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Biomedical subjects

J Cai

Publications and source records attributed to J Cai.

At least 19 recordsLinked to original sources
PubMed2026

Mechanisms of Hexavalent Chromium-Induced Reproductive Toxicity: A Focus on the Ovary and Placenta.

Hexavalent Chromium (Cr(VI)) is a Group A carcinogen, mutagen, and teratogen. Cr(VI) has been used by more than 50 industries, and its contamination of drinking water is widespread across the United States (U.S.). Epidemiological data of women who lived in Willits, California, U.S., indicate that environmental exposure to Cr(VI) adversely affects pregnancy outcomes and the health of their immediate offspring, resulting in a low birth rate, pregnancy loss, and spontaneous abortion, and their children (F1 offspring) experienced birth defects. However, the molecular mechanisms behind Cr(VI)-induced reproductive and developmental toxicity are poorly understood. Cr(VI) enters cells through anion transporters and is rapidly reduced to Cr(III) by endogenous antioxidants within the cell. Cr(III) forms adducts with DNA, which can block DNA replication and transcription; abnormal repair can lead to DNA double-strand breaks, mutations, micronucleus formation, chromosomal abnormalities, and increased genomic instability. Cr(VI) induces oxidative stress via the Fenton reaction, generating free radicals, and depleting antioxidants, thereby promoting apoptosis via p53-dependent and independent pathways, resulting in follicular atresia and accelerated reproductive aging. Antioxidant supplementation with resveratrol, vitamin C, and edaravone mitigates Cr(VI) toxicity in the ovary. Cr(VI) disrupts meiosis in metaphase II oocytes by causing DNA strand breaks, altering F-actin dynamics, disturbing microtubules, and leading to chromosome missegregation. Gestational exposure to Cr(VI) also disrupts placental function through multiple mechanisms by targeting trophoblast lineages. The current review focuses on genotoxicity, oxidative stress, and other mechanisms by which Cr(VI) disrupts the female reproductive and endocrine systems, with particular emphasis on the ovary and placenta.

Hexavalent chromium↗
PubMed2001

A statistical model for the evaluation of barrier contraceptive efficacy.

This paper describes an approach for the analysis of barrier contraceptive efficacy trials that accounts for timing frequency of intercourse and compliance. We allow exposure variables to vary for each act of intercourse and we control for timing of each act through a specific parametric function of the day of the act relative to the last day of the follicular phase of the cycle. The model can be used to examine the level of protection provided by a barrier versus no contraceptive method even when no control group of non-users is studied, as long as there are acts with no barrier use during the fertile window. We present results of a simulation study which examines performance of estimators and power under a variety of scenarios, including situations where an accurate benchmark for ovulation day is not available. As compared to the survival analysis approach commonly used in this setting, simulation results show that the new approach yields considerable gains in power to detect differences between the efficacy of contraceptive methods. An application to data from the FemCap versus diaphragm trial show results consistent with previous findings suggesting superiority of the diaphragm but also provides new evidence of the per act protection provided by both methods.

Biometry↗
PubMed2001

Bis(beta-alaninium) biphenyl-4,4'-disulfonate.

In the crystal structure of the title compound, 2C(3)H(8)NO(2)(+).C(12)H(8)O(6)S(2)(2-), N-H...O hydrogen bonds formed between the amino H atoms and the sulfonate O atoms give rise to the assembly of cationic beta-alaninium dimers and centrosymmetric biphenyl-4,4'-disulfonate anions into an extended two-dimensional layer. The resulting hydrogen-bonded ribbons can be described as C(2)(2)(6)R(4)(4)(12) according to graph-set notation. C-H...O hydrogen bonds between adjacent sheets further extend the structure into a three-dimensional arrangement.

Alanine↗
PubMed2001

Diaquabis(ethylenediamine)copper(II) bis[tris(ethylenediamine)nickel(II)] tris(naphthalene-2,6-disulfonate) tetrahydrate.

