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Biomedical subjects

K Zhang

Publications and source records attributed to K Zhang.

At least 343 records · Page 19Linked to original sources

Cellular localization of transforming growth factor-beta expression in bleomycin-induced pulmonary fibrosis.

Bleomycin-induced pulmonary fibrosis is associated with increased lung transforming growth factor-beta (TGF-beta) gene expression, but cellular localization of the source of this expression has not been unequivocally established. In this study, lung fibrosis was induced in rats by endotracheal bleomycin injection on day 0 and, on selected days afterwards, lungs were harvested for in situ hybridization, immunohistochemical and histochemical analyses for TGF-beta 1 mRNA and protein expression, and cell identification. The results show that control lungs express essentially no detectable TGF-beta 1 mRNA or protein in the parenchyma. Before day 3 after bleomycin treatment, scattered bronchiolar epithelial cells, mononuclear cells, and eosinophils expressed elevated levels of TGF-beta 1. Between days 3 and 14, there was a major increase in the number of eosinophils, myofibroblasts, and fibroblasts strongly expressing TGF-beta 1 mRNA and protein. TGF-beta 1-producing cells were predominantly localized within areas of injury and active fibrosis. After day 14, the intensity and number of TGF-beta 1-expressing cells significantly declined and were predominantly found in fibroblasts in fibrotic areas. The expression of TGF-beta 1 protein was generally coincident with that for mRNA with the exception of bronchiolar epithelial cells in which strong protein expression was unaccompanied by a commensurate increase in mRNA. The study demonstrates that myofibroblasts, fibroblasts, and eosinophils represent the major sources of increased lung TGF-beta 1 expression in this model of pulmonary fibrosis.

Animals↗

Germ-line human epsilon heavy chain gene RNA transcripts utilize the full range of alternative 3' splicing seen in productive epsilon mRNA.

An early step in immunoglobulin isotype switching involves the initiation of active transcription of downstream heavy chain loci while they are still in germ-line configuration. This results in the production of 'sterile' germ-line RNA transcripts that do not contain VDJ sequences, the role of which in isotype switching is under intense scrutiny. We investigated whether such human epsilon germ-line transcripts employ the full complement of complex alternative 3' RNA splicing, splicing we have recently reported occurring with productive epsilon mRNA transcripts. Using a reverse transcriptase polymerase chain reaction (RT-PCR) strategy, in which the 5' primer was located in the I region of the epsilon gene, a region expressed in germ-line but not productive (VDJ containing) epsilon transcripts, we showed that the full range of alternative 3' epsilon splices occur with germ-line transcripts. These results demonstrate that epsilon 3' splicing events are independent of 5' isotype DNA switching. Additionally, we showed that, just as with mature epsilon mRNA, the relative production of the various epsilon germ-line mRNA isoforms was responsive to modulation by stimuli such as interleukin-10 (IL-10). Thus B cells, when stimulated to produce epsilon germ-line transcripts, generate a family of germ-line mRNA that differ not only in their initiation sites but, more importantly, also differ in their 3' sequences, sequences that could be important in regulation of the parent gene itself. Furthermore, by discontinuous or trans-splicing, cells could utilize these various epsilon germ-line transcripts to produce the full range of mature IgE proteins prior to undergoing deletional recombination of isotype switching.

Base Sequence↗

[The preliminary study of insulin resistance in pregnancy induced hypertension].

OBJECTIVE: To observe the changes of glucose metabolism in late pregnancy and to reveal the relationship between insulin resistance and pregnancy induced hypertension (PIH). METHODS: The 75g oral glucose tolerance test (OGTT) was performed in 30 cases with PIH (37-41 weeks gestation), 30 cases of normal pregnancy and 12 non-pregnant women. The levels of serum glucose, insulin and C-peptide were measured by radioimmunoassay, and the areas under the curve (AUC) were calculated. RESULTS: There were significant increases of the peak level or AUC of insulin in PIH (61.42 +/- 48.72, 137.12 +/- 81.12 mIU/L) and in normal pregnant group (70.46 +/- 58.42, 150.37 +/- 104.76 mIU/L) compared with non-pregnant controls (17.12 +/- 11.03, 34.38 +/- 16.01 mIU/L) (P < 0.01), however, they had a similar glucose levels before or after GTT (P > 0.05). Furthermore, there was no correlationship between systolic or diastolic blood pressure and the fasting insulin or the AUC. CONCLUSIONS: Insulin resistance and hyperinsulinemia were found in late pregnancy, but the changes of insulin resistance in PIH cases was not significant. So, there was no definitive relationship between insulin resistance and the rising of blood bressure of PIH.

