[Study on the fit testing for the workers wearing hearing protection device in machinery manufacturing enterprises].

Objective: To investigate the occupational noise hazards in five machinery manufacturing enterprises, and to evaluate the individual noise reduction values and influencing factors of workers wearing hearing protection device (HPD) by individual fit testing. Methods: From November 2021 to January 2022, 5 machinery manufacturing enterprises in Bao'an District of Shenzhen were selected to conduct an occupational health survey to understand the noise exposure level of workers. The 3MTM E-A-RfitTM fitness test system was used to test the baseline individual sound attenuation value level (PAR) of the daily wear of the ear protecters for 485 workers in typical noise working positions. Workers whose PAR values could not meet the requirements of noise reduction at work were instructed to wear and repeated tests were conducted. PAR results of the workers before and after the intervention were collected and analyzed. Results: The noise workers who received the suitability test were mainly distributed in 24 types of work, the job noise exposure level was 80.2 dB (A) ~ 95.0 dB (A), and the job noise excess rate was 52.5% (138/263). The median baseline PAR [M (Q(1), Q(3)) ] for 485 workers was 6.0 (0.0, 14.0) dB. The baseline PAR of male workers, those with more than 15 years of working experience, those with more than 15 years of using ear guards, those who considered ear guards comfortable to wear, those with college degree or above, and those exposed to noise level 90 dB (A) were higher, and the difference was statistically significant (P<0.05). A total of 275 workers (56.7%) did not pass the baseline PAR test, and there was no statistically significant difference in the intervention rate of workers in different noise groups (P>0.05). PAR in subjects who did not pass baseline after intervention increased from 0.0 (0.0, 3.0) dB to 15.0 (12.0, 18.2) dB. Conclusion: The workplace noise hazard of machinery manufacturing enterprises is serious, and there is a great difference between the baseline PAR and the nominal value of the hearing guard worn by the noise exposed workers. The intervention measures can effectively improve the protective effect of wearing ear protectors.

[A study on the hearing protection and intervention effects of silicone earplug usage among manufacturing workers].

Objective: To assess the efficacy of silicone earplugs in protecting workers exposed to noise in a typical manufacturing environment, and to provide training interventions for workers who do not achieve the anticipated noise reduction levels, as well as examining the spectral characteristics of earplug attenuation. Methods: From June to August 2022, a total of 294 noise-exposed workers in two manufacturing enterprises equipped with the same type of earplug were studied by cluster sampling method, by conducting questionnaire surveys, collecting data, fitting tests, and providing trainings, the current noise exposure levels of workers in the industry as well as the perception about the earplug were understood. Additionally, the attenuation before and after intervention in workplace were measured, the spectral characteristics of noise reduction were were described and compared. Results: The percentage of workers with Personal Attenuation Rating (PAR) of 0 is 32.7% (96/294), and the baseline pass rates are all below 60%. There were no significant differences in pass rates based on gender, age, noise exposure, education level, or cognition of earplug effectiveness. After adjusting the way that earplugs are worn or changing the type of earplugs, all workers were able to meet their noise reduction requirements. The median PAR improvement for both companies is above 10 dB. The noise attenuation of the earplug vary with frequency, with lower attenuation at 4 000 Hz and higher attenuation at 8 000 Hz, showing some deviation from the nominal values. Conclusion: The difference between the actual sound attenuation value of earplugs and the nominal value is related to the noise frequency. When using silicone earplugs, attention should be paid to the spectral composition of the noise in the workplace.

[Quantitative risk assessment of occupational exposure to PCDD/Fs in the waste incineration industry].

