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Sample records for low-grade mucosa-associated lymphoid

  1. Duodenal Mucosa-Associated Lymphoid Tissue Lymphomas: Two Cases and the Evaluation of Endoscopic Ultrasonography

    PubMed Central

    Kim, Su Jin; Choi, Choel Woong; Ha, Jong Kun; Hong, Young Mi; Park, Jin Hyun; Park, Soo Bum; Kang, Dae Hwan

    2013-01-01

    Mucosa-associated lymphoid tissue lymphoma mainly arises in the stomach, with fewer than 30% arising in the small intestine. We describe here two cases of primary duodenal mucosa-associated lymphoid tissue lymphoma which were evaluated by endoscopic ultrasonography. A 52-year-old man underwent endoscopy due to abdominal pain, which demonstrated a depressed lesion on duodenal bulb. Endoscopic ultrasonographic finding was hypoechoic lesion invading the submucosa. The other case was a previously healthy 51-year-old man. Endoscopy showed a whitish granular lesion on duodenum third portion. Endoscopic ultrasonography image was similar to the first case, whereas abdominal computed tomography revealed enlargement of multiple lymph nodes. The first case was treated with eradication of Helicobacter pylori, after which the mucosal change and endoscopic ultrasound finding were normalized in 7 months. The second case was treated with cyclophosphamide, vincristine, prednisolone, and rituximab every 3 weeks. After 6 courses of chemotherapy, the patient achieved complete remission. PMID:24143321

  2. Central Role of Core Binding Factor ?2 in Mucosa-Associated Lymphoid Tissue Organogenesis in Mouse

    PubMed Central

    Nagatake, Takahiro; Fukuyama, Satoshi; Sato, Shintaro; Okura, Hideaki; Tachibana, Masashi; Taniuchi, Ichiro; Ito, Kosei; Shimojou, Michiko; Matsumoto, Naomi; Suzuki, Hidehiko; Kunisawa, Jun; Kiyono, Hiroshi

    2015-01-01

    Mucosa-associated lymphoid tissue (MALT) is a group of secondary and organized lymphoid tissue that develops at different mucosal surfaces. Peyer’s patches (PPs), nasopharynx-associated lymphoid tissue (NALT), and tear duct-associated lymphoid tissue (TALT) are representative MALT in the small intestine, nasal cavity, and lacrimal sac, respectively. A recent study has shown that transcriptional regulators of core binding factor (Cbf) ?2 and promotor-1-transcribed Runt-related transcription factor 1 (P1-Runx1) are required for the differentiation of CD3?CD4+CD45+ lymphoid tissue inducer (LTi) cells, which initiate and trigger the developmental program of PPs, but the involvement of this pathway in NALT and TALT development remains to be elucidated. Here we report that Cbf?2 plays an essential role in NALT and TALT development by regulating LTi cell trafficking to the NALT and TALT anlagens. Cbf?2 was expressed in LTi cells in all three types of MALT examined. Indeed, similar to the previous finding for PPs, we found that Cbf?2?/? mice lacked NALT and TALT lymphoid structures. However, in contrast to PPs, NALT and TALT developed normally in the absence of P1-Runx1 or other Runx family members such as Runx2 and Runx3. LTi cells for NALT and TALT differentiated normally but did not accumulate in the respective lymphoid tissue anlagens in Cbf?2?/? mice. These findings demonstrate that Cbf?2 is a central regulator of the MALT developmental program, but the dependency of Runx proteins on the lymphoid tissue development would differ among PPs, NALT, and TALT. PMID:26001080

  3. A case of primary mucosa-associated lymphoid tissue lymphoma of the vagina.

    PubMed

    Yoshinaga, Kousuke; Akahira, Jun-Ichi; Niikura, Hitoshi; Ito, Kiyoshi; Moriya, Takuya; Murakami, Takashi; Kameoka, Jun-Ichi; Ichinohasama, Ryo; Okamura, Kunihiro; Yaegashi, Nobuo

    2004-09-01

    We report the first case of primary mucosa-associated lymphoid tissue (MALT) lymphoma of the vagina, the diagnosis of which is supported by genetic and immunophenotypic studies. A 65-year-old, para 2 woman presented to our hospital in July 1997 with a history of prolonged vaginal discharge. Although cytologic examination suggested possible malignancy, a biopsy of the vaginal wall was diagnosed as chronic inflammation. In June 2000, she underwent gynecologic examination because of anuria. Excisional biopsy revealed subepithelial infiltration of atypical lymphoid cells that stained for CD20, CD79a, and BCL-2; stained weakly for IgM; and did not stain for CD3, CD5, CD7, CD10, CD56, CD23, and IgD, suggesting marginal zone B-cell lineage. Monoclonality was detected by Southern blot analysis, and this patient was finally diagnosed as having primary MALT lymphoma of the vagina. She received 3 cycles of chemotherapy (THP-COP) and concurrent radiation to the whole pelvis. The patient is alive and well 40 months after treatment. Because the vagina is one of the mucosa-associated tissues, MALT lymphoma, though rare, must be included in the differential diagnosis of the vaginal neoplasms. PMID:15343521

  4. Sensitive detection of PrPCWD in rectoanal mucosa-associated lymphoid tissue from preclinical white-tailed deer

    Technology Transfer Automated Retrieval System (TEKTRAN)

    This report summarizes the comparative diagnostic performance of postmortem rectoanal mucosa-associated lymphoid tissue (RAMALT) sampling in four white-tailed deer test populations: from Wisconsin, a sample of free-ranging deer and a captive herd; and from Saskatchewan, Canada, two captive herds. Th...

  5. Helicobacter pylori (H. pylori) molecular signature in conjunctival mucosa-associated lymphoid tissue (MALT) lymphoma.

    PubMed

    Chan, C-C; Smith, J A; Shen, D F; Ursea, R; LeHoang, P; Grossniklaus, H E

    2004-10-01

    Conjunctival mucosa-associated lymphoid tissue (MALT) lymphoma is an extranodal marginal zone B-cell lymphoma that is characterized by an exaggerated clonal expansion of B cells, which implicate a pathological proliferative response to antigen(s) including bacteria. Helicobacter pylori (H. pylori) infection is recognized as one of the causative agents of gastric MALT lymphoma; however, it has not been reported in extra gastric MALT lymphoma. We studied 5 patients (4 adults and 1 child) with salmon-colored conjunctival lesions. One patient also had a history of abnormal bone marrow biopsy a year earlier with lymphoid aggregates involving 5% of the overall bone marrow. The conjunctival lesions of the 5 patients were biopsied. Histopathological diagnoses were consistent with conjunctival MALT lymphoma. Lymphoma and normal conjunctival cells were microdissected using laser capture microscopy or manual techniques. DNA was extracted and subjected to PCR amplification using H. pylori gene-specific primers from the urease B and vac/m2 gene. Cells from chronic conjunctivitis (normal lymphocytes), conjunctival human T-cell lymphotropic virus type-1/adult T-cell leukemia/lymphoma (HTLV-1/ATL), and orbital B-cell lymphoma were also microdissected, processed and analyzed. PCR amplification and Southern blot hybridization demonstrated H. pylori DNA in the conjunctival MALT lymphoma cells of 4/5 cases. The negative case was the one with a history of abnormal bone marrow. In contrast, H. pylori gene was not detected in normal conjunctival cells from the cases of MALT lymphoma or the lymphocytes, ATL and orbital B-lymphoma cells from the controls. These data suggest that H. pylori may play a role in conjunctival MALT lymphoma. PMID:15375765

  6. Helicobacter pylori and gastric mucosa-associated lymphoid tissue lymphoma: Recent progress in pathogenesis and management

    PubMed Central

    Nakamura, Shotaro; Matsumoto, Takayuki

    2013-01-01

    Recent progress in the research regarding the molecular pathogenesis and management of gastric mucosa-associated lymphoid tissue (MALT) lymphoma is reviewed. In approximately 90% of cases, Helicobacter pylori (H. pylori) infection plays the causative role in the pathogenesis, and H. pylori eradication is nowadays the first-line treatment for this disease, which leads to complete disease remission in 50%-90% of cases. In H. pylori-dependent cases, microbe-generated immune responses, including interaction between B and T cells involving CD40 and CD40L co-stimulatory molecules, are considered to induce the development of MALT lymphoma. In H. pylori-independent cases, activation of the nuclear factor-?B pathway by oncogenic products of specific chromosomal translocations such as t(11;18)/API2-MALT1, or inactivation of tumor necrosis factor alpha-induced protein 3 (A20) are considered to contribute to the lymphomagenesis. Recently, a large-scale Japanese multicenter study confirmed that the long-term clinical outcome of gastric MALT lymphoma after H. pylori eradication is excellent. Treatment modalities for patients not responding to H. pylori eradication include a “watch and wait” strategy, radiotherapy, chemotherapy, rituximab immunotherapy, and a combination of these. Because of the indolent behavior of MALT lymphoma, second-line treatment should be tailored in consideration of the clinical stage and extent of the disease in each patient. PMID:24363507

  7. Two cases with pulmonary mucosa-associated lymphoid tissue lymphoma successfully treated with clarithromycin.

    PubMed

    Ishimatsu, Yuji; Mukae, Hiroshi; Matsumoto, Kiyoshi; Harada, Tatsuhiko; Hara, Atsuko; Hara, Shintaro; Amenomori, Misato; Fujita, Hanako; Sakamoto, Noriho; Hayashi, Tomayoshi; Kohno, Shigeru

    2010-09-01

    A 70-year-old woman with a history of sinobronchial syndrome was admitted to the hospital because of a cough, sputum, and abnormal chest shadow. She was diagnosed with pulmonary mucosa-associated lymphoid tissue lymphoma (p-MALToma) based on results of a pathologic examination and the gene rearrangements in the Ig heavy chain on Southern blot hybridization. Although p-MALToma did not regress with conventional therapy, it was reduced after long-term treatment with clarithromycin (CAM) (200 mg/d). A 57-year-old woman with a history of Sjögren syndrome and lymphocytic interstitial pneumonia had a mass lesion in the left lower lung field. CT image-guided biopsy established a diagnosis of p-MALToma. The p-MALToma regressed with long-term treatment with CAM (200 mg/d), whereas Helicobacter pylori (HP) eradication therapy was not effective in concurrent atrophic gastritis with HP. It is suggested that CAM, a macrolide antibiotic, may be effective in some patients with p-MALToma. PMID:20822996

  8. Helicobacter pylori-negative gastric mucosa-associated lymphoid tissue lymphomas: A review

    PubMed Central

    Asano, Naoki; Iijima, Katsunori; Koike, Tomoyuki; Imatani, Akira; Shimosegawa, Tooru

    2015-01-01

    Since Isaacson and Wright first reported on the extra-nodal marginal zone B-cell lymphoma of the stomach in 1983, following studies have clarified many aspects of this disease. We now know that the stomach is the most affected organ by this disease, and approximately 90% of gastric mucosa-associated lymphoid tissue (MALT) lymphomas are related to Helicobacter pylori (H. pylori) infection. This implies that approximately 10% of gastric MALT lymphomas occur independent of H. pylori infection. The pathogenesis of these H. pylori-negative gastric MALT lymphomas remains unclear. To date, there have been several speculations. One possibility is that genetic alterations result in nuclear factor-kappa B (NF-?B) activation. Among these alterations, t(11;18)(q21;q21) is more frequently observed in H. pylori-negative gastric MALT lymphomas, and such translocation results in the synthesis of fusion protein API2-MALT1, which causes canonical and noncanonical NF-?B activation. Another possibility is infection with bacteria other than H. pylori. This could explain why H. pylori eradication therapy can cure some proportions of H. pylori-negative gastric MALT lymphoma patients, although the bacteria responsible for MALT lymphomagenesis are yet to be defined. Recent advances in endoscopy suggest magnifying endoscopy with narrow band imaging as a useful tool for both detecting gastric MALT lymphoma lesions and judging the response to treatment. A certain proportion of H. pylori-negative gastric MALT lymphoma patients respond to eradication therapy; hence, H. pylori eradication therapy could be considered as a first-line treatment for gastric MALT lymphomas regardless of their H. pylori infection status. PMID:26185372

  9. Diagnosis of preclinical CWD in farmed white-tailed deer in Canada by the immunohistochemical examination of recto-anal mucosa- associated lymphoid tissue (RAMALT)

    Technology Transfer Automated Retrieval System (TEKTRAN)

    This report summarizes the comparative diagnostic performance of postmortem rectoanal mucosa-associated lymphoid tissue (RAMALT) sampling in two white-tailed deer farms from Saskatchewan, Canada. The apparent prevalence of disease in these two farms was 21% and 31%. None of these deer were demonstra...

  10. Neonatal thymectomy favors Helicobacter pylori-promoted gastric mucosa-associated lymphoid tissue lymphoma lesions in BALB/c mice.

    PubMed

    Chrisment, Delphine; Dubus, Pierre; Chambonnier, Lucie; Hocès de la Guardia, Anaïs; Sifré, Elodie; Giese, Alban; Capone, Myriam; Khairallah, Camille; Costet, Pierre; Rousseau, Benoît; Hubert, Christophe; Burlen-Defranoux, Odile; Varon, Christine; Bandeira, Antonio; Mégraud, Francis; Lehours, Philippe

    2014-08-01

    Neonatal thymectomy in BALB/c mice has been described as a model of gastric mucosa-associated lymphoid tissue (MALT) lymphoma (GML). By using this experimental system, we screened, for the first time to our knowledge, Helicobacter pylori GML-associated strains for their capacity to promote disease. A cohort of BALB/c mice underwent thymectomy at day 3 after birth (d3Tx). Successful thymic ablation was evaluated by the degree of lymphopenia in blood samples collected at 4 weeks of age. d3Tx and non-thymectomized controls were infected with either GML strains (B38 or B47) or control strains (SS1 or TN2GF4). Gastric samples collected at 6, 12, and 18 months after infection were studied for bacteria content, and submitted to histological, immunochemical, molecular, and immunological analyses. Severe gastric inflammation was only observed in d3Tx mice. In these animals, the gastric lamina propria was infiltrated with lymphoid cells organized in follicles composed of B cells with few infiltrating T cells. PCR of D/J IgH gene segments proved the monoclonality of infiltrating B cells, which strongly correlated with the presence of lymphoepithelial lesions. B-cell infiltrates were particularly prominent in mice infected with the B47-GML strain. No pathological changes were detected in noninfected d3Tx mice. We identified new H. pylori isolates adapted to the mouse stomach with high potential of GML development, which is only revealed in hosts rendered lymphopenic by neonatal thymic ablation. PMID:24909507

  11. Risk Potentiality of Frontline Radiotherapy Associated Cataract in Primary Ocular Adnexal Mucosa-associated Lymphoid Tissue Lymphoma

    PubMed Central

    Cho, Won-Kyung; Lee, Sung-Eun; Paik, Ji-Sun; Cho, Seok-Goo

    2013-01-01

    Purpose To elucidate risk potentiality of frontline radiotherapy associated cataracts in primary ocular adnexal mucosa-associated lymphoid tissue lymphoma (OAML). Methods Data from eight consecutive patients of 41 total OAML patients who had undergone cataract surgery after frontline radiotherapy were analyzed. Results The median patient age was 46 years (range, 36 to 69 years). The median total radiation dose was 3,780 cGy (range, 3,060 to 4,500 cGy), and the mean duration from radiation irradiation to cataract surgery was 36.60 ± 8.93 months. Preoperative lens opacification was primarily at the posterior lens subcapsule, and best-corrected visual acuity (BCVA) was 0.43 ± 0.21. Patients underwent the phacoemulsification surgical procedure with posterior chamber intraocular lens insertion. The average BCVA improved to 0.90 ± 0.14 after cataract surgery. Two patients underwent posterior continuous curvilinear capsulorhexis, and one had posterior capsule rupture. For posterior capsule opacification (PCO), three patients received Nd:YAG laser posterior capsulotomy after the initial surgery, and one patient is currently under consideration for laser posterior capsulotomy. Conclusions Radiotherapy increased posterior subcapsule opacification at a relatively young age in primary OAML. Phacoemulsification was a manageable procedure without severe complications, and final visual outcomes were good. However, because after-cataracts progressed earlier than did senile cataracts, close follow-up should be considered for PCO management. PMID:23908569

  12. Marginal zone B-cell lymphoma of the pulmonary mucosa-associated lymphoid tissue: A case report

    PubMed Central

    LI, HONG; WANG, TING; WEI, XIAOHONG; DANG, XIAOMIN

    2015-01-01

    Marginal zone B-cell lymphoma of the pulmonary mucosa-associated lymphoid tissue (pulmonary MALT-MZL) is a common type of primary pulmonary lymphoma, but is rare as a pulmonary malignant tumor. In the present study, a 49-year-old male patient was admitted to The First Affiliated Hospital of Xi'an JiaTong University (Xi'an, China) with a pulmonary lesion in the right upper lung. The patient was diagnosed with pulmonary MALT-MZL subsequent to undergoing chest computed tomography (CT), a routine blood test, pathological and histological examinations, a transbronchial lung biopsy and bronchoscopy. A chest CT scan revealed right middle lobe consolidation and inflammatory signs, accompanied by mediastinal lymphadenopathy in the anterior basal segment of the upper lobe and CT angiogram signs. Bronchial stenosis and swollen mucosa were observed by bronchoscopy. The tissue section of the transbronchial lung biopsy specimens revealed diffusely infiltrated monocytoid B-cell lymphocytes and a lymphoepithelial lesion. The tissue was found to be positive for cluster of differentiation (CD)20, B-cell lymphoma 2 and CD79a expression, but negative for CD3, CD5, cyclin D1 and ?-light chain expression. CD21 and CD23, located in the residual follicular dendritic cells, were detected by immunohistochemical staining. The clinical manifestations of pulmonary MALT-MZL are non-specific and misdiagnosis frequently occurs in clinical practice. Therefore, an appropriate invasive biopsy procedure is necessary for early and accurate diagnosis of pulmonary MALT-MZL. Clinical presentation that includes periodic fever and distended bronchi in pulmonary consolidation may indicate a diagnosis of MALT-MZL. Pulmonary MALT-MZL belongs to the category of indolent lymphoma and accurate clinical diagnosis is challenging. The results in the present study may provide additional evidence for the accurate diagnosis of this rare entity.

  13. Molecular pathogenesis of lymphomas of mucosa-associated lymphoid tissue-from (auto)antigen driven selection to the activation of NF-?B signaling.

    PubMed

    Zhang, YiAn; Wei, Zheng; Li, Jing; Liu, Peng

    2015-12-01

    Lymphomas of mucosa-associated lymphoid tissue (MALT) are typically present at sites such as the stomach, lung or urinary tract, where lymphoid tissues scatter in mucosa lamina propria, intra- or sub-epithelial cells. The infection of certain pathogens, such as Helicobacter pylori, Chlamydophila psittaci, Borrelia burgdorferi, hepatitis C virus, or certain autoantigens cause these sites to generate a germinal center called the "acquired lymphoid tissue". The molecular pathogenesis of MALT lymphoma is a multi-step process. Receptor signaling, such as the contact stimulation of B cell receptors and CD4 positive T cells mediated by CD40/CD40-ligand and T helper cell type 2 cytokines like interleukin-4, contributes to tumor cell proliferation. A number of genetic alterations have been identified in MALT lymphoma, and among them are important translocations, such as t(11;18)(q21;q21), t(1;14)(p22;q32), t(14;18)(q32;q21) and t(3;14)(p13;q32). Fusion proteins generated by these translocations share the same NF-?B signaling pathway, which is activated by the caspase activation and recruitment domain containing molecules of the membrane associated guanylate kinase family, B cell lymphoma-10 and MALT1 (CBM) protein complex. They act downstream of cell surface receptors, such as B cell receptors, T cell receptors, B cell activating factors and Toll-like receptors, and participate in the biological process of MALT lymphoma. The discovery of therapeutic drugs that exclusively inhibit the antigen receptor signaling pathway will be beneficial for the treatment of B cell lymphomas in the future. PMID:26612043

  14. A Multicenter Phase II Study of Local Radiation Therapy for Stage IEA Mucosa-Associated Lymphoid Tissue Lymphomas: A Preliminary Report From the Japan Radiation Oncology Group (JAROG)

    SciTech Connect

    Isobe, Koichi Kagami, Yoshikazu; Higuchi, Keiko; Kodaira, Takeshi; Hasegawa, Masatoshi; Shikama, Naoto; Nakazawa, Masanori; Fukuda, Ichiro; Nihei, Keiji; Ito, Kana; Teshima, Teruki; Matsuno, Yoshihiro; Oguchi, Masahiko

    2007-11-15

    Purpose: The aim of this study was to evaluate the efficacy and toxicity of moderate dose radiation therapy (RT) for mucosa-associated lymphoid tissue (MALT) lymphoma in a prospective multicenter phase II trial. Methods and Materials: The subjects in this study were 37 patients with MALT lymphoma between April 2002 and November 2004. There were 16 male and 21 female patients, ranging in age from 24 to 82 years, with a median of 56 years. The primary tumor originated in the orbit in 24 patients, in the thyroid and salivary gland in 4 patients each, and 5 in the others. The median tumor dose was 30.6 Gy (range, 30.6-39.6 Gy), depending on the primary site and maximal tumor diameter. The median follow-up was 37.3 months. Results: Complete remission (CR) or CR/unconfirmed was achieved in 34 patients (92%). The 3-year overall survival, progression-free survival, and local control probability were 100%, 91.9%, and 97.3%, respectively. Thirteen patients experienced Grade 1 acute toxicities including dermatitis, mucositis, and conjunctivitis. One patient developed Grade 2 taste loss. Regarding late toxicities, Grade 2 reactions including hypothyroidism, and radiation pneumonitis were observed in three patients, and Grade 3 cataract was seen in three patients. Conclusions: This prospective phase II study demonstrated that moderate dose RT was highly effective in achieving local control with acceptable morbidity in 37 patients with MALT lymphoma.

  15. Radiation Therapy Administration and Survival in Stage I/II Extranodal Marginal Zone B-Cell Lymphoma of Mucosa-Associated Lymphoid Tissue

    SciTech Connect

    Olszewski, Adam J. Desai, Amrita

    2014-03-01

    Purpose: To determine the factors associated with the use of radiation therapy and associated survival outcomes in early-stage marginal zone lymphoma of the mucosa-associated lymphoid tissue (MALT). Methods and Materials: We extracted data on adult patients with stage I/II MALT lymphoma diagnoses between 1998 and 2010 recorded in the Surveillance, Epidemiology, and End Results (SEER) database. We studied factors associated with radiation therapy administration in a logistic regression model and described the cumulative incidence of lymphoma-related death (LRD) according to receipt of the treatment. The association of radiation therapy with survival was explored in multivariate models with adjustment for immortal time bias. Results: Of the 7774 identified patients, 36% received radiation therapy as part of the initial course of treatment. Older patients; black or Hispanic men; white, Hispanic, and black women; and socioeconomically disadvantaged and underinsured patients had a significantly lower chance of receiving radiation therapy. Radiation therapy administration was associated with a lower chance of LRD in most sites. In cutaneous, ocular, and salivary MALT lymphomas, the 5-year estimate of LRD after radiation therapy was 0%. The association of radiation therapy with overall survival in different lymphoma sites was heterogeneous, and statistically significant in cutaneous (hazard ratio 0.45, P=.009) and ocular (hazard ratio 0.47, P<.0001) locations after multivariate adjustment. Conclusions: Demographic factors are associated with the use of radiation therapy in MALT lymphoma. Clinicians should be sensitive to those disparities because the administration of radiation therapy may be associated with improved survival, particularly in cutaneous and ocular lymphomas.

  16. Long-Term Outcome and Patterns of Failure in Primary Ocular Adnexal Mucosa-Associated Lymphoid Tissue Lymphoma Treated With Radiotherapy

    SciTech Connect

    Hashimoto, Naoki; Sasaki, Ryohei; Nishimura, Hideki; Yoshida, Kenji; Miyawaki, Daisuke; Nakayama, Masao; Uehara, Kazuyuki; Okamoto, Yoshiaki; Ejima, Yasuo; Azumi, Atsushi; Matsui, Toshimitsu; Sugimura, Kazuro

    2012-03-15

    Purpose: To evaluate the long-term treatment outcome and disease behavior of primary ocular adnexal MALT (mucosa-associated lymphoid tissue) lymphoma (POAML) after treatment with radiotherapy. Methods and Materials: Seventy-eight patients (42 male, 36 female) diagnosed with stage I POAML between 1991 and 2010 at Kobe University Hospital were included. The median age was 60 years (range, 22-85 years). The median radiation dose administered was 30.6 Gy. Rituximab-based targeted therapy and/or chemotherapy was performed in 20 patients (25.6%). Local control (LC), recurrence-free survival (RFS), and overall survival (OS) rates were calculated using the Kaplan-Meier method. Results: The median follow-up duration was 66 months. Major tumor sites were conjunctiva in 37 patients (47.4%), orbita in 29 (37.2%), and lacrimal glands in 12 (15.4%). The 5- and 10-year OS rates were 98.1% and 95.3%, respectively. The 5- and 10-year LC rates were both 100%, and the 5- and 10-year RFS rates were 88.5% and 75.9%, respectively. Patients treated with a combination of radiotherapy and targeted therapy and/or chemotherapy had a trend for a better RFS compared with those treated with radiotherapy alone (p = 0.114). None developed greater than Grade 2 acute morbidity. There were 14 patients who experienced Grade 2 morbidities (cataract: 14; retinal disorders: 7; dry eye: 3), 23 patients who had Grade 3 morbidities (cataract: 23; dry eye: 1), and 1 patient who had Grade 4 glaucoma. Conclusions: Radiotherapy for POAML was shown to be highly effective and safe for LC and OS on the basis of long-term observation. The absence of systemic relapse in patients with combined-modality treatment suggests that lower doses of radiation combined with targeted therapy may be worth further study.

  17. Primary Radiation Therapy in Patients With Localized Orbital Marginal Zone B-Cell Lymphoma of Mucosa-Associated Lymphoid Tissue (MALT Lymphoma)

    SciTech Connect

    Son, Seok Hyun; Choi, Byung Ock; Kim, Gi Won; Yang, Suk Woo; Hong, Young Seon; Choi, Ihl Bohng; Kim, Yeon Sil

    2010-05-01

    Purpose: To evaluate the outcomes of patients with localized orbital marginal zone B-cell lymphoma of the mucosa-associated lymphoid tissue (MALT lymphoma) who were treated with radiotherapy (RT). Methods and Materials: We retrospectively reviewed the records of 46 patients who were treated with RT for pathologically confirmed localized stage IE marginal zone B-cell lymphoma of MALT. The radiation dose ranged from 21.6 to 45 Gy (median, 30.6 Gy) at 1.8-2.0 Gy per fraction. Median follow-up duration was 32.3 months (range, 3.1-113.6 months). Results: Forty-three patients (93%) achieved complete remission (CR), and three patients (7%) achieved partial remission (PR). Five-year relapse-free survival, cause-specific survival, and overall survival were 93%, 100%, and 100%, respectively. Among the patients with CR, two had recurrence at three sites. One patient relapsed locally and was successfully salvaged with reirradiation. The other patient relapsed in a distant site and was successfully treated with six cycles of CHOP chemotherapy. Late complications were noted in four patients. Two patients developed cataracts at 26 and 37 months after completion of RT. The other two patients developed nasolacrimal duct obstructions at 4 and 11 months after completion of RT. Conclusion: Our study showed that a modest dose of RT is an excellent treatment modality with low complication and recurrence rates. We suggest that a dose of 30.6 Gy is tolerable and sufficient for treating orbital MALT lymphoma. Even following recurrence, successful salvage is possible with RT or chemotherapy.

  18. Genetic errors of the human caspase recruitment domain-B-cell lymphoma 10-mucosa-associated lymphoid tissue lymphoma-translocation gene 1 (CBM) complex: Molecular, immunologic, and clinical heterogeneity.

    PubMed

    Pérez de Diego, Rebeca; Sánchez-Ramón, Silvia; López-Collazo, Eduardo; Martínez-Barricarte, Rubén; Cubillos-Zapata, Carolina; Ferreira Cerdán, Antonio; Casanova, Jean-Laurent; Puel, Anne

    2015-11-01

    Three members of the caspase recruitment domain (CARD) family of adaptors (CARD9, CARD10, and CARD11) are known to form heterotrimers with B-cell lymphoma 10 (BCL10) and mucosa-associated lymphoid tissue lymphoma-translocation gene 1 (MALT1). These 3 CARD-BCL10-MALT1 (CBM) complexes activate nuclear factor ?B in both the innate and adaptive arms of immunity. Human inherited defects of the 3 components of the CBM complex, including the 2 adaptors CARD9 and CARD11 and the 2 core components BCL10 and MALT1, have recently been reported. Biallelic loss-of-function mutant alleles underlie several different immunologic and clinical phenotypes, which can be assigned to 2 distinct categories. Isolated invasive fungal infections of unclear cellular basis are associated with CARD9 deficiency, whereas a broad range of clinical manifestations, including those characteristic of T- and B-lymphocyte defects, are associated with CARD11, MALT1, and BCL10 deficiencies. Interestingly, human subjects with these mutations have some features in common with the corresponding knockout mice, but other features are different between human subjects and mice. Moreover, germline and somatic gain-of-function mutations of MALT1, BCL10, and CARD11 have also been found in patients with other lymphoproliferative disorders. This broad range of germline and somatic CBM lesions, including loss-of-function and gain-of-function mutations, highlights the contribution of each of the components of the CBM complex to human immunity. PMID:26277595

  19. Vorinostat in Treating Patients With Low-Grade Non-Hodgkin's Lymphoma

    ClinicalTrials.gov

    2015-12-08

    Extranodal Marginal Zone Lymphoma of Mucosa-Associated Lymphoid Tissue; Nodal Marginal Zone Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma

  20. Lymphoid infiltrates of the salivary glands: pathology, biology and clinical significance.

    PubMed

    DiGiuseppe, J A; Corio, R L; Westra, W H

    1996-05-01

    Lymphoid infiltrates of the salivary glands are common to a variety of pathologic conditions including autoimmune disorders, malignant lymphomas, and immunoregulatory responses to parenchymal neoplasms. Clearly, the correct identification of these salivary gland lymphoid infiltrates has important implications regarding patient prognosis and management. Immunophenotypic and molecular analyses have demonstrated that many lesions formerly regarded as myoepithelial sialadentis or benign lymphoepithelial lesion in fact represent neoplastic lymphoid proliferations with the potential for extrasalivary dissemination. In the most recent classification scheme of non-Hodgkin's lymphomas, these neoplasms fall within the spectrum of low-grade B-cell lymphoma of mucosa-associated lymphoid tissue. In the early stages of HIV infection, patients may develop salivary gland enlargement resulting from cystic lymphoepithelial lesions. These lesions are thought to reflect a localized manifestation of persistent generalized lymphadenopathy. Although HIV-associated salivary gland disease is regarded as a benign condition, malignant lymphoma has been described in association with some of these lesions, and further work is required to define more precisely the risk of salivary gland lymphoma in HIV-infected patients. Tumor-associated lymphoid proliferation refers to a prominent lymphoid reaction accompanying certain epithelial tumors of the salivary glands. Although tumor-associated lymphoid proliferation has not received as much attention as other types of salivary lymphoid infiltrates, it is a common phenomenon that is sometimes mistaken for an intraparotid lymph node harboring metastatic carcinoma. PMID:8804813

  1. Pembrolizumab in Treating Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia or Other Low-Grade B-Cell Non-Hodgkin Lymphomas

    ClinicalTrials.gov

    2015-11-16

    Recurrent Chronic Lymphocytic Leukemia; Recurrent Extranodal Marginal Zone Lymphoma of Mucosa-Associated Lymphoid Tissue; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Lymphoplasmacytic Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Nodal Marginal Zone Lymphoma; Recurrent Small Lymphocytic Lymphoma; Recurrent Splenic Marginal Zone Lymphoma; Refractory Extranodal Marginal Zone Lymphoma of Mucosa-Associated Lymphoid Tissue; Refractory Follicular Lymphoma; Refractory Lymphoplasmacytic Lymphoma; Refractory Nodal Marginal Zone Lymphoma; Refractory Splenic Marginal Zone Lymphoma; Waldenstrom Macroglobulinemia

  2. Elevation of serum interleukins 8, 4, and 1? levels in patients with gastrointestinal low-grade B-cell lymphoma.

    PubMed

    Miyata-Takata, Tomoko; Takata, Katsuyoshi; Toji, Tomohiro; Goto, Naoe; Kasahara, Senji; Takahashi, Takeshi; Tari, Akira; Noujima-Harada, Mai; Miyata, Takafumi; Sato, Yasuharu; Yoshino, Tadashi

    2015-01-01

    Proinflammatory cytokines that are produced by helper T cells (Th) regulate immune reactions, facilitate class switching of B cells, and prolong the lifespan of B and T cells. Eradication therapy using antibiotics is sometimes effective against gastrointestinal (GI) malignant lymphoma, suggesting that the tumor development or progression is affected by the inflammatory microenvironment. In the present study, serum samples from 148 patients with various subtypes of malignant lymphoma were tested for 11 proinflammatory Th1/Th2 cytokines. In the comparison by subtype or GI lesions, serum interleukin (IL)-8 (P?=?6.7E-05), IL-4 (P?=?7.5E-05), and IL-1? (P?=?0.0043) levels showed significant differences among subtypes, being particularly elevated in follicular lymphomas (FL) and mucosa-associated lymphoid tissue (MALT) lymphomas. Serum IL-8 levels were elevated in GI-FL and MALT lymphomas, and serum IL-4 and IL-1 ? levels were elevated in MALT lymphomas. These findings show that GI low-grade B-cell lymphoma could develop against the background of an inflammatory microenvironment. Thus, these cytokines may be useful as diagnostic markers and could provide new insights into tumor development. PMID:26674732

  3. Elevation of serum interleukins 8, 4, and 1? levels in patients with gastrointestinal low-grade B-cell lymphoma

    PubMed Central

    Miyata-Takata, Tomoko; Takata, Katsuyoshi; Toji, Tomohiro; Goto, Naoe; Kasahara, Senji; Takahashi, Takeshi; Tari, Akira; Noujima-Harada, Mai; Miyata, Takafumi; Sato, Yasuharu; Yoshino, Tadashi

    2015-01-01

    Proinflammatory cytokines that are produced by helper T cells (Th) regulate immune reactions, facilitate class switching of B cells, and prolong the lifespan of B and T cells. Eradication therapy using antibiotics is sometimes effective against gastrointestinal (GI) malignant lymphoma, suggesting that the tumor development or progression is affected by the inflammatory microenvironment. In the present study, serum samples from 148 patients with various subtypes of malignant lymphoma were tested for 11 proinflammatory Th1/Th2 cytokines. In the comparison by subtype or GI lesions, serum interleukin (IL)-8 (P?=?6.7E?05), IL-4 (P?=?7.5E?05), and IL-1? (P?=?0.0043) levels showed significant differences among subtypes, being particularly elevated in follicular lymphomas (FL) and mucosa-associated lymphoid tissue (MALT) lymphomas. Serum IL-8 levels were elevated in GI-FL and MALT lymphomas, and serum IL-4 and IL-1 ? levels were elevated in MALT lymphomas. These findings show that GI low-grade B-cell lymphoma could develop against the background of an inflammatory microenvironment. Thus, these cytokines may be useful as diagnostic markers and could provide new insights into tumor development. PMID:26674732

  4. Low-Grade Gliomas

    PubMed Central

    Forst, Deborah A.; Nahed, Brian V.; Loeffler, Jay S.

    2014-01-01

    Low-grade gliomas (LGGs) are a diverse group of primary brain tumors that often arise in young, otherwise healthy patients and generally have an indolent course with longer-term survival in comparison with high-grade gliomas. Treatment options include observation, surgery, radiation, chemotherapy, or a combined approach, and management is individualized based on tumor location, histology, molecular profile, and patient characteristics. Moreover, in this type of brain tumor with a relatively good prognosis and prolonged survival, the potential benefits of treatment must be carefully weighed against potential treatment-related risks. We review in this article current management strategies for LGG, including surgery, radiotherapy, and chemotherapy. In addition, the importance of profiling the genetic and molecular properties of LGGs in the development of targeted anticancer therapies is also reviewed. Finally, given the prevalence of these tumors in otherwise healthy young patients, the impact of treatment on neurocognitive function and quality of life is also evaluated. PMID:24664484

  5. Rituximab, Cyclophosphamide, Bortezomib, and Dexamethasone in Treating Patients With Relapsed or Refractory Low-Grade Follicular Lymphoma, Waldenstrom Macroglobulinemia, or Mantle Cell Lymphoma

    ClinicalTrials.gov

    2015-01-16

    Extranodal Marginal Zone Lymphoma of Mucosa-Associated Lymphoid Tissue; Nodal Marginal Zone Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; Splenic Marginal Zone Lymphoma; Waldenstrom Macroglobulinemia

  6. TLR9 Agonist SD-101, Ipilimumab, and Radiation Therapy in Treating Patients With Low-Grade Recurrent B-cell Lymphoma

    ClinicalTrials.gov

    2015-05-19

    Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Nodal Marginal Zone B-cell Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Small Lymphocytic Lymphoma; Splenic Marginal Zone Lymphoma

  7. Rituximab and Dexamethasone in Treating Patients With Low-Grade Non-Hodgkin Lymphoma

    ClinicalTrials.gov

    2011-08-11

    Contiguous Stage II Grade 1 Follicular Lymphoma; Contiguous Stage II Grade 2 Follicular Lymphoma; Contiguous Stage II Marginal Zone Lymphoma; Cutaneous B-cell Non-Hodgkin Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Nodal Marginal Zone B-cell Lymphoma; Noncontiguous Stage II Grade 1 Follicular Lymphoma; Noncontiguous Stage II Grade 2 Follicular Lymphoma; Noncontiguous Stage II Marginal Zone Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Marginal Zone Lymphoma; Splenic Marginal Zone Lymphoma; Stage I Grade 1 Follicular Lymphoma; Stage I Grade 2 Follicular Lymphoma; Stage I Marginal Zone Lymphoma; Stage III Grade 1 Follicular Lymphoma; Stage III Grade 2 Follicular Lymphoma; Stage III Marginal Zone Lymphoma; Stage IV Grade 1 Follicular Lymphoma; Stage IV Grade 2 Follicular Lymphoma; Stage IV Marginal Zone Lymphoma; Waldenstrom Macroglobulinemia

  8. Probiotics modify human intestinal mucosa-associated microbiota in patients with colorectal cancer.

    PubMed

    Gao, Zhiguang; Guo, Bomin; Gao, Renyuan; Zhu, Qingchao; Wu, Wen; Qin, Huanlong

    2015-10-01

    Studies using animal models have demonstrated that probiotics may have a beneficial role in the prevention of colorectal cancer (CRC); however, the underlying mechanism of the beneficial effects of interventional probiotic treatment on gut microbiota has remained elusive. In the present study, pyrosequencing of the V3 region of the 16S rRNA genes was conducted in order to determine the extent to which probiotics alter the microbiota. The observations of the present study indicated that the microbial structure of cancerous tissue differed significantly from that of healthy individuals and that the CRC microbiota exhibited lower diversity. It was indicated that interventional treatment with probiotics increased the density and diversity of mucosal microbes, and altered the mucosa?associated microbiota. Pyrosequencing demonstrated that probiotics significantly reduced (5?fold) the abundance of a bacterial taxon assigned to the genus Fusobacterium, which had been previously suggested to be a contributing factor to increase tumorigenesis. Accordingly, interventional probiotic therapy is suggested to be able to improve the composition of the mucosal microbial flora and significantly reduce the abundance of mucosa-associated pathogens in patients with CRC. PMID:26238090

  9. Adjuvant activity of naturally occurring monophosphoryl lipopolysaccharide preparations from mucosa-associated bacteria.

    PubMed

    Chilton, Paula M; Hadel, Diana M; To, Thao T; Mitchell, Thomas C; Darveau, Richard P

    2013-09-01

    Natural heterogeneity in the structure of the lipid A portion of lipopolysaccharide (LPS) produces differential effects on the innate immune response. Gram-negative bacterial species produce LPS structures that differ from the classic endotoxic LPS structures. These differences include hypoacylation and hypophosphorylation of the diglucosamine backbone, both differences known to decrease LPS toxicity. The effect of decreased toxicity on the adjuvant properties of many of these LPS structures has not been fully explored. Here we demonstrate that two naturally produced forms of monophosphorylated LPS, from the mucosa-associated bacteria Bacteroides thetaiotaomicron and Prevotella intermedia, function as immunological adjuvants for antigen-specific immune responses. Each form of mucosal LPS increased vaccination-initiated antigen-specific antibody titers in both quantity and quality when given simultaneously with vaccine antigen preparations. Interestingly, adjuvant effects on initial T cell clonal expansion were selective for CD4 T cells. No significant increase in CD8 T cell expansion was detected. MyD88/Toll-like receptor 4 (TLR4) and TRIF/TLR4 signaling pathways showed equally decreased signaling with the LPS forms studied here as with endotoxic LPS or detoxified monophosphorylated lipid A (MPLA). Natural monophosphorylated LPS from mucosa-associated bacteria functions as a weak but effective adjuvant for specific immune responses, with preferential effects on antibody and CD4 T cell responses over CD8 T cell responses. PMID:23798540

  10. [Low-grade gliomas in adults].

    PubMed

    Kratzsch, Tobias; Gautschi, Oliver P; Kuhn, Susanne A; Hottinger, Andreas F; Hildebrandt, Gerhard; Stienen, Martin N

    2014-11-12

    Low-grade gliomas (LGG) are brain tumors with a low or intermediate biological aggressiveness. According to histopathological features, they are further specified as grade I or II by WHO criteria. Diffuse astrocytomas, oligodendrogliomas, and mixed gliomas are the most common LGG. They mainly affect young patients in their 3rd to 5th decade and often manifest with epileptic seizures. A macroscopically complete or near-complete tumor resection that does not induce additional neurological deficits, is recommended as first line therapy in surgically accessible tumors, as a significant benefit for overall survival has been demonstrated. The indication for adjuvant chemo- or radiotherapy must be discussed interdisciplinary in each case. MGMT promotor methylation, LOH 1p/19q, as well as the status of somatic mutations within IDH1/2 gene constitute biomarkers that may predict response to adjuvant therapy and may correlate to overall survival. These and other biomarkers could be of benefit in future managing plans to offer patients with LGG an individually tailored, optimal treatment. PMID:25391745

  11. Texas Tech Researchers Discover Low-Grade Nonwoven Cotton

    E-print Network

    Rock, Chris

    Texas Tech Researchers Discover Low-Grade Nonwoven Cotton Picks Up 50 Times Own Weight of Oil Nonwoven cotton could become the new picker-upper for oil spills. Texas Tech University researchers recently discovered that low-grade cotton made into an absorbent nonwoven mat can collect up to 50 times

  12. Characterization of mucosa-associated bacterial communities of the mouse intestine by terminal restriction fragment length polymorphism: Utility of sampling strategies

    E-print Network

    Selinger, Brent

    Characterization of mucosa-associated bacterial communities of the mouse intestine by terminal 2009 Keywords: Intestine Mucosa-associated bacteria Single-stranded artifacts T-RFLP Statistical for recovering bacterial community DNA associated with intestinal mucosa of mice (i.e. mechanical agitation

  13. Characteristics of Fecal and Mucosa-Associated Microbiota in Chinese Patients With Inflammatory Bowel Disease

    PubMed Central

    Chen, Liping; Wang, Wei; Zhou, Rui; Ng, Siew C.; Li, Jin; Huang, Meifang; Zhou, Feng; Wang, Xin; Shen, Bo; A. Kamm, Michael; Wu, Kaichun; Xia, Bing

    2014-01-01

    Abstract The intestinal microbiota plays an important role in the pathogenesis of inflammatory bowel disease (IBD), and geographical and genetic backgrounds impact the composition of the intestinal microbiota. However, there is a lack of evidence regarding the overall changes and characteristics of fecal-associated microbiota (FAM) and mucosa-associated microbiota (MAM) in Chinese patients with IBD. We recruited 26 patients with Crohn’s disease (CD), 46 patients with ulcerative colitis (UC), and 21 healthy individuals; we collected matched fresh fecal and mucosal samples from the same subjects. The microbial communities were studied by 454-pyrosequencing. Community-wide changes in FAM and MAM were observed in patients with IBD. The proportion of several butyrate-producing bacteria, such as of the genera Roseburia, Coprococcus, and Ruminococcus were significantly reduced, whereas the pathogens Escherichia-Shigella and Enterococcus were prevalent in patients with IBD. FAM and MAM were similar between CD and UC. FAM differed from MAM in healthy individuals and patients with UC. In conclusion, the compositions of FAM and MAM were altered in patients with IBD. The reduction of butyrate-producing bacteria and the increase in opportunistic pathogens might be associated with the pathogenesis of IBD. PMID:25121355

  14. Ageing combines CD4 T cell lymphopenia in secondary lymphoid organs and T cell accumulation in gut associated lymphoid tissue

    PubMed Central

    2014-01-01

    Background CD4 T cell lymphopenia is an important T cell defect associated to ageing. Higher susceptibility to infections, cancer, or autoimmune pathologies described in aged individuals is thought to partly rely on T cell lymphopenia. We hypothesize that such diverse effects may reflect anatomical heterogeneity of age related T cell lymphopenia. Indeed, no data are currently available on the impact of ageing on T cell pool recovered from gut associated lymphoid tissue (GALT), a crucial site of CD4 T cell accumulation. Results Primary, secondary and tertiary lymphoid organs of C57BL/6 animals were analysed at three intervals of ages: 2 to 6 months (young), 10 to 14 months (middle-aged) and 22 to 26 months (old). We confirmed that ageing preferentially impacted CD4 T cell compartment in secondary lymphoid organs. Importantly, a different picture emerged from gut associated mucosal sites: during ageing, CD4 T cell accumulation was progressively developing in colon and small intestine lamina propria and Peyer’s patches. Similar trend was also observed in middle-aged SJL/B6 F1 mice. Interestingly, an inverse correlation was detected between CD4 T cell numbers in secondary lymphoid organs and colonic lamina propria of C57BL/6 mice whereas no increase in proliferation rate of GALT CD4 T cells was detected. In contrast to GALT, no CD4 T cell accumulation was detected in lungs and liver in middle-aged animals. Finally, the concomitant accumulation of CD4 T cell in GALT and depletion in secondary lymphoid organs during ageing was detected both in male and female animals. Conclusions Our data thus demonstrate that T cell lymphopenia in secondary lymphoid organs currently associated to ageing is not sustained in gut or lung mucosa associated lymphoid tissues or non-lymphoid sites such as the liver. The inverse correlation between CD4 T cell numbers in secondary lymphoid organs and colonic lamina propria and the absence of overt proliferation in GALT suggest that marked CD4 T cell decay in secondary lymphoid organs during ageing reflect redistribution of CD4 T cells rather than generalized CD4 T cell decay. Such anatomical heterogeneity may provide an important rationale for the diversity of immune defects observed during ageing. PMID:24829607

  15. Mucosa-Associated Faecalibacterium prausnitzii Phylotype Richness Is Reduced in Patients with Inflammatory Bowel Disease.

    PubMed

    Lopez-Siles, Mireia; Martinez-Medina, Margarita; Abellà, Carles; Busquets, David; Sabat-Mir, Miriam; Duncan, Sylvia H; Aldeguer, Xavier; Flint, Harry J; Garcia-Gil, L Jesús

    2015-11-01

    Faecalibacterium prausnitzii depletion in intestinal diseases has been extensively reported, but little is known about intraspecies variability. This work aims to determine if subjects with gastrointestinal disease host mucosa-associated F. prausnitzii populations different from those hosted by healthy individuals. A new species-specific PCR-denaturing gradient gel electrophoresis (PCR-DGGE) method targeting the 16S rRNA gene was developed to fingerprint F. prausnitzii populations in biopsy specimens from 31 healthy control (H) subjects and 36 Crohn's disease (CD), 23 ulcerative colitis (UC), 6 irritable bowel syndrome (IBS), and 22 colorectal cancer (CRC) patients. The richness of F. prausnitzii subtypes was lower in inflammatory bowel disease (IBD) patients than in H subjects. The most prevalent operational taxonomic units (OTUs) consisted of four phylotypes (OTUs with a 99% 16S rRNA gene sequence similarity [OTU99]), which were shared by all groups of patients. Their distribution and the presence of some disease-specific F. prausnitzii phylotypes allowed us to differentiate the populations in IBD and CRC patients from that in H subjects. At the level of a minimum similarity of 97% (OTU97), two phylogroups accounted for 98% of the sequences. Phylogroup I was found in 87% of H subjects but in under 50% of IBD patients (P = 0.003). In contrast, phylogroup II was detected in >75% of IBD patients and in only 52% of H subjects (P = 0.005). This study reveals that even though the main members of the F. prausnitzii population are present in both H subjects and individuals with gut diseases, richness is reduced in the latter and an altered phylotype distribution exists between diseases. This approach may serve as a basis for addressing the suitability of F. prausnitzii phylotypes to be quantified as a putative biomarker of disease and depicting the importance of the loss of these subtypes in disease pathogenesis. PMID:26296733

  16. Mucosa-Associated Bacterial Microbiome of the Gastrointestinal Tract of Weaned Pigs and Dynamics Linked to Dietary Calcium-Phosphorus

    PubMed Central

    Mann, Evelyne; Schmitz-Esser, Stephan; Zebeli, Qendrim; Wagner, Martin; Ritzmann, Mathias; Metzler-Zebeli, Barbara U.

    2014-01-01

    Dietary composition largely influences pig’s gastrointestinal microbiota and represents a useful prophylactic tool against enteric disturbances in young pigs. Despite the importance for host-microbe interactions and bacterial colonization, dietary responses of the mucosa-associated bacterial communities are less well investigated. In the present study, we characterized the mucosa-associated bacterial communities at the Pars non-glandularis of the stomach, ileum and colon, and identified shifts in these communities in response to different dietary calcium-phosphorus (Ca-P) contents (100% versus 190% of the Ca and P requirements) in combination with two basal diets (wheat-barley- or corn-based) in weaned pigs. Pyrosequencing of 16S rRNA genes from 93 mucosal samples yielded 447,849 sequences, clustering into 997 operational taxonomic units (OTUs) at 97% similarity level. OTUs were assigned to 198 genera belonging to 14 different phyla. Correlation-based networks revealed strong interactions among OTUs at the various gastrointestinal sites. Our data describe a previously not reported high diversity and species richness at the Pars non-glandularis of the stomach in weaned pigs. Moreover, high versus adequate Ca-P content significantly promoted Lactobacillus by 14.9% units (1.4 fold change) at the gastric Pars non-glandularis (P?=?0.035). Discriminant analysis revealed dynamic changes in OTU composition in response to dietary cereals and Ca-P contents at all gastrointestinal sites which were less distinguishable at higher taxonomic levels. Overall, this study revealed a distinct mucosa-associated bacterial community at the different gut sites, and a strong effect of high Ca-P diets on the gastric community, thereby markedly expanding our comprehension on mucosa-associated microbiota and their diet-related dynamics in weaned pigs. PMID:24466298

  17. Desalination using low grade heat sources

    NASA Astrophysics Data System (ADS)

    Gude, Veera Gnaneswar

    A new, low temperature, energy-efficient and sustainable desalination system has been developed in this research. This system operates under near-vacuum conditions created by exploiting natural means of gravity and barometric pressure head. The system can be driven by low grade heat sources such as solar energy or waste heat streams. Both theoretical and experimental studies were conducted under this research to evaluate and demonstrate the feasibility of the proposed process. Theoretical studies included thermodynamic analysis and process modeling to evaluate the performance of the process using the following alternate energy sources for driving the process: solar thermal energy, solar photovoltaic/thermal energy, geothermal energy, and process waste heat emissions. Experimental studies included prototype scale demonstration of the process using grid power as well as solar photovoltaic/thermal sources. Finally, the feasibility of the process in reclaiming potable-quality water from the effluent of the city wastewater treatment plant was studied. The following results have been obtained from theoretical analysis and modeling: (1) The proposed process can produce up to 8 L/d of freshwater for 1 m2 area of solar collector and evaporation chamber respectively with a specific energy requirement of 3122 kJ for 1 kg of freshwater production. (2) Photovoltaic/thermal (PV/T) energy can produce up to 200 L/d of freshwater with a 25 m2 PV/T module which meets the electricity needs of 21 kWh/d of a typical household as well. This configuration requires a specific energy of 3122 kJ for 1 kg of freshwater production. (3) 100 kg/hr of geothermal water at 60°C as heat source can produce up to 60 L/d of freshwater with a specific energy requirement of 3078 kJ for 1 kg of freshwater production. (4) Waste heat released from an air conditioning system rated at 3.25 kW cooling, can produce up to 125 L/d of freshwater. This configuration requires an additional energy of 208 kJ/kg of freshwater along with the waste heat released from the condenser of air-conditioning system. This additional energy requirement is about 60% of the energy required by a multi stage flash distillation process. The experimental studies were conducted in three phases. In the first phase, electric power from grid as energy source was used to demonstrate the feasibility of the proposed process. These tests showed that freshwater production rate of 0.25 kg/hr can be sustained at evaporation temperatures as low as 40°C with specific energy input of 3,370 kJ/kg, at efficiencies ranging from 65 to 70% during the winter. In the second phase, experiments were conducted utilizing direct solar thermal energy and photovoltaic energy as well. Four different combinations of energy sources were studied. The following results were obtained from these experimental studies: (1) Utilizing direct solar energy produced 4.9 L/d of freshwater with an evaporator area of 1 m2 with an average efficiency of 61%. This yield is two times that can be obtained from a flat solar still. The specific energy requirement for this configuration is 4157 kJ for production of 1 kilogram freshwater; (2) Utilizing direct solar energy with aid of a reflector produced 7.5 L/d of freshwater with an average efficiency more than 80%. The specific energy requirement for this configuration is 3118 kJ for production of 1 kilogram freshwater; (3) Utilizing direct solar energy during sunlight hours and photovoltaic energy during non-sunlight hours produced 12 L/d of freshwater with 1 m2 evaporator area and 6 m2 photovoltaic areas respectively. The specific energy requirement for this configuration is 2926 kJ for production of 1 kilogram freshwater. Finally, the feasibility of this process in reclaiming potable-quality water from the effluent of a domestic wastewater treatment plant was studied. The process was able to achieve the following reductions: total dissolved solids from 727 mg/L to 21 mg/L (97%); nitrates from 2.4 mg/L to <0.1 mg/L (> 95%); ammonia from 23.2 mg/L to < 0.5 mg/L (> 97%); and

  18. Localized Orbital Mucosa-Associated Lymphoma Tissue Lymphoma Managed With Primary Radiation Therapy: Efficacy and Toxicity

    SciTech Connect

    Goda, Jayant Sastri; Le, Lisa W.; Lapperriere, Normand J.; Millar, Barbara-Ann; Payne, David; Gospodarowicz, Mary K.; Wells, Woodrow; Hodgson, David C.; Sun, Alexander; Simpson, Rand; Tsang, Richard W.

    2011-11-15

    Purpose: To evaluate the clinical outcomes and late effects of radiation therapy (RT) in localized primary orbital mucosa-associated lymphoma tissue (MALT) lymphoma (POML). Methods and Materials: From 1989 to 2007, 89 patients with Stage IE POML received RT. The median age was 56 years old. Sites involved conjunctiva (59 patients [66%]), lacrimal gland (20 patients [23%]), and soft tissue (10 patients [11%]). Megavoltage beam(s) was used in 91%, electrons in 7%, and orthovoltage in 2% of cases. The dose given was 25 Gy in 97% and 30 Gy in 3% of patients. Lens shielding was possible in 57% of patients. Results: The median follow-up was 5.9 years. Complete response or unconfirmed complete response was seen in 88 patients (99%). Relapse occurred in 22 patients (25%). First relapse sites were local (2 patients [9%]), in the contralateral orbit (5 patients [23%]), and distant (15 patients [68%]). The 7-year overall survival (OS), cause-specific survival (CSS), relapse-free survival (RFS), and local control (LC) rates were 91%, 96%, 64%, and 97%, respectively. Radiation-related late sequelae were documented in 40 patients (45%). Cataracts were observed in 22 patients (Grade 1 in 2 patients; Grade 3 in 20 patients). The incidence of Grade 3 cataract at 7 years was 25%. Other late sequelae (n = 28) were dry eye(s) (22 patients [Grade 1 in 14 patients; Grade 2 in 2 patients; Grade 3 in 2 patients; n/s in 4 patients), keratitis (3 patients), macular degeneration/cystoid edema (2 patients), and vitreous detachment (1 patient). Five patients developed Grade 3 noncataract late effects. Lens shielding reduced the incidence of Grade 3 cataract and all Grade {>=}2 late sequelae. Seventeen patients (16 with cataracts) underwent surgery; 23 patients were treated conservatively. The outcome for managing late effects was generally successful, with 30 patients completely improved, and 9 patients with persisting late sequelae (10%). Conclusions: POML responds favorably to moderate doses of RT but results in significant late morbidity. The majority of late effects were successfully managed. Lens shielding reduced the risk of cataracts and other late sequelae.

  19. Low-Grade Carotid Stenosis: Implications of MR Imaging.

    PubMed

    Mossa-Basha, Mahmud; Wasserman, Bruce A

    2016-02-01

    Although treatment guidelines are well established for symptomatic patients with greater than 69% carotid stenosis on catheter angiography, optimal management of lower degrees of stenosis remain unclear. Vessel wall MR imaging of the carotid arteries has proved helpful in the evaluation of plaque burden and vulnerable plaque characteristics, and in stratifying risk in low-grade carotid stenosis. This article discusses the pathophysiology and imaging of atherosclerotic plaques resulting in low-grade carotid stenosis, and the corresponding stroke risk and association with plaque elsewhere in the cardiovascular system. PMID:26610665

  20. Neurodevelopmental Outcomes of Children with Low-Grade Gliomas

    ERIC Educational Resources Information Center

    Ris, M. Douglas; Beebe, Dean W.

    2008-01-01

    As a group, children with low-grade gliomas (LGGs) enjoy a high rate of long-term survival and do not require the intensity of neurotoxic treatments used with higher risk pediatric brain tumors. Because they are generally considered to have favorable neurobehavioral outcomes, they have not been studied as thoroughly as higher-grade brain tumors by…

  1. Validation of Use of Rectoanal Mucosa-Associated Lymphoid Tissue for Immunohistochemical Diagnosis of Chronic Wasting Disease in White-Tailed Deer (Odocoileus virginianus)

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The transmissible spongiform encephalopathies are a family of fatal neurodegenerative diseases characterized by accumulation of abnormal prion proteins in the brain. The abnormal prion protein is the major constituent of the infectious agent and is a reliable marker for disease. The occurrence of ...

  2. Clinical Features, Treatment and Outcome of Mucosa-Associated Lymphoid Tissue (MALT) Lymphoma of the Ocular Adnexa: Single Center Experience of 60 Patients

    PubMed Central

    Kiesewetter, Barbara; Lukas, Julius; Kuchar, Andreas; Mayerhoefer, Marius E.; Streubel, Berthold; Lagler, Heimo; Müllauer, Leonhard; Wöhrer, Stefan; Fischbach, Julia; Raderer, Markus

    2014-01-01

    Background Orbital marginal zone B-cell lymphoma (OAML) constitutes for the most frequent diagnosis in orbital lymphoma. Relatively little data, however, have been reported in larger cohorts of patients staged in a uniform way and no therapy standard exists to date. Material and Methods We have retrospectively analyzed 60 patients diagnosed and treated at our institution 1999–2012. Median age at diagnosis was 64 years (IQR 51–75) and follow-up time 43 months (IQR 16–92). All patients had undergone uniform extensive staging and histological diagnosis was made by a reference pathologist according to the WHO classification. Results The majority of patients presented with stage IE (n?=?40/60, 67%), three had IIE/IIIE and the remaining 17 stage IVE. Seven patients with IVE had bilateral orbital disease whereas the others showed involvement of further organs. Treatment data were available in 58 patients. Local treatment with radiotherapy (14/58, 24%) or surgery (3/58, 5%) resulted in response in 82% of patients. A total of 26 patients (45%) received systemic treatment with a response rate of 85%. Nine patients received antibiotics as initial therapy; response rate was 38%. Watchful-waiting was the initial approach in 6/58 patients. In total 28/58 patients (48%) progressed and were given further therapy. Median time-to-progression in this cohort was 20 months (IQR 9–39). There was no difference in time-to-progression after first-line therapy between the different therapy arms (p?=?0.14). Elevated beta-2-microglobulin, plasmacytic differentiation, autoimmune disorder and site of lymphoma were not associated with a higher risk for progress. Conclusion Our data underscore the excellent prognosis of OAML irrespective of initial therapy, as there was no significant difference in time-to-progression and response between local or systemic therapy. In the absence of randomized trials, the least toxic individual approach should be chosen for OAML. PMID:25077481

  3. Is Invasive Micropapillary Serous Carcinoma a Low-grade Carcinoma?

    PubMed

    Ohishi, Yoshihiro; Imamura, Hiroko; Aman, Murasaki; Shida, Kaai; Kaku, Tsunehisa; Kato, Kiyoko; Oda, Yoshinao

    2016-01-01

    "Invasive micropapillary serous carcinoma" has been proposed as a synonym for low-grade serous carcinoma by some expert pathologists. In contrast, Singer and colleagues reported that some serous carcinomas with conspicuous invasive micropapillary pattern (SC-IMPs) can show high-grade nuclear atypia. However, the molecular features of such tumors have not been well documented. The aim of this study was to demonstrate and emphasize the fact that high-grade serous carcinoma confirmed by immunohistochemistry and molecular analysis can show conspicuous invasive micropapillary pattern. We selected 24 "SC-IMPs" and investigated: (1) their morphologic features; (2) the immunostaining pattern of p53 protein; and (3) KRAS/BRAF/TP53 gene mutations. The 24 SC-IMPs were subdivided into low-grade and high-grade tumors based primarily on the nuclear atypia, with the mitotic rate used as a secondary feature: low grade (n=5) and high grade (n=19). Low-grade SC-IMPs were characterized by low-mitotic activity, absence of abnormal mitosis, presence of serous borderline tumor, occasional BRAF mutation, and infrequent TP53 mutation. High-grade SC-IMPs were characterized by high-mitotic activity, presence of abnormal mitosis, conventional high-grade serous carcinoma, frequent TP53 mutation, and lack of KRAS/BRAF mutation. We demonstrated that high-grade serous carcinoma confirmed by aberrant p53 immunostaining and molecular analysis can show conspicuous invasive micropapillary pattern, validating Singer and colleague's report. Serous carcinoma with conspicuous invasive micropapillary pattern should not be readily regarded as low-grade serous carcinoma. Nuclear grade is the most important diagnostic feature in the SC-IMPs. PMID:26166721

  4. Total lymphoid irradiation

    SciTech Connect

    Sutherland, D.E.; Ferguson, R.M.; Simmons, R.L.; Kim, T.H.; Slavin, S.; Najarian, J.S.

    1983-05-01

    Total lymphoid irradiation by itself can produce sufficient immunosuppression to prolong the survival of a variety of organ allografts in experimental animals. The degree of prolongation is dose-dependent and is limited by the toxicity that occurs with higher doses. Total lymphoid irradiation is more effective before transplantation than after, but when used after transplantation can be combined with pharmacologic immunosuppression to achieve a positive effect. In some animal models, total lymphoid irradiation induces an environment in which fully allogeneic bone marrow will engraft and induce permanent chimerism in the recipients who are then tolerant to organ allografts from the donor strain. If total lymphoid irradiation is ever to have clinical applicability on a large scale, it would seem that it would have to be under circumstances in which tolerance can be induced. However, in some animal models graft-versus-host disease occurs following bone marrow transplantation, and methods to obviate its occurrence probably will be needed if this approach is to be applied clinically. In recent years, patient and graft survival rates in renal allograft recipients treated with conventional immunosuppression have improved considerably, and thus the impetus to utilize total lymphoid irradiation for its immunosuppressive effect alone is less compelling. The future of total lymphoid irradiation probably lies in devising protocols in which maintenance immunosuppression can be eliminated, or nearly eliminated, altogether. Such protocols are effective in rodents. Whether they can be applied to clinical transplantation remains to be seen.

  5. Notch signaling activation in pediatric low-grade astrocytoma.

    PubMed

    Brandt, William D; Schreck, Karisa C; Bar, Eli E; Taylor, Isabella; Marchionni, Luigi; Raabe, Eric; Eberhart, Charles G; Rodriguez, Fausto J

    2015-02-01

    Pilocytic astrocytoma (PA) is the most common primary brain tumor in children; various signaling pathways have been implicated in its biology. The Notch signaling pathway has been found to play a role in the development, stem cell biology, and pathogenesis of several cancers, but its role in PA has not been investigated. We studied alterations in Notch signaling components in tumor tissue from 18 patients with PA and 4 with other low-grade astrocytomas to identify much needed therapeutic targets. We found that Notch pathway members were overexpressed at the mRNA (NOTCH1, NOTCH2, HEY1, HEY2) and protein (HES1) levels in PAs at various anatomic sites compared with non-neoplastic brain samples. These changes were not associated with specific BRAF alterations. Inhibiting the Notch pathway in the pediatric low-grade astrocytoma cell lines Res186 and Res259 using either RNA interference or a ?-secretase inhibitor resulted in variable, but significant, reduction in cell growth and migration. This study suggests a potential role for Notch signaling in pediatric low-grade astrocytoma tumorigenesis and that Notch signaling may be a viable pathway therapeutic target. PMID:25575134

  6. Low Grade Heat Recovery- A Unique Approach at Polysar Limited 

    E-print Network

    Shyr, S.

    1988-01-01

    exchangers in Canada saves energy for Polysar Limited. This unique retrofit proj~t has not only increased the recovery of low grade heat but also Integrated and optimized the operation of two dif~erent .w~ter treatment facilities. The estimated annual...IOn. This retrofit project involved an in~ov~tive application ~f a high efficiency plate heat exchanger whIch Integrated a 1940 s water treatment facility with that of a 1980's versIOn. The resulting benefits went much beyond improved I?w grade heat recovery...

  7. Histopathological spectrum of polymorphous low-grade adenocarcinoma

    PubMed Central

    Surya, Varun; Tupkari, Jagdish V; Joy, Tabita; Verma, Priyanka

    2015-01-01

    Polymorphous low-grade adenocarcinomas (PLGA) are distinctive salivary gland neoplasms, with an almost exclusive propensity to arise from the minor salivary glands. PLGA frequently manifests as an asymptomatic, slow-growing mass within the oral cavity, which must be separated from adenoid cystic carcinoma and benign mixed tumor for therapeutic and prognostic considerations. We report a case of a 67-year-old male, who presented with a long-standing mass in the palate. This lesion was diagnosed as PLGA based on histopathological findings, which was further confirmed by the immunohistochemical marker.

  8. Association of carcinoid tumor and low grade glioma

    PubMed Central

    2012-01-01

    Background Lung carcinoid tumor and low grade glioma are two uncommon malignancies. Patients and methods We report the case of 24-year-old man who presented with respiratory disease. Imaging investigations showed a right lung tumor and histological analysis confirmed a typical carcinoid tumor. As part of initial staging, brain MRI revealed an asymptomatic right frontal lesion. First, a right pulmonary lobectomy was performed without adjuvant treatment. In second time, brain tumorectomy was performed. Histological examination confirmed the diagnosis of low grade glioma (LGG). The patient remained in complete remission 2.5 years after the initial diagnosis. Results This is the first case reporting the association between LGG and lung carcinoid tumor, while no association between LGG and a systemic tumor have been published to date. Association of lung carcinoid tumor with other malignant diseases has been reported but remained uncommon. Only minimal data support a potential molecular common origin. Conclusion This exceptional association may be fortuitous. However, their concomitant diagnoses suggest a potential association between both rare diseases. A genetic susceptibility remains possible. PMID:23137305

  9. Brittle frictional mountain building 3. Low-grade metamorphism

    NASA Astrophysics Data System (ADS)

    Barr, Terence D.; Dahlen, F. A.; McPhail, D. C.

    1991-06-01

    An active fold-and-thrust belt in unchanging tectonic and climatic conditions exhibits a dynamic steady state, with the flux of rocks accreted at the toe balanced by the flux of rocks eroded off the top. Rocks entering the toe are buried and heated before they are uplifted and eroded; this results in a characteristic map pattern of low-grade metamorphism on the surface. Metamorphic isograds are generally parallel to the regional strike of a fold-and-thrust belt, with the grade increasing progressively from unmetamorphosed and zeolite facies near the deformation front up to greenschist facies in the highest mountains; such a pattern is observed in the active fold-and-thrust belt of Taiwan. This paper examines the origin of this low-grade syntectonic metamorphism, using a previously developed mechanical and thermal model of a steady state fold-and-thrust belt as a basis. To model the metamorphism, we develop a petrogenetic grid for rocks of basaltic composition, considering phases within the chemical system CaO-MgO-Al2O3-SiO2-H2O. Equilibria diagnostic of stable low-grade mineral assemblages are mapped onto a cross section of the Taiwan fold-and-thrust belt, using the calculated fluid pressure and temperature distributions within the wedge. The variation of metamorphic grade along the surface is predicted by assuming that there is no retrograde metamorphism. The most important mechanical factor controlling the degree of metamorphism in an active fold-and-thrust belt is the amount of frictional heating, both on the basal decollement fault and within the deforming brittle wedge. Frictional heating raises temperatures in the deepest portions of the Taiwan fold-and-thrust belt by 200° C to 250° C; the resulting high temperatures, in excess of 400° C, are responsible for the extensive greenschist facies metamorphism. The amount of heating is well constrained by the observed heat flow anomaly, geochronological data, and the critical wedge taper; the best-fitting coefficient of basal friction in Taiwan is ?b = 0.5 ± 0.2. Underplating of footwall rocks by the assimilation of duplexes along the decollement fault is not considered to be a significant process in Taiwan, because of the observed balance between the accretionary influx at the toe and the erosive efflux off the top. In other fold-and-thrust belts, however, underplating can significantly increase the outcrop width of higher metamorphic grades on the surface by increasing the flux of rocks through the higher fluid pressure and temperature regions within the wedge.

  10. Reductive Leaching of Low-Grade Pyrolusite with Formic Acid

    NASA Astrophysics Data System (ADS)

    Lu, Youzhi; Ma, Huaju; Huang, Runjun; Yuan, Aiqun; Huang, Zengwei; Zhou, Zeguang

    2015-08-01

    The extraction of manganese from low-grade pyrolusite is investigated using formic acid as reductant in sulfuric acid medium. The effects of volumes of formic acid, concentration of sulfuric acid, liquid to solid ratio (L/S), leaching time, and temperature on leaching efficiency of manganese, iron, and aluminum are valuated with single-factor experiments. The results show that the leaching efficiency of manganese reached 90.08 pct with 80.70 pct of iron and 31.55 pct of aluminum under the optical conditions: 15 pct H2SO4(v/v) 60 ml, 4 ml formic acid, and 2 hours leaching time at 363 K (90 °C).

  11. Low Grade Myofibroblastic Sarcoma Occurred in the Scalp

    PubMed Central

    Yee, Gi Taek

    2015-01-01

    Low-grade myofibroblastic sarcoma (LGMS) is a rare sarcoma with myofibroblastic differentiation. LGMS has a propensity for local recurrence and is associated with a low risk of metastatic spread. A 26-year-old man presented with a 12-month history of a slow growing palpable hard mass in the right parietal scalp. Enhanced CT scan of head showed a 3×4 cm sized well-defined and heterogeneously enhancing scalp mass. The patient underwent excision of the tumor. The histological and immunohistochemical features were consistent with a LGMS. We performed re-operation for remnant tumor removal after diagnosis. After 14 months of surgery, the patient was well-being state. PMID:26587195

  12. Extrachromosomal driver mutations in glioblastoma and low grade glioma

    PubMed Central

    Garieri, Marco; Makrythanasis, Periklis; Falconnet, Emilie; Guipponi, Michel; Vannier, Anne; Radovanovic, Ivan; Bena, Frederique; Forestier, Françoise; Schaller, Karl; Dutoit, Valerie; Clement-Schatlo, Virginie; Dietrich, Pierre-Yves; Antonarakis, Stylianos E

    2014-01-01

    Alteration of the number of copies of Double Minutes (DMs) with oncogenic EGFR mutations in response to tyrosine kinase inhibitors (TKIs) is a novel adaptive mechanism of glioblastoma. Here we provide evidence that such mutations in DMs, called here Amplification-Linked Extrachromosomal Mutations (ALEMs), originate extrachromosomally and could therefore be completely eliminated from the cancer cells. By exome sequencing of 7 glioblastoma patients we reveal ALEMs in EGFR, PDGFRA and other genes. These mutations together with DMs are lost by cancer cells in culture. We confirm the extrachromosomal origin of such mutations by showing that wild type and mutated DMs may coexist in the same tumor. Analysis of 4198 tumors suggests the presence of ALEMs across different tumor types with the highest prevalence in glioblastomas and low grade gliomas. The extrachromosomal nature of ALEMs explains the observed drastic changes in the amounts of mutated oncogenes (like EGFR or PDGFRA) in glioblastoma in response to environmental changes. PMID:25471132

  13. Interaction of low-grade metamorphic coals with methanol

    SciTech Connect

    S.I. Zherebtsov

    2007-06-15

    How conditions of alkylation of low-grade metamorphic coals with methanol in the presence of benzenesulfonic acid influence the yield of extractable matter was experimentally studied and relevant regression equations were obtained. It was shown that catalytic methylation considerably increases the yield of the extractable matter, as well as reducing the thermal stability of modified samples and alters the elemental composition of the samples and their extracts. A possible mechanism of coal methylation is discussed on the basis of regression models and experimental results. The interaction of the coal matter with the alkylating agent presumably involves the formation of the carbocation and its reaction with the coal organic matter. Both depolymerization reactions and the addition reactions of a portion of extractable compounds, the alkylating agent, and the catalyst with the high-molecular mass coal matrix take place.

  14. AMG 319 Lymphoid Malignancy FIH

    ClinicalTrials.gov

    2015-02-16

    Cancer; Chronic Lymphocytic Leukemia; Diffuse Large Cell Lymphoma; Hematologic Malignancies; Hematology; Leukemia; Low Grade Lymphoma; Lymphoma; Mantle Cell Lymphoma; Non-Hodgkin's Lymphoma; Oncology; Oncology Patients; T Cell Lymphoma; Tumors

  15. Human Mucosa-Associated Invariant T Cells Accumulate in Colon Adenocarcinomas but Produce Reduced Amounts of IFN-?.

    PubMed

    Sundström, Patrik; Ahlmanner, Filip; Akéus, Paulina; Sundquist, Malin; Alsén, Samuel; Yrlid, Ulf; Börjesson, Lars; Sjöling, Åsa; Gustavsson, Bengt; Wong, S B Justin; Quiding-Järbrink, Marianne

    2015-10-01

    Mucosa-associated invariant T (MAIT) cells are innate-like T cells with a conserved TCR ?-chain recognizing bacterial metabolites presented on the invariant MHC-related 1 molecule. MAIT cells are present in intestinal tissues and liver, and they rapidly secrete IFN-? and IL-17 in response to bacterial insult. In colon cancer, IL-17-driven inflammation promotes tumor progression, whereas IFN-? production is essential for antitumor immunity. Thus, tumor-associated MAIT cells may affect antitumor immune responses by their secreted cytokines. However, the knowledge of MAIT cell presence and function in tumors is virtually absent. In this study, we determined the frequency, phenotype, and functional capacity of MAIT cells in colon adenocarcinomas and unaffected colon lamina propria. Flow cytometric analyses showed significant accumulation of MAIT cells in tumor tissue, irrespective of tumor stage or localization. Colonic MAIT cells displayed an activated memory phenotype and expression of chemokine receptors CCR6 and CCR9. Most MAIT cells in unaffected colon tissues produced IFN-?, whereas only few produced IL-17. Colonic MAIT cells also produced TNF-?, IL-2, and granzyme B. In the tumors, significantly lower frequencies of IFN-?-producing MAIT cells were seen, whereas there were no differences in the other cytokines analyzed, and in vitro studies showed that secreted factors from tumor tissue reduced IFN-? production from MAIT cells. In conclusion, MAIT cells infiltrate colon tumors but their ability to produce IFN-? is substantially reduced. We suggest that MAIT cells have the capacity to promote local immune responses to tumors, but factors in the tumor microenvironment act to reduce MAIT cell IFN-? production. PMID:26297765

  16. Low-grade albuminuria in children with obstructive sleep apnea.

    PubMed

    Varlami, Vasiliki; Malakasioti, Georgia; Alexopoulos, Emmanouel I; Theologi, Vasiliki; Theophanous, Eleni; Liakos, Nikolaos; Daskalopoulou, Euphemia; Gourgoulianis, Konstantinos; Kaditis, Athanasios G

    2013-06-01

    Small urinary protein loss (low-grade albuminuria or microalbuminuria) may reflect altered permeability of the glomerular filtration barrier. In the present study, it was hypothesized that children with obstructive sleep apnea have an increased risk of microalbuminuria compared with control subjects without sleep-disordered breathing. Albumin-to-creatinine ratio was measured in morning spot urine specimens collected from consecutive children with or without snoring who were referred for polysomnography. Three groups were studied: (i) control subjects (no snoring, apnea-hypopnea index < 1 episode h(-1) ; n = 31); (ii) mild obstructive sleep apnea (snoring, apnea-hypopnea index = 1-5 episodes h(-1) ; n = 71); and (iii) moderate-to-severe obstructive sleep apnea (snoring, apnea-hypopnea index > 5 episodes?h(-1) ; n = 27). Indications for polysomnography in control subjects included nightmares, somnambulism and morning headaches. An albumin-to-creatinine ratio > median value in the control group (1.85 mg of albumin per g of creatinine) was defined as elevated. Logistic regression analysis revealed that children with moderate-to-severe obstructive sleep apnea, but not those with mild obstructive sleep apnea, had increased risk of elevated albumin-to-creatinine ratio relative to controls (reference) after adjustment for age, gender and presence of obesity: odds ratio 3.8 (95% confidence interval 1.1-12.6); P = 0.04 and 1.5 (0.6-3.7); P > 0.05, respectively. Oxygen desaturation of hemoglobin and respiratory arousal indices were significant predictors of albumin-to-creatinine ratio (r = 0.31, P = 0.01; and r = 0.43, P < 0.01, respectively). In conclusion, children with moderate-to-severe obstructive sleep apnea are at significantly higher risk of increased low-grade excretion of albumin in the morning urine as compared with control subjects without obstructive sleep apnea. These findings may reflect altered permeability of the glomerular filtration barrier related to nocturnal hypoxemia and sympathetic activation which are induced by obstructive sleep apnea. PMID:23228180

  17. Outcomes of Multidisciplinary Management in Pediatric Low-Grade Gliomas

    SciTech Connect

    Oh, Kevin S.; Hung, Jonathan; Robertson, Patricia L.; Garton, Hugh J.; Muraszko, Karin M.; Sandler, Howard M.; Hamstra, Daniel A.

    2011-11-15

    Purpose: To evaluate the outcomes in pediatric low-grade gliomas managed in a multidisciplinary setting. Methods and Materials: We conducted a single-institution retrospective study of 181 children with Grade I-II gliomas. Log-rank and stepwise Cox proportional hazards models were used to analyze freedom from progression (FFP) and overall survival (OS). Results: Median follow-up was 6.4 years. Thirty-four (19%) of patients had neurofibromatosis Type 1 (NF1) and because of their favorable prognosis were evaluated separately. In the 147 (81%) of patients without NF1, actuarial 7-year FFP and OS were 67 {+-} 4% (standard error) and 94 {+-} 2%, respectively. In this population, tumor location in the optic pathway/hypothalamus was associated with worse FFP (39% vs. 76%, p < 0.0003), but there was no difference in OS. Age {<=}5 years was associated with worse FFP (52% vs. 75%, p < 0.02) but improved OS (97% vs. 92%, p < 0.05). In those with tissue diagnosis, gross total resection (GTR) was associated with improved 7-year FFP (81% vs. 56%, p < 0.02) and OS (100% vs. 90%, p < 0.03). In a multivariate model, only location in the optic pathway/hypothalamus predicted worse FFP (p < 0.01). Fifty patients received radiation therapy (RT). For those with less than GTR, adjuvant RT improved FFP (89% vs. 49%, p < 0.003) but not OS. There was no difference in OS between patient groups given RT as adjuvant vs. salvage therapy. In NF1 patients, 94% of tumors were located in the optic pathway/hypothalamus. With a conservative treatment strategy in this population, actuarial 7-year FFP and OS were 73 {+-} 9% and 100%, respectively. Conclusions: Low-grade gliomas in children {<=}5 years old with tumors in the optic pathway/hypothalamus are more likely to progress, but this does not confer worse OS because of the success of salvage therapy. When GTR is not achieved, adjuvant RT improves FFP but not OS. Routine adjuvant RT can be avoided and instead reserved as salvage.

  18. Second Surgery in Insular Low-Grade Gliomas

    PubMed Central

    Ius, Tamara; Pauletto, Giada; Cesselli, Daniela; Isola, Miriam; Turella, Luca; Budai, Riccardo; DeMaglio, Giovanna; Eleopra, Roberto; Fadiga, Luciano; Lettieri, Christian; Pizzolitto, Stefano; Beltrami, Carlo Alberto; Skrap, Miran

    2015-01-01

    Background. Given the technical difficulties, a limited number of works have been published on insular gliomas surgery and risk factors for tumor recurrence (TR) are poorly documented. Objective. The aim of the study was to determine TR in adult patients with initial diagnosis of insular Low-Grade Gliomas (LGGs) that subsequently underwent second surgery. Methods. A consecutive series of 53 patients with insular LGGs was retrospectively reviewed; 23 patients had two operations for TR. Results. At the time of second surgery, almost half of the patients had experienced progression into high-grade gliomas (HGGs). Univariate analysis showed that TR is influenced by the following: extent of resection (EOR) (P < 0.002), ?VT2T1 value (P < 0.001), histological diagnosis of oligodendroglioma (P = 0.017), and mutation of IDH1 (P = 0.022). The multivariate analysis showed that EOR at first surgery was the independent predictor for TR (P < 0.001). Conclusions. In patients with insular LGG the EOR at first surgery represents the major predictive factor for TR. At time of TR, more than 50% of cases had progressed in HGG, raising the question of the oncological management after the first surgery. PMID:26539503

  19. Immunohistochemical analysis of MDM2 and CDK4 distinguishes low-grade osteosarcoma from benign mimics.

    PubMed

    Yoshida, Akihiko; Ushiku, Tetsuo; Motoi, Toru; Shibata, Tatsuhiro; Beppu, Yasuo; Fukayama, Masashi; Tsuda, Hitoshi

    2010-09-01

    Parosteal osteosarcoma and low-grade central osteosarcoma are two types of low-grade osteosarcoma that show similar clinical behaviors, histological features, and genetic background (ie, amplified sequences of 12q13-15, including MDM2 and CDK4). Low-grade osteosarcoma is often confused with benign lesions, and ancillary techniques to enhance diagnostic accuracy have been awaited. This study explores the use of MDM2 and CDK4 immunohistochemistry for the histological diagnosis of low-grade osteosarcoma. We studied 23 cases of low-grade osteosarcoma from 21 patients (parosteal osteosarcoma (n=14), low-grade central osteosarcoma (n=9)) and 40 cases of benign histological mimics (myositis ossificans (n=11), fibrous dysplasia (n=14), osteochondroma (n=6), desmoplastic fibroma (n=1), florid reactive periostitis (n=4), Nora's lesion (n=3), and turret exostosis (n=1)). Low-grade osteosarcoma labeled for MDM2 in 16 cases (70%) and for CDK4 in 20 cases (87%). All low-grade osteosarcomas expressed one or both markers (100%), with 13 cases (57%) expressing both. Staining pattern was diffuse in most cases, and the majority expressed moderate or strong intensity for either antibody. MDM2/CDK4 immunostaining was shown irrespective of low-grade osteosarcoma histological subtype. In contrast, only 1 Nora's lesion out of the 40 miscellaneous benign processes showed immunoreactivity for MDM2 or CDK4. The combination of these two markers thus shows 100% sensitivity and 97.5% specificity for the diagnosis of low-grade osteosarcoma. MDM2 and CDK4 immunostains therefore reliably distinguish low-grade osteosarcoma from benign histological mimics, and their combination may serve as a useful adjunct in this difficult differential diagnosis. PMID:20601938

  20. High-grade pelvic sarcoma after radiation therapy for low-grade endometrial stromal sarcoma

    SciTech Connect

    Chumas, J.C.; Patsner, B.; Mann, W.J. )

    1990-03-01

    A high-grade heterologous pelvic sarcoma arose in a 60-year-old woman 15 years after she received whole-pelvic radiation for a low-grade endometrial stromal sarcoma. This complication must be considered in determining therapy for low-grade endometrial sarcomas, which are usually inherently of indolent biological behavior.

  1. Low-Grade Cotton Collects 50 Times Its Weight in Oil http://dailyfusion.net/2014/08/low-grade-cotton-collects-oil-30972/[9/2/2014 4:11:41 PM

    E-print Network

    Rock, Chris

    Low-Grade Cotton Collects 50 Times Its Weight in Oil http://dailyfusion.net/2014/08/low-grade-cotton-collects-oil-30972/[9/2/2014 4:11:41 PM] Knowledge is Power prev next Low-Grade Cotton Collects 50 Times Its Weight ABOUT CONTACT ADVERTISE SUBSCRIBE +SUBMIT NEWS Search #12;Low-Grade Cotton Collects 50 Times Its Weight

  2. Prospects for production of synthetic liquid fuel from low-grade coal

    NASA Astrophysics Data System (ADS)

    Shevyrev, Sergei; Bogomolov, Aleksandr; Alekssev, Maksim

    2015-01-01

    In the paper, we compare the energy costs of steam and steam-oxygen gasification technologies for production of synthetic liquid fuel. Results of mathematic simulation and experimental studies on gasification of low-grade coal are presented.

  3. Charging-free electrochemical system for harvesting low-grade thermal energy

    E-print Network

    Yang, Yuan

    Efficient and low-cost systems are needed to harvest the tremendous amount of energy stored in low-grade heat sources (<100 °C). Thermally regenerative electrochemical cycle (TREC) is an attractive approach which uses the ...

  4. An electrochemical system for efficiently harvesting low-grade heat energy

    E-print Network

    Lee, Seok Woo

    Efficient and low-cost thermal energy-harvesting systems are needed to utilize the tremendous low-grade heat sources. Although thermoelectric devices are attractive, its efficiency is limited by the relatively low ...

  5. Thermoelectric energy converter for generation of electricity from low-grade heat

    DOEpatents

    Jayadev, T.S.; Benson, D.K.

