ABSTRACT
Objective: To understand the health status of solar greenhouse workers, to provide scientific basis for the development of occupational high incidence diseases prevention and control strategies. Methods: In July 2019, a random cluster sampling method was used to select 245 workers engaged in solar greenhouse vegetable cultivation in Daba Village, Jingyuan County, Baiyin City, Gansu Province as the solar greenhouse operation group. Matched by gender, age, marital status, body mass index (BMI), 282 people from adjacent Shaliang Village who did not engage in solar greenhouse operation were selected as the control group. Field investigation and health examination were carried out among the study subjects. The general situation, facial features examination results, ophthalmic examination results, bone and joint examination results and skin examination results were compared between the two groups. And the multiple logistic regression analysis was used to analyze the influencing factors of abnormal bone and joint examination (upper limbs, lower limbs, hands and spine bone joints) in study subjects. Results: There were statistically significant differences in smoking age and alcohol consumption between the two groups (P<0.001). Compared with the control group, the abnormal detection rates of nose examination, throat examination, slit lamp examination, conjunctival examination, lower limb bone joint examination, hand bone joint examination, spine examination, head and neck skin examination, trunk skin examination, upper limb skin examination, and lower limb skin examination in the solar greenhouse operation group were higher, and the differences were statistically significant (χ(2)=11.53, 7.94, 9.92, 27.93, 79.32, 81.42, 9.43, 6.79, 9.76, 4.34, 8.29, P<0.05). Multivariate logistic regression analysis showed that after adjusting for gender, age, marital status, education level, BMI, compared with the control group, solar greenhouse operation was a risk factor for abnormal bone and joint examination (OR=1.178, 95%CI: 1.151-2.143, P=0.001) . Conclusion: Solar greenhouse operation has a certain harmful effect on health of workers, and solar greenhouse workers have an increased risk of abnormal diseases of upper limbs, lower limbs, hands and spine bone joints.
Subject(s)
Occupational Exposure , Humans , Male , Female , Incidence , Adult , Occupational Diseases/epidemiology , Occupational Diseases/etiology , Risk Factors , Middle Aged , Sunlight , China/epidemiology , Logistic ModelsABSTRACT
OBJECTIVE: To evaluate the effect of equal temperature bladder irrigation on bladder spasm, postoperative bleeding, vital signs and discomfort of chills in patients of transurethral resection of prostate using meta-analysis. METHODS: Several electronic databases included Cochrane Library, PubMed, Embase, China National Knowledge Infrastructure (CNKI), Wanfang, VIP, China Biology Medicine (CBM) were searched systematically for published randomized controlled trial about equal temperature bladder irrigation in patients with transurethral resection of prostate before November 20, 2019. Two reviewers selected independently the literature in the light of the inclusion and exclusion criteria, assessed the risk of bias by quality assessment and extracted data which were consisted of clinical efficacy indexes, such as incidence of bladder spasm, severity of bladder spasm, incidence of tube plugging, amount of bladder flushing fluid, time of bladder flushing, heart rate, systolic pressure, diastolic pressure, and incidence of chills. Data were pooled using fixed-effects model or random-effects model, and the summary effect measure was calculated by risk ratio (RR) or mean difference (MD) and 95% confidence interval (95%CI). Meta-analysis was performed by Review Manager 5.3 Software. RESULTS: In the study, 13 randomized controlled trails met the requirement with a total of 2 033 patients of transurethral resection of prostate were included, of whom 1 015 were carried out with equal temperature bladder irrigation and 1 018 with room temperature bladder irrigation. The results of meta-analysis showed that incidence of bladder spasm [RR=0.51, 95%CI (0.45, 0.57), P < 0.001], severity of bladder spasm [MD=-1.61, 95%CI (-2.00, -1.23), P < 0.001], incidence of urinary blockage [RR=0.29, 95%CI (0.19, 0.44), P < 0.001], dosage of bladder irrigation [MD=-6.75, 95%CI (-7.33, -6.17), P < 0.001], time of bladder rinse [MD=-7.60, 95%CI (-11.91, -3.29), P < 0.001], heart rate [MD=-13.68, 95%CI (-15.19, -12.17), P < 0.001], systolic pressure [MD=-29.26, 95%CI (-31.92, -26.59), P < 0.001], diastolic pressure [MD=-29.36, 95%CI (-31.75, -26.98), P < 0.001], incidence of chills and discomfort [MD=0.37, 95%CI (0.31, 0.44), P < 0.001] in equal temperature group of the patients with transurethral resection of prostate had significantly statistical difference compared with room temperature group. CONCLUSION: Based on current available evidence, equal temperature bladder irrigation reduced the incidence of bladder spasm and urinary blockage, relieved bladder spasm, reduced dosage and time of bladder irrigation, and hardly affected normal vital signs and increased the patient' s comfort.
