The effect of hyperbaric oxygen preconditioning on heat shock protein 72 expression following in vitro stress in human monocytes

Hyperbaric oxygen (HBO) is thought to confer protection to cells via a cellular response to free radicals. This process may involve increased expression of heat shock proteins, in particular the highly inducible heat shock protein 72 (Hsp72). Healthy male volunteers (n = 16) were subjected to HBO for 1 h at 2.8 ATA. Inducible Hsp72 expression was measured by flow cytometry pre-, post- and 4 h-post HBO. Peripheral blood mononuclear cells (PBMC) were isolated from whole blood via density centrifugation pre-, post- and 4 h post-HBO. PBMC were then subjected to an in vitro heat shock at 40°C or hypoxia at 37°C (5% O₂) with a control at 37°C. Cells were then analysed for Hsp72 expression by flow cytometry. Monocytes showed no significant changes in Hsp72 expression following HBO. No detectable Hsp72 was seen in lymphocytes or neutrophils. Following in vitro hypoxic exposure, a significant increase in Hsp72 expression was observed in monocytes isolated immediately post- (p = 0.006) and 4 h post-HBO (p = 0.010) in comparison to control values. HBO does not induce Hsp72 expression in PBMC. The reported benefits of HBO in terms of pre-conditioning are not due to inducement of Hsp72 expression in circulating blood cells, but may involve an enhancement of the stress response.     

Association of <Emphasis Type="Italic">ADAM33</Emphasis> gene polymorphisms with adult-onset asthma and its severity in an Indian adult population

ADAM33, a member of the ADAM (a disintegrin and metalloprotease) gene family, is an asthma susceptibility gene originally identified by positional cloning. In the present study, we investigated the possible association of five single-nucleotide polymorphisms (SNPs) in the ADAM33 (rs511898, rs528557, rs44707, rs597980 and rs2787094) with adult-onset asthma in an Indian population. The study included 175 patients with mild intermittent (n = 44), mild persistent (n = 108) or moderate persistent (n = 23) subgroups of asthma, and 253 nonasthmatic control individuals. SNPs were genotyped with the help of restriction fragment length polymorphism polymerase chain reaction (RFLP-PCR) method, and data were analysed using chi-square test and logistic regression model. Bonferroni’s correction for multiple comparisons was applied for each hypothesis. Genotypes and allele frequencies of SNPs rs511898 and rs528557 were significantly associated with adult-onset asthma (P = 0.010-<0.001). A significant association of the homozygous mutant genotype and mutant alleles of SNPs rs2787094, rs44707 and rs597980 with the asthma was also observed (P = 0.020-<0.001). A positive association between asthma and haplotypes AGCCT, GGCCT, AGACT, GCAGT, GGACT, ACCCC and AGACC were also found (P = 0.036-<0.001, OR = 2.07–8.49). Haplotypes AGCGT, GCAGC, ACAGC, ACAGT, GGAGC and GGCGT appear to protect against asthma (P = 0.013-<0.0001, OR = 0.34–0.10). Our data suggest that ADAM33 gene polymorphisms serve as genetic risk factors for asthma in Indian adult population.     

Extracellular heat shock protein 70 (HSPA1A) and classical vascular risk factors in a general population

Atherosclerosis is a chronic inflammatory and autoimmune disease. Candidate molecules/autoantigens include heat shock proteins (HSPs); Hsp70 (HSPA1A) is one of the best studied HSPs. Various studies have shown a correlation between extracellular Hsp70 (eHsp70) and anti-Hsp70/anti-Hsp60 antibody concentration and development of atherosclerosis. A random sample of 456 people aged 40–60 (218 males, 234 females) was studied to investigate the prevalence of traditional vascular risk factors and eHsp70 and anti-Hsp70/anti-Hsp60 antibodies levels, according to the risk of vascular disease. Task Force Chart was applied for classification. Subjects were divided into three groups: G0 (with no vascular risk factor or a risk lower than 5%), n = 239; G1 (moderated 10–20% risk, who do not have established disease) n = 161; and G2 (established atherosclerosis disease) n = 52. eHsp70 and anti-Hsp70 were significantly lower in the atherosclerosis group (group 2) with respect to the other groups. Disease-free people showed the highest anti-Hsp60 concentration compared with the other two groups. A correlation has not been demonstrated between the concentrations of circulating Hsp70 (HSPA1A), anti-Hsp70, and anti-Hsp60 and classical vascular risk factors and C-reactive protein. Low levels of eHsp70 and anti-Hsp70 antibodies should be considered as candidate FRV. Simultaneous decrease of eHsp70 and anti-Hsp70 antibodies would be explained by circulating immune complex formation, and both could be proposed as biomarkers for the progression of atherosclerotic disease. Levels of circulating anti-Hsp60 antibodies may constitute a marker of inflammation in atherosclerosis.     

