Mixed mucin-producing and squamous differentiated tumor of the uterine cervix: a report of a case as adenosquamous carcinoma in situ.

We report a non-invasive mixed mucin-producing and squamous differentiated tumor of the uterine cervix. This tumor was composed of two cell types: mucin-producing cells and non-mucin-producing cells. These cells were intimately mixed with each other, and showed intraepithelial spreading. The mucin-producing cells showed signet-ring or columnar shapes, and were localized to the lower-to-upper epithelial layer. The non-mucin-producing cells had eosinophilic cytoplasms with a monotonous appearance through the epithelium. Mitosis was sometimes observed in both cell types. Immunohistochemically, both cell types were positive for p16(INK4A) . The non-mucin-producing cells were positive for p63 and 34ßE12, suggesting squamous differentiation. Although most mucin-producing cells were p63(-) , a few of them were p63(+) and many 34ßE12 immunoreactive cells were found in the mucin-producing cells. This tumor was adenosquamous carcinoma in situ.

m-Calpain induction in vascular endothelial cells on human and mouse atheromas and its roles in VE-cadherin disorganization and atherosclerosis.

BACKGROUND: Although dysfunction of VE-cadherin-mediated adherence junctions in vascular endothelial cells (ECs) is thought to be one of the initial steps of atherosclerosis, little is known regarding how VE-cadherin is disrupted during atherogenic development. This study focused on the role of calpain, an intracellular cysteine protease, in the proteolytic disorganization of VE-cadherin and subsequent progression of atherosclerosis. METHODS AND RESULTS: Increased expression of m-calpain was observed in aortic ECs in atherosclerotic lesions in humans and low-density lipoprotein receptor-deficient (ldlr(-/-)) mice. Furthermore, proteolytic disorganization of VE-cadherin was shown in aortic ECs in ldlr(-/-) and apolipoprotein E-deficient (apoE(-/-)) mice. Long-term administration of calpain inhibitors into these mice attenuated atherosclerotic lesion development and proinflammatory responses, as well as VE-cadherin disorganization, without normalization of plasma lipid profiles. Furthermore, in vivo transfection of m-calpain siRNA to ldlr(-/-) mice prevented disorganization of VE-cadherin and proatherogenic hyperpermeability in aortic ECs. Treatment of cultured ECs with oxidized LDL, lysophosphatidylcholine, or LDL pretreated with secreted phospholipase A(2) led to the induction of m-calpain but not of µ-calpain, thereby eliciting selective m-calpain overactivation. These data suggest that lysophosphatidylcholine-induced m-calpain directly cleaves a juxtamembrane region of VE-cadherin, resulting in dissociation of ß-catenin from the VE-cadherin complex, disorganization of adherence junctions, and hyperpermeability in ECs. CONCLUSIONS: Subtype-selective induction of m-calpain in aortic ECs during atherosclerotic progression is associated with proteolytic disorganization of VE-cadherin and proatherogenic hyperpermeability in cells. Thus, a strategy to selectively inhibit m-calpain may be useful for the therapeutic treatment of patients with atherosclerosis.

CD20 gene deletion causes a CD20-negative relapse in diffuse large B-cell lymphoma.

In diffuse large B-cell lymphoma (DLBCL), a CD20-negative relapse is clinically significant because it is associated with chemo-refractory phenotypes and loss of a therapeutic target. The alteration of the CD20 gene is reported as infrequent in CD20-negative relapse in B-cell lymphoma. We established a DLBCL cell line with loss of CD20 expression (SD07) from a patient at CD20-negative relapse. She was initially diagnosed with CD20-positive DLBCL and received repeated immuno-chemotherapy that included rituximab. SD07, which has an immunoglobulin κ rearrangement identical to that of lymphoma cells at CD20-negative relapse, showed homozygous deletion of the CD20 gene with loss of the copy number of 11q12. SD07 is the first case in which it is proven that the loss of CD20 expression in relapsed DLBCL is the result of deletion of the CD20 gene. Deletion of the CD20 gene is a molecular mechanism of CD20-negative relapse in a subset of DLBCL.

Serum HER2 levels determined by two methods in patients with metastatic breast cancer.