The title mixed-metal compound, [Cu(C(2)H(8)N(2))(2)(H(2)O)(2)][Ni(C(2)H(8)N(2))(3)](2)(C(10)H(6)O(6)S(2))(3).4H(2)O, was obtained during investigations of the porous frameworks constructed by amino-coordinated metal complex cations and large organic anions. All three naphthalene-2,6-disulfonate anions and the [Cu(en)(2)(H(2)O)(2)](2+) cation are located on crystallographic inversion centers and assemble into an extended two-dimensional network through intermolecular hydrogen bonds, creating cavities in which the [Ni(en)(3)](2+) cations and water molecules are included.

Journal Article↗
PubMed2001

Comparison of simultaneous distillation extraction and solid-phase microextraction for the determination of volatile flavor components.

Traditional simultaneous distillation extraction (SDE) and solid-phase microextraction (SPME) techniques were compared for their effectiveness in the extraction of volatile flavor compounds from various mustard paste samples. Each method was used to evaluate the responses of some analytes from real samples and calibration standards in order to provide sensitivity comparisons between the two techniques. Experimental results showed traditional SDE lacked the sensitivity needed to evaluate certain flavor volatiles, such as 1,2-propanediol. Dramatic improvements in the extraction ability of the SPME fibers over the traditional SDE method were noted. Different SPME fibers were investigated to determine the selectivity of the various fibers to the different flavor compounds present in the mustard paste samples. Parameters that might affect the SPME, such as the duration of absorption and desorption, temperature of extraction, and the polarity and structure of the fiber were investigated. Of the various fibers investigated, the PDMS-DVB fiber proved to be the most desirable for these analytes.

Chromatography, Liquid↗
PubMed2001

Vascular endothelial growth factor (VEGF) is an autocrine growth factor for VEGF receptor-positive human tumors.

Angiogenesis is required for the progression of tumors from a benign to a malignant phenotype and for metastasis. Malignant tumor cells secrete factors such as vascular endothelial growth factor (VEGF), which bind to their cognate receptors on endothelial cells to induce angiogenesis. Here it is shown that several tumor types express VEGF receptors (VEGFRs) and that inhibition of VEGF (VEGF antisense oligonucleotide AS-3) or VEGFRs (neutralizing antibodies) inhibited the proliferation of these cell lines in vitro. Furthermore, this effect was abrogated by exogenous VEGF. Thus, VEGF is an autocrine growth factor for tumor cell lines that express VEGFRs. A modified form of VEGF AS-3 (AS-3m), in which flanking 4 nucleotides were substituted with 2-O-methylnucleosides (mixed backbone oligonucleotides), retained specificity and was active when given orally or systemically in vitro and in murine tumor models. In VEGFR-2-expressing tumors, VEGF inhibition may have dual functions: direct inhibition of tumor cell growth and inhibition of angiogenesis.

Animals↗
PubMed2001

Functional expression of multidrug resistance protein 1 in Pichia pastoris.

