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职业病危害因素接触史是诊断职业病的前提，尤其是对诊断结论有异议，申请职业病鉴定时尤为重要。本文报告1例职业性石棉所致肺癌的职业病鉴定病例，探讨诊断鉴定过程中职业病危害因素接触史的判定问题，以利于更好地开展职业病诊断与鉴定工作。.

The DArk Matter Particle Explorer (DAMPE) is a satellite-borne experiment, in operation since 2015, aimed at studying high-energy gamma rays and cosmic nuclei fluxes. Of the various sub-detectors in the DAMPE payload, the Silicon-Tungsten tracKer-converter (STK) plays a significant role in the charge measurement of incoming ions. Depending on the angle of inclination of the impinging particle and its position of impact on these strips, the collected charge can spread between the strips which results in some fractional signal loss. The $\eta$ variable is used to identify this spread of charge across the strips and correct for the associated charge loss. This brings us closer to accurate determination of particle charge which is crucial for ensuring a good discrimination between particles. The $\eta$-correction is, therefore, expected to play an important role in the determination of heavy ions by the DAMPE detector. It has helped reduce the proton background for the helium identification in STK by a factor of 1.5 for MIP tracks. It has been sucessfully applied to carbon nuclei and its application to heavier nuclei is currently being studied.

Since its launch, in December 2015, the satellite-based DAMPE (DArk Matter Particle Explorer) particle detector is taking data smoothly. The Silicon-Tungsten tracKer-converter (STK) of DAMPE consists of six tracking planes (6x, 6y) of single-sided silicon micro-strip detectors mounted on seven support trays. The STK is able to measure the charge and precisely reconstruct the track of traversing charged particles. Tungsten plates (1 mm thick) are integrated in the second, third and fourth tray from the top to serve as $\gamma \rightarrow e^+e^−$ converters. Commissioned rapidly after the launch, the STK is running extremely well since then. The STK in-orbit calibration and performance during its first more than 5 years of operation, including the noise behaviour and the thermal and mechanical stability, are presented in this contribution.

The DArk Matter Particle Explorer (DAMPE) is the first Chinese cosmic-ray direct detection experiment. It has been operating smoothly on-orbit since its successful launch at the end of 2015. Currently, its sub-detectors and the satellite are in good working order. The DAMPE payload employs a BGO Calorimeter for energy measurements, trigger and e/p identification. The calorimeter is constructed of 308 BGO crystals, and PMTs are coupled to the crystals with optical filters to readout scintillation light. In this work, we present the status and performance of the calorimeter, including status of detector units, energy measurement, especially in TeV range, detector endurance, and long term performance in a duration of 65 months.

The Fermi bubbles are two large structures above and below the Galactic Plane. They are first discovered by Fermi-LAT and thought to be related to the jet or the wind from the Galactic center. The DArk Matter Particle Explorer (DAMPE) is a space-borne high energy particle telescope aiming at measuring cosmic rays and photons in a broad energy range. In this work, we use 4.8 years of DAMPE photon data to search for the emission from the Fermi Bubbles. We calculate the TS values of the lobes and the significance of its curved spectrum. The obtained spectral parameters are then compared with those from the Fermi-LAT. We also search for the emission from the cocoon in the southeast part of lobes. Since the Galactic diffuse emission (GDE) model is a major source of systematic uncertainty, we also switch to the GDE models calculated with Galprop and evaluate the influence.

The DArk Matter Particle Explorer (DAMPE), a space-based high energy particle detector, has been operated on-orbit for more than five years. The large geometric factor and good charge resolution enable DAMPE to have very good potential to measure cosmic-rays up to 100 TeV. Knowledge of the boron to carbon (B/C) flux ratio is very important in understanding the prop- agation of cosmic rays, especially in TeV energy range. In this contribution, the latest progress of the B/C flux ratio analysis based on the flight data collected by DAMPE during the 5 years of operation, is presented.

