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Biomedical subjects

G Popescu

Publications and source records attributed to G Popescu.

At least 19 recordsLinked to original sources

Cloning of a cDNA for a second retinol dehydrogenase type II. Expression of its mRNA relative to type I.

A retinol dehydrogenase, RoDH(1), which recognizes holo-cellular retinol-binding protein (CRBP) as substrate, has been cloned, expressed, and identified as a short-chain dehydrogenase/reductase (Chai, X., Boerman, M. H. E. M., Zhai, Y., and Napoli, J. L. (1995) J. Biol. Chem. 270, 3900-3904). This work reports the cloning and expression of a cDNA encoding a RoDH isozyme, RoDH(II). The predicted amino acid sequence verifies RoDH(II) as a short-chain dehydrogenase/reductase, 82% identical with RoDH(I). RoDH(II) recognized the physiological form of retinol as substrate, CRBP, with a Km of 2 mM. Similar to microsomal RoDH and RoDH(I), RoDH(II) had higher activity with NADP rather than NAD, was stimulated by ethanol and phosphatidyl choline, was not inhibited by the medium-chain alcohol dehydrogenase inhibitor 4-methylpyrazole, but was inhibited by phenylarsine oxide and the short-chain dehydrogenase/reductase inhibitor carbenoxolone. Northern blot analysis detected RoDH(I) and RoDH(II) mRNA only in rat liver, but RNase protection assays revealed RoDH(I) and RoHD(II) mRNA in kidney, lung, testis, and brain. These data indicate that short-chain dehydrogenases/reductase isozymes expressed tissue-distinctively catalyze the first step of retinoic acid biogenesis from the physiologically most abundant substrate, CRBP.

Alcohol Oxidoreductases

Radiotherapy of malignant subdiaphragmatic implants in advanced ovarian carcinoma: a new technique.

We report the development of a new technique using remote afterloading intraoperative radiation therapy to deliver a tumoricidal dose to diaphragmatic tumor implants. A multi-positional lucite applicator was designed based on anatomic studies of the diaphragmatic surface to accommodate a high dose rate iridium source in a series of needles placed 1.5 cm apart. The applicator curvature can vary from planar to full accommodation of the diaphragmatic surface with a constant source to surface distance of 0.5 cm. The applicator has been piloted in three patients with ovarian carcinoma with residual subdiaphragmatic disease found at second look laparotomy, to deliver a dose of 1,500 to 2,000 cGy at 0.5 cm. Tolerance of the diaphragm and hepatic surface has been excellent. There were no postoperative complications and no deterioration in liver function studies. The additional postoperative external beam irradiation directed with the aid of surgically placed clips and gated to respiratory movements permits achievement of a tumoricidal dose while limiting the treated volume and related toxicities.

Brachytherapy

Hysterectomy with extended surgical staging and radiotherapy versus hysterectomy alone and radiotherapy in stage I endometrial cancer: a comparison of complication rates.

Extended surgical staging (ESS) has been added to total hysterectomy and bilateral salpingo-oophorectomy (TAHBSO) in patients with clinical Stage I endometrial cancer in order to better define patterns of metastatic spread and the response to treatment. Adjuvant radiotherapy has a demonstrated efficacy in decreasing central recurrence in Stage I disease. The combined use of radical surgery and pelvic radiotherapy for cervical cancer patients results in an increased incidence of complications. This study compares major complication rates in Stage I endometrial cancer patients who underwent either TAHBSO with ESS or TAHBSO alone followed by adjuvant external beam radiotherapy (RT). Records of 52 patients with clinical stage I endometrial cancer were reviewed. Thirty-two patients underwent TAHBSO plus ESS and 20 patients had TAHBSO alone. All patients received postoperative, whole pelvis external radiotherapy. Four patients suffered complications potentially related to treatment which required rehospitalization, and all 4 were in the group which had undergone ESS. A comparison of complication rates between the ESS + RT group (4/37 or 10.8%) and TAHBSO + RT group (0/20) suggested a trend toward significance (P less than 0.10). Treatment protocols using extended surgical staging prior to adjuvant radiotherapy in Stage I endometrial cancer should examine complications potentially related to this combination, to further define treatment risks and benefits.

Adult

Postoperative adjuvant external-beam radiotherapy in surgical stage I endometrial carcinoma.

A combined surgical and radiotherapeutic approach is widely in Stage I endometrial adenocarcinoma. The technique and timing of the radiotherapy varies from center to center. Postoperative external-beam (EB) radiotherapy has the advantage of patient selection based upon surgical findings, comprehensive treatment of the pelvic nodal and vaginal cuff areas, and elimination of the need for an intracavitary procedure. Although frequently utilized, this technique is surprisingly poorly described in the medical literature. From 1979 to 1986, 46 surgical Stage I patients received adjuvant postoperative EB therapy at Georgetown University Hospital (GUH) (Washington, DC). Indications for treatment were Grade greater than or equal to 2 and/or depth of myometrial invasion of greater than 33%. The 5-year actuarial survival was 90% with a disease-free survival of 82%. The failure rate within the irradiated field was 6.5% with a distant failure rate of 8.7%. The rate of significant long-term complications was acceptable at 6.5%. The authors conclude that postoperative EB radiotherapy is an effective adjuvant therapy with results comparable to other available radiotherapeutic techniques.

Adenocarcinoma

Prelesional events in atherogenesis. Accumulation of extracellular cholesterol-rich liposomes in the arterial intima and cardiac valves of the hyperlipidemic rabbit.

Biochemical, physiologic, and ultrastructural modifications which appear in the aortic intima and atrioventricular valves before monocyte diapedesis and foam cell formation were investigated in rabbits fed a cholesterol-rich diet. In the first 2 weeks of the diet, while plasma beta-VLDL cholesterol was increased up to 15-fold, the intima showed an enhanced uptake and deposition of dietary 3H-cholesterol, 125I-beta-VLDL, and the fluorescent beta-VLDL-1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine conjugate. beta-VLDL-gold complex perfused in situ was transcytosed across endothelium by plasmalemmal vesicles. Concomitantly, within the intima, a progressive accumulation of extracellular densely packed uni- or multilamellar vesicles took place. These commonly occurred in cell-free subendothelial spaces and were not associated with any sign of cytolysis. In freeze-fracture preparations, these vesicles appeared as smooth surfaces, suggesting the absence of translamellar proteins. Upon incubation with filipin, these extracellular liposomes (EL) displayed characteristic approximately 20 nm filipin-sterol complexes, revealing the presence of preparations unesterified cholesterol in the phospholipid lamellas. EL deposition was paralleled by proliferation of basal lamina-like material, microfibrils, and proteoglycans, and continued to increase during foam cell formation. For the entire period of our experiments, the endothelium was morphologically intact, and no platelet involvement was detected. The results show that an early prelesional ultrastructural change in lesion-prone aortic and valvular areas is the accumulation of extracellular phospholipid liposomes rich in unesterified cholesterol.

Animals