BACKGROUND: The role and the optimal measurement method of serum HER2 levels are not defined in patients with metastatic breast cancer (MBC). We prospectively assessed the prognostic value of serum HER2 levels in MBC using two methods, enzyme immunoassay (EIA) and chemiluminescence immunoassay (CLIA). METHODS: We collected blood samples from patients with MBC at baseline and at subsequent 3- to 4-week intervals up to 12 weeks. Samples were divided, and serum HER2 levels were determined using EIA and CLIA. We also determined whether serum HER2 levels had decreased by ≥20% at first follow-up. These results were evaluated against overall survival, progression-free survival, and tumor response. RESULTS: We obtained 196 samples from 52 patients. In 59 samples from patients who received trastuzumab, serum HER2 positivity rates were significantly lower for EIA (n = 22) than for CLIA (n = 33, P = 0.042); in 137 samples from patients who did not receive trastuzumab, there was no significant difference in rates of serum HER2 positivity for CLIA (n = 83) and EIA (n = 80). Serum HER2 level at baseline, the level at first follow-up, and a decrease of ≥20% between baseline and first follow-up were not associated with overall survival, progression-free survival, and tumor response. CONCLUSIONS: Chemiluminescence immunoassay was a more sensitive method than EIA for measuring serum HER2 levels in patients who received trastuzumab. However, because serum HER2 levels did not correlate with patient outcome, we do not currently recommend measuring serum HER2 levels by either method for prognostic evaluation in patients with MBC.

Prognostic value of HER2-positive circulating tumor cells in patients with metastatic breast cancer.

BACKGROUNDS: The presence of ≥5 circulating tumor cells (CTCs) in 7.5 ml blood is a poor prognostic marker in metastatic breast cancer (MBC). However, the role of human epidermal growth factor receptor 2 (HER2) status in CTCs is not known. METHODS: We prospectively assessed the prognostic value of this parameter for patients with MBC who started a new line of systemic therapy. The CTC count (≥5 or <5) and the HER2 status in CTCs at the initiation of the therapy and 3-4 weeks later (first follow-up) were determined. RESULTS: The median follow-up time of the 52 enrolled patients was 655.0 days (18-1,275 days). HER2-positive CTCs were present in 14 of the 52 patients (26.9%) during the study period. Eight of 33 patients (24.2%) with HER2-negative primary tumors had HER2-positive CTCs during the study period. At first follow-up, patients with HER2-positive CTCs had significantly shorter progression-free (n = 6; P = 0.001) and overall (P = 0.013) survival than did patients without HER2-positive CTCs (n = 43) in log-rank analysis. In multivariate analysis, HER2-positive CTCs at first follow-up (P = 0.029) and the number of therapies patients received before this study (P = 0.006) were independent prognostic factors in terms of progression-free survival. The number of therapies (P = 0.001) and a count of ≥5 CTCs (P = 0.043) at baseline were independent prognostic factors in terms of overall survival. CONCLUSIONS: We showed that HER2 status in CTCs may be a prognostic factor for MBC. Well-powered prospective studies are necessary to determine the potential role of HER2-targeted therapies for patients with HER2-positive CTCs and HER2-negative primary tumors.

Clinicopathological and molecular features of colorectal serrated neoplasias with different mucosal crypt patterns.

