Postmenopausal women treated for breast cancer with insulin resistance: clinical, analytical, cross-sectional.

This study aims to investigate the potential association between serum levels of cytokines, HSP60, HSP70 and IR (HOMA-IR) in postmenopausal women. We conducted a cross-sectional study involving 381 postmenopausal women, including 94 with a breast cancer diagnosis and 278 without. We analyzed anthropometric and laboratory measurements. Immunoassays were used to measure cytokines (TNF-α, IL-10, and IL-6) as well as heat shock proteins (HSP) 60 and 70 in the serum using the ELISA technique. Women diagnosed with breast cancer showed higher levels of HOMA-IR, IL-6, TNF, and HSP60, and lower levels of IL-10 and HSP70 compared to women without cancer. An association was found between HSP70 and HOMA-IR only in women with breast cancer (ß = 0.22, p = .030; without cancer: ß = 0.04, p = .404), regardless of age, waist circumference, smoking, and physical activity. No associations were observed between cytokines, HSP60, and HOMA-IR in both groups of women. HSP70 is positively associated with IR in women diagnosed with breast cancer.

The Effects of Endurance Exercise and Diet on Atherosclerosis in Young and Aged ApoE-/- and Wild-Type Mice.

BACKGROUND: Atherosclerosis is the leading cause of death worldwide. The disease development is by and large driven by old age and lifestyle factors, such as diet, physical activity, and smoking. In the present study, we have investigated the effect of exercise and diet on the development of atherosclerosis in young and aged mice. OBJECTIVE: This study aimed at comparing multiple age-dependent factors that may influence atherosclerosis in a transgenic mouse model. METHODS: Young (14 weeks) and aged (49-52 weeks) C57BL/6 wild-type (WT) and atherosclerosis-prone ApoE-/- mice were subjected to physical endurance exercise on a treadmill, with or without a high-fat diet. Five weeks later, the frequencies of regulatory T cells (TREGs) in lymph nodes were assessed by flow cytometry, plasmatic cytokines (interleukin [IL]-1ß, IL-6, IL-10, IL-17, interferon-γ, tumor necrosis factor-α, and transforming growth factor [TGF]-ß1) levels were determined by Luminex assay. Lipids (cholesterol and triglycerides) and anti-heat shock protein 60 (HSP60) autoantibodies were measured by ELISA. Aortic lesion sizes were assessed by en face imaging. Microarray analysis and qPCR of skeletal muscle gene expression were also performed. RESULTS: Exercise leads to a reduction of aortic lesions in young ApoE-/- and aged WT mice independent of diet. In most groups, this reduction was followed by an increased proportion of TREGs and TGF-ß1 levels. Moreover, gene expression analysis showed that exercise seems to affect the AMPK signaling pathway. In particular, PGC-1α1 mRNA was induced in aged WT mice, whereas it was reduced in young ApoE-/- mice. In addition, GSEA analysis showed a marked reduction in the insulin signaling pathway in aged ApoE-/- mice. CONCLUSION: Practicing endurance exercise seems to be enough for reducing early aortic lesion formation, independent of diet. However, this was only true in mice with smaller aortic lesions, since mice with large, advanced, complicated atherosclerotic plaques did not show any reduction in lesion size with exercise training.

First detection of heat shock protein 60 and 70 in the serum of early pregnant bitches.

