Immunogenicity of recombinant human interleukin-2: Biological features and clinical relevance

The immunogenicity of recombinant interleukin-2 (rIL-2, EuroCetus, Amsterdam, Netherlands) was studied in seventy-six patients receiving different subcutaneous immunotherapy regimens. Patients presented with progressive metastatic renal cell carcinoma, malignant melanoma, colorectal cancer, B-cell lymphoma, and Hodgkin's disease. An enzyme immunoassay (EIA) was employed to screen patients for development of non-neutralizing antibodies against rIL-2, antibody specificity was confirmed by a standard Western blot. Neutralizing serum activity against rIL-2 was detected using a standard CTLL mouse proliferation assay. Additionally, serum levels of soluble interleukin-2 receptors and lymphocyte subsets expressing the CD56 natural killer (NK) associated antigen were measured.In a proportion of approximately 35% to 90% of the patients treated, non-neutralizing antibodies against rIL-2 could be detected after all treatment courses were evaluated. Antibodies were of the IgG, IgM, IgA and IgD subtypes. None of the 76 patients exhibited serum neutralizing activity after one treatment course. Five patients exhibited neutralizing anti-rIL-2 serum activity after two or more treatment courses of systemic rIL-2. In three of these patients, antibodies neutralized both recombinant and natural IL-2. Patients developing neutralizing anti-rIL-2 antibodies, exhibited significantly lower serum sIL-2 receptor levels upon the emergence of serum neutralizing activity than patients without antibody. Additionally, NK cell associated CD56 positivity was significantly lower in patients who exhibited neutralizing anti-rIL-2 serum activity than in patients who did not. A significant decrease in levels of soluble IL-2 receptors and CD56 NK cell positivity was observed, when comparing values prior to and after onset of serum neutralizing activity against rIL-2. However, while emergence of neutralizing antibodies to rIL-2 diminished rIL-2 induced biological activation, it did not coincide with abrogation of treatment response.Abbreviations rIL-2 recombinant interleukin-2 - EIA enzyme immuno assay - rIFN-2 recombinant interferon- 2     

Xanthan production from olive-mill wastewaters

Olive mill wastewaters (OMW) are a by-product from olive oil manufacture that cause environmental pollution. These wastes have been used as substrate for the production of the extracellular polysaccharide xanthan by Xanthomonas campestris NRRL B1459-S4L41. Growth and xanthan production on dilute OMW as a sole source of nutrients were obtained at OMW concentrations below 60%, yielding a maximal xanthan production of 4.4gl⁻¹ at 30–40% OMW concentration. Addition of nitrogen and/or salts led to significantly increased xanthan yields with a maximum of 7.7gl⁻¹. The N/salts supplements also allowed an increase in the optimal OMW concentration. Inocula pre-grown on OMW can be used. Results suggest that an improved xanthan yield could be obtained with adequate balance between waste concentration and nitrogen or salt supplementation. OMW is proposed as a low-cost substrate for xanthan production with the additional environmental benefit of this use.     

大鼠胼胝体内神经肽Y免疫反应阳性纤维的发育

本实验用免疫组织化学ＡＢＣ法研究了大鼠胼胝体内神经肽Ｙ免疫反应阳性（ＮＰＹ－ＩＲ）纤维的生后发育。结果发现,许多ＮＰＹ－ＩＲ纤维在大鼠出生时便存在于胼胝体内。ＮＰＹ－ＩＲ胼胝体纤维的密度在生后１周内继续逐渐增高,在第２周内达到最高峰。之后,ＮＰＹ－ＩＲ胼胝体纤维的密度逐渐下降,至第３周末时接近成年时的水平,即仅有少量ＮＰＹ－ＩＲ纤维存在于胼胝体内。这些结果提示在大鼠早期生后发育过程中许多ＮＰＹ－ＩＲ胼胝体纤维是暂时性的,其作用可能与大脑皮质的机能发育有关。     

Effects of epidermal growth factor on deoxyribonucleic acid synthesis and stomach weight in hypophysectomized adult mice

Epidermal growth factor (EGF) or saline was administered intraperitonally to hypophysectomized adult male CD2F₁ mice or intact controls at 0700 hr. Subgroups of mice were killed at 4, 8, or 12 hr after injection. EGF was shown to stimulate [³H]TdR incorporation into DNA into several organs as previously reported. The response to EGF was found to be enhanced in both hypophysectomized and fasted mice. Differences in [³H]TdR incorporation into DNA, corneal epithelium mitotic index, RNA in pancreas and kidney of hypophysectomized and intact mice are reported. EGF was shown to result in stomach enlargement due to increased luminal contents in both hypophysectomized and intact mice.     