OBJECTIVES: Endoscopic examination shows that serrated neoplasias (SNs), such as serrated adenomas and sessile serrated adenomas, exhibit different mucosal crypt patterns. However, it remains unclear whether advanced serrated polyps with different mucosal crypt patterns have different clinicopathological or molecular features. METHODS: We classified the mucosal crypt patterns of 86 SNs into three types (hyperplastic, adenomatous, and mixed pattern) and evaluated their clinicopathological and molecular features. RESULTS: We found significant differences in the proliferative activity status between SNs with mixed/adenomatous patterns and those with the hyperplastic patterns. SNs with the hyperplastic pattern were frequently located in the proximal colon and had a macroscopically superficial appearance, whereas SNs with the adenomatous pattern were often located in the distal colon and had a protruding appearance. Furthermore, a significant difference was observed in the frequency of the CpG island methylator phenotype (CIMP), involving the methylation of two or more CIMP-related genes (MINT1, MINT2, MINT31, p16, and MLH1), between SNs with the hyperplastic pattern and those with the mixed/adenomatous patterns (18/32 (56%) vs. 8/28 (29%) or 7/26 (27%); P=0.0309 or P=0.0249, respectively). Moreover, the prevalence of KRAS mutations was significantly higher in SNs with the adenomatous pattern than in those with the hyperplastic pattern (7/26 (27%) vs. 1/32 (3%); P=0.0173). In comparison with other patterns, the mixed pattern was detected more frequently in mixed serrated polyps (MSPs), which contain separate histological components. Some MSPs exhibited concordant molecular alterations among the different histological components. CONCLUSIONS: The clinicopathological and molecular features of SNs correlated strongly with their mucosal crypt patterns, which were observed using chromoendoscopy.

Preventive effects of heregulin-beta1 on macrophage foam cell formation and atherosclerosis.

RATIONALE: Human heregulins, neuregulin-1 type I polypeptides that activate proliferation, differentiation, and survival of glial cells, neurons, and myocytes, are expressed in macrophage foam cells within human coronary atherosclerotic lesions. Macrophage foam cell formation, characterized by cholesterol ester accumulation, is modulated by scavenger receptor class A (SR-A), acyl-coenzyme A:cholesterol acyltransferase (ACAT)1, and ATP-binding cassette transporter (ABC)A1. OBJECTIVE: The present study clarified the roles of heregulins in macrophage foam cell formation and atherosclerosis. METHODS AND RESULTS: Plasma heregulin-beta(1) levels were significantly decreased in 31 patients with acute coronary syndrome and 33 patients with effort angina pectoris compared with 34 patients with mild hypertension and 40 healthy volunteers (1.3+/-0.3, 2.0+/-0.4 versus 7.6+/-1.4, 8.2+/-1.2 ng/mL; P<0.01). Among all patients with acute coronary syndrome and effort angina pectoris, plasma heregulin-beta(1) levels were further decreased in accordance with the severity of coronary artery lesions. Expression of heregulin-beta(1) was observed at trace levels in intracoronary atherothrombosis obtained by aspiration thrombectomy from acute coronary syndrome patients. Heregulin-beta(1), but not heregulin-alpha, significantly reduced acetylated low-density lipoprotein-induced cholesterol ester accumulation in primary cultured human monocyte-derived macrophages by reducing SR-A and ACAT1 expression and by increasing ABCA1 expression at both mRNA and protein levels. Heregulin-beta(1) significantly decreased endocytic uptake of [(125)I]acetylated low-density lipoprotein and ACAT activity, and increased cholesterol efflux to apolipoprotein (Apo)A-I from human macrophages. Chronic infusion of heregulin-beta(1) into ApoE(-/-) mice significantly suppressed the development of atherosclerotic lesions. CONCLUSIONS: This study provided the first evidence that heregulin-beta(1) inhibits atherogenesis and suppresses macrophage foam cell formation via SR-A and ACAT1 downregulation and ABCA1 upregulation.

Chromosome 17 polysomy in circulating tumor cells in patients with metastatic breast cancer: a case series.

The human epidermal growth factor receptor 2 (HER2) gene is located on the long arm of chromosome 17 (Chr-17). While primary tumors with Chr-17 polysomy (polysomy 17) are histopathologically similar to HER2-negative tumors, the role of polysomy 17 in circulating tumor cells (CTCs) is still unknown. We report the detection rate of polysomy 17 in CTCs in patients with metastatic breast cancer (MBC). We determined the CTC count per 7.5 ml blood and polysomy 17 in CTCs at 3- to 4-week intervals up to 12 weeks in 52 patients. Polysomy was defined as Chr-17 ≥2.2. CTCs were detected in 40 of 52 patients (76.9%) during the study period, in 32 of the 52 patients (61.5%) at baseline, and in 21 of 49 patients (42.9%) at 3-4 weeks. Polysomy 17 in CTCs was present in 10 of 52 patients (19.2%) during the study period, in 5 of 52 patients (9.6%) at baseline, and in 7 of 49 patients (14.3%) at 3-4 weeks. The individual patient counts of polysomy 17 in CTCs/total count of CTCs examined for polysomy 17 at 3-4 weeks were 1/1, 1/7, 1/7, 2/27, 2/30, 2/50, and 3/50. Six of the 7 patients with polysomy 17 in CTCs had HER2-negative primary tumors. None of the CTCs displaying polysomy 17 themselves had HER2 amplification by FISH. In summary, polysomy 17 in CTCs was observed in only a small population of patients with MBC. We should prospectively evaluate its prognostic value in both HER2-positive and -negative metastatic breast cancer.

