The level of Hsp27 in lymphocytes is negatively associated with a higher risk of lung cancer

Heat shock proteins (Hsps) can protect cells, organs, and whole organisms against damage caused by abnormal environmental hazards. Some studies have reported that lymphocyte Hsps may serve as biomarkers for evaluating disease status and exposure to environmental stresses; however, few epidemiologic studies have examined the associations between lymphocyte Hsps levels and lung cancer risk. We examined lymphocyte levels of Hsp27 and Hsp70 in 263 lung cancer cases and age- and gender-matched cancer-free controls by flow cytometry. Multivariate logistic regression models were used to estimate the association between lymphocyte Hsps levels and lung cancer risk. Our results showed that Hsp27 levels were significantly lower in lung cancer cases than in controls (16.5 vs 17.8 mean fluorescence intensity, P < 0.001). This was not observed for Hsp70 levels. Further stratification analysis revealed that lymphocyte Hsp27 levels were negatively associated with lung cancer risk especially in males and heavy smokers. There was a statistical trend of low odd ratios (95% confidence intervals) and upper tertile levels of Hsp27 [1.000, 0.904 (0.566–1.444) and 0.382 (0.221–0.658, P _trend = 0.001) in males and 1.000, 0.9207 (0.465–1.822) and 0.419 (0.195–0.897, P _trend = 0.036) in heavy smokers] after adjustment for confounding factors. These results suggest that lower lymphocyte Hsp27 levels might be associated with an increased risk of lung cancer. Our findings need to be validated in a large prospective study. Feng Wang and Maohui Feng contributed equally to this work.     

Plasma levels of Hsp70 and anti-Hsp70 antibody predict risk of acute coronary syndrome

Although immune reactions against heat shock proteins have been implicated in the pathogenesis of atherosclerosis, conflicting associations between Hsp70, anti-Hsp70 antibody and coronary heart disease (CHD) have been reported. This study assessed whether there is a significant association between extracellular human Hsp70, anti-Hsp70 antibody and acute coronary syndrome (ACS) and stable angina (SA), and examined dynamic changes in Hsp70 and anti-Hsp70 antibody levels induced by acute myocardial infarction (AMI). Plasma Hsp70 and anti-Hsp70 antibody levels in 291 patients with ACS (179 AMI, 112 unstable angina), 126 patients with SA and 417 age and sex-matched healthy subjects, and in 40 patients after admission for AMI, and on day 2, 3, and 7 after the onset of AMI were determined using enzyme-linked immunosorbent assays. Hsp70 levels were significantly higher in ACS and SA and anti-Hsp70 antibody levels were only markedly lower in ACS than controls. After adjustment for traditional CHD risk factors, increasing levels of Hsp70 were significantly associated with an increased risk and severity of ACS (P for trend < 0.001), whereas increasing levels of anti-Hsp70 antibody were associated with a decreased risk of ACS (P for trend = 0.0003). High levels of Hsp70 combined with low levels of anti-Hsp70 antibody had a joint effect on the risk of ACS (OR, 5.14, 95% CI, 3.00-8.79; P < 0.0001). In patients with AMI, Hsp70 levels decreased rapidly from days 1-7 after onset, whereas anti-Hsp70 antibody levels increased in patients with AMI. These findings suggest that higher Hsp70 levels or lower anti-Hsp70 antibody levels are independently associated with a higher risk of ACS. Higher Hsp70 levels and lower anti-Hsp70 antibody levels combine to further increase this risk.     

Functional specificity of the mitochondrial DnaJ protein, Mdj1p, in Saccharomyces cerevisiae

Inactivation of the gene for the mitochondrial DnaJ homolog, Mdj1p, in Saccharomyces cerevisiae results in temperature sensitivity and the loss of respiratory activity; the latter phenotype has been attributed to the loss of mitochondrial DNA. To investigate the functional specificity of Mdj1p, non-mitochondrial DnaJ proteins were targeted to mitochondria and tested for their ability to substitute for Mdj1p. The tested DnaJ proteins were able to complement the two Mdj1p-linked phenotypes, i.e., respiratory activity and growth at 37 °C, to different extents, ranging from full to very poor complementation. All DnaJ homologs ensured faithful propagation of the mitochondrial genome. N-terminal fragments of Mdj1p and Escherichia coli DnaJ comprising the well-characterized J domain partially substituted for Mdj1p. As the only hitherto known function of the N-terminal fragment is modulation of the substrate binding activity of the cognate Hsp70, we conclude that both Mdj1p-linked phenotypes – maintenance of respiratory activity and the ability to grow at elevated temperature – involve a mitochondrial Hsp70 partner protein. Received: 8 October 1999 / Accepted: 21 January 2000     