Overexpression of the multidrug resistance-associated protein (MRP1) causes multidrug resistance in cultured cells. MRP1 transports a large number of glutathione, glucuronide, and sulfate-conjugated organic anions by an ATP-dependent efflux mechanism. Six other MRP proteins exist (MRP2-7), and mutations in some of these genes cause major pathological conditions in humans. A detailed characterization of the structure and mechanism of action of these proteins requires an efficient expression system from which large amounts of active protein can be obtained. We report the expression of a recombinant MRP1 in the methylotrophic yeast Pichia pastoris. The protein is expressed in the membrane fraction of these cells, as a stable and underglycosylated 165 kDa peptide. Expression levels are very high, and 30 times superior to those seen in multidrug-resistant HeLa/MRP1 transfectants. MRP1 expressed in P. pastoris binds 8-azido[alpha-(32)P]ATP in a Mg(2+)-dependent and EDTA-sensitive fashion, which can be competed by a molar excess of ADP and ATP. Under hydrolysis conditions (at 37 degrees C), orthovanadate induces trapping of the 8-azido[alpha-(32)P]nucleotide in MRP1, which can be further modulated by known MRP1 ligands. MRP1 is also labeled by a photoactive analogue of rhodamine 123 (IAARh123) in P. pastoris/MRP1 membranes, and this can be competed by known MRP1 ligands. Finally, MRP1-positive membrane vesicles show ATP-dependent uptake of LTC(4). Thus, MRP1 expressed in P. pastoris is active and shows characteristics of MRP1 expressed in mammalian cells, including drug binding, ligand-modulated formation of the MRP1-MgADP-P(i) intermediate (ATPase activity), and ATP-dependent substrate transport. The successful expression of catalytically active and transport-competent MRP1 in P. pastoris should greatly facilitate the efficient production and isolation of the wild type or inactive mutants of MRP1, or of other MRP proteins for structural and functional characterization.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2001

Solid-state structures of group 1 and group 2 metal 1,5-naphthalenedisulfonates: systematic investigation of lamellar three-dimensional networks constructed by metal arenedisulfonate.

Seven Group 1 and Group 2 1,5-naphthalenedisulfonates (1,5-nds) have been synthesized and structurally characterized by single-crystal X-ray diffraction, IR spectroscopy and thermal gravimetric analysis. For Group 1 metal complexes, with M = Li(+) (1), Na(+) (2) and K(+) (3), all crystallize in the same space group (P2(1)/c) with the same composition, [M(2)(1,5-nds)(H(2)O)(2)]. They adopt similar three-dimensional packing arrangements with the metal-sulfonate inorganic layers pillared by naphthalene rings. However, the coordination behavior of three metal cations toward the SO(3)(-) group and water molecule are different, resulting in different architectures for the inorganic portion. For Group 2 complexes with M = Mg(2+) (4), Ca(2+) (5), Sr(2+) (6) and Ba(2+) (7), Mg(2+) shows no direct coordination by the SO(3)(-) group while Ca(2+) is coordinated by four SO(3)(-) groups and a two-dimensional network is formed. Complexes (6) and (7) are isostructural, adopting the same three-dimensional, inorganic-organic pillared framework as seen for (1)-(3). The coordination behavior of the metal cations in these structures neatly illustrates the increase in coordination strength with decreasing charge/radius ratio for Group 1 and Group 2 metal cations with large organic anions.

Journal Article↗
PubMed2001

Changes in body mass index prior to baseline among participants who are ill or who die during the early years of follow-up.

The association between body mass index (weight (kg)/height (m)(2)) and mortality may be confounded by preexisting illness. A method commonly used to control for this confounding is the exclusion of participants who have certain diseases at baseline and/or those who die during the early years of follow-up. The authors used data from the Atherosclerosis Risk in Communities (ARIC) Study (n = 14,088) to determine whether participants identified by these criteria had different changes in body mass index than other participants. Weight change was measured over a 3-year interval between study entry (1987-1989) and reexamination (1990-1993), and information on vital status was collected over the subsequent 5 years. Mean change in body mass index was -0.54 (95% confidence interval (CI): -0.90, -0.12) among participants who died in the first year of follow-up, -0.03 (95% CI: -0.18, 0.12) among those who died in the first 4 years of follow-up, and 0.36 (95% CI: 0.33, 0.39) among those who survived for at least 5 years. Participants who died during the first 4 years were over twice as likely as survivors to have changed from the obese category (body mass index >or=30) to the nonobese category (odds ratio = 2.14; 95% CI: 1.44, 3.17). Mean change in body mass index prior to baseline was not different among ill participants compared with those who were healthy, but the odds of converting from obese to nonobese were higher in ill participants than in healthy ones (odds ratio = 1.29; 95% CI: 1.01, 1.67).

