Metabolic effects of chronic emetine treatment.
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Biomedical subjects
Publications and source records attributed to W C Yang.
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Radioautographic DNA labeling and rosetting techniques were combined to study the development of surface IgM, Fc, and complement receptors (FcR, CR) on small lymphocyte populations in mouse bone marrow. [3H]thymidine was either infused continuously to label newly formed cells for periods up to 4 days, or injected daily, 21--35 days before use, to label a sample of long-lived cells. Bone marrow cells were incubated with sensitized sheep erythrocytes to detect surface IgM, FcR, and CR, respectively, and examined radioautographically after cytocentrifugation. During [3H]thymidine infusion, marrow small lymphocytes lacking surface markers were the first to show [3H]thymidine labeling. Most of these cells became labeled by 4 days (IgM--ve, 89%; FcR--ve, 92%; Cr--ve, 88%). Labeling of small lymphocytes bearing surface IgM, FcR, and Cr began after an initial lag and increased to high values by 4 days (IgM + ve, 73%; FcR + ve, 82%; CR + ve, 83%). Labeled IgM + ve small lymphocytes formed progressively larger rosettes as cell age increased. Some proliferating large lymphoid cells formed rosettes for IgM, FcR, and CR. Labeled long-lived small lymphocytes expressed surface IgM, FcR, and CR, the incidence of each receptor being uniformly high (38--43%) and the rosettes tending to be larger than those formed by newly formed lymphocytes. In double-surface marker studies, FcR and CR rosettes were formed by some IgM--ve small lymphocytes as well as IgM + ve cells in the marrow. After transfusion of marrow cells from donor mice infused with [3H]thymidine for 24 h, many labeled newly formed lymphocytes homed into the splenic red pulp of unlabeled syngeneic recipients. Subsequently, these cells showed a rapid increase in the incidence of rosettes for surface IgM, FcR, and CR, together with a progressive enlargement of each type of rosette. Although all the labeled small lymphocytes recovered from the spleen developed both surface IgM and FcR by 3 days, only approximately one-half developed CR. The results demonstrate that most of the small lymphocytes bearing FcR, CR, and surface IgM in mouse bone marrow are newly formed indigenous cells. Each receptor becomes detectable by rosetting soon after the small lymphocytes are first produced. The newly formed, marrow-derived small lymphocytes are able to continue their development of surface IgM, FcR, and CR after migrating into the spleen, consistent with a maturation of primary B lymphocytes. In addition, the data indicate the genesis in mouse marrow of a non-B lineage of lymphocytes (notably, IgM--ve FcR + ve cells.). A minority of small lymphocytes bearing IgM, FcR, and CR in mouse marrow are long-lived cells, presumptive recirculating immigrants, differing in receptor status from the newly formed cells. The results are discussed with regard to the heterogeneity of marrow lymphocytes and proposed models of primary B lymphocyte and null lymphocyte production.
Ultrastructural changes in the retinal pigment epithelium (RPE) and adjacent photoreceptor cells have been followed in the Wistar rat during the course of long-term vitamin A deficiency. Of particular interest has been the discovery of unusual concentric aggregates within the photoreceptor outer segments and the inner cytoplasm of the RPE. The aggregates were present throughout the course of the retinal degeneration induced by vitamin A deficiency and could be identified in the RPE either by themselves in the apical cytoplasm or within phagolysosomes. It is postulated that the concentric aggregates result initially from abnormal formation or condensation of outer segment membranes and are then slowly degraded by lysosomal action in the RPE cytoplasm. In addition, acid phosphatase activity and typical phagosomes (shed outer segment packets) have been demonstrated in the cytoplasm of the RPE of the vitamin A deficient rats. The latter findings indicate that, at least to some extent, the normal phagocytic and lytic processes of the RPE are retained in this nutritional disorder.
A case of cerebral vasospasm complicating intracranial aneurysm surgery is presented. Angiographic findings under hypertension and normotension revealed a paradoxical response of involved vessels suggesting that normal autoregulation is either lost or overcome by spasm.
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Two cases of relapsing juvenile chronic subdural hematoma with late relapse in adult life are presented and the literature reviewed. Both patients contracted subdural hematoma early in life; its persistence resulted in characteristic skull deformitites. The patients led an asymptomatic life until a second head trauma caused rebleeding into the old hematoma sac with recurring symptoms and signs. The source of rebleeding is the outer subdural membrane. Radiographic features vary, depending on the location and size of the subdural hematoma. The significance of localized thickening of the cranium is stressed in refining the differential diagnosis.
