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Biomedical subjects

Y F Cheng

Publications and source records attributed to Y F Cheng.

At least 109 records · Page 6Linked to original sources

Nephrolithiasis and nephrocalcinosis in cerebrotendinous xanthomatosis: report of three siblings.

We report the existence of nephrocalcinosis (NC) and/or nephrolithiasis (NL) in three siblings with cerebrotendinous xanthomatosis (CTX). Incomplete renal tubular acidosis (RTA) type 1 is also found in these three siblings after the evaluation of renal acidification function. Although the association of RTA with NC and/or NL is well known, they are rarely reported in CTX patients.

Acid-Base Equilibrium↗

Magnetic resonance imaging of siderotic hepatic adenoma.

This is a case report of a patient with hepatic adenoma who had a magnetic resonance imaging (MRI) appearance mimicking that of adenomatous hyperplasia. The adenoma was hyperintense on T1-weighted image (T1WI) and hypointense on T2-weighted image (T2WI). Pathologically, iron deposition in hepatocytes and Kupffer cells was proved by Prussian blue stain that caused hypointensity on T2WI. Iron deposition in hepatic adenomatous hyperplasia has been documented in the past, but there are no reports of siderotic adenoma in the literature. We suggest that siderotic hepatic adenoma be included in the differential diagnosis when MRI appearance is hyperintense on T1WI and hypointense on T2WI.

Adenoma, Liver Cell↗

Analysis of derivatized peptides by capillary electrophoresis.

Thirteen synthetic prothrombin leader peptides differing only in C terminus were analyzed by capillary electrophoresis. These peptides were derivatized using the novel, fluorescent derivatizing agent, 6-aminoquinolyl-N-hydroxysuccinimidyl carbamate. Derivatized peptides were detected using fluorescence and ultraviolet absorption signals, and underivatized peptides were detected using ultraviolet absorbance at 185 nm. Data are presented which compare the analysis of the derivatized and underivatized peptides.

Amino Acid Sequence↗

Immunomodulation of experimental autoimmune uveoretinitis: a model of tolerance induction with retinal antigens.

Experimental autoimmune uveoretinitis (EAU) is a CD4+ T-lymphocyte mediated inflammation of the uveal tract and retina. As a model of human posterior uveitis it permits further understanding of the underlying immunopathogenesis of uveitis. It also allows for preclinical trials of immunosuppressive therapies and in vivo assessment of alternative strategies for immunointervention. This review highlights possible immunostrategic modalities which prevent the initiation or perpetuation of the immune response, and in particular reports on the novel effect of intranasal induction of tolerance with retinal antigens, prior to immunisation with retinal antigens. The mechanisms and potential application of this 'natural' method of immunosuppression in the treatment of autoimmune disease are discussed.

Adjuvants, Immunologic↗

Intranasal administration of retinal antigens suppresses retinal antigen-induced experimental autoimmune uveoretinitis.

Bovine retinal extract (RE) is a heterologous mixture of highly uveitogenic proteins including S-Antigen (S-Ag), interphotoreceptor retinol binding protein (IRBP) and rhodopsin, and is a potent inducer of experimental autoimmune uveoretinitis (EAU). Intranasal inoculation of Lewis rats with RE performed daily for 10 days prior to immunization with RE suppresses both the severity and the incidence of the clinical response and histopathological changes in EAU. Significant suppression of the disease in treated animals could be achieved with a total (cumulative) intranasal inoculum of 42 micrograms of antigen. Animals which were treated with extract exhibited a normal total antibody response to S-Ag, IRBP and retinal extract when compared with controls [phosphate-buffered saline (PBS) treated] animals. The antibody response in tolerized animals was predominantly anti-S-Ag IgG2a with suppression of anti-S-Ag IgM response. Treated animals had a significantly suppressed delayed-type hypersensitivity (DTH) response to retinal extract but normal response to purified protein derivative (PPD) compared to control animals. Adoptive transfer of splenocytes from treated animals also demonstrated some protection against RE-induced EAU. These results demonstrate that tolerance induction impairs the onset and severity of EAU by inhibiting the DTH response to heterologous mixture of retinal antigens.

Administration, Intranasal↗

Magnetic resonance imaging of the kidneys in paroxysmal nocturnal hemoglobinuria.

Paroxysmal nocturnal hemoglobinuria (PNH) is a blood cell disorder characterized by repeated intravascular hemolysis. Histologically, there is hemosiderin deposition in the proximal tubular cells of the renal cortex. We report a case of PNH with characteristic magnetic resonance findings. The signal intensity of the renal cortex was markedly decreased in various pulse sequences because of the T2-shortening paramagnetic effect of hemosiderin. The significance of signal intensity ratios between renal cortex and medulla, renal cortex and skeletal muscle are discussed. These ratios of the PNH patient are significantly different from those of normal controls (p = 0.0000).

