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Biomedical subjects

C Jiang

Publications and source records attributed to C Jiang.

At least 199 records · Page 11Linked to original sources
PubMed1995

Intraperitoneal 5-fluoro-2'-deoxyuridine (FUDR) and (S)-leucovorin for disease predominantly confined to the peritoneal cavity: a pharmacokinetic and toxicity study.

Intraperitoneal (IP) administration of fluorinated pyrimidines has been evaluated for ovarian and gastrointestinal malignancies in phase I, II, and III trials. The tolerance and pharmacokinetic profile of IP 5-fluoro-2'-deoxyuridine(FUDR) alone and with (R,S)-leucovorin ((R,S)-LV) have each been evaluated in previous phase I studies. FUDR doses of 3 g per day with and without (R,S)-LV doses up to 640 mg per day given IP are well tolerated. The current phase I study was designed to determine the pharmacokinetic profiles and clinical tolerance of escalating doses of the pure biologically active S-isomer of leucovorin ((S)-LV) given IP with the same dosing schedule of FUDR. A group of 16 patients with disease confined to the abdominal cavity were treated in this study. Pharmacokinetic studies of blood and peritoneal fluid, toxicity profiles, and clinical response for the first three cycles are reported here. The toxicity profile did not significantly differ from the prior two studies. All non-hematologic toxicities, such as fatigue, nausea, vomiting, diarrhea, and abdominal discomfort were less than grade 4, and most were less than grade 3. Neutropenia and thrombocytopenia were uncommon and observed only in patients with compromised bone marrow reserve. The pharmacokinetic profiles were also congruent with the previous studies and indicate a three-log advantage for FUDR. The (S)-LV profiles in the peritoneal cavity paralleled those of FUDR. Antitumor effects or absence of progression until after cessation of therapy were documented in 11 patients. At a median follow-up of 18 months 44% of patients were alive. IP administration of 3-g of FUDR and up to 640 mg (S)-LV daily for three days was well tolerated. The tolerance and antitumor effects observed during IP FUDR and LV in these studies encourage further exploration of this regimen against ovarian and gastrointestinal malignancies. The actual role and optimal dose of LV as an enhancer of the antitumor actions of FUDR administered by this route remain unknown.

Adult↗
PubMed1995

Generation and characterization of a delta F508 cystic fibrosis mouse model.

We have generated mice carrying the most common mutation in cystic fibrosis (CF), delta F508, within the cystic fibrosis (Cftr) gene. Mutant animals show pathological and electrophysiological changes consistent with a CF phenotype. delta F508-/- mice die from peritonitis and show deficiencies in cAMP-activated electrogenic Cl- transport. These mice produce delta F508 transcripts and show the temperature-dependent trafficking defect first described for the human delta F508 CFTR protein. A functional CFTR Cl- channel not demonstrated by null CF mice or present at 37 degrees C was detected following incubation of epithelial cells at 27 degrees C. Thus, these mice are an accurate delta F508 model and will be valuable for testing drugs aimed at overcoming the delta F508 trafficking defect.

Animals↗
PubMed1995

ras may mediate mammary cancer promotion by high fat.

High fat consumption has been implicated as a risk factor for breast cancer. Experimental mammary carcinogenesis studies have demonstrated that the effect of high fat consumption is mainly exerted on the postinitiation stage of the disease process. We report data that have recalled in the formulation of a new hypothesis about the effect of dietary fat on mammary carcinogenesis, namely, that it promotes the development of a subpopulation of cells lacking a specific pathogenetic characteristic. In comparison with animals fed a low-fat diet, female Sprague-Dawley rats fed high-fat diets during the promotional stage developed significantly more (number and proportion) 1-methyl-1-nitrosourea-induced mammary adenocarcinomas that did not contain a codon 12 GGA-->GAA mutation in the c-Ha-ras protooncogene. The effect was independent of the types of fat fed, i.e., corn oil vs. fish oil. A model is presented to account for the preferential promotional effect of high fat consumption on 1-methyl-1-nitrosourea-initiated mammary epithelial cells. The hypothesis that the level of dietary fat consumed affects the proportion of mammary carcinomas that occur with a particular pathogenetic characteristic, in this case, the presence or absence of a Ha-ras point mutation, has important implications on the direction of future investigations concerning fat and cancer risk.

Adenocarcinoma↗
PubMed1995

Cellular and metabolic effects of triphenylselenonium chloride in a mammary cell culture model.