Objective: To analyze the level of PCDD/Fs exposure of occupational workers in the waste incineration industry and explore the risk of occupational exposure. Methods: In September 2021, literature on environmental PCDD/Fs exposure in waste incineration plants published from the establishment of the database to February 10, 2021 was retrieved from CNKI database. A total of 1365 literatures were retrieved, and 7 met the criteria for inclusion. The US Environmental Protection Agency (EPA) inhalation risk model was used to assess and analyze carcinogenic and non-carcinogenic risks of PCDD/Fs exposure among occupational workers in the waste incineration industry. Results: A total of 86 sampling sites were included in incineration plants in 7 regions. The study of Wuhan area showed that the concentration of working environment near the waste incinerator in the same factory was the highest, followed by the rest and office area in the factory. The concentration of PCDD/Fs in waste incinerators was the highest in Southwest China (4880.00-24880.00 pg TEQ/m(3)), and the lowest in Shenzhen (0.02-0.44 pg TEQ/m(3)). According to the cancer risk assessment, with the increase of exposure years, the risk of cancer increased. The highest risk of cancer was found in the waste incineration plants in Southwest China. When the exposure period was 1 year, the risk was moderate (22.40×10(-6)-114.20×10(-6)). When the exposure time was more than 5 years, the risk of cancer was high. In Jinan, workers working near the incinerator had a moderate risk of cancer after five years of exposure. In Zhejiang, workers were at medium risk of cancer after exposure for more than 20 years. Workers in Wuhan, Shanghai, Zhejiang Province, Shenzhen and the Pearl River Delta were still at low risk of cancer after 40 years of occupational exposure. HQ>1 of workers working near the waste incinerators in Jinan, Zhejiang Province and Southwest China, and the qualitative evaluation results showed that the non-carcinogenic risk was unacceptable. Conclusion: There are great differences in PCDD/Fs of occupational exposure in waste incineration industry, and the occupational exposure exceeding the occupational exposure limit has higher carcinogenic and non carcinogenic risks.

[Analysis of verification results of protective effects of hearing protectors in different industries].

Objective: To get insight into the current practice of noise reduction effect of workers as they wore hearing protectors in different domestic enterprises and the possible affected factors. Methods: From October 2020 to April 2021, using a random sampling method, 1197 workers exposed to noise in petrochemical factories, textile factories, and parts manufacturing factories were selected as the study subjects. The noise reduction effect of hearing protectors worn by workers in daily use was tested using a hearing protector suitability testing system. The personal sound attenuation level (PAR) was compared among workers in three enterprises, Targeted intervention and repetitive testing were conducted for workers who did not meet the noise reduction effect required by the enterprise, and the changes in PAR of workers before and after the intervention were compared. The comparison of baseline PARs between two or more groups was performed using the Mann Whitney test, the comparison of baseline PARs with post intervention PARs was performed using the Wilcoxon signed rank sum test, and the comparison of qualitative data between two or more groups was performed using the Chi square test. Results: The median baseline PAR for all workers was 15 dB. Men, age<30 years old, education level at or above college level, working experience of 5 to 15 years, and those who used hearing protectors for 5 to 15 years had higher PARs, with statistically significant differences (P<0.05). The median difference in baseline PAR among workers from three enterprises was statistically significant (H=175.06, P<0.01). The median PAR of subjects who did not pass the baseline increased from 3 dB to 21 dB after intervention (Z=-27.92, P<0.01) . Conclusion: Some workers wearing hearing protectors do not meet the required PAR, and low PARs may be related to incorrect wearing methods and incorrect selection of hearing protectors. As a tool for testing, training, and assisting in selection, the hearing protector suitability testing system is of great significance for worker hearing protection.

[Research on the protective effect of hearing protective device for workers exposed to noise in a motor manufacturing enterprise].

Objective: To understand the current situation of noise hazard in a motor manufacturing enterprise, and to explore the protective effect of workers wearing hearing protective device and its possible influencing factors. Methods: In November 2021, a total of 179 noise workers wearing hearing protective devices in a motor manufacturing company in a city were selected as research objects. Personal attenuation rating (PAR) of workers wearing hearing protective devices was measured. Baseline PAR was analyzed for different subgroups of basic demographic information, noise exposure, and the use of hearing protective devices to evaluate the effect of the intervention. Baseline PAR was compared using nonparametric tests. Results: There were 179 workers from 35 positions in 4 types of work, and the over-standard noise rate was 51.2% (42/82), among which the noise exposure intensity of motor equipment debugging workers was the highest [94.4 dB (A) ]. Compared the baseline PAR of different characteristics, it was found that the baseline PAR of male workers, workers whose daily noise exposure time were <8 h, workers who had used the hearing protective devices for 10 to 14 years, and workers who thought the hearing protective devices were comfortable were all higher, and the differences were statistically significant (P<0.05). Baseline PAR passing rate was 43.0% (77/179), and PAR of 102 workers who did not pass baseline test increased from 0 (0, 3) dB before intervention to 14 (12, 16) dB after intervention, with statistical significance (P<0.05) . Conclusion: The noise hazard in this motor manufacturing enterprise is serious, and the protective effect of workers wearing hearing protective devices is not good. Gender, daily noise exposure time, years and comfort of wearing hearing protective device are the possible influencing factors of poor protective effect.