Adult↗

Radiofrequency catheter ablation of ventricular tachycardia in 26 patients.

Electrophysiology study and radiofrequency catheter ablation (RFCA) were performed in 26 patients with refractory sustained ventricular tachycardia (VT). After induction of VT, 12-lead electrocardiogram (ECG) was recorded and QRS morphology and axis of induced VT were studied to identify the origin of VT. The precise site of VT origin were localized by pace mapping and activation mapping carefully. RF energy was delivered through a big-tip deflectable electrode catheter when the earliest site of endocardial activation and a high-frequency and low-amplitude potential of Purkinje fiber, preceding surface QRS by more than 25 ms, were identified and/or a pace map was obtained showing identical QRS complexes in at least 11 of 12 ECG leads. VTs were ablated successfully in 24 of 26 patients (success rate was 92%). For successful ablation, it is essential that the pace map QRS morphology in 12 leads should be identical with that in spontaneous or induced VT as far as possible in performing pace mapping. Pace mapping is safe, simple and has no unfavourable effect hemodynamics although it takes longer time. Activation mapping takes shorter time and has a high success rate. QRS configuration in spontaneous VT can help to localize the site of VT origin. Deliberate mapping at the site suggested to bo the origin of VT by surface ECG can shorten the duration of mapping and increase the success rate of RFCA. RFCA of VT in patients without structural heart disease is effective, safe, and has a high success rate, so it may be considered as an early therapy for these patients.

Adolescent↗

[The adsorption mechanism of Pb2+, Cd2+, Ni2+ and Co2+ onto activated carbon particles].

The adsorption of Pb2+, Cd2+, Ni2+, Co2+ on activated carbon particles was studied as a function of pH and concentrations of adsorbates. These results showed that the adsorption was strongly pH-dependent and all the adsorption isotherms were in agreement with Freundlich equation. The adsorption could be explained by the surface complexation model. Conditional adsorption constants of surface complexes of Pb2+, Cd2+, Ni2+ and Co2+ with activated carbon particles were calculated by a simplified surface complexation model.

Adsorption↗

[The anatomic study of levator veli palatini muscle].

The purpose of this study was to obtain more informations about the levator veli palatini (LVP) muscle through the dissection of head and neck cadaver samples in 20 sides of normal adults, 4 sides of normal newborns and 4 sides of cleft palate newborns and histological sections in 6 normal fetuses. The results shown that the middle part of LVP is 7.9 mm in width, 3.4mm in thickness and 29mm2 on cross-section area. There are two angle relationship between LVP and the soft palate, which are 44.5 degrees angle to midline sagittal section inward and 33.0 degrees angle to coronal section forward. The LVP insertion is between the 40% to 70% of the soft palate length and only 25% insertion of LVP is located at the junction area of palatal aponeurosis and fibromuscular component of palatine raphe. Other parts of LVP insertion are merged into the midline fibromuscular component. The muscle has a close relationship with the medial part of the cartilaginous portion of Eustachian tube. The LVP is supplied by the palatal branches of ascending palatine artery and ascending pharyngeal artery, which are into the LVP at or above the level of the hard palate. The LVP nerve branches coming from the pharyngeal plexus pass through the lateral pharyngeal space. The LVP reconstruction in cleft palate repair is discussed.

Adult↗

[Effect of homoharringtonine on lens epithelial cells in rabbits].