The attention network is the structural basis of cognitive function. As one of the two known attention networks, the ventral attention network (VAN) has a significant impact on the cognitive impairment of patients with epilepsy. Nevertheless, changes in network homogeneity (NH) are rarely reported in the VAN of right temporal lobe epilepsy (rTLE) patients. Therefore, we explored the NH of the VAN in rTLE patients in this study.Seventy rTLE patients and 69 healthy controls were recruited. All participants underwent resting-state functional magnetic resonance imaging (fMRI), which was the primary method of evaluation. The executive control reaction time (ECRT) was examined via the attentional network test. The Data Processing Assistant for Resting-State fMRI (DPARSF) was used to analyze NH. The independent component analysis (ICA) and correlation analysis were used in data analysis.Compared to the control group, patients with right temporal lobe epilepsy showed a lower NH in the right superior temporal gyrus, and a longer ECRT. However, abnormal NH values had no significant association with the clinical measurements.Patients with right temporal lobe epilepsy have abnormal NH values in the VAN, and the executive functions in rTLE patients are also altered. The altered NH values in VAN may help provide new insights into the pathophysiology of cognitive impairment in rTLE.

Sparganosis is a parasitic disease caused by plerocercoid larvae of the genus Spirometra. In China, the main source of sparganosis is from Guangdong, 16.1% of the country's human sparganosis cases occur in this province. Frequent international trade of amphibians and reptiles in Guangdong may introduce new species of Spirometra into the local market. In this study, a large-scale, high-intensity sampling survey was conducted to find out the causative species and epidemic situation of Sparganosis in Guangdong. The prevalence of sparganum infection in five species of frogs (Boulengerana guentheri, Fejervarya multistriata, Hoplobatrachus chinensis, Pelophylax nigromaculatus and Quasipaa spinosa) and nine species of snakes (Elaphe carinata, Lycodon rufozonatum, Hypsiscopus plumbea, Ptyas dhumnades, P. korros, P. mucosa, Naja atra, Sinonatrix annularis and Xenochrophis piscator) was investigated in Guangdong, Southern China from May 2014 to August 2015. The results showed that 9.8% (50/511) of the frogs and 40.8% (141/ 346) of snakes were found to be infected by plerocercoids (spargana). To identify the species of the collected spargana, a partial sequence of the mitochondrial cytochrome c oxidase subunit1 gene (cox1) was amplified and sequenced. Phylogenetic analysis identified all the spargana specimens as Spirometra erinaceieuropaei. Our study indicated that S. erinaceieuropaei, a highly pathogenic parasite, is the only causative agent of sparganosis in Guangdong, China. This study suggests that the large numbers of frogs and snakes in food markets in Guangdong may impact public health in China by transmitting S. erinaceieuropaei sparganum. Additional steps should be considered by the governments and public health agencies to prevent the risk of food-associated Spirometra infections in humans in China.

The central air conditioning ventilation system plays an important role in the air circulation of buildings such as centralized isolation medical observation points and general public buildings. In order to meet the requirements of COVID-19 epidemic prevention and control, Beijing Preventive Medicine Association organized Beijing CDC and other professional institutes to write up the group standard entitled "Technical specification for health risk investigation of central air conditioning ventilation system during the COVID-19 epidemic (T/BPMA 0006-2020)" . According to the particularity of central air conditioning ventilation system risk control during the outbreak of similar respiratory infectious diseases, based on current laws and regulations and the principle of scientific, practical, consistency and normative, 8 key points of risk investigations were summarized, which were the location of fresh air outlet, air conditioning mode, air return mode, air system, air distribution, fresh air volume, exhaust and air conditioner components. The contents, process, method, data analysis and conclusion of the investigation implementation were also defined and unified. It could standardize and guide institutions such as disease control and health supervision to carry out relevant risk managements, and provided solutions and technical supports for such major public health emergencies in city operations.集中空调通风系统对集中隔离医学观察点和一般楼宇等建筑物内部的空气流通起着重要作用。为满足北京市应对新型冠状病毒肺炎疫情联防联控、平战结合的工作要求，北京预防医学会组织北京市CDC等多单位撰写了《新型冠状病毒肺炎疫情期间集中空调通风系统风险调查实施技术规范（T/BPMA 0006-2020）》团体标准，针对类似呼吸道传染病暴发流行期间集中空调风险防控特殊性，从传染病预防控制角度，以现行法律法规为基础，以"科学性、实用性、统一性、规范性"为原则，梳理归纳了集中隔离医学观察点和一般楼宇集中空调通风系统新风口位置、空调方式、空调回风方式、空调风系统、气流组织、新风量、排风和空调部件8项风险调查要点，并对调查实施内容、流程、方法、资料分析和结论建议等提出明确定义和统一要求。规范和指导疾病控制和卫生监督等机构开展相关风险防控工作，为城市管理中的此类重大突发公共卫生事件提供解决思路和标准支持。.

