ABSTRACT
Objective: To explore the genetic background and clinical features of patients with long QT syndrome type 3 (LQT3). Methods: This retrospective cohort included patients diagnosed with LQT3 at the Department of Cardiology, Renmin Hospital of Wuhan University from January 1998 to December 2022. Patients were categorized into compound type group and single type group based on the presence of a single SCN5A mutation. The two groups were followed up and the differences in baseline characteristics, electrocardiograms, and clinical events between the two groups and probands were compared. Kaplan-Meier curves were used for survival analysis, and the log-rank test was employed to compare the event-free survival rates of first cardiac events between the groups and probands. Results: A total of 97 LQT3 patients were enrolled, including 59 probands. The age at diagnosis was (23.45±19.86) years, with 46 patients (47.4%) being male. Among them, 89 patients were classified as single type group, while 8 patients were classified as compound type group. Genetic testing identified 49 SCN5A mutations, with missense mutations being the majority (91.8%), primarily located in transmembrane regions (40.8%, n=20), interdomain linker regions (28.6%, n=14), and C-terminus (22.4%, n=11). The first cardiac event occurred in 44 patients (45.4%), with an onset age of (13.82±12.50) years. The main trigger was identified as rest or sleep (54.5%, n=24). Compared with patients in single type group, patients in compound type group were younger at diagnosis ((10.35±10.28) years vs. (24.63±20.13) years, P=0.040), had a significantly higher proportion of syncope (87.5% (7/8) vs. 33.7% (30/89), P=0.009), aborted cardiac arrest (62.5% (5/8) vs. 11.2% (10/89), P=0.001), and a lower incidence of event-free survival rates of first cardiac events (12.5% (1/8) vs.58.4% (52/89), log-rank P=0.001). The probands in compound type group had a significantly higher proportion of aborted cardiac arrest comparing to probands in single type group (62.5% (5/8) vs. 17.6% (9/51), P=0.020), while the difference in the incidence rate of event-free survival rates of first cardiac events between the probands in two groups was not statistically significant (12.5% (1/8) vs. 39.2% (20/51), log-rank P=0.08). Conclusion: Compound type LQT3 patients are not uncommon. Such patients are diagnosed at a younger age and exhibit more severe phenotypes, requiring close follow-up and proactive intervention strategies.
Subject(s)
Long QT Syndrome , Mutation , NAV1.5 Voltage-Gated Sodium Channel , Humans , Male , Female , Long QT Syndrome/genetics , Retrospective Studies , Adult , Young Adult , Adolescent , Child , NAV1.5 Voltage-Gated Sodium Channel/genetics , Middle Aged , Child, Preschool , Electrocardiography , Cardiac Conduction System DiseaseABSTRACT
With the extensive application of targeted drugs, the survival rate of cancer patients has been significantly improved. However, adverse reactions to the drugs have also become apparent, especially those affecting the ocular surface, which can severely impact patients' vision and quality of life. The article systematically analyzes a variety of targeted drugs, including epidermal growth factor receptor inhibitors, human epidermal growth factor receptor 2 inhibitors, fibroblast growth factor receptor inhibitors, selective estrogen receptor modulators, vascular endothelial growth factor receptor inhibitors, aromatase inhibitors, proteasome inhibitors, antibody-drug conjugates, Bruton's tyrosine kinase inhibitors, FMS-like tyrosine kinase 3 inhibitors, and cyclin-dependent kinase inhibitors, and discusses their adverse reactions on the ocular surface. The review emphasizes the role of clinicians in monitoring and managing patients' ocular surface health and the importance of early diagnosis and intervention to ensure that patients receive optimal visual protection while undergoing antitumor treatment.