E-cadherin gene 3′-UTR C/T polymorphism in Turkish patients with nephrolithiasis

Nephrolithiasis is a complex disease and many gene polymorphisms have been associated with stone formation. In this study we aimed to investigate another possible relationship between E-cadherin gene (CHD1) 3′-UTR C/T polymorphism and calcium oxalate nephrolithiasis in the Turkish population. Study population was composed of 143 patients with nephrolithiasis and 158 control subjects. CHD1 3′-UTR C/T polymorphism was analysed using polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) technique. Genotype distribution of the investigated polymorphism was not deviated from Hardy–Weinberg equilibrium (HWE) in patients and control subjects (P > 0.05). C allele frequency was 85.7 and 85.1% in patients and controls, respectively (P = 0.836). Genotype distributions of the CHD1 3′-UTR C/T polymorphism among patients were also not significantly different from those among control subjects (P = 0.636). Our results showed that there is no association between the CHD1 gene 3′-UTR C/T polymorphism and nephrolithiasis in our population.     

SNP/haplotype associations in cytokine and cytokine receptor genes and immunity to rubella vaccine

An effective immune response to vaccination is, in part, a complex interaction of alleles of multiple genes regulating cytokine networks. We conducted a genotyping study of Th1/Th2/inflammatory cytokines/cytokine receptors in healthy children (n = 738, 11–19 years) to determine associations between individual single-nucleotide polymorphisms (SNPs)/haplotypes and immune outcomes after two doses of rubella vaccine. SNPs (n = 501) were selected using the ldSelect-approach and genotyped using Illumina GoldenGate™ and TaqMan assays. Rubella-IgG levels were measured by immunoassay and secreted cytokines by ELISA. Linear regression and post hoc haplotype analyses were used to determine associations between single SNPs/haplotypes and immune outcomes. Increased carriage of minor alleles for the promoter SNPs (rs2844482 and rs2857708) of the TNFA gene were associated with dose-related increases in rubella antibodies. IL-6 secretion was co-directionally associated (p ≤ 0.01) with five intronic SNPs in the TNFRSF1B gene in an allele dose-related manner, while five promoter/intronic SNPs in the IL12B gene were associated with variations in IL-6 secretion. TNFA haplotype AAACGGGGC (t-statistic = 3.32) and IL12B promoter haplotype TAG (t-statistic = 2.66) were associated with higher levels of (p ≤ 0.01) rubella-IgG and IL-6 secretion, respectively. We identified individual SNPs/haplotypes in TNFA/TNFRSF1B and IL12B genes that appear to modulate immunity to rubella vaccination. Identification of such “genetic fingerprints” may predict the outcome of vaccine response and inform new vaccine strategies.     

Novel SNPs in <Emphasis Type="Italic">HSP70A1A</Emphasis> gene and the association of polymorphisms with thermo tolerance traits and tissue specific expression in Chinese Holstein cattle