Over-expression of CCL3 MIP-1alpha in a blastoid mantle cell lymphoma with hypercalcemia.

We analyzed a case with the blastoid variant of mantle cell lymphoma (MCL-BV), a rare subtype of B-cell lymphoma, presenting with marked hypercalcemia at diagnosis. Enzyme-linked immunosorbent assay (ELISA) showed elevated serum levels of interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), macrophage inflammatory protein-1alpha (MIP-1alpha), and type I collagen telopeptide, but not parathyroid hormone, calcitriol or parathyroid hormone-related peptide at diagnosis, suggesting local osteoclastic hypercalcemia in this case. By reverse transcription polymerase chain reaction (RT-PCR) analysis, we found predominant expression of mRNA for MIP-1alpha in addition to those for receptor-activator of nuclear-factor kappa B ligand (RANKL), TNF-alpha, and IL-6 in lymphoma cells obtained from the patient. Furthermore, recombinant MIP-1alpha significantly stimulated (3)H-thymidine uptake by isolated MCL cells in vitro. Treatment with intravenous fluids, bisphosphonate, and methylprednisolone followed by combination chemotherapy promptly corrects the hypercalcemia and successfully induced complete remission, which was accompanied by a decrease of these cytokines in the serum, including MIP-1alpha. In the present case, MIP-1alpha, an osteoclast-activating factor produced by mantle lymphoma cells, may contribute to the development of hypercalcemia. It likely acts through RANKL expression in tumor cells and/or stroma cells, as indicated in multiple myeloma (MM) and adult T-cell leukemia/lymphoma (ATLL). Furthermore, MIP-1alpha is also involved in the development of an aggressive phenotype on MCL by stimulating proliferation of these lymphoma cells. In summary, the present study demonstrated that MIP-1alpha is an important factor in the development of both hypercalcemia and an aggressive phenotype in some types of B-cell lymphoma.

Transition from low-grade endometrial stromal sarcoma to high-grade endometrial stromal sarcoma.

We report on a case of a primary low-grade endometrial stromal sarcoma (ESS) that progressed to a secondary high-grade ESS. In the secondary tumor, the immunohistochemical profile and focal tumor cell proliferation pattern suggested that this tumor was not truly undifferentiated, but possessed features of endometrial stroma. Low-grade ESS of our patient's primary tumor showed p53 protein overexpression, which is unusual in low-grade ESS, and her secondary high-grade ESS showed more prominent p53 immunoreactivity. This indicates that low-grade ESS that shows p53 immunoreactivity might progress to high-grade ESS, and it is considered that such cases of low-grade ESS should pay attention to the prognosis. Immunoreactivity for epidermal growth factor receptor was observed in both tumors, suggesting a relationship between the primary and secondary tumors in our case. Further study requires more immunohistochemical data for cases in which low-grade ESS transitions to high-grade ESS; in particular, data on epidermal growth factor receptor expression are necessary to define new therapeutic strategies for ESS.

Impact of salusin-alpha and -beta on human macrophage foam cell formation and coronary atherosclerosis.