Subject(s)
Antineoplastic Agents , Humans , Antineoplastic Agents/adverse effects , Neoplasms/drug therapy , Drug-Related Side Effects and Adverse ReactionsABSTRACT
Objective: To provide supports for the cancer prevention and control strategies in China by comparing the disease burden, epidemic trends, 5-year relative survival rate and major determinants of common cancers between China and the United States. Methods: A descriptive secondary analysis was conducted using data extracted from the GLOBOCAN database, the Surveillance, Epidemiology, and End Results database, Global Burden of disease 2019 database, and previous studies. The main indicators included the cases of malignant tumors in different sites, the cases of deaths, the age-standardized incidence (world standard incidence) and mortality (world standard mortality), the 5-year relative survival rate, and population attributable fraction (PAF). Results: In 2022, an estimated 4.825 million new cases and 2.574 million deaths of malignant neoplasms in China. The world standard incidence rate (201.6/100 000) in China was lower than that in the United States (367.0/100 000), and the world standard mortality rate (96.5/100 000) was higher than that in the United States (82.3/100 000). Lung cancer ranked first in the disease burden of malignant tumors in China, the new cases and deaths accounted for 22.0% and 28.5% of all malignant tumors, respectively. The top three malignant tumors in China were breast cancer (11.5%), prostate cancer (9.7%) and lung cancer (9.5%), which were also among the top five causes of death. However, the second to fifth leading causes of death from malignant tumors in China were digestive system tumors (liver cancer 12.3%, stomach cancer 10.1%, colorectal cancer 9.3%, and esophageal cancer 7.3%). From 2000 to 2018, the world standard incidence of malignant tumors showed an increasing trend and the world standard mortality of malignant tumors showed a decreasing trend in China, while the world standard incidence and mortality of malignant tumors in the United States showed a significant decreasing trend after 2000. The incidence of breast cancer, colorectal cancer and thyroid cancer increased rapidly in China, while the incidence and mortality of stomach cancer, liver cancer and esophageal cancer decreased, but they still had a heavy disease burden. From 2003 to 2015, the overall 5-year relative survival rate of malignant tumors increased from 30.9% to 40.5% in China. However, with the exception of esophageal cancer, the 5-year relative survival rates of other major malignant tumors were lower than those in the United States. In 2019, the PAF of malignant tumors death attributable to potential modifiable risk factors was 48.3% in China, which was similar to the United States (49.8%). Of these, smoking was the most important attributable risk factor, and the PAF was more than 30% both in China and the United States. In addition, about 18.8% of malignant tumors were caused by preventable chronic infections, such as hepatitis B virus and Helicobacter pylori, while less than 4% of malignant tumors in the United States were caused by infection. Conclusions: China has made great progress in the prevention and treatment of malignant tumors, but it still faces a serious disease burden. The cancer spectrum is changing from developing countries to developed countries. We should pay attention to modifiable factors, take comprehensive measures, and prevent cancer scientifically.
Subject(s)
Neoplasms , Humans , China/epidemiology , United States/epidemiology , Neoplasms/epidemiology , Incidence , Risk Factors , Survival Rate , Female , Male , Prevalence , Lung Neoplasms/epidemiology , Lung Neoplasms/mortality , Breast Neoplasms/epidemiology , Breast Neoplasms/mortality , Databases, Factual , Prostatic Neoplasms/epidemiology , Esophageal Neoplasms/epidemiology , Esophageal Neoplasms/mortality , Digestive System Neoplasms/epidemiology , Colorectal Neoplasms/epidemiology , Liver Neoplasms/epidemiology , Thyroid Neoplasms/epidemiologyABSTRACT
Objective: To determine the total and age-specific cut-off values of total prostate specific antigen (tPSA) and the ratio of free PSA divided total PSA (fPSA/tPSA) for screening prostate cancer in China. Methods: Based on the Chinese Colorectal, Breast, Lung, Liver, and Stomach cancer Screening Trial (C-BLAST) and the Tianjin Common Cancer Case Cohort (TJ4C), males who were not diagnosed with any cancers at baseline since 2017 and received both tPSA and fPSA testes were selected. Based on Cox regression, the overall and age-specific (ï¼60, 60-ï¼70, and ≥70 years) accuracy and optimal cut-off values of tPSA and fPSA/tPSA ratio for screening prostate cancer were evaluated with time-dependent receiver operating characteristic curve (tdROC) and area under curve (AUC). Bootstrap resampling was used to internally validate the stability of