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Biomedical subjects

J J Yang

Publications and source records attributed to J J Yang.

139 records · Page 8Linked to original sources

Percutaneous absorption of anthracene in the rat: comparison of in vivo and in vitro results.

The present study was conducted to evaluate the applicability of in vitro percutaneous absorption techniques to estimate in vivo absorption of polynuclear aromatic (PNA) compounds commonly found in mineral oils. The percutaneous absorption of 14C-labeled anthracene, a three-ring PNA, was compared in a six-day in vivo and in vitro experiment with female Sprague-Dawley rats following a single topical dose (9.3 micrograms/cm2). In vivo absorption was measured by the presence of 14C radioactivity in urine, feces and tissues and in vitro absorption by penetration of radioactivity through excised skin into the receptor fluid of Franz-type diffusion cells. Several modifications of standard diffusion cell techniques were used which are known to enhance the absorption of lipophilic compounds. Anthracene was observed to readily penetrate the skin in both experiments and the total amounts absorbed in vivo and in vivo were seen to gradually coalesce over time. Within six days after application, 52.3 and 55.9% of the administered anthracene was absorbed in vivo and in vitro, respectively.

Animals↗

Oxygen consumption of mammalian myocardial cells in culture: measurements in beating cells attached to the substrate of the culture dish.

A Lucite attachment which permitted the measurement of oxygen consumption in cells in culture without manipulating the cells was constructed. The attachment fit over commercially available dishes for cell culture and had an oxygen electrode built into it. Oxygen uptake of cells in culture was thus measured. Cells were attached to the substrate of the culture dish during the measurements and could be observed in an inverted phase microscope. Cells did not show any morphological changes, e.g., cell shapes or beating rate in case of myocardial cells, before and after the measurements of oxygen consumption. Using this method the rate of oxygen consumption was determined in rat myocardial and heart non-muscle cells in culture and also in HeLa and L6 cell lines. Myocardial cells in culture had an approximately four times higher rate of oxygen uptake compared with heart non-muscle, HeLa, and L6 cells. The oxygen uptake of beating myocardial cells was higher by about 50% compared with quiescent myocardial cells.

Animals↗

Effects of adriamycin on enzymes of adenine nucleotide metabolism in heart cell cultures.

Effects of adriamycin (ADM) treatment on rat heart cells in culture were examined. ADM treatment (lug/ml) for 3 hr, 48 to 51hr of culture age, had no effect on oxygen consumption, myosin content or myosin ATPase activity. In contrast, the activities of creatine kinase, adenylate kinase and adenosine deaminase were significantly lower in ADM-treated cells than in corresponding controls at 72 and 96 hr of culture age. Fall in the activities of these key enzymes of adenine nucleotide metabolism would lead to disturbances in energy metabolism, and results in the functional impairment of heart cells.

Adenine Nucleotides↗

Isozymes of creatine kinase in mammalian cell cultures.

Previous studies on the energy metabolism of rat myocardial cells in culture supported the hypothesis that the creatine-phosphocreatine-creatine kinase system plays an important role in the intracellular transport of energy from the mitochondria to the myofibrils and in the regulation of energy production coupled to energy utilization in this model system. Effective functional compartmentation of ATP could result from the binding of creatine kinase to cellular organelles (e.g., myofibrils and mitochondria) such that high energy charge at the myofibrils is maintained by the reverse creatine kinase reaction, while phosphocreatine is synthesized mainly at the mitochondria in the forward creatine kinase reaction. It was, therefore, essential to demonstrate the presence of mitochondrial creatine kinase in the cultured myocardial cells to support this hypothesis, particularly since the mitochondrial creatine kinase was reportedly absent in fetal hearts. Using electrophoresis on cellulose acetate strips, the mitochondrial creatine kinase isozyme, as well as MM, MB, and BB isozymes, have now been demonstrated in myocardial cultures derived from neonatal rats. The mitochondrial creatine kinase increased with age in culture and with age of animal from which the culture is derived. Furthermore, the addition of creatine to culture media stimulates its synthesis. The mitochondrial creatine kinase isozyme was not detected in nonmuscle cells in culture derived from the neonatal rat hearts, nor in L6 muscle cell line. Phosphocreatine was present in all cells, but the regulation of energy metabolism and energy shuttle by creatine-phosphocreatine-creatine kinase could be operative only in the cells where the mitochondrial creatine kinase is present. This regulatory mechanism provides for an efficient system concomitant with the continuous energy demand of the myocardium; it is not ubiquitous and its development in myocardial cells seems to be triggered postnatally.

