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Biomedical subjects

T S Chang

Publications and source records attributed to T S Chang.

At least 19 recordsLinked to original sources
PubMed2001

Negative regulation of the SAPK/JNK signaling pathway by presenilin 1.

Presenilin 1 (PS1) plays a pivotal role in Notch signaling and the intracellular metabolism of the amyloid beta-protein. To understand intracellular signaling events downstream of PS1, we investigated in this study the action of PS1 on mitogen-activated protein kinase pathways. Overexpressed PS1 suppressed the stress-induced stimulation of stress-activated protein kinase (SAPK)/c-Jun NH(2)-terminal kinase (JNK) in human embryonic kidney 293 cells. Interestingly, two functionally inactive PS1 mutants, PS1(D257A) and PS1(D385A), failed to inhibit UV-stimulated SAPK/JNK. Furthermore, H(2)O(2-) or UV-stimulated SAPK activity was higher in mouse embryonic fibroblast (MEF) cells from PS1-null mice than in MEF cells from PS(+/+) mice. MEF(PS1(-/-)) cells were more sensitive to the H(2)O(2)-induced apoptosis than MEF(PS1(+/+)) cells. Ectopic expression of PS1 in MEF(PS1(-/-)) cells suppressed H(2)O(2)-stimulated SAPK/JNK activity and apoptotic cell death. Together, our data suggest that PS1 inhibits the stress-activated signaling by suppressing the SAPK/JNK pathway.

Animals↗
PubMed2001

Glutathione S-transferase mu modulates the stress-activated signals by suppressing apoptosis signal-regulating kinase 1.

Apoptosis signal-regulating kinase 1 (ASK1) is a mitogen-activated protein kinase kinase kinase that can activate the c-Jun N-terminal kinase and the p38 signaling pathways. It plays a critical role in cytokine- and stress-induced apoptosis. To further characterize the mechanism of the regulation of the ASK1 signal, we searched for ASK1-interacting proteins employing the yeast two-hybrid method. The yeast two-hybrid assay indicated that mouse glutathione S-transferase Mu 1-1 (mGSTM1-1), an enzyme involved in the metabolism of drugs and xenobiotics, interacted with ASK1. We subsequently confirmed that mGSTM1-1 physically associated with ASK1 both in vivo and in vitro. The in vitro binding assay indicated that the C-terminal portion of mGSTM1-1 and the N-terminal region of ASK1 were crucial for binding one another. Furthermore, mGSTM1-1 suppressed stress-stimulated ASK1 activity in cultured cells. mGSTM1-1 also blocked ASK1 oligomerization. The ASK1 inhibition by mGSTM1-1 occurred independently of the glutathione-conjugating activity of mGSTM1-1. Moreover, mGSTM1-1 repressed ASK1-dependent apoptotic cell death. Taken together, our findings suggest that mGSTM1-1 functions as an endogenous inhibitor of ASK1. This highlights a novel function for mGSTM1-1 insofar as mGSTM1-1 may modulate stress-mediated signals by repressing ASK1, and this activity occurs independently of its well-known catalytic activity in intracellular glutathione metabolism.

Animals↗
PubMed2001

Knowledge-based computer-aided detection of masses on digitized mammograms: a preliminary assessment.

The purpose of this work was to develop and evaluate a computer-aided detection (CAD) scheme for the improvement of mass identification on digitized mammograms using a knowledge-based approach. Three hundred pathologically verified masses and 300 negative, but suspicious, regions, as initially identified by a rule-based CAD scheme, were randomly selected from a large clinical database for development purposes. In addition, 500 different positive and 500 negative regions were used to test the scheme. This suspicious region pruning scheme includes a learning process to establish a knowledge base that is then used to determine whether a previously identified suspicious region is likely to depict a true mass. This is accomplished by quantitatively characterizing the set of known masses, measuring "similarity" between a suspicious region and a "known" mass, then deriving a composite "likelihood" measure based on all "known" masses to determine the state of the suspicious region. To assess the performance of this method, receiver-operating characteristic (ROC) analyses were employed. Using a leave-one-out validation method with the development set of 600 regions, the knowledge-based CAD scheme achieved an area under the ROC curve of 0.83. Fifty-one percent of the previously identified false-positive regions were eliminated, while maintaining 90% sensitivity. During testing of the 1,000 independent regions, an area under the ROC curve as high as 0.80 was achieved. Knowledge-based approaches can yield a significant reduction in false-positive detections while maintaining reasonable sensitivity. This approach has the potential of improving the performance of other rule-based CAD schemes.

