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Biomedical subjects

G Lee

Publications and source records attributed to G Lee.

At least 343 records · Page 19Linked to original sources

Progression in hepatocarcinogenesis: differences in growth and behavior of transplants of early and later hepatocyte nodules in the rat spleen.

Hepatocyte nodules were induced in Fischer 344 rats using the resistant hepatocyte model. Nodules harvested at 5, 24, or 25 weeks after initiation were isolated, diced, and transplanted into the spleen of normal rats and observed for periods up to 104 weeks. In the first experiment, 50% of the animals developed hepatocellular carcinoma, some with invasion and metastasis, by 70 to 104 weeks. In the second experiment, transplants of 5-week nodules grew very slowly and diffusely in the spleen, as did normal liver, but retained at least some of their phenotypic properties. In contrast, transplants of 25-week nodules grew into nodules up to 2.5 cm in diameter by 70 weeks. Two of the larger nodules had smaller nodules within resembling trabecular carcinoma. Transplants from the liver surrounding the 25-week nodules did not grow and produced no nodules by 70 weeks after transplantation. The implications of these observations in the study of progression in hepatocarcinogenesis are discussed briefly.

Animals↗

Influences of diethylnitrosamine on longevity of surrounding hepatocytes and progression of transplanted persistent nodules during phenobarbital promotion of hepatocarcinogenesis.

The possibility that phenobarbital (PB) selectively promotes liver nodule development by decreasing survival of surrounding hepatocytes previously exposed to diethylnitrosamine (DENA) was evaluated. Livers of F-344 rats were labelled with [3H-methyl]-thymidine (3H-TdR) during developmental or regenerative growth. Neonatal rats given 3H-TdR between days 3 and 12 were subjected at 12 weeks of age to partial hepatectomy (PH) followed 24 hr later by DENA (10 mg/kg) or saline. Subsequent administration of PB (0.1% in drinking water) for 28 weeks reduced total liver label to 46 +/- 10% (saline group) or 40 +/- 4% (DENA group). Adult male rats initiated with DENA (200 mg/kg) and later labelled with 3H-TdR after PH also lost total liver label during 28 weeks' promotion with PB (0.05% in water) at rates similar to those exhibited by noninitiated rats given PB, and by DENA-treated or control rats not given PB. Large persistent (12 weeks) liver nodules generated by DENA in the Solt-Farber model were transplanted as small fragments into the spleens of syngeneic rats previously given 0, 100 or 200 mg/kg of DENA. Subsequent exposure to PB (0.05% in drinking water for 40 weeks) or Aroclor 1254 (6 X 300 mg/kg per month) promoted nodule and cancer development only in livers of DENA-initiated recipients. Surviving transplanted nodules remained as small microscopic clusters even after 40 weeks of promotion. However, PB increased transplant survival (50% vs. 21% in controls) whereas Aroclor reduced it to 8%. These findings indicate that promotion of liver nodules by PB occurs without enhanced mortality of surrounding hepatocytes previously damaged by DENA. They further suggest that promoters such as PB and PCBs do not directly influence the progression of established persistent nodules.

Animals↗

Effects of simultaneous viewing and vaporization of plaques using the steerable, laser-heated metal cap in the atherosclerotic monkey model.

A steerable, fiberoptic catheter coupled to a laser light guide tipped with a metal cap was used. Four monkeys fed an atherogenic diet for 7-8 years were angiographed and were found to have extensive mural plaque in the iliac arteries. Plaque sites in these monkeys were vaporized using the laser-heated metal cap. Energies of 1.5-9 Joules were employed. Application of the energy was tangential of perpendicular to the plaque. Lased sites were examined histologically at 24 hr or at 3 months after treatment. No effect was seen at 1.5 Joules. Three to six Joules tangentially produced a superficial lesion that extended into the tunica intima. Six Joules perpendicularly produced a burn into the tunica adventitia, with damage to the vasavasorum. Nine Joules tangentially produced a burn into the tunica media. Three months after treatment, this lased site showed no stenosis or aneurysm formation.

Animals↗

Secular rates and correlates for gastroschisis in California (1968-1977).

