Human diseases Neurological disorders

The use of hGH extracted from the pituitaries of deceased human donors came to an abrupt end in 1985, when a link between treatment and Creutzfeldt-Jakob disease (CJD, a rare, but fatal, neurological disorder) was discovered. In this year, a young man who had received hGH therapy some 15 years previously died from CJD, which, investigators concluded, he had contracted from infected pituitary extract (CJD appears to be caused by a prion). At least an additional 12 CJD cases suspected of being caused in the same way have subsequently been documented. Fortunately, several recombinant hGH (rhGH) preparations were coming onstream at that time (Table 8.8), and now all hGH preparations used clinically are derived from recombinant sources. Currently, in excess of 20 000 people are in receipt of rhGH therapy. 

When Pol II transcription halts at the site of a DNA lesion, TFIIH can interact with the lesion and recruit the entire nucleotide-excision repair complex. Genetic loss of certain TFIIH subunits can produce human diseases. Some examples are xeroderma pigmentosum (see Box 25-1) and Cockayne s syndrome, which is characterized by arrested growth, photosensitivity, and neurological disorders. ... 

Somatropin extracted from cadaveric human pituitaries was used to treat growth hormone-deficient patients until several cases of the fatal degenerative neurological disorder Creutzfeldt-Jakob disease were reported in the mid-1980s. Of 267 cases of iatrogenic Creutzfeldt-Jakob disease, 139 were caused by human cadaver-derived somatropin (SEDA-25, 479). 

The 1-carboxy-TlQs 91-94 shown in Fig. 24 have been detected only by GC-MS methods it is not known whether they occur naturally as racemic mixtures or in the form of enantiomers. Salsolinol-1-carboxylic acid (91) was detected in human urine (205) and in the caudate nucleus (206). Dideoxynorlaudanosoline-1-carboxylic acid (92) was found in small amounts in rat brain, but is present in enhanced amounts in phenylketo-nuric patients (207). It is believed that TIQ 92 may be responsible for the neurological disorders which develop during the disease. Carboxylic acids 93 and 94 were detected in the urine of parkinsonian patients undergoing L-dopa therapy, and the methyl ether 94 was the mqjor metabolite (174). 

Previous studies have used proteome comparisons to study such neurological disorders as Alzheimer s disease (AD), Parkinson s disease (PD), frontotemporal dementia, schizophrenia, and Creutzfeldt-Jacob disease. Some examples of utilizing proteomics approaches for discovery of biomarkers for neurological disorders in human CSF are given in Table 49.2. 

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