    1980-05-27

    A thermoelectric energy conversion device which includes a plurality of thermoelectric elements is described. A hot liquid is supplied to one side of each element and a cold liquid is supplied to the other side of each element. The thermoelectric generator may be utilized to produce power from low-grade heat sources such as ocean thermal gradients, solar ponds, and low-grade geothermal resources. (WHK)

  6. Plasma-enhanced gasification of low-grade coals for compact power plants

    SciTech Connect

    Uhm, Han S.; Hong, Yong C.; Shin, Dong H.; Lee, Bong J.

    2011-10-15

    A high temperature of a steam torch ensures an efficient gasification of low-grade coals, which is comparable to that of high-grade coals. Therefore, the coal gasification system energized by microwaves can serve as a moderately sized power plant due to its compact and lightweight design. This plasma power plant of low-grade coals would be useful in rural or sparsely populated areas without access to a national power grid.

  7. Intramedullary Spinal Cord and Leptomeningeal Metastases from Intracranial Low-grade Oligodendroglioma

    PubMed Central

    Verma, Nipun; Nolan, Craig; Hirano, Miki; Young, Robert J

    2015-01-01

    We present an unusual case of a patient with an intracranial low-grade oligodendroglioma who developed recurrence with an intramedullary spinal cord metastasis and multiple spinal leptomeningeal metastases. The intramedullary spinal cord metastasis showed mild enhancement similar to the original intracranial primary, while the multiple spinal leptomeningeal metastases revealed no enhancement. This is the seventh reported case of symptomatic intramedullary spinal cord metastasis from a low-grade oligodendroglioma. PMID:24667044

  8. Subjective Quality of Life in Persons with Low-Grade Glioma and Their Next of Kin

    ERIC Educational Resources Information Center

    Edvardsson, Tanja I.; Ahlstrom, Gerd I.

    2009-01-01

    Patients with low-grade glioma have a longer survival than patients with highly malignant glioma, and for this reason questions of quality of life (QoL) are of particular importance to such patients as well as to their next of kin. No studies have been found in which both adult patients with low-grade glioma and their next of kin have estimated…

  9. Plasma-enhanced gasification of low-grade coals for compact power plants

    NASA Astrophysics Data System (ADS)

    Uhm, Han S.; Hong, Yong C.; Shin, Dong H.; Lee, Bong J.

    2011-10-01

    A high temperature of a steam torch ensures an efficient gasification of low-grade coals, which is comparable to that of high-grade coals. Therefore, the coal gasification system energized by microwaves can serve as a moderately sized power plant due to its compact and lightweight design. This plasma power plant of low-grade coals would be useful in rural or sparsely populated areas without access to a national power grid.

  10. Taking the temperature of low-grade and very low-grade ductile fabrics: equilibrium and disequilibrium mineral assemblages

    NASA Astrophysics Data System (ADS)

    Cao, Shuyun; Neubauer, Franz; Bernroider, Manfred; Genser, Johann

    2013-04-01

    Many ductile shear zones like ductile low-angle normal faults on top of, and oblique-slip faults bordering, metamorphic core complexes exhibit a regular pattern of fabrics which usually show decreasing temperature and pressure conditions during their formation. This is because the presence of rocks with a dominant but different mineralogy results in shear concentration in the rheological weakest layer. These dominant fabric-forming minerals are with decreasing temperature: feldspar at >450 °C, quartz at >300 °C and calcite <300 °C. Fabrics and textures formed at higher temperatures are preserved in microlithons surrounded by micro-shear zones. This allows determine semiquantitively the temperature and pressure of several fabric-forming events within one rock, where generally disequilibrium is present between micro-lithon and surrounding micro-shear zones. We tested this approach using the white mica barometry and chlorite on two shear zones bordering two distinct metamorphic core complexes. The low-grade Rechnitz metamorphic core complex at the eastern termination of the Eastern Alps, which formed within an extensional setting and is surrounded by a contemporaneously formed Neogene sedimentary basin. Microstructural and textural analysis has revealed the co-existence of microstructures ranging from middle-temperatures to low-temperatures, which overprinted deformation features within the Rechnitz metamorphic core complex. Quartz displays abundant evidence for early high-temperature plastic deformation (e.g. dynamic recrystallization, polygonal grains with straight grain boundaries forming 120° triple junctions) (D2). In some cases, preferred orientations of crystallographic axes are missing and white mica was overgrowing the penetrative foliation. These features suggest annealing during subsequent metamorphism and deformation at high temperature conditions. The high-temperature microstructures and textures are in part or entirely altered by subsequent late low-temperature shearing. Certain minerals such as white mica showed extensive grain-size reduction in mylonites and some are completely transformed into extremely fine grains. The later low-temperature deformational overprint during shearing was affected by ductile low-angle normal faulting. According to backscatter electron analysis (BSE), two microfabric types are observed in white mica and chlorite, (1) type I-microlithons, the older generation with coarse-grained white mica and chlorite occurring in the micro-lithons, where chlorite is sometimes associated with white mica, are seemingly in equilibrium with the surrounding mineral assemblage; and (2) type II-micro-shear zones. The sheared generation has very fine-grained sheared bands, which represent mixtures of white mica and chlorite with apparent disequilibrium boundaries. In most cases, the thermometry calculations from the coarse chlorite grains (microfabric type-I) yield a main result ranging from 328 to 376 °C. In the microfabric type II, the thermometry results from the sheared chlorite grains yield a temperature ranging from 305 to 132 °C. The later temperature is clearly sub-greenschist facies. The lower temperature group is interpreted to result from late-stage hydrothermal overprint, which affected older microfabrics. Chlorite is seemingly accessible to late-stage resetting. Phengitic compositions with high-Si white micas occur in the microfabric type I micro-lithons, however, some phengitic high-Si compositions are also from the micro-shear zone (micro-type II). We note that there is a continuous range of phengitic white mica to nearly pure muscovite. Phengitic white mica is common in all samples of the lower unit together with white mica of lower phengite content. The lower unit experienced, therefore, high-pressure metamorphism, and white mica grains are partly reset to low-pressure white mica indicating decompression. Decompression occurred during shearing and as a result of tectonic exhumation. Detailed microstructural and textural analysis reveals that the movement along the Mou

  11. Innate Lymphoid Cells in Cancer.

    PubMed

    Vallentin, Blandine; Barlogis, Vincent; Piperoglou, Christelle; Cypowyj, Sophie; Zucchini, Nicolas; Chéné, Matthieu; Navarro, Florent; Farnarier, Catherine; Vivier, Eric; Vély, Frédéric

    2015-10-01

    The world of lymphocytes has recently expanded. A group of cells, innate lymphoid cells (ILC), has been defined. It includes lymphoid cells that have been known for decades, such as natural killer (NK) cells and lymphoid tissue-inducer (LTi) cells. NK cells recognize a vast array of tumor cells, which they help to eliminate through cytotoxicity and the production of cytokines, such as IFN?. Advances in our understanding of NK-cell biology have led to a growing interest in the clinical manipulation of these cells in cancer. The other ILCs are found mostly in the mucosae and mucosal-associated lymphoid tissues, where they rapidly initiate immune responses to pathogens without the need for specific sensitization. Here, we outline the basic features of ILCs and review the role of ILCs other than NK cells in cancer. Much of the role of these ILCs in cancer remains unknown, but several findings should lead to further efforts to dissect the contribution of different ILC subsets to the promotion, maintenance, or elimination of tumors at various anatomic sites. This will require the development of standardized reagents and protocols for monitoring the presence and function of ILCs in human blood and tissue samples. PMID:26438443

  12. Delayed osseous metastasis from low-grade endometrial stromal sarcoma: Uncommon occurrence deserving recognition.

    PubMed

    Chow, Louis Tsun Cheung

    2015-10-01

    Despite excellent prognosis, low-grade endometrial stromal sarcoma (ESS) is notorious for late recurrence even in stage I disease. Bone metastases are distinctly rare and only six cases have so far been reported. Two patients presented with back pain due to spinal metastatic low-grade ESS after 15 and 9?years free of disease after resection of the stage 1 primary uterine tumor. Plain radiograph showed an ivory first lumbar vertebra in the first patient and an osteolytic lesion involving the second thoracic vertebra in the second. In both cases, magnetic resonance imaging showed vertebral tumor with intra-spinal extension and spinal cord compression; biopsy confirmed the diagnosis of metastatic low-grade ESS. The first patient received palliative radiotherapy and chemotherapy while the second underwent surgical decompression followed by adjuvant radiotherapy and chemotherapy. The neurologic symptoms in both patients returned 12?months afterwards and progressed relentlessly despite adjuvant chemotherapy and radiotherapy. The first patient developed multiple bone and lung metastasis, culminating in death 44?months after recurrence. While surviving at 24?months from recurrent disease, the second became paraplegic with double incontinence and was wheelchair bound. Delayed osseous metastatic low-grade ESS, although uncommon, deserves recognition given the predilection for spine as the site of involvement. In such a location, where complete surgical removal is notoriously difficult, if not impossible, the prognosis of spinal metastatic low-grade ESS appears grave with considerable morbidity and mortality. PMID:26171849

  13. Stress Induces Endotoxemia and Low-Grade Inflammation by Increasing Barrier Permeability

    PubMed Central

    de Punder, Karin; Pruimboom, Leo

    2015-01-01

    Chronic non-communicable diseases (NCDs) are the leading causes of work absence, disability, and mortality worldwide. Most of these diseases are associated with low-grade inflammation. Here, we hypothesize that stresses (defined as homeostatic disturbances) can induce low-grade inflammation by increasing the availability of water, sodium, and energy-rich substances to meet the increased metabolic demand induced by the stressor. One way of triggering low-grade inflammation is by increasing intestinal barrier permeability through activation of various components of the stress system. Although beneficial to meet the demands necessary during stress, increased intestinal barrier permeability also raises the possibility of the translocation of bacteria and their toxins across the intestinal lumen into the blood circulation. In combination with modern life-style factors, the increase in bacteria/bacterial toxin translocation arising from a more permeable intestinal wall causes a low-grade inflammatory state. We support this hypothesis with numerous studies finding associations with NCDs and markers of endotoxemia, suggesting that this process plays a pivotal and perhaps even a causal role in the development of low-grade inflammation and its related diseases. PMID:26029209

  14. The Beckett System Recovery and Utilization of Low Grade Waste Heat From Flue Gas 

    E-print Network

    Henderson, W. R.; DeBiase, J. F.

    1983-01-01

    The Beckett Heat Recovery is a series of techniques for recovering low-grade waste heat from flue gas. Until the cost of fossil fuels began rising rapidly, flue gas below 600 F was considered economically unworthy of reclaim. This paper...

  15. Raman spectroscopic carbonaceous material thermometry of low-grade metamorphic rocks: Calibration and application to

    E-print Network

    Rahl, Jeffrey M.

    Raman spectroscopic carbonaceous material thermometry of low-grade metamorphic rocks: Calibration/low-temperature metamorphic rocks exposed there. The metamorphic rocks below the detach- ment (the Plattenkalk and Phyllite HP­LT metamorphic rocks, which were initially accreted at ~35 km. We argue that the bulk

  16. Aerobic Training Improved Low-Grade Inflammation in Obese Women with Intellectual Disability

    ERIC Educational Resources Information Center

    Ordonez, F. J.; Rosety, M. A.; Camacho, A.; Rosety, I.; Diaz, A. J.; Fornieles, G.; Garcia, N.; Rosety-Rodriguez, M.

    2014-01-01

    Background: Obesity is a major health problem in people with intellectual disabilities. It is also widely accepted that low-grade systemic inflammation associated to obesity plays a key role in the pathogenic mechanism of several disorders. Fortunately, physical activity has shown to improve inflammation in people with metabolic syndrome and type…

  17. Charging-free electrochemical system for harvesting low-grade thermal energy

    E-print Network

    Cui, Yi

    blue analog | nanomaterials | batteries Avast amount of low-grade heat ( conversion (4­7) and organic Rankine cycles (1, 8), are being actively pursued but face their own challenges to electricity, the electrochemical cell is discharged from A+B to C+D at T1 and recharged at a differ- ent

  18. Mouse Low-Grade Gliomas Contain Cancer Stem Cells with Unique Molecular and Functional

    E-print Network

    Kornfeld, S. Kerry

    Article Mouse Low-Grade Gliomas Contain Cancer Stem Cells with Unique Molecular and Functional-Grade Gliomas Contain Cancer Stem Cells with Unique Molecular and Functional Properties Yi-Hsien Chen,1 Lucy D that LGG cancer stem cells have unique molecular and functional properties relevant to brain cancer

  19. A thermally regenerative ammonia-based battery for efficient harvesting of low-grade thermal

    E-print Network

    A thermally regenerative ammonia-based battery for efficient harvesting of low-grade thermal energy to be efficiently converted into electrical power in a thermally regenerative ammonia-based battery (TRAB) using copper-based redox couples [Cu(NH3)4 2+ /Cu and Cu(II)/Cu]. Ammonia addition to the anolyte (2 M ammonia

  20. Enhancing Low-Grade Thermal Energy Recovery in a Thermally Regenerative Ammonia Battery Using

    E-print Network

    Enhancing Low-Grade Thermal Energy Recovery in a Thermally Regenerative Ammonia Battery Using batteries with SGE technologies in what was called a thermally regenerative ammonia battery (TRAB).[10, but not the catholyte, because this cre- A thermally regenerative ammonia battery (TRAB) is a new ap- proach

  1. Low-grade osteogenic sarcoma arising in medullary and surface osseous locations.

    PubMed

    Antonescu, C R; Huvos, A G

    2000-11-01

    Osteosarcomas represent a heterogeneous group of tumors with different histologic and clinical features, biologic behavior, and therapy. Histologic grading has remained the most important factor for predicting the clinical progression of osteosarcomas. Some of the most common diagnostic problems in surgical pathology related to low-grade osteogenic sarcoma are addressed. PMID:11996175

  2. (18)F-Fluorodeoxyglucose (FDG)-positron emission tomography/computed tomography in mucosa-associated lymphoid tissue lymphoma: variation in (18)F-FDG avidity according to site involvement.

    PubMed

    Park, Seol Hoon; Lee, Jong Jin; Kim, Hye Ok; Lee, Dong Yun; Suh, Cheolwon; Jung, Hwoon-Yong; Choi, Kee Don; Kim, Do Hoon; Huh, Jooryung; Ryu, Jin-Sook

    2015-12-01

    The purpose of this study was to determine the (18)F-FDG avidity of MALT lymphoma and the additional utility of (18)F-FDG PET/CT in MALT lymphoma staging. Pretreatment (18)F-FDG PET/CT scans of 222 patients with 227 MALT lymphoma lesions were retrospectively analyzed. (18)F-FDG avidity of lesions was noted in 28%. The proportion was lower for gastric MALT lymphomas than for non-gastric lesions (9% vs. 60%, p < 0.0001) and higher for mass-forming lesions than for superficial lesions (82% vs. 2%, p < 0.0001). (18)F-FDG PET/CT showed the presence of additional lesions in 23 patients: four of six true-positive lesions had (18)F-FDG avid primary lesions, and 15 of 17 false-positive lesions had (18)F-FDG-non avid lesions. (18)F-FDG avidity differed according to the location and gross morphologic characteristics of the MALT lymphoma. Most gastric MALT lymphomas were superficial and had low (18)F-FDG avidity. For staging, (18)F-FDG PET/CT can be helpful mainly for (18)F-FDG avid primary MALT lymphomas. PMID:25804932

  3. Neurodevelopmental Outcomes of Extremely Low Gestational Age Neonates with Low Grade Periventricular-Intraventricular Hemorrhage

    PubMed Central

    Payne, Allison H.; Hintz, Susan R.; Hibbs, Anna Maria; Walsh, Michele C.; Vohr, Betty R.; Bann, Carla M.; Wilson-Costello, Deanne E.

    2014-01-01

    Objective To compare neurodevelopmental outcomes at 18–22 months corrected age for extremely low gestational age infants with low grade (Grade 1 or 2) periventricular-intraventricular hemorrhage to infants with either no hemorrhage or severe (Grade 3 or 4) hemorrhage on cranial ultrasound. Design Longitudinal observational study Setting Sixteen centers of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network Participants 1472 infants born at <27 weeks gestational age between 2006–2008 with ultrasound results within the first 28 days of life and surviving to 18–22 months with complete follow-up assessments were eligible. Main Exposure Low grade periventricular-intraventricular hemorrhage Outcome Measures Outcomes included cerebral palsy, gross motor functional limitation, Bayley III cognitive and language scores, and composite measures of neurodevelopmental impairment. Regression modeling evaluated the association of hemorrhage severity with adverse outcomes while controlling for potentially confounding variables and center differences. Results Low grade hemorrhage was not associated with significant differences in unadjusted or adjusted risk of any adverse neurodevelopmental outcome compared to infants without hemorrhage. Compared with low grade hemorrhage, severe hemorrhage was associated with decrease in adjusted continuous cognitive (?3.91, [95% Confidence Interval [CI]: ?6.41, ?1.42]) and language (?3.19 [?6.19, ?0.19]) scores as well as increased odds of each adjusted categorical outcome except severe cognitive impairment (OR: 1.46 [0.74, 2.88]) and mild language impairment (OR: 1.35 [0.88, 2.06]). Conclusion At 18–22 months, the neurodevelopmental outcomes of extremely low gestational age infants with low grade periventricular-intraventricular hemorrhage are not significantly different from those without hemorrhage. PMID:23460139

  4. Expression of TYMS in lymph node metastasis from low-grade glioma

    PubMed Central

    DING, BINGQIAN; GAO, MING; LI, ZHENJIANG; XU, CHENYANG; FAN, SHAOKANG; HE, WEIYA

    2015-01-01

    The aim of the present study was to investigate the expression of thymidylate synthase (TYMS) in the primary foci and metastatic lymph nodes of low-grade glioma, and to analyze the function of TYMS in the lymph node metastases from low-grade glioma. The study included 93 cases of surgically resected and pathologically confirmed low-grade glioma, form patients treated at Huaihe Hospital of Henan University (Kaifeng, China). The following clinical data was obtained from each patient: Gender, age, subjective symptoms (dizziness, headache, a feeling of pressure in the head, etc.), site of disease, tumor type, pathological stage, degree of differentiation and lymph node involvement. The surgically resected gliomas and dissected cervical lymph nodes were immunohistochemically stained, and DNA was extracted from the tumor and lymph node tissues samples for polymerase chain reaction sequencing and amplification. The expression of TYMS in the primary foci and metastatic lymph nodes of low-grade glioma was examined. Additionally, the association between pathological features and the postoperative survival rate of the patients was analyzed. The primary lesions of all 93 cases exhibited positive TYMS expression and 43/157 (27.39%) lymph nodes exhibited positive TYMS expression. Factors that significantly influenced the postoperative survival rate of the patients, included the metastasis of the cervical lymph nodes (P<0.01), the number of dissected cervical lymph nodes (P<0.01) and the degree of differentiation (P<0.05). The metastasis of the cervical lymph nodes was the only independent risk factor affecting postoperative disease-free survival. The risk of recurrence in patients with metastasis of the cervical lymph nodes was 6.3-fold higher than in those without metastasis (P<0.01). Thus, the results of the present study provide a theoretical basis for accurately predicting the prognosis of patients with low-grade malignant brain glioma, reducing the conjecture involved in selecting postoperative treatment strategies and improving therapeutic efficacy. PMID:26622711

  5. Glycated haemoglobin A1c is associated with low-grade albuminuria in Chinese adults

    PubMed Central

    Huang, Xiaolin; Zhou, Yulin; Xu, Baihui; Sun, Wanwan; Lin, Lin; Sun, Jichao; Xu, Min; Lu, Jieli; Bi, Yufang; Wang, Weiqing; Xu, Yu; Ning, Guang

    2015-01-01

    Background and objective Diabetes is a strong risk factor for cardiovascular diseases, whereas few studies have investigated simultaneously the associations of glycated haemoglobin A1c (HbA1c), fasting blood glucose (fasting plasma glucose (FPG)) and 2?h postload blood glucose (2?h PG) with low-grade albuminuria, which is an earlier marker of cardiovascular diseases in the general population. Our study aimed to investigate and compare associations of HbA1c, FPG, and 2?h PG levels with risks of low-grade albuminuria in the middle-aged and elderly Chinese. Design and methods This was a cross-sectional study involving 9188 participants aged 40?years or older. All participants underwent a standard 75?g oral glucose tolerance test. Low-grade albuminuria was defined as the highest quartile of urinary albumin-to-creatinine ratio (ACR) (>6.10?mg/g in males and >8.76?mg/g in females) in respondents without microalbuminuria or macroalbuminuria. Results HbA1c, FPG and 2?h PG were all significantly correlated with urinary ACR after adjustment for confounders (all p values <0.0001). After adjustment for HbA1c, the relationships of FPG and 2?h PG with ACR reduced to null. HbA1c levels were still significantly associated with ACR after further adjustment for FPG and 2?h PG. Multiple logistic regression showed that risks of low-grade albuminuria were positively associated with HbA1c levels in a dose–response manner. Compared with participants with HbA1c ?37?mmol/mol (5.5%), ORs (95% CIs) for low-grade albuminuria were 1.05 (0.94 to 1.18), 1.25 (1.04 to 1.50), 1.40 (1.04 to 1.90) and 2.21 (1.61 to 3.03) for HbA1c categories of 38–42?mmol/mol (5.6–6.0%), 43–48?mmol/mol (6.1–6.5%), 49–53?mmol/mol (6.6–7.0%), and >53?mmol/mol (7.0%), respectively (pfor trend <0.0001). Conclusions HbA1c, but not FPG or 2?h PG, was independently associated with an increased risk of low-grade albuminuria in the middle-aged and elderly Chinese. PMID:26243552

  6. Low-grade adenocarcinoma of endolymphatic sac mimicking jugular paraganglioma at clinical and neuroradiological examination.

    PubMed

    Roncaroli, F; Giangaspero, F; Piana, S; Andreoli, A; Ricci, R

    1997-01-01

    We report a case of low-grade adenocarcinoma of endolymphatic sac origin mimicking jugular paraganglioma at clinical and neuroradiological examination. The lesion occurred in a 72-year-old male who presented with a long-standing history of right-sided hearing loss and a few-week history of progressive facial nerve palsy and right aural pain. At histology, the tumor was composed of pseudoglandular spaces with papillary infoldings. Lumina contained colloid-like material. The lesion was surgically removed with suboccipital approach following endoarterial embolization. This study emphasizes that low-grade adenocarcinomas of endolymphatic sac origin extending to posterior cranial fossa and jugular paraganglioma may be indistinguishable preoperatively at clinical and radiological levels. PMID:9323449

  7. Endoscopic diagnosis of an MRI-occult, low-grade glioma with ependymal dissemination.

    PubMed

    Margetis, Konstantinos; Rajappa, Prajwal; Cope, William; Pisapia, David; Souweidane, Mark M

    2015-10-01

    A 21-year-old man presented with triventricular hydrocephalus due to a tectal mass. He underwent an endoscopic third ventriculostomy, and multiple nodules were identified at the floor of the third ventricle intraoperatively. Surgical pathology of one of these lesions demonstrated that the tissue represented a low-grade astrocytoma. The case highlights the existing potential of neuroendoscopy to reveal neuroimaging-occult lesions, in spite of the significant advances of MRI. Furthermore, the combination of the age of the patient, the nonenhancing MRI appearance, and the multifocality of the lesions constitutes a rare and interesting neoplastic presentation within the brain. The constellation of findings likely represents dissemination of a low-grade tectal glioma via the CSF compartment. PMID:26140294

  8. Intracranial Undifferentiated Sarcoma Arising from a Low-Grade Glioma: A Case Report and Literature Review

    PubMed Central

    Kim, Bum-Joon; Kim, Jong-Hyun; Chung, Hung-Seob

    2015-01-01

    Undifferentiated sarcomas are rarely identified in the intracranial region. A 23-year-old man was admitted with a chief complaint of headache. Initial magnetic resonance images showed signs of low-grade glioma in the frontal lobe. Stereotactic biopsy was performed, and a diagnosis of diffuse astrocytoma was confirmed. Three months later, the patient presented with a high-grade tumor as seen on imaging studies. He underwent total resection of the tumor and histopathological tests identified an undifferentiated sarcoma. The patient died eight months later due to massive tumor bleeding. To the best of our knowledge, this is the first report of undifferentiated sarcoma arising from low-grade glioma without any chemotherapy or radiotherapy. PMID:26180618

  9. A new thermal cycle using low grade heat temperature pressure potential amplifier

    SciTech Connect

    Schlichtig, R.C.

    1983-12-01

    The science of thermodynamics, which arose in the 19th century, largely through the genius of Maxwell, directs that greater efficiency is achieved in heat engines with the use of high temperature and thus high grade heat input. Since then nearly all research dealing with heat engines has involved high temperature heat sources whether depletable fuel, nuclear or solar. But we are living in an ocean of renewable low grade heat with small temperature differentials. Choice of research has been to work with such low grade heat sources, following the leads suggested by two hitherto unpublished new principles which were found and incorporated in my Washington State University master's thesis in 1932. After much searching the operation of these principles was found in the case of absorption of refrigerants in certain alcohols. The unique behavior of these fluid solutions made a new thermal cycle possible.

  10. High-grade Transformation of Low-grade B-cell Lymphoma: Pathology and Molecular Pathogenesis.

    PubMed

    Agbay, Rose Lou Marie C; Loghavi, Sanam; Medeiros, L Jeffrey; Khoury, Joseph D

    2016-01-01

    Patients with low-grade (clinically indolent) lymphomas are at risk to undergo transformation to high-grade (clinically aggressive) lymphoma, although transformation only occurs in a subset of patients. When transformation occurs it is a critical event that determines the course of disease and is associated with unfavorable patient outcomes. Accurate detection of transformation, predictive biomarkers, and identification of specific molecular pathways implicated in the pathobiology of transformation will facilitate personalized therapeutic approaches and underpin advances in clinical outcomes. In this article, we present an update of the clinical and pathologic diagnostic criteria for low-grade B-cell lymphoma transformation and discuss the molecular alterations involved in the pathogenesis of this biological phenomenon. PMID:26658667

  11. Low-grade fibromatosis-like spindle cell carcinoma of the breast.

    PubMed

    Dwyer, Jessica B; Clark, Beth Z

    2015-04-01

    Low-grade fibromatosis-like spindle cell carcinoma is a rare tumor in the breast, and represents a variant of the very heterogeneous group of metaplastic carcinomas of the breast. These tumors warrant distinction because of their resemblance to pure fibromatosis, their propensity for local recurrence, and their favorable prognosis among the metaplastic carcinomas of the breast. The diagnosis is potentially challenging, particularly on core needle biopsies, because of the morphologic overlap with other low-grade spindle cell lesions. Recognition of a proliferation of cytologically bland spindle cells with areas of epithelial differentiation in combination with immunohistochemistry using antibodies against cytokeratins and myoepithelial markers should aid in producing a definitive diagnosis. These tumors can be locally aggressive with an increased incidence of local recurrence, but the potential for lymph node or distant metastasis is low. Complete excision with adequate margins is considered curative in the majority of cases. PMID:25822766

  12. Low-grade extraskeletal osteosarcoma of the chest wall: case report and review of literature

    PubMed Central

    2010-01-01

    Background Low-grade extraskeletal osteosarcomas (ESOS) are extremely rare. Case presentation We present the first case of low-grade ESOS of the chest wall, which occurred in a 30-year-old man. Because of initial misdiagnosis and patient's refusal of surgery, the diagnosis was done after a 4-year history of a slowly growing mass in soft tissues, leading to a huge (30-cm diameter) calcified mass locally extended over the left chest wall. Final diagnosis was helped by molecular analysis of MDM2 and CDK4 oncogenes. Unfortunately, at this time, no surgical treatment was possible due to loco-regional extension, and despite chemotherapy, the patient died one year after diagnosis, five years after the first symptoms. Conclusion We describe the clinical, radiological and bio-pathological features of this unique case, and review the literature concerning low-grade ESOS. Our case highlights the diagnostic difficulties for such very rare tumours and the interest of molecular analysis in ambiguous cases. PMID:21106072

  13. Low-grade endometrial stromal sarcoma with intravenous extension to the heart.

    PubMed

    Gabal, Samia; Ashour, Zeinab; Hamada, Ghada; Aziz, Saied Abdel; Khairy, Hussein; Badawy, Hesham; Hamada, Emad Mahmoud; Saied, Karim

    2009-01-01

    Endometrial stromal sarcoma (ESS) is a rare neoplasm of uterine origin. Intracardiac metastasis from this tumor is extremely infrequent. This report describes a 24-year-old woman from Yemen who had irregular vaginal bleeding shortly after spontaneous abortion. She developed left-lower-limb swelling, diagnosed by duplex scanning and magnetic resonance imaging as deep venous thrombosis in the inferior vena cava (IVC) that extended into the iliac veins on both sides, as well as the left femoral vein and right atrium. She developed acute respiratory distress, from which she recovered after transfer to the intensive care unit. Transesophageal echocardiography showed a large mass occupying the right atrium and ventricle and another mass in the right ventricular outflow tract with areas of cavitations. The tumor appeared to come from the IVC and extended through the right atrium and right ventricle into the pulmonary artery, ending in several digit-like projections. After surgical resection of the intracardiac mass, pathologic examination revealed a low-grade ESS that was confirmed by immunohistochemistry. The patient underwent panhysterectomy and IVC debridement. Pathologic examination revealed infiltrating low-grade endometrial sarcoma invading the myometrium and left adnexa, with intravenous extension into the pelvic veins and the IVC to the right side of the heart. This case shows that despite its well-known good prognostic nature, low-grade ESS may behave as an aggressive malignancy. PMID:19295944

  14. Gemcitabine Hydrochloride, Carboplatin, Dexamethasone, and Rituximab in Treating Patients With Previously Treated Lymphoid Malignancies

    ClinicalTrials.gov

    2013-11-25

    Adult Nasal Type Extranodal NK/T-cell Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Cutaneous B-cell Non-Hodgkin Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Hepatosplenic T-cell Lymphoma; Intraocular Lymphoma; Nodal Marginal Zone B-cell Lymphoma; Noncutaneous Extranodal Lymphoma; Peripheral T-cell Lymphoma; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Small Lymphocytic Lymphoma; Small Intestine Lymphoma; Splenic Marginal Zone Lymphoma; Testicular Lymphoma; Waldenstrom Macroglobulinemia

  15. Monoclonal Antibody Therapy Before Stem Cell Transplant in Treating Patients With Relapsed or Refractory Lymphoid Malignancies

    ClinicalTrials.gov

    2015-12-07

    Adult Nasal Type Extranodal NK/T-cell Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Cutaneous B-cell Non-Hodgkin Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Hepatosplenic T-cell Lymphoma; Intraocular Lymphoma; Nodal Marginal Zone B-cell Lymphoma; Noncutaneous Extranodal Lymphoma; Peripheral T-cell Lymphoma; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Small Lymphocytic Lymphoma; Refractory Hairy Cell Leukemia; Small Intestine Lymphoma; Splenic Marginal Zone Lymphoma; T-cell Large Granular Lymphocyte Leukemia; Testicular Lymphoma; Waldenström Macroglobulinemia

  16. Hibernation alters the diversity and composition of mucosa-associated bacteria while enhancing antimicrobial defence in the gut of 13-lined ground squirrels.

    PubMed

    Dill-McFarland, Kimberly A; Neil, Katie L; Zeng, Austin; Sprenger, Ryan J; Kurtz, Courtney C; Suen, Garret; Carey, Hannah V

    2014-09-01

    The gut microbiota plays important roles in animal nutrition and health. This relationship is particularly dynamic in hibernating mammals where fasting drives the gut community to rely on host-derived nutrients instead of exogenous substrates. We used 16S rRNA pyrosequencing and caecal tissue protein analysis to investigate the effects of hibernation on the mucosa-associated bacterial microbiota and host responses in 13-lined ground squirrels. The mucosal microbiota was less diverse in winter hibernators than in actively feeding spring and summer squirrels. UniFrac analysis revealed distinct summer and late winter microbiota clusters, while spring and early winter clusters overlapped slightly, consistent with their transitional structures. Communities in all seasons were dominated by Firmicutes and Bacteroidetes, with lesser contributions from Proteobacteria, Verrucomicrobia, Tenericutes and Actinobacteria. Hibernators had lower relative abundances of Firmicutes, which include genera that prefer plant polysaccharides, and higher abundances of Bacteroidetes and Verrucomicrobia, some of which can survive solely on host-derived mucins. A core mucosal assemblage of nine operational taxonomic units shared among all individuals was identified with an average total sequence abundance of 60.2%. This core community, together with moderate shifts in specific taxa, indicates that the mucosal microbiota remains relatively stable over the annual cycle yet responds to substrate changes while potentially serving as a pool for 'seeding' the microbiota once exogenous substrates return in spring. Relative to summer, hibernation reduced caecal crypt length and increased MUC2 expression in early winter and spring. Hibernation also decreased caecal TLR4 and increased TLR5 expression, suggesting a protective response that minimizes inflammation. PMID:25130694

  17. The IL-17A-producing CD8+ T-cell population in psoriatic lesional skin comprises mucosa-associated invariant T cells and conventional T cells.

    PubMed

    Teunissen, Marcel B M; Yeremenko, Nataliya G; Baeten, Dominique L P; Chielie, Saskia; Spuls, Phyllis I; de Rie, Menno A; Lantz, Olivier; Res, Pieter C M

    2014-12-01

    IL-17A is pivotal in the etiology of psoriasis, and CD8(+) T cells with the ability to produce this cytokine (Tc17 cells) are over-represented in psoriatic lesions. Here we demonstrate that the frequency of Tc17 cells in peripheral blood of psoriasis patients correlated with the clinical severity of the disease. Analysis of cutaneous-associated lymphocyte antigen expression showed that the blood Tc17 population contains a significantly higher proportion of cells with skin-homing potential compared with the CD8(+) T-cell population lacking IL-17A/IL-22 expression. IL-17A-producing CD8(+) T cells in blood have previously been reported to belong mainly to the mucosa-associated invariant T-cell (MAIT cell) lineage characterized by TCR V?7.2 chain, CD161, IL-18R?, and multidrug transporter ABCB1 expression. We demonstrate the presence of CD8(+) MAIT cells in the dermis and epidermis of psoriatic plaques, as well as healthy skin; however, IL-17A-producing CD8(+) MAIT cells were predominantly found in psoriatic skin. Notably, we observed IL-17A production in a large proportion of psoriatic plaque-derived CD8(+) T cells devoid of MAIT cell characteristics, likely representing conventional CD8(+) T cells. In conclusion, we provide supporting evidence that implicates Tc17 cells in the pathogenesis of psoriasis and describe the presence of innate CD8(+) MAIT cells in psoriatic lesions as an alternative source of IL-17A. PMID:24945094

  18. Innate lymphoid cells involve in tumorigenesis.

    PubMed

    Tian, Zhiqiang; van Velkinburgh, Jennifer C; Wu, Yuzhang; Ni, Bing

    2016-01-01

    Innate lymphoid cells (ILCs) promptly initiate cytokine responses to pathogen exposure in the mucosa and mucosal-associated lymphoid tissues. ILCs were recently categorized as being of the lymphoid lineage and have been classified into three groups. ILCs play important roles in immunity against pathogens, and an anti-tumor immune-related function was recently demonstrated. In this review we discuss whether and how ILCs involve in the tumorigenesis, providing new insights into the mechanisms underlying the particular functions of ILCs as well as the potential targets for tumor intervention. PMID:25604320

  19. Imaging growth and isocitrate dehydrogenase 1 mutation are independent predictors for diffuse low-grade gliomas

    PubMed Central

    Gozé, Catherine; Blonski, Marie; Le Maistre, Guillaume; Bauchet, Luc; Dezamis, Edouard; Page, Philippe; Varlet, Pascale; Capelle, Laurent; Devaux, Bertrand; Taillandier, Luc; Duffau, Hugues; Pallud, Johan

    2014-01-01

    Background We explored whether spontaneous imaging tumor growth (estimated by the velocity of diametric expansion) and isocitrate dehydrogenase 1 (IDH1) mutation (estimated by IDH1 immunoexpression) were independent predictors of long-term outcomes of diffuse low-grade gliomas in adults. Methods One hundred thirty-one adult patients with newly diagnosed supratentorial diffuse low-grade gliomas were retrospectively studied. Results Isocitrate dehydrogenase 1 mutations were present in 107 patients. The mean spontaneous velocity of diametric expansion was 5.40 ± 5.46 mm/y. During follow-up (mean, 70 ± 54.7 mo), 56 patients presented a malignant transformation and 23 died. The median malignant progression-free survival and the overall survival were significantly longer in cases of slow velocity of diametric expansion (149 and 198 mo, respectively) than in cases of fast velocity of diametric expansion (46 and 82 mo; P < .001 and P < .001, respectively) and in cases with IDH1 mutation (100 and 198 mo, respectively) than in cases without IDH1 mutation (72 mo and not reached; P = .028 and P = .001, respectively). In multivariate analyses, spontaneous velocity of diametric expansion and IDH1 mutation were independent prognostic factors for malignant progression-free survival (P < .001; hazard ratio, 4.23; 95% CI, 1.81–9.40 and P = .019; hazard ratio, 2.39; 95% CI, 1.19–4.66, respectively) and for overall survival (P < .001; hazard ratio, 26.3; 95% CI, 5.42–185.2 and P = .007; hazard ratio, 17.89; 95% CI, 2.15–200.1, respectively). Conclusions The spontaneous velocity of diametric expansion and IDH1 mutation status are 2 independent prognostic values that should be obtained at the beginning of the management of diffuse low-grade gliomas in adults. PMID:24847087

  20. Age-related nonrandom chromosomal abnormalities in human low-grade astrocytomas.

    PubMed

    Thiel, G; Lozanova, T; Vogel, S; Kintzel, D; Jänisch, W; Witkowski, R

    1993-07-01

    We report a cytogenetic investigation of 55 low-grade astrocytomas in 52 patients, 15 children and 37 adults. In addition to numerical aberrations such as trisomy 7 and gonosomal losses, we found structural and/or numerical aberrations of chromosome 1 in eight astrocytomas. There was a striking difference between the rearranged chromosomes in pediatric and adult patients. Whereas the pediatric tumors revealed monosomies 1p with accompanying trisomy 1q, the astrocytomas in adults showed partial or complete monosomies 1q. PMID:8340108

  1. A new thermal cycle using low grade heat temperature pressure potential amplifier

    SciTech Connect

    Schlichtig, R.C.

    1983-12-01

    The science of thermodynamics, which arose in the 19th century, largely through the genius of Maxwell, directs that greater efficiency is achieved in heat engines with the use of high temperature and thus high grade heat input. Since then nearly all research dealing with heat engines has involved high temperature heat sources whether depletable fuel, nuclear or solar. But we are living in an ocean of renewable low grade heat with small temperature differentials. After much searching the operation of these principles was found in the case of absorption of refrigerants in certain alcohols. The unique behavior of these fluid solutions made a new thermal cycle possible.

  2. Intrathecal liposomal cytarabine in combination with temozolomide in low-grade oligoastrocytoma with leptomeningeal dissemination.

    PubMed

    Passarin, Maria Grazia; Moretto, Giuseppe; Musso, Anna Maria; Ottaviani, Sarah; Masotto, Barbara; Ghimenton, Claudio; Iuzzolino, Paolo; Buffone, Ebba; Rudà, Roberta; Soffietti, Riccardo; Vattemi, Emanuela; Pedersini, Rebecca

    2010-05-01

    Leptomeningeal dissemination of low-grade gliomas is an uncommon event. A 43-year old male presented with dizziness, gait ataxia, and diplopia. A nonenhancing lesion in the right cerebellar peduncle was identified, subtotally resected, and diagnosed as a grade II astrocytoma. After one year a nodular spread in the brain and leptomeninges was diagnosed, so the patient started chemotherapy with temozolomide and liposomal cytarabine. Complete remission was achieved after 12 months of treatment and the patient is still free from the disease after a follow-up of 24 months. We suggest that this combination may be a valuable treatment option. PMID:19876600

  3. Total lymphoid irradiation in alloimmunity and autoimmunity

    SciTech Connect

    Strober, S.

    1987-12-01

    Total lymphoid irradiation has been used as an immunosuppressive regimen in autoimmune disease and organ transplantation. The rationale for its use originated from studies of patients with Hodgkin disease, in whom this radiotherapy regimen was noted to induce profound and long-lasting immune suppression and yet was well tolerated, with few long-term side effects. Total lymphoid irradiation is a unique immunosuppressive regimen that produces a selective (and long-lasting) reduction in the number and function of helper T cells and certain subsets of B cells. Conventional immunosuppressive drugs show little selectivity, and their effects are short-lived. The most important aspect of total lymphoid irradiation is the potential for achieving transplantation tolerance and permanent remissions in autoimmune disease in laboratory animals. Attempts are being made to achieve similar goals in humans given total lymphoid irradiation, so that immunosuppressive drugs can be ultimately withdrawn from transplant recipients and patients with lupus nephritis. 28 references.

  4. Total lymphoid irradiation and discordant cardiac xenografts

    SciTech Connect

    Kaplan, E.; Dresdale, A.R.; Diehl, J.T.; Katzen, N.A.; Aronovitz, M.J.; Konstam, M.A.; Payne, D.D.; Cleveland, R.J. )

    1990-01-01

    Total lymphoid irradiation can prolong concordant cardiac xenografts. The effects of total lymphoid irradiation in a discordant xenograft model (guinea pig to rat) were studied with and without adjuvant pharmacologic immunosuppression. Inbred Lewis rats were randomly allocated to one of four groups. Group 1 (n = 6) served as a control group and rats received no immunosuppression. Group 2 (n = 5) received triple-drug therapy that consisted of intraperitoneal azathioprine (2 mg/kg), cyclosporine (20 mg/kg), and methylprednisolone (1 mg/kg) for 1 week before transplantation. Group 3 animals (n = 5) received 15 Gy of total lymphoid irradiation in 12 divided doses over a 3-week period. Group 4 (n = 6) received both triple-drug therapy and total lymphoid irradiation as described for groups 2 and 3. Complement-dependent cytotoxicity assay was performed to determine if a correlation between complement-dependent cytotoxicity and rejection-free interval existed. Rejection was defined as cessation of graft pulsation and was confirmed by histologic test results. Only groups 1 and 2 showed a difference in survival (group 1, 6.9 +/- 1.0 minutes; group 2, 14.2 +/- 2.7 minutes, p = 0.02). Although total lymphoid irradiation did decrease complement-dependent cytotoxicity, linear regression revealed no correlation between complement-dependent cytotoxicity and graft survival (coefficient of correlation, 0.30). Unlike concordant cardiac xenografts, total lymphoid irradiation with or without triple-drug therapy does not prolong graft survival.

  5. Whole-genome sequencing identifies genetic alterations in pediatric low-grade gliomas.

    PubMed

    Zhang, Jinghui; Wu, Gang; Miller, Claudia P; Tatevossian, Ruth G; Dalton, James D; Tang, Bo; Orisme, Wilda; Punchihewa, Chandanamali; Parker, Matthew; Qaddoumi, Ibrahim; Boop, Fredrick A; Lu, Charles; Kandoth, Cyriac; Ding, Li; Lee, Ryan; Huether, Robert; Chen, Xiang; Hedlund, Erin; Nagahawatte, Panduka; Rusch, Michael; Boggs, Kristy; Cheng, Jinjun; Becksfort, Jared; Ma, Jing; Song, Guangchun; Li, Yongjin; Wei, Lei; Wang, Jianmin; Shurtleff, Sheila; Easton, John; Zhao, David; Fulton, Robert S; Fulton, Lucinda L; Dooling, David J; Vadodaria, Bhavin; Mulder, Heather L; Tang, Chunlao; Ochoa, Kerri; Mullighan, Charles G; Gajjar, Amar; Kriwacki, Richard; Sheer, Denise; Gilbertson, Richard J; Mardis, Elaine R; Wilson, Richard K; Downing, James R; Baker, Suzanne J; Ellison, David W

    2013-06-01

    The most common pediatric brain tumors are low-grade gliomas (LGGs). We used whole-genome sequencing to identify multiple new genetic alterations involving BRAF, RAF1, FGFR1, MYB, MYBL1 and genes with histone-related functions, including H3F3A and ATRX, in 39 LGGs and low-grade glioneuronal tumors (LGGNTs). Only a single non-silent somatic alteration was detected in 24 of 39 (62%) tumors. Intragenic duplications of the portion of FGFR1 encoding the tyrosine kinase domain (TKD) and rearrangements of MYB were recurrent and mutually exclusive in 53% of grade II diffuse LGGs. Transplantation of Trp53-null neonatal astrocytes expressing FGFR1 with the duplication involving the TKD into the brains of nude mice generated high-grade astrocytomas with short latency and 100% penetrance. FGFR1 with the duplication induced FGFR1 autophosphorylation and upregulation of the MAPK/ERK and PI3K pathways, which could be blocked by specific inhibitors. Focusing on the therapeutically challenging diffuse LGGs, our study of 151 tumors has discovered genetic alterations and potential therapeutic targets across the entire range of pediatric LGGs and LGGNTs. PMID:23583981

  6. Adult Supratentorial Low-Grade Glioma: Long-Term Experience at a Single Institution

    SciTech Connect

    Bauman, Glenn; Fisher, Barbara; Watling, Christopher; Cairncross, J. Gregory; Macdonald, David

    2009-12-01

    Purpose: To report the long-term follow-up of a cohort of adult patients with supratentorial low-grade glioma treated at a single institution. Methods and Materials: A cohort of 145 adult patients treated at the London Regional Cancer Program between 1979 and 1995 was reviewed. Results: With a median follow-up of 105 months, the median progression-free survival was 61 months (95% confidence interval, 53-77), and the median overall survival was 118 months (95% confidence interval, 93-129). The 10- and 20-year progression-free and overall survival rate was 18% and 0% and 48% and 22%, respectively. Cox regression analysis confirmed the importance of age, histologic type, presence of seizures, Karnofsky performance status, and initial extent of surgery as prognostic variables for overall and cause-specific survival. Function among long-term survivors without tumor progression was good to excellent for most patients. Conclusion: Low-grade glioma is a chronic disease, with most patients dying of their disease. However, long-term survival with good function is possible. Survival is determined primarily by the disease factors with selection and timing of adjuvant treatments having less influence on outcome.

  7. Charging-free electrochemical system for harvesting low-grade thermal energy

    PubMed Central

    Yang, Yuan; Lee, Seok Woo; Ghasemi, Hadi; Loomis, James; Li, Xiaobo; Kraemer, Daniel; Zheng, Guangyuan; Cui, Yi; Chen, Gang

    2014-01-01

    Efficient and low-cost systems are needed to harvest the tremendous amount of energy stored in low-grade heat sources (<100 °C). Thermally regenerative electrochemical cycle (TREC) is an attractive approach which uses the temperature dependence of electrochemical cell voltage to construct a thermodynamic cycle for direct heat-to-electricity conversion. By varying temperature, an electrochemical cell is charged at a lower voltage than discharge, converting thermal energy to electricity. Most TREC systems still require external electricity for charging, which complicates system designs and limits their applications. Here, we demonstrate a charging-free TREC consisting of an inexpensive soluble Fe(CN)63?/4? redox pair and solid Prussian blue particles as active materials for the two electrodes. In this system, the spontaneous directions of the full-cell reaction are opposite at low and high temperatures. Therefore, the two electrochemical processes at both low and high temperatures in a cycle are discharge. Heat-to-electricity conversion efficiency of 2.0% can be reached for the TREC operating between 20 and 60 °C. This charging-free TREC system may have potential application for harvesting low-grade heat from the environment, especially in remote areas. PMID:25404325

  8. Low-grade inflammation, diet composition and health: current research evidence and its translation.

    PubMed

    Minihane, Anne M; Vinoy, Sophie; Russell, Wendy R; Baka, Athanasia; Roche, Helen M; Tuohy, Kieran M; Teeling, Jessica L; Blaak, Ellen E; Fenech, Michael; Vauzour, David; McArdle, Harry J; Kremer, Bas H A; Sterkman, Luc; Vafeiadou, Katerina; Benedetti, Massimo Massi; Williams, Christine M; Calder, Philip C

    2015-10-01

    The importance of chronic low-grade inflammation in the pathology of numerous age-related chronic conditions is now clear. An unresolved inflammatory response is likely to be involved from the early stages of disease development. The present position paper is the most recent in a series produced by the International Life Sciences Institute's European Branch (ILSI Europe). It is co-authored by the speakers from a 2013 workshop led by the Obesity and Diabetes Task Force entitled 'Low-grade inflammation, a high-grade challenge: biomarkers and modulation by dietary strategies'. The latest research in the areas of acute and chronic inflammation and cardiometabolic, gut and cognitive health is presented along with the cellular and molecular mechanisms underlying inflammation-health/disease associations. The evidence relating diet composition and early-life nutrition to inflammatory status is reviewed. Human epidemiological and intervention data are thus far heavily reliant on the measurement of inflammatory markers in the circulation, and in particular cytokines in the fasting state, which are recognised as an insensitive and highly variable index of tissue inflammation. Potential novel kinetic and integrated approaches to capture inflammatory status in humans are discussed. Such approaches are likely to provide a more discriminating means of quantifying inflammation-health/disease associations, and the ability of diet to positively modulate inflammation and provide the much needed evidence to develop research portfolios that will inform new product development and associated health claims. PMID:26228057

  9. Filamentous microbial fossil from low-grade metamorphosed basalt in northern Chichibu belt, central Shikoku, Japan

    NASA Astrophysics Data System (ADS)

    Sakakibara, M.; Sugawara, H.; Tsuji, T.; Ikehara, M.

    2014-05-01

    The past two decades have seen the reporting of microbial fossils within ancient oceanic basalts that could be identical to microbes within modern basalts. Here, we present new petrographic, mineralogical, and stable isotopic data for metabasalts containing filamentous structures in a Jurassic accretionary complex within the northern Chichibu Belt of the Yanadani area of central Shikoku, Japan. Mineralized filaments within these rocks are present in interstitial domains filled with calcite, pumpellyite, or quartz, and consist of iron oxide, phengite, and pumpellyite. ?13CPDB values for filament-bearing calcite within these metabasalts vary from -2.49‰ to 0.67‰. A biogenic origin for these filamentous structures is indicated by (1) the geological context of the Yanadani metabasalt, (2) the morphology of the filaments, (3) the carbon isotope composition of carbonates that host the filaments, and (4) the timing of formation of these filaments relative to the timing of low-grade metamorphism in a subduction zone. The putative microorganisms that formed these filaments thrived between eruption (Late Paleozoic) and accretion (Early Jurassic) of the basalt. The data presented here indicate that cryptoendolithic life was present within water-filled vesicles in pre-Jurassic intraplate basalts. The mineralogy of the filaments reflects the low-grade metamorphic recrystallization of authigenic microbial clays similar to those formed by the encrustation of prokaryotes in modern iron-rich environments. These findings suggest that a previously unusual niche for life is present within intraplate volcanic rocks in accretionary complexes.

  10. Magnetic Separation and Magnetic Properties of Low-Grade Manganese Carbonate Ore

    NASA Astrophysics Data System (ADS)

    Wu, Y.; Shi, B.; Ge, W.; Yan, C. J.; Yang, X.

    2015-02-01

    The relation between the magnetic separation behavior and magnetic properties of a low-grade manganese ore was analyzed before and after treatment by direct reduction with coal. It was found that raw ore with an initial average grade of 10.39% Mn and consisting of diamagnetic and paramagnetic minerals can be concentrated by high-intensity magnetic separation to produce a salable product with a grade of 22.75% Mn and a recovery of 89.88%. In contrast, direct reduction of the ore results in a new Mn-Fe oxide phase formed with a combination of ferromagnetic and paramagnetic properties, thereby increasing the magnetic susceptibilities of the ore by almost two orders of magnitude. The grade of Mn for the roasted ore could only be concentrated to 15.49% with a recovery of 66.67%. Therefore, it is concluded that the low-grade manganese ores with antiferromagnetic and paramagnetic (or diamagnetic, but not strongly ferromagnetic) properties could be efficiently beneficiated via high-intensity magnetic separation.

  11. The global diabetes epidemic as a consequence of lifestyle-induced low-grade inflammation.

    PubMed

    Kolb, H; Mandrup-Poulsen, T

    2010-01-01

    The recent major increase in the global incidence of type 2 diabetes suggests that most cases of this disease are caused by changes in environment and lifestyle. All major risk factors for type 2 diabetes (overnutrition, low dietary fibre, sedentary lifestyle, sleep deprivation and depression) have been found to induce local or systemic low-grade inflammation that is usually transient or milder in individuals not at risk for type 2 diabetes. By contrast, inflammatory responses to lifestyle factors are more pronounced and prolonged in individuals at risk of type 2 diabetes and appear to occur also in the pancreatic islets. Chronic low-grade inflammation will eventually lead to overt diabetes if counter-regulatory circuits to inflammation and metabolic stress are compromised because of a genetic and/or epigenetic predisposition. Hence, it is not the lifestyle change per se but a deficient counter-regulatory response in predisposed individuals which is crucial to disease pathogenesis. Novel approaches of intervention may target these deficient defence mechanisms. PMID:19890624

  12. Tectonic setting of the low-grade metamorphic rocks of the Dabie Orogen, central eastern China

    NASA Astrophysics Data System (ADS)

    Xu, Shutong; Wu, Weiping; Lu, Yiqun; Wang, Dehua

    2012-04-01

    The tectonic setting on both the northern and southern sides of the Dabie Mountains reveals that low-grade metamorphic rocks are important constituents produced by the subduction of the oceanic crust prior to collision between the Sino-Korean and Yangtze cratons. The Zhangbaling Group/Mulanshan schist is a pre-Ordovician oceanic crust. The Sujiahe and Xinyang/Foziling Groups are trench sediments of the Ordovician-Devonian age, and constitute an accretionary prism associated with subduction. The Yangshan coal measures/Meishan Group was a forearc basin sediment of Carboniferous age, and was overthrust by the accretionary prism during collision. The Susong Group is composed of passive continental margin sediments of the Yangtze craton. Backarc basin sediments are postulated to be concealed by Mesozoic-Cenozoic sediments to the north of the Dabie Mountains. High-ultrahigh pressure terrains are exotic tectonic slices exhumed from depths, located between low-grade metamorphic rocks, and disturb the integrity of the earlier subduction orogen. Subduction occurred during the Ordovician to Devonian periods, and collision initiated at the beginning of the Permian.

  13. Simultaneous Purification and Perforation of Low-Grade Si Sources for Lithium-Ion Battery Anode.

    PubMed

    Jin, Yan; Zhang, Su; Zhu, Bin; Tan, Yingling; Hu, Xiaozhen; Zong, Linqi; Zhu, Jia

    2015-11-11

    Silicon is regarded as one of the most promising candidates for lithium-ion battery anodes because of its abundance and high theoretical capacity. Various silicon nanostructures have been heavily investigated to improve electrochemical performance by addressing issues related to structure fracture and unstable solid-electrolyte interphase (SEI). However, to further enable widespread applications, scalable and cost-effective processes need to be developed to produce these nanostructures at large quantity with finely controlled structures and morphologies. In this study, we develop a scalable and low cost process to produce porous silicon directly from low grade silicon through ball-milling and modified metal-assisted chemical etching. The morphology of porous silicon can be drastically changed from porous-network to nanowire-array by adjusting the component in reaction solutions. Meanwhile, this perforation process can also effectively remove the impurities and, therefore, increase Si purity (up to 99.4%) significantly from low-grade and low-cost ferrosilicon (purity of 83.4%) sources. The electrochemical examinations indicate that these porous silicon structures with carbon treatment can deliver a stable capacity of 1287 mAh g(-1) over 100 cycles at a current density of 2 A g(-1). This type of purified porous silicon with finely controlled morphology, produced by a scalable and cost-effective fabrication process, can also serve as promising candidates for many other energy applications, such as thermoelectrics and solar energy conversion devices. PMID:26492222

  14. Effect of desliming on the magnetic separation of low-grade ferruginous manganese ore

    NASA Astrophysics Data System (ADS)

    Tripathy, Sunil Kumar; Banerjee, P. K.; Suresh, Nikkam

    2015-07-01

    In the present investigation, magnetic separation studies using an induced roll magnetic separator were conducted to beneficiate low-grade ferruginous manganese ore. The feed ore was assayed to contain 22.4% Mn and 35.9% SiO2, with a manganese-to-iron mass ratio (Mn:Fe ratio) of 1.6. This ore was characterized in detail using different techniques, including quantitative evaluation of minerals by scanning electron microscopy, which revealed that the ore is extremely siliceous in nature and that the associated gangue minerals are more or less evenly distributed in almost all of the size fractions in major proportion. Magnetic separation studies were conducted on both the as-received ore fines and the classified fines to enrich their manganese content and Mn:Fe ratio. The results indicated that the efficiency of separation for deslimed fines was better than that for the treated unclassified bulk sample. On the basis of these results, we proposed a process flow sheet for the beneficiation of low-grade manganese ore fines using a Floatex density separator as a pre-concentrator followed by two-stage magnetic separation. The overall recovery of manganese in the final product from the proposed flow sheet is 44.7% with an assay value of 45.8% and the Mn:Fe ratio of 3.1.

  15. Scalable Production of Si Nanoparticles Directly from Low Grade Sources for Lithium-Ion Battery Anode.

    PubMed

    Zhu, Bin; Jin, Yan; Tan, Yingling; Zong, Linqi; Hu, Yue; Chen, Lei; Chen, Yanbin; Zhang, Qiao; Zhu, Jia

    2015-09-01

    Silicon, one of the most promising candidates as lithium-ion battery anode, has attracted much attention due to its high theoretical capacity, abundant existence, and mature infrastructure. Recently, Si nanostructures-based lithium-ion battery anode, with sophisticated structure designs and process development, has made significant progress. However, low cost and scalable processes to produce these Si nanostructures remained as a challenge, which limits the widespread applications. Herein, we demonstrate that Si nanoparticles with controlled size can be massively produced directly from low grade Si sources through a scalable high energy mechanical milling process. In addition, we systematically studied Si nanoparticles produced from two major low grade Si sources, metallurgical silicon (?99 wt % Si, $1/kg) and ferrosilicon (?83 wt % Si, $0.6/kg). It is found that nanoparticles produced from ferrosilicon sources contain FeSi2, which can serve as a buffer layer to alleviate the mechanical fractures of volume expansion, whereas nanoparticles from metallurgical Si sources have higher capacity and better kinetic properties because of higher purity and better electronic transport properties. Ferrosilicon nanoparticles and metallurgical Si nanoparticles demonstrate over 100 stable deep cycling after carbon coating with the reversible capacities of 1360 mAh g(-1) and 1205 mAh g(-1), respectively. Therefore, our approach provides a new strategy for cost-effective, energy-efficient, large scale synthesis of functional Si electrode materials. PMID:26258439

  16. Low-Grade, Nonintestinal Nonsalivary Sinonasal Adenocarcinoma Associated With an Exophytic Schneiderian Papilloma: A Case Report.

    PubMed

    Blumberg, Jeffrey M; Escobar-Stein, Juliana; Vining, Eugenia M; Prasad, Manju L

    2015-12-01

    Sinonasal adenocarcinoma is a rare tumor of the head and neck accounting for 10% to 20% of all primary malignancies of the nose and paranasal sinuses. There tumors are classified as salivary, intestinal and nonintestinal, nonsalivary. Low-grade nonintestinal nonsalivary are rare tumors whose diagnosis is essentially that of exclusion. Here we present the first case of one such tumor associated with an exophyic Schneiderian papilloma. A 71-year-old retired aerospace engineer presented with a 1-year history of severe nasal obstruction. Endoscopy and compted tomography imaging demonstrated a polypoid lesion occupying his entire right nasal cavity extending into and filling the nasopharynx. Biopsy suggested adenocarcinoma, at least in situ and the patient subsequently underwent complete resection. Pathologic evaluation demonstrated polypoid tumor consistent with a low-grade papillary adenocarcinoma with micropapillary architecture associated with a small amount of residual exophytic Schneiderian papilloma. Immunohistochemistry revealed diffuse expression of CK7, CK 5/6, and S100 protein in tumor cells. Expression of p63 was seen in basal cells only. Tumor cells did not show expression of CK20, CDX2 (intestinal markers), mammaglobin, GATA3 (salivary markers), PAX8, WT1, nor estrogen, progesterone, or androgen receptors confirming its nonintestinal nonsalivary differentiation. PMID:26261100

  17. Low-grade inflammation disrupts structural plasticity in the human brain.

    PubMed

    Szabó, C; Kelemen, O; Kéri, S

    2014-09-01

    Increased low-grade inflammation is thought to be associated with several neuropsychiatric disorders characterized by decreased neuronal plasticity. The purpose of the present study was to investigate the relationship between structural changes in the human brain during cognitive training and the intensity of low-grade peripheral inflammation in healthy individuals (n=56). A two-month training (30 min/day) with a platformer video game resulted in a significantly increased volume of the right hippocampal formation. The number of stressful life events experienced during the past year was associated with less pronounced enlargement of the hippocampus. However, the main predictor of hippocampal volume expansion was the relative peripheral expression of Nuclear Factor-?B (NF-?B), a transcription factor playing a central role in the effect of pro-inflammatory cytokines. Interleukin-6 (IL-6) and C-reactive protein levels were not related to hippocampal plasticity when NF-?B was taken into consideration. These results suggest that more intensive peripheral inflammation is associated with weaker neuronal plasticity during cognitive training. PMID:24929068

  18. Novel immunotherapies in lymphoid malignancies.

    PubMed

    Batlevi, Connie Lee; Matsuki, Eri; Brentjens, Renier J; Younes, Anas

    2016-01-01

    The success of the anti-CD20 monoclonal antibody rituximab in the treatment of lymphoid malignancies provided proof-of-principle for exploiting the immune system therapeutically. Since the FDA approval of rituximab in 1997, several novel strategies that harness the ability of T cells to target cancer cells have emerged. Reflecting on the promising clinical efficacy of these novel immunotherapy approaches, the FDA has recently granted 'breakthrough' designation to three novel treatments with distinct mechanisms. First, chimeric antigen receptor (CAR)-T-cell therapy is promising for the treatment of adult and paediatric relapsed and/or refractory acute lymphoblastic leukaemia (ALL). Second, blinatumomab, a bispecific T-cell engager (BiTE(®)) antibody, is now approved for the treatment of adults with Philadelphia-chromosome-negative relapsed and/or refractory B-precursor ALL. Finally, the monoclonal antibody nivolumab, which targets the PD-1 immune-checkpoint receptor with high affinity, is used for the treatment of Hodgkin lymphoma following treatment failure with autologous-stem-cell transplantation and brentuximab vedotin. Herein, we review the background and development of these three distinct immunotherapy platforms, address the scientific advances in understanding the mechanism of action of each therapy, and assess the current clinical knowledge of their efficacy and safety. We also discuss future strategies to improve these immunotherapies through enhanced engineering, biomarker selection, and mechanism-based combination regimens. PMID:26525683

  19. Investigation of denitrifying microbial communities within an agricultural drainage system fitted with low-grade weirs.

    PubMed

    Baker, Beth H; Kröger, Robert; Brooks, John P; Smith, Renotta K; Prince Czarnecki, Joby M

    2015-12-15

    Enhancing wetland characteristics in agricultural drainage ditches with the use of low-grade weirs, has been identified as a best management practice (BMP) to mitigate nutrient runoff from agriculture landscapes. A major objective of utilizing low-grade weirs as a BMP includes fostering environments suitable for the biogeochemical removal of nitrogen via denitrification. This study examined the spatial resolution of microbial communities involved in denitrification in agricultural drainage systems fitted with low-grade weirs. Appropriate sampling scales of microbial communities were investigated using 16S rRNA and denitrification functional genes nosZ, nirS, and nirK via quantitative polymerase chain reaction (qPCR) and terminal-restriction fragment length polymorphism (T-RFLP) analysis. Genes 16S rRNA, nosZ, and nirS were all successfully detected in soil samples, while nirK was below the detection limit throughout the study. Utilizing a combination of three sampling regimes (management, reach, catchment) was found to be effective in capturing microbial community patterns, as ANOVA results revealed nosZ gene abundance was significantly greater at the management rather than reach scale (p = 0.045; F = 3.311), although, no significant differences were observed in 16S rRNA or nirS between sampling scales (p > 0.05). A Pearson correlation matrix confirmed that 16S rRNA and nosZ gene abundances were positively correlated with soil carbon (C), nitrogen (N), and moisture, while nirS abundance was only positively correlated with soil C and soil moisture. This highlights the potential for wetland-like characteristics to be recovered in agricultural drainage systems, as weir proximity is observed to enhance soil moisture and conditions for N remediation. This study provides the basis for additional investigations of these unique environments in the Mississippi Alluvial Valley and a starting point for adaptive management to enhance agricultural drainage systems for microbial communities towards nutrient remediation goals. PMID:26414296

  20. Low-Grade Endometrial Stromal Sarcoma with Inferior Vena Cava Extension: First Report in Korea

    PubMed Central

    Kim, Mi-Hyeong; Jung, Chan-Kwon; Hwang, Jeong-Kye; Moon, In-Sung; Kim, Ji-Il

    2014-01-01

    Low-grade endometrial stromal sarcoma (LGESS) with intravascular extension is very rare, with only 26 cases having been reported. We experienced a case of LGESS with inferior vena cava (IVC) extension. A 60-year-old female presented with left leg edema. She had a history of total hysterectomy, and was diagnosed of leiomyoma at that time. On imaging study, tumor masses were located around both common iliac veins (CIV), and within the CIV and IVC. The pelvic masses on both side and IVC mass were resected, and then the patient received adjuvant hormonal therapy and radiotherapy over the remnant pelvic masses. LGESS with IVC extension is difficult to distinguish from intravascular leiomyomatosis. LGESS is a malignant disease and commonly recurs, even in early stages. Accurate diagnosis, complete resection, proper adjuvant therapy and close follow-up are very important. PMID:26217626

  1. New Strategies in Pediatric Gliomas: Molecular Advances in Pediatric Low-Grade Gliomas as a Model

    PubMed Central

    Raabe, Eric; Kieran, Mark W.; Cohen, Kenneth J.

    2015-01-01

    Pediatric low-grade gliomas (pLGG) account for more brain tumors in children than any other histologic subtype. While surgery, chemotherapy and radiation remain the mainstay of upfront treatment, recent advances in molecular interrogation of pLGG have shown a small number of recurring genetic mutations in these tumors that might be exploited therapeutically. Notable findings include abnormalities in the RAS/MAP kinase pathway such as NF-1 loss or BRAF activation and mTOR activation. Recent identification of activating re-arrangements in c-MYB and MYBL1 in pediatric diffuse astrocytoma also provide candidates for therapeutic intervention. Targeting these molecularly identified pathways may allow for improved outcomes for patients as pediatric oncology moves into the era of biology-driven medicine. PMID:23881924

  2. Bilateral Serous Psammocarcinoma of Ovary: Rare Variant Low Grade Serous Carcinoma

    PubMed Central

    Jena, Saubhagya Kumar; Mishra, Pritinanda; Mohapatra, Vandana; Singh, Sweta

    2015-01-01

    Serous psammocarcinoma is a rare variant of serous carcinoma arising from either ovary or peritoneum, characterized by massive psammoma body formation, low grade cytologic features, and invasiveness. Its clinical behavior is similar to serous borderline tumors with relatively favorable prognosis. We report herein a case of a 60-year-old postmenopausal woman who presented with abdominal distension. Contrast enhanced computed tomography (CECT) revealed calcified pelvic masses with ascites. Elevated serum CA-125 (970?U/mL) suggested malignant ovarian neoplasm. Patient underwent exploratory laparotomy with primary debulking surgery. Histopathology showed bilateral serous psammocarcinoma of ovary with invasive implants on omentum. Adjuvant chemotherapy was advised in view of advanced stage disease, although its benefits are poorly defined due to rarity of the tumor. However, patient opted out of it and is now on follow-up. PMID:26557397

  3. A preliminary report on the rapid fluorimetric determination of uranium in low-grade ores

    USGS Publications Warehouse

    Grimaldi, F.S.; Levine, Harry

    1950-01-01

    A simple and very rapid fluorimetric procedure is described for the determination of uranium in low-grade shale and phosphate ores. The best working range is from 0.001 to about 0.04 percent U. The procedure employs batch extraction of uranium nitrate by ethyl acetate, using aluminum nitrate as the salting agent, prior to the visual fluorimetric estimation. The procedure is especially designed to save reagents; only 9.5 g of aluminum nitrate and 10 ml of ethyl acetate being used for one analysis. The solution of the sample by means of a fusion with NaOH-NaNO3 flux is rapid. After fusion the sample is immediately extracted without removing silica and other hydrolytic precipitates. Aluminum nitrate very effectively ties up fluoride and phosphate, thus eliminating steps required for their removal.

  4. Seizures in low-grade gliomas: natural history, pathogenesis, and outcome after treatments

    PubMed Central

    Rudà, Roberta; Bello, Lorenzo; Duffau, Hugues; Soffietti, Riccardo

    2012-01-01

    Seizures represent a common symptom in low-grade gliomas; when uncontrolled, they significantly contribute to patient morbidity and negatively impact quality of life. Tumor location and histology influence the risk for epilepsy. The pathogenesis of tumor-related epilepsy is multifactorial and may differ among tumor histologies (glioneuronal tumors vs diffuse grade II gliomas). Gross total resection is the strongest predictor of seizure freedom in addition to clinical factors, such as preoperative seizure duration, type, and control with antiepileptic drugs (AEDs). Epilepsy surgery may improve seizure control. Radiotherapy and chemotherapy with alkylating agents (procarbazine + CCNU+ vincristine, temozolomide) are effective in reducing the frequency of seizures in patients with pharmacoresistant epilepsy. Newer AEDs (levetiracetam, topiramate, lacosamide) seem to be better tolerated than the old AEDs (phenobarbital, phenytoin, carbamazepine), but there is lack of evidence regarding their superiority in terms of efficacy. PMID:23095831

  5. Intrapelvic dissemination of early low-grade endometrioid stromal sarcoma due to electronic morcellation

    PubMed Central

    Choo, Kyoung-Ja; Lee, Hyun Joo; Lee, Tae Sung; Kim, Ju Hyun; Koh, Suk Bong

    2015-01-01

    Endometrioid stromal sarcoma is a rare malignancy that originates from mesenchymal cells. It is classified into low-grade endometrioid stromal sarcoma (LGESS) and high-grade endometrioid stromal sarcoma. Ultrasonographic findings of LGESS resemble those of submucosal myomas, leading to the possible preoperative misdiagnosis of LGESS as uterine leiomyoma. Electronic morcellation during laparoscopic surgery in women with LGESS can result in iatrogenic intraabdominal dissemination and a poorer prognosis. Here, we report a patient with LGESS who underwent a supracervical hysterectomy and electronic morcellation for a presumed myoma in another hospital. Disseminated metastatic lesions of LGESS in the posterior cul-de-sac and rectal serosal surface were absent on primary surgery, but found during reexploration. In conclusion, when LGESS is found incidentally following previous morcellation during laparoscopic surgery for presumed benign uterine disease, we highly recommend surgical reexploration, even when there is no evidence of a metastatic lesion in imaging studies. PMID:26430669

  6. A Rare Pathology: Low-Grade Fibromyxoid Sarcoma of the Maxilla.

    PubMed

    Spalthoff, Simon; Bredt, Martin; Gellrich, Nils-Claudius; Jehn, Philipp

    2016-01-01

    Low-grade fibromyxoid sarcoma (LGFMS) is a rare tumor with a benign histologic appearance and fully malignant behavior. To date, only 5 cases of LGFMS in the maxillofacial region have been reported. This report describes the case of a 16-year-old boy who was referred to the authors' hospital with an intraosseous myxofibroblastic tumor, probably of the LGFMS type, of the right maxilla. Radical resection with wide safe margins and secondary reconstruction with a free forearm flap were performed. Six-month follow-up showed no sign of recurrence or metastasis. The authors review the scientific literature and discuss different tumor locations and treatment strategies for those in the maxillofacial region. The present case is the sixth reported case of LGFMS in the maxillofacial region (intraosseous LGFMS of the maxilla), adding another facet to the literature regarding this rare soft tissue tumor. PMID:26455471

  7. Low Grade Peritoneal Mucinous Carcinomatosis Associated with Human Papilloma Virus Infection: Case Report

    PubMed Central

    Gatalica, Zoran; Foster, Jason M.; Loggie, Brian W.

    2008-01-01

    Pseudomyxoma peritonei is a clinical syndrome characterized by peritoneal dissemination of a mucinous tumor with mucinous ascites. The vast majority of the pseudomyxoma peritoneis are associated with mucinous neoplasms of the appendix. We describe a case of pseudomyxoma peritonei associated with mucinous adenocarcinoma of the cervix in a 60-year-old woman. The patient developed low grade mucinous peritoneal carcinomatosis 8 years after hysterectomy for cervical adenocarcinoma. No other primary mucinous tumor was identified and peritoneal carcinomatosis tested positive for high-risk human papilloma virus (HPV), showing both integrated and episomal pattern. HPV has been previously associated with development of cervical carcinomas (both squamous and mucinous) but neither has cervical adenocarcinoma nor HPV been implicated in development of pseudomyxoma peritonei. To the best of our knowledge, this is the first description of HPV-associated malignancy presenting as pseudomyxoma peritonei. PMID:18925701

  8. Diagnostic Challenges of Low-Grade Central Osteosarcoma of Jaw: a Literature Review

    PubMed Central

    Tabatabaei, Seyd Hosein; Jahanshahi, Gholamreza; Dehghan Marvasti, Farzad

    2015-01-01

    Low Grade Central Osteosarcoma (LGCO) is a rare subtype of osteosarcoma that is less aggressive than conventional osteosarcoma. The importance of LGCO lies in the fact that regarding microscopic and radiographic features, it occasionally simulates some benign jaw lesions and would consequently be misdiagnosed in many patients. The present study was conducted to collect the information and descriptive analyses related to ten cases reported between 1987 and 2010, including a sample reported by the authors emphasizing on diagnostic errors and the prevailing misdiagnosis. The aforementioned reports were gathered in full-texts through Google and PubMed search engines. Conclusion The results of this study showed that the pathologists should exactly evaluate the clinical, radiographic, and histopathologic features in order to observe the evidence of invasion. PMID:26046099

  9. Study of Supercritical Carbon Dioxide Power Cycle for Low Grade Heat Conversion

    SciTech Connect

    Vidhi, Rachana; Goswami, Yogi D.; Chen, Huijuan; Stefanakos, Elias; Kuravi, Sarada; Sabau, Adrian S

    2011-01-01

    Research on supercritical carbon dioxide power cycles has been mainly focused on high temperature applications, such as Brayton cycle in a nuclear power plant. This paper conducts a comprehensive study on the feasibility of a CO2-based supercritical power cycle for low-grade heat conversion. Energy and exergy analyses of the cycle were conducted to discuss the obstacles as well as the potentials of using supercritical carbon dioxide as the working fluid for supercritical Rankine cycle, Carbon dioxide has desirable qualities such as low critical temperature, stability, little environmental impact and low cost. However, the low critical temperature might be a disadvantage for the condensation process. Comparison between a carbon dioxide-based supercritical Rankine cycle and an organic fluid-based supercritical Rankine cycle showed that the former needs higher pressure to achieve the same efficiency and a heat recovery system is necessary to desuperheat the turbine exhaust and pre-heat the pressure charged liquid.

  10. Use of fludarabine in the treatment of mantle cell lymphoma, Waldenström's macroglobulinemia and other uncommon B- and T-cell lymphoid malignancies.

    PubMed

    Johnson, Stephen A

    2004-01-01

    After initial efforts using fludarabine as a single agent in the treatment of acute leukemia, its activity at lower and safer doses was demonstrated in chronic lymphocytic leukemia (CLL) patients who were refractory or had relapsed from traditional chemotherapies, representing a highly effective therapy for this condition. Fludarabine was also rapidly shown to be beneficial as first-line therapy in CLL. There is now considerable evidence that fludarabine is an effective agent in non-Hodgkin's lymphoma and in combination therapy for acute myeloid leukemia. Further, good responses are achieved when fludarabine-based approaches are used as conditioning regimens prior to transplantation procedures. The actions of fludarabine are not restricted to these settings and its potential role in the treatment of a range of uncommon T- and B-cell lymphoid malignancies is slowly emerging. This review will focus on the characteristics and treatment options for two B-cell disorders, mantle cell lymphoma and Waldenström's macroglobulinemia, with emphasis on the clinical activity of fludarabine. Additionally, the advantages of using fludarabine-containing regimens for a range of other lymphoproliferative conditions will also be discussed. These include B-cell neoplasms such as the CLL variant prolymphocytic leukemia, hairy cell leukemia and mucosa-associated lymphoid tissue-derived lymphomas; the T-cell disorders cutaneous T-cell lymphoma, angioimmunoblastic lymphadenopathy and other rarer T-cell diseases; and aggressive variants of non-Hodgkin's lymphoma including Richter's syndrome. PMID:15079153

  11. Risk factors for recurrence and prognosis of low-grade endometrial adenocarcinoma; vaginal versus other sites.

    PubMed

    Moschiano, Elizabeth J; Barbuto, Denise A; Walsh, Christine; Singh, Kanwaljit; Euscher, Elizabeth D; Roma, Andres A; Ali-Fehmi, Rouba; Frauenhoffer, Elizabeth E; Montiel, Delia P; Kim, Insun; Djordjevic, Bojana; Malpica, Anais; Hong, Sung Ran; Silva, Elvio G

    2014-05-01

    Endometrial adenocarcinoma is the most common gynecologic cancer in the United States. The prognosis is generally favorable, however, a significant number of patients do develop local or distant recurrence. The most common site of recurrence is vaginal. Our aim was to better characterize patients with vaginal recurrence of low-grade endometrioid adenocarcinoma with respect to associated tumor parameters and clinical outcome. We compiled 255 cases of low-grade (FIGO Grade I or II) endometrioid adenocarcinoma on hysterectomy specimens with lymph node dissection. A total of 113 cases with positive lymph nodes or recurrent disease were included in our study group. Seventy-three cases (13 Grade 1, 60 Grade 2) developed extravaginal recurrence and 40 cases (7 Grade 1, 33 Grade 2) developed vaginal recurrence. We evaluated numerous tumor parameters including: percentage myoinvasion, presence of microcystic, elongated, and fragmented pattern of myoinvasion, lymphovascular space invasion, and cervical involvement. Clinical follow-up showed that 30% (34/113) of all patients with recurrent disease died as a result of their disease during our follow-up period, including 31 (42.5%) with extravaginal recurrence and 3 (7.5%) with primary vaginal recurrence (P=0.001). The 3 patients with vaginal recurrence developed subsequent extravaginal recurrence before death. Vaginal recurrence patients show increased cervical involvement by tumor, but lack other risk factors associated with recurrent disease at other sites. There were no deaths among patients with isolated vaginal recurrence, suggesting that vaginal recurrence is not a marker of aggressive tumor biology. PMID:24681738

  12. Benign and low grade variants of mixed mesodermal tumor (adenosarcoma) of the ovary and adnexal region.

    PubMed

    Kao, G F; Norris, H J

    1978-09-01

    Eleven examples of a rare group of neoplasms composed of both epithelial and mesenchymal components are reported. Ten arose from the ovary and one arose separately in the para-ovarian region. The neoplasms are distinctive in that the stoma is more cellular than that of adenofibromas, but epithelial component is not malignant, as in carcinosarcoma and mixed mesodermal tumors, and the stoma is not sarcomatous in the low grade varieties. The 11 cases were highly variable in the cellularity and atypism of the stromal cells. The term, adenosarcoma, for these tumors is not acceptable because some were too low a grade to be regarded as sarcomas, and reports of the uterine counterpart disclose that some contain heterologous elements. For that reason, a term that will embrace the full spectrum of changes in the stroma--benign through sarcomatous--is needed. We propose that they be regarded as variants of mixed mesodermal tumor so that both the benign neoplasms and low grade sarcomas can be accommodated under one designation. Of the 11 cases, five lowest grade examples were all confined to the ovary and did not recur after surgical excision, but some of these were borderline in malignancy and probably would have progressed if untreated. Two of the 3 intermediate grade neoplasms extended beyond the ovary but were arrested by surgical excision. The 3 highest grade neoplasms were overly sarcomatous. One of these extended beyond the ovary but was arrested by combination chemotherapy. The para-ovarian adenosarcoma (also high grade) metastasized and proved fatal. PMID:698918

  13. Low-grade coals: a review of some prospective upgrading technologies

    SciTech Connect

    Hassan Katalambula; Rajender Gupta

    2009-07-15

    There is a growing need of using low-grade coals because of higher quest for power generation. In the present carbon-constrained environment, there is a need of upgrading these coals in terms of moisture, ash, and/or other trace elements. The current paper reviews technologies used mainly categorized as drying for reducing moisture and cleaning the coal for reducing mineral content of coal and related harmful constituents, such as sulfur and mercury. The earliest upgrading of high-moisture lignite involved drying and manufacturing of briquettes. Drying technologies consist of both evaporative and non-evaporative (dewatering) types. The conventional coal cleaning used density separation in water medium. However, with water being a very important resource, conservation of water is pushing toward the development of dry cleaning of coal. There are also highly advanced coal-cleaning technologies that produce ultra-clean coals and produce coals with less than 0.1% of ash. The paper discusses some of the promising upgrading technologies aimed at improving these coals in terms of their moisture, ash, and other pollutant components. It also attempts to present the current status of the technologies in terms of development toward commercialization and highlights on problems encountered. It is obvious that still the upgrading goal has not been realized adequately. It can therefore be concluded that, because reserves for low-grade coals are quite plentiful, it is important to intensify efforts that will make these coals usable in an acceptable manner in terms of energy efficiency and environmental protection. 68 refs., 7 figs.

  14. Molecular profiling of low grade serous ovarian tumours identifies novel candidate driver genes.

    PubMed

    Hunter, Sally M; Anglesio, Michael S; Ryland, Georgina L; Sharma, Raghwa; Chiew, Yoke-Eng; Rowley, Simone M; Doyle, Maria A; Li, Jason; Gilks, C Blake; Moss, Phillip; Allan, Prue E; Stephens, Andrew N; Huntsman, David G; deFazio, Anna; Bowtell, David D; Gorringe, Kylie L; Campbell, Ian G

    2015-11-10

    Low grade serous ovarian tumours are a rare and under-characterised histological subtype of epithelial ovarian tumours, with little known of the molecular drivers and facilitators of tumorigenesis beyond classic oncogenic RAS/RAF mutations. With a move towards targeted therapies due to the chemoresistant nature of this subtype, it is pertinent to more fully characterise the genetic events driving this tumour type, some of which may influence response to therapy and/or development of drug resistance. We performed genome-wide high-resolution genomic copy number analysis (Affymetrix SNP6.0) and mutation hotspot screening (KRAS, BRAF, NRAS, HRAS, ERBB2 and TP53) to compare a large cohort of ovarian serous borderline tumours (SBTs, n = 57) with low grade serous carcinomas (LGSCs, n = 19). Whole exome sequencing was performed for 13 SBTs, nine LGSCs and one mixed low/high grade carcinoma. Copy number aberrations were detected in 61% (35/57) of SBTs, compared to 100% (19/19) of LGSCs. Oncogenic RAS/RAF/ERBB2 mutations were detected in 82.5% (47/57) of SBTs compared to 63% (12/19) of LGSCs, with NRAS mutations detected only in LGSC. Some copy number aberrations appeared to be enriched in LGSC, most significantly loss of 9p and homozygous deletions of the CDKN2A/2B locus. Exome sequencing identified BRAF, KRAS, NRAS, USP9X and EIF1AX as the most frequently mutated genes. We have identified markers of progression from borderline to LGSC and novel drivers of LGSC. USP9X and EIF1AX have both been linked to regulation of mTOR, suggesting that mTOR inhibitors may be a key companion treatment for targeted therapy trials of MEK and RAF inhibitors. PMID:26506417

  15. Low grade cotton nonwoven collects up to 50 times its own weight in oil http://www.innovationintextiles.com/nonwovens/low-grade-cotton-nonwoven-collects-up-to-50-times-its-own-weight-in-oil/?utm_source=news_alerts&utm_medium=email&utm_campaign=news_alerts

    E-print Network

    Rock, Chris

    Low grade cotton nonwoven collects up to 50 times its own weight in oil http://www.innovationintextiles.com/nonwovens/low-grade-cotton-nonwoven-collects-up-to-50-times-its-own-weight-in-oil/?utm_source FREE Innovation in Textiles membership. Sign up now... HOME > NONWOVENS & CONVERTING > LOW GRADE COTTON

  16. Radiolabeled Monoclonal Antibody and Combination Chemotherapy Before Stem Cell Transplant in Treating Patients With High-Risk Lymphoid Malignancies

    ClinicalTrials.gov

    2015-12-14

    Adult Nasal Type Extranodal NK/T-cell Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; B-cell Adult Acute Lymphoblastic Leukemia; B-cell Chronic Lymphocytic Leukemia; Cutaneous B-cell Non-Hodgkin Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Hepatosplenic T-cell Lymphoma; Intraocular Lymphoma; Nodal Marginal Zone B-cell Lymphoma; Noncutaneous Extranodal Lymphoma; Peripheral T-cell Lymphoma; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Hairy Cell Leukemia; Small Intestine Lymphoma; Splenic Marginal Zone Lymphoma; T-cell Adult Acute Lymphoblastic Leukemia; T-cell Large Granular Lymphocyte Leukemia; Testicular Lymphoma; Waldenström Macroglobulinemia

  17. O8.03LOW GRADE DIFFUSE ASTROCYTOMA - PROGNOSTIC FACTORS TO ANAPLASTIC TRANSFORMATION

    PubMed Central

    Izquierdo, C.; Majos, C.; Simó, M.; Lucas, A.; Macià, M.; Plans, G.; Gil, M.; Velasco, R.; Bruna, J.

