Search PubMed⌕ Search

Biomedical subjects

G Li

Publications and source records attributed to G Li.

At least 919 records · Page 51Linked to original sources
PubMed1993

Conserved transducer coupling but different effector linkage upon expression of the myeloid fMet-Leu-Phe receptor in insulin secreting cells.

In neutrophils fMet-Leu-Phe activates phospholipase C via a pertussis toxin sensitive G-protein and induces granule secretion. We have transfected a human cDNA sequence encoding the fMet-Leu-Phe receptor into the insulin secreting cell line RINm5F to study receptor-effector coupling with special regard to secretion. Stable overexpression resulted in membrane hyperpolarization, reduction of cAMP accumulation and inhibition of insulin secretion upon exposure of cells to fMet-Leu-Phe with EC50 values in the pmol range. As in the neutrophil, nanomolar concentrations of ligand induced membrane depolarization and activation of phospholipase C, with subsequent mobilization and influx of calcium. In permeabilized cells the inhibitory effect of fMet-Leu-Phe on secretion was partially retained indicating a direct action of the fMet-Leu-Phe receptor on exocytosis. Pertussis toxin abolished the effects of fMet-Leu-Phe. Our results suggest conserved coupling from fMet-Leu-Phe receptor to pertussis toxin sensitive transducers analogous to the mechanism in neutrophils. However, the net biological effect of receptor activation is determined by additional factors intrinsic to the host cell.

Alanine↗
PubMed1993

Enhanced patency of venous Dacron grafts by endothelial cell sodding.

The effect of microvessel endothelial cell (EC) sodding on the patency of Dacron grafts interposed in canine inferior vena cava was studied. EC were harvested enzymatically from canine omentum and isolated by density gradient centrifugation. Preclotted, knitted Dacron grafts were sodded with > 10(6) EC/cm2 surface. The results demonstrate significant improvement in patency of sodded grafts placed in the inferior vena cava as compared with control grafts (p < 0.001 in grafts with a distal arteriovenous fistula and p < 0.05 in grafts without a distal fistula). The neointima of the sodded grafts were thinner and scanning electron microscopy confirmed the presence of a confluent layer of EC. In addition, the production of prostacyclin but not thromboxane A2 was significantly enhanced in the sodded grafts as compared with controls. We conclude that microvessel EC sodding of Dacron grafts significantly improves the patency rate and inhibits neointimal thickening of the prosthesis. The mechanism is unknown but may involve a more rapid endothelialization of the graft surface with the potential of producing more prostacyclin and less thromboxane A2.

Animals↗
PubMed1993

Does hypothermia or hyperventilation affect enflurane MAC reduction following partial cardiopulmonary bypass in dogs?

This study in dogs determined the effect of systemic cooling and arterial hypocarbia during cardiopulmonary bypass (CPB) on the requirements for enflurane anaesthesia (MAC) before and after CPB. Twelve mongrel dogs were each anaesthetized with enflurane in oxygen on two separate occasions. End-tidal enflurane concentration was measured with a Puritan-Bennett Anaesthesia Agent Monitor. Using the tail-clamp method, MAC was determined twice with a one-hour interval between measurements (MAC 1 and MAC 2). Partial CPB was then initiated using femoral arterio-venous cannulation and maintained for one hour. Following separation from CPB, MAC was again determined twice with a one hour interval between measurements (MAC 3 and MAC 4). Dogs were randomly assigned according to PaCO2 management during CPB (low, 17.6 +/- 8.6 mmHg vs high, 38.9 +/- 11.5 mmHg), and then subjected to two experimental conditions. The first experiment on each dog was undertaken using normothermia during CPB (warm, 35-37 degrees C) while the second experiment (at least two weeks later) was conducted using hypothermia during CPB (cold, 30 degrees C). Analysis of the data, using ANOVA for repeated measures, revealed MAC 3 (1.95 +/- 0.33%, post-CPB) to be reduced when compared with MAC 1 (2.18 +/- 0.28%, P < 0.01) or MAC 2 (2.10 +/- 0.22%, P < 0.01), determined before CPB. Multivariate repeated measures analysis revealed no independent effects of hypothermia or arterial hypocarbia during CPB, on MAC reduction. By the time of the second experiment in each dog (two weeks later), MAC had returned to baseline levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia, Inhalation↗
PubMed1993

Development of hearing in neonatal rats: air and bone conducted ABR thresholds.

