Regeneration After Radiation- and Immune-Mediated Tissue Injury Is Not Enhanced by Type III Interferon Signaling.

PURPOSE: Type I interferon (IFN-I) and interleukin (IL)-22 modulate regeneration of the thymus and intestinal epithelial cells (IECs) after cytotoxic stress such as irradiation. Radiation-induced damage to thymic tissues and IECs is a crucial aspect during the pathogenesis of inadequate immune reconstitution and acute graft-versus-host disease (GVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) with myeloablative total body irradiation (TBI), respectively. IL-22 and IFN-I reduce the severity of acute GVHD after allo-HSCT with myeloablative TBI. However, the role of biologically related type III interferon (IFN-III), also known as interferon lambda (IFN-λ) or IL-28, in this context is unclear. We therefore studied the role of the IFN-III pathway in thymic regeneration and GVHD after TBI and allo-HSCT. METHODS AND MATERIALS: Cohoused wild-type (WT) and IFN-III receptor-deficient (IL-28 receptor alpha subunit-deficient/IL-28Ra-/-) mice were analyzed in models of TBI-induced thymus damage and a model of GVHD after allo-HSCT with myeloablative TBI. PASylated IFN-III (PASylated IL-28A, XL-protein GmbH) was generated to prolong the plasma half-life of IFN-III. Pharmacologic activity and the effects of PASylated IL-28A on radiation-induced thymus damage and the course of GVHD after allo-HSCT with myeloablative TBI were tested. RESULTS: The course and severity of GVHD after myeloablative TBI and allo-HSCT in IL-28Ra-/- mice was comparable to those in WT mice. Activation of the IFN-III pathway by PASylated IL-28A did not significantly modulate GVHD after allo-HSCT with TBI. Furthermore, IL28Ra-/- mice and WT mice showed similar thymus regeneration after radiation, which could also not be significantly modulated by IFN-III receptor engagement using PASylated IL-28A. CONCLUSIONS: We analyzed the role of IFN-III signaling during radiation-mediated acute tissue injury. Despite molecular and biologic homologies with IFN-I and IL-22, IFN-III signaling did not improve thymus regeneration after radiation or the course of GVHD after myeloablative TBI and allo-HSCT.

Acute ablation of DP thymocytes induces up-regulation of IL-22 and Foxn1 in TECs.

Thymic epithelial cells (TECs) provide the basic architecture for the development of thymocytes. TEC is regenerative after impairment in thymus of young mice. However, how this regeneration program is governed remains unclear. Transcription factor Foxn1 is a central mediator of the differentiation and function of TEC. We examined the relation between thymic injury and Foxn1 in TEC. Total body irradiation (TBI) treatments induced up-regulation of Foxn1 in TEC, which was abolished when thymic function recovered. Specific depletion of double positive (DP) thymocytes triggered the up-regulation of Foxn1. On the other hand, extracellular IL-22 is a potential regulator of homeostasis of TEC. We demonstrated that TBI treatments also induced the up-regulation of intrathymic IL-22. Expression pattern of Foxn1 shares similar characteristics with IL-22. Furthermore, Foxn1 related genes that regulate the function of TEC were also up-regulated. Thus, our data reveal that TBI treatment triggers regeneration program of TEC.

Necropsy findings in dogs that died during grooming or other pet service procedures.

Procedures involved in grooming, bathing, and other pet services can often lead animals to death. Of the necropsies of 1391 animals carried out at a private diagnostic laboratory in Sao Paulo, Brazil from 2004 to 2009, 94 were dogs that died during the above-mentioned procedures. Young male dogs and small breeds like Poodle Miniature, Yorkshire Terrier, and Lhasa Apso were most frequently observed. Blunt-force trauma was responsible for the deaths of 31% of the animals, with a higher incidence of trauma to the head, characterized chiefly by fractures and nervous tissue lesions. In the other 69% of cases, the animals showed signs of stress, and died due to pulmonary edema and hemorrhage. As we cannot rule out the intentional character in some situations, this article provides veterinary forensic support for veterinarians and pet owners, especially in lawsuits, helping in finding the cause of animal's death in such pet services.

Diffuse thymic fibrosis: histologic pattern of injury or distinct entity?