the optimal cut-off value, and the PLCO study was used to externally validate the accuracy under different cut-off values. Results: A total of 5 180 participants were included in the study, and after a median follow-up of 1.48 years, a total of 332 prostate cancer patients were included. In the total population, the tdAUC of tPSA and fPSA/tPSA screening for prostate cancer were 0.852 and 0.748, respectively, with the optimal cut-off values of 5.08 ng/ml and 0.173, respectively. After age stratification, the age specific cut-off values of tPSA in the <60, 60-<70, and ≥70 age groups were 3.13, 4.82, and 11.54 ng/ml, respectively, while the age-specific cut-off values of fPSA/tPSA were 0.153, 0.135, and 0.130, respectively. Under the age-specific cut-off values, the sensitivities of tPSA screening for prostate cancer in males <60, 60-70, and ≥70 years old were 92.3%, 82.0%, and 77.6%, respectively, while the specificities were 84.7%, 81.3%, and 75.4%, respectively. The age-specific sensitivities of fPSA/tPSA for screening prostate cancer were 74.4%, 53.3%, and 55.9%, respectively, while the specificities were 83.8%, 83.7%, and 83.7%, respectively. Both bootstrap's internal validation and PLCO external validation provided similar results. The combination of tPSA and fPSA/tPSA could further improve the accuracy of screening. Conclusion: To improve the screening effects, it is recommended that age-specific cut-off values of tPSA and fPSA/tPSA should be used to screen for prostate cancer in the general risk population.
Subject(s)
Early Detection of Cancer , Prostate-Specific Antigen , Prostatic Neoplasms , Humans , Male , Prostatic Neoplasms/diagnosis , Prostatic Neoplasms/blood , Prostate-Specific Antigen/blood , Aged , Middle Aged , Early Detection of Cancer/methods , Age Factors , ROC Curve , China , Sensitivity and Specificity , Mass Screening/methods , Area Under CurveABSTRACT
Posterior chamber phakic intraocular lens (pIOL) implantation has been widely adopted for the correction of refractive errors. Among pIOLs, the Implantable Collamer Lens is the most common choice. The selection of the appropriate pIOL size and achieving the desired postoperative vault to minimize complications has consistently been a focal point in academic research. With the advancement of ophthalmic biometric measurement technology and the application of artificial intelligence in the field of medicine, numerous new technologies and methods for pIOL size selection and vault prediction have emerged in recent years. This paper provides a comprehensive review on the topic of how to choose the pIOL size and predict the vault.
Subject(s)
Myopia , Phakic Intraocular Lenses , Humans , Artificial Intelligence , Myopia/surgery , Lens Implantation, Intraocular/methods , Anterior ChamberABSTRACT
The cornea is a transparent tissue with significant refractive and barrier functions. Corneal epithelium constitutes the first line of defense against foreign pathogens. Corneal epithelial cells interact to form a functionally selective permeability barrier. Dysfunction of this barrier leads to corneal impairment followed by a series of ocular surface diseases and even blindness. Tight junctions (TJ), located at the top of the intercellular space of corneal epithelial superficial cells, play a critical role in establishing and maintaining the barrier function. Previous studies have shown that destruction of the TJ acts as a crucial step of the occurrence and progression of multiple ocular surface diseases. Understanding the fundamental features and functions of the TJ, noticing the risk factors of TJ disruption, and clarifying the key role of TJ in the pathogenesis of various ocular surface diseases will help to better understand and treat ocular surface diseases.
Subject(s)
Corneal Diseases , Epithelium, Corneal , Cornea , Epithelium, Corneal/pathology , Humans , Permeability , Tight Junctions/pathologyABSTRACT
Choroidal thinning is an important feature of high myopia and has a negative correlation with the degree of myopia. However, due to the limitations of choroidal imaging, specific changes in choroidal thickness and vasculature are unclear. In recent years, the development of optical coherence tomography technology and optical coherence tomography angiography technology has made it possible to solve the problem. Emergence of biomarkers that objectively quantify choroidal thickness and vascular changes will help us understand the pathogenesis of high myopia and provide new ideas for the prognosis and treatment of myopia. In this review, in order to provide reference for clinical work, we summarize recent advances in the application of the two technologies in observing morphological changes of the choroid in high myopia and discuss the problems and prospects when they are combined with artificial intelligence for choroidal imaging. (Chin J Ophthalmol, 2021, 57: 459-464).