While the human full-term neonate can hear at birth, in the rat the onset of auditory function as monitored by recording auditory nerve-brainstem evoked responses (ABR) has been reported to begin on post-natal day (PND) 12-14 and reaches adult thresholds at about 22 days. In order to determine the factors involved in this late onset and then rapid threshold improvement in rats, the ABR to both air conducted (AC) and bone-conducted (BC) auditory stimulation was determined in neonatal rats. ABR to maximal intensity BC stimuli (55 dB above adult rat ABR threshold--55 dB HL*) could be recorded from PND 7-8 while AC responses to 80 dB HL* stimuli, only from PND 11. The air-bone gap (a measure of conductive immaturities only) disappeared on PND 15. This shows that there are both conductive (external and middle ear--Air-bone gap) and sensori-neural (inner ear--BC threshold) immaturities in the neonatal rat; the conductive factors are resolved by PND 15 while the sensori-neural continue after that. With respect to conductive factors, it seems that the state of the ear canal is not important while the chief conductive factors involved probably include mesenchyme resorption and/or ossicular ossification. The chief sensori-neural factor may be the development of the endocochlear potential. It is likely that the human fetus in-utero undergoes similar stages of development.

Acoustic Stimulation↗
PubMed1993

Long-term potentiation in the hippocampus induced by platelet-activating factor.

Platelet-activating factor (PAF) is an ether phospholipid that serves as an autacoid in a wide range of biological processes. We found that when PAF was added to hippocampal slices, it induced a stable and concentration-dependent increase in excitatory postsynaptic potential and population spike recordings (long-term potentiation [LTP]). The PAF effect was blocked by the PAF receptor antagonists BN 52021 and WEB 2086 and the N-methyl-D-aspartate receptor antagonists MK 801 and 2-amino-5-phosphonovalerate. However, these PAF receptor antagonists did not block LTP induced by high frequency stimulation. The facilitation induced by PAF could not be reversed by PAF receptor antagonists. Induction of either PAF-or tetanus-triggered facilitation occluded the subsequent expression of the other, suggesting a common pathway. LTP is a type of synaptic plasticity associated with the formation of memory, and PAF may play an important modulatory role in this process.

Action Potentials↗
PubMed1993

Human immunodeficiency virus type 1 infection requires reverse transcription of nascent viral RNA.

We have previously shown that during human immunodeficiency virus type 1 (HIV-1) infection in vitro continued reverse transcription is required for stable HIV-1 production, but entry by progeny virus is not. To determine the source of the viral RNA reverse-transcribed late in infection, we employed inhibitors of HIV-1 transmission, reverse transcription, and proteolysis of the Gag-Pol polyprotein to interrupt HIV-1 infection in vitro. The kinetics of synthesis of viral DNA, RNA, and proteins was examined. During single-cycle infection, inhibition of reverse transcription 24-72 hr after infection delayed production of viral RNA and protein 10 days. Although viral DNA was detected in Southern blots, inhibition of Gag-Pol processing or transient inhibition of reverse transcription blocked its expression. We propose that after initial reverse transcription of input virion RNA is complete, newly synthesized HIV-1 RNA is reverse-transcribed before its export in virions to yield the viral DNA required for stable HIV-1 production.

Cells, Cultured↗
PubMed1993

Vaginal reconstruction with an island flap of the inferior epigastric vascular pedicle.