Thymic fibrosis in the absence of another primary thymic lesion, such as a neoplasm or cyst, is unusual. We identified 6 cases of primary extensive thymic fibrosis that developed in 3 men and 3 women, aged 28 to 60 years, mean 48 years. Patients had limited or no symptoms. Two patients had dyspnea and 1 had cough and hemoptysis. One female patient had myasthenia gravis. The lesions measured 3.5 to 17 cm in greatest dimension, mean 8 cm, and were confined to the anterior mediastinum as determined by imaging, intraoperative notes, and/or gross examination. All cases showed diffuse fibrosis with variable collagen deposition, lymphoplasmacytic infiltrates, and involution/atrophy of thymus. One case had rare IgG4-positive plasma cells and focal obliterative phlebitis. The histology showed overlap with that of IgG4-related sclerosing disease, which to our knowledge has not been documented earlier in this location. Although the etiology of the lesions is undetermined, altered immunity and/or infection may play a role.

[Regenerative activity of muscle tissue and thymus status in young and old mdx mice with muscle injury and wound xenoplasty].

Responses of the skeletal muscle tissue and thymus to muscle injury (complete transection) and wound xenoplasty with the minced muscle tissue of newborn rats (tissue therapy) were studied in mdx mice aged 12-16 and 40-48 weeks. The muscle tissue of mdx mice has genetic defects causing chronic dystrophic processes in it. The muscle tissue of young mdx mice proved to retain a relatively high capacity for regeneration. Under conditions of tissue therapy of the wound, the formation of muscle fibers from muscle cells of the graft and active regeneration of muscle fibers in the recipient mice were observed, and no structural defects were detected in the thymus. The capacity of posttraumatic regeneration in old mdx mice was lower. The xenogenic graft was undergoing resorption, thereby suppressing regeneration of muscle fibers and causing further tissue destruction in the injured muscle. The thymus parenchyma was subject to degenerative changes such as the formation of gaps, hemorrhagic foci, and increased numbers of macrophages and mast cells.

Histiocitosis de células de Langerhans con afectación tímica como manifestación única de la enfermedad / the Langerhans´ cell histiocytosis with thymic localization as initial and exclusive place

La histiocitosis de células de Langerhans (HCL), conocida también como Histiocitosis X es una enfermedad granulomatosa poco frecuente de etiología no aclarada que puede tener manifestaciones y localizaciones diversas, sin embargo la localización tímica como lugar inicial y exclusivo de presentación de HCL es bastante inusual. Se presenta el caso de un paciente que debutó con una clínica inespecífica, donde las pruebas de imagen pusieron de manifiesto una masa en mediastino anterior y que tras los análisis anatomopatológicos e inmunohistoquímicos evidenciaron una proliferación de células de Langerhans y eosinófilos siendo positiva para CD1a y S-100 confirmando el diagnóstico de HCL

The Langerhans’cell histiocytosis (LCH), also known as Histiocitosis X it is an illness not very frequent granulomatosus etiology not clarified yet, that it can have different manifestations and localizations, however the thymic localization as initial and exclusive place gives presentation HCL it is quite unusual. The present case is presented a patient that debuted with a clinical unspecific, where the tests give image they put she gives apparent a mass in previous mediastinum and that after the pathologic and immunohistochemical analysis they evidenced a proliferation Langerhans’s cells and eosinophils it being positive for CD1a and S-100 confirming the diagnosis of the LCH

[The morphological characteristics of the microcirculatory bed of the thymic capsule in the dynamics of the posttraumatic period]. / Morfologicheskie osobennosti mikrotsirkuliatornogo rusla kapsuly vilochkovoi zhelezy v dinamike posttravmaticheskogo perioda.

Describes the status of microvessels of thymic capsule in mechanical injury. Features the changes occurring in the capsular microvessels in the course of the posttraumatic period and the morphology of all the components involved.

Histopathologic investigations of acute and subchronic toxicities of some organotin compounds in chickens.

The acute and subchronic oral toxicities of 4 organotin derivatives were investigated in chickens. The LD50 values oscillated between 200 and 400 mg/kg bw and revealed a moderate or weak toxicity. Subchronic dosing with 2 doses from each compound at 2 and 10 mg/kg bw induced dose-dependent lesions seen at necropsy and histologic examinations. Involution of the thymus and bursa Fabricius, fatty degeneration of the liver, and nephrotic syndromes were the most evident effects. The butyltin derivatives induced more drastic lesions than did the phenyltins.

