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

To investigate the extent of genetic heterogeneity in the genus Isospora infecting patients in Thailand, a total of 38 fecal samples containing Isospora oocysts from human immunodeficiency virus/acquired immunodeficiency syndrome patients (n = 30), corticosteroid-treated patients (n = 3) and immunocompetent individuals (n = 5) were recruited for analysis. Remarkable variation in the maximum width and length of oocysts both within and between isolates was observed. However, the average length-width ratio of oocysts was within the range for I. belli (> 1.2). Ex vivo sporogonic development of freshly passed oocysts in feces from three of these isolates was observed longitudinally, showing that 27% of these oocysts underwent complete sporulation. Interestingly, 95% of sporulated oocysts contained two sporocysts in an oocyst with four sporozoites in each sporocyst, and Caryospora-like oocysts, characterized by eight sporozoites enclosed by a single sporocyst, were also detected (5%). The small subunit ribosomal RNA (rRNA), 5.8S rRNA, internal transcribed spacer 1 (ITS-1), and ITS-2 were highly conserved, indicating that there were no cryptic species or extensive strain variation.
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PMID:Morphologic and molecular characterization of Isospora belli oocysts from patients in Thailand. 1762 Jun 39

Highly active antiretroviral therapy dramatically decreases in vivo viral replication to levels below the level of clinical detection, but does not eradicate HIV-1 infection on the basis of persistent low-level or cryptic viral replication and latent provirus in resting CD4+ T lymphocytes. Immune activation therapy has begun to be used in attempts to increase the turnover rate of the latent virus reservoir through activation of infected cells that comprise this reservoir, in order to promote cell death and accelerate virus clearance. Recent reports have not demonstrated complete virus ablation. Autologous hematopoietic cell transplantation now appears as a safe, feasible, and reasonable approach for Aids-related lymphoma in patients who meet criteria for transplantation. The hypothesis is based on the possibility that hematopoietic stem cells from a HIV-positive patient could be collected before the patient becomes infected with HIV. Then, the proposed treatment consists of the following assumptions. HAART keeps viral replication below the level of detection, limiting the infection to latent provirus in resting CD4+ T lymphocytes. It is presumed here that myeloablative conditioning regimen can lead to the killing of all the cells that, in theory, harbour the virus. The following transplantation of the autologous hematopoietic stem cells, collected before HIV infection, would allow the complete recovery. The hypothesis is to be tested on a suitable animal model. After the collection of hematopoietic stem cells, the animal is experimentally infected with the immunodeficiency virus. HAART is given after plasma viral RNA becomes detectable. By myeloablative conditioning regimen all the cells harbouring the virus are supposed to be killed. Then, as the viral load is kept undetectable by HAART, the animal undergoes autologous hematopoietic stem cell transplantation. Antiretroviral therapy is interrupted a month after engraftment has taken place. Although hematopoietic stem cells from man before infection with HIV are unlikely to be available, a successful test on the animal would suggest a new approach which could allow the cure of HIV in future.
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PMID:A novel approach to HIV therapy: highly active antiretroviral therapy and autologous hematopoietic cell transplantation. 1768 7

Cryptic major histocompatibility complex class I epitopes have been detected in several pathogens, but their importance in the immune response to AIDS viruses remains unknown. Here, we show that Mamu-B*17(+) simian immunodeficiency virus (SIV)mac239-infected rhesus macaques that spontaneously controlled viral replication consistently made strong CD8(+) T lymphocyte (CD8-TL) responses against a cryptic epitope, RHLAFKCLW (cRW9). Importantly, cRW9-specific CD8-TL selected for viral variation in vivo and effectively suppressed SIV replication in vitro, suggesting that they might play a key role in the SIV-specific response. The discovery of an immunodominant CD8-TL response in elite controller macaques against a cryptic epitope suggests that the AIDS virus-specific cellular immune response is likely far more complex than is generally assumed.
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PMID:AIDS virus specific CD8+ T lymphocytes against an immunodominant cryptic epitope select for viral escape. 1795 73