    2014-01-01

    INTRODUCTION: Low grade gliomas (LGG) comprise nearly 20% of all central nervous system (CNS) glial tumors. LGG are characterized by their infiltrative growth and frequent tumor recurrence with malignant progression. They have a heterogeneous clinical behavior being histological, first line resection, velocity of diameter tumor expansion during pretherapeutic period,tumor volume, contrast enhancement and patients' characteritics the only described factors for identifying patients at risk of progression. The identification and validation of new imaging prognostic factors would help to minimize potential treatment-related side effects in LGG. OBJECTIVE: The aim of our study was to analyze the impact of clinical (gender, age, first symptom), histological (gemistocytic) and neuroimaging (tumor growth ratio at 6 months- GR6m) factors on malignant progression in a cohort of diffuse low grade astrocytomas. We conducted serial volumetric analysis using Flair sequences. The time to malignant progression (TMP) was defined as time between histological diagnose and first MRI showing contrast enhancement or histology proven progression. RESULTS: Patients' mean age was 42.5 ± 14.6 years with a male:female ratio of 1.7:1. Median Pignatti index (PI) was 2 (1-4). The median TMP was of 4.76 (0.33-11.8) years. Nearly half (48.2%) of the patients showed a malignant progression. This group had a higher GR6m (49% versus 3%, p = 0.032). A cut-point of GR6m < 2% obtained by ROC analysis showed a sensitivity and specificity of 92.3% and 71% (p = 0.001). In the multivariate analysis the GR6m < 2% (HR: 5.23, 95% CI (1.4-19.61), P = 0.014), gemistocytic component (HR 8, 95% CI (1.6-39.3), p = 0.01) and a PI of 3-4 (HR : 6.94, 95% CI (1.64-29.4), p = 0.008) were identified as independent predictors of TMP. CONCLUSIONS: GR6m resulted as independent prognostic factor of TMP. In addition, our study confirmed PI and gemystocitic histology as prognostic factors on TMP.It is important to define new prognostic factors to anaplastic transformation due to individualized treatment in patients.

  18. The behavior of magnesium isotopes in low-grade metamorphosed mudrocks

    NASA Astrophysics Data System (ADS)

    Wang, Shui-Jiong; Teng, Fang-Zhen; Rudnick, Roberta L.; Li, Shu-Guang

    2015-09-01

    Magnesium isotopic compositions of mudrocks metamorphosed at sub-greenschist facies from three lower Paleozoic basins (northern Lake District, southern Lake District, and Southern Uplands) in the British Caledonides were measured in order to understand the behavior of Mg isotopes during diagenesis and low-grade metamorphism. Carbonate-free mudrocks from the northern Lake District have heavy ?26Mg values varying from -0.17 to +0.25. By contrast, Mg isotopic compositions of carbonate-bearing mudrocks from the southern Lake District and Southern Uplands vary more widely, with ?26Mg ranging from -0.74 to -0.08. Acid leaching experiments on the latter show that the leachates have higher Ca/Al and Ca/K ratios than the residues due to the dissolution of leachable carbonates. The ?26Mg values of leachates (-1.54 to -0.21) are always lower than the corresponding residues (?26Mg = -0.39 to +0.09), consistent with isotopically light Mg in carbonates. A rough, negative correlation between ?26Mg and Mg/Al for the residual silicate fraction of mudrocks suggests that their Mg isotopic compositions are controlled by the relative proportion of illite/muscovite and chlorite. Global clastic sediments display highly variable Mg isotopic compositions that are negatively correlated with CaO/Al2O3 and CaO/TiO2, implying that carbonates introduce light Mg isotopes to sediments, although the silicate end member itself has a wide range of ?26Mg, depending on its mineralogy. Magnesium isotopic compositions of mudrocks, as well as their silicate and carbonate fractions, do not vary systemically as metamorphism proceeds from diagenesis to low-grade metamorphism, suggesting limited Mg isotope fractionation during low-temperature metamorphic dehydration (<300 °C). The general decrease of Mg fraction (by mass) contributed by carbonate with increasing metamorphic grade suggests that dissolution or decomposition of carbonates during metamorphism expelled light Mg isotopes. Thus, the Mg isotopic compositions of the silicate fractions in clastic sediments more faithfully reflect their provenance signatures. Our study shows that Mg isotopes can be used to study sedimentary diagenesis, and Mg isotopes may prove a useful tracer of sediments recycled into the mantle given their heterogeneous ?26Mg values.

  19. Organoselenium Small Molecules and Chromium(III) Complexes for Intervention in Chronic Low-grade Inflammation and Type 2 Diabetes.

    PubMed

    Zhou, Jun; Xu, Huibi; Huang, Kaixun

    2016-01-01

    There is growing evidence to suggest that chronic, low-grade inflammation occurs in abdominal obesity, insulin resistance, type 2 diabetes mellitus and related complications, and that proinflammatory cytokines play an important role in the onset and progression of type 2 diabetes. These findings consequently provide new opportunities for the use of anti-inflammatory strategies to correct the metabolic disorders. Discovery of new synthetic bioactive small molecules to interfere with chronic, low-grade inflammation and type 2 diabetes has attracted considerable attention in medicinal chemistry. To date, a number of organoselenium small molecules and chromium(III) complexes have been shown to have the potential to alleviate chronic low-grade inflammation and type 2 diabetes, including ebselen, selenomethionine, chromium picolinate, chromium dinicocysteinate, chromium phenylalaninate, trinuclear chromium propionate, chromium histidinate, chromium nicotinate, etc. Here, we review recent advances in development of organoselenium small molecules and chromium(III) complexes to intervene in chronic low-grade inflammation and type 2 diabetes, and discuss their mode of action, potential molecular mechanisms and toxicity. PMID:26311428

  20. The association between obesity and fluid intelligence impairment is mediated by chronic low-grade inflammation.

    PubMed

    Spyridaki, Eirini C; Simos, Panagiotis; Avgoustinaki, Pavlina D; Dermitzaki, Eirini; Venihaki, Maria; Bardos, Achilles N; Margioris, Andrew N

    2014-11-28

    Published evidence suggests that obesity impairs cognition. Development of chronic low-grade inflammation (CLGI) represents the earliest consequence of obesity. The present study investigated the association between obesity and fluid intelligence impairment and assessed the potential mediating role of CLGI and psychological (depression/anxiety symptoms), lifestyle (exercise) and physiological (metabolic dysfunction indices) factors in this association. Clinically healthy participants (n 188), grouped as per BMI, underwent cognitive (General Ability Measure for Adults), psychological (Beck Depression Inventory-II and State-Trait Anxiety Inventory) and activity (Godin leisure-time physical activity) measurements. Biochemical parameters included the following: (a) indices of CLGI (high-sensitivity C-reactive protein, erythrocyte sedimentation rate and fibrinogen); (b) insulin resistance (Homeostasis Model Assessment of Insulin Resistance index); (c) adiposity (plasma adiponectin). An inverse association between elevated BMI and fluid intelligence was observed, with obese participants displaying significantly poorer performance compared with age-matched normal-weight peers. Structural equation modelling results were consistent with a negative impact of obesity on cognition that was mediated by CLGI. The results of the present study support the hypothesis that reduced general cognitive ability is associated with obesity, an adverse effect mainly mediated by obesity-associated activation of innate immunity. PMID:25315424

  1. Membrane-free battery for harvesting low-grade thermal energy.

    PubMed

    Yang, Yuan; Loomis, James; Ghasemi, Hadi; Lee, Seok Woo; Wang, Yi Jenny; Cui, Yi; Chen, Gang

    2014-11-12

    Efficient and low-cost systems are desired to harvest the tremendous amount of energy stored in low-grade heat sources (<100 °C). An attractive approach is the thermally regenerative electrochemical cycle (TREC), which uses the dependence of electrode potential on temperature to construct a thermodynamic cycle for direct heat-to-electricity conversion. By varying the temperature, an electrochemical cell is charged at a lower voltage than discharged; thus, thermal energy is converted to electricity. Recently, a Prussian blue analog-based system with high efficiency has been demonstrated. However, the use of an ion-selective membrane in this system raises concerns about the overall cost, which is crucial for waste heat harvesting. Here, we report on a new membrane-free battery with a nickel hexacyanoferrate (NiHCF) cathode and a silver/silver chloride anode. The system has a temperature coefficient of -0.74 mV K(-1). When the battery is discharged at 15 °C and recharged at 55 °C, thermal-to-electricity conversion efficiencies of 2.6% and 3.5% are achieved with assumed heat recuperation of 50% and 70%, respctively. This work opens new opportunities for using membrane-free electrochemical systems to harvest waste heat. PMID:25307065

  2. Clinical Epidemiology of Low-Grade and Dedifferentiated Osteosarcoma in Norway during 1975 and 2009

    PubMed Central

    Berner, Kjetil; Johannesen, Tom Børge; Bruland, Øyvind S.

    2015-01-01

    Purpose. To describe epidemiological, clinical characteristics and treatment outcomes of low-grade osteosarcoma (LGOS), including dedifferentiated osteosarcoma (DLGOS). Method. We analysed a nationwide cohort comprised of patients with histologically verified LGOS and DLGOS between 1975 and 2009, based on registry sources supplemented with clinical records from hospitals involved in sarcoma management. Results. Fifty-four patients were identified, 12 of whom had DLGOS. The annual incidence for all patients was 0.3 per million, with the peak incidence in the third decade of the life. Fifteen patients experienced local relapses during follow-up and ten developed metastatic diseases, including three at primary diagnosis. Patients with DLGOS dominated the metastatic relapse group. The five-year sarcoma-specific survival rate was 91%, with no documented improvement over time. Free margin following surgical resection of the primary tumour had a positive impact on survival. As expected, both local relapse and metastasis during follow-up were associated with an unfavourable outcome. Radiotherapy predicted poor survival due to the selection of high-risk patients in need of such treatment. Neither higher age nor axial tumour localisation was adverse prognostic factors. Conclusion. LGOS has an excellent prognosis when surgically resected with a free margin; however, LGOS has the potential to dedifferentiate and metastasize with a poor outcome. PMID:26412976

  3. Low-grade glial tumor with features of astroblastoma in a dog.

    PubMed

    Cowart, J R; Schulman, F Y; Mena, H

    2005-05-01

    A 12-year-old, neutered, male Belgian Malinois/Great Dane cross dog presented with a 5-month history of weakness and lack of endurance followed by acute onset of rear limb ataxia. At autopsy, a 9 x 16 mm, multilobular, firm, white to tan, expansile mass was found in the cerebellum. Mild dilatation of the lateral ventricles was also noted. Histologically, there was a well-demarcated glial neoplasm composed of medium-sized astrocytic elements that had homogeneous cytoplasm, sometimes with globular eosinophilic inclusions, irregular peripherally located nuclei with a single nucleolus, and short cytoplasmic processes. Prominent perivascular pseudorosettes with cellular processes in contact with blood vessels were present. Some blood vessels exhibited hyalinized walls. Mitotic figures were not observed. Immunohistochemically, neoplastic cells expressed glial fibrillary acidic protein and vimentin. These features are consistent with an astroblastoma. This is the first clinicopathologic correlation and detailed description of a low-grade glial tumor with features of astroblastoma in a dog. PMID:15872386

  4. Enhancing low-grade thermal energy recovery in a thermally regenerative ammonia battery using elevated temperatures.

    PubMed

    Zhang, Fang; LaBarge, Nicole; Yang, Wulin; Liu, Jia; Logan, Bruce E

    2015-03-01

    A thermally regenerative ammonia battery (TRAB) is a new approach for converting low-grade thermal energy into electricity by using an ammonia electrolyte and copper electrodes. TRAB operation at 72?°C produced a power density of 236 ± 8 Wm(-2), with a linear decrease in power to 95 ± 5 Wm(-2) at 23?°C. The improved power at higher temperatures was due to reduced electrode overpotentials and more favorable thermodynamics for the anode reaction (copper oxidation). The energy density varied with temperature and discharge rates, with a maximum of 650 Wh m(-3) at a discharge energy efficiency of 54% and a temperature of 37?°C. The energy efficiency calculated with chemical process simulation software indicated a Carnot-based efficiency of up to 13% and an overall thermal energy recovery of 0.5%. It should be possible to substantially improve these energy recoveries through optimization of electrolyte concentrations and by using improved ion-selective membranes and energy recovery systems such as heat exchangers. PMID:25684619

  5. Optimal radiation fractionation for low-grade gliomas: Insights from a mathematical model.

    PubMed

    Galochkina, Tatiana; Bratus, Alexander; Pérez-García, Víctor M

    2015-09-01

    We study optimal radiotherapy fractionations for low-grade glioma using mathematical models. Both space-independent and space-dependent models are studied. Two different optimization criteria have been developed, the first one accounting for the global effect of the tumor mass on the disease symptoms and the second one related to the delay of the malignant transformation of the tumor. The models are studied theoretically and numerically using the method of feasible directions. We have searched for optimal distributions of the daily doses dj in the standard protocol of 30 fractions using both models and the two different optimization criteria. The optimal results found in all cases are minor deviations from the standard protocol and provide only marginal potential gains. Thus, our results support the optimality of current radiation fractionations over the standard 6 week treatment period. This is also in agreement with the observation that minor variations of the fractionation have failed to provide measurable gains in survival or progression free survival, pointing out to a certain optimality of the current approach. PMID:26113284

  6. Treatment options and neurocognitive outcome in patients with diffuse low-grade glioma.

    PubMed

    Klein, M

    2015-12-01

    In the management of patients with low-grade glioma (LGG) there still is controversy on how surgical intervention, radiotherapy, and chemotherapy contribute to an ameliorated progression-free survival, overall survival, and treatment-related neurotoxicity. With the ongoing changes in treatment options for these patients, neurocognitive functioning is an increasingly important outcome measure, because neurocognitive impairments can have a large impact on self-care, social and professional functioning, and consequently on health-related quality of life. Many factors contribute to neurocognitive outcome, such as direct and indirect tumor effects, seizures, medication, and oncological treatment. Although the role of radiotherapy has been studied extensively, the adverse effects on neurocognitive function of other treatment-related factors remain elusive. This not only holds for resective surgery, where the use of intraoperative stimulation mapping has a high potential benefit concerning survival and patient functioning, but also for the use of chemotherapy that might have some interesting new applications, like the facilitation of total resection for initially primary or recurrent diffuse LGG tumors. This paper will discuss these treatment options in LGG patients and their potential effects on neurocognitive functioning. PMID:26375636

  7. Telomerase Deficiency Causes Alveolar Stem Cell Senescence-associated Low-grade Inflammation in Lungs.

    PubMed

    Chen, Ruping; Zhang, Kexiong; Chen, Hao; Zhao, Xiaoyin; Wang, Jianqiu; Li, Li; Cong, Yusheng; Ju, Zhenyu; Xu, Dakang; Williams, Bryan R G; Jia, Jihui; Liu, Jun-Ping

    2015-12-25

    Mutations of human telomerase RNA component (TERC) and telomerase reverse transcriptase (TERT) are associated with a subset of lung aging diseases, but the mechanisms by which TERC and TERT participate in lung diseases remain unclear. In this report, we show that knock-out (KO) of the mouse gene Terc or Tert causes pulmonary alveolar stem cell replicative senescence, epithelial impairment, formation of alveolar sacs, and characteristic inflammatory phenotype. Deficiency in TERC or TERT causes a remarkable elevation in various proinflammatory cytokines, including IL-1, IL-6, CXCL15 (human IL-8 homolog), IL-10, TNF-?, and monocyte chemotactic protein 1 (chemokine ligand 2 (CCL2)); decrease in TGF-?1 and TGF?RI receptor in the lungs; and spillover of IL-6 and CXCL15 into the bronchoalveolar lavage fluids. In addition to increased gene expressions of ?-smooth muscle actin and collagen 1?1, suggesting myofibroblast differentiation, TERC deficiency also leads to marked cellular infiltrations of a mononuclear cell population positive for the leukocyte common antigen CD45, low-affinity Fc receptor CD16/CD32, and pattern recognition receptor CD11b in the lungs. Our data demonstrate for the first time that telomerase deficiency triggers alveolar stem cell replicative senescence-associated low-grade inflammation, thereby driving pulmonary premature aging, alveolar sac formation, and fibrotic lesion. PMID:26518879

  8. Optimization of reaction conditions for the electroleaching of manganese from low-grade pyrolusite

    NASA Astrophysics Data System (ADS)

    Zhang, Xing-ran; Liu, Zuo-hua; Fan, Xing; Lian, Xin; Tao, Chang-yuan

    2015-11-01

    In the present study, a response surface methodology was used to optimize the electroleaching of Mn from low-grade pyrolusite. Ferrous sulfate heptahydrate was used in this reaction as a reducing agent in sulfuric acid solutions. The effect of six process variables, including the mass ratio of ferrous sulfate heptahydrate to pyrolusite, mass ratio of sulfuric acid to pyrolusite, liquid-to-solid ratio, current density, leaching temperature, and leaching time, as well as their binary interactions, were modeled. The results revealed that the order of these factors with respect to their effects on the leaching efficiency were mass ratio of ferrous sulfate heptahydrate to pyrolusite > leaching time > mass ratio of sulfuric acid to pyrolusite > liquid-to-solid ratio > leaching temperature > current density. The optimum conditions were as follows: 1.10:1 mass ratio of ferrous sulfate heptahydrate to pyrolusite, 0.9:1 mass ratio of sulfuric acid to pyrolusite, liquid-to-solid ratio of 0.7:1, current density of 947 A/m2, leaching time of 180 min, and leaching temperature of 73°C. Under these conditions, the predicted leaching efficiency for Mn was 94.1%; the obtained experimental result was 95.7%, which confirmed the validity of the model.

  9. Fast thermal calibration of low-grade inertial sensors and inertial measurement units.

    PubMed

    Niu, Xiaoji; Li, You; Zhang, Hongping; Wang, Qingjiang; Ban, Yalong

    2013-01-01

    The errors of low-cost inertial sensors, especially Micro-Electro Mechanical Systems (MEMS) ones, are highly dependent on environmental conditions such as the temperature. Thus, there is a need for the development of accurate and reliable thermal compensation models to reduce the impact of such thermal drift of the sensors. Since the conventional thermal calibration methods are typically time-consuming and costly, an efficient thermal calibration method to investigate the thermal drift of a full set of gyroscope and accelerometer errors (i.e., biases, scale factor errors and non-orthogonalities) over the entire temperature range in a few hours is proposed. The proposed method uses the idea of the Ramp method, which removes the time-consuming process of stabilizing the sensor temperature, and addresses its inherent problems with several improvements. We change the temperature linearly for a complete cycle and take a balanced strategy by making comprehensive use of the sensor measurements during both heating and cooling processes. Besides, an efficient 8-step rotate-and-static scheme is designed to further improve the calibration accuracy and efficiency. Real calibration tests showed that the proposed method is suitable for low-grade IMUs and for both lab and factory calibration due to its efficiency and sufficient accuracy. PMID:24036581

  10. Resetting of RbSr ages of volcanic rocks by low-grade burial metamorphism

    USGS Publications Warehouse

    Asmeroma, Y.; Damon, P.; Shafiqullah, M.; Dickinson, W.R.; Zartman, R.E.

    1991-01-01

    We report a nine-point RbSr whole-rock isochron age of 70??3 Ma (MSWD 3.97) for Mid-Jurassic volcanic rocks. The same rocks have also been dated by the UThPb method on zircon, giving a crystallization age of 166 ?? 11 Ma, over twice as old as the RbSr age. The data demonstrate that whole-rock RbSr ages of volcanic rocks, even lava flows with SiO2 content as low as 57 wt.%, are susceptible to complete resetting. The rocks range in composition from rhyodacite tuffs to andesite lavas. The complete breakdown of all major minerals that contain Rb and Sr resulted in an alteration mineral assemblage consisting of phengite, albite, secondary quartz, and minor amounts of chlorite and epidote. Phengite is the K-bearing product of the breakdown of biotite and K-feldspar. Pressure during low-grade metamorphism of the volcanic rocks, estimated from phengite composition to have been in the range of 4 to 6 kbar, points to thrust-related burial as the main cause of resetting. Consequently, such reset isochrons may date large-scale events such as regional thrusting and metamorphism. The coherent resetting of the RbSr isochron suggests large-scale pervasive fluid movement during thrust-related burial metamorphism. ?? 1991.

  11. Low-grade, M1 metamorphism of the western metamorphic belt near Juneau, Alaska

    SciTech Connect

    Himmelberg, G.R. . Dept. of Geology); Brew, D.A.; Ford, A.B. )

    1993-04-01

    The western metamorphic belt is part of the Coast plutonic-metamorphic complex of western Canada and southeastern Alaska that developed as a result of tectonic overlap and/or compressional thickening of crustal rocks during collision of the Alexander terrane and Gravina assemblage on the west against the Yukon Prong and Stikine terranes to the east. Sub-greenschist to lower greenschist facies metabasalts exposed along the west end of the western metamorphic belt near Juneau, Alaska record the earliest metamorphic event (M1). These low-grade rocks are gradational with younger, higher-grade assemblages that define an inverted metamorphic gradient (metamorphic event M5). The most common metamorphic mineral assemblages are chlorite-epidote-actinolite with or without pumpellyite and stilpnomelane. There is no systematic distribution of metamorphic mineral assemblages in the study area, and all assemblages are in the pumpellyite-actinolite facies near the transition to the lower greenschist facies. Different low-variance assemblages can be attributed to minor differences in pressure, temperature, or X[sub CO[sub 2

  12. A dynamic model for the optimization of oscillatory low grade heat engines

    SciTech Connect

    Markides, Christos N.; Smith, Thomas C. B.

    2015-01-22

    The efficiency of a thermodynamic system is a key quantity on which its usefulness and wider application relies. This is especially true for a device that operates with marginal energy sources and close to ambient temperatures. Various definitions of efficiency are available, each of which reveals a certain performance characteristic of a device. Of these, some consider only the thermodynamic cycle undergone by the working fluid, whereas others contain additional information, including relevant internal components of the device that are not part of the thermodynamic cycle. Yet others attempt to factor out the conditions of the surroundings with which the device is interfacing thermally during operation. In this paper we present a simple approach for the modeling of complex oscillatory thermal-fluid systems capable of converting low grade heat into useful work. We apply the approach to the NIFTE, a novel low temperature difference heat utilization technology currently under development. We use the results from the model to calculate various efficiencies and comment on the usefulness of the different definitions in revealing performance characteristics. We show that the approach can be applied to make design optimization decisions, and suggest features for optimal efficiency of the NIFTE.

  13. Modeling and simulation of a low-grade urinary bladder carcinoma.

    PubMed

    Bunimovich-Mendrazitsky, Svetlana; Pisarev, Vladimir; Kashdan, Eugene

    2015-03-01

    In this work, we present a mathematical model of the initiation and progression of a low-grade urinary bladder carcinoma. We simulate the crucial processes affecting tumor growth, such as oxygen diffusion, carcinogen penetration, and angiogenesis, within the framework of the urothelial cell dynamics. The cell dynamics are modeled using the discrete technique of cellular automata, while the continuous processes of carcinogen penetration and oxygen diffusion are described by nonlinear diffusion-absorption equations. As the availability of oxygen is necessary for tumor progression, processes of oxygen transport to the tumor growth site seem most important. Our model yields a theoretical insight into the main stages of development and growth of urinary bladder carcinoma with emphasis on the two most common types: bladder polyps and carcinoma in situ. Analysis of histological structure of bladder tumor is important to avoid misdiagnosis and wrong treatment. We expect our model to be a valuable tool in the study of bladder cancer progression due to the exposure to carcinogens and the oxygen dependent expression of genes promoting tumor growth. Our numerical simulations have good qualitative agreement with in vivo results reported in the corresponding medical literature. PMID:25637778

  14. Human Papillomavirus Test for Triage of Japanese Women With Low-Grade Squamous Intraepithelial Lesions.

    PubMed

    Iwata, Takashi; Hasegawa, Toshihiko; Ochiai, Kazunori; Takizawa, Ken; Umezawa, Satoshi; Kuramoto, Hiroyuki; Ohmura, Mineo; Kubushiro, Kaneyuki; Arai, Hiroharu; Sakamoto, Masaru; Motoyama, Teiichi; Watanabe, Kayoko; Aoki, Daisuke

    2015-12-01

    We evaluated high-risk human papillomavirus (HR-HPV) DNA testing for high-grade cervical intraepithelial neoplasia (CIN) lesions by cobas HPV test and diagnostic HPV16/18 genotyping in Japanese women with low-grade squamous intraepithelial lesions. Of 357 patients, HR-HPV positivity prevalence was 75.6%, and 21.3% had grade 2 or higher CIN lesions (CIN2+), with the highest prevalence at 30 to 34 years. Negative predictive values of HR-HPV for CIN2+ in our patients were 93.1% (any age) and 94.9% (40-50 years). Absolute risk for CIN2+ in HR-HPV positive and HPV16/18 positive individuals was 25.9 and 35.1, respectively. Relative risk for CIN2+ lesions was 5.1 for HPV16/18 positive versus HR-HPV negative, and 3.8 for HR-HPV positive versus HR-HPV negative women. Predictive values of CIN2+ positive were higher for HPV16/18 positive women (any age) than 12 other HPV positive-genotypes, and highest (50%) at 40-50 years. The HPV16/18 genotyping might prevent women (>40 years) at risk of high-grade CIN lesions from undergoing unnecessary colposcopy/overtreatment of nonprogressive lesions. PMID:26092278

  15. Clinical Management of Seizures in Patients With Low-Grade Glioma

    PubMed Central

    Piotrowski, Anna F.; Blakeley, Jaishri

    2015-01-01

    Seizures, transient disruptions of normal brain electrical activity, are common for patients with low-grade glioma (LGG) and significantly affect quality of life. Up to 75% of patients with a LGG will have seizures in the course of their disease (compared with 1%–2% of the general population). Depending on the type of abnormal electrical activity, the functional implications of seizure can impact any domain, including mental status, sensation or strength. In most cases, either the seizure or the medications used to treat the seizure may contribute to cognitive and psychosocial difficulties of various degrees of severity. Hence, effective management of seizures is a major priority for patients with LGG. Evidence-based guidelines suggest that levetiracetam is the best first-line agent for treatment of seizures in this population due to both its efficacy and tolerability. An important consideration in the field of neuro-oncology is that levetiracetam has very few drug interactions. Unfortunately, approximately one-third of patients with LGG have refractory epilepsy where additional agents such as valproic acid, or lacosamide, lamotrigine and nonpharmacologic therapies such as diet-based interventions, epilepsy surgery, and devices are considered. PMID:26050593

  16. Low-grade toxicity after conformal radiation therapy for prostate cancer-impact of bladder volume

    SciTech Connect

    Pinkawa, Michael . E-mail: mpinkawa@ukaachen.de; Fischedick, Karin; Asadpour, Branka; Gagel, Bernd; Piroth, Marc D.; Eble, Michael J.

    2006-03-01

    Purpose: To assess the impact of dose-volume histogram parameters on low-grade toxicity after radiotherapy for prostate cancer. Methods and Materials: Eighty patients have been surveyed prospectively before (time A), at the last day (B), 2 months after (C), and 16 months (median) after (D) radiotherapy (70.2 Gy) using a validated questionnaire (Expanded Prostate Cancer Index Composite). Dose-volume histograms were correlated with urinary and bowel function/bother scores. Results: The initial bladder volume and the percentage of the bladder volume receiving 10%-90% of the prescription dose significantly correlated with urinary function/bother scores (significant cutoff levels found for all dose levels). Pain with urination proved to be mainly an acute problem, subsiding faster for patients with larger bladder volumes and smaller volumes inside particular isodose lines. At time D, persisting problems with smaller initial bladder volumes were a weak stream and an increased frequency of urination. Though bladder volume and planning target volume both independently have an influence on dose-volume histogram parameters for the bladder, bladder volume plays the decisive role for urinary toxicity. Conclusions: The patient's ability to fill the bladder has a major impact on the dose-volume histogram and both acute and late urinary toxicity.

  17. Low-grade risk of hypercoagulable state in patients suffering from diabetes mellitus type 2*

    PubMed Central

    Ruszkowska-Ciastek, Barbara; Sokup, Alina; Wernik, Tomasz; Rhone, Piotr; Góralczyk, Krzysztof; Bielawski, Kornel; Fija?kowska, Agata; Nowakowska, Aleksandra; Rhone, El?bieta; Ro??, Danuta

    2015-01-01

    Objective: Diabetes, including type 1 and type 2, is associated with the hypercoagulable state. The aim of this study is to evaluate the concentration of selected hemostatic parameters and vascular endothelial growth factor-A (VEGF-A) in diabetic subjects. Methods: The study was conducted in 62 patients with diabetes. Group I consisted of 27 patients having uncontrolled diabetes with microalbuminuria and Group II included 35 well-controlled diabetic patients. The control group was made up of 25 healthy volunteers. In the citrate plasma, the concentrations of tissue factor (TF), tissue factor pathway inhibitor (TFPI), thrombin-antithrombin (TAT) complexes, and D-dimer were assayed. Serum concentrations of VEGF-A, lipid profile, creatinine, and plasma fasting glucose were measured and in the versene plasma the concentration of HbA1c was determined. Results: In the patients with uncontrolled diabetes, higher concentrations of TF, TFPI, and VEGF-A were observed, as compared with the well-controlled diabetics group and the control group. A significantly lower activity of antiplasmin was reported in patients from Group I as compared with the control group. In Group I, using the multivariate regression analysis, the glomerular filtration rate was independently associated with VEGF-A and dependently associated with total cholesterol. Conclusions: The study showed higher concentrations of TF and TFPI in the patients with uncontrolled diabetes with microalbuminuria, which is associated with rapid neutralization of the thrombin formation, since TFPI inhibits the complex of TF/VIIa/Ca2+. The manifestation of the above suggestions is the correct TAT complexes and D-dimer, which indicates a low grade of prothrombotic risk in this group of patients, but a higher risk of vascular complications. PMID:26365121

  18. Cellular metabolic regulators: Novel indicators of low-grade inflammation in humans

    PubMed Central

    Haimovich, Beatrice; Zhang, Zhiyong; Calvano, Jacqueline E; Calvano, Steve E; Kumar, Ashwini; Macor, Marie A; Corbett, Siobhan; Coyle, Susette M; Lowry, Stephen F.

    2015-01-01

    Introduction The Toll like receptor 4 (TLR4) ligand endotoxin triggers robust systemic inflammatory responses in humans at doses > 1.0 ng/kg. In this study we tested the hypothesis that evidence of TLR4-induced responses would be detectable in leukocytes challenged with endotoxin doses that are below the threshold needed to trigger a characteristic systemic inflammatory phenotype in humans. Methods Subjects were challenged with endotoxin at 1, 0.5, or 0.1 ng/kg (n=5 per dose). Systemic responses were monitored for 24 hour. Blood samples, collected at designated interval for up to 24 hours post-challenge, were used to determine plasma cytokines levels, total and differential leukocyte counts, expression of leukocyte cell surface receptors, and changes in the leukocyte transcriptome. Western blotting was used to determine changes in leukocyte protein expression. Results We found that in vivo endotoxin at concentrations <1.0 ng/kg triggers weak and variable responses in humans. In marked contrast, we show that endotoxin at a concentration as low as 0.1 ng/kg triggers a transient decline in cellular ATP levels in leukocytes. This is associated with the appearance of a unique protein expression signature in leukocytes. The protein expression signature includes three prominent features: i) AMP-activated protein kinase subunit ? (AMPK?) degradation, ii) increased HIF-1? expression, and iii) autophagy, collectively indicative of a regulated metabolic response. An indistinguishable response phenotype was observed in human leukocytes treated with endotoxin in vitro. Discussion These data demonstrate for the first time in humans that a TLR4 ligand concentration that is below the threshold needed to trigger clinically evident systemic inflammatory manifestations initiates a transient decline in ATP levels, AMPK? degradation, HIF-1? expression, and autophagy in leukocytes. This establishes that low-grade TLR4 activation exerts control over leukocyte metabolism in the absence of systemic inflammatory indicators. PMID:23817504

  19. Low-grade cribriform cystadenocarcinoma of the palatal gland: A case report

    PubMed Central

    KOKABU, SHOICHIRO; NOJIMA, JUNYA; KAYANO, HIDEKAZU; YODA, TESTUYA

    2015-01-01

    Low-grade cribriform cystadenocarcinoma (LGCCC) is a malignant salivary gland tumor. LGCCC occurs rarely, with the parotid gland being the most commonly afflicted site. Few cases arise in other sites. The present study reports a case of LGCCC that occurred at the palatal gland of the hard palate. A 56-year-old female was referred to Saitama Medical University Hospital (Moroyama, Saitama, Japan) due to an intraoral mass. Since cytological examination and biopsy led to a diagnosis favoring a neoplasm, but with uncertain malignant potential, the tumor was resected with a safe surgical margin. The specimen was thoroughly examined. Microscopically, there was a well-demarcated, unilocular cyst with the lumen lined by tumor cells. The tumor cells were arranged in tubular, cribriform and solid structures in the area of the intracystic mass lesions. Nuclear atypia was inconspicuous, although mitotic figures were observed throughout the tumor. Neither local nor perineural invasion was present. On immunohistochemistry, the tumor cells were diffusely positive for S-100 protein. Myoepithelial markers, calponin and p63, highlighted the cells rimming the cystic mass. The final histopathological diagnosis was of LGCCC. The tumor was completely resected. At 1 year post-resection, the patient exhibited no recurrence or distant metastasis. LGCCC is regarded as clinically indolent. However, there is little literature available to aid with prognosis prediction due to the rarity of LGCCC cases. Thus, greater experience and longer follow-up periods are necessary to find the optimal/curative treatment for patients with LGCCC and to clarify the pathophysiology.

  20. Evidence for low-grade metamorphism, hydrothermal alteration, and diagenesis on mars from phyllosilicate mineral assemblages

    USGS Publications Warehouse

    Ehlmann, B.L.; Mustard, J.F.; Clark, R.N.; Swayze, G.A.; Murchie, S.L.

    2011-01-01

    The enhanced spatial and spectral resolution provided by the Compact Reconnaissance Imaging Spectrometer for Mars (CRISM) on the Mars Reconnaissance Orbiter (MRO) has led to the discovery of numerous hydrated silicate minerals on Mars, particularly in the ancient, cratered crust comprising the southern highlands. Phases recently identified using visible/near-infrared spectra include: smectite, chlorite, prehnite, high-charge phyllosilicates (illite or muscovite), the zeolite analcime, opaline silica, and serpentine. Some mineral assemblages represent the products of aqueous alteration at elevated temperatures. Geologic occurrences of these mineral assemblages are described using examples from west of the Isidis basin near the Nili Fossae and with reference to differences in implied temperature, fluid composition, and starting materials during alteration. The alteration minerals are not distributed homogeneously. Rather, certain craters host distinctive alteration assemblages: (1) prehnite-chlorite-silica, (2) analcime-silica-Fe,Mg-smectite-chlorite, (3) chlorite-illite (muscovite), and (4) serpentine, which furthermore has been found in bedrock units. These assemblages contrast with the prevalence of solely Fe,Mg-smectites in most phyllosilicate-bearing terrains on Mars, and they represent materials altered at depth then exposed by cratering. Of the minerals found to date, prehnite provides the clearest evidence for subsurface, hydrothermal/metamorphic alteration, as it forms only under highly restricted conditions (T = 200 400??C). Multiple mechanisms exist for forming the other individual minerals; however, the most likely formation mechanisms for the characteristic mineralogic assemblages observed are, for (1) and (2), low- grade metamorphism or hydrothermal (400??C has not been found.

  1. Proton Therapy in Pediatric Skull Base and Cervical Canal Low-Grade Bone Malignancies

    SciTech Connect

    Habrand, Jean-Louis Schneider, Ralf M.D.; Alapetite, Claire; Feuvret, Loic; Petras, Slavo; Datchary, Jean; Grill, Jacques; Noel, Georges; Helfre, Sylvie; Ferrand, Regis; Bolle, Stephanie; Sainte-Rose, Christian

    2008-07-01

    Purpose: To evaluate outcomes and tolerance of high-dose photon and proton therapy in the management of skull base and cervical canal primary bony malignancies in children. Patients and Methods: Thirty children were treated postoperatively with high-dose photon-proton (29 patients) or protons-only (1 patient) radiotherapy. Twenty-six patients had chordomas (CH), 3 had low-grade chondrosarcomas (CS), and 1 had an aggressive chondroma (AC). The mean age was 12.8 years. At the time of radiation, all but 1 patient had a gross residue. The anatomic sites affected were skull base (n 16), cervical canal (n = 1), or both (n = 13). Mean total dose was 68.4 cobalt Gray equivalents, conventionally fractionated. Results: With a mean follow-up of 26.5 months, 5 of 30 children failed locally: 5 of 5 lesions were CH, 5 of 5 patients had experienced pain at presentation (p = 0.03), and 4 of 5 had cervical extension (p = 0.07). The 5-year overall survival/progression-free survival rates for CS and CH were 100%/100% and 81%/77%, respectively. Side effects were scored according to the National Cancer Institute Common Terminology Criteria for Adverse Events v3.0. Acute toxicity ranged between 0 and 2. Late toxicity of radiotherapy was severe in 1 patient (Grade 3 auditory) and minor or mild in the rest of the population (7 patients with Grade 2 pituitary dysfunction). Conclusions: High-dose combined fractionated photon-proton therapy is well tolerated in children and allows excellent local control with minimal long-term toxicity.

  2. A disconnection account of subjective empathy impairments in diffuse low-grade glioma patients.

    PubMed

    Herbet, Guillaume; Lafargue, Gilles; Moritz-Gasser, Sylvie; Menjot de Champfleur, Nicolas; Costi, Emanuele; Bonnetblanc, François; Duffau, Hugues

    2015-04-01

    Human empathic experience is a multifaceted psychological construct which arises from functional integration of multiple neural networks. Despite accumulating knowledge about the cortical circuitry of empathy, almost nothing is known about the connectivity that may be concerned in conveying empathy-related neural information. To bridge this gap in knowledge, we studied dispositional empathy in a large-sized cohort of 107 patients who had undergone surgery for a diffuse low-grade glioma. The self-report questionnaire used enabled us to obtain a global measure of subjective empathy but also, importantly, to assess the two main components of empathy (cognitive and emotional). Data were processed by combining voxelwise and tractwise lesion-symptom analyses. Several major findings emerged from our analyses. First of all, topological voxelwise analyses were inconclusive. Conversely, tractwise multiple regression analyses, including all major associative white matter pathways as potential predictors, yielded to significant models explaining substantial part of the behavioural variance. Among the main results, we found that disconnection of the left cingulum bundle was a strong predictor of a low cognitive empathy (p<0.0005 Bonferroni-corrected). Similarly, we found that disconnection of the right uncinate fasciculus and the right inferior fronto-occipital fasciculus predicted, respectively, a low (p<0.05 Bonferroni-corrected) and a high (p<0.05 Bonferroni-corrected) subjective empathy. Finally, although we failed to relate emotional empathy to disruption of a specific tract, correlation analyses indicated a positive association between this component of empathy and the volumes of residual lesion infiltration in the right hemisphere (p<0.01). Taken as a whole, these findings provide key fundamental insights into the anatomical connectivity of empathy. They may help to better understand the pathophysiology of empathy impairments in pathological conditions characterized by abnormalities of long-range anatomical connectivity, such as autism spectrum disorders, schizophrenia and fronto-temporal dementia. PMID:25687031

  3. An extraction process to recover vanadium from low-grade vanadium-bearing titanomagnetite.

    PubMed

    Chen, Desheng; Zhao, Hongxin; Hu, Guoping; Qi, Tao; Yu, Hongdong; Zhang, Guozhi; Wang, Lina; Wang, Weijing

    2015-08-30

    An extraction process to recover vanadium from low-grade vanadium-bearing titanomagnetite was developed. In this study, a mixed solvent system of di(2-ethylhexyl) phosphate (D2EHPA) and tri-n-butyl phosphate (TBP) diluted with kerosene was used for the selective extraction of vanadium from a hydrochloric acid leaching solution that contained low vanadium concentration with high concentrations of iron and impurities of Ca, Mg, and Al. In the extraction process, the initial solution pH and the phase ratio had considerable functions in the extraction of vanadium from the hydrochloric acid leaching solution. Under optimal extraction conditions (i.e., 30-40°C for 10min, 1:3 phase ratio (O/A), 20% D2EHPA concentration (v/v), and 0-0.8 initial solution pH), 99.4% vanadium and only 4.2% iron were extracted by the three-stage counter-current extraction process. In the stripping process with H2SO4 as the stripping agent and under optimal stripping conditions (i.e., 20% H2SO4 concentration, 5:1 phase ratio (O/A), 20min stripping time, and 40°C stripping temperature), 99.6% vanadium and only 5.4% iron were stripped by the three-stage counter-current stripping process. The stripping solution contained 40.16g/LV2O5,0.691g/L Fe, 0.007g/L TiO2, 0.006g/L SiO2 and 0.247g/L CaO. A V2O5 product with a purity of 99.12% V2O5 and only 0.026% Fe was obtained after the oxidation, precipitation, and calcination processes. The total vanadium recovered from the hydrochloric acid leaching solution was 85.5%. PMID:25840036

  4. Evolving management of low grade glioma: No consensus amongst treating clinicians.

    PubMed

    Field, K M; Rosenthal, M A; Khasraw, M; Sawkins, K; Nowak, A K

    2016-01-01

    Following the widely publicized presentation of the Radiation Therapy Oncology Group (RTOG) 9802 data, we sought to understand how these data had been translated to the management of low grade gliomas (LGG) by Australian neuro-oncology clinicians. The de novo management of LGG is transitioning to include postoperative radiotherapy and chemotherapy after the RTOG 9802 study results demonstrated a survival benefit in this setting. In 2014, neurosurgeons, radiation oncologists and neuro-oncologists who were members of the Australian Cooperative Trials Group for Neuro-oncology (COGNO), as well as additional attendants of the COGNO annual scientific meeting, were surveyed. The survey presented six LGG clinical scenarios and asked respondents to select their preferred management strategy. Some additional questions included the respondents' approach to 1p/19q testing and chemotherapy preferences. The response rate was 30.2% (61/202), with the majority (77%) working in tertiary referral neuro-oncology centers. There was no consensus regarding the management approach for each scenario, with postsurgery observation alone remaining a popular strategy. Only 25% of respondents reported that their institution routinely tests for 1p/19q status in LGG, although 69% were of the opinion that all LGG patients should be tested. The majority (81%) preferred to use temozolomide rather than the procarbazine, lomustine, and vincristine combination as the first line chemotherapy for LGG, but only 44% would actually use it in this setting. Up front chemotherapy, prior to radiotherapy, would be considered by 52% of respondents for certain LGG patients. This survey assessed the management strategies for LGG since the updated RTOG 9802 data were presented. It demonstrates no consensus in the postoperative treatment approaches for LGG. PMID:26601811

  5. Foliage responses of spruce trees to long-term low-grade sulfur dioxide deposition.

    PubMed

    Meng, F R; Bourque, C P; Belczewski, R F; Whitney, N J; Arp, P A

    1995-01-01

    Foliage on spruce trees (Picea rubens Sarg.) growing on dry SO(2) deposition zones (dry SO(2) deposition ranging from 0.5 and 8.5 S kg ha(-1) year(-1)) downwind from a SO(2) emission source was analyzed to assess chronic effects of long-term low-grade SO(2) deposition on net photosynthesis, stomatal conductance, dark respiration, stomatal antechamber wax structures, elemental concentrations in and on foliage (bulk and surficial concentrations), and types of epiphytic fungi that reside in the phylloplane. Elemental distributions on stomatal antechambers, on fungal colonies, and on smooth surfaces between stomates and fungus colonies were determined with a scanning electronic microscope (SEM) by way of X-ray scanning. It was found that net photosynthesis of newly developed spruce foliage (current-year, and 1-year-old) was not significantly affected by the local SO(2) deposition rates. Sulfur dioxide deposition, however, may have contributed to the gradual decrease in net photosynthesis with increasing needle age. Dark respiration rates were significantly higher on foliage taken from high SO(2) deposition zones. Stomatal rod-web structures deteriorated to flakes with increasing needle age and increasing SO(2) deposition. Further inspection of the needle surfaces revealed an increasing abundance of fungal colonies with increasing needle age. Many fungal taxa were isolated and identified. It was found that black yeasts responded positively, and Xylohypha pinicola responded negatively to high rates of SO(2) deposition. Surficial concentrations of elements such as P, S, K, Cl, Ca were about 10 times higher on fungal colonies than on smooth needle surfaces. Surficial Ca contents on 4 or 5-year-old needles decreased with increasing SO(2) deposition, but surficial S concentrations remained the same. In contrast, bulk foliar Ca and S concentrations increased with increasing SO(2) deposition. PMID:15091479

  6. P17MANAGEMENT AND OUTCOMES OF MIDLINE LOW-GRADE GLIOMAS

    PubMed Central

    Waqar, Mueez; Hanif, Shahid; Rathi, Nitika; Das, Kumar; Zakaria, Rasheed; Brodbelt, Andrew R.; Walker, Carol; Jenkinson, Michael

    2014-01-01

    INTRODUCTION: Low-grade gliomas (LGGs) are slow-growing and diffusely infiltrating tumours constituting 25-30% of adult gliomas. Rarely, these tumours may arise in the cerebral midline, including the thalamus, hypothalamus, tectum and brainstem. Here we present a contemporary experience with midline LGGs. METHOD: Midline LGGs were identified from a retrospective database of adult patients who received a histological diagnosis of WHO grade II glioma between 2006-2012 at a single institution. Location, radiological data and clinical outcomes were collected. IDH1 status was assessed by immunohistochemistry. RESULTS: 18 patients with midline LGGs were identified, with a median age of 45. Most received biopsy upon diagnosis, though asymptomatic patients with tectal tumours underwent active surveillance. Oligodendroglial tumours were much less common than in a comparable group of lobar tumours (6% vs 38%, Fisher's Exact Test, p = 0.007). Only one tumour was immunopositive for IDH1 (6%). Radiological diagnosis correlated with histology in only 71% of patients. Median survival of midline LGGs was 48 months (3-90 months) and radiological features such as contrast enhancement, size and radiological diagnosis did not predict survival in this cohort. Median overall survival of midline LGGs was less than lobar LGGs (Log-rank, p = 0.006), though differences became insignificant when considering only biopsied astrocytomas in both locations (Log-rank, p = 0.491). CONCLUSION: Diagnosis of midline LGGs is complicated by both limitations of biopsy and imaging. Midline tumours have a poorer prognosis compared to lobar equivalents and survival differences are probably due to the absence of significant surgical intervention in midline locations.

  7. Solidification/stabilisation of electric arc furnace waste using low grade MgO.

    PubMed

    Cubukcuoglu, B; Ouki, S K

    2012-02-01

    This study aims to evaluate the potential of low grade MgO (LGMgO) for the stabilisation/solidification (S/S) of heavy metals in steel electric arc furnace wastes. Relevant characteristics such as setting time, unconfined compressive strength (UCS) and leaching behaviour assessed by acid neutralisation capacity (ANC), monolithic and granular leaching tests were examined in light of the UK landfill Waste Acceptance Criteria (WAC) for disposal. The results demonstrated that all studied mix designs with Portland cement type 1 (CEM1) and LGMgO, CEM1-LGMgO 1:2 and 1:4 at 40% and 70% waste addition met the WAC requirements by means of UCS, initial and final setting times and consistence. Most of the ANC results met the WAC limits where the threshold pH values without acid additions were stable and between 11.9 and 12.2 at 28d. Granular leaching results indicate fixation of most of the metals at all mix ratios. An optimum ratio was obtained at CEM1-LGMgO 1:4 at 40% waste additions where none of the metals leaching exceeded the WAC limits and hence may be considered for landfill disposal. The monolithic leaching test results showed that LGMgO performed satisfactorily with respect to S/S of Zn, as the metal component present at the highest concentration level in the waste exhibited very little leaching and passed the leaching test requirement at all mix ratios studied. However, its performance with respect to Pb, Cd and Cr was less effective in reducing their leaching suggesting a higher cumulative rate under those leaching regimes. PMID:22172635

  8. Clinical value of chromosome arms 19q and 11p losses in low-grade gliomas

    PubMed Central

    Alentorn, Agustí; van Thuijl, Hinke F.; Marie, Yannick; Alshehhi, Hussa; Carpentier, Catherine; Boisselier, Blandine; Laigle-Donadey, Florence; Mokhtari, Karima; Scheinin, Ilari; Wesseling, Pieter; Ylstra, Bauke; Capelle, Laurent; Hoang-Xuan, Khê; Sanson, Marc; Delattre, Jean-Yves; Reijneveld, Jaap C.; Idbaih, Ahmed

    2014-01-01

    Background Diffuse low-grade gliomas (LGGs) form a heterogeneous subgroup of gliomas in adults. Chromosome (chr) arms 1p/19q codeletion and IDH mutation have been shown to be closely associated with oligodendroglial phenotype and better prognosis. We sought to identify relevant biomarkers in non 1p/19q codeleted LGGs. Methods We characterized a retrospective series of 126 LGGs using genomic arrays, microsatellite analysis, IDH sequencing, MGMT promoter methylation assay, and p53 expression analysis. Results Our study confirms that 1p/19q codeletion, mutually exclusive with p53 overexpression, was associated with: (i) better prognosis, (ii) oligodendroglial phenotype, (iii) MGMT promoter methylation, and (iv) IDH mutation. Interestingly, 1p/19q codeleted tumors occur in older patients at diagnosis. Our study shows that non 1p/19q codeleted LGGs can be divided in 5 main genomic subgroups: (i) 11p loss, (ii) 19q loss (iii) 7 gain, (iv) 19 gain, and (v) unclassified. In non 1p/19q codeleted LGGs, we demonstrated that (i) 11p loss is associated with astrocytoma phenotype and has an independent negative prognostic value, and (ii) 19q loss diminished the favorable prognostic value of IDH mutation. Our findings were validated in an independent cohort of 98 LGGs. Conclusion Novel genomic entities and biomarkers have been identified in non 1p/19q codeleted LGGs. Our findings may help to stratify non 1p/19q codeleted LGGs, facilitating future individualization of treatment. Further prospective studies are warranted to support our findings. PMID:24335697

  9. Learning and Memory Following Conformal Radiation Therapy for Pediatric Craniopharyngioma and Low-Grade Glioma

    SciTech Connect

    Di Pinto, Marcos; Conklin, Heather M.; Li, Chenghong; Merchant, Thomas E.

    2012-11-01

    Purpose: The primary objective of this study was to examine whether children with low-grade glioma (LGG) or craniopharyngioma had impaired learning and memory after conformal radiation therapy (CRT). A secondary objective was to determine whether children who received chemotherapy before CRT, a treatment often used to delay radiation therapy in younger children with LGG, received any protective benefit with respect to learning. Methods and Materials: Learning and memory in 57 children with LGG and 44 children with craniopharyngioma were assessed with the California Verbal Learning Test-Children's Version and the Visual-Auditory Learning tests. Learning measures were administered before CRT, 6 months later, and then yearly for a total of 5 years. Results: No decline in learning scores after CRT was observed when patients were grouped by diagnosis. For children with LGG, chemotherapy before CRT did not provide a protective effect on learning. Multiple regression analyses, which accounted for age and tumor volume and location, found that children treated with chemotherapy before CRT were at greater risk of decline on learning measures than those treated with CRT alone. Variables predictive of learning and memory decline included hydrocephalus, shunt insertion, younger age at time of treatment, female gender, and pre-CRT chemotherapy. Conclusions: This study did not reveal any impairment or decline in learning after CRT in overall aggregate learning scores. However, several important variables were found to have a significant effect on neurocognitive outcome. Specifically, chemotherapy before CRT was predictive of worse outcome on verbal learning in LGG patients. In addition, hydrocephalus and shunt insertion in craniopharyngioma were found to be predictive of worse neurocognitive outcome, suggesting a more aggressive natural history for those patients.

  10. Longitudinal Investigation of Adaptive Functioning Following Conformal Irradiation for Pediatric Craniopharyngioma and Low-Grade Glioma

    SciTech Connect

    Netson, Kelli L.; Conklin, Heather M.; Wu, Shengjie; Xiong, Xiaoping; Merchant, Thomas E.

    2013-04-01

    Purpose: Children treated for brain tumors with conformal radiation therapy experience preserved cognitive outcomes. Early evidence suggests that adaptive functions or independent-living skills may be spared. This longitudinal investigation prospectively examined intellectual and adaptive functioning during the first 5 years following irradiation for childhood craniopharyngioma and low-grade glioma (LGG). The effect of visual impairment on adaptive outcomes was investigated. Methods and Materials: Children with craniopharyngioma (n=62) and LGG (n=77) were treated using conformal or intensity modulated radiation therapy. The median age was 8.05 years (3.21-17.64 years) and 8.09 years (2.20-19.27 years), respectively. Serial cognitive evaluations including measures of intelligence quotient (IQ) and the Vineland Adaptive Behavior Scales (VABS) were conducted at preirradiation baseline, 6 months after treatment, and annually through 5 years. Five hundred eighty-eight evaluations were completed during the follow-up period. Results: Baseline assessment revealed no deficits in IQ and VABS indices for children with craniopharyngioma, with significant (P<.05) longitudinal decline in VABS Communication and Socialization indices. Clinical factors associated with more rapid decline included females and preirradiation chemotherapy (interferon). The only change in VABS Daily Living Skills correlated with IQ change (r=0.34; P=.01) in children with craniopharyngioma. Children with LGG performed below population norms (P<.05) at baseline on VABS Communication, Daily Living Indices, and the Adaptive Behavior Composite, with significant (P<.05) longitudinal decline limited to VABS Communication. Older age at irradiation was a protective factor against longitudinal decline. Severe visual impairment did not independently correlate with poorer adaptive outcomes for either tumor group. Conclusions: There was relative sparing of postirradiation functional outcomes over time in this sample. Baseline differences in functional abilities before the initiation of irradiation suggested that other factors influence functional outcomes above and beyond the effects of irradiation.

  11. Invasive low-grade papillary urothelial carcinoma: an immunohistochemical study of 26 cases.

    PubMed

    Tian, Wei; Epstein, Jonathan I

    2015-12-01

    Invasive low-grade papillary urothelial carcinoma (LGPUC) is rare. We studied the immunohistochemical (IHC) expressions of CK20, p53, E-cadherin, phosphatase and tension homolog (PTEN), and Ki-67 in both noninvasive and invasive components in 26 cases. In the noninvasive component of LGPUC, 81% showed CK20 expression, and 50% showed p53 labeling. There was a wide range of Ki-67 labeling from less than 5% to 70%. All cases had intact PTEN except 1 that showed focal clonal PTEN loss in both noninvasive and subjacent invasive components. All cases had preserved strong and diffuse E-cadherin expression in both noninvasive and invasive components. There was no significant change between the noninvasive and invasive components in the IHC labeling of these markers, although 7 (33%) of 21 cases showed decreased CK20 expression to a certain extent in the invasive component. Only 2 cases showed significant increase of p53 expression in the invasive component compared with the noninvasive component. Two cases showed increase of Ki-67 labeling from less than 5% in the noninvasive to 20% and 40%, respectively, in the invasive component. High Ki-67 labeling was present in a significant portion of invasive LGPUC cases in both noninvasive and invasive components, much higher than in previous studies of noninvasive LGPUC. Whether higher Ki-67 in these cases is associated with more aggressive disease warrants further study. In general, it is not very helpful to use immunostains in diagnosis and predicting prognosis. This is the largest series to study the IHC characteristics of this entity. PMID:26391571

  12. Anti-phosphorylated histone H3 expression in Barrett's esophagus, low-grade dysplasia, high-grade dysplasia, and adenocarcinoma.

    PubMed

    Goodarzi, Mahmoud; Correa, Arlene M; Ajani, Jaffer A; Swisher, Stephen G; Hofstetter, Wayne L; Guha, Sushovan; Deavers, Michael T; Rashid, Asif; Maru, Dipen M

    2009-12-01

    The high interobserver variability in grading dysplasia in Barrett's esophagus demands a biomarker that can be applied in routine surgical pathology practice. Immunohistochemistry for phosphorylated histone H3 is a reliable marker of identifying mitotic figures and has not been evaluated in Barrett's esophagus-associated neoplastic lesions. We retrospectively studied the expression of phosphorylated histone H3 in 88 endoscopic biopsy samples of Barrett's esophagus without dysplasia (n=19), indefinite for dysplasia (n=11), low-grade dysplasia (n=27), high-grade dysplasia (n=19), or adenocarcinoma (n=12) from a sample of 54 patients. The samples were included after consensus diagnosis of two gastrointestinal pathologists on the hematoxylin-eosin (HE)-stained sections. Anti-phosphorylated histone H3-labeled mitotic figures were counted per 10 consecutive high-power fields (HPFs) in three distinct regions: surface epithelium, upper 2/3, and lower 1/3 of the crypts. Anti-phosphorylated histone H3-labeled mitotic counts for the three compartments of the crypts and the total scores for Barrett's esophagus, indefinite for dysplasia, low-grade dysplasia, high-grade dysplasia, and adenocarcinoma were compared using the Mann-Whitney U test. For each compartment, the number of anti-phosphorylated histone H3-positive nuclei was higher in low-grade dysplasia than in Barrett's esophagus without dysplasia or indefinite for dysplasia (P<0.001), but no difference was found between Barrett's esophagus without dysplasia and indefinite for dysplasia. High-grade dysplasia biopsies had significantly more anti-phosphorylated histone H3-labeled mitotic figures in the surface epithelium than the low-grade dysplasia (P<0.001). Adenocarcinoma had higher anti-phosphorylated histone H3-labeled mitotic figures than the high-grade dysplasia (P<0.001). Our data support the previous findings of expansion of the proliferative zone and importance of surface mitotic figure in the progression of Barrett's esophagus-low-grade dysplasia-high-grade dysplasia. In addition, phosphorylated histone H3 is a potential supportive marker to histology in differentiating low-grade dysplasia from indefinite for dysplasia and high-grade dysplasia from adenocarcinoma in the mucosal biopsy samples. PMID:19734842

  13. Tertiary lymphoid structures in cancer and beyond.

    PubMed

    Dieu-Nosjean, Marie-Caroline; Goc, Jérémy; Giraldo, Nicolas A; Sautès-Fridman, Catherine; Fridman, Wolf Herman

    2014-11-01

    Tertiary lymphoid structures (TLS) are ectopic lymphoid formations found in inflamed, infected, or tumoral tissues. They exhibit all the characteristics of structures in the lymph nodes (LN) associated with the generation of an adaptive immune response, including a T cell zone with mature dendritic cells (DC), a germinal center with follicular dendritic cells (FDC) and proliferating B cells, and high endothelial venules (HEV). In this review, we discuss evidence for the roles of TLS in chronic infection, autoimmunity, and cancer, and address the question of whether TLS present beneficial or deleterious effects in these contexts. We examine the relationship between TLS in tumors and patient prognosis, and discuss the potential role of TLS in building and/or maintaining local immune responses and how this understanding may guide therapeutic interventions. PMID:25443495

  14. The lymphoid follicle variant of dermatomyositis

    PubMed Central

    Pehl, Debora; Aronica, Eleonora; Schonenberg-Meinema, Dieneke; Schneider, Udo; Heppner, Frank L.; de Visser, Marianne; Goebel, Hans H.; Stenzel, Werner

    2014-01-01

    Objective: To investigate the clinical and morphologic spectrum of early adult–onset dermatomyositis (DM), an inflammatory disease that affects small vessels of the muscle and the skin. Methods: Histologic evaluation of frozen muscle samples was employed to visualize the cellular organization of ectopic lymphoid structures in muscle biopsies obtained from 2 patients diagnosed with DM. Clinical presentation and morphologic features, as well as treatment and follow-up, were assessed and documented. Electron microscopy was used to confirm the light microscopic diagnosis of DM. Clonality analysis of B-cell populations using PCR was performed. Results: Muscle biopsy of both patients fulfilled the morphologic European Neuromuscular Centre criteria of DM. Analyses of muscle biopsy samples revealed ectopic lymphoid follicle-like structures that showed a remarkable similarity to secondary lymphoid organs (SLOs) with distinct T- and B-cell compartmentalization. Our 2 patients exhibited an atypical and mild clinical presentation and responded favorably to therapy. Conclusions: The clinical and histopathologic features of DM can be atypical, and the presence of SLOs is not inevitably linked to an unfavorable prognosis. PMID:25340071

  15. The use of dual growing rods to correct spinal deformity secondary to a low-grade spinal cord astrocytoma

    PubMed Central

    Kuhn, Elizabeth N.; Muthigi, Akhil; Frino, John; Powers, Alexander K.

    2015-01-01

    Pediatric intramedullary spinal cord astrocytomas are rare, and the majority are low grade, typically carrying a low risk of mortality, but a high risk of morbidity. Quality of life is, therefore, an important consideration in treating concomitant progressive kyphoscoliosis. Compared with fusion-based spinal stabilization, fusionless techniques may limit some complications related to early instrumentation of the developing spine. Another consideration is the timing of radiation therapy relative to both spinal maturity and spinal instrumentation. To date, there have been no reports of the use of a fusionless technique to treat spinal deformity secondary to an intramedullary spinal cord tumor. Herein, we report the use of fusionless spinal stabilization with dual growing rods in a boy with low-grade spinal cord astrocytoma after radiation therapy. PMID:26468485

  16. Tissue residency of innate lymphoid cells in lymphoid and nonlymphoid organs.

    PubMed

    Gasteiger, Georg; Fan, Xiying; Dikiy, Stanislav; Lee, Sue Y; Rudensky, Alexander Y

    2015-11-20

    Innate lymphoid cells (ILCs) contribute to barrier immunity, tissue homeostasis, and immune regulation at various anatomical sites throughout the body. How ILCs maintain their presence in lymphoid and peripheral tissues thus far has been unclear. We found that in the lymphoid and nonlymphoid organs of adult mice, ILCs are tissue-resident cells that were maintained and expanded locally under physiologic conditions, upon systemic perturbation of immune homeostasis and during acute helminth infection. However, at later time points after infection, cells from hematogenous sources helped to partially replenish the pool of resident ILCs. Thus, ILCs are maintained by self-renewal in broadly different microenvironments and physiological settings. Such an extreme "sedentary" lifestyle is consistent with the proposed roles of ILCs as sentinels and local keepers of tissue function. PMID:26472762

  17. Studies on the production of ultra-clean coal by alkali-acid leaching of low-grade coals

    SciTech Connect

    Nabeel, A.; Khan, T.A.; Sharma, D.K.

    2009-07-01

    The use of low-grade coal in thermal power stations is leading to environmental pollution due to the generation of large amounts of fly ash, bottom ash, and CO{sub 2} besides other pollutants. It is therefore important to clean the coal before using it in thermal power stations, steel plants, or cement industries etc. Physical beneficiation of coal results in only limited cleaning of coal. The increasing environmental pollution problems from the use of coal have led to the development of clean coal technologies. In fact, the clean use of coal requires the cleaning of coal to ultra low ash contents, keeping environmental norms and problems in view and the ever-growing need to increase the efficiency of coal-based power generation. Therefore this requires the adaptation of chemical cleaning techniques for cleaning the coal to obtain ultra clean coal having ultra low ash contents. Presently the reaction conditions for chemical demineralization of low-grade coal using 20% aq NaOH treatment followed by 10% H{sub 2}SO{sub 4} leaching under reflux conditions have been optimized. In order to reduce the concentration of alkali and acid used in this process of chemical demineralization of low-grade coals, stepwise, i.e., three step process of chemical demineralization of coal using 1% or 5% aq NaOH treatment followed by 1% or 5% H{sub 2}SO{sub 4} leaching has been developed, which has shown good results in demineralization of low-grade coals. In order to conserve energy, the alkali-acid leaching of coal was also carried out at room temperature, which gave good results.

  18. Upgrading of consumer characteristics of granulated solid fuel from mixture of low-grade coal and biomass

    NASA Astrophysics Data System (ADS)

    Kuzmina, J. S.; Milovanov, O. Yu; Sinelshchikov, V. A.; Sytchev, G. A.; Zaichenko, V. M.

    2015-11-01

    Effect of torrefaction on consumer characteristics of fuel pellets made of low-grade and agricultural waste is shown. Data on the volatile content, ash content, calorific value and hygroscopicity for initial pellets and pellets, heat-treated at various temperatures are presented. The experimental study of the combustion process of initial and heat-treated pellets showed that torrefaction of pellets leads to a decreasing of the ignition temperature and an increasing of the efficiency of boiler plant.

  19. Separation and Extraction of Bismuth and Manganese from Roasted Low-Grade Bismuthinite and Pyrolusite: Thermodynamic Analysis and Sulfur Fixing

    NASA Astrophysics Data System (ADS)

    Zhan, Jing; Wang, Zhi-Jian; Zhang, Chuan-Fu; Hwang, Jiann-Yang; Xia, Chu-Ping

    2015-05-01

    A new environmentally friendly technology with higher recovery of bismuth is proposed to extract bismuth from low-grade bismuthinite and co-production MnSO4 from low-grade pyrolusite. The effects of simultaneous roasting process parameters on the sulfur-fixing rate and MnSO4 formation rate are investigated. Based on the Pourbaix diagram of metal-sulfur-oxygen system, the behavior of bismuth, manganese, and associated metal elements such ferrous, copper, lead, and sulfur in the bismuthinite and pyrolusite during roasting process is analyzed. The experimental results show that Bi in the ores can be converted into bismuth oxide or oxygen bismuth sulfate, and most of Mn in the ores can react with SO2 from bismuthinite to form MnSO4, which agree with thermodynamic analysis. A maximum of sulfur-fixing rate of 98.14% and MnSO4 formation rate of 70.2% are obtained under the conditions of 1.4 for the molar ratio of MnO2 to total sulfur in mixing ores of bismuthinite and pyrolusite ( n(MnO2)/ n(S)), 923 K for the roasting temperature, 2 h for roasting time, 140 L/h for air rate, and less than 74 ?m for particle size. The ultimate recovery rate of bismuth reaches 96.25% by selective leaching of the roasted product, purification of leaching solution, and hydrolysis, which is higher than the current applied technology for the low-grade bismuthinite.

  20. Genomic analysis of diffuse pediatric low-grade gliomas identifies recurrent oncogenic truncating rearrangements in the transcription factor MYBL1

    PubMed Central

    Ramkissoon, Lori A.; Horowitz, Peleg M.; Craig, Justin M.; Ramkissoon, Shakti H.; Rich, Benjamin E.; Schumacher, Steven E.; McKenna, Aaron; Lawrence, Michael S.; Bergthold, Guillaume; Brastianos, Priscilla K.; Tabak, Barbara; Ducar, Matthew D.; Van Hummelen, Paul; MacConaill, Laura E.; Pouissant-Young, Tina; Cho, Yoon-Jae; Taha, Hala; Mahmoud, Madeha; Bowers, Daniel C.; Margraf, Linda; Tabori, Uri; Hawkins, Cynthia; Packer, Roger J.; Hill, D. Ashley; Pomeroy, Scott L.; Eberhart, Charles G.; Dunn, Ian F.; Goumnerova, Liliana; Getz, Gad; Chan, Jennifer A.; Santagata, Sandro; Hahn, William C.; Stiles, Charles D.; Ligon, Azra H.; Kieran, Mark W.; Beroukhim, Rameen; Ligon, Keith L.

    2013-01-01

    Pediatric low-grade gliomas (PLGGs) are among the most common solid tumors in children but, apart from BRAF kinase mutations or duplications in specific subclasses, few genetic driver events are known. Diffuse PLGGs comprise a set of uncommon subtypes that exhibit invasive growth and are therefore especially challenging clinically. We performed high-resolution copy-number analysis on 44 formalin-fixed, paraffin-embedded diffuse PLGGs to identify recurrent alterations. Diffuse PLGGs exhibited fewer such alterations than adult low-grade gliomas, but we identified several significantly recurrent events. The most significant event, 8q13.1 gain, was observed in 28% of diffuse astrocytoma grade IIs and resulted in partial duplication of the transcription factor MYBL1 with truncation of its C-terminal negative-regulatory domain. A similar recurrent deletion-truncation breakpoint was identified in two angiocentric gliomas in the related gene v-myb avian myeloblastosis viral oncogene homolog (MYB) on 6q23.3. Whole-genome sequencing of a MYBL1-rearranged diffuse astrocytoma grade II demonstrated MYBL1 tandem duplication and few other events. Truncated MYBL1 transcripts identified in this tumor induced anchorage-independent growth in 3T3 cells and tumor formation in nude mice. Truncated transcripts were also expressed in two additional tumors with MYBL1 partial duplication. Our results define clinically relevant molecular subclasses of diffuse PLGGs and highlight a potential role for the MYB family in the biology of low-grade gliomas. PMID:23633565

  1. Value added products with popular low grade rice varieties of Andhra Pradesh.

    PubMed

    Anitha, G; Rajyalakshmi, P

    2014-12-01

    Eight Popular Low Grade Rice Varieties (PLRVs) MTU 3626, MTU 1001, MTU 1010, MTU 4870 and NLR 145, NLR 34242, NLR 30491, NLR 34449, (developed and released by ANGR agricultural University, Andhra Pradesh) having poor cooking quality were selected for the study. ANGRAU variety BPT 5204 popularly consumed as staple rice was used as check. Eight products of traditional/commercial importance were standardized incorporating PLRVs as a major ingredient in the form of rice flour (burfi, noodles and extruded snack product and vennaundalu (butter coated balls), palathalikalu (dough rolled into strips, steamed/cooked in milk); rice semolina (instant kheer mix and instant upma mix), and flaked rice (nutritious bar). The products were evaluated for nutritional, cooking quality characteristics, consumer acceptability and shelf-life. Consumer acceptability of the PLR products was carried out with 60 farm women based on 9 point hedonic scale. Shelf-life of the products (packed in both metalized PP and PE pouches) was evaluated monthly for chemical, microbiological and sensory parameters. Energy values of control and PLR products showed no significant difference. Upon cooking, PLR Noodles showed no significant difference with water absorption and volume but more (p?

  2. Molecular fingerprinting reflects different histotypes and brain region in low grade gliomas

    PubMed Central

    2013-01-01

    Background Paediatric low-grade gliomas (LGGs) encompass a heterogeneous set of tumours of different histologies, site of lesion, age and gender distribution, growth potential, morphological features, tendency to progression and clinical course. Among LGGs, Pilocytic astrocytomas (PAs) are the most common central nervous system (CNS) tumours in children. They are typically well-circumscribed, classified as grade I by the World Health Organization (WHO), but recurrence or progressive disease occurs in about 10-20% of cases. Despite radiological and neuropathological features deemed as classic are acknowledged, PA may present a bewildering variety of microscopic features. Indeed, tumours containing both neoplastic ganglion and astrocytic cells occur at a lower frequency. Methods Gene expression profiling on 40 primary LGGs including PAs and mixed glial-neuronal tumours comprising gangliogliomas (GG) and desmoplastic infantile gangliogliomas (DIG) using Affymetrix array platform was performed. A biologically validated machine learning workflow for the identification of microarray-based gene signatures was devised. The method is based on a sparsity inducing regularization algorithm l1l2 that selects relevant variables and takes into account their correlation. The most significant genetic signatures emerging from gene-chip analysis were confirmed and validated by qPCR. Results We identified an expression signature composed by a biologically validated list of 15 genes, able to distinguish infratentorial from supratentorial LGGs. In addition, a specific molecular fingerprinting distinguishes the supratentorial PAs from those originating in the posterior fossa. Lastly, within supratentorial tumours, we also identified a gene expression pattern composed by neurogenesis, cell motility and cell growth genes which dichotomize mixed glial-neuronal tumours versus PAs. Our results reinforce previous observations about aberrant activation of the mitogen-activated protein kinase (MAPK) pathway in LGGs, but still point to an active involvement of TGF-beta signaling pathway in the PA development and pick out some hitherto unreported genes worthy of further investigation for the mixed glial-neuronal tumours. Conclusions The identification of a brain region-specific gene signature suggests that LGGs, with similar pathological features but located at different sites, may be distinguishable on the basis of cancer genetics. Molecular fingerprinting seems to be able to better sub-classify such morphologically heterogeneous tumours and it is remarkable that mixed glial-neuronal tumours are strikingly separated from PAs. PMID:23947815

  3. Advanced Energy and Water Recovery Technology from Low Grade Waste Heat

    SciTech Connect

    Dexin Wang

    2011-12-19

    The project has developed a nanoporous membrane based water vapor separation technology that can be used for recovering energy and water from low-temperature industrial waste gas streams with high moisture contents. This kind of exhaust stream is widely present in many industrial processes including the forest products and paper industry, food industry, chemical industry, cement industry, metal industry, and petroleum industry. The technology can recover not only the sensible heat but also high-purity water along with its considerable latent heat. Waste heats from such streams are considered very difficult to recover by conventional technology because of poor heat transfer performance of heat-exchanger type equipment at low temperature and moisture-related corrosion issues. During the one-year Concept Definition stage of the project, the goal was to prove the concept and technology in the laboratory and identify any issues that need to be addressed in future development of this technology. In this project, computational modeling and simulation have been conducted to investigate the performance of a nanoporous material based technology, transport membrane condenser (TMC), for waste heat and water recovery from low grade industrial flue gases. A series of theoretical and computational analyses have provided insight and support in advanced TMC design and experiments. Experimental study revealed condensation and convection through the porous membrane bundle was greatly improved over an impermeable tube bundle, because of the membrane capillary condensation mechanism and the continuous evacuation of the condensate film or droplets through the membrane pores. Convection Nusselt number in flue gas side for the porous membrane tube bundle is 50% to 80% higher than those for the impermeable stainless steel tube bundle. The condensation rates for the porous membrane tube bundle also increase 60% to 80%. Parametric study for the porous membrane tube bundle heat transfer performance was also done, which shows this heat transfer enhancement approach works well in a wide parameters range for typical flue gas conditions. Better understanding of condensing heat transfer mechanism for porous membrane heat transfer surfaces, shows higher condensation and heat transfer rates than non-permeable tubes, due to existence of the porous membrane walls. Laboratory testing has documented increased TMC performance with increased exhaust gas moisture content levels, which has exponentially increased potential markets for the product. The TMC technology can uniquely enhance waste heat recovery in tandem with water vapor recovery for many other industrial processes such as drying, wet and dry scrubber exhaust gases, dewatering, and water chilling. A new metallic substrate membrane tube development and molded TMC part fabrication method, provides an economical way to expand this technology for scaled up applications with less than 3 year payback expectation. A detailed market study shows a broad application area for this advanced waste heat and water recovery technology. A commercialization partner has been lined up to expand this technology to this big market. This research work led to new findings on the TMC working mechanism to improve its performance, better scale up design approaches, and economical part fabrication methods. Field evaluation work needs to be done to verify the TMC real world performance, and get acceptance from the industry, and pave the way for our commercial partner to put it into a much larger waste heat and waste water recovery market. This project is addressing the priority areas specified for DOE Industrial Technologies Program's (ITP's): Energy Intensive Processes (EIP) Portfolio - Waste Heat Minimization and Recovery platform.

  4. Mechanisms of organogenesis of primary lymphoid follicles.

    PubMed

    Beyer, Tilo; Meyer-Hermann, Michael

    2008-04-01

    Primary lymphoid follicles (PLFs) in secondary lymphoid tissue (SLT) of mammals are the backbone for the formation of follicular dendritic cell (FDC) networks. These are important for germinal center reactions during which affinity maturation creates optimized antibodies in adaptive immune responses. In the context of organogenesis, molecular requirements for the formation of follicles have been identified. The present study complements these findings with a simulation of the dynamics of the PLF formation, and a critical analysis of the relevant molecular interactions. In contrast to other problems of pattern formation, the homeostasis of cell populations in SLTs is not governed by a growth-death balance but by a flow equilibrium of migrating cells. The influx of cells into these tissues has been extensively studied. However, less information is available about the efflux of lymphocytes from SLTs. This study formulates the minimal requirements for cell efflux that guarantee a flow equilibrium and, thus, a stable PLF. The model predicts that in addition to already identified regulatory mechanisms, a negative regulation of the generation of FDCs is required. Furthermore, a comparison with data concerning the microanatomy of SLTs yields the conclusion that dynamical changes of the lymphatic endothelium during the formation of FDC networks are necessary to understand the genesis and maintenance of follicles. PMID:18334502

  5. Missed low-grade infection in suspected aseptic loosening has no consequences for the survival of total hip arthroplasty.

    PubMed

    Boot, Willemijn; Moojen, Dirk Jan F; Visser, Els; Lehr, A Mechteld; De Windt, Tommy S; Van Hellemondt, Gijs; Geurts, Jan; Tulp, Niek J A; Schreurs, B Wim; Burger, Bart J; Dhert, Wouter J A; Gawlitta, Debby; Vogely, H Charles

    2015-12-01

    Background and purpose - Aseptic loosening and infection are 2 of the most common causes of revision of hip implants. Antibiotic prophylaxis reduces not only the rate of revision due to infection but also the rate of revision due to aseptic loosening. This suggests under-diagnosis of infections in patients with presumed aseptic loosening and indicates that current diagnostic tools are suboptimal. In a previous multicenter study on 176 patients undergoing revision of a total hip arthroplasty due to presumed aseptic loosening, optimized diagnostics revealed that 4-13% of the patients had a low-grade infection. These infections were not treated as such, and in the current follow-up study the effect on mid- to long-term implant survival was investigated. Patients and methods - Patients were sent a 2-part questionnaire. Part A requested information about possible re-revisions of their total hip arthroplasty. Part B consisted of 3 patient-related outcome measure questionnaires (EQ5D, Oxford hip score, and visual analog scale for pain). Additional information was retrieved from the medical records. The group of patients found to have a low-grade infection was compared to those with aseptic loosening. Results - 173 of 176 patients from the original study were included. In the follow-up time between the revision surgery and the current study (mean 7.5 years), 31 patients had died. No statistically significant difference in the number of re-revisions was found between the infection group (2 out of 21) and the aseptic loosening group (13 out of 152); nor was there any significant difference in the time to re-revision. Quality of life, function, and pain were similar between the groups, but only 99 (57%) of the patients returned part B. Interpretation - Under-diagnosis of low-grade infection in conjunction with presumed aseptic revision of total hip arthroplasty may not affect implant survival. PMID:26364842

  6. Cognitive function after radiotherapy for supratentorial low-grade glioma: A North Central Cancer Treatment Group prospective study

    SciTech Connect

    Laack, Nadia N.; Brown, Paul D. . E-mail: brown.paul@mayo.edu; Ivnik, Robert J.; Furth, Alfred F. M.S.; Ballman, Karla V.; Hammack, Julie E.; Arusell, Robert M.; Shaw, Edward G.; Buckner, Jan C.

    2005-11-15

    Purpose: To evaluate the effects of cranial radiotherapy (RT) on cognitive function in patients with supratentorial low-grade glioma. Methods and Materials: Twenty adult patients with supratentorial low-grade glioma were treated with 50.4 Gy (10 patients) or 64.8 Gy (10 patients) localized RT. The patients then were evaluated with an extensive battery of psychometric tests at baseline (before RT) and at approximately 18-month intervals for as long as 5 years after completing RT. To allow patients to serve as their own controls, cognitive performance was evaluated as change in scores over time. All patients underwent at least two evaluations. Results: Baseline test scores were below average compared with age-specific norms. At the second evaluation, the groups' mean test scores were higher than their initial performances on all psychometric measures, although the improvement was not statistically significant. No changes in cognitive performance were seen during the evaluation period when test scores were analyzed by age, treatment, tumor location, tumor type, or extent of resection. Conclusions: Cognitive function was stable after RT in these patients evaluated prospectively during 3 years of follow-up. Slight improvements in some cognitive areas are consistent with practice effects attributable to increased familiarity with test procedures and content.

  7. Crystal-storing histiocytosis involving the kidney in a low-grade B-cell lymphoproliferative disorder.

    PubMed

    Sethi, Sanjeev; Cuiffo, Barry P; Pinkus, Geraldine S; Rennke, Helmut G

    2002-01-01

    Intracellular crystal formation in histiocytes in multiple myeloma and other lymphoproliferative disorders is an uncommon presentation. In all cases, crystal formation is associated with accumulation of histiocytes containing light chain or immunoglobulin inclusions, and the disorder has been termed crystal-storing histiocytosis. We report a case of crystal-storing histiocytosis affecting the kidney with prominent infiltration of the mesangium by large mononuclear and multinuclear cells that contained eosinophilic crystalline material in the setting of a low-grade B-cell lymphoproliferative disorder. The interstitium did not contain similar crystal-containing histiocytes. On electron microscopy, the mononuclear and multinuclear cells in the mesangium were filled with rhomboid and needle-shaped crystals. Immunofluorescence studies showed the material to be positive for lambda light chains but negative for kappa light chains. To our knowledge, this is the first report of crystal-storing histiocytosis involving the kidney in a low-grade B-cell lymphoproliferative disorder with an immunophenotype of a marginal zone lymphoma and of exclusive expansion of the mesangium by infiltrating histiocytes containing needle-shaped and rhomboid crystals that were positive for lambda light chains. We report this case to illustrate an unusual finding of mesangial infiltration by crystal-storing histiocytes, and we review the literature of renal involvement by crystal-storing histiocytosis and crystal deposition in lymphoproliferative disorders. PMID:11774118

  8. Group 2 innate lymphoid cells in disease.

    PubMed

    Halim, Timotheus Y F

    2016-01-01

    Group 2 innate lymphoid cells (ILC2) are now recognized as an important innate source of type-2 effector cytokines. Although initially associated with mucosal tissues, it is clear that ILC2 are present in diverse anatomical locations. The function of ILC2 at these sites is equally varied, and although ILC2 represent a relatively minor population, they are fundamentally important regulators of innate and adaptive immune processes. As such, there is much interest to understand the role of ILC2 in diseases with a type-2 inflammatory component. This review explores the known roles of ILC2 in disease, and the diseases that show associations or other strong evidence for the involvement of ILC2. PMID:26306498

  9. Benign Lymphoid Hyperplasia Presenting as Bilateral Scleral Nodules

    PubMed Central

    Cumba, Ricardo J.; Vazquez-Botet, Rene

    2015-01-01

    Purpose. To report a case of transient lymphoid hyperplasia presenting as bilateral nodular scleral mass in a young male patient. Design. Observational case report. Methods. Chart review. Causes of scleritis were considered and excluded based on detailed history, physical examination, and laboratory investigations. Results. Excisional biopsy of scleral lesions indicated lymphoid tissue. Immunohistochemical studies revealed a polyclonal population of T and B cells consistent with a benign reactive process. Conclusions. Chronic exposure of the ocular adnexa to many allergens and irritants may lead to activation of the inflammatory cascade. In severely allergic patients activation may be exponential and elicit an immune-mediated response resulting in a transient lymphoid reactive process. PMID:26421203

  10. Type 3 innate lymphoid cell depletion is mediated by TLRs in lymphoid tissues of simian immunodeficiency virus-infected macaques.

    PubMed

    Xu, Huanbin; Wang, Xiaolei; Lackner, Andrew A; Veazey, Ronald S

    2015-12-01

    Innate lymphoid cells (ILCs) type 3, also known as lymphoid tissue inducer cells, plays a major role in both the development and remodeling of organized lymphoid tissues and the maintenance of adaptive immune responses. HIV/simian immunodeficiency virus (SIV) infection causes breakdown of intestinal barriers resulting in microbial translocation, leading to systemic immune activation and disease progression. However, the effects of HIV/SIV infection on ILC3 are unknown. Here, we analyzed ILC3 from mucosal and systemic lymphoid tissues in chronically SIV-infected macaques and uninfected controls. ILC3 cells were defined and identified in macaque lymphoid tissues as non-T, non-B (lineage-negative), c-Kit(+)IL-7R?(+) (CD117(+)CD127(+)) cells. These ILC3 cells highly expressed CD90 (?63%) and aryl hydrocarbon receptor and produced IL-17 (?63%), IL-22 (?36%), and TNF-? (?72%) but did not coexpress CD4 or NK cell markers. The intestinal ILC3 cell loss correlated with the reduction of total CD4(+) T cells and T helper (Th)17 and Th22 cells in the gut during SIV infection (P < 0.001). Notably, ILC3 could be induced to undergo apoptosis by microbial products through the TLR2 (lipoteichoic acid) and/or TLR4 (LPS) pathway. These findings indicated that persistent microbial translocation may result in loss of ILC3 in lymphoid tissues in SIV-infected macaques, further contributing to the HIV-induced impairment of gut-associated lymphoid tissue structure and function, especially in mucosal tissues.-Xu, H., Wang, X., Lackner, A. A., Veazey, R. S. Type 3 innate lymphoid cell depletion is mediated by TLRs in lymphoid tissues of simian immunodeficiency virus-infected macaques. PMID:26283536

  11. Secondary Lymphoid Organs: Responding to Genetic and Environmental Cues in Ontogeny and the Immune Response1

    PubMed Central

    Ruddle, Nancy H.; Akirav, Eitan M.

    2009-01-01

    Secondary lymphoid organs (SLOs) include lymph nodes (LNs), spleen, Peyer’s patches (PPs) and mucosal tissues- the nasal associated lymphoid tissue (NALT), adenoids, and tonsils. Less discretely anatomically defined cellular accumulations include the bronchus associated lymphoid tissue (BALT), cryptopatches, and isolated lymphoid follicles (ILFs). All SLOs serve to generate immune responses and tolerance. SLO development depends on the precisely regulated expression of cooperating lymphoid chemokines and cytokines LT?, LT?, RANKL, TNF, IL-7, and perhaps IL-17. The relative importance of these factors varies between the individual lymphoid organs. Participating in the process are lymphoid tissue initiator (ltin), lymphoid tissue inducer (ltind), and lymphoid tissue organizer (lto) cells. These cells, and others that produce the crucial cytokines, maintain SLOs in the adult. Similar signals regulate the transition from inflammation to ectopic or tertiary lymphoid tissues (TLOs). PMID:19661265

  12. The optimisation of stope leaching: a laboratory investigation into the extraction of uranium from a low-grade ore

    NASA Astrophysics Data System (ADS)

    Penman, Kristina Mary

    Nuclear power continues to make an important contribution to energy production in many countries around the world. Uranium mining is the first step in the production cycle of nuclear power. In order to enable low-grade uranium ore bodies to be developed as economically viable resources, low input mining techniques, such as stope leaching, are gaining interest. This thesis presents the results of research undertaken into the optimisation of stope leaching from a low grade uranium ore. Stope leaching was simulated in the laboratory by submitting crushed ore samples to successive saturated (flooding) and unsaturated (rest period) cycles. Experiments were carried out over a 52 week period using seven different protocols. The effects of rest period and lixiviant composition on uranium extraction rates were investigated. Rest period was varied by flooding at weekly, twice weekly, 2 weekly and 4 weekly intervals.. Four different lixiviants were investigated, tap water, Fe(III) sulfate, a nutrient solution and recycled leachate. Maximum uranium extractions over 52 weeks were: 57.7% for Fe(III) sulfate lixiviant with a 2 week rest period and 57.4% for tap water with a 4 week rest period. The introduction (via the lixiviant) or development (via oxidation of accessory pyrite) of low pH and Fe(III) and sulfate-rich interstitial water is thought to have provided conditions conducive to uranium oxidation and dissolution. The 4 week rest period is considered to have provided sufficient time for microbially assisted pyrite oxidation to develop similar conditions in the interstitial water as were provided by the addition of a Fe(III) sulfate lixiviant. All other protocols lead to less than 35% uranium extraction. Shorter rest periods did not allow time for sufficient pyrite oxidation to occur and the addition of a nutrient solution buffered pH which did not favour uranium dissolution. These findings have significant implications for low-grade uranium recovery by demonstrating that extraction achieved through the use of costly oxidising agents can be attained, in the same time frame, by using tap water and decreasing the number of cycles..