[Effect of separate and combined effects of plutonium-239, hexachlorobutadiene and tributyl phosphate on the thymus gland of rats]. / Vliianie razdel'nogo i sochetannogo deistviia plutoniia-239, geksakhlorbutadiena, tributilfosfata na vilochkovuiu zhelezu krys.

It has been established in the experiment on rats exposed to a joint action of plutonium-239, hexachlorobutadiene and ++tributyl phosphate, that manifestations of disturbances from radiation and chemical factors which are more expressed under a joint exposure, are characteristic of the thymus gland damage pattern. As far as lymphocytes count in the organ is concerned, the effect of the joint exposure is no more than additive.

The possible role of fungal infections in AIDS.

The acquired immunodefficiency syndrome (AIDS) is characterized by a gross defect in the cell-mediated immune response. However, infection with human immunodeficiency virus (HIV), which is the generally accepted etiological factor of AIDS, cannot explain by itself the following problems: why do not some of the seropositive subjects develop AIDS or AIDS-related complex; why are some of the patients with AIDS seronegative for HIV and its corresponding antibodies; what is the reason why some of the healthy seronegative subjects from groups at a high risk for AIDS (homosexuals, hemophiliacs and drug abusers) have low T-helper to T-suppressor ratios. We suggest that some additional factor is necessary for the development of AIDS. We propose that the factor needed is a 'partial functional thymectomy'. We suspect that slow fungal infections, producing thymotoxic metabolites, may be a major cause for the latter.

[Resuscitation measures and petechial thymus hemorrhages in sudden infant death]. / Reanimationsmassnahmen und petechiale Thymus-Blutungen beim plötzlichen Kindstod.

In 45 cases of sudden infant death syndrome (SIDS) in which unsuccessful attempts at resuscitation had been made and in 21 cases without attempted resuscitation, systematic histological investigations were carried out on the thymus. In these investigations, petechial hemorrhages were detected in 82% of the cases with attempted resuscitation and in 76% of the cases without attempted resuscitation. The histological distribution pattern of the petechial thymus hemorrhages did not differ notably between the two groups. The pattern of findings indicates that the hemorrhages had already developed during the death agony and that the typical histological distribution pattern with an increased occurrence of petechial in the cortical zone was altered by massive attempts at resuscitation in individual cases.

[The thymus in exposure to pain]. / Vilochkovaia zheleza pri bolevykh vozdeistviiakh.

The effect of isotonic solution and microtrauma of the gastrocnemius muscle to the structure and cell composition in various zones of the thymus has been studied on mature white male rats on the first, 7th and 14th days of the experiment. At injection of the isotonic solution (sodium chloride) the part of small lymphocytes decreases and that of the large and middle ones--increases (it is mostly manifested on the 7th day of the experiment). The amount of immature plasma cells increases sharply at the same time, and that of mature cells--fluctuates during the experiment. The number of the mitotically dividing cells decreases. To some extent grows the part of the reticuloepitheliocytes; this demonstrates that migration of the lymphoid line cells from the thymus becomes greater. Pricks of the syringe needle do not produce any statistically significant changes.

Pneumodiastino e tomografia computadorizada no diagnóstico de lesöes do timo / Pneumomediastinum and computerized tomography in the diagnosis of thymus injuries

Utilizou-se o pneumomediastino, com a técnica de punçäo supra-esternal, para exame do mediastino em 41 pacientes, 7 dos quais associados à tomografia computadorizada. Dois outros pacientes foram submetidos apenas à tomografia. A principal indicaçäo está em pequenas lesöes do timo, tendo sido diagnosticados 5 casos de timoma, 2 de cisto tímico, 34 de hiperplasia e 1 normal. O timo normal no adulto näo ultrapassa 5 mm de espessura por 25 mm de largura, embora seu comprimento seja variável. Qualquer alteraçäo de suas dimensöes é facilmente diagnosticada por ambos os métodos. Nas pequenas lesöes, principalmente nas näo invasívas, o pneumomediastino é täo diagnóstico quanto a tomografia computadorizada, sendo este método nitidamente superior nas grandes lesöes e no estadiamento dos timomas invasivos