Heat shock proteins (HSPs) belong to a group of cellular stress proteins. Heat shock protein 10 immunoregulates and promotes growth during early gestation in humans, while HSP70 is considered to regulate autophagy and apoptosis during pregnancy and parturition. Both HSPs are detectable in the serum and placentas of early pregnant women and considered to contribute to the establishment of pregnancy. Within this pilot study we aimed (1) to assess whether HSPs 10, 60 and 70 are measurable in the serum of healthy early pregnant and non-pregnant bitches, and (2) to explore whether measurable differences between groups indicate pregnancy. Blood was collected from 31 bitches on days 7, 14 and 21 after mating. At 21 days post mating, all bitches were examined for pregnancy by ultrasonography; 23 were pregnant, and the eight non-pregnant bitches served as controls. Pregnant bitches had normal parturitions and gave birth to healthy puppies. The serum concentrations of HSPs 10, 60 and 70 were measured by electrophoresis and western blot. Serum HSP10 was not detectable. Average serum HSP70 concentration was significantly (d7, P = 0.030; d14, P = 0.023; d21, P = 0.030) lower in pregnant animals at all days investigated, while serum HSP60 was significantly lower at day 21 of gestation (P = 0.024) when compared to the controls. HSP 60 and HSP70 concentrations correlated positively (d7, r = +0.386, P = 0.021; d14, r = 0.450, P = 0.008; d21, r = +0.472, P = 0.006). We conclude that in pregnant bitches, serum concentrations of HSP60 and HSP70 are significantly decreased between days 7 and 21 of gestation, in comparison to non-pregnant bitches in early dioestrus, raising the question about intrauterine functions during the peri-implantation period.

Secretion of heat shock -60, -70 kD protein, IL-1ß and TNFα levels in serum of a term normal pregnancy and patients with pre-eclampsia development.

The extracellular heat shock proteins (eHsp) family act as molecular chaperones regulating folding, transporting protein and are associated with immune modulation in different physiological and pathological processes. They have been localized in different gestational tissues and their concentration in amniotic fluid and serum has been determined. In the present study, we proposed to determine the concentration of eHsp-60, -70, IL-1ß and TNFα in the serum of pregnant patients with 34 weeks of gestation with and without clinical evidences of preeclampsia (PE). Our results indicate significant increase of these markers in patients with PE with respect to healthy pregnant patients without active labor. Finally, the concentration of eHsp-60 and -70 correlated positively with the hepatic dysfunction markers uric acid, lactate dehydrogenase (LDH), glutamic oxaloacetic transaminase (GOT) glutamic pyruvic transaminase (GPT), and inflammatory IL-1ß and TNFα response. In conclusion, our results demonstrate a strong associated between Hsp and marker of hepatic dysfunction.

Autoimmunity to HSP60 during diet induced obesity in mice.

Adaptive immunity has been implicated in adipose tissue inflammation, obesity and its adverse metabolic consequences. No obesity-related autoantigen has yet been identified, although heat shock protein 60 (HSP60) has been implicated in other autoimmune diseases. We investigated whether feeding a high-fat diet to C57BL/6J mice would cause autoimmunity to HSP60 and whether immunomodulation with peptides from HSP60 would reverse the resulting obesity or metabolic dysfunction. Obese mice had higher circulating levels of HSP60 associated with increased T-lymphocyte proliferation responses and the emergence of circulating IgG1 and IgG2c antibody levels against HSP60. Treatment with escalating doses of a mixture of three proven immunomodulatory HSP60 peptides did not reduce weight but completely reversed the increase in VLDL/LDL levels and partially reversed the glucose intolerance in obese mice. Obese mice mount an autoimmune response to HSP60, which partly underlies the resulting metabolic disturbances.

Association between Heat Shock Protein-60 and Development of Atrial Fibrillation: Results from the Multi-Ethnic Study of Atherosclerosis (MESA).

BACKGROUND: During atrial fibrillation (AF), a high rate of myocyte activation causes cellular stress and initiates the process of atrial remodeling, which further promotes persistence of AF. Although heat shock proteins (HSPs) have been shown to prevent atrial remodeling and suppress the occurrence of AF in cellular and animal experimental models, increased levels of HSP-60 have been observed in patients with postoperative AF, likely reflecting a response to cellular stress. To better understand the role of HSP-60 in relation to AF, we examined the association of HSP-60 levels in relation to the future development of AF in the Multi-Ethnic Study of Atherosclerosis (MESA). METHODS: MESA is a cohort study that recruited 6,814 participants aged 45-84 years and free of known cardiovascular disease at baseline (2000-2002) from six field centers. We investigated 983 participants, selected at random from the total cohort, who had HSP-60 measured and were free of AF at baseline. We tested the association of HSP-60 levels with the incidence of AF using multivariate Cox models after adjustment for demographics, clinical characteristics, and biomarkers. RESULTS: During an average of 10.6 years of follow-up, 77 participants developed AF. We did not observe a significant association between the log-transformed HSP-60 levels and development of AF on either unadjusted or multivariate analysis (adjusted hazard ratio: 1.02 per unit difference on natural log scale, 95% confidence interval: 0.77-1.34 ln (ng/mL). CONCLUSION: Contrary to the findings from the preclinical studies, which demonstrated an important role of HSP-60 in the pathogenesis of AF, we did not observe a significant association between HSP-60 and occurrence of AF.