Subject(s)
Prostatic Hyperplasia , Transurethral Resection of Prostate , Male , Humans , Transurethral Resection of Prostate/adverse effects , Transurethral Resection of Prostate/methods , Urinary Bladder/surgery , Chills , Temperature , Prostatic Hyperplasia/surgery , Randomized Controlled Trials as TopicABSTRACT
OBJECTIVE: To investigate the correlation between drinking habits and pathological characteristics of patients with upper tract urothelial carcinoma (UTUC). METHODS: A preoperative questionnaire survey was conducted to understand the drinking habits of UTUC patients who were admitted to the Department of Urology, Peking University First Hospital for radical nephroureterectomy within one year from August 2020 to July 2021, and statistical analysis was performed in combination with their postoperative pathological characteristics. The statistical procedure was performed using SPSS 22.0 software, and firstly, the preliminary analysis was performed one by one using the columnar χ2 test on the pathological characteristics of UTUC tumors as the dependent variable and the factors related to patients' general information, past history and drinking habits as the independent variables, and the independent variables that met P < 0.2 between the case and control groups for each dependent variable were specified for screening. The screened variables were included in the binary Logistic regression analysis. A difference of P < 0.05 was used to indicate a statistically significant difference. RESULTS: A total of 239 patients, 134 males and 105 females, with a mean age of (68.1±9.98)years and a median disease duration of 4.8 months, were included in this study. Multifactorial Logistic regression results suggested that after adjusting for the effects of other variables, UTUC patients who had the habit of drinking at least once every hour during the daytime had a significantly increased risk of high grade (G3) tumors(OR=1.941, 95%CI: 0.352-1.029, P < 0.01); these patients also had a significantly decreased risk of multifocal UTUC tumors (OR=0.344, 95% CI: 1.18-5.582, P=0.004). The patients who had the habit of drinking over 100 mL water each time had a significantly decreased risk of mutifocal UTUC incidence (OR=0.477, 95%CI: 0.225-1.012, P=0.046). Patients who pay attention to daily water intakes had a significantly increased risk of renipelvic carcinoma (OR=2.530, 95%CI: 1.434-4.463, P=0.001) and a significantly decreased risk of ureteral carcinoma (OR=0.314, 95%CI: 0.172-0.573, P < 0.01). Other variables included in the regression model did not differ significantly in their effects on the occurrence of tumor pathological characteristics. CONCLUSION: Having the awareness of drinking water every 1 h during the day, drinking over 100 mL water each time, having the awareness of daily drinking habits correlated significantly with pathological characteristics of UTUC such as the presence of G3 tumor, multifocal tumors and location of the tumor. This conclusion still needs to be verified by subsequent trials with higher levels of evidence.