Adult↗

Nasal administration of retinal antigens suppresses the inflammatory response in experimental allergic uveoretinitis. A preliminary report of intranasal induction of tolerance with retinal antigens.

Current immunotherapy of posterior uveitis is non-specific and limited by drug toxicity and unpredictable relapses on therapy. Alternative modes of therapy being investigated using the rat model of experimental autoimmune uveoretinitis (EAU) have included the induction of tolerance with oral administration of milligram quantities of retinal antigens. In this preliminary report we demonstrate that tolerance to retinal antigens can be induced via the upper respiratory tract with microgram doses of antigen, preventing subsequent induction of EAU.

Animals↗

Retinal antigen specific lymphocytes, TCR-gamma delta T cells and CD5+ B cells cultured from the vitreous in acute sympathetic ophthalmitis.

CD5+ B lymphocytes and TCR gamma-delta T lymphocytes, phenotypes implicated in the pathogenesis of autoimmune disease, were isolated from the vitreous in a case of acute sympathetic ophthalmitis. These cells were obtained using a method which allows the selective maintainance in vitro of in vivo activated T lymphocytes. Dual colour flow cytometry showed that after 3 days culture in IL-2 containing medium 61% of cells were CD5/CD19 + ve and 41% CD3/TCR gamma delta + ve. Of the total CD3 + ve population, 15% were gamma/delta negative. These cells formed a population which also responded in a proliferation assay to retinal antigens. Histologically the eye showed a marked mononuclear cell infiltration of the retina, ciliary body and choroid. Granulomatous lesions within the choroid contained lymphocytes, plasma cells and multinucleate giant cells. Immunocytochemistry showed lymphocyte populations to be predominantly CD2 + ve CD3 + ve T lymphocytes of the CD4 sub-set. Distribution of monocytes/macrophages throughout the lesions and restriction of B-lymphocytes to granulomata were all consistent with a DTH type reaction. Despite immunosuppressive therapy, the expression of activation antigens HLA-DR and ICAM-1 on infiltrating and resident ocular tissue cells was high, although IL-2 receptor (CD25) expression was virtually absent. Flow cytometric analysis of peripheral blood cells prior to treatment with Cyclosporin-A showed systemic activation of lymphocytes, with high levels of HLA-DR and CD25 expression and a raised CD4/CD8 ratio.

Antigens↗

Post-capillary Immobilon-P membrane fraction collection for capillary electrophoresis.

A simple, cost-effective and efficient method of continuous fraction collection for capillary electrophoresis is described. The method employs a membrane, such as polyvinylidene difluoride, onto which the separated components from a capillary electrophoresis capillary are directly collected to overcome the problem of analyte dilution and to facilitate the fraction collection process. Model proteins are separated and collected onto a polyvinylidene difluoride membrane.

Animals↗

Linear pharmacokinetics of haloperidol in the rat.

Pharmacokinetics of haloperidol in the rat following intravenous bolus doses of 0.5, 1.0, and 2.5 mg kg-1, respectively, were investigated. It was found that haloperidol was a high extraction ratio drug with a total blood clearance averaging 83 ml min-1 kg-1. The volumes of distribution were large with a mean of 5.5 1 kg-1 (Vc), 11.11 kg-1 (V beta), and 9.61 kg-1 (Vss), respectively. The terminal half-life was 1.5 h. The disposition kinetics of haloperidol was found to be linear over the dose range studied. After constant intravenous infusions of haloperidol by different infusion rates during 12 h, steady-state levels were reached in the blood. The measured steady-state blood concentrations were consistent with those predicted by a biexponential infusion model based on the parameters obtained from the intravenous bolus study. The total blood clearance at steady-state was concentration-independent within the investigated range of 5 to 20 ng ml-1.

Analysis of Variance↗

Immunocytochemical analysis of blood lymphocytes in uveitis.