Triphenylselenonium chloride, a novel synthetic organic selenium compound in which selenium is bonded to three unsubstituted benzene rings, possesses significant chemopreventive activity against chemically-induced mammary carcinogenesis. The effects of triphenylselenonium chloride on a mammary tumor cell line (MOD) were compared to selenite, a reference compound in selenium chemoprevention research. It was observed that triphenylselenonium chloride treatment exerted a cytostatic effect in the absence of membrane damage or DNA strand breaks. The observed cytostasis was associated with a selenium concentration-dependent inhibition of cell proliferation, measured by [3H]thymidine incorporation into DNA, and delayed cell cycle progression. In contrast, selenite treatment rapidly induced DNA damage and cell death. These marked differences were observed across the same levels of cellular selenium. In addition, triphenylselenonium chloride treatment increased glucose consumption and lactate production, indicating an effect of the compound on cellular energy metabolism. Collectively these observations demonstrate that the toxic activities associated with selenite treatment do not occur when cells are treated with triphenylselenonium chloride. This compound represents a new type of selenium compound that exerts significant cellular effects through mechanisms distinct from those induced by selenite.

Animals↗
PubMed1995

Multiple trait analysis of genetic mapping for quantitative trait loci.

We present in this paper models and statistical methods for performing multiple trait analysis on mapping quantitative trait loci (QTL) based on the composite interval mapping method. By taking into account the correlated structure of multiple traits, this joint analysis has several advantages, compared with separate analyses, for mapping QTL, including the expected improvement on the statistical power of the test for QTL and on the precision of parameter estimation. Also this joint analysis provides formal procedures to test a number of biologically interesting hypotheses concerning the nature of genetic correlations between different traits. Among the testing procedures considered are those for joint mapping, pleiotropy, QTL by environment interaction, and pleiotropy vs. close linkage. The test of pleiotropy (one pleiotropic QTL at a genome position) vs. close linkage (multiple nearby nonpleiotropic QTL) can have important implications for our understanding of the nature of genetic correlations between different traits in certain regions of a genome and also for practical applications in animal and plant breeding because one of the major goals in breeding is to break unfavorable linkage. Results of extensive simulation studies are presented to illustrate various properties of the analyses.

Algorithms↗
PubMed1995

Oestrogen relaxes human epicardial coronary arteries through non-endothelium-dependent mechanisms.

BACKGROUND: Oestrogen-replacement therapy is associated with a reduced incidence of cardiovascular disease. The acute administration of oestrogen improves myocardial ischemia in women with coronary heart disease. In this study we investigated the relaxing effect of oestradiol-17 beta on human coronary arteries in vitro and determined the role of endothelial modulation in this relaxation by using isolated human coronary arteries. METHODS: Atherosclerosis-free epicardial arteries from men and women were removed from patients undergoing heart or combined heart and lung transplantation. The arteries were cut into ring segments and placed into organ baths containing Tyrode's solution. Changes in isometric tension were measured. The relaxing response to oestradiol-17 beta (10(-10) - 10(-5) mol/l) was investigated and the effects of endothelium, NGmonomethyl-L-arginine and indomethacin on the response of oestradiol-17 beta were assessed. RESULTS: Oestradiol-17 beta (10(-10) - 10(-5) mol/l) induced significant relaxation in coronary arteries pre-contracted with the thromboxane A2 analog (U46619; 3 x 10(-8) mol/l). Relaxation was significantly greater in coronary arteries from female patients. No significant differences were observed between arteries with or without endothelium nor after nitric oxide synthase or cyclo-oxygenase inhibition. These results indicate that oestradiol-17 beta induces human coronary artery relaxation via an endothelium-independent mechanism in vitro. The sex of the patients significantly affects sensitivity of the coronary arterial rings to oestrogen. CONCLUSION: Oestradiol-17 beta-induced coronary relaxation may play an important role in regulation of coronary tone, and may partly explain why oestrogen improves myocardial ischemia in women and why it protects postmenopausal women from the risk of developing coronary heart disease.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1995

Counting total cell numbers microscopically on stained films.

Two main sources of error in the conventional stained film cell count method, i.e. errors from imperfect spreading of the suspension and uneven distribution of cells in the film, have been eliminated by counting all the cells in the film. Staining solution and sodium alginate were added to the suspension before spreading over the slide. With a microsyringe, 20-microliters suspension was spread in two bands of ca 1.7 mm x 60 mm each. Then total cells could be counted easily in the x 100 magnification field by moving the slide in one direction. Results were satisfactory. Coefficients of variation were 2.6 and 1.1% in two separate yeast determinations each with five replicates. For counting higher magnifications, a suitable image analyser for automating the method is believed worthy of study.

Colony Count, Microbial↗
PubMed1995

[Comparative study on baicalin contents in 4 traditional Chinese medicinal preparations of ying huang].

The contents of baicalin in four different traditional Chinese medicinal preparations of Ying Huang were determined by HPLC. The contents of baicalin in Ying Huang tablets, Ying Huang oral liquid, Ying Huang injection and Ying Huang granules are respectively: 124.18 mg/g, 21.12 mg/ml, 12.39 mg/ml and 6.79 mg/g. The HPLC method suggested in this paper can be used for quality control in the production of Ying Huang preparations.