This paper presents a new method of vaginal reconstruction. On the basis of anatomic study, we designed an island flap obtained from the upper abdomen to carry the deep inferior epigastric vasculature. At operation, the flap was transferred to the artificial cavity created between the urinary bladder and rectum for vaginal reconstruction. Eight patients received the operation. Complete survival of the flap occurred in seven patients, and one flap failed because of a twist in the flap vascular pedicle. During a follow-up of 6 months to 2 years, it was found that the reconstructed vaginal wall was not only soft but also elastic, and the patients were able to have a satisfying sexual life after marriage.

Adult↗
PubMed1993

Inhibition of Rev activity and human immunodeficiency virus type 1 replication by antisense oligodeoxynucleotide phosphorothioate analogs directed against the Rev-responsive element.

The interaction between the Rev protein of human immunodeficiency virus type 1 and its highly structured and conserved RNA target, the Rev-responsive element, is required for virus replication. We demonstrate that antisense oligodeoxynucleotide phosphorothioate analogs directed against the Rev-responsive element effectively inhibit Rev activity, as well as human immunodeficiency virus type 1 replication, and are candidates for antiviral therapy.

Base Sequence↗
PubMed1993

Human immunodeficiency virus type 1 DNA synthesis, integration, and efficient viral replication in growth-arrested T cells.

Human immunodeficiency virus type 1 (HIV-1) replicates efficiently in nonproliferating monocytes and macrophages but not in resting primary T lymphocytes. To determine the contribution of cell division to the HIV-1 replicative cycle in T cells, we evaluated HIV-1 expression, integration of proviral DNA, and production of infectious progeny virus in C8166 T-lymphoid cells blocked in cell division by treatment with either mitomycin, a DNA cross-linker, or aphidicolin, a DNA polymerase alpha inhibitor. The arrest of cell division was confirmed by assay of [3H]thymidine uptake; the nondividing cells remained viable for at least 3 days after treatment. HIV-1 was expressed and replicated equally well in nondividing and dividing C8166 cells, as judged by the comparison of the levels of p24 core antigens in culture supernatants, the proportion of cells expressing HIV-1 specific antigens, the pattern and quantity of HIV-1 DNA present in the extrachromosomal and total cellular DNA fractions, and the biological activity of progeny viruses. A polymerase chain reaction-based viral DNA integration assay indicated that HIV-1 provirus was integrated in C8166 cells treated with either of the two inhibitors of cell division. Similar results were obtained by using growth-arrested Jurkat T-lymphoid cells. We conclude that cell division and cellular DNA synthesis are not required for efficient HIV-1 expression in T cells.

Aphidicolin↗
PubMed1993

The signal for translational readthrough of a UGA codon in Sindbis virus RNA involves a single cytidine residue immediately downstream of the termination codon.

The nucleotide sequences surrounding termination codons influence the efficiency of translational readthrough. In this report, we examined the sequence requirement for efficient readthrough of the UGA codon in the Sindbis virus genomic RNA which regulates production of the putative viral RNA polymerase, nsP4. The UGA codon and its neighboring nucleotide sequences were subcloned into a heterologous coding context, and readthrough efficiency was measured by cell-free translation of RNA transcripts in rabbit reticulocyte lysates. The CUA codon immediately downstream of the UGA codon was found to be sufficient for efficient translational readthrough. Further mutagenesis of residues in the CUA triplet demonstrated that mutations at the second or third residues following the UGA codon (U and A, respectively) had little effect on readthrough efficiency. In contrast, replacement of the cytidine residue immediately downstream of the UGA codon with any of the other three nucleotides (U, A, or G) dramatically reduced the readthrough efficiency from approximately 10% to less than 1%. These results show that a simple sequence context can allow efficient readthrough of UGA codons in a mammalian translation system. Interestingly, compilation studies of nucleotide sequences surrounding eukaryotic termination codons indicate a strong bias against cytidine residues immediately 3' to UGA termination codons. Taken together with our results, this bias may reflect a selective pressure for efficient translation termination for most eukaryotic gene products.

Amino Acid Sequence↗
PubMed1993

Contractile responses and signal transduction of endothelin-1 in aorta and mesenteric vasculature of adult spontaneously hypertensive rats.