Breast Neoplasms↗
PubMed2001

Soft-copy mammographic readings with different computer-assisted detection cuing environments: preliminary findings.

PURPOSE: To assess the performance of radiologists in the detection of masses and microcalcification clusters on digitized mammograms by using different computer-assisted detection (CAD) cuing environments. MATERIALS AND METHODS: Two hundred nine digitized mammograms depicting 57 verified masses and 38 microcalcification clusters in 85 positive and 35 negative cases were interpreted independently by seven radiologists using five display modes. Except for the first mode, for which no CAD results were provided, suspicious regions identified with a CAD scheme were cued in all the other modes by using a combination of two cuing sensitivities (90% and 50%) and two false-positive rates (0.5 and 2.0 per image). A receiver operating characteristic study was performed by using soft-copy images. RESULTS: CAD cuing at 90% sensitivity and a rate of 0.5 false-positive region per image improved observer performance levels significantly (P < .01). As accuracy of CAD cuing decreased so did observer performances (P < .01). Cuing specificity affected mass detection more significantly, while cuing sensitivity affected detection of microcalcification clusters more significantly (P < .01). Reduction of cuing sensitivity and specificity significantly increased false-negative rates in noncued areas (P < .05). Trends were consistent for all observers. CONCLUSION: CAD systems have the potential to significantly improve diagnostic performance in mammography. However, poorly performing schemes could adversely affect observer performance in both cued and noncued areas.

Area Under Curve↗
PubMed2001

NQ-Y15 inhibits the calcium mobilization by elevation of cyclic AMP in rat platelets.

2-1(4-Cyanophenyl)aminol-3-chloro-1,4-naphthalenedione (NQ-Y15) is a dual action drug which acts as a thromboxane A2 (TXA2) synthase inhibitor and TXA2/PGH2 receptor antagonist. In the present study, we examined the effects of NQ-Y15 on Ca2+ mobilization, which is the common event in various types of platelet activation, in arachidonic acid (AA)-stimulated rat platelets. The elevation of cytosolic Ca2+ concentration ([Ca2+]i) induced by AA was inhibited by NQ-Y15 in a concentration-dependent manner. This inhibition-effect of NQ-Y15 was found to be based on the suppression of the rise in [Ca2+]i by the inhibition of both Ca2+ release from internal stores and Ca2+ influx from the extracellular space. Our successive trial was focused on the role of cyclic AMP (cAMP) in the action of NQ-Y15, because cAMP was reported to be increased by dual action drugs such as picotamide and to inhibit the increase in [Ca2+]i. NQ-Y15 was confirmed to increase cAMP in AA-stimulated rat platelets. These results suggested that NQ-Y15 might inhibit the rise in [Ca2+]i in AA-treated rat platelets by increasing cAMP, which is involved in the inhibition of platelet activation.

Animals↗
PubMed2000

Improvement in macular function after retinal translocation surgery in a patient with age-related macular degeneration.

PURPOSE: To assess focal electroretinographic findings before and after retinal translocation surgery in a patient with age-related macular degeneration. METHOD: Case report. A 79-year-old man with a well-defined subfoveal choroidal neovascular membrane from age-related macular degeneration underwent preoperative and postoperative focal electroretinography. RESULTS: After retinal translocation surgery, best-corrected Snellen visual acuity improved from 9/200 to 20/60. A significant increase in mean foveal amplitude, from 0.08 microV to 0.16 microV (P = 0.008) was recorded. CONCLUSION: Age-related macular degenerative changes in visual acuity and foveal electroretinogram amplitude may be reversible after retinal translocation surgery.

Aged↗
PubMed2000

Use of preoperative MR imaging in the management of endometrial carcinoma: cost analysis.

PURPOSE: To compare the cost of magnetic resonance (MR) imaging and its ability to direct the use of lymph node dissection with the cost and ability of conventional surgery for the staging of endometrial carcinoma. MATERIALS AND METHODS: Preoperative MR images of 25 patients who underwent hysterectomy for endometrial carcinoma were retrospectively evaluated. MR imaging results were compared with those of intraoperative gross dissection of the uterus and final histopathologic examination. Medicare reimbursements for two scenarios were compared in each patient. In the MR imaging scenario, the necessity for lymph node dissection was based on MR imaging results and histologic findings at biopsy. In the actual scenario, lymph node dissection was performed at the surgeon's discretion on the basis of findings at gross dissection of the uterus and histologic examination at biopsy. RESULTS: The cost of the MR imaging scenario, as defined by Medicare reimbursements, was 1% ($1, 265/$148,500) less than that of the actual scenario. In the MR imaging scenario, all patients who required lymph node dissection received it, and 86% of the lymph node dissections performed were necessary. In the actual scenario, one necessary lymph node dissection was not performed, and only 31% of the lymph node dissections performed were necessary. CONCLUSION: Staging with MR imaging has costs and accuracy similar to those of the current method of staging with intraoperative gross dissection of the uterus. In addition, MR imaging decreases the number of unnecessary lymph node dissections.