Adenosine Triphosphate↗

Mitochondrial creatine kinase in mammalian myocardial cells in culture.

Previous studies on the energy metabolism of rat myocardial cells in culture supported the hypothesis that the creatine-phosphorylcreatine-creatine kinase system is essential for intracellular transport of energy from the mitochondria to the myofibrils and in the regulation of energy production to meet energy utilization. Effective functional compartmentation of ATP could result from the binding of creatine kinase to cellular organelles (e.g., myofibrils and mitochondria) so that the high-energy charge at the myofibrils is maintained by the reverse creatine kinase reaction, whereas phosphorylcreatine is synthesized mainly at the mitochondria in the forward creatine kinase reaction. It was essential to demonstrate the presence of mitochondrial creatine kinase to support the hypothesis. Using polyacrylamide gel electrophoresis and electrophoresis on cellulose acetate strips, the mitochondrial creatine kinase isozyme, as well as MM, MB, and BB isozymes, has now been demonstrated in myocardial cells in culture. Nonmuscle cells in culture also derived from neonatal rat hearts lack the mitochondrial creatine kinase isozyme. Total creatine kinase in myocardial cells is greatly decreased by treatment of the cells with adriamycin, a cardiotoxic chemotherapeutic agent, and the relative amounts of the isozymes are altered. The mitochondrial creatine kinase seems to be reduced less than either the BB or MM isozymes.

Adenosine Triphosphate↗

The formation of azoxy-2-phenylethane during the biological oxidation of phenylethylamine by rabbit liver microsomes.

Incubation of phenylethylamine with rabbit liver microsomes, divalent manganese and a NADPH generating system leads to the formation of azoxy-2-phenylethane, among other metabolic products. Approximately 38 nmol of the azoxy compound is formed form 10 mumol of phenylethylamine during a 30 min incubation. Azoxy-2-phenylethane was identified by comparison of its chromatographic (thin-layer, high pressure liquid and gas chromatography) properties with those of an authentic standard and was confirmed by mass spectrometry. The metabolism of phenylethylamine to azoxy-2-phenylethane appears completely dependent on the presence of divalent manganese; no reaction was observed in the absence of this metal or in the presence of equivalent concentrations of cupric ions. Azoxy-2-phenylethane was mutagenic, with S-9 activation, in S. typhimurium strains TA 100 and TA 1535 but not in TA 98 or TA 1537. This report constitutes the first demonstration of the formation of an aliphatic azoxy compound from the corresponding amine by a mammalian system.

Animals↗

Replicative and unscheduled DNA synthesis in adriamycin-treated myocardial cells.

The effect of the potent antitumor antibiotic adriamycin (ADM) on chromosome integrity, DNA replication, and unscheduled DNA synthesis was investigated in cultured rat cardiac cells. Chromosome distribution, autoradiography, and [3H]thymidine (dThd) incorporation studies were carried out on separate cultures. A 3-hr pulse of ADM at a concentration of 1 microgram/ml was sufficient to cause chromosomal aberrations that were evident for up to 3 days post-ADM treatment. At the same ADM dosage, DNA replication was depressed for up to 6 days by as much as 90%, yet the ability of the cardiac cells to repair UV-damaged DNA was not impaired. However, cells exposed to higher concentrations of ADM failed to undergo significant UV-induced repair.

Animals↗

Metabolic involvement in adriamycin cardiotoxicity.

The cardiotoxic effects of adriamycin were studied in mammalian myocardial cells in culture as a model system. Adriamycin inhibited cell growth and the rhythmic contractions characteristic of myocardial cells in culture. A possible involvement of energy metabolism was suggested previously, and in this study the adenylate energy charge and phosphorylcreatine mole fraction were determined in the adriamycin-treated cells. The adenylate energy charge was found to be significantly decreased, while the phophorylcreatine mole fraction was unchanged. Such disparity suggests an inhibition of creatine phosphokinase. The addition of 1 mM adenosine to the myocardial cell cultures markedly increases the ATP concentration through a pathway reportedly leading to a compartmentalized ATP pool. In the adriamycin-treated cells, the addition of adenosine increased the adenylate charge and, concomitant with this inrcease, the cells' functional integrity, in terms of percentage of beating cells and rate of contractions, was maintained.

