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)

We tested the hypothesis that the loss of immunological reactivity in HIV-1-infected persons may result partly from a virus-induced metabolic disorder. Patients who are infected with the acquired immunodeficiency syndrome (AIDS)-associated human immunodeficiency virus 1 were found to have, on average, markedly elevated and highly variable plasma glutamate concentrations. A similar elevation of the extracellular glutamate concentration was found to inhibit DNA synthesis in cultures of mitogenically stimulated lymphocytes. An even stronger inhibition was seen with the structural analogue quisqualate, and a moderate inhibition was seen with N-methyl-D-aspartate and kainate, i.e. with well established pharmacological probes for the excitatory glutamate receptors in the vertebrate central nervous system. The inhibitory effect of glutamate was compensated by adding cysteine or relatively large numbers of 'splenic adherent cells' to the culture. Elevated extracellular glutamate levels were also found to reduce the capacity of murine macrophages, human blood monocytes, and murine fibroblastoid cells (L929 cells) to release acid-soluble thiol (cysteine) into the extracellular space. The three cell types differed, however, with respect to their sensitivity against the three structural analogues of glutamate. The elevated glutamate concentration was not non-specifically toxic for cultured macrophages, since glycolytic activity and arginase activity were not inhibited. Implications of these observations for the pathogenetic mechanism of AIDS are discussed.
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PMID:Elevated plasma glutamate concentrations in HIV-1-infected patients may contribute to loss of macrophage and lymphocyte functions. 257 75

The authors pointed out that contamination may be exogenous, as a result of invasive diagnostic techniques, patient preparation, surgery, catheter insertion and wound dressing, or endogenous, especially in patients with specific risk factors (age, metabolic disorder, malnutrition, immunodeficiency) and aspecific risk factors (anesthesia, blood transfusion, surgery). Pharmacologic prophylaxis of infection may be unspecific (artificial nutrients, anticoagulants, immunomodulators) or specific (antibiotics). Prophylaxis is indicated in clean-contaminated and contaminated surgery; antibiotic chemoprophylaxis is also indicated in risk patients and permanent prosthesis surgery. The authors emphasized that antibiotics are no substitution for careful surgery.
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PMID:Short-term antimicrobial prophylaxis in surgery. The state of the art. 273 12

Developmental defects interrupting the normal evolution of immunocytes can explain many of the congenital immunodeficiency syndromes. Observations accumulated during the last decade have, however, shown that this is not the only cause, and that many diseases have signs of immunodeficiency as an accompanying feature. Severe combined immunodeficiency (SCID) is a good example of the multiple etiology of similar clinical features--they are phenocopies of a well-delineated hereditary disease. A number of recently described syndromes are reviewed, albeit an incomplete list. Metabolic disorders due to inactivity of enzymes may present characteristic ID. Some of them are explained by lack or increased need of co-enzymes (like biotin or zinc). In other syndromes, better understanding of the pathogenesis might pin down the primary failure to one single point, as shown in the hyper IgE syndrome. Other fundamental disturbances are located in the chromosome itself, eg decreased repair capacity, deletion, translocation. An attempt is made to propose a general classification accommodating all etiologic factors known to date which lead to immunodeficiency. It is obvious that within this framework the same clinical syndrome may be repeated.
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PMID:Protean appearances of immunodeficiencies: syndromes and inborn errors involving other systems which express associated primary immunodeficiency. 636 Feb 43

Over the past 10 years, in conjunction with the broad availability of potent antiretroviral regimens, the care of human immunodeficiency virus (HIV)-infected patients has shifted from prevention and treatment of opportunistic infections and malignancies to management of the metabolic and related complications associated with HIV infection and its treatment. Metabolic disorders, including lipodystrophy, dyslipidemia, and insulin resistance, occur at a high rate in HIV-infected individuals receiving highly active antiretroviral therapy (HAART). These disorders are associated with increased risk of cardiovascular disease and have become an important cause of morbidity and mortality in HIV-infected patients. Herein, we present the case of a patient with HIV infection who responded well to HAART but developed multiple complications potentially related to this therapy. This article reviews the clinical characteristics of the metabolic and skeletal disturbances observed in HIV infection and discusses strategies for their management.
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PMID:Metabolic and skeletal complications of HIV infection: the price of success. 1690 89

