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Biomedical subjects

A Chang

Publications and source records attributed to A Chang.

At least 253 records · Page 14Linked to original sources
PubMed1988

PUVA and UVB inhibit the intra-epidermal accumulation of polymorphonuclear leukocytes.

Healthy volunteers were treated on test areas with UVB irradiation or topical PUVA therapy. The trauma-induced and leukotriene B4 (LTB4)-induced intra-epidermal accumulation of polymorphonuclear leukocytes (PMN) was quantified after these treatments, using elastase as a marker enzyme. Both UVB and PUVA treatment caused a profound inhibition of trauma- and LTB4-induced PMN accumulation. This observation indicates that reduction of the transepidermal migration of PMN might be part of the mechanism of action of UV therapies in psoriasis. Several possibilities are discussed to explain this hypothesis.

Adult↗
PubMed1988

Development of secretagogue responsiveness in the pancreas.

Epithelial cells are bound by a plasma membrane that is divided into apical and basolateral domains. In turn, the species of membrane proteins within these polarized plasmalemmal domains define the structural and functional specializations of the epithelium. Currently, research into the mechanisms whereby epithelial cell polarity is generated is a major thrust in cell biology. The topic discussed here will focus on recent studies carried out by us on the genesis of regulated secretion in the developing pancreatic acinar cell--that is, the secretory pathway responsive to second-messenger elevation after hormonal stimulation. In the developing rat pancreas, acinar cells complete cytodifferentiation 1 day before birth yet do not discharge secretory proteins from zymogen granules in response to the secretagogue cholecystokinin (CCK). The cause of this refractoriness to CCK does not lie at the receptor level, since the number, affinity, and plasmalemmal location of the receptor and its ability to generate second messengers after interaction with the ligand has already appeared. However, 1 day after birth, the acinar cell is able to discharge secretory proteins by exocytosis through the regulated secretory pathway in response to CCK. The acquisition of distal stimulus-secretion coupling events in the perinatal period has been found to correlate with developmental changes in Ca2+/calmodulin-dependent protein kinase II and its phosphorylated substrates. The relevance of the studies reported here to the complex and coexistent regulated and constitutive secretory pathways in the pancreatic acinar cell will be discussed.

Animals↗
PubMed1988

Topical application of clobetasol-17-propionate inhibits the intra-epidermal accumulation of polymorphonuclear leukocytes.

The in vivo effect of topical clobetasol-17-propionate (CP) on the leukotriene B4- and trauma-induced intra-epidermal accumulation of polymorphonuclear leukocytes (PMN) was investigated in normal volunteers. PMN accumulation was assessed using elastase, a specific and sensitive marker for these cells. A profound inhibition of PMN accumulation was shown in the first 2 days of treatment with CP, an effect that faded away after a treatment of 2 weeks.

Administration, Topical↗
PubMed1988

Intra-epidermal accumulation of polymorphonuclear leukocytes in persistent palmoplantar pustulosis during treatment with acitretin.

Six patients with persistent palmoplantar pustulosis were treated with acitretin, and the clinical response was compared with the effect on the intra-epidermal accumulation of polymorphonuclear PMN leukocytes. A prompt improvement of pustule formation and subsequently decreased scaling and erythema was seen in all patients. Following discontinuation of therapy, a relapse occurred within 2 weeks. With dosages of 45 or 55 mg/day, the clinical scores were only slightly better than with 25 or 35 mg/day. In patients using 25 mg acitretin a day, the leukotriene B4-induced intra-epidermal accumulation of polymorphonuclear leukocytes was not affected. However, a dosage of 35 mg/day resulted in a significant inhibition of PMN accumulation, dosages of 45 and 55 mg/day causing an even more pronounced inhibition of this process. Although the effect of different dosages of acitretin is not clearly expressed in the severity scores, the dose-dependent effect on PMN chemotaxis in vivo might be of relevance when combination therapies are considered, in order to achieve a complete clinical clearance.

Acitretin↗
PubMed1987

Secondary structure predictions and medium range interactions.

