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Biomedical subjects

Guha Krishnaswamy

Publications and source records attributed to Guha Krishnaswamy.

32 records · Page 2Linked to original sources
PubMed2004

Dermatology for the practicing allergist: Tinea pedis and its complications.

Tinea pedis is a chronic fungal infection of the feet, very often observed in patients who are immuno-suppressed or have diabetes mellitus. The practicing allergist may be called upon to treat this disease for various reasons. Sometimes tinea infection may be mistaken for atopic dermatitis or allergic eczema. In other patients, tinea pedis may complicate allergy and asthma and may contribute to refractory atopic disease. Patients with recurrent cellulitis may be referred to the allergist/immunologist for an immune evaluation and discovered to have tinea pedis as a predisposing factor. From a molecular standpoint, superficial fungal infections may induce a type2 T helper cell response (Th2) that can aggravate atopy. Th2 cytokines may induce eosinophil recruitment and immunoglobulin E (IgE) class switching by B cells, thereby leading to exacerbation of atopic conditions. Three groups of fungal pathogens, referred to as dermatophytes, have been shown to cause tinea pedis: Trychophyton sp, Epidermophyton sp, and Microsporum sp. The disease manifests as a pruritic, erythematous, scaly eruption on the foot and depending on its location, three variants have been described: interdigital type, moccasin type, and vesiculobullous type. Tinea pedis may be associated with recurrent cellulitis, as the fungal pathogens provide a portal for bacterial invasion of subcutaneous tissues. In some cases of refractory asthma, treatment of the associated tinea pedis infection may induce remission in airway disease. Very often, protracted topical and/or oral antifungal agents are required to treat this often frustrating and morbid disease. An evaluation for underlying immuno-suppression or diabetes may be indicated in patients with refractory disease.

Journal Article↗
PubMed2004

Inhibition of GM-CSF production in fibroblast-monocyte coculture by prednisone and effects of rhGM-CSF on human lung fibroblasts.

Fibroblasts play a sentinel role in asthmatic disease. They are the main constituents of connective tissue and are increased in number in the asthmatic lung. They are also capable of secreting a diverse repertoire of cytokines and are able to be activated by pro-inflammatory cytokines and cell-cell contact. Previously we have reported that normal human lung fibroblasts (NHLF) can be activated by monocytes (U937) through cell-cell contact to produce GM-CSF. Here we show that GM-CSF production from NHLF activated by monocyte contact is inhibited by prednisone, a synthetic glucocorticoid used in the treatment of asthma. GM-CSF is an acidic glycoprotein that potentiates development of cells in the granulocyte and macrophage lineage and is secreted at sites of peripheral inflammation. The receptor for GM-CSF was found on NHLF by flow cytometry and was able to be up-regulated by interleukin (IL)-1 beta, tumor necrosis factor (TNF)-alpha and recombinant human (rh) GM-CSF. To test autocrine effects of GM-CSF on fibroblasts, rh GM-CSF was used in proliferation studies and was found to decrease fibroblast proliferation. Prednisone was used to block NF-kappaB activation and GM-CSF gene expression as well. These data indicate mechanism of action and treatment for cell-cell contact mediated inflammation of infiltrating monocytes with fibroblasts as seen in asthma and other diseases like graft versus host disease.

Anti-Inflammatory Agents↗
PubMed2004

The role of human mast cell-derived cytokines in eosinophil biology.

