Biomedical subjects

S Chang

Publications and source records attributed to S Chang.

At least 73 records · Page 4Linked to original sources

PubMed2000

Telomere dysfunction promotes non-reciprocal translocations and epithelial cancers in mice.

Aged humans sustain a high rate of epithelial cancers such as carcinomas of the breast and colon, whereas mice carrying common tumour suppressor gene mutations typically develop soft tissue sarcomas and lymphomas. Among the many factors that may contribute to this species variance are differences in telomere length and regulation. Telomeres comprise the nucleoprotein complexes that cap the ends of eukaryotic chromosomes and are maintained by the reverse transcriptase, telomerase. In human cells, insufficient levels of telomerase lead to telomere attrition with cell division in culture and possibly with ageing and tumorigenesis in vivo. In contrast, critical reduction in telomere length is not observed in the mouse owing to promiscuous telomerase expression and long telomeres. Here we provide evidence that telomere attrition in ageing telomerase-deficient p53 mutant mice promotes the development of epithelial cancers by a process of fusion-bridge breakage that leads to the formation of complex non-reciprocal translocations--a classical cytogenetic feature of human carcinomas. Our data suggest a model in which telomere dysfunction brought about by continual epithelial renewal during life generates the massive ploidy changes associated with the development of epithelial cancers.

Adenocarcinoma↗

PubMed2000

Determination of distribution coefficients of priority polycyclic aromatic hydrocarbons using solid-phase microextraction

The determination of distribution coefficients is important for prediction of the chemical pathways of organic compounds in the environment. Solid-phase microextraction (SPME) is a convenient and effective method to measure the distribution of chemicals in a two-phase system. In the present study, the SPME distribution coefficient (K(spme)) of 16 priority aromatic hydrocarbons (PAHs) was determined with 100-microm poly(dimethylsiloxane) (PDMS) and 85-microm polyacrylate (PA) fibers. The partition coefficients and LeBas molar volumes were used to describe the linearity of the log K(spme) values of PAHs. Also, the validation of the distribution coefficient was examined using different sample volumes. The extraction time was dependent on the types of PAHs, and 20 min to 60 h was needed to reach equilibrium. The determined log K(spme) values ranged from 3.02 to 5.69 and from 3.37 to 5.62 for 100-microm PDMS and 85-microm PA fibers, respectively. Higher K(spme) values of low-ring PAHs were observed using 85-microm PA fiber. Good linear relationships between log K(ow) and log K(spme) for PAHs from naphthalene to benzo[alpha]pyrene and from naphthalene to chrysene for 100-microm PDMS and 85-microm PA fibers, respectively, were obtained. The correlation coefficients were 0.969 and 0.967, respectively. The linear relationship between log K(spme) and the LeBas molar volume was only up to benz[alpha]anthracene for 85-microm PA fiber and up to chrysene for 100-microm PDMS fiber. Moreover, the effect of sample volume can be predicted using the partition coefficient theory and excellent agreement was obtained between the experimental and theoretical absorbed amounts of low-ring PAHs. This result shows that the determined log K(spme) is more accurate than the previous method for estimating analytes with log K(ow) < 6 as well as for predicting the partitioning behaviors between SPME fiber and water.

Journal Article↗

PubMed2000

Inducible nitric oxide synthase transcription in human lung transplantation.

BACKGROUND: Recent animal data suggest that inducible nitric oxide synthase (iNOS) mRNA expression in the bronchoalveolar lavage (BAL) may be useful for the diagnosis of lung rejection. The aim of this study was to evaluate iNOS mRNA transcription in the BAL fluid of human lung allografts. METHODS: iNOS mRNA transcription was quantified by competitive reverse transcription-polymerase chain reaction in 51 BAL cell pellets of lung transplant patients. According to bacteriological and histological results, BAL samples were divided into three groups: normal (n=21), acute rejection (AR, n=15), and infection (INF, n=15). RESULTS: Compared with the control group, iNOS transcription increased significantly with INF (P=0.0005) but only slightly with AR (P>0.05). INF values were significantly higher than AR values (P=0.0029). CONCLUSION: BAL iNOS mRNA transcript determination by competitive reverse transcription-polymerase chain reaction may be useful in differentiating infected from normal and/or acutely rejecting allografts.

