硫酸多糖对体外人脐静脉内皮细胞损伤的保护作用

研究表明,硫酸多糖体外对多聚阳离子和氧自由基损伤的人脐静脉内皮细胞有保护作用。肝素、硫酸软骨素A抗多聚阳离子损伤作用比同浓度低分子肝素和甘糖酯强。肝素、硫酸软骨素A、甘糖酯抗氧自由基损伤作用优于同浓度低分子肝素。结果显示硫酸多糖有保护血管内皮的作用,其作用可能与所带阴离子基团有关。     

Protective cytotoxic T lymphocyte responses against paramyxoviruses induced by epitope-based DNA vaccines: involvement of IFN-gamma

Plasmid DNA vectors have been constructed with minigenes encoding a single cytotoxic T lymphocyte (CTL) epitope from either the M2 protein of respiratory syncytial virus (RSV) or from the nucleoprotein of measles virus (MV) with or without a signal sequence (also called secretory or leader sequence). Following intradermal immunization, plasmids in which the CTL epitopes were expressed in-frame with the signal sequence were more effective at inducing peptide- and virus- specific CTL responses than plasmids expressing CTL epitopes without the signal sequence. This immunization resulted in protection against MV-induced encephalitis and a significant reduction in viral load following RSV challenge. The reduction of viral load following RSV challenge was abrogated by prior injection with anti-IFN-gamma antibodies. These results highlight the ability of epitope-based DNA immunization to induce protective immune responses to well-defined epitopes and indicate the potential of this approach for the development of vaccines against infectious diseases.      

Response from lieberman and colleagues

Respond on comments on Lieberman's article: Cyclosiloxanes Produce Fatal Liver and Lung Damage in Mice. Environ Health Perspect 107:161-165     

The effects of recombinant-DNA-derived interferons on the growth of myeloid progenitor cells

Interferons (IFNs) have been shown to have significant effects on hematopoietic cell growth. Previous studies defining these effects have utilized mouse and human alpha-, beta-, and gamma-IFN isolated from supernatants of stimulated cells. Despite purification, the possible presence of other lymphokines and soluble factors remains a concern. In this study, the effects of gene-cloned alpha- and gamma-IFN on colony- forming units of granulocyte/macrophage (CFU-GM) progenitors cultured from the peripheral blood of normal volunteers were examined. In addition, blast cell colonies from one patient with acute myelogenous leukemia (AML) were studied. The growth of normal CFU-GM and AML blast cell colonies was inhibited in a dose-dependent manner by gamma- and alpha-IFN. gamma-IFN was ten to 100 times more potent than alpha-IFN in that this species of IFN reduced colony formation by greater than 50% at concentrations of less than 15 antiviral U/mL. The effects of gamma- IFN were neutralized by a monoclonal antibody specific for gamma-IFN. These in vitro studies indicate that human gamma-IFN may be an important modulator of myelopoiesis. Although these data indicate a possible efficacy of gamma-IFN in the treatment of AML, the in vitro results should be considered for their in vivo significance.     

Outpatient morning report

To clarify the use of outpatient morning report in internal medicine residency programs, we conducted a national survey of internal medicine residency directors and a local survey of a cohort of residents at a large teaching hospital. The program directors reported a 24% prevalence of outpatient morning report. The cohort of residents reported that the conference contributed much to their education by meeting specific learning needs and covering topics not covered elsewhere in their residency training. Presented at the Annual Meeting, Society of General Internal Medicine, San Francisco, Calif, April 30, 1999.     

Estimating the Cost to U.S. Health Departments to Conduct HIV Surveillance

Objectives

HIV case surveillance is a primary source of information for monitoring HIV burden in the United States and guiding the allocation of prevention and treatment funds. While the number of people living with HIV and the need for surveillance data have increased, little is known about the cost of surveillance. We estimated the economic cost to health departments of conducting high-quality HIV case surveillance.

Methods

We collected primary data on the unit cost and quantity of resources used to operate the HIV case surveillance program in Michigan, where HIV burden (i.e., the number of HIV cases) is moderate to high (n=14,864 cases). Based on Michigan''s data, we projected the expected annual HIV surveillance cost for U.S., state, local, and territorial health departments. We based our cost projection on the variation in the number of new and established cases, area-specific wages, and potential economies of scale.

Results

We estimated the annual total HIV surveillance cost to the Michigan health department to be $1,286,524 ($87/case), the annual total cost of new cases to be $108,657 ($133/case), and the annual total cost of established cases to be $1,177,867 ($84/case). Our projected median annual HIV surveillance cost per health department ranged from $210,600 in low-HIV burden sites to $1,835,000 in high-HIV burden sites.

