Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0021051 (immunodeficiency)
 71,517 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Although the clinical and epidemiologic features of progressive disseminated histoplasmosis (PDH) in the acquired immunodeficiency syndrome (AIDS) have been well described, the pathologic and pulmonary aspects remain to be fully defined. A retrospective review of three patients and a prospective study of four more with PDH and AIDS recently admitted to an inner city hospital in a non-endemic area were used to elucidate these features more fully. All patients were men aged 23 to 46 years, born in endemic areas, who had immigrated to the US seven to 15 years before the onset of their illnesses. Five had been exposed to human immunodeficiency virus (HIV) through intravenous drug use (one was also a homosexual), and two through heterosexual contacts. Respiratory symptoms were evident in five of the seven patients, fever in seven, weight loss in seven, hepatomegaly in four, splenomegaly in three, peripheral adenopathy in three, and gastrointestinal symptoms in three. PDH was the initial or only opportunistic infection in five patients. Bilateral nodular infiltrates (4/7), bilateral interstitial infiltrates (2/7), and mediastinal adenopathy associated with pleural effusion (1/7) were the chest roentgenographic findings. Histoplasma capsulatum was isolated from five of five bronchoalveolar lavages, four of four transbronchial biopsies, one of one endobronchial biopsy, one of one brushing, one of one pleural biopsy, three of three lymph node biopsies, two of two bone marrow biopsies, one of one liver biopsy, and three of four peripheral blood smears. Granuloma formation was seen in only three of 12 biopsies. There were ten or more fungi per monocyte in almost all tissues, some with extracellular forms.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Disseminated histoplasmosis in AIDS. Clinicopathologic features in seven patients from a non-endemic area. 234 42

Phagocytosis of Mycobacterium tuberculosis by human monocytes or macrophages is classically followed by granuloma formation in vivo. Granuloma are comprised of cells of the monocyte lineage together, in many instances, with antigen-specific T lymphocytes. Development of granuloma depends upon recruitment of both cell types, but recruitment of monocytes is pivotal as these cells secrete anti-mycobacterial cytokines and IL-8, a T cell chemoattractant. We have therefore investigated gene regulation of Monocyte Chemotactic Protein 1 (MCP-1), an important monocyte chemotactic cytokine, following phagocytosis of particulate material (latex beads and zymosan) and live M. tuberculosis by two human monocytic cell lines. In THP-1 cells and phenotypically more differentiated Mono Mac 6 cells, MCP-1 mRNA accumulation was first detectable by Northern analysis of 4 hours and increased over 24 hours. Magnitude and kinetics of MCP-1 gene expression was independent of the biochemical nature of the phagocytic stimulus, M. tuberculosis strain virulence or pre-treatment with anti-TNF. In contrast to the uniform effect of different phagocytic stimuli on MCP-1 gene expression, we have shown that M. tuberculosis but not latex or zymosan, increased IL-8 gene expression, a chemotactic agent for T cells. In additional experiments with THP-1 cells infected with human immunodeficiency virus (HIV), viral infection did not alter MCP-1 gene expression following phagocytosis. MCP-1 gene expression appears to be a conserved antigen-independent response of human monocytic cells which is activated following particulate phagocytosis. MCP-1 gene expression may thus be involved in recruitment of monocytes during granuloma formation.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Phagocytosis of Mycobacterium tuberculosis or particulate stimuli by human monocytic cells induces equivalent monocyte chemotactic protein-1 gene expression. 768 73