Heat stress induces heat shock proteins (HSPs) expression and HSP70 family is one of them that have been reported to involve in cellular protection against heat stress. But whether there is any association of genetic variation in the HSP70A1A gene with thermo tolerance is unknown. PCR-SSCP and DNA sequencing were used to detect possible SNPs in HSP70A1A gene in 890 Chinese Holstein cattle. Three fragments were amplified and five novel mutations were found in HSP70A1A gene in Chinese Holstein cattle. G/A mutation was found at nucleotide 1524 in coding region that resulting two genotypes of AA and AB. T/C mutation was found at nucleotide 3494 in 3′-UTR resulting three genotypes of CC, CD and DD. The other three point mutations, G/C at nucleotide 6400, C/T at nucleotide 6600 and G/A at nucleotide 6601 were also found in 3′-UTR resulting six genotypes of EE, EF, FF, EG, FG and GG. Linkage disequilibrium (LD) analysis showed that the nucleotide 6400, 6600 and 6601 were in strong LD (D > 0.75). Association analysis indicated that AB, DD and FF genotype were the thermo tolerance genotype. SBYE Green I was used to quantify HSP70A1A mRNA expression in different tissues through quantitative real-time PCR assay. The results of the real-time PCR showed that the expression of HSP70A1A mRNA in the heart was significantly higher than that in the other tissues (P < 0.05). We presume that these mutations could be used in marker assisted selection for anti-heat stress cows in our breeding program.     

Serum heat shock protein 27 antigen and antibody levels appear to be related to the macrovascular complications associated with insulin resistance: a pilot study

Heat shock protein 27 (Hsp27) is over-expressed when cells are exposed to stressful conditions that include oxidative stress. Oxidative stress has been implicated in the pathogenesis of cardiovascular disease (CVD), diabetes and insulin resistance. We have investigated the concentrations of serum Hsp27 antigen and antibodies in subjects from different glycaemic categories, who either did or did not have established CVD. Serum Hsp27 antigen and antibody levels (immunoglobulins M and G (IgM and IgG)) were determined by enzyme-linked immunosorbent assays (ELISAs) in 68 individuals: 26 with normal glucose tolerance (NGT), 10 with (+) and 16 without (−) a history of CVD and 42 individuals with varying degrees of glucose intolerance (GI; 21 with and 21 without a history of CVD). Insulin sensitivity was determined in each subject using indices derived from the homeostasis model assessment of sensitivity and the insulin sensitivity index for glycaemia. Serum Hsp27 concentrations were significantly higher in GI (+CVD) subjects compared to GI (−CVD) subjects (p = 0.03), NGT (−CVD) subjects (p = 0.02) and NGT (+CVD) subjects (p = 0.04) and were positively correlated to fasting plasma glucose for all subjects (r = 0.28, p = 0.03). IgM antibody levels were significantly higher in GI (+CVD) subjects compared to NGT (−CVD) group (p = 0.02) and were inversely related to fasting insulin concentrations (r = −0.27, p = 0.04) and the 2-h insulin concentrations (r = −0.29, p = 0.03) for all subjects. Serum IgG antibody levels were higher in GI (+CVD) group compared to GI (−CVD) group (p = 0.06). In conclusion, Hsp27 and its antibody concentrations appear to relate to the presence of cardiovascular complications in patients with GI.     

Interaction of serum 70-kDa heat shock protein levels and <Emphasis Type="Italic">HspA1B</Emphasis> (+1267) gene polymorphism with disease severity in patients with chronic heart failure

Background Circulating heat shock protein 70 (Hsp70) is present in the circulation of healthy individuals and in patients with various disorders, including chronic heart failure (CHF). However, the source and routes of release of Hsp70 is only partially characterised in clinical samples. Aims The purpose of this study was to study the clinical and biological correlates of Hsp70 in a CHF population and, for the first time, to investigate the association of HspA1B (also known as Hsp70-2) +1267 alleles with serum Hsp70 levels. Methods A total of 167 patients (123 men, 44 women) with <45% left ventricular ejection fraction (LVEF) were enrolled; serum Hsp70 level was determined by enzyme-linked immunosorbent assay and HspA1B +1267 polymorphism by polymerase chain reaction–restriction fragment length polymorphism. Results Increased Hsp70 levels were present in patients with severe CHF (NYHA III–IV) as compared to the group of NYHA I–II (p = 0.003). Hsp70 levels correlated with LVEF, NT-proBNP, serum bilirubin, aspartate aminotransferase, alanine aminotransferase, γGT (p < 0.05) concentrations in patients with severe CHF, although no correlation was observed between Hsp70 and CRP, TNF-α, or IL-6. HspA1B allele G was associated with higher Hsp70 levels (p = 0.001) in patients in NYHA IV class as compared to carriers of allele A. Conclusions Serum Hsp70 levels were associated with disease severity in heart failure patients. An interaction with the presence of HspA1B +1267 allele G was observed for Hsp70 concentrations. Hsp70 correlates with markers of heart function and hepatic injury, but not with signs of inflammation.     

