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  • The American Association of Immunologists (AAI)  (13)
  • Institute of Physics Publishing (IOP)  (9)
  • Blackwell Science Ltd  (6)
  • Cold Spring Harbor Laboratory Press  (4)
  • 1
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Science Ltd
    Scandinavian journal of immunology 53 (2001), S. 0 
    ISSN: 1365-3083
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Morphological and functional heterogeneity of the splenic macrophage (Mφ) population was studied in Leishmania donovani (LD) infected BALB/c mice. On a discontinuous percoll gradient two distinct Mφ populations were separated. They differed significantly in size as evident from Scanning Electron Microscopy (SEM). Morphologically, the bigger Mφ (LM) showed surface projections, whereas the smaller Mφ (SM) was round. As regards the antigen-presenting abilities, the LM of infected animals showed defective antigen-presenting abilities at a later stage of the disease, i.e. 6 months post infection (6I-LM) but not earlier, whereas the SM population remained functionally intact throughout the course of the infection. Further, the 6I-LM showed a much enhanced Ad status as compared to their controls. Interestingly, both the 6I-LM and the control set showed a comparable level of binding of a known Ad restricted peptide. Despite the presence of sufficient Ad molecules and the ability to bind the appropriate peptide, 6I-LM were unable to stimulate peptide specific T-cell hybridoma. Further, the 6I-LM showed an increase in membrane fluidity and distorted morphology with membrane fissure and blebs as evident from SEM. It is possible that an increase in the membrane fluidity may lead to the defective antigen-presenting ability of 6I-LM. Thus, the LD infection functionally keep the 6I-LM out of antigen presentation and this may contribute to the defective cell mediated immune response in leishmaniasis.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1365-3083
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: The expression of chemokines and chemokine receptors was studied in Leishmania donovani (LD)-infected human mononuclear phagocytes and the human monocytic cell line THP1. Our studies showed that LD infection caused the upregulation of three β chemokines (macrophage inflammatory protein-1 alpha (MIP-1α), MIP-1β and RANTES (regulated on activation normal T cell expressed and secreted)), one α chemokine (interleukin-8 (IL-8)) and the CC chemokine receptor 5 (CCR5) but not CCR1, as evident from reverse transcriptase-polymerase chain reaction (RT-PCR) analysis. The CCR5 upregulation in human mononuclear phagocytes and THP1 cells was also evident by confocal microscopy. The possible association of such upregulation in relation to Leishmania and human immunodeficiency virus (HIV) coinfection was discussed.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Science Ltd
    International journal of dermatology 39 (2000), S. 0 
    ISSN: 1365-4632
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Science Ltd
    International journal of dermatology 43 (2004), S. 0 
    ISSN: 1365-4632
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Tetracyclines (TCN) were introduced in 1948 as broad-spectrum antibiotics that may be used in the treatment of many common infections in children and adults. One of the side-effects of tetracyclines is incorporation into tissues that are calcifying at the time of their administration. They have the ability to chelate calcium ions and to be incorporated into teeth, cartilage and bone, resulting in discoloration of both the primary and permanent dentitions. This permanent discoloration varies from yellow or gray to brown depending on the dose or the type of the drug received in relation to body weight. Minocycline hydrochloride, a semisynthetic derivative of tetracycline often used for the treatment of acne, has been shown to cause pigmentation of a variety of tissues including skin, thyroid, nails, sclera, teeth, conjunctiva and bone. Adult-onset tooth discoloration following long-term ingestion of tetracycline and minocycline has also been reported. The remarkable side-effect of minocycline on the oral cavity is the singular occurrence of “black bones”, “black or green roots” and blue-gray to gray hue darkening of the crowns of permanent teeth. The prevalence of tetracycline and minocycline staining is 3–6%. The mechanism of minocycline staining is still unknown. Most of the reviewed literature consisted of case reports; longitudinal clinical trials are necessary to provide more information on the prevalence, severity, etiology and clinical presentation of tetracycline and TCN-derivative staining in the adult population.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1365-2486
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Biology , Energy, Environment Protection, Nuclear Power Engineering , Geography