This study reports on an epidemiological investigation of gastroschisis using birth certificate data from California for the period of 1968-1977. Gastroschisis has been reported to be on the increase in a number of countries. The distribution of the 166 California gastroschisis cases reported during this time period indicated a clear upward secular trend (P less than .001) with the rate per 1,000 increasing from .006 in 1968 to .089 by 1977. This secular trend was observed in every maternal age group and for gravidity level 1. Gastroschisis also occurred more frequently among younger mothers (P less than .001) and low gravidity mothers (P less than .001). Omphalocele, another eventration defect, was also examined but did not display an upward secular trend.

Abdominal Muscles↗

Carcinogen-induced mdr overexpression is associated with xenobiotic resistance in rat preneoplastic liver nodules and hepatocellular carcinomas.

We have previously reported the isolation of a human breast cancer cell line resistant to doxorubicin (adriamycin; AdrR MCF-7 cells) that has also developed the phenotype of multidrug resistance (MDR). MDR in this cell line is associated with increased expression of mdr (P glycoprotein) gene sequences. The development of MDR in AdrR MCF-7 cells is also associated with changes in the expression of several phase I and phase II drug-detoxifying enzymes. These changes are remarkably similar to those associated with development of xenobiotic resistance in rat hyperplastic liver nodules, a well-studied model system of chemical carcinogenesis. Using an mdr-encoded cDNA sequence isolated from AdrR MCF-7 cells, we have examined the expression of mdr sequences in rat livers under a variety of experimental conditions. The expression of mdr increased 3-fold in regenerating liver. It was also elevated (3- to 12-fold) in several different samples of rat hyperplastic nodules and in four of five hepatomas that developed in this system. This suggests that overexpression of mdr, a gene previously associated with resistance to antineoplastic agents, may also be involved in the development of resistance to xenobiotics in rat hyperplastic nodules. In addition, although the acute administration of 2-acetylaminofluorene induced an 8-fold increase in hepatic mdr-encoded RNA, performance of a partial hepatectomy either before or after administration of 2-acetylaminofluorene resulted in a greater than 80-fold increase in mdr gene expression over that in normal untreated livers. This represents an important in vivo model system in which to study the acute regulation of this drug resistance gene.

2-Acetylaminofluorene↗

Differential photoabsorption using argon laser radiation on atherosclerotic plaque in non-hemolyzed and hemolyzed blood.

Since argon laser radiation (488 to 514 nm) can vaporize human atherosclerotic plaque, we determined whether different blood media--hemolyzed versus non-hemolyzed blood--can alter photoabsorption of atherosclerotic plaque. Forty cadaveric aortic fibrous plaque samples were fitted onto small vials containing 0.02 ml of either non-hemolyzed blood or hemolyzed blood over the surface of the plaque. The distal end of a 400-mu core diameter quartz fiber was directed onto the surface of the plaque and the proximal end of the fiber was connected to an argon laser. The vaporized area and depth of plaque penetration were measured and the estimated volume of crater formation was derived. Following 2.5, 5, 10 and 20 J of laser energies, vaporized volumes were 0.12, 0.72, 0.97 and 4.09 mm3, respectively, for hemolyzed blood and were 0 (p less than 0.01), 0 (p less than 0.01), 0.92 (NS) and 4.39 mm3 (NS), respectively, for non-hemolyzed blood. Laser radiation destroys red blood cells; the higher the energies, the greater the hemolysis. Thus, different blood media such as hemolyzed and non-hemolyzed blood can alter photoabsorption of atherosclerotic plaque. Low level argon laser absorption upon plaque can occur under hemolyzed blood but not under non-hemolyzed blood. Since higher levels of argon laser energies cause greater lysis of red blood cells, comparable degrees of plaque ablation are observed under either blood medium.

Arteriosclerosis↗

An increase in in vitro fertilization ability of low-density human sperm capacitated by multiple-tube swim-up.

Comparison was made of the efficacy of multiple-tube swim-up (MT-SU) and single-tube swim-up (ST-SU) preparations on inducing human sperm fertilization ability in semen samples of less than 60 million motile sperm/ml. Two parallel groups of in vitro fertilization (IVF) patients possessing sperm density of this category had their sperm capacitated by MT-SU or ST-SU. The MT-SU patients' sperm fertilized 71 +/- 6.0% of eggs retrieved in comparison to 39 +/- 7.9% in the parallel ST-SU patients (P less than 0.001). Similarly, MT-SU increased the rate of human sperm penetration into zona-free hamster eggs. The increased fertilization rate of MT-SU sperm was not from acceleration of the acrosome reaction, but may be attributed to the higher efficiency of MT-SU in removing antifertility factors present in the seminal plasma from sperm.

