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Biomedical subjects

A Li

Publications and source records attributed to A Li.

At least 181 records · Page 10Linked to original sources
PubMed1998

Ventilatory effects of glial dysfunction in a rat brain stem chemoreceptor region.

Glia are thought to be important in brain extracellular fluid ion and pH regulation, but their role in brain stem sites that sense pH and stimulate breathing is unknown. Using a diffusion pipette, we administered the glial toxin, fluorocitrate (FC; 1 mM) into one such brain stem region, the retrotrapezoid nucleus (RTN) for 45-60 min. This dose and time period were chosen so that the effects of FC would be largely reversible. Within minutes, tissue pH decreased, and respiratory output increased. Both recovered almost completely after cessation of FC administration. The response to systemic CO2 stimulation was unaffected by FC treatment compared with that following control diffusion. Anatomic analysis showed, at the center of FC administration, some small (mean diameter = 5.1 micrometer) cells that stained for DEAD Red, a marker for altered cell membrane permeability, and some fragmented glia (glial fibrillary acidic protein immunohistochemistry). The average RTN tissue volume that contained such DEAD Red-positive cells was 271 nl, approximately 23% of the volume of one RTN region. Reversible disruption of glia in the RTN, a region known to contain central chemoreception, results in an acidic local pH and in stimulation of respiratory output.

Animals↗
PubMed1998

Brain stem lesion size determined by DEAD red or conjugation of neurotoxin to fluorescent beads.

Neurotoxin microinjected into the retrotrapezoid nucleus of anesthetized rats decreases phrenic activity and eliminates the response to CO2. In unanesthetized rats, such treatment has no effect on awake, resting breathing and decreases CO2 sensitivity by 40% (M. Akilesh, M. Kamper, A. Li, and E. E. Nattie. J. Appl. Physiol. 82: 469-479, 1997). One important factor in explaining these disparate results is the actual size of the anatomic lesion. In the present study, we injected ibotenic acid into the retrotrapezoid nucleus of anesthetized rats and evaluated lesion size by using two new approaches: 1) DEAD red, a fluorescent probe that enters impaired cells through leaky membranes and binds to nucleic acids, and 2) conjugation of toxin to fluorescent beads. With the use of DEAD red, the region containing labeled dying cells was 313 +/- 104 nl (n = 4), six times larger than the initial injected volume, and the physiological effects on phrenic amplitude, the CO2 response, and blood pressure began within minutes and were substantial. With conjugated toxin, in theory, neuronal damage would be limited to the region of detectable fluorescence (49 +/- 10 nl; n = 4). Effects on phrenic amplitude, CO2 sensitivity, and blood pressure were absent until approximately 2 h postinjection. Control experiments, with 2 h of in vitro incubation of the neurotoxin-microbead conjugate and injection of the supernatant after centrifugation, showed similar results that suggest release of conjugated neurotoxin. We conclude that DEAD red provides a useful means to monitor neuronal impairment in acute studies in vivo. Conjugation of neurotoxin to microbeads may be less reliable in this regard.

Animals↗
PubMed1998

Saikosaponin b2 induces differentiation without growth inhibition in cultured B16 melanoma cells.

Treatment with 5 microM of saikosaponin (SS) b2 for 30 days was found to induce differentiation of B16 melanoma cells, with potentiation of expressions of melanogenesis and tyrosinase. To explore the mechanism of this effect, we observed the cell growth, cell cycle and morphology, and found that SSb2 did not affect any of these parameters. That is, SSb2 induced the differentiation of B16 melanoma cells without growth inhibition or cytotoxicity under conditions of low dose and long-term treatment. Phorbol ester, a protein kinase C (PKC) activator, markedly inhibited the expressions of melanogenesis and tyrosinase in both the control B16 melanoma cells and the long-term treated B16 melanoma cells. Down-regulation of the PKC activity may be involved in the effects of SSb2.

Animals↗
PubMed1998

Evolution of interstellar dust and its relevance to life's origin: laboratory and space experiments.

