Alpha,beta-unsaturated carbonyl compounds: inhibition of rat liver glutathione S-transferase isozymes and chemical reaction with reduced glutathione

Monoclonal antibodies have been obtained by fusing mouse myeloma cells with spleen cells of mice immunized with crude thyroid membranes. Among the antibodies reactive with different thyroid antigenic components, three were found to specifically react with TSH receptor molecules. These antibodies displayed characteristic staining patterns on frozen sections of thyroid tissue from patients with various thyroid diseases upon identification of antibody binding by indirect peroxidase staining. No specific reactivity was detected with tissue from other human organs, such as pancreas, liver, fat, and muscle. The results demonstrate that the immunoperoxidase technique and the specificity of the monoclonal antibodies produced permitted the identification of cellular constituents that might be important antigens in autoimmune thyroid disease.     

Surgery for lung cancer: age alone is not a contraindication

A retrospective analysis of the clinical features, operative procedures, postoperative complications and subsequent survival of 70 (50 male) elderly patients undergoing surgery for lung cancer compared with 74 (53 male) younger patients treated at the same hospital during the same period was performed, to determine if elderly people with lung cancer are less likely to benefit from and/or tolerate surgery. The elderly group had to wait longer for operation (p = 0.001) and were more likely to have pre-existing disease (p = 0.019). In contrast, they had fewer recognised postoperative complications (p = 0.032) and there was no difference between the two groups in perioperative mortality and subsequent survival. Surgical treatment of localised lung cancer represents the best chance for cure and this study suggests that age should not be a consideration in the decision to operate or not. The patient's general state of health should be assessed and management decisions based on individual status rather than on age.     

Heat shock treatment decreases the mortality of sepsis in rats

Sepsis is an increasingly common and lethal diagnosis in hospitalized patients. In spite of the advances in antibiotics and medical equipment, the mortality rate has not been improved in the last decade. Recently, heat shock proteins (Hsps) have been well documented to play a self-protective role in almost all living cells under various pathological and physiological stresses through a mechanism known as thermotolerance or cross tolerance. The present study was designed to investigate the expression of Hsp72 and the protective role of pre-induction of Hsps in the mortality during different phases of sepsis. Adult male Sprague-Dawley rats were employed in the study. Sepsis was induced by cecal ligation and puncture (CLP). Heat shock treatment was performed 16 hrs before sepsis induction by heating the rats whole-bodily with an electric heating pad under general anesthesia. The mortality rates with time in both control and preheated groups were monitored. Hsp72 was detected by SDS-PAGE, Western blotting and immunostaining in the brain, heart, liver, kidney, lung, adrenal gland, muscle and lymphocytes. The results show that both early (9 hrs post-CLP) and late (18 hrs post-CLP) sepsis failed to increase the synthesis of Hsp72. Previous induction of Hsps by heat shock treatment significantly decreased the mortality rate of late sepsis. Applying a sufficient inducer to lymphocytes of late sepsis reversed the synthesis of Hsp72 from inactive state into an over-expressive situation in vitro. These results suggest that Hsps are involved in the pathogenesis of sepsis and the involvement of Hsps during the progression of sepsis could add to a first line of host defense against invasive pathogens. Searching for an acceptable agent or less invasive method that leads to increased Hsps expression may provide a means for better treatment of severe infection.     

Microstructure and diffraction pattern changes resulted from long—term aging of martensite CuZnAlMnNi shape memory alloy

Microstructures of a CuZnAlMnNi shape memory alloy in the as-quenched and long-term aged conditions were investigated by transmission electron microscopy.Aged for one year in martensite phase,an equilbrium α-phase with fcc structure was observed in the M18R martensite matrix,accompanied by the appearance of a novel diffractionn pattern.By analysis,it was suggested that the novel pattern results from the α-phase and the martensite matrix remaining in seven fine plates which produce intense secondary diffraction effect when the diffraction beams enter from one phase into another.     

Influence of pH on release of phenytoin sodium from slow-release dosage forms

Physicochemical factors influencing the release of phenytoin sodium from slow-release dosage forms were studied. Some of these factors were solubility and intrinsic dissolution rate as functions of pH, type of dosage form, pH of dissolution medium used, and conversion of the sodium salt to free acid (phenytoin). The innovator's product, Extended Phenytoin Sodium Capsule (Dilantin Kapseal, 100 mg, Parke-Davis), and two experimental formulations (one nondisintegrating tablet containing polymeric materials and the other a solid dispersion in an erodible matrix) served as the slow-release dosage forms. The sodium salt converts to practically insoluble phenytoin in the gastrointestinal pH range of 1 to 8. Due to such a conversion inside or at the surface of slow-release dosage forms, the release of drug in this pH range was incomplete. The extent of drug release also varied with the type of formulation used. In contrast, complete dissolution could be obtained in water because the pH of the medium gradually rose from approximately 6 to approximately 9.2 where the drug solubility was higher. Although several phenytoin sodium products might have similar dissolution rates in water, the extents of drug release under gastrointestinal pH conditions (pH 1-8) could differ greatly, thus supporting the Food and Drug Administration recognition that the similarity in dissolution profiles in water does not assure that the products are bioequivalent. The reported lower steady-state level of phenytoin in human plasma following oral administration of a slow-release dosage form may be related to incomplete drug release.     

Bacteriology of tonsil and adenoid and sampling techniques of adenoidal bacteriology

Twenty-six laboratories including 22 Blood Transfusion Centres in England, Scotland, Wales and Northern Ireland participated in a collaborative study to assess the suitability of proposed working standards for hepatitis B surface antigens (HBsAg) for use in the UK Blood Transfusion Service. Data from 88 assays indicated that all laboratories could detect HBsAg in the proposed working standard at a concentration of 0.5 IU/ml. Samples containing HBsAg at a concentration of 0.125 IU/ml were scored positive in 80% of assays and it was concluded that this would be a suitable concentration for inclusion in a monitor sample which would indicate whether the sensitivity of an assay system in routine use is varying over a period of time. The use of a batch of 'provisional' working standard tested under field conditions over a period of 4 months has been monitored. HBsAg was not detected in only 2 out of 6,523 assays.     

Structural basis for the binding of a globular antifreeze protein to ice

Antifreeze proteins (AFPs) have the unique ability to adsorb to ice and inhibit its growth. Many organisms ranging from fish to bacteria use AFPs to retard freezing or lessen the damage incurred upon freezing and thawing. The ice-binding mechanism of the long linear alpha-helical type I AFPs has been attributed to their regularly spaced polar residues matching the ice lattice along a pyramidal plane. In contrast, it is not known how globular antifreeze proteins such as type III AFP that lack repeating ice-binding residues bind to ice. Here we report the 1.25 A crystal structure of recombinant type III AFP (QAE isoform) from eel pout (Macrozoarces americanus), which reveals a remarkably flat amphipathic ice-binding site where five hydrogen-bonding atoms match two ranks of oxygens on the [1010] ice prism plane in the <0001> direction, giving high ice-binding affinity and specificity. This binding site, substantiated by the structures and properties of several ice-binding site mutants, suggests that the AFP occupies a niche in the ice surface in which it covers the basal plane while binding to the prism face.