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Bilirubin elevations are demonsfrated in dark urine and clay-colored stools, and liver. The resulting venous back- pressure results in peripheral and pulmonary dysfunctional congestion. Davidson et al, US patent No. Heart failure related disease represents a major public health issue due to an overall increase in prevalence and incidence in aging populations with a greater proportion of survivors of acute myocardial infarction AMI Kannel et al, , Br. Alternatively, viral vectors may be used that provide for transient expression of nucleic acid molecules. These sites are shown in Tables , 31, 33, 34, , 56, 58, 59, 62, 63 all sequences are 5′ to 3′ in the tables; X can be any base-paired sequence, the actual sequence is not relevant here.

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Antiarrhythmic agents can be used in order to reduce the risk of sudden death in patients suffering from cardiac disease.

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Successful malignant transformation in human cells was accomplished for the first time by ectopic expression of hTERT in combination with two oncogenes, SV40 large-T and H- ras. In addition, the ribozyme is a highly specific inhibitor of gene expression, with the specificity of inhibition depending not only on the base-pairing mechanism of binding to the target RNA, but also on the mechanism of target RNA cleavage.

Even a healthy, fransplanted heart can become diseased in response to the various stresses of mechanical, hemodynamic, hormonal, and pathological stimuli associated with extrinsic risk factors.

The present body of knowledge in telomerase research indicates the need for methods to assay telomerase activity and for compounds that can regulate telomerase expression for research, diagnostic, trait alteration, animal health and therapeutic use. Soc,; Scaringe et al,Nucleic Acids Res. For a review of current ifam strategies, see Schmajuk et al,Iam.

Full-length or partially full-length, internally-labeled target RNA for ribozyme cleavage assay is prepared by in vitro transcription in the presence of [a- 32 p] CTP, passed over a G 50 Sephadex column by spin chromatography and used as substrate RNA without further purification.


Synthetic analogs of fumagillin were later synthesized resulting in the discovery of TNP-which is 50 times more potent of an inhibitor than fumagillin and is less toxic in mice Ingber, D. Subsfrate RNA and the specific RNA cleavage products generated by ribozyme cleavage are visualized on an autoradiograph ofthe gel.

The risk of becoming a chronic HBsAg carrier is dependent upon the mode of acquisition of infection as well as the age ofthe individual at the time of infection. Deprotection ofthe RNA is performed using either a two-pot or one-pot protocol.

It appears that the reverse transcription as well as plus strand synthesis may occur in the completed core particle. The method of synthesis used followed the procedure for normal RNA synthesis as described above and in Usman et al. These observations indicate that hTERT mediated telomere maintenance is essential for the formation of human ocam cells Hahn, W.

By “consisting of is meant including, and limited to, whatever follows the phrase “consisting of. Generally, at least 5 bases on each arm are able to bind to, or otherwise interact with, the target RNA.

Cao et al, US patent No.

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Protein tyrosine kinase Src is dependant on myristoylation for activity and has been identified as an upstream regulator of human vascular endothelial growth factor VEGF expression through hypoxic induction in solid tumors Mukhopadhyay, D. Hepatitis B ica, generally self-limiting and will resolve in approximately 6 months.

Physiol,6, describe a mouse model for the study of regulatory effects of phospholamban on cardiac function in intact mice. In this invention, the product of these properties is increased or not significantly less than fold decreased in vivo compared to an all RNA ribozyme or all DNA enzyme.

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Column 2 is washed to isolate the active molecules for further processing as described in the scheme shown in Figure This pool of active molecules may also contain some molecules that are not active to cleave the target inactive molecules but have dissociated from the column. Multiplication ofthe HBV genome begins within the nucleus of an infected cell.


The internal control to control for possible Taq polymerase inhibition generates a band of 36 nt. As an initial screen, assays o are carried out for 1 hour at 37 C using a final concentration of either 40 nM or 1 dx-4130 ribozyme, i. Iccam “aryl” group refers to an aromatic group which has at least one ring having a conjugated pi electron system and includes carbocyclic aryl, heterocyclic aryl and biaryl groups, all of which may be optionally substituted.

Idam effects resulting from treatment with type 1 interferons can be divided into four general categories including: Assays for PTPase activity and tyrosine phosphorylation of insulin-receptor subsfrate 1 are described.

The hepatitis delta virus motif is described by Perrotta and Been, Biochemistry 31, In a non-limiting example, small scale syntheses are conducted on a Applied Biosystems, Inc. Alternately, substrates are 5’p-end labeled using Icaj polynucleotide kinase enzyme.

This class of drug carriers resists opsonization and elimination by ivam mononuclear phagocytic system MPS or RESthereby enabling longer blood circulation times and enhanced tissue exposure for the encapsulated drug Lasic et al. He et al,Circulation, describe endogenous expression of mutant phospholamban and phospholamban antisense RNA to investigate the corresponding effect on SERC A2a activity and cardiac myocyte contractility.

In addition, most patients with compensated liver disease are asymptomatic and the minority with symptoms report only minor symptoms such as dyspepsia and weakness.

A, 90, ; Thompson et al,Nucleic Icma Res.