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Biomedical subjects

M L Zucker

Publications and source records attributed to M L Zucker.

29 records · Page 2Linked to original sources

Production of herpes simplex virus type 1 thymidine kinase in the presence of thymidine analogues.

Treatment of herpes simplex virus type 1 (HSV-1) infected Vero, BHK, BHKtk- and LMtk- cells with 5-iodo-5'-amino-2',5'-dideoxyuridine (AIdUrd) caused increased synthesis of ICP36 and an increase in HSV-1 thymidine kinase (tk) activity at late times of infection. The overproduced ICP36 was identified as the HSV-1 encoded tk protein by immunoprecipitation. Whereas the thymidine analogue 5'-amino-5'-deoxythymidine (AdThd) caused an increase in HSV-1 tk synthesis and activity in wild type Vero and BHK cells, 5-iodo-2'-deoxyuridine (IdUrd) caused a similar increase only in tk- cells (LMtk-, BHKtk-). In vivo and in vitro stabilization studies using a [35S]methionine pulse-chase experiment or heat inactivation studies with purified HSV-1 tk revealed that stabilization of tk by the analogues could not account for the extent of the observed increase. Since overproduction of tk is observed only at late times of infection, it is suggested that the presence of these thymidine analogues in either the viral DNA or the cellular nucleotide pools is responsible for the observed differential effects.

Animals↗

Platelet function in hypercholesterolemics before and after hypolipidemic drug therapy.

Platelet function parameters were studied in type II hyperlipoproteinemics in relation to baseline and drug-induced changes in serum cholesterol levels. There were no significant differences between 28 type II hyperlipoproteinemics and 19 normal subjects in baseline values for platelet aggregation, thromboxane generation, sensitivity to prostacyclin, plasma platelet factor 4 or beta-thromboglobulin. Eleven of the hyperlipoproteinemic patients were treated with a combination of the cholesterol-lowering drugs probucol and colestipol. The drug treatment resulted in statistically significant lowering of serum total and low-density lipoprotein (LDL)-cholesterol levels (30% reduction of mean LDL-cholesterol, p less than 0.01); however, there was no significant change in any of the platelet function parameters after the drug treatment compared with placebo. These results provide evidence against a relationship between serum cholesterol levels and in vitro platelet function.

Adult↗

Infection and transformation of mouse cells by human adenovirus type 2.

The susceptibilities of C57Bl/6J mouse embryo fibroblasts (MEF) and baby mouse kidney (BMK) cells to infection or transformation by adenovirus type 2 have been compared to those of rat embryo fibroblasts (REF). Both MEF and BMK cells were some 10-fold less permissive to replication of the virus than were REF cells, even though similar fractions of all three cell types, a maximum of 50-60%, produced viral tumor and structural antigens. This observation suggests that a very late step in adenovirus production, such as assembly or maturation, occurs much less efficiently in mouse cells than it does in rat cells. No significant differences in the frequencies of transformation, as assayed by the appearance of foci of morphologically transformed cells, were observed following transfection of adenovirus type 2 or type 5 DNA into the three cell types. However, it proved extremely difficult to establish permanent lines of adenovirus-transformed mouse cells: only 2 of more than 100 attempts were successful, compared to a success rate of close to 100% with adenovirus type 2-transformed REF or SV40-transformed MEF or BMK cells. The two lines of type 2 adenovirus-transformed MEF that were established have been shown to retain and express viral genetic information.

Adenoviruses, Human↗

The effect of variable fat diets and cholesterol-lowering drugs on Antithrombin III levels in hyperlipoproteinemic and normal subjects.