Objective To select and develop a SNP-STR multiplex amplification system with genetic markers compatible with current STR databases. To understand its genetic polymorphisms in Sichuan Han population and its application value in DNA mixture analysis. Methods Based on the STR genetic markers in commercial kits, SNPs adjacent to these STR markers were selected to be SNP-STR genetic markers. A SNP-STR multiplex amplification system with genetic markers based on allele-specific amplification was constructed using allele-specific amplification primers. The genetic polymorphism of the system in the Sichuan Han population was investigated and the efficiency of systems with different numbers of loci to detect the two individual DNA mixture samples was evaluated. Results An allele-specific multiplex amplification system constituted of 13 SNP-STR genetic markers was selected and constructed. In Sichuan Han population, the heterozygosity of each locus ranged from 0.76 to 0.88, and the combined discrimination power reached 0.999 999 999 999 999 968. In the analysis of the two individual DNA mixture samples： for single-locus amplification, the genotype of the minor components can still be detected when the mixture ratio reaches 1 000∶1; for multiple loci multiplex amplification, the maximum mixture ratio can reach 500∶1. As the number of loci in the system increased, the detection efficiency of the minor components in the DNA mixture decreased. Conclusion SNP-STR genetic markers have a higher polymorphism than STR. The multiplex amplification system made of SNP-STR genetic markers has a better analysis efficiency for mixed samples than traditional STR multiplex amplification system.SNP-STR遗传标记复合扩增体系的构建及法医学应用.目的 筛选并构建与目前STR数据库兼容的SNP-STR遗传标记复合扩增体系，调查其在四川汉族群体中的遗传多态性，并探讨其在混合DNA样本分析中的应用价值。 方法 以现有商业试剂盒中使用的STR遗传标记为基础，筛选与STR遗传标记相邻的SNP位点并组成SNP-STR遗传标记。运用SNP等位基因设计特异性引物，构建基于等位基因特异性扩增的SNP-STR遗传标记复合扩增体系。调查该体系在四川汉族群体的遗传多态性，并评价不同位点数目的体系对两个体混合DNA样本的检测效能。 结果 筛选并构建了由13个SNP-STR遗传标记构成的等位基因特异性复合扩增体系。在四川汉族群体中，各位点杂合度为0.76~0.88，累积个体识别率达0.999 999 999 999 999 968。在对两个体混合DNA的分析中：单位点扩增时，混合样本的混合比例达到1 000∶1时依然可以检测到少量成分所特有的分型；多位点复合扩增时，混合比例最大可达500∶1；随着体系中位点数量的增加，对混合DNA中少量成分的检测效能降低。 结论 SNP-STR遗传标记较STR具有更高的多态性，其构成的复合扩增体系对混合样本的分析效能优于传统的STR复合扩增体系。.法医遗传学；多态性，单核苷酸；短串联重复；等位基因特异性聚合酶链反应；混合DNA.

The objective of this paper was to study the effects of PYR-ARG-PRO-ARG-LEU-SER-HIS-YSGLY-PRO-MET-PRO-PHE-OH (APELIN-13) on the expression of inflammatory factors interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and interferon-γ (IFN-γ) in rats with experimental autoimmune neuritis (EAN). A total of 30 rats were divided into a control group, an EAN group, and an APELIN-13 group. Enzyme-linked immunosorbent assay (ELISA) was used to detect the levels of IL-6, TNF-α, and IFN-γ in rat plasma. Real-time quantitative Polymerase Chain Reaction (PCR) and Western blot were used to detect the protein and mRNA expression of IL-6, TNF-α, and IFN-γ in rat lymph nodes. In the EAN group, the infiltration of various types of inflammatory cells and focal demyelination were observed near the nerve fascicles of sciatic nerves. Compared with the EAN group, the infiltration of inflammatory cells and demyelination in the APELIN-13 group decreased significantly. The levels of plasma IL-6, TNF-α, and IFN-γ in the EAN group were significantly higher than those in the control group (P0.05) but significantly lower than those in the APELIN-13 group (P0.05). Compared with the control group, the mRNA and protein expression of IL-6, TNF-α, and IFN-γ increased significantly (P0.05) in the EAN group but decreased significantly in the APELIN-13 group (P0.05). In conclusion, APELIN-13 exerted a protective effect against EAN in rats.

