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Biomedical subjects

Y Chu

Publications and source records attributed to Y Chu.

At least 55 records · Page 3Linked to original sources

[Changes of surfactant A and B in alveolar type II cells in hamster with elastase-induced emphysema].

OBJECTIVE: To observe the changes of surfactant A and B (SP-A and SP-B) in alveolar type II cells of lungs in hamsters with elastase-induced emphysema. METHODS: After intratracheal instilling of elastase, hamsters were killed at the 30th, 60th and 90th day of the experiment respectively. Slides of lung tissue were examined under light microscope and measured by calculating the mean linear intercepts. Then the slides were stained under immunohistochemistry procedures and measured by using a morphometric analysis system. Meanwhile, slides were also checked by electron microscopy. RESULTS: In comparison with the normal group, MLI of the elastase group was significantly increased (P < 0.01). Immunohistochemistry showed that the percentage of both SP-A and SP-B positive cells was significantly decreased 30 days after the intratracheal instilling of elastase (from 48.0% +/- 3.0% to 9.5% +/- 4.0% and from 28.0% +/- 4.0% to 13.3% +/- 4.1%, respectively; P < 0.01), however, a time-dependent recovery 90 days after instilling was seen. Electron microscopy showed a significantly decrease of the number of lamellae. CONCLUSION: The decrease of SP-A and SP-B in alveolar type II cells seems to play an important role in the development of emphysema.

Animals↗

[Study on clinical and laboratory features of preleukemia patients].

OBJECTIVE: To explore prospective diagnostic criteria for preleukemia. METHODS: A case control study of the discrepancies of clinical and laboratory features between patients with preleukemia and those with chronic aplastic anemia (CAA) or atypical paroxysmal nocturnal hemoglubinuria (a-PNH). RESULTS: There were eight variables of significance: (1) lymphocytoid micromegakaryocytes in marrow; (2) immature granulocytes in peripheral blood; (3) >or= 2% myeloblasts in marrow; (4) positive periodic acid schiff (PAS) staining of nucleated erythrocytes; (5) myeloid differentiation index >or= 1.8; (6) clonal karyotypic abnormalities; (7) negative sister chromatid differentiation; (8) > 4.0 cluster/colony ratio of granulocyte-macrophage colony-forming units (CFU-GM). The following criteria was assigned: A: To meet (1) and at least two of the other seven variables; B: To meet at least four of the eight variables. All of the patients with preleukemia met A or B and none of the patients with CAA or a-PNH did. CONCLUSION: Preleukemia is different from CAA or a-PNH. It has its own clinical and laboratory features, which may be useful for prospective diagnosis.

Adolescent↗

[Preventive and therapeutic effect of Chinese herbs naofeikang on experimental emphysema and pulmonary artery hypertension in hamsters].

OBJECTIVE: To observe preventive and therapeutic effect of Chinese herbs Naofeikang on hypoxic pulmonary artery hypertension of elastase-induced emphysema hamsters and investigate its mechanism. METHODS: Hamsters for 30 days after intratracheally-instilled elastase, were kept in hypoxia environment under normal atmospheric pressure for 15 days, 50 hamsters were divided into prevention group (Prv), treatment group (T), emphysema + hypoxia (EH), and control group(N). Mean pulmonary artery pressure (MPAP) was measured before hamsters were killed. And then right ventricle hypertrophy index (RVHI) was measured, as well as circulating endothelial cells (CEC) and cells recoveries from bronchoalveolar lavage fluid (BALF) were counted. Meanwhile, pulmonary tissue changes were studied under light microscope with morphometric analysis. RESULTS: Compared with EH group, MPAP, CEC, and cells recoveries of BALF of Prv and T groups were significantly decreased (P < 0.05 or P < 0.01); Mean linear intercept and percentage of arterial media area of Prv and T groups had totally a significant difference (P < 0.01) in comparison with EH group. CONCLUSIONS: Chinese herbs Naofeikang could lower pulmonary hypertension, preserve vessel endothelial cells and lessen the inflammatory reaction in pulmonary tissue. Thereby, it could hinder the further development of emphysema and inhibit the remodeling of pulmonary small artery.

Animals↗

Assay of 6-mercaptopurine and its metabolites in patient plasma by high-performance liquid chromatography with diode-array detection.