  13. Hippocampal Dosimetry Predicts Neurocognitive Function Impairment After Fractionated Stereotactic Radiotherapy for Benign or Low-Grade Adult Brain Tumors

    SciTech Connect

    Gondi, Vinai; Hermann, Bruce P.; Mehta, Minesh P.; Tome, Wolfgang A.

    2013-02-01

    Purpose: To prospectively evaluate the association between hippocampal dose and long-term neurocognitive function (NCF) impairment for benign or low-grade adult brain tumors treated with fractionated stereotactic radiotherapy (FSRT). Methods and Materials: Adult patients with benign or low-grade adult brain tumors were treated with FSRT per institutional practice. No attempt was made to spare the hippocampus. NCF testing was conducted at baseline and 18 months follow-up, on a prospective clinical trial. Regression-based standardized z scores were calculated by using similar healthy control individuals evaluated at the same test-retest interval. NCF impairment was defined as a z score {<=}-1.5. After delineation of the bilateral hippocampi according to the Radiation Therapy Oncology Group contouring atlas, dose-volume histograms were generated for the left and right hippocampi and for the composite pair. Biologically equivalent doses in 2-Gy fractions (EQD{sub 2}) assuming an {alpha}/{beta} ratio of 2 Gy were computed. Fisher's exact test and binary logistic regression were used for univariate and multivariate analyses, respectively. Dose-response data were fit to a nonlinear model. Results: Of 29 patients enrolled in this trial, 18 completed both baseline and 18-month NCF testing. An EQD{sub 2} to 40% of the bilateral hippocampi >7.3 Gy was associated with impairment in Wechsler Memory Scale-III Word List (WMS-WL) delayed recall (odds ratio [OR] 19.3; p = 0.043). The association between WMS-WL delayed recall and EQD{sub 2} to 100% of the bilateral hippocampi >0.0 Gy trended to significance (OR 14.8; p = 0.068). Conclusion: EQD{sub 2} to 40% of the bilateral hippocampi greater than 7.3 Gy is associated with long-term impairment in list-learning delayed recall after FSRT for benign or low-grade adult brain tumors. Given that modern intensity-modulated radiotherapy techniques can reduce the dose to the bilateral hippocampi below this dosimetric threshold, patients should be enrolled in ongoing prospective trials of hippocampal sparing during cranial irradiation to confirm these preliminary results.

  14. Hippocampal Dosimetry Predicts Neurocognitive Function Impairment After Fractionated Stereotactic Radiotherapy for Benign or Low-Grade Adult Brain Tumors

    SciTech Connect

    Gondi, Vinai; Hermann, Bruce P.; Mehta, Minesh P.; Tome, Wolfgang A.

    2012-07-15

    Purpose: To prospectively evaluate the association between hippocampal dose and long-term neurocognitive function (NCF) impairment for benign or low-grade adult brain tumors treated with fractionated stereotactic radiotherapy (FSRT). Methods and Materials: Adult patients with benign or low-grade adult brain tumors were treated with FSRT per institutional practice. No attempt was made to spare the hippocampus. NCF testing was conducted at baseline and 18 months follow-up, on a prospective clinical trial. Regression-based standardized z scores were calculated by using similar healthy control individuals evaluated at the same test-retest interval. NCF impairment was defined as a z score {<=}-1.5. After delineation of the bilateral hippocampi according to the Radiation Therapy Oncology Group contouring atlas, dose-volume histograms were generated for the left and right hippocampi and for the composite pair. Biologically equivalent doses in 2-Gy fractions (EQD{sub 2}) assuming an {alpha}/{beta} ratio of 2 Gy were computed. Fisher's exact test and binary logistic regression were used for univariate and multivariate analyses, respectively. Dose-response data were fit to a nonlinear model. Results: Of 29 patients enrolled in this trial, 18 completed both baseline and 18-month NCF testing. An EQD{sub 2} to 40% of the bilateral hippocampi >7.3 Gy was associated with impairment in Wechsler Memory Scale-III Word List (WMS-WL) delayed recall (odds ratio [OR] 19.3; p = 0.043). The association between WMS-WL delayed recall and EQD{sub 2} to 100% of the bilateral hippocampi >0.0 Gy trended to significance (OR 14.8; p = 0.068). Conclusion: EQD{sub 2} to 40% of the bilateral hippocampi greater than 7.3 Gy is associated with long-term impairment in list-learning delayed recall after FSRT for benign or low-grade adult brain tumors. Given that modern intensity-modulated radiotherapy techniques can reduce the dose to the bilateral hippocampi below this dosimetric threshold, patients should be enrolled in ongoing prospective trials of hippocampal sparing during cranial irradiation to confirm these preliminary results.

  15. Clinical Outcomes and Late Endocrine, Neurocognitive, and Visual Profiles of Proton Radiation for Pediatric Low-Grade Gliomas

    SciTech Connect

    Greenberger, Benjamin A.; Pulsifer, Margaret B.; Ebb, David H.; MacDonald, Shannon M.; Jones, Robin M.; Butler, William E.; Huang, Mary S.; Marcus, Karen J.; Oberg, Jennifer A.; Tarbell, Nancy J.; Yock, Torunn I.

    2014-08-01

    Purpose/Objective(s): Primary low-grade gliomas are common brain tumors of childhood, many of which require radiation therapy (RT) as definitive treatment. Increased conformality of RT could decrease the incidence and severity of late effects. We report our experience with 32 pediatric patients treated with proton RT. Methods and Materials: Thirty-two pediatric patients with low-grade gliomas of the brain or spinal cord were treated with proton RT from 1995 to 2007. Sixteen patients received at least 1 regimen of chemotherapy before definitive RT. The median radiation dose was 52.2 Gy{sub RBE} (48.6-54 Gy{sub RBE}). Results: The median age at treatment was 11.0 years (range, 2.7-21.5 years), with a median follow-up time of 7.6 years (range, 3.2-18.2 years). The 6-year and 8-year rates of progression-free survival were 89.7% and 82.8%, respectively, with an 8-year overall survival of 100%. For the subset of patients who received serial neurocognitive testing, there were no significant declines in Full-Scale Intelligence Quotient (P=.80), with a median neurocognitive testing interval of 4.5 years (range, 1.2-8.1 years) from baseline to follow-up, but subgroup analysis indicated some significant decline in neurocognitive outcomes for young children (<7 years) and those with significant dose to the left temporal lobe/hippocampus. The incidence of endocrinopathy correlated with a mean dose of ?40 Gy{sub RBE} to the hypothalamus, pituitary, or optic chiasm. Stabilization or improvement of visual acuity was achieved in 83.3% of patients at risk for radiation-induced injury to the optic pathways. Conclusions: This report of late effects in children with low-grade gliomas after proton RT is encouraging. Proton RT appears to be associated with good clinical outcome, especially when the tumor location allows for increased sparing of the left temporal lobe, hippocampus, and hypothalamic-pituitary axis.

  16. A comparative contrast perception phantom image of brain CT study between high-grade and low-grade liquid crystal displays (LCDs) in electronic medical charts.

    PubMed

    Yoshimura, Kumiko; Shimamoto, Kazuhiro; Ikeda, Mitsuru; Ichikawa, Katsuhiro; Naganawa, Shinji

    2011-04-01

    The purpose of this study was to clarify whether non-medical-grade liquid crystal displays (LCDs) are acceptable for the soft-copy reading of brain CTs. Four kinds of color LCDs with different image quality levels were used: medical-grade LCD, low-grade general LCD calibrated with the grayscale display function (GSDF), low-grade general LCD calibrated with gamma 2.2 and a notebook personal computer display panel. In Osirix's standard window setting for brain CTs, the average CT values of brain parenchyma in 100 cases were correlated with a grayscale level ranging from 71 to 91 in a 256-step grayscale. At these gray levels, the image contrast on the two low-grade LCDs calibrated with gamma 2.2 was higher than that on the medical-grade LCD. Eleven healthy volunteers participated in the contrast perception study, which used electronically generated target phantom images that simulated subtle abnormalities with a low or high attenuation difference in brain parenchyma. The three low-grade LCDs showed correct response rates and reaction times that were superior to those of the medical-grade display. The grayscale calibrations, GSDF or gamma 2.2, are likely to be more critical than the display grade, suggesting that the use of a low-grade LCD may be acceptable in the image contrast of brain CT. PMID:20591711

  17. Prescribing Optimal Nutrition and Physical Activity as “First-Line” Interventions for Best Practice Management of Chronic Low-Grade Inflammation Associated with Osteoarthritis: Evidence Synthesis

    PubMed Central

    Dean, Elizabeth; Gormsen Hansen, Rasmus

    2012-01-01

    Low-grade inflammation and oxidative stress underlie chronic osteoarthritis. Although best-practice guidelines for osteoarthritis emphasize self-management including weight control and exercise, the role of lifestyle behavior change to address chronic low-grade inflammation has not been a focus of first-line management. This paper synthesizes the literature that supports the idea in which the Western diet and inactivity are proinflammatory, whereas a plant-based diet and activity are anti-inflammatory, and that low-grade inflammation and oxidative stress underlying osteoarthritis often coexist with lifestyle-related risk factors and conditions. We provide evidence-informed recommendations on how lifestyle behavior change can be integrated into “first-line” osteoarthritis management through teamwork and targeted evidence-based interventions. Healthy living can be exploited to reduce inflammation, oxidative stress, and related pain and disability and improve patients' overall health. This approach aligns with evidence-based best practice and holds the promise of eliminating or reducing chronic low-grade inflammation, attenuating disease progression, reducing weight, maximizing health by minimizing a patient's risk or manifestations of other lifestyle-related conditions hallmarked by chronic low-grade inflammation, and reducing the need for medications and surgery. This approach provides an informed cost effective basis for prevention, potential reversal, and management of signs and symptoms of chronic osteoarthritis and has implications for research paradigms in osteoarthritis. PMID:23346399

  18. Prognostic factors in low-grade supratentorial astrocytomas: a uni-multivariate statistical analysis in 76 surgically treated adult patients.

    PubMed

    Nicolato, A; Gerosa, M A; Fina, P; Iuzzolino, P; Giorgiutti, F; Bricolo, A

    1995-09-01

    A retrospective uni-multivariate statistical analysis was performed on 32 prognostic factors to investigate their importance in predicting survival in a series of 76 adult patients with low-grade supratentorial astrocytomas treated over a 13-year period. The end point used for this study was the length of survival. The median survival time was 40 months. Overall actuarial survival at 2, 5, and 10 years was 69%, 38%, and 22%, respectively. Radical resection of the neoformation, a higher preoperative Karnofsky performance status (KPS) score, and an age younger than 50 years are strongly correlated with survival; postoperative radiotherapy appears to be associated with increased survival only in patients under 50 years of age. PMID:8545771

  19. Histone deacetylase inhibitors and epigenetic regulation in lymphoid malignancies.

    PubMed

    Markozashvili, Diana; Ribrag, Vincent; Vassetzky, Yegor S

    2015-12-01

    A vast majority of lymphomas and leukaemias are results of translocations. These translocations produce various genetic and epigenetic changes that lead to oncogenesis. This opens an opportunity to use a relatively new class of anti-cancer agents, inhibitors of histone deacetylases (HDACi) to target lymphoid malignancies. Surprisingly, the rational basis for treatment of lymphomas with HDACi is far from clear, although some positive results have been obtained. Here we analyze the effect of histone deacetylase (HDAC) inhibitors on lymphoid malignancies. PMID:26423245

  20. Impact of 14-day bed rest on serum adipokines and low-grade inflammation in younger and older adults.

    PubMed

    Jurdana, Mihaela; Jenko-Pražnikar, Zala; Mohorko, Nina; Petelin, Ana; Jakus, Tadeja; Šimuni?, Boštjan; Pišot, Rado

    2015-12-01

    Ageing and inactivity both contribute to systemic inflammation, but the effects of inactivity on inflammation in healthy elderly individuals have not been elucidated. We hypothesised that 14-day bed rest could affect the pro- and anti-inflammatory markers in young subjects differently than in older adults. A short-term 14-day horizontal bed rest study (BR14) has been used as a model of inactivity in two groups of healthy male volunteers: 7 aged 18-30 years (young) and 16 aged 55-65 years (older adults). The effects of inactivity on inflammation were compared. Key low-grade inflammation mediators, tumour necrosis factor ? (TNF-?), interleukin-6 (IL-6), visfatin, resistin, and anti-inflammatory adiponectin were measured in fasting serum samples, collected at baseline (BDC) and post BR14. Young responded to BR14 by increasing serum visfatin and resistin while older adults responded to BR14 by increasing IL-6 and TNF-?. In addition, serum adiponectin increased in all participants. Data from correlation analysis demonstrated positive association between ? serum visfatin and ? IL-6 in both groups, while ? serum adiponectin was negatively associated with ? TNF-? in young and positively associated with ? resistin in the older adults. As little as 14 days of complete physical inactivity (BR14) negatively affected markers of low-grade inflammation in both groups, but the inflammation after BR14 was more pronounced in older adults. The effect of BR14 on IL-6 and resistin differed between young and older adults. Inflammatory responses to BR14 in older adults differed from those reported in the literature for obese or subjects in pathological states, suggesting potentially different mechanisms between inactivity- and obesity-induced inflammations. PMID:26564239

  1. Factors Influencing Neurocognitive Outcomes in Young Patients With Benign and Low-Grade Brain Tumors Treated With Stereotactic Conformal Radiotherapy

    SciTech Connect

    Jalali, Rakesh; Mallick, Indranil; Dutta, Debnarayan

    2010-07-15

    Purpose: To present the effect of radiotherapy doses to different volumes of normal structures on neurocognitive outcomes in young patients with benign and low-grade brain tumors treated prospectively with stereotactic conformal radiotherapy (SCRT). Methods and Materials: Twenty-eight patients (median age, 13 years) with residual/progressive brain tumors (10 craniopharyngioma, 8 cerebellar astrocytoma, 6 optic pathway glioma and 4 cerebral low-grade glioma) were treated with SCRT to a dose of 54 Gy in 30 fractions over 6 weeks. Prospective neuropsychological assessments were done at baseline before RT and at subsequent follow-up examinations. The change in intelligence quotient (IQ) scores was correlated with various factors, including dose-volume to normal structures. Results: Although the overall mean full-scale IQ (FSIQ) at baseline before RT remained unchanged at 2-year follow-up after SCRT, one third of patients did show a >10% decline in FSIQ as compared with baseline. Logistic regression analysis demonstrated that patients aged <15 years had a significantly higher chance of developing a >10% drop in FSIQ than older patients (53% vs. 10%, p = 0.03). Dosimetric comparison in patients showing a >10% decline vs. patients showing a <10% decline in IQ revealed that patients receiving >43.2 Gy to >13% of volume of the left temporal lobe were the ones to show a significant drop in FSIQ (p = 0.048). Radiotherapy doses to other normal structures, including supratentorial brain, right temporal lobe, and frontal lobes, did not reveal any significant correlation. Conclusion: Our prospectively collected dosimetric data show younger age and radiotherapy doses to left temporal lobe to be predictors of neurocognitive decline, and may well be used as possible dose constraints for high-precision radiotherapy planning.

  2. Low-grade Metamorphism of Cretaceous Basins from the Colombian Andes: Testing Tectonic Models with Paleogeothermal Gradients

    NASA Astrophysics Data System (ADS)

    Mejia, D.; Cardona, A.; Collo, G.; Zapata, S.; Leon, S.

    2014-12-01

    The Cretaceous tectonic evolution of the northern Andes include the formation of several sedimentary basins interpreted formed in rift or arc-back-arc settings. Such basin were formed in association with the subduction of the Pacific plate, the opening of the Caribbean or the growth of allocthonous oceanic arcs and were extensively deformed in the Late Cretaceous initiation of Andean orogeny. Tectonic models for these basins have been mainly postulated from the stratigraphic interpretations or regional characterization of the tectonomagmatic affinity of volcanic rocks. Less attention have been paid on the pontential to evaluate the tectonic history from the characterization of the paleothermal record recorded in diagenetic and very low grade metamorphic evolution of the pelitic rock. In the Central Cordillera outcrops two main Albian Cretaceous units: the Abejorral formation which is characterized by a pelitic succession with minor sandstones beds and the Quebradagrande Complex that include intercalations of volcanic and pelitic rocks. Such relatively deep accumulation environment is contemporaneous with shallow carbonates and pelitic succesions in the Eastern Cordillera of the Colombian Andes. Rocks from the Eastern Cordillera that have been widely characterized due to their relation with petroleum exploration are characterized limited development of cleavage and well defined sedimentary structures. In contrast field field relations have shown that the central Cordillera units are characterized by the development of a well defined slaty cleavage, limited development of quartz veins. Published vitrinite constraints from the Eastern Cordillera have revealed very high burial temperatures which is compatible with proposed extensional setting during burial and accumulation. New illite and chlorite mineralogical characterization is being obtained on the Abejorral and Quebradagrande formation in order to test if the low grade metamorphic record still preserved the high geothermal gradient expected from an accumulation environment and the quick transition from extension to compression.

  3. NR4A1 is associated with chronic low-grade inflammation in patients with type 2 diabetes.

    PubMed

    Huang, Qi; Xue, Junli; Zou, Runmei; Cai, Li; Chen, Jing; Sun, Li; Dai, Zhe; Yang, Fan; Xu, Yancheng

    2014-11-01

    Type 2 diabetes (T2D) is a common disorder characterized by chronic low-grade inflammation. In the present study, the expression levels of nuclear receptor subfamily 4 group A member 1 (NR4A1) and the correlation with inflammatory cytokine production and free fatty acids (FFAs) in patients with T2D and healthy participants were investigated. NR4A1 expression levels in peripheral blood mononuclear cells (PBMCs) from patients with T2D (n=30) and healthy controls (n=34) were analyzed. In addition, the levels of fasting blood glucose (FBG), fasting plasma insulin (FIN), FFAs, total cholesterol (TC), triglyceride (TG), high-density lipoprotein-cholesterol (HDL-C) and low-density lipoprotein-cholesterol (LDL-C) were analyzed, and the homeostasis model assessment (HOMA) was used to estimate the insulin resistance (IR). Additionally, PBMCs from healthy subjects were cultured with or without 250 ?M palmitic acid (PA). Levels of NR4A1, tumor necrosis factor-? (TNF-?) and interleukin-6 (IL-6) in the PBMCs were also analyzed. The basal expression levels of NR4A1, TNF-? and IL-6 were higher in the T2D patients when compared with the controls. In addition, the levels of FFAs, TG and LDL-C, as well as the HOMA-IR, were higher in T2D patients. Furthermore, NR4A1 expression was demonstrated to positively correlate with the HOMA-IR and the levels of FFAs, TNF-?, IL-6, FIN and FBG. Furthermore, 250 ?M PA stimulation was shown to increase NR4A1 expression and the secretion of inflammatory cytokines in the cultured PBMCs. Therefore, increased NR4A1 expression levels are correlated with a chronic low-grade inflammatory state and the disorder of lipid metabolism in patients with T2D. PMID:25289075

  4. Membrane-based osmotic heat engine with organic solvent for enhanced power generation from low-grade heat.

    PubMed

    Shaulsky, Evyatar; Boo, Chanhee; Lin, Shihong; Elimelech, Menachem

    2015-05-01

    We present a hybrid osmotic heat engine (OHE) system that uses draw solutions with an organic solvent for enhanced thermal separation efficiency. The hybrid OHE system produces sustainable energy by combining pressure-retarded osmosis (PRO) as a power generation stage and membrane distillation (MD) utilizing low-grade heat as a separation stage. While previous OHE systems employed aqueous electrolyte draw solutions, using methanol as a solvent is advantageous because methanol is highly volatile and has a lower heat capacity and enthalpy of vaporization than water. Hence, the thermal separation efficiency of a draw solution with methanol would be higher than that of an aqueous draw solution. In this study, we evaluated the performance of LiCl-methanol as a potential draw solution for a PRO-MD hybrid OHE system. The membrane transport properties as well as performance with LiCl-methanol draw solution were evaluated using thin-film composite (TFC) PRO membranes and compared to the results obtained with a LiCl-water draw solution. Experimental PRO methanol flux and maximum projected power density of 47.1 L m(-2) h(-1) and 72.1 W m(-2), respectively, were achieved with a 3 M LiCl-methanol draw solution. The overall efficiency of the hybrid OHE system was modeled by coupling the mass and energy flows between the thermal separation (MD) and power generation (PRO) stages under conditions with and without heat recovery. The modeling results demonstrate higher OHE energy efficiency with the LiCl-methanol draw solution compared to that with the LiCl-water draw solution under practical operating conditions (i.e., heat recovery<90%). We discuss the implications of the results for converting low-grade heat to power. PMID:25839239

  5. The beneficial role of anti-inflammatory dietary ingredients in attenuating markers of chronic low-grade inflammation in aging.

    PubMed

    Panickar, Kiran S; Jewell, Dennis E

    2015-08-01

    Aging in humans is associated with chronic low-grade inflammation (systemic), and this condition is sometimes referred to as "inflammaging". In general, canines also age similarly to humans, and such aging is associated with a decline in mobility, joint problems, weakened muscles and bones, reduced lean body mass, cancer, increased dermatological problems, decline in cognitive ability, reduced energy, decreased immune function, decreased renal function, and urinary incontinence. Each of these conditions is also associated with an increase in pro-inflammatory cytokines. An inflammatory state characterized by an increase in pro-inflammatory markers including but not restricted to tumor necrosis factor-?, interleukin-6, IL-1?, and C-reactive protein (CRP) is believed to contribute to or worsen a general decline in biological mechanisms responsible for physical function with aging. Nutritional management of inflammation in aging dogs is important in maintaining health. In particular, natural botanicals have bioactive components that appear to have robust anti-inflammatory effects and, when included in the diet, may contribute to a reduction in inflammation. While there are scientific data to support the anti-inflammatory effects and the efficacy of such bioactive molecules from botanicals, the clinical data are limited and more studies are needed to validate the efficacy of these ingredients. This review will summarize the role of dietary ingredients in reducing inflammatory molecules as well as review the evidence available to support the role of diet and nutrition in reducing chronic low-grade systemic inflammation in animal and human studies with a special reference to canines, where possible. PMID:26124060

  6. T- wave axis deviation is associated with biomarkers of low-grade inflammation. Findings from the MOLI-SANI study.

    PubMed

    Bonaccio, Marialaura; Di Castelnuovo, Augusto; Rago, Livia; de Curtis, Amalia; Assanelli, Deodato; Badilini, Fabio; Vaglio, Martino; Costanzo, Simona; Persichillo, Mariarosaria; Cerletti, Chiara; Donati, Maria Benedetta; de Gaetano, Giovanni; Iacoviello, Licia

    2015-11-25

    T-wave axis deviation (TDev) may help identifying subjects at risk for major cardiac events and mortality, but the pathogenesis of TDev is not well established; in particular, the possible association between TDev and inflammation is unexplored and unknown. We aimed at investigating the association between low-grade inflammation and TDev abnormalities by conducting a cross-sectional analysis on 17,507 subjects apparently free from coronary heart and haematological diseases enrolled in the MOLI-SANI study. TDev was measured from a standard 12-lead resting electrocardiogram. High sensitivity (Hs) C-reactive protein (CRP), leukocyte (WBC) and platelet counts, neutrophil or granulocyte to lymphocyte ratios were used as markers of inflammation. In multivariable model subjects reporting high CRP levels had higher odds of having borderline and abnormal TDev (OR=1.70; 95?%CI: 1.53-1.90 and OR=1.72; 95?%CI: 1.23-2.41, respectively); the association was still significant, although reduced, after controlling for body mass index (OR=1.17; 95?%CI: 1.05-1.32, for borderline and OR=1.46; 95?%CI: 1.03-2.08, for abnormal). Similarly, higher neutrophil or granulocyte to lymphocyte ratios were associated with increased odds of having abnormal TDev. Neither platelet nor leukocyte counts were associated with abnormal TDev. The relationship between CRP with TDev abnormalities was significantly stronger in men, in non- obese or normotensive individuals, and in those without metabolic syndrome. In conclusion, C-reactive protein and some cellular biomarkers of inflammation such as granulocyte or neutrophil to lymphocyte ratios were independently associated with abnormal TDev, especially in subjects at low CVD risk. These results suggest that a low-grade inflammation likely contributes to the pathogenesis of T- wave axis deviation. PMID:26155907

  7. Long-Term Results of Brachytherapy With Temporary Iodine-125 Seeds in Children With Low-Grade Gliomas

    SciTech Connect

    Korinthenberg, Rudolf; Neuburger, Daniela; Trippel, Michael; Ostertag, Christoph; Nikkhah, Guido

    2011-03-15

    Purpose: To retrospectively review the results of temporary I-125 brachytherapy in 94 children and adolescents with low-grade glioma. Methods and Materials: Treatment was performed in progressive tumors roughly spherical in shape with a diameter of up to 5 cm, including 79 astrocytomas, 5 oligodendrogliomas, 4 oligoastrocytomas, 1 ependymoma, and 5 other tumors. Location was suprasellar/chiasmal in 44, thalamic/basal ganglia in 18, hemispheric in 15, midbrain/pineal region in 13, and lower brainstem in 3. Initially, 8% of patients were free of symptoms, 47% were symptomatic but not disabled, and 30% were slightly, 6% moderately, and 3% severely disabled. Results: 5- and 10-year survival was 97% and 92%. The response to I-125 brachytherapy over the long term was estimated after a median observation period of 38.4 (range, 6.4-171.0) months. At that time, 4 patients were in complete, 27 in partial, and 18 in objective remission; 15 showed stable and 30 progressive tumors. Treatment results did not correlate with age, sex, histology, tumor size, location, or demarcation of the tumor. Secondary treatment became necessary in 36 patients, including 19 who underwent repeated I-125 brachytherapy. At final follow-up, the number of symptom-free patients had risen to 21%. Thirty-eight percent showed symptoms without functional impairment, 19% were slightly and 11% moderately disabled, and only 4% were severely disabled. Conclusions: Response rates similar to those of conventional radiotherapy or chemotherapy can be anticipated with I-125 brachytherapy in tumors of the appropriate size and shape. We believe it to be a useful contribution to the treatment of low-grade gliomas in children.

  8. Membrane-Based Osmotic Heat Engine with Organic Solvent for Enhanced Power Generation from Low-Grade Heat

    SciTech Connect

    Shaulsky, E; Boo, C; Lin, SH; Elimelech, M

    2015-05-05

    We present a hybrid osmotic heat engine (OHE) system that uses draw solutions with an organic solvent for enhanced thermal separation efficiency. The hybrid OHE system produces sustainable energy by combining pressure-retarded osmosis (PRO) as a power generation stage and membrane distillation (MD) utilizing low-grade heat as a separation stage. While previous OHE systems employed aqueous electrolyte draw solutions, using methanol as a solvent is advantageous because methanol is highly volatile and has a lower heat capacity and enthalpy of vaporization than water. Hence, the thermal separation efficiency of a draw solution with methanol would be higher than that of an aqueous draw solution. In this study, we evaluated the performance of LiCl-methanol as a potential draw solution for a PRO-MD hybrid OHE system. The membrane transport properties as well as performance with LiCl methanol draw solution were evaluated using thin-film composite (TFC) PRO membranes and compared to the results obtained with a LiCl water draw solution. Experimental PRO methanol flux and maximum projected power density of 47.1 L m(-2) h(-1) and 72.1 W m(-2), respectively, were achieved with a 3 M LiCl-methanol draw solution. The overall efficiency of the hybrid OHE system was modeled by coupling the mass and energy flows between the thermal separation (MD) and power generation (PRO) stages under conditions with and without heat recovery. The modeling results demonstrate higher ORE energy efficiency with the LiCl methanol draw solution compared to that with the LiCl water draw solution under practical operating conditions (i.e., heat recovery <90%). We discuss the implications of the results for converting low-grade heat to power.

  9. Long-term survival and functional status of patients with low-grade astrocytoma of spinal cord

    SciTech Connect

    Robinson, Clifford G.; Prayson, Richard A.; Hahn, Joseph F.; Kalfas, Iain H.; Whitfield, Melvin D.; Lee, S.-Y.; Suh, John H. . E-mail: suhj@ccf.org

    2005-09-01

    Purpose: To determine survival and changes in neurologic function and Karnofsky performance status (KPS) in a series of patients treated for low-grade astrocytoma of the spinal cord during the past two decades. Methods: This study consisted of 14 patients with pathologically confirmed low-grade astrocytoma of the spinal cord who were treated between 1980 and 2003. All patients underwent decompressive laminectomy followed by biopsy (n = 7), subtotal resection (n = 6), or gross total resection (n = 1). Ten patients underwent postoperative radiotherapy (median total dose 50 Gy in 28 fractions). The overall survival, progression-free survival, and changes in neurologic function and KPS were measured. Results: The overall survival rate at 5, 10, and 20 years was 100%, 75%, and 60%, respectively. The progression-free survival rate at 5, 10, and 20 years was 93%, 80%, and 60%, respectively. Neither overall survival nor progression-free survival was clearly correlated with any patient, tumor, or treatment factors. Neurologic function and KPS worsened after surgery in 8 (57%) of 14 and 9 (69%) of 13 patients, respectively. At a mean follow-up of 10.2 years, neurologic function had stabilized or improved in 8 (73%) of 11 remaining patients, but the KPS had worsened in 5 (50%) of 10. Most patients who were employed before surgery were working at last follow-up. Conclusion: Patients who undergo gross total resection of their tumor may be followed closely. Patients who undergo limited resection should continue to receive postoperative RT (50.4 Gy in 1.8-Gy fractions). The functional measures should be routinely evaluated to appreciate the treatment outcomes.

  10. Humanized hemato-lymphoid system mice.

    PubMed

    Theocharides, Alexandre P A; Rongvaux, Anthony; Fritsch, Kristin; Flavell, Richard A; Manz, Markus G

    2016-01-01

    Over the last decades, incrementally improved xenograft mouse models, supporting the engraftment and development of a human hemato-lymphoid system, have been developed and now represent an important research tool in the field. The most significant contributions made by means of humanized mice are the identification of normal and leukemic hematopoietic stem cells, the characterization of the human hematopoietic hierarchy, and their use as preclinical therapy models for malignant hematopoietic disorders. Successful xenotransplantation depends on three major factors: tolerance by the mouse host, correct spatial location, and appropriately cross-reactive support and interaction factors such as cytokines and major histocompatibility complex molecules. Each of these can be modified. Experimental approaches include the genetic modification of mice to faithfully express human support factors as non-cross-reactive cytokines, to create free niche space, the co-transplantation of human mesenchymal stem cells, the implantation of humanized ossicles or other stroma, and the implantation of human thymic tissue. Besides the source of hematopoietic cells, the conditioning regimen and the route of transplantation also significantly affect human hematopoietic development in vivo. We review here the achievements, most recent developments, and the remaining challenges in the generation of pre-clinically-predictive systems for human hematology and immunology, closely resembling the human situation in a xenogeneic mouse environment. PMID:26721800

  11. Long-term treatment of residual or recurrent low-grade endometrial stromal sarcoma with aromatase inhibitors: A report of two cases and a review of the literature

    PubMed Central

    RYU, HYEWON; CHOI, YOON-SEOK; SONG, IK-CHAN; YUN, HWAN-JUNG; JO, DEOG-YEON; KIM, SAMYONG; LEE, HYO JIN

    2015-01-01

    Endometrial stromal sarcoma (ESS) occurs rarely and accounts for only 0.2% of all uterine malignancies. ESS usually expresses estrogen and progesterone receptors, and is regarded as hormone-sensitive. Due to the rarity of these tumors, there are only few case series on the use of aromatase inhibitors in the treatment of low-grade ESS. The present study reports the cases of two patients with residual or recurrent low-grade ESS who experienced long-term disease-free survival following treatment with letrozole. The study also reviews the literature with regard to the data on aromatase inhibitors used in patients with low-grade ESS. In total, 30 patients with recurrent or residual low-grade ESS who were treated with aromatase inhibitors were identified, including the present cases. Among the 30 patients, the overall response rate of advanced low-grade ESS to aromatase inhibitors was 77.4% (complete response, 25.8%; partial response, 51.6%) and the disease control rate was 90.3%. The response rate of first-line treatment was similar to that of second-line therapy or higher (84.6 vs. 72.2%; P=0.453). Duration of aromatase inhibitor treatment ranged from 1.5 to 168 months (median, 26.5 months). The aromatase inhibitors showed minimal adverse effects. In conclusion, aromatase inhibitors, particularly third-generation drugs, are a well-tolerated class of medications that are effective in the treatment of advanced low-grade ESS, with a favorable toxicity profile. PMID:26722331

  12. The Lymphoid Variant of Hypereosinophilic Syndrome

    PubMed Central

    Lefèvre, Guillaume; Copin, Marie-Christine; Staumont-Sallé, Delphine; Avenel-Audran, Martine; Aubert, Hélène; Taieb, Alain; Salles, Gilles; Maisonneuve, Hervé; Ghomari, Kamel; Ackerman, Félix; Legrand, Fanny; Baruchel, André; Launay, David; Terriou, Louis; Leclech, Christian; Khouatra, Chahera; Morati-Hafsaoui, Chafika; Labalette, Myriam; Borie, Raphäel; Cotton, François; Gouellec, Noémie Le; Morschhauser, Franck; Trauet, Jacques; Roche-Lestienne, Catherine; Capron, Monique; Hatron, Pierre-Yves; Prin, Lionel; Kahn, Jean-Emmanuel

    2014-01-01

    Abstract The CD3-CD4+ aberrant T-cell phenotype is the most described in the lymphoid variant of hypereosinophilic syndrome (L-HES), a rare form of HES. Only a few cases have been reported, and data for these patients are scarce. To describe characteristics and outcome of CD3-CD4+ L-HES patients, we conducted a national multicentric retrospective study in the French Eosinophil Network. All patients who met the recent criteria of hypereosinophilia (HE) or HES and who had a persistent CD3-CD4+ T-cell subset on blood T-cell phenotyping were included. Clinical and laboratory data were retrospectively collected by chart review. CD3-CD4+ L-HES was diagnosed in 21 patients (13 females, median age 42 years [range, 5–75 yr]). Half (48%) had a history of atopic manifestations. Clinical manifestations were dermatologic (81%), superficial adenopathy (62%), rheumatologic (29%), gastrointestinal (24%), pulmonary (19%), neurologic (10%), and cardiovascular (5%). The median absolute CD3-CD4+ T-cell count was 0.35?G/L (range, 0.01–28.3), with a clonal TCR?? rearrangement in 76% of patients. The mean follow-up duration after HES diagnosis was 6.9 ± 5.1 years. All patients treated with oral corticosteroids (CS) (n?=?18) obtained remission, but 16 required CS-sparing treatments. One patient had a T-cell lymphoma 8 years after diagnosis, and 3 deaths occurred during follow-up. In conclusion, clinical manifestations related to CD3-CD4+ T cell-associated L-HES are not limited to skin, and can involve all tissue or organs affected in other types of HE. Contrary to FIP1L1-PDGFRA chronic eosinophilic leukemia patients, CS are always effective in these patients, but CS-sparing treatments are frequently needed. The occurrence of T-cell lymphoma, although rare in our cohort, remains a major concern during follow-up. PMID:25398061

  13. Total lymphoid irradiation for multiple sclerosis

    SciTech Connect

    Devereux, C.K.; Vidaver, R.; Hafstein, M.P.; Zito, G.; Troiano, R.; Dowling, P.C.; Cook, S.D.

    1988-01-01

    Although chemical immunosuppression has been shown to benefit patients with chronic progressive multiple sclerosis (MS), it appears that chemotherapy has an appreciable oncogenic potential in patients with multiple sclerosis. Accordingly, we developed a modified total lymphoid irradiation (TLI) regimen designed to reduce toxicity and applied it to a randomized double blind trial of TLI or sham irradiation in MS. Standard TLI regimens were modified to reduce dose to 1,980 rad, lowering the superior mantle margin to midway between the thyroid cartilage and angle of the mandible (to avert xerostomia) and the lower margin of the mantle field to the inferior margin of L1 (to reduce gastrointestinal toxicity by dividing abdominal radiation between mantle and inverted Y), limiting spinal cord dose to 1,000 rad by custom-made spine blocks in the mantle and upper 2 cm of inverted Y fields, and also protecting the left kidney even if part of the spleen were shielded. Clinical efficacy was documented by the less frequent functional scale deterioration of 20 TLI treated patients with chronic progressive MS compared to to 20 sham-irradiated progressive MS patients after 12 months (16% versus 55%, p less than 0.03), 18 months (28% versus 63%, p less than 0.03), and 24 months (44% versus 74%, N.S.). Therapeutic benefit during 3 years follow-up was related to the reduction in lymphocyte count 3 months post-irradiation (p less than 0.02). Toxicity was generally mild and transient, with no instance of xerostomia, pericarditis, herpes zoster, or need to terminate treatment in TLI patients. However, menopause was induced in 2 patients and staphylococcal pneumonia in one.

  14. Organic Fluids and Passive Cooling in a Supercritical Rankine Cycle for Power Generation from Low Grade Heat Sources

    NASA Astrophysics Data System (ADS)

    Vidhi, Rachana

    Low grade heat sources have a large amount of thermal energy content. Due to low temperature, the conventional power generation technologies result in lower efficiency and hence cannot be used. In order to efficiently generate power, alternate methods need to be used. In this study, a supercritical organic Rankine cycle was used for heat source temperatures varying from 125°C to 200°C. Organic refrigerants with zero ozone depletion potential and their mixtures were selected as working fluid for this study while the cooling water temperature was changed from 10-25°C. Operating pressure of the cycle has been optimized for each fluid at every heat source temperature to obtain the highest thermal efficiency. Energy and exergy efficiencies of the thermodynamic cycle have been obtained as a function of heat source temperature. Efficiency of a thermodynamic cycle depends significantly on the sink temperature. At areas where water cooling is not available and ambient air temperature is high, efficient power generation from low grade heat sources may be a challenge. Use of passive cooling systems coupled with the condenser was studied, so that lower sink temperatures could be obtained. Underground tunnels, buried at a depth of few meters, were used as earth-air-heat-exchanger (EAHE) through which hot ambient air was passed. It was observed that the air temperature could be lowered by 5-10°C in the EAHE. Vertical pipes were used to lower the temperature of water by 5°C by passing it underground. Nocturnal cooling of stored water has been studied that can be used to cool the working fluid in the thermodynamic cycle. It was observed that the water temperature can be lowered by 10-20°C during the night when it is allowed to cool. The amount of water lost was calculated and was found to be approximately 0.1% over 10 days. The different passive cooling systems were studied separately and their effects on the efficiency of the thermodynamic cycle were investigated. They were then combined into a novel condenser design that uses passive cooling technology to cool the working fluid that was selected in the first part of the study. It was observed that the efficiency of the cycle improved by 2-2.5% when passive cooling system was used.

  15. Characterization of nasal cavity-associated lymphoid tissue in ducks.

    PubMed

    Kang, Haihong; Yan, Mengfei; Yu, Qinghua; Yang, Qian

    2014-05-01

    The nasal mucosa is involved in immune defense, as it is the first barrier for pathogens entering the body through the respiratory tract. The nasal cavity-associated lymphoid tissue (NALT), which is found in the mucosa of the nasal cavity, is considered to be the main mucosal immune inductive site in the upper respiratory tract. NALT has been found in humans and many mammals, which contributes to local and systemic immune responses after intranasal vaccination. However, there are very few data on NALT in avian species, especially waterfowl. For this study, histological sections of the nasal cavities of Cherry Valley ducks were used to examine the anatomical location and histological characteristics of NALT. The results showed that several lymphoid aggregates are present in the ventral wall of the nasal cavity near the choanal cleft, whereas several more lymphoid aggregates were located on both sides of the nasal septum. In addition, randomly distributed intraepithelial lymphocytes and isolated lymphoid follicles were observed in the regio respiratoria of the nasal cavity. There were also a few lymphoid aggregates located in the lamina propria of the regio vestibularis, which was covered with a stratified squamous epithelium. This study focused on the anatomic and histological characteristics of the nasal cavity of the duck and performed a systemic overview of NALT. This will be beneficial for further understanding of immune mechanisms after nasal vaccination and the development of effective nasal vaccines for waterfowls. PMID:24585532

  16. The development of high-grade serous carcinoma from atypical proliferative (borderline) serous tumors and low-grade micropapillary serous carcinoma: a morphologic and molecular genetic analysis.

    PubMed

    Dehari, Reiko; Kurman, Robert J; Logani, Sanjay; Shih, Ie-Ming

    2007-07-01

    Recently, we have proposed a model for the development of ovarian surface epithelial tumors. In this model, all histologic types of surface epithelial tumors are divided into 2 categories designated type I and type II which correspond to 2 pathways of tumorigenesis. Type I tumors include low-grade serous carcinoma, mucinous carcinoma, endometrioid carcinoma, malignant Brenner tumor, and clear cell carcinoma which develop slowly in a stepwise fashion from well-recognized precursors, namely atypical proliferative (borderline) tumors. Type II tumors are high-grade, rapidly growing tumors that typically have spread beyond the ovaries at presentation. They include high-grade serous carcinoma ("moderately" and "poorly" differentiated), malignant mixed mesodermal tumors (carcinosarcomas), and undifferentiated carcinoma. These tumors are rarely associated with morphologically recognizable precursor lesions and it has been proposed that they develop "de novo" from ovarian inclusion cysts. This model implies that the pathogenesis of type I and type II tumors are separate and independent but it is not clear whether some type II tumors develop from type I tumors. In this study, we attempted to address this issue by determining the clonality of 6 cases of high-grade serous carcinomas that were closely associated with atypical proliferative serous (borderline) tumors and invasive low-grade micropapillary serous carcinomas. We reviewed 210 ovarian serous tumors from the surgical pathology files of the Johns Hopkins Hospital and identified 3 high-grade serous carcinoma that were directly associated with atypical proliferative serous (borderline) tumors and 3 that were associated with invasive low-grade micropapillary serous carcinomas. A morphologic continuum between the high-grade carcinoma and the low-grade tumors was observed in 4 cases whereas in the remaining 2 cases the high-grade and low-grade components were separate. Mutational analyses for KRAS, BRAF, and p53 genes were performed on microdissected samples from the high-grade and low-grade tumor areas for each case. All 6 tumors demonstrated wild-type BRAF and p53 genes. Only 2 of the 6 cases were informative from a molecular genetic standpoint. In those 2 cases we found the same mutations of KRAS in both the atypical proliferative serous (borderline) tumor and the high-grade serous carcinoma component of the tumor, indicating a clonal relationship. The above results suggest that the majority of high-grade and low-grade carcinomas develop independently but in rare cases, a high-grade serous carcinoma may arise from an atypical proliferative serous (borderline) tumor. PMID:17592266

  17. Pollution control and metal resource recovery for low grade automobile shredder residue: a mechanism, bioavailability and risk assessment.

    PubMed

    Singh, Jiwan; Lee, Byeong-Kyu

    2015-04-01

    Automobile shredder residue (ASR) is considered as hazardous waste in Japan and European countries due to presence of heavy metals. This study was carried on the extraction characteristics of heavy metals (Mn, Fe, Ni, and Cr) from automobile shredder residue (ASR). The effects of pH, temperature, particle size, and liquid/solid ratio (L/S) on the extraction of heavy metals were investigated. The recovery rate of Mn, Fe, Ni, and Cr increased with increasing extraction temperature and L/S ratio. The lowest pH 2, the highest L/S ratio, and the smallest particle size showed the highest recovery of heavy metals from ASR. The highest recovery rates were in the following order: Mn > Ni > Cr > Fe. Reduction of mobility factor for the heavy metals was observed in all the size fractions after the recovery. The results of the kinetic analysis for various experimental conditions supported that the reaction rate of the recovery process followed a second order reaction model (R(2) ? 0.95). The high availability of water-soluble fractions of Mn, Fe, Ni, and Cr from the low grade ASR could be potential hazards to the environment. Bioavailability and toxicity risk of heavy metals reduced significantly with pH 2 of distilled water. However, water is a cost-effective extracting agent for the recovery of heavy metals and it could be useful for reducing the toxicity of ASR. PMID:25690411

  18. An Efficient Technology for Smelting Low Grade Bismuth-Lead Concentrate: Oxygen-Rich Side Blow Process

    NASA Astrophysics Data System (ADS)

    Chen, Lin; Hao, Zhandong; Yang, Tianzu; Xiao, Hui; Liu, Weifeng; Zhang, Duchao; Bin, Shu; Bin, Wanda

    2015-09-01

    An efficient technology for low-grade bismuth-lead concentrate smelting is reported. In the process, two oxygen-rich side blow furnaces (OSBF) are used for oxidative smelting of the concentrate and reductive smelting of the oxidized slag from the upstream furnace, respectively. Slags are collected from the OSBFs by certain intervals during an operation period and analyzed by inductively coupled plasma-atomic emission spectrum, x-ray diffraction and scanning electron microscopy. Analysis for the oxidized slag revealed that spherical or oval metallic inclusions with sizes range from submicron to 40 ?m in diameter are randomly embedded in the glassy matrix. On the one hand, the metal content of the inclusions is close to that of the bottom metal alloy, indicating metal inclusions are physically entrained in the oxidized slag. On the other hand, metal inclusions are not identified in the reduced slag, disclosing the strong metal-slag separation ability of the OSBF. The bismuth content of the reduced slag is about 0.05 wt.%, which is 6-10 times lower than that of the traditional pyrometallurgical processes.

  19. Cellular automata (CA) simulation of the interaction of vehicle flows and pedestrian crossings on urban low-grade uncontrolled roads

    NASA Astrophysics Data System (ADS)

    Chen, Qun; Wang, Yan

    2015-08-01

    This paper discusses the interaction of vehicle flows and pedestrian crossings on uncontrolled low-grade roads or branch roads without separating barriers in cities where pedestrians may cross randomly from any location on both sides of the road. The rules governing pedestrian street crossings are analyzed, and a cellular automata (CA) model to simulate the interaction of vehicle flows and pedestrian crossings is proposed. The influence of the interaction of vehicle flows and pedestrian crossings on the volume and travel time of the vehicle flow and the average wait time for pedestrians to cross is investigated through simulations. The main results of the simulation are as follows: (1) The vehicle flow volume decreases because of interruption from pedestrian crossings, but a small number of pedestrian crossings do not cause a significant delay to vehicles. (2) If there are many pedestrian crossings, slow vehicles will have little chance to accelerate, causing travel time to increase and the vehicle flow volume to decrease. (3) The average wait time for pedestrians to cross generally decreases with a decrease in vehicle flow volume and also decreases with an increase in the number of pedestrian crossings. (4) Temporal and spatial characteristics of vehicle flows and pedestrian flows and some interesting phenomena such as "crossing belt" and "vehicle belt" are found through the simulations.

  20. Delay effects in the response of low-grade gliomas to radiotherapy: a mathematical model and its therapeutical implications.

    PubMed

    Pérez-García, Víctor M; Bogdanska, Magdalena; Martínez-González, Alicia; Belmonte-Beitia, Juan; Schucht, Philippe; Pérez-Romasanta, Luis A

    2015-09-01

    Low-grade gliomas (LGGs) are a group of primary brain tumours usually encountered in young patient populations. These tumours represent a difficult challenge because many patients survive a decade or more and may be at a higher risk for treatment-related complications. Specifically, radiation therapy is known to have a relevant effect on survival but in many cases it can be deferred to avoid side effects while maintaining its beneficial effect. However, a subset of LGGs manifests more aggressive clinical behaviour and requires earlier intervention. Moreover, the effectiveness of radiotherapy depends on the tumour characteristics. Recently Pallud et al. (2012. Neuro-Oncology, 14: , 1-10) studied patients with LGGs treated with radiation therapy as a first-line therapy and obtained the counterintuitive result that tumours with a fast response to the therapy had a worse prognosis than those responding late. In this paper, we construct a mathematical model describing the basic facts of glioma progression and response to radiotherapy. The model provides also an explanation to the observations of Pallud et al. Using the model, we propose radiation fractionation schemes that might be therapeutically useful by helping to evaluate tumour malignancy while at the same time reducing the toxicity associated to the treatment. PMID:24860116

  1. Use of mesophilic and thermophilic bacteria for the improvement of copper extraction from a low-grade ore

    NASA Astrophysics Data System (ADS)

    Darezereshki, E.; Schaffie, M.; Lotfalian, M.; Seiedbaghery, S. A.; Ranjbar, M.

    2011-04-01

    Bioleaching was examined for copper extraction from a low grade ore using mesophilic and moderate thermophilic bacteria. Five equal size columns were used for the leaching of the ore. Sulfuric acid solution with a flow rate of 3.12 L·m-2·h-1 and pH 1.5 passed through each column continuously for 90 d. In the first and the second column, bioleaching was performed without agglomeration of the ore and on the agglomerated ore, respectively. 28wt% of the copper was extracted in the first column after 40 d, while this figure was 38wt% in the second column. After 90 d, however, the overall extractions were almost the same for both of them. Bioleaching with mesophilic bacteria was performed in the third column without agglomeration of the ore and in the fourth column on the agglomerated ore. After 40 d, copper extractions in the third and the fourth columns were 62wt% and 70wt%, respectively. Copper extractions were 75wt% for both the columns after 90 d. For the last column, bioleaching was performed with moderate thermophilic bacteria and agglomerated ore. Copper extractions were 80wt% and 85wt% after 40 and 90 d, respectively. It was concluded that crushing and agglomeration of the ore using bacteria could enhance the copper extraction considerably.

  2. Recovery of valuable metals from a low-grade nickel ore using an ammonium sulfate roasting-leaching process

    NASA Astrophysics Data System (ADS)

    Liu, Xin-wei; Feng, Ya-li; Li, Hao-ran; Yang, Zhi-chao; Cai, Zhen-lei

    2012-05-01

    Metal leaching from a low-grade nickel ore was investigated using an ammonium sulfate roasting-water leaching process. The nickel ore was mixed with ammonium sulfate, followed by roasting and finally leaching with water. During the process the effects of the amount of ammonium sulfate, roasting temperature, and roasting time on the leaching recovery of metal elements were analyzed. The optimum technological parameters were determined as follows: ammonium sulfate/ore ratio, 0.8 g/g; roasting temperature, 400°C; and roasting time, 2 h. Under the optimum condition the leaching recoveries of Ni, Cu, Fe, and Mg were 83.48%, 76.24%, 56.43%, and 62.15%, respectively. Furthermore, the dissolution kinetics of Ni and Mg from the nickel ore was studied. The apparent activation energies for the leaching reaction of Ni and Mg were 18.782 and 10.038 kJ·mol-1, which were consistent with the values of diffusion control reactions. Therefore, the results demonstrated that the leaching recoveries of Ni and Mg were controlled by diffusion.

  3. How Commonly Is the Diagnosis of Gastric Low Grade Dysplasia Upgraded following Endoscopic Resection? A Meta-Analysis

    PubMed Central

    Zhao, Guangfeng; Xue, Meng; Hu, Yingying; Lai, Sanchuan; Chen, Shujie; Wang, Liangjing

    2015-01-01

    Gastric dysplasia is a well-known precancerous lesion. Though the diagnosis of gastric low grade dysplasia (LGD) is generally made from endoscopic forceps biopsy (EFB), the accuracy is doubtful after numerous EFB-proven gastric LGD were upgraded to gastric high grade dysplasia (HGD) or even carcinoma (CA) by further diagnostic test with the procedure of endoscopic resection (ER). We aimed to evaluate the upgraded diagnosis rate (UDR) and the risk factors by ER in EFB-proven gastric LGD lesions. Two investigators independently searched studies reporting the UDR by ER in EFB-proven gastric LGD lesions from databases and analyzed the overall UDR, HGD-UDR and CA-UDR. The pooled UDR by ER in EFB-proven gastric LGD lesions was 25.0% (95% CI, 20.2%-29.8%), made up of HGD-UDR and CA-UDR by rates of 16.7% (95% CI, 12.8%-20.6%) and 6.9% (95% CI, 4.2%-9.6%) respectively. Lesion size larger than 2 cm, surface with depression and nodularity under endoscopic examinations were the major risk factors associated with UDR. In conclusion, one quarter of EFB-proven gastric LGD lesions will be diagnosed as advanced lesions, including gastric HGD (16.7%) and gastric CA (6.9%) by ER. The diagnosis of those LGD lesions with an endoscopic diameter larger than 2cm, and depressed or nodular surface are more likely to be upgraded after ER. PMID:26182344

  4. Cortical and Standard Trajectory Pedicle Screw Fixation Techniques in Stabilizing Multisegment Lumbar Spine with Low Grade Spondylolisthesis

    PubMed Central

    ?nceo?lu, Serkan

    2015-01-01

    Background Cortical screw (CS) fixation has been recently proposed as an alternative to the standard pedicle screw (PS) fixation technique. Biomechanical studies involving individual screw pullout and single level motion segment stabilization showed comparable performance of both techniques. However, whether this new fixation technique can be applied to the stabilization of multilevel lumbar segments with significant destabilization has been unclear. Purpose To compare stability of CS fixation to the traditional PS fixation in an unstable 3 level spondylolisthesis model. Study Design This is a biomechanical study comparing cortical trajectory pedicle screw fixation to traditional trajectory pedicle screw fixation in an unstable cadaveric model using nondestructive flexibility test. Methods Eight fresh frozen cadaveric lumbar spines (T12- S1) were obtained. After intact baseline testing, a 3-level lowgrade spondylolisthesis was simulated at the L1-4. Each specimen was instrumented with the PS and CS fixation systems. Standard nondestructive flexibility test was performed. Range of motion at each level was compared between the constructs during flexion-extension, lateral bending, and axial rotation. Results The destabilization model significantly increased the ROM in all planes (P<0.05). Both fixation techniques provided significant reduction in the ROM (P<0.05). There was no significant difference in ROM between the PS and CS groups in any of planes (P>0.05). Conclusions Cortical trajectory pedicle screw fixation provided stabilization to multilevel lumbar segment with low-grade spondylolisthesis comparable to the standard trajectory pedicle screw construct. PMID:26484009

  5. IL-22 regulates lymphoid chemokine production and assembly of tertiary lymphoid organs

    PubMed Central

    Barone, Francesca; Nayar, Saba; Campos, Joana; Cloake, Thomas; Withers, David R.; Toellner, Kai-Michael; Zhang, Yang; Fouser, Lynette; Fisher, Benjamin; Bowman, Simon; Rangel-Moreno, Javier; Garcia-Hernandez, Maria de la Luz; Randall, Troy D.; Lucchesi, Davide; Bombardieri, Michele; Pitzalis, Costantino; Luther, Sanjiv A.; Buckley, Christopher D.

    2015-01-01

    The series of events leading to tertiary lymphoid organ (TLO) formation in mucosal organs following tissue damage remain unclear. Using a virus-induced model of autoantibody formation in the salivary glands of adult mice, we demonstrate that IL-22 provides a mechanistic link between mucosal infection, B-cell recruitment, and humoral autoimmunity. IL-22 receptor engagement is necessary and sufficient to promote differential expression of chemokine (C-X-C motif) ligand 12 and chemokine (C-X-C motif) ligand 13 in epithelial and fibroblastic stromal cells that, in turn, is pivotal for B-cell recruitment and organization of the TLOs. Accordingly, genetic and therapeutic blockade of IL-22 impairs and reverses TLO formation and autoantibody production. Our work highlights a critical role for IL-22 in TLO-induced pathology and provides a rationale for the use of IL-22–blocking agents in B-cell–mediated autoimmune conditions. PMID:26286991

  6. CCL21 Expression Pattern of Human Secondary Lymphoid Organ Stroma Is Conserved in Inflammatory Lesions with Lymphoid Neogenesis

    PubMed Central

    Manzo, Antonio; Bugatti, Serena; Caporali, Roberto; Prevo, Remko; Jackson, David G.; Uguccioni, Mariagrazia; Buckley, Christopher D.; Montecucco, Carlomaurizio; Pitzalis, Costantino

    2007-01-01

    CCL21 is a homeostatic lymphoid chemokine instrumental in the recruitment and organization of T cells and dendritic cells into lymphoid T areas. In human secondary lymphoid organs (SLOs), CCL21 is produced by cells distributed throughout the T zone, whereas high endothelial venules (HEVs) lack CCL21 mRNA. A critical question remains whether the development of ectopic lymphoid tissue (ELT) in chronic inflammation recapitulates the features of SLOs. Thus, we systematically investigated in situ the cellular sources of CCL21 in SLOs and ELTs in several human diseases characterized by lymphoid neogenesis. By in situ hybridization and the use of combinatorial cell markers, we show that CCL21-producing vessels in inflamed tissues systematically display typical markers of lymphatic vessels, whereas, as in SLOs, ectopic HEVs do not synthesize detectable levels of CCL21. We also provide first-time evidence that a common pattern of CCL21 expression by CD45-negative myofibroblast-like cells localized in extra-HEV position and organized in a fibroblastic reticular network similarly characterizes human SLOs and organized ELTs. Altogether, our results demonstrate that in humans the pattern of CCL21 production in SLOs is maintained during inflammation and that the phenotypic and functional properties of stromal cells, found in SLO T-cell areas, are reproduced at ectopic sites. PMID:17982129

  7. Introduction of transplantation tolerance after total lymphoid irradiation: cellular mechanisms

    SciTech Connect

    Strober, S.; King, D.P.; Gottlieb, M.; Hoppe, R.T.; Kaplan, H.S.

    1981-04-01

    High-dose fractionated total lymphoid irradiation (TLI) is a safe, routine regimen used to treat patients with lymphoid malignancies. Although few side effects are associated with the regimen, a profound suppression of cell-mediated immunity is observed for several years after therapy, as judged by both in vivo and in vitro assays. A profound immunosuppression has also been observed in mice and rats given TLI. Recently, we have achieved similar results using TLI in nonmatched bone marrow transplantation in outbred dogs. The experimental work in animals and underlying cellular mechanisms are reviewed here.

  8. Researchers Discover Low-Grade Nonwoven Cotton Picks Up 50 Times Own Weight of Oil | ACS in the News http://acsinthenews.org/?p=2263[9/29/2014 9:20:33 AM

    E-print Network

    Rock, Chris

    Researchers Discover Low-Grade Nonwoven Cotton Picks Up 50 Times Own Weight of Oil | ACS Cotton Picks Up 50 Times Own Weight of Oil Posted on July 31, 2014 Seeing is Bead-Lieving Scientists visits) "Researchers discover low-grade nonwoven cotton picks up 50 times own weight of oil" July 31

  9. Semiautomatic segmentation and follow-up of multicomponent low-grade tumors in longitudinal brain MRI studies

    SciTech Connect

    Weizman, Lior; Sira, Liat Ben; Joskowicz, Leo; Rubin, Daniel L.; Yeom, Kristen W.; Constantini, Shlomi; Shofty, Ben; Bashat, Dafna Ben

    2014-05-15

    Purpose: Tracking the progression of low grade tumors (LGTs) is a challenging task, due to their slow growth rate and associated complex internal tumor components, such as heterogeneous enhancement, hemorrhage, and cysts. In this paper, the authors show a semiautomatic method to reliably track the volume of LGTs and the evolution of their internal components in longitudinal MRI scans. Methods: The authors' method utilizes a spatiotemporal evolution modeling of the tumor and its internal components. Tumor components gray level parameters are estimated from the follow-up scan itself, obviating temporal normalization of gray levels. The tumor delineation procedure effectively incorporates internal classification of the baseline scan in the time-series as prior data to segment and classify a series of follow-up scans. The authors applied their method to 40 MRI scans of ten patients, acquired at two different institutions. Two types of LGTs were included: Optic pathway gliomas and thalamic astrocytomas. For each scan, a “gold standard” was obtained manually by experienced radiologists. The method is evaluated versus the gold standard with three measures: gross total volume error, total surface distance, and reliability of tracking tumor components evolution. Results: Compared to the gold standard the authors' method exhibits a mean Dice similarity volumetric measure of 86.58% and a mean surface distance error of 0.25 mm. In terms of its reliability in tracking the evolution of the internal components, the method exhibits strong positive correlation with the gold standard. Conclusions: The authors' method provides accurate and repeatable delineation of the tumor and its internal components, which is essential for therapy assessment of LGTs. Reliable tracking of internal tumor components over time is novel and potentially will be useful to streamline and improve follow-up of brain tumors, with indolent growth and behavior.

  10. p53 protein in low-grade astrocytomas: a study with long-term follow-up.

    PubMed Central

    Iuzzolino, P.; Ghimenton, C.; Nicolato, A.; Giorgiutti, F.; Fina, P.; Doglioni, C.; Barbareschi, M.

    1994-01-01

    The immunohistochemical expression of p53 protein (p53) was examined in 52 patients out of a series of 66 patients with low-grade astrocytomas with long-term follow-up. All patients were also evaluated for several clinical and histological features, among which only preoperative Karnofsky score and the extent of surgery were statistically significant parameters to predict outcome on multivariate analysis. p53 accumulation was seen in 46.1% of patients, with a wide range of percentage of positive cells. Median survival for p53-positive and p53-negative patients was 41 and 37 months respectively. The survival curves of p53-positive and -negative patients were not statistically different. However, the curves showed a trend towards a more aggressive course in p53-positive patients beginning 3-4 years after surgery. Five years after diagnosis the survival estimate with the Kaplan-Meier method was 21.2% for patients with p53-positive tumours and 45.9% for patients with p53-negative tumours. This trend is not due to different distribution of major clinical prognostic factors (age, incomplete resection or Karnofsky status). The trend could be related to the time needed by the p53-positive clone to outgrow the rest of the p53-negative neoplastic cell population. This hypothesis is further supported by the fact that the five recurrences which were surgically removed (one anaplastic astrocytoma and four glioblastomas) derived from p53-positive tumours and were themselves intensely p53 positive. Images Figure 1 PMID:8123492

  11. Positive fibroblast growth factor receptor 3 immunoreactivity is associated with low-grade non-invasive urothelial bladder cancer

    PubMed Central

    POYET, CÉDRIC; HERMANNS, THOMAS; ZHONG, QING; DRESCHER, EVA; EBERLI, DANIEL; BURGER, MAXIMILIAN; HOFSTAEDTER, FERDINAND; HARTMANN, ARNDT; STÖHR, ROBERT; ZWARTHOFF, ELLEN C.; SULSER, TULLIO; WILD, PETER J.

    2015-01-01

    In addition to conventional clinicopathological parameters, molecular markers are also required in order to predict the course of disease in patients with urothelial bladder cancer (BC). Little is known about fibroblast growth factor receptor 3 (FGFR3) immunoreactivity and the clinical significance it may possess with regard to BC. The present study aimed to investigate the immunoreactivity of FGFR3 in primary urothelial bladder tumours, with regard to clinicopathological features and FGFR3 mutation status. Tissue microarrays were used to immunohistochemically analyse FGFR3 expression in 255 primary, unselected patients with BC. FGFR3 mutations were detected using SNaPshot analysis. Positive FGFR3 immunoreactivity was identified in 113/207 analysable cases (54.6%), and was significantly associated with FGFR3 mutation (P<0.001), low tumour stage (P<0.001), low histological grade (P<0.001) and a papillary growth pattern (P<0.001). Positive FGFR3 immunostaining (P=0.002) and FGFR3 mutation (P=0.002) were found to be significantly associated with increased disease-specific survival following univariate analysis, demonstrating a median follow-up period of 75 months. Using multivariate analyses, FGFR3 immunoreactivity was found not to be independent of classical pathological parameters. Immunohistochemical expression of FGFR3 is an early occurrence during the carcinogenesis of papillary non-invasive BC. The presence of FGFR3 immunoreactivity in non-invasive papillary urothelial carcinomas may be utilised as an indicator of tumours possessing low-grade features and good prognosis. PMID:26722237

  12. Hydrometallurgical recovery of heavy metals from low grade automobile shredder residue (ASR): An application of advanced Fenton process (AFP).

    PubMed

    Singh, Jiwan; Lee, Byeong-Kyu

    2015-09-15

    To investigate the leaching and recovery of heavy metals from low-grade automobile shredder residue (ASR), the effects of nitric acid (HNO3) and hydrogen peroxide (H2O2) concentrations, liquid/solid (L/S) ratio, leaching temperature and ASR particle size fractions on the heavy metal leaching rate were determined. The heavy metals were recovered by fractional precipitation and advanced Fenton process (AFP) at different pHs. The toxicity characteristic leaching procedure (TCLP) test was also performed in the residue remaining after heavy metal leaching to evaluate the potential toxicity of ASR. The heavy metal leaching efficiency was increased with increasing HNO3 and H2O2 concentrations, L/S ratio and temperature. The heavy metal leaching efficiencies were maximized in the lowest ASR size fraction at 303 K and L/S ratio of 100 mL/g. The kinetic study showed that the metal leaching was best represented by a second-order reaction model, with a value of R(2) > 0.99 for all selected heavy metals. The determined activation energy (kJ/mol) was 21.61, 17.10, 12.15, 34.50, 13.07 and 11.45 for Zn, Fe, Ni, Pb, Cd and Cr, respectively. In the final residue, the concentrations of Cd, Cr and Pb were under their threshold limits in all ASR size fractions. Hydrometallurgical metal recovery was greatly increased by AFP up to 99.96% for Zn, 99.97% for Fe, 95.62% for Ni, 99.62% for Pb, 94.11% for Cd and 96.79% for Cr. AFP is highly recommended for the recovery of leached metals from solution even at low concentrations. PMID:26143080

  13. Evidence for Chronic Low-Grade Systemic Inflammation in Individuals with Agoraphobia from a Population-Based Prospective Study

    PubMed Central

    Wagner, En-Young N.; Wagner, Jan T.; Glaus, Jennifer; Vandeleur, Caroline L.; Castelao, Enrique; Strippoli, Marie-Pierre F.; Vollenweider, Peter; Preisig, Martin; von Känel, Roland

    2015-01-01

    Background Anxiety disorders have been linked to an increased risk of incident coronary heart disease in which inflammation plays a key pathogenic role. To date, no studies have looked at the association between proinflammatory markers and agoraphobia. Methods In a random Swiss population sample of 2890 persons (35-67 years, 53% women), we diagnosed a total of 124 individuals (4.3%) with agoraphobia using a validated semi-structured psychiatric interview. We also assessed socioeconomic status, traditional cardiovascular risk factors (i.e., body mass index, hypertension, blood glucose levels, total cholesterol/high-density lipoprotein-cholesterol ratio), and health behaviors (i.e., smoking, alcohol consumption, and physical activity), and other major psychiatric diseases (other anxiety disorders, major depressive disorder, drug dependence) which were treated as covariates in linear regression models. Circulating levels of inflammatory markers, statistically controlled for the baseline demographic and health-related measures, were determined at a mean follow-up of 5.5 ± 0.4 years (range 4.7 – 8.5). Results Individuals with agoraphobia had significantly higher follow-up levels of C-reactive protein (p = 0.007) and tumor-necrosis-factor-? (p = 0.042) as well as lower levels of the cardioprotective marker adiponectin (p = 0.032) than their non-agoraphobic counterparts. Follow-up levels of interleukin (IL)-1? and IL-6 did not significantly differ between the two groups. Conclusions Our results suggest an increase in chronic low-grade inflammation in agoraphobia over time. Such a mechanism might link agoraphobia with an increased risk of atherosclerosis and coronary heart disease, and needs to be tested in longitudinal studies. PMID:25875094

  14. Resecting diffuse low-grade gliomas to the boundaries of brain functions: a new concept in surgical neuro-oncology.

    PubMed

    Duffau, H

    2015-12-01

    The traditional dilemma making surgery for diffuse low-grade gliomas (DLGGs) challenging is underlain by the need to optimize tumor resection in order to significantly increase survival versus the risk of permanent neurological morbidity. Development of neuroimaging led neurosurgeons to achieve tumorectomy according to the oncological limits provided by preoperative or intraoperative structural and metabolic imaging. However, this principle is not coherent, neither with the infiltrative nature of DLGGs nor with the limited resolution of current neuroimaging. Indeed, despite technical advances, MRI still underestimates the actual spatial extent of gliomas, since tumoral cells are present several millimeters to centimeters beyond the area of signal abnormalities. Furthermore, cortical and subcortical structures may be still crucial for brain functions despite their invasion by this diffuse tumoral disease. Finally, the lack of reliability of functional MRI has also been demonstrated. Therefore, to talk about "maximal safe resection" based upon neuroimaging is a non-sense, because oncological MRI does not show the tumor and functional MRI does not show critical neural pathways. This review proposes an original concept in neuro-oncological surgery, i.e. to resect DLGG to the boundaries of brain functions, thanks to intraoperative electrical mapping performed in awake patients. This paradigmatic shift from image-guided resection to functional mapping-guided resection, based upon an accurate study of brain connectomics and neuroplasticity in each patient throughout tumor removal has permitted to solve the classical dilemma, by increasing both survival and quality of life in DLGG patients. With this in mind, brain surgeons should also be neuroscientists. PMID:25907410

  15. Design and Numerical Simulation of a Symbiotic Thermoelectric Power Generation System Fed by a Low-Grade Heat Source

    NASA Astrophysics Data System (ADS)

    Faraji, Amir Yadollah; Singh, Randeep; Mochizuki, Masataka; Akbarzadeh, Aliakbar

    2014-06-01

    All liquid heating systems, including solar thermal collectors and fossil-fueled heaters, are designed to convert low-temperature liquid to high-temperature liquid. In the presence of low- and high-temperature fluids, temperature differences can be created across thermoelectric devices to produce electricity so that the heat dissipated from the hot side of a thermoelectric device will be absorbed by the cold liquid and this preheated liquid enters the heating cycle and increases the efficiency of the heater. Consequently, because of the avoidance of waste heat on the thermoelectric hot side, the efficiency of heat-to-electricity conversion with this configuration is better than that of conventional thermoelectric power generation systems. This research aims to design and analyze a thermoelectric power generation system based on the concept described above and using a low-grade heat source. This system may be used to generate electricity either in direct conjunction with any renewable energy source which produces hot water (solar thermal collectors) or using waste hot water from industry. The concept of this system is designated "ELEGANT," an acronym from "Efficient Liquid-based Electricity Generation Apparatus iNside Thermoelectrics." The first design of ELEGANT comprised three rectangular aluminum channels, used to conduct warm and cold fluids over the surfaces of several commercially available thermoelectric generator (TEG) modules sandwiched between the channels. In this study, an ELEGANT with 24 TEG modules, referred to as ELEGANT-24, has been designed. Twenty-four modules was the best match to the specific geometry of the proposed ELEGANT. The thermoelectric modules in ELEGANT-24 were electrically connected in series, and the maximum output power was modeled. A numerical model has been developed, which provides steady-state forecasts of the electrical output of ELEGANT-24 for different inlet fluid temperatures.

  16. Significance of a minor high-grade component in a low-grade noninvasive papillary urothelial carcinoma of bladder.

    PubMed

    Reis, Leonardo O; Taheri, Diana; Chaux, Alcides; Guner, Gunes; Mendoza Rodriguez, Maria A; Bivalacqua, Trinity J; Schoenberg, Mark P; Epstein, Jonathan I; Netto, George J

    2016-01-01

    To assess the clinicopathological features and prognostic significance of the presence of 5% or less high-grade component in otherwise low-grade noninvasive bladder urothelial carcinoma, referred to as mixed-grade (MG) urothelial carcinoma, we reviewed all archival cases with such diagnosis between 2005 and 2014. Clinicopathological and outcome parameters were compared to those in our previously reported low- and high-grade noninvasive bladder urothelial carcinoma cohorts (LGUC and HGUC, respectively). The study included 31 MG urothelial carcinomas. Mean patient age was 67.6 years, and mean follow-up was 39.7 months. Intravesical treatment was administered in 15 patients (48.4%). Recurrence occurred in 14 cases (45.2%): 10 as LGUC and 4 as HGUC; there was no stage progression. Mean time to progression was 9 months (5-17 months), and there was no death of disease. MG urothelial carcinoma stage progression and dead of disease rates were comparable to that of LGUC. MG urothelial carcinoma stage progression was significantly lower than that of HGUC, P = .002, using Pearson ?(2) test. MG urothelial carcinoma patients with no intravesical treatment had higher incidence rate of grade progression (25%) compared to LGUC patients (7.9%); however, the difference was not statistically significant. MG urothelial carcinoma had a prognosis closer to "pure" LGUC than "pure" HGUC. Untreated MG urothelial carcinoma may have a higher rate of grade progression than LGUC, although more data are needed before this issue can be definitively addressed. Until such data are available, it is reasonable to keep MG urothelial carcinoma as a distinct grade category with potential management implications. PMID:26520419

  17. p53 protein in low-grade astrocytomas: a study with long-term follow-up.

    PubMed

    Iuzzolino, P; Ghimenton, C; Nicolato, A; Giorgiutti, F; Fina, P; Doglioni, C; Barbareschi, M

    1994-03-01

    The immunohistochemical expression of p53 protein (p53) was examined in 52 patients out of a series of 66 patients with low-grade astrocytomas with long-term follow-up. All patients were also evaluated for several clinical and histological features, among which only preoperative Karnofsky score and the extent of surgery were statistically significant parameters to predict outcome on multivariate analysis. p53 accumulation was seen in 46.1% of patients, with a wide range of percentage of positive cells. Median survival for p53-positive and p53-negative patients was 41 and 37 months respectively. The survival curves of p53-positive and -negative patients were not statistically different. However, the curves showed a trend towards a more aggressive course in p53-positive patients beginning 3-4 years after surgery. Five years after diagnosis the survival estimate with the Kaplan-Meier method was 21.2% for patients with p53-positive tumours and 45.9% for patients with p53-negative tumours. This trend is not due to different distribution of major clinical prognostic factors (age, incomplete resection or Karnofsky status). The trend could be related to the time needed by the p53-positive clone to outgrow the rest of the p53-negative neoplastic cell population. This hypothesis is further supported by the fact that the five recurrences which were surgically removed (one anaplastic astrocytoma and four glioblastomas) derived from p53-positive tumours and were themselves intensely p53 positive. PMID:8123492

  18. Low-grade endotoxemia contributes to chronic inflammation in hemodialysis patients: examination with a novel lipopolysaccharide detection method.

    PubMed

    Terawaki, Hiroyuki; Yokoyama, Keitaro; Yamada, Yukiko; Maruyama, Yukio; Iida, Rinako; Hanaoka, Kazushige; Yamamoto, Hiroyasu; Obata, Toru; Hosoya, Tatsuo

    2010-10-01

    Chronic inflammation has recently been proposed to play a major role in the development of cardiovascular disease and mortality among advanced chronic kidney disease (CKD) patients; however, why advanced CKD promotes chronic inflammation is still unclear. We hypothesized that a very low level of plasma endotoxin (lipopolysaccharide [LPS]) contributes to chronic inflammation in advanced CKD patients. We measured the plasma LPS levels using a novel LPS detection method (ESP method, a method for endotoxin detection using laser scattering photometry) concurrently with serum C-reactive protein (CRP) levels and various blood tests in 17 stable hemodialysis (HD) patients. As a result, the median LPS levels measured by the ESP method was 0.23 pg/mL (range, 0.01-3.89) (inflow, start of HD), 0.22 pg/mL (<0.01-9.97) (outflow, start of HD), 0.37 pg/mL (<0.01-7.42) (inflow, end of HD), and 1.07 pg/mL (<0.01-10.66) (dialysate), respectively; statistically significant differences were not detected between them. The predialysis median CRP level was 0.19 mg/dL (0.04-3.02). The logarithm of plasma LPS independently correlated with serum CRP (R = 0.595, P = 0.0103). In multiple (forward stepwise) regression analysis, in which CRP was determined to be the criterion variable, LPS (log), albumin, and the white blood cell count were adopted as independent explanatory variables (R = 0.401, -0.397 and 0.387, respectively). In conclusion, the present study revealed a significant relationship between LPS and CRP using the novel ESP method, and suggested that very low-grade endotoxemia is contributing to systemic inflammation in HD patients. PMID:21175546

  19. Childhood and adolescent lymphoid and myeloid leukemia.

    PubMed

    Pui, Ching-Hon; Schrappe, Martin; Ribeiro, Raul C; Niemeyer, Charlotte M

    2004-01-01

    Remarkable progress has been made in the past decade in the treatment and in the understanding of the biology of childhood lymphoid and myeloid leukemias. With contemporary improved risk assessment, chemotherapy, hematopoietic stem cell transplantation and supportive care, approximately 80% of children with newly diagnosed acute lymphoblastic leukemia and 50% of those with myeloid neoplasm can be cured to date. Current emphasis is placed not only on increased cure rate but also on improved quality of life. In Section I, Dr. Ching-Hon Pui describes certain clinical and biologic features that still have prognostic and therapeutic relevance in the context of contemporary treatment programs. He emphasizes that treatment failure in some patients is not due to intrinsic drug resistance of leukemic cells but is rather caused by suboptimal drug dosing due to host compliance, pharmacodynamics, and pharmacogenetics. Hence, measurement of minimal residual disease, which accounts for both the genetic (primary and secondary) features of leukemic lymphoblasts and pharmacogenomic variables of the host, is the most reliable prognostic indicator. Finally, he contends that with optimal risk-directed systemic and intrathecal therapy, cranial irradiation may be omitted in all patients, regardless of the presenting features. In Section II, Dr. Martin Schrappe performs detailed analyses of the prognostic impact of presenting age, leukocyte count, sex, immunophenotype, genetic abnormality, early treatment response, and in vitro drug sensitivity/resistance in childhood acute lymphoblastic leukemia, based on the large database of the Berlin-Frankfurt-Münster consortium. He also succinctly summarizes the important treatment components resulting in the improved outcome of children and young adolescents with this disease. He describes the treatment approach that led to the improved outcome of adolescent patients, a finding that may be applied to young adults in the second and third decade of life. Finally, he believes that treatment reduction under well-controlled clinical trials is feasible in a subgroup of patients with excellent early treatment response as evidenced by minimal residual disease measurement during induction and consolidation therapy. In Section III, Dr. Raul Ribeiro describes distinct morphologic and genetic subtypes of acute myeloid leukemia. The finding of essentially identical gene expression profiling by DNA microarray in certain specific genetic subtypes of childhood and adult acute myeloid leukemia suggests a shared leukemogenesis. He then describes the principles of treatment as well as the efficacy and toxicity of various forms of postremission therapy, emphasizing the need of tailoring therapy to both the disease and the age of the patient. Early results suggest that minimal residual disease measurement can also improve the risk assessment in acute myeloid leukemia, and that cranial irradiation can be omitted even in those with central-nervous-system leukemia at diagnosis. In Section IV, Dr. Charlotte Niemeyer describes a new classification of myelodysplastic and myeloproliferative diseases in childhood, which has greatly facilitated the diagnosis of myelodysplastic syndromes and juvenile myelomonocytic leukemia. The recent discovery of somatic mutations in PTPN11 has improved the understanding of the pathobiology and the diagnosis of juvenile myelomonocytic leukemia. Together with the findings of mutations in RAS and NF1 in the other patients, she suggests that pathological activation of RAS-dependent pathways plays a central role in the leukemogenesis of this disease. She then describes the various treatment approaches for both juvenile myelomonocytic leukemia and myelodysplastic syndromes in the US and Europe, emphasizing the differences between childhood and adult cases for the latter group of diseases. She also raises some controversial issues regarding treatment that will require well-controlled international clinical trials to address. PMID:15561680

  20. Association between low-grade albuminuria and hearing impairment in a non-diabetic Korean population: The Korea National Health and Nutrition Examination Survey (2011-2013).

    PubMed

    Kang, Seok Hui; Jung, Da Jung; Choi, Eun Woo; Park, Jong Won; Cho, Kyu Hyang; Yoon, Kyung Woo; Do, Jun Young

    2015-12-01

    Introduction The objective of the present study was to examine the association between low-grade albuminuria and hearing impairment in the non-diabetic population. Materials and methods Data from the Korean National Health and Nutrition Examination Survey 2011-2013 were used in the analyses. Participants were excluded from this study if they were younger than 19 years old, or had urine albumin/creatinine ratio (UACR)???30?mg/g or diabetes mellitus. There were 10?608 participants included in this study. The participants were divided into three groups according to their UACR tertiles. Results There were 1560; 1561; and 1552 male and 1982; 1975; and 1978, female participants in the low, middle, and high tertile groups, respectively. The results indicated the association between low-grade albuminuria and the numbers of metabolic syndrome (MetS) components or Framingham risk score, and the presence of MetS or the proportions of participants at high cardiovascular risk. Univariate and multivariate linear regression analyses demonstrated an association between the UACR and average hearing threshold (AHT) that was observed in both sexes. Multivariate analyses showed that mean AHTs in the low, middle, and high tertile groups were, respectively, 16.127 dB, 17.139 dB, and 18.604 dB for men, and 14.842 dB, 15.100 dB, and 16.353 dB, respectively, for women. Low-frequency, mid-frequency, and high-frequency hearing thresholds according to UACR tertiles showed similar trends. In both sexes, multivariate logistic regression analyses revealed that participants in the low and middle tertile groups had a decreased risk for hearing loss compared to participants in the high tertile group. Conclusion Low-grade albuminuria was associated with hearing impairment in the non-diabetic participants of this study. Key messages Low-grade albuminuria is associated with MetS and cardiovascular risk in the non-diabetic population. Low-grade albuminuria is associated with hearing thresholds and hearing loss in the non-diabetic population. Participants with low-grade albuminuria may be closely monitored for hearing impairment. PMID:26542850

  1. Targeting bone marrow lymphoid niches in acute lymphoblastic leukemia.

    PubMed

    Uy, Geoffrey L; Hsu, Yen-Michael S; Schmidt, Amy P; Stock, Wendy; Fletcher, Theresa R; Trinkaus, Kathryn M; Westervelt, Peter; DiPersio, John F; Link, Daniel C

    2015-12-01

    In acute lymphoblastic leukemia (ALL) the bone marrow microenvironment provides growth and survival signals that may confer resistance to chemotherapy. Granulocyte colony-stimulating factor (G-CSF) potently inhibits lymphopoiesis by targeting stromal cells that comprise the lymphoid niche in the bone marrow. To determine whether lymphoid niche disruption by G-CSF sensitizes ALL cells to chemotherapy, we conducted a pilot study of G-CSF in combination with chemotherapy in patients with relapsed or refractory ALL. Thirteen patients were treated on study; three patients achieved a complete remission (CR/CRi) for an overall response rate of 23%. In the healthy volunteers, G-CSF treatment disrupted the lymphoid niche, as evidenced by reduced expression of CXCL12, interleukin-7, and osteocalcin. However, in most patients with relapsed/refractory ALL expression of these genes was markedly suppressed at baseline. Thus, although G-CSF treatment was associated with ALL cell mobilization into the blood, and increased apoptosis of bone marrow resident ALL cells, alterations in the bone marrow microenvironment were modest and highly variable. These data suggest that disruption of lymphoid niches by G-CSF to sensitize ALL cells to chemotherapy may be best accomplished in the consolidation where the bone marrow microenvironment is more likely to be normal. PMID:26467815

  2. Mechanisms and clinical applications of chromosomal instability in lymphoid malignancy.

    PubMed

    Krem, Maxwell M; Press, Oliver W; Horwitz, Marshall S; Tidwell, Timothy

    2015-10-01

    Lymphocytes are unique among cells in that they undergo programmed DNA breaks and translocations, but that special property predisposes them to chromosomal instability (CIN), a cardinal feature of neoplastic lymphoid cells that manifests as whole chromosome- or translocation-based aneuploidy. In several lymphoid malignancies translocations may be the defining or diagnostic markers of the diseases. CIN is a cornerstone of the mutational architecture supporting lymphoid neoplasia, though it is perhaps one of the least understood components of malignant transformation in terms of its molecular mechanisms. CIN is associated with prognosis and response to treatment, making it a key area for impacting treatment outcomes and predicting prognoses. Here we will review the types and mechanisms of CIN found in Hodgkin lymphoma, non-Hodgkin lymphoma, multiple myeloma and the lymphoid leukaemias, with emphasis placed on pathogenic mutations affecting DNA recombination, replication and repair; telomere function; and mitotic regulation of spindle attachment, centrosome function, and chromosomal segregation. We will discuss the means by which chromosome-level genetic aberrations may give rise to multiple pathogenic mutations required for carcinogenesis and conclude with a discussion of the clinical applications of CIN and aneuploidy to diagnosis, prognosis and therapy. PMID:26018193

  3. ID’ing Innate and Innate-like Lymphoid Cells

    PubMed Central

    Verykokakis, Mihalis; Zook, Erin C.; Kee, Barbara L.

    2014-01-01

    Summary The immune system can be divided into innate and adaptive components that differ in their rate and mode of cellular activation, with innate immune cells being the first responders to invading pathogens. Recent advances in the identification and characterization of innate lymphoid cells have revealed reiterative developmental programs that result in cells with effector fates that parallel those of adaptive lymphoid cells and are tailored to effectively eliminate a broad spectrum of pathogenic challenges. However, activation of these cells can also be associated with pathologies such as autoimmune disease. One major distinction between innate and adaptive immune system cells is the constitutive expression of ID proteins in the former and inducible expression in the latter. ID proteins function as antagonists of the E protein transcription factors that play critical roles in lymphoid specification as well as B and T-lymphocyte development. In this review, we examine the transcriptional mechanisms controlling the development of innate lymphocytes, including natural killer cells and the recently identified innate lymphoid cells (ILC1, ILC2, and ILC3), and innate-like lymphocytes, including natural killer T cells, with an emphasis on the known requirements for the ID proteins. PMID:25123285

  4. 'Managing' the immune system with total lymphoid irradiation

    SciTech Connect

    Strober, S.

    1981-06-01

    Total lymphoid irradiation (TLI), which in the past was limited to the treatment of malignant disease, is now emerging as a practical technique in the management of unwanted immune reactions in the areas of transplant tolerance and various autoimmune diseases. Current studies are particularly promising for application of TLI in rheumatoid arthritis and lupus nephritis.

