2 in the rat heart during normoxia, hypoxia and reoxygenation.

6-Ketoprostaglandin F1 alpha↗

Opioid receptor and calcium channel regulation of adenylyl cyclase, modulated by GM1, in NG108-15 cells: competitive interactions.

GM1 ganglioside was previously shown to function as a specific regulator of excitatory opioid activity in dorsal root ganglion neurons and F11 hybrid cells, as seen in its facilitation of opioid-induced activation of adenylyl cyclase and its ability to dramatically reduce the threshold opioid concentration required to prolong the action potential duration. The elevated levels of GM1 resulting from chronic opioid exposure of F11 cells were postulated to cause the ensuing opioid excitatory supersensitivity. We now show that GM1 promotes opioid (DADLE)-induced activation of adenylyl cyclase in NG108-15 cells which possess the delta-type of receptor. In keeping with previous studies of other systems, this can be envisioned as conformational interaction of GM1 with the receptor that results in uncoupling of the receptor from Gi and facilitated coupling to Gs. This would also account for the observation that DADLE-induced attenuation of forskolin-stimulated adenylyl cyclase was reversed by GM1, provided the cells were not pretreated with pertussis toxin. When the cells were so pretreated, GM1 evoked an unexpected attenuation of forskolin-stimulated adenylyl cyclase attributed to GM1-promoted influx of calcium which was postulated to inhibit a calcium-sensitive form of adenylyl cyclase. This is concordant with several studies showing GM1 to be a potent modulator of calcium flux. Pertussis toxin in these experiments exerted dual effects, one being to promote interaction of the delta-opioid receptor with Gs through inactivation of Gi, and the other to enhance the GM1-promoted influx of calcium by inactivation of Go; the latter is postulated to function as constitutive inhibitor of the relevant calcium channel. NG108-15 cells thus provide an interesting example of competitive interaction between two GM1-regulated systems involving enhancement of both opioid receptor excitatory activity and calcium influx.

Adenylate Cyclase Toxin↗

The detection of minimal lymphoma by molecular and combined culture-molecular methods.

Seventy-four patients from a prospective randomized trial comparing autologous bone marrow (ABM) versus blood stem cell (BSC) transplantation after high-dose chemotherapy for intermediate and high grade non-Hodgkin's lymphoma (NHL) were studied for the presence of residual lymphoma prior to transplantation. Pre-transplant bone marrow (BM), peripheral blood (PB) and the ABM or BSC harvest were studied by molecular assays immediately after collection and at weekly intervals after the initiation of in vitro cultures. B-NHLs with t(14:18) at the major breakpoint region (mbr) were monitored by detecting cells with the translocation. Other B-NHLs were monitored with tumour-specific primers and probes to the immunoglobulin heavy chain (IgH) gene complementary determining region (CDR) III. T-NHLs were similarly monitored using the T-cell receptor gamma chain gene V-J junctional region as the tumour-specific marker. Of the 74 patients, seven did not have adequate tumour biopsies for molecular characterization. Of the remaining 67 cases, 35 had identifiable markers for follow-up studies and 20/35 cases (52%) had tumour cells detected in either the pretransplant BM/PB samples or the ABM/BSC harvest. Residual tumours were detected at a high frequency in T-NHL (100%) and t(14;18)+ B-NHL (86%) but at a lower frequency in B-NHLs without t(14,18) (44%). In five cases, one or more of the samples were initially negative for residual lymphoma but became positive after a period of culture; additional studies confirmed that in vitro culture enhanced the sensitivity of tumour detection in about half of these samples. Molecular assay for minimal residual disease can be performed in the setting of multicentre prospective clinical trials. The substantial frequency of failure of obtaining tumour-specific IgH CDRIII sequences in paraffin-embedded B-NHLs argues for the storage of frozen tumour samples for possible molecular studies.

Base Sequence↗

Endogenous synthesis of arginine plays an important role in maintaining arginine homeostasis in postweaning growing pigs.

