Diabetes mellitus after renal transplantation.
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Adult↗
Biomedical subjects
C Huang
Publications and source records attributed to C Huang.
Immunohistochemical detection of human basophils in late-phase skin reactions.
BACKGROUND: Human basophils are difficult to detect with classic histochemical stains at sites of allergic inflammation. The 2D7 anti-basophil monoclonal antibody was used to identify basophils in skin during the late-phase response to a cutaneous allergen challenge. METHODS: The 2D7 monoclonal antibody was used on protease-digested sections of skin biopsy specimens obtained 6 and 24 hours after an allergen or buffer challenge. The skin chamber technique was used to compare buffer- and allergen-challenged sites at 6 hours, and intradermal injection of allergen was used to compare allergen-challenged sites at 6 and 24 hours. RESULTS: Dramatic increases in the numbers of 2D7+ cells and in tissue staining by 2D7 were observed 6 hours after allergen challenge compared with buffer challenge. Histamine levels in skin chamber fluid varied with 2D7+ cell concentrations. By 24 hours, 2D7+ cells and tissue staining appeared to diminish but were still detectable in the allergen-challenged sites. Basophils localized primarily in and around blood vessels, whereas mast cells remained mostly in the superficial dermis. Mast cells were 2D7- in both the allergen- and buffer-challenged skin. Metachromatic staining of 2D7+ basophils with toluidine blue was absent in these tissue sections. CONCLUSIONS: The 2D7 monoclonal antibody provides a more sensitive and precise marker than histochemical staining for human basophil involvement during the late-phase response to an allergen challenge. Basophil infiltration was observed at 6 hours only after allergen challenge and persisted at similar levels by 24 hours.
Allergens↗
Risk of melanoma in medium-sized congenital melanocytic nevi: a follow-up study.
BACKGROUND: The risk of the occurrence of malignant melanoma (MM) in medium-sized (1.5 to 19.9 cm in diameter) congenital melanocytic nevi (CMN) is the subject of controversy. Universally accepted recommendations regarding the management of such lesions have not been made. OBJECTIVE: Our purpose was to assess the risk of MM arising in medium-sized CMN. METHODS: The study included 230 medium-sized CMN in 227 patients, first seen in a private dermatology practice from 1955 to 1996, who were followed up for MM arising within their CMNs. Criteria for entry into the study included (1) a clinically diagnosed medium-sized CMN, (2) minimum follow-up period of 1 year, and (3) a photograph of the lesion in the patient's medical record. RESULTS: No MM occurred in a medium-sized CMN during an average follow-up of 6.7 years (median, 5.8 years) to an average age of 25.5 years (median, 19.1 years). CONCLUSION: The results of this short-term follow-up study do not support the view that there is a clinically significantly increased risk for MM arising in banal-appearing medium-sized CMN or that prophylactic excision of all such lesions is mandatory. Lifelong medical observation seems a reasonable alternative for many medium-sized CMN.
Adolescent↗
Potentiation of insulin-induced phosphatidylinositol-3 kinase activity by phorbol ester is mediated by protein kinase C epsilon.
Our previous results have demonstrated that phorbol 12-myristate 13-acetate (TPA) and insulin synergistically stimulate the activity of phosphatidylinositol-3 kinase (PI-3 kinase) and PI-3 kinase plays an important role in both of TPA-induced AP-1 activation and cell transformation in tumour promotion sensitive (P+) JB6 cells. In the present study, we investigated the role of PKC and its isozymes in the synergistic induction of PI-3 kinase by TPA and insulin. Bisindolylmaleimide inhibits TPA- and TPA+ insulin-induced PI-3 kinase activity. Pretreatment of cells for 24 h with TPA has significant inhibitory effects on TPA-induced PI-3 kinase activity and abolishes the synergistic effect of TPA and insulin-stimulated PI-3 kinase activity. Furthermore, overexpression of a dominant negative PKC epsilon, but not dominant negative PKC alpha, blocks the synergistic effect of TPA and insulin-induced PI-3 kinase activity. These results indicate that the potentiation effect of TPA on insulin-induced PI-3 kinase activity is specific through PKC epsilon in JB6 cells.