The contractile responses and generation of intracellular second messengers in response to endothelin-1 (ET-1), a potent vasoconstrictor peptide released locally by endothelial cells and involved in the regulation of vascular tone, were investigated in different segments of the vascular tree of adult 18-week-old spontaneously hypertensive rats (SHR) as compared with age-matched Wistar-Kyoto (WKY) rats. Aorta rings of SHR showed lower maximum response to ET-1 in comparison with WKY rats. Rings of the main superior mesenteric artery of SHR and WKY showed similar responses to ET-1. Small mesenteric resistance arteries of SHR, mounted on a wire myograph, developed similar tension to those of WKY rats in response to ET-1. The dose-response of inositol phosphates to ET-1 was significantly blunted in thoracic aorta of SHR compared with WKY rats, whereas it was similar in the mesenteric arterial bed. Baseline 1,2-diacylglycerol content was higher in thoracic aorta of SHR than WKY, while it was similar in the mesenteric arterial bed of the two strains. The response of 1,2-diacylglycerol to ET-1 was blunted in aorta of SHR, whereas no significant differences in diacylglycerol accumulation could be found in mesenteric vessels between SHR and WKY. In small mesenteric arteries, the dose-response to ET-1 of cytosolic free calcium, measured with the fluorescent dye Fura 2-AM, was similar in the two groups of rats. We conclude that in the aorta of 18-week-old SHR there is reduced generation of second messengers (inositol phosphates and diacylglycerol), which underlies its decreased response to ET-1. In mesenteric vessels (both proximal and distal) signal transduction is similar in SHR and WKY, and as a result contractile responses in both species are comparable. The responses to ET-1 of the arterial tree in terms of contractility and second messenger generation may reflect the adaptive processes taking place as a consequence of elevated blood pressure within the arterial wall of different segments of the vasculature of SHR.

Animals↗
PubMed1993

Disposition of ibuprofen in patients with liver cirrhosis. Stereochemical considerations.

Following a single oral dose of racemic ibuprofen 600mg the stereoselective disposition of its enantiomers was studied in 8 patients with moderate to severe cirrhosis. Compared with the elimination half-life (t1/2) of (-)-R- and (+)-S-ibuprofen in 8 healthy age-matched controls (1.7 +/- 0.3h and 1.8 +/- 0.5h, respectively), t1/2 was prolonged significantly (p < 0.045 and < 0.001, respectively) in patients with cirrhosis (t1/2 = 3.1 +/- 1.7h and 3.4 +/- 1.0h, respectively). Whereas the low amounts excreted unchanged into urine differed slightly in both groups studied, much less (p < 0.01) conjugated ibuprofen was recovered either as the R-enantiomer (0.9 +/- 0.4% vs 4.1 +/- 2.8% of the dose) or the S-enantiomer (6.4 +/- 2.5% vs 26.5 +/- 12.9% of the dose) in patients with cirrhosis. Metabolic inversion of the inactive (-)-R-ibuprofen to the active (+)-S-ibuprofen may be impaired in hepatic dysfunction since the normal ratio of areas under the curve (AUC) for R- and S-enantiomers (0.79 +/- 0.18) was significantly (p < 0.02) higher in patients with cirrhosis (1.10 +/- 0.28). In a second study, a single oral dose of 400mg (+)-S-ibuprofen was administered to 8 healthy volunteers and 8 patients with cirrhosis. Elimination of this enantiomer was slightly impaired as could be seen from the prolonged t1/2 (1.6 +/- 0.1h vs 2.6 +/- 0.5h; p < 0.001) and the increase in AUC (101 +/- 35 vs 144 +/- 41 mg/L.h; p = 0.041). In conclusion, in patients with liver disease, hepatic elimination of ibuprofen is impaired. This should be taken into consideration especially if the racemic drug is used. Direct administration of the active (+)-S-enantiomer seems to offer less vulnerable treatment.

Adult↗