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Biomedical subjects

Y M Zhang

Publications and source records attributed to Y M Zhang.

At least 73 records · Page 4Linked to original sources

Biomechanical evaluation of posterior and anterior lumbar interbody fusion techniques.

This study determined the biomechanical differences between anterior and posterior lumbar interbody fusion (ALIF and PLIF). Ten cadaveric spines were tested. Five specimens had ALIF and five had PLIF at L4-L5. Stabilization was performed with pedicle screws and rods (Cotrel-Dubboset, Sofamor-Danek, Memphis, TN, U.S.A.). Angular motion was measured in flexion, extension, bending, and torsion on the intact, instrumented, and "fused" specimens. Instrumentation alone caused a significant decrease in segmental motion in all loading modes (p < 0.01). After the simulated fusion procedures, all specimens were most stable in flexion, and significantly less stable in extension (p = 0.04). Comparing directly, ALIF was significant more stable in left torsion (p = 0.03) with trends in left bending (p = 0.08) and right torsion (p = 0.07). Thus, from a purely biomechanical perspective, ALIF appears to be slightly superior to PLIF.

Adult↗

Drug resistance during indinavir therapy is caused by mutations in the protease gene and in its Gag substrate cleavage sites.

Two different responses to the therapy were observed in a group of patients receiving the protease inhibitor indinavir. In one, suppression of virus replication occurred and has persisted for 90 weeks (bDNA, < 500 human immunodeficiency virus type 1 [HIV-1] RNA copies/ml). In the second group, a rebound in virus levels in plasma followed the initial sharp decline observed at the start of therapy. This was associated with the emergence of drug-resistant variants. Sequence analysis of the protease gene during the course of therapy revealed that in this second group there was a sequential acquisition of protease mutations at amino acids 46, 82, 54, 71, 89, and 90. In the six patients in this group, there was also an identical mutation in the gag p7/p1 gag protease cleavage site. In three of the patients, this change was seen as early as 6 to 10 weeks after the start of therapy. In one patient, a second mutation occurred at the gag p1/p6 cleavage site, but it appeared 18 weeks after the time of appearance of the p7/p1 mutation. Recombinant HIV-1 variants containing two or three mutations in the protease gene were constructed either with mutations at the p7/p1 cleavage site or with wild-type (WT) gag sequences. When recombinant HIV-1-containing protease mutations at 46 and 82 was grown in MT2 cells, there was a 68% reduction in its rate of replication compared to the WT virus. Introduction of an additional mutation at the gag p7/p1 protease cleavage site compensated for the partially defective protease gene. Similarly, rates of replication of viruses with mutations M46L/I, I54V, and V82A in protease were enhanced both in the presence and in the absence of Indinavir when combined with mutations in the gag p7/p1 and the gag p1/p6 cleavage sites. Optimal rates of virus replication require protease cleavage of precursor polyproteins. A mutation in the cleavage site that enhanced the availability of a protein that was rate limiting for virus maturation would confer on that virus a significant growth advantage and may explain the uniform emergence of viruses with alterations at the p7/p1 cleavage site. This is the first report of the emergence of mutations in the gag p7/p1 protease cleavage sites in patients receiving protease therapy and identifies this change as an important determinant of HIV-1 resistance to protease inhibitors in patient populations.

Anti-HIV Agents↗

[Isoflavones from Glycyrrhiza eurycarpa].

A new isoflavone, named eurycarpin A and a new natural product isoflavone named eurycarpin B have been isolated from the roots of Glycyrrhiza eurycarpa P. C. Li. Their structures were determined to be 7,2',4'-trihydroxy-3'-(3,3-dimethylallyl) isoflavone(I) and 7,2'-dihydroxy-6",6"-dimethylpyrano-(2",3":4',3') isoflavone(II) on the basis of spectroscopic analysis (UV, EI-MS, 1HNMR, 13CNMR, NOE difference and HMBC). In addition, three known isoflavones, licoisoflavone A, calycosin and formononetin, were obtained for the first time from this plant.

Drugs, Chinese Herbal↗

[Studies on the ganoderic acid, a new constituents from the fruiting body of Ganoderma lucidum (Fr.) Karst].

Three compounds have been isolated from the dichloromethane soluble fraction of the fruiting body of Ganoderma lucidum (Fr.) Karst. On basis of spectral analyses (UV, IR, MS, 1HNMR, 13CNMR and 2D-NMR), they were identified as 3, 7-dioxo-lanosta-8, 24(E)-dien-26-oic acid (I), 7 beta-15 alpha-dihydroxy-3, 11, 23-trioxo-5 alpha-lanost-8-en-26-oic acid (II) and 3 beta, 7 beta, 15 alpha-trihydroxy-11, 23-dioxo-5 alpha-lanosta-8-en-26-oic acid (III). Compound I is a new compound named ganoderic acid DM.

