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G Li

Publications and source records attributed to G Li.

At least 613 records · Page 34Linked to original sources
PubMed1997

Design of peptides, proteins, and peptidomimetics in chi space.

Peptide and protein biological activities depend on their three dimensionals structures in the free state and when interacting with their receptors/acceptors. The backbone conformations such as alpha-helix, beta-sheet, beta-turn, and so forth provide critical templates for the three-dimensional structure, but the overall shape and intrinsic stereoelectronic properties of the peptide or protein important for molecular recognition, signal transduction, enzymatic specificity, immunomodulation, and other biological effects depend on arrangement of the side chain groups in three-dimensional chi space (their chi 1, chi 2, etc. torsional angles). In this paper we explore approaches to the de novo design of polypeptides and peptidomimetics with biased or specific conformational/topographical properties in chi space. We consider computational and experimental methods that can be used to examine the effects of specific structural modifications in constraining side chain groups of amino acid residues and their similarities in chi space to the natural amino acids to evaluate what sort of mimetics are likely to mimic normal amino acids. We then examine some of the asymmetric synthetic methods that are being developed to obtain the amino acid mimetics. Finally, we consider selected examples in the literature where these specialized amino acids have been incorporated in biologically active peptides and the specific insights they have provided regarding the topographical requirements for bioactive peptide potency, selectivity, and other biochemical and pharmacological properties. Constraints in chi space show great promise as useful tools in peptide, protein, and peptidomimetic de novo design of structures and pharmacophores with specific stereostructural, biochemical and biological properties.

Drug Design↗
PubMed1997

Strain activation of bovine aortic smooth muscle cell proliferation and alignment: study of strain dependency and the role of protein kinase A and C signaling pathways.

Smooth muscle cell (SMC) phenotype can be altered by physical forces as demonstrated by cyclic strain-induced changes in proliferation, orientation, and secretion of macromolecules. However, the magnitude of strain required and the intracellular coupling pathways remain ill defined. To examine the strain requirements for SMC proliferation, we selectively seeded bovine aortic SMC either on the center or periphery of silastic membranes which were deformed with 150 mm Hg vacuum (0-7% center; 7-24% periphery). SMC located in either the center or peripheral regions showed enhanced proliferation compared to cells grown under the absence of cyclic strain. Moreover, SMC located in the center region demonstrated significantly (P < 0.005) greater proliferation as compared to those in the periphery. In contrast, SMC exposed to high strain (7-24%) demonstrated alignment perpendicular to the strain gradient, whereas SMC in the center (0-7%) remained aligned randomly. To determine the mechanisms of these phenomena, we examined the effect of cyclic strain on bovine aortic SMC signaling pathways. We observed strain-induced stimulation of the cyclic AMP pathway including adenylate cyclase activity and cyclic AMP accumulation. In addition, exposure of SMC to cyclic strain caused a significant increase in protein kinase C (PKC) activity and enzyme translocation from the cytosol to a particulate fraction. Further study was conducted to examine the effect of strain magnitude on signaling, particularly protein kinase A (PKA) activity as well as cAMP response element (CRE) binding protein levels. We observed significantly (P < 0.05) greater PKA activity and CRE binding protein levels in SMC located in the center as compared to the peripheral region. However, inhibition of PKA (with 10 microM Rp-cAMP) or PKC (with 5-20 ng/ml staurosporine) failed to alter either the strain-induced increase in SMC proliferation or alignment. These data characterize the strain determinants for activation of SMC proliferation and alignment. Although strain activated both the AC/cAMP/PKA and the PKC pathways in SMC, singular inhibition of PKA and PKC failed to prevent strain-induced alignment and proliferation, suggesting either their lack of involvement or the multifactorial nature of these responses.

Activating Transcription Factor 2↗
PubMed1997

Evaluation of the effect of joint constraints on the in situ force distribution in the anterior cruciate ligament.