Body Mass Index↗
PubMed2001

Role of mitochondrial dysfunction in S-(1,2-dichlorovinyl)-l-cysteine-induced apoptosis.

The nephrotoxicity of trichloroethylene and dichloroacetylene has previously been linked to mitochondrial dysfunction induced by the metabolite S-(1,2-dichlorovinyl)-l-cysteine (DCVC). In this study, we examined whether key biochemical steps associated with mitochondria occur in DCVC-induced apoptosis in cultured porcine proximal tubular LLC-PK1 cells. DCVC caused a decrease in mitochondrial membrane potential (mt Delta Psi) beginning at 4 h and a release of cytochrome c into the cytoplasm at 6 h. Caspase-3-like activity was detected at 6 h and extensive DNA fragmentation was observed at 8 h. Decreases in cellular ATP were not evident until 8 h and later, even though electron microscopy showed that the mitochondria were extensively swollen. Aminooxyacetic acid (AOAA), an inhibitor of cysteine-conjugate beta-lyase, protected against mitochondrial changes and apoptosis. Overexpression of the antiapoptotic Bcl-2 protein desensitized LLC-PK1 cells to DCVC-induced apoptosis. These results support the interpretation that mitochondrial release of cyt c and cyt c-dependent activation of caspase-3 could have a central role in nephrotoxicity due to haloalkene-derived cysteine S-conjugates.

Aminooxyacetic Acid↗
PubMed2001

Significant correlation between micrometastasis in the lymph nodes and reduced expression of E-cadherin in early gastric cancer.

BACKGROUND: E-cadherin has been recognized as an important factor associated with tumor metastasis. However, the relationship between micrometastasis in the lymph nodes and the expression of E-cadherin in the primary tumor in gastric cancer remains unclear. METHODS: Two consecutive sections of 4522 lymph nodes from 162 patients with early gastric cancer were prepared for simultaneous hematoxylin and eosin (H&E) and cytokeratin (CK) staining. Sections of primary tumors from 135 of these patients were prepared for E-cadherin immunostaining. RESULTS: The incidence of lymph node involvement was significantly increased, from 6.8% (11/162 patients) by H&E staining, to 27% (43/162 patients) by CK immunostaining (P < 0.0001). Micrometastasis in the lymph node was found in 32 of 151 (21%) patients who had no lymph node metastasis evidenced by H&E staining. Micro-lymph node metastasis was frequently found in tumors with a diameter more than 1.0 cm, of those that were poorly differentiated, deeply invaded, showed lymphatic on vascular invasion, and in those that showed reduced expression of E-cadherin. Loss of expression of E-cadherin in the primary tumor was closely correlated with micro-lymph node metastasis. Patients with tumors with micro-lymph node metastasis detected by CK immunostaining had a significantly lower 5-year survival rate (P < 0.01) than those without such metastases. CONCLUSION: Tumors more than 1.0 cm in diameter and those that exhibit poor differentiation, deep invasion (i.e., to the submucosa), lymphatic or vascular invasion, and reduced expression of E-cadherin are risk factors for lymph node metastasis in early gastric cancer. Thus, it is recommended that cancers confined to the mucosa (m-cancers) that are more than 1.0 cm in diameter should not be treated with limited surgery without lymphadenectomy.

Adult↗
PubMed2001

Covalent binding of acrylonitrile to specific rat liver glutathione S-transferases in vivo.