Rapid, Sensitive Detection of Bartonella quintana by Loop-Mediated Isothermal Amplification of the groEL Gene.

Trench fever, caused by Bartonella quintana, is recognized as a re-emerging and neglected disease. Rapid and sensitive detection approaches are urgently required to monitor and help control B. quintana infections. Here, loop-mediated isothermal amplification (LAMP), which amplifies target DNA at a fixed temperature with high sensitivity, specificity and rapidity, was employed to detect B. quintana. Thirty-six strains, including 10 B. quintana, 13 other Bartonella spp., and 13 other common pathogens, were applied to verify and evaluate the LAMP assay. The specificity of the LAMP assay was 100%, and the limit of detection was 125 fg/reaction. The LAMP assay was compared with qPCR in the examination of 100 rhesus and 20 rhesus-feeder blood samples; the diagnostic accuracy was found to be 100% when LAMP was compared to qPCR, but the LAMP assay was significantly more sensitive (p < 0.05). Thus, LAMP methodology is a useful for diagnosis of trench fever in humans and primates, especially in low-resource settings, because of its rapid, sensitive detection that does not require sophisticated equipment.

Damage-associated molecular patterns and immune activation in bipolar disorder.

OBJECTIVE: Immune activation in bipolar disorder (BD) has been frequently reported. Damage-associated molecular patterns (DAMPs) are key players in the immune activation reaction. The aim of this study was to assess DAMP levels in drug-free patients with BD during acute episodes. METHOD: Serum levels of a predetermined set of DAMPs were assessed in drug-free patients with BD (n = 20) during an acute mood episode. We also included two control groups: healthy subjects, used as a negative control (n = 20); and patients with sepsis, used as a positive control for severe immune activation (n = 20). RESULTS: Multivariate analysis using generalized linear mixed model indicated that all DAMPs differed as a function of group membership after controlling for age and addressing multiplicity (P < 0.0006 for all comparisons). Follow-up analyses showed higher levels in BD subjects of circulating cell-free (ccf) nuclear (n)DNA (P = 0.02), HSP70 (P = 0.03) and HSP90α (P = 0.02) as compared to healthy subjects. Also, patients with BD showed lower levels of ccf nDNA (P = 0.04), HSP60 (P = 0.03), HSP70 (P = 0.01), and HSP90α (P = 0.002) as compared to patients with sepsis and higher levels of ccf mitochondrial DNA (P < 0.0001). CONCLUSION: The present findings may be linked to the inflammatory activity previously described among patients with BD and may help in the development of more targeted and personalized treatments for patients under acute episodes of BD.

Decreased serum heat shock protein 60 levels in newly diagnosed immune thrombocytopenia patients.

Immune thrombocytopenia (ITP) is an autoimmune disease characterized by peripheral thrombocyte destruction. In some autoimmune disorders, heat-shock proteins (HSP) are suggested to be an important antigenic factor. In this study, we demonstrated the serum free levels of HSP60, HSP70, anti-HSP60, and anti-HSP70 in ITP patients and healthy controls. Twenty-eight newly diagnosed ITP patients, 35 ITP patients in chronic phase, and 25 healthy controls were enrolled to this study. Serum levels of HSP60, HSP70, anti-HSP60, and anti-HSP70 were determined by the ELISA method. Serum HSP60 levels of newly diagnosed ITP patients were significantly decreased when compared with both chronic phase ITP patients and healthy controls. HSP60 levels of ITP patients (both newly diagnosed and chronic phase) with thrombocyte counts more than 30 × 10(9)/L were significantly increased compared with ITP patients with thrombocyte counts less than 30 × 10(9)/L and there was a positive correlation between thrombocyte counts and serum free HSP60 levels in ITP patients. This is the first study demonstrating the extracellular HSP levels in adult ITP patients. HSPs are shown to have a place in the pathogenesis of many autoimmune disorders. Low level of HSP60 may lead to lack of anti-inflammatory response due to less Treg activation, hence, could be a counterpart in the pathogenesis of ITP. Further studies are needed to understand the role of HSPs in the pathogenesis of ITP and whether they can be used for diagnosis, prognosis, and treatment of ITP.

