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免疫检查点抑制剂（ICI）能阻断肿瘤的免疫逃逸机制，其临床适应证在不断扩展，极大地改善了多种晚期恶性肿瘤患者的临床预后，但免疫相关不良事件的报道也随之增加。心包疾病是最常见ICI相关心血管不良反应，起病隐匿，在急性期具有高致死率。该综述展示了近几年来ICI相关心包疾病的发病概况、致病机制、临床表现、监测和处理原则等方面的研究进展，以期提高临床医师对该疾病的认识和应对能力。.

Background Arginase is involved in the development of ischemia-reperfusion injury by regulating nitric oxide (NO) bioactivity via competition with NO synthase (NOS) for their common substrate L-arginine. Erythrocytes are known to contain high levels of arginase that may reduce export of cardioprotective NO bioactivity. Aim To determine the role of arginase 1 in erythrocytes for cardiac protection against myocardial ischemia-reperfusion injury. Methods A tie2 cre-flox mouse model, in which arginase 1 was deleted (Arg 1-KO) in hematopoietic and endothelial cells, was developed. In vivo ischemia-reperfusion was performed in anaesthetized mice by left anterior descending coronary artery ligation (30 min ischemia and 120 min reperfusion). To determine the specific role of erythrocytes, an isolated perfused mouse heart model was applied. Erythrocytes from Arg 1-KO and wild type (WT) mice were given to isolated hearts from WT mice at the onset of global ischemia. After 40 min ischemia, the recovery of left ventricular developed pressure (LVDP) during 60 min reperfusion was recorded as an indicator of cardiac functional recovery. All animal experiments and procedures were performed according to the guidelines by the U.S National Institutes of Health (NIH publication no 85–23, revised 1996) Results Following in vivo ischemia-reperfusion, infarct size was smaller in Arg 1-KO mice than in WT mice (Fig. A). A similar degree of infarct size reduction was obtained by i.v. administration of an arginase inhibitor in WT mice. The cardioprotective effect observed in Arg 1-KO mice was abolished by the NOS inhibitor L-NMMA (Fig. A). In isolated buffer-perfused hearts, there was no difference in the post-ischemic recovery of LVDP between Arg 1-KO and WT hearts. When erythrocytes from Arg 1-KO mice were administrated to isolated WT mouse hearts, the post-ischemic recovery of LVDP was significantly improved compared to hearts given erythrocytes from WT mice. Also, the cardioprotective effect of erythrocytes from Arg 1-KO mice was abolished by pre-incubation of the erythrocytes with the NOS inhibitor L-NAME (Fig. B) or the inhibitor of soluble guanylyl cyclase ODQ (Fig. C). Conclusion Arginase 1 in erythrocyte plays an important role in regulating cardioprotection mediated via the NO-soluble guanylyl cyclase pathway. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): Swedish Heart and Lung Foundation (20190266),The Swedish Research Council (2020-01372)

The design of uranium-based thermoelectric (TE) materials presents a novel and intriguing strategy for directly converting nuclear heat into electrical power. Using high-level first-principles approach combined with accurate solution of Boltzmann transport equation, we demonstrate that a giant n-type power factor of 13.8 mW m

It has been demonstrated that many promising thermoelectric materials, such as tetradymite compounds are also three-dimensional topological insulators. In both cases, a fundamental question is the evaluation of carrier relaxation time, which is usually a rough task due to the complicated scattering mechanisms. Previous works using the simple deformation potential theory or considering complete electron-phonon coupling are, however, restricted to small systems. By adopting a data-driven method named SISSO (Sure Independence Screening and Sparsifying Operator) with the training data obtained via deformation potential theory, we propose an efficient and physically interpretable descriptor to evaluate the relaxation time, using tetradymites as prototypical examples. Without any input from first-principles calculations, the descriptor contains only several elemental properties of the constituent atoms, and could be utilized to quickly and reliably predict the carrier relaxation time of a substantial number of tetradymites with arbitrary stoichiometry.