PURPOSE: To study the effects of Homoharringtonine (Hh) on lens epithelial cells (LEC) in rabbits for the possibility of preventing or treating the development of after cataract. METHODS: Lens epithelial cells from the right eyes of 9 New Zealand Albino rabbits were processed for light microscope and transmission electronic microscope 30 minutes, 3 days and 60 days after phacoemulsification by the use of Hh (20 micrograms/ ml) in balanced salt solution (BSS) as irrigating solution. LEC from the left eyes of the same rabbits served as controls after phacoemulsification by the use of BSS. Clinical examinations were also performed in all eyes before and after the surgery. RESULTS: Hh as irrigating solution during phacoemulsification had antiproliferative effects on LEC 3 days postoperatively, the Hh treated eyes developed less LEC proliferation than the controls. Though the development of after cataract formation (Soemmering ring) could not be prevented in both Hh treated eyes and controls 60 days after phacoemulsification, the ultrastructural study of LEC from the Hh treated eyes indicated some changes of cytoplasm such as vacuolation of organelles. CONCLUSION: It is suggested that increasing the concentration of Hh in irrigating solution for phacoemulsification and prolonging the existence of Hh in aqueous humor may have more effects on the inhibition of the proliferation of LEC. From the results of this preliminary study a pharmacological means of prevention and treatment of after cataract may be indicated.

Animals↗

A secreted mucin carrying sialyl-Lewis a from colon carcinoma cells binds to E-selectin and inhibits HL-60 cell adhesion.

Sialyl-Lewis x and a are known as ligands for E-selectin (ELAM-I) involved in leukocyte-endothelial adhesion. L-CanAg (light cancer antigen), secreted by a colon carcinoma cell line COLO 205, is a soluble mucin-type glycoprotein expressing sialyl-Lewis a antigens. L-CanAg was purified from spent culture medium by trichloracetic acid precipitation and Superose 6 gel filtration. With a monoclonal antibody against E-selectin (BBAI) as a positive control, the purified L-CanAg was shown to bind to E-selectin-Fc coated into plastic microtiter wells and to the surface of transiently E-selectin-transfected COS-I cells in a Ca(2+)-dependent way. Immunofluorescent double labelling showed that both BBAI and L-CanAg stained the same cells and morphological co-localization on E-selectin-transfected COS-I cells. Like BBAI, L-CanAg can inhibit leukocyte HL-60 cell adhesion to E-selectin-transfected COS-I cells, and this inhibition can be blocked by a F(ab')2 fragment directed against the sialyl-Lewis a epitope.

Antigens, Neoplasm↗

Starvation in vivo for aminoacyl-tRNA increases the spatial separation between the two ribosomal subunits.

Structures in situ of individual ribosomes in E. coli have been determined by computer-aided electron microscope tomography using a tilt series of positively stained embedded cellular sections. Amino acid starvation of a bacterial culture, causing a deficiency for aminoacyl-tRNA, induces a spatial separation between the ribosomal subunits compared with ribosomes in exponentially growing cells. Eight ribosomes from each growth condition were aligned to each other, and the two average structures were determined. Comparison of these suggests that the distance between the two subunits increases by approximately 3 nm upon starvation for aminoacyl-tRNA during protein synthesis. Ribosomes in most other states of the translational elongation cycle in exponentially growing cells show a more compact structure than previously realized.

Amino Acids↗

Lung monocyte chemoattractant protein-1 gene expression in bleomycin-induced pulmonary fibrosis.

Recent studies indicate that monocyte chemoattractant protein-1 (MCP-1) may play an important role in pulmonary inflammation. In vitro studies show that a number of cell types are capable of producing MCP-1. In this study, MCP-1 expression in lungs of rats with bleomycin (BLM)-induced pulmonary fibrosis is examined to evaluate its cellular origin and potential role in pathogenesis. Lung fibrosis was induced in male Fisher 344 rats by endotracheal injection on day 0. On selected days after injection, lungs were harvested for in situ and Northern hybridization analyses for MCP-1 mRNA expression, immunochemical and histochemical analyses for MCP-1 protein expression, and identification of cell type. Northern analysis revealed significant elevation in lung MCP-1 mRNA expression beginning on day 3 post-BLM treatment, increasing to a peak on day 7, and then decreasing toward control levels after day 21. In situ hybridization combined with histochemical staining with chromotrope 2R indicate that most of the cells expressing MCP-1 mRNA at these time points are primarily eosinophils. A few scattered reactive fibroblasts, some mononuclear cells, epithelial cells, and cells of certain blood vessel walls also express this mRNA. Increased MCP-1 protein expression also was found to be predominantly within and adjacent to eosinophils. The eosinophils expressing this mRNA were found predominantly within areas of active fibrosis. The kinetics of increase in the number of cells expressing significant MCP-1 mRNA in lung sections paralleled that for MCP-1 mRNA expression, as assessed by Northern analysis. These results, for the first time, demonstrate that MCP-1 is up-regulated significantly in this rat animal model, and that infiltrating eosinophils represent the major cellular source for this increased MCP-1 expression.