The function of the anterior cruciate ligament was investigated for different conditions of kinematic constraint placed on the intact knee using a six-degree-of-freedom robotic manipulator combined with a universal force-moment sensor. To do this, the in situ forces and force distribution within the porcine anterior cruciate ligament during anterior tibial loading up to 100 N were compared at 30, 60, and 90 degrees of flexion under: (a) unconstrained, five-degree-of-freedom knee motion, and (b) constrained, one-degree-of-freedom motion (i.e., anterior translations only). The robotic/universal force-moment sensor testing system was used to both apply the specified external loading to the intact joint and measure the resulting kinematics. After tests of the intact knee were completed, all soft tissues except the anterior cruciate ligament were removed, and these motions were reproduced such that the in situ force and force distribution could be determined. No significant differences in the magnitude of in situ forces in the anterior cruciate ligament were found between the unconstrained and constrained testing conditions. In contrast, the direction of in situ force changed significantly; the force vector in the unconstrained case was more parallel with the direction of the applied tibial load. In addition, the distribution of in situ force between the anteromedial and posterolateral bundles of the ligament was nearly equal for all flexion angles for the unconstrained case, whereas the anteromedial bundle carried higher forces than the posterolateral bundle at both 60 and 90 degrees of flexion for the constrained case. This demonstrates that the constraint conditions placed on the joint have a significant effect on the apparent role of the anterior cruciate ligament. Specifically, constraining joint motion to one degree of freedom significantly alters both the direction and distribution of the in situ force in the ligament from that observed for unconstrained joint motion (five degrees of freedom). Furthermore, the changes observed in the distribution of force between the anteromedial and posterolateral bundles for different constraint conditions may help elucidate mechanisms of injury by providing new insight into the response of the anterior cruciate ligament to different types of external knee loading.

Animals↗
PubMed1997

In situ forces in the anterior cruciate ligament and its bundles in response to anterior tibial loads.

The anterior cruciate ligament has a complex fiber anatomy and is not considered to be a uniform structure. Current anterior cruciate ligament reconstructions succeed in stabilizing the knee, but they neither fully restore normal knee kinematics nor reproduce normal ligament function. To improve the outcome of the reconstruction, it may be necessary to reproduce the complex function of the intact anterior cruciate ligament in the replacement graft. We examined the in situ forces in nine human anterior cruciate ligaments as well as the force distribution between the anteromedial and posterolateral bundles of the ligament in response to applied anterior tibial loads ranging from 22 to 110 N at knee flexion angles of 0-90 degrees. The analysis was performed using a robotic manipulator in conjunction with a universal force-moment sensor. The in situ forces were determined with no device attached to the ligament, while the knee was permitted to move freely in response to the applied loads. We found that the in situ forces in the anterior cruciate ligament ranged from 12.8 +/- 7.3 N under 22 N of anterior tibial load applied at 90 degrees of knee flexion to 110.6 +/- 14.8 N under 110 N of applied load at 15 degrees of flexion. The magnitude of the in situ force in the posterolateral bundle was larger than that in the anteromedial bundle at knee flexion angles between 0 and 45 degrees, reaching a maximum of 75.2 +/- 18.3 N at 15 degrees of knee flexion under an anterior tibial load of 110 N. The magnitude of the in situ force in the posterolateral bundle was significantly affected by knee flexion angle and anterior tibial load in a fashion remarkably similar to that seen in the anterior cruciate ligament. The magnitude of the in situ force in the anteromedial bundle, in contrast, remained relatively constant, not changing with flexion angle. Significant differences in the direction of the in situ force between the anteromedial bundle and the posterolateral bundle were found only at flexion angles of 0 and 60 degrees and only under applied anterior tibial loads greater than 66 N. We have demonstrated the nonuniformity of the anterior cruciate ligament under unconstrained anterior tibial loads. Our data further suggest that in order for the anterior cruciate ligament replacement graft to reproduce the in situ forces of the normal anterior cruciate ligament, reconstruction techniques should take into account the role of the posterolateral bundle in addition to that of the anteromedial bundle.

