Biomedical subjects

Wei Qian

Publications and source records attributed to Wei Qian.

At least 37 records · Page 2Linked to original sources

PubMed2005

Comparative and functional genomic analyses of the pathogenicity of phytopathogen Xanthomonas campestris pv. campestris.

Xanthomonas campestris pathovar campestris (Xcc) is the causative agent of crucifer black rot disease, which causes severe losses in agricultural yield world-wide. This bacterium is a model organism for studying plant-bacteria interactions. We sequenced the complete genome of Xcc 8004 (5,148,708 bp), which is highly conserved relative to that of Xcc ATCC 33913. Comparative genomics analysis indicated that, in addition to a significant genomic-scale rearrangement cross the replication axis between two IS1478 elements, loss and acquisition of blocks of genes, rather than point mutations, constitute the main genetic variation between the two Xcc strains. Screening of a high-density transposon insertional mutant library (16,512 clones) of Xcc 8004 against a host plant (Brassica oleraceae) identified 75 nonredundant, single-copy insertions in protein-coding sequences (CDSs) and intergenic regions. In addition to known virulence factors, full virulence was found to require several additional metabolic pathways and regulatory systems, such as fatty acid degradation, type IV secretion system, cell signaling, and amino acids and nucleotide metabolism. Among the identified pathogenicity-related genes, three of unknown function were found in Xcc 8004-specific chromosomal segments, revealing a direct correlation between genomic dynamics and Xcc virulence. The present combination of comparative and functional genomic analyses provides valuable information about the genetic basis of Xcc pathogenicity, which may offer novel insight toward the development of efficient methods for prevention of this important plant disease.

Bacterial Proteins↗

PubMed2005

Stable transfection of extrinsic Smac gene enhances apoptosis-inducing effects of chemotherapeutic drugs on gastric cancer cells.

AIM: To explore the feasibility of enhancing apoptosis-inducing effects of chemotherapeutic drugs on human gastric cancer cells by stable transfection of extrinsic Smac gene. METHODS: After Smac gene was transferred into gastric cancer cell line MKN-45, subclone cells were obtained by persistent G418 selection. Cellular Smac gene expression was determined by RT-PCR and Western blotting. After treatment with mitomycin (MMC) as an apoptotic inducer, in vitro cell growth activities were investigated by trypan blue-staining method and MTT colorimetry. Cell apoptosis and its rates were determined by electronic microscopy, annexin V-FITC and propidium iodide staining flow cytometry. Cellular caspase-3 protein expression and its activities were assayed by Western blotting and colorimetry. RESULTS: When compared with MKN-45 cells, the selected subclone cell line MKN-45/Smac had significantly higher Smac mRNA (3.12+/-0.21 vs 0.82+/-0.14, t = 7.52, P<0.01) and protein levels (4.02+/-0.24 vs 0.98+/-0.11, t = 8.32, P<0.01). After treatment with 10 microg/mL MMC for 6-24 h, growth inhibition rate of MKN-45/Smac (15.8+/-1.2-54.8+/-2.9%) was significantly higher than that of MKN-45 (5.8+/-0.4- 24.0+/-1.5%, t = 6.42, P<0.01). Partial MKN-45/Smac cancer cells presented characteristic morphological changes of apoptosis under the electronic microscope with an apoptosis rate of 36.4+/-2.1%, which was significantly higher than that of MKN-45 (15.2+/-0.8%, t = 9.25, P<0.01). Compared with MKN-45, caspase-3 expression levels in MKN-45/Smac were improved significantly (3.39+/-0.42 vs 0.96+/-0.14, t = 8.63, P<0.01), while its activities were 3.25 times as many as those of MKN-45 (0.364+/-0.010 vs 0.112+/-0.007, t = 6.34, P<0.01). CONCLUSION: Stable transfection of extrinsic Smac gene and its over-expression in gastric cancer cell line can significantly enhance cellular caspase-3 expression and activities, ameliorate apoptosis-inducing effects of mitomycin C on cancer cells, which is a novel strategy to improve chemotherapeutic effects on gastric cancer.

