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Biomedical subjects

A Li

Publications and source records attributed to A Li.

At least 235 records · Page 13Linked to original sources
PubMed1996

Serum haptoglobin suppresses T-lymphocyte functions following burns.

It is well known that serum immunosuppressive factors play an important role in the mechanism of postburn immunosuppression. This study was intended to investigate the effect of haptoglobin, purified from the serum of burned patients by affinity chromatography, on the proliferation and interleukin-2 (IL-2) secretion of normal murine thymocytes induced by ConA and the proliferation of IL-2 dependent cell line (CTLL-2) stimulated by recombinant human IL-2, so as to elucidate the role of serum haptoglobin in postburn T-lymphocyte dysfunction. The results showed that purified haptoglobin, at the level equivalent to the concentration found in serum of burned patients, significantly inhibited the proliferation and IL-2 secretion of normal murine thymocytes as well as CTLL-2 proliferation; whereas it exhibited no immunosuppressive effects at the level equivalent to the concentration found in serum of normal volunteers. According to the results reported here, it is suggested that extraordinary increase in serum haptoglobin level may be an important factor of impaired T-lymphocyte responses following burns.

Animals↗
PubMed1996

[Dynamic changes of endothelin in sera of rats at early burn stage and its effects on endothelial cell permeability in vitro].

The dynamic changes of endothelin in sera of early burnt rats and the effects of endothelin-1 on the permeability of vascular endothelial cells were investigated. In the early phase of 30% (II degree) total body surface area (TBSA) burn rat model, we measured the concentration of endothelins in plasma, the water contents in main organs and the permeability of endothelial monolayer cultured on micropore membrane to Hank's solution or 5 g/L albumin Hank's solution. Endothelin concentration in burnt rat sera was firstly increased dramatically, showing a peak at 6 hours postburn, and then remained significantly higher than the basic level (P < 0.01). The changes of endothelin were correlated with the alteration in water contents in main organs after burn. Moreover, if the cultured endothelial cells were exposed to 0, 1, 10, 100 nmol/L endothelin 1 for 60 min, it was found that the filtration volume (Jv) and the filtration coefficient (Kf) of endothelial monolayer were significantly enhanced as determined by either Hank's or albumin (5 g/L) perfusion, while the osmotic reflection coefficient (sigma) (to protein) decreased in a dose-dependent pattern. The present results suggest that the postburn elevated endothelin may not only mediate the blood flow distribution via potent vasoconstriction, but also directly increase the vascular permeability. The mechanism(s) of the latter event needs to be further clarified.

Animals↗
PubMed1996

[Determination of placental alkaline phosphatase (PLAP) for detecting the damages of alveolar type I cells caused by smoke inhalation].

The placental alkaline phosphatase (PLAP) is a marker enzyme of alveolar type I cells. To evaluate the damages of alveolar type I cells and its relations with the development of acute lung injury caused by smoke inhalation, the present study was designed to observe the dynamic changes in PLAP contents in plasma and bronchoalveolar lavage fluid (BALF). Following the induction of smoke inhalation injury in rat, the arterial blood gas levels, lung water volume, total protein and albumin contents in BALF, and PLAP contents in plasma and BALF were determined respectively in normal control and injured animals at 2, 6, 12 and 24 h after injury. The pathomorphology of lung tissues was also observed. It was found that after smoke inhalation, animals showed acute respiratory failure and serious pulmonary edema. The total protein and albumin levels in BALF increased markedly. Both PLAP contents in plasma and BALF also increased dramatically, and there was a significant positive correlation between the changes in the PLAP and the total protein contents in BALF. The pathomorphologically serious structural damage of alveolar type I cells were also found. PLAP may be not only a marker of alveolar type I cells injury, but also interrelated with the permeability increase of alveolar-capillary membrane after smoke inhalation.

Alkaline Phosphatase↗
PubMed1996

[Multiple organ failure in burn patients combined with inhalation injury].