Subject(s)
Artificial Intelligence , Myopia , Angiography , Choroid/diagnostic imaging , Humans , Tomography, Optical CoherenceABSTRACT
OBJECTIVE: The relationship between hypertension and the mechanism of the expression of T-lymphocyte Kv1.3 channels in vascular aging has been analyzed in this study based on the gender and age matches' principle. PATIENTS AND METHODS: Thirty patients have been consecutively chosen with vascular aging caused by hypertension (group A), while 30 cases of high blood pressure not merged with vascular aging (group B) were chosen, and 30 cases of healthy volunteers (group C), conforming to gender and age 1:1 and the closest matching principle, were studied. The aim of this study was to separate the peripheral blood mononuclear cells and give intervention of 0.2 nmol/L ANGII to CD4 + T-lymphocytes, and store them in the incubator 48 h. The difference of Kv1.3 channel current of CD4 + T-lymphocyte, mRNA, angiotensin receptor (AT1R) protein mRNA, and IFN-γ density has also been compared. RESULTS: The membrane capacitance, peak current, and current density of group A, are higher than those of the other two groups, and the differences have statistical significance (p<0.05). After adding ANGII intervention to group A, the expression levels of T-lymphocyte Kv1.3 potassium channels mRNA, AT1R mRNA, and IFN-γ are significantly increased, so that the difference has statistical significance p<0.05, while the other two groups have no significant change (p>0.05). The levels of Kv1.3 potassium channels, AT1R mRNA, and IFN-γ of group A before and after the intervention are significantly higher than those of the other two groups, and the differences are statistically significant (p<0.05). CONCLUSIONS: Vascular aging caused by hypertension may be linked to the increase of Kv1.3 potassium channel activity of T-lymphocyte, while ANGII can improve the high expression of Kv1.3 potassium channel and AT1R, to stimulate lymph cells to secrete IFN-γ.
Subject(s)
Blood Vessels/growth & development , Blood Vessels/physiopathology , Hypertension/physiopathology , Adult , Aged , Aging , Blood Vessels/diagnostic imaging , CD4-Positive T-Lymphocytes/metabolism , Female , Humans , Kv1.3 Potassium Channel/metabolism , Male , Middle Aged , Receptor, Angiotensin, Type 1/biosynthesis , Receptor, Angiotensin, Type 1/metabolism , Sex Characteristics , T-Lymphocytes/metabolism , Ultrasonography, DopplerABSTRACT
Objective: To study intracranial mixed germ cell tumor diagnosis and reasonable treatment strategy. Methods: Clinical data of 17 patients with intracranial mixed germ cell tumor in Tsinghua university Yuquan hospital from October 2012 to October 2016 were retrospective analysed, including the characteristics of the general, the serum tumor markers of AFP, ß-HCG, and CEA, imaging findings, pathological results, treatment methods and prognosis. Results: There were 10 cases of male, 7 cases of female. The average age was (11.1±5.2) years old. Nine cases were gross total resection of lesions and 8 cases were subtotal resection of lesions. Eight cases (47.1%) were without recurrence and had more than four courses of chemotherapy after surgery, of which, 7 cases belonged to the gross total resection, and 1 case belonged to the subtotal resection. Nine (52.9%) patients relapsed, including 2 cases of the gross total resection and 7 cases of the subtotal resection. Among them, 4 cases were given second operations and 6 cases obtained satisfactory therapeutic effect by chemotherapy combined radiotherapy. There were 12 of 17 patients with pathological types contain teratoma (including mature, immature or malignant teratoma) ingredients, accounting for 70.6%. The average follow-up time was (17.5±12.1) months, 4 cases (23.5%) patients died. Conclusion: The diagnosis of intracranial mixed germ cell tumors needs comprehensive consideration of tumor markers in serum or cerebrospinal fluid, chemotherapy and radiotherapy before operation and pathological results. The gross total resection helps to reduce the chances of tumor recurrence. Rational chemotherapy and radiotherapy is helpful to prognosis.