Antibiotics, Antineoplastic↗

PubMed2005

Effects of intestinal trefoil, factor on colonic mucosa in experimental colitis of rats.

In order to investigate the protective effects of intestinal trefoil factor (ITF) on colonic mucosa in experimental colitis of rats, ITF was detected by RT-PCR and immunohistochemistry at different time points. Three days after colitis induction, rats were treated with either 0.9% saline solution or rhITF. Pathological changes and the expression of iNOS mRNA, NO, MDA and SOD were measured respectively. It was found that ITF was mainly located in goblet cells, significantly higher in model group than in normal group (P<0.05). rhITF could increase the iNOS mRNA expression and NO contents, and there was statistically significant difference between rhITF group and model group (P<0.05). rhITF also caused an increase of MDA and a decrease of SOD, but there was no significant difference between two groups. These results indicated that ITF has apparent therapeutic effects in ulcerative colitis, which may be associated with iNOS and NO.

Acetic Acid↗

PubMed2005

Two-channel gastric electrical stimulation accelerates delayed gastric emptying induced by vasopressin.

The aim of this study was to investigate the effects of two-channel gastric electrical stimulation (GES) on delayed gastric emptying, gastric dysrhythmias, and motion sickness-like symptoms induced by vasopressin. Seven dogs implanted with four pairs of gastric electrodes and a duodenal cannula were studied in four randomized sessions (saline, vasopressin, single-channel GES, and two-channel GES). The experiment in each session was conducted sequentially as follows: 30-min baseline, ingestion of a liquid meal, 30-min iv infusion of vasopressin or saline, and two 30-min postprandial recordings. In the GES sessions, GES was applied via the first pair of electrodes for single-channel GES or the first and third pairs of electrodes for two-channel GES. Gastric emptying was collected every 15 min via the cannula for a period of 90 min. Results were as follows. (1) Vasopressin induced gastric dysrhythmias, motion sickness-like symptoms, and delayed gastric emptying (P < 0.01, ANOVA). (2) GES normalized gastric dysrhythmias (P < 0.01) but showed no effects on vasopressin-induced emetic response. (3) Two-channel GES improved delayed gastric emptying induced by vasopressin. In comparison with the vasopressin session, two-channel GES, but not single-channel GES, significantly increased gastric emptying at 30 min (43.9+/-12.6 vs. 27.5+/-7.7%; P < 0.03), 60 min (75.3+/-15.1 vs. 54.0+/-17.8%; P < 0.05), and 90 min (91.6+/-9.8 vs. 80.3+/-9.0%; P < 0.05). GES with long pulses is able to normalize gastric dysrhythmias. Two-channel GES improves delayed gastric emptying induced by vasopressin.

Animals↗

PubMed2005

CAD-aided mammogram training.

RATIONALE AND OBJECTIVES: Although computer-aided detection (CAD) improves the diagnosis rate of early breast cancer, it has not been well integrated into radiology residency and technician training program. Moreover, CAD performance studies ignore the reader's training and experience with CAD. The purpose of this study was to investigate whether CAD training via a cognitive-perceptual based hypermedia program has effects on the performance studies of mammogram reading. MATERIALS AND METHODS: Three observers read a pretest set of 80 breast cancer cases (43 negative, 23 benign, and 14 malignant cancer cases). During 4 weeks' training, the observers used a hypermedia instructional program in CAD-aided mammography interpretation. The program includes modules of CAD attention-focusing schemes, CAD procedural knowledge, and case-based simulations in mammography interpretation in consensus with CAD. By the end of the fourth week of the training, they reviewed a posttest set of cases. Data were analyzed with multireader, multicase receiver operating characteristic methods. RESULTS: Three readers performed better in mammogram reading after training in CAD knowledge than they did before CAD training. CAD training and experience improved the performance of CAD-aided mammography interpretation. CONCLUSION: A statistically significant difference was found in each observer's performance in CAD-aided mammogram reading before and after the training. CAD training will influence the perception, recognition, and interpretation of early breast cancer and CAD performance studies. Furthermore, the young generation of radiologic professionals can have more training in various attention-focusing features, declarative knowledge, procedural knowledge, and conditional knowledge of CAD and incorporate them into their knowledge base and strategic processing for the purpose of improving the accuracy of mammography interpretation performance.

