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Biomedical subjects

H Luo

Publications and source records attributed to H Luo.

At least 217 records · Page 12Linked to original sources

Rapamycin-induced long-term allograft survival depends on persistence of alloantigen.

In this study the mechanism of rapamycin-induced long-term allograft tolerance was investigated in a rat model. We have demonstrated that the tolerance is strain specific, but is not organ specific. The tolerized rats failed to generate high levels of donor-specific cytotoxic Ab and cytotoxic cells in vivo. Removal of the alloantigen from the tolerized rats with or without concomitant thymectomy could break down the status of tolerance, and the rats regained the capability to reject the grafts and to develop specific cytotoxic Ab and cytotoxic cells. These results clearly indicate that the maintenance of the rapamycin-induced long-term tolerance to allografts depends on the persistence of alloantigens. Mechanistically, we have shown that the reduced IL-2 production and the reduced antigenicity of the graft in the tolerized rat contribute to, but are not solely responsile for, the tolerance. The results of adoptive transfer experiments suggest that regulatory cells or suppressive serum factors are not involved in the tolerance. The fact that the removal of the alloantigen in the thymectomized rat could reverse the tolerance, indicates that there is no clonal deletion. We propose that chronic desensitization due to prolonged engagement of TCR by persistent alloantigens is the major mechanism at the late stage of the rapamycin-induced allograft tolerance.

Animals↗

Identification of clozapine N(+)-glucuronide in the urine of patients treated with clozapine using electrospray mass spectrometry.

Clozapine N(+)-glucuronide was detected in the urine of five patients chronically treated with clozapine. Identification was made on the basis that the material isolated from urine had the same high-performance liquid chromatographic retention time and positive electrospray mass spectra as that of an authentic reference standard of clozapine N(+)-glucuronide. These results indicate that electrospray mass spectrometry is a valuable technique in the analysis of low-molecular-weight biologically derived N(+)-glucuronide metabolites.

Adult↗

The effect of rapamycin on T cell development in mice.

Rapamycin (RAPA) is a strong immunosuppressant with a chemical structure similar to that of FK506, although it acts by a mechanism different from both FK506 and cyclosporin A. The effect of RAPA on T cell development in mice was investigated in this study. RAPA caused significant thymic atrophy. The major histological change in the RAPA-treated thymus was thinning of the cortex. No other apparent damage in the cortex or medulla was observed. Consistent with these histological findings, in vivo thymocyte cycling was blocked by RAPA before the S phase, and the ex vivo and in vitro proliferation of the thymocytes was also strongly repressed by the drug. According to electron microscopy and DNA fragmentation assays, RAPA did not induce apoptosis. These results indicate that the repressed thymocyte proliferation is a major mechanism causing RAPA-induced thymic atrophy. Further, RAPA had no effect on thymocyte apoptosis induced by anti-CD3 or ionomycin, and the drug did not interfere with deletion of CD4+8+ thymocytes or peripheral V beta 6+ T cells induced by anti-CD3 or Mls-1a, respectively. These data suggest that RAPA does not hamper the negative selection. There was a relative increase in the CD3- fraction of the de novo developing CD4 and CD8 double-positive (DP) thymocytes in the RAPA-treated mice. Moreover, there were relative increases of the CD3-fractions of the CD4 or CD8 single-positive (SP) cells in both the thymi and periphery. The generation of the CD3-SP under the influence of RAPA could be used as a useful model for further study of the function and signal transduction of these CD3-defective SP cells.

Animals↗

Expression of a G-protein beta subunit-related gene during lymphocyte activation.

Using a subtractive strategy, we have cloned an activation-related gene from a human B cell cDNA library. Sequence analysis revealed that this gene was identical to H12.3, a gene belonging to an expanding family of guanine nucleotide-binding protein beta subunits. The expression of H12.3 was inducible in the late phase of mitogen-stimulated T and B cells. In T cells, IL-2 and IL-4 by themselves had no direct effect on the expression of H12.3, but they could augment the level of steady-state H12.3 mRNA stimulated by phytohemagglutinin. On the other hand, IFN-gamma and IL-6 had no obvious effect on the expression in B cells with or without Staphylococcus aureus Cowan I-stimulation. Cyclosporin A, a strong immunosuppressant, inhibited the mitogen-stimulated expression of H12.3, but rapamycin, another such agent, did not. In synchronized Jurkat cells, the expression of H12.3 had no cell cycle-dependent decrease in S and G2/M phase, while cyclin E, which controls the progression of the cell cycle in late G1 phase, did show a periodic expression pattern. The results suggest that H12.3 might be involved in regulation of lymphocyte activation.

Animals↗

Catheter-delivered high intensity, low frequency ultrasound induces vasodilation in vivo.

