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Biomedical subjects

J Cai

Publications and source records attributed to J Cai.

At least 37 records · Page 2Linked to original sources

Pesticide use and menstrual cycle characteristics among premenopausal women in the Agricultural Health Study.

Menstrual cycle characteristics may have implications for women's fecundability and risk of hormonally related diseases. Certain pesticides disrupt the estrous cycle in animals. The authors investigated the cross-sectional association between pesticide use and menstrual function among 3,103 women living on farms in Iowa and North Carolina. Women were aged 21-40 years, premenopausal, not pregnant or breastfeeding, and not taking oral contraceptives. At study enrollment (1993-1997), women completed two self-administered questionnaires on pesticide use and reproductive health. Exposures of interest were lifetime use of any pesticide and hormonally active pesticides. Menstrual cycle characteristics of interest included cycle length, missed periods, and intermenstrual bleeding. The authors used generalized estimating equations to assess the association between pesticide use and menstrual cycle characteristics, controlling for age, body mass index, and current smoking status. Women who used pesticides experienced longer menstrual cycles and increased odds of missed periods (odds ratio = 1.5, 95% confidence interval: 1.2, 1.9) compared with women who never used pesticides. Women who used probable hormonally active pesticides had a 60-100% increased odds of experiencing long cycles, missed periods, and intermenstrual bleeding compared with women who had never used pesticides. Associations remained after control for occupational physical activity.

Adult↗

Associations of fitness and fatness with mortality in Russian and American men in the lipids research clinics study.

OBJECTIVE: To examine the relative size of the effects of fitness and fatness on mortality in Russian men, and to make comparison to US men. DESIGN: Prospective closed cohort. SUBJECTS: 1359 Russian men and 1716 US men aged 40-59 y at baseline (1972-1977) who were enrolled in the Lipids Research Clinics Study. MEASUREMENTS: Fitness was assessed using a treadmill test and fatness was assessed as body mass index (BMI) calculated from measured height and weight. Hazard ratios were calculated using proportional hazard models that included covariates for age, education, smoking, alcohol intake and dietary keys score. All-cause and cardiovascular disease (CVD) mortality were assessed through 1995. RESULTS: In Russian men, fitness was associated with all-cause and CVD mortality, but fatness was not. For mortality from all causes, compared to the fit-not fat, the adjusted hazard ratios were 0.87 (95% CI: 0.55, 1.37) among the fit-fat, 1.86 (95% CI: 1.31, 2.62) among the unfit-not fat and 1.68 (95% CI: 1.06, 2.68) among the unfit-fat. Among US men, the same hazard ratios were 1.40 (95% CI: 1.07, 1.83), 1.41 (95% CI: 1.12, 1.77) and 1.54 (95% CI: 1.24, 2.06), respectively. There were no statistically significant interactions between fitness and fatness in either group of men for all-cause or CVD mortality. CONCLUSION: The effects of fitness on mortality may be more robust across populations than are the effects of fatness.

Adult↗

Facial dysgenesis: a novel facial syndrome with chromosome 7 deletion p15.1-21.1.

We describe a female neonate with a unique constellation of features including anophthalmia and cryptophthalmos, temporal remnant "eye tags," bilateral cleft lip, unilateral cleft palate, a proboscis with absent nasal septum, choanal atresia, micrognathia, square stoma, and bilateral external auditory canal atresia. Gross brain structure, pituitary function, limbs, trunk, and genitalia were normal. Skeletal survey, echocardiogram and abdominal viscera were unremarkable except for a split central sinus of the right kidney. BAER exam indicated she could hear and temporal CT confirmed the presence of cochlea and possible ossicles. Cytogenetic evaluation revealed an interstitial deletion at chromosome 7p15.1-21.1. TWIST, a gene encoding a transcription factor involved in craniofacial development, is deleted by FISH analysis. The absence of a mutation on the non-deleted allele of TWIST as determined by sequencing virtually eliminates complete loss of the TWIST gene as the cause of this patient's severe phenotype. The HOXA gene cluster also encodes transcription factors that are crucial for directing cephalad to caudad somatic fetal development. HOXA1, the most telomeric of the 13 members of the HOXA gene cluster, is located at the centromeric boundary of the patient's chromosome 7 deletion. By FISH analysis, neither allele of HOXA1 is deleted and sequencing reveals no mutations. Haploinsufficiency or complete loss of the HOXA1 gene also does not appear to cause this patient's severe phenotype. Previous reports of chromosome 7p15-21 deletions do not have phenotypes similar to this patient.

Chromosome Banding↗

Noise and motion correction in dynamic contrast-enhanced MRI for analysis of atherosclerotic lesions.

Dynamic contrast-enhanced MRI of atherosclerotic vessels after contrast agent injection may provide unique information regarding lesion structure and vulnerability. The high-resolution images necessary for viewing lesion substructures, however, are often corrupted by patient motion and low signal-to-noise ratios, making pixel-level analyses difficult. This article presents a postprocessing method that enables pixel-level analysis of dynamic images by eliminating motion and enhancing image quality. Noise and motion correction are performed using optimal statistical methods under the assumption that noise and contrast agent dynamics are random processes. The method is demonstrated and validated on dynamic images of atherosclerotic plaques in human carotid arteries.

Algorithms↗

Automating the drug scheduling of cancer chemotherapy via evolutionary computation.

This paper presents the optimal control of drug scheduling in cancer chemotherapy using a distributed evolutionary computing software. Unlike conventional methods that often require gradient information or hybridization of different approaches in drug scheduling, the proposed evolutionary optimization methodology is simple and capable of automatically finding the near-optimal solutions for complex cancer chemotherapy problems. It is shown that different number of variable pairs in evolutionary representation for drug scheduling can be easily implemented via the software, since the computational workload is shared and distributed among multiple computers over the Internet. Simulation results show that the proposed evolutionary approach produces excellent control of drug scheduling in cancer chemotherapy, which are competitive or equivalent to the best solutions published in literature.

Antineoplastic Agents↗

The pathogenesis of diabetic retinopathy: old concepts and new questions.

Hyperglycaemia appears to be a critical factor in the aetiology of diabetic retinopathy and initiates downstream events including: basement membrane thickening, pericyte drop out and retinal capillary non-perfusion. More recently, focus has been directed to the molecular basis of the disease process in diabetic retinopathy. Of particular importance in the development and progression of diabetic retinopathy is the role of growth factors (eg vascular endothelial growth factor, placenta growth factor and pigment epithelium-derived factor) together with specific receptors and obligate components of the signal transduction pathway needed to support them. Despite these advances there are still a number of important questions that remain to be answered before we can confidently target pathological signals. How does hyperglycaemia regulate retinal vessels? Which growth factors are most important and at what stage of retinopathy do they operate? What is the preferred point in the growth factor signalling cascade for therapeutic intervention? Answers to these questions will provide the basis for new therapeutic interventions in a debilitating ocular condition.

Diabetes Mellitus↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