Cell-mediated immune responses in recurrent herpesvirus infections. I. Lymphocyte proliferation assay.

Studies in immunosuppressed and immunodeficient patients indicate that the cell-mediated immune response appears to be responsible for controlling reactivated herpesvirus infections. In this study, the various parameters of a herpesvirus (types 1 and 2) antigen specific lymphocyte proliferation assay were optimized and used to evaluate individuals with clinical, recurrent HSV-1 and HSV-2 infections. Normal individuals with neutralizing antibody to HSV-1 or HSV-2 responded to virus antigen in culture as well as individuals with recurrent disease. Normal individuals without neutralizing antibody responded with a significantly lower response. Specificity of the lymphocyte proliferation assay was observed most strikingly in normal individuals with a rare HSV-1 infection during the vesicular eruption. Specificity was also observed by determining the ratio of the response to HSV-1 as compared to the response to HSV-2. Evaluated in this manner, individuals with recurrent HSV-1 infections had significantly higher ratios than individuals with HSV-2 infections and vice versa. Data from individuals with recurrent disease was compared to that of normal individuals to determine whether the former demonstrated a specific alteration in this response. Individuals with recurrent disease were found to have higher neutralizing antibody titers than normals. The neutralizing antibody titers in normal individuals correlated well with the lymphocyte proliferation assay results, whereas a similar evaluation in individuals with recurrent disease gave a negative correlation. The ratio of HSV-1 response/HSV-2 response also demonstrated a suppressed response in recurrent infections to the homologous virus during active disease, which disappeared when the individual was convalescent. These studies indicate that individuals with recurrent HSV infections have virus antigen specific alterations of their cell-mediated immune response, which can be associated with their disease.     

Choline-containing bacteriophage receptors in Streptococcus pneumoniae.

Choline-containing teichoic acid seems to be essential for the adsorption of bacteriophage Dp-1 to pneumococci. This conclusion is based on the following observations: In contrast to pneumococci grown in choline-containing medium, cells grown in medium containing ethanolamine or other submethylated aminoalcohols instead of choline were found to be resistant to infection by Dp-1. Live choline-grown bacteria and heat- or UV-inactivated cells and purified cell walls prepared from these cells were capable of adsorbing phage Dp-1; ethanolamine-grown pneumococci or cell wall preparations were unable to do so. Adsorption of Dp-1 to choline-containing cell walls was competitively inhibited by phosphorylcholine and by several choline-containing soluble cell surface components, such as the Forssman antigen and the teichoic acid-glycan complexes formed by autolytic cell wall degradation. Cell walls prepared from pneumococci grown in ethanolamine or phosphorylethanolamine were inactive. Electron microscopic studies with pneumococci that had segments of choline-containing cell wall material amid ethanolamine-containing regions indicated that the Dp-1 phage particles adsorbed exclusively to the choline-containing surface areas. We suggest that the choline residues of the pneumococcal teichoic acid are essential components of the Dp-1 phage receptors in this bacterium.     

Creatine kinase elevations in marathon runners: relationship to training and competition.

Elevation of creatine kinase (CK) in serum after exertion is a reliable marker of skeletal muscle injury. Limited data exist on CK levels in conditioned athletes after endurance training and competition. Serum CK was measured by a kinetic UV method (normal < 100 U/L) in 15 long distance runners before (pre-race), 24 hours after (post-race) and four weeks following (post-race) the 1979 Boston Marathon. CK levels were elevated throughout the study. Mean values for all runners and for those finishing before and after three hours and 30 minutes are as follows: Post-race CK was significantly elevated among the ten faster as compared to the five slower runners (p = 0.025). Elevations of creatine kinase drawn 24 hours post-marathon are inversely related to finishing times among the runners tested.     

The effect of secretin and cholecystokinin-pancreozymin on the secretion of bile in the anaesthetized rabbit.

Effects of secretin and Cholecystokinin-Pancreozymin (CCK-PZ) on the secretion of bile in anaesthetized rabbits have been studied. Single injections of secretin (5.0 u.kg(-1) significantly increased the flow of bile irrespectively of whether the cystic duct was free or had been tied. A sustained increase in bile flow could be obtained by the continuous infusion of secretin. Cholecystokinin-Pancreozymin was effective in increasing the bile flow in doses of 1.0 u.kg(-1). Much of the effect could be attributed to contraction of the gallbladder but a significant increase in flow could still be elicited after ligation of the cystic duct. Our findings strongly suggest that the biliary secretion in rabbits is not as different from the general pattern as has previously been suggested.