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)

Currently, there is no treatment to cure transmissible spongiform encephalopathies. By taking advantage of the 'prion-resistant' polymorphisms Q171R and E219K that naturally exist in sheep and humans, respectively, we have evaluated a therapeutic approach of lentiviral gene transfer. Here, we show that VSV-G (vesicular stomatitis virus G glycoprotein) pseudotyped FIV-(feline immunodeficiency virus) derived vectors carrying the mouse Prnp gene in which these mutations have been inserted, are able to inhibit prion replication in chronically prion-infected cells. Because lentiviral tools are able to transduce post-mitotic cells such as neurons or cells of the lymphoreticular system, this result might help the development of gene- or cell-therapy approaches to prion disease.
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PMID:Inhibition of PrPSc formation by lentiviral gene transfer of PrP containing dominant negative mutations. 1549 72

(1) Infectious agents capable of entering the central nervous system (CNS) produce some of the most dreaded diseases known to man. The infectious agent within the CNS is often protected by the blood-brain barrier (BBB), shielded from endogenous and exogenous anti-infectious agents. (2) The use of in vitro methods offers many advantages to the study of how infectious agents interact with the BBB. Two such agents which negotiate the BBB early in the course of disease before damage to the BBB are the autoimmune deficiency syndrome virus, or human immunodeficiency virus 1, and scrapie prion. Our laboratories have used in vitro methods to study these agents. (3) Here, we review some of the results form our laboratories and those of others.
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PMID:In vitro methods in the study of viral and prion permeability across the blood-brain barrier. 1596 6

A bispecific enzyme-linked signal-enhanced immunoassay (BiELSIA) was developed with markedly increased sensitivity. Antimyosin, the detection antibody, was linked to the signal probespecific antibody. Probes consisted of diethylenetriamine pentaacetic acids attached to polylysine modified with up to seven or eight horseradish peroxidase (HRP) units. Each bispecific antibody bound two polymer probes, providing twice the signal. Using BiELSIA in a competitive inhibition immunoassay format with an average of 1.5, 3, 4.5, 6, and 7.5 HRP units per polymer-probe, the sensitivity of standard enzyme-linked immunosorbent assay (10(13) mole) was increased to 10(15), 10(18), 10(19), 10(20), and 10(-21) mol (< or = 1,000 molecules), respectively. BiELSIA detected cardiac myosin heavy chain fragments in sera of patients obtained at the time of emergency department admission for acute myocardial infarction, but not in normal sera. This technology should be applicable for detection of cancer, human immunodeficiency virus, prion, and other antigens that are present in concentrations too low for detection by current immunoassays.
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PMID:Bispecific enzyme-linked signal-enhanced immunoassay with subattomole sensitivity. 1597 93

The transplant of cells of human origin is an increasingly complex sector of medicine which entails great opportunities for the treatment of a range of diseases. Stem cell banks should assure the quality, traceability and safety of cultures for transplantation and must implement an effective programme to prevent contamination of the final product. In donors, the presence of infectious micro-organisms, like human immunodeficiency virus, hepatitis B virus, hepatitis C virus and human T cell lymphotrophic virus, should be evaluated in addition to the possibility of other new infectious agents (e.g. transmissible spongiform encephalopathies and severe acute respiratory syndrome). The introduction of the nucleic acid amplification can avoid the window period of these viral infections. Contamination from the laboratory environment can be achieved by routine screening for bacteria, fungi, yeast and mycoplasma by European pharmacopoeia tests. Fastidious micro-organisms, and an adventitious or endogenous virus, is a well-known fact that will also have to be considered for processes involving in vitro culture of stem cells. It is also a standard part of current good practice in stem cell banks to carry out routine environmental microbiological monitoring of the cleanrooms where the cell cultures and their products are prepared. The risk of viral contamination from products of animal origin, like bovine serum and mouse fibroblasts as a "feeder layer" for the development of embryonic cell lines, should also be considered. Stem cell lines should be tested for prion particles and a virus of animal origin that assure an acceptable quality.
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PMID:Microbiological control in stem cell banks: approaches to standardisation. 1601 32

Amphotericin B is a medically important antifungal antibiotic that is also active against human immunodeficiency virus, Leishmania parasites, and prion diseases. The therapeutic use of amphotericin B is restricted by severe side effects that can be moderated by liposomal formulation or structural alteration. Chemical modification has shown that suppression of charge on the exocyclic carboxyl group of amphotericin B substantially reduces toxicity. We report targeted deletions of the amphN cytochrome P450 gene from the chromosome of the amphotericin-producing bacterium Streptomyces nodosus. The mutant strains produced amphotericin analogues in which methyl groups replace the exocyclic carboxyl groups. These compounds retained antifungal activity and had reduced hemolytic activity.
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PMID:Biosynthesis of amphotericin derivatives lacking exocyclic carboxyl groups. 1607 35