Subject(s)
Carcinoma, Transitional Cell , Ureteral Neoplasms , Urinary Bladder Neoplasms , Carcinoma, Transitional Cell/surgery , Female , Habits , Humans , Male , Neoplasm Recurrence, Local/epidemiology , Retrospective Studies , Ureteral Neoplasms/epidemiology , Ureteral Neoplasms/surgery , Urinary Bladder Neoplasms/surgery , WaterABSTRACT
Objective: To analyze the folate status among women of childbearing age worldwide from 2000 to 2020, and explore the impact of socioeconomic factors on folate status, so as to provide support for the formulation of relevant supplementary policies in China in the future. Methods: The "folate" "folic acid" "deficiency" "status" "women" "childbearing" and "reproductive" were used as Chinese and English keywords to systematically search CNKI and PubMed database. Global Health Data Exchange database (GDHx), Biomarkers Reflecting Inflammation and Nutritional Determinants of Anemia datasets (BRINDA) and Ground Work publications were systematically searched with "micronutrients" and "nutrition" as keywords. The retrieval time was from January 1, 2000 to August 31, 2020, and the language was restricted to English and Chinese. After title, abstract and full-text screening, a total of 45 literatures were included. The folate status of women of childbearing age in the eligible literature was analyzed, and the income and folate status were tested by Kruskal Wallis H test and Nemenyi test. Results: The M (Q1, Q3) of serum folate deficiency rate and erythrocyte folate insufficiency rate in women of childbearing age were 15.0% (3.5%, 37.0%) and 49.0% (22.0%, 83.0%). There were great differences in serum folate status and serum folate deficiency rate among women of childbearing age in different income countries. The serum folate deficiency rate of women of childbearing age in low-income countries was significantly higher than that in middle and high-income countries. Conclusion: The folate status of women of childbearing age in most countries has not reached the ideal state from 2000 to 2020. More studies on folate supplementation programs should be carried out.
Subject(s)
Anemia , Folic Acid Deficiency , Erythrocytes , Female , Folic Acid , Folic Acid Deficiency/epidemiology , Humans , Nutritional StatusABSTRACT
Objective: The study investigated and analyzed the health-related quality of life of diabetes patients in Gansu province before and after the healthcare reform and its influencing factors, so as to provide scientific evidence to improve the health-related quality of life of diabetes patients. Methods: The study used data of the fourth and sixth national health service household survey in Gansu province before (2008) and after (2018) medical reform separately, and EQ-5D health utility index was calculated on the basis of Chinese time frade-off values for EuroQol Five-Dimensions Questionnaire Utility Value scoring system. Results: Compared with the period before the healthcare reform, the five dimensions of EQ-5D for residents, aged 15 and above in Gansu, changed significantly after the healthcare reform: action capability improved by 8.08% (27.43% vs. 19.35%), self-care improved by 16.16% (26.55% vs. 10.39%), normal activity improved by 8.97% (28.32% vs. 19.35%), pain/discomfort worsened by 1.38% (38.05% vs. 39.43%), anxiety/depression worsened by 1.83% (16.81% vs. 18.64%), and the EQ-VAS score increased by 3.36 (60.53 vs. 63.89). The health utility index increased by 0.04 (0.83 vs. 0.87). Multivariate regression analysis results showed that the dimension influence factors were not completely consistent, on the whole, the health-related quality of life of diabetes patients with older age, lower education level, no physical exercise and multi chronic diseases was worse (P<0.05), and multiple chronic disease had the most serious effect on the health of patients with diabetes. The health-related quality of life of diabetes patients with the medical insurance in urban area and after the new medical reform was higher (P<0.05). Conclusion: The new healthcare reform has active influence on the health-related quality of life of diabetes patients in Gansu province, health care providers and policy makers should pay attention to the impacts of multi prechronic diseases on the health-related quality of life of diabetes patients and the mental health of patients with diabetes.
