Translactational induction of CYP4A expression in 10.5-day neonatal rats by the hypolipidemic drug clofibrate

Lactating mothers of 7.5-day neonatal rats were injected intraperitoneally with 500 mg kg-1 clofibrate for 3 consecutive days at 24-hour intervals; 24 hours after the final injection, the maternal cytochrome P450 4A (CYP4A) mRNA levels had risen 14- and 2.5-fold above the constitutive levels of expression seen in the liver and kidney, respectively. Lactational transfer of clofibrate to the suckling 10.5-day litter was demonstrated by the 15- and 5-fold elevation observed in the neonatal hepatic and renal CYP4A mRNAs, respectively, following suckling from drug-induced mothers. A significant decrease in the relative liver weights of these neonatal pups was seen following clofibrate exposure via maternal milk, in total contrast to the normally observed increase in liver/body weight ratios of rats treated with clofibrate. Western blot analysis using a polyclonal goat anti-rat CYP4A1 antibody also demonstrated a rise in the CYP4A protein levels in both the mothers and their litters following maternal clofibrate treatment.     

Serial coronary angiographic evidence that antioxidant vitamin intake reduces progression of coronary artery atherosclerosis

OBJECTIVE: To explore the association of supplementary and dietary vitamin E and C intake with the progression of coronary artery disease. DESIGN: A subgroup analysis of the on-trial antioxidant vitamin intake database acquired in the Cholesterol Lowering Atherosclerosis Study, a randomized, placebo-controlled, serial angiographic clinical trial evaluating the risk and benefit of colestipol-niacin on coronary artery disease progression. SETTING: Community- and university-based cardiac catheterization laboratories. SUBJECTS: A total of 156 men aged 40 to 59 years with previous coronary artery bypass graft surgery. INTERVENTION: Supplementary and dietary vitamin E and C intake (nonrandomized) in association with cholesterol-lowering diet and either colestipol-niacin or placebo (randomized). OUTCOME: Change per subject in the percentage of vessel diameter obstructed because of stenosis (%S) determined by quantitative coronary angiography after 2 years of randomized therapy on all lesions, mild/moderate lesions (< 50%S), and severe lesions (> or = 50%S). RESULTS: Overall, subjects with supplementary vitamin E intake of 100 IU per day or greater demonstrated less coronary artery lesion progression than did subjects with supplementary vitamin E intake less than 100 IU per day for all lesions (P = .04) and for mild/moderate lesions (P = .01). Within the drug group, benefit of supplementary vitamin E intake was found for all lesions (P = .02) and mild/moderate lesions (P = .01). Within the placebo group, benefit of supplementary vitamin E intake was not found. No benefit was found for use of supplementary vitamin C exclusively or in conjunction with supplementary vitamin E, use of multivitamins, or increased dietary intake of vitamin E or vitamin C. CONCLUSIONS: These results indicate an association between supplementary vitamin E intake and angiographically demonstrated reduction in coronary artery lesion progression. Verification from carefully designed, randomized, serial arterial imaging end point trials is needed.     

Morphologic changes in arterial grafts in rabbit ears

The morphology of auto- and allografted segments of rabbit central ear arteries was studied at various times after grafting. Autografts showed thrombosis only in the immediate postoperative period. Autografts developed intimal thickenings whose cellular elements at all stages were almost exclusively myointimal in type. Their medial smooth muscle cells were viable at all stages. Allografts frequently thrombosed within 8 weeks of grafting. Intimal thickenings that developed in the first 6 weeks in allografts mainly contained infiltrating hematogenous cells with few myointimal cells. Immune cells infiltrated all of the layers of allograft walls, and the smooth muscle cells of their medias showed increasingly severe degeneration and by 8 weeks had completely disappeared. In long established allografts, the intima was extremely thick and contained myointimal cells and fibrous tissue. Their medias were fibrosed. In long standing allografts, immune cell infiltration was no longer present. The thrombosis of allografted arteries that occurred within 8 weeks of grafting was related to immunologic events observed within the vessel grafts. Differences between myointimal cells and smooth muscle cells with regard to their morphology and orientation were identified. A possible origin of myointimal cells from endothelial cells is suggested.     