To define the clinical features and prevention and treatment of multiple organ failure (MOF) developed in burn patients combined with inhalation injury, a retrospective clinical study on 4834 burn patients admitted into the Institute from Jan, 1977 to Aug, 1991, in which 366 cases sustained inhalation injury, was performed. It was shown that postburn MOF occurred in 115 cases among the 4834 victims, with an incidence of 2.38%. However, of the 366 cases with inhalation injury 76 were complicated with MOF, an incidence as high as 20.77%, approximately occupying two-thirds of the postburn MOF. The incidence and mortality of MOF were higher when there was inhalation injury. It occurred earlier. More respiratory complications, higher incidence of lung and cardiac failure as well as severe shock were observed. Moreover, hypoxemia and acidosis were found to be more severe in MOF patients with inhalation injury than those without. It is suggested that good control of inhalation injury and burn shock, as well as the ischemic-hypoxic damage of visceral tissues might be of great importance for the prevention and treatment of MOF in burn patients combined with inhalation injury.

Adult↗
PubMed1996

[Anti-tumor effects of heiji (radix Astilbes chinensis].

The experimental results indicate that the herb Heiji is able to suppress the growth of transplantable tumor (S180) in mice by 30%-51% (P < 0.01), prolong the vital stage of the EAC transplanted mice by 44% (P < 0.01) and raise the lymphocyte transformation rate in lower concentrations in vivo. It follows that Heiji has positive anti-tumor effects and deserves further research as a new anti-tumor herb.

Animals↗
PubMed1996

[An experimental study on the anticancerous effects of CD3-TIL derived from human primary hepatic carcinoma].

In this study, CD3-TIL produced by in vito induction with CD3 and IL-2 (CD3-TIL) was compared with TIL stimulated by only IL-2 (TIL) in their in vitro proliferation, and both in vitro and in vivo anticancerous effects. It was found that CD3 at the concentration of 100 ng/ml was the most suitable stimulus of in vitro TIL proliferation (CD3-TIL) which was significantly greater than that by simple IL-2 stimulation. Also in vitro anticancerous activity of CD3-TIL was greater than TIL. CD3-TIL significantly inhibited tumor growth, causing shrinkage of tumor mass, and prolonging the life span of the nude mouse with tumor burden.

Animals↗
PubMed1995

Functional assay of plasma antithrombin using polyethylene glycol (PEG) defibrinated plasma.

Polyethylene glycol(PEG) was used to precipitate fibrinogen to prepare defibrinated plasma in the two stage clotting assay of antithrombin activity. Five percent PEG-8000 precipitated fibrinogen from plasma without loss of antithrombin activity in the defibrinated plasma. Fibrin degradation products(FDP) as high as 640 ug/ml did not interfere the two stage clotting assay using PEG defibrinated plasma possibly because part of FDP was precipitated by PEG in the process of plasma defibrination. The two stage clotting assay was very sensitive to the changes of antithrombin activity in the range of 60%-100% of normal level. The assay was reproducible and correlated with chromogenic assay. The decrease of plasma antithrombin activity in a baboon septic shock model was demonstrated with this assay.

Animals↗
PubMed1995

Neurotensin increases the cationic conductance of rat substantia nigra dopaminergic neurons through the inositol 1,4,5-trisphosphate-calcium pathway.

Whole-cell patch-clamp recordings were used to investigate electrophysiological effects of neurotensin on acutely isolated dopaminergic (DA) neurons of the rat substantia nigra pars compacta (SNC). During current-clamp recordings, neurotensin depolarized DA neurons and triggered action potentials. Under voltage-clamp recordings, neurotensin evoked an inward current at a holding potential of -50 mV. Neurotensin-induced inward currents reversed the direction at -5 mV and became smaller as the membrane potential was hyperpolarized from -75 mV. With potassium-free recording solutions, neurotensin evoked voltage-insensitive cationic currents. With sodium-free external solution, neurotensin also caused inward currents by reducing the inwardly rectifying potassium conductance. Neurotensin-induced inward currents mainly resulted from an increase in a non-selective cationic conductance. Neurotensin-evoked cationic currents were inhibited by the intracellular perfusion of 1 mM guanosine-5'-O-(2-thiodiphosphate). In DA neurons internally perfused with 0.5 mM guanosine-5'-O-(3-thiotriphosphate), the cationic current produced by neurotensin became irreversible. Pretreating DA neurons with 500 ng/ml pertussis toxin (PTX) did not significantly affect the ability of neurotensin to evoke cationic currents. Internal perfusion of heparin (2 mg/ml), an inositol 1,4,5-trisphosphate (IP3) receptor antagonist, and buffering intracellular calcium with the Ca(2+)-chelator BAPTA (10 mM) suppressed neurotensin-induced cationic currents. Dialyzing DA neurons with protein kinase C (PKC) inhibitors, staurosporine and PKC(19-31), failed to prevent neurotensin from evoking cationic currents. It is concluded that PTX-insensitive G-proteins mediate neurotensin-induced enhancement of the cationic conductance of SNC DA neurons.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Gallbladder mucosal protein secretion during development of experimental cholecystitis.