Subject(s)
Diabetes Mellitus , Quality of Life , Aged , Diabetes Mellitus/therapy , Health Care Reform , Health Status , Humans , State MedicineABSTRACT
OBJECTIVE: To analyze the prognostic factors affecting the failure of transvaginal repair of vesicovaginal fistula (VVF). METHODS: A retrospective nested case-control study was conducted. A total of 15 patients who underwent unsuccessful transvaginal vesicovaginal fistula repair in the Department of Urology, Peking University First Hospital from January 2014 to December 2020 were enrolled as the case group. A total of 60 patients receiving transvaginal vesicovaginal fistula repair by the same surgeon within the same time range, were selected as the control group. The age, body mass index (BMI), etiology of vesicovaginal fistula, associated genitourinary malformation, frequency of repair, characteristics of fistula, surgical procedure, postoperative recovery and other factors were compared between the case group and the control group, and the influencing factors of failure were analyzed. RESULTS: The BMI of the case group was (26.3±3.9) kg/m2, the diameter of vaginal fistula was (1.5±0.8) cm, and the operative time of transvaginal repair was (111.8±19.8) min. The proportion of the patients with genitourinary malformations was 4/15, the proportion of the patients with multiple vaginal repairs was 13/15, the proportion of the patients with concurrent ureteral reimplantation was 6/15, and the proportion of the patients with postoperative fever was 5/15. In the control group, the BMI was (23.9±3.0) kg/m2, the diameter of vaginal fistula was (0.8±0.5) cm, the operative time of transvaginal repair was (99.9±19.7) min, the rate of associated genitourinary malformation was 2/60, the rate of multiple transvaginal repair was 18/60, the rate of concurrent ureteral reimplantation was 5/60, and no postoperative fever was found. Compared with the control group, the case group had higher BMI (P=0.013), bigger vaginal fistula (P=0.002), longer time of operation (P=0.027), higher proportion of genitourinary malformations (P=0.013), higher proportion of repeated transvaginal repair (P < 0.001), higher proportion of ureter reimplantation (P=0.006), and higher proportion of postoperative fever (P < 0.001). Multivariate analysis showed that fistula diameter ≥1 cm (OR=10.45, 95%CI=1.90-57.56, P=0.007) and repeated transvaginal repair (OR=16.97, 95%CI=3.17-90.91, P=0.001) were independent prognostic factors for VVF failure in transvaginal repair. CONCLUSION: Fistula diameter ≥1 cm and repeated transvaginal repair are independent prognostic factors of failure in transvaginal repair.
Subject(s)
Vesicovaginal Fistula , Case-Control Studies , Female , Gynecologic Surgical Procedures , Humans , Prognosis , Retrospective Studies , Treatment Outcome , Vesicovaginal Fistula/etiology , Vesicovaginal Fistula/surgeryABSTRACT
Objective: To compare and analyze the effect of minimally invasive surgery and traditional open surgery in patients with spinal canal tumors, including intraspinal and extraspinal communication tumors. Methods: From 2017 to 2019, 31 patients (minimally invasive channel group) were included in the neurosurgery department of Huashan Hospital Affiliated to Fudan University, and 38 patients (open operation group) were selected as the control group. From the aspects of intraoperative condition, operative effect, postoperative muscle injury, postoperative complications, postoperative spinal stability, the minimally invasive access group and the open operation group were compared and analyzed. Results: The bleeding volume (70.2 ml±4.9 ml), operation time (164.7 min±16.0 min) and hospitalization days (9.5±2.5) in the minimally invasive access group were significantly lower than those in the open operation group (P<0.001). The creatine kinase CK (363.9 U/L±51.6 U/L) in the minimally invasive group was significantly lower than that in the open group (514.2 U/L±68.3 U/L) (P<0.001). According to Panjabi standard, the effect of spinal cord stability in minimally invasive group was significantly lower than that in open operation group (P<0.001), and the symptom improvement rate in minimally invasive group was significantly higher than that in open hand group (P<0.05). Conclusions: Compared with the open surgery, the amount of bleeding, the length of incision, the time of operation and the days of hospitalization were significantly shorter, the degree of muscle damage was also significantly reduced, the incidence of complications was lower, the impact of spinal stability was smaller, and the overall advantage was obvious.