A scheme is presented for an analog investigation of long term irradiation of ices and organics following the cyclic evolution of interstellar dust. The irradiation is proposed to be performed at cryogenic temperatures on a space platform, and with an enhancement of the solar ultraviolet flux using a concave mirror, grating combination which eliminates the visual and infrared from the sample surface.

Carbon↗
PubMed1998

[Exploration for an early discriminant model of non-skeletal phase in endemic fluorosis exposed to coal-burning].

OBJECTIVE: To detect, diagnose and treat for endemic fluorosis earlier. METHODS: Six kinds of indices, such as environmental fluoride level, were collected from the population in epidemic and non-epidemic areas of endemic fluorosis with a 1:1 paired-match design. A discriminant analysis model was established by multivariate analysis. Levels of fluoride in environment and biological materials were determined by fluoride electrode method. Living condition of the subjects were measured and interviewed. Function of skeletons and joints was measured. Biochemical and enzyme indices were measured with reagent kits and gel electrophoresis. Other indices were measured by interview. All data collected were analyzed by SAS and MDAS computer software. RESULTS: There was significant overall difference between four kinds of discriminant functions, with an overall agreement of 85.78% (83.33% to 98.86%), based on resubstitution with sampled data. Posterior probabilities for new classification of sampled data automatically and randomly produced from a computer were 86.39% to 99.99%. CONCLUSION: The discriminant functions mentioned above, except for the third one with a too small sample size, can be used in early discrimination of endemic fluorosis caused by exposure to coal burning, or in evaluation for the effectiveness of pharmaceutical therapy, with a power of 95%.

Adolescent↗
PubMed1998

[Reconstruction of esophagus by microsurgical technique in forty-five cases].

Reconstruction and repair of atresia or defect of the upper portion of esophagus is difficult. From November 1980 to December 1997, forth-five cases, consisting 35 males and 10 females, were treated with microsurgical technique. The 45 patients fell into the following groups as esophageal atresia of various causes in 21 cases, anastomotic fistula or stenosis following reconstruction of esophagus in 7 cases and late carcinoma of esophagus in 17 cases. The types of reconstruction consisted of transfer of free jejunum with its lower portion carrying a vascular pedicle in 24 cases, free transfer of jejunal graft in 15 cases, free vascularized jejunal graft in 2 cases and free vascularized tubular skin graft in 4 cases. After a follow-up of 6-19 months besides eight cases died from late esophageal carcinoma, thirty-seven cases were survived and could take food by mouth. All of the benign cases could return to work. In patients having late esophageal carcinoma, the operative procedure could improve the life quality and facilitate chemotherapy and radiotherapy.

Adolescent↗
PubMed1998

[Expression of mRNA for endothelin-1 and its receptors in rat kidney after burn injury].

OBJECTIVE AND METHODS: We studied expression of messenger RNAS for endothelin-1 (ET-1) and its receptor subunits (ETA, ETB) by northern blot hybridization and in situ hybridization in rat kidney following 30% TBSA full thickness burns. RESULTS: Expressions of that ET-1, ETA, and ETB mRNA expression are all evidently increased at 1 hour postburn. ET-1 and ETA reached its maximal mRNA expression at 3 hour postburn. ET-1 mRNA distributed primarily on glomerular endothelial cells and tubular epithelial cells in cortex. ETA mRNA predominantly presented on smooth muscle cells of small arterioles in renal cortex. However, the peak time of ETB mRNA expression is at 6 hour postburn and mainly localized on renal medullary tubular epithelial and collecting duct cells. CONCLUSION: These findings suggest that 1. ET-1 acts principally as a local paracrine/autocrine peptide. 2. Increased ET-1 that activated ETA receptors accentuated expression on vascular smooth muscle cells will result in renal cortex ischemia. 3. Accentuated expression of ETB receptor on tubular epithelial cells may induce renal natriuretic action and reduction of water execretion. 4. Increased ET-1 and its receptors in kidney play an important role in the pathogenesis and development of renal function impairment following severe burn.