Analysis of Variance↗

PubMed2000

Highly Stereoselective and Efficient Hydrosilylation of Terminal Alkynes Catalyzed by

With [RuCl(2)(p-cymene)](2) as a catalyst, extremely high regio- and stereoselectivity was observed in the hydrosilylation reaction of various terminal alkynes under mild conditions to afford beta-(Z)-vinylsilanes in excellent yields. A dramatic directing effect was also observed when alkynes having a hydroxyl group at the beta position to the triple bond were employed as a substrate, and in these cases regioisomeric alpha-vinylsilanes were generated with excellent selectivity.

Journal Article↗

PubMed2000

Spatial confinement of laser light in active random media

We have observed spatial confinement of laser light in micrometer-sized random media. The optical confinement is attributed to the disorder-induced scattering and interference. Our experimental data suggest that coherent amplification of the scattered light enhances the interference effect and helps the spatial confinement. Using the finite-difference time-domain method, we simulate lasing with coherent feedback in the active random medium.

Journal Article↗

PubMed2000

Zinc increases the excitability of dopaminergic neurons in rat substantia nigra.

The effect of zinc ions (Zn(2+)) on the neuronal excitability of substantia nigra (SN) where the zinc level is known higher in Parkinsonian brains than that in normal brains has not yet been elucidated. We, therefore, examined the effect of Zn(2+) on the intrinsic electrical properties of dopaminergic SN neurons, using a whole-cell recording method. Zn(2+) hyperpolarized dopaminergic SN neurons at resting state. Also Zn(2+) shortened the duration of evoked spikes, developed a fast afterhyperpolarization, and increased their firing frequency. Voltage-clamp studies showed that Zn(2+) decreased 4-aminopyridine-sensitive outward currents, suggesting that a transient A-like potassium channel be one of the major targets Zn(2+) can modulate in the SN neurons.

4-Aminopyridine↗

PubMed2000

The nonhomologous end-joining pathway of DNA repair is required for genomic stability and the suppression of translocations.

We have used spectral karyotyping to assess potential roles of three different components of the nonhomologous DNA end-joining pathway in the maintenance of genomic stability in mouse embryonic fibroblasts (MEFs). MEFs homozygous for mutations that inactivate either DNA ligase IV (Lig4) or Ku70 display dramatic genomic instability, even in the absence of exogenous DNA damaging agents. These aberrant events range from chromosomal fragmentation to nonreciprocal translocations that can involve several chromosomes. DNA-dependent protein kinase catalytic subunit deficiency also promotes genome instability. Deficiency for the p53 cell cycle checkpoint protein has little effect on spontaneous levels of chromosomal instability in Lig4-deficient fibroblasts. However, in the context of ionizing radiation treatment, p53 deficiency allowed visualization of massive acute chromosomal destruction in Lig4-deficient MEFs, which in surviving cells manifested as frequent nonreciprocal translocations. We conclude that nonhomologous DNA end-joining plays a crucial role as a caretaker of the mammalian genome, and that an alternative repair pathway exists that often leads to nonreciprocal translocations.

Animals↗

PubMed2000

Anopheles gambiae pilot gene discovery project: identification of mosquito innate immunity genes from expressed sequence tags generated from immune-competent cell lines.

Together with AIDS and tuberculosis, malaria is at the top of the list of devastating infectious diseases. However, molecular genetic studies of its major vector, Anopheles gambiae, are still quite limited. We have conducted a pilot gene discovery project to accelerate progress in the molecular analysis of vector biology, with emphasis on the mosquito's antimalarial immune defense. A total of 5,925 expressed sequence tags were determined from normalized cDNA libraries derived from immune-responsive hemocyte-like cell lines. The 3,242 expressed sequence tag-containing cDNA clones were grouped into 2,380 clone clusters, potentially representing unique genes. Of these, 1,118 showed similarities to known genes from other organisms, but only 27 were identical to previously known mosquito genes. We identified 38 candidate genes, based on sequence similarity, that may be implicated in immune reactions including antimalarial defense; 19 of these were shown experimentally to be inducible by bacterial challenge, lending support to their proposed involvement in mosquito immunity.

Animals↗

PubMed2000

Quantification of cytotoxic T-cell gene transcripts in human lung transplantation.