Subject(s)
Lumbar Vertebrae , Spinal Neoplasms , Humans , Minimally Invasive Surgical Procedures , Retrospective Studies , Treatment OutcomeABSTRACT
OBJECTIVE: To explore risk factors of urinary incontinence (UI) and influences of UI on quality of life in female medical staff from Beijing. METHODS: One hundred and forty-six female medical personnel were included in the present study through the convenient sampling method in Peking University First Hospital. The questionnaires contained the following information: demographic information, daily urination condition, the severity of UI [international consultation on incontinence questionnaire short form (ICI-Q-SF)], and the influences of UI on quality of life (QOL). We excluded the subjects who were in pregnancy or had urinary infection, neurogenic bladder, or urethral stricture. We used SPSS 21.0 software (IBM Corp, Armonk, NY) for statistical analysis. The Kolmogorov-Smirnov test determined the normality of the continuous variables. Means and standard deviation presented continuous variables in normality. Median and range presented continuous variables without normality. Frequency and percentile were used to present categorical or ranked variables. RESULTS: There were 63 out of 146 (43.2%) female medical staff suffering from UI. The mean age and body mass index of the whole study cohort were (39.4±9.9) years and (22.3±3.4) kg/m2. The median delivery times of all the subjects were 1 time (range: 0-3 times). Fifty out of 146 (34.2%) subjects had transvaginal delivery history. Chronic constipation was diagnosed in 32 subjects (21.9%). No significant difference in daytime micturition and nocturia times were found between the UI and non-UI subjects. According to the multivariate analysis, chronic constipation (OR=4.95, 95%CI=1.81-13.53, P=0.002) and transvaginal delivery history (OR=3.50, 95%CI=1.49-8.21, P=0.004) were independent risk factors for UI. The non-UI subjects had superior quality of life than the UI subjects in terms of incontinence quality of life (I-QOL) total scores and all sub-scores of avoidance and limiting behaviors, psychosocial impacts, and social embarrassment (P<0.001). In addition, avoidance and limiting behaviors (r=-0.449, P<0.001), psychosocial impacts (r=-0.538, P<0.001), and social embarrassment (r=-0.454, P<0.001) of the 63 UI subjects were equally influenced by the incontinence symptom. CONCLUSION: UI is not uncommon in female medical staff. The quality of life of medical faculty is influenced by UI in terms of avoidance and limiting behaviors, psychosocial impacts, and social embarrassment. Chronic constipation and transvaginal delivery history were independent risk factors for UI.
Subject(s)
Quality of Life , Urinary Incontinence , Adult , Female , Humans , Medical Staff , Middle Aged , Pregnancy , Risk Factors , Surveys and QuestionnairesABSTRACT
Prevalence of disseminated Penicillium marneffei infection is not known in human immunodeficiency virus (HIV)-infected patients. This retrospective study aimed to evaluate the prevalence of and risk factors for disseminated P. marneffei infection in HIV-infected patients during 2004-11 in Guangzhou, China. We tested 8131 archived HIV-infected patient serum samples for P. marneffei-specific mannoprotein (Mp1p) antigen using a highly sensitive and specific ELISA that we previously established. The CD4 count of 2686 cases was determined by flow cytometry. Logistic regression was used to assess predictors of Mp1p antigenaemia. The overall prevalence of disseminated penicilliosis as detected by positive serum Mp1p antigen was 9.36% (761/8131), in good concordance with Platelia™ Aspergillus immunoassay. During 2004-11, the prevalence increased to a peak of 12.58% (158/1256) in 2010 and decreased in 2011. Penicilliosis was strongly associated with progression from HIV to AIDS (OR 4.66, 95% CI 3.94-5.51, p <0.001) and humidity (OR 1.02, 95% CI 1.01-1.03, p 0.002). Disseminated penicilliosis occurred mainly during the rainy seasons (p <0.001). For 2686 cases with known CD4 count, logistic regression showed that CD4 count of <200 cells/µL was a risk factor for penicilliosis (OR 2.90, 95% CI 1.10-7.66, p 0.032), especially when it was <50 cells/µL (OR 24.26, 95% CI 10.63-55.36, p <0.001) during which 28.06% of patients developed disseminated penicilliosis. In conclusion, approximately 9.36% of the HIV-infected patients in our study developed disseminated penicilliosis. Rapid diagnosis may be achieved by performing serological surveillance for Mp1p antigenaemia as a routine procedure for all HIV-infected patients with CD4 count of <50 cells/µL.