Functional and immunological Antithrombin III (AT III) levels were studied in normal and hyperlipoproteinemic subjects undergoing crossover therapeutic trials of either diets or hypocholesterolemic drugs. The diet trial subjects, 7 hyperlipoproteinemics and 15 normals, were randomly assigned to crossover between a high saturated fat diet (P/S ratio 1:8) and a high polyunsaturated fat diet (P/S ratio 4:1) for periods of 6-8 weeks, preceded by a baseline period on regular American diet (P/S ratio 1:1). For the drug trials, 33 type II A or B hyperlipoproteinemics were treated in random and double-blind fashion with Colestipol (20 gm/day) or both, for periods of 3 months, preceded by a double placebo period. Mean low density lipoprotein cholesterol levels were significantly different (p less than 0.001) between high saturated and high polyunsaturated fat diets (157 +/- 37 mg/dl vs 137 +/- 31 mg/dl respectively, mean +/- S.D.) and between placebo and drug treatment periods (226 +/- 51 mg/dl vs 183 +/- 44 mg/dl respectively, mean + S.D.). There was no difference in basal functional or immunological AT III levels between normal and hyperlipoproteinemics. AT III levels did not correlate significantly with cholesterol or triglyceride levels and remained unchanged despite significant reductions in serum cholesterol related to the diet and drug therapy. There appears to be no significant association between baseline or post treatment serum cholesterol levels and functional or immunological AT III. Thus, changes in AT III are unlikely to play a role in the link between hypercholesterolemia and thrombosis.

Adult↗

The use of blood and blood components in 1,769 patients undergoing open-heart surgery.

There has been a decrease in the use of whole blood and red cell transfusions during and after open-heart operations in the greater Kansas City area from an average of slightly more than 9 units per patient from 1969 through 1971, to just over 3 units per patient from 1975 through 1977. In 1977, 1,256 patients, or 71% of 1,769 patients, underwent coronary artery bypass exclusively and had an average transfusion utilization of 2.6 units. All other open-heart operations averaged 4.7 units per patient. Hemodilution and the acceptance of hematocrits between 25 and 30% in open-heart operations are probably the main factors responsible for lower transfusion use per patient, while the increased proportion of patients undergoing coronary artery bypass accounts for a further decrease in the average amount of blood used per patient. It is of note that blood transfused to patients having an open-heart operation was not significantly fresher than blood for routine use, yet hemostasis was not a problem as evidenced by the small use of fresh-frozen plasma in 67 patients (3.8%) and platelet concentrates in 42 patients (2.4%).

Adult↗

Prophylactic and therapeutic use of anticoagulants in inherited antithrombin III deficiency.

A family with a pronounced history of venous thrombotic disease is described. Several members were found to have reduced antithrombin III levels. Heparin cofactor activity was reduced in the antithrombin III-deficient plasma. The proposita, who presented with bilateral iliofemoral vein thrombosis early in pregnancy, was treated initially with heparin, and after the 12th week of pregnancy was maintained on oral anticoagulants until she was 38 weeks pregnant. Heparin was then given and continued throughout the delivery period and for 10 days postpartum with no evidence of recurrent thrombosis. The effect of infusing 5 units of fresh frozen plasma on the antithrombin III level and the response to heparin were minimal and short-lived. Oral anticoagulatns produced a rise in the antithrombin III level. These results demonstrate the importance of maintaining antithrombin III-deficient subjects on long-term oral anticoagulant therapy.

Adult↗

How to successfully influence laboratory test utilization.

In 1994, we discovered that our hospital was higher than the 75th percentile in the average number of laboratory tests performed per inpatient discharge compared with other teaching hospitals with a case mix index of greater than 1.35. Because of the diversity and volume of tests offered, no single project would have significantly affected the number of tests ordered per patient. Pathologists together with the administrative director and section managers identified areas of potential improvement, noting tests that were high volume, expensive, difficult to perform, or of questionable medical benefit. We relied on a combination of administrative changes and physician education initiatives to influence physician test-ordering behavior. The impact of these initiatives was measured by reviewing monthly revenue and usage reports before and after changes were implemented. Each of these initiatives helped to gradually decrease the average number of inpatient tests per discharge from 44 in the first quarter of 1994 to 29 in the third quarter of 1999. Compared with our peer group, our hospital's rank has steadily improved from the 75th to the 15th percentile.

Benchmarking↗