    Notes: Two experiments assessed the effect of current and elevated levels of ultravioletB (UV-B) radiation on forage crop production. The effect of current levels of UV-B radiation was assessed by comparing the growth of eight cultivars of four legume and four grass species for three growing seasons (1994–96) under simulated sward conditions in the field. An exclusion system using cellulose diacetate or polyester covers provided comparable growing conditions for the plants, except for the presence or absence of ambient UV-B radiation, respectively. The second experiment studied the effect of elevated levels of UV-B on eight cultivars of two legume and two grass species in the greenhouse under simulated sward conditions. Natural lighting with sufficient supplemental light was used to provide ideal growing conditions for a 16-h day length. Separate sets of UV lights were installed to provide UV-B levels at approximately the same intensity as would be found in mid summer, and 33% and 66% more than this value. A fourth treatment consisted of removing UV-B radiation by using a polyester filter. Plant production was measured in both experiments. In 1994, field herbage yields from all young grass and legume seedlings were not significantly affected by the exclusion of ambient UV-B radiation, with the exception of alfalfa. Intra-specific variations with alfalfa yields were found for reduced levels of UV-B radiation. In general, these trends persisted as stands matured during two post seeding years. In the second experiment, no significant differences were observed for all tested species with increasing levels of UV-B radiation, except with some alfalfa cultivars and one birdsfoot trefoil cultivar. Collectively, these results demonstrate that in the northern latitudes young and mature plants of the studied species are resistant to current and potentially higher levels of solar UV-B radiation, with the exception of some alfalfa cultivars. The yield of these cultivars increased under enhanced levels of UV-B radiation in the greenhouse and decreased when UV-B was excluded in the field.
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  • 6
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Science Ltd
    International journal of dermatology 39 (2000), S. 0 
    ISSN: 1365-4632
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: In November 1997, approximately 1 year before being evaluated at the Mayo Clinic, Rochester, a 63-year-old woman presented with erosive tongue lesions that were diagnosed by her physician as oral lichen planus. The lesions responded well to 3 months of treatment with systemic and topical corticosteroids and topical antiyeast medication. She stopped taking the medications and had a relapse. A few months after the oral lesions developed, her left eyelid became ptotic. Results of magnetic resonance imaging of her brain were normal, and the ptosis resolved spontaneously after 2 weeks. One year later, her right eyelid began to droop, and the results of edrophonium testing were positive. She was prescribed prednisone, 30 mg daily, and pyridostigmine, as needed. The ptosis improved, but never fully resolved. Radiography revealed a left ‘‘thyroid nodule,’' but computed tomography did not show a mediastinal mass. She was advised to have the ‘‘nodule’' removed surgically and came to the Mayo Clinic, Rochester, for a second opinion.Her medical history was significant for the following: tinnitus, glaucoma, early bilateral cataracts, and long-standing hypertension, for which she took losartan, 50 mg twice daily. Other medications included: prednisone, 30 mg daily; pyridostigmine as needed; famotidine, 40 mg daily; and eyedrops for glaucoma. She denied any history of hyperthyroidism or hypothyroidism, head and neck irradiation, family history of thyroid disease, or diplopia. Hepatitis serologic studies revealed hepatitis B exposure and recovery, hepatitis C immunity, and a previous hepatitis A viral infection.On examination at the Mayo Clinic, Rochester, an erosive hypertrophic plaque was noted on the posterior dorsal half of the tongue, and vesicles and erythematous erosions on the hard and soft palates ( 〈link href="#f2.1"〉Fig. 1a). A lace-like white pattern was seen on the buccal mucosa bilaterally, and a small erosive patch on the left buccal mucosa ( 〈link href="#f2.1b"〉Fig. 1b). Ocular and nasal mucous membranes were normal in appearance, and there were no pertinent skin findings. Dermatopathologic examination of an excisional biopsy specimen from the left dorsum of the tongue demonstrated an ulcer with epitheliomatous hyperplasia and a granulomatous reaction, presumably due to yeast infection. Silver staining showed hyphae and yeast at the base of the tongue ulcer. The results of the direct immunofluorescence study were negative and revealed no lichenoid changes on hematoxylin and eosin staining. Indirect immunofluorescence testing of the serum revealed a 1 : 80 titer of basement membrane zone antibodies, reflecting pemphigoid. This test was positive on repeat study. Salt-split skin on monkey esophagus revealed an epidermal pattern of basement membrane zone antibodies. Treatment included fluocinonide gel applied to the involved areas four times daily and oral antiyeast therapy (fluconazole, 200 mg once daily by mouth) while the rest of the evaluation was being completed.