Acrylonitrile (AN) is an industrial vinyl monomer that is acutely toxic. When administered to rats, AN covalently binds to tissue proteins in a dose-dependent but nonlinear manner [Benz, F. W., Nerland, D. E., Li, J., and Corbett, D. (1997) Fundam. Appl. Toxicol. 36, 149-156]. The nonlinearity in covalent binding stems from the fact that AN rapidly depletes liver glutathione after which the covalent binding to tissue proteins increases disproportionately. The identity of the tissue proteins to which AN covalently binds is unknown. The experiments described here were conducted to begin to answer this question. Male Sprague-Dawley rats were injected subcutaneously with 115 mg/kg (2.2 mmol/kg) [2,3-(14)C]AN. Two hours later, the livers were removed, homogenized, and fractionated into subcellular components, and the radioactively labeled proteins were separated on SDS-PAGE. One set of labeled proteins was found to be glutathione S-transferase (GST). Specific labeling of the mu over the alpha class was observed. Separation of the GST subunits by HPLC followed by scintillation counting showed that AN was selective for subunit rGSTM1. Mass spectral analysis of tryptic digests of the GST subunits indicated that the site of labeling was cysteine 86. The reason for the high reactivity of cysteine 86 in rGSTM1 was hypothesized to be due to its potential interaction with histidine 84, which is unique in this subunit.

Acrylonitrile↗
PubMed2001

Evidence for cocaine and methylecgonidine stimulation of M(2) muscarinic receptors in cultured human embryonic lung cells.

1. Muscarinic cholinoceptor stimulation leads to an increase in guanylyl cyclase activity and to a decrease in adenylyl cyclase activity. This study examined the effects of cocaine and methylecgonidine (MEG) on muscarinic receptors by measurement of cyclic GMP and cyclic AMP content in cultured human embryonic lung (HEL299) cells which specifically express M(2) muscarinic receptors. 2. A concentration-dependent increase in cyclic GMP production was observed in HEL299 cells incubated with carbachol, cocaine, or MEG for 24 h. The increase in cyclic GMP content was 3.6 fold for 1 microM carbachol (P < 0.01), 3.1 fold for 1 microM cocaine (P < 0.01), and 7.8 fold for 1 microM MEG (P < 0.001), respectively. This increase in cyclic GMP content was significantly attenuated or abolished by the muscarinic receptor antagonist atropine or the M(2) blocker methoctramine. 3. In contrast, cocaine, MEG, and carbachol produced a significant inhibition of cyclic AMP production in HEL299 cells. Compared to the control, HEL299 cells treated with 1 microM cocaine decreased cyclic AMP production by 30%. MEG and carbachol at 1 microM decreased cyclic AMP production by 37 and 38%, respectively. Atropine or methoctramine at 1 or 10 microM significantly attenuated or abolished the cocaine-induced decrease in cyclic AMP production. However, the antagonists alone had neither an effect on cyclic GMP nor cyclic AMP production. Pretreatment of HEL299 cells with pertussis toxin prevented the cocaine-induced reduction of cyclic AMP production. 4. Western blot analysis showed that HEL299 cells specifically express M(2) muscarinic receptors without detectable M(1) and M(3). Incubation of HEL299 cells with cocaine, carbachol, and atropine did not alter the expression of M(2) protein levels. However, the inducible isoform of nitric oxide synthase (iNOS) was induced in the presence of cocaine or carbachol and this induction was significantly attenuated after addition of atropine or methoctramine. 5. The present data show that cocaine and MEG significantly affect cyclic GMP and cyclic AMP production in cultured HEL299 cells. Our results also show that these effects result from the drug-induced stimulation of M(2) muscarinic receptors accompanied with no alterations of receptor expression. However, the induction of iNOS by cocaine may result in the increase in cyclic GMP production.

Blotting, Western↗
PubMed2001

Detoxification of endotoxin by endodontic irrigants and calcium hydroxide.

The effects of endodontic irrigants and calcium hydroxide on lipopolysaccharide (LPS; endotoxin) were analyzed using the highly selective technique of mass spectrometry/gas chromatography with selected ion monitoring. An aqueous solution of LPS was mixed with one of a variety of endodontic irrigants for 30 min. Because it is a commonly used interappointment dressing, calcium hydroxide was also applied to LPS for 1, 2, or 5 days. LPS inactivation was measured by quantitation of free fatty acid release. Water, EDTA, ethanol, 0.12% chlorhexidine, chlorhexidine + sodium hypochlorite, and sodium hypochlorite alone showed little breakdown of LPS. Long-term calcium hydroxide--as well as 30-min exposure to an alkaline mixture of chlorhexidine, ethanol, and sodium hypochlorite--did detoxify LPS molecules by hydrolysis of ester bonds in the fatty acid chains of the lipid A moiety.