Drugs, Chinese Herbal↗

Emergence of protease inhibitor resistance mutations in human immunodeficiency virus type 1 isolates from patients and rapid screening procedure for their detection.

Patient human immunodeficiency virus type 1 (HIV-1) isolates that are resistant to protease inhibitors may contain amino acid substitutions L10I/V, M46L/I, G-48V, L63P, V82A/F/T, I84V, and L90M in the protease gene. Substitutions at positions 82 and/or 90 occur in variants that display high levels of resistance to certain protease inhibitors. Nucleotide substitutions at these two sites also lead to the loss of two HindII restriction enzyme digestion sites, and these changes make possible a rapid procedure for the detection of drug-resistant variants in patients on protease inhibitor therapy. This procedure was used to detect the emergence of mutated viruses at various times after the initiation of therapy with the HIV-1 protease inhibitor indinavir. The method includes viral RNA isolation from plasma and reverse transcription PCR amplification of the protease gene with fluorescence-tagged primers. The PCR product is digested with HindII, the cleavage products are separated on a urea-acrylamide gel in a DNA sequencer, and the extent of cleavage is automatically analyzed with commercially available software. In viruses from 34 blood samples from four patients, mutations leading to an amino acid change at residue 82 appeared as early as 6 weeks after the start of therapy and persisted throughout the course of the study period (48 weeks). Mutations leading to double substitutions at residues 82 and 90 were seen at a lower frequency and appeared later than the change at position 82. The changes detected by restriction enzyme cleavage were confirmed by DNA sequencing of the cloned protease genes by reverse transcription PCR amplification of viral RNA from isolates in plasma. In addition to the changes at positions 82 and 90, we have identified M46L/I, G48V, and I54V substitutions in isolates derived from indinavir-treated patients. HindII analysis of uncloned, PCR-amplified DNA offers a rapid screening procedure for the detection of virus isolates containing mutations at amino acid residues 82 and 90 in the HIV-1 protease gene. By using other restriction enzymes, the same method can be used to detect additional protease drug-resistant variants and is generally applicable for the detection of mutations.

Amino Acid Sequence↗

Triggered propagated contractions in rat cardiac trabeculae. Inhibition by octanol and heptanol.

We studied the role of Ca2+ diffusion through gap junctions (GJs) in triggering and propagation of damage-induced contractions in cardiac muscle (TPCs) by evaluating effects of the GJ blockers octanol and heptanol (O&H) on TPCs. TPCs were elicited in trabeculae from rat right ventricle superfused with Krebs-Henseleit solution at 20 degrees C and 0.7 to 1.75 mmol/L [Ca2+]o. Force was measured with a silicon strain gauge; sarcomere length, by laser diffraction techniques. O&H (3 to 300 mumol/L) decreased force, propagation velocity, and triggering rate of TPCs in a dose-dependent manner. At 300 mumol/L, O&H decreased TPC force to 21.3% and 25.7%, propagation velocity to 15.4% and 13.0%, and triggering rate to 26.5% and 25.7%. At 300 mumol/L. O&H decreased twitch force to 79.0% and 77.8% and reduced time to 90% relaxation by 10% to 15%. Above 1 mmol/L, O&H abolished twitch force and TPCs. Image analysis of spread of the fluorescence profile of microinjected fura 2 salt revealed an effective diffusion coefficient for fura 2 of 21.0 +/- 3.3 microns2/s, which decreased to 12.6+/-1.5 and 7.07 +/- 0.7 microns2/s after 1 and 3 hours of exposure, respectively, to 100 mumol/L octanol, with a time constant of decline of 1.5+/-0.5 hours. These results are consistent with the hypothesis that propagation of TPCs is due to Ca(2+)-induced Ca2+ release mediated by Ca2+ diffusion from cell to cell through GJs. Reduction of propagation velocity reduces the number of activated sarcomeres in the TPC, which reduces TPC force. O&H slow triggering of TPCs, presumably by blocking Ca2+ diffusion from myocytes within damaged areas to adjacent normal cells.

Animals↗

Tissue factor expression in an animal model of hydronephrosis.

