Influenza virus-induced alterations of cytochrome P-450 enzyme activities following exposure of mice to coal and diesel particulates

We have investigated a relationship between two detoxication systems, metabolic detoxication through the cytochrome P-450 (P-450) pathway and resistance to infection through interferon (IFN), in mice infected with influenza virus following exposure to coal dust (CD) and diesel exhaust (DE) particulates. Mice were exposed by inhalation to filtered air (FA; control), CD, or DE for 1 month and then inoculated intranasally (IN) with influenza virus. During infection, 7-ethoxycoumarin deethylase (7ECdeEt'ase) and ethylmorphine demethylase (EMdeMe'ase) (monooxygenases), and NADPH cytochrome c reductase (NADPH c red'ase) were measured in liver microsomes. Temporal patterns of enzyme activities were observed with control animals. EMdeMe'ase and NADPH c red'ase exhibited peak values at Day 4 postinfection (27.6 and 482 nmole/min/mg protein, respectively), compared to initial activities (9.1 and 307 nmole/min/mg protein, respectively). 7ECdeEt'ase activity decreased between Days 1-3 postvirus infection and thereafter returned to the original value (1.7 nmole/min/mg protein). When the mice were first exposed to CD or DE particulates for 1 month prior to influenza infection, changes in enzyme temporal patterns were observed. The increased EMdeMe'ase activity at Day 4 was not observed in mice exposed to CD and was reduced in mice exposed to DE. Preexposure to either particulate resulted in the abolition of the increased Day 4 activity of NADPH c red'ase. The 7ECdeEt'ase postinfection temporal pattern was not affected by a preexposure to either particulate. Estimates of the enzyme activities after the 1-month exposure to FA, CD, or DE but before virus infection indicated no changes due to particulate exposure alone. Under these conditions of particulate exposure and virus infection, serum IFN levels in the mice used in this study peaked at Days 4-5 and were unaffected by the 1-month preexposure to CD or DE (Hahon et al., (1985). The data suggest the relationship that exists between metabolic detoxication and resistance to infection in normal mice was altered during a short-term preexposure to CD or DE.     

Genotoxicity studies of rodents exposed to coal dust and diesel emission particulates

Genotoxicity studies with mice and/or rats have been conducted to evaluate the potential mutagenic hazard associated with exposures of coal miners to diesel emission particulates (DEP) and/or coal dusts (CD). Rats and mice were exposed to filtered air, DEP, and/or CD for periods ranging from 3 months to 2 years. Levels of respirable particulates were maintained at 2 mg/m3 in all exposed groups. DEP and/or CD were collected in the inhalation chambers in which animals were exposed. Urine samples were collected for 5 consecutive days from rats exposed to DEP and/or CD for 3, 6, and 24 months. The particulate samples extracted with dichloromethane and the urine samples concentrated with XAD-2 columns were analyzed for mutagenic activity by the Ames Salmonella/microsome assay system. Peripheral blood lymphocytes from rats exposed for 3 months were analyzed for sister chromatid exchanges (SCE). The femur bone marrow cells from rats exposed for 24 months and mice exposed for 6 months were analyzed for micronuclei in both polychromatic and normochromatic erythrocytes. The results indicate that the solvent extract of DEP was mutagenic, while no mutagenic activity was found for the CD extract. Combination of CD and DEP did not show any synergistic effect. No mutagenic activity was found for urine samples from rats exposed to DEP and/or CD for up to 2 years. A slight increase in the micronucleated polychromatic erythrocytes over the control level was found in mice exposed to DEP and DEP plus CD for 6 months but the increase was not statistically significant. No increase in micronuclei was detected in rats exposed for 24 months. The frequencies of SCE in the peripheral lymphocytes of the 3-month-exposed rats were similar for control and DEP plus CD-exposed groups.     