Insufficient length of right renal vein (RV) increases the difficulty of venous anastomosis and blocks the promotion of transplantation of both kidneys, which could significantly reduce operative time and donor numbers. This study sought to discover a quick, safe method of venous anastomosis for right kidney donation.Three venous anastomotic methods (n = 20 in each group) were used for right donor kidney heterotopic transplantation: End-to-side, vena cava bypass, and modified end-to-end, namely, harvesting the right donor kidney with a part of the vena cava and then anastomosing the proximal end to the recipient RV followed by a ligation of the distal end. The conventional end-to-end venous anastomosis was used for left donor kidney orthotopic transplantation as a control (n = 60). We compared operative times and complications.The operative time of the modified end-to-end group (18.45 ± 0.69 minutes) and end-to-side group (17.95 ± 1.54 minutes) were both less than the vena caval bypass group (32.60 ± 2.84 minutes); (P.05), but equal to the control group (17.60 ± 1.89; P.05). The overall complication rate among the modified end-to-end group (2/20) was less than those for the end-to-side (8/20) and vena caval bypass groups (9/20; P.05), but similar to the control group (7/60; P.05).A modified end-to-end technique is the preferred venous anastomotic method for right donor kidney transplantation.

Polymerase chain reaction (PCR) provides a foundation for simple sequence repeat molecular marker-assisted selection (SSR MAS) in soybean. This PCR system and its various conditions have been optimized by many researchers. However, current research on the optimization of the PCR system focuses on double-primer PCR products. We compared single- and double-SSR primer PCR products from 50 soybean samples and found that the use of single-PCR primers in the reaction system can lead to amplified fragments of portions of the SSR primers in the PCR process, resulting in both false-positives and fragment impurity of double-primer PCR amplification, inconvenient for subsequent analysis. We used "single-primer PCR correction" to eliminate interference caused by single-primer nonspecific PCR amplification and improve PCR quality. Using this method, the precision and success rates of SSR MAS in soybean can be increased.

The non-stoichiometric compositions of Bi layered structural SrBi4Ti4O15 ferroelectric materials (SrBi4+2xTi4O15+3x, x=−0·04, −0·02, 0, 0·02 and 0·04) are investigated as the main precursors to find the influence of Bi2O3 content on the characteristics of SrBi4Ti4O15 ceramics. The effect of compositional variation on the sintering and the dielectric characteristics of SrBi4Ti4O15 ceramics are deduced with the aid of X-ray diffraction patterns, scanning electron microscopy observation and dielectric–temperature curves. From the scanning electron microscopy observations, the SrBi3·92Ti4O14·88 and SrBi3·96Ti4O14·94 ceramics reveal two phased grain growth, bar typed and irregularly disc typed grains coexist; the other SrBi4+2xTi4O15+3x ceramics reveal irregularly disc typed grains. From the X-ray patterns, the Bi2Ti2O7 and SrTiO3 phases are observed in the SrBi3·92Ti4O14·88 and SrBi3·96Ti4O14·94 ceramics. Except the SrBi3·96Ti4O14·94 ceramics, the other SrBi4+2xTi4O15+3x ceramics have revealed a spli...

The Saccharomyces cerevisiae REV3 gene encodes the catalytic subunit of a non-essential DNA polymerase zeta, which is required for mutagenesis. The rev3 mutants significantly reduce both spontaneous and DNA damage-induced mutation rates. We have identified human cDNA clones from two different libraries whose deduced amino acid sequences bear remarkable homology to the yeast Rev3, and named this gene hREV3. The hREV3 gene was mapped to chromosome 1p32-33 by fluorescence in situ hybridization. The hREV3 encodes an mRNA of >10 kb, and its expression varies in different tissues and appears to be elevated in some but not all of the tumor cell lines we have examined. In light of recent reports of a putative mouse REV3, these results indicate that mammalian cells may also contain a mutagenic pathway which aids in cell survival at the cost of increased mutation.