This study was conducted to determine whether endogenous synthesis of arginine plays a role in regulating arginine homeostasis in postweaning pigs. Pigs were fed a sorghum-based diet containing 0. 98% arginine and were used for studies at 75 d of age (28.4 kg body weight). Mitochondria were prepared from the jejunum and other major tissues for measuring the activities of Delta1-pyrroline-5-carboxylate (P5C) synthase and proline oxidase (enzymes catalyzing P5C synthesis from glutamate and proline, respectively) and of ornithine aminotransferase (OAT) (the enzyme catalyzing the interconversion of P5C into ornithine). For metabolic studies, jejunal enterocytes were incubated at 37 degrees C for 30 min in Krebs-Henseleit bicarbonate buffer containing 2 mmol/L L-glutamine, 2 mmol/L L-[U-14C]proline, and 0-200 micromol/L gabaculine (an inhibitor of OAT). The activities of P5C synthase, proline oxidase and OAT were greatest in enterocytes among all of the tissues studied. Incubation of enterocytes with gabaculine resulted in decreases (P < 0.05) in the synthesis of ornithine and citrulline from glutamine and proline. When gabaculine was orally administered to pigs (0.83 mg/kg body weight) to inhibit intestinal synthesis of citrulline from glutamine and proline, plasma concentrations of citrulline (-26%) and arginine (-22%) decreased (P < 0.05), whereas those of alanine (+21%), ornithine (+17%), proline (+107%), taurine (+56%) and branched-chain amino acids (+21-40%) increased (P < 0.05). On the basis of dietary arginine intake and estimated arginine utilization, the endogenous synthesis of arginine in the 28-kg pig provided >/=50.2% of total daily arginine requirement. Taken together, our results suggest an important role for endogenous synthesis of arginine in regulating arginine homeostasis in postweaning growing pigs, as previously shown in neonatal pigs.

Animals↗

Glucocorticoids play an important role in mediating the enhanced metabolism of arginine and glutamine in enterocytes of postweaning pigs.

Weaning is associated with increased intestinal metabolism of glutamine and arginine as well as elevated plasma concentrations of cortisol (the major circulating glucocorticoid) in pigs. The objective of this study was to determine if cortisol plays an important role in mediating the enhanced amino acid metabolism in enterocytes of weaned pigs by administering RU486 (a glucocorticoid receptor antagonist). Eighteen 21-d-old pigs were randomly assigned to three groups of six. Two of these groups received intramuscular injections of 0 or 10 mg RU486 per kg body weight 5 min before and 24 and 72 h after weaning to a corn-soybean meal-based diet. The third group was allowed to suckle freely from sows. When the pigs were 29 d old, jugular venous blood was obtained and pigs were killed for preparation of jejunal enterocytes. The activities of arginase, argininosuccinate synthase (ASS), argininosuccinate lyase (ASL) and pyrroline-5-carboxylate (P5C) synthase were measured. For metabolic studies, cells were incubated for 0 or 30 min at 37 degrees C in 2 mL of Krebs-bicarbonate buffer (pH 7.4) containing 0 or 2 mmol/L L-[U-14C]arginine or 2 mmol/L L-[U-14C]glutamine. In comparison with suckling pigs, weaning resulted in increases in the following: 1) the activities of arginase, ASS, ASL and P5C synthase, 2) the metabolism of arginine to CO2, proline and ornithine, and 3) the conversion of glutamine to ornithine, citrulline and CO2. The effects of the administration of RU486 were as follows: 1) attenuation of the increase in arginase activity and the production of ornithine from arginine, 2) abolition of the induction of ASL and P5C synthase, and 3) prevention of the increase in glutamine metabolism and the production of proline and CO2 from arginine in enterocytes of weaned pigs. These data suggest that glucocorticoids play an essential role in mediating the enhanced intestinal degradation of arginine and glutamine during weaning.

