Immunohistochemistry or Molecular Analysis : Which Method Is Better for Subtyping Craniopharyngioma?

Craniopharyngioma (CP) is mainly classified into two pathological subtypes: adamantinomatous (ACP) and papillary (PCP). CTNNB1 (β-catenin) mutations are detected in ACPs, and the BRAF V600E mutation is detected in PCPs. However, genetic analysis is not always possible in general medical practice. In this study, we investigated whether immunohistochemistry could replace genetic analysis as an aid in subtype diagnosis. Here, 38 CP patients who had undergone their first tumor resection were included. Among the 38 cases, 22 were morphologically diagnosed as ACP, 10 cases were diagnosed as PCP, and six cases were diagnosed as undetermined CP that were morphologically difficult to classify as either ACP or PCP. Results of immunohistochemistry and genetic analysis and clinical features were compared. Based on the immunohistochemistry, 26 (22 ACPs and four undetermined CPs) showed nuclear β-catenin expression, 11 (nine PCPs and two undetermined CPs) exhibited positive BRAF V600E immunostaining and one PCP showed membranous β-catenin expression and negative for BRAF V600E immunostaining. Among the 26 nuclear β-catenin expression cases, 11 had CTNNB1 mutations; however, 15 cases had mutations of neither CTNNB1 nor BRAF V600E. All 11 BRAF V600E immunopositive cases had BRAF V600E mutations. When comparing clinical features between, pediatric patients and those with tumor calcification and less solid components on MRI more commonly had nuclear β-catenin expression tumors than BRAF V600E immunopositive tumors, reflecting the differences in clinical features between ACP and PCP. Accordingly, immunohistochemistry can replace genetic analysis as an aid to determine the subtype diagnosis of CP in general medical practice

Minichromosome Maintenance 2 Bound with Retroviral Gp70 Is Localized to Cytoplasm and Enhances DNA-Damage-Induced Apoptosis

The interaction of viral proteins with host-cellular proteins elicits the activation of cellular signal transduction pathways and possibly leads to viral pathogenesis as well as cellular biological events. Apoptotic signals induced by DNA-damage are remarkably up-regulated by Friend leukemia virus (FLV) exclusively in C3H hosts; however, the mechanisms underlying the apoptosis enhancement and host-specificity are unknown. Here, we show that C3H mouse-derived hematopoietic cells originally express higher levels of the minichromosome maintenance (MCM) 2 protein than BALB/c- or C57BL/6-deriverd cells, and undergo more frequent apoptosis following doxorubicin-induced DNA-damage in the presence of the FLV envelope protein gp70. Dual transfection with gp70/Mcm2 reproduced doxorubicin-induced apoptosis even in BALB/c-derived 3T3 cells. Immunoprecipitation assays using various deletion mutants of MCM2 revealed that gp70 bound to the nuclear localization signal (NLS) 1 (amino acids 18–24) of MCM2, interfered with the function of NLS2 (amino acids 132–152), and suppressed the normal nuclear-import of MCM2. Cytoplasmic MCM2 reduced the activity of protein phosphatase 2A (PP2A) leading to the subsequent hyperphosphorylation of DNA-dependent protein kinase (DNA-PK). Phosphorylated DNA-PK exhibited elevated kinase activity to phosphorylate P53, thereby up-regulating p53-dependent apoptosis. An apoptosis-enhancing domain was identified in the C-terminal portion (amino acids 703–904) of MCM2. Furthermore, simultaneous treatment with FLV and doxorubicin extended the survival of SCID mice bearing 8047 leukemia cells expressing high levels of MCM2. Thus, depending on its subcellular localization, MCM2 plays different roles. It participates in DNA replication in the nucleus as shown previously, and enhances apoptosis in the cytoplasm

On the origin and evolution of the asteroid Ryugu: A comprehensive geochemical perspective

Presented here are the observations and interpretations from a comprehensive analysis of 16 representative particles returned from the C-type asteroid Ryugu by the Hayabusa2 mission. On average Ryugu particles consist of 50% phyllosilicate matrix, 41% porosity and 9% minor phases, including organic matter. The abundances of 70 elements from the particles are in close agreement with those of CI chondrites. Bulk Ryugu particles show higher δ18O, Δ17O, and ε54Cr values than CI chondrites. As such, Ryugu sampled the most primitive and least-thermally processed protosolar nebula reservoirs. Such a finding is consistent with multi-scale H-C-N isotopic compositions that are compatible with an origin for Ryugu organic matter within both the protosolar nebula and the interstellar medium. The analytical data obtained here, suggests that complex soluble organic matter formed during aqueous alteration on the Ryugu progenitor planetesimal (several 10’s of km), <2.6 Myr after CAI formation. Subsequently, the Ryugu progenitor planetesimal was fragmented and evolved into the current asteroid Ryugu through sublimation