Effects of low sulfur fuel and a catalyzed particle trap on the composition and toxicity of diesel emissions

In this study we compared a "baseline" condition of uncontrolled diesel engine exhaust (DEE) emissions generated with current (circa 2003) certification fuel to an emissions-reduction (ER) case with low sulfur fuel and a catalyzed particle trap. Lung toxicity assessments (resistance to respiratory viral infection, lung inflammation, and oxidative stress) were performed on mice (C57Bl/6) exposed by inhalation (6 hr/day for 7 days). The engine was operated identically (same engine load) in both cases, and the inhalation exposures were conducted at the same exhaust dilution rate. For baseline DEE, this dilution resulted in a particle mass (PM) concentration of approximately 200 microg/m3 PM, whereas the ER reduced the PM and almost every other measured constituent [except nitrogen oxides (NOx)] to near background levels in the exposure atmospheres. These measurements included PM, PM size distribution, PM composition (carbon, ions, elements), NOx, carbon monoxide, speciated/total volatile hydrocarbons, and several classes of semivolatile organic compounds. After exposure concluded, one group of mice was immediately sacrificed and assessed for inflammation and oxidative stress in lung homogenate. Another group of mice were intratracheally instilled with respiratory syncytial virus (RSV), and RSV lung clearance and inflammation was assessed 4 days later. Baseline DEE produced statistically significant biological effects for all measured parameters. The use of low sulfur fuel and a catalyzed trap either completely or nearly eliminated the effects.     

A study of heart and blood of rodents inhaling diesel engine exhaust particulates

The in vivo effects of inhalation of diesel engine exhaust (DEE) were evaluated in 128 rats and 146 guinea pigs. They were exposed in special chambers to three different dose levels of DEE particulates; 250, 750, and 1500 μg/m³, for 20 hr/day and 5.5 days/week. Rats were sacrificed after 13, 16.7, 25.7, 42, 52, and 78 weeks exposure, while guinea pigs were sacrificed after 6, 13, 17, 26, 42, 52, and 78 weeks exposure. Each group of each species was compared to its own age-matched control group. Morphometric analysis of the heart revealed no significant alterations in mass which could be assigned to inhalation of DEE at any dosage level or duration of exposure in either species. This included an assessment of the relative wet weights of the right ventricle, left ventricle, combined ventricles, combined atria, and ratio of right to left ventricle weights. Likewise, hematology was not changed in either species at any dosage level or duration of exposure by inhalation of DEE.     

Engine-operating load influences diesel exhaust composition and cardiopulmonary and immune responses

Background: The composition of diesel engine exhaust (DEE) varies by engine type and condition, fuel, engine operation, and exhaust after treatment such as particle traps. DEE has been shown to increase inflammation, susceptibility to infection, and cardiovascular responses in experimentally exposed rodents and humans. Engines used in these studies have been operated at idle, at different steady-state loads, or on variable-load cycles, but exposures are often reported only as the mass concentration of particulate matter (PM), and the effects of different engine loads and the resulting differences in DEE composition are unknown.Objectives: We assessed the impacts of load-related differences in DEE composition on models of inflammation, susceptibility to infection, and cardiovascular toxicity.Methods: We assessed inflammation and susceptibility to viral infection in C57BL/6 mice and cardiovascular toxicity in APOE^–/– mice after being exposed to DEE generated from a single-cylinder diesel generator operated at partial or full load.Results: At the same PM mass concentration, partial load resulted in higher proportions of particle organic carbon content and a smaller particle size than did high load. Vapor-phase hydrocarbon content was greater at partial load. Compared with high-load DEE, partial-load DEE caused greater responses in heart rate and T-wave morphology, in terms of both magnitude and rapidity of onset of effects, consistent with previous findings that systemic effects may be driven largely by the gas phase of the exposure atmospheres. However, high-load DEE caused more lung inflammation and greater susceptibility to viral infection than did partial load.Conclusions: Differences in engine load, as well as other operating variables, are important determinants of the type and magnitude of responses to inhaled DEE. PM mass concentration alone is not a sufficient basis for comparing or combining results from studies using DEE generated under different conditions.     