Drug Combinations↗
PubMed1995

[The investigation on actinomycete population and resources in some areas in Yunnan. IX. The actinomycetes in the west and the northeast of Yunnan].

Two hundred of soil samples of primeval forest, secondary forest, wasteland, nonirrigated farmland, vegetable farmland and paddy farmland were collected from both the west and the northeast of Yunnan in February, 1989. The actinomycetes in the samples were isolated and identified by various methods. This paper discussed the actinomycete population and its difference in the both areas of Yunnan.

Actinomyces↗
PubMed1994

Oxygen deprivation inhibits a K+ channel independently of cytosolic factors in rat central neurons.

1. K+ channel modulation has been shown to be an integral and important cellular response to O2 deprivation. Although part of this modulation occurs as a result of changes in concentrations of several cytosolic factors such as ATP and Ca2+, it is unknown whether there are mechanisms other than those originating from the cytosol. To test the hypothesis that membrane-delimited mechanisms participate in the O2-sensing process and are involved in the modulation of K+ channel activity in central neurons, we performed experiments using patch-clamp techniques and dissociated cells from the rat neocortex and substantia nigra. 2. Whole-cell outward currents were studied in voltage-clamp mode using Na(+)-free or low-Na+ (5 mM, with 1 microM tetrodotoxin) extracellular medium plus 0.5 mM Co2+. O2 deprivation produced a biphasic response in current amplitude, i.e. an initial transient increase followed by a pronounced decrease in outward currents. The reduction in outward currents was a reversible process since perfusion with a medium of PO2 > 100 mmHg (1 mmHg = 133 Pa) led to a complete recovery. 3. In cell-free excised membrane patches, we found that a specific K+ current (large conductance, inhibited by micromolar concentrations of ATP and activated by Ca2+) was reversibly inhibited by lack of O2. This was characterized by a marked decrease in channel open-state probability and a slight reduction in unitary conductance. The magnitude of channel inhibition by O2 deprivation was closely dependent on O2 tension. The PO2 level for 50% channel inhibition was about 10 mmHg with little or no inhibition at PO2 > or = 20 mmHg. 4. Single-channel kinetic analysis showed that channel open times consisted of two components and closed times were composed of three. The hypoxia-induced inhibition of K+ channel activity was mediated by selective suppression of the longer time constant channel openings without significantly affecting closed time constants. This led to an increase in frequency of opening and closing and rapid channel flickerings. 5. Our data showed that O2 deprivation had no effect on another K+ current characterized by a much smaller conductance and Ca2+ independence. This provides evidence for the selective nature of the hypoxia-induced inhibition of some species of K+ channels. 6. These results therefore provide the first evidence for regulation of K+ channel activity by O2 deprivation in cell-free excised patches from central neurons.

Adenosine Triphosphate↗
PubMed1994

A direct mechanism for sensing low oxygen levels by central neurons.

The cascade of cellular events that is triggered by low O2 levels in the central nervous system depends on initial sensing mechanisms that can be crucial in determining the overall cell response, adaptation, or injury. In this report, we demonstrate that the activity of an identified K+ channel is regulated directly by environmental O2. Membrane ionic currents were recorded from neurons of the neocortex and the substantia nigra and studied by using whole-cell or excised membrane patches. O2 deprivation reversibly induced an initial transient increase in whole-cell outward currents, and this was followed by a pronounced decrease in these currents. In cell-free excised membrane patches, lack of O2 reversibly inhibited a class of K+ channels that are inhibited by ATP and activated by Ca2+. K+ channel inhibition depended on pO2 level, with a 50% inhibition at approximately 11 torr (1 torr = 6.9 kPa). By the use of specific agents that chelate metal in metal-containing O2-sensing centers, including heme, nonheme iron, copper, and flavin, we also demonstrated that iron-center but not copper-center blockers inhibited the channel in excised patches in a similar fashion as low pO2. These results strongly suggest that K+ channel activity is modulated during O2 deprivation by nonheme iron-containing proteins that are associated with channel molecules, thus providing evidence for a direct O2-sensing mechanism in neuronal membranes.

Animals↗
PubMed1994

Selenite induction of DNA strand breaks and apoptosis in mouse leukemic L1210 cells.

The effects of selenite on DNA integrity, cell viability, and long-term proliferative potential of mouse leukemic L1210 cells were examined in this study. Selenite treatment resulted in concentration-dependent increases in DNA single-strand breaks and double-strand breaks, as detected by a modified filter elution assay. A time-course experiment showed that DNA single-strand breaks preceded DNA double-strand breaks. Agarose gel electrophoresis of DNA extracted from selenite-treated cells displayed a nucleosomal fragmentation pattern that is characteristic of apoptotic cell death. The involvement of a Ca2+,Mg(2+)-dependent endonuclease responsible for DNA double-strand fragmentation was implied by the observation that two inhibitors of endonuclease activity, i.e. aurintricarboxylic acid and zinc, blocked selenite-induced DNA double-strand breaks. These inhibitors also prevented selenite-induced cell death as defined by loss of ability to exclude trypan blue dye. Selenite treatment severely impaired the colony-forming ability of cells capable of trypan blue exclusion. The induction of DNA strand breaks and commitment to apoptosis may explain the selenite-mediated growth inhibition and loss of long-term proliferative potential.