BACKGROUND: Human salusins, related bioactive polypeptides with mitogenic effects on vascular smooth muscle cells and fibroblasts and roles in hemodynamic homeostasis, may be involved in the origin of coronary atherosclerosis. Macrophage foam cell formation, characterized by cholesterol ester accumulation, is modulated by scavenger receptor (cholesterol influx), acyl-coenzyme A:cholesterol acyltransferase-1 (ACAT-1; storage cholesterol ester converted from free cholesterol), and ATP-binding cassette transporter A1 (cholesterol efflux). METHODS AND RESULTS: Serum salusin-alpha levels were decreased in 173 patients with angiographically proven coronary artery disease compared with 40 patients with mild hypertension and 55 healthy volunteers (4.9+/-0.6 versus 15.4+/-1.1 and 20.7+/-1.5 pmol/L, respectively; P<0.0001). Immunoreactive salusin-alpha and -beta were detected in human coronary atherosclerotic plaques, with dominance of salusin-beta in vascular smooth muscle cells and fibroblasts. After 7 days in primary culture, acetylated low-density lipoprotein-induced cholesterol ester accumulation in human monocyte-derived macrophages was significantly decreased by salusin-alpha and increased by salusin-beta. Salusin-alpha significantly reduced ACAT-1 expression in a concentration-dependent manner. In contrast, salusin-beta significantly increased ACAT-1 expression by 2.1-fold, with a maximal effect at 0.6 nmol/L. These effects of salusins were abolished by G-protein, c-Src tyrosine kinase, protein kinase C, and mitogen-activated protein kinase kinase inhibitors. ACAT activity and ACAT-1 mRNA levels were also significantly decreased by salusin-alpha and increased by salusin-beta; however, neither salusin-alpha nor salusin-beta affected scavenger receptor A function assessed by [125I]acetylated low-density lipoprotein endocytosis or scavenger receptor class A and ATP-binding cassette transporter A1 expression. CONCLUSIONS: Our results indicate that the 2 salusin isoforms have opposite effects on foam cell formation in human monocyte-derived macrophages. Development of atherosclerosis may be accelerated by salusin-beta and suppressed by salusin-alpha via ACAT-1 regulation.

Expression of the fluoropyrimidine-metabolizing enzymes in bladder cancers as measured by the Danenberg tumor profile.

5-Fluorouracil (5-FU) and its prodrugs are used to treat various cancers. Response to 5-FU-based chemotherapy and expression of 5-FU-related enzymes differ among cancers. The objective of the present study was to investigate the relationship between the expression of 5-FU-related enzymes and clinicopathologic factors in bladder cancer. Formalin-fixed, paraffin-embedded sections of 44 bladder cancers and 27 normal bladders were included in this study. After laser capture microdissection, "Danenberg tumor profile," was performed for the measurement of 5-FU-related enzymes. There was no significant difference between dihydropyrimidine hydrogenase (DPD) mRNA expression in bladder cancer and in normal bladder. On the contrary, mRNA expressions of orotate phosphoribosyltransferase (OPRT), thymidylate synthase (TS), and thymidine phosphorylase (TP) in bladder cancer were higher than those in normal bladder. Compared with previously reported DPD mRNA expressions in other types of cancer, DPD mRNA expression in bladder cancer was relatively low. The 5-FU-related enzymatic condition of bladder cancer is favorable for 5-FU.

Clinicopathological comparison of the World Health Organization/Wotherspoon score to the Groupe d'Etude des Lymphomes de l'Adult grade for the post-treatment evaluation of gastric mucosa-associated lymphoid tissue lymphoma.

BACKGROUND AND AIM: The World Health Organization (WHO) has adopted criteria for the histological differential diagnosis of gastric extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (GML) based on the criteria proposed by Wotherspoon in 1993 (WHO/Wotherspoon score). These histological criteria are commonly used by pathologists for initial diagnoses, but have not been adopted uniformly for the post-treatment evaluation of GML. In 2003, the Groupe d'Etude des Lymphomes de l'Adult (GELA) proposed a new histological grading system (GELA grade) in preference to use of the WHO/Wotherspoon score for post-treatment evaluation. In the present study, we compared the WHO/Wotherspoon and GELA systems to examine which histological criterion is better for post-treatment evaluation. METHODS: Fourteen cases of GML under long-term follow up were initially diagnosed according to the WHO criteria with detailed immunohistology, and were periodically evaluated with both histological criteria after anti-Helicobacter pylori treatment. They were also evaluated based on histological stromal changes accompanying the disappearance of lymphoma tissue. RESULTS: The study showed strong similarities between the WHO/Wotherspoon and GELA systems and no clear advantage of either system for post-treatment evaluation. The GELA grade could not be used for the evaluation of changes in the degree of lymphoma infiltration from pre- to post-treatment because the four-item scale is not comparable with the formal six-point WHO/Wotherspoon scale. Stromal changes in the lamina propria, including an empty appearance and fibrosis, were correlated with lymphoma reduction after treatment and appear to be good indicators for post-treatment evaluation. CONCLUSION: We propose the utilization of the WHO/Wotherspoon score accompanied by the assessment of stromal changes for the post-treatment evaluation of GML.