A 74-year-old man was admitted with abdominal discomfort, fever and chills in the previous 2 weeks. Physical examination revealed a vague Murphys’ sign on abdominal palpation. Abdominal ultrasonography demonstrated a distended gallbladder and acute cholecystitis was initially diagnosed. He underwent a laparoscopy and multiple caseous nodules …

We report on the first unambiguous observation of macroscopic quantum tunneling (MQT) in a single submicron Bi(2)Sr(2)CaCu(2)O(8+delta) surface intrinsic Josephson junction (IJJ) by measuring its temperature-dependent switching current distribution. All relevant junction parameters were determined in situ in the classical regime and were used to predict the behavior of the IJJ in the quantum regime via MQT theory. Experimental results agree quantitatively with the theoretical predictions, thus confirming the MQT picture. Furthermore, the data also indicate that the surface IJJ, where the current flows along the c axis of the crystal, has the conventional sinphi current-phase relationship.

A new catalytic-kinetics spectrophotometric method for the determination of horseradish peroxidase was developed. It was based on the catalytic effect of horseradish peroxidase (HRP) on the coloration reaction, in which the reduced rhodamine B was oxidized by H2O2 in pH 6.80 phosphate buffer. It was found that reduced rhodamine B stocking solution could be steady in 0.25% beta-CD solution. The kinetic behavior of the reaction and the effects of some experimental conditions were investigated and discussed in detail. The method has been applied to determine HRP with a satisfactory result. The calibration curve is linear over the range 15-250 pg.10 mL-1 of HRP (r = 0.9989). The limit of detection was 12 pg.10 mL-1 and the relative standard derivative RSD is 4.25% by determining for 20 pg.10 mL-1 HRP (n = 10).

To deal with the further investigation field by discussing the status and present problem of traditional Tibetan medicine.Previous relevant investigations and literatures were summed up in the field. The present situation of traditional Tibetan medicine in China was analysed.The textual research, basic medicinal property, exploration of developable medicinal resource and protection of endangered medicinal species etc. were elaborated and the key problem of further investigation in 21st century was expounded.The textual research, basic medicinal property, exploration of develoable medicinal resources, especially monographic study on protection of major endangered medicinal resources should be intensified. Domestication and cultivation, and exploration of good-quality medicinal resources, quality evaluation and exploitation of effectual prescriptions are the focal field in the study of traditional Tibetan medicine.

Mechanisms accounting for protection of the fetal semiallograft from maternal immune cells remain incompletely understood. In other contexts, interactions between TRAIL (TNF-related apoptosis-inducing ligand/Apo-2L) and its receptors kill activated lymphocytes. The purpose of this study was therefore to investigate the potential of the TRAIL/TRAIL-R system to protect the placenta against immune cell attack. Analysis by Northern blotting demonstrated mRNAs encoding TRAIL as well as the four TRAIL receptors (DR4, DR5, DcR1/TRID, DcR2/TRUNDD) in human placentas. Immunohistochemical experiments demonstrated that TRAIL protein is prominent in syncytiotrophoblast, an uninterrupted placental cell layer that is continuously exposed to maternal blood, as well as in macrophage-like placental mesenchymal cells (Hofbauer cells). Studies on cell lines representing trophoblasts (Jar, JEG-3 cells) and macrophages (U937, THP-1 cells) showed that both lineages contained TRAIL mRNA and that steady state levels of transcripts were increased 2- to 11-fold by IFN-gamma. By contrast, cell lineage-specific differences were observed in expression of the TRAIL-R genes. Although all four lines contained mRNA encoding the apoptosis-inducing DR5 receptor, only trophoblast cells contained mRNA encoding the DcR1 decoy receptor and only macrophages contained DcR2 decoy receptor transcripts. DR4 mRNA was present only in THP-1 cells and was the only TRAIL-R transcript increased by IFN-gamma. Cytotoxicity assays revealed that the two trophoblast cell lines were resistant, whereas the two macrophage lines were partially susceptible to killing by rTRAIL. Collectively, the results are consistent with a role for the TRAIL/TRAIL-R system in the establishment of placental immune privilege.

We have cloned the human mutY gene (hMYH) from both genomic and cDNA libraries. The human gene contains 15 introns and is 7.1 kb long. The 16 exons encode a protein of 535 amino acids that displays 41% identity to the Escherichia coli protein, which provides an important function in the repair of oxidative damage to DNA and helps to prevent mutations from oxidative lesions. The human mutY gene maps on the short arm of chromosome 1, between p32.1 and p34.3.

