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Biomedical subjects

S Chen

Publications and source records attributed to S Chen.

At least 1,621 records · Page 90Linked to original sources

Acute and subacute toxicity study of water-soluble polyalkylsulfonated C60 in rats.

Polyalkylsulfonated C60, or FC4S, a highly water-soluble caged fullerene derivative, is believed to be a free radical remover or an antioxidant in biological systems. A 50 mg/ml aqueous solution was prepared as a master solution and administered to female Sprague-Dawley CD(Crl:CD(SD)BR) rats in a single-dose acute toxicity study or a 12-day subacute toxicity study where rats were given the solution daily. In a study of the median lethal dose (LD50), no rats died after oral administration, and thus FC4S was considered to be nontoxic if administered orally. In an LD50 intraperitoneal injection study, rats died within 30 hr after injection; the LD50 was determined to be approximately 600 mg per kilogram of body weight. Rats injected with the compound intraperitoneally or intravenously immediately eliminated the compound through the kidney; the kidney appeared to be the primary target organ. The compound induced a distinct lysosome-overload nephrosis, a phagolysosomal nephropathy characterized by a tinctorial difference between the outer cortex and the inner cortex and the medulla. The affected outer cortex showed a diffuse degeneration, with the presence of numerous large vacuoles and cytoplasmic aggregates in the tubular epithelium. The phagolysosomal nephropathy was detected in rats after acute exposure as well as in the surviving rats following 1 intraperitoneal injection of 500 mg/kg or intravenous injection of 100 mg/kg. Ultrastructural investigation revealed numerous membranous conglomerates characteristic of phagolysosomal and/or lysosomal inclusions in the cytoplasm of the renal tubular epithelium. These conglomerates were confined to the vacuole, electron-dense, and unevenly stained. They varied in size and shape and were fused or aggregated. Occasional phagolysosomes were also observed in the endothelial cells of the peritubular plexus. A preliminary study of microsomal enzyme activity analysis revealed a suppression effect of liver cytochrome P-450-dependent monooxygenase activities, including cytochrome P-450, cytochrome b5, and benzo(a)pyrene hydroxylase, but an increased level of kidney cytochrome P-450-dependent monooxygenase activities, including NADPH-cytochrome P-450 reductase. The significance of these enzyme alterations was not well determined. Further study is needed to clarify the correlation between the alterations of microsomal enzyme activity and the nephropathy of lysosomal overload-induced changes. These changes may serve as a biological marker in toxicity screening tests for this class of compound.

Administration, Oral↗

The absence of genital human papillomavirus DNA in virginal women.

Our aim was to determine the prevalence of human papillomavirus (HPV) infection in virginal women and to establish if other forms of sexual activity not involving penetration may contribute to the transmission of this infection. Female patients attending medical practitioners, and female high school students were recruited. Each participant answered an anonymous self answer questionnaire and collected a tampon specimen. Tampons were analysed for the presence of human papillomavirus by the polymerase chain reaction (L1 general primer and probe). Fifty-five female participants who were of a mean age of 18 years (range 13-41) were recruited. Twenty-three reported non-penetrative sexual activity. None of the 55 women had evidence of HPV infection (0%, upper 95% confidence interval 5.4%). Twelve tampons from sexually active women with normal Papanicolaou smears and a mean age of 26 years (range 19-44) attending a hospital clinic were analysed at the same time and four were found to be positive (P = 0.0006). We conclude that HPV infection prior to sexual intercourse, as determined by tampons specimens, is rare, even in those participating in other forms of sexual activity.

Adolescent↗

Long-term correction of albumin levels in the Nagase analbuminemic rat: repopulation of the liver by transplanted normal hepatocytes under a regeneration response.

Numerous studies have reported successful transplantation of hepatocytes with demonstration of function. However, none have shown long-term correction of a liver-related metabolic defect. Male Nagase analbuminemic rats, immunosuppressed with cyclosporin-A, were transplanted with normal hepatocytes (2 x 10(7) cells/rat) isolated from allogeneic male Sprague-Dawley rat donors. Hepatocytes were selectively transplanted via the portal vein tributary into the posterior liver lobes of Nagase analbuminemic rats. Following 2 wk, to allow engraftment, selected transplanted rats (Group I) were reoperated and the portal venous branch supplying the anterior liver lobes was permanently ligated, resulting in their atrophy and induction of regeneration in the residual transplant-bearing lobes. Control rats consisted of: Group II-transplanted with normal hepatocytes without portal branch ligation; Group III-transplanted with analbuminemic hepatocytes with portal branch ligation; and Group IV-nontransplanted analbuminemic rats with portal branch ligation. The experimental period extended to 3 mo posttransplantation. All rats transplanted with normal hepatocytes demonstrated a significant elevation in serum albumin levels (ELISA). Group I rats had dramatic elevations in serum albumin to near normal levels (1.78 +/- 0.20 g/dl), and maintained these levels until the end of the experiment. Albumin levels in Group II rats reached 0.26 +/- 0.07 g/dl (p < 0.001), whereas Group III and IV rats showed no changes in serum albumin levels throughout the experiment. Immunohistology of liver tissue obtained from Group I rats, demonstrated large numbers (22.6 +/- 7.5%) of albumin-positive hepatocytes populating the recipient liver. This is the first report of near-total and sustained correction of a genetic defect in liver function in an experimental animal model following allogeneic hepatocyte transplantation.