Subject(s)
Antigens, Fungal/blood , Fungemia/epidemiology , Fungemia/microbiology , HIV Infections/complications , Membrane Glycoproteins/blood , Penicillium/isolation & purification , Adult , CD4 Lymphocyte Count , China/epidemiology , Enzyme-Linked Immunosorbent Assay , Epidemiological Monitoring , Female , Flow Cytometry , Humans , Retrospective Studies , Risk Factors , Seroepidemiologic StudiesABSTRACT
Aspergillus fumigatus is one of the most prominent opportunistic fungal pathogens in immunocompromised hosts. Early recognition of this infection along with prompt antifungal therapy may increase the survival rate. We expressed two potential bio-markers of A. fumigatus infection-galactomannoprotein Afmp1p and Afmp4p in Pichia pastoris. We generated 33 monoclonal antibodies (MAbs), 20 against recombinant Afmp1p (rAfmp1p) and the other 13 against recombinant Afmp4p (rAfmp4p). Subsequently, we developed two antigen-capture enzyme-linked immunosorbent assays (ELISAs) which employed MAbs as both the capture and the detection antibodies for rAfmp1p and rAfmp4p. The two antigen-capture ELISAs specifically detected Afmp1p/Afmp4p in cultures of A. fumigatus and had no cross-reaction with other tested pathogenic fungi, including Penicillium marneffei and other pathogenic Aspergillus species. The Afmp1p-captured ELISA would be positive even when the culture supernatant of A. fumigatus had been diluted to 128-fold of its original concentration. The two antigen ELISAs could capture circulating or excreted antigens during the acute phase of invasive aspergillosis (IA) in the animal model, and had no cross-reactivity to other Aspergillus-challenged animal models. We developed two antigen-capture ELISAs for the laboratory diagnosis of A. fumigatus infection. These two antigen-capture ELISAs may be useful in the clinical diagnosis of aspergillosis.
Subject(s)
Antibodies, Fungal , Antibodies, Monoclonal , Antigens, Fungal/analysis , Aspergillosis/diagnosis , Clinical Laboratory Techniques/methods , Fungemia/diagnosis , Membrane Glycoproteins/analysis , Mycology/methods , Animals , Disease Models, Animal , Enzyme-Linked Immunosorbent Assay/methods , Rabbits , Sensitivity and SpecificityABSTRACT
We cloned the AFMP1 gene, which encodes the first antigenic cell wall galactomannoprotein in Aspergillus fumigatus. AFMP1 codes for a protein, Afmp1p, of 284 amino acid residues, with a few sequence features that are present in Mp1p, the antigenic cell wall mannoprotein in Penicillium marneffei that we described previously, as well as several other cell wall proteins of Saccharomyces cerevisiae and Candida albicans. It contains a serine- and threonine-rich region for O glycosylation, a signal peptide, and a putative glycosylphosphatidyl inositol attachment signal sequence. Specific anti-Afmp1p antibody was generated with recombinant Afmp1p protein purified from Escherichia coli to allow further characterization of Afmp1p. Afmp1p has a high affinity for Galanthus nivalis agglutinin, a characteristic indicative of a mannoprotein. Furthermore, it was recognized by a rat monoclonal antibody against the galactofuran side chain of galactomannan, indicating that it is a galactomannoprotein. Ultrastructural analysis by immunogold staining indicated that Afmp1p is present in the cell walls of the hyphae and conidia of A. fumigatus. Finally, it was observed that patients with aspergilloma and invasive aspergillosis due to A. fumigatus develop a specific antibody response against Afmp1p. This suggested that the recombinant protein and its antibody may be useful for serodiagnosis in patients with aspergilloma or invasive aspergillosis, and the protein may represent a good cell surface target for host humoral immunity.
