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D Su

Publications and source records attributed to D Su.

33 records · Page 2Linked to original sources
PubMed1996

Cellular localization of Pan-trk immunoreactivity and trkC mRNA in the enteric nervous system.

The members of the trk family of tyrosine receptor kinases, trkA, trkB, and trkC, are the functional receptors for neurotrophins, a family of related neurotrophic factors. In this study, we investigated 1) the distribution of neurotrophin receptors in the developing and adult rat digestive tract with a pan-trk antibody that recognizes all known trks and 2) the cellular localization of trk-encoding mRNAs in the adult gut with single-stranded RNA probes specific for trkA, trkB, and trkC. In the developing myenteric plexus, trk immunoreactivity was present at embryonic day (ED) 14. Cells and fibers immunoreactive for trk could be visualized in the myenteric plexus at ED 16. At this age, dense staining was found in thick bundles of fibers in proximity to the myenteric plexus in the longitudinal muscle and in association with blood vessels in the mesentery. At ED 18, trk immunoreactivity was also seen in thin processes running from the myenteric plexus into the circular muscle, and in fibers and cells in intrapancreatic ganglia. By ED 20, immunoreactive staining was quite dense in both the myenteric and submucosal plexuses. At birth, virtually all enteric ganglia displayed strong trk immunoreactivity; the intensity of the staining at this age made it difficult to discern individual cells. During postnatal development, there was a decrease in cell body staining and an increase in the density of trk-containing fibers that became widely distributed to the gut wall and pancreas. The adult pattern of trk immunoreactivity was established between postnatal days 5 and 10. In adults, trk immunoreactivity was found in numerous enteric and intrapancreatic ganglion cells and in dense networks of fibers innervating all the layers of the gut, the pancreas, and vasculature. The trkC mRNA was expressed in adult enteric ganglion cells of both the myenteric and submucous plexus. By contrast, the trkA and trkB mRNAs could not be detected in enteric ganglia. All three trk mRNAs were expressed in dorsal root ganglia, which were used as positive controls. The density and wide distribution of trk immunoreactivity together with its persistence in adulthood support the concept that neurotrophins play a broad role in the digestive system from development through adult life, perhaps being involved in differentiation, phenotypic expression, and tissue maintenance. The presence of trkC mRNA in enteric neurons along with recent evidence that neurotrophin-3 plays a role in the development of the enteric nervous system suggest that trkC and neurotrophin-3 are a major neurotrophin system in the gastrointestinal tract.

Animals↗
PubMed1996

Chemosensitization of human hepatocellular carcinoma cells with cyclosporin A in post-liver transplant patient plasma.

We previously showed that combined neoadjuvant doxorubicin (DOX) treatment and orthotopic liver transplantation produced a 3-year tumor-free survival rate of 54% in stage II-IVa nonresectable hepatocellular carcinomas (HCCs). These patients received posttransplant immunosuppressive doses of cyclosporin A (CsA). CsA has been shown to modify the function of a membrane P-glycoprotein (Pgp) whose overexpression is associated with a multidrug-resistant (MDR1) phenotype. This study utilized HCC cell lines to characterize the in vitro chemomodulatory properties of CsA as found in posttransplant patient plasma to consider the hypothesis that CsA may prolong posttransplant survival by enhancing the therapeutic efficacy of DOX against multidrug-resistant hepatoma cells. We characterized Pgp expression in the HCC lines Hep3B, Hep G2, and SK-HEP-1 by immunohistochemistry and the reverse transcription-polymerase chain reaction. The combined cytotoxicity of DOX + CsA was examined by [3H]thymidine uptake and flow cytometric drug-retention assays. Pgp expression was assessed further after prolonged (10-day) treatment with CsA. Hep3B and Hep G2 cells expressed low to moderate levels of Pgp. The effective DOX dose required for inhibiting MDR1(+) Hep3B and Hep G2 cell proliferation by 50% (DOX IC50) was 44.5 ng/ml and 43.5 microgram/ml, as compared with 10.7 ng/ml for Pgp-negative SK-HEP-1 cells. Optimal concentrations of CsA (0.8 micrometer) lowered DOX IC50 for Hep3B cells and Hep G2 cells by 6-fold and 4-fold, respectively. Similarly, plasma from patients containing immunosuppressive levels of CsA lowered DOX IC50 of the MDR1(+) Hep G2 cells by up to 4-fold. Prolonged exposure to CsA did not affect its chemosensitizing capacity or Pgp expression of HCC cells. PSC-833, a nonimmunosuppressive analogue of CsA, was equally effective in reducing the DOX IC50 of MDR1(+) HCC cells. CsA and PSC-833 increased drug retention by approximately 75%, but did not significantly affect hepatoma cell viability or Pgp expression. Pharmacological concentrations of cyclosporin analogues, including one nonimmunosuppressive form, enhance DOX cytotoxicity of MDR1(+) HCC cells by modulating drug retention. CsA as found in posttransplant patient plasma enhanced DOX cytotoxicity to human MDR1(+) hepatoma cells in vitro, albeit at less than optimal chemosensitizing concentrations. Prolonged exposure to CsA did not affect its chemosensitizing properties or block Pgp expression of HCC cells. These findings support our hypothesis that in vivo immunosuppressive levels of CsA may enhance DOX chemotherapeutic efficacy on MDR1(+) HCC cells.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1995