We studied the surface expression of activation markers IL2-R, HLA-DR and CD45-RO on peripheral T-lymphocytes in two groups of patients (n = 26) with idiopathic uveoretinitis, compared with controls. Thirteen patients were analysed by alkaline phosphatase anti-alkaline phosphatase (APAAP) immunocytochemistry, which demonstrated a significant rise in expression of HLA-DR and IL2-R surface markers. Flow cytometric analysis was performed on a further 13 patients, which confirmed a significant rise in IL2-R expression in uveitis patients. Within this group systemic activation was confined to patients with idiopathic retinal vasculitis. Dual flow cytometry confirmed a CD4+,IL2--R+ T--lymphocyte phenotype. A further 4 patients with retinal vasculitis who had been treated with cyclosporin A demonstrated a 32% reduction in IL2-R expression over a 3-month period. Analysis of CD45-RO and CD5+ cells was found to be uninformative in this study. We have demonstrated activated peripheral lymphocytes in patients predominantly with retinal vasculitis, the significance of which is discussed.

Biomarkers↗

CT findings of pediatric thoracic actinomycosis: report of four cases.

Thoracic actinomycosis is an uncommon disease, which may mimic malignancy, lymphoma or tuberculosis of the chest. In the past three years, four cases of thoracic actinomycosis have been found in children at our hospital. Their computed tomography (CT) findings included pulmonary infiltrates, a chest wall mass, pleural and pericardial effusion, mediastinum involvement and rib changes. Although the final diagnosis of Actinomyces infection depends on a bacterial culture and pathology, CT can play an important role in establishing the diagnosis and evaluating the extent of the disease.

Actinomycosis↗

Integrin expression in malignant melanoma.

Invasion of melanoma cells into the underlying interstitial stromal matrix is the initial step for subsequent local and distant metastasis. The invading tumor cell must interact with the extracellular matrix during the early stages of invasion and later during penetration of lymphatic and blood vessels. This interaction with different types of extracellular matrix predicts that the invasive cell must possess surface adhesion receptors with diverse ligand specificities, including the capacity to bind different types of collagens and adhesive glycoproteins. Metastatic melanoma cells do in fact express multiple adhesion receptors, including several of the receptors from the integrin family of heterodimers. The integrin receptors can be either extremely specific for a single ligand or capable of binding multiple ligands. It is likely that the tumor cell's repertoire of adhesion receptors may influence not only its adhesive properties but its metastatic characteristics as well. There is evidence that normal melanocytes have an integrin profile distinct from that of melanoma cells. In particular, melanocytes adhere poorly to laminin while metastatic melanoma cells bind well to this ligand. This difference in adhesion between the two cell types appears to reflect the fact that melanoma cells express a melanoma-specific integrin (alpha 7 beta 1) that binds laminin and is not detectable in normal melanocytes. The presence of increased laminin receptors and enhanced laminin binding in melanoma cells may contribute to the malignant phenotype.

Animals↗

The integrin complex alpha v beta 3 participates in the adhesion of microvascular endothelial cells to fibronectin.

Fibronectin is a major adhesive glycoprotein of the vascular basement membrane. Since fibronectin is also found in the interstitium, it may be important not only for attachment but also for endothelial cell migration during neovascularization. We have analyzed how human dermal microvascular endothelial cells use their diverse set of integrin receptors to interact with this ligand. Immunofluorescent staining with specific antibodies identified both beta 1 and beta 3 integrin receptor complexes in focal adhesion plaques on cells adhering to immobilized fibronectin. Adhesion assays with blocking monoclonal antibodies implicated both beta 1 and beta 3 complexes, specifically alpha 5 beta 1 and alpha v beta 3, in the initial adhesion of cells to fibronectin. Finally, ligand affinity chromatography of extracts of surface radiolabeled cells established that both alpha 5 beta 1 and alpha v beta 3 could bind to the 110-kDa cell-binding fragment of fibronectin. An additional receptor complex composed of an alpha v subunit and a beta 5-like subunit was also detected. These results provide evidence that microvascular endothelial cells use multiple integrin receptors, from several beta families, to attach to fibronectin surfaces.

Cell Adhesion↗

Laminin-binding integrin alpha 7 beta 1: functional characterization and expression in normal and malignant melanocytes.

A novel integrin, alpha 7 beta 1, that specifically binds with high affinity to laminin has been identified on melanoma cells. This complex was purified from both human and murine melanoma cells by laminin-affinity chromatography, and the alpha 7 subunit was recovered after gel electrophoresis. N-terminal amino acid sequence analysis of the alpha 7 subunit from both human and mouse cells verifies that this integrin is distinct from other alpha chains in the beta 1 family, although strikingly similar to the alpha 6 subunit. By using specific proteolytically derived fragments of laminin, it was determined that the alpha 7 beta 1 complex binds selectively to the E8 region, which represents part of the long arm of laminin. In contrast, the receptor failed to bind to the P1 fragment, which contains the intersection of the short arms of laminin. Although the alpha 7 beta 1 complex was commonly expressed in melanoma cells, this integrin was not detected in normal melanocytes, suggesting that alpha 7 expression may be associated with malignant transformation. These results establish the existence of a novel integrin that binds to the E8 domain of laminin and appears to mediate cell adhesion to this ligand.