Ternary half-Heusler compounds with widely tunable electronic structures, present a new platform to discover topological insulators. Due to time-consuming computations and synthesis procedures, the identification of new topological insulators is however a rough task. Here, we adopt a compressed-sensing approach to rapidly screen potential topological insulators in half-Heusler family, which is realized via a two-dimensional descriptor that only depends on the fundamental properties of the constituent atoms. Beyond the finite training data, the proposed descriptor is employed to screen many new half-Heusler compounds, including those with integer and fractional stoichiometry, and a larger number of possible topological insulators are predicted.

Carbon-based structures are a superior alternative for unleashing the thermoelectric potential of earth-abundant and environmentally friendly materials. Here we design a hybrid graphene/h-BN superlattice monolayer and investigate its thermoelectric properties based on density functional theory and accurate solution of Boltzmann transport equations. Compared with that of pristine graphene, the lattice thermal conductivity of the superlattice structure is more than two orders of magnitude lower ascribed to the significantly increased phonon scattering originating from the mixed-bond characteristics. Besides, the obvious valley anisotropy near the electronic band edge leads to an ultrahigh power factor along the zigzag direction, which in turn gives an n-type ZT value as high as 2.5 at 1100 K. Moreover, it is interesting to find that the thermoelectric performance of p-type system can be enhanced to be comparable with that of n-type one by appropriate substitution of the nitrogen atom with phosphorus, which can suppress the lattice thermal conductivity but nearly have no effect on the hole transport.

The night images obtained with an all-sky camera can provide spatial and time sampling, which can be used for measurement cloud coverage measurement and meteor monitoring. The astrometric calibration of an all-sky camera is necessary because of strong field distortions. We use machine learning to complete the calibration of an all-sky camera. In order to prepare the data sets needed for machine learning, a particle swarm optimization algorithm is used to determine the parameters of the method proposed by Borovicka in 1995. Machine learning can transform plate coordinates to celestial coordinates and transform celestial coordinates to plate coordinates. The actual test shows that the standard deviation of residuals is of the order of 1′ for the transformation from plate coordinates to celestial coordinates and the standard deviation of residuals is of the order of 0.3 px for the transformation from celestial coordinates to the plate coordinates.

Topological semimetals have attracted tremendous attention from the science community owing to their exotic electronic structures. It is generally assumed that metallic or similar systems exhibit rather poor thermoelectric performance due to very small Seebeck coefficients. Here we demonstrate by first-principles calculations and Boltzmann transport theory that the Dirac semimetal Na2AgSb is an exception because of its strong band asymmetry around the Fermi level. In addition, the system shows ultralow lattice thermal conductivity caused by the rattling of the Na atoms in the cage-like framework of Ag and Sb atoms. As a consequence, one can realize certain decoupling of the thermoelectric transport coefficients, and a considerable ZT value of 1.3 can be reached at 300 K in the p-type Na2AgSb. The present work highlights the promising possibility of semimetals or similar systems for high-performance thermoelectric applications.

Two-dimensional layered materials have attracted tremendous attention due to their extraordinary physical and chemical properties. Using first-principles calculations and Boltzmann transport theory, we give an accurate prediction of the thermoelectric properties of hexagonal boron phosphide (BP) bilayer, where the carrier relaxation time is treated within the framework of electron-phonon coupling. It was found that the lattice thermal conductivity of BP bilayer is much lower than that of its monolayer structure, which can be attributed to the presence of van der Waals interactions. On the other hand, the graphene-like BP bilayer shows very high carrier mobility with a moderate band gap of 0.88 eV. As a consequence, a maximum $p$-type $\mathit{ZT}$ value of \ensuremath{\sim}1.8 can be realized along the $x$ direction at 1200 K, which is amazingly high for systems consisting of light elements only. Moreover, we obtain almost identical $p$- and $n$-type $\mathit{ZT}$ of \ensuremath{\sim}1.6 along the $y$ direction, which is very desirable for fabrication of thermoelectric modules with comparative efficiencies. Collectively, these findings demonstrate the great advantages of the layered structures containing earth-abundant elements for environmentally friendly thermoelectric applications.