麻杏石甘汤及其加味对A型流感病毒感染小鼠T细胞亚群的影响

目的研究麻杏石甘汤及其加味对A型流感病毒感染小鼠T细胞亚群的影响。方法用甲型流感病毒鼠肺适应株经鼻腔接种小鼠,建立感染模型。实验设10倍麻杏石甘汤组、5倍麻杏石甘汤组、感染模型组、正常对照组。正常对照组、感染模型组灌胃给生理盐水,其它各组灌胃给相应浓度的药物,1次/d,0.4 ml/次,连续8 d。最后一次给药后禁水、禁食8 h,取标本进行T细胞亚群百分率的检测。结果10倍麻杏石甘汤加味方组CD3 、CD4 T细胞亚群百分率、CD4 /CD8 比值显著高于感染模型组(P<0.05),CD8 T细胞亚群百分率显著低于感染模型组(P<0.05)。10倍麻杏石甘汤组、5倍麻杏石甘汤加味方组CD8 T细胞亚群百分率显著低于感染模型组(P<0.05)。结论10倍临床最大用量的麻杏石甘汤和5倍临床最大用量的麻杏石甘汤加味方能明显调整流感病毒感染小鼠T细胞亚群的百分率。     

Effect of diesel exhaust on immune responses in C57BL/6 mice intranasally immunized with pollen antigen

To investigate the effect of diesel exhaust or particle-free diesel gas on immune responses in IgE low responder mice, C57BL/6 mice immunized intranasally with sugi basic protein were exposed to diesel exhaust or diesel gas components. We evaluated the changes in lymphocyte subpopulations, cell proliferation, chemokine production of cervical lymph nodes cells, and antigen-specific-antibody levels in plasma. Exposure to diesel gas decreased the percentage of CD4+ and TCR-beta+ T cells of cervical lymph nodes from immunized mice. Culture supernatants of cervical lymph nodes cells from diesel gas-exposed mice had significantly increased levels of macrophage inflammatory protein-1alpha and thymus and activation-regulated chemokine, but exposure to diesel exhaust did not affect it. Antigen-specific IgG2a titers in plasma were significantly enhanced after their exposure to diesel exhaust or gas. In contrast, exposure to diesel exhaust or gas markedly decreased antigen-specific IgG1 titers in immunized mice. These facts indicate that concurrent exposure to allergen and diesel exhaust or diesel gas modulates chemokine production in cervical lymph nodes cells and antibody production in plasma differentially.     

Distribution of isomers of BHC and related histopathology of liver in hexachlorocyclohexane (technical grade BHC) fed mice

In an attempt to correlate body burden and related liver histopathology after exposure to 500 ppm benzene hexachloride, 6- to 8-wk-old male and female mice were fed benzene hexachloride with their mash diet for a 6-month period. The mice were divided into 8 groups (12/group; 6 experimental, 6 control) and were sacrificed by group monthly. During the first month, 3 groups of mice were sacrificed after 10, 20, and 30 days of treatment, respectively. A dose-related increase in liver weight was found in test animals (P less than .01). The histopathology of liver showed clear, oval cells; hypertrophied cells with foci; and neoplastic nodules that were apparent during the final 3- to 6-month period. Few oval and hypertrophied cells were found in control animals. The alpha isomer concentration of benzene hexachloride rose during the first 2 months of treatment, but declined after that time. A transient rise was noted for the beta isomer concentration of benzene hexachloride at the end of the 6-month period. The gamma isomer concentration was elevated during the initial 3 months of treatment, but declined during the subsequent 3 months. The results present definitive changes suggestive of precancerous states.     

流感病毒感染的树突状细胞免疫调节机制

目的揭示流感病毒感染导致重症化肺炎的树突细胞免疫调控机制。方法 6～8周龄C57BL/6小鼠构建对照组（VEH）、扎那米韦处理组（Z）和扎那米韦、塞来昔布和美沙拉秦联合处理组（Z＋C＋M）的实验动物模型,流式细胞分析树突状细胞免疫提呈能力和T细胞的免疫能力;ELISA方法分析促炎性细胞因子水平。结果在流感病毒感染后4 d和6 d,Z＋C＋M组的MHC Class I、MHC Class II、CD80和CD86荧光强度表达量显著低于VEH组和Z组（P〈0.05）;Z＋C＋M组的CD4＋T细胞和CD8＋T细胞数量显著低于VEH组和Z组（P〈0.05）;Z＋C＋M组的促炎性细胞因子IL-1β,TNF-α和IL-6水平显著低于VEH组和Z组（P〈0.05）。结论树突状细胞抗原提呈能力的强弱对流感病毒感染重症化肺炎的形成起着非常重要的作用。     

Recombinant murine gammaherpesvirus 68 (MHV-68) as challenge virus to test efficacy of vaccination against chronic virus infections in the mouse model