[Risk assessment on noise-induced hearing loss of 488 workers in a petrochemical plant].

Objective: To assess the risk of noise-induced hearing loss in workers from a petrochemical plant. Methods: In October 2020, 488 male workers exposed to noise in a petrochemical plant in Guangdong Province were selected by cluster sampling. Acoustics-Estimation of Noise-Induced Hearing Loss (ISO 1999: 2013) was used to assess the risk of noise-induced hearing loss of workers, and individual fit testing was used to evaluate the sound attenuation obtained by the workers. The risk assessment results and fitness test results of workers with different hearing levels were compared. Results: The average noise exposure equivalent sound level of the workers in the petrochemical plant was 86.7 dB (A) . The median of PARs (personal attenuation ratings) was 16 (4, 23) dB. There were statistically significant differences in age and service years among workers with different hearing results (P<0.05) , but no statistically significant differences in noise intensity and PARs (P>0.05) . According to risk assessment results of ISO 1999: 2013, the current risk of high-frequency hearing loss in 488 workers were negligible risk and acceptable risk. The risk of noise-induced deafness weredivided into three levels: negligible risk in 452 workers (92.7%) , medium risk in 27 workers (5.5%) and high risk in 9 workers (1.8%) . The risk of high-frequency hearing loss in next 5 to 15 years for workers with noise exposure level of >94 to 97 dB and >97 dB or above would be medium risk or above. The risk of noise-induced deafness in next 5 to 15 years for workers exposed to noise withlevel of 91 to 94 dB would be medium risk or above. Conclusion: The risk of noise-induced hearing loss in workers from the petrochemical plant is high in next 5 to 15 years, and noise prevention and control measures need to be strengthened. ISO1999: 2013 assessment method may underestimate the risk of hearing loss among workers.

[Application of multiple exposure assessment methods in occupational health risk assessment of trichloroethylene in electroplating enterprises].

Objective: To explore the applicability of different exposure assessment methods in occupational health risk assessment of trichloroethylene (TCE) occupation posts in electroplating enterprise. Methods: In November 2018, the occupational health risk assessments are conducted in trichloroethylene (TCE) occupation posts of 6 metal plating enterprises in a street in Shenzhen by using the qualitative risk assessment, semi-quantitative risk assessment (including contact ratio method, contact index method and synthesis index method) and quantitative risk assessment method (including non-carcinogenic and carcinogenic risk assessment methods) , and the results of different methods are compared. Results: The results of qualitative assessment method are all level 4 (high risk) ; the results of contact ratio method show that the risk level is level 5 (very high risk) ; the results of contact index method and Synthesis index method show that the risk level is level 3 and level 4, 66.7% and 33.3% respectively; Non-carcinogenic risk assessment results show that TCE jobs are "unacceptable"; carcinogenic risk assessment results in carcinogenic inhalation excess risk of 50% each being "unacceptable" and "acceptable". The results of the six risk assessment methods showed that there were 3 "substantially consistent", 1 "partially consistent", and 2 "inconsistent" among the 6 companies. Conclusion: Synthesis index method and the carcinogenic risk assessment method are more suitable for occupational health risks of TCE occupation posts.

[Relationship between occupational stress, psychological capital and depressive symptoms among female workers in five electronic manufacturing enterprises].