Several authors have proposed that predictions of protein secondary structure derived from statistical information about the known structures can be improved when information about neighboring residues participating in short and medium range interactions is included. A substantial improvement shown here indicates that current methods of including this information are not more successful than methods that do not. Evaluations of the Chou and Fasman method (Adv. Enzymol. 47 (1978) 45-148), that does not include information about interactions (except in averaging), have shown it to be about 49% correct for three states (helix, beta-sheet and undefined). In comparison, the method of Garnier et al. (J. Mol. Biol. 120 (1978) 97-120), that explicitly includes information about neighboring residues, has an accuracy of 57% residues correct for three states. However, we have obtained an 8% improvement for predictions of secondary structure based on the algorithm by Chou and Fasman. The improvements are obtained by eliminating many rules and by choosing the best decision constants for structure assignments. The simplified method described here is 57% correct for three states using preference values calculated in 1978.

Amino Acids↗
PubMed1987

Constitutive protein secretion from the exocrine pancreas of fetal rats.

Two general kinds of exocytotic secretion of proteins are known: that which is stimulated by secretagogues; and constitutive exocytosis, which is unable to be stimulated. The exocrine pancreas has often been cited as a model system for the first kind of secretion. However, the release of digestive enzymes from the exocrine pancreas of 1-day prenatal rats cannot be stimulated by secretagogues; therefore, its secretion is constitutive. To gain insight into the intracellular pathways which mediate secretion in the fetal gland, we examined the kinetics of release of newly synthesized proteins. We find that fetal pancreas in a steady state of secretion releases pulse-labeled secretory proteins in two kinetically distinct phases. The first phase occurring during 0-6.5 h of chase comprises approximately 12% of total incorporated radioactivity, the second phase beginning at greater than 7 h of chase comprises the remainder. Based on analysis by electron microscope autoradiography, radiolabel is localized during the first phase of secretion in immature granules/condensing vacuoles, Golgi compartments, and few mature granules. The second phase of secretion occurs when radiolabel is predominantly in mature granules. We propose that secretion occurs via (at least) 2 exocytotic routes, both of which are constitutive in fetal pancreatic tissue.

Animals↗
PubMed1987

5-Fluorouracil and high-dose folic acid treatment for metastatic colon cancer.

Twenty-two patients with metastatic colorectal cancer were treated with a regimen of 5-fluorouracil 600 mg/m2 (maximum, 1.0 g) i.v./week and folic acid 140 mg/m2 i.v. given 1 h prior to the 5-FU. This study was undertaken in an attempt to confirm the in vitro finding that inhibition of thymidylate synthetase by 5-fluorouracil is prolonged by the presence of folates. There were four partial responses (18%) with mean duration 4 months. Dose-limiting toxicity was enteritis, seen in 12 patients (58%), and causing hospitalization in seven patients. Enteritis was shown to be due to the folic acid in most patients. Two patients died from leukopenia, enteritis, and sepsis. Mean serum folate levels at the time of 5-FU injection were 36 microM. This regimen is no more effective than 5-FU alone and has significantly more serious toxicity. Further investigation of this regimen is not recommended.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1987

An endogenous inducer of sexual development in Aspergillus nidulans.

During development of the homothallic ascomycete Aspergillus nidulans, asexual sporulation is followed by sexual sporulation. We report here the detection of a solvent-extractable activity which inhibits asexual sporulation and stimulates premature sexual sporulation. This activity, called precocious sexual inducer (psi), is overproduced by certain mutants that are blocked in both modes of sporulation. Using partially purified preparations of psi, biological response could be elicited with as little as 50 ng of material. We suggest that psi is a hormone-precursor which is converted to a hormone by normal sporulating strains that respond to psi, but not by the asporogenous mutants that overproduce psi. The stability of psi activity gives promise that the compound can be purified and identified.

Aspergillus nidulans↗
PubMed1987

The evaluation of a pregnancy test (Tandem ICON) in the management of ectopic pregnancy.

A comparison was made between the Tandem ICON and Gravindex tests in the management of suspected ectopic pregnancy in 38 patients. The Tandem ICON test was significantly more accurate than the Gravindex in predicting an ectopic pregnancy. After the exclusion of cases with intrauterine pregnancy, there was no error when the Tandem ICON test was used, but 8 false negative cases were found with the Gravindex.

Antibodies, Monoclonal↗
PubMed1987

Adrenal gland: MR imaging.