Cellular sites of expression of the neurokinin-1 receptor in the rat gastrointestinal tract.

In the digestive system, substance P is an excitatory transmitter to muscle, a putative excitatory neuro-neuronal transmitter, a vasodilator, and a mediator in inflammatory processes. Many of the biological effects of substance P are mediated by a high-affinity interaction with the tachykinin receptor neurokinin-1. The aim of the present study was to identify the sites of expression of this receptor in the rat stomach and intestine by immunohistochemistry with a polyclonal antiserum raised to the intracellular C-terminal portion of the rat neurokinin-1 receptor. Neurokinin-1 receptor immunoreactivity is present in a large population of enteric neurons. The relative density of these neurons along the gut is colon > ileum >> stomach. In the intestine, stained neurons have a smooth cell body with processes that can be followed within and between plexuses, and make close approaches to other neuronal cells, but do not appear to project outside the plexuses, suggesting that they are interneurons. In the stomach, neurokinin-1 receptor-immunoreactive neurons are infrequent and have a poorly defined and irregular shape. Neurokinin-1 receptor immunoreactivity is also localized to numerous non-neuronal cells in the inner portion of the circular muscle layer of the small intestine, which have the appearance of small dark smooth muscle cells or interstitial cells of Cajal. These cells are postulated to form a "stretch-sensitive" system with the deep muscular plexus and thus constitute an important site of regulation of muscle activity. Double labeling immunofluorescence was used to simultaneously localize neurokinin-1 receptor and substance P/tachykinin immunoreactivities. These experiments demonstrate that in the enteric plexuses, substance P/tachykinin-immunoreactive varicose fibers encircle the cell bodies of most neurokinin-1 receptor-containing neurons, and in the inner portion of the circular muscle layer of the small intestine they lie close to neurokinin-1 receptor-immunoreactive non-neuronal cells. In addition, some enteric neurons express both neurokinin-1 receptor and substance P/tachykinin immunoreactivities. The present study provides strong evidence that the neurokinin-1 receptor is the tachykinin receptor mediating the actions of substance P on enteric neurons and smooth muscle.

Animals↗
PubMed1994

Determination of the number of sucrose and acceptor binding sites for Leuconostoc mesenteroides B-512FM dextransucrase, and the confirmation of the two-site mechanism for dextran synthesis.

In previous studies on dextransucrase using pulse and chase experiments with [14C]sucrose, Robyt et al. [Arch. Biochem. Biophys. 165 (1974) 634-640] proposed a two-site insertion mechanism to explain the data for the synthesis of dextran. To further establish the validity of the two-site mechanism, the number of sucrose binding sites at the active site have been determined by using equilibrium dialysis with 6-deoxysucrose, a strong competitive inhibitor for dextransucrase. A ligand binding plot gave a straight line that indicated there were two sucrose binding sites at the active site. A similar experiment was performed using the acceptor, maltose. The ligand binding plot for maltose also gave a straight line and indicated that there was one acceptor binding site at the active site. These results corroborate the proposed two-site mechanism for dextran synthesis. To further test the two-site mechanism, dextransucrase was partially inactivated to varying extents by reaction with diethylpyrocarbonate, which chemically modifies essential active-site histidines. The various partially inactivated enzymes were assayed for dextran synthesis and for the synthesis of maltose acceptor products. A plot of the log of the relative percentage of dextran synthesized and acceptor products synthesized against varying degrees of enzyme inactivation showed that the synthesis of dextran decreased to a greater extent than did the decrease of the synthesis of acceptor product. The proposed mechanism requires two sucrose sites for the synthesis of dextran and only one sucrose site for the synthesis of acceptor product. When one site is modified, the synthesis of dextran stops, but the synthesis of acceptor products can continue at the other site. Thus, the greater loss of dextran synthesis in comparison with the lesser loss of acceptor product synthesis by enzymes modified to varying degrees, gives further evidence for the two-site mechanism for dextran synthesis.