Animals↗
Prostaglandin E2 receptor EP3alpha subtype: the role of N-glycosylation in ligand binding as revealed by site-directed mutagenesis.
Functional mouse prostaglandin E2 (PGE2) receptor EP3alpha subtype has been expressed in insect cells using a baculovirus system (Huang C. and Tai H.-H. Biochem J 1995; 307: 493-498). EP3alpha receptor has two potential sites (Asn-X-Ser/Thr), Asn 16 and Asn 193, for N-glycosylation. The role of glycosylation in ligand binding of the EP3alpha receptor was investigated by site-directed mutagenesis. Asn was mutated to Gln in each of the two potential glycosylation sites in the EP3alpha receptor. Recombinant wild-type and mutant EP3alpha receptors were expressed in insect cells using baculovirus. Ligand binding assay indicated that the affinity of PGE2 binding was reduced by 50% in the Gln 193 mutant EP3alpha receptor, while the specificity of ligand binding was unaltered. The affinity for PGE2 binding was not affected in the Gln 16 mutant EP3alpha receptor. However, its specificity was partially changed as the EP3-specific agonist became less effective in displacing the [3H]-PGE2 binding to the mutant receptor. These results indicated that N-glycosylation of the EP3alpha receptor could partially affect the affinity and specificity of the ligand binding.
Animals↗
Total synthesis of (R,S)-sophoraflavanone C
Sophoraflavanone C, a C-8 geranylflavanone natural product originally isolated from Echinosophora koreensis, has been synthesized in racemic form in six steps, starting from 2,4, 6-trihydroxyacetophenone and 2,4-dihydroxybenzaldehyde.
Journal Article↗
Molecular cloning and nucleotide sequence of 3'-terminal region of classical swine fever virus LPC vaccine strain.
A cDNA of the 3'-terminus of classical swine fever virus (LPC vaccine strain) was cloned and sequenced. The 3431 nucleotides and deduced amino acid sequences were compared with those of other pestiviruses, and the similarity of nucleotide sequences and deduced amino acid sequences were found to be 84-95% and 95-98%, respectively. Similar to other isolates of classical swine fever virus, the sequenced region included the non-structural gene p58 (NS5A) and part of p76 (NS5B) gene. The p76 gene of LPC vaccine strain also contained a highly conserved motif G-D-D (Gly-Asp-Asp) that is present in the RNA replicase of positive-stranded RNA viruses. With the sequence data currently available, we carried out a phylogenetic analysis and obtained a genealogical relationship among members of the classical swine fever virus.
Amino Acid Sequence↗
Regulation and function of mast cell proteases in inflammation.
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Animals↗
Method for measuring the spatial variability of aerosol penetration through respirator filters.
Fibrous filter media are widely used in respirators to remove airborne particulate matter from the inhaled airflow of workers. The N95 half-mask particulate respirator appears to be the most frequently used respirator under the new NIOSH regulation, 42 CFR 84. Considerable spatial variability in light penetration through the fibrous filter medium of an N95 respirator can be seen by visual observation when it is held to the light. This variability is due to the way in which the fibers are manufactured and laid down to form the filter medium. Similar spatial variability is expected in the aerosol penetration through the filters. Therefore, a test method has been developed for measuring the spatial variability in aerosol penetration. The main components of this method are an aerosol generator, a filter test stand with a movable sampling inlet, an aerosol size spectrometer, and an aerosol photometer. Measurements with the filter media of N95 respirators, tested at average filtration velocities corresponding to light, moderate, and heavy work loads, have shown spatial variations in aerosol penetration in excess of 100% relative to the average aerosol penetration for the entire respirator. N95 respirators are required to be at least 95% efficient (i.e., less than 5% penetrating) at the most penetrating particle size, when tested at 85 L/min. Tests with the new method have shown that the aerosol penetration of the most penetrating particles of about 0.1 micron diameter may locally be higher than 5%, while the average aerosol penetration of 0.1 micron particles is less than 5%.
Aerosols↗
Demonstration of multilineage chimerism in a nonhuman primate concordant xenograft model.
