Boxing, diseases associated with

EMBL Nucleotide Sequence Database. SWISS-PROT consists of core sequence data with minimal redundancy, citation and extensive annotations including protein function, post-translational modifications, domain sites, protein structural information, diseases associated with protein deficiencies and variants. SWISS-PROT and TrEMBL are available at EBI site, http //www.ebi.ac.uk/swissprot/, and ExPASy site, http //www.expasy.ch/sprot/. From the SWISS-PROT and TrEMBL page of ExPASy site, click Full text search (under Access to SWISS-PROT and TrEMBL) to open the search page (Figure 11.3). Enter the keyword string (use Boolean expression if required), check SWISS-PROT box, and click the Submit button. Select the desired entry from the returned list to view the annotated sequence data in Swiss-Prot format. An output in the fasta format can be requested. Links to BLAST, feature table, some ExPASy proteomic tools (e.g., Compute pI/Mw, ProtParam, ProfileScan, ProtScale, PeptideMass, ScanProsite), and structure (SWISS-MODEL) are provided on the page. 

Given the role of H. pylori infection in gastric cancer and duodenal ulcer disease, one must note that certain interleukin-1 gene cluster polymorphisms (suspected of increasing production of interleukin-1-/1) are associated with a predisposition to hypochlorhydria and gastric cancer [52]. One of these host DNA polymorphisms involves a TATA box. 

One such product (tradename Beromun) has been approved for general medical use (Box 9.2). Most clinical interest in TNF, however, now centres around neutralizing its biological effects in situations where overexpression of TNF induces negative clinical effects. TNF has been firmly implicated in mediating many of the adverse effects associated with dozens of diseases (Table 9.7). Administration of anti-TNF monoclonal antibodies or soluble forms of the TNF receptor should help reduce the severity of many of the symptoms of these diseases. 

The release of glucose from the glycogen stores in the liver is mediated by glucose 6-phosphatase, which is apparently embedded within the membranes of the endoplasmic reticulum. A labile enzyme, it consists of a 357-residue catalytic subrmit,251/252 which may be associated with other subunits that participate in transport.252 253 A deficiency of this enzyme causes the very severe type la glycogen storage disease (see Box 20-D).251 253 Only hepatocytes have significant glucose 6-phosphatase activity. 

Some people with elevated lipoprotein levels have VLDL that migrates on electrophoresis in the (3 band rather than the pre-(3 band (see Box 2-A). The presence of the (3-VLDL is associated with a high incidence of artery disease,218 which is most likely to develop in persons homozygous for a genetic variant of apolipoprotein E. The problem may arise because apo-E is required for receptor-mediated uptake of VLDL, which interacts both with tissue LDL receptors and with hepatic apo-E receptors. Genes for many of the... 

Chapters 11 and 31. Since cancers contain multiple mutations, they are complex diseases. However, many specific susceptibility loci are being located, including some for breast cancer (Box 11-D),392 prostate cancer,393 and familial adenomatous polyposis, a hereditary disease leading to colon cancer.388 394 Cancer has long been known to be associated with chromosome instability including deletion and insertion mutations at simple repeat sequences, frame-shift mutations,395 DNA breakage, translocation,396 and losses or gains of whole chromosomes 397... 

Epilepsy may arise also from defects in a GABA transporter1145 or receptor.1146 One form of epilepsy is a triple-repeat disease of cystatin B (Table 26-4). Mutation in potassium channels,1147 glutamate receptors,1148 absence of neuropeptide Y,1149 and absence of L-isoaspartyl / D-aspartyl O-methyltransferase (Box 12-A)1150 have all been associated with epilepsy. 

One of the best-understood autoimmune diseases is myasthenia gravis, a condition associated with a decrease in the number of functional post-synaptic nicotinic acetylcholine receptors (Fig. 30-23) in neuromuscular junctions. e The resulting extreme muscular weakness can be fatal. Myasthenia gravis is not rare and affects about one in 10,000 peopled An interesting treatment consists of the administration of physostigmine, diisopropyl-phosphofluoridate (Chapter 12, Section C,l), or other acetylcholinesterase inhibitors (Box 12-E). These very toxic compounds, when administered in controlled amounts, permit accumulation of higher acetylcholine concentration with a resultant activation of muscular contraction. The same compounds... 

Note. None of these medications have FDA indication for the treatment of Alzheimer s disease. The literature and practice guidelines support the use of these medications for specific target symptoms. The FDA has issued a black box warning regarding the use of certain antipsychotic medications in the elderly, especially haloperidol, olanzapine, and risperidone. The warning notes that the use of these drugs is associated with an increase in death rates when used by the elderly patients with dementia. 

BOX 27-1 Diseases Other than Cystic Fibrosis Associated With an Elevated Sweat Electrolyte Concentration... 

Measurement of 1,25 (OH) 2D is usefiil in detecting inadequate or excessive hormone production in the evaluation of hypercalcemia, hypercalciuria, hypocalcemia, and bone and mineral disorders (Box 49-10). Because activated macrophages convert 25(OH)D to l,25(OH)2D, serum concentrations of 1,25(OH)2D are often increased in sarcoidosis, tuberculosis, other granulomatous diseases. Rarely is lymphoma associated with increased concentrations of 1,25(0H)2D. Concentrations of l,25(OH)2D are elevated in vitamin D-dependent rickets type II and in l,25(OH)2D intoxication, and may be elevated in primary hyperparathyroidism. Fatients with primary hyperparathyroidism and... 

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