BACKGROUND: Hydronephrosis is associated with interstitial fibrosis and occlusion of renal capillaries by fibrin. However, the mechanisms leading to fibrin formation is unknown. METHODS AND RESULTS: Twenty days after unilateral ligation of the ureter, interstitial fibrosis occurred in the ligated kidney. Fibrosis was preceded by infiltration of inflammatory cells (macrophages, B and T lymphocytes). Staining with an antibody against von Willebrand factor demonstrated newly formed capillaries in the fibrosing tissue as well as prominent fibrin deposition. Fibrin staining was found around vessels, in the interstitium, the glomeruli, and tubuli. Fibrin deposition was less prominent in the non-ligated kidney and almost absent in sham-operated animals. The expression of tissue factor, the central initiator of coagulation, was induced within 5 days after ligation in the operated kidney but not in the sham-operated animals. Tissue factor positivity was observed by immunohistochemistry in vascular endothelial cells, the vessel wall, tubular epithelial cells, glomerular capsular cells, Bowman's space and in the interstitium. Tissue factor induction was due to increased transcription, since in-situ hybridization showed increased levels of mRNA in the ligated kidney compared to sham-operated rats. The tissue factor gene is under control of the transcription factors activator protein-1 (AP-1) and nuclear factor-kappa B (NF-kappa B). When extracts of operated organs were compared with kidneys of sham-operated rats or contralateral kidneys in electrophoretic mobility shift assays, an increase in AP-1 and NF-kappa B binding activity to their respective binding sites in the tissue factor gene was observed in the operated, but not in the contralateral kidney or kidneys of sham-operated animals. CONCLUSION: Ureteral ligation leads to infiltration of inflammatory cells, increased AP-1 and NF-kappa B expression in the kidney, resulting in increased tissue factor transcription and translation, and ultimately in increased fibrin deposition.

Animals↗

Role of the nucleus raphe obscurus in the inhibition of rostral ventrolateral medullary neurones induced by stimulation in the ventrolateral periaqueductal grey matter of the rabbit.

Experiments have been carried out to investigate the pathways which mediate the inhibitory influence of the ventrolateral periaqueductal grey matter (vlatPAG) on neurones in the rostral ventrolateral medulla (RVLM). In anaesthetized rabbits, 20-ms trains of electrical stimulation in the vlatPAG inhibited ongoing activity of neurones in the RVLM to < 30% of the control level. The inhibition was blocked after microinjections of 500-1000 nl local anaesthetic (4% lignocaine, n = 9) or 0.2 M glycine (n = 4) into nucleus raphe obscurus (NRO). We suggest that the inhibitory influence of the vlatPAG on neurones in the RVLM is mediated by a relay in NRO.

Animals↗

Persistence of four related human immunodeficiency virus subtypes during the course of zidovudine therapy: relationship between virion RNA and proviral DNA.

Human immunodeficiency virus (HIV) virion RNA and proviral DNA sequences have been examined over a 1-year period in an HIV-seropositive patient, commencing with the start of zidovudine treatment. By characterizing the variable V3 and V4 env domains, four related but structurally discrete genotypes could be identified prior to the start of therapy and during the subsequent 60-week period of therapy. Each of the four subtypes showed a unique pattern in the preservation of glycosylation sites. A comparison of the V3 amino acid sequences in peripheral blood mononuclear cell proviral DNA and plasma virion RNA at 0, 24, 36, and 60 weeks demonstrated that proviral DNA did not serve as a predictor of the structure of virion RNA. HIV virion RNA subtype 3 was the most prevalent virion RNA subtype at three of the four periods studied, yet no corresponding proviral DNA was detected. Other virion subtypes have been observed, but only on a transient basis. The present data are consistent with a model of HIV infection in which related but different HIV substrains coexist and evolve independently within an individual. Characterization of virion RNA may be required to identify the unique properties of the virus involved in disease progression; characterization of proviral DNA will not yield this information.

Amino Acid Sequence↗

Immunization of monkeys with baculovirus-dengue type-4 recombinants containing envelope and nonstructural proteins: evidence of priming and partial protection.

Groups of rhesus monkeys were immunized with baculovirus-dengue type-4 (DEN-4) recombinant-infected cell extracts. One recombinant contained all of the DEN-4 structural proteins and two nonstructural (NS) proteins (C-M-E-NS1-NS2a), while the other was a fusion protein containing a portion of the respiratory syncytial virus G glycoprotein and DEN-4 envelope glycoprotein (RSVG-E). Both preparations were immunogenic; all monkeys receiving either immunogen responded with the production of antivirion antibodies in enzyme immunoassays. All except one monkey receiving the recombinant b(C-M-E-NS1-NS2a) made antibodies to NS1. One monkey that received b(RSVG-E) showed the production of low levels of neutralizing antibodies. Following challenge with unmodified DEN-4 virus, seven of nine monkeys in the immunized group became infected and were viremic for a mean of 4.1 days. The control, sham-inoculated monkeys were also viremic; the mean number of days of viremia in this group was 4.7 days. The remaining monkeys in the immunized group (n = 7), although not protected, had evidence of priming. Hemagglutination inhibition antibody responses following challenge indicated an anamnestic response in this group of animals. Based on these results, it was concluded that future immunization schedules should be altered to optimize immune responses and that immunization with more potent and purified immunogens would probably result in higher seroconversion rates and antibody levels in monkeys.

