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Biomedical subjects

R C Wang

Publications and source records attributed to R C Wang.

32 records · Page 2Linked to original sources

Mechanisms of resistance to etoposide and teniposide in acquired resistant human colon and lung carcinoma cell lines.

Stable acquired resistance to etoposide (VP-16) or teniposide (VM-26) in HCT116 human colon carcinoma cells and A549 human lung adenocarcinoma cells, was previously obtained by weekly 1-h exposures to either drug (B. H. Long, Natl. Cancer Inst. Monogr., 4: 123-127, 1987). The purpose of this study was to identify possible mechanisms of resistance present in these cells by using human mdr1 and topoisomerase II DNA probes, antibodies to these gene products, and P4 phage unknotting assay for topoisomerase II activities. HCT116(VP)35 cells were 9-, 7-, and 6-fold resistant to VP-16, VM-26, and Adriamycin, respectively, and showed no cross-resistance to colchicine and actinomycin D. These cells had no differences in mdr1 gene, mdr1 mRNA, or P-glycoprotein levels but displayed decreased levels of topoisomerase II mRNA and enzyme activity without any alteration of drug sensitivity displayed by the enzyme. HCT116(VM)34 cells were 5-, 7-, and 21-fold resistant to VP-16, VM-26, and Adriamycin; were cross-resistant to colchicine (7-fold) and actinomycin D (18-fold); and possessed a 9-fold increase in mdr1 mRNA and increased P-glycoprotein without evidence of mdr1 gene amplification. No alterations in topoisomerase II gene or mRNA levels, enzyme activity, or drug sensitivity were observed. A549(VP)28 and A549(VM)28 cells were 8-fold resistant to VP-16 and VM-26 and 3-fold resistant to Adriamycin. Both lines were not cross-resistant to colchicine or actinomycin D but were hypersensitive to cis-platinum. No alterations in mdr1 gene, mdr1 mRNA, or P-glycoprotein levels, but lower topoisomerase II mRNA levels and decreased enzyme activities, were observed. Of the four acquired resistant cell lines, resistance is likely related to elevated mdr1 expression in one line and to decreased topoisomerase II expression in the other three lines.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Analysis of the membrane organization of an Escherichia coli protein translocator, HlyB, a member of a large family of prokaryote and eukaryote surface transport proteins.

Haemolysin B (HlyB) is essential for secretion of the 107 x 10(3) Mr haemolysin A protein from Escherichia coli and is a member of a family of highly conserved, apparently ATP-dependent surface proteins in many organisms. We have shown in this study that both HlyB and HlyD fractionate primarily with the cytoplasmic membrane of E. coli and are accessible to proteases after removal of the outer membrane. We have measured experimentally the topological organization of HlyB within the membrane by construction of fusions to beta-lactamase as a reporter. The predicted folding of HlyB, with a minimum of six transmembrane segments, does not always coincide with regions of highest average hydrophobicity. This suggests that HlyB may have a novel organization within the bilayer. From our data and comparative sequence analysis, we have been able to predict very similar topological models for the other members of the HlyB family.

Amino Acid Sequence↗

Long-term problems in patients with tracheoesophageal puncture.

Two hundred forty-seven patients, followed up a mean of 18 months and up to 108 months, were retrospectively studied for problems related to or affecting tracheoesophageal puncture for voice restoration. Active cases, as well as those inactive and decreased, were included. There were 154 patients with primary and 93 with secondary tracheoesophageal puncture. Problems were encountered at least once in 137 cases (55%). The 20 types of problems identified occurred in frequencies ranging from 0.4% to 21%. Most difficulties developed within the first 6 months and in general were easily managed. However, problems such as recalcitrant leakage, difficulty with changing the prosthesis, and dislodgment of the prosthesis led to permanent tracheoesophageal puncture tract closure in 18 patients (7%).

Esophagostomy↗

Detection of the target progenitor cells of granulomonopoietic enhancing activity.

Macrophage-derived granulomonopoietic enhancing activity (GM-EA) is a novel mediator that amplifies colony formation of myeloid progenitor cells (CFU-GM) in conjunction with colony-stimulating factors (CSFs), and is distinct from other hematopoietic synergizing factors such as interleukin (IL)-1, IL-4, and IL-6. In the present study, we try to ascertain whether or not there is a GM-EA-specific responsive myeloid progenitor cell population. Human bone marrow cells deleted of adherent cells and T lymphocytes were separated by velocity sedimentation into three subpopulations with respective sedimentation rates (millimeters per hour) of 7.4 +/- 0.4, 6.0 +/- 0.6, and 4.7 +/- 0.3. These subpopulations corresponded to the day 7 CFU-GM, day 14 CFU-GM, and the earlier myeloid progenitor cells, pre-CFU-GM, respectively. Pre-CFU-GM failed to respond to the colony-inducing effect of GM-CSF but could be stimulated by GM-EA alone to generate small clusters (5 to 25 cells) in soft agar after 14 days of incubation. Correspondingly, suspension preculture of the fractionated bone marrow cells also showed that only the progenitor cells with low sedimentation rate (4.7 mm/h) could be activated by GM-EA to generate CFU-GM. Taken together, our results suggest that the specific target cell of GM-EA is the pre-CFU-GM, and that GM-EA acts on these cells as a growth/maturation factor, but on the day 7 and day 14 CFU-GM as a synergistic growth factor.

Bone Marrow↗

Unknown primary squamous cell carcinoma metastatic to the neck.