Adult↗
PubMed1997

Assessment of cell proliferation in regenerating bone during distraction osteogenesis at different distraction rates.

An experimental model of lengthening of the lower limb was used to study the morphology and cellular proliferation of regenerating bone tissue after 20% lengthening at four rates of distraction. Groups of rabbits were killed at different times 1-8 weeks after surgery. The regenerated area was divided into three zones: fibrous, primary mineralization front, and new bone. As the rate of distraction increased, the size of the fibrous zone increased and that of the new bone zone decreased. Necrosis, formation of cysts, and cartilage were found in the regenerated area at the higher distraction rates. Cell proliferation was assessed by in vivo labelling with bromodeoxyuridine, and the positive staining index for anti-bromodeoxyuridine antibody was calculated in the zones of the regenerated tissue. The index values for the fibrous zones and the new bone zones did not differ significantly in any of the groups. The value increased significantly (p < 0.05) in the primary mineralization front as the rate of distraction increased from 0.3 to 0.7 mm/day, but there was no further significant increase at higher distraction rates. In conclusion, cell proliferation was increased at all of the higher rates (more than 0.3 mm/day) of distraction studied. Higher rates of distraction caused tissue damage. A distraction rate of 0.7 mm/day appeared optimal for cell proliferation and histological characteristics.

Animals↗
PubMed1997

Molecular cloning, nucleotide sequencing, and expression of genes encoding alcohol dehydrogenases from the thermophile Thermoanaerobacter brockii and the mesophile Clostridium beijerinckii.

Proteins play a pivotal role in thermophily. Comparing the molecular properties of homologous proteins from thermophilic and mesophilic bacteria is important for understanding the mechanisms of microbial adaptation to extreme environments. The thermophile Thermoanaerobacter (Thermoanaerobium) brockii and the mesophile Clostridium beijerinckii contain an NADP(H)-linked, zinc-containing secondary alcohol dehydrogenase (TBADH and CBADH) showing a similarly broad substrate range. The structural genes encoding the TBADH and the CBADH were cloned, sequenced, and highly expressed in Escherichia coli. The coding sequences of the TB adh and the CB adh genes are, respectively, 1056 and 1053 nucleotides long. The TB adh gene encoded an amino acid sequence identical to that of the purified TBADH. Alignment of the deduced amino acid sequences of the TB and CB adh genes showed a 76% identity and a 86% similarity, and the two genes had a similar preference for codons with A or T in the third position. Multiple sequence alignment of ADHs from different sources revealed that two (Cys-46 and His-67) of the three ligands for the catalytic Zn atom of the horse-liver ADH are preserved in TBADH and CBADH. Both the TBADH and CBADH were homotetramers. The substrate specificities and thermostabilities of the TBADH and CBADH expressed inE. coli were identical to those of the enzymes isolated from T. brockii and C. beijerinckii, respectively. A comparison of the amino acid composition of the two ADHs suggests that the presence of eight additional proline residues in TBADH than in CBADH and the exchange of hydrophilic and large hydrophobic residues in CBADH for the small hydrophobic amino acids Pro, Ala, and Val in TBADH might contribute to the higher thermostability of the T. brockii enzyme.

Journal Article↗
PubMed1997

Effect of total alkaloid of Peganum harmala L. in the treatment of experimental haemosporidian infections in cattle.

Cattle experimentally infected with Babesia bigemina or Theileria sergenti or mixed infestations of the two parasites were treated with Total Alkaloid of Peganum harmala L. The results showed that treatment was effective against B. bigemina infection, had a marked effect on the course of infection with T. sergenti and some effect on the course of the mixed infection.

Alkaloids↗
PubMed1997

Factors influencing MAC reduction after cardiopulmonary bypass in dogs.