Aging↗

Obtaining clone-specific primer and probe for the immunoglobulin heavy-chain gene from paraffin-embedded tissue of B-cell lymphoma: technical considerations.

The complementarity determining region (CDR) III of the immunoglobulin heavy-chain (IgH) gene is a tumor-specific marker for B-cell malignancies that has been widely exploited for the monitoring of minimal residual disease in B-precursor acute lymphocytic leukemia. There are a number of technical problems in applying the same technology for B-cell non-Hodgkin's lymphoma (B-NHL). Several procedures have been useful in overcoming these unique problems encountered in obtaining the tumor-specific sequence of the IgH-CDRIII in B-NHL, including the use of denaturing gradient gel electrophoresis or micromanipulation of tissue sections in separating the tumor-specific CDRIII products from those of contaminating normal B-lymphocytes. Minor modifications of a commercial kit greatly improve the purity of the polymerase chain reaction (PCR) products for sequencing. Modifications of the 5'-ends of the VH and IH primers, coupled with the cycle sequencing technique, make it possible to obtain unambiguous sequences on direct sequencing of short PCR products. Computer informatics and programs that facilitate the design of tumor-specific primers and probes from CDRIII sequences are described.

DNA Primers↗

Real-time feedback of body center of gravity for postural training of elderly patients with peripheral neuropathy.

A system that estimates and displays, in real-time, the location of the center of gravity of the human body relative to the feet was developed and then used in a biofeedback training program for improving the postural instability caused by deterioration of the proprioceptive system in elderly patients with significant diabetic sensory neuropathy during perturbations of a support platform. Training sessions were scheduled three times a week for four weeks and consisted of continuous perturbations of the support platform for the standing subject. Postural stability of each subject was evaluated before, during and after training on a weekly basis. After twelve sessions of training, subjects who received visual feedback showed greater reduction in total number of falls and in fall magnitude defined by force in the body suspension cord, and longer delay in time between perturbation and fall than NFB group.

Biofeedback, Psychology↗

Effects of guan-mu-tong (Caulis aristolochiae manshuriensis) in combination with other natural products on normal and preneoplastic mammary gland growth in mice.

The effects of combined treatment with Guan-mu-tong (Gmt: Caulis aristolochiae manshuriensis) and other major components of Shi-Liu-Wei-Liu-Qi-Yin (SLWLQY), a Chinese herbal medicine prescribed for breast diseases, on normal and preneoplastic mammary gland growth were investigated. SHN virgin mice were divided into 6 groups at 3 months of age and treated with the samples in drinking water as shown in Table 2 for 8 weeks. Each sample was extracted repeatedly with hot water, dried in vacuo and dissolved with tap water at the concentration indicated in Table 2. Normal and preneoplastic mammary gland growth and thymidylate synthetase activity in the mammary gland were inhibited by Gmt alone; but its effect was affected slightly by the further addition of other products. However, the excretion of urinary components, which is abnormally low in SHN mice, was gradually enhanced by the addition of other products to Gmt and was highest by SLWLQY. The elongated estrous/metestrous stage of the estrous cycle induced by Gmt+Zq was returned to the control level by further addition of other products and by SLWLQY. The normal parameters in this strain during this age period such as body weight change, food and water intake and immune system were affected little by all treatments. All these findings strongly suggest that one of the principles of prescribing Chinese herbal medicines is to normalize the physical conditions, which, in turn, contributes to therapy and protection from diseases.

Animals↗

Rat adipose tissue amino acid metabolism in vivo as assessed by microdialysis and arteriovenous techniques.