A reversed-phase high-performance liquid chromatography (HPLC) method was developed to determine 6-mercaptopurine (MP) and seven of its metabolites (6-thioguanine, 6-thioxanthine, 6-mercaptopurine riboside, 6-thioguanosine, 6-thioxanthine riboside, 6-methylmercaptopurine and 6-methylmercaptopurine riboside) simultaneously in human plasma. A volume of 100 microl of plasma was used. Protein was removed from the sample by a simple and easy ultrafiltration step and ultrafiltrate was directly injected onto the HPLC system. Analytes were detected and confirmed with a diode-array detector before quantitation at 295 and 330 nm. The limit of detection for the analytes ranged from 20 to 50 nM. For the majority of patients receiving a 1 g/m2 MP intravenous infusion, MP and all metabolites except 6-thioguanine and 6-methylmercaptopurine riboside were present. This method serves as useful tool to characterize pharmacokinetics and pharmacodynamics of MP in oncology patients, and the small volume of plasma lends itself to pediatric studies.

Antimetabolites, Antineoplastic↗

Lentiviral gene transfer to the nonhuman primate brain.

Lentiviral vectors infect quiescent cells and allow for the delivery of genes to discrete brain regions. The present study assessed whether stable lentiviral gene transduction can be achieved in the monkey nigrostriatal system. Three young adult Rhesus monkeys received injections of a lentiviral vector encoding for the marker gene beta galatosidase (beta Gal). On one side of the brain, each monkey received multiple lentivirus injections into the caudate and putamen. On the opposite side, each animal received a single injection aimed at the substantia nigra. The first two monkeys were sacrificed 1 month postinjection, while the third monkey was sacrificed 3 months postinjection. Robust incorporation of the beta Gal gene was seen in the striatum of all three monkeys. Stereological counts revealed that 930,218; 1,192,359; and 1,501,217 cells in the striatum were beta Gal positive in monkeys 1 (n = 2) and 3 (n = 1) months later, respectively. Only the third monkey had an injection placed directly into the substantia nigra and 187,308 beta Gal-positive cells were identified in this animal. The injections induced only minor perivascular cuffing and there was no apparent inflammatory response resulting from the lentivirus injections. Double label experiments revealed that between 80 and 87% of the beta Gal-positive cells were neurons. These data indicate that robust transduction of striatal and nigral cells can occur in the nonhuman primate brain for up to 3 months. Studies are now ongoing testing the ability of lentivirus encoding for dopaminergic trophic factors to augment the nigrostriatal system in nonhuman primate models of Parkinson's disease.

Animals↗

Examining the immune response in sentinel lymph nodes of mice and men.

Recently, it was recognized that an immune response develops along one of two major pathways. One leads to a destructive immune response (type 1), while the alternative leads to a nondestructive immune response (type 2). Our studies in animal models suggest that therapeutic vaccines induce a tumor-specific type 1 immune response while ineffective vaccines induce a type 2 response. These results have led us to examine the immune response in sentinel lymph nodes draining tumor vaccines of patients entered onto clinical trials for melanoma, breast and renal cell cancer.

Animals↗

Mechanisms of photoreceptor death and survival in mammalian retina.

The mammalian retina, like the rest of the central nervous system, is highly stable and can maintain its structure and function for the full life of the individual, in humans for many decades. Photoreceptor dystrophies are instances of retinal instability. Many are precipitated by genetic mutations and scores of photoreceptor-lethal mutations have now been identified at the codon level. This review explores the factors which make the photoreceptor more vulnerable to small mutations of its proteins than any other cell of the body, and more vulnerable to environmental factors than any other retinal neurone. These factors include the highly specialised structure and function of the photoreceptors, their high appetite for energy, their self-protective mechanisms and the architecture of their energy supply from the choroidal circulation. Particularly important are the properties of the choroidal circulation, especially its fast flow of near-arterial blood and its inability to autoregulate. Mechanisms which make the retina stable and unstable are then reviewed in three different models of retinal degeneration, retinal detachment, photoreceptor dystrophy and light damage. A two stage model of the genesis of photoreceptor dystrophies is proposed, comprising an initial "depletion" stage caused by genetic or environmental insult and a second "late" stage during which oxygen toxicity damages and eventually destroys any photoreceptors which survive the initial depletion. It is a feature of the model that the second "late" stage of retinal dystrophies is driven by oxygen toxicity. The implications of these ideas for therapy of retinal dystrophies are discussed.

Age Factors↗

Localization of IgG in the normal and dystrophic rat retina after laser lesions.