Bacteriological Techniques↗
PubMed2001

Trans-(DL-isoleucinato-N,O)[tris(2-aminoethyl)amine-kappa(4)N]cobalt(III)diperchlorate..

The racemic title compound, trans-[N,N-bis(2-aminoethyl)-1,2-ethanediamine-kappa(4)N](DL-isoleucinato-N,O)cobalt(III) diperchlorate, [Co(C(6)H(18)N(4))(C(6)H(12)NO(2))](ClO(4))(2), crystallizes in the enantiomorphous space group P2(1)2(1)2(1) with Z = 12 (Z' = 3). Each of the three cations in the asymmetric unit represents a different chirality of the isoleucine ligand; two of them are R (or D) and the third is the S (or L) enantiomer. The mixture crystallizes in a so-called unbalanced crystallization, in which the cations adopt a chiral array of composition RRS or SSR, depending on the crystal selected for data collection.

Journal Article↗
PubMed2001

Structures of three cis-beta1 and three cis-beta2 isomers of [Co(trien)(aminoacidato)]2+ complexes.

The crystal structures and absolute configurations of three cis-beta(1) and three cis-beta(2) isomers of [Co(trien)(L-aminoacidato)](2+), namely beta(1)-Lambda(SSS)(lambdalambdadelta)/(lambdadeltadelta)-[Co(trien)(L-isoleucinato)](ClO(4))(2), L-isoleucinato(triethylenetetramine)cobalt(III) diperchlorate (1), beta(1)-Lambda(SRS)(lambdadeltalambda)-[Co(trien)(L-valinato)](ClO(4))(2), L-valinato(triethylenetetramine)cobalt(III) diperchlorate (2), beta(1)-Delta(RSS)(deltalambdadelta)-[Co(trien)(L-pyroglutamato)]ClO(4), L-pyroglutamato(triethylenetetramine)cobalt(III) perchlorate (3), beta(2)-Delta(RRS)(deltadeltalambda)-[Co(trien)(L-isoleucinato)]I(2).H(2)O, L-isoleucinato(triethylenetetramine)cobalt(III) diiodide monohydrate (4), beta(2)-Delta(RRS)(deltadeltalambda)-[Co(trien)(L-isoleucinato)](ClO(4))(2).2H(2)O, L-isoleucinato(triethylenetetramine)cobalt(III) diperchlorate dihydrate (5), and beta(2)-Lambda(SSS)(deltalambdalambda)[Co(trien)(L-leucinato)](ClO(4))(2).2H(2)O, L-leucinato(triethylenetetramine)cobalt(III) diperchlorate dihydrate (6), have been determined. Both beta(1) and beta(2) isomers form inter-cation hydrogen-bonding interactions through double or triple hydrogen bonds which link the cations into helices. However, the motifs of the interactions are different in beta(1) and beta(2) isomers, resulting in different packing structures. A localized hydrophobic area is observed in the packing structure of (1), a unique feature amongst these six structures. This work describes the first synthesis of the beta(1) isomer by direct reaction between amino acids and cis-alpha-[Co(trien)Cl(2)]Cl in mildly basic solution.

Journal Article↗
PubMed2001

Maximum of the weighted Kaplan-Meier tests with application to cancer prevention and screening trials.

A class of maximum weighted Kaplan-Meier test statistics is described where the weight functions are chosen from a family of smooth functions. The investigated test statistic is robust and sensitive to a variety of alternatives that are often observed in cancer prevention and screening trials. A simulation study is performed to compare the size and power properties between the proposed test statistics and some existing ones. We illustrate the procedure using data from a clinical trial of a breast cancer screening program.

Biometry↗