Animals↗

Vascular origin of Kaposi's sarcoma. Expression of leukocyte adhesion molecule-1, thrombomodulin, and tissue factor.

We studied seven cases of Kaposi's sarcomas (KS) obtained from patients with AIDS and one KS from a patient without HIV infection. Antigen expression was studied by immunocytochemistry and mRNA expression by in situ hybridisation. The markers tested were endothelial leukocyte adhesion molecule-1, thrombomodulin, and tissue factor. In all tumors (AIDS and non-AIDS associated) these markers reacted positive, indicating transcription and translation of these genes in KS. The synthesis and expression of tissue factor and thrombomodulin suggests that KS is a tumor that has tissue factor-mediated thrombin formation under the control of thrombomodulin. The expression of thrombomodulin and endothelial leukocyte adhesion molecule-1 provides evidence for the vascular origin of KS.

Acquired Immunodeficiency Syndrome↗

[Clinical significance of soluble interleukin-2 receptor in patients with pulmonary tuberculosis].

The levels of soluble interleukin-2 receptor (sIL-2R) among patients with various pulmonary diseases were measured by using sandwich ELISA. The levels of sIL-2R were significantly elevated in patients with active pulmonary tuberculosis and acute pneumonia when compared with healthy controls. The concentrations of sIL-2R in patients with active pulmonary tuberculosis decreased in accordance with improvement of other laboratory parameters. The clinical significance and possible mechanism of increasing of sIL-2R in patients with pulmonary tuberculosis were discussed.

Antitubercular Agents↗

[Acute renal failure caused by viper: report of 48 cases].

Viper is common in China and its secretion is a mixture consisting of both hemo-toxin and neuro-toxin that cause acute renal failure and respiratory paralysis. In 4860 cases of snake-bites treated from 1984 to 1991, 48 (0.99%) resulted in acute renal failure. After treatment, 43 cases were completely recovered and 5 (10.4%) died of serious failure. Because the toxicity of viper directly attacks both kidneys and toxaemia may cause massive hemolysis to rapidly develop acute renal failure. Instant etiological treatment, alkalization urine, peritoneal dialysis are necessary to sustain the function of heart, liver and lung.

Acute Kidney Injury↗

Gamma and delta chain gene rearrangement of T cell receptor in acute lymphoblastic leukemia.

The immunophenotype, rearrangements of T cell receptor (TCR) gamma and delta chain genes as well as the immunoglobulin heavy chain (IgH) gene were studied in 37 cases of morphologically defined acute lymphoblastic leukemia (ALL). According to the expression of differentiation antigens, 8 cases were classified as T-ALL, 26 B lineage ALL, 2 acute undifferentiated leukemia (AUL) and myeloid phenotype. An order of TCR gene rearrangements was observed in T-ALL, with the rearrangement of delta gene preceding that of gamma gene. Both genes were also found frequently rearranged and/or deleted in high proportions of the ALL of B cell lineage. However, the patterns of gene rearrangements were somewhat different between the T and B lineage ALLs. In contrast, the IgH gene rearrangements were observed only in the B lineage ALL. The immunogenotype analysis of ALL proved to be a useful marker of the clonality and provided us with important information on early human lymphoid differentiation. We conclude that the determination of TCR gamma gene V-J junctional sequence can be used as clonal marker for detecting the minimal residual disease during clinical remission.

Adolescent↗

Glycosylation using a one-electron-transfer, homogeneous reagent. Application to an efficient synthesis of the trimannosyl core of N-glycosylproteins.

Double glycosylation of methyl 2,4-di-O-benzyl-beta-D-mannopyranoside with ethyl 2-O-benzoyl-3,4,6-tri-O-benzyl-1-thio-alpha-D-mannopyranoside using as promoter tris(4-bromophenyl)ammoniumyl hexachloroantimonate, a stable, commercial, and crystalline radical cation, afforded after debenzoylation methyl 2,4-di-O-benzyl-3,6-di-O-(3,4,6-tri-O-benzyl-alpha-D-mannopyranoside in excellent yield. Other mannosyl donors were also investigated.

Carbohydrate Sequence↗