Biomedical subjects

R M Wang

Publications and source records attributed to R M Wang.

28 records · Page 2Linked to original sources

PubMed1994

Evidence of a paracrine role of neuropeptide-Y in the regulation of insulin release from pancreatic islets of normal and dexamethasone-treated rats.

Recent evidence suggests that a number of a paracrine regulatory peptides, including neuropeptide-Y (NPY), are synthesized within pancreatic islets. We have, therefore, assessed the role of NPY on insulin release from isolated perifused rat islets. NPY release was detectable at 2.1 (95% confidence interval, 1.6-2.6) attomoles/islet.min from the perifused islets of control rats when the glucose concentration was 2.8 mM and decreased by 62% (P = 0.01) on changing to 20 mM glucose. The initial insulin release was 0.7 (0.3-1.6) fmol/islet.min, and it was increased 4-fold (P < 0.001) by high glucose. Simultaneously, pancreatic glucagon release was decreased 85% (P < 0.001), and somatostatin release was decreased 25% (P = 0.06). In contrast, in islets from rats given dexamethasone (4 mg/kg.day) for 10 days, NPY release was 6-fold increased by high glucose. NPY (100 nM) decreased insulin release by 44% (P < 0.001). To determine the influence of naturally present islet NPY on insulin release, immunoneutralization with NPY antiserum was employed. With control rat islets, insulin release was increased 3-fold with NPY antiserum (P = 0.02) in the presence of 2.8 mM glucose and elevated 2-fold at 8 mM glucose (P < 0.001). NPY immunoneutralization similarly increased insulin release from the perifused islets of rats treated with dexamethasone. Our results suggest that NPY is produced by pancreatic islets, and its expression is dependent on the prevailing endocrine environment. Islet NPY appears to constrain insulin release under a variety of conditions. NPY may be an important intraislet paracrine hormone.

Animals↗

PubMed1990

Cytophotometric DNA analysis on canine stomach carcinogenesis induced by ENNG.

DNA content and nuclear area were measured by microspectrophotometry in gastric carcinogenesis of three adult wolfdogs induced by N-ethyl-N'-nitro-N-nitrosoguanidine (ENNG). The mean values and standard deviations of DNA content and nuclear area in normal gastric mucosa were 10.03 +/- 2.30 AU and 28.76 +/- 5.85/microns2; those in atrophic gastritis were 12.04 +/- 3.34 AU and 28.69 +/- 8.02/microns2; in mild dysplasia 13.52 +/- 3.73 AU and 28.23 +/- 8.12/microns2; in moderate dysplasia 20.88 +/- 4.57 AU and 47.58 +/- 10.74/microns2; in severe dysplasia 24.01 +/- 4.48 AU and 56.64 +/- 12.53/microns2; in well-differentiated adenocarcinoma 33.07 +/- 9.38 AU and 72.99 +/- 15.57/microns. These figures were different (P less than 0.01). The nuclear area of gastric carcinoma increased with DNA content (r = 0.73, P less than 0.01). The distribution patterns of DNA content in the histogram showed that diploidy was decreased and polyploidy increased in cancer cells. These findings indicate that DNA ploidy patterns and nuclear area can be useful indices for differentiating carcinoma from precancerous lesions.

Animals↗

PubMed1989

Elimination of chemoresistant multiple myeloma clonogenic colony-forming cells by combined treatment with a plasma cell-reactive monoclonal antibody and a P-glycoprotein-reactive monoclonal antibody.

Patients with multiple myeloma (MM) commonly become refractory to chemotherapy despite a favorable response to induction treatment. We examined the effectiveness of a previously characterized plasma cell-reactive monoclonal antibody, MM4, in eliminating MM clonogenic colony-forming cells (CCC) with a multidrug-resistant (MDR) phenotype. Experiments were performed using MM cell lines that exhibit 6 (RPMI 8226/DOX6)- and 40 (RPMI 8226/DOX40)-fold resistance to doxorubicin (DOX). Both lines were selected from the chemosensitive MM line RPMI 8226/S and were cross-resistant to mitoxantrone, acronycine, etoposide, and vincristine. Surface marker analysis conducted in this study showed that DOX6 and DOX40 overexpressed the MDR1 gene product p170. Both MDR lines remained reactive to the plasma cell-reactive monoclonal antibodies MM4 and PCA-1 and expressed the relevant cytoplasmic immunoglobulin light chain. Treatment with MM4 and rabbit complement (C') was equally cytotoxic to RPMI 8226/S [80 +/- 5.6% (SD)], DOX6 [74 +/- 8.5], and DOX40 cells [75 +/- 11.3%], based on short-term chromium release studies. Furthermore, MM4 + C' deleted up to 3 logs of CCC colonies from chemosensitive and MDR lines (RPMI 8226/S, 99.87 +/- 0.11%; DOX6, 99.91 +/- 0.08%; DOX40, 99.55 +/- 0.44%). By comparison, the P-glycoprotein-reactive monoclonal antibody MRK-16 and C' inhibited tumor colony formation of MDR cells (8226/DOX6, 95.71 +/- 2.51%; 8226/DOX40, 99.61 +/- 0.43%) but affected that of chemosensitive cells only slightly (8.9 +/- 17.8%). In an attempt to optimize the depletion of myeloma CCC, MM4 was used together with MRK-16. This approach resulted in uniform depletion of myeloma clonogenic colony-forming cells from the chemosensitive (98.32 +/- 1.53%, n = 4) and MDR lines (8226/DOX6, 98.83 +/- 0.08%, n = 4; 8226/DOX40 99.29 +/- 0.62, n = 7) but did not result in enhanced CCC depletion. When DOX40 cells were mixed with normal bone marrow (BM) in the ratio of 90:10 (BM:MM), either MM4 or MRK-16 and C' depleted MM colonies (98.8 +/- 0.71% and 98.10 +/- 1.0%, respectively) without affecting the majority of BM progenitor cells. These observations suggest that either MM4 or MRK-16 is useful for depleting MDR myeloma clonogenic colony-forming cells.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed1989