Absolute quantitation of low abundance plasma APL1ß peptides at sub-fmol/mL Level by SRM/MRM without immunoaffinity enrichment.

Selected/multiple reaction monitoring (SRM/MRM) has been widely used for the quantification of specific proteins/peptides, although it is still challenging to quantitate low abundant proteins/peptides in complex samples such as plasma/serum. To overcome this problem, enrichment of target proteins/peptides is needed, such as immunoprecipitation; however, this is labor-intense and generation of antibodies is highly expensive. In this study, we attempted to quantify plasma low abundant APLP1-derived Aß-like peptides (APL1ß), a surrogate marker for Alzheimer's disease, by SRM/MRM using stable isotope-labeled reference peptides without immunoaffinity enrichment. A combination of Cibacron Blue dye mediated albumin removal and acetonitrile extraction followed by C18-strong cation exchange multi-StageTip purification was used to deplete plasma proteins and unnecessary peptides. Optimal and validated precursor ions to fragment ion transitions of APL1ß were developed on a triple quadruple mass spectrometer, and the nanoliquid chromatography gradient for peptide separation was optimized to minimize the biological interference of plasma. Using the stable isotope-labeled (SI) peptide as an internal control, absolute concentrations of plasma APL1ß peptide could be quantified as several hundred amol/mL. To our knowledge, this is the lowest detection level of endogenous plasma peptide quantified by SRM/MRM.

[Antibodies to Hsp60 in newborn babies, to whom during the intervention for critical inborn heart failure, autologous cord blood was transfused, in early and late postoperative period].

The titre of antibodies to Hsp60 (heat shock protein) enhancement in the blood serum is considered a biological marker of poor state of organism. Comparative investigation was done on the antibodies titre to Hsp60 in the blood serum of a newborn babies, suffering critical inborn heart failure, to whom autologous cord blood or the donor's blood components was transfused, in early and remote postoperative period. In early postoperative period the lowering of the antibodies titre to Hsp60 in the blood serum was observed in comparison with them preoperatively, in a late period (in 2 yrs) in all the blood serum samples investigated antibodies to Hsp60 were not revealed. In 35% of patients, to whom the donor's blood components were transfused, there was registered the enhancement of the antibodies to Hsp60 titre in early postoperative period. High titre of antibodies have associated with enhanced rate of complications. In late postoperative period antibodies to Hsp60 were revealed in 20% of the examined patients.

Antigen-specificity of oligoclonal abnormal protein bands in multiple myeloma after allogeneic stem cell transplantation.

Myeloma patients may develop oligoclonal immunoglobulins, so-called abnormal protein bands (APB), after stem cell transplantation. APB do not correspond to the patient's paraprotein and confer a good prognosis. We set out to investigate whether such APB represent a humoral anti-myeloma immune response by screening immunoglobulins of 15 myeloma patients after allogeneic stem cell transplantation and a control group of healthy donors for reactivity with myeloma protein extracts. While the immunoglobulins of healthy donors did not react with myeloma protein extracts, patient-derived immunoglobulins showed variable levels of interaction, depending on the presence of APB on immunofixation. Most commonly, we detected interactions with heat-shock proteins, followed by neutral alpha-glucosidase, alpha-enolase and vimentin, as well as proliferating cell nuclear antigen and MAGEA4. More than 80% of targets were upregulated in myeloma. Heat-shock protein 60 (HSP60) was subsequently evaluated as an exemplary antigen. We found that HSP60 was aberrantly displayed on the surface of primary myeloma cells. Indeed, patient-derived APB-containing immunoglobulins recognized surface HSP60 suggesting that this antigen becomes accessible to the immune system after aberrant membrane exposition. We conclude that immunoglobulin fractions with APB recognize recurrent myeloma antigens and that this humoral response may contribute to the more favorable prognosis in patients with APB.