Eosinophil-mediated diseases, such as allergic asthma, eosinophilic fasciitis, and certain hypersensitivity pulmonary disorders, are characterized by eosinophil infiltration and tissue injury. Mast cells and T cells often colocalize to these areas. Recent data suggest that mast cells can contribute to eosinophil-mediated inflammatory responses. Activation of mast cells can occur by antigen and immunoglobulin E (IgE) via the high-affinity receptor (FcepsilonRI) for IgE. The liberation of proteases, leukotrienes, lipid mediators, and histamine can contribute to tissue inflammation and allow recruitment of eosinophils to tissue. In addition, the synthesis and expression of a plethora of cytokines and chemokines (such as granulocyte-macrophage colony-stimulating factor [GM-CSF], interleukin-1 [IL-1], IL-3, IL-5, tumor necrosis factor-alpha [TNF-alpha], and the chemokines IL-8, regulated upon activation normal T cell expressed and secreted [RANTES], monocyte chemotactic protein-1 [MCP-1], and eotaxin) by mast cells can influence eosinophil biology. Stem cell factor (SCF)-c-kit, cytokine-cytokine receptor, and chemokine-chemokine receptor (CCR3) interactions leading to nuclear factor kappaB (NF-kappaB), mitogen-activated protein kinase (MAPK) expression, and other signaling pathways can modulate eosinophil function. Eosinophil hematopoiesis, activation, survival, and elaboration of mediators can all be regulated thus by mast cells in tissue. Moreover, because eosinophils can secrete SCF, eosinophils can regulate mast cell function in a paracrine manner. This two-way interaction between eosinophils and mast cells can pave the way for chronic inflammatory responses in a variety of human diseases. This review summarizes this pivotal interaction between human mast cells and eosinophils.

Cell Adhesion Molecules↗
PubMed2003

Human lung fibroblasts express interleukin-6 in response to signaling after mast cell contact.

Asthma is a chronic inflammatory disease of the airways. Mast cell-derived cytokines may mediate both airway inflammation and remodeling. It has also been shown that fibroblasts can be the source of proinflammatory cytokines. In the human airways, mast cell-fibroblast interactions may have pivotal effects on modulating inflammation. To study this further, we cocultured normal human lung fibroblasts (NHLF) with a human mast cell line (HMC-1) and assayed for production of interleukin (IL)-6, an important proinflammatory cytokine. When cultured together, NHLF/HMC-1 contact induced IL-6 secretion. Separation of HMC-1 and NHLF cells by a porous membrane inhibited this induction. HMC-1-derived cellular membranes caused an increase in IL-6 production in NHLF. Activation of p38 MAPK was also seen in cocultures by Western blot, whereas IL-6 production in cocultures was significantly inhibited by the p38 inhibitor SB203580. IL-6 production in cocultures was minimally inhibited by a chemical inhibitor of nuclear factor-kappaB (Bay11), indicating that nuclear factor-kappaB may have a minimal role in signaling IL-6 production in mast cell/fibroblasts cocultures. Blockade of inter-cellular adhesion molecule-1, tumor necrosis factor-RI, and surface IL-1beta with neutralizing antibodies failed to significantly decrease IL-6 production in our coculture, indicating that other receptor-ligand associations may be responsible for this activation. These novel studies reveal the importance of cell-cell interactions in the complex milieu of airway inflammation.

Anti-Inflammatory Agents↗
PubMed2003

Autoimmune progesterone dermatitis and its manifestation as anaphylaxis: a case report and literature review.

OBJECTIVE: Autoimmune progesterone dermatitis is a rare cyclic premenstrual reaction to progesterone produced during the luteal phase of a woman's menstrual cycle with a variety of presentations including erythema multiforme, eczema, urticaria, angioedema, and progesterone-induced anaphylaxis. We present a case of progesterone-induced anaphylaxis and a review of literature focusing on its diagnosis and therapy. DATA SOURCES: We surveyed all the literature in English back to 1921 when the first case was published. First, we researched the terms progesterone anaphylaxis, autoimmune progesterone dermatitis, cyclic urticaria, using the PubMed resource. Then we included articles found within these publications' reference sections. STUDY SELECTION: We selected articles based on whether the cases described appeared to fit the description of the entity autoimmune progesterone dermatitis. All cases included had dermatologic reactions occurring during the luteal phase of the menstrual period, positive skin or intramuscular reactions to progesterone, and treatment amenable to anovulatory agents and/or hysterectomy with bilateral salpingo-oophorectomy. RESULTS: We found approximately 50 published cases of autoimmune progesterone dermatitis, and only nine known cases of its manifestation as anaphylaxis. These cases, including the case described by us, are summarized, and successful diagnostic and therapeutic approaches in the literature are reviewed. CONCLUSIONS: Autoimmune progesterone dermatitis is a rare entity associated with progesterone production of the luteal phase of a woman's menstrual cycle. It can be diagnosed using intradermal or intramuscular progesterone tests and can be treated by disrupting the ovulation cycle using specific medications or by oopherectomy.