PURPOSE: To test the hypothesis that access to extravasated plasma protein IgG may influence photoreceptor survival following laser photocoagulation and to determine whether this correlates with the retinal glial reaction. METHODS: A total of 45 rats (18 Royal College of Surgeons (RCS) dystrophic and 18 RCS-rdy+ congenic control) were used for this experiment. Nine non-lasered littermates of same age were used as controls. The superior retinas of postnatal day 23 rats were irradiated with a grid pattern of 40 argon green laser lesions of 50 microm in diameter and two powers (150 and 300 mW) for 0.2 s. At various times after laser lesions (up to 14 days), animals were perfused, the retinas snap frozen and sectioned on a cryostat. A one-step immunohistochemical technique was used by incubating with rabbit anti-rat IgG conjugated directly to horseradish peroxidase. Adjacent sections were processed using an antibody to glial fibrillary acidic protein (GFAP) by the standard avidin-biotin complex method. RESULTS: The labelling pattern for extravasated IgG after laser lesion was very similar in both RCS and RCS-rdy+ rat retinas. At 6, 12 and 24 h after lesions, IgG immunoreactivity (IR) was very intense in the lesion core and flanks. The outer plexiform layer (OPL) and photoreceptor inner segments provided a ready pathway for lateral spread of IgG. However, in the outer nuclear layer (ONL), IgG localization was much more restricted. Despite very intense IgG IR in the ONL of the coagulated lesion core, there was always a very sharply delineated boundary where the label abruptly halted. The GFAP labelling in both RCS dystrophic and RCS-rdy+ congenic control rat retinas showed that this boundary was between normal and necrotic cells because there was a core where GFAP was not produced by Müller cells. By 2 days after lesions, the coagulated cells in the lesion core were being removed by phagocytic cells that were IgG IR. Labelled phagocytic cells were also found among the inner and outer segment region on the lesion flanks. There was still IgG IR in the lesion, but the label was faint. No IgG IR was found in the retina at 3, 4, 7 and 14 days after lesions. Absorption control with pure rat IgG showed the label to be specific. CONCLUSIONS: The extravasated IgG was derived from the choroidal circulation because at no stage was IgG localized around the retinal vasculature. The IgG labelling was surprisingly widespread and, therefore, did not correlate with photoreceptor sparing, although it preceded the widespread Müller cell expression of GFAP and may, therefore, trigger glial reaction.

Animals↗

Anti-inflammatory effects of total saponins of Panax notoginseng.

AIM: To study the anti-inflammatory effects of total saponins of Panax notoginseng (PnS). METHODS: Rat air-pouch acute inflammatory model was established with s.c. carrageenan (Car, 25 mg.kg-1). The protein content in exudate was measured. Micro-acid titration assay and radioimmunoassay (RIA) were applied respectively to investigate effects of PnS on phospholipase A2 (PLA2) activity and dinoprostone (Din) content in exudate. Fura-2 fluorescence technique was used to determine the intracellular free calcium concentration in neutrophils (Neu-[Ca2+]i). RESULTS: At 12 h, PnS 60-240 mg.kg-1 i.p. reduced Neu counts, protein content [(7.7 +/- 1.3) to (4.4 +/- 1.4) g.L-1], and Din content [(1619 +/- 391) to (883 +/- 268) ng.L-1]; inhibited the PLA2 activity in exudate [(248 +/- 42) to (157 +/- 35) kU.L-1] in a dose-dependent manner. PnS 60, 120, and 240 mg.kg-1 lowered the level of Neu-[Ca2+]i with the inhibitory rate of 9.1%, 33.2%, and 39.4%, respectively. CONCLUSION: PnS has an obvious anti-inflammatory effect and its mechanisms are related to the inhibition of the Neu-[Ca2+]i level and PLA2 activity, and reduction of Din content.

Animals↗

[Antilymphocyte globulin combining with cyclosporine A in the treatment of severe aplastic anemia].

OBJECTIVE: To explore more effective regimen for severe aplastic anemia (SAA). METHODS: A prospective, randomized clinical trial was conducted to determine whether the outcome of SAA patients treated with the combination of antilymphocyte globulin(ALG) and cyclosporine A(CsA) (intensive immunosuppressive therapy, IIST) was better than that with ALG alone (non-intensive immunosuppressive therapy, NIIST). RESULTS: The response rate of IIST group(83.7%) was significantly higher than that of NIIST group(57.6%), with a lower risk of early mortality and a shorter time to red cell transfusion independence. Furthermore, the recovery of bone marrow BFU-E and CFU-GM of the responding patients was more complete in IIST group than in NIIST group. CONCLUSIONS: The treatment outcome was better with IIST than with NIIST for SAA.

Adolescent↗

Subclasses of warm autoantibody IgG in patients with autoimmune hemolytic anemia and their clinical implications.

