Personal Factors Affecting Therapeutic Responses to BCG Vaccination in Asthmatics

PURPOSE: Bacille Calmette-Guerin (BCG) vaccination has been reported to be an effective treatment for asthma in several animal models. This study investigated whether the response to BCG treatment in asthma depends on subject clinical characteristics. METHODS: Stable asthma patients were vaccinated with BCG. One month later, alterations in pulmonary function after vaccination and their relationships with subject clinical characteristics were determined. RESULTS: Of 149 patients with asthma, 54 (36.2%) showed a good or fair response to BCG. The DeltaFEV1 after vaccination was significantly related to age (r=-0.348, P0.05). A good/fair response was highly prevalent in atopic females compared with atopic males, especially among those aged < or =50 years (90.9% vs. 40.0%, P=0.024). Age (P<0.001, odds ratios (OR)=0.92, confidence interval (CI)=0.88-0.96) and atopy (P<0.01, OR=4.95, CI=1.70-14.44) were significant predictors for a good/fair response in females. However, blood eosinophil counts (P<0.05, OR=1.18, CI=1.01-1.39) and FEV1 % best (P<0.001, OR=0.86, CI=0.79-0.94), but not age or atopy, were significant predictors in males. Approximately three-quarters of the males were smokers. CONCLUSIONS: The therapeutic effect of BCG in asthma may differ according to patient clinical characteristics. The greatest benefit occurred in young atopic females. Asthma activity indices, such as eosinophilia and FEV1 % best, were more predictive of a good/fair response in males; this may have been related to cigarette smoking.

Implication of phosphorylation of the myosin II regulatory light chain in insulin-stimulated GLUT4 translocation in 3T3-F442A adipocytes

In adipocytes, insulin stimulates glucose transport primarily by promoting the translocation of GLUT4 to the plasma membrane. Requirements for Ca2+/ calmodulin during insulin-stimulated GLUT4 translocation have been demonstrated; however, the mechanism of action of Ca2+ in this process is unknown. Recently, myosin II, whose function in non-muscle cells is primarily regulated by phosphorylation of its regulatory light chain by the Ca2+/calmodulin-dependent myosin light chain kinase (MLCK), was implicated in insulin-stimulated GLUT4 translocation. The present studies in 3T3- F442A adipocytes demonstrate the novel finding that insulin significantly increases phosphorylation of the myosin II RLC in a Ca2+-dependent manner. In addition, ML-7, a selective inhibitor of MLCK, as well as inhibitors of myosin II, such as blebbistatin and 2,3-butanedione monoxime, block insulin- stimulated GLUT4 translocation and subsequent glucose transport. Our studies suggest that MLCK may be a regulatory target of Ca2+/calmodulin and may play an important role in insulin-stimulated glucose transport in adipocytes.

Changes in the Rate of Renin Secretion During Cell Cycle of As 4.1 Cells / 대한신장학회잡지

BACKGROUND: Renin is secreted from the juxtaglomerular (JG) cells in response to a wide variety of extracellular stimuli. To study the underlying mechanism of regulation of renin secretion at molecular level, pure JG cell lines (As 4.1) cloned from renal JG tumor was used. In this study, to explore the feasibility of As 4.1 cells as an in vitro model for renin secretion, the changes of renin secretion from As 4.1 in culture during cell cycle were characterized. METHODS: To address this issue, As 4.1s were synchronized in G0, G1, S, G2, early M and late M phase during experiment. RESULTS: The rate of renin secretion was above 1 ng AI/well/hr in G0, G2/M and early mitotic phase and 0.5 ng AI/well/hr in G1, G1/S, S and late mitotic phase. ML-7 (6x10(-5) M), an inhibitor of MLCK which is known to stimulate renin secretion, increased the rate of renin secretion much greater in G1, G1/S, S and late M phase than the other phases; in particular, in early mitotic phase it had no stimulation. On the other hand, the rate of renin secretion was not influenced through out cell cycles by calyculin A, an inhibitor of type 1 protein phosphatase. Forskolin, an activator of adenlyate cyclase resulting in an elevation of intracellular cyclic AMP, stimulated renin secretion only in S phase in a concentration dependent manner. CONCLUSION: The present study demonstrated that As 4.1 cells in culture secrete active renin in much the similar manner to JG cells in situ but its rate varies during each phase of the cell cycle. Thus As 4.1 cells can be utilized as an in vitro model for renin secretion. But, changes in the rate of renin secretion and the secretory responses to stimulators or inhibitors during cell cycle must be considered in conducting experiments to elucidate the cellular and molecular mechanism of the renin secretion.