Acetylglucosaminidase↗

Extract from Arca granosa L. inhibits proliferation of human tumour cell lines with kidney and lung origin.

Marine organisms are being considered increasingly as sources of anti-tumour agents. The extract from Arca granosa L. has been shown to decrease the growth of tumours and this study was undertaken to determine its ability and mechanism of inhibition. The extract inhibited the proliferation of six human tumour cell lines from different origins with varying sensitivity. The cell lines Ketr-3, A549 and NCl-H460 with kidney or lung origins were more sensitive to the extract than those of the HepG-2, MCF-7 and MGC-803 cells from other origins. In the three sensitive cell lines (Ketr-3, A549 and NCI-H460) the extract was shown to block different phases of the cell cycle progression and inhibit DNA synthesis in a concentration-dependent manner. It was concluded that the extract from A. granosa is potentially a novel anti-tumour agent, especially on kidney and lung tumour cell lines.

Animals↗

Oxygen fluxes and ammonia removal efficiencies in constructed treatment wetlands.

Ammonia-removal efficiency in constructed wetlands is often limited by the amount of oxygen available in the system. In this study, the oxygen-transfer rates to laboratory-scale, subsurface-flow and free-water-surface constructed wetlands were quantified for two input concentrations of ammonia, 10 and 50 mg nitrogen/L, both with and without Typha latifolia. Rates of oxygen diffusion into the subsurface-flow constructed wetlands were 6.01 to 7.92 g/m2 x d and were strongly correlated with ammonia concentration in the water. In contrast, low oxygen diffusion rates of 1.36 to 1.76 g/m2 x d were observed for the free-water-surface system. The presence of Typha latifolia had small but consistent effects on atmospheric oxygen-diffusion rates and ammonia-removal efficiencies in both the subsurface-flow and free-water-surface systems. The observed small effects were consistent with measurements of oxygen inputs from T. latifolia roots. Only approximately 0.023 g/m2 x d of oxygen was released from roots of T. latifolia, as measured using the titanium (III) citrate buffer method. The results for the ammonia-removal rates of the laboratory-scale constructed wetlands were further verified using pilot-scale constructed wetlands under greenhouse conditions.

Ammonia↗

Role of digitalis-like substance in the hypertension of streptozotocin-induced diabetes and simulated weightlessness in rats.

We have examined the role of plasma Na+-K+ pump inhibitor (SPI) in the hypertension of streptozotocin induced insulin dependent diabetes (IDDM) in reduced renal mass rats. The increase in blood pressure (BP) was associated with an increase in extracellular fluid volume (ECFV), and SPI and a decrease in myocardial Na+,K+ATPase (NKA) activity, suggesting that increased SPI, which inhibits cardiovascular muscle (CVM) cell NKA activity, may be involved in the mechanism of IDDM-hypertension. In a second study, using prolonged suspension resulted in a decrease in cardiac NKA activity, suggesting that cardiovascular deconditioning following space flight might in part result from insufficient SPI.

Animals↗

Effect of tear film stability on fluctuation of vision after photorefractive keratectomy.

PURPOSE: To evaluate the difference in tear film break-up between normal eyes and eyes after photorefractive keratectomy (PRK) and its impact on quality of vision in PRK eyes. METHODS: Seventy-seven normal eyes and 76 eyes with no ocular pathology except refractive error that had PRK were enrolled. Tear film break-up time was determined under slit-lamp microscopy with fluorescent staining. Two videokeratographs (TMS-1) were taken before and immediately after tear film break-up. Surface asymmetry index, surface regularity index, and subtractive maps were analyzed to evaluate corneal topographic changes before and after tear film break-up. RESULTS: The distribution of tear film break-up in the central cornea was different in PRK eyes than in normal eyes (P < .0001). Distributions of tear film break-up after PRK were localized more in the upper and lower temporal regions than in normal eyes; incidence of tear film break-up in the central cornea was decreased. There were no significant differences in tear film break-up between normal eyes and eyes after PRK (P = .69). Twelve PRK patients (24 eyes, 32%) experienced fluctuation of vision and fatigue during normal activities after PRK. We divided eyes after PRK into two groups (with and without fluctuation of vision) and found a statistically significant difference in surface asymmetry index before tear film break-up between the two groups (P = .0092). CONCLUSION: The distribution of tear film break-up is changed after PRK. Eyes after PRK experienced more fluctuation of vision than normal eyes.

