Anti-Apoptotic Effect of Nerve Growth Factor Is Lost in Congenital Insensitivity to Pain with Anhidrosis (CIPA) B Lymphocytes

Congenital insensitivity to pain with anhidrosis (CIPA) is identified as a genetic disorder of mutations in the human TrkA known as high affinity receptor of nerve growth factor (NGF). NGF signal through TrkA promotes anti-apoptotic activity in hematopoietic cells including B lymphocytes. Here we studied the effect of NGF on anti-apoptotic activity by using human EBV-immortalized B lymphoblastoid cell lines (EB-LCLs) derived from a patient with CIPA and the associated carriers of CIPA. The TrkA(mt/mt) EB-LCL derived from the CIPA patient and the TrkA(wt/mt) EB-LCL derived from the carrier with the heterozygous TrkA mutation did not show any responses to NGF on anti-apoptotic activity. We concluded that this phenomenon is one of the pathogeneses of CIPA.     

Melanocyte lysis by cytotoxic T lymphocytes recognizing the MART-1 melanoma antigen in HLA-A2 patients with Vogt Koyanagi Harada disease

The MART-1/Melan-A melanoma antigen recognized by the majorityof HLA-A2-restricted tumorinfiltrating lymphocytes is a selfantigen expressed on melanocytes and the retina. We have investigatedwhether Vogt–Koyanagi–Harada (VKH) disease and sympatheticophthalmia (SO), systemic inflammatory disorders affecting variousorgans containing melanocytes, are autoimmune diseases directedtoward the MART-1 antigen. In two of three patients with VKHdisease and one patient with SO, CD8⁺ T cell clones (TCC) fromintraocular fluid of HLA-A2⁺ patients lysed T2 cells when pulsedwith a HLA-A2-binding MART-1 peptide, but not a HLA-A2-bindingpMel-17 or tyrosinase peptide, in a HLA-A2-restricted manner.These CD8⁺ TCC lysed both melanocytes and melanoma cells ina HLA-A2-restricted manner. In addition, CD8⁺ TCC recognizinga HLA-A2-binding MART-1 peptide were also established from peripheralblood mononuclear cells of a patient with VKH disease. In contrast,either CD4⁺ TCC from these patients or CD8⁺ TCC from the intraocularfluid of HLA-A2⁺ patients with uveitis associated with Behcet'sdisease or HTLV-I uveitis did not show this cytotoxicity. Theresults demonstrate that the MART-1 peptide-specific cytotoxicT lymphocytes lyse melanocytes in the eye of patients with VKHdisease or SO, suggesting that these diseases are autoimmunediseases directed toward the MART-1 antigen in HLA-A2⁺ patients.     

Distribution of facial motoneurons innervating the common facial muscles of the rabbit and rat

The distribution of the facial neurons that innervate several facial muscles was determined in the rabbit and the rat by examining the retrograde transport of horseradish peroxidase (HRP). The target muscles were musculus levator nasolabialis, m. levator labii superioris, m. zygomaticus, and m. buccinator pars buccalis, as well as m. parietoauricularis and m. depressor anguli oris in the rabbit and m. levator auricularis posterioris in the rat. Localization of the retrogradely labeled neurons within the ipsilateral facial nucleus was confirmed for all facial muscles examined. Our results showed that m. levator nasolabialis was innervated by neurons located in the dorsal subnucleus, while the motoneurons innervating m. buccinator pars buccalis were distributed within the dorsal part of the intermediate subnucleus of the facial nucleus in the both species. Localization of the labeled motoneurons innervating m. zygomaticus and m. levator labii superioris showed the difference in the distribution within the facial nucleus among the species. Neurons innervating m. parietoauricularis and m. levator auricularis posterioris were localized in somewhat different subregions of the medial subnucleus in these species. M. depressor anguli oris was innervated by the neurons distributed within the intermediate subnucleus of the facial nucleus in the rabbit. Thus, our findings revealed that there is species-specific motor innervation pattern in rabbits and rats, despite several movement of the face is supplied by the homologous facial muscles.     

Estimation of apoptosis and cell proliferation in histiocytic necrotizing lymphadenitis using immunohistochemical double staining

The aim of the present study was to estimate the relationship between apoptosis and cell proliferation in histiocytic necrotizing lymphadenitis (HNL). Fifteen patients with HNL were retrospectively analyzed. The patients were divided into three groups according to the proportion of the necrotic area as follows: necrosis (+), necrotic area <25%; necrosis (++), necrotic area 25–50%; and necrosis (+++), necrotic area >50%. Immunohistochemical double staining was performed for CD3 plus caspase-3 and for Ki-67 plus caspase-3 and positive cells were counted in two areas: one without and one with obvious apoptotic features. Most caspase-3-positive cells were also stained for CD3 (area exhibiting obvious apoptotic features: average, 92.3%). Furthermore, various proportions of both Ki-67- and caspase-3-positive cells were detected in all the groups (range, 5–70%). In the area with obvious apoptotic changes, the average percentage of both Ki-67- and caspase-3-positive cells (38.6%) was higher than that in the area without obvious apoptotic features (16.3%). A proportion of cells in HNL undergo proliferation and apoptosis simultaneously, such as neoplastic cells, thereby exhibiting rapid cell cycles.     