Heat shock protein 70 is upregulated in the intestine of intrauterine growth retardation piglets

The objective of this study is to investigate the expression and distribution of heat shock protein 70 (Hsp70) in the intestine of intrauterine growth retardation (IUGR) piglets. Samples from the duodenum, prejejunum, distal jejunum, ileum, and colon of IUGR and normal-body-weight (NBW) piglets were collected at birth. The results indicated that the body and intestine weight of IUGR piglets were significantly lower than NBW piglets. The villus height and villus/crypt ratio in jejunum and ileum of IUGR piglets were significantly reduced compared to NBW piglets. These results indicated that IUGR causes abnormal gastrointestinal morphologies and gastrointestinal dysfunction. The mRNA of hsp70 was increased in prejejunum (P < 0.05), distal jejunum (P < 0.05), and colon in IUGR piglets. However, the hsp70 mRNA in ileum of piglets with IUGR was decreased. Similar to hsp70 mRNA, the protein levels of Hsp70 in prejejunum (P < 0.05), distal jejunum, and colon (P < 0.05) in IUGR piglets were higher than those in NBW piglets. These results indicated that the expression of Hsp70 in the intestinal piglets was upregulated by IUGR, and different intestinal sites had different responses to stress. Meanwhile, the localization of Hsp70 in the epithelial cells of the whole villi and intestinal gland rather than in the lamina propria and myenteron suggested that Hsp70 has a cytoprotective role in epithelial cell function and structure.     

The effect of sodium balance on sweat sodium secretion and plasma aldosterone concentration

The effect of manipulating sodium intake upon sweat sodium secretion was investigated during heat acclimation. Twenty-five male subjects were confined to an environmental chamber at a temperature of 25°C for 3 days, and then acclimated to heat by a further 5 days at 40°C. The subjects' daily sodium intake was controlled throughout as follows: high (HNa), 348.4 (0.8) mmol · day⁻¹, n = 7; moderate (MNa), 174.1 (0.6) mmol · day⁻¹, n = 9; or low (LNa), 66.3 mmol · day⁻¹, n = 9. Sodium losses were estimated from urinary, faecal and sweat collections using a whole-body washdown method. Plasma aldosterone concentration was also measured from venous blood sampled each morning. Measurements of body temperature and heart rate during the heat exposure phase indicated a degree of heat acclimation. During this heat phase there was a reduction (P < 0.01) in sweat sodium secretion for all three conditions which was greatest for the LNa condition, although this finding was not significant (P < 0.1). In the LNa condition, plasma aldosterone concentration increased (P < 0.05) prior to heat exposure, and the secretion of aldosterone was potentiated (P < 0.01) during the heat exposure in comparison with the MNa condition. In contrast, the HNa diet produced a fall (P < 0.05) in plasma aldosterone concentration prior to heat exposure and an attenuation of aldosterone secretion thereafter. These findings are inconsistent with the hypothesis that retention of sweat sodium is dependent upon a net body sodium deficit, but demonstrate that aldosterone secretion is potentiated under such conditions. Accepted: 22 May 1988     

Increased circulating heat shock protein 70 levels in pregnant asthmatics

Asthma is one of the most common diseases complicating pregnancy and represents a risk factor for several maternal and perinatal complications. The natural history of asthma is known to change in pregnancy, but very few data are available in the terms of pathomechanism of this change during gestation. Circulating heat shock protein 70 (Hsp70) levels are decreased in healthy pregnancy, which might reflect physiological immunotolerance. The aim of our study was to determine the serum levels of Hsp70 in asthmatic women during gestation. Forty pregnant women with bronchial asthma and 40 healthy pregnant women matched for maternal and gestational age were involved in this case-control study. Serum Hsp70 levels were measured using the ELISA Kit of R&D Systems. Spirometry and oxygen saturation measurements were performed in asthmatic patients. In asthmatic pregnant women, an increase of serum Hsp70 levels was observed compared to healthy pregnant women (median (25–75 percentile): 0.44 ng/ml (0.36–0.53) versus 0.21 ng/ml (0–0.27), p < 0.001). Fetal birth weight of asthmatic mothers was significantly smaller than of healthy controls, but in the normal range (3,230 g (2,690–3,550) versus 3,550 g (3,450–3,775), p < 0.05). A statistically significant negative correlation between maternal age and serum Hsp70 concentrations (Spearman R = −0.48, p = 0.0018) and a significant positive correlation between gestational age and serum Hsp70 levels (Spearman R = 0.83, p < 0.001) were detected in healthy pregnant women. In conclusion, this study proves an elevation of circulating Hsp70 levels during asthmatic pregnancy compared to healthy pregnant women. However, further studies are warranted to determine the role of circulating Hsp70 in the pathogenesis of maternal and perinatal complications of asthma in pregnancy.     

