Comparative cell signalling activity of ultrapure recombinant chaperonin 60 proteins from prokaryotes and eukaryotes

Heat-shock protein (hsp)60/chaperonin 60 is a potent immunogen which has recently been claimed to have cell-signalling actions upon myeloid and vascular endothelial cells. The literature is controversial with different chaperonin 60 proteins producing different patterns of cellular activation and the ever-present criticism that activity is the result of bacterial contaminants. To clarify the situation we have cloned, expressed and purified to homogeneity the chaperonin 60 proteins from Chlamydia pneumoniae, Helicobacter pylori and the human mitochondrion. These highly purified proteins were compared for their ability to stimulate human peripheral blood mononuclear cell (PBMC) cytokine synthesis and vascular endothelial cell adhesion protein expression. In spite of their significant sequence homology, the H. pylori protein was the most potent PBMC activator with the human protein the least potent. PBMC activation by C. pneumoniae and human, but not H. pylori, chaperonin 60 was blocked by antibody neutralization of Toll-like receptor-4. The C. pneumoniae chaperonin 60 was the most potent endothelial cell activator, with the human protein being significantly less active than bacterial chaperonin 60 proteins. These results have implications for the role of chaperonin 60 proteins as pathological factors in autoimmune and cardiovascular disease, and raise the possibility that each of these proteins may result in different pathological effects in such diseases.     

In-vitro contraction of the equine aortic valve

BACKGROUND AND AIM OF THE STUDY: The equine aortic valve is subject to non-inflammatory degenerative changes, associated with aortic valvular regurgitation (AR). This disease shares pathological and epidemiological features with AR in humans, and may serve as a useful model to study in-vitro functional responses associated with aging and disease. The study aim was to determine the contractile properties of the normal equine aortic valve. METHODS: The contractile responses of equine aortic valves to angiotensin II, the thromboxane-mimetic U44069, endothelin-1, 5-hydroxytryptamine and the alpha-adrenoceptor agonists medetomidine, norepinephrine and phenylephrine were studied in vitro in organ baths. Selective antagonists were used to confirm the receptors involved. RESULTS: The order of potency of the agents causing contraction of equine aortic valve segments was angiotensin II > endothelin-1 > U44069 > medetomidine norepinephrine phenylephrine. 5-Hydroxytryptamine did not cause contraction of the equine aortic valve. The contractile response to angiotensin II was abolished by the AT1 receptor antagonist Sar1-Ile8-Angiotensin II, and that of U44069 by the thromboxane TXA2 receptor (TP) antagonist SQ29548. The contractile effects of endothelin-1 were blocked by the ET(A) receptor antagonist BQ123, but not by the ET(B) receptor antagonist BQ788. Yohimbine inhibited the contractile effects of phenylephrine, suggesting an alpha-2 adrenoceptor-mediated response. CONCLUSION: Equine aortic valves contract in response to a number of physiologically important endocrine, paracrine and neuronal mediators. Regulation of valvular tone could therefore be important in the normal functioning of the valve, and further understanding of these mechanisms may lead to insights into the pathophysiology of naturally occurring equine aortic insufficiency. In this respect, the horse should be considered as a model of the human condition.     

Therapeutic effectiveness and safety of outdated human red blood cells rejuvenated to improve oxygen transport function, frozen for about 1.5 years at 80 C, washed, and stored at 4 C for 24 hours prior to rapid infusion

After storage at 4 C for 20 to 28 days, red blood cells were biochemically modified to improve their oxygen transport function which had deteriorated during liquid storage. The solution used for rejuvenation contained pyruvate, inosine, glucose, phosphate, and adenine (PIGPA Solution B). The rejuvenated red blood cells were frozen with 40% W/V glycerol in a polyolefin plastic bag and were stored in the frozen state for about 1.5 years at −80 C. After thawing and washing the red blood cells were stored at 4 C in a sodium chloride- glucose-phosphate solution for 24 hours before transfusion. A pool of four to ten units was rapidly transfused to each of 14 elderly anemic recipients, 11 of whom had cardiopulmonary insufficiency. Recovery of the red blood cells after the freeze-thaw process was about 97 per cent, and after the freeze-thaw-wash process about 90 per cent. The 24− hour posttransfusion survival values were about 75 per cent, and the long-term survival values were about 85 days depending on the disease state of the recipient. The red blood cells had 1.5 times normal 2.3- DPG levels and a decreased affinity for oxygen at the time of transfusion and were able to delivery oxygen at high oxygen tension immediately after the rapid infusion of pools of from four to ten units through a 40-or 170-micron filter. Plasma hemoglobin levels were consistent with extravascular sequestration of nonviable red blood cells, and uric acid levels were not increased during the immediate 24− hour posttransfusion period.     

急性冠脉综合征患者强化他汀治疗与心衰入院危险

目的:确定强化他汀治疗是否可以降低高危患者心衰(HF)的入院危险。背景:强化他汀治疗与缺血性事件的关系已被证实,但其与HF发生危险的关系还不确定。方法:PROVEIT-TIMI2(2ThePravastatinorAtorvastatinEvaluationandInfectionTrial-ThrombolysisInMyocardialInfarction,22帕伐他汀或阿托伐他汀评价与感染试验——心肌梗死溶栓22)研究将4162例患者进行随机分组,分别接强化他汀(阿托伐他汀80mg)或中度他汀(帕伐他汀40mg)治疗。在平均24个月的随访期中,因心住院发生在随机分组后的30多天。并测量基线的型利钠肽(BNP)水平。结果:阿…     

Esophageal Function in Diabetes Mellitus with Special Reference to Acid Studies and Relationship to Peripheral Neuropathy

Esophageal function in 20 subjects with diabetes mellitus was assessed using esophageal manometry, 24-hr ambulatory esophageal pH monitoring, and esophageal scintigraphy. Seven patients had abnormal esophageal manometric studies, and this abnormality was significantly associated with peripheral neuropathy. Almost half of the subjects studied demonstrated excessive gastroesophageal acid reflux, but there was no correlation between the likelihood of abnormal reflux and the presence of peripheral neuropathy. Esophageal scintigraphy was relatively insensitive in the detection of abnormal esophageal function in diabetics.     

Prevalence of high Epworth Sleepiness Scale scores in a rural population

BACKGROUND:

Increased daytime sleepiness is an important symptom of obstructive sleep apnea (OSA). OSA is frequently underdiagnosed, and the Epworth Sleepiness Scale (ESS) can be a useful tool in alerting physicians to a potential problem involving OSA.

OBJECTIVE:

To measure the prevalence and determinants of daytime sleepiness measured using the ESS in a rural community population.

METHODS:

A community survey was conducted to examine the risk factors associated with ESS in a rural population in 154 households comprising 283 adults. Questionnaire information was obtained regarding physical factors, social factors, general medical history, family medical history, ESS score, and self-reported height and weight. Multivariable binary logistic regression analysis based on the generalized estimating equations approach to account for clustering within households was used to predict the relationship between a binary ESS score outcome (normal or abnormal) and a set of explanatory variables.

RESULTS:

The population included 140 men (49.5%) and 143 women (50.5%) with an age range of 18 to 97 years (mean [± SD] 52.0±14.9 years). The data showed that 79.2% of the study participants had an ESS score in the normal range (0 to 10) and 20.8% had an ESS score >10, which is considered to be abnormal or high sleepiness. Multivariable regression analysis revealed that obesity was significantly associated with an abnormal or high sleepiness score on the ESS (OR 3.40 [95% CI 1.31 to 8.80).

CONCLUSION:

High levels of sleepiness in this population were common. Obesity was an important risk factor for high ESS score.