The development of experimental cholecystitis produced by lysophosphatidylcholine is associated with reversal of the normal absorptive characteristics of gallbladder mucosa, resulting in the intraluminal accumulation of water, glycoprotein, and protein. The purpose of the present study was to attempt to ascertain if the protein leaks into the lumen because of the cytolytic properties of lysophosphatidylcholine or if it is due to an active secretory process and to characterize the protein produced. Experiments were performed on anesthetized cats undergoing gallbladder perfusion with and without lysophosphatidylcholine. The amount of protein in the perfusate was measured and albumin clearance from blood to gallbladder lumen was calculated with and without the administration of vesicular transport inhibitors. In separate experiments, control and lysophosphatidylcholine (LPC) produced gallbladder perfusates were collected and the protein subjected to SDS-PAGE to ascertain the nature of the protein secreted. Inhibitors of both microtubular and microfilament activity decreased the protein accumulation and clearance produced by lysophosphatidylcholine. Gallbladder white blood cell accumulation and inflammation as evaluated by beta-glucuronidase and prostaglandin E levels were not significantly altered by cytochalasin or colchicine administration. Lysophosphatidylcholine also produced significant increases in perfusate LDH levels. The protein produced was primarily a 66-kDa protein. Transfer of the protein to a nitrocellulose membrane and immunoblotting with anti-albumin antibody demonstrated that the protein was albumin. The results suggest that during the development of cholecystitis, lysophosphatidylcholine produces albumin accumulation in the gallbladder primarily by inducing an active secretory process resulting in gallbladder distension.

Albumins↗
PubMed1995

Lysophosphatidylcholine-stimulated protein and glycoprotein production by human gallbladder mucosal cells.

It has been demonstrated in experimental cholecystitis in cats produced by lysophosphatidylcholine that the development of inflammation is associated with the exsorption of a large amount of protein into the gallbladder lumen. It was subsequently demonstrated that in feline experimental cholecystitis the protein produced was albumin and that its production was decreased by vesicular transport inhibitors, suggesting an active secretory process. In the present study, the effect of lysophosphatidylcholine on protein production by fresh, isolated human gallbladder mucosal cells was evaluated. Isolated gallbladder mucosal cells were incubated with [14C]leucine for 24 hr in tissue culture medium. The cells readily incorporated the radioactive label into cellular protein, a process inhibited by cycloheximide. Exposure of the cells to lysophosphatidylcholine for 1 hr in buffer solution resulted in loss of intracellular protein into the buffer solution. Exposure of the cells for 1 hr prior to lysophosphatidylcholine administration to vesicular transport inhibitors, colchicine, and cytochalasin B and to 4 degrees C culture conditions failed to alter the lysophosphatidylcholine-produced passage of the 14C label extracellularly. SDS-PAGE evaluation of the protein produced demonstrated that human gallbladder mucosal cells continuously produced a 66-kDa protein that was not increased by increasing concentration of lysophosphatidylcholine and a 14-kDa protein that increased with increasing concentrations of lysophosphatidylcholine. Employing Western blotting with specific antibodies, the 66-kDa protein was demonstrated to not be albumin but a 66-kDa glycoprotein, and the 14-kDa protein was demonstrated to contain phospholipase A2. Human gallbladder mucosal cells produced a protein and glycoprotein in response to lysophosphatidylcholine by a mechanism not related to vesicular transport.

Carbon Radioisotopes↗
PubMed1995

Safety and immunogenicity study of the auxotrophic Shigella flexneri 2a vaccine SFL1070 with a deleted aroD gene in adult Swedish volunteers.