Cryptosporidium, agent of cryptosporidiosis, is an ubiquitous protozoan organism causing diarrhoea especially in severe immunosuppressed patients. Cryptosporidium has been detected with increasing frequency in the gastrointestinal tract, but involvement of the stomach is rarely reported and discloses an underlying immunodeficiency state. We report the case of 67-year-old man, a heavy smoker, who presented with a history of epigastric pain with an altered general condition. Upper gastrointestinal endoscopy showed no significant mucosal abnormalities. The biopsy revealed a chronic active gastritis with Cryptosporidium parasites lining cryptic epithelium. Systematic chest X ray showed a right suspect parenchymatous opacity. Bronchoscopy with multiple biopsies concluded to a small cell lung carcinoma. Through this rare initial manifestation of immunocompromised state related to cancer we will discuss the role of gastrointestinal endoscopy with biopsies in the diagnosis of cryptosporidiosis.
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PMID:[Gastric cryptosporidiosis revealing a small cell lung carcinoma (Tunisia)]. 1843 2

Highly active antiretroviral therapy (HAART) can potently suppress human immunodeficiency virus (HIV) replication and prevent progression to AIDS. However, HAART does not cure infected patients. Instead, HIV persists in latently infected CD4+ T cells and various cryptic cellular reservoirs. Hence, under current therapy regimens, patients must continue taking HAART for the remainder of their lives. Eliminating residual replication-competent virus is critical if eradication of HIV is to be achieved. While this challenge is formidable, we describe here a number of innovative approaches intended to further deplete HIV in HAART-treated patients. New antiretroviral drugs that target different viral proteins and stages of the virus life cycle, compounds that enhance anti-HIV immune responses and novel gene therapy approaches may each play a role in improving long-term suppression of the virus. Moreover, methods for more specifically and efficiently inducing HIV from latency and eliminating the newly activated host cells are also under development.
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PMID:Eradication of HIV: current challenges and new directions. 1898 48

Highly active antiretroviral therapy (HAART) has markedly decreased morbidity and mortality in human immunodeficiency virus type 1 (HIV-1)-infected individuals in the developed world. Successful therapy often results in stable plasma levels of HIV-1 RNA below the limits of detection of commercial assays. Nonetheless, HIV-1 has not been cured by HAART. The causes of persistence of HIV infection in the face of current therapy appear to be multifactorial: latent but replication-competent provirus in resting CD4+ T cells, cryptic viral expression below the limits of detection of clinical assays, and viral sanctuary sites might all contribute to persistence. Clearance of HIV infection will almost certainly require a multimodality approach that includes potent suppression of HIV replication, therapies that reach all compartments of residual HIV replication and depletion of any reservoirs of persistent, quiescent proviral infection. This review highlights the basic mechanisms for the establishment and maintenance of viral reservoirs and pharmaceutical approaches towards their elimination.
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PMID:Pharmaceutical approaches to eradication of persistent HIV infection. 1920 67

We measured T-cell responses to human immunodeficiency virus type 1 (HIV-1) cryptic epitopes encoded by regions of the viral genome not normally translated into viral proteins. T-cell responses to cryptic epitopes and to regions normally spliced out of the HIV-1 viral proteins Rev and Tat were detected in HIV-1-infected subjects.
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PMID:Transcriptional errors in human immunodeficiency virus type 1 generate targets for T-cell responses. 1957 Nov 7

We analyzed antibody responses in sera from feline immunodeficiency virus (FIV)-infected and uninfected cats. A strong antiviral response to the viral surface glycoprotein (SU) was noted in both natural and experimental infections. In addition, 143 of 226 FIV-infected animals (63%) also expressed antibodies to the primary binding receptor, CD134, whereas cats infected with other feline RNA viruses, including calicivirus, coronavirus, herpesvirus, and feline leukemia virus, did not. Both affinity-purified anti-CD134 and anti-SU antibodies blocked FIV infection ex vivo. FACS analyses revealed that the anti-CD134 antibodies bound to a cryptic epitope on the receptor that was only exposed when SU bound to CD134. Anti-CD134 binding caused displacement of SU from the surface of the cell and inhibition of infection. The presence of antibodies to CD134 correlated with lower virus loads and a better overall health status in FIV(+) cats, whereas anti-SU antibodies were present independent of health status. The findings are consistent with a role for antireceptor antibodies in protection from virus spread and disease progression.
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PMID:Improved health and survival of FIV-infected cats is associated with the presence of autoantibodies to the primary receptor, CD134. 1990 42