Efficient vaccines against AIDS, Hepatitis C and other persistent virus infections are urgently needed. Vaccine development has been especially hampered by the lack of suitable small animal models to reliably test the protective capacity of candidate vaccines against such chronic viral infections. A natural mouse pathogen such as MHV-68 that persists lifelong after infection, appears to be a particularly promising candidate for a more relevant model system. Here, we investigated infections with recombinant MHV-68 as novel mouse challenge model to test the efficacy of heterologous vaccines based on recombinant modified vaccinia virus Ankara (MVA). To apply ovalbumin (OVA) as a model antigen, we constructed the recombinant virus MHV-68-OVA by BAC technology and characterized genetic stability and replicative capacity of the virus in vitro and in vivo. We demonstrated the ability of MHV-68-OVA to produce ovalbumin upon tissue culture infection. Moreover, the use of MHV-68-OVA-infected target cells allowed for efficient ex vivo amplification of OVA-specific, MHC class I-restricted CD8 T cells derived from MVA-OVA-vaccinated C57BL/6 mice. Finally, we immunized C57BL/6 mice with MVA-OVA and challenged the animals with MHV-68-OVA testing different time points and routes of infection. Vaccinated mice were infected with MHV-68-OVA but showed reduced viral loads in the acute and latent phase of challenge infection. These data strongly suggest the usefulness of the MHV-68 challenge model for further evaluation of recombinant vaccines against persisting virus infections.     

PBPK modeling/Monte Carlo simulation of methylene chloride kinetic changes in mice in relation to age and acute, subchronic, and chronic inhalation exposure.

During a 2-year chronic inhalation study on methylene chloride (2000 or 0 ppm; 6 hr/day, 5 days/week), gas-uptake pharmacokinetic studies and tissue partition coefficient determinations were conducted on female B6C3F1, mice after 1 day, 1 month, 1 year, and 2 years of exposure. Using physiologically based pharmacokinetic (PBPK) modeling coupled with Monte Carlo simulation and bootstrap resampling for data analyses, a significant induction in the mixed function oxidase (MFO) rate constant (Vmaxc) was observed at the 1-day and 1-month exposure points when compared to concurrent control mice while decreases in glutathione S-transferase (GST) rate constant (Kfc) were observed in the 1-day and 1-month exposed mice. Within exposure groups, the apparent Vmaxc maintained significant increases in the 1-month and 2-year control groups. Although the same initial increase exists in the exposed group, the 2-year Vmaxc is significantly smaller than the 1-month group (p < 0.001). Within group differences in median Kfc values show a significant decrease in both 1-month and 2-year groups among control and exposed mice (p < 0.001). Although no changes in methylene chloride solubility as a result of prior exposure were observed in blood, muscle, liver, or lung, a marginal decrease in the fat:air partition coefficient was found in the exposed mice at p = 0.053. Age related solubility differences were found in muscle:air, liver:air, lung:air, and fat:air partition coefficients at p < 0.001, while the solubility of methylene chloride in blood was not affected by age (p = 0.461). As a result of this study, we conclude that age and prior exposure to methylene chloride can produce notable changes in disposition and metabolism and may represent important factors in the interpretation for toxicologic data and its application to risk assessment.     