  5. Lymphoid organs function as major reservoirs for human immunodeficiency virus.

    PubMed Central

    Pantaleo, G; Graziosi, C; Butini, L; Pizzo, P A; Schnittman, S M; Kotler, D P; Fauci, A S

    1991-01-01

    The total number of human immunodeficiency virus type 1 (HIV-1)-infected circulating CD4+ T lymphocytes is considered to be a reflection of the HIV burden at any given time during the course of HIV infection. However, the low frequency of HIV-infected circulating CD4+ T lymphocytes and the low level or absence of plasma viremia in the early stages of infection do not correlate with the progressive immune dysfunction characteristic of HIV infection. In this study, we have determined whether HIV-infected circulating CD4+ T lymphocytes are a correct reflection of the total pool of HIV-infected CD4+ T cells (i.e., HIV burden). To this end, HIV burden has been comparatively analyzed in peripheral blood and lymphoid tissues (lymph nodes, adenoids, and tonsils) from the same patients. The presence of HIV-1 DNA in mononuclear cells isolated simultaneously from peripheral blood and lymphoid tissues of the same patients was determined by polymerase chain reaction amplification. We found that the frequency of HIV-1-infected cells in unfractionated or sorted CD4+ cell populations isolated from lymphoid tissues was significantly higher (0.5-1 log10 unit) than the frequency in peripheral blood. Comparable results were obtained in five HIV seropositive patients in the early stages of disease and in one patient with AIDS. These results demonstrate that a heavy viral load does reside in the lymphoid organs, indicating that they may function as major reservoirs for HIV. In addition, the finding of a heavy viral load in the lymphoid organs of patients in the early stages of disease may explain the progressive depletion of CD4+ T lymphocytes and the immune dysfunction associated with the early stages of HIV infection. Images PMID:1682922

  6. Peripheral ameloblastoma with histologically low-grade malignant features of the buccal mucosa: a case report with immunohistochemical study and genetic analysis.

    PubMed

    Goda, Hiroyuki; Nakashiro, Kohichi; Ogawa, Ikuko; Takata, Takashi; Hamakawa, Hiroyuki

    2015-01-01

    Peripheral ameloblastoma (PA), a rare and unusual variant of odontogenic tumors, comprises about 1% of all ameloblastomas. PA is an exophytic growth localized to the soft tissues overlying the tooth-bearing areas of the jaws, and the initial diagnosis is often fibrous epulis. PA with histologically low-grade malignant features is extremely rare. We report a case of peripheral ameloblastoma with histologically low-grade malignant features in a 69-year-old woman that presented with a hemorrhage from a tumor on the right buccal mucosa. The tumor was surgically removed by blunt dissection, with no evidence of recurrence after two years and six months. After the case presentation, microscopic and genetic findings are discussed. PMID:25973109

  7. [Cervical myelopathy after low grade distortion of the cervical spine. Possible association with pre-existing spondylosis of the cervical spine].

    PubMed

    Aurich, M; Hofmann, G O; Gras, F M

    2015-04-01

    A patient with spondylosis deformans of the cervical spine with no neurological deficits developed rapidly progressive tetraparesis 1 day after a whiplash injury due to a car accident (rear end collision), although initially there were no clinical symptoms. Surgical decompression and spondylodesis led to relief of the neurological deficits. This case demonstrates that even a low grade whiplash injury (grade 1) can cause severe neurological symptoms later and that a degenerative disease of the spine is a predisposing factor. PMID:25336350

  8. Fueling the debate: Are outcomes better after posterior lumbar interbody fusion (PLIF) or after posterolateral fusion (PLF) in adult patients with low-grade adult isthmic spondylolisthesis?

    PubMed Central

    Barbanti Bròdano, G.; Lolli, F.; Martikos, K.; Gasbarrini, A.; Bandiera, S.; Greggi, T.; Parisini, P.; Boriani, S.

    2010-01-01

    Study design:?Retrospective cohort study. Clinical question:?Do more adult patients affected by low grade isthmic spondylolisthesis have significant clinical and radiological improvement following posterior lumbar interbody fusion (PLIF) than those who receive posterolateral fusion (PLF)? Methods:?One hundred and fourteen patients affected by adult low grade isthmic spondylolisthesis, treated with posterior lumbar interbody fusion or posterolateral fusion, were reviewed. Clinical outcome was assessed by means of the questionnaires ODI, RMDQ and VAS. Radiographic evaluation included CT, MRI, and x-rays. The results were analyzed using the Student t-test. Results:?The two groups were similar with respect to demographic and surgical characteristics. At an average follow-up of 62.1 months, 71 patients were completely reviewed. Mean ODI, RMDQ and VAS scores didn't show statistically significant differences. Fusion rate was similar between the two groups (97% in PLIF group, 95% in PLF group). Major complications occurred in 5 of 71 patients reviewed (7%): one in the PLIF group (3.6%), four in the PLF group (9.3%). Pseudarthrosis occurred in one case in the PLIF group (3,6%) and in two cases in PLF group (4.6%). Conclusions:?In our series, there does not appear to be a clear advantage of posterior lumbar interbody fusion (PLIF) over posterolateral fusion (PLF) in terms of clinical and radiological outcome for treatment of adult low grade isthmic spondylolisthesis. PMID:23544021

  9. Comparison of indium-labeled-leukocyte imaging with sequential technetium-gallium scanning in the diagnosis of low-grade musculoskeletal sepsis. A prospective study

    SciTech Connect

    Merkel, K.D.; Brown, M.L.; Dewanjee, M.K.; Fitzgerald, R.H. Jr.

    1985-03-01

    We prospectively compared sequential technetium-gallium imaging with indium-labeled-leukocyte imaging in fifty patients with suspected low-grade musculoskeletal sepsis. Adequate images and follow-up examinations were obtained for forty-two patients. The presence or absence of low-grade sepsis was confirmed by histological and bacteriological examinations of tissue specimens taken at surgery in thirty of the forty-two patients. In these thirty patients, the sensitivity of sequential Tc-Ga imaging was 48 per cent, the specificity was 86 per cent, and the accuracy was 57 per cent, whereas the sensitivity of the indium-labeled-leukocyte technique was 83 per cent, the specificity was 86 per cent, and the accuracy was 83 per cent. When the additional twelve patients for whom surgery was deemed unnecessary were considered, the sensitivity of sequential Tc-Ga imaging was 50 per cent, the specificity was 78 per cent, and the accuracy was 62 per cent, as compared with a sensitivity of 83 per cent, a specificity of 94 per cent, and an accuracy of 88 per cent with the indium-labeled-leukocyte method. In patients with a prosthesis the indium-labeled-leukocyte image was 94 per cent accurate, compared with 75 per cent accuracy for sequential Tc-Ga imaging. Statistical analysis of these data demonstrated that the indium-labeled-leukocyte technique was superior to sequential Tc-Ga imaging in detecting areas of low-grade musculoskeletal sepsis.

  10. Validation of EORTC Prognostic Factors for Adults With Low-Grade Glioma: A Report Using Intergroup 86-72-51

    SciTech Connect

    Daniels, Thomas B.; Brown, Paul D.; Felten, Sara J.; Wu, Wenting; Buckner, Jan C.; Arusell, Robert M.; Curran, Walter J.; Abrams, Ross A.; Schiff, David; Shaw, Edward G.

    2011-09-01

    Purpose: A prognostic index for survival was constructed and validated from patient data from two European Organisation for Research and Treatment of Cancer (EORTC) radiation trials for low-grade glioma (LGG). We sought to independently validate this prognostic index with a separate prospectively collected data set (Intergroup 86-72-51). Methods and Materials: Two hundred three patients were treated in a North Central Cancer Treatment Group-led trial that randomized patients with supratentorial LGG to 50.4 or 64.8 Gy. Risk factors from the EORTC prognostic index were analyzed for prognostic value: histology, tumor size, neurologic deficit, age, and tumor crossing the midline. The high-risk group was defined as patients with more than two risk factors. In addition, the Mini Mental Status Examination (MMSE) score, extent of surgical resection, and 1p19q status were also analyzed for prognostic value. Results: On univariate analysis, the following were statistically significant (p < 0.05) detrimental factors for both progression-free survival (PFS) and overall survival (OS): astrocytoma histology, tumor size, and less than total resection. A Mini Mental Status Examination score of more than 26 was a favorable prognostic factor. Multivariate analysis showed that tumor size and MMSE score were significant predictors of OS whereas tumor size, astrocytoma histology, and MMSE score were significant predictors of PFS. Analyzing by the EORTC risk groups, we found that the low-risk group had significantly better median OS (10.8 years vs. 3.9 years, p < 0.0001) and PFS (6.2 years vs. 1.9 years, p < 0.0001) than the high-risk group. The 1p19q status was available in 66 patients. Co-deletion of 1p19q was a favorable prognostic factor for OS vs. one or no deletion (median OS, 12.6 years vs. 7.2 years; p = 0.03). Conclusions: Although the low-risk group as defined by EORTC criteria had a superior PFS and OS to the high-risk group, this is primarily because of the influence of histology and tumor size. Co-deletion of 1p19q is a prognostic factor. Future studies are needed to develop a more refined prognostic system that combines clinical prognostic features with more robust molecular and genetic data.

  11. Beyond NK cells: the expanding universe of innate lymphoid cells.

    PubMed

    Cella, Marina; Miller, Hannah; Song, Christina

    2014-01-01

    For a long time, natural killer (NK) cells were thought to be the only innate immune lymphoid population capable of responding to invading pathogens under the influence of changing environmental cues. In the last few years, an increasing amount of evidence has shown that a number of different innate lymphoid cell (ILC) populations found at mucosal sites rapidly respond to locally produced cytokines in order to establish or maintain homeostasis. These ILC populations closely mirror the phenotype of adaptive T helper subsets in their repertoire of secreted soluble factors. Early in the immune response, ILCs are responsible for setting the stage to mount an adaptive T cell response that is appropriate for the incoming insult. Here, we review the diversity of ILC subsets and discuss similarities and differences between ILCs and NK cells in function and key transcriptional factors required for their development. PMID:24982658

  12. Beyond NK Cells: The Expanding Universe of Innate Lymphoid Cells

    PubMed Central

    Cella, Marina; Miller, Hannah; Song, Christina

    2014-01-01

    For a long time, natural killer (NK) cells were thought to be the only innate immune lymphoid population capable of responding to invading pathogens under the influence of changing environmental cues. In the last few years, an increasing amount of evidence has shown that a number of different innate lymphoid cell (ILC) populations found at mucosal sites rapidly respond to locally produced cytokines in order to establish or maintain homeostasis. These ILC populations closely mirror the phenotype of adaptive T helper subsets in their repertoire of secreted soluble factors. Early in the immune response, ILCs are responsible for setting the stage to mount an adaptive T cell response that is appropriate for the incoming insult. Here, we review the diversity of ILC subsets and discuss similarities and differences between ILCs and NK cells in function and key transcriptional factors required for their development. PMID:24982658

  13. Pseudolymphoma (reactive lymphoid hyperplasia) of the liver: A clinical challenge

    PubMed Central

    Kwon, Yong Kyong; Jha, Reena C; Etesami, Kambiz; Fishbein, Thomas M; Ozdemirli, Metin; Desai, Chirag S

    2015-01-01

    Reactive lymphoid hyperplasia (RLH), also known as pseudolymphoma or nodular lymphoid lesion of the liver is an extremely rare condition, and only 51 hepatic RLH cases have been described in the literature since the first case was described in 1981. The majority of these cases were asymptomatic and incidentally found through radiological imaging. The precise etiology of hepatic RLH is still unknown, but relative high prevalence of autoimmune disorder in these cases suggests an immune-based liver disorder. Imaging features of hepatic RLH often suggest malignant lesions such as hepatocellular carcinoma and cholangiocarcinoma. In this report, we discuss two cases of hepatic RLH in patients with autoimmune hepatitis. We also present pathologic and magnetic resonance imaging findings, including one case utilizing a hepatocellular contrast agent, Eovist. Definitive diagnosis of hepatic RLH often requires surgical excision. PMID:26609347

  14. Total lymphoid irradiation in refractory systemic lupus erythematosus

    SciTech Connect

    Ben-Chetrit, E.; Gross, D.J.; Braverman, A.; Weshler, Z.; Fuks, Z.; Slavin, S.; Eliakim, M.

    1986-07-01

    In two patients with systemic lupus erythematosus, conventional therapy was considered to have failed because of persistent disease activity and unacceptable side effects. Both were treated with total lymphoid irradiation without clinical benefit, despite adequate immunosuppression as documented by markedly reduced numbers of circulating T lymphocytes and T-lymphocyte-dependent proliferative responses in vitro. The first patient developed herpes zoster, gram-negative septicemia, neurologic symptoms, and deterioration of lupus nephritis. The second patient developed massive bronchopneumonia, necrotic cutaneous lesions, and progressive nephritis and died 2 weeks after completion of radiotherapy. These observations, although limited to two patients, indicate that total lymphoid irradiation in patients with severe systemic lupus erythematosus should be regarded as strictly experimental.

  15. Clinical outcomes of childhood x-irradiation for lymphoid hyperplasia

    SciTech Connect

    Pottern, L.M.

    1987-01-01

    A prospective study was conducted to explore the relationship between childhood x-irradiation for lymphoid hyperplasia and the subsequent development of thyroid gland and other head and neck disorders. All individuals under 18 years of age who were x-irradiated for lymphoid hyperplasia during the years 1938-69 at Children's Hospital Medical Center, Boston comprised the exposed population. The comparison group consisted of non-exposed, surgically treated individuals. The study included a health questionnaire and a clinical examination component. A history of thyroid cancer was reported by 11 exposed subjects and no non-exposed subjects. Significantly elevated standardized incidence ratios of thyroid cancer were seen for both exposed males and females, 19.9 and 12.1, respectively. The average thyroid radiation dose was 25.8 rads and the mean latency period was 17.3 years.

  16. Immunosuppression and organ transplantation tolerance using total lymphoid irradiation

    SciTech Connect

    Slavin, S.; Strober, S.; Fuks, Z.; Kaplan, H.S.

    1980-01-01

    Total lymphoid irradiation (TLI) is a method which delivers irradiation daily in fractionated doses (200 rads) to lymphoid organs while shielding bones, lungs, and the majority of the gastrointestinal tract. TLI is lymphocytopenic in mice, rats, dogs, and humans, and both T cells and B cells are eliminated from the circulation. TLI permits establishment of specific and long-lasting tolerance to alloantigens. Permanent acceptance of allogeneic bone marrow cells without graft-versus-host disease was achieved in rats and dogs across major histocompatibility barriers. Recipients were tolerant to allografts of skin, hearts, and kidney from animals syngeneic to marrow donors or to organs from the marrow donor. This approach may be suitable for pancreas transplantation in diabetes.

  17. Treatment of intractable rheumatoid arthritis with lymphoid irradiation

    SciTech Connect

    Strober, S.; Kotzin, B.L.; Hoppe, R.T.; Slavin, S.; Gottlieb, M.; Calin, A.; Fuks, Z.; Kaplan, H.S.

    1981-01-01

    Subdiaphragmatic lymphoid radiation was used as an alternative to cytotoxic drug therapy to treat six patients with progressive erosive rheumatoid arthritis. All were previously unresponsive to conventional therapy. Radiation (4,000 rad) was given to subdiaphragmatic lymphoid tissues in fractionated doses of 150 to 250 rad each. Three of the six patients demonstrated long-lasting clinical improvement with a decrease in synovitis and morning stiffness and an increase in joint function. All six patients showed a profound depression in the peripheral blood lymphocyte count which persisted for at least six months. The irradiation was well tolerated; there have been no serious complications due to radiotherapy with follow-up ranging from 13 to 36 months. The substantial efficacy in some patients and the lack of severe toxicity in all suggests that radiotherapy deserves further study as an alternative to cytotoxic drugs in the treatment of rheumatoid arthritis.

  18. Evidence that somatostatin is localized and synthesized in lymphoid organs

    SciTech Connect

    Aguila, M.C.; McCann, S.M. ); Dees, W.L.; Haensly, W.E. )

    1991-12-15

    Because several peptides originally found in the pituitary as within the central nervous system have been localized in lymphoid tissues and because somatostatin (somatotropin-release-inhibiting hormone, SRIH) can act on cells of the immune system, the authors searched for this peptide in lymphoid organs. The authors demonstrated that SRIH mRNA exists in lymphoid tissue, albeit in smaller levels that in the periventricular region of the hypothalamus, the brain region that contains the highest level of this mRNA. SRIH mRNA was found in the spleen and thymus of male rats and in the spleen, thymus, and bursa of Fabricius of the chicken. Its localization in the Bursa indicates that the peptide must be present in B lymphocytes since this is the site of origin of B lymphocytes in birds. The SRIH concentration in these lymphoid organs as determined by radioimmunoassay was greater in the thymus than in the spleen of the rat. Fluorescence immunocytochemistry revealed the presence of SRIH-positive cells in clusters inside the white pulp and more dispersed within the red pulp of the spleen of both the rat and the chicken. The thymus from these species also contained SRIH-positive cells within the medulla and around the corticomedullary junction. In the chicken, there were large cluster of SRIH-positive cells in the medullary portion of each nodule of the bursa of Fabricius. The results indicate that SRIH is synthesized and stored in cells of the immune system. SRIH may be secreted from these cells to exert paracrine actions that alter the function of immune cells in spleen and thymus.

  19. Cellular mechanisms of tolerance after total lymphoid irradiation (TLI)

    SciTech Connect

    Strober, S.; King, D.P.; Gottlieb, M.S.; Hoppe, R.T.; Kaplan, H.S.

    1981-03-01

    In this review article on the cellular mechanisms of tolerance after total lymphoid irradiation (TLI), the effect of radiation dose and time of bone marrow infusion in mice are studied. TLI is compared to whole body irradiation with respect to the development of graft-host reaction and the number of stable chimeras obtained. The relationship between nonspecific suppressor cells and the development of tolerance after TLI is discussed. (KRM)

  20. Identification of a novel lymphoid population in the murine epidermis

    PubMed Central

    Almeida, Francisca F.; Tenno, Mari; Brzostek, Joanna; Li, Jackson LiangYao; Allies, Gabriele; Hoeffel, Guillaume; See, Peter; Ng, Lai Guan; Fehling, Hans Jörg; Gascoigne, Nicholas R. J.; Taniuchi, Ichiro; Ginhoux, Florent

    2015-01-01

    T cell progenitors are known to arise from the foetal liver in embryos and the bone marrow in adults; however different studies have shown that a pool of T cell progenitors may also exist in the periphery. Here, we identified a lymphoid population resembling peripheral T cell progenitors which transiently seed the epidermis during late embryogenesis in both wild-type and T cell-deficient mice. We named these cells ELCs (Epidermal Lymphoid Cells). ELCs expressed Thy1 and CD2, but lacked CD3 and TCR??/?? at their surface, reminiscent of the phenotype of extra- or intra- thymic T cell progenitors. Similarly to Dendritic Epidermal T Cells (DETCs), ELCs were radioresistant and capable of self-renewal. However, despite their progenitor-like phenotype and expression of T cell lineage markers within the population, ELCs did not differentiate into conventional T cells or DETCs in in vitro, ex vivo or in vivo differentiation assays. Finally, we show that ELC expressed NK markers and secreted IFN-? upon stimulation. Therefore we report the discovery of a unique population of lymphoid cells within the murine epidermis that appears related to NK cells with as-yet-unidentified functions. PMID:26223192

  1. Treatment of intractable lupus nephritis with total lymphoid irradiation

    SciTech Connect

    Strober, S.; Field, E.; Hoppe, R.T.; Kotzin, B.L.; Shemesh, O.; Engleman, E.; Ross, J.C.; Myers, B.D.

    1985-04-01

    Ten patients with lupus nephritis and marked proteinuria (3.9 g or more/d) that did not respond adequately to treatment with prednisone alone or prednisone in combination with azathioprine were treated with total lymphoid irradiation in an uncontrolled feasibility study. Within 6 weeks after the start of total lymphoid irradiation, the serum albumin level rose in all patients in association with a reduction in the serum level of anti-DNA antibodies, an increase in the serum complement level, or both. Improvement in these variables persisted in eight patients followed for more than 1 year, with the stabilization or reduction of the serum creatinine level. Urinary leakage of albumin was substantially reduced in all patients. Side effects associated with radiotherapy included transient constitutional complaints in ten patients, transient blood element depressions in three, localized viral and bacterial infections in four, and ovarian failure in one. The results suggest that total lymphoid irradiation may provide an alternative to cytotoxic drugs in the treatment of lupus nephritis.

  2. Total lymphoid irradiation in the Wistar rat: technique and dosimetry

    SciTech Connect

    Hoogenhout, J.; Kazem, I.; de Jong, J.

    1983-01-01

    The technical and dosimetric aspects of total lymphoid irradiation (TLI) in the Wistar rat were evaluated as part of a set-up to develop a new model for tumor xenotransplantation. Information obtained from anatomical dissections, radionuclide imaging of the spleen, lymphography and chromolymphography was used to standardize the localization portals cut out in a lead plate. The two portals encompassed the lymphoid tissue above and below the diaphragm. A specially designed masonite phantom was used to measure the dose distribution in the simulated target volumes. Ionization chamber dosimetery, thermoluminescence dosimetry and film densitometry were used for measuring exposure and absorbed dose. Irradiation was performed with 250 kV X rays (HVL 3.1 mm Cu). The dose rate was regulated by adjusting the treatment distance. The dose inhomogeneity measured in the target volumes varied between 80-100%. The side scatter dose to non target tissues under the shielded area between the two portals ranged between 20-30%. The technique and dosimetry of total lymphoid irradiation in Wistar rats are now standardized and validated and pave the way for tumor xenotransplantation experiments.

  3. A Stromal Cell Niche for Human and Mouse Type 3 Innate Lymphoid Cells.

    PubMed

    Hoorweg, Kerim; Narang, Priyanka; Li, Zhi; Thuery, Anne; Papazian, Natalie; Withers, David R; Coles, Mark C; Cupedo, Tom

    2015-11-01

    Adaptive immunity critically depends on the functional compartmentalization of secondary lymphoid organs. Mesenchymal stromal cells create and maintain specialized niches that support survival, activation, and expansion of T and B cells, and integrated analysis of lymphocytes and their niche has been instrumental in understanding adaptive immunity. Lymphoid organs are also home to type 3 innate lymphoid cells (ILC3), innate effector cells essential for barrier immunity. However, a specialized stromal niche for ILC3 has not been identified. A novel lineage-tracing approach now identifies a subset of murine fetal lymphoid tissue organizer cells that gives rise exclusively to adult marginal reticular cells. Moreover, both cell types are conserved from mice to humans and colocalize with ILC3 in secondary lymphoid tissues throughout life. In sum, we provide evidence that fetal stromal organizers give rise to adult marginal reticular cells and form a dedicated stromal niche for innate ILC3 in adaptive lymphoid organs. PMID:26378073

  4. Psychological stress contributed to the development of low-grade fever in a patient with chronic fatigue syndrome: a case report

    PubMed Central

    2013-01-01

    Background Low-grade fever is a common symptom in patients with chronic fatigue syndrome (CFS), but the mechanisms responsible for its development are poorly understood. We submit this case report that suggests that psychological stress contributes to low-grade fever in CFS. Case presentation A 26-year-old female nurse with CFS was admitted to our hospital. She had been recording her axillary temperature regularly and found that it was especially high when she felt stress at work. To assess how psychological stress affects temperature and to investigate the possible mechanisms for this hyperthermia, we conducted a 60-minute stress interview and observed the changes in the following parameters: axillary temperature, fingertip temperature, systolic blood pressure, diastolic blood pressure, heart rate, plasma catecholamine levels, and serum levels of interleukin (IL)-1? and IL-6 (pyretic cytokines), tumor necrosis factor-? and IL-10 (antipyretic cytokines). The stress interview consisted of recalling and talking about stressful events. Her axillary temperature at baseline was 37.2°C, increasing to 38.2°C by the end of the interview. In contrast, her fingertip temperature decreased during the interview. Her heart rate, systolic and diastolic blood pressures, and plasma levels of noradrenaline and adrenaline increased during the interview; there were no significant changes in either pyretic or antipyretic cytokines during or after the interview. Conclusions A stress interview induced a 1.0°C increase in axillary temperature in a CFS patient. Negative emotion-associated sympathetic activation, rather than pyretic cytokine production, contributed to the increase in temperature induced by the stress interview. This suggests that psychological stress may contribute to the development or the exacerbation of low-grade fever in some CFS patients. PMID:23497734

  5. Neutralizing Anti-IL20 Antibody Treatment Significantly Modulates Low Grade Inflammation without Affecting HbA1c in Type 2 Diabetic db/db Mice

    PubMed Central

    Mayer, Christopher; Bergholdt, Regine; Cucak, Helena; Rolin, Bidda Charlotte; Sams, Anette; Rosendahl, Alexander

    2015-01-01

    Low grade inflammation is present in pre-clinical and human type 2 diabetes. In this process, several cytokines like IL-1? and inflammatory cells like macrophages are activated and demonstrated to participate to the disease initiation and progression. IL-20 is a cytokine known to play non-redundant roles in progression of several inflammatory diseases. To address the therapeutic effect of inhibiting the IL-20 pathway in diabetes, diabetic db/db mice were treated with neutralizing anti-IL20 antibodies in vivo and both metabolic and inflammatory parameters were followed. Diabetic islets expressed the IL-20 cytokine and all IL-20 receptor components in elevated levels compared to resting non-diabetic islets. Islets were responsive to ex vivo IL-20 stimulation measured as SOCS induction and KC and IL-6 production. Neutralizing anti-IL20 treatment in vivo had no effect on HbA1c or weight although the slope of blood glucose increase was lowered. In contrast, anti-IL20 treatment significantly reduced the systemic low-grade inflammation and modulated the local pancreatic immunity. Significant reduction of the systemic IL-1? and MCP-1 was demonstrated upon anti-IL20 treatment which was orchestrated with a reduced RANTES, IL-16 and IL-2 but increased TIMP-1, MCP-1 and IL-6 protein expression locally in the pancreas. Interestingly, anti-IL20 treatment induced an expansion of the myeloid suppressor CD11bGr1int macrophage while reducing the number of CD8 T cells. Taken together, anti-IL20 treatment showed moderate effects on metabolic parameters, but significantly altered the low grade local and systemic inflammation. Hence, future combination therapies with anti-IL20 may provide beneficial therapeutic effects in type 2 diabetes through a reduction of inflammation. PMID:26162095

  6. An optimized protocol for isolating lymphoid stromal cells from the intestinal lamina propria.

    PubMed

    Stzepourginski, Igor; Eberl, Gérard; Peduto, Lucie

    2015-06-01

    Mesenchymal stromal cells in lymphoid organs, also called lymphoid stromal cells (LSCs), play a pivotal role in immunity by forming specialized microenvironments that provide signals for leukocyte migration, positioning, and survival. Best characterized in lymphoid organs, LSCs are also abundant in the intestinal mucosa, which harbors a rich repertoire of immune cells. However, the lack of efficient procedures for isolation and purification of LSCs from the intestine has been a major limitation to their characterization. Here we report a new method to efficiently isolate, in addition to immune cells, viable lymphoid stromal cells and other stromal subsets from the intestinal lamina propria for subsequent phenotypic and functional analysis. PMID:25599879

  7. Inflammatory profiles in the non-pregnant state predict offspring birth weight at Cebu: evidence for intergenerational effects of low grade inflammation

    PubMed Central

    Kuzawa, Christopher W.; Tallman, Paula S.; Adair, Linda S.; Lee, Nanette; McDade, Thomas W.

    2012-01-01

    Background Although maternal infection and inflammation during pregnancy can adversely affect offspring birth weight (BW), whether low grade inflammation in the non-pregnant state predicts BW is unknown. Aim Evaluate relationships between offspring BW and pro- and anti-inflammatory factors measured in parous but non-pregnant women. Subjects and methods Data come from 234 parous Filipino females (21.5 ± 0.3 yr) in the Cebu Longitudinal Health and Nutrition Survey, a population-based birth cohort in Metropolitan Cebu, Philippines. Pro-inflammatory [Interleukin-6 (IL-6), Interleukin-1 beta (IL-1?), tumor necrosis factor alpha (TNF?), C-reactive protein (CRP)] and anti-inflammatory [Interleukin-10 (IL-10)] factors were measured in fasting plasma when the women were not pregnant, and related to recalled offspring BW. Results BW in female offspring was lower only among women with high IL-1?. Although pro-inflammatory cytokines did not predict BW in male offspring, women with higher anti-inflammatory IL-10 gave birth to larger males. Women with a combination of low inflammatory (IL-6) and high anti-inflammatory (IL-10) factors (interaction p<0.104) gave birth to the largest males. Conclusion Immune factors measured outside of pregnancy predict offspring BW in these young women. Stable variation in inflammatory phenotype could impact the gestational environment of offspring, thus pointing to potential intergenerational effects of chronic low-grade inflammation. PMID:22690728

  8. Spiradenocarcinoma with low-grade basal cell adenocarcinoma pattern: report of a case with varied morphology and wild type TP53.

    PubMed

    Petersson, Fredrik; Nga, Min En

    2012-03-01

    We present a patient with a 2-cm spiradenocarcinoma of the left arm resembling low-grade salivary gland basal cell adenocarcinoma. In addition to showing attributes of conventional spiradenoma, the benign component showed prominent areas of cystic change with focal apocrine differentiation, glands with and without mucinous differentiation, clear cell change and focal adenoid cystic carcinoma-like areas. The malignant component was composed of nodules of basaloid cells arranged in sheets with variable tendency to luminal differentiation. The nuclear atypia was low-grade, and the mitotic index was high in the malignant component (to 8/10 high power fields). Immunohistochemically, there was diffuse but variable positivity for cytokeratin 7 in both the benign and malignant components. Epithelial membrane antigen was focally positive, highlighting cells with ductal (luminal) differentiation. Expression of p63 was observed in 50 and 80% of the cells in the benign and malignant components, respectively. Calponin was negative. The proliferative index (MIB-1/Ki-67) was <3% in the benign component and up to 10% in the malignant component. Although the malignant component displayed patchy areas with nuclear p53 immunoreactivity with variable intensity, no mutation in the TP53 gene was identified. PMID:22077486

  9. Ubiquitous Transgenic Overexpression of C-C Chemokine Ligand 2: A Model to Assess the Combined Effect of High Energy Intake and Continuous Low-Grade Inflammation

    PubMed Central

    Rodríguez-Gallego, Esther; Hernández-Aguilera, Anna; Mariné-Casadó, Roger; Rull, Anna; Beltrán-Debón, Raúl; Menendez, Javier A.; Vazquez-Martin, Alejandro; Sirvent, Juan J.; Martín-Paredero, Vicente; Corbí, Angel L.; Sierra-Filardi, Elena; Aragonès, Gerard; García-Heredia, Anabel; Camps, Jordi; Alonso-Villaverde, Carlos; Joven, Jorge

    2013-01-01

    Excessive energy management leads to low-grade, chronic inflammation, which is a significant factor predicting noncommunicable diseases. In turn, inflammation, oxidation, and metabolism are associated with the course of these diseases; mitochondrial dysfunction seems to be at the crossroads of mutual relationships. The migration of immune cells during inflammation is governed by the interaction between chemokines and chemokine receptors. Chemokines, especially C-C-chemokine ligand 2 (CCL2), have a variety of additional functions that are involved in the maintenance of normal metabolism. It is our hypothesis that a ubiquitous and continuous secretion of CCL2 may represent an animal model of low-grade chronic inflammation that, in the presence of an energy surplus, could help to ascertain the afore-mentioned relationships and/or to search for specific therapeutic approaches. Here, we present preliminary data on a mouse model created by using targeted gene knock-in technology to integrate an additional copy of the CCl2 gene in the Gt(ROSA)26Sor locus of the mouse genome via homologous recombination in embryonic stem cells. Short-term dietary manipulations were assessed and the findings include metabolic disturbances, premature death, and the manipulation of macrophage plasticity and autophagy. These results raise a number of mechanistic questions for future study. PMID:24453432

  10. Near-infrared (NIR) spectroscopy. A new method for arthroscopic evaluation of low grade degenerated cartilage lesions. Results of a pilot study

    PubMed Central

    Spahn, Gunter; Plettenberg, Holger; Kahl, Enrico; Klinger, Hans M; Mückley, Thomas; Hofmann, Gunther O

    2007-01-01

    Background Arthroscopy is a highly sensitive method of evaluating high-grade cartilage lesions but the detection of low-grade lesions is often is unreliable. Objective measurements are required. A novel NIRS (near-infrared-spectroscopy) device for detection of low-grade cartilage defects was evaluated in a preliminary clinical study. Methods In 12 patients who had undergone arthroscopy, the cartilage lesions within the medial knee compartment were classified according to the ICRS protocol. With a NIR spectrometer system and an optical probe, similar in design to a hook used for routine arthroscopy, the optical properties of cartilage were measured during arthroscopy. Results The mean ratio of 2 NIR absorption bands of intact cartilage 3.8 (range 2.3 to 8.7).was significantly lower than that of cartilage with grade 1 lesions (12.8, range 4.8 to 19.6) and grade 2 lesions (13.4, range 10.4 to 15.4). No differences were observed between grade 1 and grade 2 lesions. Conclusion NIRS can be used to distinguish between ICRS grade 1 lesions and healthy cartilage during arthroscopic surgeries. The results of this clinical study demonstrate the potential of NIRS to objectify classical arthroscopic grading systems. PMID:17535439

  11. Cell cycle and apoptosis regulatory proteins, proliferative markers, cell signaling molecules, CD209, and decorin immunoreactivity in low-grade myxofibrosarcoma and myxoma.

    PubMed

    Cates, Justin M M; Memoli, Vincent A; Gonzalez, Raul S

    2015-08-01

    The histologic differential diagnosis between intramuscular myxoma and low-grade myxofibrosarcoma can be quite difficult in some cases. To identify a diagnostic immunohistochemical marker, we compared the staining profiles of 19 different antigens, including cell cycle proteins, apoptosis proteins, and proliferative markers, and selected other signaling and structural proteins in these two tumors. Ten cases each of intramuscular myxoma and low-grade myxofibrosarcoma were stained with antibodies directed against apoptosis regulatory proteins (Bcl2, activated caspase-3, phospho-H2A.X, and cleaved PARP), cell cycle regulatory proteins (Rb1, Cyclin-A, CDKN1B, and Cdt1), proliferative markers (KI67, MCM2, phospho-histone H3, and geminin), cell signalling molecules (c-Myc, EGF, EGFR, PLA2G4A, and HSP90), a dendritic cell marker (CD209), and the extracellular matrix proteoglycan decorin. Staining patterns of myxoma and myxofibrosarcoma were compared using Fisher's exact test and the Mann-Whitney test. For each potential diagnostic marker studied, the proportions of cases scored as positive on both dichotomous or ordinal scales were not significantly different between myxoma and myxofibrosarcoma. Myxoma and myxofibrosarcoma share a common immunophenotype for each of the markers studied. Distinction between these tumors is still predominantly based on morphologic criteria. PMID:25940995

  12. Innate lymphoid cells drive interleukin-23-dependent innate intestinal pathology.

    PubMed

    Buonocore, Sofia; Ahern, Philip P; Uhlig, Holm H; Ivanov, Ivaylo I; Littman, Dan R; Maloy, Kevin J; Powrie, Fiona

    2010-04-29

    The key role of interleukin (IL)-23 in the pathogenesis of autoimmune and chronic inflammatory disorders is supported by the identification of IL-23 receptor (IL-23R) susceptibility alleles associated with inflammatory bowel disease, psoriasis and ankylosing spondylitis. IL-23-driven inflammation has primarily been linked to the actions of T-helper type 17 (TH17) cells. Somewhat overlooked, IL-23 also has inflammatory effects on innate immune cells and can drive T-cell-independent colitis. However, the downstream cellular and molecular pathways involved in this innate intestinal inflammatory response are poorly characterized. Here we show that bacteria-driven innate colitis is associated with an increased production of IL-17 and interferon-gamma in the colon. Stimulation of colonic leukocytes with IL-23 induced the production of IL-17 and interferon-gamma exclusively by innate lymphoid cells expressing Thy1, stem cell antigen 1 (SCA-1), retinoic-acid-related orphan receptor (ROR)-gammat and IL-23R, and these cells markedly accumulated in the inflamed colon. IL-23-responsive innate intestinal cells are also a feature of T-cell-dependent models of colitis. The transcription factor ROR-gammat, which controls IL-23R expression, has a functional role, because Rag-/-Rorc-/- mice failed to develop innate colitis. Last, depletion of Thy1+ innate lymphoid cells completely abrogated acute and chronic innate colitis. These results identify a previously unrecognized IL-23-responsive innate lymphoid population that mediates intestinal immune pathology and may therefore represent a target in inflammatory bowel disease. PMID:20393462

  13. Gallium scanning in lymphoid interstitial pneumonitis of children with AIDS

    SciTech Connect

    Schiff, R.G.; Kabat, L.; Kamani, N.

    1987-12-01

    Lymphoid interstitial pneumonitis (LIP) is a frequent pulmonary complication in the child with the acquired immune deficiency syndrome (AIDS) and human immunodeficiency virus (HIV) infection. We report the gallium scan findings in two children with AIDS and LIP. Gallium scintigraphy in both children demonstrated increased radionuclide concentration throughout the lungs, a pattern indistinguishable scintigraphically from that of Pneumocystis carinii pneumonia (PCP). This should alert nuclear medicine practitioners and referring physicians to another cause of diffusely increased gallium uptake in the lungs of patients with AIDS.

  14. The Good, the Bad, or the Pretty: IL-17 Builds Lymphoid Tissues in the Brain.

    PubMed

    Becher, Burkhard

    2015-12-15

    Lymph node development depends on well-orchestrated interactions between lymphoid tissue inducer cells and stromal cells. In this issue of Immunity, Pikor and colleagues (2015) find that signals from IL-17-producing T helper cells can alter the stromal microenvironment of the inflamed brain to generate a neo-lymphoid organ that drives further inflammation. PMID:26682978

  15. Radiation therapy of conjunctival and orbital lymphoid tumors

    SciTech Connect

    Jereb, B.; Lee, H.; Jakobiec, F.A.; Kutcher, J.

    1984-07-01

    Lymphoid tumors of the conjuctiva and orbit are rare and remain localized in the majority of cases. Sometimes it is not possible either clinically or histologically to differentiate between a non-Hodgkin's lymphoma (NHL) and benign lymphoid hyperplasia. A series of 24 patients is reported. Nineteen were classified as having malignant NHL and 5 benign hyperplasia; 1 of these 5 later developed metastases, however. All patients had systemic work-up: 18 had Stage I, 1 had Stage II, and 5 had Stage IV disease. All patients received local radiation therapy with doses of 2400 to 2750 rad in 2-3 weeks for lesions of the eyelid and conjunctiva, and between 3000 and 3750 rad in 3-4 weeks for retrobulbar lesions. A method of shielding the lens with a lead block mounted on a low vac lens is described, and the dose distribution within the eye and orbit is presented. Patients who were treated with doses higher than 3000 rad experienced conjunctivitis and skin erythema that resolved completely. No other effects of radiation on normal structures of the ocular adnexa were observed in the 20 patients who are alive and without signs of tumor 10-46 months with a median follow-up time of 22 months.

  16. Trafficking of. cap alpha. -L-fucosidase in lymphoid cells

    SciTech Connect

    DiCioccio, R.A.; Brown, K.S.

    1987-05-01

    The quantity of ..cap alpha..-L-fucosidase in human serum is determined by heredity. The mechanism controlling levels of the enzyme in serum is unknown. To investigate this, lymphoid cell lines derived from individuals with either low, intermediate or high ..cap alpha..-L-fucosidase in serum were established. Steady state levels of extracellular ..cap alpha..-L-fucosidase protein and activity overlapped among the cell lines. Thus, in vivo serum phenotypes of ..cap alpha..-L-fucosidase are not adequately expressed in this system. ..cap alpha..-L-Fucosidase was also metabolically labelled with /sup 35/S-methionine, immunoprecipitated, and examined by SDS-PAGE. Cells pulse-labelled from 0.25-2 h had a major intracellular form of enzyme (Mr = 58,000). Cells pulsed for 1.5 h and chased for 21 h with unlabeled methionine had an intracellular form of Mr = 60,000 and an extracellular form of Mr = 62,000. Cells treated with chloroquine had only the 58,000-form both intra- and extra-cellularly. Moreover, chloroquine did not effect the quantitative distribution of ..cap alpha..-L-fucosidase between cells and medium. In fibroblasts, chloroquine enhanced the secretion of newly made lysosomal enzymes and blocked the processing of intercellular enzyme forms from a higher to a lower molecular mass. Thus, there are trafficking differences between ..cap alpha..-L-fucosidase in lymphoid cells and lysosomal enzymes in fibroblasts. This suggests that alternative targeting mechanisms for lysosomal enzymes exist in these cells.

  17. Postirradiation recovery of lymphoid cells in the rat

    SciTech Connect

    Farnsworth, A.; Wotherspoon, J.S.; Dorsch, S.E.

    1988-09-01

    Whole-body irradiation has been extensively used to remove immune responsiveness in rodent recipients in adoptive allograft assays. This study was undertaken to determine the relative radioresistance and the tempo of regeneration, following whole-body irradiation, of cells involved in the allograft response. Six distinct cell populations have been identified in the lymphoid tissues of rats subjected to sublethal whole-body irradiation. The relative representation of these subpopulations was significantly different from that in nonirradiated controls. NK cells, macrophages, and plasma cells, which are present in very low numbers in cell suspensions prepared from normal lymphoid tissues, made up a significant proportion of the residual/regenerating population in the tissues of rats recovering from whole-body irradiation. More significantly perhaps, the mature T cell populations showed a significant increase in the T cytotoxic/suppressor to T helper cell ratio. These observations support the suggestion that a number of the cell types within the mixed cell population observed in the rejecting indicator grafts of irradiated recipients in adoptive allograft assays are host derived. The finding that the T cytotoxic/suppressor population is apparently more radioresistant than the T helper population supports a conclusion that graft rejection in irradiated recipients, restored with pure populations of T helper cells, may not be directly mediated by the injected cells but may be the result of collaboration between these and host-derived cytotoxic cell populations.

  18. Sustained improvement of intractable rheumatoid arthritis after total lymphoid irradiation

    SciTech Connect

    Field, E.H.; Strober, S.; Hoppe, R.T.; Calin, A.; Engleman, E.G.; Kotzin, B.L.; Tanay, A.S.; Calin, H.J.; Terrell, C.P.; Kaplan, H.S.

    1983-08-01

    Total lymphoid irradiation (TLI) was administered to 11 patients who had intractable rheumatoid arthritis that was unresponsive to conventional medical therapy, including aspirin, multiple nonsteroidal antiinflammatory drugs, gold salts, and D-penicillamine. Total lymphoid irradiation was given as an alternative to cytotoxic drugs such as azathioprine and cyclophosphamide. After radiotherapy, 9 of the 11 patients showed a marked improvement in clinical disease activity as measured by morning stiffness, joint tenderness, joint swelling, and overall functional abilities. The mean improvement of disease activity in all patients ranged from 40-70 percent and has persisted throughout a 13-28 month followup period. This improvement permitted the mean daily steroid dose to be reduced by 54%. Complications included severe fatigue and other constitutional symptoms during radiotherapy, development of Felty's syndrome in 1 patient, and an exacerbation of rheumatoid lung disease in another. After therapy, all patients exhibited a profound T lymphocytopenia, and a reversal in their T suppressor/cytotoxic cell to helper cell ratio. The proliferative responses of peripheral blood mononuclear cells to phytohemagglutinin, concanavalin A, and allogeneic leukocytes (mixed leukocyte reaction) were markedly reduced, as was in vitro immunoglobulin synthesis after stimulation with pokeweed mitogen. Alterations in T cell numbers and function persisted during the entire followup period, except that the mixed leukocyte reaction showed a tendency to return to normal values.

  19. Treatment of intractable rheumatoid arthritis with total lymphoid irradiation

    SciTech Connect

    Kotzin, B.L.; Strober, S.; Engleman, E.G.; Calin, A.; Hoppe, R.T.; Kansas, G.S.; Terrell, C.P.; Kaplan, H.S.

    1981-10-01

    Eleven patients with intractable rheumatoid arthritis were treated with total lymphoid irradiation (total dose, 2000 rad) in an uncontrolled feasibility study, as an alternative to long-term therapy with cytotoxic drugs such as cyclophosphamide and azathioprine. During a follow-up period of five to 18 months after total lymphoid irradiation, there was a profound and sustained suppression of the absolute lymphocyte count and in vitro lymphocyte function, as well as an increase in the ratio of Leu-2 (suppressor/cytotoxic) to Leu-3 (helper) T cells in the blood. Persistent circulating suppressor cells of the mixed leukocyte response and of pokeweed mitogen-induced immunoglobulin secretion developed in most patients. In nine of the 11 patients, these changes in immune status were associated with relief of joint tenderness and swelling and with improvement in function scores. Maximum improvement occurred approximately six months after irradiation and continued for the remainder of the observation period. Few severe or chronic side effects were associated with the radiotherapy.

  20. Treatment of intractable rheumatoid arthritis with total lymphoid irradiation

    SciTech Connect

    Kotzin, B.L.; Strober, S.; Engleman, E.G.; Calin, A.; Hoppe, R.T.; Kansas, G.S.; Terrell, C.P.; Kaplan, H.S.

    1981-10-22

    Eleven patients with intractable rheumatoid arthritis were treated with total lymphoid irradiation (total dose, 2000 rad) in an uncontrolled feasibility study, as an alternative to long-term therapy with cytotoxic drugs such as cyclophosphamide and azathioprine. During a follow-up period of five to 18 months after total lymphoid irradiation, there was a profound and sustained suppression of the absolute lymphocyte count and in vitro lymphocyte function, as well as an increase in the ratio of Leu-2 (suppressor/cytotoxic) to Leu-3 (helper) T cells in the blood. Persistent circulating suppressor cells of the mixed leukocyte response and of pokeweek mitogen-induced immunoglobulin secretion developed in most patients. In nine of the 11 patients, these changes in immune status were associated with relief of joint tenderness and swelling and with improvement in function scores. Maximum improvement occurred approximately six months after irradiation and continued for the remainder of the observation period. Few severe or chronic side effects were associated with the radiotherapy.

  1. Intestinal mucosa and intra-abdominal lymphoid tissues of the platypus, Ornithorhynchus anatinus.

    PubMed

    Osogoe, B; Tsujii, T; Liszczynsky, H R; Naora, H; Seno, S

    1991-03-01

    The morphological features of the intestinal mucosa and intra-abdominal lymphoid tissues of the platypus were examined. The mucosal surface of the intestine was characterized by the formation of large folds instead of the finger-like villi found in placental mammals. The lamina propria of the mucosal fold was well developed and contained numerous lymphocytes, expressing the lymphoid nature which is characteristic of the lamina propria of mammalian intestines. Although numerous well-developed Peyer's patches were observed in the ileum, solitary lymphoid nodules could not be found anywhere in the small intestine. Other intra-abdominal lymphoid tissues, particularly mesenteric lymphoid nodules, were well developed. However, each nodule represented a single follicle in contrast to the mammalian mesenteric lymph node which is composed of numerous follicles fused together. On the basis of the above findings, the tissues in question are considered to be at an evolutionary level preceding that of placental mammals. PMID:2062481

  2. Topographic and quantitative relationship between prostate inflammation, proliferative inflammatory atrophy and low-grade prostate intraepithelial neoplasia: A biopsy study in chronic prostatitis patients

    PubMed Central

    VRAL, A.; MAGRI, V.; MONTANARI, E.; GAZZANO, G.; GOURVAS, V.; MARRAS, E.; PERLETTI, G.

    2012-01-01

    Inflammatory processes are important components in the pathogenesis of many human cancers. According to the ‘injury and regeneration’ model for prostate carcinogenesis, injury caused by pathogens or pro-inflammatory cytotoxic agents would trigger proliferation of prostatic glandular cells, leading to the appearance of epithelial lesions named ‘Proliferative Inflammatory Atrophy’ (PIA). Inflammatory cells infiltrating the prostate would release genotoxic reactive oxygen species, leading atrophic cells to neoplastic progression. The hypothesis pointing to PIA as risk-lesion for prostate cancer has been extensively investigated at the cellular and molecular levels, but few morphological data are available linking PIA or prostatic intraepithelial neoplasia (PIN) to inflammation or clinical prostatitis. We investigated at the morphological level 1367 prostate biopsies from 98 patients with a recent history of chronic prostatitis, and 32 patients with biopsies positive for carcinoma. Our results show that i) PIA is found more frequently in biopsy cores containing a severe or moderate inflammatory focus, compared to NON-PIA lesions (partial or cystic atrophy); ii) the PIA lesion post-atrophic hyperplasia is more frequently found in tissues showing mild or no inflammation; iii) the extent of PIA per patient correlates with the burden of moderate or severe inflammation, whereas NON-PIA lesions do not; iv) low-grade PIN is in over 90% of cases emerging from normal, non-atrophic glands and is more frequently found in biopsy cores with absent or mild inflammatory burden; v) the inverse relationship between the prevalence of low-grade PIN and the extent of PIA lesions per patient is described by a power law function, suggesting the low likelihood of the concomitant presence of these lesions in the same tissue; vi) NON-PIA lesions correlate inversely with neoplasia in patients with prostate cancer; vii) the total scores of the NIH-CPSI questionnaire correlate with both PIA and inflammation burdens at diagnosis of prostatitis but not after pharmacological intervention. These results point to a positive association between tissue inflammation, clinical prostatitis and the putative cancer risk-lesion PIA, but do not support a model whereby low-grade PIN would arise from PIA. PMID:23026863

  3. Mucinous spindle and tubular renal cell carcinoma: analysis of chromosomal aberration pattern of low-grade, high-grade, and overlapping morphologic variant with papillary renal cell carcinoma.

    PubMed

    Peckova, Kvetoslava; Martinek, Petr; Sperga, Maris; Montiel, Delia Perez; Daum, Ondrej; Rotterova, Pavla; Kalusová, Kristýna; Hora, Milan; Pivovarcikova, Kristýna; Rychly, Boris; Vranic, Semir; Davidson, Whitney; Vodicka, Josef; Dubová, Magdaléna; Michal, Michal; Hes, Ondrej

    2015-08-01

    The chromosomal numerical aberration pattern in mucinous tubular and spindle renal cell carcinoma (MTSRCC) is referred to as variable with frequent gains and losses. The objectives of this study are to map the spectrum of chromosomal aberrations (extent and location) in a large cohort of the cases and relate these findings to the morphologic variants of MTSRCC. Fifty-four MTSRCCs with uniform morphologic pattern were selected (of 133 MTSRCCs available in our registry) and divided into 3 groups: classic low-grade MTSRCC (Fuhrman nucleolar International Society of Urological Pathology grade 2), high-grade MTSRCC (grade 3), and overlapping MTSRCC with papillary renal cell carcinoma (RCC) morphology. Array comparative genomic hybridization analysis was applied to 16 cases in which DNA was well preserved. Four analyzable classic low-grade MTSRCCs showed multiple losses affecting chromosomes 1, 4, 8, 9, 14, 15, and 22. No chromosomal gains were found. Four analyzable cases of MTSRCC showing overlapping morphology with PRCC displayed a more variable pattern including normal chromosomal status; losses of chromosomes 1, 6, 8, 9, 14, 15, and 22; and gains of 3, 7, 16, and 17. The group of 4 high-grade MTSRCCs exhibited a more uniform chromosomal aberration pattern with losses of chromosomes 1, 4, 6, 8, 9, 13, 14, 15, and 22 and without any gains detected. (1) MTSRCC, both low-grade and high-grade, shows chromosomal losses (including 1, 4, 6, 8, 9, 13, 14, 15, and 22) in all analyzable cases; this seems to be the most frequent chromosomal numerical aberration in this type of RCC. (2) Cases with overlapping morphologic features (MTSRCC and PRCC) showed a more variable pattern with multiple losses and gains, including gains of chromosomes 7 and 17 (2 cases). This result is in line with previously published morphologic and immunohistochemical studies that describe the broad morphologic spectrum of MTSRCC, with changes resembling papillary RCC. (3) The diagnosis of MTSRCC in tumors with overlapping morphology (MTSRCC and PRCC) showing gains of both chromosomes 7 and 17 remains questionable. Based on our findings, we recommend that such tumors should not be classified as MTSRCC but rather as PRCC. PMID:26009022

  4. Neuropsychological status in children and young adults with benign and low-grade brain tumors treated prospectively with focal stereotactic conformal radiotherapy

    SciTech Connect

    Jalali, Rakesh . E-mail: rjalali@medscape.com; Goswami, Savita; Sarin, Rajiv; More, Niteen; Siddha, Manish; Kamble, Rashmi

    2006-11-15

    Purpose: To present prospective neuropsychological data at baseline and follow-up in children and young adults with benign and low-grade gliomas treated with focal stereotactic conformal radiotherapy (SCRT). Methods and Materials: A total of 22 patients (age 4-25 years) with residual/progressive benign and low-grade brain tumors considered suitable for SCRT underwent detailed and in-depth neuropsychological and cognitive testing at baseline before SCRT. The test battery included measurement of age-adjusted intelligence quotients (IQs) and cognitive parameters of visual, spatial, visuomotor, and attention concentrations. Anxiety was measured using the State-Trait Anxiety Inventory for Children and Hamilton Anxiety Rating Scale for patients >16 years old. Patients were treated with high-precision conformal radiotherapy under stereotactic guidance to a dose of 54 Gy in 30 fractions. All neuropsychological assessments were repeated at 6 and 24 months after SCRT completion and compared with the baseline values. Results: The baseline mean full-scale IQ before starting RT for patients <16 years was 82 (range, 33-105). For those >16 years, the corresponding value was 72 (range, 64-129). Of 20 evaluable patients, 14 (70%) had less than average IQs at baseline, even before starting radiotherapy. The verbal IQ, performance IQ, and full-scale IQ, as well as other cognitive scores, did not change significantly at the 6- and 24-month follow-up assessments for all patients. The memory quotient in older children and young adults was maintained at 6 and 24 months after SCRT, with a mean value of 93 and 100, respectively, compared with a mean baseline value of 81 before RT. The mean anxiety score in children measured by the C1 and C2 components of the State-Trait Anxiety Inventory for Children (STAIC) was 48 and 40, respectively, which improved significantly to mean values of 30 and 26, respectively, at the 24-month follow-up assessment (p = 0.005). The mean depression score in patients >16 years old was 23 at baseline and had improved to 17 and 14 at the 6-month and 24-month follow-up assessments, respectively. Conclusion: Our data demonstrated neuropsychological impairment in a cohort of young patients with benign and low-grade tumors even before starting radiotherapy. SCRT, however, did not result in any additional worsening. These encouraging results need to be validated in a study with a larger number of patients and longer follow-up.

  5. Dermatan Sulfate-Free Mice Display Embryological Defects and Are Neonatal Lethal Despite Normal Lymphoid and Non-Lymphoid Organogenesis.

    PubMed

    Stachtea, Xanthi N; Tykesson, Emil; van Kuppevelt, Toin H; Feinstein, Ricardo; Malmström, Anders; Reijmers, Rogier M; Maccarana, Marco

    2015-01-01

    The epimerization of glucuronic acid into iduronic acid adds structural variability to chondroitin/dermatan sulfate polysaccharides. Iduronic acid-containing domains play essential roles in processes such as coagulation, chemokine and morphogen modulation, collagen maturation, and neurite sprouting. Therefore, we generated and characterized, for the first time, mice deficient in dermatan sulfate epimerase 1 and 2, two enzymes uniquely involved in dermatan sulfate biosynthesis. The resulting mice, termed DKO mice, were completely devoid of iduronic acid, and the resulting chondroitin sulfate chains were structurally different from the wild type chains, from which a different protein binding specificity can be expected. As a consequence, a vast majority of the DKO mice died perinatally, with greatly variable phenotypes at birth or late embryological stages such as umbilical hernia, exencephaly and a kinked tail. However, a minority of embryos were histologically unaffected, with apparently normal lung and bone/cartilage features. Interestingly, the binding of the chemokine CXCL13, an important modulator of lymphoid organogenesis, to mouse DKO embryonic fibroblasts was impaired. Nevertheless, the development of the secondary lymphoid organs, including the lymph nodes and spleen, was normal. Altogether, our results indicate an important role of dermatan sulfate in embryological development and perinatal survival. PMID:26488883

  6. Dermatan Sulfate-Free Mice Display Embryological Defects and Are Neonatal Lethal Despite Normal Lymphoid and Non-Lymphoid Organogenesis

    PubMed Central

    Stachtea, Xanthi N.; Tykesson, Emil; van Kuppevelt, Toin H.; Feinstein, Ricardo; Malmström, Anders; Reijmers, Rogier M.; Maccarana, Marco

    2015-01-01

    The epimerization of glucuronic acid into iduronic acid adds structural variability to chondroitin/dermatan sulfate polysaccharides. Iduronic acid-containing domains play essential roles in processes such as coagulation, chemokine and morphogen modulation, collagen maturation, and neurite sprouting. Therefore, we generated and characterized, for the first time, mice deficient in dermatan sulfate epimerase 1 and 2, two enzymes uniquely involved in dermatan sulfate biosynthesis. The resulting mice, termed DKO mice, were completely devoid of iduronic acid, and the resulting chondroitin sulfate chains were structurally different from the wild type chains, from which a different protein binding specificity can be expected. As a consequence, a vast majority of the DKO mice died perinatally, with greatly variable phenotypes at birth or late embryological stages such as umbilical hernia, exencephaly and a kinked tail. However, a minority of embryos were histologically unaffected, with apparently normal lung and bone/cartilage features. Interestingly, the binding of the chemokine CXCL13, an important modulator of lymphoid organogenesis, to mouse DKO embryonic fibroblasts was impaired. Nevertheless, the development of the secondary lymphoid organs, including the lymph nodes and spleen, was normal. Altogether, our results indicate an important role of dermatan sulfate in embryological development and perinatal survival. PMID:26488883

  7. 40Ar/39Ar Data for White Mica, Biotite, and K-Feldspar Samples from Low-Grade Metamorphic Rocks in the Westminster Terrane and Adjacent Rocks, Maryland

    USGS Publications Warehouse

    Kunk, Michael J.; McAleer, Ryan

    2008-01-01

    This report contains reduced 40Ar/39Ar data of white mica and K-feldspar mineral separates and matrix of a whole rock phyllite, all from low-grade metamorphic rocks of the Westminster terrane and adjacent strata in central Maryland. This report presents these data in a preliminary form, but in more detail than can be accommodated in todays professional journals. Also included in this report is information on the location of the samples and a brief description of the samples. The data contained herein are not interpreted in a geological context, and care should be taken by readers unfamiliar with argon isotopic data in the use of these results; many of the individual apparent ages are not geologically meaningful. This report is primarily a detailed source document for subsequent publications that will integrate these data into a geological context.

  8. Combined cytotoxic effect of UV-irradiation and TiO2 microbeads in normal urothelial cells, low-grade and high-grade urothelial cancer cells.

    PubMed

    Imani, Roghayeh; Verani?, Peter; Igli?, Aleš; Kreft, Mateja Erdani; Pazoki, Meysam; Hudoklin, Samo

    2015-03-01

    The differentiation of urothelial cells results in normal terminally differentiated cells or by alternative pathways in low-grade or high-grade urothelial carcinomas. Treatments with traditional surgical and chemotherapeutical approaches are still inadequate and expensive, as bladder tumours are generally highly recurrent. In such situations, alternative approaches, using irradiation of the cells and nanoparticles, are promising. The ways in which urothelial cells, at different differentiation levels, respond to UV-irradiation (photolytic treatment) or to the combination of UV-irradiation and nanoparticles (photocatalytic treatment), are unknown. Here we tested cytotoxicity of UV-irradiation on (i) normal porcine urothelial cells (NPU), (ii) human low-grade urothelial cancer cells (RT4), and (iii) human high-grade urothelial cancer cells (T24). The results have shown that 1 minute of UV-irradiation is enough to kill 90% of the cells in NPU and RT4 cultures, as determined by the live/dead viability assay. On the other hand, the majority of T24 cells survived 1 minute of UV-irradiation. Moreover, even a prolonged UV-irradiation for 30 minutes killed <50% of T24 cells. When T24 cells were pre-supplemented with mesoporous TiO2 microbeads and then UV-irradiated, the viability of these high-grade urothelial cancer cells was reduced to <10%, which points to the highly efficient cytotoxic effects of TiO2 photocatalysis. Using electron microscopy, we confirmed that the mesoporous TiO2 microbeads were internalized into T24 cells, and that the cell's ultrastructure was heavily compromised after UV-irradiation. In conclusion, our results show major differences in the sensitivity to UV-irradiation among the urothelial cells with respect to cell differentiation. To achieve an increased cytotoxicity of urothelial cancer cells, the photocatalytic approach is recommended. PMID:25385056

  9. T-cell-predominant lymphoid hyperplasia in a tattoo*

    PubMed Central

    Souza, Erica Sales; Rocha, Bruno de Oliveira; Batista, Everton da Silva; de Oliveira, Rodrigo Ferreira; Farre, Lourdes; Bittencourt, Achilea Lisboa

    2014-01-01

    Cutaneous lymphoid hyperplasia (CLH) can be idiopathic or secondary to external stimuli, and is considered rare in tattoos. The infiltrate can be predominantly of B or T-cells, the latter being seldom reported in tattoos. We present a case of a predominantly T CLH, secondary to the black pigment of tattooing in a 35-year-old patient, with a dense infiltrate of small, medium and scarce large T-cells. Analysis of the rearrangement of T-cells receptor revealed a polyclonal proliferation. Since the infiltrate of CLH can simulate a T lymphoma, it is important to show that lesions from tattoos can have a predominance of T-cells. PMID:25387518

  10. Prolonged heart xenograft survival using combined total lymphoid irradiation and cyclosporine

    SciTech Connect

    Knechtle, S.J.; Halperin, E.C.; Saad, T.; Bollinger, R.R.

    1986-05-01

    Total lymphoid irradiation and cyclosporine have profound immunosuppressive properties and permit successful heart allotransplantation. Cyclosporine used alone has not permitted consistently successful transplantation between species in all cases. Total lymphoid irradiation has not been applied to xenotransplantation. The efficacy of total lymphoid irradiation alone and in combination with cyclosporine was examined using an animal model of heart xenotransplantation. Heterotopic heart transplants were performed using inbred Syrian hamsters as donors and Lewis rats as recipients. Total lymphoid irradiation was administered preoperatively over 3 weeks for a total dose of 15 gray. Cyclosporine was started on the day of surgery and was given as a daily intramuscular injection of 2.5, 5, or 10 mg/kg/day until rejection was complete. Neither total lymphoid irradiation nor cyclosporine alone markedly prolonged graft survival. However, combined total lymphoid irradiation and cyclosporine, 5 or 10 mg/kg/day, dramatically prolonged graft survival to greater than 100 days in most recipients. There were no treatment-related deaths. In conclusion, combined total lymphoid irradiation and cyclosporine permit successful long-term survival of heart xenotransplants in this hamster-to-rat model.

  11. Lymphoid Organ-Resident Dendritic Cells Exhibit Unique Transcriptional Fingerprints Based on Subset and Site

    PubMed Central

    Elpek, Kutlu G.; Bellemare-Pelletier, Angelique; Malhotra, Deepali; Reynoso, Erika D.; Lukacs-Kornek, Veronika; DeKruyff, Rosemarie H.; Turley, Shannon J.

    2011-01-01

    Lymphoid organ-resident DC subsets are thought to play unique roles in determining the fate of T cell responses. Recent studies focusing on a single lymphoid organ identified molecular pathways that are differentially operative in each DC subset and led to the assumption that a given DC subset would more or less exhibit the same genomic and functional profiles throughout the body. Whether the local milieu in different anatomical sites can also influence the transcriptome of DC subsets has remained largely unexplored. Here, we interrogated the transcriptional relationships between lymphoid organ-resident DC subsets from spleen, gut- and skin-draining lymph nodes, and thymus of C57BL/6 mice. For this purpose, major resident DC subsets including CD4 and CD8 DCs were sorted at high purity and gene expression profiles were compared using microarray analysis. This investigation revealed that lymphoid organ-resident DC subsets exhibit divergent genomic programs across lymphoid organs. Interestingly, we also found that transcriptional and biochemical properties of a given DC subset can differ between lymphoid organs for lymphoid organ-resident DC subsets, but not plasmacytoid DCs, suggesting that determinants of the tissue milieu program resident DCs for essential site-specific functions. PMID:21886840

  12. Locally elevated cortisol in lymphoid organs of the developing zebra finch but not Japanese quail or chicken.

    PubMed

    Taves, Matthew D; Losie, Jennifer A; Rahim, Titissa; Schmidt, Kim L; Sandkam, Benjamin A; Ma, Chunqi; Silversides, Frederick G; Soma, Kiran K

    2016-01-01

    Glucocorticoids are important for production of functional lymphocytes and immunity. In altricial neonates, adrenal glands are unresponsive and local glucocorticoid synthesis in lymphoid organs may be necessary to support lymphocyte development. Precocial neonates, in contrast, have fully responsive adrenal glucocorticoid production, and lymphoid glucocorticoid synthesis may not be necessary. Here, we found that in altricial zebra finch hatchlings, lymphoid organs had dramatically elevated endogenous glucocorticoid (and precursor) levels compared to levels in circulating blood. Furthermore, while avian adrenals produce corticosterone, finch lymphoid organs had much higher levels of cortisol, an unexpected glucocorticoid in birds. In contrast, precocial Japanese quail and chicken offspring did not have locally elevated lymphoid glucocorticoid levels, nor did their lymphoid organs contain high proportions of cortisol. These results show that lymphoid glucocorticoids differ in identity, concentration, and possibly source, in hatchlings of three different bird species. Locally-regulated glucocorticoids might have species-specific roles in immune development. PMID:26366679

  13. Histological and immunohistological investigation of lymphoid tissue in the platypus (Ornithorhynchus anatinus).

    PubMed

    Connolly, J H; Canfield, P J; McClure, S J; Whittington, R J

    1999-08-01

    The gross and histological appearance and the distribution of T and B lymphocytes and plasma cells are described for lymphoid tissues obtained from 15 platypuses. The spleen was bilobed and surrounded by a thick capsule of collagen, elastic fibres and little smooth muscle. White pulp was prominent and included germinal centres and periarterial lymphoid sheaths. Red pulp contained haematopoietic tissue. A thin lobulated thymus was located within the mediastinum overlying the heart. The cortex of lobules consisted of dense aggregates of small and medium lymphocytes, scattered macrophages and few reticular epithelial cells. In the medulla, Hassall's corpuscles were numerous, lymphocytes were small and less abundant, and reticular cells were more abundant than in the cortex. Lymphoid nodules scattered throughout loose connective tissue in cervical, pharyngeal, thoracic, mesenteric and pelvic sites measured 790 +/- 370 microm (mean +/- S.D., n = 39) in diameter, the larger of which could be observed macroscopically. These consisted of single primary or secondary follicles supported by a framework of reticular fibres. Macrophages were common in the germinal centres. The platypus had a full range of gut-associated lymphoid tissue. No tonsils were observed macroscopically but histologically they consisted of submucosal follicles and intraepithelial lymphocytes. Peyer's patches were not observed macroscopically but histologically they consisted of several prominent submucosal secondary follicles in the antimesenteric wall of the intestine. Caecal lymphoid tissue consisted of numerous secondary follicles in the submucosa and densely packed lymphocytes in the lamina propria. Bronchus-associated lymphoid tissue was not observed macroscopically but was identified in 7 of 11 platypus lungs assessed histologically. Lymphoid cells were present as primary follicles associated with bronchi, as aggregates adjacent to blood vessels and as intraepithelial lymphocytes. The distribution of T lymphocytes, identified with antihuman CD3 and CD5, and B lymphocytes and plasma cells, identified with antihuman CD79a and CD79b and antiplatypus immunoglobulin, within lymphoid tissues in the platypus was similar to that described in therian mammals except for an apparent relative paucity of B lymphocytes. This study establishes that the platypus has a well-developed lymphoid system which is comparable in histological structure to that in therian mammals. It also confirms the distinctiveness of its peripheral lymphoid tissue, namely lymphoid nodules. Platypus lymphoid tissue has all the essential cell types, namely T and B lymphocytes and plasma cells, to mount an effective immune response against foreign antigens. PMID:10529053

  14. Hepatic Expression of Secondary Lymphoid Chemokine (CCL21) Promotes the Development of Portal-Associated Lymphoid Tissue in Chronic Inflammatory Liver Disease

    PubMed Central

    Grant, Allister J.; Goddard, Sarah; Ahmed-Choudhury, Jalal; Reynolds, Gary; Jackson, David G.; Briskin, Michael; Wu, Lijun; Hübscher, Stefan G.; Adams, David H.

    2002-01-01

    The chronic inflammatory liver disease primary sclerosing cholangitis (PSC) is associated with portal inflammation and the development of neolymphoid tissue in the liver. More than 70% of patients with PSC have a history of inflammatory bowel disease and we have previously reported that mucosal addressin cell adhesion molecule-1 is induced on dendritic cells and portal vascular endothelium in PSC. We now show that the lymph node-associated chemokine, CCL21 or secondary lymphoid chemokine, is also strongly up-regulated on CD34+ vascular endothelium in portal associated lymphoid tissue in PSC. In contrast, CCL21 is absent from LYVE-1+ lymphatic vessel endothelium. Intrahepatic lymphocytes in PSC include a population of CCR7+ T cells only half of which express CD45RA and which respond to CCL21 in migration assays. The expression of CCL21 in association with mucosal addressin cell adhesion molecule-1 in portal tracts in PSC may promote the recruitment and retention of CCR7+ mucosal lymphocytes leading to the establishment of chronic portal inflammation and the expanded portal-associated lymphoid tissue. This study provides further evidence for the existence of portal-associated lymphoid tissue and is the first evidence that ectopic CCL21 is associated with lymphoid neogenesis in human inflammatory disease. PMID:11943728

  15. Combined Proteomics and Transcriptomics Identifies Carboxypeptidase B1 and Nuclear Factor ?B (NF-?B) Associated Proteins as Putative Biomarkers of Metastasis in Low Grade Breast Cancer.

    PubMed

    Bouchal, Pavel; Dvo?áková, Monika; Roumeliotis, Theodoros; Bortlí?ek, Zbyn?k; Ihnatová, Ivana; Procházková, Iva; Ho, Jenny T C; Maryáš, Josef; Imrichová, Hana; Budinská, Eva; Vyzula, Rostislav; Garbis, Spiros D; Vojt?šek, Bo?ivoj; Nenutil, Rudolf

    2015-07-01

    Current prognostic factors are insufficient for precise risk-discrimination in breast cancer patients with low grade breast tumors, which, in disagreement with theoretical prognosis, occasionally form early lymph node metastasis. To identify markers for this group of patients, we employed iTRAQ-2DLC-MS/MS proteomics to 24 lymph node positive and 24 lymph node negative grade 1 luminal A primary breast tumors. Another group of 48 high-grade tumors (luminal B, triple negative, Her-2 subtypes) was also analyzed to investigate marker specificity for grade 1 luminal A tumors. From the total of 4405 proteins identified (FDR < 5%), the top 65 differentially expressed together with 30 previously identified and control markers were analyzed also at transcript level. Increased levels of carboxypeptidase B1 (CPB1), PDZ and LIM domain protein 2 (PDLIM2), and ring finger protein 25 (RNF25) were associated specifically with lymph node positive grade 1 tumors, whereas stathmin 1 (STMN1) and thymosin beta 10 (TMSB10) associated with aggressive tumor phenotype also in high grade tumors at both protein and transcript level. For CPB1, these differences were also observed by immunohistochemical analysis on tissue microarrays. Up-regulation of putative biomarkers in lymph node positive (versus negative) luminal A tumors was validated by gene expression analysis of an independent published data set (n = 343) for CPB1 (p = 0.00155), PDLIM2 (p = 0.02027) and RELA (p = 0.00015). Moreover, statistically significant connections with patient survival were identified in another public data set (n = 1678). Our findings indicate unique pro-metastatic mechanisms in grade 1 tumors that can include up-regulation of CPB1, activation of NF-?B pathway and changes in cell survival and cytoskeleton. These putative biomarkers have potential to identify the specific minor subpopulation of breast cancer patients with low grade tumors who are at higher than expected risk of recurrence and who would benefit from more intensive follow-up and may require more personalized therapy. PMID:25903579

  16. Microstructural, geothermobarometric and geochronological constraints on the complex Alpine collisional history recorded on the low-grade "Psunj Complex" metamorphic rocks of the Slavonian Mts. (Croatia)

    NASA Astrophysics Data System (ADS)

    Balen, Dražen

    2014-05-01

    Metamorphic rocks of the Slavonian Mts. (NE Croatia) cropping out on the SW edge of the Pannonian Basin belong to the Bihor nappe system of Tisia Mega-Unit i.e. of the lithospheric fragment broken off from the southern margin of the European plate. The present-day position of this Unit resulted from complex regional-scale Mesozoic and Cenozoic movements during the Alpine-Carpathian-Dinaridic orogenic system geodynamic evolution. Usually, the metamorphic rocks of the Slavonian Mts. are interpreted as a part of igneous-metamorphic complex belonging to metamorphic belt formed during or even prior to the Variscan orogeny. Until recently, the Alpine metamorphic evolution was considered insignificant and often neglected or described just in general terms due to considerable lack of geothermobarometric, phase equilibrium, fossil and/or geochronological age constraints. The chlorite schists are widely distributed lithology in the area, comprising simple peak metamorphic mineral assemblage chlorite + plagioclase (albite) + muscovite + quartz ± garnet and are associated to the local complex called Psunj complex (PsC). Metamorphic conditions for non-garnetiferous chlorite schists are obtained with chlorite (Al(IV)) thermometry and white mica barometry are 300 °C and 2.4±0.6 kbar. The chlorite schists are thrusted over (~ to the NE) microtectonically similar chloritoid-bearing schists that reached peak P-T values of 3.5-4 kbar and 340-380 °C. At least two distinct penetrative low-grade metamorphic foliations recorded in the chlorite schists are accompanied by existence of different populations of small (~3.5 µm) low-Th monazites, giving an average age 99±15 Ma. Histogram of obtained ages shows two peaks at 120 and 80 Ma while age modelling recognized two peaks at 113±20 and 82±23 Ma. First Alpine (113±20 Ma) event represents a rare record of late Early Cretaceous thermal event that affected Bihor nappe system. The age contradicts common opinion that Bihor nappe escaped thermal changes during east-facing thrusting i.e. "Austrian orogeny". The second (82±23 Ma) monazite age population is tentatively associated with Late Cretaceous regional orogenic event characterized by low-grade low-pressure metamorphism. The post-tectonic growth of chloritoid (in chloritoid schist) with respect to S2 foliation indicates that the major phase of Alpine deformation predates the peak metamorphic conditions (thermal climax) leaving opened the possibility for detection of three distinct events during the Cretaceous. Hence, the prograde Alpine metamorphic event(s) had a more significant influence on the evolution of the southern part of Tisia Mega-Unit than previously considered.

  17. Disparity of mixed lymphocyte reactivity to cultured cells of human T and B lymphoid lines.

    PubMed

    Pauly, J L; Minowada, J; Han, T; Moore, G E

    1975-03-01

    Repeated attempts with difference assays and experimental conditions failed to detect significant peripheral blood lymphocyte reactivity in one-way mixed lymphocyte reactions to irradiated or mitomycin C-treated cells of the "leukemic" T lymphoid line RPMI 8402. In contrast, consistently high levels of peripheral blood lymphocyte reactivity were obtained with cells of six B lymphoid lines established from the same blood sample used to initiate this T lymphoid line. Although attempts to define the reason why these cultured T cells did not initiate a mixed lymphocyte reaction were not successful, evidence indicates that this inability may be an intrinsic characteristic common to three other T lymphoid lines (MOLT-4, CCRF-CEM, and CCRF-HSB-2), also established from patients with relapsed acute lymphoblastic leukemia. PMID:123598

  18. Characterization of lymphoid cells in the blood of healthy adults: sequential immunological, cytochemical and cytokinetic studies

    SciTech Connect

    Hirt, A.; Wagner, H.P.

    1980-01-01

    With a new method, sequential immunological, cytochemical and cytokinetic studies were done on lymphoid cells in the peripheral blood of 12 healthy adults. Every single lymphoid cell could therefore be characterized by the following markers: surface immunoglobulins (sIg); rosetting with sheep red blood cells (E); unspecific acid alpha-naphthyl acetate esterase (ANAE); and 3HdT incorporation. Significantly more E+sIg-ANAE-cells (51% and 22% of all lymphoid cells, respectively). Of all ANAE+ cells 90% were E+, but 64% of all ANAE- cells were also E+. In all individuals a subpopulation of E+sIg+ cells was found. The esterase pattern of these cells was similar to that of E-sIg+ cells. The overall labeling index of the lymphoid cells examined was less than or equal to 0.2%.

  19. The interbranchial lymphoid tissue of Atlantic Salmon (Salmo salar L) extends as a diffuse mucosal lymphoid tissue throughout the trailing edge of the gill filament.

    PubMed

    Dalum, Alf S; Austbø, Lars; Bjørgen, Håvard; Skjødt, Karsten; Hordvik, Ivar; Hansen, Tom; Fjelldal, Per G; Press, Charles McL; Griffiths, David J; Koppang, Erling O

    2015-09-01

    The teleost gill forms an extensive, semipermeable barrier that must tolerate intimate contact with the surrounding environment and be able to protect the body from external pathogens. The recent discovery of the interbranchial lymphoid tissue (ILT) has initiated an anatomical and functional investigation of the lymphoid tissue of the salmonid gill. In this article, sectioning of gill arches in all three primary planes revealed an elongation of the ILT outward along the trailing edge of the primary filament to the very distal end, a finding not previously described. This newly found lymphoid tissue was investigated using a range of morphological and transcriptional tools. Avoiding potential salinity-related effects, the study focused on two fresh-water life stages-smoltifying juveniles and mature adults. Aggregates of T-cells continuous with the ILT were found within the thick epithelial lining of the trailing edge of the filament in considerably larger numbers than seen in the epithelium of the leading edge and of the interlamellar area. Only a few of these cells were identified as CD8?(+) -cells, and there was a significantly (P < 0.05) higher relative expression of CD4- than of CD8- related genes in all gill segments investigated. Numerous major histocompatibility complex class II(+) -cells were distributed uniformly throughout the filament epithelial tissue. Few Ig(+) -cells were detected. Overall, the morphological features and comparable immune gene expression of the previously described ILT and the filament trailing edge lymphoid tissue suggest a close functional and anatomical relationship. We propose that the anatomical definition of the ILT must be broadened to include both the previously described ILT (to be renamed proximal ILT) and the trailing edge lymphoid tissue (to be named distal ILT). This extended anatomical localisation identifies the ILT as a widely distributed mucosal lymphoid tissue in the gill of Atlantic salmon. PMID:26011185

  20. Decidual-trophoblast interactions: decidual lymphoid cell populations in basal and parietal decidua.

    PubMed

    Haller, H; Tedesco, F; Rukavina, D; Radillo, O; Gudelj, L; Beer, A E

    1995-02-01

    Immunohistochemical analysis of tissue specimens from human pregnancy decidua basalis in contact with invasive trophoblast of chorion frondosum and decidua parietalis in contact with non-invasive chorion laeve do not differ in the frequency of lymphoid cells of the following phenotypes (CD2, CD4, CD8, CD14, CD21 and gamma/delta TCR). A practical implication of this observation is that the collection of lymphoid cells from whole decidua by curettage for functional studies is justified. PMID:7539495

  1. Treatment of lupus nephritis with total lymphoid irradiation. Observations during a 12-79-month followup

    SciTech Connect

    Strober, S.; Farinas, M.C.; Field, E.H.; Solovera, J.J.; Kiberd, B.A.; Myers, B.D.; Hoppe, R.T.

    1988-07-01

    Seventeen patients with intractable lupus nephritis and nephrotic syndrome were treated with total lymphoid irradiation. Statistically significant improvement in mean renal disease and serologic activity parameters occurred within 3 months and persisted for at least 3 years. Although there was a marked reduction of T helper cell numbers and function after total lymphoid irradiation, recovery of these parameters was not associated with a return of disease activity. Risks of sterility, severe infections, and hematologic malignancy appeared to be lower than with alkylating agents.

  2. The Role of TOX in the Development of Innate Lymphoid Cells

    PubMed Central

    Seehus, Corey R.; Kaye, Jonathan

    2015-01-01

    TOX, an evolutionarily conserved member of the HMG-box family of proteins, is essential for the development of various cells of both the innate and adaptive immune system. TOX is required for the development of CD4+ T lineage cells in the thymus, including natural killer T and T regulatory cells, as well as development of natural killer cells and fetal lymphoid tissue inducer cells, the latter required for lymph node organogenesis. Recently, we have identified a broader role for TOX in the innate immune system, demonstrating that this nuclear protein is required for generation of bone marrow progenitors that have potential to give rise to all innate lymphoid cells. Innate lymphoid cells, classified according to transcription factor expression and cytokine secretion profiles, derive from common lymphoid progenitors in the bone marrow and require Notch signals for their development. We discuss here the role of TOX in specifying CLP toward an innate lymphoid cell fate and hypothesize a possible role for TOX in regulating Notch gene targets during innate lymphoid cell development. PMID:26556952

  3. Maternal retinoids control type 3 innate lymphoid cells and set the offspring immunity

    NASA Astrophysics Data System (ADS)

    van de Pavert, Serge A.; Ferreira, Manuela; Domingues, Rita G.; Ribeiro, Hélder; Molenaar, Rosalie; Moreira-Santos, Lara; Almeida, Francisca F.; Ibiza, Sales; Barbosa, Inês; Goverse, Gera; Labão-Almeida, Carlos; Godinho-Silva, Cristina; Konijn, Tanja; Schooneman, Dennis; O'Toole, Tom; Mizee, Mark R.; Habani, Yasmin; Haak, Esther; Santori, Fabio R.; Littman, Dan R.; Schulte-Merker, Stefan; Dzierzak, Elaine; Simas, J. Pedro; Mebius, Reina E.; Veiga-Fernandes, Henrique

    2014-04-01

    The impact of nutritional status during fetal life on the overall health of adults has been recognized; however, dietary effects on the developing immune system are largely unknown. Development of secondary lymphoid organs occurs during embryogenesis and is considered to be developmentally programmed. Secondary lymphoid organ formation depends on a subset of type 3 innate lymphoid cells (ILC3) named lymphoid tissue inducer (LTi) cells. Here we show that mouse fetal ILC3s are controlled by cell-autonomous retinoic acid (RA) signalling in utero, which pre-sets the immune fitness in adulthood. We found that embryonic lymphoid organs contain ILC progenitors that differentiate locally into mature LTi cells. Local LTi cell differentiation was controlled by maternal retinoid intake and fetal RA signalling acting in a haematopoietic cell-autonomous manner. RA controlled LTi cell maturation upstream of the transcription factor ROR?t. Accordingly, enforced expression of Rorgt restored maturation of LTi cells with impaired RA signalling, whereas RA receptors directly regulated the Rorgt locus. Finally, we established that maternal levels of dietary retinoids control the size of secondary lymphoid organs and the efficiency of immune responses in the adult offspring. Our results reveal a molecular link between maternal nutrients and the formation of immune structures required for resistance to infection in the offspring.

  4. Classification of lymphoid neoplasms: the microscope as a tool for disease discovery

    PubMed Central

    Harris, Nancy Lee; Stein, Harald; Isaacson, Peter G.

    2008-01-01

    In the past 50 years, we have witnessed explosive growth in the understanding of normal and neoplastic lymphoid cells. B-cell, T-cell, and natural killer (NK)–cell neoplasms in many respects recapitulate normal stages of lymphoid cell differentiation and function, so that they can be to some extent classified according to the corresponding normal stage. Likewise, the molecular mechanisms involved the pathogenesis of lymphomas and lymphoid leukemias are often based on the physiology of the lymphoid cells, capitalizing on deregulated normal physiology by harnessing the promoters of genes essential for lymphocyte function. The clinical manifestations of lymphomas likewise reflect the normal function of lymphoid cells in vivo. The multiparameter approach to classification adopted by the World Health Organization (WHO) classification has been validated in international studies as being highly reproducible, and enhancing the interpretation of clinical and translational studies. In addition, accurate and precise classification of disease entities facilitates the discovery of the molecular basis of lymphoid neoplasms in the basic science laboratory. PMID:19029456

  5. Low-grade metamorphism in the eastern Southern Alps: Distribution, conditions, timing and implications for the tectonics of the Alps and NW Dinarides

    NASA Astrophysics Data System (ADS)

    Neubauer, Franz; Heberer, Bianca; Genser, Johann; Friedl, Getrude

    2014-05-01

    Based on 40Ar/39Ar dating of newly-grown syntectonic metamorphic white mica (sericite), we recognize for the first time the timing of Alpine low-grade metamorphism in the eastern part of the Southalpine unit: (1) A Silurian phyllite of Seeberg inlier located to the south of the Periadriatic fault yields a plateau age at c. 75 Ma suggesting a Late Cretaceous age of previously recognized low-grade (Rantitsch & Rainer, 2003) metamorphism. (2) Within the Tolmin nappe, four sericite plateau ages of mainly Middle Triassic volcanics are at c. 51 Ma (Early Eocene). The Late Cretaceous age in the Seeberg inlier is considered to record ductile deformation during formation of a retro-wedge related to the Eo-Alpine orogeny in the Austroalpine units in the Eastern Alps exposed north of the future Periadriatic fault. The Eocene age at the boundary of very low-grade to low-grade metamorphism in the Tolmin nappe (Rainer et al., 2009) relates to the emplacement of the Southalpine nappe complex onto the Dinarides and is contemporaneous with the initial ductile deformation in the Dinarides during Adria-directed shortening and formation of a siliciclastic flysch belt in front of the SW-directed growing fold-thrust belt (Placer, 2008). Similar rare Late Cretaceous and dominant Eocene ages within post-Variscan units are virtually more widespread in the Southalpine unit and Dinarides as considered before. These regions include the Collio basin (Feijth, 2002) and the Eder unit (Läufer et al., 1996) in the western and central Southern Alps, in the internal NW Dinarides (Borojevi? Šoštari? et al., 2012) and the Mid Bosnian Schist Mountains (Pami? et al., 2004) and Lim Paleozoic unit in the central Dinarides (Ilic et al., submitted). Consequently, the Southalpine unit and Dinarides were affected by two stages of metamorphism, Late Cretaceous (ca. 80 to 75 Ma) and Eocene (ca. 51 - 40 Ma), both stages are related to back-thrusting. The ages of metamorphism are different from those in the main body of the Alpine orogen exposed north of the E-trending Periadriatic fault. In previous interpretations, the eastern Southalpine unit was considered to differ in many respects from Alpine units north of the Periadriatic fault including (1) no Alpine metamorphic overprint and, therefore, (2) also no Alpine ductile deformation in contrast to amphibolite- and even eclogite- grade metamorphism (ca. 100 - 85 Ma) in Austroalpine units north of the fault, and by (3) S- to SW-, Adria-directed vergency of the deformation of mostly Eocene to Neogene age in contrast to all units basically directed to the north and northwest, towards the stable European plate. The Southalpine unit is considered as back-thrust of the Middle-Late Eocene plate collision between Stable Europe and the Alpine thrust wedge (Doglioni & Bosellini, 1987). The new data from the eastern part of the Southalpine unit challenge this view and imply a steadily but slowly growing Adria-directed thrust wedge between Maastrichtian and Early Eocene times. Acknowledement: The work has been supported by the Austrian Science Fund (project no. 22,110). References Borojevi? Šoštari?, S. Neubauer, F., Handler, R., Palinkaš, L. A., 2012. Variscan vs. Alpine tectonothermal events in NW-Dinarides: constraints from 40Ar/39Ar dating. Geologica Carpathica, 63, 441-452. Doglioni, C., Bosellini, A., 1987. Eoalpine and mesoalpine tectonics in the Southern Alps. Geologische Rundschaus, 76, 735-754. Feijth, J., 2002. Paleozoic and Mesozoic tectonometamorphic development and geochronology of the Orobic chain (Southern Alps, Lombardy, Italy). PhD thesis, Faculty of Engineering and Applied Geosciences, Technical University of Berlin, 136 p. Ili?, A., Neubauer, F., Handler, R. (submitted). Formation of a structural dome due to transpression: The Lim unit in Central Dinarides. Journal of Structural Geology. Läufer, A.L., Frisch, W., Steinitz, G., Loeschke, J., 1997. Exhumed fault-bounded Alpine blocks along the Periadriatic lineament: the Eder unit (Carnic Alps, Austria). Geologische Rundschau, 86, 612-626. P

  6. Catalytic-Oxidative Leaching of Low-Grade Complex Zinc Ore by Cu (II) Ions Produced from Copper Ore in Ammonia-Ammonium Sulfate Solution

    NASA Astrophysics Data System (ADS)

    Liu, Zhi Xiong; Yin, Zhou Lan; Hu, Hui Ping; Chen, Qi Yuan

    2012-10-01

    The catalytic-oxidative leaching of a mixed ore, which consists of low-grade oxide copper ore and oxide zinc ore containing ZnS, was investigated in ammonia-ammonium sulfate solution. The effect of the main parameters, such as mass ratio of copper ore to zinc ore, liquid-to-solid ratio, concentration of lixivant, leaching time, and temperature, was studied. The optimal leaching conditions with a maximum extraction of Cu 92.6 pct and Zn 85.5 pct were determined as follows: the mass ratio of copper ore to zinc ore 4/10 g/g, temperature 323.15 K (50 °C), leaching time 6 hours, stirring speed 500 r/min, liquid-to-solid ratio 3.6/1 cm3/g, concentration of lixivant including ammonia 2.0 mol/dm3, ammonium sulfate 1.0 mol/dm3, and ammonium persulfate 0.3 mol/dm3. It was found that ZnS in the oxide zinc ore could be extracted with Cu(II) ion, which was produced from copper ore and was used as the catalyst in the presence of ammonium persulfate.