Vesicular transport as a new paradigm in short-term regulation of transepithelial transport

The vectorial transepithelial transport of water and electrolytes in the renal epithelium is achieved by the polarized distribution of various transport proteins in the apical and basolateral membrane. The short-term regulation of transepithelial transport has been traditionally thought to be mediated by kinetic alterations of transporter without changing the number of transporters. However, a growing body of recent evidence supports the possibility that the stimulus-dependent recycling of transporter-carrying vesicles can alter the abundance of transporters in the plasma membrane in parallel changes in transepithelial transport functions. The abundance of transporters in the plasma membrane is determined by net balance between stimulus-dependent exocytic insertion of transporters into and endocytic retrieval of them from the plasma membrane. The vesicular recycling occurs along the tracts of the actin microfilaments and microtubules with associated motors. This review is to highlight the importance of vesicular transport in the short-term regulatory process of transepithelial transport in the renal epithelium. In the short-term regulation of many other renal transporters, vesicular transport is likely to be also involved. Thus, vesicular transport is now emerged as a wide-spread general regulatory mechanism involved in short-term regulation of renal functions.

Role of Ca2+ in the stimulation of glucose transport by insulin in adipocytes

We investigated the role of Ca2+ and protein kinases/phosphatases in the stimulatory effect of insulin on glucose transport. In isolated rat adipocytes, the simple omission of CaCl2 from the incubation medium significantly reduced, but did not abolish, insulin-stimulated 2-deoxy glucose (2-DG) uptake. Pre-loading adipocytes with intracellular Ca2+ chelator, 5,5'-dimethyl bis (o-aminophenoxy)ethane-N,N,N'N' tetraacetic acetoxymethyl ester (5,5'-dimethyl BAPTA/AM) completely blocked the stimulation. Insulin raised intracellular Ca2+ concentration ((Ca2+)i) about 1.7 times the basal level of 72+/-5 nM, and 5,5'-dimethyl BAPTA/AM kept it constant at the basal level. This correlation between insulin-induced increases in 2-DG uptake and (Ca2+)i indicates that the elevation of (Ca2+)i may be prerequisite for the stimulation of glucose transport. Studies with inhibitors (ML-9, KN-62, cyclosporin A) of Ca2+-calmodulin dependent protein kinases/phosphatases also indicate an involvement of intracellular Ca2+. Additional studies with okadaic acid and calyculin A, protein phosphatase-1 (PP-1) and 2A (PP-2A) inhibitors, indicate an involvement of PP-1 in insulin action on 2-DG uptake. These results indicate an involvement of Ca2+-dependent signaling pathway in insulin action on glucose transport.

Lipocortin 1 mediates the suppressive effects of dexamethasone on CoNinduced proliferative response and nitric oxide production in rat splenic leukocytes

Lipocortin 1 has been proposed as a putative mediator of anti-inflammatory actions of glucocorticoids. We investigated the role of lipocortin 1 in the effect of dexamethasone using rat splenic leukocytes. Concanavalin A(ConA; 1-microgram/ml) increased the leukocyte proliferation and nitric oxide(NO) generation, which were measured as (3H)-thymidine uptake by the cells and nitrite accumulation in the culture media, respectively. Dexamethasone suppressed CoNinduced cell proliferation, in a concentration-dependent manner with EC-50 around 50nM. The addition of anti-lipocortin 1 (Anti-LC1) reversed dexamethasone effects: 0.24, 1.2, 6 microgram/ml of Anti-LC1 reversed dexamethasone(50nM)-induced suppression of thymidine uptake by 9+/-3%, 16+/-3%, 36+/-5%, respectively; 0.24, 1.2, and 6-microgram/ml of Anti-LC1 reversed dexamethasone-induced decrease of nitrite concentration by 49 +/- 16%, 61 +/- 20%, 77 +/- 19 %, respectively. The present data indicate that lipocortin 1 mediates, at least in part, glucocorticoids-induced suppression of leukocyte proliferation and blockade of NO generation.

Changes in Insulin Sensitivity and Insulin Secretory Function in Hyperthyroid Patients / 대한내분비학회지

The impairement of glucose metabolism is frequently associated in hyperthyroidism. The present study was performed to determine the effect of the thyroid hormone excess on insulin sensitivity and on insulin secretory function in vivo. Ten newly diagnosed hyperthyroid patients and fifteen healthy control subjects were subjected to frequently sampled intravenous glucose tolerance tests(FSIGT) after an overnight fast. Insulin sensitivity, represented by the insulin sensitivity index(S_1), was assessed by minimal model analysis of FSIGT data. Insulin secretion was measured by the total area under the insulin curve after glucose load.The results were as follows.1) The K_G values, which represent glucose tolerance, were not different between the hyperthyroid patients and the normals(2.2+-0.3 vs. 2.5+-0.3%/min, p>0.05).2) S_1 was significantly decreased in the hyperthyroid patients in comparison to the normals(7.5+-1.4 vs. 2.6+-0.3X10

The effect of insulin on glycogen synthase activity in individualskeletal muscle in rat

No abstract available.

Importance of transcapillary insulin transport on dynamics ofinsulin action in the non-steady state

No abstract available.