Based on first-principles calculations and symmetry arguments, we reveal that the non-centrosymmetric ternary tetradymite BiSbTe3 possesses exotic dual topological features of Weyl semimetallic phases with Z 2 index (1:000). The results show that the helical Dirac-type surface states protected by the time-reversal symmetry are present in the vicinity of the Brillouin zone center, which is consistent with the experimental report. Furthermore, we show that four pairs of Weyl points reside exactly at the Fermi level, which are guaranteed to be located on high-symmetry planes due to mirror symmetries. The helical surface states and the projected Weyl nodes are well separated in the momentum space, facilitating their observations in experiments. This work not only uncovers a unique quantum phenomenon with dual topological features in the tetradymite family but also paves a fascinating avenue for exploring the coexistence of multi-topological states with wide applications.

The design of uranium-based thermoelectric (TE) materials presents a novel and intriguing strategy for directly converting nuclear heat into electrical power. Using high-level first-principles approach combined with accurate solution of Boltzmann transport equation, we demonstrate that a giant n-type power factor of 13.8 mW m−1 K−2 and a peak ZT value of 2.2 can be realized in the heavy-fermion UN2 compound at 700 K. Such promising TE performance arises from the large degeneracy (N v = 14) of heavy conduction band coupled with weak electron–phonon interactions, which is in principle governed by the strong Coulomb correlation among the partially filled U-5f electrons in the face-centered cubic structure. Collectively, our theoretical work suggests that the energetic UN2 could serve as both excellent heat source and efficient power convertor, which also uncovers an underexplored area for TE research.

Half-Heusler compounds usually exhibit relatively higher lattice thermal conductivity that is undesirable for thermoelectric applications. Here we demonstrate by first-principles calculations and Boltzmann transport theory that the BiBaK system is an exception, which has rather low thermal conductivity as evidenced by very small phonon group velocity and relaxation time. Detailed analysis indicates that the heavy Bi and Ba atoms form a cage-like structure, inside which the light K atom rattles with larger atomic displacement parameters. In combination with its good electronic transport properties, the BiBaK shows a maximum n-type ZT value of 1.9 at 900 K, which outperforms most half-Heusler thermoelectric materials.

The electronic and phonon transport properties of graphene-like boron phosphide (BP), boron arsenide (BAs), and boron antimonide (BSb) monolayers are investigated using first-principles calculations combined with the Boltzmann theory. By considering both the phonon-phonon and electron-phonon scatterings, we demonstrate that the strong bond anharmonicity in the BAs and BSb monolayers can dramatically suppress the phonon relaxation time but hardly affect that of electron. As a consequence, both systems exhibit comparable power factors with that of the BP monolayer but much lower lattice thermal conductivities. Accordingly, a maximum ZT value above 3.0 can be realized in both BAs and BSb monolayers at optimized carrier concentration. Interestingly, very similar p - and n-type thermoelectric performance is observed in the BSb monolayer along the zigzag direction, which is of vital importance in the fabrication of thermoelectric modules with comparable efficiencies.

Methamphetamine （MAMP） is a kind of amphetamine-type stimulants （ATS） which contains one chiral carbon atom in its structure. Therefore a pair of enantiomers, S-（+）-MAMP and R-（-）-MAMP exist. R type and S type methamphetamines possess similar physicochemical properties, but has largely different pharmacological and toxic effects. S-（+）-MAMP is the main component of addictive drug "Ice" at present, seriously affecting human health and public safety. The separation analysis and mechanism of toxic effects discussions on MAMP are the current research focuses. This paper reviews the research progress of separation analysis methods and toxic effects of methamphetamine enantiomers to provide reference for forensic study and forensic practice.甲基苯丙胺对映异构体手性分离方法及其毒性作用的研究进展.甲基苯丙胺（methamphetamine，MAMP）是一种苯丙胺类化学物质，其结构中含有1个手性碳原子，因此存在1对对映异构体，即S-（+）-甲基苯丙胺和R-（-）-甲基苯丙胺。R型和S型甲基苯丙胺物理化学性质相近，但药理、毒理作用差异巨大。S-（+）-MAMP是目前成瘾性毒品“冰毒”的主要成分，严重影响着人体健康与公共安全，其分离分析及毒性作用机制探讨均是目前的热点研究内容。本文综述了甲基苯丙胺对映异构体的分离分析方法及其毒性作用研究进展，以期为法医学研究和应用提供参考。.法医毒物学；甲基苯丙胺；对映异构体；毒性作用；综述.