Prior studies from our laboratory have demonstrated that a nonmyeloablative conditioning regimen can induce transient mixed chimerism and renal allograft tolerance between MHC disparate cynomolgus monkeys. We have also shown that this preparative regimen can be extended to a concordant baboon to cynomolgus xenograft model by adding, to the post transplant protocol, therapy designed to prevent antibody production. Here we examine the use of brequinar (BQR) for this purpose and the efficacy of two new reagents developed to demonstrate the establishment of chimerism in the xenograft recipients. The cynomolgus recipients were conditioned with WBI (300 cGy), TI (700 cGy), ATG, cyclosporine, and brequinar sodium. To detect engraftment of the donor marrow, we prepared a polyclonal cynomolgus anti-baboon antibody (CABA) and a monoclonal antibody (215.1), which distinguish baboon and cynomolgus lymphocytes and granulocytes. We employed flow cytometry analysis to detect multilineage chimerism in the xenograft recipients. Five of the six recipients monitored using our new reagents (CABA and 215.1) developed detectable chimerism and only one of these animals lost its kidney to rejection. However, other complications have not permitted assessment of long-term outcome. The features of the multilineage chimerism included the detection of donor granulocytes (1.8-77.4%) and lymphocytes (2.4-22.2%) for 9 to 37 days. Our new reagents permit the detection of multilineage mixed chimerism, which may be a predictor of xenograft tolerance. We also conclude that brequinar may be effective in preventing antibody formation, but because of its toxicity, it is probably not the drug of choice for extension of the mixed chimerism protocol to concordant xenografts.
Animals↗
Role of phosphatidylinositol 4,5-bisphosphate in Ras/Rac-induced disruption of the cortactin-actomyosin II complex and malignant transformation.
Oncogenic Ras mutants such as v-Ha-Ras cause a rapid rearrangement of actin cytoskeleton during malignant transformation of fibroblasts or epithelial cells. Both PI-3 kinase and Rac are required for Ras-induced malignant transformation and membrane ruffling. However, the signal transduction pathway(s) downstream of Rac that leads to membrane ruffling and other cytoskeletal change(s) as well as the exact biochemical nature of the cytoskeletal change remain unknown. Cortactin/EMS1 is the first identified molecule that is dissociated in a Rac-phosphatidylinositol 4,5-biphosphate (PIP2)-dependent manner from the actin-myosin II complex during Ras-induced malignant transformation; either the PIP2 binder HS1 or the Rac blocker SCH51344 restores the ability of EMS1 to bind the complex and suppresses the oncogenicity of Ras. Furthermore, while PIP2 inhibits the actin-EMS1 interaction, HS1 reverses the PIP2 effect. Thus, we propose that PIP2, an end-product of the oncogenic Ras/PI-3 kinase/Rac pathway, serves as a second messenger in the Ras/Rac-induced disruption of the actin cytoskeleton and discuss the anticancer drug potential of PIP2-binding molecules.
3T3 Cells↗
Role of ANG II in mediating somatosensory-induced renal nerve-dependent antinatriuresis in the rat.
This study examined the renal nerve-dependent renal hemodynamic and tubular responses to somatosensory stimulation in the anesthetized rat by use of subcutaneously applied capsaicin when the action of ANG II was blocked peripherally or selectively within the brain. Activation of skin somatosensory receptors caused a transient reversible 10-15% increase in blood pressure, and while renal perfusion pressure was regulated at control levels, there was a transient fall in urine flow and sodium excretion even though both renal blood flow and glomerular filtration rate were unchanged. These reflexly induced excretory responses were abolished when the renal nerves were sectioned. Administration of the ANG II AT1-receptor antagonist, losartan, either intravenously at 3 or 10 mg/kg or locally into the lateral cerebroventricles at 15 microg plus 7.5 microg/h, had no effect on capsaicin-induced vasopressor responses but blocked the reductions in urine flow and sodium excretion. These findings are consistent with ANG II being involved in at least two stages in the reflex, one centrally and one at the periphery.
Analysis of Variance↗
Low molecular weight heparin reduces triglyceride, VLDL and cholesterol/HDL levels in hyperlipidemic diabetic patients on hemodialysis.