At the turn of the last century, infectious diseases represented an important cause of health morbidity and behavioral changes. Neurosyphilis, for example, was relatively common at the time and often led to the development of cognitive impairment and dementia. With the advent of effective antibiotic treatment, the association between infectious diseases and dementia became increasingly less frequent, although a resurgence of interest in this area has taken place during the past 15 years with the emergence of acquired immunodeficiency syndrome (AIDS) and variant Creutzfeldt-Jakob disease (vCJD). This paper reviews the most frequent infectious causes of dementia, including prion diseases, as well as infections caused by herpes virus, human immunodeficiency virus (HIV), toxoplasmosis, cryptococcus, cytomegalovirus, syphilis, borrelia and cysticercosis.
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PMID:Dementia associated with infectious diseases. 1624 Apr 84

Over the past 20 years, transmissions of human immunodeficiency virus (HIV), hepatitis B virus or hepatitis C virus have been virtually eliminated from plasma-derived or recombinant therapy in the USA, a record that can be largely attributed to the use of effective screening and inactivation technologies for known pathogens. The next significant threat will likely come from the emergence of a new, blood-borne infectious disease, perhaps one transmitted by a non-lipid-enveloped virus or prion, for which current inactivation methods are ineffective. Following the HIV crisis of the 1980s, government, patient advocacy groups, medical and scientific communities and the manufacturers of clotting therapies can learn from the past and approach potential threats from emerging pathogens in a proactive and productive manner. For clinicians, this includes actively engaging patients in a dialogue about all the factors that may influence their choice of clotting factor therapies, including emerging pathogens, patient convenience, consistency and reliability of supply, relative cost/benefit ratios, reimbursement issues (where applicable), patient preference and brand loyalty. It is our obligation as healthcare providers to understand potential risks and help make proactive decisions with our patients, decisions that often must be made in an environment of scientific uncertainty. Threats from infectious agents that were once deemed theoretical can, and often do, ultimately become real, with serious implications for morbidity and mortality.
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PMID:The physician's role in selecting a factor replacement therapy. 1644 14

Prion diseases are neurodegenerative disorders associated in most cases with the accumulation in the central nervous system of PrPSc (conformationally altered isoform of cellular prion protein (PrPC); Sc for scrapie), a partially protease-resistant isoform of the PrPC. PrPSc is thought to be the causative agent of transmissible spongiform encephalopathies. The mechanisms involved in the intercellular transfer of PrPSc are still enigmatic. Recently, small cellular vesicles of endosomal origin called exosomes have been proposed to contribute to the spread of prions in cell culture models. Retroviruses such as murine leukemia virus (MuLV) or human immunodeficiency virus type 1 (HIV-1) have been shown to assemble and bud into detergent-resistant microdomains and into intracellular compartments such as late endosomes/multivesicular bodies. Here we report that moloney murine leukemia virus (MoMuLV) infection strongly enhances the release of scrapie infectivity in the supernatant of coinfected cells. Under these conditions, we found that PrPC, PrPSc and scrapie infectivity are recruited by both MuLV virions and exosomes. We propose that retroviruses can be important cofactors involved in the spread of the pathological prion agent.
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PMID:Retrovirus infection strongly enhances scrapie infectivity release in cell culture. 1672 7

For a brief period, modern medical science was considered to have relegated infectious disease to that of a minor clinical challenge. However, several infectious diseases have emerged or re-emerged in recent years, raising epidemiological concerns, as well as issues over the availability of effective measures of control and treatment. Invariably, these infectious agents have been studied carefully in relation to the safety of blood products, often resulting in concern and action. Emerging diseases arise from many sources. Some are the result of viruses crossing the species barrier from animals to humans. In addition, combinations of these newly identified viruses may make each more difficult to treat, as in the case of human immunodeficiency virus and hepatitis C virus coinfection. Still others can arise from completely new biological mechanisms, such as the prion disease variant Creutzfeldt-Jacob disease, which has spread from infected cattle to humans, particularly in the United Kingdom. The emergence of new viruses and new disease sources has had a significant impact on coagulation factor therapies and blood donation policies. We must deal with these multiple threats and their potential to compromise the safety of our blood supply.
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PMID:Hemophilia therapy and blood-borne pathogen risk. 1680 29

We studied the efficacy of virus reduction by three process steps (polyethylene glycol 4000 (PEG) precipitation, pasteurization, and 15nm virus filtration) in the manufacturing of C1-inhibitor NF. The potential prion removing capacity in this process was estimated based on data from the literature. Virus studies were performed using hepatitis A virus (HAV) and human immunodeficiency virus (HIV) as relevant viruses and bovine viral diarrhea virus (BVDV), canine parvovirus (CPV) and pseudorabies virus (PRV) as model viruses, respectively. In the PEG precipitation step, an average reduction in infectious titer of 4.5log(10) was obtained for all five viruses tested. Pasteurization resulted in reduction of infectious virus of >6log(10) for BVDV, HIV, and PRV; for HAV the reduction factor was limited to 2.8log(10) and for CPV it was zero. Virus filtration (15nm) reduced the infectious titer of all viruses by more than 4.5log(10). The overall virus reducing capacity was >16log(10) for the LE viruses. For the NLE viruses CPV and HAV, the overall virus reducing capacities were >8.7 and >10.5log(10), respectively. Based on literature and theoretical assumptions, the prion reducing capacity of the C1-inhibitor NF process was estimated to be >9log(10).
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PMID:Viral safety of C1-inhibitor NF. 1707 Nov 3


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