Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0086543 (cataract)
 29,165 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The prostaglandins produce elevation of intraocular pressure and breakdown of the blood-aqueous barrier. They act via the secondary messenger system, cyclic AMP. Although the pathogenesis of many forms of ocular inflammation, both external and internal, is unclear, it is evident that some forms of ocular inflammation are prostaglandin-mediated, at least in part. Others may be totally mediated by prostaglandin synthesis. At present the corticosteroids are the mainstay of therapy of these conditions. However, the corticosteroids are poor inhibitors of prostaglandin synthesis and have many deleterious side effects such as induction of ocular hypertension, cataract, and infection. The search for new agents that will obviate these side effects and be more specific for the disease process is crucial. The discovery that the mode of action of many nonsteroidal anti-inflammatory agents is via inhibition of prostaglandin synthesis places a premium on elucidating which of these agents is most effective and least toxic in the eye and by which route of administration. The arachidonic acid screening model is ideal for initially choosing which agent has the greatest potential clinically. Arachidonic acid, a PGE2 precursor, when given topically also elevates intraocular pressure and aqueous humor protein, and these effects are blocked by the nonsteroidal anti-inflammatory drugs. This occurs if the arachidonic acid is injected into the vitreous humor, too, providing evidence that this in vivo model involves intraocular mechanisms. Utilizing the arachidonic acid system, a comparative study of nonsteroidal inhibitors of prostaglandin synthesis shows that the most effective of 14 agents were flurbiprofen solution and suspensions of polysorbate-dispersed indoxole, meclofenamic acid, indomethacin, and clonixin. Animal uveitis is not an ideal model for the human condition. Nevertheless, proving the superior efficacy of a screened drug in this system will identify those drugs to be tested in the human disease states. Only after the very few best drugs of this nature are identified should the ultimate steps of human testing be initiated.
 ...
PMID:Prostaglandins, nonsteroidal anti-inflammatory agents and eye disease. 19 83

Myotonic dystrophy (MyD) is a multisystemic disorder characterized by muscle atrophy, myotonia and cataract. Although a number of reports have been accumulated showing the presence of bone changes in MyD patients, there are few published papers in which calcium metabolism was precisely examined. In the previous paper, we reported that intestinal calcium absorption was increased in MyD patients due to the elevation of plasma 1,25(OH)2D level. The present study was designed to elucidate the mechanism of increased level of serum 1,25(OH)2D concentration in MyD patients. Calcium tolerance tests were performed in 13 patients with MyD, 13 patients with other neuromuscular disorders (non-MyD) and 12 healthy control subjects according to the method of Broadus et al. Immunoreactive PTH (iPTH) levels and cyclic AMP (cAMP) levels were measured using commercially available RIA kits. The basal plasma calcium levels in MyD were slightly higher than those in the other two groups, but the difference was not statistically significant. The plasma 1,25(OH)2D levels, calcemic responses and calciuric responses in MyD were significantly higher than those in the other two groups. Serum iPTH levels in MyD (0.462 +/- 0.320 ng/ml, Mean +/- SD) were significantly higher than those in the other two groups (normal subjects 0.175 +/- 0.092, non-MyD 0.200 +/- 0.111; p less than 0.02). Nephrogenous cyclic AMP (NcAMP) levels in MyD (2.094 +/- 3.244 nmol/100 ml GF) were also higher than those in normal subjects (0.907 +/- 0.212, p less than 0.05) and in non-MyD (0.929 +/- 0.335, p less than 0.05). There was a significant correlation between serum iPTH levels and NcAMP levels, and therefore it might be possible to accept that these two measurements reflect the level of parathyroid function.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:[Abnormal calcium metabolism in myotonic dystrophy (II): Increased level of nephrogenous cyclic AMP and serum immunoreactive parathyroid hormone]. 285 65

Sensitive high-performance liquid chromatography methods were employed to assess regional distribution of adenine, guanosine and uridine nucleotides in clear and cataractous human eye lenses. According to slit-lamp examination, three forms of senile cataract were distinguished: (1) supranuclear or deep cortical cataract (typical senile cataract), (2) primary nuclear cataract (cataracta brunescens) and (3) subcapsular cortical cataract associated either with a supranuclear (3a) or a secondary nuclear cataract (3b). Except for AMP, which was highest in the nuclear fraction, all other nucleotides (ATP, ADP, GTP, and UTP) were predominantly located in the anterior cortex (plus epithelium) of clear as well as cataractous lenses, that is, ATP levels in the nucleus amounted to 20% of those found in the anterior cortex (plus epithelium); ATP levels in the posterior cortex were about 60% of those in the anterior cortex (plus epithelium). Significant differences in the absolute regional nucleotide level existed between the different forms of cataract. Highest ATP levels were found in the anterior cortex (plus epithelium) of clear lenses and deep or supranuclear cortical cataract. The ATP level was slightly diminished in primary nuclear cataract and in supranuclear cortical cataract when associated with an early subcapsular cortical cataract. ATP levels were depressed to less than 30% in the anterior cortex (plus epithelium) of lenses with a subcapsular cortical cataract when associated with either an early secondary nuclear or a mature cataract. Furthermore, the ATP/ADP ratio was decreased in this form of senile cataract. The decrease in lens nucleotide level did not correlate with increased age. These data suggest that decreases in regional ATP level are a secondary event and do not appear to be causally involved in the genesis of the 'cataracta senilis'.
 ...
PMID:Nucleotide levels in human lens: regional distribution in different forms of senile cataract. 292 Jul 83