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.     

A Pilot Study on Zinc Levels in Patients with Rheumatoid Arthritis

The aim of the study was to evaluate zinc levels in three biological compartments (serum, erythrocytes and hair) in patients with rheumatoid arthritis (RA) as compared to healthy individuals. Zinc levels in serum, erythrocytes and hair (in 74 patients with RA and 30 healthy individuals) were assessed by atomic absorption spectroscopy. The mean hair zinc content was significantly lower in RA patients as compared to healthy individuals (p < 0.001). Moreover, a positive correlation was observed in the RA patient group between the erythrocyte zinc levels and the prednisone dose (r _s = 0.48, p < 0.05), and a negative correlation was found in this population between the serum zinc levels and disease duration (r _s = −0.42, p < 0.0006). In conclusion, it seems that hair may be a useful complementary study material for evaluating “zinc status” in rheumatoid arthritis patients.     

Human Hsp40 proteins, DNAJA1 and DNAJA2, as potential targets of the immune response triggered by bacterial DnaJ in rheumatoid arthritis

Hsp40 proteins of bacterial and human origin are suspected to be involved in the pathogenesis of rheumatoid arthritis (RA). It has been shown that sera of RA patients contain increased levels of antibodies directed to bacterial and human Hsp40s. The aim of this work was to explore immunological similarities between the bacterial (DnaJ) and human (DNAJA1 and DNAJA2) Hsp40 proteins in relation to their possible involvement in the RA. Using polyclonal antibodies directed against a full-length DnaJ or its domains, against DNAJA1 and DNAJA2, as well as monoclonal anti-DnaJ antibodies, we found immunological similarities between the bacterial and human Hsp40s. Both ELISA and Western blotting showed that these similarities were not restricted to the conserved J domains but were also present in the C-terminal variable regions. We also found a positive correlation between the levels of the anti-DnaJ and anti-DNAJA1 antibodies in the sera of RA patients. This finding supports the molecular mimicry hypothesis that human Hsp40 could be the targets of antibodies originally directed against bacterial DnaJ in RA.     

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.     

The time-profile of the PBMC HSP70 response to in vitro heat shock appears temperature-dependent

Summary. Heat shock proteins (HSPs) are synthesised by cells subsequent to a stress exposure and are known to confer protection to the cell in response to a second challenge. HSP induction and decay are correlated to thermotolerance and may therefore be used as a biomarker of thermal history. The current study tested the temperature-dependent nature of the heat shock response and characterised its time profile of induction. Whole blood from 6 healthy males (Age: 26 ± (SD) 2 yrs; Body mass 74.2 ± 3.8 kgs; VO_2max: 49.1 ± 4.0 ml·kg⁻¹·min⁻¹) were isolated and exposed to in vitro heat shock (HS) at 37, 38, 39, 40, and 41 °C for a period of 90 min. After HS the temperature was returned to 37 °C and intracellular HSP70 was quantified from the leukocytes at 0, 2, 4, and 6 h after heat treatment. The concentration of HSP70 was not different between temperatures (P > 0.05), but the time-profile of HSP70 synthesis appeared temperature-dependent. At control (37 °C) and lower temperatures (38–39 °C) the mean HSP70 concentration increased up to 4 h post HS (P < 0.05) and then returned towards baseline values by 6 h post HS. With in vitro hyperthermic conditions (40–41 °C), the time-profile was characterised by a sharp rise in HSP70 levels immediately after treatment (P < 0.05 for 40 °C at 0 h), followed by a progressive decline over time. The results suggest a temperature-dependent time-profile of HSP70 synthesis. In addition, the temperature at which HSP70 is inducted might be lower than 37 °C.     