Breast Neoplasms↗

PubMed2005

Standardization for image characteristics in telemammography using genetic and nonlinear algorithms.

As the soft copy reading and computer assisted diagnosis (CAD) in mammography become more and more important, the standardization of digital images becomes paramount. Telemammography and telemedicine requires the standardization for image characteristics, such as image resolution, bit-depth and intensity response. Soft copy reading and CAD in mammography are both dependent on the characteristics of the source of the digital data, either direct digital mammography or digitized screen-film mammography. An algorithm developed on images from one database may not perform well as on images from another database (with a different digitization). In this paper, we describe two methods based on a genetic algorithm and a nonlinear algorithm for standardization of digitized and digital mammography. The proposed standardization techniques are based on geometric and intensity transformations that are discovered using a set of calibration images. A set of transformation algorithm is used to search for the best standardization.

Algorithms↗

PubMed2005

A comparison between nitric oxide output in the nose and sinuses: A pilot study in one volunteer.

From a study of nitric oxide (NO) output in the nose and sinuses it seems that: (i) the results obtained regarding the regulation of NO output in the nose do not necessarily apply to the sinuses; (ii) the results obtained for one group of sinuses may not apply to another; and (iii) NO output in the sinuses does not behave as one would expect if it serves to protect against infection.A pilot study was undertaken in one subject to determine whether the control of NO output in the nose differs from that in the sinuses.NO output was measured by aspirating different gaseous concentrations of oxygen (and/or carbon dioxide) through the nasal airways or punctured maxillary and frontal sinuses before and after i.v. administration of L-arginine (20 mg/kg). In the absence of gaseous oxygen in the nose or maxillary antrum, the effect of L-arginine on NO output was the same as that in the presence of oxygen. In the frontal sinus, the effect of L-arginine on NO output was blocked by the absence of gaseous oxygen. NO output in the nose and frontal sinus showed similar changes after either i.v. administration of L-arginine or removal of oxygen from the air. NO output in the maxillary antrum was virtually unaffected by either procedure. NO output in the nose was largely unaffected by the gaseous carbon dioxide content but that in the frontal and maxillary sinuses was profoundly inhibited by it. In both sinuses, suppression of NO output by carbon dioxide was countered by oxygen. Alterations in the oxygen or carbon dioxide content of the maxillary antrum did not alter NO output in the frontal sinus, or vice versa. After i.v. infusion of L-arginine, nasal NO output remained elevated for >1 h.

Arginine↗

PubMed2005

A novel method of measuring gas phase nitric oxide concentration in cell cultures.

This is the first report on the measurement of nitric oxide (NO) concentrations in the gas phase in a squamous cell culture. The technique may permit the assessment of NO output under conditions that aim to mimic facets of pathology in relatively inaccessible tissues. The primary aim of this study was to devise a method to detect the NO concentration produced by cell cultures in the gas phase of a culture flask. A secondary aim was to determine whether the effect of hypoxia or radiation on NO production in a human squamous cell carcinoma cell culture would be detectable with this technique. The NO concentration was measured off-line using a rapid-response chemiluminescent analyzer. The gas samples were aspirated from cell culture flasks (i) under normal culture conditions, (ii) under conditions of hypoxia and (iii) following radiation of human head and neck squamous cell carcinoma cell line cultures. Elevated levels of the gas phase NO concentration were consistently obtained from the cell culture flasks using this experimental set-up. Hypoxia and radiation diminished NO production.

Carcinoma, Squamous Cell↗

PubMed2005

Antinociceptive property of tegaserod in a rat model of chronic visceral hypersensitivity.