〈figure xml:id="f2.1"〉1(a)〈mediaResource alt="image" href="urn:x-wiley:00119059:IJD035-2:IJD_035_2_f1a"/〉Erosive hypertrophic tongue plaque.〈figure xml:id="f2.1b"〉 (b)  〈mediaResource alt="image" href="urn:x-wiley:00119059:IJD035-2:IJD_035_2_f1b"/〉Erosive patch on the buccal mucosa.As part of the evaluation of the ptosis, a myasthenia gravis antibody panel was performed. It revealed the following abnormalities: striated muscle antibody at 1 : 480 (reference range, 〈1 : 60), acetylcholine receptor binding antibody at 6.33 nmol/L (reference range, ≤ 0.02 nmol/L), acetylcholine receptor blocking antibody at 31% (reference range, 0–25%), and acetylcholine receptor modulating antibody at 100% (reference range, 0–20%), suggesting thymoma. Treatment included pyridostigmine, 30–45 mg 3–4 times daily, to control the myasthenia symptoms, while the ill-defined neck mass was being evaluated.A mildly enlarged thyroid was noted on physical examination. Hematology panel revealed thyroid-stimulating hormone (TSH) levels in the low normal range; the thyroid microsomal antibody was normal. Chest radiography showed minor tracheal deviation, and a previous computed tomogram showed what appeared to be a 3-cm enlarged mass in the thyroid. Ultrasonographically guided thyroid biopsy did not show malignancy, but a benign mesenchymal-type tumor was found and surgical excision was planned. Intraoperatively, a thymoma of the left cervical thymic tongue was found.At 6 months' follow-up, the ptosis and oral mucosal lesions had improved significantly, although she continued topical corticosteroid therapy intermittently for minor erosive oral disease.
    Type of Medium: Electronic Resource
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  • 7
    Publication Date: 2013-06-02
    Description: Comparative functional genomics studies the evolution of biological processes by analyzing functional data, such as gene expression profiles, across species. A major challenge is to compare profiles collected in a complex phylogeny. Here, we present Arboretum, a novel scalable computational algorithm that integrates expression data from multiple species with species and gene phylogenies to infer modules of coexpressed genes in extant species and their evolutionary histories. We also develop new, generally applicable measures of conservation and divergence in gene regulatory modules to assess the impact of changes in gene content and expression on module evolution. We used Arboretum to study the evolution of the transcriptional response to heat shock in eight species of Ascomycota fungi and to reconstruct modules of the ancestral environmental stress response (ESR). We found substantial conservation in the stress response across species and in the reconstructed components of the ancestral ESR modules. The greatest divergence was in the most induced stress, primarily through module expansion. The divergence of the heat stress response exceeds that observed in the response to glucose depletion in the same species. Arboretum and its associated analyses provide a comprehensive framework to systematically study regulatory evolution of condition-specific responses.
    Electronic ISSN: 1549-5469
    Topics: Biology , Medicine
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  • 8
    Publication Date: 2015-02-07
    Description: Many of the biological properties of C5a are mediated through activation of its receptor (C5aR1), the expression of which has been demonstrated convincingly on myeloid cells, such as neutrophils, monocytes, and macrophages. In contrast, conflicting results exist regarding C5aR1 expression in dendritic cells (DCs) and lymphoid lineage cells. In this article, we report the generation of a floxed GFP-C5aR1 reporter knock-in mouse. Using this mouse strain, we confirmed strong C5aR1 expression in neutrophils from bone marrow, blood, lung, and spleen, as well as in peritoneal macrophages. Further, we show C5aR1 expression in lung eosinophils, lung- and lamina propria–resident and alveolar macrophages, bone marrow–derived DCs, and lung-resident CD11b + and monocyte-derived DCs, whereas intestinal and pulmonary CD103 + DCs stained negative. Also, some splenic NKT cells expressed GFP, whereas naive NK cells and B2 cells lacked GFP expression. Finally, we did not observe any C5aR1 expression in naive or activated CD4 + Th cells in vitro or in vivo. Mating the floxed GFP-C5aR1 mouse strain with LysMCre mice, we were able to specifically delete C5aR1 in neutrophils and macrophages, whereas C5aR1 expression was retained in DCs. In summary, our findings suggest that C5aR1 expression in mice is largely restricted to cells of the myeloid lineage. The novel floxed C5aR1 reporter knock-in mouse will prove useful to track C5aR1 expression in experimental models of acute and chronic inflammation and to conditionally delete C5aR1 in immune cells.