Adenosine↗

Decrease of estrogen receptors induced by 17 beta-estradiol and progesterone in cultured rabbit endometrial cells.

A whole cell technique to measure estradiol receptors in cultured rabbit endometrial cells is described. The estradiol receptors measured appear to be composed of at least two components: one component has high affinity but low capacity, while the other component has low affinity but high capacity. Using the assay, the effects of estradiol and progesterone pretreatment were examined on the estradiol receptor levels. It was found that both of the hormones decreased the number of estrogen receptors in the cultured cells. The finding that estradiol decreased its own receptors was unexpected and its possible relevance is discussed.

Animals↗

Stigmata: an algorithm to determine structural commonalities in diverse datasets.

An algorithm, Stigmata, is described, which extracts structural commonalities from chemical datasets. It is discussed using several illustrative examples and a pharmaceutically interesting set of dopamine D2 agonists. The commonalities are determined using two-dimensional topological chemical descriptions and are incorporated into the key feature of the algorithm, the modal fingerprint. Flexibility is built into the algorithm by means of a user-defined threshold value, which affects the information content of the modal fingerprint. The use of the modal fingerprint as a diversity assessment tool, as a database similarity query, and as a basis for color mapping the determined commonalities back onto the chemical structures is demonstrated.

Algorithms↗

Field studies on 32P movement and P leaching from flooded paddy soils in the region of Taihu Lake, China.

Field experiments were done in two sites, Yixing and Changshu, Jiangsu province, China, to study P movement and leaching in flooded paddy soils. P movement in soil was investigated by using the KH2 32PO4 tracker method, and the amount of P leached from the soil layer in different depths was estimated by measuring P concentrations in the soil solution and saturated hydraulic conductivities in field. Determination was done about one month after P application. There was 46% and 42% of total 32P retained in the 0-5cm layer of soil in the Yixing site and in the Changshu site respectively. The 32P retained in the 25-30 cm layer was only about 1-2% of the total 32P added. Furthermore, 8.01% of 32P in the soil of Yixing site and 16.8% of 32P in the soil of Changshu site was lost from the layer 0-30 cm soil. The seasonal amounts of P leached from the top soil layer and from bottom layer are about 4.5-5.8% and 1.6-2.1% of the total P application, respectively. Changes of total P concentrations in soil solutions during rice growth showed that the fertilizer P applied before flooding of the paddy fields suffered a flash leaching loss and a slow leaching loss. We concluded that the fertilizer P could quickly move in the flooded paddy rice field and parts of it can enter into surface water and ground water. Unless the P application is well managed the risk of P loss and consequently environmental pollution exist.

Agriculture↗

Hydroxyethyl starch inhibits intestinal production of cytokines and activation of transcription factors in endotoxaemic rats.

We studied the effect of hydroxyethyl starch (HES) on intestinal production of cytokines and activation of transcription factors in sepsis. Septic rats, induced by intraperitoneal lipopolysaccharide (LPS) (5 mg/kg), were treated with intravenous HES (16 ml/kg) or saline (64 ml/kg). Rat ileal tissues were collected at 2 h, 3 h or 6 h after LPS challenge. Levels of tumour necrosis factor alpha (TNF-alpha), interleukin (IL) 1beta, IL-6, IL-8 and IL-10, cytokine mRNAs, activities of nuclear factor kappa-B (NF-KB) and activator protein-1 (AP-1), and the number of ileal myeloperoxidase (MPO)-positive cells were determined for each group. HES significantly reduced the LPS-induced increase in intestinal levels of TNF-alpha, IL-1beta, IL-6, IL-8 and their corresponding mRNAs. HES also decreased the number of MPO-positive cells induced by LPS and inhibited activation of NF-kappaB and AP-1. The results suggest that in sepsis, HES may down-regulate intestinal pro-inflammatory cytokine production via suppression of NF-kappaB and AP-1 activation.

Animals↗