Acrosome↗

Activating and 'anxiogenic' effects of corticotropin releasing factor are not inhibited by blockade of the pituitary-adrenal system with dexamethasone.

Central administration of corticotropin releasing factor (CRF) in rats produces pituitary-adrenal activation and a variety of "anxiogenic-like" effects. The present study was designed to explore the contribution of the peripheral pituitary-adrenocortical axis in mediating these CRF responses. Intraventricularly administered CRF produced suppression of responding in the conflict test and a marked locomotor activation. Neither behavioral effect was altered by the prior administration of dexamethasone in a dose that blocked pituitary-adrenal activation to CRF. These results support the hypothesis that behavioral effects of CRF are mediated by its action at central sites and not via an action on the pituitary-adrenocortical system.

Animals↗

Correlation of coronary angioscopic to angiographic findings in coronary artery disease.

An Olympus ultrathin fiberscope, 1.8 mm outer diameter, was inserted intraluminally into 11 stenoses of the left anterior descending and circumflex coronary arteries in 8 patients at coronary bypass surgery. Intraluminal views were obtained by coupling the angioscope to a color video camera and videotape recorder, and compared with preoperative coronary angiographic findings in right and left anterior oblique views. Atherosclerotic plaque was observed as yellow-white mass attached onto the luminal lining, which may be large enough to virtually obliterate the vascular lumen. Angioscopy provided a topographic view and cross-sectional picture of stenosis not observed by angiography. Single-plane angioscopic cross-sectional stenotic lumens correlated well (r = 0.90, p less than 0.001) with calculated angiographic luminal narrowings. However, with subtotal obstruction, lesion length must be assessed angiographically. Coronary angioscopy can be a useful adjunct to angiography by providing the added dimension of the true cross-sectional view of obstruction.

Coronary Angiography↗

Intrinsic B lymphocyte and macrophage defects in C3H/HeJ mice.

C3H/HeJ mice are genetically defective in their responsiveness to lipopolysaccharide (LPS). Their B cells also have a characteristically low cloning efficiency in semisolid agar cultures, where LPS does not seem to be required. Adherent macrophages facilitate clonal proliferation in such cultures via diffusible substances. C3H/HeJ macrophages functioned poorly in this respect, and addition of normal C3HeB/FeJ macrophages to cultures of C3H/HeJ B cells did not lead to normal colony numbers. Although immune interferon can stimulate normal resident peritoneal macrophages to function well in semisolid agar cultures, it did not improve the cloning efficiency of C3H/HeJ cells. Similarly, addition of indomethacin or interleukin 1 to the cultures did not reveal that abnormally elevated production of prostaglandins or a deficiency in interleukin 1 are responsible for poor C3H/HeJ colony formation. These results indicate that C3H/HeJ mice have defects intrinsic to both B cells and macrophages that are not overcome by interferon. Purified B cells from these mice cloned poorly and did not respond to stimulation in liquid cultures with anti-mu-coated beads plus factors. There was a tendency for the poor cloning of C3H/HeJ B cells to improve with age.

Animals↗

Corticotropin releasing factor (CRF) receptor antagonist blocks activating and 'anxiogenic' actions of CRF in the rat.

The effectiveness of a recently synthesized corticotropin releasing factor (CRF) antagonist, alpha-helical CRF9-41, in reversing the locomotor activating and proconflict effects of CRF was evaluated. The CRF receptor antagonist (50, 100 and 200 micrograms, i.c.v.) produced a dose-related attenuation of the response-suppressing effects of CRF in a conflict model of anxiety. The antagonist also effectively suppressed the marked locomotor activation produced by CRF. No discernible intrinsic effects on behavior were noted when the antagonist was administered alone. These results suggest that the behavioral effects of CRF are receptor-mediated phenomena and point to the potential usefulness of a CRF antagonist in understanding the function of endogenous CRF in mediating responses to stressful stimuli.

Animals↗

Rapid purification and properties of protein kinase C from bovine adrenal medulla.

Protein kinase C was purified from bovine adrenal medulla using a rapid procedure which resulted in an approximate 1500-fold increase in specific activity. The characteristics of the enzyme are reported and for the first time it is possible to compare the effects of TPA on secretion from intact and permeabilized cells with the effect of TPA on protein kinase C purified from the same secretory tissue.

Adrenal Medulla↗