BACKGROUND: Low molecular weight heparin (LMWH) provides a safe and effective alternative for hemodialysis anticoagulation. While unfractionated (UF) heparin has been implicated in hyperlipidemia, the effect of LMWH on the lipid profile in nondiabetic patients is controversial in chronic hemodialysis. The effect of LMWH in diabetic patients, a high risk group of hyperlipidemia, has not been studied. METHOD: LMWH was tested for its safety and efficacy in 10 nondiabetic Taiwanese patients. To evaluate influence of lipid profile, a crossover study was carried out in 10 type II diabetic patients with poor blood sugar control associated with high triglyceride (430.4 +/- 101.1 mg/dl) and total cholesterol levels (219.2 +/- 12.7 mg/dl) using UF heparin for more than 1 year. These patients were subjected to Fraxiparine, an LMWH, for 6 months and then switched back to UF heparin for another 6 months. Lipid profiles were measured every 2 months without prescribing lipid-lowering agents and the blood sugar was maintained at stationary levels. RESULTS: LMWH is safe and effective in Taiwanese patients as a single bolus injection and maintains a 9.4% higher platelet count immediate postdialysis compared to UF heparin. With high HbA1c levels (9.6 +/- 0.6%), mean triglyceride and VLDL levels started to decrease at the 4th month after LMWH treatment and reached a 34% reduction in triglyceride, a 26.2% reduction in VLDL, and a 19% reduction of total cholesterol/HDL ratio at the 6th month. Increments of triglyceride levels were found at the 6th month after a switch back to UF heparin. The levels of total cholesterol, LDL-cholesterol, HDL-cholesterol, apolipoprotein A-1 and B remained unchanged. CONCLUSION: LMWH may be beneficial to lipid control in hyperlipidemic diabetic patients on hemodialysis.
Adult↗
Determination of concentration of cytosolic NADH-cytochrome b5 reductase in erythrocytes from normal Chinese adults, neonates and patients with hereditary methemoglobinemia by double-antibody sandwich ELISA.
NADH-cytochrome b5 reductase (b5R), present in various tissues of the body, is a redox enzyme of multiple functions. The deficiency of the enzyme leads to hereditary methemoglobinemia. With rabbit anti-b5R antibody for plate coating and enzyme-labeled anti-b5R monoclonal antibody as reporter, we have developed a sandwich ELISA procedure for the determination of b5R concentration. This procedure is sensitive to a wide range of linearity, and convenient in coping with large numbers of samples. Using this novel method, cytosolic b5R concentration in the erythrocytes of 30 normal Chinese adults was estimated to be 25.63+/-8.54 ng/mg Hb. It was found that the concentration of red cell soluble b5R of five newborns was significantly lower than that of normal adults and soluble b5R was undetectable in the erythrocytes of 4 patients with type I hereditary methemoglobinemia. Our results demonstrated that the reduced b5R activity in red cell cytosol of both neonates and type I hereditary methemoglobinemic patients results largely or mainly from the lowered b5R concentration. Our novel method might be further exploited for in-depth investigation of the relationship between the qualitative and quantitative changes of b5R with regard to physiological and pathological conditions.
Adult↗
Reduced integrin alpha3 expression as a factor of poor prognosis of patients with adenocarcinoma of the lung.
