Severe combined immunodeficient

Poly(ethylene glycol) (PEG) molecules attached to adenosine deaminase (ADA) have been used in patients exhibiting symptoms of the severe combined immunodeficiency syndrome (SCID) caused by ADA deficiency. The modified enzyme has a plasma half-life of weeks as compared to the unmodified enzyme (minutes) (248). PEG-L-asparaginase has induced remissions in patients with non-Hodgkin s lymphoma (248). However, one disadvantage of PEG-enzyme treatment is its expense, ie, a year s treatment costs about 60,000 (248). 

ADA SCID (adenosine deaminase-defective severe combined immunodeficiency) is a fatal genetic disorder caused by defects in the gene that encodes adenosine deaminase (ADA). 

SC ID Severe combined immunodeficiency syndrome sCRl Soluble type-1 complement receptors... 

In vivo studies were carried on the aziridinated cyclopent[Z ]indole quinone out before it was discovered that the aziridinyl ring did not participate in DNA alkylation. The results in Fig. 7.22 for the B16 melanoma syngraft model reveal that there was substantial reduction of tumor mass at 3 mg/kg. However, toxicity (animal deaths) became apparent at 5 mg/kg. On the other hand, human lung cancer xenografts in SCID (severe combined immunodeficient) mice were reduced to 50% mass with 3x1 mg/kg doses without any animal deaths. 

Other diseases Autoimmune diseases Amyloidosis Aplastic anemia Paroxysmal nocturnal hemoglobinuria Fanconi s anemia Thalassemia major Sickle cell anemia Severe combined immunodeficiency Inborn errors of metabolism... 

Low levels or absence of adenosine deaminase (ADA) is associated with one form of severe combined immunodeficiency disease (SCID) characterized by B-andT-lymphocyte dysfunction due to toxic effects of deoxyadenosine (HI9). Most patients present as infants with failure to thrive, repeated infections, severe lymphopenia, and defective cellular and humoral immunity. Disease severity is correlated with the degree of deoxyadenosine nucleotide pool expansion and inactivation of S-adenosylhomocysteine hydrolase in red blood cells. Up to now, more than 40 mutations have been identified (A4, H20, S5, S6). The majority of the basic molecular defects underlying ADA deficiency of all clinical phenotypes are missense mutations. Nonsense mutations, deletions ranging from very large to single nucleotides, and splicing mutations have also been reported. It is likely that severe... 

Two types of antibody libraries can be constructed, immune or non-immune. Immune libraries are constructed by immunizing the animal of interest with an antigen(s). In the case of humans, the source can be volunteers with the disease or condition under study (Persson et al., 1991). Human antibodies have also been obtained from severe combined immunodeficiency mice populated with human peripheral blood... 

Maczek C, Bock G, Jurgens G, Schonitzer D, Dietrich H, Wick G (1998) Environmental influence on age-related changes of human lymphocyte membrane viscosity using severe combined immunodeficiency mice as an in vivo model. Exp Gerontol 33(5) 485—498... 

The theoretical complications posed by random chromosomal integration became a medical reality in 2002, when two children who had received retroviral-based gene therapy 2 years previously developed a leukaemic-like condition. The initial clinical trial aimed to treat X-linked severe combined immunodeficiency (SCID-X1), a hereditary disorder in which T-lymphocytes and NK cells in particular do not develop, due to a mutation in the gene coding for the yc cytokine receptor subunit. The clinical consequence is near abolition of a functional immune system. 

Roth, M.D. et al., Cocaine enhances human immunodeficiency virus replication in a model of severe combined immunodeficient mice implanted with human peripheral blood leukocytes, J. Infect. Dis., 185, 701, 2002. 

Recently, it has been possible to grow cells of the human immune system in special mice. These mice carry a genetic defect called severe combined immunodeficiency (SCID), which leaves them with crippled immune systems, much like those in AIDS patients. Because SCID mice lack functional cellular immunity, it is possible to implant them with human cells without tissue rejection taking place. Researchers have recently developed techniques to implant human fetal tissues containing stem cells for the blood into SCID mice. It is then possible to reconstitute these mice with functional human immune system cells, including T lymphocytes and B lymphocytes. They have also found that if these SCID mice are infected by HIV, the virus will establish infection in the human tissue and destroy the T helper lymphocytes, just as it does in humans. Thus, it may be possible to study some of the mechanisms by which HIV attacks the immune system in these mice. In addition, they may be very useful for testing potential antiviral drugs. 

Currently, there is stUl a gap for the potential of gene therapy to be fulfilled. Gene therapy clinical trials have been conducted for diseases such as severe combined immunodeficiency disease (SCID, bubble baby syndrome), sickle cell anemia, cystic fibrosis, familial hypercholesterolemia, and Gaucher disease. 

Radiosensitive sever combined immunodeficiency (RS-SCID) Artemis... 

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