Objective: To explore the relationship between occupational stress, psychological capital and depressive symptoms among electronic manufacturing female workers in the Pearl River Delta region. Methods: Using cluster sampling method, 845 female workers from 5 electronic manufacturing enterprises in the Pearl River Delta region were selected as research subjects from June to August 2017. The Effort Reward Imbalance questionnaire (ERI) , Psychological Capital questionnaire-24 (PCQ-24) and Patient Health questionnaire-9 (PHQ-9) were applied to measure the level of occupational stress, psychological capital and depressive symptoms in female workers. Results: Effort (r=0.197, P<0.01) and over commitment (r=-0.260, P<0.01) were positively correlated with the score of depressive symptoms, and the rewards was negatively correlated with depressive symptoms (r=-0.211, P<0.01) . The reward and over-commitment for depressive symptoms were accounted for 8.2%. Psychological capital was negatively correlated with depressive symptoms, and plays a partly mediating role in the relationship between occupational stress and depressive symptoms of female workers. The psychological capital for depressive symptoms was accounted for 8.7%. Conclusion: Occupational stress can affects the depressive symptoms of electronic manufacturing female workers, or indirectly affect depressive symptoms through psychological capital, reduce occupational stress and improve psychological capital as a way to relieve the depressive symptoms of female workers.

[Application of three semi-quantitative risk assessment methods in electroplating enterprises].

Objective: To apply the semi-quantitative risk assessment model in the Technical Guidelines for Occupational Health Risk Assessment of Chemical Hazardous Factors in the Workplace to assess the occupational health risk of electroplating enterprises and explore its applicable conditions and characteristics. Methods: Three electroplating enterprises were selected as the research objects. Occupational hygiene survey and hazard factor detection were conducted on the spot. Three semi-quantitative risk assessment methods were used to assess the risk, and the evaluation results were compared. Results: The consistency between the contact index method and the comprehensive index method was strong. The weighted Kappa value was 0.946 and the P value was less than 0.001, but the consistency between the contact ratio method, the contact index method and the comprehensive index method was poor. The weighted Kappa value was 0.345 and 0.391, and the P value was 0.009 and 0.004, respectively. When the contact concentration is less than 50% OELs, the evaluation results of the contact ratio method are lower than those of the exponential method and the comprehensive exponential method. The consistency of the three methods was the highest when the contact concentration (>50%) and (OELs, the results of the contact ratio method are higher than those of the index method and the comprehensive index method. Conclusion: Contact ratio method is suitable for occupational health risk assessment under the condition of incomplete occupational health information and for enterprise managers to identify key control points of health risk through self-assessment; Contact index method is suitable for hazard risk assessment of occupational hazards without sampling test conditions or OELs, and pre-assessment of occupational hazards of construction projects without access to analogical test data. The index method is suitable for occupational health risk assessment with available testing data and complete occupational health information.

A seven-transmembrane, G protein-coupled receptor, FPRL1, mediates the chemotactic activity of serum amyloid A for human phagocytic cells.

We have previously reported (Badolato, R., J.M. Wang, W.J. Murphy, A. R. Lloyd, D.F. Michiel, L.L. Bausserman, D.J. Kelvin, and J.J. Oppenheim. 1994. J. Exp. Med. 180:203; Xu, L., R. Badolato, W.J. Murphy, D.L. Longo, M. Anver, S. Hale, J.J. Oppenheim, and J.M. Wang. 1995. J. Immunol. 155:1184.) that the acute phase protein serum amyloid A (SAA) is a potent chemoattractant for human leukocytes in vitro and mouse phagocytes in vivo. To identify the signaling mechanisms, we evaluated patterns of cross-desensitization between SAA and other leukocyte chemoattractants. We found that the chemotactic bacterial peptide, N-formyl- methionyl-leucyl-phenylalanine (fMLP), was able to specifically attenuate Ca2+ mobilization in human phagocytes induced by SAA, but only at very high concentrations, suggesting that SAA uses a low affinity fMLP receptor. Here we demonstrate that SAA selectively induced Ca2+ mobilization and migration of HEK cells expressing FPRL1, a human seven-transmembrane domain phagocyte receptor with low affinity for fMLP, and high affinity for lipoxin A4. Furthermore, radiolabeled SAA specifically bound to human phagocytes and FPRL1-transfected 293 cells. In contrast, SAA was not a ligand or agonist for FPR, the high affinity fMLP receptor. Thus, SAA is the first chemotactic ligand identified for FPRL1. Our results suggest that FPRL1 mediates phagocyte migration in response to SAA.

Prognostic and predictive values of CXCL10 in colorectal cancer.