Improved adaptation to heat,cold, and solvent tolerance in <Emphasis Type="Italic">Lactobacillus plantarum</Emphasis>

The effect of overproducing each of the three small heat shock proteins (Hsp; Hsp 18.5, Hsp 18.55, and Hsp 19.3) was investigated in Lactobacillus plantarum strain WCFS1. Overproduction of the three genes, hsp 18.5, hsp 18.55, and hsp 19.3, translationally fused to the start codon of the ldhL gene yielded a protein of approximately 19 kDa, as estimated from Tricine sodium dodecyl sulfate–polyacrylamide gel electrophoresis in agreement with the predicted molecular weight of small Hsps. Small Hsp overproduction alleviated the reduction in growth rate triggered by exposing exponentially growing cells to heat shock (37 or 40°C) and cold shock (12°C). Moreover, overproduction of Hsp 18.55 and Hsp 19.3 led to an enhanced survival in the presence of butanol (1% v/v) or ethanol (12% v/v) treatment suggesting a potential role of L. plantarum small Hsps in solvent tolerance.     

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.     

Serum level of soluble Hsp70 is associated with vascular calcification

It has been previously reported that serum levels of 70-kDa heat shock protein (Hsp70) are elevated in peripheral artery disease. The aim of the present study was to examine whether increased serum Hsp70 levels are related to the extent of arterial calcification and standard laboratory parameters of patients with peripheral artery disease, as well as to markers of inflammation (C-reactive protein), atherosclerosis (homocysteine), and calcification (fetuin-a). One hundred eighty chronic atherosclerotic patients with significant carotid stenosis and/or lower extremity vascular disease were enrolled in this cross-sectional study. Systemic atherosclerosis and calcification was assessed by ultrasound (carotid intima–media thickness (IMT), presence of calcification at the abdominal aorta, carotid and femoral bifurcations, and aortic and mitral cardiac valves). Standard serum markers of inflammation, diabetes, renal function, ankle-brachial indexes, and traditional risk factors for atherosclerosis were noted. Serum Hsp70 levels were measured with enzyme-linked immunosorbent assay. Standard laboratory parameters (clinical chemistry), C-reactive protein (CRP), and homocysteine levels were determined by an autoanalyzer using the manufacturer’s kits. Fetuin-a levels were measured by radial immunodiffusion. Patients’ median age was 64 (57–71) years, 69% were men, and 34.5% had diabetes. Serum heat shock protein 70 levels were significantly higher in patients with more severe arterial calcification (p < 0.02) and showed significant positive correlations with serum bilirubin (r = 0.23, p = 0.002) and homocysteine levels (r = 0.18, p = 0.02). Serum Hsp70 did not correlate with body mass index, IMT, CRP, or fetuin-a levels in this cohort. Logistic regression analysis confirmed the association between sHsp70 and calcification score (OR, 2.189; CI, 1.156–4.144, p = 0.016) and this correlation remained significant (OR, 2.264; CI, 1.021–5.020, p = 0.044) after the adjustment for age, sex, eGFR, smoking, CRP, and homocysteine levels. Our data show that serum Hsp70 levels correlate with the severity of atherosclerosis in patients with carotid artery disease and chronic lower limb ischemia. These data support a putative role for plasma Hsp70 in the development of arterial calcification. Nevertheless, further studies are required to investigate the usefulness of circulating Hsp70 level as a marker of atherosclerotic calcification.     

Association of immune parameters with clinical outcome in stage III colon cancer: results of Southwest Oncology Group Protocol 9009