Amino Acid Sequence↗

Role of laminin-binding integrin in the invasion of basement membrane matrices by fibrosarcoma cells.

Laminin is a large glycoprotein that is found in basement membranes and promotes cell adhesion and migration. In human fibrosarcoma cells we detected the presence of an integrin complex, with a Mr of 140,000/120,000 under nonreducing conditions, that bound specifically to laminin-Sepharose columns. Immunoprecipitation with monoclonal antibodies characterized this complex as alpha 6 beta 1. Attachment of the fibrosarcoma cells to laminin substrates was completely inhibited in the presence of anti-alpha 6 beta 1 antibody, while attachment to fibronectin and type IV collagen was unaffected. When seeded onto reconstituted basement membrane, the fibrosarcoma cells spread out, migrated, and invaded the matrix. In the presence of anti-beta 1 or anti-alpha 6 beta 1 antibodies, initial invasion through the matrix was inhibited. The results indicate that the HT1080 cells express the alpha 6 beta 1 complex and that it mediates their attachment to laminin. Furthermore, this receptor appears to be important during initial attachment and subsequent invasion of basement membrane-like matrices.

Amino Acid Sequence↗

Plant sterol inhibition of abscisic acid-induced perturbations in phospholipid bilayers.

Abscisic acid (ABA)-induced phospholipid bilayer perturbations (permeability and lipid vesicle aggregation) are shown to be reversed by incorporation of a commercially available mixture of plant sterols (60% beta-sitosterol, 27% campesterol and 13% dihydrobrassicasterol) into the membranes. As little and 5 membrane mol% plant sterol inhibits ABA-stimulated permeability of both saturated and unsaturated mixed phosphatidylcholine/phosphatidylethanolamine bilayers to the fluorescent anion carboxyfluorescein by more than 50%. The same conclusion was reached by an osmotic swelling technique for the uncharged permeant solute erythritol. Hormone-induced carboxyfluorescein permeability to mixed acyl chain phosphatidylcholine bilayers was similarly inhibited by the sterols, but only if the membranes were tested at a temperature where liquid crystal and gel states coexist. The plant sterols were also shown to prevent the ABA-induced fusion of mixed phosphatidylcholine/phosphatidylethanolamine bilayers. The ABA effect on membranes is inhibited equally by plant sterols as well as cholesterol. From these experiments a possible role is suggested for plant sterols in controlling the mode of action of ABA.

Abscisic Acid↗

Human microvascular endothelial cells use beta 1 and beta 3 integrin receptor complexes to attach to laminin.

Microvascular endothelial cells (MEC) use a set of surface receptors to adhere not only to the vascular basement membrane but, during angiogenic stimulation, to the interstitium. We examined how cultured human MEC interact with laminin-rich basement membranes. By using a panel of monoclonal antibodies, we found that MEC cells express a number of integrin-related receptor complexes, including alpha 1 beta 1, alpha 2 beta 1, alpha 3 beta 1, alpha 5 beta 1, alpha 6 beta 1, alpha V beta 3. Attachment to laminin, a major adhesive protein in basement membranes, was studied in detail. Blocking monoclonal antibodies specific to different integrin receptor complexes showed that the alpha 6 beta 1 complex was important for MEC adhesion to laminin. In addition, blocking antibody also implicated the vitronectin receptor (alpha V beta 3) in laminin adhesion. We used ligand affinity chromatography of detergent-solubilized receptor complexes to further define receptor specificity. On laminin-Sepharose columns, we identified several integrin receptor complexes whose affinity for the ligand was dependent on the type of divalent cation present. Several beta 1 complexes, including alpha 1 beta 1, alpha 2 beta 1, and alpha 6 beta 1 bound strongly to laminin. In agreement with the antibody blocking experiments, alpha V beta 3 was found to bind well to laminin. However, unlike binding to its other ligands (e.g., vitronectin, fibrinogen, von Willebrand factor), alpha V beta 3 interaction with laminin did not appear to be Arg-Gly-Asp (RGD) sensitive. Finally, immunofluorescent staining demonstrated both beta 1 and beta 3 complexes in vinculin-positive focal adhesion plaques on the basal surface of MEC adhering to laminin-coated substrates. The results indicate that both these subfamilies of integrin heterodimers are involved in promoting MEC adhesion to laminin and the vascular basement membrane.

Antibodies, Monoclonal↗