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Biomedical subjects

S Chang

Publications and source records attributed to S Chang.

At least 199 records · Page 11Linked to original sources

Cloning of a cDNA for a chitinase homologue which lacks chitin-binding sites and is down-regulated by water stress and wounding.

A cDNA clone (pLP6) of a gene which is repressed under water deficit was isolated from a loblolly pine (Pinus taeda L.) cDNA library and characterized. The predicted polypeptide encoded by pLP6 bears strong resemblance to a number of Class I chitinases. However, LP6 lacks most of the amino-terminal and, consequently the signal peptide, cysteine-rich chitin-binding domain and glycine/proline-rich "hinge' region, diagnostic of Class I chitinases, are absent. Although the cDNA is similar in size to its mRNA, the long open reading frame encoding the LP6 protein commences halfway through the mRNA, implying a 5'-untranslated region of over 700 nucleotides. Subfragments from the 5' end of pLP6 hybridize to the same mRNA as do probes consisting of the entire cDNA. Reverse transcription(RT)-PCR experiments confirm that the cDNA derives from a single mRNA molecule. Analysis of the 5'-UTR revealed six upstream open reading frames and four inverted repeat structures. Expression of the pLP6 gene is repressed by water deficit stress and wounding. Possible functions and origin of this gene are discussed.

Amino Acid Sequence↗

Does the presence of heparin and dexamethasone in the vitrectomy infusate reduce reproliferation in proliferative vitreoretinopathy?

BACKGROUND: Reproliferation following vitrectomy for proliferative vitreoretinopathy (PVR) causes redetachment in up to 55% of cases. Heparin and corticosteroids have each been shown to inhibit the development of proliferative vitreoretinopathy (PVR) in experimental models. However, little information is available on the use of these agents in humans. METHODS: In this pilot study, 62 eyes of 62 patients with severe PVR requiring vitrectomy were prospectively randomized to receive either BSS Plus (control) or BSS Plus with heparin and dexamethasone (HD) in the infusate. RESULTS: After one operation, the retina was reattached in 42 (71%) of 59 eyes: 22 (65%) of 34 eyes in the control group and 20 (80%) of 25 eyes in the HD group (P = 0.16). Reproliferation developed in 26.5% of the control group (9 of 34 eyes) and 16% of the HD group (4 of 25 eyes; P = 0.26). Postoperative hemorrhage was significantly more frequent in the HD group (P = 0.02) but did not influence final visual or anatomic outcome. Hypotony was less frequent in the HD group but the difference was not significant (P = 0.063). CONCLUSION: The trend from this randomized pilot study suggests that HD supplementation of the vitrectomy infusate may reduce the reproliferation rate in PVR and possibly reduce the rate of hypotony. Postoperative hemorrhage was more frequent with HD but did not cause redetachment or alter visual outcome. A multicenter trial involving more patients would be required to better evaluate the efficacy of HD as a pharmacologic adjunct to PVR surgery.

Adolescent↗

Initial characterization and autoradiographic localization of a novel sigma/opioid binding site in immune tissues.

High concentrations of novel, haloperidol- and DTG-inaccessible (+)-[3H]-3-PPP binding sites were found in human peripheral blood leukocytes rat spleen and splenocytes, but not in rat brain. Splenic sites were localized in a course punctate pattern in the marginal zones and red pulp. The pharmacology of the splenic sites was: (-)-SKF 10,047 > or = naltrexone = (-)-pentazocine > (+)-pentazocine = (-)-3-PPP = (+)-SKF 10,047 > or = (+)-3-PPP > or = dextrorphan > dextromethorphan > PCP > clorgyline. DTG, haloperidol, TCP, (-)-deprenyl and SKF 525-A did not complete. Binding activity was destroyed by heating and phospholipase C, but not by proteases or glycosidases. These sites may be involved in immunomodulation by opiate and sigma receptor agonists.

Animals↗

Heterophilic interactions of DM-GRASP: GRASP-NgCAM interactions involved in neurite extension.