BACKGROUND: Differentiating between acute rejection and cytomegalovirus (CMV) infection is one of the major challenges of lung transplantation. The aims of this study were to: (1) quantify the transcription of the cytotoxic T lymphocyte (CTL) effector molecules in the bronchoalveolar lavage (BAL) of lung transplant recipients and (2) evaluate the clinical usefulness of this technique. METHODS: Sixty-six single-lung, double-lung, or heart-lung transplant patients were prospectively enrolled in the study. BAL was performed either for routine surveillance or for acute graft dysfunction. RNA was extracted from BAL cell pellets and underwent competitive reverse transcription-assisted polymerase chain reaction (RT-PCR) for perforin, granzyme B, granulysin, and Fas ligand. Gene transcript analysis was compared to clinical diagnosis established by conventional methods [BAL microbiological and transbronchial biopsy (TBB) analyses]. RESULTS: After exclusion of several BAL according to the study criteria, 62 BAL were submitted for data analysis. Significantly higher expression of all the analyzed transcripts was found during CMV infection, compared with each of the other defined diagnostic categories, namely nonsignificant pathology, acute rejection, and nonviral pulmonary infection. CONCLUSION: Quantification by competitive RT-PCR of the CTL effector molecule transcripts (perforin, granzyme B, granulysin, and Fas ligand) could represent a valuable tool for the differential diagnosis of graft dysfunction in lung transplantation.

Adult↗

PubMed2000

Inhibition of experimental liver cirrhosis in mice by telomerase gene delivery.

Accelerated telomere loss has been proposed to be a factor leading to end-stage organ failure in chronic diseases of high cellular turnover such as liver cirrhosis. To test this hypothesis directly, telomerase-deficient mice, null for the essential telomerase RNA (mTR) gene, were subjected to genetic, surgical, and chemical ablation of the liver. Telomere dysfunction was associated with defects in liver regeneration and accelerated the development of liver cirrhosis in response to chronic liver injury. Adenoviral delivery of mTR into the livers of mTR(-/-) mice with short dysfunctional telomeres restored telomerase activity and telomere function, alleviated cirrhotic pathology, and improved liver function. These studies indicate that telomere dysfunction contributes to chronic diseases of continual cellular loss-replacement and encourage the evaluation of "telomerase therapy" for such diseases.

Adenoviridae↗

PubMed2000

New soft-tipped instruments for foveal translocation surgery with 360 degrees retinotomy.

Foveal translocation surgery with 360 degrees retinotomy involves several surgical procedures, including creation of a total retinal detachment, rotation of the retina, and complete reattachment of the retina. Some of these procedures, which are time-consuming and difficult to perform, may damage the retina when conventional surgical instruments are used. To make these procedures safer and easier, we have developed 3 soft instruments: an atraumatic forceps, a modified Chang double-barrel cannula with a silicone tip, and a light pipe with a silicone tip. The atraumatic forceps allows the surgeon to grasp and peel off the retina with less damage during the creation of retinal detachment. A bimanual technique using the other 2 instruments allows surgeons to rotate and reattach the detached retina easily and safely. We believe that these soft-tipped instruments make foveal translocation a less complicated surgery.

Choroidal Neovascularization↗

PubMed2000

Low-dose genistein induces cyclin-dependent kinase inhibitors and G(1) cell-cycle arrest in human prostate cancer cells.

Genistein, a naturally occurring isoflavone found chiefly in soy products, reportedly has antiprostate cancer effects, but the mechanisms underlying these effects are unknown. We studied the antiproliferative and apoptosis-inducing effects of genistein in the androgen-sensitive human prostate cancer cell line LNCaP. Viable cell number was assessed by the 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide assay; cell-cycle progression and apoptosis were evaluated by flow cytometry; apoptosis was also assessed by a histone enzyme-linked immunosorbent assay; and the expression of several cell-cycle- and apoptosis-related genes and their gene products was determined by northern blot analysis, western blot analysis, and/or assays based on polymerase chain reaction. Physiologic concentrations of genistein (< or = 20 microM) decreased LNCaP viable cell number in a dose-dependent manner, induced a G(1) cell-cycle block, decreased prostate-specific antigen mRNA expression, and increased p27(KIP1) and p21(WAF1) (mRNA and protein) but had no effect on apoptosis or the mRNA expression of the apoptosis- and cell-cycle-related markers bcl-2, bax, Rb, and proliferating cell nuclear antigen. Higher concentrations of genistein (> 20 microM) did induce apoptosis. We conclude that genistein (at physiologic concentrations) exerts potent antiproliferative effects on LNCaP cells by inducing a G(1) cell-cycle block. The antiproliferative effects of genistein may be mediated by increased levels of p27(KIP1) and p21(WAF1), which are negative cell-cycle regulators that act as cyclin-dependent kinase inhibitors and that have been recently linked with prostate carcinogenesis. These findings may provide insights into the mechanisms underlying the apparent antiprostate cancer effects of soy consumption observed in epidemiologic studies.