OBJECTIVE: To explore the mechanism of autoimmune hemolysis and establish a more sensitive test for autoimmune hemolytic anemia (AIHA). METHODS: IgG subclasses were tested in 40 patients with idiopathic or secondary AIHA by Coombs test with monoclonal antibodies. Hb, TBil, RC and FHb, as hemolytic parameters, were used to analyze the clinical implications of subclasses of AIHA warm autoantibody IgG. RESULTS: In most patients IgG incomplete warm autoantibody was IgG1 (27 patients), but IgG3 (20 patients), rarely IgG2 (14 patients) and IgG4 (9 patients) also occurred. Three groups were analyzed: Group A included 20 patients with IgG3; Group B included 14 patients with IgG1 bit without IgG3; Group C included 6 patients without IgG1 and IgG3. There were significant differences (P < 0.01) between groups in Hb, TBil, RC and FHb. Moreover, we also found that the sensitivity of Coombs test with polyclonal antiserums was 90.0%, while that of Coombs test with monoclonal antibodies was 97.5%. The effect of treatment was worst in patients with positive IgG3 autoantibody, whose hemolysis recurred frequently. CONCLUSION: IgG3 autoantibody was the most effective in bringing about red cell destruction, IgG1 autoantibody was less effective, IgG2 even less, whereas IgG4 autoantibody was shown to hardly affect red cell survival. Coombs test with monoclonal antibodies was more sensitive than that with polyclonal antiserums. Patients' respondence to treatment correlated with the type of IgG subclasses.

Adult↗

[The clinical implications of IgG subclass in 84 patients with autoimmune hemolytic anemia].

OBJECTIVE: To evaluate the clinical implications of IgG subclass in autoimmune hemolytic anemia(AIHA). METHODS: Data of 84 AIHA patients were retrospectively analyzed. RESULTS: In the 84 patients, IgG1 + IgG3 + C3d accounted for 45.0%, IgG1 + IgG3 15.5%, IgG1 + C3d 11.0%, C3d 10.7%, IgG1 9.5% and IgG3 + C3d 8.3%. IgG3 patients had the most severity of clinical and laboratory findings, followed by IgG1 patients. In IgG1 and IgG3 subgroups, the severity of hemolysis was positively correlated with the score of Coombs' test. The response rates of IgG3 and IgG1 patients were 68.2% and 100%, respectively. CONCLUSION: In AIHA, the basic predominant IgG subclass is IgG1. IgG3 has a greater potential for red-cell destruction than IgG1 and C3d.

Adolescent↗

Constitutive telomerase activity in cells with tissue-renewing potential from estrogen-regulated rat tissues.

To investigate the role of telomerase in estrogen-regulated rodent tissues, we assayed the activity levels of this enzyme and measured cell proliferation and indicators of cellularity in vagina, mammary gland, and uterus from virgin, pregnant, ovariectomized, and ovariectomized estradiol-treated rats. No association was observed between telomerase activity and increased cell proliferation. Telomerase activity was significantly higher (P=0.003) in vagina obtained from ovariectomized rats (very low proliferation) than in vagina from ovariectomized and estradiol-treated rats (high proliferation, high differentiation). The high telomerase levels observed in vagina from ovariectomized rats indicates that the same epithelial compartment (i.e., basal layer) that has the potential to reconstitute the epithelium also contains the cells that express telomerase. The lower telomerase activity in the keratinized (differentiated) vagina was probably due to dilution of the number of telomerase-producing cells by the terminally differentiated non-telomerase-producing cells. Similar results were observed in uterus from ovariectomized versus ovariectomized and estradiol-treated rats. Telomerase activity was highest in uterus from pregnant rats. Telomerase levels in samples from total mammary gland fat pads varied considerably between groups and appeared to be representative of the amount of epithelium present in the sample. Interestingly, when mammary gland samples from the same animals were obtained from pure epithelial organoid preparations, no differences in telomerase activity could be distinguished between animals or groups. Overall these data suggest that telomerase activity, particularly in rat vagina and uterus, appears to be associated with a cell subpopulation showing proliferative and tissue reconstitution potential and not directly associated with proliferation status per se.

Animals↗

Treatment of severe aplastic anemia with an immunosuppressive agent plus recombinant human granulocyte-macrophage colony-stimulating factor and erythropoietin.

To evaluate the therapeutic potential of hematopoietic growth factors (HGFs) during immunosuppressive treatment (IST) of severe aplastic anemia (SAA), 38 patients with newly diagnosed SAA received IST alone (group I), or IST plus recombinant human erythropoietin and granulocyte-macrophage colony-stimulating factor (rhEPO + rhGM-CSF) (group II). Eleven patients in each group received antilymphocyte globulin (ALG) for IST, and eight patients in each group received cyclosporine (CSA). Complete remission rates at one year were 26% and 74% for group I and group II patients, respectively. The ALG-treated subgroup showed the greatest differences between treatments. Compared with patients receiving ALG alone, patients treated with ALG plus HGFs had significantly better one-year survival (100% vs. 54.5%, P < 0.05), complete remission rates (91% vs. 36%, P < 0.05), more rapid and complete hematologic recovery, greater reductions in transfusion requirements, and lower infection rates. The data suggest a potential role for rhEPO + rhGM-CSF therapy in SAA patients receiving IST.

Adolescent↗