Adult↗

Characterization of cellular pathways involved in glioblastoma response to the chemotherapeutic agent 1, 3-bis(2-chloroethyl)-1-nitrosourea (BCNU) by gene expression profiling.

The effectiveness of chemotherapy for human cancers is limited by pharmacokinetic parameters such as variation in metabolism and is determined by the cellular response. In this work, we aimed to gain a more holistic understanding of the molecular basis of glioma response to the DNA-alkylating agent 1, 3-bis(2-chloroethyl)-1-nitrosourea (BCNU) by using a systematic approach: we investigated the expression of 588 genes with various cellular functions in a BCNU-resistant glioblastoma cell line and a BCNU-sensitive subline before and after treatment with BCNU. Our gene expression profiling revealed major differences in gene expression between these two cell lines, especially after treatment with BCNU. One striking example was that BCNU decreased the expression of six DNA-repair genes in sensitive but not in resistant cells. In sensitive cells, BCNU treatment resulted in the induction of two MAP kinase genes; this finding suggests that the specific response to BCNU in sensitive cells may involve the Jun kinase signal transduction pathway. After BCNU treatment, marked induction of tumor necrosis factor was detected only in sensitive cells, suggesting that tumor necrosis factor is a mediator of BCNU-induced cell death. Bcl-2 family members were not altered by BCNU in sensitive cells, suggesting that BCNU-induced cell death may be independent of the bcl-2 pathway. Results of the present study demonstrate that gene expression profiling may facilitate identification of cellular pathways associated with specific responses to chemotherapeutic agents and contribute to an understanding of the molecular basis of drug action.

Antineoplastic Agents, Alkylating↗

Pulmonary function laboratory, the Mason Clinic.

This laboratory, equipped to perform more than a score of different tests, provides diagnostic support for 125 board-certified physicians in joint private practice and for the 320-bed Virginia Mason Hospital. Nearly half of the 50 outpatients seen each day in the laboratory have been referred by physicians outside the Seattle area.

Group Practice↗

Induction of aromatase expression by aminoglutethimide, an aromatase inhibitor that is used to treat breast cancer in postmenopausal women.

Aromatase, a cytochrome P450, catalyzes three consecutive hydroxylation reactions converting C19 androgens to aromatic C18 estrogenic steroids. Aminoglutethimide (AG) is an aromatase inhibitor used to treat estrogen-dependent breast cancer. While AG is effective in inhibiting aromatase, it was found that aromatase activity in tumors of some breast cancer patients elevated after AG treatment (Miller and O'Neill, Steroids, 50: 245-252, 1987). These results may explain why some patients failed therapy after extensive AG treatment. Recently, we found that AG treatment increased aromatase activity in SK-BR-3, JAR, and HepG2 cell lines in a dose- and incubation time-dependent manner. AG induction is thought to occur at the transcriptional level because the aromatase mRNA level elevated after AG treatment in SK-BR-3 and HepG2 cells, as demonstrated by reverse transcription-polymerase chain reaction (RT-PCR) analysis, and AG treatment did not increase aromatase activity in aromatase cDNA transfected cell lines (driven by the beta-actin promoter). Our primer-specific RT-PCR analysis revealed that in SK-BR-3 cells, AG enhanced the action of a promoter which is different from promoter I.1, I.3, or II. Furthermore, since the AG induction was found to be suppressed by SQ 22536, an adenylate cyclase inhibitor, a cAMP-dependent mechanism might be involved. Our study provides an insight as to why some patients fail therapy after extensive AG treatment.

Adenine↗

Quantitative MR evaluation of intracranial epidermoid tumors by fast fluid-attenuated inversion recovery imaging and echo-planar diffusion-weighted imaging.