BACKGROUND: Anaesthetic requirements may be reduced following surgery employing cardiopulmonary bypass (CPB). This study, in dogs, determined the role of a) volatile agents (enflurane [E] vs isoflurane [I]), b) oxygenator (bubble [B] vs membrane [M]), and c) presence [FL] vs absence [NoFL] of an in-line arterial filter in the bypass circuit in altering anaesthetic requirements following CPB. METHODS: Male mongrel dogs were anaesthetized with either enflurane (n = 24) or isoflurane (n = 24). They were randomly assigned to one of eight groups (n = 6 per group); Group 1 (E/B/FL), Group 2 (E/M/FL), Group 3 (E/M/NoFL), Group 4 (E/B/NoFL), Group 5 (I/M/FL), Group 6 (I/B/FL), Group 7 (I/M/NoFL) or Group 8 (I/B/NoFL). MAC was determined using the tail-clamp method at hourly intervals, twice before and three times after a one hour normothermic perfusion using aortoatrial cannulation and CPB. RESULTS: Prior to CPB, MAC was reproducible (enflurane: MAC1 2.17 +/- 0.29 vs MAC2 2.14 +/- 0.28%; isoflurane: MAC1 1.42 +/- 0.31 vs MAC2 1.41 +/- 0.33%) and differed among groups only for the volatile agent employed. Following CPB, MAC was reduced in all groups (P < 0.05 vs pre-CPB measurements) except Group 1 (E/B/FL). The degree of MAC reduction in other groups ranged from 39-64% and was not different based on type of agent employed, use of a membrane or bubble oxygenator, or presence or absence of an in-line arterial filter. CONCLUSION: In dogs, MAC reduction following CPB was variable, not related to type of volatile agent employed, use of a membrane or bubble oxygenator, or presence or absence of an in-line arterial filter. The explanation for reductions in anaesthetic requirements following CPB in this model remains speculative.

Anesthetics↗
PubMed1997

A comparison of different methods in predicting static pressure distribution in articulating joints.

Pressure distribution along the contact surface of an articulating joint model was analyzed using different numerical and analytical methods: a discrete rigid element method [rigid-body-spring-model (RBSM)], the finite element method (FEM), a simplified elasticity solution (SES) and the modified Hertzian (MH) theory. The FEM and MH methods modeled joints interposed with elastic layers, while the RBSM and SES methods assumed a simplified joint with a rigid convex indenter on an elastic concave surface. Results for an axisymmetric joint model indicate that all of these methods predict similar pressure distributions on joint surfaces. In non-axisymmetric deformation mode, the RBSM method and FEM calculation showed good agreement in contact pressure prediction. Compared to the other three methods, the RBSM is relatively simple and effective in predicting joint contact pressure under symmetric and non-symmetric loading. The computational efficiency of the RBSM method is particularly attractive for pre-operative planning of reconstructive surgical procedures in orthopaedics in which geometric changes dictate the eventual outcome of the surgery.

Biomechanical Phenomena↗
PubMed1997

Contribution of the eighth nerve and cranial nerve nuclei to the short-latency vestibular evoked potentials in cats.

The object of this study was to assess the contributions of the vestibular nerve and various cranial nerve nuclei to the short-latency vestibular evoked potentials in cat. The following nuclei were investigated: vestibular nuclei and the third, sixth, and tenth cranial nerve nuclei. In unilateral labyrinthectomized cats, we performed suboccipital craniectomy and partial cerebellectomy to place bipolar electrodes into the neural structures under investigation. The surface-recorded vestibular evoked potentials (far field) were compared with the potentials recorded intracranially in response to the same acceleration impulses. The exact locations were later confirmed histologically. Reversible lesions also were induced by injection of lidocaine 2%. The results indicate that the first wave of the vestibular evoked potentials originates in the vestibular nerve, and the second wave is mainly generated in the superior and medial vestibular nuclei. The third, sixth, and tenth cranial nerve nuclei apparently contribute to the later waves of the vestibular evoked potentials, particularly waves 3 and 4.