Animals↗

Vitronectin-driven human keratinocyte locomotion is mediated by the alpha v beta 5 integrin receptor.

Vitronectin is a soluble serum factor that is known to promote epiboly of keratinocytes in explant cultures and enhance cell spreading and attachment to matrix. Recently, vitronectin was demonstrated to promote human keratinocyte locomotion. The mechanism(s) by which vitronectin enhances keratinocyte migration is unknown. In this study, we quantitated the vitronectin-driven migration of human keratinocytes in the presence of antibodies to vitronectin receptors. We found that vitronectin's effect of promoting human keratinocyte migration was inhibited by antibody-directed against the alpha v beta 5 receptor. In addition, we surface-labeled human keratinocytes, chromatographed extracts of the cell membranes on a vitronectin column, and then immunoprecipitated the bound and eluted proteins with antibodies to specific vitronectin receptors. We identified the vitronectin receptors on human keratinocytes as bands of 150,000 and 100,000 daltons without reduction and as 125,000 and 110,000 daltons under reducing conditions. Immunoprecipitation with specific antibodies identified the major receptor to be the alpha v beta 5 integrin. In addition, we quantitated vitronectin-driven migration of human keratinocytes in the presence of Arg-Gly-Asp (RGD) and control peptides. We found that the presence of RGD, but not control peptide, inhibited vitronectin-driven migration of human keratinocytes. These studies demonstrate that human keratinocytes express vitronectin receptors and use the alpha v beta 5 receptor for cellular locomotion.

Antibodies↗

Cell cycle-dependent modulation of alpha-interferon-inducible gene expression and activation of signaling components in Daudi cells.

To investigate cell cycle-dependent expression of interferon (IFN)-induced genes and signaling pathways, we examined the modulation of IFN-inducible gene expression and p91 activation, and JAK-1 and Tyk-2 kinases' activation in human Burkitt's lymphoma Daudi cells which were synchronized at different points in the cell cycle progression. We observed that each one of 100-, 67-, and 46-kDa 2'-5'-oligoadenylate synthetase (2-5(A)-synthetase) proteins had a unique expression pattern in different phases of the cell cycle which was different from the expression of 2-5(A)-synthetase proteins in exponentially growing Daudi cells. The cell cycle-dependent changes in the overall levels of expression of 2-5(A)-synthetase proteins correlated well with the induction of expression of 2-5(A)-synthetase mRNA as well as the appearance of IFN stimulatory gene factor-3 and expression and activation of p91 in cells released from the G1/S block in the absence of exogenous IFN-alpha. In addition, cells from the G1/S phase exhibited increased tyrosine phosphorylation of JAK-1 and Tyk-2 kinases and p91 by IFN-alpha as compared with asynchronized cells. Enhanced stimulation of activation of JAK-1, Tyk-2, and p91 by IFN-alpha was progressively reduced from G1/S to G2/M to pass G2/M. These findings demonstrate that the levels of constitutive and inducible expression of IFN-alpha-inducible genes, activation of p91, and tyrosine phosphorylation of JAK-1 and Tyk-2 kinases are differentially influenced by the state of the cell cycle.

2',5'-Oligoadenylate Synthetase↗

CD58 (LFA-3) stimulation provides a signal for human isotype switching and IgE production distinct from CD40.