Augmentation of lymphokine-activated killer cell cytotoxicity by monoclonal antibodies against human small cell lung carcinoma.

This study examined the lymphokine-activated killer (LAK) cell cytotoxicity on monoclonal antibody (MoAb)-bound tumor cells from the human small cell lung carcinoma cell lines H69 and H128. LAK cells were generated from normal peripheral blood mononuclear cells by incubation with interleukin 2 for 3 or more days. Cells from the LAK culture were cytotoxic to natural killer-sensitive (K562, 84% cytotoxicity) and natural killer-resistant (Daudi, 85%; H69 and H128, 69% and 97%, respectively) cell lines, and to freshly excised human lung (49%) and breast (57%) tumors. LAK cytotoxicity to H69 or H128 cells was significantly augmented by target cell preincubation with the small cell lung carcinoma-reactive MoAbs 1096 (increases of up to 271%) or 5023 (up to 223%). SCLC 5023 or 1096 did not enhance LAK cytotoxicity to Daudi cells of lymphoblastoid origin. Pretreatment of LAK cells with an anti-Fc receptor antibody blocked MoAb augmentation by 1096 or 5023 (but not LAK cytotoxicity), suggesting that LAK-MoAb interaction may be mediated by Fc binding. LAK activity coincided with emergence of a large cell [interleukin 2-stimulated large mononuclear leukocyte (LML)] subset expressing the CD16 and NKH-1 surface determinants. Serial immunophenotyping of the LAK cell culture harvested at Days 3, 5, and 7 indicated that the level of LAK cytotoxicity, with or without MoAb augmentation, correlated with frequency of NKH-1-reactive LMLs. These observations support the hypothesis that LAK cytotoxicity is mediated by a NKH-1-reactive LML subpopulation. Antitumor cytotoxicity may be augmented by tumor-reactive MoAbs through Fc binding to this LML subset.

Antibodies, Monoclonal↗

PubMed1988

Processing of 2-aminofluorene and 2-acetylaminofluorene DNA adducts in Chinese hamster ovary cells.

The effects of 2-aminofluorene (AF) DNA damage on cytotoxicity and DNA-mediated genetic transformation were investigated in Chinese hamster ovary (CHO) cells. N-Acetoxy-2-acetylaminofluorene (NA-AAF) treatment of DNA repair-proficient AT3-2 cells and UVL-10, a UV-hypersensitive mutant cell line derived from AT3-2, showed that UVL-10 cells were markedly more sensitive than AT3-2 cells to NA-AAF cytotoxicity. Analysis of cellular DNA from NA-AAF-treated cell cultures showed that AF was the predominant DNA adduct formed in both cell lines, while formation of 2-acetylaminofluorene (AAF) DNA adducts was not detected in cellular DNA samples of either cell line. Analysis of AF adduct removal showed that kinetics and extent of AF removal were similar in both cell lines. The effects of cellular processing of AAF DNA adducts in CHO cells were examined by introducing plasmid pSV2gpt DNA containing AAF damage into AT3-2 and UVL-10 cell lines by transfection. For comparative purposes, AF-containing pSV2gpt was also used in parallel experiments. In transfection experiments with AAF-containing pSV2gpt DNA, yields of gpt+ transformants declined relative to control frequencies in a much more pronounced manner in repair-deficient UVL-10 cells than in repair-proficient AT3-2 cells. In contrast, transfection with pSV2gpt DNA containing AF adducts had no apparent effect on transformation frequencies in either cell line, even at very high levels of modification. Results of co-transformation experiments in which transfected AAF-containing pSV2gpt DNA molecules were not subjected to selection for phenotype showed that in repair-deficient UVL-10 cells, AAF damage in pSV2gpt apparently interfered with the ultimate association of transfected DNA with recipient cell DNA.

2-Acetylaminofluorene↗

PubMed1988