OBJECTIVE: To establish a model of chronic visceral hypersensitivity in rats and to investigate the effect of tegaserod, a partial 5-hydroxytryptamine-4 receptor agonist, on visceral hypersensitivity. METHODS: Neonate Sprague-Dawley rats at 8-21 days after birth underwent colorectal distension once daily. Adult rats aged 8-10 postnatal weeks underwent colorectal distension and the abdominal withdrawal reflex (AWR) during the distension was determined. The AWR score was recorded before and after intraperitoneal administration of either tegaserod (treatment group: 0.3 mg/kg) or vehicle (control group). RESULTS: Changes in the AWR score were dependent on the pressure intensity of the colorectal distension (P < 0.01). At pressures of 40, 60 and 80 mmHg, the AWR scores in the model rats with visceral hypersensitivity were significantly higher than those recorded in the control group (1.95 +/- 0.16 vs 1.35 +/- 0.15, 2.82 +/- 0.12 vs 2.17 +/- 0.13, 3.20 +/- 0.14 vs 2.59 +/- 0.14, P < 0.01). Compared with the controls, tegaserod significantly decreased the AWR scores at the distension pressures of 40, 60 and 80 mmHg (1.95 +/- 0.50 vs 1.32 +/- 0.55, 3.05 +/- 0.48 vs 2.32 +/- 0.54, 3.25 +/- 0.63 vs 2.77 +/- 0.51, P < 0.05). CONCLUSIONS: Adult rats can develop chronic visceral hypersensitivity after transient colorectal mechanical irritation during their postnatal period. Tegaserod increases the pain threshold to noxious stimuli, suggesting an antinociceptive property in its effect on visceral hypersensitivity.

Animals↗

PubMed2004

BAK overexpression mediates p53-independent apoptosis inducing effects on human gastric cancer cells.

BACKGROUND: BAK (Bcl-2 homologous antagonist/killer) is a novel pro-apoptotic gene of the Bcl-2 family. It has been reported that gastric tumors have reduced BAK levels when compared with the normal mucosa. Moreover, mutations of the BAK gene have been identified in human gastrointestinal cancers, suggesting that a perturbation of BAK-mediated apoptosis may contribute to the pathogenesis of gastric cancer. In this study, we explored the therapeutic effects of gene transfer mediated elevations in BAK expression on human gastric cancer cells in vitro. METHODS: Eukaryotic expression vector for the BAK gene was constructed and transferred into gastric cancer cell lines, MKN-45 (wild-type p53) and MKN-28 (mutant-type p53). RT-PCR and Western Blotting detected cellular BAK gene expression. Cell growth activities were detected by MTT colorimetry and flow cytometry, while apoptosis was assayed by electronic microscopy and TUNEL. Western Blotting and colorimetry investigated cellular caspase-3 activities. RESULTS: BAK gene transfer could result in significant BAK overexpression, decreased in vitro growth, cell cycle G0/G1 arrest, and induced apoptosis in gastric cancer cells. In transferred cells, inactive caspase-3 precursor was cleaved into the active subunits p20 and p17, during BAK overexpression-induced apoptosis. In addition, this process occurred equally well in p53 wild-type (MKN-45), or in p53 mutant-type (MKN-28) gastric cancer cells. CONCLUSIONS: The data presented suggests that overexpression of the BAK gene can lead to apoptosis of gastric cancer cells in vitro, which does not appear to be dependent on p53 status. The action mechanism of BAK mediated apoptosis correlates with activation of caspase-3. This could be served as a potential strategy for further development of gastric cancer therapies.

Apoptosis↗

PubMed2004

Ipsilateral-mammogram computer-aided detection of breast cancer.