Histopathology of bone marrow reconstitution after umbilical cord blood transplantation for hematological diseases.

To study hematopoietic reconstitution in umbilical cord blood transplantation (CBT), bone marrow (BM) histology was investigated in 35 biopsies after bone marrow transplantation (BMT) and in 40 biopsies after CBT. BM biopsies were obtained at different times after transplantation and were evaluated for cellularity, number of megakaryocytes and CD34-positive cells, and fibrosis. In biopsies up to 29 days after BMT, cellularity was increased and megakaryocytes were observed, but at 29 days after CBT, biopsies showed severe cellular depletion and almost no megakaryocytes. In addition, fewer CD34-positive cells were observed after CBT compared to after BMT. After day 30 after CBT, hematopoietic recovery of the BM was gradually observed and after day 100 after transplantation, no essential differences were observed between BMT and CBT. Hematopoietic recovery of the BM after CBT was delayed compared to that after BMT, but engraftment of donor cells after CBT was also observed in histopathologically. To the best of the authors' knowledge this is the first histopathological description of BM reconstitution after CBT.

Lobular endocervical glandular hyperplasia might become a precursor of adenocarcinoma with pyloric gland features.

We report a case of adenocarcinoma with pyloric gland features, which appears to have originated from lobular endocervical glandular hyperplasia (LEGH). Hematoxylin and eosin staining, as well as histochemical and immunohistochemical stainings were performed on formalin-fixed and paraffin-embedded specimens. LEGH was observed in the conization specimens. In the hysterectomy specimens, LEGH, atypical LEGH, and mucinous adenocarcinoma coexisted. The adenocarcinoma was located at a site distant from the transition zone. p16(INK4a) immunopositivity was extremely rare. Front formation was observed, and a transition from benign-looking columnar cells of LEGH to adenocarcinoma was recognized. These findings suggested that the adenocarcinoma with pyloric gland features arose from LEGH. LEGH is no longer regarded as a pseudoneoplastic lesion, and it is necessary to consider that LEGH is able to transform into a precursor lesion and to develop into an adenocarcinoma with pyloric gland features.

Clear cell adenocarcinoma arising from a giant cystic adenomyosis: a case report with immunohistochemical analysis of laminin-5 gamma2 chain and p53 overexpression.

We report a case of a clear cell adenocarcinoma arising from a giant cystic adenomyosis, with immunohistochemical analysis of p53 and laminin-5 gamma2 chain overexpression. Microscopically, not only clear cell adenocarcinoma showing myometrial invasion but also single-layered clear cell adenocarcinoma cells lining the cyst wall were observed. Transition from these single-layered tumor cells to papillary proliferative lesions of various degrees was recognized. Moreover, these tumor cells were continuous with minimal atypical cells. Although the tumor cells within the uterus showed a low positive cell ratio for p53, the metastatic foci showed a remarkable p53 overexpression. Laminin-5 gamma2 chain expression was low in papillary proliferation and high in myometrial invasion and metastatic foci. The single-layered tumor cells showing non-invasive proliferation also contained laminin-5 gamma2 chain-positive cells. When non-invasive tumor cells were considered to be at an early stage in tumor progression, some tumor cells had already acquired an invasive feature. p53 overexpression was not related to expression of the laminin-5 gamma2 chain.

The GCB subtype of diffuse large B-cell lymphoma is less frequent in Asian countries.