The electronic and phonon transport properties of quaternary tetradymite BiSbSeTe2 are investigated by using a first-principles approach and Boltzmann transport theory. Unlike the binary counterpart Bi2Te3, we obtain a pair of Rashba splitting bands induced by the absence of an inversion center. Such unique characteristics could lead to a large Seebeck coefficient even at a relatively higher carrier concentration. Besides, we find an ultralow lattice thermal conductivity of BiSbSeTe2, especially along the interlayer direction, which can be traced to the extremely small phonon relaxation time mainly induced by the mixed covalent bonds. As a consequence, a considerably large ZT value of ~2.0 can be obtained at 500 K, indicating that the unique lattice structure of BiSbSeTe2 caused by isoelectronic substitution could be an advantage to achieve high thermoelectric performance.

A total of 420 individuals belonged to 18 native teak (Tectona grandis L.f.) provenances from all four distributed countries and 10 introduced provenances were analyzed to for genetic variation, structure and genetic origin using SSR markers. The unbiased gene diversity for each provenance ranged from 0.4692 to 0.8523 with a mean value 0.6612, showing high variation within teak provenances and variation in India provenances was highest than in other countries’ provenances.AMOVA analysis showed that the majority of variation existed within provenances (84.760%) and also substantial variation among countries (10.586%). As more as possible plus trees from large population should be selected or conserved in order to keep genetic variability for future improvement. Different countries populations should be preserved in the natural habitat or collected for ex site conservation with cooperation and region-wise strategies.A Mantel test revealed significant correlation between genetic distances and geographic distances of teak provenances (R=0.7355, P

Low-dimensional layered materials have attracted tremendous attentions due to their wide range of physical and chemical properties and potential applications in electronic devices. Using first-principles method taking into account the quasiparticle self-energy correction and Boltzmann transport theory, the electronic transport properties of ZrSe3 monolayer are investigated, where the carrier relaxation time is accurately calculated within the framework of electron-phonon coupling. It is demonstrated that the high power factor of the monolayer can be attributed to the grooved bands near the conduction band minimum. Combined with the low lattice thermal conductivity obtained by solving the phonon Boltzmann transport equation, a considerable n-type ZT value of ~2.4 can be achieved at 800 K in the ZrSe3 monolayer.

BaTiO3 (BTO) nano-films were implanted with iron by means of ion-implantation. According to the results of X-ray diffraction (XRD) and Raman analysis, all the films are single-phase with tetragonal structure. Upon the increase of Fe dosage, on one hand, there is a decrease in c/a ratio of the unit cells. As the grain size and surface roughness of the Fe-implanted films decrease, the well crystallized film was obtained. Consequently, both decreasing of coercivity and boosting of magnetization were observed simultaneously. With the decline of the grain size and surface roughness during thermal treatment of the Fe-implanted films, there is an improvement of Fe distribution across the BTO matrix. Consequently, there is a decrease of coercivity and rise of magnetization. Upon the decrease of Fe dosage, on the other, there is a decline in magnetization, and a ferroelectric hysteresis loop is observed at a Fe dosage of 3.0 × 1014 cm− 2. Additionally, the dependence of capacitance on the applied magnetic field and its frequency were also monitored.