BACKGROUND: The role of CXCL10 in progression and prognosis of colorectal cancer (CRC) has been studied for years, yet results remain controversial. AIM: This study aims to explore the relationship between CXCL10 and CRC progression and prognosis. METHODS: We evaluated plasma CXCL10 in CRC patients using ELISA. We also performed a meta-analysis of the associations between CXCL10 and overall survival (OS), disease-free survival (DFS), disease-specific survival (DSS), relapse-free survival (RFS), and clinicopathological features. Finally, correlations between CXCL10 and methylation or immune infiltration were performed using TCGA data. RESULTS: ELISA analysis showed that CXCL10 was associated with age, red blood cells, blood platelets, and blood urea nitrogen. A separate analysis of 3,763 patients from 24 studies revealed that there were significant associations between low CXCL10 expression and OS (HR 1.25, 95% CI 1.01-1.53), DFS (HR 1.65, 95% CI 1.17-2.34), and RFS (HR 1.43, 95% CI 1.20-1.71) in CRC. Additionally, downregulated CXCL10 expression was significantly correlated with age [odds ratio (OR) 1.31, 95% CI 1.13-1.52], metastasis (OR 1.34, 95% CI 1.11-1.63), recurrence (OR 1.46, 95% CI 1.16-1.83), tumor location (OR 1.88, 95% CI 1.58-2.24), differentiation (OR 0.57, 95% CI 0.35-0.93), microsatellite instability (OR 0.23, 95% CI 0.15-0.35), BRAF mutation (OR 1.62, 95% CI 1.25-2.08), p53 mutation (OR 0.28, 95% CI 0.16-0.47), and CIMP (OR 0.27, 95% CI 0.17-0.43). Furthermore, significant associations were observed between CXCL10 and methylation and immune infiltration. CONCLUSIONS: The study suggests that CXCL10 might be a potential target for the treatment of CRC. TRIAL REGISTRATION: NCT03189992. Registered 4 June 2017, https://www.clinicaltrials.gov/ct2/show/study/NCT03189992?term=NCT03189992&rank=1 .

HIV-1 envelope gp41 is a potent inhibitor of chemoattractant receptor expression and function in monocytes.

HIV-1 uses CD4 and chemokine receptors as cofactors for cellular entry. The viral envelope transmembrane protein gp41 is thought to participate in viral fusion with CD4(+) cells. We investigated whether gp41 interacts with chemokine receptors on human monocytes by testing its effect on the capacity of cells to respond to chemokine stimulation. Monocytes preincubated with gp41 of the MN strain showed markedly reduced binding, calcium mobilization, and chemotaxis in response to a variety of chemokines as well as to the bacterial peptide fMLP. This generalized inhibition of monocyte activation by chemoattractants required the presence of CD4, since the effect of gp41 was only observed in CD4(+) monocytes and in HEK293 cells cotransfected with chemokine receptors and an intact CD4, but not a CD4 lacking its cytoplasmic domain. Confocal microscopy showed that gp41 caused internalization of CXCR4 in HEK293 cells provided they were also cotransfected with intact CD4. In addition, pretreatment of monocytes with protein kinase C inhibitors partially reversed the inhibitory effect of gp41. Thus, gp41, which had not previously been implicated as interacting with HIV-1 fusion cofactors, downregulates chemoattractant receptors on monocytes by a CD4-dependent pathway.

The Profile of Angiogenic Factors in Vitreous Humor of the Patients with Proliferative Diabetic Retinopathy.

OBJECTIVE: To explore the expression profile of angiogenic factors associated with proliferative diabetic retinopathy (PDR). METHODS: Undiluted vitreous humor samples were obtained from 10 diabetic patients with PDR (10 eyes) and 9 non-diabtic patients (9 eyes). The concentrations of 60 angiogenic factors in the vitreous humor samples were measured by RayBio Angiogenic Cytokine Antibody Array. Some differentially expressed factors were further confirmed in vitreous humor by enzyme-linked immunosorbent assay (ELISA). RESULTS: Compared with the non-diabetic controls, 20 differentially expressed factors with more than 1.50 fold changes were detected in patients with PDR. The median concentration of vascular endothelial growth factor (VEGF), interleukin 6 (IL-6), angiopoietin (ANG)-1, ANG-2, urokinase-type plasminogen activator receptor (uPAR), Follistatin and matrix metalloproteinases 9 (MMP-9) was significantly increased in vitreous samples from PDR compared to controls (P < 0.05). However, (MCP)-1, Angiogenin and Leptin was significantly lower in PDR eyes compared to controls (P < 0.05). In the verification assay using ELISA, ANG-1, ANG-2, IL-6, VEGF, MMP-9, hepatocyte growth factor (HGF) and placenta growth factor (PIGF) concentration were increased in patients with PDR compared to controls (all P-values < 0.05). CONCLUSION: This is the first report of a comprehensive multiplex analysis to identify angiogenic factors associated with PDR. These angiogenic factors may contribute to the pathogenesis of PDR and may be targets for therapeutic strategies of PDR.