Subject(s)
Antibodies, Fungal/blood , Antigens, Fungal , Aspergillosis/diagnosis , Aspergillus fumigatus/immunology , Membrane Glycoproteins , Amino Acid Sequence , Antigens, Fungal/analysis , Antigens, Fungal/genetics , Antigens, Fungal/immunology , Aspergillus fumigatus/genetics , Aspergillus fumigatus/ultrastructure , Base Sequence , Cloning, Molecular , Humans , Membrane Glycoproteins/analysis , Membrane Glycoproteins/genetics , Membrane Glycoproteins/immunology , Molecular Sequence Data , Sequence Analysis, DNA , Serologic TestsABSTRACT
A 23 kDa peptide of the major structural protein of the hepatitis E virus (HEV) expressed in E. coli was found to naturally interact with one another to form homodimers and the peptide was recognized strongly in its dimeric form by HEV reactive human sera. To determine if the peptide may confer protection against HEV infection, three monkeys were immunized with the purified peptide and three were given placebo. Both groups of animals were challenged with 10(5) genome equivalent dose of the homologous strain of HEV. All control animals excreted the virus for 10-12 days beginning 5 days after the infection. The viral genome was also present in the peripheral blood monocyte (PBMC) samples from two animals, but it was not detected in the plasma samples from any of the animals. The infection in two control animals was accompanied by HEV seroconversion. Immunization was found to abrogate HEV stool excretion in two animals and reduced the viral excretion to one day in the third. None of the immunized animals showed detectable HEV in plasma or PBMC samples nor did the animals showed evidence of HEV seroconversion. These results suggested that immunization with the bacterially expressed peptide may prevent experimental infection of primates with the homologous strain of HEV.
Subject(s)
Escherichia coli/genetics , Hepatitis E virus/immunology , Hepatitis E/prevention & control , Peptides/genetics , Peptides/therapeutic use , Animals , Glutathione Transferase/biosynthesis , Hepatitis E/virology , Immunization Schedule , Macaca mulatta , Recombinant Fusion Proteins/biosynthesis , Recombinant Fusion Proteins/therapeutic use , Viral Envelope Proteins/biosynthesis , Viral Envelope Proteins/genetics , Viral Envelope Proteins/isolation & purificationABSTRACT
A 23 kDa peptide locating to amino acid residues 394 to 604 of the major Hepatitis E Virus (HEV) structural protein was expressed in E. coli. This peptide was found to interact naturally with one another to form homodimers and it was recognized strongly and commonly in its dimeric form by HEV reactive human sera. The antigenic activity associated with the dimeric form was abrogated when the dimer was dissociated into monomer and the activity was reconstituted after the monomer was re-associated into dimer again. The dimeric form of the peptide elicited a vigorous antibody response in experimental animals and the resulting antisera were found to cross-react against HEV, effecting an efficient immune capture of the virus. These results attributed the antigenic activity associated with the dimeric form of the peptide to conformational antigenic determinants generated as a result of interaction between the peptide molecules. It is suggested that some of these antigenic determinants may be expressed by the HEV capsid and raised the possibility of this bacterially expressed peptide as an HEV vaccine candidate.
Subject(s)
Hepatitis E virus/chemistry , Hepatitis E/virology , Viral Structural Proteins/genetics , Animals , Blotting, Western , Epitopes/biosynthesis , Epitopes/chemistry , Epitopes/immunology , Escherichia coli/genetics , Hepatitis Antibodies/blood , Hepatitis Antigens/biosynthesis , Hepatitis Antigens/chemistry , Hepatitis Antigens/immunology , Hepatitis E/blood , Humans , Immune Sera/immunology , Open Reading Frames , Rabbits , Recombinant Proteins/biosynthesis , Recombinant Proteins/immunology , Viral Structural Proteins/chemistry , Viral Structural Proteins/immunologyABSTRACT
Antitumor immune responses are mediated primarily by T cells. Downregulation of the major histocompatibility complex (MHC) and the molecules that costimulate the immune response is associated with defective signaling by tumor cells for T-cell activation. In vitro treatment with a combination of cytokines significantly increased the expression of MHC class I and adhesion molecules on tumor cell surfaces. When tumor cells were first incubated with a bispecific monoclonal antibody that binds antigen on tumor cells to CD28 on T cells, the modified tumor cells become immunogenic and are able to stimulate naive T cells, generating tumor-specific cytotoxic T cells in vitro. Immunization with the modified tumor cells elicits an immune response mediated by CD8+ T cells. This response protected against a challenge with parental tumor cells and cured established tumors. The approach was effective in both low immunogenic and nonimmunogenic tumor model systems. Modification of tumor cells with this two-step procedure may provide a strategy for development of tumor vaccines that is effective for cancer immunotherapy.