  7. Histologically low-grade, yet biologically high-grade, fibrosarcomas of the mandible and maxilla in dogs: 25 cases (1982-1991).

    PubMed

    Ciekot, P A; Powers, B E; Withrow, S J; Straw, R C; Ogilvie, G K; LaRue, S M

    1994-02-15

    Medical records of 25 dogs with histologically low-grade fibrous masses of the maxilla and mandible were reviewed. Most of the dogs had extensive clinical histories and had had previous biopsies of the affected regions, from which specimens were often interpreted as benign fibrous connective tissue. The most common breed represented was Golden Retriever (13/25 dogs, 52%). Skull radiographs were evaluated for 22 dogs, and 16 dogs (72%) had evidence of bone lysis. At admission, none of the dogs had radiographic evidence of pulmonary metastasis. On subsequent examinations and necropsy, prevalence of pulmonary metastasis was 12% (3/25 dogs) and of regional lymph node metastasis, 20% (5/25 dogs). Histologic appearance of all specimens was similar and was characterized by proliferation of fibrous connective tissue, with moderate to low cellularity, that aggressively infiltrated adjacent normal tissue. Treatment modalities varied considerably. Surgical excision in combination with radiation therapy, surgery alone, radiation therapy alone, and radiation therapy used adjunctly with localized hyperthermia prolonged survival times in some dogs. The clinical signs, tumor behavior, and histologic characteristics of these lesions were distinctive from those in previously described oral fibrosarcomas in dogs. Comparatively, these tumors most closely resembled aggressive fibromatoses in human beings in regard to clinical signs, local invasive behavior, and histologic appearance, but differed in the prevalence of metastasis. PMID:8163417

  8. Saccharomyces boulardii Administration Changes Gut Microbiota and Reduces Hepatic Steatosis, Low-Grade Inflammation, and Fat Mass in Obese and Type 2 Diabetic db/db Mice

    PubMed Central

    Everard, Amandine; Matamoros, Sébastien; Geurts, Lucie; Delzenne, Nathalie M.

    2014-01-01

    ABSTRACT Growing evidence shows that gut microbes are key factors involved in the regulation of energy homeostasis, metabolic inflammation, lipid metabolism, and glucose metabolism. Therefore, gut microbiota modulations caused by selectively fermented oligosaccharides or probiotic bacteria constitute an interesting target in the physiopathology of obesity. However, to date, no probiotic yeast has been investigated in this context. Therefore, our study aimed to evaluate the impact of the most-studied probiotic yeast (i.e., Saccharomyces boulardii Biocodex) on obesity and associated metabolic features, such as fat mass development, hepatic steatosis, and low-grade inflammation, in obese mice. S. boulardii was administered daily by oral gavage to leptin-resistant obese and type 2 diabetic mice (db/db) for 4 weeks. We found that S. boulardii-treated mice exhibited reduced body weight, fat mass, hepatic steatosis, and inflammatory tone. Interestingly, these effects of S. boulardii on host metabolism were associated with local effects in the intestine. S. boulardii increased cecum weight and cecum tissue weight but also induced dramatic changes in the gut microbial composition at the phylum, family, and genus levels. These gut microbiota changes in response to S. boulardii may also be correlated with the host metabolism response. In conclusion, this study demonstrates for the first time that S. boulardii may act as a beneficial probiotic treatment in the context of obesity and type 2 diabetes. PMID:24917595

  9. Immunohistochemistry and Fluorescence In Situ Hybridization Can Inform the Differential Diagnosis of Low-Grade Noninvasive Urothelial Carcinoma with an Inverted Growth Pattern and Inverted Urothelial Papilloma

    PubMed Central

    Lu, Yong-Ming; Zhang, Hui-Zhi; Wang, Tao; Yang, Xiao-Qun; Sun, Meng-Hong; Wang, Chao-Fu

    2015-01-01

    Urothelial carcinoma (UC) comprises a heterogeneous group of epithelial neoplasms with diverse biological behaviors and variable clinical outcomes. Distinguishing UC histological subtypes has become increasingly important because prognoses and therapy can dramatically differ among subtypes. In clinical work, overlapping morphological findings between low-grade noninvasive UC (LGNUC), which exhibits an inverted growth pattern, and inverted urothelial papilloma (IUP) can make subclassification difficult. We propose a combination of immunohistochemistry (IHC) and molecular cytogenetics for subtyping these clinical entities. In our study, tissue microarray immunohistochemical profiles of Ki-67, p53, cytokeratin 20 (CK20) and cyclinD1 were assessed. Molecular genetic alterations such as the gain of chromosomes 3, 7 or 17 or the homozygous loss of 9p21 were also assessed for their usefulness in differentiating these conditions. Based on our analysis, Ki-67 and CK20 may be useful for the differential diagnosis of these two tumor types. Fluorescence in situ hybridization (FISH) can also provide important data in cases in which the malignant nature of an inverted urothelial neoplasm is unclear. LGNUC with an inverted growth pattern that is negative for both Ki-67 and CK20 can be positively detected using FISH. PMID:26208279

  10. Cardiac Troponin Testing in Idiopathic Inflammatory Myopathies and Systemic Sclerosis-Spectrum Disorders: Biomarkers to Distinguish between Primary Cardiac Involvement and Low Grade Skeletal Muscle Disease Activity

    PubMed Central

    Hughes, Michael; Lilleker, James B; Herrick, Ariane L; Chinoy, Hector

    2015-01-01

    Primary cardiac involvement, an under-recognised manifestation of the idiopathic inflammatory myopathies (IIM) and systemic sclerosis (SSc)-spectrum disorders, is associated with significant mortality. Within these two conditions, traditional skeletal muscle enzyme testing may not effectively distinguish between skeletal and cardiac muscle involvement, especially in patients with subclinical cardiac disease. Accurate biomarkers are thus required to screen for cardiac disease, to better inform both therapeutic decision-making and treatment response. The widespread uptake of cardiac troponin testing has revolutionised the management of acute coronary syndromes. Whereas cardiac troponin I (cTnI) appears specific to the myocardium, cardiac troponin T (cTnT) is also expressed by skeletal muscle, including regenerating skeletal muscle tissue. There is increasing interest about the role of cardiac troponins as a putative biomarker of primary cardiac involvement in IIM and SSc-spectrum disorders. Herewith we discuss subclinical cardiac disease in IIM and SSc-spectrum disorders, the respective roles of cTnI and cTnT testing, and the re-expression of cTnT within regenerating skeletal muscle tissue. There remains wide variation in access to cardiac troponin testing nationally and internationally. We propose two pragmatic clinical pathways using cardiac troponins, preferably measuring concomitant cTnT followed by confirmatory (cardiac) cTnI to screen patients for subclinical cardiac disease and/or low-grade skeletal muscle disease activity, and also an agenda for future research, and also an agenda for future research. PMID:25732174

  11. Cardiac troponin testing in idiopathic inflammatory myopathies and systemic sclerosis-spectrum disorders: biomarkers to distinguish between primary cardiac involvement and low-grade skeletal muscle disease activity.

    PubMed

    Hughes, Michael; Lilleker, James B; Herrick, Ariane L; Chinoy, Hector

    2015-05-01

    Primary cardiac involvement, an under-recognised manifestation of the idiopathic inflammatory myopathies (IIM) and systemic sclerosis (SSc)-spectrum disorders, is associated with significant mortality. Within these two conditions, traditional skeletal muscle enzyme testing may not effectively distinguish between skeletal and cardiac muscle involvement, especially in patients with subclinical cardiac disease. Accurate biomarkers are thus required to screen for cardiac disease, to better inform both therapeutic decision-making and treatment response. The widespread uptake of cardiac troponin testing has revolutionised the management of acute coronary syndromes. While cardiac troponin I (cTnI) appears specific to the myocardium, cardiac troponin T (cTnT) is also expressed by skeletal muscle, including regenerating skeletal muscle tissue. There is increasing interest about the role of cardiac troponins as a putative biomarker of primary cardiac involvement in IIM and SSc-spectrum disorders. Herewith we discuss subclinical cardiac disease in IIM and SSc-spectrum disorders, the respective roles of cTnI and cTnT testing, and the re-expression of cTnT within regenerating skeletal muscle tissue. There remains wide variation in access to cardiac troponin testing nationally and internationally. We propose two pragmatic clinical pathways using cardiac troponins, preferably measuring concomitant cTnT followed by confirmatory (cardiac) cTnI to screen patients for subclinical cardiac disease and/or low-grade skeletal muscle disease activity, and also an agenda for future research. PMID:25732174

  12. Low-temperature formation of pyrrhotite from magnetite sup + pyrite: Evidence from low-grade metamorphism and implications for magnetite preservation during deep burial

    SciTech Connect

    Gillett, S.L. )

    1991-03-01

    Early magnetite in sedimentary rocks must be preserved to retain a paleomagnetic signature; however, reactions such as Fe{sub 3}O{sub 4} + 3 FeS{sub 2} + CH{sub 4}' = (organic matter) = 6 FeS' (pyrr.) + CO{sub 2} + 2 H{sub 2}O tend to the right for temperatures less than {approximately}200C. Such low temperatures strongly imply that magnetite can be destroyed merely by deep burial. Such pyrrhotite formation is illustrated by very low-grade metamorphism in a contact aureole surrounding the Jurassic Notch Peak stock in the central House Range of western Utah. The stock invades a Cambrian sedimentary sequence containing miogeoclinal limestones with intercalated siltstones. Limestones in the aureole yield a scattered, two-polarity remagnetization, residing in pyrrhotite, which extends into rocks that appear unmetamorphosed (temperatures {approximately}250C). The pyrrhotite could not have been precipitated from externally derived fluids because oxygen isotopic data from the limestones show no influence of magmatic or phreatic water; hence, it must have formed in situ, as in the above equation. Outside the aureole, a characteristic magnetization is preserved that apparently reflects late Paleozoic remagnetization and that probably resides in authigenic magnetite. Hence, it appears that this relatively late magnetite was in turn destroyed by modest reheating from the pluton. In general, thermal remagnetization of sedimentary rocks is probably rare: chemical changes probably have a much more profound effect on the paleomagnetic signatures.

  13. Treatment of experimental myasthenia gravis with total lymphoid irradiation

    SciTech Connect

    de Silva, S.; Blum, J.E.; McIntosh, K.R.; Order, S.; Drachman, D.B.

    1988-07-01

    Total lymphoid irradiation (TLI) has been reported to be effective in the immunosuppressive treatment of certain human and experimental autoimmune disorders. We have investigated the effects of TLI in Lewis rats with experimental autoimmune myasthenia gravis (EAMG) produced by immunization with purified torpedo acetylcholine receptor (AChR). The radiation is given in 17 divided fractions of 200 rad each, and nonlymphoid tissues are protected by lead shielding. This technique suppresses the immune system, while minimizing side effects, and permits the repopulation of the immune system by the patient's own bone marrow cells. Our results show that TLI treatment completely prevented the primary antibody response to immunization with torpedo AChR, it rapidly abolished the ongoing antibody response in established EAMG, and it suppressed the secondary (anamnestic) response to a boost of AChR. No EAMG animals died during TLI treatment, compared with six control animals that died of EAMG. TLI produces powerful and prompt immunosuppression and may eventually prove useful in the treatment of refractory human myasthenia gravis.

  14. Replacement of donor lymphoid tissue in small-bowel transplants

    PubMed Central

    Iwaki, Yuichi; Starzl, Thomas E.; Yagihashi, Atsuhito; Taniwaki, Satoshi; Abu-Elmagd, Kareem; Tzakis, Andreas; Fung, John; Todo, Satoru

    2010-01-01

    The presence of recipient lymphocytes in grafts is thought to equate with rejection. Thus, we wished to follow the fate of lymphocytes after transplant of the small bowel. Three complete small-bowel transplants, two with the liver from the same donor also transplanted, were done successfully. Patients were immunosuppressed with FK 506. 5 to 11% of lymphocytes in the recipients’ peripheral blood were of donor origin during the early postoperative period when there were no clinical signs of graft-versus-host disease. However, donor cells were no longer detectable after 12 to 54 days. Serial biopsy specimens of the grafted small bowel showed progressive replacement of lymphocytes in the lamina propria by those of the recipient’s HLA phenotype. Lymphoid repopulation was complete after 10 to 12 weeks but the epithelial cells of the intestine remained those of the donor. The patients are on enteral alimentation after 5, 6, and 8 months with histopathologically normal or nearly normal intestines. Re-examination of assumptions about the rejection of intestinal grafts and strategies for its prevention are required following these observations. PMID:1707470

  15. Post-conversion sialylation of prions in lymphoid tissues

    PubMed Central

    Srivastava, Saurabh; Makarava, Natallia; Katorcha, Elizaveta; Savtchenko, Regina; Brossmer, Reinhard; Baskakov, Ilia V.

    2015-01-01

    Sialylated glycans on the surface of mammalian cells act as part of a “self-associated molecular pattern,” helping the immune system to recognize “self” from “altered self” or “nonself.” To escape the host immune system, some bacterial pathogens have evolved biosynthetic pathways for host-like sialic acids, whereas others recruited host sialic acids for decorating their surfaces. Prions lack nucleic acids and are not conventional pathogens. Nevertheless, prions might use a similar strategy for invading and colonizing the lymphoreticular system. Here we show that the sialylation status of the infectious, disease-associated state of the prion protein (PrPSc) changes with colonization of secondary lymphoid organs (SLOs). As a result, spleen-derived PrPSc is more sialylated than brain-derived PrPSc. Enhanced sialylation of PrPSc is recapitulated in vitro by incubating brain-derived PrPSc with primary splenocytes or cultured macrophage RAW 264.7 cells. General inhibitors of sialyltranserases (STs), the enzymes that transfer sialic acid residues onto terminal positions of glycans, suppressed extrasialylation of PrPSc. A fluorescently labeled precursor of sialic acid revealed ST activity associated with RAW macrophages. This study illustrates that, upon colonization of SLOs, the sialylation status of prions changes by host STs. We propose that this mechanism is responsible for camouflaging prions in SLOs and has broad implications. PMID:26627256

  16. Blimp-1 is a tumor suppressor gene in lymphoid malignancies.

    PubMed

    Hangaishi, Akira; Kurokawa, Mineo

    2010-01-01

    B lymphocyte-induced maturation protein (Blimp-1) is a transcriptional factor, which controls the terminal differentiation of mature B cells to plasma cells. Blimp-1 is also called positive regulatory domain I-binding factor-1 (PRDI-BF1) or PR (PRDI-BF1-RIZ) domain zinc finger protein 1 (PRDM1). Furthermore, Blimp-1 is located in chromosome 6q21-22.1, a region frequently deleted in several tumors including lymphoid malignancies and has been supposed to be a candidate of tumor suppressor gene. Recently, mutational inactivation of Blimp-1 has been identified in a subset of diffuse large B-cell lymphomas of the activated B-cell type. In addition, an important role for Blimp-1 in maintaining the homeostasis of effector T cells is emerging and high expression of Blimp-1beta, a splicing variant of Blimp-1, have been presumed to be associated with poor prognosis in T cell lymphoma although this aspect of the gene needs further investigation. For this reason, we focused on the tumor suppressor function of Blimp-1 on not only B but also T cell malignancies in this review. PMID:20047096

  17. Composition, Development, and Function of Uterine Innate Lymphoid Cells

    PubMed Central

    Balmas, Elisa; Boulenouar, Selma; Gaynor, Louise M.; Kieckbusch, Jens; Gardner, Lucy; Hawkes, Delia A.; Barbara, Cynthia F.; Sharkey, Andrew M.; Brady, Hugh J. M.; Brosens, Jan J.; Moffett, Ashley; Colucci, Francesco

    2015-01-01

    Innate lymphoid cells (ILCs), including NK cells, contribute to barrier immunity and tissue homeostasis. In addition to the role of uterine NK cells in placentation and fetal growth, other uterine ILCs (uILCs) are likely to play roles in uterine physiology and pathology. In this article, we report on the composition of uILCs in the endometrium during the luteal phase and in the decidua during early pregnancy. Whereas nonkiller uILC1s and uILC2s are barely detectable in mouse and not detected in humans, a sizeable population of uILC3s is found in human endometrium and decidua, which are mostly NCR+ and partially overlap with previously described IL-22–producing uterine NK cells. Development of mouse uILC3 is Nfil3 independent, suggesting unique features of uILCs. Indeed, although the cytokine production profile of mouse uILCs recapitulates that described in other tissues, IL-5, IL-17, and IL-22 are constitutively produced by uILC2s and uILC3s. This study lays the foundation to understand how ILCs function in the specialized uterine mucosa, both in tissue homeostasis and barrier immunity and during pregnancy. PMID:26371244

  18. Composition, Development, and Function of Uterine Innate Lymphoid Cells.

    PubMed

    Doisne, Jean-Marc; Balmas, Elisa; Boulenouar, Selma; Gaynor, Louise M; Kieckbusch, Jens; Gardner, Lucy; Hawkes, Delia A; Barbara, Cynthia F; Sharkey, Andrew M; Brady, Hugh J M; Brosens, Jan J; Moffett, Ashley; Colucci, Francesco

    2015-10-15

    Innate lymphoid cells (ILCs), including NK cells, contribute to barrier immunity and tissue homeostasis. In addition to the role of uterine NK cells in placentation and fetal growth, other uterine ILCs (uILCs) are likely to play roles in uterine physiology and pathology. In this article, we report on the composition of uILCs in the endometrium during the luteal phase and in the decidua during early pregnancy. Whereas nonkiller uILC1s and uILC2s are barely detectable in mouse and not detected in humans, a sizeable population of uILC3s is found in human endometrium and decidua, which are mostly NCR(+) and partially overlap with previously described IL-22-producing uterine NK cells. Development of mouse uILC3 is Nfil3 independent, suggesting unique features of uILCs. Indeed, although the cytokine production profile of mouse uILCs recapitulates that described in other tissues, IL-5, IL-17, and IL-22 are constitutively produced by uILC2s and uILC3s. This study lays the foundation to understand how ILCs function in the specialized uterine mucosa, both in tissue homeostasis and barrier immunity and during pregnancy. PMID:26371244

  19. In vitro stimulation of murine lymphoid cell cultures by levamisole.

    PubMed Central

    Merluzzi, V J; Badger, A M; Kaiser, C W; Cooperband, S R

    1975-01-01

    Levamisole has been reported to act as an immunological adjuvant. Experiments reported here on the effect of this agent on a variety of murine lymphoid culture systems were designed to gain an insight into its mechanism of action. We have found levamisole to be a weak mitogen for mouse spleen cells producing a dose related response which peaks at 48 hr in culture. The drug acted to augment the response of spleen cells to sub-optimal concentrations of concanavalin A, but had no unusual effect on the lipopolysaccharide stimulation of B-cell DNA synthesis in vitro. Levamisole was directly stimulatory on enriched T-cell populations and was found to have two actions: (1) to stimulate a subpopulation of T cells and (2) to augment the response of suboptimal mitogen concentrations of concanavalin A. In addition, we have found that murine thymocytes stimulated by concanavalin A were greatly potentiated in the presence of levamisole, but this population of cells could not be stimulated directly by the drug. PMID:1083786

  20. The Detection of Glycosaminoglycans in Pancreatic Islets and Lymphoid Tissues

    PubMed Central

    Bogdani, Marika; Simeonovic, Charmaine; Nagy, Nadine; Johnson, Pamela Y.; Chan, Christina K.; Wight, Thomas N.

    2014-01-01

    Summary In this chapter, we describe the detection of the glycosaminoglycans hyaluronan and heparan sulfate in pancreatic islets and lymphoid tissues. The identification of hyaluronan in tissues is achieved by utilizing a highly specific hyaluronan binding protein (HABP) probe that interacts with hyaluronan in tissue sections. The HABP probe is prepared by enzymatic digestion of the chondroitin sulfate proteoglycan aggrecan which is present in bovine nasal cartilage, and is then biotinylated in the presence of bound hyaluronan and the link protein. Hyaluronan is then removed by gel filtration chromatography. The biotinylated HABP - link protein complex is applied to tissue sections and binding of the complex to tissue hyaluronan is visualized by enzymatic precipitation of chromogenic substrates. To determine hyaluronan content in tissues, tissues are first proteolytically digested to release hyaluronan from the macromolecular complexes that this molecule forms with other extracellular matrix constituents. Digested tissue is then incubated with HABP. The hyaluronan - HABP complexes are extracted and the hyaluronan concentration in the tissue is determined using an ELISA-like assay. Heparan sulfate is identified in mouse tissues by Alcian blue histochemistry and indirect immunohistochemistry. In human tissues, heparan sulfate is best detected by indirect immunohistochemistry using a specific anti-heparan sulfate monoclonal antibody. A biotinylated secondary antibody is then applied in conjunction with streptavidin-peroxidase and its binding to the anti-heparan sulfate antibody is visualized by enzymatic precipitation of chromogenic substrates. PMID:25325969

  1. Immunocompetence of normal human appendiceal lymphoid cells: in vitro studies.

    PubMed Central

    Kawanishi, H

    1987-01-01

    In order to study the activity of immunocompetent lymphocytes in normal human adult mucosal lymphoid tissues in the gut, viable mononuclear cells (MNC) from surgically removed appendices were isolated with a rapid and improved technique, and their immune reactivity determined in vitro. Nearly two-thirds of the isolated cells were B cells, composed of sIgM (30%), sIgA (19%) and sIgG (12%), less than one-third of cells being T cells, composed of OKT4+ helper/inducer T cells (18%) and OKT8+ suppressor/cytotoxic T cells (9%). Isolated B cells were responsive to SAC (Cowan type I Staphylococcus aureus) with marked augmentation of IgG production, but not to lipopolysaccharides (LPS). In the presence or absence of pokeweed mitogen (PWM) and protein A, all isotype-specific Ig production was augmented along with increasing ratios of autologous T cells to B cells, whereas in the presence of anti-HLA-DR antibodies the production of IgA and IgM was reduced to a great extent. Finally, in vitro induction of concanavalin A (Con A)-induced suppressor T (Ts) cells was less than that of helper T (Th) cells. Thus, normal adult appendiceal (Ap) lymphocyte reactivity is predominated by helper T (Th) cells; IgA isotype-specific Ig production appears to be largely regulated by the autoreactive Th subset. This responsiveness to exogenous stimuli may play an important role in the gut mucosal immune responsiveness. PMID:3493205

  2. Clinical drawbacks of total lymphoid irradiation: the cons

    SciTech Connect

    Myers, L.W.; Ellison, G.W.; Fahey, J.L.; Tesler, A.; Gottlieb, M.S.

    1988-07-01

    Success has been reported with use of total lymphoid irradiation (TLI) in organ transplant recipients and in patients with rheumatoid arthritis and other autoimmune diseases. In a well-conducted randomized double blind clinical trial, Cook et al have found that TLI was superior to sham irradiation of patients with multiple sclerosis (MS). However, it is clear from looking at this data that not all patients responded to TLI and that with time disease activity returned. Our own experience with TLI in two MS patients was very disappointing. Despite its apparent benefit in some conditions, considerable drawbacks are associated with TLI. These include high financial cost, unpleasant treatment-related side effects, and the possibility that more serious morbidity as well as mortality may be treatment-related. Furthermore, the optimum therapeutic regimen for TLI has not yet been established. Issues related to cumulative dose, dose per fraction, frequency of fractions, field of irradiation, and interaction with other therapies still need clarification. For these reasons we do not recommend TLI as a treatment for MS.

  3. Type-2 innate lymphoid cells in human allergic disease

    PubMed Central

    Barlow, Jillian L.; McKenzie, Andrew N.J.

    2014-01-01

    Purpose of review Recent decades have seen allergic diseases become endemic in a number of developed countries. Understanding the inflammatory processes that dictate these allergic responses is therefore important. Recent findings Critical to many allergic responses is the inappropriate release of the type-2 immune-regulatory cytokines: interleukin-4, interleukin-5, interleukin-9, and interleukin-13. The study of these inflammatory mediators has led directly to the development of two new asthma treatments: anti-interleukin-5 and anti-interleukin-13. Until recently, T helper 2 cells were considered to be the major cellular source of type-2 cytokines; however, a paradigm shift occurred with the discovery of a novel population, type-2 innate lymphoid cells (ILC2s), that can produce huge levels of type-2 cytokines and are sufficient to induce allergy in mice. This discovery raises interesting questions about how innate and adaptive type-2 immunity might interact to induce relapsing and remitting episodes of allergy in patients. Summary It is essential that alongside the mechanistic investigation using model organisms, the roles of ILC2s in human disease be explored. Here, we discuss how ILC2 traits, discovered in mouse models, have informed research in humans and how newly identified human ILC2 pathways might provide potential therapeutic benefits in the future. PMID:25115682

  4. Lymphoid tissue during irradiation of tumors with pulsing laser's radiation

    NASA Astrophysics Data System (ADS)

    Moskalik, Konstantin G.

    2002-06-01

    The structure of the regional lymph nodes and the thymus was studied in the experiments upon the mice of the line C57BL with the subcutaneous interwoven melanoma B16 in the periods from one hour to 12 days after the radiation of melanoma with one irradiation impulse of the Nd laser with the energy density of 400 J/cm2. During the first 3 days after the irradiation of tumor with laser radiation the impoverishment of lymph nodes and thymus with lymphocytes takes place because of their intensified migration from these organs to the blood channel. Then one can see the restoration of the lymph nodes and thymus structure. The restoration of lymphopoiesis in the lymph nodes went on in the first place because of the poiesis in the follicles which consist of B-lymphocytes. Consequently, the lymphoid tissue plays a great role in the reorganization of the immunological status of the organism. Reorganization can be seen during the treatment of tumors with laser radiation, and it takes place in the first instance because of the reinforcement of the humoral immunity.

  5. INTEGRIN FUNCTION IN T CELL HOMING TO LYMPHOID AND NON-LYMPHOID SITES: GETTING THERE AND STAYING THERE

    PubMed Central

    DeNucci, Christopher C.; Mitchell, Jason S.; Shimizu, Yoji

    2009-01-01

    The continuous recirculation of naïve T cells and their subsequent migration to tissue following activation is crucial for maintaining protective immunity against invading pathogens. The preferential targeting of effector and memory T cells to tissue is instructed during priming and mediated by cell surface expressed adhesion receptors such as integrins. Integrins are involved in nearly all aspects of T cell life, including naive T cell circulation, activation, and finally effector T cell trafficking and localization. Recent research has revealed that microenvironmental factors present during T cell priming result in the specific regulation of adhesion/integrin and chemokine receptor expression. Once antigen-experienced T cells enter tissue, further changes in integrin expression may occur that is critical for T cell localization, retention, effector function, and survival. This review will discuss the function of integrin expression on T cells and the multiple roles integrins play on naïve T cells and in directing effector T cell trafficking to non-lymphoid sites in order to maintain protective adaptive immunity at body barriers. PMID:19496742

  6. Lymphocyte trafficking and HIV infection of human lymphoid tissue in a rotating wall vessel bioreactor

    NASA Technical Reports Server (NTRS)

    Margolis, L. B.; Fitzgerald, W.; Glushakova, S.; Hatfill, S.; Amichay, N.; Baibakov, B.; Zimmerberg, J.

    1997-01-01

    The pathogenesis of HIV infection involves a complex interplay between both the infected and noninfected cells of human lymphoid tissue, the release of free viral particles, the de novo infection of cells, and the recirculatory trafficking of peripheral blood lymphocytes. To develop an in vitro model for studying these various aspects of HIV pathogenesis we have utilized blocks of surgically excised human tonsils and a rotating wall vessel (RWV) cell culture system. Here we show that (1) fragments of the surgically excised human lymphoid tissue remain viable and retain their gross cytoarchitecture for at least 3 weeks when cultured in the RWV system; (2) such lymphoid tissue gradually shows a loss of both T and B cells to the surrounding growth medium; however, this cellular migration is reversible as demonstrated by repopulation of the tissue by labeled cells from the growth medium; (3) this cellular migration may be partially or completely inhibited by embedding the blocks of lymphoid tissue in either a collagen or agarose gel matrix; these embedded tissue blocks retain most of the basic elements of a normal lymphoid cytoarchitecture; and (4) both embedded and nonembedded RWV-cultured blocks of human lymphoid tissue are capable of productive infection by HIV-1 of at least three various strains of different tropism and phenotype, as shown by an increase in both p24 antigen levels and free virus in the culture medium, and by the demonstration of HIV-1 RNA-positive cells inside the tissue identified by in situ hybridization. It is therefore reasonable to suggest that gel-embedded and nonembedded blocks of human lymphoid tissue, cocultured with a suspension of tonsillar lymphocytes in an RWV culture system, constitute a useful model for simulating normal lymphocyte recirculatory traffic and provide a new tool for testing the various aspects of HIV pathogenesis.

  7. Prognostic impact of extent of vascular invasion in low-grade encapsulated follicular cell-derived thyroid carcinomas: a clinicopathologic study of 276 cases.

    PubMed

    Xu, Bin; Wang, Laura; Tuttle, R Michael; Ganly, Ian; Ghossein, Ronald

    2015-12-01

    Continuous controversy surrounds the predictive value of the degree of vascular invasion (VI) in low-grade encapsulated follicular cell-derived thyroid carcinomas (LGEFCs). Some guidelines advocate conservative therapy in LGEFCs with focal VI. There is therefore a need to assess the survival rates of LGEFC patients with various degrees of VI to better stratify patients for subsequent therapy. Furthermore, the prognostic effect of VI within the different histotypes of LGEFCs is not well known. A total of 276 patients with LGEFCs were subjected to a meticulous histopathologic analysis. They were classified as encapsulated papillary thyroid carcinoma, encapsulated follicular carcinoma (EFC), and encapsulated Hurthle cell carcinoma (EHCC). Of the 276 patients, 24 had extensive VI (EVI) (?4 foci) and 28 displayed focal (<4 foci) VI. EHCC and EFC showed a much higher rate of EVI than encapsulated papillary thyroid carcinoma. Median follow-up was 6 years. All 14 tumors with adverse behavior harbored distant metastases (DMs), of which 9 had DMs at presentation. All 3 patients without EVI who had aggressive carcinomas harbored DMs at presentation. EVI was an independent predictor of poor recurrence-free survival. Excluding cases with DMs at presentation, only patients with EVI had recurrence, and all relapsed cases were EHCC. EVI is an independent predictor of recurrence-free survival in LGEFCs. EHCC with EVI has a particularly high risk of recurrence. When DMs are not found at presentation, patients with focal VI are at a very low risk of recurrence even if not treated with radioactive iodine. PMID:26482605

  8. Combined Oral Contraception and Obesity Are Strong Predictors of Low-Grade Inflammation in Healthy Individuals: Results from the Danish Blood Donor Study (DBDS)

    PubMed Central

    Sørensen, Cecilie J.; Pedersen, Ole B.; Petersen, Mikkel S.; Sørensen, Erik; Kotzé, Sebastian; Thørner, Lise W.; Hjalgrim, Henrik; Rigas, Andreas S.; Møller, Bjarne; Rostgaard, Klaus; Riiskjær, Mads; Ullum, Henrik; Erikstrup, Christian

    2014-01-01

    Background C-reactive protein (CRP) is a well-established marker of inflammation. The level of CRP is affected by several lifestyle factors. A slightly increased CRP level, also known as low-grade inflammation (LGI), is associated with increased risk of several diseases, especially cardiovascular disease. The aim of this study was to identify predictors of increased CRP levels in healthy individuals. We therefore assessed CRP in a large cohort of blood donors. Methods We measured plasma CRP levels in 15,684 participants from the Danish Blood Donor Study. CRP was measured by a commercial assay. Furthermore, all participants completed a standard questionnaire on smoking status, alcohol consumption, physical activity, diet, and various body measurements. Female participants also reported the use of contraception, childbirth, and menopausal status. The relationship between LGI (defined here as a plasma CRP level between 3 mg/L and 10 mg/L) and predictors was explored by multivariable logistic regression analysis. Results were presented as odds ratios (OR) with 95% confidence intervals (CI). Results We found LGI in a total of 1,561 (10.0%) participants. LGI was more frequent in women using combined oral contraception (OC) (29.9%) than in men (6.1%) and women not using OC (7.9%). Among premenopausal women, OC was the strongest predictor of LGI (odds ratio?=?8.98, p<0.001). Additionally, body mass index (BMI) and waist circumference were positively associated with LGI. Conclusion High BMI and abdominal obesity strongly predicted LGI among healthy individuals. However, the most striking finding was the high prevalence of LGI among premenopausal women who used combined oral contraception. Although the significance of CRP as a marker of inflammation is well known, the role of CRP in pathogenesis is still uncertain. The impact of oral contraception on CRP levels should nevertheless be considered when CRP is used in risk assessment. PMID:24516611

  9. A Genetic Dichotomy between Pure Sclerosing Epithelioid Fibrosarcoma (SEF) and Hybrid SEF/Low Grade Fibromyxoid Sarcoma: A Pathologic and Molecular Study of 18 cases

    PubMed Central

    Prieto-Granada, Carlos; Zhang, Lei; Chen, Hsiao-Wei; Sung, Yun-Shao; Agaram, Narasimhan P; Jungbluth, Achim; Antonescu, Cristina R

    2014-01-01

    Sclerosing epithelioid fibrosarcoma (SEF) is a rare soft tissue tumor exhibiting considerable morphologic overlap with low grade fibromyxoid sarcoma (LGFMS). Moreover, both SEF and LGFMS show MUC4 expression by immunohistochemistry. While the majority of LGFMS cases are characterized by a FUS-CREB3L1 fusion, both FUS-CREB3L2 and EWSR1-CREB3L1 fusions were recently demonstrated in a small number of LGFMS and SEF/LGFMS hybrid tumors. In contrast, recent studies pointed out that SEF harbor frequent EWSR1 rearrangements, with only a minority of cases showing FUS-CREB3L2 fusions. In an effort to further characterize the molecular characteristics of pure SEF and hybrid SEF/LGFMS lesions, we undertook a clinicopathologic, immunohistochemical and genetic analysis of a series of 10 SEF and 8 hybrid SEF/LGFMS tumors. The mortality rate was similar between the two groups, 44% within the pure SEF group and 37% in the hybrid SEF/LGFMS with a mean overall follow-up of 66 months. All but one pure SEF and all hybrid SEF/LGFMS tested cases showed MUC4 immunoreactivity. The majority (90%) of pure SEF cases showed EWSR1 gene rearrangements by FISH with only one case exhibiting FUS rearrangement. Of the 9 EWSR1 positive cases, 6 cases harbored CREB3L1 break-apart, two had CREB3L2 rearrangement (a previously unreported finding) and one lacked evidence of CREB3L1/2 abnormalities. In contrast, all hybrid SEF/LGFMS tumors exhibited FUS and CREB3L2 rearrangements. These results further demarcate a relative cytogenetic dichotomy between pure SEF, often characterized by EWSR1 rearrangements, and hybrid SEF/LGFMS, harboring FUS-CREB3L2 fusion; the latter group recapitulating the genotype of LGFMS. PMID:25231134

  10. Hybrid pressure retarded osmosis-membrane distillation system for power generation from low-grade heat: thermodynamic analysis and energy efficiency.

    PubMed

    Lin, Shihong; Yip, Ngai Yin; Cath, Tzahi Y; Osuji, Chinedum O; Elimelech, Menachem

    2014-05-01

    We present a novel hybrid membrane system that operates as a heat engine capable of utilizing low-grade thermal energy, which is not readily recoverable with existing technologies. The closed-loop system combines membrane distillation (MD), which generates concentrated and pure water streams by thermal separation, and pressure retarded osmosis (PRO), which converts the energy of mixing to electricity by a hydro-turbine. The PRO-MD system was modeled by coupling the mass and energy flows between the thermal separation (MD) and power generation (PRO) stages for heat source temperatures ranging from 40 to 80 °C and working concentrations of 1.0, 2.0, and 4.0 mol/kg NaCl. The factors controlling the energy efficiency of the heat engine were evaluated for both limited and unlimited mass and heat transfer kinetics in the thermal separation stage. In both cases, the relative flow rate between the MD permeate (distillate) and feed streams is identified as an important operation parameter. There is an optimal relative flow rate that maximizes the overall energy efficiency of the PRO-MD system for given working temperatures and concentration. In the case of unlimited mass and heat transfer kinetics, the energy efficiency of the system can be analytically determined based on thermodynamics. Our assessment indicates that the hybrid PRO-MD system can theoretically achieve an energy efficiency of 9.8% (81.6% of the Carnot efficiency) with hot and cold working temperatures of 60 and 20 °C, respectively, and a working solution of 1.0 M NaCl. When mass and heat transfer kinetics are limited, conditions that more closely represent actual operations, the practical energy efficiency will be lower than the theoretically achievable efficiency. In such practical operations, utilizing a higher working concentration will yield greater energy efficiency. Overall, our study demonstrates the theoretical viability of the PRO-MD system and identifies the key factors for performance optimization. PMID:24724732

  11. Dietary proteins improve endothelial function under fasting conditions but not in the postprandial state, with no effects on markers of low-grade inflammation.

    PubMed

    Teunissen-Beekman, Karianna F M; Dopheide, Janneke; Geleijnse, Johanna M; Bakker, Stephan J L; Brink, Elizabeth J; de Leeuw, Peter W; Schalkwijk, Casper G; van Baak, Marleen A

    2015-12-01

    Endothelial dysfunction (ED) and low-grade inflammation (LGI) have a role in the development of CVD. The two studies reported here explored the effects of dietary proteins and carbohydrates on markers of ED and LGI in overweight/obese individuals with untreated elevated blood pressure. In the first study, fifty-two participants consumed a protein mix or maltodextrin (3×20 g/d) for 4 weeks. Fasting levels and 12 h postprandial responses of markers of ED (soluble intercellular adhesion molecule 1 (sICAM), soluble vascular cell adhesion molecule 1 (sVCAM), soluble endothelial selectin and von Willebrand factor) and markers of LGI (serum amyloid A, C-reactive protein and sICAM) were evaluated before and after intervention. Biomarkers were also combined into mean Z-scores of ED and LGI. The second study compared 4 h postprandial responses of ED and LGI markers in forty-eight participants after ingestion of 0·6 g/kg pea protein, milk protein and egg-white protein. In addition, postprandial responses after maltodextrin intake were compared with a protein mix and sucrose. The first study showed significantly lower fasting ED Z-scores and sICAM after 4 weeks on the high-protein diet (P?0·02). The postprandial studies found no clear differences of ED and LGI between test meals. However, postprandial sVCAM decreased more after the protein mix compared with maltodextrin in both studies (P?0·04). In conclusion, dietary protein is beneficial for fasting ED, but not for fasting LGI, after 4 weeks of supplementation. On the basis of Z-scores, postprandial ED and LGI were not differentially affected by protein sources or carbohydrates. PMID:26400262

  12. Disturbed functional brain networks and neurocognitive function in low-grade glioma patients: a graph theoretical analysis of resting-state MEG

    PubMed Central

    Bosma, Ingeborg; Reijneveld, Jaap C; Klein, Martin; Douw, Linda; van Dijk, Bob W; Heimans, Jan J; Stam, Cornelis J

    2009-01-01

    Background To understand neurophysiological mechanisms underlying cognitive dysfunction in low-grade glioma (LGG) patients by evaluating the spatial structure of 'resting-state' brain networks with graph theory. Methods Standardized tests measuring 6 neurocognitive domains were administered in 17 LGG patients and 17 healthy controls. Magnetoencephalography (MEG) recordings were conducted during eyes-closed 'resting state'. The phase lag index (PLI) was computed in seven frequency bands to assess functional connectivity between brain areas. Spatial patterns were characterized with graph theoretical measures such as clustering coefficient (local connectivity), path length (global integration), network small world-ness (ratio of clustering coefficient/path length) and degree correlation (the extent to which connected nodes have similar degrees). Results Compared to healthy controls, patients performed poorer on psychomotor functioning, attention, information processing, and working memory. Patients displayed higher short- and long-distance synchronization and clustering coefficient in the theta band, whereas a lower clustering coefficient and small world-ness were observed in the beta band. A lower degree correlation was found in the upper gamma band. LGG patients with higher clustering coefficient, longer path length, and lower degree correlations in delta and lower alpha band were characterized by poorer neurocognitive performance. Conclusion LGG patients display higher short- and long-distance synchronization within the theta band. Network analysis revealed changes (in particularly the theta, beta, and upper gamma band) suggesting disturbed network architecture. Moreover, correlations between network characteristics and neurocognitive performance were found, Widespread changes in the strength and spatial organization of brain networks may be responsible for cognitive dysfunction in glioma patients. PMID:19698149

  13. Long-Term Outcome of 4,040 Children Diagnosed With Pediatric Low-Grade Gliomas: An Analysis of the Surveillance Epidemiology and End Results (SEER) Database

    PubMed Central

    Bandopadhayay, Pratiti; Bergthold, Guillaume; London, Wendy B; Goumnerova, Liliana C; Morales La Madrid, Andres; Marcus, Karen J; Guo, Dongjing; Ullrich, Nicole J; Robison, Nathan J; Chi, Susan N; Beroukhim, Rameen; Kieran, Mark W; Manley, Peter E

    2014-01-01

    Background Children with pediatric low-grade gliomas (PLGG) are known to have excellent 10-year survival rates; however the outcomes of adult survivors of PLGG are unknown. We identified patients diagnosed with PLGG diagnosed between 1973 and 2008 through the Surveillance Epidemiology and End Results (SEER) database to examine outcomes of adult survivors of PLGG. Procedure Four thousand and forty patients with either WHO grade I or II PLGG were identified and outcome data retrieved. Two analyses were performed to assess survival and risk of death from tumor. Competing risks analysis was conducted and cumulative incidence curves of death due to disease were generated. Cox proportional hazards regression was performed, with adjustment for non-disease death. Kaplan–Meier curves for overall cancer specific survival (OS) were also generated. Results The 20-year OS was 87% ± 0.8% and the 20-year cumulative incidence of death due to glioma was 12% ± 0.8%. The incidence of death after transition to adulthood (age greater than 22 years) was slightly lower, with 20-year cumulative incidence of disease death of 7% ± 1.8%. Year of diagnosis, age of diagnosis, histology, WHO grade, primary site, radiation, and degree of initial resection were prognostic in univariate analysis, while the administration of radiation was the greatest risk of death in multivariate analysis of OS (hazard ratio = 3.9). Conclusions PLGGs are associated with an excellent long-term survival, with a low likelihood of PLGG related death in adult survivors. Treatment strategies for pediatric tumors should therefore aim for disease control during childhood and adolescence with an emphasis on minimizing long-term treatment induced toxicities. PMID:24482038

  14. A genetic dichotomy between pure sclerosing epithelioid fibrosarcoma (SEF) and hybrid SEF/low-grade fibromyxoid sarcoma: a pathologic and molecular study of 18 cases.

    PubMed

    Prieto-Granada, Carlos; Zhang, Lei; Chen, Hsiao-Wei; Sung, Yun-Shao; Agaram, Narasimhan P; Jungbluth, Achim A; Antonescu, Cristina R

    2015-01-01

    Sclerosing epithelioid fibrosarcoma (SEF) is a rare soft tissue tumor exhibiting considerable morphologic overlap with low-grade fibromyxoid sarcoma (LGFMS). Moreover, both SEF and LGFMS show MUC4 expression by immunohistochemistry. While the majority of LGFMS cases are characterized by a FUS-CREB3L1 fusion, both FUS-CREB3L2 and EWSR1-CREB3L1 fusions were recently demonstrated in a small number of LGFMS and SEF/LGFMS hybrid tumors. In contrast, recent studies pointed out that SEF harbor frequent EWSR1 rearrangements, with only a minority of cases showing FUS-CREB3L2 fusions. In an effort to further characterize the molecular characteristics of pure SEF and hybrid SEF/LGFMS lesions, we undertook a clinicopathologic, immunohistochemical and genetic analysis of a series of 10 SEF and 8 hybrid SEF/LGFMS tumors. The mortality rate was similar between the two groups, 44% within the pure SEF group and 37% in the hybrid SEF/LGFMS with a mean overall follow-up of 66 months. All but one pure SEF and all hybrid SEF/LGFMS-tested cases showed MUC4 immunoreactivity. The majority (90%) of pure SEF cases showed EWSR1 gene rearrangements by fluorescence in situ hybridization with only one case exhibiting FUS rearrangement. Of the nine EWSR1 positive cases, six cases harbored CREB3L1 break-apart, two had CREB3L2 rearrangement (a previously unreported finding) and one lacked evidence of CREB3L1/2 abnormalities. In contrast, all hybrid SEF/LGFMS tumors exhibited FUS and CREB3L2 rearrangements. These results further demarcate a relative cytogenetic dichotomy between pure SEF, often characterized by EWSR1 rearrangements, and hybrid SEF/LGFMS, harboring FUS-CREB3L2 fusion; the latter group recapitulating the genotype of LGFMS. PMID:25231134

  15. Hybrid Pressure Retarded Osmosis-Membrane Distillation System for Power Generation from Low-Grade Heat: Thermodynamic Analysis and Energy Efficiency

    SciTech Connect

    Lin, SH; Yip, NY; Cath, TY; Osuji, CO; Elimelech, M

    2014-05-06

    We present a novel hybrid membrane system that operates as a heat engine capable of utilizing low-grade thermal energy, which is not readily recoverable with existing technologies. The closed-loop system combines membrane distillation (MD), which generates concentrated and pure water streams by thermal separation, and pressure retarded osmosis (PRO), which converts the energy of mixing to electricity by a hydro-turbine. The PRO-MD system was modeled by coupling the mass and energy flows between the thermal separation (MD) and power generation (PRO) stages for heat source temperatures ranging from 40 to 80 degrees C and working concentrations of 1.0, 2.0, and 4.0 mol/kg NaCl. The factors controlling the energy efficiency of the heat engine were evaluated for both limited and unlimited mass and heat transfer kinetics in the thermal separation stage. In both cases, the relative flow rate between the MD permeate (distillate) and feed streams is identified as an important operation parameter. There is an optimal relative flow rate that maximizes the overall energy efficiency of the PRO-MD system for given working temperatures and concentration. In the case of unlimited mass and heat transfer kinetics, the energy efficiency of the system can be analytically determined based on thermodynamics. Our assessment indicates that the hybrid PRO-MD system can theoretically achieve an energy efficiency of 9.8% (81.6% of the Carnot efficiency) with hot and cold working temperatures of 60 and 20 degrees C, respectively, and a working solution of 1.0 M NaCl. When mass and heat transfer kinetics are limited, conditions that more closely represent actual operations, the practical energy efficiency will be lower than the theoretically achievable efficiency. In such practical operations, utilizing a higher working concentration will yield greater energy efficiency. Overall, our study demonstrates the theoretical viability of the PRO-MD system and identifies the key factors for performance optimization.

  16. Reactive lymphoid hyperplasia of the liver mimicking hepatocellular carcinoma: incidental finding of two cases

    PubMed Central

    Lv, Ang; Liu, Wendy; Qian, Hong-Gang; Leng, Jia-Hua; Hao, Chun-Yi

    2015-01-01

    Reactive lymphoid hyperplasia is a rare disease that forms a mass-like lesion and is characterized by the proliferation of non-neoplastic, polyclonal lymphocytes forming follicles. We recently encountered 2 cases of reactive lymphoid hyperplasia of liver, both of which were asymptomatic and mimicked hepatocellular carcinoma by various imaging modalities. Based on the clinical impression of hepatocellular carcinoma, surgical resections were performed. Microscopic findings revealed that both lesions consisted of an aggregation of lymphocytes consisting of predominantly B-cells, with multiple lymphoid follicles positive for CD10 and negative for bcl-2, consistent with the diagnosis of reactive lymphoid hyperplasia. Polyclonality of both lesions was further confirmed by B cell receptor gene rearrangement study. The incidence of reactive lymphoid hyperplasia in the liver is exceedingly rare, and it is difficult to differentiate such lesions from hepatic malignancies based upon clinical grounds. The clinicopathological findings and literature review of this report may be helpful to improve the clinical decision-making. PMID:26191310

  17. African Lungfish Reveal the Evolutionary Origins of Organized Mucosal Lymphoid Tissue in Vertebrates.

    PubMed

    Tacchi, Luca; Larragoite, Erin T; Muñoz, Pilar; Amemiya, Chris T; Salinas, Irene

    2015-09-21

    One of the most remarkable innovations of the vertebrate adaptive immune system is the progressive organization of the lymphoid tissues that leads to increased efficiency of immune surveillance and cell interactions. The mucosal immune system of endotherms has evolved organized secondary mucosal lymphoid tissues (O-MALT) such as Peyer's patches, tonsils, and adenoids. Primitive semi-organized lymphoid nodules or aggregates (LAs) were found in the mucosa of anuran amphibians, suggesting that O-MALT evolved from amphibian LAs ?250 million years ago. This study shows for the first time the presence of O-MALT in the mucosa of the African lungfish, an extant representative of the closest ancestral lineage to all tetrapods. Lungfish LAs are lymphocyte-rich structures associated with a modified covering epithelium and express all IGH genes except for IGHW2L. In response to infection, nasal LAs doubled their size and increased the expression of CD3 and IGH transcripts. Additionally, de novo organogenesis of inducible LAs resembling mammalian tertiary lymphoid structures was observed. Using deep-sequencing transcriptomes, we identified several members of the tumor necrosis factor (TNF) superfamily, and subsequent phylogenetic analyses revealed its extraordinary diversification within sarcopterygian fish. Attempts to find AICDA in lungfish transcriptomes or by RT-PCR failed, indicating the possible absence of somatic hypermutation in lungfish LAs. These findings collectively suggest that the origin of O-MALT predates the emergence of tetrapods and that TNF family members play a conserved role in the organization of vertebrate mucosal lymphoid organs. PMID:26344090

  18. Cooperating mechanisms of CXCR5 and CCR7 in development and organization of secondary lymphoid organs.

    PubMed

    Ohl, Lars; Henning, Golo; Krautwald, Stefan; Lipp, Martin; Hardtke, Svenja; Bernhardt, Gunter; Pabst, Oliver; Förster, Reinhold

    2003-05-01

    Homeostatic chemokines participate in the development of secondary lymphoid organs and later on in the functional organization of these tissues. The development of lymph nodes (LNs) and Peyer's patches depends on the recruitment of CD3- CD4+ interleukin (IL)-7R alpha hi cells to sites of future organ development. CD3- CD4+ IL-7R alpha hi cells express the chemokine receptor CXCR5 and might be attracted by its ligand CXCL13, which is secreted by mesenchymal cells. Mesenchymal cells also secrete CCL19, a ligand for CCR7, yet it is not clear whether CCR7 and CCL19 are important for secondary lymphoid organ development. Analyzing CXCR5-/- CCR7-/- double deficient mice we now show that these mice lack all examined peripheral LNs suggesting a profound role for both receptors in secondary lymphoid organ development. We demonstrate that CD3- CD4+ IL-7R alpha hi cells express CXCR5 as well as CCR7 indicating that both receptors cooperate during an early step of secondary lymphoid organ development. Furthermore, CXCR5-/- CCR7-/- mice display a severely disturbed architecture of mesenteric LN and spleen. Due to an impaired migration of B cells into the white pulp, CXCR5-/- CCR7-/- mice fail to develop B cell follicles but show small clusters of unorganized lymphocytes in the spleen. These data demonstrate a cooperative function of CXCR5 and CCR7 in lymphoid organ organogenesis and organization. PMID:12732661

  19. Cooperating Mechanisms of CXCR5 and CCR7 in Development and Organization of Secondary Lymphoid Organs

    PubMed Central

    Ohl, Lars; Henning, Golo; Krautwald, Stefan; Lipp, Martin; Hardtke, Svenja; Bernhardt, Günter; Pabst, Oliver; Förster, Reinhold

    2003-01-01

    Homeostatic chemokines participate in the development of secondary lymphoid organs and later on in the functional organization of these tissues. The development of lymph nodes (LNs) and Peyer's patches depends on the recruitment of CD3? CD4+ interleukin (IL)-7R?hi cells to sites of future organ development. CD3? CD4+ IL-7R?hi cells express the chemokine receptor CXCR5 and might be attracted by its ligand CXCL13, which is secreted by mesenchymal cells. Mesenchymal cells also secrete CCL19, a ligand for CCR7, yet it is not clear whether CCR7 and CCL19 are important for secondary lymphoid organ development. Analyzing CXCR5?/? CCR7?/? double deficient mice we now show that these mice lack all examined peripheral LNs suggesting a profound role for both receptors in secondary lymphoid organ development. We demonstrate that CD3? CD4+ IL-7R?hi cells express CXCR5 as well as CCR7 indicating that both receptors cooperate during an early step of secondary lymphoid organ development. Furthermore, CXCR5?/? CCR7?/? mice display a severely disturbed architecture of mesenteric LN and spleen. Due to an impaired migration of B cells into the white pulp, CXCR5?/? CCR7?/? mice fail to develop B cell follicles but show small clusters of unorganized lymphocytes in the spleen. These data demonstrate a cooperative function of CXCR5 and CCR7 in lymphoid organ organogenesis and organization. PMID:12732661

  20. Disagreement in high-grade/low-grade intraepithelial neoplasia and high-risk/low-risk HPV infection: clinical implications for anal cancer precursor lesions in HIV-positive and HIV-negative MSM.

    PubMed

    Pimenoff, V N; Félez-Sánchez, M; Tous, S; Clavero, O; Godínez, J M; Klaustermeier, J; Saunier, M; Molijn, A; Alemany, L; Quint, W; Bosch, F X; de Sanjosé, S; McCloskey, J; Bravo, I G

    2015-06-01

    Anal condylomata are common in HIV-positive individuals and among men who have sex with men (MSM). Generally attributable to infection by low-risk human papillomaviruses (HPVs), condylomata are considered benign low-grade squamous intraepithelial lesions (SILs). However, anal condylomata have occasionally been linked to high-grade SIL and to oncogenic, high-risk HPVs. Here we describe the range of intraepithelial lesions and of the associated HPVs in heterosexual men and women and MSM. Perianal and anal condylomata were collected from 243 patients (56 heterosexual women, 61 heterosexual men and 126 MSM, including 41 HIV-positive MSM). We assessed lesion histology and HPV genotype. Prevalence estimates and Poisson models were used. Irrespective of HIV infection status, MSM showed a higher proportion of condylomata as high-grade SILs compared to heterosexual men/women. High-grade SILs were also more prevalent in anal than in perianal lesions in all patient groups. HIV-positive MSM exhibited increased prevalence ratio (4.6; 95% confidence interval 2.1-10.0) of perianal low-grade SILs containing only high-risk HPVs compared to HIV-negative MSM. In addition, more than 64% of anal SILs with a high-grade component, regardless of HIV infection, were exclusively associated with low-risk HPVs. In anal condylomata, both high-grade and low-grade SILs can be associated with high-risk and/or low-risk HPVs. Particularly, low-grade perianal SILs associated with high-risk HPVs were common in HIV-positive MSM, while presence of only low-risk HPVs in high-grade SILs were common in both MSM groups. Our findings sound a note of caution for the common clinical practice for the treatment of anal condylomata as benign lesions in MSM and HIV-positive patients. PMID:25700891

  1. Leukemia derived growth factors produced by human malignant T-lymphoid cell lines.

    PubMed

    Uittenbogaart, C H; Nishanian, P G; Anisman, D J; Erikson, T K; Fahey, J L

    1986-03-01

    An autocrine (noninterleukin 2) growth factor, which we term leukemia derived growth factor (LDGF), has previously been found in the culture supernatant of the human malignant T-lymphoid cell line MOLT-4f. We now show that two other human malignant T-lymphoid cell lines, CCRF-CEM and CCRF-HSB-2 also produce such a factor. All three factors, i.e., the LDGF from MOLT-4f, CCRF-CEM, and CCRF-HSB-2 are similar to each other both in biological activity and in physicochemical characteristics. In addition to their autocrine activity, these LDGFs stimulate the growth of other malignant T-lymphoid cell lines, but they do not stimulate B-lymphoblastoid or myeloid cell lines. The results therefore suggest that these LDGFs are T-cell specific. PMID:3080240

  2. Clinical and immunologic effects of fractionated total lymphoid irradiation in refractory rheumatoid arthritis

    SciTech Connect

    Trentham, D.E.; Belli, J.A.; Anderson, R.J.; Buckley, J.A.; Goetzl, E.J.; David, J.R.; Austen, K.F.

    1981-10-22

    Ten patients with refractory rheumatoid arthritis were given 3000 rad of fractionated total lymphoid irradiation in an uncontrolled therapeutic trial. Total lymphoid irradiation was associated with objective evidence of considerable clinical improvement in eight patients and with reduced blood lymphocyte counts in all 10. On completion of irradiation, there was an abrogation of lymphocyte reactivity in vitro in the patients with clinical responses, but abnormal antibody activities characteristic of rheumatoid arthritis and normal components of humoral immunity were not suppressed. Partial recrudescence of arthritis occurred shortly after a year after the completion of irradiation and was paralleled by a restitution of lymphocyte concentrations and responsiveness to mitogens to levels similar to those observed before irradiation. These data provide further evidence of T-cell involvement in the pathogenesis of rheumatoid arthritis and demonstrate that total lymphoid irradiation can induce temporary relief, but they do not ascertain whether the natural history of this disease was altered.

  3. Clinical and immunologic effects of fractionated total lymphoid irradiation in refractory rheumatoid arthritis

    SciTech Connect

    Trentham, D.E.; Belli, J.A.Anderson, R.J.; Buckley, J.A.; Goetzl, E.J.; David, J.R.; Austen, K.F.

    1981-10-01

    Ten patients with refractory rheumatoid arthritis were given 3000 rad of fractionated total lymphoid irradiation in an uncontrolled therapeutic trial. Total lymphoid irradiation was associated with objective evidence of considerable clinical improvement in eight patients and with reduced blood lymphocyte counts in all 10. On completion of irradiation, there was an abrogation of lymphocyte reactivity in vitro in the patients with clinical responses, but abnormal antibody activities characteristic of rheumatoid arthritis and normal components of humoral immunity were not suppressed. Partial recrudescence of arthritis occurred shortly before a year after the completion of irradiation and was paralleled by a restitution of lymphocyte concentrations and responsiveness to mitogens to levels similar to those observed before irradiation. These data provide further evidence of T-cell involvement in the pathogenesis of rheumatoid arthritis and demonstrate that total lymphoid irradiation can induce temporary relief, but they do not ascertain whether the natural history of this disease was altered.

  4. Variation of illite/muscovite 40Ar/39Ar age spectra during progressive low-grade metamorphism: an example from the US Cordillera

    NASA Astrophysics Data System (ADS)

    Verdel, Charles; van der Pluijm, Ben A.; Niemi, Nathan

    2012-09-01

    40Ar/39Ar step-heating data were collected from micron to submicron grain-sizes of correlative illite- and muscovite-rich Cambrian pelitic rocks from the western United States that range in metamorphic grade from the shallow diagenetic zone (zeolite facies) to the epizone (greenschist facies). With increasing metamorphic grade, maximum ages from 40Ar/39Ar release spectra decrease, as do total gas ages and retention ages. Previous studies have explained similar results as arising dominantly or entirely from the dissolution of detrital muscovite and precipitation/recrystallization of neo-formed illite. While recognizing the importance of these processes in evaluating our results, we suggest that the inverse correlation between apparent age and metamorphic grade is controlled, primarily, by thermally activated volume diffusion, analogous to the decrease in apparent ages with depth observed for many thermochronometers in borehole experiments. Our results suggest that complete resetting of the illite/muscovite Ar thermochronometer occurs between the high anchizone and epizone, or at roughly 300 °C. This empirical result is in agreement with previous calculations based on muscovite diffusion parameters, which indicate that muscovite grains with radii of 0.05-2 ?m should have closure temperatures between 250 and 350 °C. At high anchizone conditions, we observe a reversal in the age/grain-size relationship (the finest grain-size produces the oldest apparent age), which may mark the stage in prograde subgreenschist facies metamorphism of pelitic rocks at which neo-formed illite/muscovite crystallites typically surpass the size of detrital muscovite grains. It is also approximately the stage at which neo-formed illite/muscovite crystallites develop sufficient Ar retentivity to produce geologically meaningful 40Ar/39Ar ages. Results from our sampling transect of Cambrian strata establish a framework for interpreting illite/muscovite 40Ar/39Ar age spectra at different stages of low-grade metamorphism and also illuminate the transformation of illite to muscovite. At Frenchman Mtn., NV, where the Cambrian Bright Angel Formation is at zeolite facies conditions, illite/muscovite 40Ar/39Ar data suggest a detrital muscovite component with an apparent age ?967 Ma. The correlative Carrara Fm. is at anchizone conditions in the Panamint and Resting Spring Ranges of eastern California, and in these locations, illite/muscovite 40Ar/39Ar data suggest an early Permian episode of subgreenschist facies metamorphism. The same type of data from equivalent strata at epizone conditions (greenschist facies) in the footwall of the Bullfrog/Fluorspar Canyon detachment in southern Nevada reveals a period of slow-to-moderate Late Cretaceous cooling.

  5. A musculoskeletal model of low grade connective tissue inflammation in patients with thyroid associated ophthalmopathy (TAO): the WOMED concept of lateral tension and its general implications in disease

    PubMed Central

    Moncayo, Roy; Moncayo, Helga

    2007-01-01

    Background Low level connective tissue inflammation has been proposed to play a role in thyroid associated ophthalmopathy (TAO). The aim of this study was to investigate this postulate by a musculoskeletal approach together with biochemical parameters. Methods 13 patients with TAO and 16 controls were examined. Erythrocyte levels of Zn, Cu, Ca2+, Mg, and Fe were determined. The musculoskeletal evaluation included observational data on body posture with emphasis on the orbit-head region. The angular foot position in the frontal plane was quantified following gait observation. The axial orientation of the legs and feet was evaluated in an unloaded supine position. Functional propioceptive tests based on stretch stimuli were done by using foot inversion and foot rotation. Results Alterations in the control group included neck tilt in 3 cases, asymmetrical foot angle during gait in 2, and a reaction to foot inversion in 5 cases. TAO patients presented facial asymmetry with displaced eye fissure inclination (mean 9.1°) as well as tilted head-on-neck position (mean 5.7°). A further asymmetry feature was external rotation of the legs and feet (mean 27°). Both foot inversion as well as foot rotation induced a condition of neuromuscular deficit. This condition could be regulated by gentle acupressure either on the lateral abdomen or the lateral ankle at the acupuncture points gall bladder 26 or bladder 62, respectively. In 5 patients, foot rotation produced a phenomenon of moving toes in the contra lateral foot. In addition foot rotation was accompanied by an audible tendon snapping. Lower erythrocyte Zn levels and altered correlations between Ca2+, Mg, and Fe were found in TAO. Conclusion This whole body observational study has revealed axial deviations and body asymmetry as well as the phenomenon of moving toes in TAO. The most common finding was an arch-like displacement of the body, i.e. eccentric position, with foot inversion and head tilt to the contra lateral side and tendon snapping. We propose that eccentric muscle action over time can be the basis for a low grade inflammatory condition. The general implications of this model and its relations to Zn and Se will be discussed. PMID:17319961

  6. The pattern of myometrial invasion as a predictor of lymph node metastasis or extrauterine disease in low-grade endometrial carcinoma.

    PubMed

    Euscher, Elizabeth; Fox, Patricia; Bassett, Roland; Al-Ghawi, Hayma; Ali-Fehmi, Rouba; Barbuto, Denise; Djordjevic, Bojana; Frauenhoffer, Elizabeth; Kim, Insun; Hong, Sun Rang; Montiel, Delia; Moschiano, Elizabeth; Roma, Andres; Silva, Elvio; Malpica, Anais

    2013-11-01

    The purpose of this study was to examine predictors of lymph node (LN) metastases or extrauterine disease (ED) in low-grade (FIGO grade 1 or 2) endometrioid carcinoma (LGEC) in a multi-institutional setting. For LGEC with and without LN metastasis or ED, each of the 9 participating institutions evaluated patients' age, tumor size, myometrial invasion (MI), FIGO grade, % solid component, the presence or absence of papillary architecture, microcystic, elongated, and fragmented glands (MELF), single-cell/cell-cluster invasion (SCI), lymphovascular invasion (LVI), lower uterine segment (LUS) and cervical stromal (CX) involvement, and numbers of pelvic and para-aortic LNs sampled. A total of 304 cases were reviewed: LN(+) or ED(+), 96; LN(-)/ED(-), 208. Patients' ages ranged from 23 to 91 years (median 61 y). Table 1 summarizes the histopathologic variables that were noted for the LN(+) or ED(+) group: tumor size ?2 cm, 93/96 (97%); MI>50%, 54/96 (56%); MELF, 67/96 (70%); SCI, 33/96 (34%); LVI, 79/96 (82%); >20% solid, 65/96 (68%); papillary architecture present, 68/96 (72%); LUS involved, 64/96 (67%); and CX involved, 41/96 (43%). For the LN(-)/ED(-) group, the results were as follows: tumor size ?2 cm, 152/208 (73%); MI>50%, 56/208 (27%); MELF, 79/208 (38%); SCI, 19/208 (9%); LVI, 56/208 (27%); >20% solid, 160/208 (77%); papillary architecture present, 122/208 (59%); LUS involved, 77/208 (37%); CX involved, 24/208 (12%). There was no evidence of a difference in the number of pelvic or para-aortic LNs sampled between groups (P=0.9 and 0.1, respectively). After multivariate analysis, the depth of MI, CX involvement, LVI, and SCI emerged as significant predictors of advanced-stage disease. Although univariate analysis pointed to LUS involvement, MELF pattern of invasion, and papillary architecture as possible predictors of advanced-stage disease, these were not shown to be significant by multivariate analysis. This study validates MI, CX involvement, and LVI as significant predictors of LN(+) or ED(+). The association of SCI pattern with advanced-stage LGEC is a novel finding. PMID:24061515

  7. p16 staining has limited value in predicting the outcome of histological low-grade squamous intraepithelial lesions of the cervix.

    PubMed

    Sagasta, Amaia; Castillo, Paola; Saco, Adela; Torné, Aureli; Esteve, Roser; Marimon, Lorena; Ordi, Jaume; Del Pino, Marta

    2016-01-01

    In order to evaluate the usefulness of p16 staining in predicting the outcome of histological low-grade squamous intraepithelial lesion/cervical intraepithelial neoplasia grade 1 (LSIL/CIN1) we prospectively recruited all the patients referred to colposcopy from 2003 to 2011 due to abnormal screening test results and diagnosed with LSIL/CIN1 at biopsy (n=507). All biopsies were stained for p16 and re-evaluated after three years by the same gynecological pathologist using the LAST criteria. Follow-up was conducted every 6 months and included a Pap test (liquid-based cytology), high-risk human papillomavirus testing (Hybrid Capture 2 test), and colposcopy. The mean follow-up was 28 months. An outcome diagnosis of HSIL was defined as a histological diagnosis of high-grade SIL/CIN (HSIL/CIN2-3). The diagnosis of LSIL/CIN1 was confirmed in 416 out of 507 biopsies (82%), whereas 58 (11%) were reclassified as negative and 33 (6%) as HSIL/CIN2-3. During follow-up, 86/507 women initially diagnosed with LSIL/CIN1 (17%) showed an outcome diagnosis of HSIL/CIN2-3, with the rate of HSIL final diagnosis of 3% (2/58) in the women with biopsies reclassified as negative, 17% (70/416) in the group with confirmed LSIL and 42% (14/33) in the women with biopsies reclassified as HSIL (P<0.001). p16 was positive in 245/507 patients (48%) and in 210/416 patients (50%) with confirmed LSIL/CIN1 at re-evaluation. Although positive p16 immunostaining was associated with risk of HSIL/CIN2-3 outcome in the multivariate analysis (Hazard ratio (HR) 1.9; 95% confidence interval (CI): 1.2-3.1; P=0.009) in the overall group of patients with LSIL/CIN1, this association was not verified in the subset of patients with confirmed LSIL/CIN1 after re-evaluation (HR: 1.6; 95% CI: 0.9-2.6; P=0.095). In conclusion, in LSIL/CIN1 lesions p16 should be limited to equivocal cases in which HSIL/CIN2 is included in the differential diagnosis since it has low value in clinical practice as a marker of progression of LSIL/CIN1. PMID:26541274

  8. Raman spectroscopic carbonaceous material thermometry of low-grade metamorphic rocks: Calibration and application to tectonic exhumation in Crete, Greece [rapid communication

    NASA Astrophysics Data System (ADS)

    Rahl, Jeffrey M.; Anderson, Kristin M.; Brandon, Mark T.; Fassoulas, Charalambos

    2005-12-01

    We present new Raman spectra data of carbonaceous material (CM) to extend the range of the Raman spectra of CM thermometer (RSCM) to temperatures as low as 100 °C. Previous work has demonstrated that Raman spectroscopy is an excellent tool to describe the degree of graphitization of CM, a process that is independent of pressure but strongly dependent on metamorphic temperature. A linear relationship between temperature and the Raman parameter R2 (derived from the area of the defect band relative to the ordered graphite band) forms the basis of a previous thermometer. Because R2 shows little variability in low-temperature samples, 330 °C serves as a lower limit on the existing thermometer. Herein, we present Raman spectra from a suite of low-temperature (100 to 300 °C) samples from the Olympics Mountains and describe other aspects of the Raman spectra of CM that vary over this range. In particular, the Raman parameter R1 (the ratio of heights of the disordered peak to ordered peak) varies regularly between 100 and 350 °C. These data, together with published results from higher-temperature rocks, are used to calibrate a modified RSCM thermometer, applicable from 100 to 700 °C. Application to low-grade metasediments in the Otago region in the South Island of New Zealand gives temperatures consistent with previous estimates, demonstrating the reliability of the modified RSCM thermometer. We apply the modified RSCM thermometer to 53 samples from Crete to evaluate the role of the Cretan detachment fault in exhuming Miocene high pressure/low-temperature metamorphic rocks exposed there. The metamorphic rocks below the detachment (the Plattenkalk and Phyllite-Quartzite units) give metamorphic temperatures that range from 250 to 400 °C, consistent with previous petrologic estimates. We also demonstrate that the Tripolitza unit, which lies directly above the detachment, gives an average metamorphic temperature of about 260 °C. The modest break in metamorphic temperature in central Crete indicates that the Cretan detachment accounts for only 5 to 7 km of exhumation of the underlying HP-LT metamorphic rocks, which were initially accreted at ˜ 35 km. We argue that the bulk of the exhumation (˜ 28 km out of 35 km total) occurred by pervasive brittle stretching and erosion of structural units above the detachment.

  9. Ultrastructural study of M cells from colonic lymphoid nodules obtained by colonoscopic biopsy.

    PubMed

    Fujimura, Y; Hosobe, M; Kihara, T

    1992-07-01

    The present study was undertaken to investigate ultrastructurally the epithelium covering lymphoid nodules obtained from colonoscopic biopsies of the human colon and rectum. Colonoscopy using the dye spraying contrast method was performed in nine patients who showed x-ray evidence of lymphonodular hyperplasia. Fifty-two colonoscopical biopsy specimens of lymphoid nodules were obtained from the ascending, transverse, and descending colon and rectosigmoid region. All specimens were observed by light and electron microscopy. Light microscopy disclosed large lymphoid follicles protruding into the lumen with a "dome-type" configuration. These extended to the lamina propria of the mucosa and were associated with a massive lymphoid aggregation extending as far as the muscularis mucosa from the submucosa. The epithelium covering these nodules contained a few goblet cells and many lymphocytes. Observation of the elevated surface at the apex by scanning electron microscopy revealed M cells with sparse microvilli in the dome epithelium surrounded by crypts. Transmission electron microscopy disclosed M cells enfolding many immature or mature lymphocytes and plasmocytes. The M cells had cytoplasmic microvilli (so-called "microfolds") on their surfaces, well-developed tubulovesicular systems, and vacuoles in the cytoplasm. The basic structure of the M cells as observed by scanning and transmission electron microscopy was the same as that of M cells in the Peyer's patches of humans and mice. The apical surface of the colonic lymphoid follicles in Crohn's disease patients was associated with erosions observed by scanning electron microscopy. The erosions proved to be the naked surface of the dome after removal of the epithelium, and many holes from 2.0 to 6.0 microns in diameter were observed on the naked surface. At high magnification, lymphocytes were seen projecting from holes (18%) on the naked surface of the dome. These ultrastructural findings indicate that human colonic lymphoid follicles are very similar to those seen in other species. PMID:1618058

  10. Long-term followup of rheumatoid arthritis patients treated with total lymphoid irradiation

    SciTech Connect

    Tanay, A.; Field, E.H.; Hoppe, R.T.; Strober, S.

    1987-01-01

    Total lymphoid irradiation was administered to 32 patients with intractable rheumatoid arthritis. Twenty-four patients showed at least a 25% improvement in 3 of 4 disease activity parameters, which persisted during the followup period of up to 48 months. Eight of the 32 patients required adjunctive immunosuppressive drug therapy to maintain improvement. Four patients died after total lymphoid irradiation; the causes of death were acute myocardial infarction (1 patient), pulmonary embolism (1 patient), and rheumatoid lung disease complicated by respiratory infection (2 patients). After therapy, patients exhibited a prolonged reduction in the number and function of circulating T helper cells.

  11. Dissection of the mechanisms of immune injury in rheumatoid arthritis, using total lymphoid irradiation

    SciTech Connect

    Gaston, J.S.; Strober, S.; Solovera, J.J.; Gandour, D.; Lane, N.; Schurman, D.; Hoppe, R.T.; Chin, R.C.; Eugui, E.M.; Vaughan, J.H.

    1988-01-01

    Eleven patients with intractable rheumatoid arthritis were treated with total lymphoid irradiation. After radiotherapy, there was a marked decrease in the number and function of peripheral blood helper/inducer (Leu-3+) T lymphocytes, in the spontaneous secretion of interleukin-1 by synovial biopsy specimens, and in the activity of the joint disease. In contrast, levels of IgM, IgA, and IgG rheumatoid factors and C3 concentrations in blood and synovial fluid samples did not change significantly after therapy with total lymphoid irradiation.

  12. Allograft tolerance in pigs after fractionated lymphoid irradiation. II. Kidney graft after conventional total lymphoid irradiation and bone marrow cell grafting

    SciTech Connect

    Fradelizi, D.; Mahouy, G.; de Riberolles, C.; Lecompte, Y.; Alhomme, P.; Douard, M.C.; Chotin, G.; Martelli, H.; Daburon, F.; Vaiman, M.

    1981-05-01

    Experiments with pigs have been performed in order to establish bone marrow chimerism and kidney graft tolerance between SLA genotyped semi-incompatible animals. Recipients were conditioned by means of conventional fractionated total lymphoid irradiation (TLI) delivered by a vertical cobalt source. The principal lymphoid regions of the pig, including thymus and spleen, were submitted to irradiation. Two protocols were tested: A = 250 cGy four times a week x 13 times (TLI) (two animals) and B = 350 cGy three times a week x 8 times (TLI) (four animals). Bone marrow cells were injected 24 h after the last irradiation. One day later, bilateral nephrectomy and the graft of one kidney from the bone marrow cell donor were performed simultaneously. Results convinced us that application of the TLI protocol to humans is not yet practicable and that further experimental work is needed.

  13. Peripheral Tissue Homing Receptor Control of Naïve, Effector, and Memory CD8 T Cell Localization in Lymphoid and Non-Lymphoid Tissues

    PubMed Central

    Brinkman, C. Colin; Peske, J. David; Engelhard, Victor Henry

    2013-01-01

    T cell activation induces homing receptors that bind ligands on peripheral tissue vasculature, programing movement to sites of infection and injury. There are three major types of CD8 effector T cells based on homing receptor expression, which arise in distinct lymphoid organs. Recent publications indicate that naïve, effector, and memory T cell migration is more complex than once thought; while many effectors enter peripheral tissues, some re-enter lymph nodes (LN), and contain central memory precursors. LN re-entry can depend on CD62L or peripheral tissue homing receptors. Memory T cells in LN tend to express the same homing receptors as their forebears, but often are CD62Lneg. Homing receptors also control CD8 T cell tumor entry. Tumor vasculature has low levels of many peripheral tissue homing receptor ligands, but portions of it resemble high endothelial venules (HEV), enabling naïve T cell entry, activation, and subsequent effector activity. This vasculature is associated with positive prognoses in humans, suggesting it may sustain ongoing anti-tumor responses. These findings reveal new roles for homing receptors expressed by naïve, effector, and memory CD8 T cells in controlling entry into lymphoid and non-lymphoid tissues. PMID:23966998

  14. Abundantly expressed transcripts in the lymphoid organ of the black tiger shrimp, Penaeus monodon, and their implication in immune function.

    PubMed

    Pongsomboon, Siriporn; Wongpanya, Ratree; Tang, Sureerat; Chalorsrikul, Arthit; Tassanakajon, Anchalee

    2008-11-01

    The lymphoid organ of penaeid shrimps is proposed to play an important role in the innate immune system. To investigate the potential immune function of the lymphoid organ, we analyzed the expressed genes from the lymphoid organ of normal and Vibrio harveyi-infected Penaeus monodon using an expressed sequence tag (EST) approach. Sequence analysis of the EST clones derived from the two lymphoid organ cDNA libraries (408 clones from the normal and 625 clones from the infected libraries), revealed a high redundancy of specific transcripts. Transcripts of the lysosomal cysteine proteinases, cathepsins B and L, were abundantly expressed in the lymphoid organ of both libraries, whilst the transcripts of the related genes peritrophin and thrombospondin predominated and were found only in the V. harveyi-infected library, making them interesting candidate functional genes. Moreover, immune-related genes were found at a significant proportion (approximately 15%) in both normal and infected libraries, but different expressed genes were observed between the two libraries. The expression levels of P. monodon cathepsins B and L in the lymphoid organ following injection with either V. harveyi or white spot syndrome virus (WSSV) showed only a slight change in the transcript abundance compared to that seen in the mock-infection (control). Immunohistochemistry confirmed that cathepsin L protein was localized in the lymphoid organ with intense cathepsin L staining observed in the lymphoid organ spheroids of WSSV-infected shrimps. The results suggest that cathepsins L and B likely play a major role in the lymphoid organ function and are probably implicated in degradation of foreign material that is sequestrated in the lymphoid organ spheroids, although any additional role in control of viral or cellular mediated apoptosis remains to be evaluated. PMID:18692576

  15. A multistep adhesion cascade for lymphoid progenitor cell homing to the thymus

    E-print Network

    von Andrian, Ulrich H.

    A multistep adhesion cascade for lymphoid progenitor cell homing to the thymus M. Lucila Scimone to the thymus is essential for T cell development. We have previously reported that two subpopulations of common that CLP-2 migrate to the thymus more efficiently than any other BM-derived progenitors. Short

  16. Interleukin-27 inhibits ectopic lymphoid-like structure development in early inflammatory arthritis.

    PubMed

    Jones, Gareth W; Bombardieri, Michele; Greenhill, Claire J; McLeod, Louise; Nerviani, Alessandra; Rocher-Ros, Vidalba; Cardus, Anna; Williams, Anwen S; Pitzalis, Costantino; Jenkins, Brendan J; Jones, Simon A

    2015-10-19

    Ectopic lymphoid-like structures (ELSs) reminiscent of secondary lymphoid organs often develop at sites of chronic inflammation where they contribute to immune-mediated pathology. Through evaluation of synovial tissues from rheumatoid arthritis (RA) patients, we now show that low interleukin-27 (IL-27) expression corresponds with an increased incidence of ELS and gene signatures associated with their development and activity. The presence of synovial ELS was also noted in mice deficient in the IL-27 receptor (IL-27R) after the onset of inflammatory arthritis. Here, pathology was associated with increased synovial expression of pro-inflammatory cytokines, homeostatic chemokines, and transcriptional regulators linked with lymphoid neogenesis. In both clinical and experimental RA, synovial ELS coincided with the heightened local expression of cytokines and transcription factors of the Th17 and T follicular helper (Tfh) cell lineages, and included podoplanin-expressing T cells within lymphoid aggregates. IL-27 inhibited the differentiation of podoplanin-expressing Th17 cells, and an increased number of these cells were observed in IL-27R-deficient mice with inflammatory arthritis. Thus, IL-27 appears to negatively regulate ELS development in RA through control of effector T cells. These studies open new opportunities for patient stratification and treatment. PMID:26417004

  17. NCR(+)ILC3 concentrate in human lung cancer and associate with intratumoral lymphoid structures.

    PubMed

    Carrega, Paolo; Loiacono, Fabrizio; Di Carlo, Emma; Scaramuccia, Angelo; Mora, Marco; Conte, Romana; Benelli, Roberto; Spaggiari, Grazia Maria; Cantoni, Claudia; Campana, Stefania; Bonaccorsi, Irene; Morandi, Barbara; Truini, Mauro; Mingari, Maria Cristina; Moretta, Lorenzo; Ferlazzo, Guido

    2015-01-01

    Tertiary lymphoid structures (TLSs) are a common finding in non-small cell lung cancer (NSCLC) and are predictors of favourable clinical outcome. Here we show that NCR(+) innate lymphoid cell (ILC)-3 are present in the lymphoid infiltrate of human NSCLC and are mainly localized at the edge of tumour-associated TLSs. This intra-tumoral lymphocyte subset is endowed with lymphoid tissue-inducing properties and, on activation, produces IL-22, TNF-?, IL-8 and IL-2, and activates endothelial cells. Tumour NCR(+)ILC3 may interact with both lung tumour cells and tumour-associated fibroblasts, resulting in the release of cytokines primarily on engagement of the NKp44-activating receptor. In patients, NCR(+)ILC3 are present in significantly higher amounts in stage I/II NSCLC than in more advanced tumour stages and their presence correlate with the density of intratumoral TLSs. Our results indicate that NCR(+)ILC3 accumulate in human NSCLC tissue and might contribute to the formation of protective tumour-associated TLSs. PMID:26395069

  18. Effect of selenium and vitamin E dietary deficiencies on chick lymphoid organ development (42361)

    SciTech Connect

    Marsh, J.A.; Combs, G.F. Jr.; Whitacre, M.E.; Dietert, R.R.

    1986-09-01

    Diets specifically deficient in selenium (Se) and/or vitamin E or adequate in both nutrients were fed to chicks from the time of hatching. Lymphoid organs (bursa, thymus, and in some instances, spleen) were collected from chicks 7-35 days of age. Growth of the chicks fed these diets was monitored over the experimental period as was lymphoid organ growth. The development of the primary lymphoid organs was further assessed by histological techniques and the organ contents of vitamin E (..cap alpha..-tocopherol) and Se were determined. Specific deficiencies of either Se or vitamin E were found to significantly impair bursal growth as did a combined deficiency. Thymic growth was impaired only by the combined deficiency diet. Severe histopathological changes in the bursa resulted from the combined deficiency and these were detectable by 10-14 days after hatching. These changes were characterized by a gradual degeneration of the epithelium and an accompanying depletion of lymphocytes. Similar changes, although slower to develop and less severe, were observed in the thymus as a result of the combined deficiency. When both serum and tissue levels of vitamin E and Se were monitored, it was observed that these were rapidly and independently depleted by the specific deficiency diets. These data suggest that the primary lymphoid organs are major targets of Se and vitamin E dietary deficiencies and provide a possible mechanism by which immune function may be impaired.