Many differences exist between human and animal lenses. Firstly, ATP concentrations in human lenses remain relatively unchanged during aging, despite slowing down of carbohydrate metabolism. Secondly, growth rate, expressed either by fresh weight or by volume, decreases with age, but this evolution is much less pronounced in human than in animal lenses and in the former never stops completely. This protein synthesis appears to be reduction in a very important pathogenic factor in senile cataract. This opinion is strengthened by the fact that ATP, which hardly decreases with age in human lenses, diminishes only in the last stages of senile cataract, whereas the deficiency in protein synthesis is an early phenomenon, and precedes the first opacities. Incorporation of amino acids into soluble lens protein in vitro can be stimulated by adding to the culture medium, 5 m M dibutyryl c AMP protected by 0,5 m M isobutylmethylxanthine. Topical application to the eye of a few drops confirmed penetration of the c AMP into the lens. The theoretical possibility, always denied, of a preventive or stabilizing medicinal treatment for senile cataract, does, therefore, exist.
 ...
PMID:[Anything new concerning the human lens and senile cataract (author's transl)]. 627 66

Whilst searching for a mammalian homologue of the Drosophila glass gene we cloned a mouse cDNA whose deduced sequence encodes a 614 amino acid (aa) protein with ten Cys2-His2 (C2H2) zinc finger (Zf) motifs. Zfp64 is expressed in all developing and mature mouse tissues examined, except the mouse erythroleukemia (MEL) cell line. Zfp64 maps to the distal region of mouse chromosome 2 close to lens opacity 4 (Lop4), a semidominant cataract mutation. Sequence analysis shows that Zfp64 has multiple potential phosphorylation sites for casein kinase II (CK II), protein kinase C (PKC), tyrosine kinase (TK) and c-AMP- and c-GMP-dependent protein kinase (cA/GMPDPK).
 ...
PMID:A search for a mammalian homologue of the Drosophila photoreceptor development gene glass yields Zfp64, a zinc finger encoding gene which maps to the distal end of mouse chromosome 2. 903 7

Myotonic dystrophy (DM) is an autosomal dominant disorder characterized by peculiar clinical features. Its molecular basis is the unstable expansion of a CTG triplet repeat in the gene encoding myotonin protein kinase (Mt-PK), the nucleotide sequence of which has extensive homology to the cyclic AMP (cAMP)-dependent protein kinase gene. Extensive efforts have been made to clarify the signal transduction pathway in which the responsible gene operates, but confirming evidence has yet to be obtained. Because some symptoms in DM are similar to those in hypoparathyroidism, we divided 24 DM patients into two groups on the basis of their serum calcium levels; Group 1, those with normocalcemia (11 patients), and group 2, those with hypocalcemia (13 patients). The highly sensitive parathyroid hormone (HS-PTH) plasma levels in group 1 were within normal limits, whereas those in group 2 were abnormally high. Laboratory findings for the group 2 patients resembled those for pseudohypoparathyroidism (PHP), whereas those for group 1 patients were normal. The Ellsworth-Howard (EH) test was used to determine which type of PHP the group 2 patients belonged to. Both the phosphaturic (delta P) and urinary cAMP (UcAMP) responses were estimated. The delta P responses in group 2 were significantly lower than those in group 1, but their UcAMP responses did not differ. This is evidence that group 2 patients had PHP type II, whereas group 1 patients were normal. We also investigated whether the disease severity differed between the groups. Cataracts, ectopic calcifications, and ossifications, which are associated with PHP, were more frequent in group 2. In addition, the mean IQ in that group was significantly lower. Clinically, the group 2 signs agreed well with those of PHP, whereas for group 1 there was only a slight similarity. These results are additional evidence that the patients in group 2 have abnormal calcium metabolism, the abnormality being in the postadenylate cyclase-cAMP pathway in the renal tubular cells. The degree of (CTG)n expansion, the so-called expanded DNA fragment (EF) size, was determined by standard Southern blot analysis. The allelic EF sizes in both groups were greater than in the healthy controls. Moreover, those in group 2 were significantly longer than those in group 1. We therefore investigated whether EF size is correlated with the serum calcium and plasma PTH levels, the delta P responses in the EH test, and IQ. All these items were significantly correlated with EF size. Our findings show that the expanded DNA fragment size in DM is correlated with the degree of abnormal calcium metabolism.
 ...
PMID:Abnormal calcium metabolism in myotonic dystrophy as shown by the Ellsworth-Howard test and its relation to CTG triplet repeat length. 940 36