The antilocalization effect in a compensated HgCdTe film is observed. With an applied microwave field, both the zero-magnetic-field conductance and the dephasing time are enhanced nonlinearly with microwave power. The observation concerning the dephasing time is inconsistent with a heating mechanism. Such behavior is also in contrast to the microwave-induced suppression of weak-antilocalization and dephasing time seen for a two-dimensional electron gas of the anodic-oxidized HgCdTe. The nonlinear increase in zero-magnetic-field conductance is consistent with a microwave-assisted-hopping mechanism. The increased dephasing time can be explained qualitatively by the microwave-assisted-hopping mechanism and a microwave-induced increase in the electron density. © 2013 American Institute of Physics.

We have investigated spin-related oscillatory magnetoresistances of the two-dimensional electron gas in the inversion layer on bulk p-Hg1−xCdxTe at low temperatures. The oscillatory magnetoresistances are found to display beating pattern at low magnetic fields and to exhibit spin-splitting structure at high magnetic fields. We attribute the beating pattern to zero-field spin splitting due to spin-orbit coupling by analyzing fast-Fourier-transform results and Hall resistance. By modulating the oscillatory magnetoresistances we investigate the influence of spin-orbit coupling, Zeeman splitting, and the second populated subband on the appearance of beating patterns and the spin-splitting structure in oscillatory magnetoresistances. The strong spin-orbit coupling and the large effective g factor are demonstrated to be the significant parameters in controlling the appearance of spin-related oscillatory magnetoresistance in the inversion layer on bulk p-Hg1−xCdxTe. A good agreement between magnetoresistance dat...

A 49-year-old man was diagnosed with dilated cardiomyopathy after presenting with congestive heart failure since 1995. He experienced a flare-up of symptoms after an upper respiratory tract infection 1 week before admission to the coronary care unit (CCU). His dyspnoea improved after treatment with diuretics and inotropes. On day 4 in the CCU he developed a urinary tract infection complicated by septic shock. A central venous catheter (CVC) was inserted over the right internal jugular vein. There was difficulty in performing the catheterisation, and the procedure was prolonged due to an extremely low intravascular volume. Soon after the procedure a round opacity was noted on the chest radiograph (fig 1). At that time there was no purulent sputum, airway symptoms or physical examination compatible with pneumonia. A chest CT scan revealed air emboli in the superior vena cava (arrow, fig 2A) and wedge-shaped pulmonary infarcts with central necrosis at the bilateral lower lobes (fig 2B). Owing to lack of evidence for pulmonary infection, the necrosis was believed to be sterile. The patient died 1 week later from cardiogenic shock with multi-organ failure. Figure 1 Chest radiograph after central venous cannulation showing a round opacity of homogenous density but without airbronchogram in the right lower lung field. Figure 2 (A) Contrast-enhanced chest CT scan showing air bubble trapped around the central venous catheter in the superior vena cava (arrow). (B) Bilateral pleural-based, wedge-shaped, mass-like consolidations with central necrosis in both lower lobes. Venous air embolism can be observed during CVC insertion, after CVC removal, and during other medical procedures or interventions.1–3 In acute care settings, patients with hypovolaemia are at a higher risk of gas embolism during central venous cannulation because of the subatmospheric pressure in these vessels.1 To our knowledge, there has been no previous report of venous air pulmonary infarction mimicking round pneumonia in the English literature. Learning points Patients with a low intravascular volume are at a higher risk of developing venous gas embolism during CVC insertion. Pulmonary infarction from gas embolism can mimic round pneumonia on the chest radiograph.