Defects in purine nucleoside phosphorylase (PNP) enzyme activity result in abnormal nucleoside homeostasis, severe T cell immunodeficiency, neurological dysfunction, and early death. Protein transduction domain (PTD) can transfer molecules into cells and may help restore PNP activity in cases of PNP deficiency. However, long-term use of PTD to replace enzymes in animal models or patients has not previously been described. We fused human PNP to the HIV-TAT PTD and found that the fusion with TAT changed the retention and distribution of PNP in PNP-deficient mice. TAT induced rapid intracellular delivery of PNP into tissues, including the brain, prevented urinary excretion of PNP, and protected PNP from neutralizing antibodies, resulting in significant extension of the enzyme's biological activity in vivo. Frequent TAT-PNP injections in PNP-deficient mice corrected the metabolic disorder and immune defects with no apparent toxicity. TAT-PNP remained effective over 24 weeks of treatment, resulting in continued improvement in immune function and extended survival. Our data demonstrate that TAT changes the properties of PNP in vivo and that long-term intracellular delivery of PNP by TAT corrects PNP deficiency in mice. We provide evidence to promote further use of PTD to treat diseases that require repeated intracellular enzyme or protein delivery.
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PMID:TAT-mediated intracellular delivery of purine nucleoside phosphorylase corrects its deficiency in mice. 1696 10

Highly active antiretroviral therapy (HAART) of human immunodeficiency virus-infected patients is associated with adverse effects, such as lipodystrophy and hyperlipidemia. The lipodystrophic syndrome is characterized by a peripheral lipoatrophy and/or fat accumulation in the abdomen and neck. In order to get insights into the physiopathological mechanisms underlying this syndrome, we treated mice with protease inhibitors (PIs) over a long period of time. Although atazanavir-treated mice presented the same circulating triglyceride concentration as control mice, lopinavir-ritonavir-treated mice rapidly became hypertriglyceridemic, with triglyceride levels of 200 mg/dl, whereas control and atazanavir-treated animals had triglyceride levels of 80 mg/dl. These results obtained with mice reproduce the metabolic disorder observed in humans. White adipose tissue (WAT) was analyzed after 8 weeks of treatment. Compared to the control or atazanavir treatment, lopinavir-ritonavir treatment induced a significant 25% weight reduction in the peripheral inguinal WAT depot. By contrast, the profound epididymal WAT depot was not affected. This effect was associated with a 5.5-fold increase in SREBP-1c gene expression only in the inguinal depot. Our results demonstrate that the long-term treatment of mice with PIs constitutes an interesting experimental model with which some aspects of the lipoatrophy induced by HAART in humans may be studied.
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PMID:Long-term treatment with lopinavir-ritonavir induces a reduction in peripheral adipose depots in mice. 1700 Jul 48