    Print ISSN: 0022-1767
    Electronic ISSN: 1550-6606
    Topics: Medicine
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  • 9
    Publication Date: 2014-09-20
    Description: CD40 plays dual immunoregulatory roles in Leishmania major infection and tumor regression. The functional duality emerges from CD40-induced reciprocal p38MAPK and ERK-1/2 phosphorylations. Because phosphotyrosine-based signaling in hematopoietic cells is regulated by the phosphotyrosine phosphatase SHP-1, which is not implied in CD40 signaling, we examined whether SHP-1 played any roles in CD40-induced reciprocal signaling and anti-leishmanial function. We observed that a weaker CD40 stimulation increased SHP-1 activation. ERK-1/2 inhibition or p38MAPK overexpression inhibited CD40-induced SHP-1 activation. An ultra-low-dose, CD40-induced p38MAPK phosphorylation was enhanced by SHP-1 inhibition but reduced by SHP-1 overexpression. A reverse profile was observed with ERK-1/2 phosphorylation. SHP-1 inhibition reduced syk phosphorylation but increased lyn phosphorylation; syk inhibition reduced but lyn inhibition enhanced CD40-induced SHP-1 phosphorylation. Corroborating these findings, in L. major –infected macrophages, CD40-induced SHP-1 phosphorylation increased and SHP-1 inhibition enhanced CD40-induced p38MAPK activation and inducible NO synthase expression. IL-10 enhanced SHP-1 phosphorylation and CD40-induced ERK-1/2 phosphorylation but reduced the CD40-induced p38MAPK phosphorylation, whereas anti–IL-10 Ab exhibited reverse effects on these CD40-induced functions, identifying IL-10 as a crucial element in the SHP-1-MAPK feedback system. Lentivirally overexpressed SHP-1 rendered resistant C57BL/6 mice susceptible to the infection. Lentivirally expressed SHP-1 short hairpin RNA enhanced the CD40-induced L. major parasite killing in susceptible BALB/c mice. Thus, we establish an SHP-1–centered feedback system wherein SHP-1 modulates CD40-induced p38MAPK activation threshold and reciprocal ERK-1/2 activation, establishing itself as a critical regulator of CD40 signaling reciprocity and mechanistically re-emphasizing its role as a potential target against the diseases where CD40 is involved.
    Print ISSN: 0022-1767
    Electronic ISSN: 1550-6606
    Topics: Medicine
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  • 10
    Publication Date: 2015-09-05
    Description: Infection with antimony-resistant Leishmania donovani (Sb R LD) induces aggressive pathology in the mammalian hosts as compared with ones with antimony-sensitive L. donovani (Sb S LD) infection. Sb R LD, but not Sb S LD, interacts with TLR2/TLR6 to induce IL-10 by exploiting p50/c-Rel subunits of NF-B in infected macrophages (Ms). Most of the TLRs exploit the universal adaptor protein MyD88 to activate NF-B. We now show that infection of Ms from MyD88 –/– mice with Sb R LD gave rise to significantly higher intracellular parasite number coupled with elevated IL-10/IL-12 ratio in the culture supernatant as compared with infection in wild type (WT) Ms. These attributes were not seen with Sb S LD in similar experiments. Further, Sb R LD infection upregulated miR-466i, which binds with 3'-untranslated region, leading to the downregulation of MyD88. Infection of MyD88 –/– M or IL-12 –/– M with Sb R LD induced IL-10 surge at 4 h, whereas the same in WT M started from 12 h. Thus, absence of IL-12 in MyD88 –/– mice favored early binding of NF-B subunits to the IL-10 promoter, resulting in IL-10 surge. Infection of MyD88 –/– mice with Sb R LD showed significantly higher organ parasites coupled with ill-defined and immature hepatic granulomas, whereas in WT mice there were less organ parasites and the granulomas were well defined. From the survival kinetics it was observed that Sb R LD-infected MyD88 –/– mice died by 60 d postinfection, whereas the WT mice continued to survive. Our results demonstrate that Sb R LD has evolved a unique strategy to evade host antileishmanial immune repertoire by manipulating host MyD88 to its advantage.
    Print ISSN: 0022-1767
    Electronic ISSN: 1550-6606
    Topics: Medicine
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