甲醛对小鼠的免疫毒性及氧化损伤的研究

目的 探讨甲醛对小鼠脾脏、胸腺T细胞亚群CD3、CD4、CD8含量和超氧化物歧化酶(superoxide dismutase,SOD)活力和丙二醛(maleic dialdehyde,MDA)含量的影响.方法 将昆明种小鼠随机分成5组(即阴性对照组,1、3、5 mg/m3染毒组和阳性对照组),每组6只.染毒组用静式吸入染毒方式染毒,每天染毒2 h,持续14 d.阴性对照组在同样的染毒柜中吸入过滤的新鲜空气,处理时间与染毒组相同.阳性对照组从第8天开始,每日按40 mg/kg体重腹腔注射环磷酰胺(CP),连续7 d,测定脾脏、胸腺中T细胞亚群CD3、CD4、CD8含量、SOD活力、MDA含量.结果 随甲醛染毒剂量的增高,小鼠脾脏、胸腺CD3、CD4、CD8含量呈明显下降趋势,CD4/CD8随染毒剂量的升高而明显增大.除1 mg/m3染毒组小鼠脾脏CD3、CD4含量及3 mg/m3染毒组CD4含量外,其他染毒组CD3、CD4、CD8含量与阴性对照组比较,差异均有统计学意义(均P＜0.05或P＜0.01),并且CD3、CD4、CD8阳性细胞数与甲醛染毒剂量间有明显的剂量-反应关系(r值分别为0.771、0.660、0.914,均P＜0.01).除1 mg/m3染毒组小鼠胸腺CD3、CD4、CD8含量外,其他染毒组CD3、CD4、CD8含量与对照组比较,差异均有统计学意义(P＜0.05或P＜0.01),并且CD3、CD4、CD8阳性细胞数与甲醛染毒剂量间有明显的剂量-反应关系(r值分别为0.881、0.763、0.969,均P＜0.01),与阴性对照组比较,差异有统计学意义(P＜0.05或P＜0.01).除1 mg/m3组小鼠胸腺SOD活力与阴性对照组比较,差异无统计学意义(P＞0.05)外,其他染毒组小鼠脾脏和胸腺的SOD活力与阴性对照组比较,差异均有统计学意义(P＜0.05或P＜0.01);各染毒组小鼠胸腺和脾脏MDA含量均显著高于阴性对照组,差异有统计学意义(P＜0.05或P＜0.01).各染毒组小鼠脾脏和胸腺T细胞亚群含量分别与其脾脏和胸腺的SOD活力成正相关(P＜0.01),与MDA含量成负相关(P＜0.01).结论 甲醛可引起小鼠脾脏、胸腺T细胞亚群CD3、CD4、CD8损伤和脾脏、胸腺脂质过氧化损伤;脂质过氧化损伤可能是甲醛导致免疫损伤的作用机制之一.     

Toxicological testing of rats subjected to inhalation of diethylhydroxylamine,nitroethane, and diethylamine hydrogen sulfite

Long-Evans hooded rats were exposed by inhalation to 9–27 ppm diethylhydroxylamine and the vapor of diethylamine hydrogen sulfite. In one of three test chambers each containing 45–49 rats, the rats were also exposed to 9 ± 2 ppm of nitroethane. In the first 12 months of the experiment two males and two females from both the control chamber and the chamber containing all three gases were sacrificed at 3-month intervals. After the first year only moribund animals were sacrificed except at the very end of the study when all remaining animals were sacrificed. Although hematological and blood chemistry evaluations indicated no significant differences between the control and exposed animals, gross and microscopic pathologic findings showed some variations, especially in the first year. Very early one test animal developed a hemangioendothelioma, but no additional ones developed later. Also hydrometra of the uterus, a condition common in old virgin female rats, was found in four exposed and one control female. Chronic tracheitis was found in five exposed and two control animals. Thyroid lesions were seen in the exposed animals after 6 months exposure, but not in animals exposed 9 months or longer. Examinations for animals exposed more than 1 year indicated no significant differences between the control and test groups, except for interstitial cell tumors of the testes which showed up in 4 of the 47 exposed males that were examined compared to 0 in the 25 control males. However, this incidence (8.5%) is too small to establish any definite conclusion.     

Characterization of endotoxin and mouse allergen exposures in mouse facilities and research laboratories

OBJECTIVES: Researchers and technicians who use mice in research are exposed to complex mixtures containing mouse allergen, endotoxin and particulates from animals, bedding and feed. The particle characteristics of these different exposures, and whether they are encountered together or separately, are important to better understand their adjuvant and allergic effects. Endotoxin and mouse allergen are derived from the same animal source, but have different physicochemical attributes. It is not known if airborne exposures to these agents are correlated in the laboratory animal workplace. METHODS: Side-by-side personal and area samples for airborne endotoxin (52), mouse allergen (46) and total particulates (43) were obtained in the animal facility and laboratories of a medical research institution. Animal handlers and researchers reported time spent on work tasks with mice, symptoms upon exposure to mice and mouse sensitization was determined by skin test or RAST. RESULTS: Mean airborne endotoxin exposure was highest during mouse experiments in the animal facility at 960 pg m(-3), peaked at 3125 pg m(-3), and ranged from 46 to 678 pg m(-3) with work in mouse rooms and research labs. Mouse allergen concentrations were highest during direct mouse work and background in research labs (mean 63-68 ng m(-3), range 41-271 ng m(-3)), but were undetectable during mouse research performed under a hood. Endotoxin and mouse allergen concentrations were correlated during direct research with mice and mouse care activities. Particle counts were low, typically < 1 cm(-3), varied widely, and exhibited peaks and valleys during different work tasks. From 80-90% of particles were < 1 microm in aerodynamic diameter during background measurements. The contribution of respirable particles 1-5 microm in size increased to 25-30% during mouse care and mouse research activities, but we found no association between any particle size and endotoxin or mouse allergen concentrations. Animal handlers and researchers in the mouse facility were exposed to the highest daily endotoxin concentrations, whereas researchers working with mice in the mouse facility and in laboratories were exposed to the highest daily mouse allergen concentrations. CONCLUSIONS: These findings suggest that endotoxin and mouse allergen are co-exposures during mouse handling and research, and that control of exposure peaks may be necessary to limit allergic disease in the laboratory animal workplace.     

