Biomedical subjects

J Blankenship

Publications and source records attributed to J Blankenship.

At least 37 records · Page 2Linked to original sources

PubMed1991

A prospective, randomized trial comparing combination half-dose tissue-type plasminogen activator and streptokinase with full-dose tissue-type plasminogen activator. Kentucky Acute Myocardial Infarction Trial (KAMIT) Group.

BACKGROUND: The potential benefits of combination thrombolytic agents in the treatment of myocardial infarction remain uncertain. In a small pilot study, we demonstrated that combining half-dose tissue-type plasminogen activator (t-PA) with streptokinase (SK) achieved a high rate of infarct vessel patency and a low rate of reocclusion at half the cost of full-dose t-PA. METHODS AND RESULTS: We designed a prospective trial in which 216 patients were randomized within 6 hours of myocardial infarction to receive either the combination of half-dose (50 mg) t-PA with streptokinase (1.5 MU) during 1 hour or to the conventional dose of t-PA (100 mg) during 3 hours. Acute patency was determined by angiography at 90 minutes, and angioplasty was reserved for failed thrombolysis. Heparin and aspirin regimens were maintained until follow-up catheterization at day 7. Acute patency was significantly greater after t-PA/SK (79%) than with t-PA alone (64%, p less than 0.05). After angioplasty for failed thrombolysis, acute patency increased to 96% in both groups. Marked depletion of serum fibrinogen levels occurred after t-PA/SK compared with t-PA alone at 4 hours (37 +/- 36 versus 199 +/- 66 mg/dl, p less than 0.0001) and persisted 24 hours after therapy (153 +/- 66 versus 252 +/- 75 mg/dl, p less than 0.0001). Reocclusion (3% versus 10%, p = 0.06), reinfarction (0% versus 4%, p less than 0.05), and need for emergency bypass surgery (1% versus 6%, p = 0.05) tended to be less in the t-PA/SK group. Greater myocardial salvage was apparent in the t-PA/SK group as assessed by infarct zone function at day 7 (-1.9 SD/chord versus -2.3 SD/chord after t-PA alone, p less than 0.05). In-hospital mortality (6% versus 4%) and serious bleeding (12% versus 11%) were similar between the two groups. CONCLUSIONS: These results suggest that a less expensive regimen of half-dose t-PA with SK yields superior 90-minute patency and left ventricular function and a trend toward reduced reocclusion compared with the conventional dose of t-PA.

Adolescent↗

PubMed1989

A selective inhibitor of N8-acetylspermidine deacetylation in mice and HeLa cells without effects on histone deacetylation.

The inhibitory effects of 7-[N-(3-aminopropyl)amino]heptan-2-one (APAH) on N8-acetylspermidine deacetylation were studied. In in vitro studies, APAH produced inhibition (apparent Ki of 0.18 microM) of N8-acetylspermidine deacetylation by the 100,000g supernatant fraction of rat liver. This apparent Ki was 60-fold less than the apparent Km (11 microM) for deacetylation of the substrate, N8-acetylspermidine, suggesting that APAH could be a potent, effective inhibitor in vivo. APAH was administered to mice by intraperitoneal injection at a dose of 200 mg/kg, and polyamine and acetylpolyamine levels in liver and spleen were measured. In tissues of control mice, N8-acetylspermidine was not detectable but increased to detectable levels 30-360 min after APAH treatment. These data are consistent with inhibition of the deacetylase by APAH. Increases in putrescine and N1-acetylspermidine levels occurred in liver after APAH treatment with increases in N1-acetylspermidine levels observed in spleen. In HeLa cells, a significant increase in N8-acetylspermidine was observed following 24 h exposure to 10 microM APAH while no change occurred in the acetylation level of HeLa cell histones. In contrast, 24 h exposure to 10 mM sodium butyrate produced no change in N8-acetylspermidine levels and an increase in the acetylation level of histones H4 and H2B. These results suggest that APAH has a relatively selective inhibitory effect on N8-acetylspermidine but not histone deacetylation. This is the first report of significant levels of N8-acetylspermidine in animal tissues and of the effects of in vivo inhibition of N8-acetylspermidine deacetylase.

Acetylation↗

PubMed1986

N1-acetylspermidine is not a substrate for N-acetylspermidine deacetylase.

The specificity of N-acetylspermidine deacetylase from rat liver for the two naturally occurring forms of monoacetylated spermidine was studied. N8-Acetylspermidine is the preferred substrate in vitro for this enzyme, and, in fact, N1-acetylspermidine did not undergo deacetylation under the conditions used in this study. Thus N8-acetylspermidine is the more appropriate substrate for assaying N-acetylspermidine deacetylase activity.

Amidohydrolases↗

PubMed1984

Collagen metabolism and spicule formation in sea urchin micromeres.

The role of collagen or collagen-like protein(s) in the in vitro formation of the sea urchin embryonic skeleton was investigated using isolated micromeres of Strongylocentrotus purpuratus. Micromeres were cultured in sea water containing 4% horse serum on tissue culture plastic or an extracellular matrix of type I collagen. The effect of proline analogs and an inhibitor of collagen hydroxylation on in vitro spicule formation in both culture systems was monitored. When micromeres are cultured in the presence of proline analogs L-azetidine-2-carboxylic acid and L-3, 4-dehydroproline which disrupt collagen metabolism, spicule formation is significantly less inhibited on a collagen substratum than on plastic. Culturing micromeres on plastic in the presence of alpha, alpha'-dipyridyl, an inhibitor of collagen hydroxylation, resulted in almost complete inhibition of spicule formation. The inhibition by alpha, alpha'-dipyridyl can be overcome by culturing micromeres on collagen substratum. These results do not support the idea of collagen being the calcified organic matrix of the spicule. Rather, they suggest that micromeres synthesize a collagen-like extracellular matrix which is necessary for spicule formation. Inhibition of this activity by proline analogs or a collagen processing inhibitor can be overcome by providing the cells with a previously deposited extracellular matrix.

2,2'-Dipyridyl↗

PubMed1984

Metabolism of N1-acetylspermidine and N8-acetylspermidine in rats.

Metabolism of N1-acetylspermidine and N8-acetylspermidine in rat liver and kidney was studied in vivo. N1-Acetylspermidine was metabolized primarily to putrescine while N8-acetylspermidine underwent deacetylation to yield spermidine. The rate of metabolism of these two compounds was much greater than that of spermidine. The rate of metabolism of N8-acetylspermidine exceeded that of N1-acetylspermidine in both liver and kidney. These rapid rates of metabolism could at least in part account for the low levels of these two compounds found in tissues. The differences in routes of metabolism of N1-acetylspermidine and N8-acetylspermidine may indicate differences in cellular functions of the two compounds.

Animals↗

PubMed1983