Epithelial-mesenchymal transition of ovarian cancer cells is sustained by Rac1 through simultaneous activation of MEK1/2 and Src signaling pathways.

Epithelial-mesenchymal transition (EMT) is regarded as a crucial contributing factor to cancer progression. Diverse factors have been identified as potent EMT inducers in ovarian cancer. However, molecular mechanism sustaining EMT of ovarian cancer cells remains elusive. Here we show that the presence of SOS1/EPS8/ABI1 complex is critical for sustained EMT traits of ovarian cancer cells. Consistent with the role of SOS1/EPS8/ABI1 complex as a Rac1-specific guanine nucleotide exchange factor, depleting Rac1 results in the loss of most of mesenchymal traits in mesenchymal-like ovarian cancer cells, whereas expressing constitutively active Rac1 leads to EMT in epithelial-like ovarian cancer cells. With the aid of clinically tested inhibitors targeting various EMT-associated signaling pathways, we show that only combined treatment of mitogen-activated extracellular signal-regulated kinase 1/2 (MEK1/2) and Src inhibitors can abolish constitutively active Rac1-led EMT and mesenchymal traits displayed by mesenchymal-like ovarian cancer cells. Further experiments also reveal that EMT can be induced in epithelial-like ovarian cancer cells by co-expressing constitutively active MEK1 and Src rather than either alone. As the activities of Erk and Src are higher in ovarian cancer cells with constitutively active Rac1, we conclude that Rac1 sustains ovarian cancer cell EMT through simultaneous activation of MEK1/2 and Src signaling pathways. Importantly, we demonstrate that combined use of MEK1/2 and Src inhibitors effectively suppresses development of intraperitoneal xenografts and prolongs the survival of ovarian cancer-bearing mice. This study suggests that cocktail of MEK1/2 and Src inhibitors represents an effective therapeutic strategy against ovarian cancer progression.

Higher risk for thyroid diseases in physicians than in the general population: a Taiwan nationwide population-based secondary analysis study.

BACKGROUND: Physicians have high work stress, responsibility for night shifts and chances of exposure to medical radiation, which may increase the risk for thyroid diseases. AIM: We conducted this study to assess the risk for thyroid diseases in physicians, which remain unclear. DESIGN: We used a secondary analysis of the Taiwan National Health Insurance Research Database for this study. METHODS: After excluding thyroid diseases occurring before 2006 and residents, physicians and general population were identified by matching with age and sex in 2009 in a 1:2 ratio. The risk for thyroid diseases was compared between the physicians and general population and among physicians by tracing their medical histories between 2006 and 2012. RESULTS: In total, 28,649 physicians and 57,298 general population were identified. Physicians had a higher risk for overall thyroid diseases than the general population [odds ratio (OR): 1.27; 95% confidence interval (CI): 1.10-1.47], including individual thyroid disease: thyroid cancer (OR: 1.89; 95% CI: 1.22-2.95), hypothyroidism (OR: 1.64; 95% CI: 1.23-2.18) and thyroiditis (OR: 1.48; 95% CI: 1.00-2.19). CONCLUSIONS: We showed that physicians had a significantly higher risk for thyroid diseases than the general population. This reminds us to pay more attention to thyroid diseases in physicians. Further studies about the underlying mechanisms are warranted.

Overexpression of p8 is inversely correlated with apoptosis in pancreatic cancer.