Haplotypes of IL12B promoter polymorphisms condition susceptibility to severe malaria and functional changes in cytokine levels in Thai adults

Polymorphic variability in immune response genes, such as IL12B, encoding the IL-12p40 subunit is associated with susceptibility to severe malaria in African populations. Since the role of genetic variation in conditioning severe malaria in Thai adults is largely unexplored, the functional association between IL12B polymorphisms [i.e. IL12Bpro (rs17860508) and IL12B 3′ UTR T/G (rs3212227)], severe malaria and cytokine production was examined in patients with Plasmodium falciparum infections (n = 355) recruited from malaria endemic areas along the Thai–Myanmar border in northwest Thailand. Circulating IL-12p40 (p = 0.049) and IFN-γ (p = 0.051) were elevated in patients with severe malaria, while only IL-12p40 was significantly higher in severe malaria patients with hyperparasitaemia (p = 0.046). Carriage of the IL12Bpro1.1 genotype was associated with enhanced severity of malaria (OR, 2.34; 95% CI, 0.94–5.81; p = 0.066) and hyperparasitaemia (OR, 3.42; 95% CI, 1.17–9.87; p = 0.025) relative to the IL12Bpro2.2 genotype (wild type). Individuals with the IL12Bpro1.1 genotype also had the lowest IL-12p40 (p = 0.002) and the highest IFN-γ (p = 0.004) levels. Construction of haplotypes revealed that carriage of the IL12Bpro-2/3′ UTR-T haplotype was associated with protection against severe malaria (OR, 0.51; 95% CI, 0.29–0.90; p = 0.020) and reduced circulating IFN-γ (p = 0.06). Thus, genotypic and haplotypic variation at IL12Bpro and IL12B 3′ UTR in this population influences susceptibility to severe malaria and functional changes in circulating IL-12p40 and IFN-γ levels. Results presented here suggest that protection against severe malaria in Thai adults is associated with genotypic variants that condition enhanced IL-12p40 and reduced IFN-γ levels.     

A candidate gene for lignin composition in Eucalyptus: cinnamoyl-CoA reductase (CCR)

Lignin content and composition are considered as mandatory traits of eucalyptus breeding programs, especially for pulp, paper, and bioenergy production. In this article, we used 33 Eucalyptus urophylla full-sib families of an 8 × 8 factorial design to provide estimates of genetic parameters for lignin- and growth-related traits. Secondly, from the sequencing of the 16 unrelated founders, we described the nucleotide and haplotype variability of cinnamoyl-CoA reductase (CCR), a candidate gene for lignin-related traits encoding the cinnamoyl-CoA reductase. Finally, we tested the association between CCR polymorphisms and trait variation using a mixed linear model. A high value of narrow sense heritability was obtained for lignin content (h2 = 0.85) and S/G ratio (h2 = 0.62) indicating that these traits are under strong genetic control. High levels of nucleotide (θ_π = 0.0131) and haplotype (Hd = 0.958) diversity were detected for CCR. From an initial set of 152 biallelic single nucleotide polymorphisms (SNPs), a subset of 65 nonredundant loci was selected. Three intronic SNPs were found to be associated to the variation of S/G ratio after multiple testing correction. In the line of what has been obtained in forest trees, these SNPs explained between 2.45% and 2.87% of the genetic variance of the trait. This study demonstrates the interest of the candidate gene approach for quantitative trait nucleotide detection in Eucalyptus and paves the way to gene assisted selection of lignin composition in E. urophylla.     