Levamisole (LMS), utilized in the adjuvant treatment of patients with stage III colon cancer, is immunomodulatory. To determine whether alterations in immune parameters before, during and after 12 months of 5FU/LMS therapy correlate with disease-free survival, 38 patients enrolled on Southwest Oncology Group (SWOG) protocol 8899 received extensive lymphocyte phenotypic analysis prior to therapy and 3, 6, 12 and 15 months after treatment initiation. The median follow-up of patients is 41 months. Significant increases in the proportion and total number of CD56⁺ natural killer cells were seen, starting at 3 months and continuing until 15 months (P < 0.001). Increases in the total numbers of cells expressing CD25 (interleukin-2 receptor), VLA4 and the combinations of CD4: CD45RA and CD4:CDw29 were not evident during therapy but were seen at 15 months (P < 0.05: CD25, CD4:CDw29, CD4:CD45RA; P < 0.001: VLA4). Low levels of CD8⁺ cells prior to treatment initiation and after 3 months of therapy correlated with early relapse within the first year of 5FU/LMS treatment. Patients who have remained disease-free (n = 22, median follow-up 45 months) demonstrated increases in the total numbers of CD8⁺, CD25⁺, CD56⁺, VLA4⁺, CD4: CDw29 and CD4:CD45RA cells, primarily at 15 months. In contrast, patients who relapsed had decreased numbers of CD8⁺, CD4:CDw29, CD4: CD45RA and VLA4⁺ cells and minimal increases in CD56⁺ and CD25⁺ cells. Statistically significant differences between the late-relapse group and the group remaining disease-free were seen for CD25⁺, CD4: CD45RA and CD4:CDw29 cells at the 15-month assay time (P = 0.0276, P = 0.0349, P = 0.0178 respectively). In conclusion, multiple alterations in lymphocyte phenotype, with increases in the proportion and total number of cells involved in cell-mediated immune responses, were seen during and especially following completion of therapy with 5FU/LMS. Many of these changes are significantly associated with clinical outcome and may be useful for risk stratification of stage III colon cancer patients following completion of adjuvant therapy. Received: 9 July 1999 / Accepted: 11 August 1999     

Assessment of Minerals in Obesity-related Diseases in the Chandigarh (India) Population

Excessive Zn but normal Cu and Mg in the staple food consumed by the people of Chandigarh (Union territory and capital of Punjab and Haryana States of India) has been considered to be the major risk factor for the prevalence of obesity (33.15%) and obesity-related diseases in this region. Therefore, in the present investigations, in obesity-related diseases, the status of these minerals was estimated in their tissues, including hair, nails, and blood serum and urine, and compared with those of normal subjects. They were grouped as: normal subjects in control Group A, middle-aged diabetics in Group D_M, older diabetics in Group D_O, and diabetics with osteoarthritis in Group D+ OA, osteoarthritis in Group OA and rheumatoid arthritis in Group RA, respectively. The results evaluated in the order as: hair Zn, group D+OA>D_M>OA>A (control)>RA>D_O (p < 0.001); hair Cu, group A (control)>D_M>OA>D+OA>D_O>RA (p < 0.001); hair Mg, group A (control)>D_M>OA>D+OA>RA>D_O (p < 0.001, 0.01); hair Mn, group A (control)>RA>OA>D-OA>D_M>D_O (p < 0.001); nail Zn, group D_M>D+OA>OA>A (control)>RA>D_O (p < 0.001, 0.05); nail Cu, group A (control)>OA>D_M>D+OA>RA>D_O (p < 0.001); nail Mg, group A (control)>OA>D_M>D_O>D+OA >RA (p < 0.001); nail Mn, group A (control) >RA>OA>D+OA>D_M>D_O (p < 0.01); urine Zn, group D_O>D_M>D+OA>A (control)>RA>OA (p < 0.01); urine Cu, group RA>D+OA>D_O>OA> D_M>A (control) (p<0.001); urine Mg, group RA>OA>D+OA>D_O>D_M>A (control; p < 0.001); urine Mn, group D_O>D_M>OA>D+OA>RA>A (control; p < 0.001), respectively. The analysis of the mineral status in serum of diabetics further showed their highly significant rise from lower mean age subgroup to higher mean age subgroup than their control counter parts (p < 0.001, 0.01, and 0.05) with coincident deficiencies of Cu, Mg, and Mn in their tissues. This study would be helpful considering the status of minerals in these obesity-related diseases depending on the choice of the food consumed to improve the quality of life and prognosis for the diseases.     