In this paper, an ipsilateral multi-view computer-aided detection (CAD) scheme is presented for mass detection in digital mammograms by exploiting correlative information of suspicious lesions between mammograms of the same breast. After nonlinear tree-structured filtering for image noise suppression, two wavelet-based methods, directional wavelet transform and tree-structured wavelet transform for image enhancement, and adaptive fuzzy C-means algorithm for segmentation are employed on each mammograms of the same breast, respectively, concurrent analysis is developed for iterative analysis of ipsilateral multi-view mammograms by inter-projective feature matching analysis. A supervised artificial neural network is developed as a classifier, in which the back-propagation algorithm combined with Kalman filtering is used as training algorithm, and free-response receiver operating characteristic analysis is used to test the performance of the developed unilateral CAD system. Performance comparison has been conducted between the final ipsilateral multi-view CAD system and our previously developed single-mammogram-based CAD system. The study results demonstrate the advantages of ipsilateral multi-view CAD method combined with concurrent analysis over current single-view CAD system on false positive reduction.

Breast Neoplasms↗

PubMed2004

Construction of novel Brassica napus genotypes through chromosomal substitution and elimination using interploid species hybridization.

A synthetic Brassica napus rapeseed with genome composition of A(r)A(r)C(c)C(c), made by combining A(r) from B. rapa (A(r)A(r)) and C(c) from B. carinata (B(c)B(c)C(c)C(c)), is valuable for making new genes available to breeders and gaining heterosis in crosses. An intergenomic hybrid A(n)A(r)C(n)C(c) was made from a hybrid between natural Brassica napus (A(n)A(n)C(n)C(n)) and a synthetic rapeseed. To construct the synthetic Brassica napus, hexaploid plants (2n=54, A(r)A(r)B(c)B(c)C(c)C(c)) were first obtained through chromosome doubling of trigenomic hybrids (2n=27, A(r)B(c)C(c)) between Brassica carinata (2n=34) and B. rapa (2n=20). Pentaploid hybrids (2n=46, A(r)A(n)B(c)C(c)C(n)) were then produced by crossing the hexaploid with the pollen of natural B. napus (2n=38). Chromosomes with dual and single B(c) genomes were observed in somatic cells of hexaploid and pentaploid plants. About 80% of pollen mother cells of pentaploid hybrids had 19 or more bivalents, indicating that the bivalents from A(r)/A(n) and C(c)/C(n) chromosomes were normally formed. The occurrence of trivalents and quadrivalents at diakinesis suggested that B(c), A(n) and A(r) or B(c), C(n) and C(c) homologous pairing and exchange might happen. The variable number of laggards, 3 and 4 in most cases, were observed in the majority of PMCs at anaphase. Results from genomic in situ hybridization showed that the laggards belonged mainly to the B(c) genome, suggesting that the B(c) genome could be eliminated in the gametes of pentaploid hybrids. 16.15% of seeds derived from self-pollinated pentaploids have 38 chromosomes, and 90% of 38-chromosome seeds were completely excluded B(c) genome. The cytological results of this experiment suggested that it is possible to obtain new materials with genome composition of A(r)A(r)C(c)C(c) for rapeseed breeding.

Brassica napus↗

PubMed2004

Motilin in human milk and its elevated plasma concentration in lactating women.

BACKGROUND AND AIMS: The aims of this study were to investigate whether: (i) lactating women had an elevated plasma level of motilin; (ii) there was a correlation between the plasma motilin level and the motilin level in breast milk in lactating women; and (iii) there was a difference in motilin levels between the colostrum and mature human milk in a controlled postprandial state. METHODS: Twenty control women and 18 lactating women were enrolled in this study. All samples were drawn in a controlled postprandial state. The concentration of motilin was measured using radioimmunoassay. RESULTS: The plasma motilin level in lactating women was 434 +/- 180 pmol/L on the fifth day after delivery and 450 +/- 204 pmol/L on the 42nd day after delivery (P > 0.05). Both of these values were significantly higher than those in the control women (231 +/- 48 pmol/L, P < 0.05). The motilin level in human milk in the controlled postprandial state was 161 +/- 56 pmol/L on the fifth day and 154 +/- 60 pmol/L on the 42nd day after parturition (P = 0.7). Although there was motilin in the breast milk and an elevated plasma level of motilin in the lactating women, there was no correlation in motilin level between the blood and the breast milk. CONCLUSIONS: Motilin is elevated in the blood of lactating women and human milk contains motilin. These elevated levels of motilin sustain for a period of at least 6 weeks. Further studies are necessary to assess whether motilin is involved in the development of gastrointestinal motility in the early stage of life in infancy.