Carbonyl Reductase 3 (CBR3) Mediates 9-cis-Retinoic Acid-Induced Cytostatis and is a Potential Prognostic Marker for Oral Malignancy

The molecular mechanisms of growth suppression by retinoic acid (RA) were examined. Our results suggest that the cytostatic effects of RA could be mediated by the activation of endogenous CBR3 gene in oral squamous cell carcinomas (OSCCs), and the expression is a potential marker for oral malignancy

Synovial chondromatosis of the temporomandibular joint accompanied by loose bodies in both the superior and inferior joint compartments : case report

Synovial chondromatosis (SC) of the temporomandibular joint (TMJ) is a benign lesion characterized by the formation of metaplastic cartilaginous nodules. SC of the TMJ usually only affects the superior joint compartment of the TMJ. We report a rare case of SC of the TMJ affecting the inferior as well as superior joint compartments

Effects of Friend leukemia virus (FLV) inoculation in F1 mice and differentiation of FLV-induced leukemia

Effects of Friend leukemia virus (FLV) inoculation in F, specific pathogen free (SPF) mice were examined. Resistance to FLV was dominantly inherited both in F, hybrid mice (BDF,) (FLV-resistant & FLVsensitive with polycythemia) and F, hybrid mice (B6C3FI) (FLV-resitant & FLV-sensitive with anemia). But the population dynamics of the nucleated cell components of F, mice after FLV inoculation differed from those of FLV-resistant inbred mice. A small number of mature erythroblasts appeared in the peripheral blood of BDF, mice. In B6C3FI mice, erythroblastosis with splenomegaly and polycythemia occurred. However, all of these findings in BDF, and B6C3FI mice regressed spontaneously. In F, mice, FLV induced an intermediate reactive pattern of the two patterns that had been induced in the parental strains. The results indicate that FLV may induce leukemia with various degrees of differentiation, according to the genetic difference of the host

RELATION BETWEEN FRIEND LEUKEMIA VIRUS-INDUCED LEUKEMIA AND GENETIC CONTROL OF THE HOST

Hematological assays of inbred specific pathogen-free (SPF) mice of ten different strains inoculated with Friend leukemia virus (FLV) were performed chronologically to assess whether the genetic control of the host may play an important role in viral oncogenicity. Mice strains C57BL/6J, B 10 (H-2b) and B 10D2 (H-2d) were FLV-resistant, BALB/c, DBA/2N (H-2d), RFM (H-2f), AKR and 80% of CBA/JN (H-2k) were FLY-sensitive (polycythemia) and C3H/ He, B10Br and 20% of CBA/JN (H-2k) were FLY-sensitive (anemia). Only the AKR strain mice showed a spontaneous regression of splenomegaly. These results indicate that there is not a strong but a weak correlation between the H-2 haplotype and the reaction to FLV. The main phenomenon in the anemic mice was the monotonous proliferation of the naked blastic cell, whereas that in the polycythemic mice was the enormous increase of the mature erythroblast and the decrease of the naked blastic cell in the later phase. These facts suggest that the naked blastic cell in the mice with polycythemia are reactive and that in the mice with anemia truly neoplastic

A novel venom protein of the Asian bee (Apis cerana indica) with an affinity to human α1-microglobulin

ABSTRACTBee stings are a common health problem throughout the world and can sometimes result in fatal anaphylactic reactions. We have studied Asian bee (Apis cerana indica, Apis cerana nigrocincta and Apis dorsata) venoms and have discovered a novel protein with a molecular size of 50kDa (p50), as shown by sodium dodecyl sulfate–polyacrylamide gel electrophoresis, which has not been reported in the venom of the Western honey-bee, Apis mellifera (AM). The p50 protein showed a unique affinity to human α1-microglobulin (α1-m). As a result, p50 was purified using an affinity column with α1-m. The p50 protein was further purified by an affinity column with a monoclonal antibody raised against p50 in mice. The p50 protein induced an inflammatory reaction following injection into mouse ear; that is, degranulation of mast cells, edema, hyperemia and hyperpermeation of the local capillaries were observed. The reaction was very similar to that seen when phospholipase A2 of AM, a representative bee venom, was administered by injection. The inflammatory reaction induced by p50 was completely inhibited by mixing p50 with α1-m prior to injection. These results indicate that p50 is a unique venom component of the Asian bee that induces the inflammatory reaction and that human α1-m may be involved as a protective mechanism against bee stings of at least some Asian bee species