Proteomic data from human cell cultures refine mechanisms of chaperone-mediated protein homeostasis.

In the crowded environment of human cells, folding of nascent polypeptides and refolding of stress-unfolded proteins is error prone. Accumulation of cytotoxic misfolded and aggregated species may cause cell death, tissue loss, degenerative conformational diseases, and aging. Nevertheless, young cells effectively express a network of molecular chaperones and folding enzymes, termed here "the chaperome," which can prevent formation of potentially harmful misfolded protein conformers and use the energy of adenosine triphosphate (ATP) to rehabilitate already formed toxic aggregates into native functional proteins. In an attempt to extend knowledge of chaperome mechanisms in cellular proteostasis, we performed a meta-analysis of human chaperome using high-throughput proteomic data from 11 immortalized human cell lines. Chaperome polypeptides were about 10 % of total protein mass of human cells, half of which were Hsp90s and Hsp70s. Knowledge of cellular concentrations and ratios among chaperome polypeptides provided a novel basis to understand mechanisms by which the Hsp60, Hsp70, Hsp90, and small heat shock proteins (HSPs), in collaboration with cochaperones and folding enzymes, assist de novo protein folding, import polypeptides into organelles, unfold stress-destabilized toxic conformers, and control the conformal activity of native proteins in the crowded environment of the cell. Proteomic data also provided means to distinguish between stable components of chaperone core machineries and dynamic regulatory cochaperones.

Relationship between coronary endothelial function and coronary calcification in early atherosclerosis.

BACKGROUND: The relationship between coronary endothelial function and coronary calcification is not well established. METHODS: Forty-six patients 17 men [37%]; age, 47.4+/-11.4 years prospectively underwent testing for coronary endothelial function and measurement of coronary artery calcification (CAC). RESULTS: Log CAC scores were not significantly different between patients with normal (n=31) and abnormal (n=15) response of epicardial coronary artery diameter to acetylcholine (%CAD(Ach)) (median (25, 75 percentile) 1.1 (0.0, 3.7) vs. 0.3 (0.0, 2.4), P=.32) and with normal (n=28) and abnormal (n=18) response of coronary blood flow to acetylcholine (%CBF(Ach)) (0.5 (0.0, 3.6) vs. 0.5 (0.0, 3.2), P=.76). Log CAC scores did not correlate with %CAD(Ach) (r=0.08, P=.59), %CBF(Ach) (r=0.14, P=.35). CONCLUSIONS: In patients without significant coronary artery disease, coronary endothelial dysfunction showed no apparent association with coronary calcification. Our findings suggest that these 2 markers may represent separate, independent processes in the progression of coronary atherosclerosis.

Morbidity and outcome after sentinel lymph node dissection in patients with early-stage malignant cutaneous melanoma.

OBJECTIVE: Prospective analysis of the morbidity and outcome of the sentinel lymph node (SLN) technique in a consecutive series of patients with early-stage melanoma. METHODS: Between 1997 and 1998, 60 patients with stage IB-II malignant melanoma underwent SLN dissection. Preoperative dynamic lymphoscintigraphy with mapping of the lymph vessels and lymph nodes and location of the sentinel node was performed the day before SLN dissection. SLN was identified by use of the blue dye technique. SLN was assessed for histopathological and immunohistochemical examination. Postoperative morbidity and mortality were recorded. Follow-up consisted of repetitive clinical examination with lymph nodes status, laboratory and radiologic findings. RESULTS: Tumor-positive SLN was observed in 18% of the patients and stage II disease was found in 91% of the patients with positive SLN. Breslow thickness was the only significant factor predicting involvement of a SLN (p = 0.02). In 36% of the positive SLN, metastases could be assessed only by immunohistochemical examination. Postoperative complications after SLN dissection were observed in 5% in comparison with 36% after elective lymph node dissection. After a mean follow-up of 32 months, recurrence was observed in 3% with a mean disease-free survival of 8 months. Overall survival was 82% and 90% in patients with positive and negative SLN, respectively. Overall mortality was 15%, due to distant metastases in 78% of the cases. CONCLUSIONS: Staging of early-stage melanoma with the SLN dissection by use of the blue dye technique combined to lymphoscintigraphy and immunohistochemistry is reliable and safe, with less morbidity than elective lymphadenectomy. Long-term follow-up is mandatory to establish the exact reliability of SLN dissection.

Do childhood cancer survivors with physical performance limitations reach healthy activity levels?

BACKGROUND: The extent to which physical performance limitations affect the ability of childhood cancer survivors to reach healthy activity levels is unknown. Therefore this study aims to describe the effect of different types of limitations on activity levels in survivors. PROCEDURE: Within the Swiss Childhood Cancer Survivor Study we sent a questionnaire to all survivors (≥16 years) registered in the Swiss Childhood Cancer Registry, who survived >5 years and were diagnosed 1976-2005 aged <16 years. We measured healthy activity levels using international guidelines and assessed different kinds of performance limitations (visual impairment, weight and endurance problems, cardiorespiratory, musculoskeletal, and neurological problems, pain and fatigue syndromes). RESULTS: The sample included 1,560 survivors (75% response rate), of whom 209 (13.5%) reported they have performance limitations. Forty-two percent of survivors with limitations reached healthy activity levels, compared to 57% of survivors without limitations. Least active were survivors with vision impairments (25% active), weight and endurance problems (27.3%), cardiorespiratory problems (36.4%), and musculoskeletal problems (43.1%). After adjusting for socio-demographic variables and type of cancer, we found that survivors with limitations were 1.4 (95%CI 1.0-2.0; P = 0.047) times more likely to be inactive. CONCLUSIONS: Although many survivors with physical performance limitations maintain healthy activity levels, there is room for improvement. Adapted and targeted physical activity counseling for survivors with performance limitations might help them to raise level of activity and pursue a healthy lifestyle.