Intramedullary metastases to the spinal cord of non-neurogenic origin are exceedingly rare, comprising fewer than 1.6% of all metastases affecting the spinal canal and its contents. Plain films are normal. Irregular fusiform widening of the spinal cord is the most common myelographic feature, although nodularity is also present. Complete blockage is very rare. The authors describe the radiological features in 4 cases of intramedullary metastases of non-neurogenic origin. The differential diagnosis is discussed, and some pathogenetic mechanisms are postulated. It is important to recognize intramedullary metastases in order to plan the proper management.
Targeted ultrasound contrast materials (gas-filled microbubbles carrying ligands to endothelial selectins or integrins) have been investigated as potential molecular imaging agents. Such microbubbles normally exhibit good targeting capability at the slower flow conditions. However, in the conditions of vigorous flow, binding may be limited. Here, we describe a microbubble capable of efficient binding to targets both in slow and fast flow (exceeding 4 dyne/cm(2) wall shear stress) using a clustered polymeric form of the fast-binding selectin ligand sialyl Lewis(X). Microbubbles were prepared from decafluorobutane gas and stabilized with a monolayer of phosphatidylcholine, PEG stearate and biotin-PEG-lipid. Biotinylated PSLe(x) (sialyl Lewis(X) polyacrylamide) or biotinylated anti-P-selectin antibody (RB40.34) was attached to microbubbles via a streptavidin bridge. In a parallel plate flow chamber targeted adhesion model, PSLe(x) bubbles demonstrated specific adhesion, retention and slow rolling on P-selectin-coated plates. Efficiency of firm targeted adhesion to a P-selectin surface (140 molecules/microm(2)) was comparable for antibody-carrying bubbles and PSLe(x)-targeted bubbles at 0.68 dyne/cm(2) shear stress. At fast flow (4.45 dyne/cm(2)), PSLe(x)-targeted bubbles maintained their ability to bind, while antibody-mediated targeting dropped more than 20-fold. At lower surface density of P-selectin (7 molecules/microm(2)), targeting via PSLe(x) was more efficient than via antibody under all the flow conditions tested. Negative control casein-coated plates did not retain bubbles in the range of flow conditions studied. To confirm echogenicity, targeted PSLe(x)-bubbles were visualized on P-selectin-coated polystyrene plates by ultrasound imaging with a clinical scanner operated in pulse inversion mode; control plates lacking targeted bubbles did not show significant acoustic backscatter. In vivo, in a murine model of inflammation in the femoral vein setting, targeting efficacy of intravenously administered PSLe(x)-microbubbles was comparable with targeting mediated by anti-P-selectin antibody, and significantly exceeded the accumulation of non-targeted control bubbles. In the inflamed femoral artery setting, PSLe(x)-mediated microbubble targeting was superior to antibody-mediated targeting.
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Central vein stenosis is an indolent and underestimated complication of permanent pacemaker placement. It leads to serious problems in hemodialysis patients when arteriovenous (AV) fistulae/grafts were created at the ipsilateral arm. We, herein, reported 3 cases of AV access failure resulting from permanent pacemaker-related central vein stenosis. The pathogenesis, clinical manifestations, radiological findings, and therapeutic solution on this issue are discussed. It is mandatory to place the AV fistula/graft and permanent pacemaker wire on the opposite side for prevention of the high risk of AV access failure.
A 72 year old woman complained of transient loss of vision in the left eye. She had undergone a left carotid endarterectomy 10 years previously. Reduced ophthalmic artery pressure was found on noninvasive carotid artery testing and cerebral angiography was performed. No lesion was evident in the carotid artery, but significant ophthalmic artery stenosis was identified. We report this case as showing the occurrence of amaurosis fugax in association with ophthalmic artery stenosis.
N-nitrosodimethylamine (NDMA), a potential carcinogen, was commonly found in treated wastewater as a by-product of chlorination. As treated water is increasingly used for landscape irrigation, there is an imperative need to understand the leaching risk for NDMA in landscape soils. In this study, adsorption and incubation experiments were conducted using landscape soils planted with turfgrass, ground cover, and trees. Adsorption of NDMA was negligibly weak (K(d) < 1) in all soils, indicating that NDMA has a high potential for moving with percolating water in these soils. Degradation of NDMA occurred at different rates among these soils. At 21 degrees C, the half-life (t(1/2)) of NDMA was 4.1 d for the ground cover soil, 5.6 d for the turfgrass soil, and 22.5 d for the tree soil. The persistence was substantially prolonged after autoclaving or when incubated at 10 degrees C. The rate of degradation was not significantly affected by the initial NDMA concentration or addition of organic and inorganic nutrient sources. The relative persistence was inversely correlated with soil organic matter content, soil microbial biomass, and soil dehydrogenase activity, suggesting the importance of microorganisms in NDMA degradation in these soils. These results suggest that the behavior of NDMA depends closely on the vegetation cover in a landscape system, and prolonged persistence and increased leaching may be expected in soils with sparse vegetation due to low organic matter content and limited microbial activity.