Adult↗
PubMed2003

Regulation of nitric oxide production from macrophages by lipopolysaccharide and catecholamines.

Catecholamines are elaborated in stress responses to mediate vasoconstriction, and elevate systemic vascular resistance and blood pressure. They are elaborated in disorders such as sepsis, cocaine abuse, and cardiovascular disease. The aim of the study was to determine whether catecholamines affect nitric oxide (NO) production, as NO is a vasodilator and counteracts the harmful effects of catecholamines. RAW264.7 macrophage cells were cultured with lipopolysaccharide (LPS)+/-epinephrine, norepinephrine, and dopamine at 5x10(-6)M concentrations for 24h. Supernatants were harvested for measuring NO by spectrophotometry using the Greiss reagent and cells were harvested for detecting inducible NO synthase (iNOS) by Western blot. NO production in RAW 264.7 macrophages was increased significantly by addition of LPS (0.5-10ng/ml) in a dose-dependent fashion. The NO production induced by LPS was further enhanced by epinephrine and norepinephrine, and to a lesser extent by dopamine. These increases in NO correlated with expression of iNOS protein in these cells. The enhancing effect of iNOS synthesis by epinephrine and norepinephrine on LPS-induced macrophages was down regulated by beta-adrenoceptor antagonist, propranolol, and dexamethasone. The results suggest that catecholamines have a synergic effect on LPS in induction of iNOS synthesis and NO production, and this may mediate some of the vascular effects of infection. These data support a novel role for catecholamines in disorders such as septic shock and cocaine use, and indicate that beta-adrenoceptor antagonists and glucocorticoids may be used therapeutically for modulation of the catecholamine-NO axis in disease states.

Adrenergic beta-Antagonists↗
PubMed2003

GM-CSF induction in human lung fibroblasts by IL-1beta, TNF-alpha, and macrophage contact.

Fibroblast-derived cytokines may play crucial roles in airway inflammation. In this study, we analyzed expression of the inflammatory cytokine, granulocyte-macrophage colony-stimulating factor (GM-CSF), a major eosinophilopoietin, by normal human lung fibroblast (NHLF) cells and its regulation by monokines and macrophage contact. NHLFs were stimulated with interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha) and were cocultured with the U937 myelomonocytic cell line. The expression of GM-CSF transcripts was analyzed by reverse transcription-polymerase chain reaction (RT-PCR), and GM-CSF protein was detected by ELISA. Nuclear translocation of nuclear factor-kappaB (NF-kappaB), an important transcription factor for inflammatory gene expression, was assessed by electrophoretic mobility shift assay (EMSA). Both IL-1beta and TNF-alpha significantly enhanced the production of GM-CSF by NHLF. Coculturing of peripheral blood mononuclear cells (PBMC) with NHLF induced GM-CSF expression. This phenomenon was also seen on coculturing U937 cells or membranes derived from U937 with NHLF but was inhibited when the two types of cells were separated, suggesting a need for cell-cell contact. U937 membranes, as well as IL-1beta and TNF-alpha, induced nuclear translocation of NF-kappaB. These data support a prominent role for macrophage-fibroblast interactions in airway inflammation and fibrosis.

Antibodies, Monoclonal↗
PubMed2003

C-reactive protein as a novel biomarker. Reactant can flag atherosclerosis and help predict cardiac events.

C-reactive protein (CRP) is a relatively nonspecific marker of inflammation. However, it can be used to monitor the severity and progression of some well-defined cardiovascular diseases. For example, it can predict serious events in patients with coronary artery disease (CAD) who are hospitalized with acute coronary syndrome, myocardial infarction (MI), or advanced peripheral vascular disease. In this article, the authors review the role of CRP in the diagnosis, monitoring, and treatment of various forms of ischemic and inflammatory cardiovascular disease.

Arteriosclerosis↗
PubMed2003

Acinetobacter baumannii pneumonia: a case report and review of the literature.