The relative contribution of antibody and CD8+ T cells to vaccine immunity against West Nile encephalitis virus

West Nile virus (WNV) is a mosquito borne, neurotropic flavivirus that causes a severe central nervous system (CNS) infection in humans and animals. Although commercial vaccines are available for horses, none is currently approved for human use. In this study, we evaluated the efficacy and mechanism of immune protection of two candidate WNV vaccines in mice. A formalin-inactivated WNV vaccine induced higher levels of specific and neutralizing antibodies compared to a DNA plasmid vaccine that produces virus-like particles. Accordingly, partial and almost complete protection against a highly stringent lethal intracranial WNV challenge were observed in mice 60 days after single dose immunization with the DNA plasmid and inactivated virus vaccines, respectively. In mice immunized with a single dose of DNA plasmid or inactivated vaccine, antigen-specific CD8(+) T cells were induced and contributed to protective immunity as acquired or genetic deficiencies of CD8(+) T cells lowered the survival rates. In contrast, in boosted animals, WNV-specific antibody titers were higher, survival rates after challenge were greater, and an absence of CD8(+) T cells did not appreciably affect mortality. Overall, our experiments suggest that in mice, both inactivated WNV and DNA plasmid vaccines are protective after two doses, and the specific contribution of antibody and CD8(+) T cells to vaccine immunity against WNV is modulated by the prime-boost strategy.     

Chronic ethanol ingestion by mice increases expression of CD80 and CD86 by activated macrophages.

Results from previous studies from our laboratory have shown that T cells obtained from the spleens of C57BL/6 mice that consumed ethanol chronically have increased expression of activation markers and increased second signal-independent production of interferon-gamma (IFN-gamma). We now report that in vitro-activated CD11b(+) splenocytes obtained from C57BL/6 and BALB/c mice that consumed ethanol chronically express increased levels of the T cell co-stimulatory molecules CD80 and CD86. CD11b(+) splenocytes encompass at least two populations: the CD11b(+)Gr.1(-) population, which is primarily monocytes-macrophages, and a smaller CD11b(+)Gr.1(+) population, which is in the myelocytic-monocytic cell series and contains precursors of both macrophages and neutrophils. Evaluation of cultures of purified CD11b(+) cells, obtained from mice that consumed ethanol chronically, incubated overnight, showed increased up-regulation of CD80 and CD86 expression on Gr.1(-) mouse splenic macrophages. Results of functional studies of purified CD11b(+) cells have demonstrated that CD11b(+) cells obtained from C57BL/6 mice that were exposed to ethanol chronically secrete higher levels, in comparison with the levels secreted by CD11b(+) cells obtained from control animals, of nitric oxide and several proinflammatory cytokines after stimulation by the oligodeoxynucleotide (ODN) CpG 1826. These findings indicate that CD11b(+) splenocytes are in some way sensitized to activating stimuli by chronic ethanol exposure in vivo. Such cells may contribute to systemic immunodysregulation, including T-cell activation, by providing abnormal second signals to T cells, or through excessive release of cytokines, such as interleukin (IL)-6 or IL-12.     