The live auxotrophic Shigella flexneri 2a vaccine strain SFL1070 with a deleted aroD gene was given orally to 37 adult Swedish volunteers who received three doses within 5 days. Each dose comprised 1 x 10(5) (n = 9), 1 x 10(7) (n = 10), 1 x 10(8) (n = 9) or 1 x 10(9) (n = 9) c.f.u. S. flexneri SFL1070. One volunteer vaccinated with 1 x 10(7) and three vaccinated with 1 x 10(8) c.f.u. reported mild gastrointestinal symptoms after the first dose. Vaccination with 1 x 10(9) c.f.u. caused abdominal pain and watery diarrhoea in four volunteers who all recovered spontaneously within 72 h. S. flexneri SFL1070 was not recovered from volunteers given 1 x 10(5) c.f.u., but was shed in faeces by six volunteers vaccinated with 1 x 10(7), by all nine vaccinated with 1 x 10(8), and by seven volunteers vaccinated with 1 x 10(9) c.f.u. The mean excretion time was 2.6 (range 0-4) days in the 1 x 10(8) and the 1 x 10(9) groups. Serum antibody responses against either S. flexneri 2a and Y lipopolysaccharides (LPSs) or Shigella invasion plasmid antigens (Ipa) were seen in eight volunteers vaccinated with 1 x 10(9) (p < 0.01 to p < 0.05 for mean relative titres of IgA and IgG against S. flexneri 2a and Y LPSs), in four vaccinated with 1 x 10(8), and in two and one volunteers each vaccinated with 1 x 10(7) and 1 x 10(5) c.f.u. of S. flexneri SFL1070. Intestinal sIgA responses to the same antigens were elicited in all volunteers in the 1 x 10(9) and the 1 x 10(8) groups, and in six and one volunteers vaccinated with 1 x 10(7) and 1 x 10(5) c.f.u., respectively. The sIgA responses against S. flexneri 2a and Y LPSs were significant in all but the 1 x 10(5) group (p < 0.01 to p < 0.05). Significant antibody-secreting cell (ASC) responses specific to S. flexneri 2a LPS were seen in peripheral blood from eight volunteers each in the 1 x 10(9) and 1 x 10(8) groups and from five volunteers vaccinated with 1 x 10(7) c.f.u. (p < 0.01 to p < 0.05). The number of volunteers showing anti-Shigella Ipa ASC responses in these groups were five (p < 0.01 to p < 0.05), three and one, respectively.(ABSTRACT TRUNCATED AT 400 WORDS)

Administration, Oral↗
PubMed1995

A preliminary exploration of the relationship between tumour necrosis factor (TNF) and monocytic in vitro production of interleukin-1 (IL-1) and internal organ dysfunction in severely burned patients.

Biological assays were adopted in this study to examine the changes in serum tumour necrosis factor (TNF) activity and blood monocytic in vitro production of interleukin 1 (IL-1) in 24 severely burned patients. The myocardial and hepatic enzymes (which included aspartate aminotransferase (AST), creatine kinase (CPK), lactate dehydrogenase (LDH), alpha hydroxybutyric dehydrogenase (alpha-HBDH) and alanine amino-transferase (ALT) and some indices of biochemical metabolism (including lactic acid (LA), total protein (TP), albumin (Alb) and colloid osmotic pressure (COP)) were simultaneously measured. The results showed an evident increase in serum TNF activity and a decrease in in vitro production of IL-1 postburn; all the changes in TNF and IL-1 were correlated significantly with those of myocardial and hepatic enzymes in MOF patients. Furthermore, there were marked fever, hypoproteinaemia, tissue ischaemic and hypoxic symptoms such as hyperlacticaemia, and signs reflecting tissue hypercatabolic states. These all suggested that TNF and IL-1 might play important roles in the development of MOF.

Adolescent↗
PubMed1995

Investigation of the solution structure of chymotrypsin inhibitor 2 using molecular dynamics: comparison to x-ray crystallographic and NMR data.