Conclusions

Our analysis shows that a systematic approach to costing HIV surveillance at the health department level is feasible. For HIV surveillance, a substantial portion of total surveillance costs is attributable to maintaining established cases.An estimated 1.2 million people aged 13 years and older are living with human immunodeficiency virus (HIV) in the United States, and about 47,500 people are infected with the virus each year.^1,2 A recent HIV surveillance report shows that the number of people living with HIV increased by 8% from 2006 through 2009.³ The U.S. Centers for Disease Control and Prevention (CDC) has developed an HIV surveillance system for collecting, analyzing, and disseminating accurate information on the number of people with new HIV diagnoses (new cases) and those living with HIV infection (established cases).^4,5 Access to timely and high-quality surveillance data is essential to detect trends in the HIV burden and develop appropriate prevention and control measures.^4,6,7 The U.S. Department of Health and Human Services has closely aligned the $16 billion it spent in 2010 on HIV care, treatment, and prevention with the number of reported HIV cases in each state.⁸ HIV case surveillance additionally guides the implementation of test-and-treat prevention strategies that require data on timing of diagnosis, entry into and retention in care, and viral load (VL) suppression.^8–10 The Institute of Medicine recently identified HIV case surveillance as one of the data collection systems that could be used to monitor progress in achieving National HIV/AIDS Strategy goals.^11,12The purpose of this analysis was to estimate the economic cost to health departments to conduct high-quality HIV case surveillance, where high quality is defined as meeting or exceeding CDC data quality standards regarding the completeness and timeliness of reporting diagnosed HIV cases and ascertaining duplicate cases and deaths.^6,7 We examined potential variation in costs across health departments based on differences in the number of new vs. established HIV cases, area-specific wages, and potential economies of scale. Results from the analysis could help inform surveillance funding allocation across health departments and enable health departments to more accurately assess their own costs attributable to new and established HIV cases.     

A population-based study of testicular cancer risk among children and young adults from Norway and Utah,USA

Similar family-based cancer and genealogy data from Norway and Utah allowed comparisons of the incidence of testicular cancer (TC), and exploration of the role of Scandinavian ancestry and family history of TC in TC risk. Our study utilizes data from the Utah Population Database and Norwegian Population Registers. All males born during 1951–2015 were followed for TC until the age of 29 years. A total of 1,974,287 and 832,836 males were born in Norway and Utah, respectively, of whom 2,686 individuals were diagnosed with TC in Norway and 531 in Utah. The incidence per year of TC in Norway (10.6) was twice that observed in Utah (5.1) for males born in the last period (1980–1984). The incidence rates of TC in Utah did not differ according to the presence or absence of Scandinavian ancestry (p = 0.669). Having a brother diagnosed with TC was a strong risk factor for TC among children born in Norway and Utah, with HR = 9.87 (95% CI 5.68–17.16) and 6.02 (95% CI 4.80–7.55), respectively; with even higher HR observed among the subset of children in Utah with Scandinavian ancestry (HR = 12.30, 95% CI 6.78–22.31). A clear difference in TC incidence among individuals born in Norway and descendants of Scandinavian people born in Utah was observed. These differences in TC rates point to the possibility of environmental influence. Family history of TC is a strong risk factor for developing TC in both populations.     

A processive versus a distributive mechanism of action correlates with differences in ability of normal and xeroderma pigmentosum group A endonucleases to incise damaged nucleosomal DNA

A DNA endonuclease, isolated from the nuclei of normal human and xeroderma pigmentosum complementation group A (XPA) cells, which recognizes predominately pyrimidine dimers, was examined for the mechanism by which it locates sites of damage on UVC-irradiated DNA. In reaction mixtures with low ionic strengths (i.e. lacking KCl), the normal and XPA endonuclease locate sites of UV damage on both naked and reconstituted nucleosomal DNA by different mechanisms. On both of these substrates, the normal endonuclease acts by a processive mechanism, meaning that it binds non-specifically to DNA and scans the DNA for sites of damage, whereas the XPA endonuclease acts by a distributive one, meaning that it randomly locates sites of damage on DNA. However, while both the normal and XPA endonucleases can incise UVC irradiated naked DNA, they differ in ability to incise damaged nucleosomal DNA. The normal endonuclease showed increased activity on UVC treated nucleosomal DNA compared with naked DNA, whereas the XPA endonuclease showed decreased activity on the damaged nucleosomal substrate. Since a processive mechanism of action is sensitive to the ionic strength of the micro-environment, the KCl concentration of the reaction was increased. At 70 mM KCI, the normal endonuclease switched to a distributive mechanism of action and its ability to incise damaged nucleosomal DNA also decreased. These studies show that there is a correlation between the ability of these endonucleases to act by a processive mechanism and their ability to incise damaged nucleosomal DNA; the normal endonuclease, which acts processively, can incise damaged nucleosomal DNA, whereas the XPA endonuclease, which acts distributively, is defective in ability to incise this substrate.