Adult↗
PubMed2000

Vaginal fluid creatinine, human chorionic gonadotropin and alpha-fetoprotein levels for detecting premature rupture of membranes.

BACKGROUND: Diagnosis of premature rupture of membranes (PROM) is difficult in equivocal cases. The concentrations of human chorionic gonadotropin (hCG), alpha-fetoprotein (AFP) and creatinine are high in amniotic fluid. The purpose of this study was to determine the usefulness of vaginal fluid hCG, AFP and creatinine measurements in the detection of PROM. METHODS: About 3 ml of normal saline was used to irrigate the posterior vaginal fornix and was collected for the measurement of hCG, AFP and creatinine. The control group included 10 normal pregnant women in the third trimester (> 28 weeks of gestational age). Levels of hCG, AFP and creatinine were compared with those of 10 women with confirmed PROM. RESULTS: The median levels of vaginal fluid hCG of normal pregnant women and pregnant women with confirmed PROM were 35.0 mIU/ml and 478.0 mIU/ml (p = 0.0046), respectively. For AFP, the corresponding values were 0.80 ng/ml and 54.24 ng/ml (p < 0.0001), respectively, and for creatinine, the values were 0.05 mg/dl and 0.95 mg/dl (p < 0.0001), respectively. All three markers were significantly higher in the experimental group than in the control group. The sensitivity, specificity, positive predictive value, negative predictive value and accuracy for hCG were 80%, 70%, 72.7%, 77.8% and 75%, respectively. For AFP, these values were 90%, 100%, 100%, 90.9%, and 95.0%, respectively, and for creatinine, they were 90%, 100%, 100%, 90.9%, and 95%, respectively. The diagnostic value of AFP or creatinine level in vaginal washing may be better than that of hCG, though the difference was not statistically significant, probably due to the limited case number. CONCLUSIONS: Creatinine in vaginal fluid washings is a useful marker for PROM. It was less expensive and easier to measure than hCG and AFP, and appears to be more accurate than hCG.

Adult↗
PubMed1999

Effects of brazilin on GLUT4 recruitment in isolated rat epididymal adipocytes.

The effects of brazilin on glucose transport into isolated rat epididymal adipocytes were investigated. Brazilin increased [3H]2-deoxy-D-glucose uptake, which was characterized by an increase in Vmax with no effect on the Km value. Phenylarsine oxide, which inhibits the translocation of glucose transporters, decreased brazilin-stimulated glucose transport to the basal level. The inhibition of phosphatidylinositol 3-kinase (PI3-kinase) with wortmannin also blocked brazilin-stimulated glucose transport. Western blot analysis with an anti-GLUT4 antibody revealed that brazilin increased the translocation of GLUT4 from intracellular pools to the plasma membrane. Brazilin, in combination with phorbol ester, showed an additive effect on glucose transport. The stimulating effect of phorbol ester on glucose transport was inhibited by staurosporine, but the effect of brazilin remained unchanged. Protein kinase C activity was not influenced by brazilin treatment. The inhibition of protein synthesis showed no effect on brazilin-stimulated glucose transport, and GLUT4 content in the total membrane fraction was not altered as a result of treatment with brazilin for 4 hr. Metabolic labeling of GLUT4 with [35S]methionine showed that de novo synthesis of GLUT4 was not induced by brazilin. These data suggest that brazilin may increase glucose transport by recruitment of GLUT4 from intracellular pools to the plasma membrane of adipocytes via the activation of PI3-kinase. However, the effect of brazilin may not be mediated by GLUT4 synthesis and protein kinase C activation.

Adipocytes↗
PubMed1999

Validity of the visual function index (VF-14) in patients with retinal disease.