Subject(s)
Neoplasms, Germ Cell and Embryonal , Adolescent , Biomarkers, Tumor , Child , Child, Preschool , Chorionic Gonadotropin, beta Subunit, Human , Female , Humans , Male , Neoplasm Recurrence, Local , Prognosis , Retrospective Studies , TeratomaABSTRACT
Objective: To introduce the surgical methods and investigate the treatment effects of conjunctival lesion resection combined with transplantation of allogeneic limbal epithelia cultured in vitro for treatment of varied large conjunctival lesions. Methods: A retrospective analysis of case data of the patients receiving transplantation of allogeneic limbal epithelia cultured in vitro for large conjunctival lesions at Qingdao Eye Hospital from January 2013 to December 2015 was conducted. Fresh donor corneal limbal epithelial tissues were obtained for cellular digestion and isolation. The cells were cultured on de-epithelized amniotic membrane to form a stratified cell sheet with 3 to 5 layers of cells for reservation. Conjunctival lesions were removed, and corneal limbal epithelial cell sheets corresponding to the size of the conjunctival defects were covered on the scleral flaps, before the conjunctivae were para sutured with corneal limbal epithelial cell sheets. The stitches were removed 7 days after surgery. The treatment effects were evaluated. Results: There were 11 cases (12 eyes) in this study, including 6 cases (6 eyes) of recurrent pterygium combined with symblepharon, 3 cases (3 eyes) of conjunctival compound nevus, 1 case (1 eye) of conjunctival primary acquired melanosis, and 1 case (2 eyes) of dermoid lipoma. The patients were 6 to 69 years old, with an average age of (46±23) years old. There were 5 male patients and 6 female patients. The follow-up time was 6 to 39 months, with an average time of (24.8±12.4) months. The conjunctival lesions in all patients were more than 2 quadrants. No patients had intraoperative and postoperative complications. No obvious irritation symptoms were observed after surgery. There were a few small pieces of epithelial defects on the limbal epithelial cell sheets at the end of the operation due to operative injury. With postoperative cellular proliferation and repair, the epithelium gradually healed and tended to become firm, and the boundaries with original conjunctival epithelium gradually disappeared. The healing time of the epithelium after surgery was 3 to 7 days, with an average time of (4.5±1.2) days. No immunological rejection occurred after surgery. No recurrence of original diseases was observed among all the patients at the last follow-up. Conclusions: Transplantation of allogeneic cultured limbal epithelial cells, which was carried out for the treatment of large conjunctival lesions, witnessed rapid epithelization at the areas of lesion resection. It could reduce the risk of recurrence of original diseases and effectively avoid the occurrence of postoperative symblepharon. The postoperative inflammatory reaction was also minor. (Chin J Ophthalmol, 2017, 53:172-176).