Adult↗

PubMed2004

[Screening serum response special antibodies of U251 cell line from surface display phage antibody library].

U251 cell is a sensitive cell line to serum, which stops at G0 phase of cell cycle in no-serum medium, and recovers growth when the serum is added into no-serum medium. The cell can express corresponding proteins in different phase of cell cycle. Therefore it is very signification for the study of cell cycle regulation mechanism that explores these proteins. In this paper, the mouse antibody phage display library was added into the bottle in which the serum starvation U251 cells had been cultured, and the special antibody phages were absorbed. Then the absorbed antibody phages were amplified by adding E. coli TG1 and helper phage M13K07. Amplified antibody phages were added into bottle in which the serum cultured cell after serum starvation (follow named as serum recovered cells) were incubated, so that the cell absorbed the no-special antibody phages for the serum starvation cell and the special antibody phages were in supernatant. The remaining no-special antibody phages in the supernatant were discarded by repeating above program 3-4 times. The pure special antibody phages were gotten, and amplified by adding the host cell E. coli TG1 and helper phage M13K07. Then the host bacterium infected special antibody phage was spread on the plate medium with ampicillin, and the monoclonal antibody phages were gotten. Using same as above program, the monoclonal antibody phages absorbed specially for serum recovered U251 cells were obtained when the serum recovered cells instead of serum starvation cells and serum starvation cells instead of serum recovered cells. In this study, ninety-six positive monoclonal antibody phages that absorbed specially the serum starvation cells and eighty-two positive monoclonal antibody phages that absorbed specially the serum recovered cells were obtained. By using cell immunochemistry assay, two special signification antibodies were obtained. one (No.11) was the strong response in serum starvation cells, the other (No.2) was the strong response in serum recovered cells. The antibody No.2 had the distinctive response to the serum recovered cells in different incubation time (15min, 30min, 1h, 2h, 4h, 8h, 12h and 48h) after serum starvation. The results showed that No.2 antibody would be useful to research the factors of cell cycle regulation and apply to tumor diagnosis.

Antibodies, Neoplasm↗

PubMed2003

High-quality mutant libraries of Xanthomonas oryzae pv. oryzae and X. campestris pv. campestris generated by an efficient transposon mutagenesis system.

A novel transposon mutagenesis system for the phytopathogenic bacteria Xanthomonas oryzae pv. oryzae (Xoo) and X. campestris pv. campestris (Xcc) was developed using a Tn5-based transposome. A highly efficient transformation up to 10(6) transformants per microg transposon DNA was obtained. Southern blot and thermal asymmetric interlaced polymerase chain reaction analyses of Tn5 insertion sites suggested a random mode of transposition. The transposition was stable in the transformants for 20 subcultures. Eighteen thousand and 17000 transformants for Xoo and Xcc, respectively, were generated, corresponding to 4X ORF coverage of the genomes. The libraries will facilitate the identification of pathogenicity-related genes as well as functional genomic analysis in Xoo and Xcc.

Blotting, Southern↗

PubMed2002

Dose response of almonds on coronary heart disease risk factors: blood lipids, oxidized low-density lipoproteins, lipoprotein(a), homocysteine, and pulmonary nitric oxide: a randomized, controlled, crossover trial.