Autoreactive HSP60 epitope-specific T-cells in early human atherosclerotic lesions.

Atherosclerosis is a multifactorial chronic inflammatory disease characterized by the presence of T-cells, macrophages, and dendritic cells in the arterial intima. Classical risk factors lead to over-expression of stress proteins, especially heat shock protein 60 (HSP60). HSP60 on the surface of arterial endothelial cells (ECs) then becomes a target for pre-existing adaptive anti-HSP60 immunity resulting in infiltration of the intima by mononuclear cells. In the present study, T-cells derived from early, clinically still inapparent human atherosclerotic lesions were analyzed phenotypically and for their reactivity against HSP60 and HSP60-derived peptides. HSP60 was detected in ECs and CD40- and HLA Class II-positive cells within the intima. Effector memory CD4(+) T-cells producing high amounts of interferon-γ and low levels of interleukin-4 were the dominant subpopulation. T-cells derived from late lesions displayed a more restricted T-cell receptor repertoire to HSP60-derived peptides than those isolated from early lesions. Increased levels of soluble HSP60 and circulating anti-human HSP60 autoantibodies were found in donors with late but not early lesions. This is the first functional study of T-cells derived from early human atherosclerotic lesions that supports the previously proposed concept that HSP60-reactive T-cells initiate atherosclerosis by recognition of atherogenic HSP60 epitopes.

Relationship of self-reported exercise tolerance with inflammatory markers in women with stable ischemic heart disease.

OBJECTIVE: Ischemic heart disease (IHD) is associated with decreased exercise tolerance and it is subjectively reported as angina pectoris or dyspnea. Inflammation and pro- inflammatory cytokines are related to progression of IHD, but their level is seldom analyzed in association with self reported exercise tolerance. METHODS: Women aged 35-75 years with stable IHD from Homocysteine Slovakia study (N=175) were analyzed for monocyte chemoatractant protein-1 (MCP-1), interleukin 6 (IL-6), transforming growth factor ß1 (TGF ß1), Mannan binding lectin (MBL), heat shock proteins 60 (HSP60), carbonyl protein (CP), high sensitivity C-reactive protein (hsCRP) and oxidized glutathione (GSSG) in relation to exercise induced dyspnea or angina pectoris (AP) (≤200 m). RESULTS: Patients with dyspnea had higher HSP60 (77.3±107.2 vs 43.7±48.9 ng/ml; p=0.014) and IL-6 (2.9±1.3 vs 1.9±0.6 pg/ml; p=0.04) levels. IL-6 and HSP60 demonstrated direct correlation with dyspnea (rho=0.39; p=0.02 resp. rho=0.22; p=0.01). AP≤200 m patients showed only decreased protein carbonyl a marker of protein oxidation and increased oxidative stress (CP 61.7±27.3 vs. 72.1±23.1 pg/ml; p=0.001). CP indirectly correlates with AP≤200 m (rho=-0.25; p=0.001). CONCLUSIONS: We have found associations of pro-inflammatory cytokines and inflammation markers with dyspnea or angina pectoris, but the relationship was not consistent in our patients with stable ischemic heart disease.

Elevated anti-heat shock protein 60 antibody titer is related to white matter hyperintensities.