An advanced in vitro cervical tumor model was established by 3D printing to study the epithelial-to-mesenchymal transition (EMT), which is a very important stage of dissemination of carcinoma leading to metastatic tumors. A HeLa/hydrogel grid construct composed of gelatin, alginate, Matrigel and HeLa cells was fabricated by forced extrusion in a layer-by-layer fashion. HeLa cells rapidly proliferated, formed spheroids and presented tumorigenic characteristic in the 3D-printed structure. With the supplement of TGF-β, aggregated HeLa cells started to disintegrate, and some of them changed into fibroblast-like spindle morphology, which indicated that EMT was induced. The down-regulation of epithelial marker E-cadherin, and up-regulation of mesenchymal markers such as snail, vimentin and N-cadherin were all observed in the 3D-printed model, and performed differently in 3D and 2D models. The TGF-β induced EMT was inhibited by the treatment of disulfiram and EMT pathway inhibitor C19 in a dose dependent manner, showing great potential for future studies of a therapeutic program towards cervical tumor metastasis.

A new heavy-ion linac within a continuous-wave (CW) 4-rod radio-frequency quadrupole (RFQ) was designed and constructed as the injector for the separated-sector cyclotron (SSC) at the Heavy Ion Research Facility at Lanzhou (HIRFL). In this paper, we present the development of and the beam commissioning results for the 53.667 MHz CW RFQ. In the beam dynamics design, the transverse phase advance at zero current, sigma(0 perpendicular to), is maintained at a relatively high level compared with the longitudinal phase advance (sigma(0 parallel to)) to avoid parametric resonance. A quasi-equipartitioning design strategy was applied to control the emittance growth and beam loss. The installation error of the electrodes was checked using a FARO 3D measurement arm during the manufacturing procedure. This method represents a new approach to measuring the position shifts of electrodes in a laboratory environment and provides information regarding the manufacturing quality. The experimental results of rf measurements exhibited general agreement with the simulation results obtained using CST code. During on-line beam testing of the RFQ, two kinds of ion beams (Ar-40(8+) and O-16(5+)) were transported and accelerated to 142.8 keV/u, respectively. These results demonstrate that the SSC-Linac has made a significant progress. And the design scheme and technology experiences developed in this work can be applied to other future CW RFQs.

In t(14;18)-positive lymphoma cells, bcl-2 is expressed from a fusion mRNA transcript containing the full coding sequence of bcl-2 and 3' immunoglobulin sequences. We reported previously that antisense oligodeoxyribonucleotides directed at the bcl-2 translational start site, as well as those targeted to immunoglobulin sequences 3' of the translocation breakpoint, down-regulate bcl-2 and inhibit growth of the t(14;18)-positive lymphoma line WSU-FSCCL in vitro. We have developed a scid mouse model with this human cell line and demonstrate that antisense oligodeoxyribonucleotides targeted to immunoglobulin c(mu) sequences down-regulate bcl-2 protein expression and induce apoptosis of WSU-FSCCL cells in vivo. This leads to prolonged survival of the mice. Targeting non-oncogenic sequences outside of the breakpoints of fusion transcripts may be a clinically useful therapeutic strategy.

Objectives High-speed Maglev transportation system is an advanced technology using magnetic forces to propel, levitate, and guide the trian. Our study was to assess the EMF emitted by High-Speed Maglev Transportation System and the possible health effects of occupational exposure to the Maglev EMF. Methods The static magnetic field of Maglev were measured by Narda ETM-1 magnetic field measurement system. The time-varying EMFs of Maglev were evaluated by PMM8053 EMF measurement system. 48 employees exposed to maglev EMF were selected as occupationally exposed group while 54 employees without any Maglev EMF exposure were selected as control. Questionnaires were sent to two groups. Complete blood count was done by haematology analyzer. Blood lipid level was detected by enzymatic method. Thyroid function related hormones was evaluated by chemical immune assay. Serum melatonin level was measured by an ELISA kit. Results EMF strength of all Maglev sites was lower than the safety exposure limits of current international and Chinese national standard. The symptoms of drowsiness, memory impairment, irritability, alopecia were related to occupational exposure to maglev EMF. Abnormal rate of cholesterol and high density lipid protein in exposed group were significantly higher than control. The blood cell counts, thyroid function, and serum melatonin level had no statistical difference between two groups. Conclusions EMF emitted by the High-speed Maglev transportation system in different frequencies were lower than the exposure limits of current international and Chinese national standard. Due to the population limits, we can not draw a conclusion that occupational exposure to Maglev EMF may have adverse health effects from the previous data. However, it may gives us a clue that occupational exposure to maglev EMF may result in the alteration of neuronal function and lipid metabolism.