  19. Blockade of IL-33 release and suppression of type 2 innate lymphoid cell responses by helminth

    E-print Network

    of innate and adaptive immunity, and it is not yet known at what level helminth infection could act it is an ideal setting in which to examine the relative roles of innate and adaptive type 2 responses duringOPEN Blockade of IL-33 release and suppression of type 2 innate lymphoid cell responses by helminth

  20. Clarifying the role of Stat5 in lymphoid development and Abelson-induced transformation

    PubMed Central

    Hoelbl, Andrea; Kovacic, Boris; Kerenyi, Marc A.; Simma, Olivia; Warsch, Wolfgang; Cui, Yongzhi; Beug, Hartmut; Hennighausen, Lothar; Moriggl, Richard; Sexl, Veronika

    2010-01-01

    The Stat5 transcription factors Stat5a and Stat5b have been implicated in lymphoid development and transformation. Most studies have employed Stat5a/b-deficient mice where gene targeting disrupted the first protein-coding exon, resulting in the expression of N-terminally truncated forms of Stat5a/b (Stat5a/b?N/?N mice). We have now reanalyzed lymphoid development in Stat5a/bnull/null mice having a complete deletion of the Stat5a/b gene locus. The few surviving Stat5a/bnull/null mice lacked CD8+ T lymphocytes. A massive reduction of CD8+ T cells was also found in Stat5a/bfl/fl lck-cre transgenic animals. While ?? T-cell receptor–positive (??TCR+) cells were expressed at normal levels in Stat5a/b?N/?N mice, they were completely absent in Stat5a/bnull/null animals. Moreover, B-cell maturation was abrogated at the pre–pro-B-cell stage in Stat5a/bnull/null mice, whereas Stat5a/b?N/?N B-lymphoid cells developed to the early pro-B-cell stage. In vitro assays using fetal liver-cell cultures confirmed this observation. Most strikingly, Stat5a/bnull/null cells were resistant to transformation and leukemia development induced by Abelson oncogenes, whereas Stat5a/b?N/?N-derived cells readily transformed. These findings show distinct lymphoid defects for Stat5a/b?N/?N and Stat5a/bnull/null mice and define a novel functional role for the N-termini of Stat5a/b in B-lymphoid transformation. PMID:16493008

  1. Clarifying the role of Stat5 in lymphoid development and Abelson-induced transformation.

    PubMed

    Hoelbl, Andrea; Kovacic, Boris; Kerenyi, Marc A; Simma, Olivia; Warsch, Wolfgang; Cui, Yongzhi; Beug, Hartmut; Hennighausen, Lothar; Moriggl, Richard; Sexl, Veronika

    2006-06-15

    The Stat5 transcription factors Stat5a and Stat5b have been implicated in lymphoid development and transformation. Most studies have employed Stat5a/b-deficient mice where gene targeting disrupted the first protein-coding exon, resulting in the expression of N-terminally truncated forms of Stat5a/b (Stat5a/b(DeltaN/DeltaN) mice). We have now reanalyzed lymphoid development in Stat5a/b(null/null) mice having a complete deletion of the Stat5a/b gene locus. The few surviving Stat5a/b(null/null) mice lacked CD8(+) T lymphocytes. A massive reduction of CD8(+) T cells was also found in Stat5a/b(fl/fl) lck-cre transgenic animals. While gammadelta T-cell receptor-positive (gammadeltaTCR(+)) cells were expressed at normal levels in Stat5a/b(DeltaN/DeltaN) mice, they were completely absent in Stat5a/b(null/null) animals. Moreover, B-cell maturation was abrogated at the pre-pro-B-cell stage in Stat5a/b(null/null) mice, whereas Stat5a/b(DeltaN/DeltaN) B-lymphoid cells developed to the early pro-B-cell stage. In vitro assays using fetal liver-cell cultures confirmed this observation. Most strikingly, Stat5a/b(null/null) cells were resistant to transformation and leukemia development induced by Abelson oncogenes, whereas Stat5a/b(DeltaN/DeltaN)-derived cells readily transformed. These findings show distinct lymphoid defects for Stat5a/b(DeltaN/DeltaN) and Stat5a/b(null/null) mice and define a novel functional role for the N-termini of Stat5a/b in B-lymphoid transformation. PMID:16493008

  2. Tectono-stratigraphy and low-grade metamorphism of Late Permian and Early Jurassic accretionary complexes within the Kurosegawa belt, Southwest Japan: Implications for mechanisms of crustal displacement within active continental margin

    NASA Astrophysics Data System (ADS)

    Hara, Hidetoshi; Kurihara, Toshiyuki; Mori, Hiroshi

    2013-04-01

    We characterize the tectono-stratigraphic architecture and low-grade metamorphism of the accretionary complex preserved in the Kurosegawa belt of the Kitagawa district in eastern Shikoku, Southwest Japan, in order to understand its internal structure, tectono-metamorphic evolution, and assessments of displacement of continental fragments within the complex. We report the first ever documented occurrence of an Early Jurassic radiolarian assemblage within the accretionary complex of the Kurosegawa belt that has been previously classified as the Late Permian accretionary complex, thus providing a revised age interpretation for these rocks. The accretionary complex is subdivided into four distinct tectono-stratigraphic units: Late Permian mélange and phyllite units, and Early Jurassic mélange and sandstone units. The stratigraphy of these four units is structurally repeated due to an E-W striking, steeply dipping regional fault. We characterized low-grade metamorphism of the accretionary complex via illite crystallinity and Raman spectroscopy of carbonaceous material. The estimated pattern of low-grade metamorphism showed pronounced variability within the complex and revealed no discernible spatial trends. The primary thermal structure in these rocks was overprinted by later tectonic events. Based on geological and thermal structure, we conclude that continental fragments within the Kurosegawa belt were structurally translated into both the Late Permian and Early Jurassic accretionary complexes, which comprise a highly deformed zone affected by strike-slip tectonics during the Early Cretaceous. Different models have been proposed to explain the initial structural evolution of the Kurosegawa belt (i.e., micro-continent collision and klippe tectonic models). Even if we presuppose either model, the available geological evidence requires a new interpretation, whereby primary geological structures are overprinted and reconfigured by later tectonic events.

  3. A simple and rapid method for evaluating the survival of xeroderma pigmentosum lymphoid lines after irradiation with ultraviolet light

    SciTech Connect

    Moshell, A.N.; Tarone, R.E.; Newfield, S.A.; Andrews, A.D.; Robbins, J.H.

    1981-04-01

    A simple, rapid, and reproducible test has been developed to measure the viability of cells after irradiation with ultraviolet light (UV). Epstein-Barr virus-transformed lymphoid lines, derived from patients with xeroderma pigmentosum (XP), were irradiated with UV, and the post-UV viability of the lymphoid lines was determined by the trypan blue dye exclusion method. The relative post-UV survival of the patients' lymphoid lines was similar to the relative post-UV survival of the patients' fibroblast strains.

  4. Primary Diffuse Large B-Cell Dural Lymphoma With Bone and Subcutaneous Tissue Involvement Mimicking Meningioma.

    PubMed

    Wang, Long; Ouayang, Taohui; Zhang, Na; Song, Zhibin; Gao, Jianwei; Li, Xuguang; Wang, Fang

    2015-09-01

    Primary dural lymphoma (PDL), a rare subtype of primary central nervous system lymphoma (PCNSL), is usually a marginal zone B-cell lymphoma or low-grade B-cell lymphoma of mucosa-associated lymphoid tissue type. Primary dural invasion by diffuse large B-cell lymphoma is extremely rare, with only a few cases reported in the literature. The authors presented an unusual case of primary dural involvement by a high-grade diffuse large B-cell lymphoma that invaded parietal bone and subcutaneous tissue. The patient received tumor complete resection and cranioplasty as well as radiotherapy and chemotherapy as adjuvant treatment after surgery. During 12 months follow-up, no tumor recurrence was found. Primary dural lymphoma should be differentially diagnosed with meningioma. Once the diagnosis of PDL is established, tumor resection and adjuvant radiation and chemotherapy may obtain relatively good prognosis. PMID:26221858

  5. A Six-Month Supplementation of Mulberry, Korean Red Ginseng, and Banaba Decreases Biomarkers of Systemic Low-Grade Inflammation in Subjects with Impaired Glucose Tolerance and Type 2 Diabetes

    PubMed Central

    Kim, H.-J.; Yoon, K.-H.; Kang, M.-J.; Yim, H.-W.; Lee, K.-S.; Vuksan, V.; Sung, M.-K.

    2012-01-01

    We sought the long-term efficacy of traditionally used antidiabetic herbs in controlling blood glucose homeostasis and low-grade inflammation. Ninety-four subjects with either impaired glucose tolerance or mild T2D were randomized either to treatment arm or placebo arm and received 1?:?1?:?1 mixture of ginseng roots, mulberry leaf water extract, and banaba leaf water extract (6?g/d) for 24 weeks. Oral 75?g glucose tolerance test was performed to measure glucose and insulin responses. Blood biomarkers of low-grade inflammation were also determined. Results found no significant difference in glucose homeostasis control measure changes. However, plasma intracellular adhesion molecule-1 (ICAM-1) concentration was decreased showing a significant between-treatment changes (P = 0.037). The concentrations of vascular cell adhesion molecule-1 (VCAM-1) (P = 0.014) and ICAM-1 (P = 0.048) were decreased in the treatment group at week 24, and the oxidized low-density lipoprotein (ox-LDL) concentration was reduced at week 24 compared to the baseline value in the treatment group (P = 0.003). These results indicate a long-term supplementation of ginseng, mulberry leaf, and banaba leaf suppresses inflammatory responses in T2D. PMID:22474520

  6. Malignant lymphoma of the urinary bladder: a clinicopathological study of 11 cases

    PubMed Central

    Bates, A; Norton, A; Baithun, S

    2000-01-01

    Aim—To report the clinical and histological features and outcome of primary and secondary malignant lymphomas of the urinary bladder. Methods—Eleven cases of malignant lymphoma of the urinary bladder were obtained from the registry of cases at St Bartholomews and the Royal London Hospitals. The lymphomas were classified on the basis of their morphology and immunophenotype, and the clinical records were reviewed. Results—There were six primary lymphomas: three extranodal marginal zone lymphomas of mucosa associated lymphoid tissue (MALT) type and three diffuse large B cell lymphomas. Of the five secondary cases, four were diffuse large B cell lymphomas, one secondary to a systemic follicular follicle centre lymphoma, and one nodular sclerosis Hodgkins disease. Four patients with secondary lymphoma for whom follow up was available had died of disease within 13 months of diagnosis. Primary lymphomas followed a more indolent course. In one case, there was evidence of transformation from low grade MALT-type to diffuse large B cell lymphoma. The most common presenting symptom was haematuria. Cystoscopic appearances were of solid, sometimes necrotic tumours resembling transitional cell carcinoma, and in one case the tumours were multiple. These cases represented 0.2% of all bladder neoplasms. Conclusions—Diffuse large B cell lymphoma and MALT-type lymphoma are the most common primary malignant lymphomas of the bladder. Lymphoepithelial lesions in MALT-type lymphoma involve transitional epithelium, and their presence in high grade lymphoma suggests a primary origin owing to transformation of low grade MALT-type lymphoma. Primary and secondary diffuse large B cell lymphomas of the bladder are histologically similar, but the prognosis of the former is favourable. Key Words: bladder • lymphoma • mucosa associated lymphoid tissue lymphoma PMID:10911804

  7. Pathogenetic Importance and Therapeutic Implications of NF-?B in Lymphoid Malignancies

    PubMed Central

    Lim, Kian-Huat; Yang, Yibin; Staudt, Louis M.

    2014-01-01

    Summary Derangement of the nuclear factor ?B (NF-?B) pathway initiates and/or sustains many types of human cancer. B-cell malignancies are particularly affected by oncogenic mutations, translocations, and copy number alterations affecting key components the NF-?B pathway, most likely owing to the pervasive role of this pathway in normal B cells. These genetic aberrations cause tumors to be ‘addicted’ to NF-?B, which can be exploited therapeutically. Since each subtype of lymphoid cancer utilizes different mechanisms to activate NF-?B, several different therapeutic strategies are needed to address this pathogenetic heterogeneity. Fortunately, a number of drugs that block signaling cascades leading to NF-?B are in early phase clinical trials, several of which are already showing activity in lymphoid malignancies. PMID:22435566

  8. MicroRNAs and Glucocorticoid-Induced Apoptosis in Lymphoid Malignancies

    PubMed Central

    Sionov, Ronit Vogt

    2013-01-01

    The initial response of lymphoid malignancies to glucocorticoids (GCs) is a critical parameter predicting successful treatment. Although being known as a strong inducer of apoptosis in lymphoid cells for almost a century, the signaling pathways regulating the susceptibility of the cells to GCs are only partly revealed. There is still a need to develop clinical tests that can predict the outcome of GC therapy. In this paper, I discuss important parameters modulating the pro-apoptotic effects of GCs, with a specific emphasis on the microRNA world comprised of small players with big impacts. The journey through the multifaceted complexity of GC-induced apoptosis brings forth explanations for the differential treatment response and raises potential strategies for overcoming drug resistance. PMID:23431463

  9. Tumor xenotransplantation in Wistar rats after treatment with cyclophosphamide and total lymphoid irradiation. [X-ray

    SciTech Connect

    Hoogenhout, J.; Kazem, I.; Jerusalem, C.R.; Bakkeren, J.A.J.; de Jong, J.; Kal, H.B.; van Munster, P.J.J.

    1982-10-01

    Three-month-old male Wistar rats were treated with cyclophosphamide and total lymphoid irradiation, and C22LR mouse osteosarcoma was transplanted into the rats. The effects of immunosuppression were monitored by lymphocyte counts, serum IgG determinations, phytohemagglutinin (PHA) and concanavalin A (Con A) responses, measurement of the proportion of B cells, and histopathological studies of the lymphoid organs. At eight days after treatment, the lymphocyte counts, IgG levels, and PHA and Con A values were decreased. Mitotic activity started in the depleted B and T cell areas of the peripheral lymphatic organs two weeks after treatment. There was a 94% graft take of the osteosarcoma. It was determined that the optimum time for tumor xenograft transplantation is 4 days after treatment. The duration of growth was 11 days, and this was followed by regression up to day 21.

  10. Tumor xenotransplantation in Wistar rats after treatment with cyclophosphamide and total lymphoid irradiation

    SciTech Connect

    Hoogenhout, J.; Kazem, I.; Jerusalem, C.R.; Bakkeren, J.A.; de Jong, J.; Kal, H.B.; van Munster, P.J.

    1982-10-01

    Three-month-old male Wistar rats were treated with cyclophosphamide and total lymphoid irradiation, and C22LR mouse osteosarcoma was transplanted into the rats. The effects of immunosuppression were monitored by lymphocyte counts, serum IgG determinations, phytohemagglutinin (PHA) and concanavalin A (Con A) responses, measurement of the proportion of B cells, and histopathological studies of the lymphoid organs. At eight days after treatment, the lymphocyte counts, IgG levels, and PHA and Con A values were decreased. Mitotic activity started in the depleted B and T cell areas of the peripheral lymphatic organs two weeks after treatment. There was a 94% graft take of the osteosarcoma. It was determined that the optimum time for tumor xenograft transplantation is 4 days after treatment. The duration of growth was 11 days, and this was followed by regression up to day 21.

  11. Bystander CD4+ T lymphocytes survive in HIV-infected human lymphoid tissue

    NASA Technical Reports Server (NTRS)

    Grivel, Jean-Charles; Biancotto, Angelique; Ito, Yoshinori; Lima, Rosangela G.; Margolis, Leonid B.

    2003-01-01

    HIV infection is associated with depletion of CD4(+) T cells. The mechanisms of this phenomenon remain to be understood. In particular, it remains controversial whether and to what extent uninfected ("bystander") CD4(+) T cells die in HIV-infected individuals. We address this question using a system of human lymphoid tissue ex vivo. Tissue blocks were inoculated with HIV-1. After productive infection was established, they were treated with the reverse transcriptase inhibitor nevirapine to protect from infection those CD4(+) T cells that had not yet been infected. These CD4(+) T cells residing in HIV-infected tissue are by definition bystanders. Our results demonstrate that after nevirapine application the number of bystander CD4(+) T cells is conserved. Thus, in the context of HIV-infected human lymphoid tissue, productive HIV infection kills infected cells but is not sufficient to cause the death of a significant number of uninfected CD4(+) T cells.

  12. Lymphoid cell kinetics under continuous low dose-rate gamma irradiation: A comparison study

    NASA Technical Reports Server (NTRS)

    Foster, B. R.

    1975-01-01

    A comparison study was conducted of the effects of continuous low dose-rate gamma irradiation on cell population kinetics of lymphoid tissue (white pulp) of the mouse spleen with findings as they relate to the mouse thymus. Experimental techniques employed included autoradiography and specific labeling with tritiated thymidine (TdR-(h-3)). The problem studied involved the mechanism of cell proliferation of lymphoid tissue of the mouse spleen and thymus under the stress of continuous irradiation at a dose rate of 10 roentgens (R) per day for 105 days (15 weeks). The aim was to determine whether or not a steady state or near-steady state of cell population could be established for this period of time, and what compensatory mechanisms of cell population were involved.

  13. Transcription Factor Networks Directing the Development, Function, and Evolution of Innate Lymphoid Effectors

    PubMed Central

    Kang, Joonsoo; Malhotra, Nidhi

    2015-01-01

    Mammalian lymphoid immunity is mediated by fast and slow responders to pathogens. Fast innate lymphocytes are active within hours after infections in mucosal tissues. Slow adaptive lymphocytes are conventional T and B cells with clonal antigen receptors that function days after pathogen exposure. A transcription factor (TF) regulatory network guiding early T cell development is at the core of effector function diversification in all innate lymphocytes, and the kinetics of immune responses is set by developmental programming. Operational units within the innate lymphoid system are not classified by the types of pathogen-sensing machineries but rather by discrete effector functions programmed by regulatory TF networks. Based on the evolutionary history of TFs of the regulatory networks, fast effectors likely arose earlier in the evolution of animals to fortify body barriers, and in mammals they often develop in fetal ontogeny prior to the establishment of fully competent adaptive immunity. PMID:25650177

  14. The apical caecal diverticulum of the chicken identified as a lymphoid organ.

    PubMed Central

    Kitagawa, H; Imagawa, T; Uehara, M

    1996-01-01

    A peculiar structure, observed as a dome-like protrusion at the apex of the caecum, was investigated macroscopically and histologically in healthy White Leghorn chickens. It was hemispheric or spherical in shape and as it consisted of a lumen with a wall occupied by lymphoid tissue, this structure was designated the apical caecal diverticulum (ACD). ACD were detected in 25.2% of examined chickens and had a mean diameter and height of 1.9 mm and 1.2 mm respectively. Histologically, both the lamina propria mucosae and the submucosa of ACD consisted of well developed aggregated lymphoid nodules. Each nodule was covered by follicle-associated epithelium which contained cells resembling M cells. Some secondary nodules extended into the subserosa. The muscularis mucosae and the stratum circulae of the tunica muscularis disappeared near the entrance to ACD. The stratum longitudinale also gradually decreased in thickness around the entrance, becoming an extremely thin layer in the diverticulum wall. At the caecal apex, each stratum of the tunica muscularis was thinner than in the caecal body and separated into several muscle bundles. These bundles were occasionally displaced by developed lymphoid nodules, causing them to protrude into the subserosa. The high frequency of ACD suggests that caecal apex may be sites for immunological surveillance in the chicken caecum. In addition to the intense and frequent antiperistalsis at the apex suggested by Yasukawa (1959), possible causes for the formation of ACD included (1) the fragility of the tunica muscularis at the ACD, and (2) the local removal of the physical supporting structures by the development of lymphoid nodules. Images Fig. 1 Fig. 2 Fig. 4 Fig. 5 Fig. 6 Fig. 7 PMID:8982842

  15. Multispectral imaging reveals the tissue distribution of tetraspanins in human lymphoid organs.

    PubMed

    de Winde, Charlotte M; Zuidscherwoude, Malou; Vasaturo, Angela; van der Schaaf, Alie; Figdor, Carl G; van Spriel, Annemiek B

    2015-08-01

    Multispectral imaging is a novel microscopy technique that combines imaging with spectroscopy to obtain both quantitative expression data and tissue distribution of different cellular markers. Tetraspanins CD37 and CD53 are four-transmembrane proteins involved in cellular and humoral immune responses. However, comprehensive immunohistochemical analyses of CD37 and CD53 in human lymphoid organs have not been performed so far. We investigated CD37 and CD53 protein expression on primary human immune cell subsets in blood and in primary and secondary lymphoid organs. Both tetraspanins were prominently expressed on antigen-presenting cells, with highest expression of CD37 on B lymphocytes. Analysis of subcellular distribution showed presence of both tetraspanins on the plasma membrane and on endosomes. In addition, CD53 was also present on lysosomes. Quantitative analysis of expression and localization of CD37 and CD53 on lymphocytes within lymphoid tissues by multispectral imaging revealed high expression of both tetraspanins on CD20(+) cells in B cell follicles in human spleen and appendix. CD3(+) T cells within splenic T cell zones expressed lower levels of CD37 and CD53 compared to T cells in the red pulp of human spleen. B cells in human bone marrow highly expressed CD37, whereas the expression of CD53 was low. In conclusion, we demonstrate differential expression of CD37 and CD53 on primary human immune cells, their subcellular localization and their quantitative distribution in human lymphoid organs. This study provides a solid basis for better insight into the function of tetraspanins in the human immune response. PMID:25952155

  16. [MDCT features and anatomic-pathological basis of lymphoid neoplasm in cervico-thoracic junctional region].

    PubMed

    Ye, Yilan; Yang, Zhigang; Shao, Heng; Cheng, Jing; Tang, Sisi; Wen, Lingyi

    2012-08-01

    To determine the relevance between MDCT features and anatomic-pathological basis of lymphoid neoplasm in cervico-thoracic junctional region, we performed a retrospective analysis of 69 patients with lymphoid neoplasm (lymphoma: 41 patients; metastatic tumor: 28 patients) involving the cervico-thoracic junctional region for MDCT features and distribution of lesions. The relevance between MDCT features and the anatomic-pathological basis in this region were evaluated. Among all the 41 patients with lymphoma, 29 with NHL (70.7%), 12 with HD (29.3%). The lymphomatous lymphadenopathy mainly located in superficial lateral cervix (51.2%, 21/41) ,deep jugular chain (65.9%, 27/41), supraclavicular fossa (75.6%, 31/41), paratrachea space in anterior mediastinum (46.3%, 19/41), around aortic arch (56.1%, 23/41), aortopulmonary window (53.7%, 22/41), upper anterior mediastinum (41.5%, 17/41), subcarinal space (26.8%, 11/41) and paraesophageal space (17.1%, 7/41). 28 patients had metastatic lymphoid tumor. The primary tumor were nasopharynx tumor (5 patients), thyroid cancer (7 patients), lung cancer (10 patients), and esophageal cancer (6 patients). Most metastasis took stage by stage in the way of lymphatic return, but a minority of cases migrated jumpily. The main metastatic sites were: beside jugular chain (82.1%), supraclavicular fossa (75%), paratracheal in anterior mediastinum (60.7%), upper anterior mediastinum (64.3%), beside aortic arch (35.7%), aortopulmonary window (39.2%), and paraesophageal space (28.6%). So lymphoid neoplasms in cervico-thoracic junctional region were involving both lower cervix and upper thorax simultaneously. The MDCT features and main distribution of lesions correlated with the anatomic-pathological characteristics in this region. PMID:23016404

  17. Target Cell Destruction In Vitro by Concanavalin A-Stimulated Lymphoid Cells

    PubMed Central

    Schwartz, Howard J.; Wilson, Frank

    1971-01-01

    Guinea pig lymphoid cells obtained from lymph nodes and spleens of nonimmune animals are cytotoxic for mouse L-cell fibroblasts on incubation with concanavalin A. This effect is blocked by methyl-?-D-mannoside. The results indicate that this effect may be due to the release of a lymphotoxin by the concanavalin A-stimulated lymphocytes. ImagesFig 1Fig 2 PMID:5142268

  18. The influence of gut function on lymphoid cell populations in the intestinal mucosa of lambs.

    PubMed Central

    Reynolds, J D; Morris, B

    1983-01-01

    The number and type of lymphoid cells in the intestinal mucosa of lambs change during the first weeks after birth. The influence of gut function on these changes was examined by comparing the evolution of lymphoid cell populations in normal ileum with that in lengths of ileum which had been isolated surgically from the functional intestinal tract of the lamb before birth. The isolated lengths of ileum had a normal blood and nerve supply and they remained healthy throughout a period of at least 2 years, although they did not have a normal histological development. In comparison with normal ileum, the villi of the isolated ileal segments were much smaller and there were many fewer intraepithelial lymphocytes; the lamina propria had significantly fewer lymphocytes than the functional ileum and only a few plasma cells. When isolated ileal segments were reconnected into the intestinal tract after having been isolated from it for 1-3 months, the histology of the mucosa reverted to that of the normal gut, with the same number and types of lymphoid cells. Radiolabelled lymphoblasts collected from intestinal lymph and injected intravenously accumulated to only a small extent in isolated segments of ileum compared with either the normal or the reconnected segments of ileum. This suggested that the paucity of lymphocytes in the mucosa of the isolated segments was due to a reduced extravasation of these cells there. The influence which the gut contents exert on the lymphoid cell population in the mucosa is probably associated with antigenic stimulation but may also be related to other factors concerned in the normal digestive functions of the gut. Images Figure 1 Figure 2 Figure 3 PMID:6862523

  19. Characteristics of Nasal-Associated Lymphoid Tissue (NALT) and Nasal Absorption Capacity in Chicken

    PubMed Central

    Kang, Haihong; Yan, Mengfei; Yu, Qinghua; Yang, Qian

    2013-01-01

    As the main mucosal immune inductive site of nasal cavity, nasal-associated lymphoid tissue (NALT) plays an important role in both antigen recognition and immune activation after intranasal immunization. However, the efficiency of intranasal vaccines is commonly restricted by the insufficient intake of antigen by the nasal mucosa, resulting from the nasal mucosal barrier and the nasal mucociliary clearance. The distribution of NALT and the characteristic of nasal cavity have already been described in humans and many laboratory rodents, while data about poultry are scarce. For this purpose, histological sections of the chicken nasal cavities were used to examine the anatomical structure and histological characteristics of nasal cavity. Besides, the absorptive capacity of chicken nasal mucosa was also studied using the materials with different particle size. Results showed that the NALT of chicken was located on the bottom of nasal septum and both sides of choanal cleft, which mainly consisted of second lymphoid follicle. A large number of lymphocytes were distributed under the mucosal epithelium of inferior nasal meatus. In addition, there were also diffuse lymphoid tissues located under the epithelium of the concha nasalis media and the walls of nasal cavity. The results of absorption experiment showed that the chicken nasal mucosa was capable to absorb trypan blue, OVA, and fluorescent latex particles. Inactivated avian influenza virus (IAIV) could be taken up by chicken nasal mucosa except for the stratified squamous epithelium sites located on the forepart of nasal cavity. The intake of IAIV by NALT was greater than that of the nasal mucosa covering on non-lymphoid tissue, which could be further enhanced after intranasal inoculation combined with sodium cholate or CpG DNA. The study on NALT and nasal absorptive capacity will be benefit for further understanding of immune mechanisms after nasal vaccination and development of nasal vaccines for poultry. PMID:24391892

  20. Neutrophils and monocytes transport tumor cell antigens from the peritoneal cavity to secondary lymphoid tissues

    SciTech Connect

    Terasawa, Masao; Nagata, Kisaburo; Kobayashi, Yoshiro

    2008-12-12

    Antigen-transporting cells take up pathogens, and then migrate from sites of inflammation to secondary lymphoid tissues to induce an immune response. Among antigen-transporting cells, dendritic cells (DCs) are believed to be the most potent and professional antigen-presenting cells that can stimulate naive T cells. However, the cells that transport antigens, tumor cell antigens in particular, have not been clearly identified. In this study we have analyzed what types of cells transport tumor cell antigens to secondary lymphoid tissues. We show that neutrophils, monocytes and macrophages but not DCs engulf X-irradiated P388 leukemic cells after their injection into the peritoneal cavity, and that neutrophils and monocytes but not macrophages migrate to the parathymic lymph nodes (pLN), the blood, and then the spleen. The monocytes in the pLN comprise Gr-1{sup -} and Gr-1{sup +} ones, and some of these cells express CD11c. Overall, this study demonstrates that neutrophils and monocytes transport tumor cell antigens from the peritoneal cavity to secondary lymphoid tissues.

  1. Constitutive expression of tenascin in T-dependent zones of human lymphoid tissues.

    PubMed Central

    Chilosi, M.; Lestani, M.; Benedetti, A.; Montagna, L.; Pedron, S.; Scarpa, A.; Menestrina, F.; Hirohashi, S.; Pizzolo, G.; Semenzato, G.

    1993-01-01

    Tenascin is a major extracellular matrix glycoprotein that can interfere with the action of fibronectin by inhibiting cell adhesion and spreading. Although tenascin is able to exert important immunomodulatory activities on T and B cells and macrophages, little is known about its distribution in different lymphohemopoietic tissues. In this study we have analyzed tenascin immunoreactivity on cryostat and paraffin sections of normal and pathological lymphoid tissues using two different monoclonal antibodies. We demonstrated strong tenascin expression in all peripheral lymphoid tissues, whereas it was barely detectable in the thymus and in bone marrow. In reactive lymph nodes, tenascin was mainly found in T-dependent zones, forming a variably close-woven reticular network corresponding to fibroblastic reticulum cells and blood vessels basal laminae, showing a partial co-localization with fibronectin. In B-dependent zones, tenascin was restricted to blood vessels. Using double-marker analysis, we performed a thorough study comparing tenascin expression in different compartments of lymphoid microenvironments. Tenascin network appeared much thicker in chronically stimulated tissues, where CD4+ lymphocytes with "memory" phenotype (CD45RO+/CD45RA-) were predominant, and at sites of ongoing inflammation. In particular, a striking increase of tenascin was observed in sarcoid lymph node, as well as in myasthenic hyperplastic thymuses. In addition, tenascin can be abnormally synthesized in tissue involved by various types of lymphomas, including Hodgkin's disease and hairy cell leukemia. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 PMID:7694469

  2. A histological and immunohistochemical analysis of lymphoid tissues of the Tasmanian devil.

    PubMed

    Kreiss, Alexandre; Obendorf, David L; Hemsley, Susan; Canfield, Paul J; Woods, Gregory M

    2009-05-01

    Tasmanian devil lymphoid tissues (thymus, spleen, and lymph node) from seven animals, including pouch young, juvenile, and adult devils, were investigated using histological and immunohistochemical techniques. Antibodies against the conserved intracytoplasmic portion of CD3 and CD79b (T- and B-cell markers, respectively) and MHC II were used to label immune cells. The thymus from the juvenile devils and the pouch young had CD3+ cells that were primarily located in the medulla of the organ. The spleen consisted of red and white pulp areas with characteristic lymphoid follicles with CD79b+ and MHC II+ cells and nonfollicular T-cell-dominated periarteriolar lymphoid sheaths. Peripheral lymph nodes presented three distinct regions, outer cortex and medulla (both with primarily CD79b+ and MHC II+ cells) and paracortex (mainly CD3+ cells). Tissue architecture and distribution of the immune cells were similar to that seen in eutherian mammals and other marsupials, indicating that the Tasmanian devil has all the structural elements necessary for effective adaptive immunity. PMID:19382223

  3. VEGF signaling on hematopoietic precursors restricts B-lymphoid commitment in vitro and in vivo.

    PubMed

    Fragoso, Rita; Igreja, Cátia; Clode, Nuno; Henriques, Alexandra; Appleton, Cláudia; Zhu, Zhenping; Wu, Yan; Dias, Sérgio

    2008-10-01

    Vascular endothelial growth factor (VEGF) signals on vascular and hematopoietic cells via its receptors, VEGFR-2 (KDR) and VEGFR-1 (FLT-1). Elevated levels of VEGF, such as during tumor growth or inflammation, have been suggested to suppress hematopoiesis; most studies refer to KDR as the main receptor involved in this inhibitory effect. In the present study, having detected expression of FLT-1 in B-lymphoid precursors, we exploited the possibility that VEGF signaling via FLT-1 might affect early B-cell commitment. Using a well-established in vitro B-cell differentiation assay, we demonstrate that FLT-1 blockade promotes B-cell commitment and subsequent differentiation, while KDR blockade has no effect on B-cell commitment. In agreement, in vivo transplantation of human (CD34+) or murine (Sca1+l/Lin-) FLT-1-negative hematopoietic precursors into irradiated severe combined immune-deficient mice restored the bone marrow lymphoid compartment, while transplanting the FLT-1-positive counterpart failed to repopulate the lymphoid compartment, and unexpectedly resulted in early death of the irradiated recipients due to hematopoietic suppression. Taken together, we suggest that VEGF signaling via FLT-1 on hematopoietic precursors may restrict lymphopoiesis. PMID:18620797

  4. JunB inhibits proliferation and transformation in B-lymphoid cells.

    PubMed

    Szremska, Agnieszka P; Kenner, Lukas; Weisz, Eva; Ott, Rene G; Passegué, Emmanuelle; Artwohl, Michaela; Freissmuth, Michael; Stoxreiter, Renate; Theussl, Hans-Christian; Parzer, Sabina Baumgartner; Moriggl, Richard; Wagner, Erwin F; Sexl, Veronika

    2003-12-01

    The activator protein 1 (AP-1) member JunB has recently been implicated in leukemogenesis. Here we surveyed human lymphoma samples for expression of JunB and other AP-1 members (c-Jun, c-Fos, Fra1, JunD). JunB was strongly expressed in T-cell lymphomas, but non-Hodgkin B-cell lymphomas do not or only weakly express JunB. We therefore asked whether JunB acted as a negative regulator of B-cell development, proliferation, and transformation. We used transgenic mice that expressed JunB under the control of the ubiquitin C promoter; these displayed increased JunB levels in both B- and T-lymphoid cells. JunB transgenic cells of B-lymphoid, but not of T-lymphoid, origin responded poorly to mitogenic stimuli. Furthermore, JunB transgenic cells were found to be less susceptible to the transforming potential of the Abelson oncogene in vitro. In addition, overexpression of JunB partially protected transgenic mice against the oncogenic challenge in vivo. However, transformed B cells eventually escaped from the inhibitory effect of JunB: the proliferative response was similar in explanted tumor-derived cells from transgenic animals and those from wild-type controls. Our results identify JunB as a novel regulator of B-cell proliferation and transformation. PMID:12907453

  5. TYK2 is a key regulator of the surveillance of B lymphoid tumors.

    PubMed

    Stoiber, Dagmar; Kovacic, Boris; Schuster, Christian; Schellack, Carola; Karaghiosoff, Marina; Kreibich, Rita; Weisz, Eva; Artwohl, Michaela; Kleine, Olaf C; Muller, Mathias; Baumgartner-Parzer, Sabina; Ghysdael, Jacques; Freissmuth, Michael; Sexl, Veronika

    2004-12-01

    Aberrant activation of the JAK-STAT pathway has been implicated in tumor formation; for example, constitutive activation of JAK2 kinase or the enforced expression of STAT5 induces leukemia in mice. We show here that the Janus kinase TYK2 serves an opposite function. Mice deficient in TYK2 developed Abelson-induced B lymphoid leukemia/lymphoma as well as TEL-JAK2-induced T lymphoid leukemia with a higher incidence and shortened latency compared with WT controls. The cell-autonomous properties of Abelson murine leukemia virus-transformed (A-MuLV-transformed) TYK2(-/-) cells were unaltered, but the high susceptibility of TYK2(-/-) mice resulted from an impaired tumor surveillance, and accordingly, TYK2(-/-) A-MuLV-induced lymphomas were easily rejected after transplantation into WT hosts. The increased rate of leukemia/lymphoma formation was linked to a decreased in vitro cytotoxic capacity of TYK2(-/-) NK and NKT cells toward tumor-derived cells. RAG2/TYK2 double-knockout mice succumbed to A-MuLV-induced leukemia/lymphoma faster than RAG2(-/-)TYK2(+/-) mice. This defines NK cells as key players in tumor surveillance in Abelson-induced malignancies. Our observations provide compelling evidence that TYK2 is an important regulator of lymphoid tumor surveillance. PMID:15578097

  6. TYK2 is a key regulator of the surveillance of B lymphoid tumors

    PubMed Central

    Stoiber, Dagmar; Kovacic, Boris; Schuster, Christian; Schellack, Carola; Karaghiosoff, Marina; Kreibich, Rita; Weisz, Eva; Artwohl, Michaela; Kleine, Olaf C.; Muller, Mathias; Baumgartner-Parzer, Sabina; Ghysdael, Jacques; Freissmuth, Michael; Sexl, Veronika

    2004-01-01

    Aberrant activation of the JAK-STAT pathway has been implicated in tumor formation; for example, constitutive activation of JAK2 kinase or the enforced expression of STAT5 induces leukemia in mice. We show here that the Janus kinase TYK2 serves an opposite function. Mice deficient in TYK2 developed Abelson-induced B lymphoid leukemia/lymphoma as well as TEL-JAK2–induced T lymphoid leukemia with a higher incidence and shortened latency compared with WT controls. The cell-autonomous properties of Abelson murine leukemia virus–transformed (A-MuLV–transformed) TYK2–/– cells were unaltered, but the high susceptibility of TYK2–/– mice resulted from an impaired tumor surveillance, and accordingly, TYK2–/– A-MuLV–induced lymphomas were easily rejected after transplantation into WT hosts. The increased rate of leukemia/lymphoma formation was linked to a decreased in vitro cytotoxic capacity of TYK2–/– NK and NKT cells toward tumor-derived cells. RAG2/TYK2 double-knockout mice succumbed to A-MuLV–induced leukemia/lymphoma faster than RAG2–/–TYK2+/– mice. This defines NK cells as key players in tumor surveillance in Abelson-induced malignancies. Our observations provide compelling evidence that TYK2 is an important regulator of lymphoid tumor surveillance. PMID:15578097

  7. Pre-malignant lymphoid cells arise from hematopoietic stem/progenitor cells in chronic lymphocytic leukemia.

    PubMed

    Kikushige, Yoshikane; Miyamoto, Toshihiro

    2015-11-01

    Human malignancies progress through a multistep process that includes the development of critical somatic mutations over the clinical course. Recent novel findings have indicated that hematopoietic stem cells (HSCs), which have the potential to self-renew and differentiate into multilineage hematopoietic cells, are an important cellular target for the accumulation of critical somatic mutations in hematological malignancies and play a central role in myeloid malignancy development. In contrast to myeloid malignancies, mature lymphoid malignancies, such as chronic lymphocytic leukemia (CLL), are thought to originate directly from differentiated mature lymphocytes; however, recent compelling data have shown that primitive HSCs and hematopoietic progenitor cells contribute to the pathogenesis of mature lymphoid malignancies. Several representative mutations of hematological malignancies have been identified within the HSCs of CLL and lymphoma patients, indicating that the self-renewing long-lived fraction of HSCs can serve as a reservoir for the development of oncogenic events. Novel mice models have been established as human mature lymphoma models, in which specific oncogenic events target the HSCs and immature progenitor cells. These data collectively suggest that HSCs can be the cellular target involved in the accumulation of oncogenic events in the pathogenesis of mature lymphoid and myeloid malignancies. PMID:25644149

  8. POK/ZBTB proteins: an emerging family of proteins that regulate lymphoid development and function

    PubMed Central

    Lee, Sung-Uk; Maeda, Takahiro

    2012-01-01

    Summary The germinal center (GC) is a unique histological structure found in peripheral lymphoid organs. GCs provide an important source of humoral immunity by generating high affinity antibodies against a pathogen. The GC response is tightly regulated during clonal expansion, immunoglobulin modification, and affinity maturation, while its deregulation has a detrimental effect on immune function, leading to development of diseases such as lymphoma and autoimmunity. LRF (lymphoma/leukemia-related factor), encoded by the ZBTB7A gene, is a transcriptional repressor belonging to the POK (POZ and Krüppel)/ZBTB (zing finger and BTB) protein family. LRF was originally identified as a PLZF (promyelocytic leukemia zinc finger) homologue that physically interacts with BCL6 (B-cell lymphoma 6), whose expression is required for GC formation and associated with non-Hodgkin’s lymphoma. Recently, our group demonstrated that LRF plays critical roles in regulating lymphoid lineage commitment, mature B-cell development, and the GC response via distinct mechanisms. Here, we review POK/ZBTB protein function in lymphoid development, with particular emphasis on the role of LRF in GC B cells. PMID:22500835

  9. Rapid, Nonradioactive Detection of Clonal T-Cell Receptor Gene Rearrangements in Lymphoid Neoplasms

    NASA Astrophysics Data System (ADS)

    Bourguin, Anne; Tung, Rosann; Galili, Naomi; Sklar, Jeffrey

    1990-11-01

    Southern blot hybridization analysis of clonal antigen receptor gene rearrangements has proved to be a valuable adjunct to conventional methods for diagnosing lymphoid neoplasia. However, Southern blot analysis suffers from a number of technical disadvantages, including the time necessary to obtain results, the use of radioactivity, and the susceptibility of the method to various artifacts. We have investigated an alternative approach for assessing the clonality of antigen receptor gene rearrangements in lymphoid tissue biopsy specimens. This approach involves the amplification of rearranged ? T-cell receptor genes by the polymerase chain reaction and analysis of the polymerase chain reaction products by denaturing gradient gel electrophoresis. By use of this approach, clonal rearrangements from neoplastic lymphocytes constituting as little as 0.1-1% of the total cells in the tissue are detected as discrete bands in the denaturing gel after the gel is stained with ethidium bromide and viewed under ultraviolet light. In contrast, polyclonal rearrangements from reactive lymphocytes appear as a diffuse smear along the length of the gel. Our findings suggest that polymerase chain reaction combined with denaturing gradient gel electrophoresis may offer a rapid, nonradioactive, and sensitive alternative to Southern blot analysis for the diagnostic evaluation of lymphoid tissue biopsy specimens.

  10. CD4 regulation in human lymphoid non-T-cells: a role for the silencer element.

    PubMed

    Mouly, Enguerran; Dorival, Céline; Pflumio, Françoise; Baillou, Claude; Coulombel, Laure; Levy, Yves; Lemoine, François M; Klatzmann, David; Marodon, Gilles

    2007-01-01

    In humans, the CD4 molecule is expressed on a subset of T-cells and at various levels on myeloid and lymphoid cells. The mechanisms regulating human CD4 gene expression are yet poorly understood. We speculated that the CD4 silencer, which operates in CD8+ T-cells to repress CD4 expression, could be responsible for CD4 repression in human lymphoid non-T-cells. To test this possibility, we used lentiviral vectors carrying CD4 regulatory sequences, with or without the silencer element, to express an eGFP reporter gene. We observed that (i) in the absence of the silencer element, eGFP expression was detected in CD34+-derived B- and NK-cells that otherwise lacked endogenous CD4 mRNA, indicating active repression of the CD4 regulatory sequences and (ii) the addition of the CD4 silencer could repress eGFP expression in these same cells, as well as in human B-cells generated in vivo in NOD/SCID mice. Collectively, our results suggest that beyond its well-characterized function in T-cells, the CD4 silencer also regulates CD4 gene expression in human lymphoid non-T-cells. PMID:16630660

  11. Lymphoid irradiation in intractable rheumatoid arthritis: effects on the production of immunoglobulins and rheumatoid factors.

    PubMed Central

    Hanly, J G; Hassan, J; Moriarty, M; Whelan, A; Feighery, C; Bresnihan, B

    1985-01-01

    Changes in the production of immunoglobulins and rheumatoid factors (RF's) were studied in 20 patients with intractable rheumatoid arthritis (RA) following total doses of 750 rad or 2,000 rad lymphoid irradiation. Over a 12 month follow up period there was no consistent change in absolute serum or synovial fluid levels, or in synovial membrane production of either total IgG, IgA or IgM, or the corresponding RF fractions. The invitro production of immunoglobulins and IgM RF by peripheral blood mononuclear cells was also unaltered, except for one patient who had a dramatic rise in IgM RF production. Over the same period there was a significant overall reduction in disease activity following both doses of radiotherapy. It is concluded that the clinical response which occurs following lymphoid irradiation is not due to a reduction in RF production. Furthermore, the production of RF's appears to be unaffected by the changes in T cell immunity which occur following lymphoid irradiation. PMID:4085151

  12. Lymphoid lineage differentiation potential of mouse nuclear transfer embryonic stem cells.

    PubMed

    Eslami-Arshaghi, Tarlan; Salehi, Mohammad; Soleimani, Masoud; Gholipourmalekabadi, Mazaher; Mossahebi-Mohammadi, Majid; Ardeshirylajimi, Abdolreza; Rajabi, Hoda

    2015-09-01

    Stem cells therapy is considered as an efficient strategy for the treatment of some diseases. Nevertheless, some obstacles such as probability of rejection by the immune system limit applications of this strategy. Therefore, several efforts have been made to overcome this among which using the induced pluripotent stem cells (iPSCs) and nuclear transfer embryonic stem cell (nt-ESCs) are the most efficient strategies. The objective of this study was to evaluate the differentiation potential of the nt-ESCs to lymphoid lineage in the presence of IL-7, IL-3, FLT3-ligand and TPO growth factors in vitro. To this end, the nt-ESCs cells were prepared and treated with aforementioned growth factors for 7 and 14 days. Then, the cells were examined for expression of lymphoid markers (CD3, CD25, CD127 and CD19) by quantitative PCR (q-PCR) and flow cytometry. An increased expression of CD19 and CD25 markers was observed in the treated cells compared with the negative control samples by day 7. After 14 days, the expression level of all the tested CD markers significantly increased in the treated groups in comparison with the control. The current study reveals the potential of the nt-ESCs in differentiation to lymphoid lineage in the presence of defined growth factors. PMID:26239678

  13. Efficacy of total lymphoid irradiation in intractable rheumatoid arthritis. A double-blind, randomized trial

    SciTech Connect

    Strober, S.; Tanay, A.; Field, E.; Hoppe, R.T.; Calin, A.; Engleman, E.G.; Kotzin, B.; Brown, B.W.; Kaplan, H.S.

    1985-04-01

    Twenty-six patients participated in a randomized, double-blind study of the efficacy of total lymphoid irradiation in the treatment of intractable rheumatoid arthritis. All 26 patients, for whom therapy with gold compounds and penicillamine had failed, would ordinarily have been considered candidates for cytotoxic or antimetabolite drug therapy. Thirteen patients randomly assigned to receive full-dose total lymphoid irradiation (2000 rad) and 11 patients assigned to receive control low-dose total lymphoid irradiation (200 rad) completed radiotherapy. Alleviation of joint disease activity was significantly greater in the high-dose group as judged by morning stiffness, joint tenderness, and functional assessment (global composite score) at 3 and 6 months after radiotherapy. The high-dose group had a marked reduction in both T-lymphocyte function and numbers, but this finding was not observed in the low-dose group. Complications seen in the high-dose but not low-dose group included transient neutropenia, thrombocytopenia, pericarditis, and pleurisy.

  14. Mutation-targeted therapy with sunitinib or everolimus in patients with advanced low-grade or intermediate-grade neuroendocrine tumours of the gastrointestinal tract and pancreas with or without cytoreductive surgery: protocol for a phase II clinical trial

    PubMed Central

    Neychev, Vladimir; Steinberg, Seth M; Cottle-Delisle, Candice; Merkel, Roxanne; Nilubol, Naris; Yao, Jianhua; Meltzer, Paul; Pacak, Karel; Marx, Stephen; Kebebew, Electron

    2015-01-01

    Introduction Finding the optimal management strategy for patients with advanced, metastatic neuroendocrine tumours (NETs) of the gastrointestinal tract and pancreas is a work in progress. Sunitinib and everolimus are currently approved for the treatment of progressive, unresectable, locally advanced or metastatic low-grade or intermediate-grade pancreatic NETs. However, mutation-targeted therapy with sunitinib or everolimus has not been studied in this patient population. Methods and analysis This prospective, open-label phase II clinical trial was designed to determine if mutation-targeting therapy with sunitinib or everolimus for patients with advanced low-grade or intermediate-grade NETs is more effective than historically expected results with progression-free survival (PFS) as the primary end point. Patients ?18?years of age with progressive, low-grade or intermediate-grade locally advanced or metastatic NETs are eligible for this study. Patients will undergo tumour biopsy (if they are not a surgical candidate) for tumour genotyping. Patients will be assigned to sunitininb or everolimus based on somatic/germline mutations profile. Patients who have disease progression on either sunitinib or everolimus will crossover to the other drug. Treatment will continue until disease progression, unacceptable toxicity, or consent to withdrawal. Using the proposed criteria, 44 patients will be accrued within each treatment group during a 48-month period (a total of 88 patients for the 2 treatments), and followed for up to an additional 12?months (a total of 60?months from entry of the first patient) to achieve 80% power in order to test whether there is an improvement in PFS compared to historically expected results, with a 0.10 ? level one-sided significance test. Ethics and dissemination The study protocol was approved by the institutional review board of the National Cancer Institute (NCI-IRB Number 15C0040; iRIS Reference Number 339636). The results will be published in a peer-reviewed journal and shared with the worldwide medical community. Trial registration number NCT02315625. PMID:25991462

  15. Low CXCL13 Expression, Splenic Lymphoid Tissue Atrophy and Germinal Center Disruption in Severe Canine Visceral Leishmaniasis

    PubMed Central

    Silva, Joselli S.; Andrade, Alan C.; Santana, Claudia C.; Santos, Leina Q.; de Oliveira, Camila I.; Veras, Patrícia S. T.; Vassallo, José; dos-Santos, Washington L. C.

    2012-01-01

    Visceral leishmaniasis is associated with atrophy and histological disorganization of splenic compartments. In this paper, we compared organized and disorganized splenic lymphoid tissue from dogs naturally infected with Leishmania infantum assessing the size of the white pulp compartments, the distribution of T, B and S100+ dendritic cells, using immunohistochemistry and morphometry and the expression of CCR7 and the cytokines, CXCL13, lymphotoxin (LT)-?, LT-?, CCL19, CCL21, TNF-?, IL-10, IFN-? and TGF-?, using by real time RT-PCR. The lymphoid follicles and marginal zones were smaller (3.2 and 1.9 times, respectively; Mann-Whitney, P<0.02) in animals with disorganized splenic tissue in comparison to those with organized splenic lymphoid tissue. In spleens with disorganized lymphoid tissue, the numbers of T cells and S100+ dendritic cells were decreased in the follicles, and the numbers of B cells were reduced in both the follicles and marginal zones. CXCL13 mRNA expression was lower in animals with disorganized lymphoid tissue (0.5±0.4) compared to those with organized lymphoid tissue (2.7±2.9, both relative to 18S expression, P?=?0.01). These changes in the spleen were associated with higher frequency of severe disease (7/12) in the animals with disorganized than in animals with organized (2/13, Chi-square, P?=?0.01) splenic lymphoid tissue. The data presented herein suggest that natural infection with Leishmania infantum is associated with the impairment of follicular dendritic cells, CXCL13 expression, B cell migration and germinal center formation and associates these changes with severe clinical forms of visceral leishmaniasis. Furthermore the fact that this work uses dogs naturally infected with Leishmania infantum emphasizes the relevance of the data presented herein for the knowledge on the canine and human visceral leishmaniasis. PMID:22242159

  16. Encouraging Early Clinical Outcomes With Helical Tomotherapy-Based Image-Guided Intensity-Modulated Radiation Therapy for Residual, Recurrent, and/or Progressive Benign/Low-Grade Intracranial Tumors: A Comprehensive Evaluation

    SciTech Connect

    Gupta, Tejpal

    2012-02-01

    Purpose: To report early clinical outcomes of helical tomotherapy (HT)-based image-guided intensity-modulated radiation therapy (IMRT) in brain tumors of varying shape, size, and location. Materials and Methods: Patients with residual, recurrent, and/or progressive low-grade intracranial and skull-base tumors were treated on a prospective protocol of HT-based IMRT and followed clinicoradiologically. Standardized metrics were used for plan evaluation and outcome analysis. Results: Twenty-seven patients with 30 lesions were treated to a median radiotherapy dose of 54 Gy in 30 fractions. All HT plans resulted in excellent target volume coverage with steep dose-gradients. The mean (standard deviation) dose homogeneity index and conformity index was 0.07 (0.05) and 0.71 (0.08) respectively. At first response assessment, 20 of 30 lesions were stable, whereas 9 showed partial regression. One patient with a recurrent clival chordoma though neurologically stable showed imaging-defined progression, whereas another patient with stable disease on serial imaging had sustained neurologic worsening. With a median follow-up of 19 months (interquartile range, 11-26 months), the 2-year clinicoradiological progression-free survival and overall survival was 93.3% and 100% respectively. Conclusions: Careful selection of radiotherapy technique is warranted for benign/low-grade brain tumors to achieve durable local control with minimum long-term morbidity. Large or complex-shaped tumors benefit most from IMRT. Our early clinical experience of HT-based IMRT for brain tumors has been encouraging.

  17. Continued observation of the natural history of low-grade ductal carcinoma in situ reaffirms proclivity for local recurrence even after more than 30 years of follow-up.

    PubMed

    Sanders, Melinda E; Schuyler, Peggy A; Simpson, Jean F; Page, David L; Dupont, William D

    2015-05-01

    Opportunities to study the natural history of ductal carcinoma in situ are rare. A few studies of incompletely excised lesions in the premammographic era, retrospectively recognized as ductal carcinoma in situ, have demonstrated a proclivity for local recurrence in the original site. The authors report a follow-up study of 45 women with low-grade ductal carcinoma in situ treated by biopsy only, recognized retrospectively during a larger review of surgical pathology diagnoses and original histological slides for 26?539 consecutive breast biopsies performed at Vanderbilt, Baptist and St Thomas Hospitals in Nashville, TN from 1950 to 1989. Long-term follow-up was previously reported on 28 of these women. Sixteen women (36%) developed invasive breast carcinoma, all in the same breast and quadrant as their incident ductal carcinoma in situ. Eleven invasive breast carcinomas were diagnosed within 10 years of the ductal carcinoma in situ biopsy. Subsequent cases were diagnosed at 12, 23, 25, 29 and 42 years. Seven women, including one who developed invasive breast cancer 29 years after her ductal carcinoma in situ biopsy, developed distant metastasis, resulting in death 1-7 years postdiagnosis of invasive breast carcinoma. The natural history of low-grade ductal carcinoma in situ may extend more than four decades, with invasive breast cancer developing at the same site as the index lesion. This protracted natural history differs markedly from that of patients with high-grade ductal carcinoma in situ or any completely delimited ductal carcinoma in situ excised to negative margins. This study reaffirms the importance of complete margin evaluation in women treated with breast conservation for ductal carcinoma in situ as well as balancing recurrence risk with possible treatment-related morbidity for older women. PMID:25502729

  18. [CHARACTERISTICS OF THE REACTIONS OF THE SPLEEN LYMPHOID STRUCTURES IN MICE IN A TERRESTRIAL EXPERIMENT AND AFTER A PROLONGED SPACEFLIGHT].

    PubMed

    Grigorenko, D Ye; Sapin, M R; Yerofeyeva, L M

    2015-01-01

    Morphometric methods were used to examine the cell composition of the germinal centers of lymphoid nodules and periarteriolar lymphoid sheaths (PALS) in male C57/b16 mice aged 19-20 weeks after 30-day-long space flight, simulation of space flight factors in a terrestrial experiment and in vivarium control group. After a ground-based experiment, compared to vivarium control, the functional activity of morphological zone of T lymphocyte maturation was decreased in PALM. In the germinal centers of lymphoid nodules of mice subjected to a ground-based experiment, lymphocytopoiesis and cell blast transformation, that characterize the morpho-functional activity of this zone and humoral immunity, remained unchanged. After a spaceflight, as compared with ground-based experiment, the changes of cell composition were less expressed in PALS than in the in the germinal centers of lymphoid nodules. It is concluded that PALS are more stable morphological zones, while the germinal centers of lymphoid nodules in the spleen are specific "target zones", most sensitive to a variety of factors of a space flight. PMID:26390542

  19. Alloantigens of human lymphoid cell lines; `human Ia-like antigens'

    PubMed Central

    Koyama, K.; Nakamuro, K.; Tanigaki, N.; Pressman, D.

    1977-01-01

    Membrane glycoproteins that appear to belong to a new alloantigen system were partially purified by gel filtration and lentil-lectin affinity chromatography from a non-ionic detergent (Renex 30) solubilized membrane fraction of each of two Burkitt lymphoma cell lines, B46M and Daudi. The preparations were radioiodinated and further purified by gel filtration, lentil—lectin affinity chromatography and anti-HLA antibody affinity chromatography. The labelled preparations thus obtained did not have binding activity with any of rabbit anti-HLA, rabbit anti-human ?2-microglobulin and rabbit anti-human IgG-Fab antisera, but did have a high level of binding activity with rabbit anti-B-cell membrane antiserum. Moreover, the labelled preparations showed relatively high binding activity with some conventional HLA typing sera. Out of sixty-eight human tissue typing alloantisera tested, three (Berlin 373, Betz and TO-29-01) gave especially high binding with both of the labeled preparations. The antigens involved in reaction with these alloantisera and also with the rabbit anti-B-cell membrane antiserum contained two components, one 31,000 ? 32,000 daltons and another 24,000 ? 25,000 daltons, bound non-covalently. The alloantigens were specific to B cell type cell lines (B-lymphoid cell lines and Burkitt-lymphoma cell lines) in cultured cell lines and also to B lymphocytes in peripheral blood. In organs and tissues, however, they were found to be present widely distributed in lymphoid organs (thymus as well as spleen and lymph node) and in non-lymphoid organs (including liver, kidney, testis and heart). PMID:24587

  20. Tertiary Lymphoid Structure-Associated B Cells are Key Players in Anti-Tumor Immunity

    PubMed Central

    Germain, Claire; Gnjatic, Sacha; Dieu-Nosjean, Marie-Caroline

    2015-01-01

    It is now admitted that the immune system plays a major role in tumor control. Besides the existence of tumor-specific T cells and B cells, many studies have demonstrated that high numbers of tumor-infiltrating lymphocytes are associated with good clinical outcome. In addition, not only the density but also the organization of tumor-infiltrating immune cells has been shown to determine patient survival. Indeed, more and more studies describe the development within the tumor microenvironment of tertiary lymphoid structures (TLS), whose presence has a positive impact on tumor prognosis. TLS are transient ectopic lymphoid aggregates displaying the same organization and functionality as canonical secondary lymphoid organs, with T-cell-rich and B-cell-rich areas that are sites for the differentiation of effector and memory T cells and B cells. However, factors favoring the emergence of such structures within tumors still need to be fully characterized. In this review, we survey the state of the art of what is known about the general organization, induction, and functionality of TLS during chronic inflammation, and more especially in cancer, with a particular focus on the B-cell compartment. We detail the role played by TLS B cells in anti-tumor immunity, both as antigen-presenting cells and tumor antigen-specific antibody-secreting cells, and raise the question of the capacity of chemotherapeutic and immunotherapeutic agents to induce the development of TLS within tumors. Finally, we explore how to take advantage of our knowledge on TLS B cells to develop new therapeutic tools. PMID:25755654

  1. Melatonin inhibits cell proliferation and induces caspase activation and apoptosis in human malignant lymphoid cell lines.

    PubMed

    Sánchez-Hidalgo, Marina; Lee, Melanie; de la Lastra, Catalina A; Guerrero, Juan M; Packham, Graham

    2012-11-01

    Melatonin exerts strong anti-tumour activity via several mechanisms, including anti-proliferative and pro-apoptotic effects in addition to its potent antioxidant activity. Several studies have investigated the effects of melatonin on haematological malignancies. However, the previous studies investigating lymphoid malignancies have been largely restricted to a single type of malignancy, Burkitt's lymphoma (BL). Thus, we examined the actions of melatonin on the growth and apoptosis in a small panel of cell lines representing different human lymphoid malignancies including Ramos (Epstein-Barr virus-negative BL), SU-DHL-4 (diffuse large B cell lymphoma), DoHH2 (follicular B non-Hodgkin lymphoma) and JURKAT (acute T cell leukaemia). We showed that melatonin promotes cell cycle arrest and apoptosis in all these cells, although there was marked variations in responses among different cell lines (sensitivity; Ramos/DoHH2 > SU-DHL-4 > JURKAT). Melatonin-induced apoptosis was relatively rapid, with increased caspase 3 and PARP cleavage detected within 0.5-1 h following melatonin addition. Moreover, there was evidence for rapid processing of both caspase 9, as well as a breakdown of the mitochondrial inner transmembrane potential. On the contrary, caspase activation was detected only in SU-DHL-4 and Ramos cells following melatonin treatment suggesting that the extrinsic pathway does not make a consistent contribution to melatonin-induced apoptosis in malignant lymphocytes. Although all cell lines expressed the high-affinity melatonin receptors, MT1 and MT2, melatonin-induced caspase activation appeared to be independent these receptors. Our findings confirm that melatonin could be a potential chemotherapeutic/preventive agent for malignant lymphocytes. However, it is necessary to take into account that different lymphoid malignancies may differ in their response to melatonin. PMID:22582944

  2. High proliferative activity of Reed Sternberg associated antigen Ki-1 positive cells in normal lymphoid tissue.

    PubMed Central

    Gerdes, J; Schwarting, R; Stein, H

    1986-01-01

    An improved immunoenzymatic double labelling method was developed, which simultaneously shows the Ki-1 membrane antigen and the nuclear proliferation associated antigen, defined by monoclonal antibody Ki-67. This new approach permits in situ discrimination of cells that are proliferating or not with a particular membrane antigen. Most Ki-1 positive cells in normal lymphoid tissue also express the Ki-67 nuclear antigen and thus appear to be proliferating. As proliferating cells are more susceptible to malignant transformation than quiescent cells, it is possible that the small number of normal Ki-1 positive cells might, none the less, cause a large proportion of all lymphomas in man. Images PMID:3020097

  3. Uncoupling JAK3 activation induces apoptosis in human lymphoid cancer cells via regulating critical survival pathways

    PubMed Central

    Nagy, Zsuzsanna S.; Ross, Jeremy A.; Rodriguez, Georgialina; Bader, Julia; Dimmock, Jonathan; Kirken, Robert A.

    2010-01-01

    In the current work, we report that specific inhibition of JAK3 via NC1153 induces apoptosis of certain leukemia/lymphoma cell lines. Affymetrix microarray profiling following NC1153 treatment unveiled JAK3 dependent survival modulating pathways (p53, TGF-?, TNFR and ER stress) in Kit225 cells. IL-2 responsive NC1153 target genes were regulated in human JAK3 positive, but not in JAK3 negative lymphoid tumor cells. Moreover, primary lymphoma samples revealed that a number of these genes were reciprocally regulated during disease progression and JAK3 inhibition suggesting that downstream targets of JAK3 could be exploited in the development of novel cancer treatment regimes. PMID:20211620

  4. [Multifocal progressive leukoencephalitis in a patient given fludarabine for chronic lymphoid leukemia].

    PubMed

    Léonard, S; Hulin, C; Anxionnat, R; Grignon, Y; Taillandier, L; Vespignani, H

    2002-11-01

    A 74-year- man was hospitalized for subacute aphasia and right hemiparesis. He had had chronic lymphoid leukemia for 11 years and had been treated 5 months earlier with 3 courses of fludarabine. Magnetic resonance imaging showed lesions of the temporo-occipital white matter compatible with progressive multifocal leukoencephalitis (PML). The presence of JC virus was demonstrated first by in situ hybridation after a brain biopsy and second with polymerase chain reaction on CSF. The diagnosis of PML was confirmed. The causality of fludarabine treatment is discussed. PMID:12451348

  5. Soft tissue perineurioma with peripheral lymphoid cuff of the tongue: a case report and literature review

    PubMed Central

    Gu, Hai-Yan; Wei, Zhi-Min; Lin, Dong-Liang; Zhao, Han; Hao, Feng-Yun

    2014-01-01

    Perineurioma are rare tumors, derived from nerve sheath perineurial cells. Soft tissue perineurioma are extraordinarily rare in the tongue, with only one previous report in a child to our knowledge. Herein, we describe the first case of an adult patient who had a soft tissue perineurioma localized to the tongue, with emphasis on the clinic pathologic and immunohistochemical features of this tumor, and review the previously reported soft tissue cases. Besides, we first describe the histologic feature of peripheral lymphoid cuff in perineurioma. PMID:24482726

  6. Total lymphoid irradiation in multiple sclerosis: blood lymphocytes and clinical course

    SciTech Connect

    Cook, S.D.; Devereux, C.; Troiano, R.; Zito, G.; Hafstein, M.; Lavenhar, M.; Hernandez, E.; Dowling, P.C.

    1987-11-01

    We have found a significant relationship between blood lymphocyte count and prognosis in 45 patients receiving either total lymphoid irradiation or sham irradiation for chronic progressive multiple sclerosis. Patients with sustained lymphocyte counts less than 900 mm-3 for prolonged periods after treatment showed less rapid progression over the ensuing 3 years than did patients with multiple sclerosis who had lymphocyte counts above this level (p less than 0.01). Our results suggest that a simple laboratory test, the absolute blood lymphocyte count, may serve as a valuable barometer for monitoring the amount of immunosuppressive therapy needed to prevent progression in patients with multiple sclerosis, and possibly other autoimmune diseases.

  7. Transplantation tolerance in primates following total lymphoid irradiation and allogeneic bone marrow injection. II. Renal allographs

    SciTech Connect

    Myburgh, J.A.; Smit, J.A.; Hill, R.R.H.; Browde, S.

    1980-05-01

    A modified regimen of fractionated total lymphoid irradiation and allogeneic bone marrow (BM) injection in chacma baboons produced transplantation tolerance for allografted kidneys from the BM donors, and substantial chimerism without evidence of graft-versus-host disease. Increasing the dose of nucleated BM cells injected 4-fold over that used in liver transplantation resulted consistently in normal graft function in the early weeks after transplantation. Bone marrow injection and challenge with renal allografts could be delayed for at least 3 weeks after completion of irradiation. If it can be shown that this period can be extended even further, the protocols will be relevant to the circumstances of clinical cadaveric renal transplantation.

  8. Seroprevalence of human T-lymphotropic virus antibodies among patients with lymphoid malignancies at a tertiary center in Lagos, Nigeria

    PubMed Central

    Akinbami, Akinsegun; Durojaiye, Idris; Dosunmu, Adedoyin; John-Olabode, Sarah; Adediran, Adewumi; Oshinaike, Olajumoke; Uche, Ebele; Dada, Akinola; Odesanya, Mojeed; Okunoye, Olaitan

    2014-01-01

    Background There is a significant association of human T-lymphotropic viruses (HTLV) with lymphoid malignancies. HTLV causes a lymphoproliferative malignancy of CD4-activated cells called adult T-cell leukemia/lymphoma (ATL) and a chronic myelopathy called tropical spastic paraparesis/HTLV-1-associated myelopathy (TSP/HAM). This study aims to determine the prevalence of HTLV among patients with lymphoid malignancies at a tertiary center in Lagos. Methods A cross-sectional study was carried out at the hematology clinic of the Lagos State University Teaching Hospital. After obtaining consent, approximately 5 mL of venous blood was collected from each subject. The serum was separated and stored at ?20°C. Sera were assayed for HTLV by an enzyme-linked immunoassay (ELISA) for the determination of antibodies to HTLV-1 and -2. Western blot confirmatory testing was done on reactive samples. All patients were also screened for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg) and hepatitis C virus (HCV) by rapid kits. Results A total of 39 patients with lymphoid malignancies were enrolled, consisting of 24 (61.5%) with solid malignancies, while 15 (38.5%) had leukemia. Only two patients (5.1%) with lymphoid malignancies were reactive on the ELISA test. On confirmatory testing with Western blot, two patients (5.1%) with lymphoid malignancies were also positive for HTLV. All patients were HIV negative, but four were positive to HBsAg and HCV. There was no association between history of previous blood transfusion and positivity to HTLV (P=0.544). Conclusion A prevalence of 5.1% of HTLV among patients with lymphoid malignancies was found in this study, and previous history of blood transfusion was not found to be a significant cause of HTLV infection. PMID:25228827

  9. Immunospecific targeting of CD45 expressing lymphoid cells: towards improved detection agents of the sentinel lymph node.

    PubMed

    Liu, Tianqing; Cousins, Aidan; Chien, Chia-Chi; Kempson, Ivan; Thompson, Sarah; Hwu, Yeukuang; Thierry, Benjamin

    2013-01-28

    This study was designed to demonstrate the potential of small nanoparticulate lymphotropic contrast agents designed to bind with high affinity to lymphoid cells overexpressing the CD45 antigen. To this end, small gold nanoparticles used as model were conjugated to anti-CD45 antibodies and injected in mice in the dorsal toe of the fore/hind paw. Chemical analysis demonstrated rapid uptake and transport of the nanoparticles in the lymphatic as well as significant retention of the nanoparticles with high binding affinity to lymphoid cells in the popliteal and axillary lymph nodes in comparison to non-targeted nanoparticles. PMID:23043762

  10. THE PROLIFERATIVE AND ANAMNESTIC ANTIBODY RESPONSE OF RABBIT LYMPHOID CELLS IN VITRO

    PubMed Central

    Jacobson, E. B.; Thorbecke, G. J.

    1969-01-01

    Popliteal lymph nodes were obtained from rabbits 4 days to 9 months after a primary injection of diphtheria toxoid or bovine ?-globulin into the footpad. The ability of cells from these nodes to proliferate upon reexposure to antigen in vitro was compared to the height of the secondary response produced by tissue fragments. In addition, a comparison was made between the responsiveness of draining and contralateral lymph nodes. While the secondary antibody response in vitro increased markedly with the time after immunization at which the lymph nodes were taken from the animals, the degree of proliferation induced by antigen was highest with cells from lymph nodes taken early after priming (peak day 7) and was very much lower with lymph node cells taken longer than 3 wk after priming. This striking difference between these two responses has been discussed. Contralateral lymph nodes were much inferior to draining nodes in their ability to give a secondary antibody response in vitro, and never gave a detectable proliferative response. This difference became less marked with time after priming, but could still be demonstrated after 4 months. These results suggest a concentration of primed cells in the lymphoid tissue draining the site of injection, and a slow release of these cells into the circulation, to be distributed to the remaining lymphoid tissue. PMID:4183484

  11. Refinement of 1p36 alterations not involving PRDM16 in myeloid and lymphoid malignancies.

    PubMed

    Duhoux, Francois P; Ameye, Geneviève; Lambot, Virginie; Herens, Christian; Lambert, Frédéric; Raynaud, Sophie; Wlodarska, Iwona; Michaux, Lucienne; Roche-Lestienne, Catherine; Labis, Elise; Taviaux, Sylvie; Chapiro, Elise; Nguyen-Khac, Florence; Khac, Florence Nguyen; Struski, Stéphanie; Dobbelstein, Sophie; Dastugue, Nicole; Lippert, Eric; Speleman, Frank; Van Roy, Nadine; De Weer, An; Rack, Katrina; Talmant, Pascaline; Richebourg, Steven; Mugneret, Francine; Tigaud, Isabelle; Mozziconacci, Marie-Joëlle; Laibe, Sophy; Nadal, Nathalie; Terré, Christine; Libouton, Jeanne-Marie; Decottignies, Anabelle; Vikkula, Miikka; Poirel, Hélène A

    2011-01-01

    Fluorescence in situ hybridization was performed to characterize 81 cases of myeloid and lymphoid malignancies with cytogenetic 1p36 alterations not affecting the PRDM16 locus. In total, three subgroups were identified: balanced translocations (N?=?27) and telomeric rearrangements (N?=?15), both mainly observed in myeloid disorders; and unbalanced non-telomeric rearrangements (N?=?39), mainly observed in lymphoid proliferations and frequently associated with a highly complex karyotype. The 1p36 rearrangement was isolated in 12 cases, mainly myeloid disorders. The breakpoints on 1p36 were more widely distributed than previously reported, but with identifiable rare breakpoint cluster regions, such as the TP73 locus. We also found novel partner loci on 1p36 for the known multi-partner genes HMGA2 and RUNX1. We precised the common terminal 1p36 deletion, which has been suggested to have an adverse prognosis, in B-cell lymphomas [follicular lymphomas and diffuse large B-cell lymphomas with t(14;18)(q32;q21) as well as follicular lymphomas without t(14;18)]. Intrachromosomal telomeric repetitive sequences were detected in at least half the cases of telomeric rearrangements. It is unclear how the latter rearrangements occurred and whether they represent oncogenic events or result from chromosomal instability during oncogenesis. PMID:22039459

  12. Substrate selection influences molecular recognition in a screen for lymphoid tyrosine phosphatase inhibitors.

    PubMed

    Kulkarni, Rhushikesh A; Vellore, Nadeem A; Bliss, Matthew R; Stanford, Stephanie M; Falk, Matthew D; Bottini, Nunzio; Baron, Riccardo; Barrios, Amy M

    2013-09-01

    Assay design is an important variable that influences the outcome of an inhibitor screen. Here, we have investigated the hypothesis that protein tyrosine phosphatase inhibitors with improved biological activity could be identified from a screen by using a biologically relevant peptide substrate, rather than traditional phosphotyrosine mimetic substrates. A 2000-member library of drugs and drug-like compounds was screened for inhibitors of lymphoid tyrosine phosphatase (LYP) by using both a peptide substrate (Ac-ARLIEDNE-pCAP-TAREG-NH?, peptide 1) and a small-molecule phosphotyrosine mimetic substrate (difluoromethyl umbelliferyl phosphate, DiFMUP). The results demonstrate that compounds that inhibited enzyme activity on the peptide substrate had greater biological activity than compounds that only inhibited enzyme activity on DiFMUP. Finally, epigallocatechin-3,5-digallate was identified as the most potent inhibitor of lymphoid tyrosine phosphatase activity to date, with an IC?? of 50 nM and significant activity in T-cells. Molecular docking simulations provided a first model for binding of this potent inhibitor to LYP; this will constitute the platform for ongoing lead optimization efforts. PMID:23956195

  13. Murine isolated lymphoid follicles contain follicular B lymphocytes with a mucosal phenotype

    PubMed Central

    Wang, Caihong; McDonald, Keely G.; McDonough, Jacquelyn S.; Newberry, Rodney D.

    2006-01-01

    Isolated lymphoid follicles (ILFs) are organized intestinal lymphoid structures whose formation can be induced by luminal stimuli. ILFs have been demonstrated to act as inductive sites for the generation of immune responses directed toward luminal stimuli; however, the phenotype of the immune response initiated within ILFs has largely been uninvestigated. To gain a better understanding of the immune responses initiated within ILFs, we examined phenotypic and functional aspects of the largest cellular component of the murine ILF lymphocyte population, B lymphocytes. We observed that murine ILF B lymphocytes are composed of a relatively homogenous population of follicular B-2 B lymphocytes. Consistent with their proximity to multiple stimuli, ILF B lymphocytes displayed a more activated phenotype compared with their counterparts in the spleen and Peyer’s patch (PP). ILF B lymphocytes also expressed higher levels of immunomodulatory B7 and CD28 family members B7X and programmed death-1 compared with their counterparts in the spleen and PP. ILF B lymphocytes preferentially differentiate into IgA-producing plasma cells and produce more IL-4 and IL-10 and less interferon-? compared with their counterparts in the spleen. Immunoglobulin repertoire analysis from individual ILFs demonstrated that ILFs contain a polyclonal population of B lymphocytes. These findings indicate that murine ILFs contain a polyclonal population of follicular B-2 B lymphocytes with a phenotype similar to PP B lymphocytes and that, in unchallenged animals, ILFs promote immune responses with a homeostatic phenotype. PMID:16782693

  14. Dendritic Cells Induce Autoimmune Diabetes and Maintain Disease via De Novo Formation of Local Lymphoid Tissue

    PubMed Central

    Ludewig, Burkhard; Odermatt, Bernhard; Landmann, Salome; Hengartner, Hans; Zinkernagel, Rolf M.

    1998-01-01

    Activation of autoreactive T cells can lead to autoimmune diseases such as insulin-dependent diabetes mellitus (IDDM). The initiation and maintenance of IDDM by dendritic cells (DC), the most potent professional antigen-presenting cells, were investigated in transgenic mice expressing the lymphocytic choriomeningitis virus glycoprotein (LCMV-GP) under the control of the rat insulin promoter (RIP-GP mice). We show that after adoptive transfer of DC constitutively expressing the immunodominant cytotoxic T lymphocyte (CTL) epitope of the LCMV-GP, RIP-GP mice developed autoimmune diabetes. Kinetic and functional studies of DC-activated CTL revealed that development of IDDM was dependent on dose and timing of antigenic stimulation. Strikingly, repeated CTL activation by DC led to severe destructive mononuclear infiltration of the pancreatic islets but also to de novo formation of islet-associated organized lymphoid structures in the pancreatic parenchyma. In addition, repetitive DC immunization induced IDDM with lymphoid neogenesis also in perforin-deficient RIP-GP mice, illustrating that CD8+ T cell–dependent inflammatory mechanisms independent of perforin could induce IDDM. Thus, DC presenting self-antigens not only are potent inducers of autoreactive T cells, but also help to maintain a peripheral immune response locally; therefore, the induction of autoimmunity against previously ignored autoantigens represents a potential hazard, particularly in DC-based antitumor therapies. PMID:9782126

  15. Masitinib reverses doxorubicin resistance in canine lymphoid cells by inhibiting the function of P-glycoprotein.

    PubMed

    Zandvliet, M; Teske, E; Chapuis, T; Fink-Gremmels, J; Schrickx, J A

    2013-12-01

    Overexpression of ABC-transporters including Pgp, MRP1, and BCRP has been associated with multidrug resistance (MDR) in both human and canine oncology. Therapeutic interventions to reverse MDR are limited, but include multidrug protocols and the temporary concomitant use of inhibitors of ABC-transporters. Recently, the use of tyrosine kinase inhibitors has been proposed to overcome MDR in human oncology. One of the tyrosine kinase inhibitors, masitinib, is licensed for veterinary use in the treatment of canine mast cell tumors. Therefore, this study aimed to assess the potential of masitinib to revert MDR in canine malignant lymphoma using an in vitro model with canine lymphoid cell lines. Masitinib had a mild antiproliferative effect on lymphoid cells, inhibited Pgp function at concentrations equal to or exceeding 1 ?m and was able to reverse doxorubicin resistance. The current findings provide the rationale for a combined use of masitinib with doxorubicin in the treatment of dogs with doxorubicin-resistant malignant lymphoma but await confirmation in clinical trials. PMID:23363222

  16. Bcl11b is essential for group 2 innate lymphoid cell development

    PubMed Central

    Oliphant, Christopher J.; Englezakis, Alexandros; Yu, Yong; Clare, Simon; Rodewald, Hans-Reimer; Belz, Gabrielle; Liu, Pentao; Fallon, Padraic G.

    2015-01-01

    Group 2 innate lymphoid cells (ILC2s) are often found associated with mucosal surfaces where they contribute to protective immunity, inappropriate allergic responses, and tissue repair. Although we know they develop from a common lymphoid progenitor in the bone marrow (BM), the specific lineage path and transcriptional regulators that are involved are only starting to emerge. After ILC2 gene expression analysis we investigated the role of Bcl11b, a factor previously linked to T cell commitment, in ILC2 development. Using combined Bcl11b-tom and Id2-gfp reporter mice, we show that Bcl11b is expressed in ILC2 precursors in the BM and maintained in mature ILC2s. In vivo deletion of Bcl11b, by conditional tamoxifen-induced depletion or by Bcl11b?/? fetal liver chimera reconstitution, demonstrates that ILC2s are wholly dependent on Bcl11b for their development. Notably, in the absence of Bcl11b there is a concomitant expansion of the ROR?t+ ILC3 population, suggesting that Bcl11b may negatively regulate this lineage. Using Nippostrongylus brasiliensis infection, we reveal that the absence of Bcl11b leads to impaired worm expulsion, caused by a deficit in ILC2s, whereas Citrobacter rodentium infection is cleared efficiently. These data clearly establish Bcl11b as a new factor in the differentiation of ILC2s. PMID:25964370

  17. Plasmacytoid dendritic cells promote HIV-1–induced group 3 innate lymphoid cell depletion

    PubMed Central

    Zhang, Zheng; Cheng, Liang; Zhao, Juanjuan; Li, Guangming; Zhang, Liguo; Chen, Weiwei; Nie, Weiming; Reszka-Blanco, Natalia J.; Wang, Fu-Sheng; Su, Lishan

    2015-01-01

    Group 3 innate lymphoid cells (ILC3s) have demonstrated roles in promoting antibacterial immunity, maintaining epithelial barrier function, and supporting tissue repair. ILC3 alterations are associated with chronic inflammation and inflammatory disease; however, the characteristics and relevant regulatory mechanisms of this cell population in HIV-1 infection are poorly understood due in part to a lack of a robust model. Here, we determined that functional human ILC3s develop in lymphoid organs of humanized mice and that persistent HIV-1 infection in this model depletes ILC3s, as observed in chronic HIV-1–infected patients. In HIV-1–infected mice, effective antiretroviral therapy reversed the loss of ILC3s. HIV-1–dependent reduction of ILC3s required plasmacytoid dendritic cells (pDCs), IFN-I, and the CD95/FasL pathway, as targeted depletion or blockade of these prevented HIV-1–induced ILC3 depletion in vivo and in vitro, respectively. Finally, we determined that HIV-1 infection induces CD95 expression on ILC3s via a pDC- and IFN-I–dependent mechanism that sensitizes ILC3s to undergo CD95/FasL-mediated apoptosis. We conclude that chronic HIV-1 infection depletes ILC3s through pDC activation, induction of IFN-I, and CD95-mediated apoptosis. PMID:26301812

  18. Pattern of MEF2B expression in lymphoid tissues and in malignant lymphomas.

    PubMed

    Krenács, Dóra; Borbényi, Zita; Bedekovics, Judit; Méhes, Gábor; Bagdi, Enik?; Krenács, László

    2015-09-01

    Myocyte enhancer binding factor 2 B (MEF2B) is a member of the evolutionary conserved transcription family MEF2. MEF2B has been shown to directly control biological activity of the B cell lymphoma 6 (BCL6) gene in germinal center (GC) B cells. To validate MEF2B as an immunohistochemical marker, we studied a large consecutive series of hyperplastic lymphoid tissues (n = 38) and malignant lymphoproliferative conditions (n = 471), including all major categories of B and T cell neoplasms. In hyperplastic lymphoid tissues, MEF2B staining revealed intense and crisp nuclear expression confined to GC B cells. Unlike BCL6, MEF2B was not detected in follicular T cells. In addition, weak nuclear staining of plasma cells was noted. MEF2B staining labeled neoplastic cells of follicular lymphoma both in common and variant cases as well as in bone marrow biopsies with high sensitivity, while it was almost consistently negative in marginal zone lymphoma. Consistent MEF2B expression was found in Burkitt lymphoma and nodular lymphocyte predominant Hodgkin lymphoma as well as in the large majority of cases of mantle cell lymphoma and diffuse large cell B cell lymphoma. MEF2B protein expression showed a statistically significant association with that of BCL6 in cases of diffuse large B cell lymphoma, not otherwise specified. We conclude that MEF2B is a valuable marker of normal GC B cells, potentially useful in differential diagnosis of small B cell lymphomas. PMID:26089142

  19. A human postnatal lymphoid progenitor capable of circulating and seeding the thymus

    PubMed Central

    Six, Emmanuelle M.; Bonhomme, Delphine; Monteiro, Marta; Beldjord, Kheira; Jurkowska, Monika; Cordier-Garcia, Corinne; Garrigue, Alexandrine; Dal Cortivo, Liliane; Rocha, Benedita; Fischer, Alain; Cavazzana-Calvo, Marina; André-Schmutz, Isabelle

    2007-01-01

    Identification of a thymus-seeding progenitor originating from human bone marrow (BM) constitutes a key milestone in understanding the mechanisms of T cell development and provides new potential for correcting T cell deficiencies. We report the characterization of a novel lymphoid-restricted subset, which is part of the lineage-negative CD34+CD10+ progenitor population and which is distinct from B cell–committed precursors (in view of the absence of CD24 expression). We demonstrate that these Lin?CD34+CD10+CD24? progenitors have a very low myeloid potential but can generate B, T, and natural killer lymphocytes and coexpress recombination activating gene 1, terminal deoxynucleotide transferase, PAX5, interleukin 7 receptor ?, and CD3?. These progenitors are present in the cord blood and in the BM but can also be found in the blood throughout life. Moreover, they belong to the most immature thymocyte population. Collectively, these findings unravel the existence of a postnatal lymphoid-polarized population that is capable of migrating from the BM to the thymus. PMID:18070935

  20. Characterization of lymphokine fibronectin from guinea pig lymphoid cell culture supernatants.

    PubMed

    Godfrey, H P; Canfield, L S; Angadi, C V; Zagachin, L M; Kielpinski, G G; Colvin, R B

    1990-02-01

    Fibronectins (FN) in guinea pig lymphoid cell culture supernatants have been studied using a panel of polyclonal and monoclonal anti-FN antibodies to clarify their relationship with macrophage agglutination factor (MAggF), an inflammatory lymphokine sharing many properties with this family of high molecular weight glycoproteins. MAggF contained cellular FN epitopes, and was reversibly bound by antibodies specific for cellular FN. Enzyme-linked immunoassay and inhibition of MAggF activity by monoclonal anti-plasma FN antibodies revealed immunoreactive FN in guinea pig lymphoid cell culture supernatants to share three epitopes with plasma FN and to lack a fourth epitope present in plasma FN. Immunoreactive FN in gelatin-affinity purified lymph node cell culture supernatants was polydisperse; MAggF activity (Mr 410 kD) was associated with only 13% of total immunoreactive FN. Although a low molecular weight FN fragment (Mr 67 kD) was associated with MAggF activity in salt-fractionated peritoneal exudate culture supernatants, it was not possible to generate MAggF activity by limited proteolysis of MAggF-inactive, high molecular weight FN in lymph node cell culture supernatants. We conclude that MAggF is a cellular FN containing a number of epitopes in common with plasma FN and suggest it may be a unique species of cellular FN produced by T lymphocytes involved in initiating delayed hypersensitivity reactions. PMID:1693132

  1. The effect of PrPSc accumulation on inflammatory gene expression within sheep peripheral lymphoid tissue

    PubMed Central

    Gossner, Anton G.; Hopkins, John

    2015-01-01

    Accumulation of the misfolded prion protein, PrPSc in the central nervous system (CNS) is strongly linked to progressive neurodegenerative disease. For many transmissible spongiform encephalopathies (TSEs), peripheral lymphoid tissue is an important site of PrPSc amplification but without gross immunological consequence. Susceptible VRQ homozygous New Zealand Cheviot sheep were infected with SSBP/1 scrapie by inoculation in the drainage area of the prescapular lymph nodes. The earliest time that PrPSc was consistently detected by immunohistology in these nodes was D50 post infection. This transcriptomic study of lymph node taken before (D10) and after (D50) the detection of PrPSc, aimed to identify the genes and physiological pathways affected by disease progression within the nodes as assessed by PrPSc detection. Affymetrix Ovine Gene arrays identified 75 and 80 genes as differentially-expressed at D10 and D50, respectively, in comparison with control sheep inoculated with uninfected brain homogenate. Approximately 70% of these were repressed at each time point. RT-qPCR analysis of seven genes showed statistically significant correlation with the array data, although the results for IL1RN and TGIF were different between the two technologies. The ingenuity pathway analysis (IPA) and general low level of repression of gene expression in lymphoid tissue, including many inflammatory genes, contrasts with the pro-inflammatory and pro-apoptotic events that occur within the CNS at equivalent stages of disease progression as assessed by PrPSc accumulation. PMID:26507419

  2. Decrease of lymphoid dendritic cells in blood from malaria-infected pregnant women.

    PubMed

    Diallo, Mamadou; Aldebert, Delphine; Moreau, Jean-Charles; Ndiaye, Malick; Jambou, Ronan

    2008-11-01

    Activation of dendritic cells (DCs) during malaria is poorly documented and has mainly been studied in rodent models. We conducted studies in Senegal to better understand the relationship between DC subset activation and susceptibility of pregnant women to malaria. For each woman, samples were collected at delivery from peripheral (WB), placental (PB) and cord blood (CB). The ex vivo phenotypes of DCs were assessed using flow cytometry on whole blood. The percentage of total DCs was the same for malaria-infected or non-infected pregnant women, except for PB where a decrease in DCs was observed during infection. Lymphoid dendritic cells (LDC) also decreased in the three blood compartments of infected pregnant women and less differentiated DCs (ldDCs) increased. During infection, Human Leucocyte Antigen DR (HLA-DR) expression decreased on LDCs, myeloid DCs (MDCs) and ldDCs. IL-10 increased in the three blood compartments. These data demonstrate a modulation of DC sub-populations during placental malaria. A decrease in LDCs during placental malaria could trigger major alterations in the immune response and a change in the Th1/Th2 balance. However, elevated IL-10 observed during infection substantiates a normal micro-environment triggering normal production of DCs. The decrease in LDCs could thus be due to their migration towards spleen or other lymphoid organs. PMID:18606411

  3. Isolated lymphoid follicles are not IgA inductive sites for recombinant Salmonella

    SciTech Connect

    Hashizume, Tomomi; Momoi, Fumiki; Kurita-Ochiai, Tomoko; Kaminogawa, Shuichi; Hosono, Akira; Kataoka, Kosuke; Shinozaki-Kuwahara, Noriko; Kweon, Mi-Na; Yamamoto, Masafumi . E-mail: yamamoto.masafumi@nihon-u.ac.jp

    2007-08-24

    In this study, we investigated whether isolated lymphoid follicles (ILF) play a role in the regulation of intestinal IgA antibody (Ab) responses. The transfer of wild type (WT) bone marrow (BM) to lymphotoxin-{alpha}-deficient (LT{alpha}{sup -/-}) mice resulted in the formation of mature ILF containing T cells, B cells, and FDC clusters in the absence of mesenteric lymph nodes and Peyer's patches. Although the ILF restored total IgA Abs in the intestine, antigen (Ag)-specific IgA responses were not induced after oral immunization with recombinant Salmonella expressing fragment C of tetanus toxin. Moreover, Ag-specific cell proliferation was not detected in the ILF. Interestingly, no IgA anti-LPS Abs were detected in the fecal extracts of LT{alpha}{sup -/-} mice reconstituted with WT BM. On the basis of these findings, ILF can be presumed to play a role in the production of IgA Abs, but lymphoid nodules are not inductive sites for the regulation of Ag-specific intestinal IgA responses to recombinant Salmonella.