DM-GRASP is an immunoglobulin superfamily cell adhesion molecule that is expressed in both the developing nervous and immune system. Specific populations of neurons respond to DM-GRASP substrates appears to require homophilic interactions between DM-GRASP molecules. We were interested in determining whether DM-GRASP interacts heterophilically with other ligands as well. We have found that eleven proteins from embryonic chick brain membranes consistently bind to and elute from a DM-GRASP-Sepharose affinity column. One of these proteins is DM-GRASP itself, consistent with its known homophilic binding. Another protein, at 130 kD, is immunoreactive with monoclonal antibodies to NgCAM. Other neural cell adhesion molecules were not detected in the eluate. The DM-GRASP-Sepharose eluate also contains a potent neurite stimulating activity, which cannot be accounted for by either DM-GRASP or NgCAM. To investigate the interaction of DM-GRASP and NgCAM, antibodies against DM-GRASP were added to neuronal cultures extending neurites on an NgCAM substrate. The presence of antibodies to DM-GRASP decreased neurite extension on laminin, suggesting that the antibody is not toxic or generally inhibiting motility. We present two possible models for the DM-GRASP-NgCAM association and a hypothesis for neural cell adhesion function that features the dimerization of cell adhesion molecules.

Activated-Leukocyte Cell Adhesion Molecule↗

Molecular polymorphisms associated with host range in the highly conserved genomes of burrowing nematodes, Radopholus spp.

Six polymorphic bands of DNA were amplified from purified Radopholus citrophilus genomic DNA from one strain of each of the sibling species R. citrophilus and R. similis in random amplified polymorphic DNA analyses involving 380 single 10-base primers. Four of these polymorphic DNA fragments were successfully cloned and amplified through subsequent use of primers designed to complement the terminal sequences of the polymorphic DNA. Results of ensuing studies using mini-prepped DNA from 14 burrowing nematode strains collected from Florida, Hawaii, and Central America, characterized for their ability to parasitize citrus, indicated that a 2.4-kb fragment appeared to be associated with citrus parasitism in burrowing nematode populations from Florida. However, a fragment of comparable size was also detected in R. citrophilus from Hawaii and from burrowing nematode populations collected from Belize and Puerto Rico. Overall, findings suggest that the genome organization of the burrowing nematode sibling species R. citrophilus and R. similis is highly conserved. This remarkable genetic similarity should facilitate identification of genetic sequence related to important phenotypes such as citrus parasitism. Detection of R. citrophilus-specific DNA fragments in burrowing nematodes collected from Belize and Puerto Rico suggests that R. citrophilus is resident in some Central American countries.

Animals↗

Persistent Epstein-Barr virus infection in the common marmoset (Callithrix jacchus).

Epstein-Barr virus (EBV) infection of the common marmoset causes long-term infection, with production of antibodies to virus-induced antigens, without clinical illness. Attempts to show the presence of EBV DNA in saliva of infected animals by PCR were initially unsuccessful, although slot-blot hybridization analysis demonstrated that viral DNA was present. Further investigations showed that most samples of pilocarpine-induced saliva, and 33% of the samples of whole mouth fluids (WMF) tested, were inhibitory to PCR. Similar results were found using human WMF. A method of assessing samples of marmoset WMF for the presence of EBV, by PCR using an EBV BamHI W probe, and removing inhibition with Chelex 100, is described. A total of 202 samples from 21 EBV infected, and seven non-infected animals was tested. Five seropositive animals shed virus on every occasion, and 15 intermittently. Two marmosets, infected as neonates, showed progressively increasing humoral responses to viral antigens, and shed virus on every occasion tested over 3 years. When mated with uninfected animals, the latter seroconverted 4 and 6 weeks later, respectively, and later shed virus into their WMF. The naturally infected animals were paired with naive marmosets, and were able to pass on infection. These results establish that long-term, permissive EBV infection occurs in the common marmoset, and demonstrate again the similarities in the response to EBV between marmoset and man.

Animals↗

Optimizing the hospital management of leg ulcers.

