Increased tumor cell reactivity and complement-dependent cytotoxicity with mixtures of monoclonal antibodies against different gangliosides

Melanomas and other cancers of neuroectodermal origin express multiple cell-surface gangliosides in patterns that vary significantly even within the same tumor type. Monoclonal antibodies (mAb) against four of these gangliosides (GM2, GD2, 9-O-acetyl-GD3 and GD3) were tested alone and in combination on 14 tumor cell lines (7 melanomas, 3 neuroblastomas, 3 sarcomas and 1 astrocytoma) using flow cytometry and complement-dependent cytotoxicity (CDC) assays. Increased tumor cell recognition and CDC resulting from the combination of three or four mAb were found in 14/14 tested cell lines, and this was most striking when each mAb was used at suboptimal concentration. At these concentrations, the average mean fluorescence intensity of the 14 cell lines with individual mAb was between 3.0 and 6.8 and increased to 10.8 and 18.8 with the three- and four-mAb mixtures. The average percentage CDC-specific release with individual mAb was 2.0%–8.3%, and 12.3% and 16.6% with the three- and four-mAb combinations. The number of cell lines showing significant mean fluorescence intensity and CDC increased from 2–8/14 with single mAb to 13–14/14 with the mixtures of three or four mAb. Our experimental results support the rationale for active immunization with a polyvalent ganglioside vaccine or passive therapy with a combination of mAb to different gangliosides in patients with tumors of neuroectodermal origin. In addition, our studies have demonstrated that 9-O-acetyl-GD3 is a surprisingly effective target for immune attack, although it is a minor constituent of these cells.     

Spatial Distribution of Biochemical Parameters Indicating Biomass and Community Composition of Microbial Assemblies In Estuarine Mud Flat Sediments

The spatial distribution of communities was examined in estuarine mud flat sediments by the biochemical analysis of the lipids and lipid components extracted from the sediments. Total phospholipid was used as a measure of total biomass, and fatty acids were used as indicators of community composition. Comparisons were made among 2- by 2-m (location) and 0.2- by 0.2-m (cluster) sampling plots by using a nested analysis of variance to design an optimal sampling strategy to define the microbial content of a large, relatively homogenous area. At two of the three stations, a 2- by 2-m plot was representative of the station, but 0.2- by 0.2-m areas were in no case representative of the station. The biomass measured by the extractable phospholipid and the total lipid palmitic acid showed excellent correlation with the fatty acid “signatures” characteristic of bacteria, but showed a lower correlation with the long-chain polyenoic fatty acids characteristic of the microfauna.     

Use of the Health and Activities Limitation Index as a Measure of Quality of Life in Obesity

Objective: Obesity reduces the quality of life (QOL); however, quantification of obesity's impact on QOL is cumbersome. Utility indices reduce QOL measurements to a single numerical value that can be used in the calculation of Quality‐Adjusted Life‐Years and the cost effectiveness for obesity treatment. The purpose of this investigation is to assess the sensitivity of the Health and Activities Limitation Index (HALex) utility index to obesity. Research Methods and Procedures: The answers to five questions regarding an individual's self‐perception of his or her health status and information about limitation in daily and work activities were collected from 32,440 adults in the 1998 National Health Information Survey. Answers to the questions were scored and converted to a utility index score ranging from 0 (near‐death state) to 1 (perfect health) with no limitations. Average values for indices corresponding to differing body mass indices were obtained and significance determined by ANOVA. Results: The utility index for normal weight males and females was 0.86 ± 0.19 and fell to 0.68 ± 0.27 for superobese males and 0.60 ± 0.28 in superobese females. Utility indices fell linearly with increasing body mass index and were lower for respondents having obesity‐related comorbid conditions known to reduce the quality of life. Discussion: There is a statistically significant decrease in the QOL with increasing obesity, slightly worse for women compared with men. The Health and Activities Limitation Index can quantitate the effect obesity and its complications have on quality of life.     

The regulation of pollen tube growth in Douglas-fir following high doses of ionizing radiation

The relationship between temperature and sensitivity to gibberellin A₃ (GA₃) was studied in lettuce seedlings (Lactuca sativa L. cv. Arctic). Dose/response curves for hypocotyl elongation (10^-4 mol l^-1 to 10^-8 mol l^-1) were constructed for a range of temperatures and the slope of the linear portion of the plots used as an indication of the sensitivity to GA₃. Hypocotyls were unresponsive to GA₃ below 13°C but above this temperature sensitivity increased linearly. Plots of growth rate against temperature had inflexions between 12°C and 13°C, with slopes above this point which increased with increasing GA₃ concentration. The Q₁₀ value for response increased in a similar manner. Reaction rates of NAD-dependent malate dehydrogenase and peroxidase extracted from hypocotyls varied linearly with temperature whilst nonspecific tetrazolium reduction, a membrane based activity, showed an abrupt rate change above 14°C. Pre-exposure to GA₃ had no effect on the temperature responses of soluble or particulate enzymes.Abbreviation GA₃ gibberellin A₃     

The control of plant diseases by chemotherapy

Successful chemotherapy is obtained at present with the antibiotics, such as streptomycin, for certain bacterial and virus diseases of plants. Promising results have been obtained with chemotherapeutic chemicals other than the antibiotics in the control of plant diseases caused by species of such fungi as Botrytis, Fusarium, and Phytophthora.