Bone marrow (BM) aspiration and biopsy are used commonly in clinical practice to diagnose invasive tissue infections caused by Mycobacterium avium intracellulare (MAC), Mycobacterium tuberculosis (TB), and Histoplasma capsulatum (HC) in patients with human immunodeficiency virus-1 (HIV) infection. However, the value of these invasive procedures relative to other diagnostic approaches has not been clearly defined. To determine the value of BM culture and BM histology in the diagnosis of opportunistic MAC/TB and HC infections in immunosuppressed patients with HIV, we retrospectively reviewed the records of 56 adult patients with HIV who underwent a single BM aspiration, biopsy, and culture because of unexplained fever and/or other clinical features suggestive of MAC/TB or HC infection. Thirty-two patients (57%) were ultimately diagnosed with MAC/TB or HC infection by positive cultures of BM, blood, sputum, or bronchoalveolar lavage fluid or by the histologic detection of organisms in biopsies of BM or other tissues. The diagnostic sensitivity of BM cultures was equal to that of blood cultures (20/32, or 63%). Granuloma and/or histologically apparent organisms were seen in BM biopsy specimens in 11 of 32 individuals (34%) ultimately diagnosed with MAC/TB or HC infections. Among these 11 cases, both granuloma and acid-fast staining organisms were found in the BM biopsy specimens of 2 individuals for whom both BM and blood cultures were negative. Certain clinical symptoms and signs at the time of BM examination were found by logistic regression analysis to be significantly associated with a subsequent diagnosis of MAC/TB or HC infections; these included high fever, long duration of febrile days prior to BM examination, and elevated direct bilirubin. In conclusion, while the diagnostic sensitivity of BM cultures was found to be no greater than that of blood cultures in detecting MAC/TB or HC infections in immunosuppressed HIV+ patients, histopathologic examination of BM specimens resulted in the relatively rapid identification of nearly one third of infected patients who underwent BM examination, and also identified infections in some patients who were culture negative. These findings support the continued use of BM aspiration, biopsy, and culture for the diagnosis of opportunistic MAC/TB or HC infections in immunosuppressed HIV+ patients, particularly when selected clinical features are present.
 ...
PMID:Bone marrow aspiration, biopsy, and culture in the evaluation of HIV-infected patients for invasive mycobacteria and histoplasma infections. 1134 81

The clinical and microbiologic characteristics of 31 patients with mucosal leishmaniasis due to Leishmania (Leishmania) infantum are described. Twenty-eight (90%) patients were male. Mean age at presentation was 48 +/- 14 years. Thirteen (42%) patients had no underlying disease, while 18 (58%) patients had several other medical conditions. Fifteen (48%) patients were immunocompromised, 7 patients were infected with human immunodeficiency virus (HIV), and 3 were graft recipients. The primary location of lesions was the larynx in 11 (35%) patients, oral mucosa in 10 (32%) patients, and the nose in 5 (16%) patients. Mucosal lesions were painless in all patients but 2 and consisted of whitish, red, or violaceous nodular swelling or tumorlike masses. Ulceration was reported in 6 patients. Pathologically, the lesions showed a chronic inflammatory infiltrate. Granuloma may be seen. The localization of the lesions determined the symptomatology of the disease. Symptoms included hoarseness, difficulty swallowing, and nasal obstruction. The disease presentation was usually protracted, with a mean time from the onset of symptoms to diagnosis of 13 months (range, 3 wk-4.5 yr), and the clinical diagnosis was usually mistaken for neoplasia of the upper aerodigestive tract. No laboratory abnormalities were found in these patients due to the localized disease, apart from those attributed to underlying diseases. Parasites were easily identified in smears or sections by Giemsa stain or hematoxylin-eosin stain. Leishmania was grown in culture in 12 (60%) patients; culture was negative in 8 (40%) patients. Leishmania (Leishmania) infantum was identified in only 9 instances. The following zymodemes were reported: MON-1 (2 patients), MON-24 (2 patients), MON-27 (1 patient), and MON-34 (1 patient). Serologic test results were known in 25 patients. Serology was usually positive at low titer; 6 (24%) patients had negative serologic test results. Twenty patients were treated with antimonial compounds for between 3 and 36 days. Three patients were given drugs other than antimonial drugs. Five patients were treated only locally, by surgery (3 patients) or topical medical therapy. One patient received no therapy, and treatment was not reported in 2 cases. Patients were cured in 25 (89%) cases, and sequelae were uncommon (14%). Relapse was detected in 2 individuals and 1 patient developed visceral leishmaniasis after treatment. Two HIV-coinfected patients died of causes unrelated to leishmaniasis. The results of the present report stress the clinical importance of searching for the presence of Leishmania in patients with suspected neoplasia of the upper respiratory tract if they have visited or resided in zones endemic for Leishmania (Leishmania) infantum. The treatment of choice for these patients is not established yet, but most patients respond to antimonial compounds given for 28 days or less.
 ...
PMID:Localized mucosal leishmaniasis due to Leishmania (Leishmania) infantum: clinical and microbiologic findings in 31 patients. 1279 1