Subject(s)
Cornea/cytology , Corneal Transplantation/methods , Epithelium, Corneal , Limbus Corneae/cytology , Adult , Amnion , Conjunctiva , Conjunctival Neoplasms , Corneal Diseases , Epithelial Cells , Female , Humans , Male , Middle Aged , Neoplasm Recurrence, Local , Postoperative Complications , Retrospective Studies , Tissue Donors , Transplantation, Homologous , Visual Acuity , Wound HealingABSTRACT
OBJECTIVE: To analyze the relationship between clinical features of vasovagal syncope (VVS) and results of head-up tilt test (HUTT). METHOD: The study enrolled 146 children who were suspected with VVS from January 2014 to January 2015 in West China Second University Hospital, while other organic diseases were excluded, including 54 males and 92 females, aged from 5-17 years, whose average age was from (11.5±3.2) years old. Specified staff was assigned to inquire clinical histories, perform physical exam and HUTT composed of baseline HUTT (BHUTT) and sublingual nitroglycerin HUTT (SNHUTT). According to HUTT results, the patients were divided into two groups: HUTT positive group confirmed with VVS and HUTT negative group. The distributions of hemodynamic types and most common clinical manifestations were analyzed. The factors which were statistically significant in single factor analysis were selected to perform the Logistic regression for screening independent risk factors for HUTT positivity. RESULT: Of the 146 patients suspected with VVS, 86 cases were positive for HUTT, while 60 cases were negative. (1)HUTT hemodynamic types: In the total of 86 positive cases, 22 cases were positive at baseline for BHUTT (11 mixed response, 8 vasodepressor and 3 cardiodepressor), while 64 were positive in SNHUTT (34 mixed response, 21 vasodepressor and 9 cardiodepressor). (2)CLINICAL FEATURES: The most common manifestations in HUTT-positive group were, in order, headache or dizziness (66.3%), syncope (65.1%), chest tightness or fatigue (41.9%), nausea, vomiting or abdominal pain (25.6%), palpitation (10.5%). (3)The single factor analysis demonstrated that female (χ(2)=7.402, P=0.007), age>12 years (χ(2)=14.649, P<0.001), with family history (χ(2)=11.431, P=0.001) or flare-up of syncope (χ(2)=11.496, P=0.001) and headache or dizziness (χ(2)=5.589, P=0.018) were risk factors for positive HUTT. (4)Logistic regression analysis indicated that female (OR=2.396, P=0.006), age>12 years (OR=3.765, P=0.020), with family history (OR=1.998, P=0.023) or flare-up of syncope(OR=2.298, P=0.022) were independent risk factors for positive HUTT. CONCLUSION: Female, age>12 years, with family history or flare-up of syncope are related factors for positive HUTT.
Subject(s)
Syncope, Vasovagal/diagnosis , Syncope, Vasovagal/physiopathology , Tilt-Table Test , Abdominal Pain , Adolescent , Child , China , Dizziness , Female , Headache , Humans , Logistic Models , Male , Risk FactorsABSTRACT
The aim of this study was to explore the effect of atorvastatin intervention on plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP) and inflammatory cytokine levels in patients with heart failure (HF). One hundred and twenty-three HF patients were selected from our hospital and randomly divided into control (N = 61) and observation (N = 62) groups; the former received conventional treatment, while the latter were given conventional treatment combined with atorvastatin. Plasma NT-proBNP, inflammatory cytokines [high-sensitive C-reactive protein (hs-CRP), interleukin (IL)-6, IL-10] and cardiac function [left ventricular end-diastolic dimension (LVEDD), left ventricular ejection fraction (LVEF), end-diastolic maximum flow rate ratio (E/A)] were compared among groups. The effective rate of treating HF significantly increased after atorvastatin treatment. The plasma NT-proBNP, IL-6, IL-10, hs-CRP, and LVEDD levels significantly decreased (P < 0.05), while the LVEF and E/A levels significantly increased (P < 0.05) in the observation group compared to the control group and before intervention. The NT-proBNP and cytokine levels significantly differed among patients with different classes of heart function (P < 0.05); the NT-proBNP and cytokine levels increased with the severity of heart function. Pearson's correlation analysis revealed a negative correlation between the NT-proBNP and inflammatory cytokine levels and LVEF and E/A values, and a positive correlation between these factors and LVEDD (P < 0.05). In conclusion, atorvastatin significantly improves cardiac function; the mechanism atorvastatin action was related to the decrease in plasma NT-proBNP and inflammatory cytokine levels.