OBJECTIVE: To test the validity of the Visual Function Index (VF-14) in patients with retinal disease. DESIGN: A self-administered questionnaire package in association with clinical examination findings. PARTICIPANTS: Consecutive patients attending the Vancouver General Hospital Eye Care Centre, Vancouver, British Columbia, retina clinic between May 1 and August 15, 1998. MAIN OUTCOME MEASURES: Responses to the questionnaire package as they relate to global self-assessment scales and visual acuity. In addition, correlations were calculated between the VF-14, the 36-Item Short-Form Health Survey, a Weighted Comorbidity Scale, and visual acuity scores. RESULT: Five hundred forty-seven patients were given the questionnaire package to complete. The VF-14 demonstrated a moderately strong positive association with patient self-rating of amount of trouble, satisfaction, and overall quality of vision. Correlations between the 36-Item Short-Form Health Survey, visual acuity, and the global scales were mild to moderate. The VF-14 was moderately correlated with visual acuity in the better and the worse eyes. CONCLUSIONS: This study provides support for the validity of the VF-14 as a measure of functional impairment in patients with retinal disease. Once responsiveness has been measured and an analysis of disease subtypes has been carried out, the VF-14 will be ready for inclusion in clinical trials to evaluate patients' functional ability. Further implementation and development of this outcome measure will better our understanding of the utility of the functional assessment format for patients with retinal disease.

Adolescent↗
PubMed1999

Molecular cloning of multiple splicing variants of JIP-1 preferentially expressed in brain.

Stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK) is activated by a variety of cellular or environmental stresses. Proper regulation of the SAPK/JNK pathway may be critical for cell survival or death under various conditions. In this study, we report the molecular cloning of novel isoforms of JIP-1, which harbor a putative phosphotyrosine interaction domain and a helix-loop-helix domain, as well as an SH3 homologous region in the C terminus. Northern analysis indicates that transcription variant jip-1 is expressed in brain and kidney and transcription variants jip-2 and jip-3 are specifically expressed in brain. In situ hybridization data showed that the hybridized jip messages were heavily concentrated in adult brain, and were particularly enriched in the cerebral cortex and hippocampus, the brain regions vulnerable to pathological states such as hypoxia-ischemia, epilepsy, and Alzheimer's disease. All the deduced protein products of the jip transcription variants appear to have a similar property in that they inhibit the SAPK/JNK stimulation when overexpressed. Inhibition of SAPK activation by overexpression of the novel isoform JIP-2a resulted in suppression of etoposide-induced cell death in a neuroglioma cell line, N18TG. These findings suggest that JIP may play an important role in regulation of the SAPK pathway that is involved in stress-induced cellular responses.

Adaptor Proteins, Signal Transducing↗
PubMed1999

Prophylactic scleral buckle for prevention of retinal detachment following vitrectomy for macular hole.

AIM: To review the rate of retinal detachment after macular hole surgery in patients who received vitrectomy and scleral buckle versus those who had vitrectomy alone. METHODS: All patient charts and hospital records were examined for patients who underwent vitrectomy surgery for macular hole between September 1993 and June 1997. A total of 326 patients were identified and all were followed for a minimum of 6 months. Clinical records were examined for details of the surgical procedure, visual acuity, hole closure status, adjuvant therapies used, and postoperative retinal attachment status. Relative risks (the ratio of the incidence rate in the exposed to that in the unexposed) with 95% confidence intervals and chi(2) tests were calculated to determine which variables were associated with retinal detachment. The primary outcome measure in this review was retinal attachment status. RESULTS: Of 326 eyes which underwent surgery for macular hole during the study period, scleral buckles were utilised in 152 (46.6%) patients. Analysis revealed a detachment rate of 13.2% in patients who did not receive a scleral buckle compared with 5.9% detachment rate in those who did. Analysis of these results indicated a 2.42 times greater risk of developing a retinal detachment in patients without a scleral buckle. Complications related to the use of scleral buckles occurred in two of 152 cases (1.3%) CONCLUSIONS: A reduction in the rate of retinal detachment was noted in patients receiving prophylactic scleral buckles. Those finding suggest a possible beneficial effect of this adjunctive procedure in preventing postoperative retinal detachments. The authors are currently preparing a multicentred, prospective, clinical trial to further study this hypothesis

Adolescent↗
PubMed1999

In vitro fertilization is associated with an increased risk of hypospadias.