PURPOSE: We investigated the possible association between integrin alpha3 and motility-related protein (MRP-1), cluster of differentiation antigen 9 (CD9) gene expression in non-small-cell lung cancer (NSCLC) and evaluated the prognostic significance of integrin alpha3 expression. PATIENTS AND METHODS: We performed a retrospective study of integrin alpha3 and MRP-1/CD9 expression in resected tumor tissues from 151 NSCLC patients using quantitative reverse-transcriptase polymerase chain reaction (RT-PCR) and immunohistochemistry. RESULTS: The ratio of integrin alpha3/beta-actin expression ranged from 0 to 5.87 (mean was 0.80; median, 0.70). Using the cutoff value of 0.7, there were 78 (52%) integrin alpha3-positive tumors and 73 (48%) tumors with reduced integrin alpha3 expression. The immunohistochemical results agreed well with those of the RT-PCR assays, and 88% had no discrepancy. In case of discrepancy, the results of RT-PCR were used in specimen classification. Integrin alpha3 gene expression was independent from MRP-1/CD9 gene expression. No significant association was found between integrin alpha3 expression and the patients' clinical characteristics. The overall survival rate of patients with integrin alpha3-positive NSCLCs was only slightly better than that of individuals whose tumors had reduced integrin alpha3 expression (55.9% v 47.1%; P = .085). By comparison, the overall survival rate of patients with integrin alpha3-positive adenocarcinomas was strikingly greater than in those whose tumors had reduced gene expression (54.4% v 35.2%; P = .004). Multivariate analysis with the Cox regression model of NSCLC and adenocarcinoma indicated that integrin alpha3 expression correlated better (P = .0188 and P = .0008, respectively) with the overall survival rate than other variables, except lymph node status. CONCLUSION: No significant association was found between integrin alpha3 and MRP-1/CD9 gene expression in lung cancer. However, reduced integrin alpha3 expression is a poor prognosis factor in patients with adenocarcinomas.
Adenocarcinoma↗
Short-term and long-term fracture prediction by bone mass measurements: a prospective study.
Prospective and cross-sectional studies have demonstrated that bone mass predicts fracture risk. However, most prospective studies have been limited to a few years of follow-up. We investigated the long-term associations of bone mass with vertebral fractures using longitudinal data collected from more than 500 postmenopausal Japanese-American women in the Hawaii Osteoporosis Study. New vertebral fractures were identified during an average of 2.7 years between 1992 and 1995. Short-term fracture prediction was evaluated using bone mass (spine, calcaneus, distal radius, and proximal radius) measured at the beginning of follow-up. Long-term prediction was evaluated using bone mass measured before the follow-up period (11 years earlier for nonspine bone mass and 8 years earlier for spine). All four bone mass measurements were significant predictors of vertebral fractures identified during the subsequent 2.7 years (short-term prediction), with odds ratios (ORs) ranging from 1.5 to 1.9. The ORs for long-term prediction were slightly lower in magnitude, but the confidence intervals overlapped the short-term ORs considerably, suggesting that both long-term and short-term associations are similar in magnitude. Furthermore, cross-sectional analyses based on bone mass measurements performed at the end of follow-up (after fractures had occurred) yielded results similar to those based on prospective data (bone mass measured prior to fractures), suggesting that the relatively quick and inexpensive cross-sectional studies are useful for preliminary evaluations of new bone mass measurement techniques. The results suggest that bone mass measurements made up to 11 years earlier can predict vertebral fractures almost as well as measurements made more recently.
Asian↗
Inhibition of ultraviolet C irradiation-induced AP-1 activity by aspirin is through inhibition of JNKs but not erks or P38 MAP kinase.
The exposure of mammalian cells to ultraviolet (UV) irradiation leads to the activation of transcription factors, such as AP-1 and NFkB. We demonstrate that aspirin, a promising cancer chemopreventative agent, inhibited UVC-induced AP-1 activity in JB6 cells. In JB6 cells, UVC stimulated Erks, JNKs and P38 kinase activities; aspirin only inhibited activation of JNKs, but not the other MAP kinases. Since the transcription factor AP-1 is important for the process of tumor promotion, the inhibitory effect of aspirin on AP-1 activation suggests that it can be used as a chemopreventative agent against skin cancer.
Animals↗
Vanadium induces AP-1- and NFkappB-dependent transcription activity.
Vanadate has been reported to be involved in the causation of cancer. In this study, we found that both AP-1 and NFkappaB activities were increased after treatment with sodium vanadate in JB6 cells. Maximum induction of AP-1 and NFkappaB appeared at 48 to 72 h. Phosphorylations of Erks and p38 kinases were markedly increased at 100 microM of vanadate, while phosphorylation of JNKs was not affected. Vanadate also enhances the phosphorylation of IkappaBalpha. These results suggest that the activation of AP-1 and NFkappaB by vanadate may be mediated through enhancement of phosphorylation of Erk/p38 kinases and IkappaBalpha, respectively.
Animals↗