The contribution of central vs. peripheral mechanisms in mediating increases in plasma norepinephrine (NE) and epinephrine (Epi) during endotoxicosis were studied. Plasma catecholamine responses after endotoxin were assessed in conscious animals and in animals without central regulatory mechanisms (pithed rats). In conscious rats, endotoxin (1.5 mg/kg i.v.) induced a marked elevation in plasma NE after 90 min (3-fold), but elevations were not seen in pithed rats. Endotoxin also induced a profound increase (12- to 13-fold) in plasma Epi in conscious rats, but increases were less (2- to 3-fold) and delayed in pithed rats. These results suggest that central mechanisms are essential in plasma NE response to endotoxic challenge, whereas plasma Epi response involves both central and peripheral mechanisms, with the former being dominant. In conscious adrenal-denervated animals, plasma Epi was not elevated until 90 min postendotoxin. This delayed Epi elevation was approximately one-third of the maximal response observed in conscious adrenal-intact rats. In pithed adrenal-denervated rats, plasma Epi at 90 min postendotoxin was also increased to a level comparable to that in pithed adrenal-intact rats. These results imply that a significant fraction of peripheral release of Epi with endotoxicosis is nonneurogenic.

We evaluated the role of the baroreceptor reflex in mediating the sympathoadrenal activation during endotoxicosis, using acutely as well as chronically denervated rats. Three groups of experiments were conducted. In the first experiment, hemodynamic and plasma catecholamine responses following endotoxin (5 mg/kg iv) were measured in alpha-chloralose-anesthetized rats with acute sinoaortic baroreceptor denervation (SAD) or sham operation. In the second experiment, chronically sinoaortic-denervated rats and sham controls were used and experiments were conducted as in acute preparations. In the third experiment hydralazine (1 mg/kg iv) was given to chronically denervated rats and sham controls to evaluate the singular contribution of hypotension-evoked baroreflex disinhibition in the absence of endotoxin. In both acute and chronic preparations, endotoxin induced marked elevation of plasma norepinephrine and epinephrine in the presence as well as the absence of arterial baroreceptors (P greater than 0.05). Plasma catecholamines were significantly increased by hydralazine-induced hypotension in the sham group, but this elevation was far less than that induced by endotoxin. Hypotension alone did not significantly increase plasma catecholamines in SAD rats. These results suggest that the baroreflex is not the major factor in mediating sympathoadrenal activation during endotoxicosis and that non-baroreflex mechanisms may be involved in stimulating such activation.

In vivo and in vitro studies have shown that the vascular response to catecholamine is attenuated during endotoxemia. The mechanism of such attenuation is complex and might involve high catecholamine-induced desensitization of adrenoceptors. The purpose of this study was to assess the vascular response to adrenergic stimulation after endotoxin (ETX) administration in pithed rats. In pithed rats, sympathetic outflow is controlled by stimulation, ETX does not elevate norepinephrine (NE), and there are no compensatory reflexes. Rats were pithed, curarized, and adrenal-demedullated. Preganglionic thoracolumbar nerves were stimulated (3 Hz, 10 V, 0.5 msec) for 1 hr after pithing, at which time the first set of frequency and NE-dose responses were assessed by measuring the peak increase in diastolic blood pressure. Intravenous ETX (1.5 mg/kg or 0.5 mg/kg) or saline was administered immediately after these measurements. A sham group was designed to mimic the falling blood pressure pattern seen in the endotoxin group during 1 hr after ETX was given by gradually decreasing the stimulation frequency. The second set of frequency and NE-dose responses were evaluated 1 hr after ETX, saline, or sham treatment. Plasma NE and epinephrine (EPI) were determined before and 1 hr after ETX (1.5 mg/kg) or saline injection. The results showed that blood pressure response to adrenergic stimulation was markedly attenuated in pithed rats following both high and low doses of ETX compared with the saline and sham groups. Plasma NE was not elevated by ETX insult in pithed rats. We propose that mechanisms other than high-catecholamine-induced adrenergic desensitization or hypotension account for the attenuated adrenergic responsiveness of the vasculature following ETX.