PURPOSE: The purpose of this study was to determine if there is an increased incidence of hypospadias in male offspring conceived by in vitro fertilization (IVF). MATERIALS AND METHODS: A retrospective institutional chart review from 1988 to 1992 and data from the Maryland Birth Defects Registry were statistically analyzed to assess the risk of hypospadias with IVF. RESULTS: The data for the 5-year period indicated a 5-fold increased risk of hypospadias after IVF, with an incidence of approximately 1.5% in the IVF group and 0.3% in the control group. The only recognized difference between the groups was maternal progesterone administration in the IVF group but the cause of the increased risk of hypospadias was unknown. The distribution of hypospadias severity was similar in both groups. CONCLUSIONS: Male newborns conceived by IVF have a 5-fold increased risk of hypospadias, which may be related to maternal progesterone administration, or other maternal or fetal endocrine abnormalities that may or may not be related to infertility. Health care providers should be aware of this risk so that they can properly counsel infertile couples seeking assisted reproduction by IVF technology.

Female↗
PubMed1999

Age-related macular degeneration in Chinese-Canadians.

BACKGROUND: Ethnicity has long been suspected to play a role in the risk of macular degeneration as well as its neovascular complications. We carried out a study to determine the prevalence of retinal diseases in Chinese-Canadians presenting for fluorescein angiography compared to a matched group of Canadians of European origin. METHODS: We reviewed 20,000 consecutive fluorescein angiograms obtained between December 1987 and November 1993 at a tertiary referral centre for ophthalmic care in Vancouver. All patients identified by name as being of Chinese ancestry were identified and matched to a patient of European ancestry. The two groups were compared in regard to the prevalence of specific retinal diseases, including age-related macular degeneration (AMD). RESULTS: Among the first 10,000 fluorescein angiograms, 417 patients of Chinese ancestry were identified, of whom 61 (14.6%) had the primary diagnosis of AMD. The rate among the patients of European ancestry was 30.4% (127/417) (odds ratio [OR] 2.12, 95% confidence interval [CI] 1.79 to 2.56) (p < 0.001). A total of 88 ethnic Chinese patients were identified among the subsequent 10,000 angiograms. Pigment epithelial detachments were more than twice as common in the overall group of ethnic Chinese patients as in their counterparts of European ancestry (OR 2.6, 95% CI 0.7 to 10.1). Choroidal neovascularization was 1.6 times more common in the latter group (95% CI 0.98 to 2.8). INTERPRETATION: The findings support the growing clinical observations of a lower prevalence of AMD in nonwhite populations in addition to an increased prevalence of pigment epithelial detachments in ethnic Chinese patients.

Aged↗
PubMed1998

A long-term follow-up of choroidal osteoma.

OBJECTIVE: To provide long-term follow-up information on a large series of patients with choroidal osteoma. METHODS: Review of patients with a diagnosis of choroidal osteoma who had been examined at the Bascom Palmer Eye Institute, Miami, Fla, or known to one of us (J.D.M.G.). Information was obtained from hospital medical records or by a questionnaire sent to referring ophthalmologists. Life-table analysis was used to study the loss of vision and development of choroidal neovascularization. RESULTS: We followed up 36 patients, 31 (89%) were female, mean age, 21 years (range, 5-54 years) for a mean of 10 years (range, 2-22 years). Growth was observed for 9 (41%) of 22 well-documented osteomas. The probability of loss of visual acuity to 20/200 or worse was 58% by 10 years and 62% by 20 years. The probability of developing choroidal neovascularization was 47% by 10 years and 56% by 20 years. Successful treatment of the choroidal neovascularization with laser photocoagulation was performed for 5 (25%) of 20 patients. CONCLUSIONS: Most patients with choroidal osteomas maintain good vision in at least 1 eye, but they have a high risk of developing choroidal neovascularization. When this occurs, only a minority can be successfully treated with laser photocoagulation.

Adolescent↗
PubMed1998

Effects of Brazilin on the phospholipase A2 activity and changes of intracellular free calcium concentration in rat platelets.

Brazilin (7,11b-dihydrobenz[b]indeno[1,2-d]pyran-3,6a,9,10 (6 H)-tetrol) inhibited thrombin-,collagen- and ADP-induced aggregation of washed rat platelets. Thrombin- and collagen-induced ATP release were also inhibited by brazilin in a concentration-dependent manner. Brazilin inhibited the formation of platelet thromboxane A2 caused by thrombin, whereas it had no effect on the prostaglandin D2 formation. Brazilin inhibited [3H]-arachidonic acid liberation from membrane phospholipids of thrombin-stimulated platelets. Brazilin inhibited the rise of intracellular free calcium caused by thrombin. These results indicate that the inhibition of phospholipase (PLA2) activity and [Ca2+]i elevation might be at least a part of antiplatelet mechanism of brazilin.

Adenosine Triphosphate↗