Ubiquitin is a common factor in intermediate filament inclusion bodies of diverse type in man, including those of Parkinson's disease, Pick's disease, and Alzheimer's disease, as well as Rosenthal fibres in cerebellar astrocytomas, cytoplasmic bodies in muscle, and mallory bodies in alcoholic liver disease

Polyclonal antibodies were raised which have a high affinity for conjugated ubiquitin. Immunocytochemistry was performed on paraffin sections of tissues showing well-characterized inclusion bodies. Ubiquitin was found as a component of the intermediate filament inclusion bodies characteristic of several major diseases including Lewy bodies of Parkinson's disease, Pick bodies of Pick's disease, Mallory bodies of alcoholic liver disease, cytoplasmic bodies of a specific myopathy, and Rosenthal fibres within astrocytes. Ubiquitin was also present in the three histological lesions characteristic of Alzheimer's disease. These observations suggest a fundamental role for ubiquitin in the formation of intermediate filament inclusion bodies in man, and have implications regarding the pathogenesis of these important diseases.     

Nutritional status and cytokine-related protein breakdown in elderly patients with gastrointestinal malignancies

BACKGROUND: Age-related factors affecting cytokine-related whole-body protein breakdown and their relation to clinical outcomes in cancer patients were investigated. METHODS: For assessment of protein-calorie malnutrition and protein breakdown, the creatinine height index (CHI) and daily urinary excretion of 3-methylhistidine (3-MH) were measured in 70 patients with gastrointestinal malignancies. Perioperative cytokine profile was evaluated to assess its relation to perioperative protein catabolism. RESULTS: In elderly patients, daily 3-MH excretion during the stable preoperative period decreased with the increase of tumor interleukin (IL)-6 production, suggestive of the activation of a metabolic compensation mechanism. However, these patients showed significant increases in postoperative 3-MH excretion in accord with perioperative systemic IL-6 response, and this deterioration of the compensating mechanism seemed to be associated with poor clinical outcome. An increase in 3-MH excretion under surgical stress was positively correlated with postoperative consumption of IL-6 soluble receptor (sR) in elderly patients with nutritional depletion. CONCLUSIONS: In elderly cancer patients with protein-calorie malnutrition, metabolic compliance against intrinsic IL-6 may be compensated for in the preoperative stable period, but deteriorate from surgical insults. This mechanism might involve increased affinity of IL-6 with IL-6sR under surgical stress.     

Modification of plasma lipoproteins by hexanal,a lipid peroxidation product

Department of Biochemistry, Institute of Experimetnal Medicine, Academy of Medical Sciences of the USSR, Leningrad. (Presented by Academician of the Academy of Medical Sciences of the USSR A. N. Klimov.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 107, No. 3, pp. 294–296, March, 1989.     

严重多发伤患者并发持续炎症-免疫抑制-分解代谢综合征的早期警示因子北大核心CSCD

目的通过回顾性分析, 研究严重多发伤患者伤后并发持续炎症-免疫抑制-分解代谢综合征(persistent inflammation, immunosuppression and catabolism syndrome, PICS)的早期警示因子, 以期加深对严重创伤后慢性危重症病理变化的认识。方法收集2019年3月至2020年12月间收治于同济医院创伤外科严重多发伤患者276例。入选标准:创伤严重度评分(injury severity score, ISS)≥27分, 年龄≥18岁, 住院时间>15 d。排除标准:既往有恶性肿瘤、免疫性、消耗性、代谢性疾病史的患者。收集患者的临床资料、ISS、格拉斯哥昏迷评分(Glasgow coma scale, GCS)、序贯器官衰竭评分、APACHE Ⅱ评分, 以及伤后第3天的营养及免疫指标等资料, 通过t检验、χ^(2)检验或Mann-WhitneyU检验比较组间差异, Logistic回归分析并发PICS的早期警示因子。结果并发PICS患者为PICS组(102例), 不伴PICS的患者为N-PICS组(174例)。PICS组与N-PICS组相比, 年龄偏大, 伴发颅脑与胸部损伤多。在伤后第3天, PICS组IL-6、IL-10水平更高, Treg细胞比率更高, NK细胞计数和分类以及活化T淋巴细胞比率更低(P<0.05)。Logistic回归分析提示, 年龄>65岁(OR=2.375, 95%CI: 1.442~4.531)、同时伴有颅脑及胸部创伤(OR=2.846, 95%CI: 1.522~5.361)、GCS≤8分(OR=3.431, 95%CI: 1.843~8.512)、伤后早期IL-10>10 pg/mL(OR=2.173, 95%CI: 1.751~5.614)、Treg细胞比率>7%(OR=3.871, 95%CI: 1.723~6.312)是严重多发伤后并发PICS的早期独立危险因素。结论年龄>65岁、同时伴有颅脑及胸部创伤、GCS评分、伤后早期IL-10和Treg细胞比率可作为多发伤后并发PICS的早期警示因子。早期警示因子的发现将为早期甄别严重多发伤后潜在并发PICS的高危患者及早期采取干预措施创造可能。     

Recently elucidated energy catabolism pathways provide opportunities for novel treatments in hepatocellular carcinoma

It has long been known that tumors depend on energy production pathways that are different from those of normal cells. These unique pathways require the expression and function of tumor-specific enzymes. Some of these glycolytic enzymes, as well as other modulators of tumor behavior, have recently been elucidated. In theory, inhibiting such enzymes or appropriately affecting such modulators should deprive tumors of energy, while leaving nontransformed cells unaffected. These factors include certain hexokinases that catalyze glycolysis in tumors and can be inhibited by 3-bromopyruvate. 2-deoxyglucose is another modulator that depletes hexokinase stores and cannot undergo further catabolism, thus depriving tumors of their energy source. Other enzymes or modulators are under scrutiny and have shown promise. Preliminary experiments on animals with hepatocellular carcinoma have indeed shown very encouraging results. It appears that modulating the energy production pathways of tumors is poised to become a substantial research area for cancer treatment. This review will focus on the energy production pathways of transformed cells, highlight the differences between transformed and normal cells in this regard and summarize recent experiments that take advantage of these disparities in cancer treatment.     