Bacteria that constitute the genus Acinetobacter were originally identified in the first decade of the 20th century. However, it was not until the last decade that its role as an opportunistic pathogen was fully appreciated. It is now clear that Acinetobacter is an important cause of nosocomial infection and contributes significantly to the patient's morbidity and mortality. The prevalence of infection with A. baumannii has increased significantly during the last decade. At the same time, A. baumannii has developed one of the most impressive patterns of antibiotic resistance ever observed, establishing it as an important nosocomial pathogen. It has been nicknamed the "Gram-negative MRSA" because of its frequent resistance to commonly used antibiotics. Infection with A. baumannii should be suspected in hospitalized patients who are not responding to initial empiric antibiotic treatment, and the therapeutic approach should be customized according to when the pathogen is isolated.

Acinetobacter Infections↗
PubMed2002

Regulation of eosinophil-active cytokine production from human cord blood-derived mast cells.

Human mast cells are multifunctional tissue-dwelling cells that play a crucial role in eosinophil-dependent disorders, such as asthma and parasitic diseases, by the secretion of eosinophil-active mediators. Mast cell-derived cytokines, generated in response to cross-linking of the high-affinity IgE receptor, can regulate eosinophil activation, survival, and chemotaxis. In this study, mast cells generated from human cord blood progenitors (stem cells) were studied for eosinophil-active inflammatory cytokine expression. Cord blood-derived mast cells (CBDMC) expressed typical intracellular scroll granules and microvilli-like structures on their cell surfaces, demonstrated the presence of tryptase, and elaborated prostaglandin D2 (PGD2) after cross-linkage of the high-affinity receptor for IgE (FcepsilonRI). CBDMC expressed tumor necrosis factor-alpha (TNF-alpha) and the eosinophil-active growth factors, interleukin-5 (IL-5) and granulocyte-macrophage colony-stimulating factor (GM-CSF) after activation. (IL-1beta greatly enhanced IgE-dependent production of these cytokines in response to FcepsilonRI cross-linkage, suggesting a role for bystander/phagocytic cells in modulating mast cell function. In contrast, interferon-alpha (IFN-alpha) inhibited IL-5 and GM-CSF generation, and the glucocorticoid, dexamethasone (Dex), inhibited production of IL-5 and GM-CSF from CBDMC. A macrophage-mast cell-eosinophil axis may exist in vivo that may be susceptible to pharmacologic manipulation.

Cells, Cultured↗
PubMedDate not supplied

Urticaria and urticarial vasculitis.

Urticaria and urticarial vasculitis may be triggered by allergens, infection, autoimmunity and other immunological conditions. Careful evaluation, skin biopsy and specific laboratory tests can assist in diagnosis. The appropriate use of antihistamines, glucocorticoids, and other immunomodulators are discussed.

Angioedema↗
PubMedDate not supplied

Angiopoietin-1 inhibits doxorubicin-induced human umbilical vein endothelial cell death by modulating fas expression and via the PI3K/Akt pathway.

Angiopoietin-1 (Ang-1) is essential for the maturation of blood vessels during vasculogenesis. Besides angiogenesis, recent publications indicate that Ang-1 is also a potent survival factor for endothelial cells; however, the mechanisms by which pathways remain elusive. Doxorubicin (DOX) is a powerful anticancer drug, but its use is severely restricted by its cardiotoxicity. The authors report here that Ang-1 inhibits DOX-induced cell death in human umbilical vein endothelial cells (HUVECs). Interestingly, the DOX-induced up-regulation in Fas (CD95/APO-1) and Fas ligand expression could be blocked by Ang-1, indicating a pivotal role of Ang-1 in DOX-induced Fas and Fas ligand expression. In addition, the prevention of cell death in this model system seems to be dependent on the activation of phosphatidylinositol 3-kinase (PI3K)/Akt, as Ang-1 fails to inhibit DOX-induced cell death while PI3K/Akt pathway was blocked by the PI3K inhibitor LY294002. Moreover, Ang-1 inhibits DOX-induced up-regulation of p53 through PI3K/Akt. Therefore, Ang-1 is a potent inhibitor for DOX-induced cell death through Fas and PI3K/Akt-mediated pathways.

Angiopoietin-1↗