Reciprocal Roles for CCAAT/Enhancer Binding Protein (C/EBP) and PU.1 Transcription Factors in Langerhans Cell Commitment

Myeloid progenitor cells give rise to a variety of progenies including dendritic cells. However, the mechanism controlling the diversification of myeloid progenitors into each progeny is largely unknown. PU.1 and CCAAT/enhancing binding protein (C/EBP) family transcription factors have been characterized as key regulators for the development and function of the myeloid system. However, the roles of C/EBP transcription factors have not been fully identified because of functional redundancy among family members. Using high titer–retroviral infection, we demonstrate that a dominant-negative C/EBP completely blocked the granulocyte–macrophage commitment of human myeloid progenitors. Alternatively, Langerhans cell (LC) commitment was markedly facilitated in the absence of tumor necrosis factor (TNF)α, a strong inducer of LC development, whereas expression of wild-type C/EBP in myeloid progenitors promoted granulocytic differentiation, and completely inhibited TNFα-dependent LC development. On the other hand, expression of wild-type PU.1 in myeloid progenitors triggered LC development in the absence of TNFα, and its instructive effect was canceled by coexpressed C/EBP. Our findings establish reciprocal roles for C/EBP and PU.1 in LC development, and provide new insight into the molecular mechanism of LC development, which has not yet been well characterized

Immunohistochemical Detection of Propionibacterium acnes in Granulomas for Differentiating Sarcoidosis from Other Granulomatous Diseases Utilizing an Automated System with a Commercially Available PAB Antibody

Propionibacterium acnes is implicated in the pathogenesis of sarcoidosis. We investigated the usefulness of immunohistochemistry (IHC) with a commercially available P. acnes-specific monoclonal antibody (PAB antibody) for differentiating sarcoidosis from other granulomatous diseases. Formalin-fixed paraffin-embedded tissue samples from 94 sarcoidosis patients and 30 control patients with other granulomatous diseases were examined by the original manual IHC method. We also compared the detection frequency of P. acnes in sarcoid granulomas between manual and automated IHC methods. P. acnes was detected in sarcoid granulomas of samples obtained by transbronchial lung biopsy (64%), video-associated thoracic surgery (67%), endobronchial-ultrasound-guided transbronchial-needle aspiration (32%), lymph node biopsy (80%), and skin biopsy (80%) from sarcoidosis patients, but not in any non-sarcoid granulomas of the samples obtained from control patients. P. acnes outside granulomas, however, was frequently detected in both groups. The detection status of P. acnes in granulomas did not correlate with the clinical characteristics of sarcoidosis patients. The automated Leica system exhibited the best detection sensitivity (72%) and almost an identical localization for P. acnes in sarcoid granulomas compared with the manual method. IHC with a PAB antibody is useful for differentiating sarcoidosis from other granulomatous diseases by detecting P. acnes in granulomas. An automated method by the Leica system can be used in pathology laboratories for differential diagnosis of granulomas by IHC with the PAB antibody

Suppression of lattice thermal conductivity by mass-conserving cation mutation in multi-component semiconductors

In semiconductors almost all heat is conducted by phonons (lattice vibrations), which is limited by their quasi-particle lifetimes. Phonon-phonon interactions represent scattering mechanisms that produce thermal resistance. In thermoelectric materials, this resistance due to anharmonicity should be maximised for optimal performance. We use a first-principles lattice-dynamics approach to explore the changes in lattice dynamics across an isostructural series where the average atomic mass is conserved: ZnS to CuGaS$_2$ to Cu$_2$ZnGeS$_4$. Our results demonstrate an enhancement of phonon interactions in the multernary materials, and confirm that lattice thermal conductivity can be controlled independently of the average mass and local coordination environments.Comment: 13 pages, 4 figure

Paired Activating and Inhibitory Immunoglobulin-like Receptors, MAIR-I and MAIR-II, Regulate Mast Cell and Macrophage Activation

Immune responses are regulated by opposing positive and negative signals triggered by the interaction of activating and inhibitory cell surface receptors with their ligands. Here, we describe novel paired activating and inhibitory immunoglobulin-like receptors, designated myeloid-associated immunoglobulin-like receptor (MAIR) I and MAIR-II, whose extracellular domains are highly conserved by each other. MAIR-I, expressed on the majority of myeloid cells, including macrophages, granulocytes, mast cells, and dendritic cells, contains the tyrosine-based sorting motif and the immunoreceptor tyrosine-based inhibitory motif-like sequences in the cytoplasmic domain and mediates endocytosis of the receptor and inhibition of IgE-mediated degranulation from mast cells. On the other hand, MAIR-II, expressed on subsets of peritoneal macrophages and B cells, associates with the immunoreceptor tyrosine-based activation motif-bearing adaptor DAP12 and stimulates proinflammatory cytokines and chemokine secretions from macrophages. Thus, MAIR-I and MAIR-II play important regulatory roles in cell signaling and immune responses

A study on the scattering exposure dose in radiotherapy.

現代の医療のなかで癌治療において不可欠な存在となった放射線治療｡一方,放射線被曝はたとえわずかであってもリスクが伴い,厳しく規制されている｡ただし医療被曝はこの限りになく,過去においては癌患者に放射線治療をおこなう際の患部以外の被曝についてはあまり問題視されなかった｡これには癌の治療という前提に加え,長期生存の可能性が低く,存命中に晩発障害が発生することが低いと考えられていたからである｡しかし,集学的治療が確立した今後の放射線治療においては完治する放射線治療患者が多くなり,治癒後の余命が長くなることが予測される｡放射線被曝による確率的影響は閾値がなく,影響は当然現れるであろう｡そこで,放射線治療をおこなう際の患者の散乱線被曝線量,治療室内散乱線量,さらに高エネルギー放射線発生装置を取り扱うときに問題となっている中性子を測定した｡その結果,測定線量は治療患部外被曝,室内散乱線量ともに無視できない量であることがわかった｡中性子については,人体に影響がある線量は検出されなかったが,中性子の存在は室内物品の放射化の可能性を示唆するもので定期的な測定管理が必要である｡また,Ⅹ線撮影室用の防護衣による散乱線被曝の低減効果は放射線治療室では無意味であった｡In modern medicine, radiotherapy has proved indispensable in the treatment of cancer. However. radiation exposure is a health hazard. and is thus strictly regulated. In the past, incidental exposure was not considered to pose a considerable risk, and because radiotherapy was an effective treatment for cancer and because the possibility of the long-term survival was generally poor, the prevalence of radiation injury was thought to be low. In recent years, however, more patients are making complete recoveries, and it is believed that long-term survival is possible with future radiotherapy techniques. There is no threshold for the stochastic effects of radiation exposure, and thus such effects may be detected even at low levels. In the present study, we measured the radiation exposure due to scattered rays from the patient, incidental radiation levels in the radiotherapy room, and levels of neutron radiation. which is a problem when high-energy X-ray radiotherapy systems are used. The results showed that exposure due to scattered rays and incidental levels in the radiotherapy room cannot be dismissed. and that further investigation is warranted. As for neutron radiation, dosages were below those that are known to influence the human body, but regular measurement is necessary because it may induce radioactivity in otherwise benign equipment. In addition, a protective apron had no effect on the exposure due to scattered rays in the radiotherapy room