The native solution structure and dynamics of chymotrypsin inhibitor 2 (CI2) have been studied using a long (5.3 ns) molecular dynamics (MD) simulation without any imposed restraints. The majority of the experimentally observed spin-spin coupling constants, short- and long-range nuclear Overhauser effect (NOE) cross peaks and the amide hydrogen exchange behavior were reproduced by the MD simulation. This good correspondence suggests that the major structural features of the protein during the simulation are representative of the true protein structure in solution. Two water molecules formed hydrogen bond bridges between beta2 and beta3, in agreement with X-ray crystallographic data and a recent reassessment of the solution structure using time-averaged NMR restraints during MD refinement. The active-site loop of the protein displayed the greatest structural changes and the highest mobility. When this loop region was excluded, the average Calpha r.m.s. deviation of the simulated solution structures from the crystal structure was approximately 1.5 Angstrom from 0.5 to 5.3 ns. There is structural heterogeneity in particular regions of the NMR-derived solution structures, which could be a result of imprecision or true internal motion. A study of the distribution of mobility through the protein allows us to distinguish between these two alternatives. In particular, deviations in the active-site loop appear to be a result of heightened mobility, which is also supported by good correspondence between calculated and experimental S2 N-H order parameters. On the other hand, other ill-defined regions of the NMR-derived structures are well defined in the simulation and are probably the result of a lack of structural restraints (i.e. NOEs), as opposed to reflecting the true mobility.

Computer Simulation↗
PubMed1995

Rat retrotrapezoid nucleus iono- and metabotropic glutamate receptors and the control of breathing.

We injected 10 nl (unilateral) of glutamate receptor antagonists or agonists into the region of the retrotrapezoid nucleus and measured the phrenic nerve and blood pressure responses. The rats were chloralose-urethan anesthetized, paralyzed, vagotomized, and ventilated, and each injection location was verified anatomically. Integrated phrenic amplitude was most reliably affected. The N-methyl-D-aspartic acid (NMDA) antagonists 2-amino-5-phosphonopentanoic acid and 6-cyano-7-nitroquinoxaline-2,3-dione (which affects both NMDA and non-NMDA receptors) both decreased baseline eucapnic phrenic amplitude and the CO2 response. Glutamate increased phrenic amplitude in a dose-dependent manner, an effect blocked by prior injection of the NMDA and non-NMDA antagonists at the same site. The response duration depended on the duration of the glutamate injection: responses to 3-s injections lasted a few minutes, and responses to 60-s injections lasted for > 30 min. The long-lasting effect was reproduced by injection of the metabotropic agonist 1(S),3(R)-aminocyclopentanedicarboxylic acid at 0.01-0.02 times the glutamate dose. We conclude that the rat retrotrapezoid nucleus has an endogenous source of glutamate that maintains eucapnic phrenic output and allows expression of the CO2 response. NMDA and possibly non-NMDA receptors are involved. Their stimulation increases phrenic output via ionotropic and metabotropic receptor processes with the latter resulting in long-lasting phrenic stimulation.

Anesthesia↗
PubMed1995

Prolonged stimulation of respiration by brain stem metabotropic glutamate receptors.

Stimulation of metabotropic glutamate receptors (mGluRs) in the retrotrapezoid nucleus (RTN) of chloralose-urethan-anesthetized rats by the mGluR agonist (1S,3R)-aminocyclopentanedicarboxylic acid [(1S,3R)-ACPD; 10 nl, 1 mM] increases integrated phrenic nerve amplitude (PNA) for > 60 min. Here we ask if the mGluR antagonist (+-)-alpha-methyl-4-carboxyphenylglycine [(+-)-MCPG] can block this effect. Using multibarreled micropipettes, we first identified RTN sites that affect respiration by noting short-lived stimulation of PNA produced by brief-duration injection of glutamate (10 nl, 100 mM), a presumed ionotropic receptor response. We then injected the active or inactive isomer of (+-)-MCPG (10 nl, 10 mM) followed by (1S,3R)-ACPD or by a long-duration (60-s) injection of glutamate (10 nl, 100 mM) at the same site. Each injection location was verified anatomically. The active antagonist (+-)-MCPG itself had no significant effect on PNA, but it blocked 1) subsequent (1S,3R)-ACPD-induced PNA stimulation for 99 +/- 11 (SE) min and 2) the PNA response to 60-s glutamate injection for 66 +/- 6 min. The inactive form (-)-MCPG had no effect on (1S,3R)-ACPD-induced PNA stimulation. We conclude that 1) RTN mGluRs may be involved in respiratory control, 2) RTN mGluRs are not active in eupnea, and 3) stimulation of RTN mGluRs may require prolonged glutamate release.

Analysis of Variance↗