Exposure of firefighters to diesel emissions in fire stations

Personal sampling techniques were used to evaluate firefighter exposure to particulates from diesel engine emissions. Selected fire stations in New York, Boston and Los Angeles were studied. Firefighter exposure to total particulates increased with the number of runs conducted during an 8-hr period. In New York and Boston where the response level ranged from 7 to 15 runs during an 8-hr shift, the resulting exposure levels of total airborne particulates from diesel exhaust were 170 to 480 micrograms/m3 (TWA). Methylene chloride extracts of the diesel particulates averaged 24% of the total. The authors' findings suggest that additional research is necessary to assess fire station concentrations of vehicle diesel exhaust that may have adverse health consequences to firefighters.     

Vaccine-induced protection from infection of mice by chimeric human immunodeficiency virus type 1, EcoHIV/NL4-3

EcoHIV/NL4-3 is a chimeric human immunodeficiency virus type 1 (HIV-1) that can productively infect mice. This study tests the utility of EcoHIV/NL4-3 infection to reveal protective immune responses to an HIV-1 vaccine. Immunocompetent mice were first immunized with VRC 4306 which encodes subtype B consensus sequences of gag, pol, and nef and then were infected by EcoHIV/NL4-3. Anti-Gag antibodies were sampled during immunization and infection. The extent of EcoHIV/NL4-3 infection in spleen cells and peritoneal macrophages was determined by quantitative real-time PCR (QPCR).

Although antibody titres were not significantly different in control and vaccinated groups, VRC 4306 immunization induced protective responses that significantly reduced virus burden in both lymphocyte and macrophage compartments. These results indicate that EcoHIV/NL4-3 infection can be controlled by HIV-1 vaccine-induced responses, introducing a small animal model to test vaccine efficacy against HIV-1 infection.     

Transmission of the virus of foot and mouth disease between animals and man

The virus of foot and mouth disease causes severe epizootics in animals and infrequently evokes painful, but transient, clinical signs in man. Adults in certain occupational groups and young children are particularly exposed to risk. Infected persons may disseminate virus for up to about 14 days. The virus can be transmitted from animals to animals, from animals to man, from man to animals and, probably, from man to man. Evidence for transfer of the disease between human and animal populations is reviewed in detail and modern methods of diagnosis are described. Predisposing factors play an important role in the development of overt foot and mouth disease in man. Subclinical infection occurs. The possibility of aerial transfer of the virus between man and domestic livestock constitutes a hazard, especially to the latter. Attention is directed to the need for sophisticated diagnostic techniques, to requirements for adequate precautions in the handling and disposal of affected animals, and to hygienic measures for disease control.     

壳聚糖季铵盐(HTCC)载HSV-2型DNA疫苗pgD诱导小鼠免疫应答的初步研究

目的:制备了壳聚糖季铵盐-DNA疫苗(pgD)纳米粒复合物,并对其诱导BALB/c小鼠产生免疫应答的能力做了初步研究。方法:通过复凝聚法制备了HTCC-pgD纳米粒复合物并对其进行表征。60只BALB/c小鼠随机分成5组:①HTCC10对照组;②pcDNAkan空载体对照组;③重组质粒pgD组;④HTCC∶pgD=5∶1组;⑤HTCC∶pgD=10∶1组。各组小鼠后腿肌肉注射,注射剂量为100μg/(只.次),隔2周免疫1次,共免疫2次。末次免疫2周后,通过流式细胞仪检测外周血中CD4+、CD8+百分率,ELISA法检测血清中IgG抗体效价、IFN-γ、IL-4含量这4个方面来研究该纳米粒复合物对小鼠免疫反应的影响。结果:HTCC能与质粒pgD很好结合成纳米复合物,保护DNA免受核酸酶的降解。小鼠经免疫2次后,流式细胞仪检测外周血中CD4+T淋巴细胞亚群结果显示HTCC-pgD纳米粒复合物组的CD4+百分率要高于其他对照组(P<0.05)。血清ELISA检测IgG结果显示与对照组相比,HTCC-pgD纳米粒复合物可诱导小鼠机体产生较高滴度的IgG抗体。HTCC-pgD纳米粒复合物组的小鼠血清中IFN-γ水平与对照组相比有所上调,IL-4水平有下降。结论:通过复凝聚法制备的HTCC-pgD纳米粒复合物可诱导BALB/c小鼠产生特异性的细胞免疫和体液免疫,为HSV-2型DNA疫苗研制提供科学依据。