Antineoplastic Agents↗

PubMed2000

First operation anatomic success and other predictors of postoperative vision after complex retinal detachment repair with vitrectomy and silicone oil tamponade.

PURPOSE: To evaluate the role of first operation anatomic success compared with success after reoperation and preoperative characteristics in achieving ambulatory vision (>/=4/200) and good vision (>/=20/100) after repair of complex retinal detachment with vitrectomy and silicone oil tamponade. METHODS: A prospective, observational, multicenter study of patients who underwent vitrectomy with silicone oil for retinal detachments associated with cytomegalovirus necrotizing retinitis or a non-cytomegalovirus necrotizing retinitis etiology, including proliferative diabetic retinopathy, giant retinal tear, proliferative vitreoretinopathy, and ocular trauma. RESULTS: A higher rate of ambulatory vision was achieved in the first operation anatomic success cases, compared with the reoperation cases, for eyes with cytomegalovirus necrotizing retinitis (72% vs 50%, P < 0.01) and eyes without cytomegalovirus necrotizing retinitis (51% vs 38%, P = 0.04). For eyes with cytomegalovirus necrotizing retinitis, preoperative ambulatory vision (RR = 2.3, P < 0.0001) and reoperation (RR = 0.4, P = 0.05) were independent predictors of postoperative ambulatory vision. For eyes without cytomegalovirus necrotizing retinitis, preoperative ambulatory vision (RR = 4.0, p < 0.0001) and retinal detachment etiology (P = 0.02) were prognostic factors. Compared to eyes with trauma, eyes with giant retinal tear, proliferative vitreoretinopathy and proliferative diabetic retinopathy were 2.8 (P < 0.003), 2.2 (P = 0.01) and 1.6 (P = 0.17) times as likely to achieve postoperative ambulatory vision, respectively. Within the giant retinal tear group, a higher rate of ambulatory vision was achieved in the first operation anatomic success cases compared with the reoperation cases (66% vs 31%, P = 0.03). Although not statistically significant, similar outcomes occurred in the proliferative diabetic retinopathy (48% vs 25%) and proliferative vitreoretinopathy groups (54% vs 45%). Similar prognostic relationships were found for good visual acuity outcomes. CONCLUSIONS: First operation anatomic success, preoperative visual acuity, and giant retinal tear or proliferative vitreoretinopathy as the retinal detachment etiology are important factors that predict visual outcome.

Adult↗

PubMed2000

Development of chromatic and luminance detection contours using the sweep VEP.

This study measured the development of contrast-sweep VEP thresholds to a range of chromatic and luminance stimuli. Subjects were 14-32 week-old infants (n=21) and three adults. Stimuli were 1 c/d sine gratings reversed at 5.6 Hz. Chromaticity was varied from the L-M axis to an achromatic axis. VEP thresholds when plotted in L- and M-cone contrasts showed that: (1) VEP thresholds did not consistently locate the psychophysical isoluminance match under the same stimulus conditions; (2) About 50% of the data were described by independent chromatic and luminance mechanism, however, thresholds were limited by the cone contrast of the stimulus, phase cancellation between visual mechanisms, and the proper sampling of thresholds in L- and M-cone contrast space and; (3) No significant changes occurred in VEP detection contours across ages but suprathreshold VEP amplitudes suggested complex developmental changes. Data from previous studies showed similar results.

Adult↗

PubMed2000

Expression of the human erythrocyte glucose transporter in transitional cell carcinoma of the bladder.

OBJECTIVES: It has previously been shown that glucose uptake and use is more prevalent in carcinomas than in normal cells and tissues. We hypothesized that human erythrocyte glucose transporter (Glut-1) expression is increased in bladder transitional cell carcinoma (TCC) and that the grade of expression might correlate with the degree of malignancy. METHODS: Immunostaining of Glut-1 protein was studied in normal bladder (5 cases), benign papilloma (10 cases), superficial tumor (48 cases), and invasive tumor (31 cases) tissue. The immunoreactivity grading system used was as follows: absence of immunoreactivity in tumor cell = 0; less than 10% of the tumor cells immunoreactive = 1+; 10% to 50% of the tumor cells immunoreactive = 2+; and greater than 50% of the tumor cells immunoreactive = 3+. RESULTS: Immunostaining of Glut-1 protein was not expressed in the normal bladder or benign papilloma samples, but it was expressed in 63.0% (46 of 73) of the TCC samples. In the pattern of expression of Glut-1 protein, superficial TCC was stained focally, but invasive TCC was stained diffusely in the tumor nests. The grade of Glut-1 protein expression increased more significantly in the invasive TCC than in the superficial TCC samples (P = 0.002) and more significantly in the high nuclear grade than in the low nuclear grade samples (P = 0.007). In the superficial TCC samples, the bladder tumor recurrence rate did not significantly correlate with Glut-1 protein expression (P = 0.40). CONCLUSIONS: Our results suggest that the Glut-1 protein is not expressed in normal bladder mucosa and benign lesions, that Glut-1 protein expression is strongly associated with neoplastic progression in bladder TCC, and that Glut-1 expression does not correlate with the recurrence rate in superficial bladder TCC.