BACKGROUND: There are many reports that the antibody against heat shock protein 60 (Hsp60) is present in most patients with coronary artery disease and atherosclerosis, and that its titer correlates with disease severity. However, few reports have described the association between anti-Hsp60 antibody and cerebrovascular disease. METHODS: We determined the anti-Hsp60 antibody titer in patients with neurologic diseases and healthy subjects using enzyme-linked immunosorbent assay (ELISA) and evaluated their findings of brain magnetic resonance imaging (MRI) of the white matter. White matter hyperintensities (WMHs) on T2-weighted and fluid-attenuated inversion recovery (FLAIR) images were classified into 2 categories: periventricular hyperintensity (PVH) and deep white matter hyperintensity (DWMH). The lesions in each category were then divided into 4 grades (grades 0-3) according to the Fazekas rating scale. RESULTS: There were no significant differences in the titer between patients with neurologic diseases and healthy subjects. The mean grade of DWMHs (mean ± SD, 1.56 ± 0.70) was significantly higher in 18 subjects in the high-titer group (≥39.8 ng/mL; mean titer + 2 SD in sera from 23 healthy subjects) than in 86 subjects (mean ± SD, 0.09 ± 0.76) in the normal-titer group (<39.8 ng/mL; P < .003). The mean grade of PVHs (mean ± SD, 1.50 ± 0.71) was also significantly higher in the high-titer group than in the normal-titer group (mean ± SD, 1.17 ± 0.62; P < .02). CONCLUSIONS: A significant correlation was noted between anti-Hsp60 antibody titer and the severity of WMHs on brain MR images. We suggest that an elevated titer of the anti-Hsp60 antibody could be a risk factor for cerebral small-vessel disease.

[Changes of CK-MB and HSP 60 in electrical-injuried rats].

OBJECTIVE: To investigate the changes of creatine kinase-MB (CK-MB) and heat shock protein 60 (HSP 60) in rats without electric marks after electric injury, to identify the relationship of the CK-MB, HSP 60 and the time of electric injuries, and to evaluate the damage to cells after electric injury. METHODS: The animal model of electric injury without electric marks was established by alternating current (voltage 110 V). Automatic biochemistry analyzer was used to detect the serum CK-MB and immunohistochemical staining technology was used to analyze the tissues of myocardium and left lobe of liver. RESULTS: The amount of serum CK-MB was increased when the rats were injuried, and reached the peak at 30min. Then the amount of CK-MB began to decrease and showed a slight downward trend in 3-5 h after electric injury, and leveled off at 6 h. Immunohistochemistry staining also showed the changes of HSP 60 of rats' myocardial cells and hepatic cells regularly after electric injury. CONCLUSION: The regular changes of serum CK-MB and tissular HSP 60 in rats can be used to diagnosis electric injury and assess the injury of internal organs after the electric injury without electric marks.

Nest ectoparasites increase physiological stress in breeding birds: an experiment.

Parasites are undoubtedly a biotic factor that produces stress. Heat shock proteins (HSPs) are important molecules buffering cellular damage under adverse conditions. During the breeding season, blue tit Cyanistes caeruleus (L.) adults are affected by blood parasites, nest-dwelling parasites and biting flies, potentially affecting their HSP-mediated responses. Here, we treated females with primaquine to reduce blood parasites and fumigated nests with permethrin to reduce nest-dwelling parasites to test whether these treatments affect HSP60 level during the breeding season. Medicated females, but not controls, had a significant reduction of the intensity of infection by Haemoproteus spp. blood parasites. However, final intensity of infection did not differ significantly between groups, and we did not find an effect of medication on change in HSP60 level. Fumigation reduced the abundance of nest-dwelling parasites (mites, fleas and blowfly larvae) and engorged biting midges in nests. Females breeding in non-fumigated nests increased HSP60 levels during the season more than those breeding in fumigated nests. Furthermore, the change in HSP60 level was positively correlated with the abundance of biting midges. These results show how infections by nest ectoparasites during the breeding period can increase the level of HSPs and suggest that biting midges impose physiological costs on breeding female blue tits. Although plausible, the alternative that biting midges prefer to feed on more stressed birds is poorly supported by previous studies.

Chlamydia trachomatis and Mycoplasma genitalium plasma antibodies in relation to epithelial ovarian tumors.