  4. Resistance of T suppressor cells to cyclophosphamide administration in total-lymphoid-irradiated mice

    SciTech Connect

    Barzilay, M.; Slavin, S.; Zan-Bar, I.

    1983-05-01

    The effect of administration of cyclophosphamide (Cy) on the susceptibility of mice to tolerance induction and its influence on the rate of induced T suppressor cells in antigen-specific and nonspecific systems was assessed using mice that had undergone total lymphoid irradiation (TLI). Tolerance to bovine serum albumin (BSA) was induced in adult mice conditioned by a short course of fractionated total lymphoid irradiation with an injection of nondeaggregated BSA; Cy was administered upon termination of TLI, two days prior to administration of the tolerizing antigen. Susceptibility to tolerance induction and rate of induced T suppressor cells were assessed one month later. Cy-treated TLI mice and mice treated with TLI alone did not respond to a challenge with DNP-BSA in complete Freund's adjuvant, whereas a good response was obtained to an unrelated protein antigen. The induced T suppressor cell rate was measured by inhibition of a secondary anti DNP-BSA response in an adoptive transfer system. The rate of non-antigen-specific T suppressor cells was measured by inhibition of the mixed leukocyte reaction with Concanavalin A-induced T suppressor cells obtained from spleen cells of TLI-treated, or Cy-treated mice, or those given both treatments. The results reveal that Cy treatment of TLI-conditioned mice does not reduce the rate of induced of T suppressor cells in antigen-specific and antigen-nonspecific systems.

  5. Both rejection and tolerance of allografts can occur in the absence of secondary lymphoid tissues.

    PubMed

    Kant, Cavit D; Akiyama, Yoshinobu; Tanaka, Katsunori; Shea, Susan; Yamada, Yohei; Connolly, Sarah E; Marino, Jose; Tocco, Georges; Benichou, Gilles

    2015-02-01

    In this study, we showed that aly/aly mice, which are devoid of lymph nodes and Peyer's patches, acutely rejected fully allogeneic skin and heart grafts. They mounted potent inflammatory direct alloresponses but failed to develop indirect alloreactivity after transplantation. Remarkably, skin allografts also were rejected acutely by splenectomized aly/aly (aly/aly-spl(-)) mice devoid of all secondary lymphoid organs. In these recipients, the rejection was mediated by alloreactive CD8(+) T cells presumably primed in the bone marrow. In contrast, cardiac transplants were not rejected by aly/aly-spl(-) mice. Actually, aly/aly-spl(-) mice that spontaneously accepted a heart allotransplant and displayed donor-specific tolerance also accepted skin grafts from the same, but not a third-party, donor via a mechanism involving CD4(+) regulatory T cells producing IL-10 cytokine. Therefore, direct priming of alloreactive T cells, as well as rejection and regulatory tolerance of allogeneic transplants, can occur in recipient mice lacking secondary lymphoid organs. PMID:25535285

  6. Long non-coding RNA profiling of human lymphoid progenitor cells reveals transcriptional divergence of B cell and T cell lineages.

    PubMed

    Casero, David; Sandoval, Salemiz; Seet, Christopher S; Scholes, Jessica; Zhu, Yuhua; Ha, Vi Luan; Luong, Annie; Parekh, Chintan; Crooks, Gay M

    2015-12-01

    To elucidate the transcriptional 'landscape' that regulates human lymphoid commitment during postnatal life, we used RNA sequencing to assemble the long non-coding transcriptome across human bone marrow and thymic progenitor cells spanning the earliest stages of B lymphoid and T lymphoid specification. Over 3,000 genes encoding previously unknown long non-coding RNAs (lncRNAs) were revealed through the analysis of these rare populations. Lymphoid commitment was characterized by lncRNA expression patterns that were highly stage specific and were more lineage specific than those of protein-coding genes. Protein-coding genes co-expressed with neighboring lncRNA genes showed enrichment for ontologies related to lymphoid differentiation. The exquisite cell-type specificity of global lncRNA expression patterns independently revealed new developmental relationships among the earliest progenitor cells in the human bone marrow and thymus. PMID:26502406

  7. APMIS 114: 12730, 2006 C 2006 The Authors Printed in Denmark . All rights reserved

    E-print Network

    Gelb, Michael

    lymphoma, and gastric cancer (1). Phospholipase A2 (PLA2) is a lipolytic en- zyme that hydrolyzes pathogen and has been associated with peptic ulcer disease, gastric mucosa-associ- ated lymphoid tissue

  8. Nd isotopic and geochemical constraints on the provenance and tectonic setting of the low-grade meta-sedimentary rocks from the Trans-North China Orogen, North China Craton

    NASA Astrophysics Data System (ADS)

    Liu, Chaohui; Zhao, Guochun; Liu, Fulai; Han, Yigui

    2014-11-01

    In the Trans-North China Orogen (TNCO) of the North China Craton, low-grade supracrustal successions extensively occur in the Wutai, Lüliang, Zanhuang, Zhongtiao and Dengfeng Complexes from north to south. Meta-sedimentary samples from the Wutai and Zhongtiao Complexes were collected for geochemical and Nd isotopic studies and several samples from the Zanhuang and Dengfeng Complexes were also analyzed for Nd isotopic studies for comparative purpose. Most of the meta-siltstones and meta-sandstones from the Wutai and Zhongtiao Complexes are characterized by depletions in mobile elements like CaO, Sr and Na2O, high Chemical Index of Weathering (CIW) values and strong positive correlation between Al2O3 and TiO2, indicating intense weathering conditions. Significant post-depositional K-metasomatism is indicated in the A-CN-K diagrams for most of the analyzed samples and the relatively high pre-metasomatized Chemical Index of Alteration (CIA) values (43-87) also imply a high degree of source weathering. Depleted transitional trace elements (Ni, Cr, Co and Sc), fractionated light rare earth elements patterns, mild negative Eu anomalies in the majority of these meta-sedimentary samples point toward felsic source rocks, including the ?2.5 Ga granitics, TTG gneisses and the Paleoproterozoic granitics in the TNCO. Minor contribution from mafic rocks is evidenced from relative high contents of MgO, Fe2O3T, Sc and lower La/YbN ratios in some older sequence-set samples from the Zhongtiao Complex. Our geochemical and Nd isotopic data, combined with previous studies in the lithostratigraphic sequence, provenance and depositional age, suggest that the older and younger sequence-sets of the low-grade supracrustal successions in the TNCO were deposited in the different depositional environments. The older sequence-set was deposited in a back-arc basin between the “Andean-type” continental margin arc and the Eastern Block after ?2.1 Ga, whereas the younger sequence-set formed in a foreland basin between ?1.88 and ?1.80 Ga, which is consistent with the model that the collision between the Eastern and Western Blocks to form the Trans-North China Orogen occurred at ?1.85 Ga.

  9. Texas Tech researchers discover low-grade non-woven Cotton | Business Line http://www.thehindubusinessline.com/industry-and-economy/agri-biz/texas-tech-researchers-discover-lowgrade-nonwoven-cotton/article6277709.ece[8/25/2014 2:52:24 PM

    E-print Network

    Rock, Chris

    Texas Tech researchers discover low-grade non-woven Cotton | Business Line http://www.thehindubusinessline.com/industry-and-economy/agri-biz/texas-tech-researchers-discover-lowgrade-nonwoven-cotton Prices Cotton Prices Forest Products Prices Fruits Prices Jute Prices Oil Seeds Prices Pulses Prices Rice

  10. Crop Isolated Lymphoid Follicles and Ileal Peyer’s patches in Egg-Layer Hens Challenged with Salmonella enterica Enteritidis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The enteric pathogen Salmonella enterica Enteritidis (SE) can be harbored within the upper and lower gastrointestinal (GI) tract of chickens. Induction of immune response by SE at various alimentary tract regions may perhaps be attributable to local gut-associated lymphoid tissue (GALT). The study...

  11. Production of Multiple Brain-Like Ganglioside Species Is Dispensable for Fas-Induced Apoptosis of Lymphoid Cells

    PubMed Central

    Carpentier, Stéphane; Levade, Thierry; Cuvillier, Olivier; Portoukalian, Jacques

    2011-01-01

    Activation of an acid sphingomyelinase (aSMase) leading to a biosynthesis of GD3 disialoganglioside has been associated with Fas-induced apoptosis of lymphoid cells. The present study was undertaken to clarify the role of this enzyme in the generation of gangliosides during apoptosis triggered by Fas ligation. The issue was addressed by using aSMase-deficient and aSMase-corrected cell lines derived from Niemann-Pick disease (NPD) patients. Fas cross-linking elicited a rapid production of large amounts of complex a- and b-series species of gangliosides with a pattern and a chromatographic behavior as single bands reminiscent of brain gangliosides. The gangliosides were synthesized within the first ten minutes and completely disappeared within thirty minutes after stimulation. Noteworthy is the observation that GD3 was not the only ganglioside produced. The production of gangliosides and the onset of apoptotic hallmarks occurred similarly in both aSMase-deficient and aSMase-corrected NPD lymphoid cells, indicating that aSMase activation is not accountable for ganglioside generation. Hampering ganglioside production by inhibiting the key enzyme glucosylceramide synthase did not abrogate the apoptotic process. In addition, GM3 synthase-deficient lymphoid cells underwent Fas-induced apoptosis, suggesting that gangliosides are unlikely to play an indispensable role in transducing Fas-induced apoptosis of lymphoid cells. PMID:21629700

  12. Cellular and molecular markers in monitoring the fate of lymphoid cell culture from Penaeus monodon Fabricius (1798).

    PubMed

    Puthumana, Jayesh; Jose, Seena; Philip, Rosamma; Singh, I S Bright

    2015-12-01

    Lymphoid cell culture from penaeid shrimps has gained much acceptance as an in vitro platform to facilitate research on the development of prophylaxis, and therapeutic strategies against viruses and for cell line development. However, lymphoid cells can be used as platform for in vitro research, only if they are in metabolically and mitotically active state in vitro with unaltered cell surface receptors. Through this study, we addressed the response of lymphoid cells to a new microenvironment at cellular and molecular levels; including the study of mitotic events, DNA synthesis, expression profile of cell cycle genes, cytoskeleton organization, metabolic activity and viral susceptibility. The S-phase entry and synthesis of new DNA was recorded by immunoflourescent technique. Cdc2, CycA, CycB, EF-1? and BUB3 genes involved in cell cycle were studied in both the cells and tissue, of which EF-1? showed an elevated expression in cells in vitro (?19.7%). Cytoskeleton network of the cell was examined by studying the organization of actin filaments. As the markers for metabolic status, mitochondrial dehydrogenase, protein synthesis and glucose assimilation by the cells were also assessed. Viral susceptibility of the cell was determined using WSSV to confirm the preservation of cellular receptors. This study envisages to strengthen the shrimp cell line research and to bring forth lymphoid cell culture system as a 'model' in vitro system for shrimp and crustaceans altogether. PMID:26052014

  13. Cytotoxicity of farnesyltransferase inhibitors in lymphoid cells mediated by MAPK pathway inhibition and Bim up-regulation

    PubMed Central

    Ding, Husheng; Hackbarth, Jennifer; Schneider, Paula A.; Peterson, Kevin L.; Meng, X. Wei; Dai, Haiming; Witzig, Thomas E.

    2011-01-01

    The mechanism of cytotoxicity of farnesyltransferase inhibitors is incompletely understood and seems to vary depending on the cell type. To identify potential determinants of sensitivity or resistance for study in the accompanying clinical trial (Witzig et al, page 4882), we examined the mechanism of cytotoxicity of tipifarnib in human lymphoid cell lines. Based on initial experiments showing that Jurkat variants lacking Fas-associated death domain or procaspase-8 undergo tipifarnib-induced apoptosis, whereas cells lacking caspase-9 or overexpressing Bcl-2 do not, we examined changes in Bcl-2 family members. Tipifarnib caused dose-dependent up-regulation of Bim in lymphoid cell lines (Jurkat, Molt3, H9, DoHH2, and RL) that undergo tipifarnib-induced apoptosis but not in lines (SKW6.4 and Hs445) that resist tipifarnib-induced apoptosis. Further analysis demonstrated that increased Bim levels reflect inhibition of signaling from c-Raf to MEK1/2 and ERK1/2. Additional experiments showed that down-regulation of the Ras guanine nucleotide exchange factor RasGRP1 diminished tipifarnib sensitivity, suggesting that H-Ras or N-Ras is a critical farnesylation target upstream of c-Raf in lymphoid cells. These results not only trace a pathway through c-Raf to Bim that contributes to tipifarnib cytotoxicity in human lymphoid cells but also identify potential determinants of sensitivity to this agent. PMID:21673341

  14. IDEC-C2B8 anti-CD20 (rituximab) immunotherapy in patients with low-grade non-Hodgkin's lymphoma and lymphoproliferative disorders: evaluation of response on 48 patients.

    PubMed

    Nguyen, D T; Amess, J A; Doughty, H; Hendry, L; Diamond, L W

    1999-02-01

    This study focused on the efficacy of IDEC-C2B8 (chimeric anti-CD20) immunotherapy relative to specific subtypes of low-grade lymphoproliferative disorders/non-Hodgkin's lymphomas (LPD/NHL). Forty-eight patients with resistant or relapsed disease completed the IDEC-C2B8 infusion schedule of 375 mg/m2/wk x 4 wk. The LPD/NHL subtypes included: (a) follicular centre cell lymphoma (FCC) in 22 patients; (b) mantle cell lymphoma (MCL) in 10; (c) 1 diffuse large cell lymphoma (DLCL); and (d) the category of small lymphocytic lymphoma/chronic lymphocytic leukaemia (SLL/CLL) and related disorders in 15 patients. No patient obtained a complete remission. Ten patients (21%) achieved partial remission: 6 FCC, 2 MCL, 1 DLCL and 1 patient from the SLL/CLL group. Twenty-eight patients had stable disease and 10 progressed during immunotherapy. In patients with CLL and MCL in leukaemic phase, there was no correlation between the marked decrease in circulating neoplastic cells following antibody infusions and amelioration of the tumour burden. The results suggest that the subtype of LPD/NHL and the intensity of CD20 on the tumour cells influence the effectiveness of IDEC-C2B8. The antibody was most efficacious against FCC lymphoma. The efficacy (at the dose schedule of 375 mg/m2/wk x 4) against MCL and SLL/CLL appeared to be limited, however. PMID:10052709

  15. A case of low-grade fibromyxoid sarcoma with unusual central necrosis in a 77-year-old man confirmed by FUS-CREB3L2 gene fusion

    PubMed Central

    Kurisaki-Arakawa, Aiko; Akaike, Keisuke; Tomomasa, Ran; Arakawa, Atsushi; Suehara, Yoshiyuki; Takagi, Tatsuya; Kaneko, Kazuo; Yao, Takashi; Saito, Tsuyoshi

    2014-01-01

    INTRODUCTION Low-grade fibromyxoid sarcoma (LGFMS) is a rare soft tissue tumor typically affecting young to middle-aged adults. Despite its otherwise benign histologic appearance and indolent nature, it can display fully malignant behavior, and recurrence and metastasis can occur even decades after diagnosis. PRESENTATION OF CASE Herein, we report a case of LGFMS in the buttock of a 77-year-old man. Magnetic resonance imaging uncovered a well-demarcated tumor measuring 27 × 20 mm with a slightly high intensity on T1-weighted images (WIs) and heterogeneously high intensity on T2-WIs. Histologically, the tumor was composed of bland spindle-shaped cells in a whorled growth pattern with alternating fibrous and myxoid stroma. The tumor stroma was variably hyalinized with arcades of curvilinear capillaries and arterioles with associated perivascular fibrosis. Unusual histology, such as central necrosis and cystic formation, was also noted. Reverse transcription polymerase chain reaction from a formalin-fixed, paraffin-embedded biopsy specimen revealed a FUS-CREB3L2 gene fusion (exon6/int/exon5), leading to the diagnosis of LGFMS. DISCUSSION To the best of our knowledge, this is the second oldest patient to be diagnosed with LGFMS. CONCLUSION At the time of this report, the patient was alive with no evidence of the disease 4 months after diagnosis without any adjuvant therapy. PMID:25437654

  16. Evidence of a true pharyngeal tonsil in birds: a novel lymphoid organ in Dromaius novaehollandiae and Struthio camelus (Palaeognathae)

    PubMed Central

    2012-01-01

    Background Tonsils are secondary lymphoid organs located in the naso- and oropharynx of most mammalian species. Most tonsils are characterised by crypts surrounded by dense lymphoid tissue. However, tonsils without crypts have also been recognised. Gut-associated lymphoid tissue (GALT), although not well-organised and lacking tonsillar crypts, is abundant in the avian oropharynx and has been referred to as the “pharyngeal tonsil”. In this context the pharyngeal folds present in the oropharynx of ratites have erroneously been named the pharyngeal tonsils. This study distinguishes between the different types and arrangements of lymphoid tissue in the pharyngeal region of D. novaehollandiae and S. camelus and demonstrates that both species possess a true pharyngeal tonsil which fits the classical definition of tonsils in mammals. Results The pharyngeal tonsil (Tonsilla pharyngea) of D. novaehollandiae was located on the dorsal free surface of the pharyngeal folds and covered by a small caudo-lateral extension of the folds whereas in S. camelus the tonsil was similarly located on the dorsal surface of the pharyngeal folds but was positioned retropharyngeally and encapsulated by loose connective tissue. The pharyngeal tonsil in both species was composed of lymph nodules, inter-nodular lymphoid tissue, mucus glands, crypts and intervening connective tissue septa. In S. camelus a shallow tonsillar sinus was present. Aggregated lymph nodules and inter-nodular lymphoid tissue was associated with the mucus glands on the ventral surface of the pharyngeal folds in both species and represented the Lymphonoduli pharyngeales. Similar lymphoid tissue, but more densely packed and situated directly below the epithelium, was present on the dorsal, free surface of the pharyngeal folds and represented a small, non-follicular tonsil. Conclusions The follicular pharyngeal tonsils in D. novaehollandiae and S. camelus are distinct from the pharyngeal folds in these species and perfectly fit the classical mammalian definition of pharyngeal tonsils. The presence of a true pharyngeal tonsil differentiates these two ratite species from other known avian species where similar structures have not been described. The pharyngeal tonsils in these ratites may pose a suitable and easily accessible site for immune response surveillance as indicated by swelling and inflammation of the tonsillar tissue and pharyngeal folds. This would be facilitated by the fact that the heads of these commercially slaughtered ratites are discarded, thus sampling at these sites would not result in financial losses. PMID:22909013

  17. Heat exchangers for low grade waste heat

    SciTech Connect

    Hay, E.; Al-Witry, A.; Aroussi, A.; Hay, N.

    1996-12-31

    The paper describes a user friendly computer program written for the design and optimization of roll bond aluminum heat exchangers and its validation against experimental test data. Test results for two different designs of heat exchanger panel, one serpentine and one dimple, are also given. The dimple design is shown to be superior to the serpentine one giving a 75% increase in heat transfer for a modest increase in pressure drop. Finally, a comparison of the economics of equivalent aluminum, stainless steel and titanium units for sea-water applications is presented.

  18. Coexistent dermatofibrosarcoma protuberans and anticonvulsant-induced cutaneous lymphoid hyperplasia: diagnostic challenge

    PubMed Central

    Chu, Melinda B; Dhandha, Maulik; Guo, Aibing

    2013-01-01

    A 60-year-old African-American male patient with a history of seizures, developmental delay, long history of behavioural issues with psychotic episodes, heart, liver, thyroid and kidney diseases presented for evaluation of a right neck skin lesion. Physical examination revealed a shiny purplish-red plaque on the right neck and a thin pink plaque on the posterior neck. The lesions were similar in appearance, but different enough to warrant skin biopsy of each. Pathology demonstrated mycosis fungoides (MF) on the right neck and dermatofibrosarcoma protuberans (DFSP) on the posterior neck. The identification of two rare conditions made us reconsider our diagnosis. After further review, the right neck skin lesion was thought to be anticonvulsant-induced cutaneous lymphoid hyperplasia, not MF. This case demonstrates how insufficient skin biopsy can have significant clinical consequences. Biopsy of the right neck only would have overlooked a DFSP and incorrectly given the patient a diagnosis of MF. PMID:24306629

  19. Transcriptional programs of lymphoid tissue capillary and high endothelium reveal control mechanisms for lymphocyte homing

    PubMed Central

    Lee, Mike; Kiefel, Helena; LaJevic, Melissa D.; Macauley, Matthew S.; Kawashima, Hiroto; O'Hara, Edward; Pan, Junliang; Paulson, James C.; Butcher, Eugene C.

    2014-01-01

    Lymphocytes are recruited from blood by high-endothelial venules (HEVs). We performed transcriptomic analyses and identified molecular signatures that distinguish HEVs from capillary endothelium and that define tissue-specific HEV specialization. Capillaries displayed gene programs for vascular development. HEVs were enriched in genes for immune defense and lymphocyte migration. We identify capillary and HEV markers and candidate mechanisms for regulated lymphocyte recruitment including a lymph node HEV-selective transmembrane mucin; transcriptional control of functionally specialized carbohydrate ligands for lymphocyte L-selectin; HEV expression of molecules for transendothelial migration; and metabolic programs for lipid mediators of lymphocyte motility and chemotaxis. We also elucidate a carbohydrate recognition pathway that targets B cells to intestinal lymphoid tissues, defining CD22 as a lectin-homing receptor for mucosal HEVs. PMID:25173345

  20. Differential Effects of Notch Ligands Delta-1 and Jagged-1 in Human Lymphoid Differentiation

    PubMed Central

    Jaleco, Ana C.; Neves, Hélia; Hooijberg, Erik; Gameiro, Paula; Clode, Nuno; Haury, Matthias; Henrique, Domingos; Parreira, Leonor

    2001-01-01

    Notch signaling is known to differentially affect the development of lymphoid B and T cell lineages, but it remains unclear whether such effects are specifically dependent on distinct Notch ligands. Using a cell coculture assay we observed that the Notch ligand Delta-1 completely inhibits the differentiation of human hematopoietic progenitors into the B cell lineage while promoting the emergence of cells with a phenotype of T cell/natural killer (NK) precursors. In contrast, Jagged-1 did not disturb either B or T cell/NK development. Furthermore, cells cultured in the presence of either Delta-1 or Jagged-1 can acquire a phenotype of NK cells, and Delta-1, but not Jagged-1, permits the emergence of a de novo cell population coexpressing CD4 and CD8. Our results thus indicate that distinct Notch ligands can mediate differential effects of Notch signaling and provide a useful system to further address cell-fate decision processes in lymphopoiesis. PMID:11581320

  1. Specific fibroblastic niches in secondary lymphoid organs orchestrate distinct Notch-regulated immune responses.

    PubMed

    Fasnacht, Nicolas; Huang, Hsin-Ying; Koch, Ute; Favre, Stéphanie; Auderset, Floriane; Chai, Qian; Onder, Lucas; Kallert, Sandra; Pinschewer, Daniel D; MacDonald, H Robson; Tacchini-Cottier, Fabienne; Ludewig, Burkhard; Luther, Sanjiv A; Radtke, Freddy

    2014-10-20

    Fibroblast-like cells of secondary lymphoid organs (SLO) are important for tissue architecture. In addition, they regulate lymphocyte compartmentalization through the secretion of chemokines, and participate in the orchestration of appropriate cell-cell interactions required for adaptive immunity. Here, we provide data demonstrating the functional importance of SLO fibroblasts during Notch-mediated lineage specification and immune response. Genetic ablation of the Notch ligand Delta-like (DL)1 identified splenic fibroblasts rather than hematopoietic or endothelial cells as niche cells, allowing Notch 2-driven differentiation of marginal zone B cells and of Esam(+) dendritic cells. Moreover, conditional inactivation of DL4 in lymph node fibroblasts resulted in impaired follicular helper T cell differentiation and, consequently, in reduced numbers of germinal center B cells and absence of high-affinity antibodies. Our data demonstrate previously unknown roles for DL ligand-expressing fibroblasts in SLO niches as drivers of multiple Notch-mediated immune differentiation processes. PMID:25311507

  2. Specific fibroblastic niches in secondary lymphoid organs orchestrate distinct Notch-regulated immune responses

    PubMed Central

    Fasnacht, Nicolas; Huang, Hsin-Ying; Koch, Ute; Favre, Stéphanie; Auderset, Floriane; Chai, Qian; Onder, Lucas; Kallert, Sandra; Pinschewer, Daniel D.; MacDonald, H. Robson; Tacchini-Cottier, Fabienne; Ludewig, Burkhard

    2014-01-01

    Fibroblast-like cells of secondary lymphoid organs (SLO) are important for tissue architecture. In addition, they regulate lymphocyte compartmentalization through the secretion of chemokines, and participate in the orchestration of appropriate cell–cell interactions required for adaptive immunity. Here, we provide data demonstrating the functional importance of SLO fibroblasts during Notch-mediated lineage specification and immune response. Genetic ablation of the Notch ligand Delta-like (DL)1 identified splenic fibroblasts rather than hematopoietic or endothelial cells as niche cells, allowing Notch 2–driven differentiation of marginal zone B cells and of Esam+ dendritic cells. Moreover, conditional inactivation of DL4 in lymph node fibroblasts resulted in impaired follicular helper T cell differentiation and, consequently, in reduced numbers of germinal center B cells and absence of high-affinity antibodies. Our data demonstrate previously unknown roles for DL ligand-expressing fibroblasts in SLO niches as drivers of multiple Notch-mediated immune differentiation processes. PMID:25311507

  3. Transcriptional Programs Define Molecular Characteristics of Innate Lymphoid Cell Classes and Subsets

    PubMed Central

    Robinette, Michelle L.; Fuchs, Anja; Cortez, Victor S.; Lee, Jacob S.; Wang, Yaming; Durum, Scott K.; Gilfillan, Susan; Colonna, Marco

    2015-01-01

    The diversity of innate lymphoid cells (ILCs) is rapidly expanding. Three ILC classes have emerged, ILC1, ILC2, and ILC3, with ILC1 and ILC3 including several subsets. The classification of some subsets is unclear and it remains controversial whether NK cells and ILC1 are distinct cell types. To address these issues, we analyzed ILCs and NK cells gene expression within mouse small intestine, spleen, and liver, as part of the Immunological Genome Project. Results identify unique gene-expression patterns for some ILCs and overlapping patterns between ILC1 and NK cells, whereas few ILC subsets remain indistinguishable. A transcriptional program shared by small intestine ILCs and a core ILC signature is identified. Transcripts that suggest novel ILC functions and developmental paths are revealed and discussed. PMID:25621825

  4. Ectopic lymphoid structures function as microniches for tumor progenitor cells in hepatocellular carcinoma.

    PubMed

    Finkin, Shlomi; Yuan, Detian; Stein, Ilan; Taniguchi, Koji; Weber, Achim; Unger, Kristian; Browning, Jeffrey L; Goossens, Nicolas; Nakagawa, Shigeki; Gunasekaran, Ganesh; Schwartz, Myron E; Kobayashi, Masahiro; Kumada, Hiromitsu; Berger, Michael; Pappo, Orit; Rajewsky, Klaus; Hoshida, Yujin; Karin, Michael; Heikenwalder, Mathias; Ben-Neriah, Yinon; Pikarsky, Eli

    2015-12-01

    Ectopic lymphoid-like structures (ELSs) are often observed in cancer, yet their function is obscure. Although ELSs signify good prognosis in certain malignancies, we found that hepatic ELSs indicated poor prognosis for hepatocellular carcinoma (HCC). We studied an HCC mouse model that displayed abundant ELSs and found that they constituted immunopathological microniches wherein malignant hepatocyte progenitor cells appeared and thrived in a complex cellular and cytokine milieu until gaining self-sufficiency. The egress of progenitor cells and tumor formation were associated with the autocrine production of cytokines previously provided by the niche. ELSs developed via cooperation between the innate immune system and adaptive immune system, an event facilitated by activation of the transcription factor NF-?B and abolished by depletion of T cells. Such aberrant immunological foci might represent new targets for cancer therapy. PMID:26502405

  5. Type I interferon restricts type 2 immunopathology through the regulation of group 2 innate lymphoid cells.

    PubMed

    Duerr, Claudia U; McCarthy, Connor D A; Mindt, Barbara C; Rubio, Manuel; Meli, Alexandre P; Pothlichet, Julien; Eva, Megan M; Gauchat, Jean-François; Qureshi, Salman T; Mazer, Bruce D; Mossman, Karen L; Malo, Danielle; Gamero, Ana M; Vidal, Silvia M; King, Irah L; Sarfati, Marika; Fritz, Jörg H

    2016-01-01

    Viral respiratory tract infections are the main causative agents of the onset of infection-induced asthma and asthma exacerbations that remain mechanistically unexplained. Here we found that deficiency in signaling via type I interferon receptor led to deregulated activation of group 2 innate lymphoid cells (ILC2 cells) and infection-associated type 2 immunopathology. Type I interferons directly and negatively regulated mouse and human ILC2 cells in a manner dependent on the transcriptional activator ISGF3 that led to altered cytokine production, cell proliferation and increased cell death. In addition, interferon-? (IFN-?) and interleukin 27 (IL-27) altered ILC2 function dependent on the transcription factor STAT1. These results demonstrate that type I and type II interferons, together with IL-27, regulate ILC2 cells to restrict type 2 immunopathology. PMID:26595887

  6. Macrophage and Innate Lymphoid Cell Interplay in the Genesis of Fibrosis

    PubMed Central

    Hams, Emily; Bermingham, Rachel; Fallon, Padraic G.

    2015-01-01

    Fibrosis is a characteristic pathological feature of an array of chronic diseases, where development of fibrosis in tissue can lead to marked alterations in the architecture of the affected organs. As a result of this process of sustained attrition to organs, many diseases that involve fibrosis are often progressive conditions and have a poor long-term prognosis. Inflammation is often a prelude to fibrosis, with innate and adaptive immunity involved in both the initiation and regulation of the fibrotic process. In this review, we will focus on the emerging roles of the newly described innate lymphoid cells (ILCs) in the generation of fibrotic disease with an examination of the potential interplay between ILC and macrophages and the adaptive immune system. PMID:26635811

  7. Innate lymphoid cells in the initiation, regulation and resolution of inflammation.

    PubMed

    Sonnenberg, Gregory F; Artis, David

    2015-07-01

    A previously unappreciated cell type of the innate immune system, termed innate lymphoid cells (ILCs), has been characterized in mice and humans and found to influence the induction, regulation and resolution of inflammation. ILCs have an important role in these processes in mouse models of infection, inflammation and tissue repair. Further, disease-association studies in defined patient populations have identified significant alterations in ILC responses, suggesting a potential role for these cell populations in human health and disease. In this review we discuss the emerging family of ILCs, the role of ILCs in inflammation, and how current or novel therapeutic strategies could be used to selectively modulate ILC responses and limit chronic inflammatory diseases. PMID:26121198

  8. Interleukin-5–producing group 2 innate lymphoid cells control eosinophilia induced by interleukin-2 therapy

    PubMed Central

    Van Gool, Frédéric; Molofsky, Ari B.; Morar, Malika M.; Rosenzwajg, Michelle; Liang, Hong-Erh; Klatzmann, David; Bluestone, Jeffrey A.

    2014-01-01

    Interleukin (IL)-2 promotes regulatory T-cell development and function, and treatment with IL-2 is being tested as therapy for some autoimmune diseases. However, patients receiving IL-2 treatment also experience eosinophilia due to an unknown mechanism. Here, we show that patients receiving low-dose IL-2 have elevated levels of serum IL-5, and this correlates with their degree of eosinophilia. In mice, low-dose IL-2–anti-IL-2 antibody complexes drove group 2 innate lymphoid cells (ILC2) to produce IL-5 and proliferate. Using genetic approaches in mice, we demonstrate that activation of ILC2 was responsible for the eosinophilia observed with IL-2 therapy. These observations reveal a novel cellular network that is activated during IL-2 treatment. A better understanding of the cross talk between these cell populations may lead to more effective targeting of IL-2 to treat autoimmune disease. PMID:25323825

  9. Spatiotemporal basis of innate and adaptive immunity in secondary lymphoid tissue.

    PubMed

    Qi, Hai; Kastenmüller, Wolfgang; Germain, Ronald N

    2014-01-01

    Secondary lymphoid tissues are the sites of both innate and adaptive host defense. Aside from the relatively static nonhematopoietic stromal elements and some macrophages and dendritic cells, most of the cells in these tissues are in constant movement, but the organs maintain a defined microanatomy with preferred locations for the bulk of T cells, B cells, and other lymphocytes and subsets of myeloid cells. Here we describe both the cell dynamics and spatial organization of lymph nodes and review how both physical features and molecular cues guide cell movement to optimize host defense. We emphasize the role of locality in improving the efficiency of a system requiring rare cells to find each other and interact productively through membrane-bound or short-range secreted mediators and highlight how changes in steady-state cell positioning during an infectious challenge contribute to rapid generation of productive responses. PMID:25150013

  10. Immunosuppression and tolerance after total lymphoid irradiation (TLI). [Mice, rats, monkeys, dogs, patients

    SciTech Connect

    Strober, S.; Gottlieb, M.; Slavin, S.; King, D.P.; Hoppe, R.T.; Fuks, Z.; Bieber, C.P.; Kaplan, H.S.

    1980-09-01

    The immunosuppressive effects of total lymphoid irradiation (TLI) in humans and in several species of inbred and outbred laboratory animals have been investigated. A unique property of TLI, the prevention of the graft vs. host disease, was used to induce transplantation tolerance in order to study the mechanism of altered immunity when the celluar basis of the TLI-induced immunosuppression was examined by means of the mixed lymphocyte response (MLR), no suppression of the MLR was observed when spleen cells from unirradiated or whole body-irradiated donors were used instead of donors given TLI. These results indicated that TLI induces a population of cells in the spleen that can nonspecifically suppress the MLR.

  11. Transplantation tolerance in primates after total lymphoid irradiation and allogeneic bone marrow injection

    SciTech Connect

    Smit, J.A.; Hill, R.R.H.; Myburgh, J.A.; Browde, S.

    1980-08-01

    After total lymphoid irradiation (TLI), allogeneic bone marrow (BM) injection, and organ transplantation in baboons, there is a prolonged period of reduced lymphocyte proliferative responsiveness to polyclonal mitogens and allogeneic lymphocytes. The effect observed is greater with the use of fractionated TLI than after single doses of irradiation. Suppressor cell activity can be demonstrated in vitro in most animals by inhibition of mixed lymphocyte reactivity (MLR) by mitomycin-treated recipient lymphocytes harvested after TLI, with or without allogeneic BM injection, and organ transplantation. Preliminary data suggest the presence of both donor-specific and nondonor-specific suppression, although other interpretations are possible, and suppressor phenomena may not be responsible for the transplantation tolerance observed.

  12. Total lymphoid irradiation therapy in refractory rheumatoid arthritis. Fifteen- to forty-month followup

    SciTech Connect

    Brahn, E.; Helfgott, S.M.; Belli, J.A.; Anderson, R.J.; Reinherz, E.L.; Schlossman, S.F.; Austen, K.F.; Trentham, D.E.

    1984-05-01

    Twelve patients with refractory rheumatoid arthritis were treated with total lymphoid irradiation (TLI) to a total cumulative dose of 3,000 rads. Post-TLI morbidity/mortality included 8 patients with xerostomia, 4 with weight loss of greater than 10 kg, 3 with loss of 4 or more teeth, 3 with herpes zoster, 4 with bacterial infection that was fatal in 2, 3 with hypothyroidism, 1 with cutaneous vasculitis, and death from myocardial infarction in 1 patient and cardiorespiratory arrest in another. Ten of the patients were reevaluated 15-40 months (mean +/- SE, 30 +/- 2) after completion of TLI, and significant improvement was noted in several disease parameters including number of swollen joints, duration of morning stiffness, and 50-foot walking time. Blood lymphopenia and a decrease in helper T cells (T4) were also noted. These data suggest that changes in immunoregulation induced by TLI can produce longlasting alterations in rheumatoid arthritis, although adverse effects may limit its efficacy.

  13. Lymphoid cell kinetics under continuous low dose-rate gamma irradiation: A comparison study

    NASA Technical Reports Server (NTRS)

    Foster, B. R.

    1975-01-01

    The mechanism of cell proliferation is studied in the lymphoid tissue of the mouse spleen under the stress of continuous irradiation at a dose-rate of 10 roentgens per day for 105 days. Autoradiography and specific labeling with tritiated thymidine were utilized. It was found that at least four compensatory mechanisms maintained a near-steady state of cellular growth: (1) an increase in the proportion of PAS-positive cells which stimulate mitotic activity, (2) maturation arrest of proliferating and differentiating cells which tend to replenish the cells damaged or destroyed by irradiation, (3) an increase in the proportion of cells proliferating, and (4) an increase in the proportion of precursor cells. The results are compared to previous findings observed in the thymus.

  14. Deciphering the transcriptional switches of innate lymphoid cell programming: the right factors at the right time.

    PubMed

    Lim, A W Y; McKenzie, A N J

    2015-01-01

    Innate lymphoid cells (ILCs) are increasingly recognised as an innate immune counterpart of adaptive T-helper (TH) cells. In addition to their similar effector cytokine production, there is a strong parallel between the transcription factors that control the differentiation of T(H)1, T(H)2 and T(H)17 cells and ILC groups 1, 2 and 3, respectively. Here, we review the transcriptional circuit that specifies the development of a common ILC progenitor and its subsequent programming into distinct ILC groups. Notch, GATA-3 (GATA-binding protein 3), Nfil3 (nuclear factor interleukin-3) and Id2 (inhibitor of DNA-binding 2) are identified as early factors that suppress B- and T-cell potentials and are turned on in favour of ILC commitment. Natural killer cells, which are the cytotoxic ILCs, develop along a pathway distinct from the rest of the helper-like ILCs that are derived from a common progenitor to all helper-like ILCs (CHILPs). PLZF(-) (promyelocytic leukaemia zinc-finger) CHILPs give rise to lymphoid tissue inducer cells, while PLZF(+) CHILPs have multilineage potential and could give rise to ILCs 1, 2 and 3. Such lineage specificity is dictated by the controlled expression of T-bet (T-box expressed in T cells), ROR? (retinoic acid receptor-related orphan nuclear receptor-?), ROR?t (retinoic acid receptor-related orphan nuclear receptor-?t) and AHR (aryl hydrocarbon receptor). In addition to the type of transcription factors, the developmental stages at which these factors are expressed are crucial in specifying the fate of the ILCs. PMID:25611557

  15. A rationally designed nanoparticle for RNA interference therapy in B-lineage lymphoid malignancies

    PubMed Central

    Uckun, Fatih M.; Qazi, Sanjive; Ma, Hong; Yin, Lichen; Cheng, Jianjun

    2014-01-01

    The purposes of the present study were to further evaluate the biologic significance of the CD22?E12 molecular lesion and determine if it could serve as a molecular target for RNA interference (RNAi) therapy. We show that both pediatric and adult B-lineage lymphoid malignancies are characterized by a very high incidence of the CD22?E12 genetic defect. We provide unprecedented experimental evidence for a previously unrecognized causal link between CD22?E12 and aggressive biology of BPL cells by demonstrating that siRNA-mediated knockdown of CD22?E12 in primary BPL cells is associated with a marked inhibition of their clonogenicity. These findings provide the preclinical proof-of-concept that siRNA-mediated depletion of CD22?E12 may help develop effective treatments for high-risk and relapsed BPL patients who are in urgent need for therapeutic innovations. We also describe a unique polypeptide-based nanoparticle formulation of CD22?E12-siRNA as an RNAi therapeutic candidate targeting CD22?E12 that is capable of delivering its siRNA cargo into the cytoplasm of leukemia cells causing effective CD22?E12 depletion and marked inhibition of leukemic cell growth. Further development and optimization of this nanoparticle or other nanoformulation platforms for CD22?E12-siRNA may facilitate the development of an effective therapeutic RNAi strategy against a paradigm shift in therapy of aggressive or chemotherapy-resistant B-lineage lymphoid malignancies. PMID:25599086

  16. Pathogenic effects of human herpesvirus 6 in human lymphoid tissue ex vivo.

    PubMed

    Grivel, Jean-Charles; Santoro, Fabio; Chen, Silvia; Fagá, Giovanni; Malnati, Mauro S; Ito, Yoshinori; Margolis, Leonid; Lusso, Paolo

    2003-08-01

    Human herpesvirus 6 (HHV-6) is a potentially immunosuppressive agent that has been suggested to act as a cofactor in the progression of human immunodeficiency virus disease. However, the lack of suitable experimental models has hampered the elucidation of the mechanisms of HHV-6-mediated immune suppression. Here, we used ex vivo lymphoid tissue to investigate the cellular tropism and pathogenic mechanisms of HHV-6. Viral strains belonging to both HHV-6 subgroups (A and B) were able to productively infect human tonsil tissue fragments in the absence of exogenous stimulation. The majority of viral antigen-expressing cells were CD4(+) T lymphocytes expressing a nonnaive phenotype, while CD8(+) T cells were efficiently infected only with HHV-6A. Accordingly, HHV-6A infection resulted in the depletion of both CD4(+) and CD8(+) T cells, whereas in HHV-6B-infected tissue CD4(+) T cells were predominantly depleted. The expression of different cellular antigens was dramatically altered in HHV-6-infected tissues: whereas CD4 was upregulated, both CD46, which serves as a cellular receptor for HHV-6, and CD3 were downmodulated. However, CD3 downmodulation was restricted to infected cells, while the loss of CD46 expression was generalized. Moreover, HHV-6 infection markedly enhanced the production of the CC chemokine RANTES, whereas other cytokines and chemokines were only marginally affected. These results provide the first evidence, in a physiologically relevant study model, that HHV-6 can severely affect the physiology of secondary lymphoid organs through direct infection of T lymphocytes and modulation of key membrane receptors and chemokines. PMID:12857897

  17. Different expression of CD41 on human lymphoid and myeloid progenitors from adults and neonates.

    PubMed

    Debili, N; Robin, C; Schiavon, V; Letestu, R; Pflumio, F; Mitjavila-Garcia, M T; Coulombel, L; Vainchenker, W

    2001-04-01

    The glycoprotein (Gp) IIb/IIIa integrin, also called CD41, is the platelet receptor for fibrinogen and several other extracellular matrix molecules. Recent evidence suggests that its expression is much wider in the hematopoietic system than was previously thought. To investigate the precise expression of the CD41 antigen during megakaryocyte (MK) differentiation, CD34(+) cells from cord blood and mobilized blood cells from adults were grown for 6 days in the presence of stem cell factor and thrombopoietin. Two different pathways of differentiation were observed: one in the adult and one in the neonate cells. In the neonate samples, early MK differentiation proceeded from CD34(+)CD41(-) through a CD34(-)CD41(+)CD42(-) stage of differentiation to more mature cells. In contrast, in the adult samples, CD41 and CD42 were co-expressed on a CD34(+) cell. The rare CD34(+)CD41(+)CD42(-) cell subset in neonates was not committed to MK differentiation but contained cells with all myeloid and lymphoid potentialities along with long-term culture initiating cells (LTC-ICs) and nonobese diabetic/severe combined immune-deficient repopulating cells. In the adult samples, the CD34(+)CD41(+)CD42(-) subset was enriched in MK progenitors, but also contained erythroid progenitors, rare myeloid progenitors, and some LTC-ICs. All together, these results demonstrate that the CD41 antigen is expressed at a low level on primitive hematopoietic cells with a myeloid and lymphoid potential and that its expression is ontogenically regulated, leading to marked differences in the surface antigenic properties of differentiating megakaryocytic cells from neonates and adults. (Blood. 2001;97:2023-2030) PMID:11264167

  18. Executive Dysfunction 25 Years after Treatment with Cranial Radiotherapy for Pediatric Lymphoid Malignancies.

    PubMed

    Schuitema, Ilse; de Sonneville, Leo; Kaspers, Gertjan; van der Pal, Helena; Uyttebroeck, Anne; van den Bos, Cor; Veerman, Anjo

    2015-10-01

    The first cohorts to survive childhood lymphoid malignancies treated with cranial irradiation are now aging into adulthood, and concerns are growing about the development of radiotherapy-induced cognitive deficits in the aging brain. These deficits are hypothesized to increase over time. Their impact on daily functioning of older survivors, and the accompanying need for interventions, should be anticipated. By describing a detailed profile of executive function deficits and their associations with age, specific targets for neuropsychological intervention can be identified. Fifty survivors of childhood lymphoid malignancies and 58 related controls were assessed with the Amsterdam Neuropsychological Tasks program. The survivors were on average 31.1 (4.9) years old, treated with 22.5 (6.8) Gy cranial irradiation, and examined on average 25.5 (3.1) years after diagnosis. The survivors showed significantly decreased response speed, irrespective of the task at hand. Furthermore, we found deficits in working memory capacity, inhibition, cognitive flexibility, executive visuomotor control, attentional fluctuations, and sustained attention. Older age was associated with poorer performance on executive visuomotor control and inhibition. On executive visuomotor control, 50% of female survivors performed more than 1.5 SD below average, versus 15.4% of male survivors. The combination of visuospatial working memory problems and decreasing executive visuomotor control could result in difficulty with learning new motor skills at older ages, like walking with a cane. Deterioration of executive control and inhibition may result in decreased behavioral and emotional regulation in aging survivors. Especially the deficiency in executive visuomotor control in female survivors should be considered for (prophylactic) intervention. (JINS, 2015, 21, 657-669). PMID:26391667

  19. New Players in the Same Old Game: Disturbance of Group 2 Innate Lymphoid Cells in HIV-1 and Mycobacterium leprae Co-infected Patients

    PubMed Central

    Papotto, Pedro Henrique; Maeda, Solange; Tomimori, Jane; Xavier, Marília Brasil; Rizzo, Luiz Vicente; Kallas, Esper Georges; Carvalho, Karina Inácio

    2015-01-01

    Abstract Leprosy control is achieved through a fine-tuning of TH1 and TH2 immune response pattern balance. Given the increasing epidemiological overlay of HIV and M. leprae infections, immune response in co-infected patients consists in an important contemporary issue. Here we describe for the first time the innate lymphoid cells compartment in peripheral blood of leprosy and HIV/M. leprae co-infected patients, and show that co-infection increases group 2 innate lymphoid whilst decreasing group 1 innate lymphoid cells frequencies and function. PMID:26335023

  20. The distribution of organised lymphoid tissue in the alimentary tracts of koalas (Phascolarctos cinereus) and possums (Trichosurus vulpecula and Pseudocheirus peregrinus).

    PubMed Central

    Hemsley, S W; Canfield, P J; Husband, A J

    1996-01-01

    The anatomical arrangement of organised lymphoid tissues of the alimentary tract for 3 Australian marsupials, the koala (Phascolarctos cinereus), the common brushtail possum (Trichosurus vulpecula and the common ringtail possum (Pseudocheirus peregrinus), was determined by gross dissection and acetic acid treatment. Oropharyngeal tonsils were consistently found in the dorsolateral wall of the caudal oropharynx in all 3 species and additionally in the ventral soft palate of the koala. Aggregated lymphoid nodules (Peyer's patches) were present in the small intestine of koalas, ringtail possums and brushtail possums and were of similar appearance for all 3 species. Bilateral large intestinal lymphoid patches were detected in the caecocolic lateral wall adjacent to the termination of the ileum for all 3 species. Caecocolic patches were more complex in koalas and had mucosal folds and a central recess. In addition, solitary and grouped large intestinal lymphoid nodules were variably present in the proximal colon and caecum of the koala. In contrast, possums had solitary and grouped large intestinal lymphoid nodules present in the proximal colon and rectum but not the caecum. Aggregated lymphoid tissue was not detected in the tongue, oesophagus or stomach for all 3 species. In contrast to a previous report, this study did not find a paucity of lymphoid tissue associated with the gut of the koala. The appearance and distribution of gut-associated lymphoid tissue in koalas and possums was found to be similar to that described in other marsupials and eutherian mammals, although some variations in appearance and anatomical location were observed. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 6 PMID:8621325

  1. AK2 deficiency compromises the mitochondrial energy metabolism required for differentiation of human neutrophil and lymphoid lineages

    PubMed Central

    Six, E; Lagresle-Peyrou, C; Susini, S; De Chappedelaine, C; Sigrist, N; Sadek, H; Chouteau, M; Cagnard, N; Fontenay, M; Hermine, O; Chomienne, C; Reynier, P; Fischer, A; André-Schmutz, I; Gueguen, N; Cavazzana, M

    2015-01-01

    Reticular dysgenesis is a human severe combined immunodeficiency that is primarily characterized by profound neutropenia and lymphopenia. The condition is caused by mutations in the adenylate kinase 2 (AK2) gene, resulting in the loss of mitochondrial AK2 protein expression. AK2 regulates the homeostasis of mitochondrial adenine nucleotides (ADP, ATP and AMP) by catalyzing the transfer of high-energy phosphate. Our present results demonstrate that AK2-knocked-down progenitor cells have poor proliferative and survival capacities and are blocked in their differentiation toward lymphoid and granulocyte lineages. We also observed that AK2 deficiency impaired mitochondrial function in general and oxidative phosphorylation in particular – showing that AK2 is critical in the control of energy metabolism. Loss of AK2 disrupts this regulation and leads to a profound block in lymphoid and myeloid cell differentiation. PMID:26270350

  2. Effect of total lymphoid irradiation on IgE antibody responses in rheumatoid arthritis and systemic lupus erythematosus

    SciTech Connect

    Terr, A.I.; Moss, R.B.; Strober, S.

    1987-12-01

    Thirteen patients with rheumatoid arthritis and four patients with systemic lupus erythematosus and nephritis were treated with total lymphoid irradiation because of severe disease refractory to other forms of treatment. Serum samples before and after irradiation were tested for changes in total serum IgE and for changes in specific IgE antibodies to ryegrass pollen, dust mite, cat dander, and Alternaria. There were no statistically significant changes in total or specific IgE from lymphoid irradiation in these patients. The therapy caused a significant decrease in circulating total lymphocyte and Leu-3 (helper/inducer) T-lymphocyte counts. Therefore, reduction in circulating levels of helper/inducer T cells does not appear to influence preexisting levels of IgE antibodies.

  3. Distribution of beta 7 integrins in human intestinal mucosa and organized gut-associated lymphoid tissue.

    PubMed Central

    Farstad, I N; Halstensen, T S; Lien, B; Kilshaw, P J; Lazarovits, A I; Brandtzaeg, P; Lazarovitz, A I

    1996-01-01

    Two alternative integrins involved in mucosal homing (alpha 4 beta 7) or epithelial retention (alpha E beta 7) of lymphocytes were examined in the human gut. The distribution of the beta 7 subunit [monoclonal antibody (mAb) M301] was bimodal in that it was strongly expressed by alpha E beta 7 + cells but weakly by alpha 4 beta 7 + cells. More than 90% of intraepithelial lymphocytes (IEL), including the minor subsets of CD4+, T-cell receptor (TCR) gamma/delta +, and CD3- cells, expressed alpha E beta 7 as did most lamina propria CD8+ (88%) and a fraction (36%) of CD4+ lymphocytes. Conversely, B-lineage cells (CD19+) and macrophages (CD68+) were negative. In gut-associated lymphoid tissue (GALT: Peyer's patches and appendix) only a few (< 5%) cells were positive for alpha E beta 7 (confined to CD8+ lymphocytes and CD11c+ putative dendritic cells). A relatively small fraction of IEL (30-50%) expressed alpha 4 beta 7 (mAb Act-1), while most (70%) lamina propria T and B lymphocytes, blasts, plasma cells and macrophages were positive. In GALT, T lymphocytes expressed similar levels of alpha 4 beta 7 as in the lamina propria whereas relatively few B lymphocytes (< 50%) were positive. Isolated lamina propria CD8+, CD4+, CD19+, and CD38+ cells contained mRNA for alpha 4 and the former three subsets as well as appendix CD8+ cells also for beta 7 while only lamina propria CD8+ cells had mRNA for alpha E. Together, the results suggested that alpha E beta 7 and alpha 4 beta 7 are differentially regulated in inductive sites and effector sites of the human gut. Because lymphoid cells at both sites expressed mainly alpha 4 beta 7, this integrin may be a homing receptor on memory and effector cells bound for lamina propria as well as on naive lymphocytes extravasating in GALT. Conversely, because alpha E beta 7 was mainly expressed by CD8+ cells in epithelium and lamina propria, it was probably induced after extravasation, in agreement with the observation that IEL and a fraction of lamina propria T lymphocytes (mainly CD8+ cells) generally expressed higher levels of beta 7 than most CD4+ and B cells. Also a subset of putative dendritic cells located near the follicle-associated epithelium of GALT expressed alpha E beta 7, perhaps reflecting epithelial interaction during primary immune responses. Images Figure 5 Figure 6 PMID:8943719

  4. Cytokine Response in Multiple Lymphoid Tissues during the Primary Phase of Feline Immunodeficiency Virus Infection

    PubMed Central

    Dean, Gregg A.; Pedersen, Niels C.

    1998-01-01

    Type 1 and 2 cytokine mRNA responses were measured at various time periods and in various lymphoid compartments during the acute stage (first 4 months) of feline immunodeficiency virus (FIV) infection in laboratory cats. Cytokine responses were correlated with virus replication. Virus was detected in plasma and tissue from day 14 postinfection (p.i.) onward, peaked at 56 to 70 days, and declined greatly by 70 days. Virus replication was highest in the thymus, followed by spleen, mesenteric lymph nodes, and cervical lymph nodes. Baseline cytokine levels were highest in the mesenteric lymph nodes and lowest in the cervical lymph nodes. Cytokine upregulation after FIV infection was most dramatic in the cervical lymph nodes, with the greatest increase in interleukin-10 (IL-10) and gamma interferon (IFN-?). Cytokine transcription in the mesenteric lymph node increased above baseline by day 14 p.i. for IFN-?, IL-12p40, IL-4, and IL-10, while elevations in the spleen were mainly for IFN-?, IL-12p40 and IL-10. An increase in IFN-?, IL-10, and IL-12p40 occurred in the thymus at day 56 p.i., concomitant with the onset of thymitis. In general, type 2 cytokines (IL-4 and IL-10) were increased greater than 1 log over baseline, while the elevations in type 1 cytokines were less than 1 log. In the tissues tested, CD4+ cells were the primary source of IL-2, IL-4, and IL-10. Both CD4+ and CD8+ cells produced IFN-?, while no cytokine mRNA was detected in B cells. These results demonstrate the presence of a heterogeneous cytokine response in lymphoid tissues during the primary stage of FIV infection. The nature and intensity of the response differed from one compartment to the other and, in the case of the thymus, also with inflammatory changes. Although limited in scope, the present study confirms the usefulness of the FIV infection model in studying early cytokine events that lead to the secondary subclinical carrier state typical of most lentivirus infections. PMID:9811676

  5. Allograft tolerance in pigs after fractionated lymphoid irradiation. I. Skin grafts after partial lateral irradiation and bone marrow cell grafting

    SciTech Connect

    Vaiman, M.; Daburon, F.; Remy, J.; Villiers, P.A.; de Riberolles, C.; Lecompte, Y.; Mahouy, G.; Fradelizi, D.

    1981-05-01

    Experiments with pigs have been performed to establish bone marrow chimerism and skin graft tolerance between SLA genotyped animals. Recipients were conditioned by means of fractionated partial irradiation from lateral cobalt sources (partial lateral irradiation (PLI)). The head, neck, and lungs were protected with lead, the rest of the body being irradiated including the thymus, the majority of lymphoid organs with spleen, and most of the bone marrow sites.

  6. Lymphoid Progenitor Cells from Childhood Acute Lymphoblastic Leukemia Are Functionally Deficient and Express High Levels of the Transcriptional Repressor Gfi-1

    PubMed Central

    Purizaca, Jessica; Contreras-Quiroz, Adriana; Dorantes-Acosta, Elisa; Vadillo, Eduardo; Arriaga-Pizano, Lourdes; Fuentes-Figueroa, Silvestre; Villagomez-Barragán, Horacio; Flores-Guzmán, Patricia; Alvarado-Moreno, Antonio; Mayani, Hector; Meza, Isaura; Hernandez, Rosaura; Huerta-Yepez, Sara; Pelayo, Rosana

    2013-01-01

    Acute lymphoblastic leukemia (ALL) is the most frequent malignancy of childhood. Substantial progress on understanding the cell hierarchy within ALL bone marrow (BM) has been recorded in the last few years, suggesting that both primitive cell fractions and committed lymphoid blasts with immature stem cell-like properties contain leukemia-initiating cells. Nevertheless, the biology of the early progenitors that initiate the lymphoid program remains elusive. The aim of the present study was to investigate the ability of lymphoid progenitors from B-cell precursor ALL BM to proliferate and undergo multilineage differentiation. By phenotype analyses, in vitro proliferation assays, and controlled culture systems, the lymphoid differentiation potentials were evaluated in BM primitive populations from B-cell precursor ALL pediatric patients. When compared to their normal counterparts, functional stem and progenitor cell contents were substantially reduced in ALL BM. Moreover, neither B nor NK or dendritic lymphoid-cell populations developed recurrently from highly purified ALL-lymphoid progenitors, and their proliferation and cell cycle status revealed limited proliferative capacity. Interestingly, a number of quiescence-associated transcription factors were elevated, including the transcriptional repressor Gfi-1, which was highly expressed in primitive CD34+ cells. Together, our findings reveal major functional defects in the primitive hematopoietic component of ALL BM. A possible contribution of high levels of Gfi-1 expression in the regulation of the stem/progenitor cell biology is suggested. PMID:24198842

  7. Decreased human immunodeficiency virus type 1 plasma viremia during antiretroviral therapy reflects downregulation of viral replication in lymphoid tissue.

    PubMed Central

    Cohen, O J; Pantaleo, G; Holodniy, M; Schnittman, S; Niu, M; Graziosi, C; Pavlakis, G N; Lalezari, J; Bartlett, J A; Steigbigel, R T

    1995-01-01

    Although several immunologic and virologic markers measured in peripheral blood are useful for predicting accelerated progression of human immunodeficiency virus (HIV) disease, their validity for evaluating the response to antiretroviral therapy and their ability to accurately reflect changes in lymphoid organs remain unclear. In the present study, changes in certain virologic markers have been analyzed in peripheral blood and lymphoid tissue during antiretroviral therapy. Sixteen HIV-infected individuals who were receiving antiretroviral therapy with zidovudine for > or = 6 months were randomly assigned either to continue on zidovudine alone or to add didanosine for 8 weeks. Lymph node biopsies were performed at baseline and after 8 weeks. Viral burden (i.e., HIV DNA copies per 10(6) mononuclear cells) and virus replication in mononuclear cells isolated from peripheral blood and lymph node and plasma viremia were determined by semiquantitative polymerase chain reaction assays. Virologic and immunologic markers remained unchanged in peripheral blood and lymph node of patients who continued on zidovudine alone. In contrast, a decrease in virus replication in lymph nodes was observed in four of six patients who added didanosine to their regimen, and this was associated with a decrease in plasma viremia. These results indicate that decreases in plasma viremia detected during antiretroviral therapy reflect downregulation of virus replication in lymphoid tissue. Images Fig. 1 Fig. 2 Fig. 3 PMID:7597072

  8. Transplantability of human lymphoid cell line, lymphoma, and leukemia in splenectomized and/or irradiated nude mice

    SciTech Connect

    Watanabe, S.; Shimosato, Y.; Kuroki, M.; Sato, Y.; Nakajima, T.

    1980-07-01

    The effects of splenectomy and/or whole-body irradiation of nude mice before xenotransplantation of lymphoid cell lines, lymphoma, and leukemia were studied. Transplantation after whole-body irradiation resulted in the increased ''take'' rate of three cultured cell lines (two of T-cell-derived acute lymphocytic leukemia and one of B-cell derived acute lymphocytic leukemia) and in the tumorous growth of Burkitt-derived Raji and spontaneously transformed lymphoblastoid cell lines. With splenectomy plus irradiation as a pretreatment, tumorous growth occurred in four other cell lines which were not transplantable after irradiation only (two cell lines of Epstein-Barr virus-transformed cord blood cells and one each of null acute lymphocytic leukemia and nodular lymphoma-derived cell lines). Direct transplantation of leukemia and lymphoma cells into the pretreated mice was successful in 7 of 24 cases (29%). B-cell-derived diffuse large lymphoid lymphoma was transplantable in three of seven cases (43%). However, lymphoma and leukemia of peripheral T-cell origin was difficult to transplant even with pretreatment, and only one pleomorphic T-cell lymphoma grew to a significant size (2 cm). One tumor each of B-cell-derived diffuse large lymphoid and T-cell diffuse lymphoblastic lymphoma became transplantable.

  9. Epigenetic Regulation of Non-Lymphoid Cells by Bisphenol A, a Model Endocrine Disrupter: Potential Implications for Immunoregulation

    PubMed Central

    Khan, Deena; Ahmed, S. Ansar

    2015-01-01

    Endocrine disrupting chemicals (EDC) abound in the environment since many compounds are released from chemical, agricultural, pharmaceutical, and consumer product industries. Many of the EDCs such as Bisphenol A (BPA) have estrogenic activity or interfere with endogenous sex hormones. Experimental studies have reported a positive correlation of BPA with reproductive toxicity, altered growth, and immune dysregulation. Although the precise relevance of these studies to the environmental levels is unclear, nevertheless, their potential health implications remain a concern. One possible mechanism by which BPA can alter genes is by regulating epigenetics, including microRNA, alteration of methylation, and histone acetylation. There is now wealth of information on BPA effects on non-lymphoid cells and by comparison, paucity of data on effects of BPA on the immune system. In this mini review, we will highlight the BPA regulation of estrogen receptor-mediated immune cell functions and in different inflammatory conditions. In addition, BPA-mediated epigenetic regulation of non-lymphoid cells is emphasized. We recognize that most of these studies are on non-lymphoid cells, and given that BPA also affects the immune system, it is plausible that BPA could have similar epigenetic regulation in immune cells. It is hoped that this review will stimulate studies in this area to ascertain whether or not BPA epigenetically regulates the cells of the immune system. PMID:26097467

  10. Lactational alcohol exposure elicits long-term immune deficits and increased noradrenergic synaptic transmission in lymphoid organs

    SciTech Connect

    Gottesfeld, Z. ); LeGrue, S.J. )

    1990-01-01

    Increasing evidence suggests that the sympathetic nervous system plays an important role in immunomodulation. While chronic alcohol consumption has been associated with immune deficits, the effects of exposure to alcohol during early postnatal life on subsequent immunocompetence and activity of sympathetic neurons in lymphoid organs are not known. This study examined the long-term effects of lactational alcohol consumption on cellular immune responses and noradrenergic synaptic transmission in lymphoid and other organs of the young adult C57BL/6 mouse. The data show that exposure to alcohol via the mother's milk was associated with long-term deficits in cellular immunity, including suppression of the local graft vs host and contact hypersensitive responses. The animals also displayed enhanced noradrenergic synaptic transmission and decreased {beta}-adrenoceptor density selectively in lymphoid organs. These neuroimmune changes are particularly striking since body weight-gain of the suckling pups was normal and their blood alcohol concentration was considerably lower than that of the alcohol-consuming dam. This suggests an increased sensitivity of the nascent immune and nervous systems during the critical period of early postnatal development.

  11. Human herpesvirus 7 infection of lymphoid and myeloid cell lines transduced with an adenovirus vector containing the CD4 gene.

    PubMed Central

    Yasukawa, M; Inoue, Y; Ohminami, H; Sada, E; Miyake, K; Tohyama, T; Shimada, T; Fujita, S

    1997-01-01

    It has been reported recently that CD4 is a major component of the receptor for human herpesvirus 7 (HHV-7), which has been newly identified as a T-lymphotropic virus. To investigate further the role of CD4 in HHV-7 infection, we examined the susceptibility to HHV-7 infection of various CD4-negative or weakly positive cell lines into which the cDNA for CD4 was transferred using an adenovirus vector (Adex1CACD4). Of 13 cell lines transduced with Adex1CACD4, including T-lymphoid, B-lymphoid, monocytoid, and myeloid cell lines, one T-lymphoid cell line, one monocytoid cell line, and two cell lines established from the blast crisis of chronic myelogenous leukemia showed high susceptibility to HHV-7 infection. Taken together with the results of previous studies, these data suggest strongly that CD4 is a major component of the binding receptor for HHV-7. This study also shows that HHV-7 may be able to infect CD4-positive hematopoietic precursor cells as well as T lymphocytes. PMID:8995705

  12. Preclinical studies on NSC290205 aza-steroid alkylator activity in combination with adriamycin against lymphoid leukaemia.

    PubMed

    Trafalis, Dimitrios T P; Tsavdaridis, Dimitrios; Camoutsis, Charalambos; Karayiani, Venetia; Mourelatos, Dionysios; Dalezis, Panayotis; Athanassiou, Athanasios; Pangalis, Gerassimos A; Papageorgiou, Athanasios

    2005-02-01

    Summary NSC290205 (A) is an hybrid synthetic antineoplastic ester that is a combination of a d-lactam derivative of androsterone and an alkylating derivative of N,N-bis(2-chloroethyl)aniline. We tested NSC290205 for synergistic antileukaemic activity with adriamycin (ADR), (i) in vitro against the human lymphoid leukaemia cell lines: CCRF-CEM, MOLT-4, and RPMI-8226, (ii) in vivo against P388 lymphocytic and L1210 lymphoid murine leukaemias (at incipient and advanced phase). Our results indicated significant cytostatic and cytotoxic synergy of NSC290205 and ADR in vitro. We further examined these results in vivo by replacing cyclophosphamide in the standard CHOP (cyclophosphamide, hydroxydaunomycin, Oncovin, prednisone) regimen with NSC290205 (AHOP) and comparing the efficiency of these two regimens in vivo. Although treatment of P388 and L1210 with cyclophosphamide or NSC290205 alone yielded equivalent results, AHOP produced a clear benefit for survival compared with CHOP against advanced leukaemias, confirming the in vitro observations [higher percentage increase in median lifespan of treated animals over the untreated (control): 188% and 239% in L1210, 308% and 353% in P388, P < 0.01, for CHOP and AHOP respectively]. AHOP also proved to be more genotoxic and cytostatic than CHOP, inducing higher sister chromatid exchange levels and cell division delays on P388 cells in vivo. NSC290205 showed superior antineoplastic potential against lymphoid leukaemia and significant synergy with ADR, producing an excellent therapeutic outcome. PMID:15667536

  13. Immune suppression of human lymphoid tissues and cells in rotating suspension culture and onboard the International Space Station

    PubMed Central

    Fitzgerald, Wendy; Chen, Silvia; Walz, Carl; Zimmerberg, Joshua; Margolis, Leonid

    2013-01-01

    The immune responses of human lymphoid tissue explants or cells isolated from this tissue were studied quantitatively under normal gravity and microgravity. Microgravity was either modeled by solid body suspension in a rotating, oxygenated culture vessel or was actually achieved on the International Space Station (ISS). Our experiments demonstrate that tissues or cells challenged by recall antigen or by polyclonal activator in modeled microgravity lose all their ability to produce antibodies and cytokines and to increase their metabolic activity. In contrast, if the cells were challenged before being exposed to modeled microgravity suspension culture, they maintained their responses. Similarly, in microgravity in the ISS, lymphoid cells did not respond to antigenic or polyclonal challenge, whereas cells challenged prior to the space flight maintained their antibody and cytokine responses in space. Thus, immune activation of cells of lymphoid tissue is severely blunted both in modeled and true microgravity. This suggests that suspension culture via solid body rotation is sufficient to induce the changes in cellular physiology seen in true microgravity. This phenomenon may reflect immune dysfunction observed in astronauts during space flights. If so, the ex vivo system described above can be used to understand cellular and molecular mechanisms of this dysfunction. PMID:19609626

  14. A Chemokine Expressed in Lymphoid High Endothelial Venules Promotes the Adhesion and Chemotaxis of Naive T Lymphocytes

    NASA Astrophysics Data System (ADS)

    Gunn, Michael D.; Tangemann, Kirsten; Tam, Carmen; Cyster, Jason G.; Rosen, Steven D.; Williams, Lewis T.

    1998-01-01

    Preferential homing of naive lymphocytes to secondary lymphoid organs is thought to involve the action of chemokines, yet no chemokine has been shown to have either the expression pattern or the activities required to mediate this process. Here we show that a chemokine represented in the EST database, secondary lymphoid-tissue chemokine (SLC), is expressed in the high endothelial venules of lymph nodes and Peyer's patches, in the T cell areas of spleen, lymph nodes, and Peyer's patches, and in the lymphatic endothelium of multiple organs. SLC is a highly efficacious chemoattractant for lymphocytes with preferential activity toward naive T cells. Moreover, SLC induces firm adhesion of naive T lymphocytes via ? 2 integrin binding to the counter receptor, intercellular adhesion molecule-1, a necessary step for lymphocyte recruitment. SLC is the first chemokine demonstrated to have the characteristics required to mediate homing of lymphocytes to secondary lymphoid organs. In addition, the expression of SLC in lymphatic endothelium suggests that the migration of lymphocytes from tissues into efferent lymphatics may be an active process mediated by this molecule.

  15. Marginal reticular cells: a stromal subset directly descended from the lymphoid tissue organizer.

    PubMed

    Katakai, Tomoya

    2012-01-01

    The architecture of secondary lymphoid organs (SLOs) is supported by several non-hematopoietic stromal cells. Currently it is established that two distinct stromal subsets, follicular dendritic cells and fibroblastic reticular cells, play crucial roles in the formation of tissue compartments within SLOs, i.e., the follicle and T zone, respectively. Although stromal cells in the anlagen are essential for SLO development, the relationship between these primordial cells and the subsets in adulthood remains poorly understood. In addition, the roles of stromal cells in the entry of antigens into the compartments through some tissue structures peculiar to SLOs remain unclear. A recently identified stromal subset, marginal reticular cells (MRCs), covers the margin of SLOs that are primarily located in the outer edge of follicles and construct a unique reticulum. MRCs are closely associated with specialized endothelial or epithelial structures for antigen transport. The similarities in marker expression profiles and successive localization during development suggest that MRCs directly descend from organizer stromal cells in the anlagen. Therefore, MRCs are thought to be a crucial stromal component for the organization and function of SLOs. PMID:22807928

  16. Interleukin-33 and Interferon-? Counter-Regulate Group 2 Innate Lymphoid Cell Activation during Immune Perturbation.

    PubMed

    Molofsky, Ari B; Van Gool, Frédéric; Liang, Hong-Erh; Van Dyken, Steven J; Nussbaum, Jesse C; Lee, Jinwoo; Bluestone, Jeffrey A; Locksley, Richard M

    2015-07-21

    Group 2 innate lymphoid cells (ILC2s) and regulatory T (Treg) cells are systemically induced by helminth infection but also sustain metabolic homeostasis in adipose tissue and contribute to tissue repair during injury. Here we show that interleukin-33 (IL-33) mediates activation of ILC2s and Treg cells in resting adipose tissue, but also after helminth infection or treatment with IL-2. Unexpectedly, ILC2-intrinsic IL-33 activation was required for Treg cell accumulation in vivo and was independent of ILC2 type 2 cytokines but partially dependent on direct co-stimulatory interactions via ICOSL-ICOS. IFN-? inhibited ILC2 activation and Treg cell accumulation by IL-33 in infected tissue, as well as adipose tissue, where repression increased with aging and high-fat diet-induced obesity. IL-33 and ILC2s are central mediators of type 2 immune responses that promote tissue and metabolic homeostasis, and IFN-? suppresses this pathway, likely to promote inflammatory responses and divert metabolic resources necessary to protect the host. PMID:26092469

  17. Phenotypic characterisation of peripheral blood lymphoid cells in people exposed to fibrous zeolite.

    PubMed Central

    Ozesmi, M; Karlsson-Parra, A; Hillerdal, G; Forsum, U

    1986-01-01

    Among inhabitants of the village of Karain in Turkey there is an extremely high incidence of malignant mesothelioma, most probably due to exposure to erionite, which is a fibrous zeolite and similar in appearance and properties to asbestos. This mineral may be found in the dust in the village. To characterise possible disturbances in the immune system of people exposed to fibrous zeolite, a phenotypic characterisation of lymphoid cells in the peripheral blood of 74 immigrants to Sweden from Karain was performed. Compared with normal controls, the mean percentages of Leu 4+ cells (Pan-T) and Leu 3a+ cells ("helper/inducer" T cells) were significantly decreased, whereas the mean percentage of Leu 2a+ cells ("suppressor/cytotoxic" T cells) was normal, leading to a significant reduction of the Leu 3a/Leu 2a subset ratio. The percentage of B cells (Leu 12+ cells) was significantly increased, whereas the percentages of both HLA-DR+ and HLA-DQ+ cells were normal. The percentage of natural killer cells (NK) and killer (K) cells as defined by the monoclonal anti-Leu 7 and anti-Leu 11b were also normal. These findings indicate that exposure to fibrous zeolite causes a numerical imbalance between the two phenotypically different T cell subsets similar to that seen in asbestos exposed individuals. PMID:3026434

  18. The Neurotrophic Receptor Ntrk2 Directs Lymphoid Tissue Neovascularization during Leishmania donovani Infection

    PubMed Central

    Dalton, Jane E.; Glover, Amy C.; Hoodless, Laura; Lim, Eng-Kiat; Beattie, Lynette; Kirby, Alun; Kaye, Paul M.

    2015-01-01

    The neurotrophic tyrosine kinase receptor type 2 (Ntrk2, also known as TrkB) and its ligands brain derived neurotrophic factor (Bdnf), neurotrophin-4 (NT-4/5), and neurotrophin-3 (NT-3) are known primarily for their multiple effects on neuronal differentiation and survival. Here, we provide evidence that Ntrk2 plays a role in the pathologic remodeling of the spleen that accompanies chronic infection. We show that in Leishmania donovani-infected mice, Ntrk2 is aberrantly expressed on splenic endothelial cells and that new maturing blood vessels within the white pulp are intimately associated with F4/80hiCD11bloCD11c+ macrophages that express Bdnf and NT-4/5 and have pro-angiogenic potential in vitro. Furthermore, administration of the small molecule Ntrk2 antagonist ANA-12 to infected mice significantly inhibited white pulp neovascularization but had no effect on red pulp vascular remodeling. We believe this to be the first evidence of the Ntrk2/neurotrophin pathway driving pathogen-induced vascular remodeling in lymphoid tissue. These studies highlight the therapeutic potential of modulating this pathway to inhibit pathological angiogenesis. PMID:25710496

  19. Secondary lymphoid tissue chemokine (SLC/CCL21)/CCR7 signaling regulates fibrocytes in renal fibrosis

    PubMed Central

    Sakai, Norihiko; Wada, Takashi; Yokoyama, Hitoshi; Lipp, Martin; Ueha, Satoshi; Matsushima, Kouji; Kaneko, Shuichi

    2006-01-01

    Fibrocytes are a distinct population of bloodborne cells that share markers of leukocytes as well as mesenchymal cells. We hypothesized that CCR7-positive fibrocytes migrate into the kidney in response to secondary lymphoid tissue chemokine (SLC/CCL21) and contribute to renal fibrosis. To investigate this hypothesis, renal fibrosis was induced by unilateral ureteral obstruction in mice. A considerable number of fibrocytes dual-positive for CD45 and type I collagen (ColI) or CD34 and ColI infiltrated the interstitium, reaching a peak on day 7. Most fibrocytes were positive for CCR7, and CCL21/CCR7 blockade reduced the number of infiltrating fibrocytes. CCL21 and MECA79 dual-positive vessels were also detected in the interstitium. The blockade of CCL21/CCR7 signaling by anti-CCL21 antibodies reduced renal fibrosis, which was confirmed by a decrease in fibrosis in CCR7-null mice with concomitant reduction in renal transcripts of pro ?1 chain of ColI and TGF-?1. The number of F4/80-positive macrophages decreased along with renal transcripts of monocyte chemoattractant protein 1 (MCP-1/CCL2) after the blockade of CCL21/CCR7 signaling. These findings suggest that CCR7-positive fibrocytes infiltrate the kidney via CCL21-positive vessels, thereby contributing to the pathogenesis of renal fibrosis. Thus, the CCL21/CCR7 signaling of fibrocytes may provide therapeutic targets for combating renal fibrosis. PMID:16966615

  20. Control of Dichotomic Innate and Adaptive Immune Responses by Artery Tertiary Lymphoid Organs in Atherosclerosis

    PubMed Central

    Weih, Falk; Gräbner, Rolf; Hu, Desheng; Beer, Michael; Habenicht, Andreas J. R.

    2012-01-01

    Tertiary lymphoid organs (TLOs) emerge in tissues in response to non-resolving inflammation such as chronic infection, graft rejection, and autoimmune disease. We identified artery TLOs (ATLOs) in the adventitia adjacent to atherosclerotic plaques of aged hyperlipidemic ApoE?/? mice. ATLOs are structured into T cell areas harboring conventional dendritic cells and monocyte-derived DCs; B cell follicles containing follicular dendritic cells within activated germinal centers; and peripheral niches of plasma cells. ATLOs also show extensive neoangiogenesis, aberrant lymphangiogenesis, and high endothelial venule (HEV) neogenesis. Newly formed conduit networks connect the external lamina of the artery with HEVs in T cell areas. ATLOs recruit and generate lymphocyte subsets with opposing activities including activated CD4+ and CD8+ effector T cells, natural and induced CD4+ T regulatory (nTregs; iTregs) cells as well as B-1 and B-2 cells at different stages of differentiation. These data indicate that ATLOs organize dichotomic innate and adaptive immune responses in atherosclerosis. In this review we discuss the novel concept that dichotomic immune responses toward atherosclerosis-specific antigens are carried out by ATLOs in the adventitia of the arterial wall and that malfunction of the tolerogenic arm of ATLO immunity triggers transition from silent autoimmune reactivity to clinically overt disease. PMID:22783198

  1. Acute myeloid and chronic lymphoid leukaemias and exposure to low-level benzene among petroleum workers

    PubMed Central

    Rushton, L; Schnatter, A R; Tang, G; Glass, D C

    2014-01-01

    Background: High benzene exposure causes acute myeloid leukaemia (AML). Three petroleum case–control studies identified 60 cases (241 matched controls) for AML and 80 cases (345 matched controls) for chronic lymphoid leukaemia (CLL). Methods: Cases were classified and scored regarding uncertainty by two haematologists using available diagnostic information. Blinded quantitative benzene exposure assessment used work histories and exposure measurements adjusted for era-specific circumstances. Statistical analyses included conditional logistic regression and penalised smoothing splines. Results: Benzene exposures were much lower than previous studies. Categorical analyses showed increased ORs for AML with several exposure metrics, although patterns were unclear; neither continuous exposure metrics nor spline analyses gave increased risks. ORs were highest in terminal workers, particularly for Tanker Drivers. No relationship was found between benzene exposure and risk of CLL, although the Australian study showed increased risks in refinery workers. Conclusion: Overall, this study does not persuasively demonstrate a risk between benzene and AML. A previously reported strong relationship between myelodysplastic syndrome (MDS) (potentially previously reported as AML) at our study's low benzene levels suggests that MDS may be the more relevant health risk for lower exposure. Higher CLL risks in refinery workers may be due to more diverse exposures than benzene alone. PMID:24357793

  2. Reappraisal of histogenesis in the bursal lymphoid follicle of the chicken.

    PubMed

    Lupetti, M; Dolfi, A; Giannessi, F; Bianchi, F; Michelucci, S

    1990-03-01

    The development of the bursal follicle and the appearance of the follicle-associated epithelial (FAE) cell and the reticuloepithelial (REp) cell were studied. The stages of development of the bursal follicle were observed by light and electron microscopy; an anticytokeratin monoclonal antibody was also used. At the beginning of follicle development, a mesenchymal cell cluster is observed in the tunica propria; the cluster becomes wedged in a niche of the surface epithelium, and gradually it is completely surrounded by the epithelium itself, which closes under the clump of mesenchymal cells. The epithelial cells lying upon the mesenchymal clump become necrotic, and a number of mesenchymal cells bulge out, forming the FAE cells. The epithelial cells that have closed under the mesenchymal nodule become stratified and form the REp cells; they become star-shaped because the medullary-lymphoid cells grow between them. Finally, the cortex is formed, possibly as a result of the migration of medullary cells before they peripheralize. It is concluded that FAE cells are not specialized epithelial cells, as they do not react to an anticytokeratin monoclonal antibody; on the contrary, they are formed by mesenchymal stemcells that bulge into the lumen and change their character after moving into the epithelium. The REp cells appear in the follicular primordium shortly after the bursal follicle begins to develop; the pronounced reactivity of the REp cells to an anticytokeratin monoclonal antibody supports the hypothesis of their epithelial origin. PMID:1690947

  3. KAP1 regulates gene networks controlling mouse B lymphoid cell differentiation and function

    PubMed Central

    de Sio, Francesca R. Santoni; Massacand, Joanna; Barde, Isabelle; Offner, Sandra; Corsinotti, Andrea; Kapopoulou, Adamandia; Bojkowska, Karolina; Dagklis, Antonis; Fernandez, Marylise; Ghia, Paolo; Thomas, James H.; Pinschewer, Daniel; Harris, Nicola; Trono, Didier

    2013-01-01

    Chromatin remodeling is fundamental for B cell differentiation. Here, we explored the role in this process of KAP1, the cofactor of KRAB-ZFP transcriptional repressors. B lymphoid-specific Kap1 knockout mice displayed reduced numbers of mature B cells, lower steady-state levels of antibodies and accelerated rates of decay of neutralizing antibodies following viral immunization. Transcriptome analyses of Kap1-deleted B splenocytes revealed an upregulation of PTEN, the enzymatic counter-actor of PIK3 signaling, and of genes encoding DNA damage response factors, cell-cycle regulators and chemokine receptors. ChIP/seq studies established that KAP1 bound at or close to a number of these genes, and controlled chromatin status at their promoters. Genome-wide, KAP1-binding sites avoided active B cell-specific enhancers and were enriched in repressive histone marks, further supporting a role for this molecule in gene silencing in vivo. Likely responsible for tethering KAP1 to at least some of these targets, a discrete subset of KRAB-ZFPs is enriched in B lymphocytes. This work thus reveals the role of KRAB/KAP1-mediated epigenetic regulation in B cell development and homeostasis. PMID:22452978

  4. KAP1 regulates gene networks controlling mouse B-lymphoid cell differentiation and function.

    PubMed

    Santoni de Sio, Francesca R; Massacand, Joanna; Barde, Isabelle; Offner, Sandra; Corsinotti, Andrea; Kapopoulou, Adamandia; Bojkowska, Karolina; Dagklis, Antonis; Fernandez, Marylise; Ghia, Paolo; Thomas, James H; Pinschewer, Daniel; Harris, Nicola; Trono, Didier

    2012-05-17

    Chromatin remodeling is fundamental for B-cell differentiation. In the present study, we explored the role of KAP1, the cofactor of KRAB-ZFP transcriptional repressors, in this process. B-lymphoid-specific Kap1-KO mice displayed reduced numbers of mature B cells, lower steady-state levels of Abs, and accelerated rates of decay of neutralizing Abs after viral immunization. Transcriptome analyses of Kap1-deleted B splenocytes revealed an up-regulation of PTEN, the enzymatic counteractor of PIK3 signaling, and of genes encoding DNA-damage response factors, cell-cycle regulators, and chemokine receptors. ChIP/seq studies established that KAP1 bound at or close to several of these genes and controlled chromatin status at their promoters. Genome wide, KAP1 binding sites lacked active B cell-specific enhancers and were enriched in repressive histone marks, further supporting a role for this molecule