An enzyme of molecular weight 32,000 comprising a single subunit has been isolated from whole cell extracts of the yeast Saccharomyces cerevisiae. In vitro, the enzyme transfers the gamma phosphate of ATP to a protein substrate, histone H4, to produce an alkali-stable phosphorylation. Modification of the substrate histidine with diethylpyrocarbonate prevented phosphorylation. Phosphoamino acid analysis of the phosphorylated substrate showed the presence of 1-phosphohistidine. Hence, the isolated enzyme is a protein histidine kinase. A novel assay for acid-labile alkali-stable protein phosphorylation was used in the purification of the kinase activity to a final specific activity of 2,700 nmol/15 min/mg. The purified enzyme phosphorylates specifically histidine 75 in histone H4 and does not phosphorylate histidine 18 nor histidine residues in any other core histone. Steady state kinetic data are consistent with an ordered sequential reaction with Km values for Mg-ATP and histone H4 of 60 and 17 microM, respectively. The protein histidine kinase requires a divalent cation such as Mg2+, Co2+, or Mn2+ but will not use Ca2+, Zn2+, Cu2+, Fe2+, spermine, or spermidine. This is the first purification of an enzyme that catalyzes N-linked phosphorylation in proteins.

The interaction of mast cells with other leukocytes during immediate hypersensitivity reactions was tested by in vivo and in vitro experiments. Intraperitoneal challenge of passively sensitized rats with antigen caused the production of peptidoleukotrienes, leukotriene (LT)B4, thromboxane (TX)B2, and 6-keto-prostaglandin (PG) F1 alpha in the peritoneal cavity. Pretreatment of the rats with thioglycollate i.p. markedly changed the amount of eicosanoids formed. When polymorphonuclear leukocytes were the predominant cell type in the peritoneal exudate, both LTC4 and 6-keto-PGF1 alpha were decreased by 75% each and TXB2 by 50%. When elicited macrophages were predominant, there was an additional reduction in LTC4 by 68% as compared with 18 hr after thioglycollate treatment, but no additional change in the other arachidonic acid metabolites. In vitro antigen challenge of passively sensitized mouse bone marrow-derived mast cells caused the release of LTC4, LTB4, 6-trans-LTB4, 5-hydroxyeicosatetraenoic (5-HETE), and TXB2. Exposure to antigen of these mast cells in the presence of resident peritoneal macrophages markedly altered eicosanoid formation. Early in the time course (2 to 15 min), macrophages markedly enhanced all 5-lipoxygenase products. However, later in the time course (30 to 120 min), these products were decreased. This decrease was reversed by catalase and superoxide dismutase, which suggests the involvement of oxygen radicals. These active oxygen species also seemed to be generated by mast cells, because these enzymes caused an increase in 5-lipoxygenase products when mast cells were challenged alone. RIA of cyclooxygenase products showed that mast cells released only TXB2 when stimulated with antigen. When they were stimulated in the presence of macrophages, TXB2 and also PGE2 and 6-keto-PGF1 alpha were synthesized. Therefore, macrophages probably contribute the PGE2 and 6-keto-PGF1 alpha. Because the same amount of TXB2 was generated whether macrophages were present or not, the mast cells seem to be the major source of this compound. These data indicate that macrophages and possibly polymorphonuclear leukocytes participate in immediate hypersensitivity reactions.

The chromatographic mobility of atriopeptin-28 or of the prohormone is markedly altered by preincubation of the peptides with heparin before separation on reverse-phase high performance liquid chromatography. Protamine prevented the heparin effect and reestablished the original migration pattern of the atrial peptides. The addition of heparin to either rat or human plasma samples did not interfere with the atriopeptin immunoreactivity. The influence of heparin on the biological activity of the atriopeptin-28 in anesthetized rats was also investigated. Infusion of heparin (30 U/min) significantly reduced the dose-dependent fall of blood pressure produced by atriopeptin-28, but did not interfere with the hypotensive effect of nitroglycerin. Similarly, infusion of heparin in volume-expanded rats markedly decreased the diuresis produced by atriopeptin-28 without altering the urine volume excreted in response to furosemide. These data suggest that the highly charged molecule heparin can modify the physical and biological properties of atriopeptins, perhaps by binding to the numerous arginine residues (i.e., 5 arginine residues in atriopeptin-28) in the atriopeptin molecules.

The experiments discussed above demonstrate that macrophages and possibly PMN modulate and contribute to immediate hypersensitivity reactions. Antigen stimulation of sensitized mast cells in vitro in the presence of macrophages showed that the latter contribute prostaglandins and modulate the 5-lipoxygenase products. Early in the time course, 5-lipoxygenase products, including leukotrienes, were enhanced and later decreased. The decrease appeared to be due to active oxygen species and may serve as a negative feedback mechanism to maintain relative homeostasis.