Granuloma formation occurs in the human body if there is a particle which persists in phagocytes and which the immune system cannot eliminate. The immune reaction of granuloma formation evolved in order to combat mycobacteria with the aim of localizing mycobacteria and to avoid spreading of mycobacteria throughout the body. Granulomatous lung diseases are often accompanied by severe, systemic inflammation. However, acute phase proteins may be only slightly elevated. The spectrum of granulomatous lung diseases is broad. Sarcoidosis is the most common granulomatous lung disease. To diagnose sarcoidosis, other infectious granulomatous lung diseases such as tuberculosis, atypical mycobacterial and fungal infection have to be ruled out. Pulmonary granuloma also evolve in the context of autoimmune diseases such as rheumatoid arthritis, granulomatosis with polyangiitis (GBA, Wegener's) and eosinophilic granulomatosis with polyangiitis (EGPA, Churg-Strauss syndrome). Furthermore, immunodeficiencies such as common variable immunodeficiency (CVID) and immune reconstitution syndrome in HIV can be associated with systemic granulomatous inflammation. Finally, occupational lung disease, particularly hypersensitivity pneumonitis, silicosis, hard metal lung, and chronic berylliosis are associated with pulmonary granuloma formation.
 ...
PMID:[Granulomatous lung and systemic diseases]. 2346 60

Histologic and phenotypic analyses of splenectomy samples from 17 patients with common variable immunodeficiency (CVID) showed the following nonspecific, evocative, white-pulp lesions: white-pulp hyperplasia (WPH) with reactive follicles, giant follicles (GFs), marginal zone hyperplasia, periarteriolar T-zone hyperplasia (PATH) and/or granulomas, which enabled us to discern 2 groups: the first (n=6) composed of WPH with reactive follicles without granulomas, and the second (n=9) characterized by the presence of granulomas with or without WPH. All specimens were Epstein-Barr virus negative by in situ hybridization. Molecular analyses revealed a polyclonal immunoglobulin heavy chain gene (IGH) rearrangement (n=12). WPH-only patients were mostly female individuals and younger at CVID onset, diagnosis, and splenectomy, but their interval between the first symptom and diagnosis was longer; they had more associated infectious events, autoimmune disease, pulmonary complications, and liver regenerative nodular hyperplasia; their IgG, IgA, and IgM concentrations were also higher. Granuloma-group patients were mostly male individuals; were older at CVID onset, diagnosis, and splenectomy; had disseminated granulomatous disease, but infectious events, autoimmune disease, pulmonary complications, and liver regenerative nodular hyperplasia were less common; their immunoglobulin concentrations were lower. Histologic comparisons between the WPH-only and granuloma groups showed more intense WPH and more intense marginal zone hyperplasia and fewer GFs in the former versus more developed PATH and more common GFs in the latter. The results of this novel comparative study of the histologic patterns of 17 CVID patients' evocative splenic lesions suggested different biological and clinical profiles.
 ...
PMID:Spleen Histologic Appearance in Common Variable Immunodeficiency: Analysis of 17 Cases. 2715 60

Chronic granulomatous disease (CGD) is a rare primary immunodeficiency that is caused by defects in the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase complex. The disease presents in most patients initially with infection, especially of the lymph nodes, lung, liver, bone, and skin. Patients with CGD are susceptible to a narrow spectrum of pathogens, and Staphylococcus aureus, Burkholderia cepacia complex, Serratia marcescens, Nocardia species, and Aspergillus species are the most common organisms implicated in North America. Granuloma formation, most frequently in the gastrointestinal and genitourinary systems, is a common complication of CGD and can be seen even before diagnosis. An increased incidence of autoimmune disease has also been described in patients with CGD and X-linked female carriers. In patients who present with signs and symptoms consistent with CGD, a flow cytometric dihydrorhodamine neutrophil respiratory burst assay is a quick and cost-effective way to evaluate NADPH oxidase function. The purpose of this review is to highlight considerations for and challenges in the diagnosis of CGD.
 ...
PMID:Considerations in the Diagnosis of Chronic Granulomatous Disease. 2974 74