Identification of Tumor Antigens in the HLA Peptidome of Patient-derived Xenograft Tumors in Mouse

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Highlights

• •Sufficient tumor tissues are often unavailable large HLA peptidome discovery.
• •Using patient derived xenograft (PDX) tumors can overcome this limitation.
• •The large PDX HLA peptidomes expand significantly those of the original biopsies.
• •The HLA peptidomes of the PDX tumors included many tumor antigens.

     

Accurate MS-based Rab10 Phosphorylation Stoichiometry Determination as Readout for LRRK2 Activity in Parkinson's Disease

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Highlights

• •MS-based clinical assay that accurately determines phospho Rab10 occupancy.
• •Stable isotope labeled phosphopeptide injected as a standard with endogenous tryptic phospho Rab peptide for accurate ratio determination.
• •Determination of pRab levels in neutrophils of Parkinson disease patients.
• •Relevance of pRab levels as marker of PD.

     

Ethical Considerations for Outcome‐adaptive Trial Designs: A Clinical Researcher's Perspective

In a typical comparative clinical trial the randomization scheme is fixed at the beginning of the study, and maintained throughout the course of the trial. A number of researchers have championed a randomized trial design referred to as ‘outcome‐adaptive randomization.’ In this type of trial, the likelihood of a patient being enrolled to a particular arm of the study increases or decreases as preliminary information becomes available suggesting that treatment may be superior or inferior. While the design merits of outcome‐adaptive trials have been debated, little attention has been paid to significant ethical concerns that arise in the conduct of such studies. These include loss of equipoise, lack of processes for adequate informed consent, and inequalities inherent in the research design which could lead to perceptions of injustice that may have negative implications for patients and the research enterprise. This article examines the ethical difficulties inherent in outcome‐adaptive trials.     

The effect of excitation on the rate of respiration in the liverwort Conocephalum conicum

Simultaneous measurements were taken of the electrical activity and the rate of respiration of thalli of Conocephalum conicum L. stimulated electrically and mechanically (by cutting). The measurements of the rate of respiration employed a modified Warburg apparatus for O₂ consumption and an infra-red gas analyzer with computer recording and data processing for CO₂ evolution. The action potential, produced by either a cut (a damaging stimulus) or an electrical stimulus (a non-damaging stimulus), caused a transient rise in the rate of respiration. The course of changes in the rate of respiration depends on the character of the excitation and the area of the thallus covered by it. If stimulation does not produce excitation, the increase in the rate of respiration does not take place, regardless of the magnitude and type of the stimulus applied.     

Immunotoxins up to the present day

Immunotoxins consist of monoclonal or polyclonal antibodies conjugated to bacterial or plant toxins. The toxins used are typically of the A-B type in which a toxic A chain is coupled to a B chain responsible for cell binding and facilitation of A chain entry into the cytosol. Two broad strategies have been followed: coupling intact toxins, or A chains alone, to antibodies. This review examines current progress inin vitro andin vivo research, including recent clinical studies, concentrating principally on ricin or ricin A chain conjugates. The future role of conjugates using membrane-acting toxins, immunolysins, is also discussed.     

流式细胞计的研制

流式细胞计是近年发展起来的一种综合应用光学机械,电子学,流体动力学,激光和计算机的高技术生物医学仪器。它在生物学基础研究和临床医学研究中有广泛的应用。我们最近研制成功国内首台多参数流式细胞计,并已通过中国科学院院级鉴定。本文介绍该仪器的原理,主要结构与技术要点和使用结果等,它将有助于我国流式细胞术及其应用研究工作的开展。     

Studies on clinical signs and haematological alterations in pneumonic aspergillosis due to Aspergillus flavus in Japanese quail

Intratracheal inoculation of 2-week old quail chicks with Aspergillus flavus spores resulted in the development of clinical signs within 24 h of infection. These were characterized by dullness, depression, anorexia, accelerated breathing, gasping and prostration leading to death. These signs continued up to 7 days followed by considerable decrease in the intensity of the symptoms as well as number of birds showing clinical signs. Mortality occurred primarily in the first week with a majority of the birds dying from 2–4 days after infection. The overall mortality during a 6-week observation period was 25%. The average body weight of the infected chicks was slightly lower than that of controls; the difference being significant at 2, 3 and 42 days post-infection. There was no appreciable difference in the mean values of haemoglobin, packed cell volume and total erythrocyte count between the infected and control chicks at any stage of infection, but total leucocyte count revealed a significant increase (p<0.05) from 3–7 days post-infection. This was due to increase in the percentage of heterophils and decrease in lymphocytes.     

Molecular cloning and nucleotide sequences of cDNAs specific for rat liver ribosomal proteins S17 and L30

cDNA clones coding for rat liver ribosomal proteins S17 and L30 have been isolated by positive hybridization-translation assay from a cDNA library prepared from 8-9S poly(A)+RNA from free polysomes of regenerating rat liver. The cDNA clone specific for S17 protein (pRS17-2) has a 466-bp insert with the poly(A) tail. The complete amino acid (aa) sequence of S17 protein was deduced from the nucleotide sequence of the cDNA. S17 protein consists of 134 aa residues with an Mr of 15 377. The N-terminal aa sequence of S17 protein determined by automatic Edman degradation is consistent with the sequence data. The aa sequence of S17 shows strong homology (76.9%) to that of yeast ribosomal protein 51 [Teem and Rosbash, Proc. Natl. Acad. Sci. USA 80 (1983) 4403-4407] in the two-thirds N-terminal region. The cDNA clone specific for L30 protein (pRL30) has a 394-bp insert. The aa sequence of L30 protein was deduced from the nucleotide sequence of the cDNA. The protein consists of 114 aa residues with an Mr of 12 652. When compared with the N-terminal aa sequence of rat liver L30 protein [Wool, Annu. Rev. Biochem. 48 (1979) 719-754], pRL30 was found not to contain the initiation codon and 5'-noncoding region. The cDNA showed twelve silent changes in the coding region, one point mutation and one base deletion in the 3'-noncoding region, compared with mouse genomic DNA for L30 protein [Wiedemann and Perry, Mol. Cell Biol. 4 (1984) 2518-2528].     

Omega-3 fatty acids and the peroxisome

The interactions between the omega-3 unsaturated fatty acids and peroxisomal function have been reviewed, in order to update and integrate knowledge in this area. Following a brief retrospective of the major clinical involvements of these fatty acids, the participation of the peroxisome in their metabolism has been appraised - the peroxisome being shown to exert a major influence on both the synthesis and degradation of the omega-3 fatty acids, with these effects flowing on to the widespread physiological implications of the derivative eicosanoids. Interactions between the omega-3 and omega-6 families of fatty acids have been discussed, as have the interdependent phenomena of peroxisome proliferation, membrane remodelling and cellular signalling. Amongst the signalling involvements covered were those of steroid hormone receptor superfamily, the phosphatidy1choline cycle, and the regulatory influences of oxygen free radicals. Comment has also been included on the separate biological roles of the individual omega-3 fatty acids, their influence on differential gene function, and on the molecular mechanisms of their pharmacological effects. It is concluded that the peroxisome is intimately involved in directing the metabolism and physiological influence of the omega-3 unsaturated fatty acids, and that this organelle merits much greater emphasis in future research aimed at unravelling the profound biological effects of these unique and multipotent compounds.