Blood flow in the carotid artery during breath-holding in relation to diving bradycardia

The present study investigated the mechanism of diving bradycardia. A group of 14 healthy untrained male subjects were examined during breath-holding either out of the water (30–33°C), in head-out immersion, or in whole-body submersion (27–29°C) in a diving pool. Blood velocity, blood volume flow in the carotid artery, diastolic blood pressure and electrocardiogram were measured and recorded during the experiments. The peak blood velocity increased by 13.6% (P < 0.01) and R-wave amplitude increased by 57.1% (P < 0.005) when the subjects entered water from air. End-diastolic blood velocity in the carotid artery increased significantly during breath-holding, e.g. increased from 0.20 (SD 0.02) m · s⁻¹ at rest to 0.33 (SD 0.04) m · s⁻¹ (P < 0.001) at 50.0 s in breath-hold submersion to a 2.0-m depth. Blood volume flow in the carotid artery increased by 26.6% (P < 0.05) at 30 s and 36.6% (P < 0.001) at 40 s in breath-hold submersion to a 2.0-m depth. Diastolic blood pressure increased by 15.4% (P < 0.01) at 60 s during breath-holding in head-out immersion. Blood volume flow, and diastolic blood pressure increased significantly more and faster during breath-holding in submersion than out of the water. There was a good negative correlation with the heart rate: the root mean square correlation coefficient r was 0.73 (P < 0.001). It was concluded that an increased accumulation of blood in the aorta and arteries at end-diastole and decreased venous return, caused by an increase in systemic peripheral resistance during breath-holding, underlies diving bradycardia. Accepted: 22 November 1996     

Genome-wide identification of heat shock proteins (Hsps) and Hsp interactors in rice: Hsp70s as a case study

Background

Heat shock proteins (Hsps) perform a fundamental role in protecting plants against abiotic stresses. Although researchers have made great efforts on the functional analysis of individual family members, Hsps have not been fully characterized in rice (Oryza sativa L.) and little is known about their interactors.

Results

In this study, we combined orthology-based approach with expression association data to screen rice Hsps for the expression patterns of which strongly correlated with that of heat responsive probe-sets. Twenty-seven Hsp candidates were identified, including 12 small Hsps, six Hsp70s, three Hsp60s, three Hsp90s, and three clpB/Hsp100s. Then, using a combination of interolog and expression profile-based methods, we inferred 430 interactors of Hsp70s in rice, and validated the interactions by co-localization and function-based methods. Subsequent analysis showed 13 interacting domains and 28 target motifs were over-represented in Hsp70s interactors. Twenty-four GO terms of biological processes and five GO terms of molecular functions were enriched in the positive interactors, whose expression levels were positively associated with Hsp70s. Hsp70s interaction network implied that Hsp70s were involved in macromolecular translocation, carbohydrate metabolism, innate immunity, photosystem II repair and regulation of kinase activities.

Conclusions

Twenty-seven Hsps in rice were identified and 430 interactors of Hsp70s were inferred and validated, then the interacting network of Hsp70s was induced and the function of Hsp70s was analyzed. Furthermore, two databases named Rice Heat Shock Proteins (RiceHsps) and Rice Gene Expression Profile (RGEP), and one online tool named Protein-Protein Interaction Predictor (PPIP), were constructed and could be accessed at http://bioinformatics.fafu.edu.cn/.

Electronic supplementary material

The online version of this article (doi:10.1186/1471-2164-15-344) contains supplementary material, which is available to authorized users.     

Changes in performance, muscle metabolites, enzymes and fibre types after short sprint training

In contrast to endurance training, little research has been carried out to investigate the effects of short (<10 s) sprint training on performance, muscle metabolism and fibre types. Nine fit male subjects performed a mean of 16 outdoor sprint running training sessions over 6 weeks. Distances sprinted were 30–80 m at 90–100% maximum speed and between 20 and 40 sprints were performed in each session. Endurance (maximal oxygen consumption; V˙O_{2 max}), sprint (10 m and 40 m times), sustained sprint (supramaximal treadmill run) and repeated sprint (6 × 40 m sprints, 24 s recovery between each) performance tests were performed before and after training. Muscle biopsy samples (vastus lateralis) were also taken to examine changes in metabolites, enzyme activities and fibre types. After training, significant improvements were seen in 40 m time (P < 0.01), supramaximal treadmill run time (P < 0.05), repeated sprint performance (P < 0.05) and V˙O_{2 max} (P < 0.01). Resting muscle concentrations of ATP and phosphocreatine did not change. Phosphorylase activity increased (P < 0.025), citrate synthase activity decreased (P < 0.01), but no significant changes were recorded in myokinase and phosphofructokinase activities. The proportion of type II muscle fibres increased significantly (P < 0.05). These results demonstrate that 6 weeks of short sprint training can improve endurance, sprint and repeated sprint ability in fit subjects. Increases in the proportion of type II muscle fibres are also possible with this type of training. Accepted: 5 January 1998