Differential susceptibility to the induction of experimental allergic orchitis (EAO) was examined in Lewis/NCr and Le-R subline rats. Lewis/NCr rats were found to be fully susceptible to the induction of EAO whereas Le-R subline rats were not. Disease resistance exhibited by Le-R rats could be overcome by including Bordetella pertussis in the immunization protocol. However, reversal of resistance with B. pertussis was dependent on the dose of rat testicular homogenate in the inoculum and found to be effective only at lower doses of antigen (10 mg/rat). Disease resistance in Le-R rats as well as B. pertussis-induced reversal of resistance did not appear to be associated with either (1) a significant difference in the number of mast cells in the ductus efferentes, the anatomic location of the earliest inflammatory infiltrates, or (2) an alteration in the phenotypic expression of either innate or B. pertussis-induced sensitivity to vasoactive amines. The results are discussed in the context of the role of B. pertussis in other animal models of organ-specific autoimmune diseases. It is proposed that the phenotypic expression of resistance to EAO in Le-R rats is a result of a mutation in a common regulatory locus affecting susceptibility to multiple autoimmune diseases and whose immunoregulatory action is normally exerted during the sensitization phase of the immune response.

Active experimental allergic orchitis (EAO) was induced in Lewis/NCr rats by immunization with homologous rat testicular homogenate. Groups of animals were studied sequentially at five day intervals for histopathologic signs of disease. Inflammatory lesions were first observed in the ductus efferentes as early as 5 days following immunization. Immunohistochemical analysis of the testes, rete testis, ductus efferentes and caput, corpus and cauda epididymis of immunized rats on day five revealed that only the ductus efferentes exhibited a significant increase in the number of interstitial cells expressing Ia antigens (MRC OX-6) as well as CD4 (W3/25) positive helper/inducer T lymphocytes, CD8 (MRC OX-8) positive cytotoxic T lymphocytes and/or natural killer cells and macrophages (MRC OX-42). Increased staining for Ia antigens was also associated with both the vascular and ductal epithelial cells whereas cells within the lumen of the ducts were consistently negative for Ia antigen expression. In contrast, there was no detectable increase in the level of expression of rat MHC class I antigens (MRC OX-18) by any of the cells of the ductus efferentes. Similarly, there was no increase in the number of MAR 18.5 and/or MRC OX-12 positive B lymphocytes. By day 15, autoimmune epididymitis was observed in the cauda and corpus epididymis with the caput becoming involved by day 20. In the testes, the first histopathologic changes observed were scattered inflammatory infiltrates on day 15 and scattered foci of aspermatogenesis on day 20. Inflammatory lesions were first seen in the rete testis and the seminiferous tubules on day 25-30 with maximal involvement occurring on day 35-40. Early inflammatory lesions in the seminiferous tubules were characterized by peritubular and/or interstitial mixed cellular infiltrates. Later lesions included granuloma formation and necrosis. Autoimmune vasitis was not seen in any of the animals studied. Control rats immunized with rat liver homogenate plus adjuvants or adjuvants alone did not exhibit any of the histopathologic lesions described above. The observed results, when compared to those of previous studies examining the sequential histo- and immunopathology of active EAO in the guinea pig and mouse, support the concept that: 1) significant species specificity may exist with regard to regional differences in susceptibility to autoimmune attack within the male reproductive tract and 2) that such differences correlate with early maximal expression of Ia by cells within the male reproductive tract.