This study investigated the effect of intravascular high intensity, low frequency catheter-delivered ultrasound on vasomotor behaviour in vivo. Catheter-delivered therapeutic ultrasound induces endothelium-independent vasodilation in vitro. To study this effect in vivo we analysed the angiograms of canine coronaries and human femoropopliteal arteries before and after ultrasound exposure. Vasomotor behaviour was studied using a computer edge detection program. We analysed the angiograms of: (1) eight canine left coronary arteries before and after ultrasound; (2) eight canine left coronaries only subjected to serial angiograms, and three canine left coronary arteries of two dogs after passing the unactivated ultrasound probe down the coronary artery infusing saline at a rate of 10-20 ml.min-1, which served as controls, and (3) eight angiographically normal human arterial sites proximal to occlusions in eight femoropopliteal arteries of patients undergoing ultrasound angioplasty for peripheral vascular disease. Vessel diameter of canine coronaries after ultrasound exposure increased from 2.3 +/- 0.3 mm to 2.8 +/- 0.3 mm (21 +/- 2.3%) (P < 0.01). There was no change in vascular diameter in controls after multiple angiograms (2.4 +/- 0.3 mm vs 2.5 +/- 0.2 mm (4.2 +/- 0.2%) (P = ns). Average vessel diameter after passage of the unactivated probe with saline infusion decreased in the left anterior descending coronary artery from 3.66 mm to 3.13 mm, and in the left circumflex coronary artery from 2.88 mm to 2.62 mm. Vessel diameter in human femoropopliteal arteries increased from 3.2 +/- 0.2 mm to 3.6 +/- 0.5 mm or by 14.3 +/- 2.9% respectively (P < 0.01) after exposure to ultrasound energy.(ABSTRACT TRUNCATED AT 250 WORDS)

Angioplasty↗

[Distribution of rabies antigen in human tongue and salivary gland].

The distribution of rabies virus antigen (RVAg) in human tongue and salivary glands from three cases was studied with ABC immunohistochemical method. Of the 5 tissue blocks from 2 tongues, large amounts of RVAg were found in 4 tissue blocks, located in the serous glands, terminal nerves, some striated muscle fibers and some covering epithelium including taste cells of circumvallate papillae. Only small amounts of RVAg were present in 4 of the 9 salivary gland blocks, either within the acini or in nerves. These results differ from that reported previously in dog, fox and skunk salivary glands, which contained abundant RVAg. The amount of RVAg in human tongue is apparently greater than that in the salivary glands. It is probable that the serous glands of the human tongue are sites of predilection for RVAg and may serve as a source of infection.

Adolescent↗

[The effects of superoxide dismutase on acute myocardial ischemia and lipid peroxidation in rabbits].

There are controversies about the action of superoxide dismutase (SOD) on acute myocardial ischemia, but report about the serial changes of serum malondialdehyde (MDA) levels after myocardial infarction and the relationship between serum levels of MDA and size of myocardial infarct has not yet been found in literature. We made a study, using the acute myocardial infarct model of New Zealand rabbits. The results indicated that SOD significantly reduced the total number of pathologic Q-wave, the myocardial infarct size and serum MDA levels. A significant correlation was found between 48-hour serum MDA levels and 48-hour infarct size. Therefore, it is suggested that free radicals might play an important role in pure acute myocardial ischemic injury; SOD, administered early, could inhibit lipid peroxidation and thus protect the myocardium, and serum MDA levels might be regarded as a specific criterion for the diagnosis of myocardial infarction.

Animals↗

Clinical observation on needling extrachannel points in treating mental depression.

Totally 20 cases of mental depression were treated by needling extrachannel points with an effective rate of 90%; comparison of these cases with 21 controls treated with amitriptyline, showed no significant difference in effect (P > 0.05). Measured with Hamilton's scale, factors of anxiety somatization, cognitive disturbance, retardation, sleep disturbance and feeling of despair in both the needling and control groups showed obvious decrease in the mean value, and the change in anxiety somatization was markedly significant in the needling group as compared with that in the controls (P < 0.01). Our studies revealed that after 6 weeks of needling the power of slow wave delta decreased while that of the fast wave alpha increased, all significantly different as compared with that before and during the treatment (P < 0.05).

Acupuncture Points↗

The gamma-tubulin-encoding gene from the basidiomycete fungus, Ustilago violacea, has a long 5'-untranslated region.

The gene (gamma-tub) encoding gamma-tubulin (gamma-Tub) was isolated from a cosmid library constructed for Ustilago violacea by using a PCR-amplified DNA fragment as a probe. About 2.8 kb of DNA sequence was analyzed and found to encode a protein of 469 amino acids highly homologous to the gamma-Tub from other organisms. There were eight introns interrupting the coding sequence. A 'TATA'-like sequence was found 389 bp upstream from the initial Met codon. No polyadenylation signal was found in the 3' non-coding region. Southern blot analyses indicated that gamma-tub is a single-copy gene. Northern blot analyses indicated that a 1.81-kb RNA species was transcribed. Primer extension experiments determined that the transcription start point (tsp) is at 58 bp downstream from the putative TATA box, with another possible tsp at 95 bp downstream. The long 5' non-coding sequence of the RNA contained several small open reading frames; their possible roles in the regulation of gamma-tub translation are discussed.

Amino Acid Sequence↗

Identification of radiolabeled metabolites of nicotine in rat bile. Synthesis of S-(-)-nicotine N-glucuronide and direct separation of nicotine-derived conjugates using high-performance liquid chromatography.

Four metabolites of nicotine, including two glucuronides, have been separated by high-performance liquid chromatography. This separation was applied to identification of biliary metabolites of radiolabeled nicotine by radiometric detection. S-(-)-Nicotine N-glucuronide was synthesized and used as a standard in method development.

Animals↗