Induction of an IgE response involves several discrete steps: 1) induction of epsilon germ line transcription, 2) DNA recombination, and 3) mature RNA transcription/translation. Here we show that ligation of B cell CD58 by CD2, its natural ligand on T cells, or by mAb, provides a novel IL-4-dependent signal for the latter two steps. Highly purified human B cells were induced to produce IgE by costimulation with IL-4 and CD58 mAb. Although CD58 ligation alone was unable to induce epsilon germ-line transcription, in concert with IL-4-stimulated epsilon germ-line transcription it induced the appearance of productive epsilon transcripts and IgE production. The direct involvement of CD2 was demonstrated: B cells cultured with IL-4 plus murine T hybridoma cells transfected with human CD2 produced IgE. A CD40 Fc fusion protein had no effect on CD58-driven IgE production while inhibiting CD40-dependent responses. Furthermore, cells from patients with common variable immunodeficiency produced IgE in response to IL-4 plus CD40 mAb but not to IL-4 plus CD58 mAb. CD58-driven IgE synthesis was IFN-gamma independent and was not enhanced by exogenous IL-6. Functional differences between CD40 and CD58 IgE stimulation were demonstrated. Thus, the CD2:CD58 ligand/counterligand system provides an alternative pathway by which cell contact signaling may regulate IgE. Given the relative importance of CD2 triggering on mucosal T cells and the mucosal location of IgE production, this may be especially true on mucosal surfaces.

Adult↗

Inhibitory effects of plant polyphenols on rat liver glutathione S-transferases.

Several novel naturally occurring flavonoids and other polyphenols exerted varying degrees of concentration-dependent inhibition on uncharacterized rat liver glutathione S-transferase (EC 2.5.1.18, GST) isoforms. The order of inhibitory potencies of the five most potent polyphenols was tannic acid > 2-hydroxyl chalcone > butein > morin > quercetin, and their IC50 values were 1.044, 6.758, 9.033, 13.710 and 18.732 microM, respectively. Their inhibitions were reversible, as indicated by dialysis experiments. The optimum pH for the inhibitions by four of the compounds (tannic acid, butein, 2-hydroxyl chalcone and morin) was in the range of pH 6.0 to 6.5, but for quercetin the optimum pH was 8.0. These potent inhibitors possess one or more of the following chemical structural features: (a) polyhydroxylation substitutions, (b) absence of a sugar moiety, (c) for the chalcones, the presence of an open C-ring and hydroxylation at either the C-2 or C-3 position, (d) for the flavonoids, the attachment of the B-ring to C-2, and (e) a double bond between C-2 and C-3. Butein exhibited a non-competitive inhibition toward both glutathione (GSH) and 1-chloro-2,4-dinitrobenzene (CDNB). Interestingly, tannic acid showed a non-competitive inhibition toward CDNB but a competitive inhibition toward GSH. The inhibitory potency of tannic acid on rat liver GSTs was concentration and substrate dependent. Using CDNB, p-nitrobenzyl chloride, 4-nitropyridine-N-oxide, and ethacrynic acid as substrates, the IC50 values for tannic acid were 1.044, 11.151, 20.206, and 57.664 microM, respectively.

Animals↗

Interferon-alpha inhibits cyclin E- and cyclin D1-dependent CDK-2 kinase activity associated with RB protein and E2F in Daudi cells.

The state of phosphorylation of retinoblastoma (RB) protein is regulated by CDK2 and CDC2 kinases. In the studies presented here, we have investigated the effect of interferon-alpha (IFN-alpha) on cyclin-dependent kinases in Daudi cells which were synchronized at different points of the cell cycle progression. We observed that the IFN-alpha enhances the expression of underphosphorylated RB protein in Daudi cells released from the G1/S, and this was closely associated with the inhibition of CDK2 kinase and not CDC2 kinase activity. The observed IFN-alpha-sensitive CDK2 kinase activity was dependent on Cyclin E and cyclin D1 but not on cyclin A and was physically associated with transcriptional factors: RB and E2F. In addition, treatment of G1/S Daudi cells with IFN-alpha also inhibited the ability of CDK2 enzyme to phosphorylate the RB protein in vitro. These results suggest possible involvement of cell cycle kinases in IFN-alpha action.

Burkitt Lymphoma↗