Acute blinding sinusitis.

Sinusitis may produce blindness, and deterioration in visual acuity is a strong indication for urgent admission and possible surgery.     

Immunostimulating properties of synthetic derivatives of muramyl dipeptide and glucosaminyl muramyl dipeptide in vitro

Production of tumor necrosis factor (TNF) and interleukin-1 (IL-1) by macrophages of the spleen and peritoneal exudate of mice as well as cytotoxic factors (CFs) by murine splenocytes after in vitro activation was estimated. All the derivatives of muramyldipeptide (MDP) and glucosaminylmuramyldipeptide (GMDP) were able to induce production of TNF and CFs. In the presence of lipopolysaccharide (LPS), the effect was always higher. The response of the spleen macrophages to the effect of the preparations was higher than that of the peritoneal ones and ++non-fractionated splenocytes. GMDP and GMDP4 especially in the presence of LPS had the highest effect on induction of IL-1 by the murine peritoneal macrophages. On the contrary, MDP induced higher IL-1 synthesis by the spleen macrophages. The most active substances with respect to production of TNF, CFs and IL-1, i.e. MDP3 and GMDP4, might be recommended for immunotherapy of syngeneic tumors in animals.     

The chimpanzee M blood-group antigen is a variant of the human M-N glycoproteins

Chimpanzee erythrocytes express strong M but weak, occasional N blood-group activity, as detected by anti-M and anti-N reagents. We have found that the M activity is carried by a major membrane glycoprotein that is similar but not identical to the human MM glycoprotein (glycophorin A). We have isolated and characterized this glycoprotein from erythrocyte membranes of four individual chimpanzees. The purified glycoproteins strongly inhibited agglutination of M cells by rabbit anti-human M sera and only weakly inhibited the agglutination of N cells by rabbit anti-human N sera. They also displayed medium-to-strong inhibitory activity against chimpanzee iso- and crossimmune antisera tested with chimpanzee erythrocytes of various V-A-B-D and W^c specificities, which are known as chimpanzee extensions of the human type M-N system and the Miltenberger counterpart, respectively. Each glycoprotein was cleaved with CNBr into three fragments, whose size, solubility, and composition were analogous to those obtained by similar treatment of the human M-N antigens. The amino-terminal fragment was found to be a glycooctapeptide whose amino acid composition and partial sequence indicated that it is an intermediate form of the human M and N glycooctapeptides. Its carbohydrate content comprised two threonine-linked saccharide units that, although similar in composition to the human threonine-linked units, were fewer in number than the three units found in the corresponding human glycooctapeptides. Structural similarities to the human antigens strongly suggest that the amino terminus bears the major antigenic determinants of the molecule, and the occurrence in this region of numerous, albeit rare, variants among humans and in chimpanzees indicates that the corresponding coding sequence of the structural gene is particularly susceptible to mutational events. We conclude that the chimpanzee M gene product is a variant of the human type and that the chimpanzee gene is an allele of the human polymorphic M-N locus.This research was supported by National Institutes of Health Grants GM 16389 and HL 19011 and March of Dimes Grant 1-661.     

Psychological Implications of Cystic Fibrosis

A psychological and psychiatric study of 11 children with cystic fibrosis revealed major psychological problems in all of them. Among the parents of the majority of these children, marked psychopathology and gross marital discord were noted. Popular literature concerning cystic fibrosis had a negative effect on the child''s attitude toward the disease. Virtually all of these patients showed a preoccupation with death. In this study, the necessity of psychiatric consultation as an integral part of current intensive treatment programs in cystic fibrosis clinics was demonstrated.     

Dimorphism in Itersonilia perplexans: Yeast and hyphal phases differ in their sensitivity to mycocins produced by tremellaceous yeasts

The monokaryotic yeast phase of the heterobasidiomycete Itersonilia perplexans, unlike the hyphal phase, was found to be sensitive to mycocins produced by killer strains of Cryptococcus humicola, Cr. laurentii, Cystofilobasidium bisporidii and Rhodotorula fujisanense. Both the yeast and hyphal phases wer resistant to mycocins of Cr. podzolicus, Filobasidium capsuligenum, Rhodotorula glutinis, Rh. mucilaginosa, Rh. pallida, Sporidiobolus johnsonii, Sb. pararoseus and Sporobolomyces alborubescens. The different sensitivity patterns of yeast and hyphal phases are probably caused by biochemical differences in the cell walls.     

Effect of in vivo Histone Hyperacetylation on the State of Chromatin Fibers

Abstract

We evaluated the contribution of in vivo histone acetylation to the folding of chromatin into its higher-order structures. We have compared high-order folding patterns of hyperacetylat- ed vs. unmodified chromatin in living green monkey kidney cells (CV1 line) using intercalator chloroquine diphospate to induce alterations in the twist of internucleosomal linker DNA. We have shown that histone hyperacetylation induced by antibiotic Trichostatin A significantly alters intercalator-mediated chromatin folding pattern.     

Monophosphoryl lipid A analogues with varying 3-O-substitution: synthesis and potent adjuvant activity

Structurally defined immunostimulatory adjuvants play important roles in the development of new generation vaccines. Here described are the syntheses of three monophosphoryl lipid A analogues (1-3) with different substitution at 3-O-position of the reducing sugar and their potent immunostimulatory adjuvant activity. The syntheses involve the preparation of glycosylation acceptors benzyl 3,4-di-O-benzyl-2-deoxy-2-[(R)-3-tetradecanoyloxytetradecanamido]-beta-D-glucopyranoside (16) and benzyl 3-O-allyl-4-O-benzyl-2-deoxy-2-[(R)-3-tetradecanoyloxytetradecanamido]-beta-D-glucopyranoside (17). The glycosylation reactions between the donor 4,6-di-O-benzylidene-2-deoxy-2-(2',2',2'-trichloroethoxycarbonylamino)-alpha-d-glucopyranosyl trichloroacetimidate (21) and acceptors 16 and 17 provide the desired beta-(1-->6)-linked disaccharides 22 and 23, respectively. Selective reductive ring opening of the 4,6-di-O-benzylidene group, installation of a phosphate group to the 4'-hydroxyl group, and the final global debenzylation produce the designed monophosphoryl lipid A analogues 1-3. All three synthetic analogues induce antigen specific T-cell proliferation and interferon-gamma (IFN-gamma) production in ex vivo experiments with a totally synthetic liposomal vaccine system. The immunostimulatory potency of compound 1-3 is in the same order of magnitude as that of the detoxified natural lipid A product isolated from Salmonella minnesota R595 (R595 lipid A). The substituent at the 3-O-position of the reducing sugar does not have much effect on the adjuvant activity of monophosphoryl lipid A analogues. The preliminary lethal toxicity study indicates that the 3-O-acylated hepta-acyl monophosphoryl lipid A may not be more toxic than its 3-O-deacylated hexa-acyl analogue.     

Reactive oxygen species and oxidative stress

Oxidative stress is defined as an imbalance between the production of reactive oxygen species (ROS) and the antioxidant capacity of the cell. For long, ROS have been considered as harmful by-products of the normal aerobic metabolism process of the mitochondria, implicated in a large variety of diseases. But there are now growing evidences that controlled ROS production also play physiological roles especially in regulating cell redox homeostasis and cell signaling. Biological ROS effects are now well documented. Data show that living organisms have not only adapted themselves to coexist with free radicals but have also developed mechanisms to use them advantageously. However their main sources and mechanisms of action remain poorly described. This review focuses on the main properties of ROS and their paradoxical effects.