BACKGROUND: Although recent studies have indicated that nut consumption may improve levels of blood lipids, nuts are not generally recommended as snacks for hyperlipidemic subjects because of their high fat content. Furthermore, the effective dose is still unknown. METHODS AND RESULTS: The dose-response effects of whole almonds, taken as snacks, were compared with low-saturated fat (<5% energy) whole-wheat muffins (control) in the therapeutic diets of hyperlipidemic subjects. In a randomized crossover study, 27 hyperlipidemic men and women consumed 3 isoenergetic (mean 423 kcal/d) supplements each for 1 month. Supplements provided 22.2% of energy and consisted of full-dose almonds (73+/-3 g/d), half-dose almonds plus half-dose muffins, and full-dose muffins. Fasting blood, expired air, blood pressure, and body weight measurements were obtained at weeks 0, 2, and 4. Mean body weights differed <300 g between treatments. The full-dose almonds produced the greatest reduction in levels of blood lipids. Significant reductions from baseline were seen on both half- and full-dose almonds for LDL cholesterol (4.4+/-1.7%, P=0.018, and 9.4+/-1.9%, P<0.001, respectively) and LDL:HDL cholesterol (7.8+/-2.2%, P=0.001, and 12.0+/-2.1%, P<0.001, respectively) and on full-dose almonds alone for lipoprotein(a) (7.8+/-3.5%, P=0.034) and oxidized LDL concentrations (14.0+/-3.8%, P<0.001), with no significant reductions on the control diet. No difference was seen in pulmonary nitric oxide between treatments. CONCLUSIONS: Almonds used as snacks in the diets of hyperlipidemic subjects significantly reduce coronary heart disease risk factors, probably in part because of the nonfat (protein and fiber) and monounsaturated fatty acid components of the nut.

Aged↗

PubMed2002

Renal toxicity of perchloroethylene and S-(1,2,2-trichlorovinyl)glutathione in rats and mice: sex- and species-dependent differences.

Suspensions of renal cells from rats and renal mitochondria from rats and mice were used to assess the sex and species dependence of acute toxicity due to perchloroethylene (Perc) and its glutathione conjugate S-(1,2,2-trichlorovinyl)glutathione (TCVG). A marked sex dependence in the acute cytotoxicity of both Perc and TCVG was observed: Perc caused significant release of lactate dehydrogenase (LDH) in isolated kidney cells from male but not female rats, and TCVG caused much more LDH release from male than female rat kidney cells. Assessment of toxicity in suspensions of isolated mitochondria from kidneys of male and female rats revealed a generally similar pattern of sensitivity, with mitochondria from males exhibiting significantly more inhibition of State 3 respiration and decrease of respiratory control ratio than mitochondria from females. Respiratory function in mitochondria from male and female mice, however, was also significantly inhibited by Perc or TCVG but exhibited little sex dependence in the degree of inhibition. Comparison with results from similar studies using the congener trichloroethylene and its glutathione conjugate suggested that Perc and TCVG are more potent nephrotoxicants. Neither Perc nor TCVG produced any significant effects on cytotoxicity or mitochondrial function in isolated hepatocytes from rats or in isolated liver mitochondria from rats or mice, suggesting that the liver is not a major acute target for Perc or its glutathione conjugate. Thus, many of the species-, sex-, and tissue-dependent differences in toxicity of Perc and TCVG that are observed in vivo are also observed in these in vitro models.

Animals↗

PubMed2002

Naphthoquinone cataract in mice: mitochondrial change and protection by superoxide dismutase.

An injection of 1,2-naphthoquinone (NQ) into the anterior chamber of mouse eye produces anterior cortical cataract. It was previously shown by histology that mitochondria in lens epithelial cells are the target of ocular drug toxicity. In this work we investigated NQ-induced cataract by closely examining morphological changes of mitochondria and other cellular organelles in the lens epithelium. Mitochondria exhibited marked swelling in 2 hrs after NQ injection but restored the normal condensed configuration at 4.5 hrs. The nuclear chromatin showed condensation at 2 hrs and returned to the normal appearance at 4.5 hrs. This was unexpected because the lens at 4.5 hrs was cataractous due to vacuole formation in fiber cell layers. The result indicates that, although lens epithelial mitochondria are the target of NQ toxicity, cataract begins to develop before mitochondria and other subcellular organelles become totally dysfunctional. At 1 week after NQ injection, most mitochondria disintegrated and the fragmented chromatin appeared to leak out through the ruptured nuclear membrane. SOD injected with NQ significantly delayed the onset of cataract and protected lens epithelial cells. A second SOD injection further delayed cataract development.

Animals↗