Binding Sites↗
PubMed1994

Recurrent cutaneous necrotizing eosinophilic vasculitis. A novel eosinophil-mediated syndrome.

BACKGROUND AND DESIGN: Review of skin biopsy specimens showing necrotizing vasculitis revealed three patients with small dermal vessel eosinophilic vasculitis and common clinical features characterized by glucocorticoid responsive pruritic erythematous, purpuric papules and angioedema associated with peripheral blood eosinophilia. Indirect immunofluorescent localization of eosinophil granule proteins, neutrophil granule proteins, and mast cell tryptase, electron-microscopic evaluation and immunoperoxidase staining for vascular cell adhesion molecule type 1, intercellular adhesion molecule type I, endothelial-leukocyte adhesion molecule type 1, and very-late activation antigen type 4 were performed. Eosinophil-active cytokines in serum were evaluated by an eosinophil survival assay. OBSERVATIONS: Eight skin biopsy specimens from the three patients all showed small-vessel necrotizing vasculitis with exclusive eosinophil infiltration. Ultrastructural study demonstrated degenerating eosinophils and eosinophil granules in proximity to damaged endothelium. The affected small vessels showed marked deposition of the toxic eosinophil granule major basic protein in the vessel walls and expression of vascular cell adhesion molecule type 1 and intercellular adhesion molecule type 1 on the endothelium with adherence of very-late activation antigen type 4-positive eosinophils; E-selectin staining was negative. The presence of interleukin 5 in serum available from one patient was detected by an eosinophil survival assay. CONCLUSIONS: We studied three patients whose cutaneous lesions showed small-vessel eosinophilic vasculitis and who presented with recurrent glucocorticoid-responsive pruritic purpuric papules and angioedema. The presence of eosinophil-active cytokines in serum and the expression of vascular cell adhesion molecule type 1 on the endothelium of affected vessels may contribute to the selective adherence and localization of activate eosinophils. Subsequent release of cytotoxic proteins such as major basic protein may result in destruction of the endothelium in this unique syndrome.

Adolescent↗
PubMed1993

Control of the synthesis of dextran and acceptor-products by Leuconostoc mesenteroides B-512FM dextransucrase.

In the maltose-acceptor reaction of Leuconostoc mesenteroides B-512FM dextransucrase, some of the D-glucose moieties of sucrose are diverted from the synthesis of dextran and are transferred to the nonreducing end of maltose to form panose. Glucose is also transferred to panose and to subsequent acceptor products to give a homologous series of isomaltosyl dextrins attached alpha-(1-->6) to maltose. Three experimental parameters were studied to obtain quantitative information about the yield and distribution of acceptor products and the yield of dextran: (a) the ratio of maltose to sucrose, (b) the concentration of maltose and sucrose, and (c) the amount of enzyme. The reactions were run with [14C]sucrose and the amount of each acceptor product and the amount of dextran synthesized were determined for (a), (b), and (c) by TLC separation and measurement of the radioactivity with a PhosphorImager. It was found that an increase in the ratio of maltose to sucrose increased the amount of acceptor products with a concomitant decrease in the synthesis of dextran. Further, as the ratio was increased, the number of acceptor-products decreased. When the concentrations of maltose and sucrose were increased and the ratio was maintained at 1:1, there also was a decrease in the amount of dextran and an increase in the amount of acceptor-products. In addition, there was a decrease in the amount of dextran and an increase in the amount and number of acceptor-products when the amount of enzyme was increased. The first acceptor-product can be exclusively obtained without the formation of any dextran, by using a specific ratio and concentration of maltose and sucrose and a specified amount of enzyme.

Autoradiography↗
PubMed1993

Drug-induced purpura simplex: clinical and histological characteristics.

Purpura simplex (PS) is a chronic condition manifesting as purpura, dermatitis and pigmentation. Histologically it is characterised by extravasation of erythrocytes and perivascular inflammation without fibrinoid necrosis. Most cases of PS are idiopathic. In order to determine if PS can be drug induced, a prospective study of 183 patients with PS was carried out. Of these, 27 patients were confirmed to be drug induced, as the purpura cleared on withdrawal of medications within four months. Lesions of drug-induced PS were significantly more generalised as compared to PS patients without a drug history. No epidermal involvement and an absence of lichenoid infiltrate characterised drug-induced as compared to idiopathic PS. NSAIDs, diuretics, meprobamate and ampicillin were the commonest offenders. We conclude that a drug-induced subgroup of PS exists and can be identified by clinical and histological features. Therefore, a careful drug history and skin biopsy are recommended in all cases of PS.