A recently identified gene, p8, has cell growth-promoting activity and is strongly induced in acute pancreatitis. In this study, we detected p8 and single-stranded DNA (ssDNA) for apoptosis by immunohistochemistry in human pancreatic cancer. The p8 was overexpressed (>30% per 1000 cancer cells) in 26 of 44 (59%) pancreatic cancers, and apoptosis (ssDNA-positive cells >10% per 1000 cancer cells) was recognized in 18 of 44 (41%) pancreatic cancers. There was a significant inverse correlation between the p8 overexpression and apoptosis (P < 0.05). Moreover, the expression pattern of high p8 and low ssDNA was seen significantly more often in lower age (<65 years), in moderately or poorly differentiated cancers, and in node-positive cases (P < 0.05). The p8 expression and apoptosis were not significantly correlated with survival. These results suggest that p8 overexpression is involved in antiapoptotic activity and the biological characteristics of pancreatic cancer.

Expression of p8 in human pancreatic cancer.

The p8 gene is a recently identified gene with mitogenic activity. p8 expression is induced in acute pancreatitis, pancreatic development, and regeneration. However, the expression of p8 in pancreatic cancer is not reported. We investigated p8 expression in 72 human pancreatic tissues, including 38 pancreatic cancers (PCs), by immunohistochemistry. p8 was overexpressed (positive cells >25% in 1,000 cells) in 71% (27 of 38) of PCs, but in only 17% (3 of 18) of chronic pancreatitis cases. There was no overexpression in mucinous cystadenoma or in normal pancreas. The p8 overexpression rate in PC was significantly higher than that in other conditions (P < 0.05). Reverse transcription-PCR analysis confirmed p8 mRNA overexpression (tumor/nontumor ratio >2) in 75% (3 of 4) of PCs. p8 was overexpressed also in human pancreatic cancer cell lines (MIA PaCa-2 and PANC-1). These results suggest that p8 is involved in the development of pancreatic cancer, reflecting its mitogenic activity.

Rapid secretion of intracellularly pre-stored interleukin-8 from rabbit platelets upon activation.

Freshly isolated rabbit platelets contained a substantial amount of intracellular interleukin-8 (IL-8) as revealed by immunohistochemistry and Western blotting analysis. Thrombin stimulation at room temperature induced platelets to secrete IL-8 rapidly, and the maximal secretion was observed within 10 min after the activations. Secreted IL-8 possessed neutrophil chemotactic activity that was neutralized by a specific neutralizing monoclonal antibody to rabbit IL-8 but not a control one. These results suggest that rabbit platelets store biologically active IL-8 intracellularly and secrete it rapidly upon activation. This study implies that platelets may be a pivotal participant in inflammatory reactions in rabbits through producing cytokines and chemokines, including IL-8.

Preparation of specific polyclonal antibodies to a C-C chemokine receptor, CCR1, and determination of CCR1 expression on various types of leukocytes.

cDNA cloning has revealed the presence of at least three distinct human receptors for macrophage inflammatory protein-1alpha (MIP-1alpha) and RANTES: C-C chemokine receptor (CCR) 1, 4, and 5. To clarify the physiological role of CCR1, we prepared specific antibodies to CCR1 by immunizing rabbits with recombinant glutathione-S-transferase (GST) fused with its NH2-terminal portion. The resultant antibodies stained positively 293 cells transfected with CCR1 cDNA but neither parental cells nor cells transfected with CXCR1 [interleukin-8 (IL-8) receptor type A] cDNA, confirming its specificity. Immunofluorescence analysis revealed that peripheral blood lymphocytes and monocytes but not neutrophils express CCR1. Positive staining of transfectants, monocytes, and lymphocytes was inhibited by the GST protein fused with the NH2-terminal portion of CCR1, further indicating that this antibody recognized the NH2-terminal portion of CC CKR1. A majority of CD3+, CD4+, CD8+, or CD16+ peripheral blood lymphocytes but not CD19+ lymphocytes expressed CCR1. Among CD4+ peripheral blood lymphocytes, CD45RO+ cells expressed a larger number of CCR1 compared with CD45RO-. Moreover, CD34+ cells in human bone marrow as well as cord blood were uniformly stained with this antibody. Furthermore, the antibody inhibited calcium mobilization in CCR1 transfectants stimulated with human rMIP-1alpha, suggesting that its NH2-terminal portion is critically involved in ligand binding or signaling. Finally, the antibody partially inhibited monocyte chemotactic activities of human rMIP-1alpha, suggesting that CCR1 is a functional receptor for MIP-1alpha on human peripheral blood monocytes.