Clinicopathologic analysis of peripheral T-cell lymphoma, follicular variant, and comparison with angioimmunoblastic T-cell lymphoma: Bcl-6 expression might affect progression between these disorders

We examined clinicopathologic findings in 17 cases of peripheral T-cell lymphoma, follicular variant (f-PTCL), and compared these findings with angioimmunoblastic T-cell lymphoma (AITL) to determine whether they were identical to the spectrum of changes seen in AITL and how each of the findings in f-PTCL were related to the characteristics of AITL. Almost all f-PTCL cases showed pathologic characteristics of AITL and immunohistochemical positivities in lymphoma cells for CD4, CD10, Bcl-6, PD-1, and CXCL13. Except for pathologic characteristics, clinicopathologic findings in f-PTCL had few significant differences from AITL. The positive rate for Bcl-6 expression in neoplastic cells was significantly associated with the frequency of polymorphic infiltrates, vascular proliferation, B-immunoblasts, clear cells, Epstein-Barr virus-positive lymphocytes, hepatosplenomegaly, and skin rash. Our study confirmed the continuity between f-PTCL and AITL. Moreover, Bcl-6 expression in f-PTCL was statistically associated with the characteristics of AITL.     

Absence of SHATI/Nat8l reduces social interaction in mice

Rapidly adapting mechanically activated channels (RA) are expressed on somatosensory neurons and thought to play a role in mechanical transduction. Because mechanical sensations can be significantly affected by temperatures, we examined thermal sensitivity of RA currents in cultured dorsal root ganglion (DRG) neurons to see if RA channel activity is highly temperature-dependent. RA currents were evoked from DRG neurons by membrane displacements and recorded by the whole-cell patch-clamp recording technique. We found that RA currents were significantly enhanced by warming temperatures from 22 to 32 °C and reduced by cooling temperatures from 24 to 14 °C. RA channel activation exhibited steep temperature-dependence with a large temperature coefficient (Q10>5) and a high activation energy (Ea>30 kcal/mol). We further showed that RA channel activation by mechanical stimulation led to membrane depolarization, which could result in action potential firing at 22 °C or 32 °C but not at 14 °C. Taken together, our results provide the measurements of thermal dynamics and activation energy of RA channels, and suggest that a high energy barrier is present for RA channels to open. These findings are in agreement with temperature sensitivity of mechanical sensations in mammals.     

Composite T lymphoblastic leukemia/lymphoma and diffuse large B-cell lymphoma: case report

This report concerns a unique case of a composite lymphoma composed of T-lymphoblastic leukemia/lymphoma (T-LBL) and diffuse large B-cell lymphoma (DLBCL) in a 72-year-old woman with generalized lymphadenopathy, splenomegaly and ascites. Laboratory findings showed increased lactate dehydrogenase and soluble interleukin-2 receptor. The biopsy specimen showed replacement of the normal architecture of the lymph nodes by a tumor containing a dual cell population composed of large lymphocytes and medium-sized lymphocytes. Sheets of large lymphocytes often were punctuated by clusters of medium-sized lymphocytes. Flow cytometry and immunohistochemical analysis showed a composite lymphoma with both T-LBL and DLBCL. The T-LBL expressed CD1a, CD3, CD4, CD8, and terminal deoxynucleotidyl transferase. The DLBCL expressed CD19 and CD20, CD23, bcl-2, bcl-6, MUM1 and immunoglobulin κ light chain. Polymerase chain reaction detected a monoclonal pattern of T-cell receptor γ and immunoglobulin heavy chain rearrangements in the same specimen. She received eight cycles of R-CHOP (rituximab+cyclophosphamide, doxorubicin, vincristine, prednisone) therapy and achieved complete remission. She has shown no signs of recurrence 20 months after the diagnosis. We describe here a very unusual and, to the best of our knowledge, an as yet never reported case of a primary composite lymphoma of T-LBL and DLBCL.     

Relevance of Fc gamma RIIIa-158V-F polymorphism to recurrence of adult periodontitis in Japanese patients.

The immunoglobulin receptor Fc gamma RIIIa (CD16) is distributed on natural killer (NK) cells, macrophages, and gamma delta T cells, and is polymorphic. Fc gamma RIIIa-158V has a higher affinity for both monomeric and immune complexed IgG1, IgG3, and IgG4 than IIIa-158F. We determined Fc gamma RIIIa-158V/F genotypes of Japanese patients with adult periodontitis. A significant over-representation of Fc gamma RIIIa-158F was found in patients with recurrence, compared with patients without recurrence, making Fc gamma RIIIA a candidate gene for recurrence risk of adult periodontitis.     

Isolation of Trichosporon asahii from environmental materials.

Trichosporon asahii is the most clinically important pathogenic yeast in the genus Trichosporon, as this species causes both deep-seated infection and summer-type hypersensitivity pneumonitis. We isolated 29 T. asahii colonies from environmental samples using the polymerase chain reaction (PCR) and dichloran rose bengal chloramphenicol (DRBC) medium. Our results suggest that T. asahii is common in nature.