Drug Eruptions↗
PubMed1992

Polymyxin B-horseradish peroxidase conjugates as tools in endotoxin research.

The peptide antibiotic Polymyxin B (PMB) binds to bacterial endotoxin (lipopolysaccharide, LPS). We prepared covalent conjugates of PMB and horseradish peroxidase (HRP) by periodation of HRP-linked oligosaccharides followed by direct condensation with PMB. In addition we prepared monoclonal antibodies (Mabs) to PMB. The PMB-HRP conjugates and anti-PMB Mabs were used to study in ELISA the binding of PMB to LPS from Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa. In addition, PMB-HRP was used to quantify lipid A in ELISA, and to stain gram-negative bacteria histochemically. For the study of PMB-LPS interaction, PMB-HRP proved to be superior to the anti-PMB Mabs. PMB-HRP conjugates are useful general probes to detect or measure lipid A and LPS of various species using very simple methods and to stain bacteria, and they may obviate the need for many specific antisera. Thus, PMB-HRP conjugates are useful probes for endotoxin research.

Antibodies, Monoclonal↗
PubMed1990

[Comparative clinical study of rheumatoid arthritis treated by triptolide and an ethyl acetate extract of Tripterygium wilfordii].

It was satisfactory using the ethyl acetate extract of Tripterygium wilfordii (TW) to treat rheumatoid arthritis (RA). The results showed that the ethyl acetate extract of TW was the effective component part of TW. Although the therapeutic effect of 15 cases with RA cured by triptolide was as effective as the ethyl acetate extract of TW, triptolide could impair some patients' hearts. This suggested that triptolide was one of the main effective elements of TW, but it was also one of the main toxic elements. Clinical research indicated that: (1) the effect of TW in treating RA was the synergistic action of elements with triptolide as the main; (2) triptolide may act as a major standard of controlling the quality of the preparation of TW and assure clinical use safely.

Adolescent↗
PubMed1989

The role of macrophages in the immunoadjuvant action of liposomes: effects of elimination of splenic macrophages on the immune response against intravenously injected liposome-associated albumin antigen.

The primary antibody response to intravenously administered and liposome-associated human serum albumin (HSA) was studied in mice under conditions where no response could be detected against the non-liposome-associated form of the antigen. The positive response against the antigen, entrapped in and/or exposed on the surfaces of liposomes, thus resulted from the adjuvant action of the liposomes. In mice intravenously injected with dichloromethylene diphosphonate (C12MDP) also entrapped in liposomes, all red pulp macrophages, marginal metallophilic macrophages and marginal zone macrophages had disappeared from the spleen 2 days after administration. Twenty-two days after such a treatment red pulp macrophages and marginal metallophilic macrophages had reappeared, but marginal zone macrophages were still absent. In mice injected with liposome-associated HSA at 2 days after treatment with the C12MDP liposomes, anti-HSA responses were severely depressed, but administration of the liposome-associated antigen 22 days after C12MDP liposomes elicited a normal response. These results point to a role of splenic macrophages in the processing of liposome-associated antigens, but marginal zone macrophages, which are located close to the open ends of the white pulp capillaries and thus are the first macrophages to meet the antigens arriving in the marginal zone are not required.

Adjuvants, Immunologic↗
PubMed1988

Cardiovascular response to emotional stress and spontaneous blood pressure variability in genetically hypertensive rats of the Lyon strain.

1. Intra-aortic blood pressure (BP) was continuously recorded in freely moving genetically hypertensive (LH), normotensive (LN) and low BP (LL) rats of the Lyon strains under basal conditions and during aversive stimulation (a jet of air for 20 min). Rats were studied when 5 and 14 weeks old. 2. The 24 h standard deviation (i.e., variability) of diastolic BP was significantly greater in LH rats of both ages than in LN and LL control rats. 3. In response to the stressor, LH rats showed larger increases in BP than age-matched controls. 4. The BP variability was related to the BP responses to stress in the whole series of rats. 5. It is concluded that the spontaneous BP variability and the BP responses to an experimental stressor rely upon a common regulatory mechanism in rats and that an increased lability of diastolic BP is a primary characteristic of Lyon hypertensive rats.

Aging↗
PubMed1979

Carcinoma arising in eccrine spiradenoma.

Two patients had carcinoma arising in eccrine spiradenoma. In both patients, recent changes in a long-standing cutaneous nodule prompted excision, and microscopic examination disclosed carcinoma intimately associated with and apparently arising from typical benign eccrine spiradenoma. One patient had lymph node metastasis.

Adenoma↗