Changes in cell proliferation and cell death might be key factors in regulating the rate of neoplasm progression and tumor growth. The extent of apoptosis and its possible relationship with cell proliferation at different stages of esophageal carcinogenesis, however, have not been characterized. In this study, 241 esophageal biopsy samples from symptom-free subjects and 38 surgically resected esophageal carcinoma tissues from a high-risk population for esophageal cancer in Henan, China, were used to analyze the changes of apoptosis and its relationship with cell proliferation as determined by proliferating cell nuclear antigen (PCNA). The apoptotic cells, identified morphologically, were located in the same proliferative compartment of hyperproliferative cell population in the esophageal epithelium. The apoptotic indices (total number of apoptotic cells and apoptotic bodies per mm2 of the tissue section) were low in the normal epithelia, and increased significantly as the lesions progressed from basal cell hyperplasia (BCH) to dysplasia (DYS) and to squamous cell carcinoma (SCC). The extent of apoptosis correlated well with the cell proliferation indices. The present findings indicate that apoptosis occurs in the early stage of esophageal carcinogenesis, and as the lesions progress, both the apoptotic index and PCNA labelled index increase, suggesting that hyperproliferative cells might be more susceptible to apoptosis.
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OBJECTIVE: To investigate the induction of nitric oxide synthase type II (iNOS) in human peritoneal mesothelial cells (HPMC) using cytokines and bacterial lipopolysaccharide (LPS). DESIGN: Confluent monolayers of HPMC were exposed to cytokines [tumor necrosis factor alpha (TNFalpha), interleukin-1 beta (IL-1beta), interferon gamma (IFNgamma)] or LPS, individually or in various double and triple combinations, for 24-72 hours. Concentrations of nitrate and nitrite in the media were quantified using the Griess reaction and used as indirect indices of nitric oxide (NO) production. The expression of iNOS was assessed using reverse transcriptase-polymerase chain reaction (RT-PCR) and Western blot. RESULTS: Neither single cytokines nor LPS was able to induce iNOS mRNA or NO production. Both double combinations of TNFalpha + IFNgamma and IL-1beta + IFNgamma were able to induce iNOS mRNA expression, but only TNFalpha + IFNgamma induced significant NO production. The triple combination of TNFalpha + IFNgamma + IL-1beta induced even more NO production than TNFalpha + IFNgamma. There was no constitutive NO synthase type III (eNOS) expression in HPMC. CONCLUSIONS: Certain combinations of cytokines could stimulate cultured HPMC to produce NO, and HPMC might be a source of intraperitoneal NO production during peritonitis.
BACKGROUND/AIMS: The impact of HCV (hepatitis C virus) infection on the long-term outcome of kidney transplant patients is controversial. METHODOLOGY: Eighty-four renal allograft recipients who were seronegative for hepatitis B surface antigen and had been screened for antibody to hepatitis C virus (anti-HCV) were included. The outcome and survival were compared between anti-HCV-positive (n = 30, group 1) and anti-HCV-negative (n = 54, group 2) kidney transplant patients. Group 1 patients were further compared to 52 anti-HCV-positive end-stage renal disease patients (group 3) who were on chronic dialysis. RESULTS: Group 1 patients had a higher prevalence of chronic hepatitis than group 2 and group 3 patients did (67% vs. 2% and 31%). Liver-related complications and deaths between group 1 and group 2, and group 1 and group 3 patients were not significantly different. The comparisons of the long-term survival between these groups showed no significant differences, despite group 3 patients had a higher overall mortality rate. Cox regression analysis confirmed that age more than 45 years was the only independent factor that affected survival in anti-HCV-positive end-stage renal disease patients with or without kidney transplantation. CONCLUSIONS: HCV infection is not a contraindication to kidney transplantation. For anti-HCV-positive end stage renal disease patients, survival is better in younger patients, and is not influenced by kidney transplantation or continuing dialysis.