BACKGROUND: Leg ulcers are common and are often the cause of a long hospital admission. However, little information is available on the efficacy and efficiency of inpatient leg ulcer management. The inpatient management of leg ulceration was examined and areas for improvement were sought. METHODS: The management of patients admitted to a teaching hospital with a primary diagnosis of leg ulceration was examined, the costs estimated and areas for improvement identified. A retrospective analysis of 174 admissions to Heidelberg Repatriation Hospital between 1 January 1991 and 31 December 1992 was performed. RESULTS: Of 119 patients, 61 had ulcers due to arterial disease and 34 due to venous disease. Over 2 years, leg ulcers accounted for 5259 inpatient bed days, a mean of 44.2 days per patient. The estimated cost exceeded $2,750,000, averaging over $12,000 per admission. Thirty-three percent of patients had no recorded investigations into the cause of their ulcer and fewer than 50% had documented improvement at discharge. CONCLUSIONS: Leg ulcers are costly due to their extended treatment on an inpatient basis. Unfortunately, hospital admission does not guarantee optimal wound healing rates. A leg ulcer protocol is proposed to minimize inpatient stay and improve investigation and management in an outpatient or community setting.

Aged↗

Responses in milk production to control of gastrointestinal nematode and paramphistome parasites in dairy cattle.

OBJECTIVE: To determine the effect of treating naturally acquired gastrointestinal nematode and paramphistome infections on milk production in dairy cattle. DESIGN: A field trial. ANIMALS: One thousand two hundred and thirty nine dairy cows. PROCEDURE: Cows were either not treated or treated with 4.5 mg/kg oxfendazole, 16.6 mg/kg oxyclozanide or 4.5 mg/kg oxfendazole and 16.6 mg/kg oxyclozanide in March, May and August. RESULTS: A significant increase in milk production, averaging 0.4 L (SE 0.2) per day, was seen when dairy cows infected with gastrointestinal nematodes and paramphistomes were treated with oxfendazole or oxfendazole and oxyclozanide in March, May and August. Cows treated with oxyclozanide alone at these times produced no more milk than untreated cows. Faecal egg counts confirmed that oxyclozanide treatment reduced paramphistome populations and oxfendazole treatment reduced nematode populations in cows over the 7-month monitoring period. CONCLUSION: When dairy cows infested with gastrointestinal nematodes and paramphistomes were treated with oxfendazole alone or oxfendazole and oxyclozanide in March, May and August milk production increased.

Animals↗

Regulation of colony-stimulating factor 1 receptor signaling by the SH2 domain-containing tyrosine phosphatase SHPTP1.

SHPTP1 (PTP1C, HCP, SHP) is an SH2 domain-containing tyrosine phosphatase expressed predominantly in hematopoietic cells. A frameshift mutation in the SHPTP1 gene causes the motheaten (me/me) mouse. These mice are essentially SHPTP1 null and display multiple hematopoietic abnormalities, most prominently hyperproliferation and inappropriate activation of granulocytes and macrophages. The me/me phenotype suggests that SHPTP1 negatively regulates macrophage proliferative pathways. Using primary bone marrow-derived macrophages from me/me mice and normal littermates, we examined the role of SHPTP1 in regulating signaling by the major macrophage mitogen colony-stimulating factor 1 (CSF-1) (also known as macrophage colony-stimulating factor). Macrophages from me/me mice hyperproliferate in response to CSF-1. In the absence of SHPTP1, the CSF-1 receptor (CSF-1R) is hyperphosphorylated upon CSF-1 stimulation, suggesting that SHPTP1 dephosphorylates the CSF-1R. At least some CSF-1R-associated proteins also are hyperactivated. SHPTP1 is associated constitutively, via its SH2 domains, with an unidentified 130-kDa phosphotyrosyl protein (P130). P130 and SHPTP1 are further tyrosyl phosphorylated upon CSF-1 stimulation. Tyrosyl-phosphorylated SHPTP1 binds to Grb2 via the Grb2 SH2 domain. Moreover, in me/me macrophages, Grb2 is associated, via its SH3 domains, with several tyrosyl phosphoproteins. These proteins are hyperphosphorylated on tyrosyl residues in me/me macrophages, suggesting that Grb2 may recruit substrates for SHPTP1. Our results indicate that SHPTP1 is a critical negative regulator of CSF-1 signaling in vivo and suggest a potential new function for Grb2.

Animals↗