Patients with the germinal center B-cell-like (GCB) subtype of diffuse large B-cell lymphoma (DLBCL) have a significantly better survival rate than those with non-GCB DLBCL. Several studies have examined the proportions of GCB and non-GCB subtypes in large series of DLBCL patients, but it remains unclear if these proportions are the same in different countries. We performed an immunohistochemical analysis of the numbers of GCB and non-GCB subtypes in a large number of patients with DLBCL in Japan and compared the results with literature data for other countries. We found that 71 of 248 patients (29%) had the GCB phenotype and 177 patients (71%) had the non-GCB subtype of DLBCL among our patient population. Assessment of data collected from other studies showed that 31% of DLBCL patients (102/330) have the GCB subtype in Asian countries, but 50% (206/416) express GCB phenotypes in Western countries; based on these data, the occurrence of the GCB subtype of DLBCL was significantly less in Asian countries (p<0.001). Since patients with the GCB phenotype of DLBCL have better survival, future studies of DLBCL should recognize the difference in the proportions of GCB and non-GCB subtypes of DLBCL between Asian and Western populations.

Expression of interleukin-17F in a mouse model of allergic asthma.

BACKGROUND: Interleukin (IL)-17F is a recently discovered cytokine and is derived from a panel of limited cell types, such as activated CD4+ T cells, basophils, and mast cells. IL-17F is known to induce several cytokines and chemokines. However, its involvement in airway inflammation has not been well understood. To this end, the expression of IL-17F and the inhibitory effects of glucocorticoids on its expression in a mouse model of asthma were examined. METHODS: Five-week-old BALB/c male mice were sensitized by intraperitoneal injection (i.p.) of ovalbumin (OVA) with alum, and challenged by daily inhalation of aerosolized 1% OVA. 24 h after last challenge (OVA/OVA), the expression of IL-17F was examined in lung tissues by immunohistochemistry and reverse-transcription polymerase chain reaction. Control mice were sensitized and challenged with saline (Sham/Sham). In addition, a group OF OVA-sensitized mice received i.p. injection of water-soluble dexamethasone (DEX) in saline 1 h before ova challenge (OVA/DEX). RESULTS: In sham-challenged mice, IL-17F was not expressed in the lungs, while, in contrast, IL-17F was predominantly expressed in bronchial epithelial cells in addition to the infiltrating inflammatory cells in OVA/OVA mice. Further, the expression of IL-17 F was significantly attenuated by the treatment of mice with DEX. CONCLUSION: These results suggest that bronchial epithelium-derived IL-17F may represent a new pharmacological target for glucocorticoids and may play a role in allergic asthma.

Recent comparability of oceanographic nutrients data: results of a 2003 intercomparison exercise using reference materials.

An intercomparison exercise was conducted using the recently developed Reference Material for Nutrients in Seawater (RMNS). Discrepancies of reported values among laboratories were greater than the homogeneity of RMNS samples and the reported analytical precision of nutrients. The variability of in-house standards of the participating laboratories might be the most likely source of interlaboratory discrepancies. Therefore, the use of common reference materials, i.e. certified RM, is essential to establish and improve the comparability of nutrient data of the world's oceans.

[Monoclonal analysis of immunoglobulin heavy chain and T-cell receptor gamma chain gene rearrangements in paraffin-embedded tissues from non-Hodgkin lymphoma patients].

Gene rearrangement is an important diagnostic marker of malignant lymphoma, and rearrangements of the immunoglobulin heavy chain (IgH) and T-cell receptor gamma chain (TCRgamma) genes are useful markers for Band T-cell lymphoma, respectively. A polymerase chain reaction (PCR) can be used to analyze clonality in formalin-fixed paraffin-embedded specimens. We performed 73 monoclonal analyses of such specimens of lymphoma tissues and examined the ability to diagnose malignant lymphoma by this method. Monoclonality of lymphoma cells was found in 71.9% and 78.9% of specimens with IgH and TCRgamma gene rearrangements, respectively. Therefore, in diagnosing cases of non-Hodgkin lymphoma in which neoplasms and reactive lymphoid tissues are difficult to identify by morphological and immunohistochemical findings, PCR-based monoclonal analysis may allow confirmation of a pathological diagnosis of malignant lymphoma.