Animals↗
PubMed1994

Start site selection by Sp1 in the TATA-less human Ha-ras promoter.

The promoter of the human Ha-ras gene is very GC-rich, has four Sp1-binding sites and no TATA element. Transcription initiates at multiple start sites spread over a 90-base pair region, with a major cluster between +1 and +11. We detected the binding of a HeLa nuclear protein to the region from +6 to +20, a region which overlaps the major cluster and includes nine start sites within its boundaries. When part of this region was mutated, the nine start sites were abolished, so the region may be an initiator. The regulatory elements of the promoter have no differential effect on start site usage. But Sp1 bound to GCIV located at -38 acts as a start site selector, increasing the activity of the start sites from +1 downstream but not the upstream sites at -31, -21, and -10. When spacers of increasing length were inserted 3' to GCIV, the major cluster dwindled, and the upstream sites became strong sites, first the one at -10 and then the one at -21. Thus start sites were strongest when put into an Sp1-selected locus 36 to 53 base pairs downstream from GCIV and weak when outside this locus. The start sites with these properties may be due to initiators.

Animals↗
PubMed1994

Membrane ionic currents and properties of freshly dissociated rat brainstem neurons.

It is well known that neuronal firing properties are determined by synaptic inputs and inherent membrane functions such as specific ionic currents. To characterize the ionic currents of brainstem cardio-respiratory neurons, cells from the hypoglossal (XII) nucleus and the dorsal motor nucleus of the vagus (DMX) were freshly dissociated and membrane ionic currents were studied under whole-cell voltage and current clamp. Both of these neurons showed a TTX-sensitive Na+ current with a much larger current density in XII than DMX neurons. This Na+ current had two (fast and slow) distinct inactivation decay components. The ratio of the magnitudes of the fast to slow component was roughly two-fold greater in DMX than in XII cells. Both DMX and XII neurons also showed a high voltage-activated Ca2+ current, but this current density was significantly greater (three-fold) in DMX than XII neurons. A relatively small amount of low-voltage activated Ca2+ current was also observed in DMX neurons, but not in the majority of XII cells. A transient and a sustained outward current components were observed in DMX cells, but only sustained currents were present in XII neurons. These outward currents had a reversal potential of about -70 mV with 3 mM external K+ and -30 mV with 25 mM K+, and substitution of K+ with cesium and tetraethylammonium suppressed more than 90% the outward currents, indicating that most outward currents were carried by K+. The transient outward current consisted of two components with one sensitive to 4-aminopyridine and the other to intracellular Ca2+. In XII neurons, BRL 38227 (lemakalim), an ATP-sensitive K+ (KATP) channel activator, increased the sustained K+ currents by 10% of control, and glibenclamide, a KATP channel blocker, decreased the sustained K+ currents by 20%. Evidence for the presence of an inward rectifier K+ current was also obtained from both XII and DMX neurons. These results on XII and DMX neurons indicate that (1) the methods used to dissociate neurons provide a useful means to overcome voltage clamp technical difficulties; (2) ion channel characteristics such as density and biophysical properties of DMX neurons are very different from those of XII neurons; and (3) several newly discovered membrane ionic currents are present in these cells.

Adenosine Triphosphate↗
PubMed1994

Use of recombinant pp38 antigen of Marek's disease virus to identify serotype 1-specific antibodies in chicken sera by western blotting.

A fowlpox recombinant expressing the pp38 antigen of Marek's disease virus has been constructed. Production of pp38 in chick embryo fibroblasts (CEF) infected at a m.o.i. of 1 pfu/cell occurred over a period of 5 days and reached a peak at 72 h after infection. The pp38 antigen could be released from infected cells by freezing and thawing. Western blot analysis showed that denatured pp38 antigen reacted with antisera from chickens inoculated with serotype 1 MDV but failed to react with antisera from chickens inoculated with MDV serotype 2 or HVT. The results suggest that MDV pp38 contains a serotype 1-specific epitope which becomes available upon denaturation of the antigen and that this could be exploited to identify MDV-specific antibodies in epidemiological studies. The relationship between pp38 and the related polypeptides pp24 and pp41 in MDV-infected cells was also examined. The results suggest that pp24 and pp38 are synthesised independently and that MDV coded proteins (probably a protein kinase) might be required to convert pp38 to pp41.

Animals↗