Increased serum heat-shock protein 70 levels reflect systemic inflammation, oxidative stress and hepatocellular injury in preeclampsia

It has been previously reported that serum levels of 70-kDa heat-shock protein (Hsp70) are elevated in preeclampsia. The aim of the present study was to examine whether increased serum Hsp70 levels are related to clinical characteristics and standard laboratory parameters of preeclamptic patients, as well as to markers of inflammation (C-reactive protein), endothelial activation (von Willebrand factor antigen) or endothelial injury (fibronectin), trophoblast debris (cell-free fetal DNA) and oxidative stress (malondialdehyde). Sixty-seven preeclamptic patients and 70 normotensive, healthy pregnant women were involved in this case-control study. Serum Hsp70 levels were measured with enzyme-linked immunosorbent assay (ELISA). Standard laboratory parameters (clinical chemistry) and C-reactive protein (CRP) levels were determined by an autoanalyzer using the manufacturer’s kits. Plasma von Willebrand factor antigen (VWF:Ag) levels were quantified by ELISA, and plasma fibronectin concentration by nephelometry. The amount of cell-free fetal DNA in maternal plasma was determined by quantitative real-time polymerase chain reaction analysis of the sex-determining region Y gene. Plasma malondialdehyde levels were measured by the thiobarbituric acid-based colorimetric assay. Serum Hsp70 levels were increased in preeclampsia. Furthermore, serum levels of blood urea nitrogen, creatinine, bilirubin and CRP, serum alanine aminotransferase and lactate dehydrogenase (LDH) activities, as well as plasma levels of VWF:Ag, fibronectin, cell-free fetal DNA and malondialdehyde were also significantly higher in preeclamptic patients than in normotensive, healthy pregnant women. In preeclamptic patients, serum Hsp70 levels showed significant correlations with serum CRP levels (Spearman R = 0.32, p = 0.010), serum aspartate aminotransferase (R = 0.32, p = 0.008) and LDH activities (R = 0.50, p < 0.001), as well as with plasma malondialdehyde levels (R = 0.25, p = 0.043). However, there was no other relationship between serum Hsp70 levels and clinical characteristics (age, parity, body mass index, blood pressure, gestational age, fetal birth weight) and laboratory parameters of preeclamptic patients, including markers of endothelial activation or injury and trophoblast debris. In conclusion, increased serum Hsp70 levels seem to reflect systemic inflammation, oxidative stress and hepatocellular injury in preeclampsia. Nevertheless, further studies are required to determine whether circulating Hsp70 plays a causative role in the pathogenesis of the disease.     

Common genetic variation in the 3′-untranslated region of gonadotropin-releasing hormone receptor regulates gene expression <Emphasis Type="Italic">in cella</Emphasis> and is associated with thyroid function,insulin secretion as well as insulin sensitivity in polycystic ovary syndrome patients

Gonadotropin-releasing hormone receptor (GNRHR) is a member of the G protein-coupled Ca(2+)-dependent family of receptors. It interacts with GnRH, whose signaling plays an important role in thyroid-stimulating hormone (TSH) secretion and insulin activity. There has been no study on the genetic effect of GNRHR on TSH secretion and insulin action in polycystic ovary syndrome (PCOS). We decided to investigate whether naturally occurring genetic variation at the human GNRHR locus is associated with thyroid function, insulin secretion and insulin sensitivity in PCOS. We undertook a systematic search for polymorphisms in GNRHR by resequencing the gene and then genotyped common single-nucleotide polymorphisms across the locus in 261 PCOS patients well-phenotyped for several metabolic traits to determine associations. A test for association of common genetic variants with susceptibility to PCOS was carried out in a large cohort of 948 subjects. Finally, we experimentally validated the marker-on-trait associations using GNRHR 3′-UTR region/reporter analysis in 293T cells. The 3′-UTR variant rs1038426 was associated with serum thyroid concentration (P = 0.007), change of insulin levels during oral glucose tolerance test (P = 0.004) and insulin sensitivity index (P = 0.014). In a functional study, 3′-UTR variant T allele increased reporter expression by a transfected luciferase reporter/GNRHR 3′-UTR expression plasmid. In conclusion, our results strongly suggest that common genetic variant in GNRHR contributes to the phenotypic expression of PCOS. The findings suggest novel pathophysiological links between the GNRHR locus and thyroid function and insulin secretion in PCOS.     