Interleukin (IL)-18 is a proinflammatory cytokine that plays an important role in both innate and adaptive immune responses against viruses and intracellular pathogens. Increased levels of circulating IL-18 from HIV-1 infected patients have been reported especially in the advanced and late stages of the disease, whereas in the initial stage serum levels of IL-18 were not increased. In contrast, low production of Il-18 was observed in vitro from peripheral blood mononuclear cells (PBMC) of HIV-1 infected patients, and these results were also observed in macaques infected with simian immunodeficiency virus (SIV). In addition, decreased IL-18 production from PBMC was significantly correlated with low production of IL-2. Furthermore, serum levels of IL-18 significantly decreased after highly active antiretroviral therapy. During the early stage of HIV-1 infection there is a decreased production of gamma interferon (IFN), IL-12 and IL-2 as well as not activation of IL-18 production and this leads to inhibition of Th1 immune response, whereas in the advanced stage of the disease, strong activation of IL-18 production along with persistent decreased production of gamma IFN, IL-12 and IL-2 may promote a Th2 immune response, which leads to persistent viral replication. Several studies have shown increased levels of IL-18 in HIV-seronegative subjects with obesity, insulin resistance and type II diabetes. Metabolic disorders, fat redistribution and cardiovascular manifestations are becoming more frequent in HIV-1 infected patients treated with antiretroviral drugs. Consequently, involvement of IL-18 in these disorders has been postulated and demonstrated in patients with lipodistrophy, or with hypertriglyceridemia. Finally, higher serum levels of IL-18 may represent an useful marker in HIV-1 infected patients with metabolic disorders and fat redistribution, as well as a sensitive predictor of cardiovascular complications in treated patients.
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PMID:Interleukin-18: a proinflammatory cytokine in HIV-1 infection. 1707 17

Inherited adenosine deaminase (ADA) deficiency is a rare metabolic disorder that causes immunodeficiency, varying from severe combined immunodeficiency (SCID) in the majority of cases to a less severe form in a small minority of patients. Five patients of Somali origin from four unrelated families, with severe ADA-SCID, were registered in the Greater London area. Patients and their parents were investigated for the nonsense mutation Q3X (ADA c7C>T), two missense mutations K80R (ADA c239A>G) and R142Q (ADA c425G>A), and a TAAA repeat located at the 3' end of an Alu element (AluVpA) positioned 1.1 kb upstream of the ADA transcription start site. All patients were homozygous for the haplotype ADA-7T/ADA-239G/ADA-425G/AluVpA7. Among 207 Somali immigrants to Denmark, the frequency of ADA c7C>T and the maximum likelihood estimate of the frequency of the haplotype ADA-7T/ADA-239G/ADA-425G/AluVpA7 were both 0.012 (carrier frequency 2.4%). Based on the analysis of AluVpA alleles, the ADA c7C/T mutation was estimated to be approximately 7,100 years old. Approximately 1 out of 5 - 10000 Somali children will be born with ADA deficiency due to an ADA c7C/T mutation, although within certain clans the frequency may be significantly higher. ADA-SCID may be a frequent immunodeficiency disorder in Somalia, but will be underdiagnosed due to the prevailing socioeconomic and nutritional deprivation.
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PMID:Carrier frequency of a nonsense mutation in the adenosine deaminase (ADA) gene implies a high incidence of ADA-deficient severe combined immunodeficiency (SCID) in Somalia and a single, common haplotype indicates common ancestry. 1718 44

Purine nucleoside phosphorylase (PNP) deficiency is a rare autosomal recessive metabolic disorder that results in combined immunodeficiency, neurologic dysfunction and autoimmunity. PNP deficiency has never been reported from Saudi Arabia or in patients with an Arabic ethnic background. We report on two Saudi girls with PNP deficiency. Both showed severe lymphopenia and neurological involvement. Sequencing of the PNP gene of one girl revealed a novel missense mutation Pro146>Leu in exon 4 due to a change in the codon from CCT>CTT. Expression of PNP (146L) cDNA in E coli indicated that the mutation greatly reduced, but did not completely eliminate PNP activity.
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PMID:Purine nucleoside phosphorylase deficiency in two unrelated Saudi patients. 1958 74

Diabetes mellitus is a common metabolic disorder that poses some degrees of immunodeficiency. This leads to the need for some specific primary prevention of infectious diseases by vaccination. An important vaccine for diabetic patients is the influenza vaccine. It is recommended that the diabetic patients should get vaccine. Here, the author performed an assessment on existed evidence to determine the usefulness of influenza vaccination in different groups of diabetic patients.
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PMID:Usefulness of influenza vaccination in different groups of diabetic patients. 2557 67


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