Abducens Nerve↗
PubMed1997

Infant mortality among various nationalities in the middle part of Guizhou, China.

This paper describes infant mortality, leading causes of death, and some associated factors among the Han, the Miao, the Bouyei and other minority nationalities in three counties of the middle part of Guizhou Province, China. The results showed that the overall infant mortality rate (IMR) in these areas was 125.7 per 1000 live births during 1985-1987. There existed a great disparity in IMR among different nationalities. The rate was 103.1 (Han), 148.8 (Miao), 161.2 (Bouyei) and 145.0 (other ethnic groups) per 1000 live births, respectively. The five leading causes of death in infants were respiratory diseases, neonatal tetanus, birth asphyxia, infectious diseases and diarrhoea. These causes of death combined resulted in an IMR of 104.1 per 1000 live births. However, these diseases varied in importance for infants of different nationalities. We considered the relationship between infant death and maternal and child health care. The location of birth, the kinds of birth attendants and utilization of health facilities might be associated with differentials of infant mortality among these nationalities. Maternal education was associated with infant survival, but it might not be the only factor in decreasing or eliminating the differential of IMR among various nationalities. Based upon the findings, it is urgent to improve maternal and child health care and investigate further cultural and sociological factors among various nationalities.

Anthropology, Cultural↗
PubMed1997

HPCE methods for the identification and quantitation of antibodies, their conjugates and complexes.

We review here much of the existing literature that deals with analysis, resolution, characterization, and (at times) quantitation of antibodies in capillary electrophoresis modes. Each major mode of CE shown applicable to antibody analysis is described, along with the major applications of that mode for antibodies. Discussions are presented as to the mechanisms of antibody resolution in CE, interactions of various buffer components with the proteins leading to resolution, and methods of quantitation for antibodies. The literature is critically reviewed with regard to true application of CE for antibody analysis, limitations, information possible, information implied, and which samples have actually been assayed by CE modes. The literature is critically reviewed up to and including 1996, both for the scientific and commercial literature, especially vendor applications and real world applications possible.

Animals↗
PubMed1997

T-2 toxin-induced apoptosis in lymphoid organs of mice.

Lymphoid organs of male and female mice of 4 strains (ICR: CD-1, BALB/c, C57BL/6 and DBA/2) were histologically and biochemically examined at 24 hours after oral inoculation of T-2 toxin (0, 2.5, 5 and 10 mg/kg b.w.). Light microscopically, dose-dependent decrease in number of lymphocytes was observed in the thymic cortex and splenic follicles. The nuclei of lymphocytes showed pyknosis or karyorrhexis, and they were positively stained by the modified TUNEL method which detects fragmented DNA in situ. Electron microscopic characteristics of damaged lymphocytes were shrinkage of the cell body, nuclear chromatin condensation and fragmentation. Agarose gel electrophoresis of DNA extracted from the thymus showed DNA fragmentation into nucleosome units, i.e. ladder formation. The above-mentioned findings clearly showed that T-2 toxin could induce apoptotic cell death in the lymphoid organs of mice. These changes were more prominent in female BALB/c and C57BL/6 mice.

Administration, Oral↗
PubMed1997

T-2 toxin-induced apoptosis in intestinal crypt epithelial cells of mice.