Until recently, knowledge of genetic causes of glomerular disease was limited to certain rare or uncommon inherited diseases, and to genes, either rare or with small effect, identified in candidate gene studies. These genetic factors accounted for only a very small fraction of kidney disease. However, the striking differences in frequency of many forms of kidney disease between African Americans and European Americans, which could not be explained completely by cultural or economic factors, pointed to a large unidentified genetic influence. Because focal segmental glomerulosclerosis (FSGS) and human immunodeficiency virus-associated collapsing glomerulopathy have striking racial disparities, we performed an admixture mapping study to identify contributing genetic factors. Admixture mapping identified genetic variants in the nonmuscle myosin heavy chain 9 gene (MYH9) as having a major influence on both FSGS and human immunodeficiency virus-associated collapsing glomerulopathy, with odds ratios from 4 to 8 and attributable fractions of 70% to 100%. Previously identified, rare, inherited MYH9 disorders point to a mechanism by which MYH9 variation disrupts the actin-myosin filaments responsible for maintaining the structure of podocytes, the cells that provide one of three filtration barriers in the glomeruli. MYH9 variation has a smaller but still highly significant effect on nondiabetic kidney disease, and a weaker but significant effect on diabetic kidney disease; it is unclear whether underlying cryptic FSGS is responsible for the MYH9 association with these diseases. The strong predicted power of MYH9 variation for disease indicates a clear role for genetic testing for these variants in personalized medicine, for assessment of genetic risk, and potentially for diagnosis.
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PMID:Genetics of focal segmental glomerulosclerosis and human immunodeficiency virus-associated collapsing glomerulopathy: the role of MYH9 genetic variation. 2034 41

The oxazolomycins (OZMs) are a growing family of antibiotics produced by several Streptomyces species that show diverse and important antibacterial, antitumor, and anti-human immunodeficiency virus activity. Oxazolomycin A is a peptide-polyketide hybrid compound containing a unique spiro-linked beta-lactone/gamma-lactam, a 5-substituted oxazole ring. The oxazolomycin biosynthetic gene cluster (ozm) was identified from Streptomyces albus JA3453 and localized to 79.5-kb DNA, consisting of 20 open reading frames that encode non-ribosomal peptide synthases, polyketide synthases (PKSs), hybrid non-ribosomal peptide synthase-PKS, trans-acyltransferases (trans-ATs), enzymes for methoxymalonyl-acyl carrier protein (ACP) synthesis, putative resistance genes, and hypothetical regulation genes. In contrast to classical type I polyketide or fatty acid biosynthases, all 10 PKS modules in the gene cluster lack cognate ATs. Instead, discrete ATs OzmM (with tandem domains OzmM-AT1 and OzmM-AT2) and OzmC were equipped to carry out all of the loading functions of both malonyl-CoA and methoxymalonyl-ACP extender units. Strikingly, only OzmM-AT2 is required for OzmM activity for OZM biosynthesis, whereas OzmM-AT1 seemed to be a cryptic AT domain. The above findings, together with previous results using isotope-labeled precursor feeding assays, are assembled for the OZM biosynthesis model to be proposed. The incorporation of both malonyl-CoA (by OzmM-AT2) and methoxymalonyl-ACP (by OzmC) extender units seemed to be unprecedented for this class of trans-AT type I PKSs, which might be fruitfully manipulated to create structurally diverse novel compounds.
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PMID:Oxazolomycin biosynthesis in Streptomyces albus JA3453 featuring an "acyltransferase-less" type I polyketide synthase that incorporates two distinct extender units. 2040 23


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