Animals↗
PubMed1998

Transsphenoidal microsurgical removal of large pituitary adenomas.

OBJECTIVE: To retrospectively analyze the diagnostic modes, transsphenoidal microsurgical technique and outcomes of 145 patients with pituitary macroadenoma or giant pituitary adenoma. METHODS: A total of 145 patients suffering from pituitary macroadenoma or giant pituitary adenoma with suprasellar extension were performed with transsphenoidal microsurgery in our department. Diagnoses were made by CT or MRI scanning. All adenomas had suprasellar extension (extension size: > 10 mm). Operations were performed via either sublabio-septo-sphenoidal approach or naso-vestibulo-sphenoidal approach under microscope. During operation, a subarachnoid catheter was inserted into the lumbar cistern, via the catheter saline was slowly injected to increase the intracranial pressure (ICP) and to deliver the suprasellar tumor into the operative field for easy removal. RESULTS: The gross total removal of adenoma in 102 patients (70.4%) and subtotal removal in 35 patients (24.1%) were achieved; partial removal was carried out in the remaining 8 patients (5.5%) with fibrous or dumbbell-shaped adenomas. There were no deaths after surgery. Long-term follow-up observation (median: 3.5 years) in 132 patients revealed good recovery in 93 (70.5%) and late recurrence in 39 (29.5%). Those patients with tumor recurrence underwent reoperation, drug therapy, radiotherapy, and radiosurgery either alone or in combination. CONCLUSION: Except for fibrous and dumbbell-shaped ones, microsurgical technique via transsphenoidal approach is a safe and effective way to remove large pituitary adenomas.

Adenoma↗
PubMed1998

[Effects of processing on toxicity and pharmacological action of flos Genkwa].

Daphne genkwa can not be taken unless the toxicity is removed. The study on the effect of processing on the toxicity and pharmacological action of Flos Genkwa has shown that the toxicity of vinegar-processed Flos Genkwa is lower than that of the rude drug, but the pharmacological action is better. Both genkwanin and its vinegar-processed imitation have antitussive and expectorant actions without marked difference in efficacy. Both yuanhuacine and its vinegar-processed imitation could cause contraction of the extracorporeal womb and the intestinal canal, and the efficacy is almost similar in the concentration of 1:10(-5)-10(-6). The gestational womb was observed more sensitive than the normal one.

Animals↗
PubMed1998

[The effects of Chinese medicine herb mixture on cell-mediated immune functions and four kinds of acute-phase reaction proteins in burn patients].

OBJECTIVE: To search for immunomodulators to improve postburn immune function disorder. METHOD: We studied the Chinese medicinal herbs. On the basis of previous data, we prepared a kind of Chinese medicinal herbal mixture and studied its effects in vivo and in vitro. RESULT: The mixture could restore the cell-mediated immune response such as the production of interleukin 2 and the T cell proliferative ability, and could also adjust the levels of serum acute-phase reaction proteins, i.e, haptoglobin, prealbumin, transferrin and alpha 1-acid glycoprotein. CONCLUSION: The Chinese herbal mixture showed immune regulatory effects on body defence imbalance and also on acute phase reaction proteins in burn patients.

Acute-Phase Proteins↗
PubMed1998

Factor Xa cleavage of tissue factor pathway inhibitor is associated with loss of anticoagulant activity.