Subject(s)
Atorvastatin/therapeutic use , Cytokines/blood , Heart Failure/blood , Heart Failure/drug therapy , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Inflammation Mediators/blood , Natriuretic Peptide, Brain/blood , Peptide Fragments/blood , Adult , Aged , Biomarkers , Case-Control Studies , Echocardiography , Female , Heart Failure/diagnosis , Heart Failure/physiopathology , Heart Function Tests , Humans , Male , Middle Aged , Treatment OutcomeABSTRACT
We conducted a case-control study to investigate the genetic variants Interleukin-1ß(IL-1ß) +3953 C/T (rs1143634), IL-6 -174G/C (rs1800795), IL-8 -251T/A (rs4073), and IL-10 -1082A/G (rs1800896) and -819C/T (rs1800871) in the development of coronary artery disease (CAD). A total of 410 individuals with CAD were enrolled between January 2012 and December 2014. Genotyping of the five gene polymorphisms was performed using the polymerase chain reaction combined with restriction fragment length polymorphism methodology. By multivariate logistic regression analysis, we found that the frequencies of the CC genotype and the C allele of IL-6 -174G/C were significantly correlated with a higher risk of CAD; the adjusted ORs (95%CIs) were 2.37 (1.37-4.14) and 1.49 (1.19-1.86), respectively. In addition, the AG and GG genotypes and the G allele of IL-10 -1082A/G were also significantly associated with a higher risk of CAD, and the ORs (95%CIs) were 1.42 (1.04-1.95), 2.16 (1.42-3.30), and 1.56 (1.27-1.93), respectively. However, IL-1ß+3953 C/T, IL-8 -251T/A, and IL-10 -819C/T did not significantly correlate with CAD risk. Our study suggests that the IL-6 -174G/C (rs1800795) and IL-10 -1082A/G (rs1800896) polymorphisms might be involved in the pathogenesis of CAD, and likely contribute to the genetic susceptibility for CAD.
Subject(s)
Coronary Artery Disease/genetics , Interleukins/genetics , Adult , Aged , Aged, 80 and over , Alleles , Case-Control Studies , Female , Gene Frequency , Genetic Association Studies , Genetic Predisposition to Disease , Genetic Variation , Humans , Interleukin-10/genetics , Interleukin-1beta/genetics , Interleukin-6/genetics , Interleukin-8/genetics , Male , Middle Aged , Polymorphism, Restriction Fragment Length , Polymorphism, Single Nucleotide , Risk FactorsABSTRACT
Dengue infection poses a serious public health problem in most tropical and subtropical areas. No effective antiviral drugs or vaccines are currently available against dengue infection. To explore the feasibility of using capsid-targeted viral inactivation (CTVI) as an antiviral strategy against dengue infection, we constructed a plasmid expressing a fusion protein consisting of staphylococcal nuclease (SN) fused to dengue 2 virus capsid protein (D2C), and investigated its effects on the production of infectious virions when introduced into BHK cells infected with dengue virus. The results indicated that D2C-SN can be expressed and tolerated in this mammalian cell culture. The enzymatically active SN moiety was incorporated into nascent virions during the process of viral assembly. By comparing the effects of incorporated SN and SN*, an enzymatically inactive missense mutant form of wild-type SN, on the infectivity of progeny virions, we clearly demonstrated that nucleolytic activity was the major antiviral mechanism. Expression of D2C-SN fusion protein as a therapeutic agent resulted in a reduction in infectious titers of 12- to 60-fold. Therefore, dengue virus may be particularly vulnerable to a CTVI therapeutic approach.
Subject(s)
Antiviral Agents/pharmacology , Dengue/drug therapy , Micrococcal Nuclease/pharmacology , Viral Envelope Proteins/pharmacology , Animals , Cell Line , Cell Survival/drug effects , Cells, Cultured , Cricetinae , Dengue Virus/drug effects , Humans , Kidney , Kinetics , Micrococcal Nuclease/genetics , Plasmids , Recombinant Fusion Proteins/pharmacology , Transfection , Viral Envelope Proteins/genetics , Virion/drug effectsABSTRACT
Tc-99m sestamibil demonstrates considerable renal uptake followed by net urinary clearance similar to that of creatinine. The authors have previously shown that renograms could be obtained in cardiac patients by imaging during the rest injection of the perfusion agent. The present study shows correlating Tc-99m sestamibi and Tc-99m DTPA studies in hypertensive patients with a spectrum of findings, including aortic aneurysms, asymmetry due to renovascular disease, cysts, bilateral renal dysfunction, and horseshoe kidney. Tc-99m sestamibi images have persisting background activity in the liver and spleen, but show renal structure and function in adequate detail. Quantitative analysis confirms that Tc-99m sestamibi has higher renal uptake, but less excretion than Tc-99m DTPA. Review of these correlating studies suggests straightforward transfer of diagnostic expertise with standard renography to this new application.