The characteristics of T-2 toxin-induced cell damage in the intestinal crypt epithelia was investigated in mice. Following T-2 toxin-inoculation (0, 2.5, 5 and 10 mg/kg b.w.), dead cells showing pyknosis were sporadically observed in the crypt epithelia, and the nuclei of these cells were strongly stained by the modified TUNEL method which detects fragmented DNA in situ. Electron microscopically, the dead cells were characterized by shrinkage of the cell body and condensation of nuclear chromatin frequently along the nuclear membrane, and such nuclei were sometimes fragmented into small pieces. These morphological characteristics are well consistent with those of apoptosis. The mitotic index in the crypt epithelia drastically decreased at 6 hours after T-2 toxin-inoculation (6 HAI), but thereafter it recovered to almost the same value with that in control mice at 48 HAI. On the other hand, the apoptotic index in the crypt epithelia increased with the lapse of time. Clear mouse strain- and sex-differences were detected in the apoptotic index but not in the mitotic index. This is the first report that T-2 toxin caused apoptotic cell death in the intestinal crypt epithelial cells.

Animals↗
PubMed1997

Transamination of 3-hydroxykynurenine to produce xanthurenic acid: a major branch pathway of tryptophan metabolism in the mosquito, Aedes aegypti, during larval development.

An electrochemically active compound was detected in the larvae of Aedes aegypti mosquitoes and progressive accumulation of this compound was observed during larval development. The compound was purified from mosquito larvae using various chromatographic techniques and spectral analysis of the purified compound resulted in its identification as xanthurenic acid. Production of xanthurenic acid results from the transamination of 3-hydroxykynuorenine, and analysis of the biochemical pathway in xanthurenic acid production revealed the presence of a particular transaminase that has a much higher specific activity to 3-hydroxykynurenine than to kynurenine in the mosquito larvae. Concentration of xanthurenic acid is closely related to the level of this transaminase activity. Results suggest that this particular transaminase plays an important role in regulating the level of 3-hydroxykynurenine in the mosquito, A. aegypti during larval development.

Aedes↗
PubMed1997

2/3 osteotomy for lengthening the mandible in dogs by gradual distraction.

Successful lengthening of the mandible by gradual distraction has been reported previously. There are various methods for osteotomy before distraction osteogenesis. In this paper, a new type of osteotomy, performed on growing dogs as a model, is reported. Ten mongrel dogs, aged 6 months, were studied. A unilateral 2/3 osteotomy was performed, and an external lengthening device was fixed to the mandible perpendicular to the osteotomy. Seven days after the operation, the mandible was lengthened by 1 mm per day. The dogs were sacrificed for histological study at the end of the distraction on days 14, 28, 56 and 120 following completion of the distraction.

Animals↗
PubMed1997

Rapid, simple and sensitive microassay for skeletal muscle homogenates in the functional assessment of the Ca-release channel of sarcoplasmic reticulum: application to diagnosis of susceptibility to malignant hyperthermia.

A microassay is demonstrated for functional characterization of the Ca(2+)-release channel (CRC) of sarcoplasmic reticulum (SR) of skeletal muscle using swine with susceptibility to malignant hyperthermia (MH). Diluted muscle homogenates, indo-1 and ratiometric dual-emission spectrofluorometry are used to monitor Ca(2+)-lowering activity in real-time in the presence and absence of ryanodine at exposures that open and close the CRC. Reactions are initiated with 50 microM CaCl2 to raise ionized Ca2+ concentration near 1 microM and MgATP to activate the Ca(2+)-ATPase pump. Oxalate is included to precipitate Ca2+ within the SR. The assay requires less than 30 mg muscle, which may be cryopreserved, and is completed within 20 min of thawing the tissue. Maximum SR Ca(2+)-ATPase pumping and CRC activities, degree of CRC activation, and Ca(2+)-buffering capacity can be determined. Using this assay we studied muscle from MH-susceptible swine and demonstrated that whereas maximal Ca(2+)-ATPase pumping and CRC activities are normal, the CRC activity after addition of a bolus of Ca2+ is 50% greater in heterozygotes and 100% greater in homozygotes for the MH mutation. Hypersensitivity to CRC agonists, such as caffeine, and an associated hyposensitivity to CRC antagonists such as Mg2+ is also demonstrated. Genotypes for the MH mutation site can be discriminated from each other by determining Ca(2+)-lowering activities and the effect of ryanodine on them.

Animals↗