In fed, anesthetized rats, microdialysis demonstrated a net release of glycerol, glutamine, serine, tyrosine, and taurine and a net uptake of glutamate, aspartate, glycine, and arginine across the inguinal adipose depot. However, the results also indicated excessive proteolysis associated with implantation of the microdialysis probe, and a novel arteriovenous difference technique was developed. Arteriovenous difference across the inguinal fat pat demonstrated a net uptake of glucose and a net release of lactate and glycerol. Starvation (48 h) resulted in higher rates of glycerol and lactate release with lower rates of glucose uptake. A net uptake of triacylglycerol was seen in starved-refed animals. Net glutamine, tyrosine, and taurine release was seen in fed and starved animals, but in starved-refed animals taurine and serine were the only amino acids showing significant release. No significant net uptake or release of ammonia, pyruvate, or alanine was observed. These experiments confirm that adipose tissue is a site of glutamine synthesis and suggest that the principal substrates are derived from intracellular proteolysis. The results also demonstrate the viability of an arteriovenous difference technique for the study of adipose tissue in the rat.

Adipocytes↗

Enhanced metabolism of arginine and glutamine in enterocytes of cortisol-treated pigs.

This study was designed to determine whether cortisol plays a role in arginine and glutamine metabolism in enterocytes and, more specifically, whether cortisol regulates metabolic changes in these cells during weaning. Twenty-eight 21-day-old suckling pigs were randomly assigned to one of four groups (7 animals in each) and received intramuscular injections of vehicle solution (sesame oil) (control group), hydrocortisone 21-acetate (HYD) (25 mg/kg body wt), RU-486 (10 mg/kg body wt) (a potent blocker of glucocorticoid receptors), or HYD plus RU-486. At 29 days of age, pigs were killed for preparation ofjejunal enterocytes. During the entire experimental period, pigs were nursed by sows. Activities of argininosuccinate synthase, argininosuccinate lyase (ASL), arginase, and pyrroline-5-carboxylate (P5C) synthase were measured. For metabolic studies, enterocytes were incubated for 30 min at 37 degrees C in 2 ml of Krebs-bicarbonate buffer (pH 7.4) containing 0, 0.5, or 2 mM [U-(14)C]arginine or [U-(14)C]glutamine. Compared with control, cortisol administration increased 1) the activities of ASL and arginase and the production of CO(2), ornithine, and proline from arginine, and 2) P5C synthase activity and the formation of glutamate, alanine, aspartate, ornithine, citrulline, proline, and CO(2) from glutamine in enterocytes. The stimulating effects of cortisol on the enzyme activities and the metabolism of arginine and glutamine were abolished by coadministration of RU-486. Our data suggest that cortisol plays an important role in regulating arginine and glutamine metabolism in enterocytes via a glucocorticoid receptor-mediated mechanism.

Amino Acids↗

Synthesis of citrulline and arginine from proline in enterocytes of postnatal pigs.

The synthesis of ornithine, citrulline, and arginine from proline was quantified in enterocytes of newborn (0-day-old) pigs, 2- to 21-day-old suckling pigs, and 29- to 58-day-old pigs weaned at 21 days of age. Mitochondria were prepared from enterocytes for measurement of proline oxidase activity. For metabolic studies, cells were incubated at 37 degrees C for 30 min in Krebs bicarbonate buffer (pH 7.4) containing 5 mM D-glucose and 0.0-5.0 mM L-[U-14C]proline with or without 2.0 mM L-glutamine. Proline oxidase activity and rates of synthesis of citrulline and arginine from proline were high in enterocytes of newborn pigs and markedly decreased in 7-day-old pigs. With increasing piglet age from 7 to 21 days, enterocyte proline oxidase activity and rate of conversion of proline into citrulline progressively increased, but the values in 21-day-old pigs remained much lower than in newborn pigs. The synthesis of ornithine, citrulline, and arginine from 0.5-5 mM proline was concentration dependent and required the addition of glutamine. About 80-90% of utilized proline carbons were recovered in ornithine plus citrulline plus arginine, with CO2 being a minor product. These results demonstrate a hitherto unrecognized pathway for the synthesis of ornithine, citrulline, and arginine via proline oxidase in enterocytes and challenge the current concept that pyrroline-5-carboxylate (P5C) is synthesized in the small intestine only from glutamine/glutamate via P5C synthase on the basis of previous work with postnatal rats.

Aging↗