Tissue factor:factor VIIa induced activation of blood coagulation is inhibited by the complex between factor Xa and tissue factor pathway inhibitor (factor Xa:TFPI). We recently reported that phospholipid-bound factor Xa reduces the high binding affinity of factor Xa:TFPI for negatively charged phospholipids by a partial degradation of TFPI (17). The present study was undertaken to elucidate the factor Xa cleavage sites in TFPI and to delineate the consequences of this proteolysis with respect to the inhibitory activity of factor Xa:TFPI. We found that phospholipid-bound factor Xa cleaves in TFPI the peptide bonds between Lys86-Thr87 and Argl99-Ala200. Interestingly, Arg199 is the P1 residue of the third Kunitz-type protease inhibitor domain. The fast cleavage of the Arg199-Ala200 bond results in a 50-70% reduction of the anticoagulant activity of factor Xa:TFPI, as determined with a dilute tissue factor assay, but is not associated with a diminished inhibitory activity of factor Xa:TFPI towards TF:factor VIIa catalyzed activation of factor X. On the other hand, the slower cleavage of the Lys86-Thr87 peptide bond was associated with both a diminished anticoagulant and anti-TF:factor VIIa activity. Dissociation of factor Xa from the cleaved TFPI was not observed. These data provide evidence for a dual role of factor Xa since it is the essential cofactor in the TFPI-controlled regulation of TF-dependent coagulation as well as a catalyst of the inactivation of TFPI.

Anticoagulants↗
PubMed1998

Proteolysis of tissue factor pathway inhibitor (TFPI) by plasmin: effect on TFPI activity.

An important regulator of the initiation of blood coagulation is the plasma glycoprotein, tissue factor pathway inhibitor (TFPI). TFPI inhibits factor Xa and factor VIIa/tissue factor complex, thereby dampens the proteolytic cascade of the tissue factor pathway. Plasma clot lysis is primarily mediated by the fibrinolytic enzyme, plasmin, which is generated through limited proteolysis of plasminogen by endogenous or exogenously administered plasminogen activators. In this study, the interaction of plasmin with recombinant E. coli-derived TFPI (rTFPI) was examined. Plasmin was found to cause a time and concentration dependent proteolysis of rTFPI, resulting in the decrease of anti-factor Xa (measured by chromogenic substrate assay) and anticoagulant (measured by tissue factor-induced clotting assay) activities. Amino-terminal sequencing of the proteolytic fragments revealed that plasmin cleaved rTFPI at K86-T87, R107-G108, R199-A200, K249-G250, and K256-R257. Western blot analysis showed that proteolysis of exogenously added rTFPI also occurred in plasma supplemented with urokinase, and this is accompanied by decrease of anticoagulant activity. These changes were abolished by addition of aprotinin, an inhibitor of plasmin. These data indicate that TFPI is susceptible to proteolysis when plasma fibrinolytic system is activated. The results taken together suggest that plasmin degradation of TFPI may contribute to rethrombosis after thrombolysis, and may contribute to the variability of the efficacy of TFPI in various thrombolysis/reocclusion studies reported previously.

Amino Acid Sequence↗
PubMed1998

Stability of secondary structural elements in a solvent-free environment. II: the beta-pleated sheets.

The stability of single beta-strands and multistrand beta-pleated sheets as elements of secondary structure is examined in the absence of intermolecular interactions. Such experimental conditions (e.g., complete removal of solvent molecules and counterions) are achieved by placing the peptide ions in the gas phase. The metastable multiply- charged peptide ions produced by electrospray ionization undergo unimolecular dissociation. Intercharge repulsion within the precursor ions gives rise to the elevated kinetic energy of fragment ions, which is measured using Mass-analyzed Ion Kinetic Energy (MIKE) spectrometry. Intercharge distances calculated based on these measurements are compared to the numbers derived from molecular mechanics calculations with charge site assignments based on relative proton affinities. Evidence is presented suggesting that single beta-strands form collapsed structures in the absence of solvents, while multistrand beta-pleated sheets are likely to retain "native-like" secondary structures under the same conditions. These results indicate that intramolecular hydrogen bonds are the major factor determining the three-dimensional arrangements of polypeptides in the gas phase, compensating both long- and short-range electrostatic repulsions. This is in good agreement with our earlier findings (Proteins 27:165170, 1997) concerning stability of helical conformation of melittin in the absence of solvent.

Mass Spectrometry↗
PubMed1998

Importance of Candida species other than Candida albicans as opportunistic pathogens.