Carcinoma, Transitional Cell↗

PubMed2000

Nutritional deficiencies and later behavioural development.

The literature on the long-term effects of nutritional deficiencies in early life is reviewed. The severity and duration of the deficiency, the stage of the children's development, the biological condition of the children and the socio-cultural context may all modify the effect. There is substantial evidence that reduced breast-feeding, small-for-gestational-age birth weight, Fe and I deficiency, and protein-energy malnutrition (PEM) are associated with long-term deficits in cognition and school achievement. However, all these conditions are associated with poverty and poor health, which may account for the association. It is difficult to establish that the long-term relationship is causal, as it requires a randomized treatment trial with long-term follow-up. Such studies are only available for I deficiency in utero and early childhood PEM. Results from these studies indicate that I deficiency has a long-term effect and PEM probably has a long-term effect.

Behavior↗

PubMed2000

Low-density lipoprotein antioxidant activity of phenolic compounds and polyphenol oxidase activity in selected clingstone peach cultivars.

The antioxidant potential of eight clingstone peach cultivars was investigated by determining phenolic compounds and inhibition of low-density lipoprotein (LDL) oxidation. Cultivars low in polyphenol oxidase (PPO) were also selected to minimize enzymatic browning. Inhibition of LDL oxidation varied from 17.0 to 37.1% in peach flesh extract, from 15.2 to 49.8% in whole peach extract, and from 18.2 to 48.1% in peel extract. Total phenols were 432.8-768.1 mg/kg in flesh extract, 483.3-803.0 mg/kg in whole extract, and 910.9-1922.9 mg/kg in peel extract. The correlation coefficient between relative LDL antioxidant activity and concentration of total phenols was 0.76. Peel PPO activity was higher than flesh activity in most cultivars. The lowest PPO and specific activities were found in the Walgant cultivar, followed by Kakamas and 18-8-23. These three cultivars combine the desirable characteristics of strong antioxidant activity, low PPO activity, and lower susceptibility to browning reactions.

Antioxidants↗

PubMed2000

Inflammatory breast cancer survival: the role of obesity and menopausal status at diagnosis.

No previous studies have evaluated the effect of body size and menopausal status at diagnosis on survival from inflammatory breast cancer (IBC). We evaluated whether obesity and menopausal status had an impact on IBC survival in a cohort of 177 female IBC patients seen from 1974 to 1993 at The University of Texas MD Anderson Cancer Center. Survival time was defined as time from diagnosis until death or censorship at last date of contact. We categorized women by body size by using the National Institutes of Health/National Heart, Lung, and Blood Institute's definitions of obesity as body mass index ((BMI) = weight in kg/(height in m)2) > or = 30, overweight as 25 < or = BMI < 30kg/m2, and normal/lean as BMI < 25 kg/m2. Cox proportional hazards analysis, adjusting for axillary lymph node involvement and chemotherapy protocol, revealed a modifying effect of menopausal status at diagnosis on the association between obesity and IBC survival (P = 0.02). Relative to postmenopausal women, premenopausal women had significantly worse survival (hazard ratio (HR) = 1.51, 95% confidence interval (CI) = 1.03-2.22). After stratifying by menopausal status, premenopausal obese women had non-significantly better survival than their leaner premenopausal counterparts (HR = 0.63, 95% CI = 0.34-1.15) while postmenopausal obese women had significantly worse survival than their leaner counterparts (HR = 1.86, 95% CI = 1.02-3.40). These findings suggest that factors associated with larger body size at diagnosis may contribute to shorter IBC survival among postmenopausal women but not premenopausal women, who were found to have poorer survival regardless of body size.

Adult↗