Polymorphism in intron 1 of the interferon-gamma gene influences both serum immunoglobulin E levels and the risk for chronic hepatitis B virus infection in Polynesians

Intron 1 of the interferon-gamma (IFNG) gene contains two polymorphisms. The 12 CA-repeat allele of the +875 IFNGCA microsatellite and the T allele of the +A874T single nucleotide polymorphism (SNP) have been associated with increased in vitro IFNG production and a variety of clinical phenotypes. The purpose of this study was to determine whether these polymorphisms influence total serum IgE levels [tsIgE] and the outcome of a hepatitis B virus (HBV) infection. IFNGCA and +A874T were typed in 186 asthmatics of Niuean ancestry and in Polynesian women with a chronic HBV infection (n = 60) and with natural immunity to the HBV (n = 66). The IFNGCA genotype was associated with [tsIgE] in asthmatic children (n = 51, p = 0.004) but not adults (n = 135, p = 0.87). The data were consistent with a co-dominant influence of the 12 CA-repeat allele on high [tsIgE]. The IFNGCA genotype was also associated with the risk for chronic HBV infection (χ ² = 11.6, p = 0.003) because of a dominant effect of the 12 CA-repeat allele on developing natural immunity in homozygotes (OR = 5.8, p = 0.003) and heterozygotes (OR = 2.7, p = 0.01). Similar associations were found for the T allele of the +A874T SNP. The possibility that these associations were due to linked alleles in the adjacent 783 bp of the promoter and 3′-untranslated region of the IFNG gene was excluded by direct sequencing. In summary, high-IFNG-producing alleles in intron 1 of the IFNG locus are associated with high [tsIgE] in asthmatic children from Niue and with natural immunity to the HBV in Polynesian women. These findings are consistent with a previous report of an association between +875 IFNGCA and [tsIgE] and provide preliminary evidence of a new association with the outcome of an HBV infection.     

Genetic variation in heat shock protein 60 gene and coronary heart disease in China: tagging-SNP haplotype analysis in a case-control study

Background High levels of circulating heat shock protein 60 (Hsp60) and antibody to human Hsp60 have been associated with greater risk of coronary heart disease (CHD) in several studies, but associations between polymorphisms of the hsp60 gene and CHD risk have not been investigated. Methods By resequencing DNA from 30 unrelated Han Chinese and using HapMap Phase I Chinese data of hsp60 gene, we selected four tagging single nucleotide polymorphisms (tagSNPs) named rs2340690, rs788016, rs2305560, and rs2565163, and determined their frequencies in 1,003 Chinese CHD patients and 1,003 age- and sex-frequency-matched controls. Furthermore, we used PHASE 2.0 software to reconstruct haplotypes and logistic regression to control for potential confounders in multivariate analyses. Results We found 13 SNPs in hsp60 gene (including four novel SNPs) in Han Chinese subjects. Our results showed no significant differences in four selected SNPs in patients with CHD and controls after adjusting for other conventional risk factors and stratifying by age, sex, smoking status, past history of hypertension and DM; however, our results showed that subjects with the GCTC haplotype had about twofold higher risk of CHD than those with the GTTC haplotype (OR = 1.91, 95%CI: 1.26–2.89, P = 0.002). Conclusions Our results suggest that the GCTC haplotype in the hsp60 gene is significantly associated with higher CHD risk in a Chinese population. The first two authors contributed equally to this paper.     

HspBP1 levels are elevated in breast tumor tissue and inversely related to tumor aggressiveness

