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Joseph F Clark

Publications and source records attributed to Joseph F Clark.

22 records · Page 2Linked to original sources
PubMed2002

Isoforms of apolipoprotein E can modulate tPA-induced clot lysis in vitro.

Apo E, and its respective isoforms, have been linked to outcome and survival in cerebral vascular and cardiovascular diseases. The effectiveness of intravenous tPA in patients with acute ischemic stroke appears to be enhanced in patients who have an Apo E2 phenotype. The ability of Apo E isoproteins (endogenous Apo E isoproteins or exogenous Apo E isoproteins) to modulate tPA-induced clot lysis in vitro was assessed using an in vitro clot assay system. Blood samples were obtained from 18-volunteers with three Apo E genotypes: E2, E3 and E4. tPA-induced clot lysis (0-4 microgram/ml tPA), was assessed in the presence or absence of supplemental Apo E2, E3 or E4 (9.8 microgram/ml). tPA-induced clot lysis was significantly (P equal or less than 0.0001) enhanced by supplementation with Apo E2 (EC50 0.20 0.06 microgram/ml) as compared to tPA alone (0.72 0.19). Apo E4 supplementation caused a significant (P < or = 0.05) inhibition of clot lysis (0.98 0.23), but there was no significant change caused by Apo E3. The genotype of the volunteer did not significantly affect the ability of the supplemental Apo E from modulating tPA-induced clot lysis. We conclude that the administration of Apo E isoproteins can modulate clot lysis in vitro. Our results suggest that the Apo E isoprotein may have an impact on clot dissolution and the effectiveness of thrombolytic therapy.

Apolipoprotein E2↗
PubMed2002

Oxidation of bilirubin produces compounds that cause prolonged vasospasm of rat cerebral vessels: a contributor to subarachnoid hemorrhage-induced vasospasm.

The authors have previously shown that bilirubin-oxidation products (BOXes) are present in CSF of subarachnoid hemorrhage patients with vasospasm, and that BOXes cause vasoconstriction in vitro. This study determined whether BOXes cause vasospasm in vivo. Identical volumes of either lysed blood or standardized amounts of BOXes were injected into the cisterna magna of adult rats. BOX injections caused 6 of 10 rats to die within 10 minutes, whereas 12 of 12 rats survived for 24 hours after blood injections. The mechanism for this significant (P < or = 0.01) increase in mortality was unclear. To directly test whether BOXes produced vasospasm, a cranial window technique was used. Application of 20 microL of 10-micromol/L bilirubin had little effect on the vessels. However, application of BOXes produced marked, dose-dependent small artery and arteriole vasospasm that approached a 90% decrease in diameter by 40 minutes after application in some vessels, and persisted for at least 24 hours. To determine if BOX-mediated vasospasm led to cortical injury, histology and immunocytochemistry were performed on animals that survived for 24 hours. There was a BOX-related stress protein response for HSP25 and HSP32 (HO-1) without evidence of infarction. The finding that the BOXes produce vasospasm of cerebral vessels in vivo, in conjunction with BOXes being found in CSF of vasospasm patients, supports our hypothesis that BOXes contribute to or cause cerebral vasospasm after subarachnoid hemorrhage.

Animals↗
PubMedDate not supplied

Magnetic resonance spectroscopy in a 9-day-old heterozygous female child with creatine transporter deficiency.

An X-linked creatine deficiency syndrome caused by mutations in the creatine transporter gene SLC6A8/CRTR mapped to Xq28 has recently been described. Essential in the recognition of this disorder is the absence of creatine on proton magnetic resonance spectroscopy (MRS) examination. A 9-day-old heterozygous female child with this syndrome demonstrated a significant reduction of creatine on proton MRS. She is a carrier of the R514X nonsense mutation.

Amino Acid Metabolism, Inborn Errors↗