The authors investigated the utility of magnetic resonance (MR) imaging in identifying the normal adrenal gland in 100 patients as well as in distinguishing adrenal adenomas (n = 12) from malignant neoplasms (n = 14). The left adrenal gland was seen in 99 of 100 cases and the right in 91 of 100 cases. The adrenals were most easily seen with T1-weighted spin-echo pulse sequences. The ratio of the intensity of the adrenal mass to that of fat at 2,100/90 (repetition time msec/echo time msec) was most helpful in distinguishing adrenal adenomas from malignant neoplasms. In contrast to other studies, the adrenal mass/liver intensity ratios were not helpful. All ten lesions with adrenal mass/fat ratios at 2,100/90 of 0.8 or greater were malignant, whereas all eight adrenal masses with a ratio less than 0.6 were adrenal adenomas. However, eight (31%) of the masses (four adenomas and four malignant neoplasms) had ratios between 0.6 and 0.8. Although MR imaging has considerable potential in characterizing adrenal masses, larger studies are needed to determine its true sensitivity and specificity.

Adenoma↗
PubMed1987

Calcium-calmodulin-stimulated protein kinase in developing pancreas.

To implicate the Ca2+-calmodulin-dependent protein kinase (CDPK) in the secretory response of pancreatic acinar cells to postnatal neurohumoral stimulation, we examined enzymatic protein kinase activity during pancreatic development. CDPK was investigated by measuring the phosphorylation of endogenous proteins and an exogenous substrate, synapsin I. Ca2+-calmodulin (CaM)-stimulated phosphorylation of endogenous proteins as well as synapsin I progressively increased in pancreatic supernatants from rats of increasing age. When compared with embryonic pancreas (1 day before birth), Ca2+-CaM-stimulated protein kinase activity increased two- and sixfold in neonatal (1 day after birth) and adult pancreas (60 days after birth), respectively, when normalized to protein content. To further characterize CDPK activity, soluble fractions prepared from embryonic, neonatal, and adult pancreas were separated by gel filtration chromatography. CDPK activities from embryonic and neonatal pancreas were contained in fractions of relative molecular weights (Mr) less than 200,000. In contrast, kinase activity from adult pancreas was predominantly comprised of a Mr approximately 550,000 species that coeluted with a type II CDPK. Increasing amounts of a Mr = 51,000 CaM-binding protein as a function of increasing age were consistent with the developmental appearance of the CaM-binding subunit of type II Ca2+-CaM-stimulated protein kinase. CaM levels increased in parallel with total Ca2+-CaM-stimulated protein kinase activity. Coordinate enhancement of type II CDPK activity and secretagogue responsiveness during pancreatic maturation may suggest a role for this enzyme in the secretory process.

Animals↗
PubMed1987

Protein C prevents the coagulopathic and lethal effects of Escherichia coli infusion in the baboon.

Gram-negative septicemia elicits multiple abnormalities of the coagulation system. Although products of coagulation can lead to clot formation, thereby potentiating organ damage, recent work has shown that low concentrations of thrombin can protect animals from the shock state. Because these amounts of thrombin also lead to formation in vivo of the anticoagulant enzyme, activated protein C, we examined the role of protein C in modulation of Escherichia coli shock in baboons. First, we infused activated protein C and lethal concentrations of E. coli organisms, which prevented the coagulopathic, hepatotoxic, and lethal effects of E. coli. Second, using an antibody to protein C we blocked protein C activation in vivo to determine if this influenced the response to lethal and sublethal concentrations of E. coli organisms. Under these conditions the response to lethal concentrations of E. coli organisms was made more severe and the response to sublethal concentrations of E. coli was made lethal. The coagulopathic, hepatotoxic, and lethal responses in this latter case were prevented by infusion of exogenous protein C.

Alanine Transaminase↗
PubMed1987

Protein C, isolation and potential use in prevention of thrombosis.

Protein C and protein S serve as natural anticoagulants. Deficiencies of these proteins are often associated with recurrent deep vein thrombosis and coumarin induced skin necrosis. These two proteins function by selectively inactivating factors Va and VIIIa, two of the "cofactors" of blood coagulation. Hence, inhibition of coagulation by this pathway complements the better known inhibition mediated by the antithrombin III-heparin system. These observations suggest that protein C and/or activated protein C may prove useful in controlling thrombosis and/or DIC. We have developed a Ca2+ dependent monoclonal antibody which allows the rapid isolation of human protein C. This rapid isolation has allowed us to demonstrate that activated protein C can protect baboons from the lethal effects of E. coli/endotoxin and that protein C supplementation can minimize fibrinogen consumption following tissue factor infusion into dogs.

Animals↗