HspBP1 is a co-chaperone that binds to and regulates the chaperone Hsp70 (Hsp70 is used to refer to HSPA1A and HSPA1B). Hsp70 is known to be elevated in breast tumor tissue, therefore the purpose of these studies was to quantify the expression of HspBP1 in primary breast tumors and in serum of these patients with a follow-up analysis after 6 to 7 years. Levels of HspBP1, Hsp70, and anti-HspBP1 antibodies in sera of breast cancer patients and healthy individuals were measured by enzyme-linked immunosorbent assay. Expression of HspBP1 was quantified from biopsies of tumor and normal breast tissue by Western blot analysis. The data obtained were analyzed for association with tumor aggressiveness markers and with patient outcome. The levels of HspBP1 and Hsp70 were significantly higher in sera of patients compared to sera of healthy individuals. HspBP1 antibodies did not differ significantly between groups. HspBP1 levels were significantly higher in tumor (14.46 ng/μg protein, n = 51) compared to normal adjacent tissue (3.17 ng/μg protein, n = 41, p < 0.001). Expression of HspBP1 was significantly lower in patients with lymph node metastasis and positive for estrogen receptors. HspBP1 levels were also significantly lower in patients with a higher incidence of metastasis and death following a 6 to 7-year follow-up. The HspBP1/Hsp70 molar ratio was not associated with the prognostic markers analyzed. Our results indicate that low HspBP1 expression could be a candidate tumor aggressiveness marker. This work was supported by FAPERGS, CNPq, and the National Institute of General Medical Sciences grant number GM072628-02 (V.G.) The expression of HspBP1 (an Hsp70 co-chaperone) was analyzed in tumor samples and sera from breast cancer patients. HspBP1 is over expressed in these tumors and a seven year follow-up analysis found an association with a poor prognosis. Chaperones have been shown to play important roles in tumor biology and immunology; therefore, we believe the data in this study will serve as a basis for the formulation of a new hypothesis on chaperone-co-chaperone interactions and their role in tumor growth.     

Copper Concentration in Body Tissues and Fluids in Normal Subjects of Southern Poland

Data on the concentration of the elements in the human body are important, for example, to estimate the amounts required to maintain a good healthy state or find their connections with morbidity and mortality. In this paper, the concentration of copper (by flame atomic absorption spectrometry) in material obtained from autopsy cases of nonpoisoned people (n = 130), aged from 14 to 80 years, between 1990–2006, is presented. The following values were found (mean ± SD in micrograms of copper per gram or per milliliter): brain 3.32 ± 1.50 (n = 43), liver 3.47 ± 1.51 (n = 79), kidney 2.15 ± 0.90 (n = 76), stomach 1.10 ± 0.76 (n = 65), intestines 1.54 ± 1.19 (n = 25), lung 1.91 ± 1.30 (n = 27), spleen 1.23 ± 0.28 (n = 3), heart 3.26 ± 0.59 (n = 5), bile 3.60 ± 1.67 (n = 13), and blood 0.85 ± 0.19 (n = 73).     

The effect of 15 consecutive days of heat–exercise acclimation on heat shock protein 70

The purpose of this study was to investigate the alterations in serum heat shock protein (Hsp) 70 levels during a 15-consecutive-day intermittent heat–exercise protocol in a 29-year-old male ultra marathon runner. Heat acclimation, for the purpose of physical activities in elevated ambient temperatures, has numerous physiological benefits including mechanisms such as improved cardiac output, increased plasma volume and a decreased core temperature (T _c). In addition to the central adaptations, the role of Hsp during heat acclimation has received an increasing amount of attention. The acclimation protocol applied was designed to correspond with the athlete’s tapering period for the 2007 Marathon Des Sables. The subject (VO₂max = 50.7 ml·kg⁻¹·min⁻¹, peak power output [PPO] = 376 W) cycled daily for 90 min at a workload corresponding to 50% of VO₂max in a temperature-controlled room (average WBGT = 31.9 ± 0.9°C). Venous blood was sampled before and after each session for measurement of serum osmolality and serum Hsp70. In addition, T _c, heart rate (HR) and power output (PO) was measured throughout the 90 min to ensure that heat acclimation was achieved during the 15-day period. The results show that the subject was successfully heat acclimated as seen by the lowered HR at rest and during exercise, decreased resting and exercising T _c and an increased PO. The heat exercise resulted in an initial increase in Hsp70 concentrations, known as thermotolerance, and the increase in Hsp70 after exercise was inversely correlated to the resting values of Hsp70 (Spearman’s rank correlation = −0.81, p < 0.01). Furthermore, the 15-day heat–exercise protocol also increased the basal levels of Hsp70, a response different from that of thermotolerance. This is, as far as we are aware, the first report showing Hsp70 levels during consecutive days of intermittent heat exposure giving rise to heat acclimation. In conclusion, a relatively longer heat acclimation protocol is suggested to obtain maximum benefit of heat acclimation inclusive of both cellular and systemic adaptations.