Serum concentrations of l‐kynurenine predict clinical outcomes of patients with peripheral T‐cell lymphoma,not otherwise specified

Indoleamine 2,3‐dioxygenase exerts intense immunomodulatory effects due to enzymatic activities that catalyze the breakdown of the essential amino acid l ‐tryptophan. The activity of indoleamine 2,3‐dioxygenase can be estimated by measuring serum l ‐kynurenine concentrations. Here, we aimed to determine the role of l ‐kynurenine as a prognostic factor for peripheral T‐cell lymphoma, not otherwise specified (PTCL‐NOS) in a retrospective analysis of data derived from 31 consecutive patients between June 2000 and March 2013 who were histologically diagnosed with PTCL‐NOS according to the World Health Organization classification and treated with 6?8 cycles of cyclophosphamide, doxorubicin or pirarubicin, vincristine, and prednisolone. l ‐kynurenine concentrations in serum samples collected at admission were measured using high‐performance liquid chromatography. The median serum concentration of l ‐kynurenine was 3.28 (range 0.92–8.16) μM. The l ‐kynurenine cutoff was set at 3.07 μM using receiver operating characteristics curves. The complete remission rates of patients with l ‐kynurenine <3.07 and ≥3.07 μM were 69% and 51%, respectively. The 5‐year overall survival (OS) rates for patients with l ‐kynurenine <3.07 and ≥3.07 μM were 80.2% and 23.4%, respectively (p < 0.001). More advanced age, poor performance status, elevated lactate dehydrogenase, an unfavorable International Prognostic Index, and a poor prognostic index for T‐cell lymphoma were significantly worse factors for OS. Multivariate analyses revealed only l ‐kynurenine as an independent prognostic factor for OS. In conclusion, serum concentrations of l ‐kynurenine might comprise a novel prognostic factor with which to determine the outcomes of treatment for PTCL‐NOS. Copyright © 2016 John Wiley & Sons, Ltd.     

北美外科感染学会第35届年会介绍

正北美外科感染学会(Surgical Infection Society,SIS)的前身为美国外科医师协会(American College of Surgeons)于1968年设立的"外科感染委员会"。SIS自创立之初便始终致力于外科感染领域的机制研究、诊断与防治策略以及针对外科医师的继续教育。SIS第35届年会于2015年8月15-18日在California召开。本届年会讨论议题涵盖脓毒症的病理生理及其药物使用策略、腹腔感染预防及治疗用抗生素的选择、软组织坏死与急性憩室炎等特殊类型感染的治疗、手术部位感染的流行病学与防治策略以及相应的基     

Factors affecting peptide catabolism by oral streptococci

The binding of a number of unsubstituted peptides to Streptococcus sanguis and Streptococcus mutans and their subsequent degradation by such cells were examined. Peptides were added to cell suspensions prepared from glucose-limited growth in a chemostat and, at appropriate time intervals, cell-free filtrates were analyzed for peptides and their constituent amino acid residues by high-pressure liquid chromatography techniques. The results indicated that peptide hydrophobicity plays a limited role in peptide binding, but that charge and chain-length are probably important. In S. sanguis, carboxypeptidase activity rapidly released C-terminal arginine (Arg); this amino acid was less rapidly released from the N-terminus but a number of other residues were also released by aminopeptidase activity. When Arg is buried in the peptide, the rate of its release depends upon the number and type of residues between it and the N-terminus. In contrast, S. mutans possessed only weak peptidase activities. The nature of its peptidase activities indicates that S. sanguis can obtain the metabolically important Arg from a variety of peptides.     

Nitrogen Balance after the Administration of a Prolonged-Release Protein Substitute for Phenylketonuria as a Single Dose in Healthy Volunteers

Nitrogen balance is the difference between nitrogen excreted as urea and nitrogen ingested, mainly in proteins. Increased circulating concentrations of amino acids (AA) in the bloodstream are usually associated with proportional increases in the production and excretion of urea. Previously, we reported results from a randomized, controlled, single-dose, crossover trial in healthy adult volunteers (n = 30) (Trial Registration: ISRCTN11016729), in which a Test product (prolonged-release AA mixture formulated with Physiomimic Technology™ (PT™)) significantly slowed down the release and reduced the peak plasma concentrations of essential AAs compared with a free AA mixture (Reference product) while maintaining essential AA bioavailability. Here, we report an assessment of the nitrogen balance from the same study. The amount of nitrogen contained in plasma AAs, levels of blood urea nitrogen (BUN) (p < 0.0001) and changes in BUN (p < 0.0001) were smaller after the Test product compared with the Reference product. These findings suggest that the production of urea in proportion to systemic AA availability was significantly smaller after the administration of the Test product compared with the Reference product and that the test product conferred the increased utilization of AAs for protein synthesis and reduced their oxidation and conversion to urea. In the clinical setting, it is possible that the effects of PT™ observed on the disposition of free AAs in this study may translate to health benefits in terms of physiological body composition and growth if used for the treatment of subjects with phenylketonuria (PKU). Further investigation in patients with PKU is warranted.