Candida species other than C. albicans have become a significant cause of infection in humans. Several of the more commonly isolated of these species are less susceptible to commonly used azole antifungal drugs, a factor that poses significant difficulties for effective treatment. The modern mycology laboratory has an important role to play in several aspects relating to these organisms, including therapy, detection, identification and epidemiological analysis. The application of molecular techniques and phylogenetic analysis has led to the identification of a new species of Candida associated with mucosal candidiasis in HIV-infected individuals named Candida dubliniensis, the clinical significance of which is currently under investigation. Molecular techniques are also being applied to the analysis of determinants involved in pathogenicity of species such as Candida glabratta. These approaches should lead to a better understanding of these organisms and there ability to cause disease and should also provide more effective treatment.

AIDS-Related Opportunistic Infections↗
PubMed1997

Investigation of the enzymatic mechanism of the yeast chorismate mutase by docking a transition state analog.

The structure of the complex of the chorismate mutase from the yeast Saccharomyces cerevisiae with a transition state analog is constructed using a suite of docking tools. The construction finds the best location for the active site in the enzyme, and the best orientation of the analog compound in the active site. The resulting complex shows extensive salt links and hydrogen bonds between the enzyme and the compound, including those mediated by water molecules. A network of polar interactions between amino acid residues is found to solidify the active site of the enzyme. The enzymatic mechanism suggested for a bacterial chorismate mutase, that the active site is by design capable of selecting an active conformer of the substrate, and of stabilizing the transition state, is apparently intact in the yeast enzyme. No direct evidence is found to support an alternative mechanism which involves specific catalytic groups, although the possibility is not eliminated. This finding reinforces the notion of a function being evolutionarily conserved via a common mechanism, rather than via sequential or structural homology.

Binding Sites↗
PubMed1997

Rapid determination of the complexity of cDNA bands extracted from DDRT-PCR polyacrylamide gels.

A band extracted from a differential display polyacrylamide gel often represents a composite of heterogeneous products. We have developed a non- radioactive method to simply and rapidly analyse its complexity. A fluorescent restriction enzyme fingerprint of the composite mixture is generated. The number of individual bands observed in this fingerprint indicates the complexity of the re-amplified cDNA mixture. Restriction fingerprints of the inserts of cDNA subclones derived from the re-amplified cDNA mixture are compared to the composite fingerprint to select those representing the most intense bands in the composite. This dramatically reduces the number of clones required for further characterisation.

Base Sequence↗
PubMed1997

Synergistic neutralization of a chimeric SIV/HIV type 1 virus with combinations of human anti-HIV type 1 envelope monoclonal antibodies or hyperimmune globulins.

A panel of 14 human IgG monoclonal antibodies (MAbs) specific for envelope antigens of the human immunodeficiency virus type 1 (HIV-1), 2 high-titer human anti-HIV-1 immunoglobulin (HIVIG) preparations, and 15 combinations of MAbs or MAb/HIVIG were tested for their ability to neutralize infection of cultured human T cells (MT-2) with a chimeric simian immunodeficiency virus (SHIV-vpu+), which expressed HIV-1 IIIB envelope antigens. Eleven MAbs and both HIVIGs were neutralizing. When used alone, the anti-CD4-binding site MAb b12, the anti-gp41 MAb 2F5, and the anti-gp120 MAb 2G12 were the most potent. When combination regimens involving two MAbs targeting different epitopes were tested, synergy was seen in all paired MAbs, except for one combination that revealed additive effects. The lowest effective antibody concentration for 50% viral neutralization (EC50) and EC90 were achieved with combinations of MAbs b12, 2F5, 2G12, and the anti-V3 MAb 694/98D. Depending on the combination regimen, the concentration of MAbs required to reach 90% virus neutralization was reduced approximately 2- to 25-fold as compared to the dose requirement of individual MAbs to produce the same effect. Synergy of the combination regimens implies that combinations of antibodies may have a role in passive immunoprophylaxis against HIV-1. The ability of SHIV to replicate in rhesus macaques will allow us to test such approaches in vivo.

Animals↗