A reappraisal of sonolucent renal masses

The authors present a differential diagnosis of echo-free renal masses and emphasize that such lesions are not always simple cysts. Of 312 renal sonograms, 15 showed sonolucent masses which proved to be something other than a simple cyst. Pathological diagnoses included abscess, hematoma, renal artery aneurysm, hydronephrosis, and homogeneous or cystic tumor. To achieve optimal diagnostic accuracy, it is insufficient to rely solely on sonolucency as demonstrated on the sonogram. Any disparities in the radiological, clinical, or ultrasonic findings demand further evaluation. Nephrotomography, angiography, aspiration biopsy, or exploration should be selected in a sequence which is appropriate to ensure correct diagnosis while minimizing the risk to the patient.     

Extramedullary myeloid cell tumors in myelodysplastic-syndromes: not a true indication of impending acute myeloid leukemia

The purpose of this report is to record a patient with myelodysplastic syndrome (MDS) associated acute myelogenous leukemia (AML) and leukemia cutis who had blast expression of the neural cell adhesion molecule (NCAM) and to review the world literature on prognostic implications of extramedullary myeloid cell tumors (granulocytic sarcoma, myeloblastoma, chloroma and leukemia cutis) in MDS and MDS associated AML. Case report and world literature from January 1965-January 1994 for all cases of MDS-associated extramedullary myeloid cell tumors (EMT) is reviewed, and the first patient with EMT, MDS associated AML and blast expression of NCAM is described. There have been 46 cases of MDS associated EMT previously reported. 32 cases occurred in the absence of AML. AML developed in 47% of these patients at a mean of 38 weeks from initial EMT. Of the patients not developing AML, median survival from initial EMT was 11 weeks. Nine patients received chemotherapy at the time of EMT and had a median survival of 36 weeks. The median survival for patients receiving conservative therapy for EMT was 48 weeks. Patients (n = 15) with EMT and MDS associated AML had a poor outcome regardless of therapy with a median survival of 11 weeks. Unlike other forms of isolated EMT, MDS associated EMT is not always a forerunner of AML. Premature induction therapy for MDS associated EMT does not appear to prolong survival. EMT in the setting of MDS associated AML is associated with a poor prognosis despite aggressive chemotherapy. Blast expression of NCAM may prove to be a risk factor for EMT in MDS associated AML.     

The additional predictive value contributed by quantitative chromatin pattern description as compared to DNA ploidy level measurement in 257 superficial bladder transitional cell carcinomas

The purpose of the present study was to demonstrate the post-translational modifications of sperm plasma membrane proteins by fatty acid acylation during sperm maturation in the epididymis. Rat epididymal spermatozoa were incubated at 37 degrees C with various concentrations (100 microCi and 1 mCi) of [9-10(n)3H]palmitic acid in a medium containing Tyrode's solution supplemented with sodium bicarbonate, sodium pyruvate and sodium lactate. The incorporation of [3H]palmitate in vitro was determined in epididymal spermatozoa and an attempt was made to identify the lipid-linked proteins of purified plasma membranes of maturing epididymal spermatozoa by autoradiography. The studies demonstrated that [3H]palmitate was covalently linked to a subset of membrane cytoskeleton proteins of maturing rat spermatozoa. The pattern of incorporation of lipid was a maturation-associated phenomenon as caput spermatozoa incorporated more radioactivity than did caudal spermatozoa. The labelled proteins appeared to be membrane-bound since 82% of radioactivity was associated with membrane fractions. Autoradiograms of SDS-PAGE gels of labelled caput sperm extract showed three prominent palmitate-incorporating protein bands of about 70, 56 and 36 kDa and few minor bands. Most of these proteins were present in the membrane fraction of caput spermatozoa. Labelled gels of both the sperm extracts and of purified membranes showed resistance to hydroxylamine treatment, suggesting that there are amide bonds between lipid and proteins. The higher incorporation of labelled palmitate by immature spermatozoa of the caput epididymis compared with mature spermatozoa from the cauda epididymis and the addition of palmitate to plasma membrane proteins of caput epididymal spermatozoa suggest that fatty acylation is a post-translational modification of sperm membrane proteins.