OBJECTIVE: To assess associations of Chlamydia trachomatis and Mycoplasma genitalium antibodies with epithelial ovarian tumors. METHODS: Plasma samples from 291 women, undergoing surgery due to suspected ovarian pathology, were analyzed with respect to C. trachomatis IgG and IgA, chlamydial Heat Shock Protein 60-1 (cHSP60-1) IgG and M. genitalium IgG antibodies. Women with borderline tumors (n=12), ovarian carcinoma (n=45), or other pelvic malignancies (n=11) were matched to four healthy controls each. RESULTS: Overall, there were no associations of antibodies with EOC. However, chlamydial HSP60-1 IgG antibodies were associated with type II ovarian cancer (P=.002) in women with plasma samples obtained >1 year prior to diagnosis (n=7). M. genitalium IgG antibodies were associated with borderline ovarian tumors (P=.01). CONCLUSION: Chlamydial HSP60-1 IgG and M. genitalium IgG antibodies are in this study associated with epithelial ovarian tumors in some subsets, which support the hypothesis linking upper-genital tract infections and ovarian tumor development.

Hepatitis B virus replication could enhance regulatory T cell activity by producing soluble heat shock protein 60 from hepatocytes.

BACKGROUND: HBcAg-specific regulatory T (T(reg)) cells play an important role in the pathogenesis of chronic hepatitis B. Soluble heat shock proteins, especially soluble heat shock protein 60 (sHSP60), could affect the function of T(reg) cells via Toll-like receptor. METHODS: We analyzed the relationship between soluble heat shock protein production and hepatitis B virus (HBV) replication with both clinical samples from HBeAg-positive patients with chronic hepatitis B (n= 24) and HBeAb-positive patients with chronic hepatitis B (n= 24) and in vitro HBV-replicating hepatocytes. Thereafter, we examined the biological effects of sHSP60 with isolated T(reg) cells. RESULTS: The serum levels of sHSP60 in patients with chronic hepatitis B were statistically significantly higher than those in patients with chronic hepatitis C (P<.01), and the levels of sHSP60 were correlated with the HBV DNA levels (r = 0.532; P<.001) but not with the alanine aminotransferase levels. Moreover, the levels of sHSP60 in HBV-replicating HepG2 cells were statistically significantly higher than those in control HepG2 cells. Preincubation of CD4(+) CD25(+) cells with recombinant HSP60 (1 ng/mL) statistically significantly increased the frequency of HBcAg-specific interleukin 10-secreting T(reg) cells. The frequency of IL7R(-)CD4(+)CD25(+) cells, the expression of Toll-like receptor 2, and the suppressive function of T(reg) cells had declined during entecavir treatment. CONCLUSION: The function of HBcAg-specific T(reg) cells was enhanced by sHSP60 produced from HBV-infected hepatocytes. Entecavir treatment suppressed the frequency and function of T(reg) cells; this might contribute to the persistence of HBV infection.

Outbreak of pneumonia associated with emergent human adenovirus serotype 14--Southeast Alaska, 2008.

BACKGROUND: In September 2008, an outbreak of pneumonia associated with an emerging human adenovirus (human adenovirus serotype 14 [HAdV-14]) occurred on a rural Southeast Alaska island. Nine patients required hospitalization, and 1 patient died. METHODS: To investigate the outbreak, pneumonia case patients were matched to control participants on the basis of age, sex, and community of residence. Participants in the investigation and their household contacts were interviewed, and serum samples and respiratory tract specimens were collected. Risk factors were evaluated by means of conditional logistic regression. RESULTS: Among 32 pneumonia case patients, 21 (65%) had confirmed or probable HAdV-14 infection. None of 32 matched control participants had evidence of HAdV-14 infection (P<.001 for the difference). Factors independently associated with pneumonia included contact with a known HAdV-14-infected case patient (odds ratio [OR], 18.3 [95% confidence interval {CI}, >or=2.0]), current smoking (OR, 6.7 [95% CI, >or=0.9]), and having neither traveled off the island nor attended a large public gathering (OR, 14.7 [95% CI, >or=2.0]). Fourteen (67%) of 21 HAdV-14-positive case patients belonged to a single network of people who socialized and often smoked together and infrequently traveled off the island. HAdV-14 infection occurred in 43% of case-patient household contacts, compared with 5% of control-participant household contacts (P = .005). CONCLUSIONS: During a community outbreak in Alaska, HAdV-14 appeared to have spread mostly among close contacts and not widely in the community. Demographic characteristics and illness patterns among the case patients were similar to those observed in other recent outbreaks of HAdV-14 infection in the United States.