Friday Facts, September 6, 2013, Vol. 183

Bureau of Nutrition and Health Promotion part of the Iowa Department of Public Health produces of weekly newsletter about the Iowa WIC Program for the State of Iowa citizen.

List of Bid Proposal Holders, September 17, 2013

List of Bid Proposal Holders

[Illustrations de Architectura privata] / Matthias Rembold, grav. ; Joseph Furttenbach, aut. du texte

Comprend : [pl.2 double après p.6 : cinq modèles de fenêtres. Principes d'architecture.] [Cote : V 4282/Microfilm R 122 209] ; [pl.3 double après p.6 : six modèles de fenêtres. Principes d'architecture.] [Cote : V 4282/Microfilm R 122 209] ; [pl.4 double après p.6 : six modèles de fenêtres. Principes d'architecture.] [Cote : V 4282/Microfilm R 122 209] ; [pl.5 double dépl. après p.6 : trois modèles de portes ou portails. Principes d'architecture.] [Cote : V 4282/Microfilm R 122 209] ; [pl.6 double dépl. après p.6 : plan d'une maison. Principes d'architecture.] [Cote : V 4282/Microfilm R 122 209] ; [pl.7 double dépl. après p.10 : plan d'une maison. Principes d'architecture.] [Cote : V 4282/Microfilm R 122 209] ; [pl.8 double dépl. après p.14 : plan d'une maison. Principes d'architecture.] [Cote : V 4282/Microfilm R 122 209] ; [pl.9 double dépl. après p.16 : plan d'une maison. Principes d'architecture.] [Cote : V 4282/Microfilm R 122 209] ; [pl.910double dépl. après p.18 : plan d'un monastère? Principes d'architecture.] [Cote : V 4282/Microfilm R 122 209] ; [pl.11 double dépl. après p.60 : coupe d'une fontaine-grotte rocaille. Principes d'architecture.] [Cote : V 4282/Microfilm R 122 209] ; [pl.12 double dépl. après p.64 : dessin de la voûte d'une fontaine-grotte rocaille. Principes d'architecture.] [Cote : V 4282/Microfilm R 122 209] ; [pl.13 double dépl. après p.68 : coupe et plan d'une fontaine-grotte rocaille avec vue du sytème hydraulique. Principes d'architecture.] [Cote : V 4282/Microfilm R 122 209] ; [pl.14 double dépl. après p.74 : plans du système hydraulique alimentant une fontaine. Principes d'architecture.] [Cote : V 4282/Microfilm R 122 209]

Friday Facts, September 13, 2013, Vol. 183

Bureau of Nutrition and Health Promotion part of the Iowa Department of Public Health produces of weekly newsletter about the Iowa WIC Program for the State of Iowa citizen.

Friday Facts, September 20, 2013, Vol. 184

Bureau of Nutrition and Health Promotion part of the Iowa Department of Public Health produces of weekly newsletter about the Iowa WIC Program for the State of Iowa citizen.

Friday Facts, September 27, 2013, Vol. 186

Bureau of Nutrition and Health Promotion part of the Iowa Department of Public Health produces of weekly newsletter about the Iowa WIC Program for the State of Iowa citizen.

Quick Reads, September 17, 2013

IDPH Quick Reads is an electronic newsletter produced by the Director’s Office at the Iowa Department of Public Health. IDPH Quick Reads are published every three to four weeks.

Carnitine deficiency in chronic critical illness.

PURPOSE OF REVIEW: New insight in mitochondrial physiology has highlighted the importance of mitochondrial dysfunction in the metabolic and neuroendocrine changes observed in patients presenting with chronic critical illness. This review highlights specifically the importance of carnitine status in this particular patient population and its impact on beta-oxidation and mitochondrial function. RECENT FINDINGS: The main function of carnitine is long chain fatty acid esterification and transport through the mitochondrial membrane. Carnitine depletion should be suspected in critically ill patients with risk factors such as prolonged continuous renal replacement therapy or chronic parenteral nutrition, and evidence of beta-oxidation impairments such as inappropriate hypertriglyceridemia or hyperlactatemia. When fatty acid oxidation is impaired, acyl-CoAs accumulate and deplete the CoA intramitochondrial pool, hence causing a generalized mitochondrial dysfunction and multiorgan failure, with clinical consequences such as muscle weakness, rhabdomyolysis, cardiomyopathy, arrhythmia or sudden death. In such situations, carnitine plasma levels should be measured along with a complete assessment of plasma amino acid, plasma acylcarnitines and urinary organic acid analysis. Supplementation should be initiated if below normal levels (20 μmol/l) of carnitine are observed. In the absence of current guidelines, we recommend an initial supplementation of 0.5-1 g/day. SUMMARY: Metabolic modifications associated with chronic critical illness are just being explored. Carnitine deficiency in critically ill patients is one aspect of these profound and complex changes associated with prolonged stay in ICU. It is readily measurable in the plasma and can easily be substituted if needed, although guidelines are currently missing.