BACKGROUND AND PURPOSE: Quantification of MR can provide objective, accurate criteria for evaluation of a given MR sequence. We quantitatively compared conventional MR sequences with fast fluid-attenuated inversion recovery (fast-FLAIR) and echo-planar diffusion-weighted (DW) MR imaging in the examination of intracranial epidermoid tumors. METHODS: Eight patients with surgically confirmed intracranial epidermoid tumors were examined with T1-weighted MR sequences, fast T2- and proton density-weighted dual-echo sequences, fast-FLAIR sequences, and DW echo-planar sequences. We measured the MR signal intensity and apparent diffusion coefficient (ADC) of epidermoid tumors, normal brain tissue, and CSF and calculated the tumor-to-brain and tumor-to-CSF contrast ratios and contrast-to-noise ratios (CNR). Results were compared among the five MR methods. RESULTS: On fast-FLAIR imaging, the mean signal intensity of epidermoid tumors was significantly higher than that of CSF but significantly lower than that of the brain; the contrast ratio and CNR of tumor-to-CSF were 4.71 and 9.17, respectively, significantly greater than the values with conventional MR imaging. On echo-planar DW imaging, epidermoid tumors showed a remarkably hyperintense signal relative to those of the brain and CSF; the mean contrast ratio and CNR of tumor-to-CSF were 13.25 and 19.34, respectively, significantly greater than those on fast-FLAIR or conventional MR imaging. The mean ADC of epidermoid tumors was 1.197 x 10(-3) mm(2)/s, significantly lower than that of CSF but higher than that of brain tissues. CONCLUSION: Fast-FLAIR imaging is superior to conventional MR imaging in depicting intracranial epidermoid tumors. Echo-planar DW imaging provides the best lesion conspicuity among the five MR methods. The hyperintensity of epidermoid tumors on echo-planar DW imaging is not caused by the diffusion restriction but by the T2 shine-through effect.

Aged↗

Review of the development, validation, and application of predictive instruments in interventional cardiology.

Within the last few years, risk assessment has become an integral part of clinical practice, particularly for thoracic surgery and interventional procedures. Risk assessment statistical models are being used in medical decision making, quality improvement tools, and as aids to patient counseling. This literature review was conducted to evaluate the types of predictive models and outcomes measures that have been examined, and methods used in development, validation, and application of these models. A Medline search performed to identify articles (limited to human studies) published in English from 1980 to 1999 resulted in 89 articles, of which 71 were evaluable. Populations studied for model development included patients undergoing coronary artery bypass graft (CABG), percutaneous transluminal coronary revascularization (PTCR), cardiac catheterization, or stenting procedures and patients with angina or stroke. The models were equally developed from a single center versus multicenter and from retrospective databases versus prospective studies. In terms of model perspectives, only three of the models measured cost or cost-effectiveness as the outcome; the remainder considered only clinical outcomes. The most commonly reported types of predictive models were developed using logistic regression and Bayesian techniques, followed by neural networks, rule-based artificial intelligence, simultaneous equation system, and multiple linear regression. Factors to consider when developing or evaluating a predictive model include uniformity of definitions of outcomes, uniformity of definitions of variables, completeness of data, number and frequency of variables, timeliness and source of data, development population characteristics, development and testing (validation) cohorts, and calibration and discrimination. Application of these models to an individual patient can spur quality improvement efforts that can lead to dramatic, system-wide improvements in outcomes.

Cardiovascular Diseases↗

Cryopreservation of apple dormant buds and shoot tips.

Shoot tips excised from apple (Malus domestica Borkh. cv. Golden Delicious) dormant buds immediately before freezing were successfully cryopreserved using three different methods (vitrification, encapsulation-dehydration and two-step freezing). Two-step freezing produced the highest in vitro growth recovery (83%) of cryopreserved shoot tips, followed by vitrification (60%) and encapsulation-dehydration (33%). By contrast, when dormant buds were cryopreserved using the two-step freezing technique, shoot tips excised from buds after rewarming and cultured in vitro displayed only 16% recovery.

Cryopreservation↗

A monoclonal anti-HLA-B27 antibody which is reactive with a linear sequence of the HLA-B27 protein is useful for the study of molecular mimicry.

In the search for cross-reactivity between bacteria and HLA-B27, three groups of investigators have identified several bacterial envelope proteins which are reactive with the monoclonal anti-HLA-B27 antibodies B27.M1 and B27.M2. Since these two antibodies react poorly with HLA-B27-derived synthetic peptides, it is not possible to locate the reactive epitopes on the HLA-B27 using synthetic peptides. Here, we introduce Ye-2, a monoclonal anti-HLA-B27 antibody which, unlike B27.M1 and B27.M2, is reactive with a synthetic peptide derived from residues 63-84 of HLA-B27.1. Analysis with a cross-reactive peptide derived from residues 226-244 of bovine carbonic anhydrase suggests that only a few of the amino acid residues in the HLA-B27-derived peptide are responsible for the reactivity. This antibody should be a useful adjunct in a preliminary assessment of whether a bacterial protein mimics HLA-B27 in primary structure.

Amino Acid Sequence↗