We analyzed retrospectively 157 cases of metastatic neck squamous cell carcinoma from unknown primary sites, treated with surgery, radiotherapy, excisional biopsy, and combined modalities. Median follow-up was 74 months, and overall actuarial survival was 55% at 5 years. The surgery-treated group, despite a higher rate of manifesting primary tumors, had significantly better survival at 5 years compared with those receiving radiation therapy, of whom 23% had residual disease after treatment. Primary tumors were discovered during follow-up in 16% overall. Different treatments yielded comparable results in lower-staged neck disease (NX, N1, N2a), while surgery appeared more effective in controlling advanced disease (N2b, N3a). Factors that affected survival include neck stage, connective tissue invasion, and presence of recurrent or residual disease after treatment.

Carcinoma, Squamous Cell↗

Cochlear implant flap complications.

In a series of 52 patients who received cochlear implants, 4 patients suffered flap complications (7.7%). The problems encountered involved the postauricular flap and were usually minor in nature. None required explantation as a direct result of these complications. Flap ischemia in a patient with Cogan's syndrome and vasculitis, two cases of suture extrusion with one having exposure of the implant, and a case of receiver unit magnet extrusion repaired with a vascularized pericranial flap based upon temporalis muscle are presented. Flap design in patients who have had postauricular incisions demands special consideration. Principles useful for avoiding complications as well as their management are discussed.

Adult↗

Down regulation of myelopoiesis by mediators inhibiting the production of macrophage-derived granulomonopoietic enhancing activity (GM-EA).

Monocyte-derived lipid-containing macrophages (MDLMs) constitutively synthesize a granulomonopoietic enhancing activity (GM-EA) that potentiates the function of granulocyte-macrophage colony-stimulating activity (GM-CSA). In the study reported, we show that GM-EA is distinct from interleukin-1 (IL-1) in biochemical and functional properties and that its production is negatively regulated by several mediators. Thus, MDLM cultures pretreated with interferon-gamma (IFN-gamma, 3 to 900 U/mL), prostaglandin E2 (PGE2, 10(-13) to 10(-8) mol/L), or lactoferrin (LF, 10(-13) to 10(-8) mol/L) invariably produced less GM-EA than untreated controls. The relative potency of inhibition was in the order of IFN-gamma greater than or equal to PGE2 greater than LF. The extent of the inhibitory effects was proportional to dosage and the duration of treatment and could be observed following only a brief exposure (two hours) of the MDLMS to physiologic doses of the mediators. Under optimal conditions, IFN-gamma (300 U/mL for 24 to 48 hours) and PGE2 (10(-9) mol/L for 24 to 48 hours) could totally abrogate the ability of the MDLMs to produce GM-EA. However, the drug-inhibited MDLMs could be reactivated to produce GM-EA by treatment with zymosan (60 micrograms/mL). These results demonstrate that a mechanism for the control of myelopoiesis by mediators such as IFN-gamma, PGE2, and LF may involve the inhibition of GM-EA production. Furthermore, this negative feedback control is reversible and can be overridden when a proper stimulatory signal is given.

Cells, Cultured↗

Identification of an acridine photoaffinity probe for trypanocidal action.

Twenty-four acridine derivatives were screened for trypanocidal activity in Trypanosoma brucei in order to determine which structural features of the acridine molecule confer maximal antiparasitic activity. The synthesis of several new azidoacridine derivatives are also reported as well as an assessment of their value as possible photoaffinity probes for the study of acridine trypanocidal action. The most effective and selective acridine trypanocides, with and without irradiation, were the 3-amino-10-methylacridinium salt derivatives. With brief irradiation, one azidoacridine, 3-amino-6-azido-10-methylacridinium chloride, showed considerable trypanocidal activity at very limiting drug concentrations (10(-7)M) and warrants consideration as a possible photoaffinity probe.

Acridines↗

Near-fatal complications of tracheotomy infections and their prevention.

Infectious complications of tracheotomy range from minor to potentially fatal. Three cases are presented: clavicular osteomyelitis; innominate artery blowout with mediastinitis; and the first reported case of necrotizing fasciitis involving the chest wall related to tracheotomy infection. All patients were debilitated, with one diabetic and another steroid-dependent. Infectious sequelae occurred as late as 8 weeks following tracheotomy. The mechanism, treatment, and prevention of tracheotomy infections are reviewed. Indications for the creation of a permanent but reversible tracheostome should be expanded to prevent infections in debilitated or immunosuppressed patients in whom decannulation is unlikely.

Fasciitis↗

Juvenile xanthogranuloma masquerading as pediatric chronic uveitis: a clinicopathologic study.

Juvenile xanthogranuloma (JXG) is a rare, pediatric histiocytic skin disorder that may affect the eye. It can present with protean ocular manifestations, including masquerade uveitis, heterochromia, hyphema, or glaucoma. It very rarely involves the retina and posterior segment; indeed, posterior involvement has been documented histopathologically in only one case. We present the case of a 2-year-old child with ocular JXG presenting as chronic, refractive uveitis, without skin or systemic findings. The blind, painful eye was enucleated and found to harbor a diffuse histiocytic process that involved both the anterior and posterior segments, including the retina and subretinal space. Histological, immunohistochemical, and electron microscopic studies confirmed the diagnosis of JXG. The pathologic classification and differential diagnosis of systemic histiocytic disorders are discussed. Since JXG can present as masquerade pediatric uveitis, this entity should be considered in children with atypical uveitis. In rare instances, JXG may involve the posterior segment and the retina, leading to retinal detachment and blindness.

Child, Preschool↗