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Biomedical subjects

A S Chen

Publications and source records attributed to A S Chen.

At least 19 recordsLinked to original sources
PubMed2005

An integrated inundation model for highly developed urban areas.

A numerical model is developed in this study with various components for simulating the complex flow phenomena in urban drainage basins. The model integrates the HEC-1 model, a 1-D dynamic channel-flow model, a 2-D non-inertia overland-flow model and the SWMM model to reflect the hydraulic processes in areas with different characteristics. The inundation of underground infrastructure during flood is also considered in the model. The typhoon Nari event in 2001, which resulted in severe flood in downtown Taipei, is simulated by the model. The result is compared with the survey records of flooded areas, which reveals the storage effect of underground infrastrucures is significant to the simulation results of highly developed urban areas.

Cities↗
PubMed2004

Orexigenic action of peripheral ghrelin is mediated by neuropeptide Y and agouti-related protein.

Ghrelin, a stomach-derived orexigenic hormone, has stimulated great interest as a potential target for obesity control. Pharmacological evidence indicates that ghrelin's effects on food intake are mediated by neuropeptide Y (NPY) and agouti-related protein (AgRP) in the central nervous system. These include intracerebroventricular application of antibodies to neutralize NPY and AgRP, and the application of an NPY Y1 receptor antagonist, which blocks some of the orexigenic effects of ghrelin. Here we describe treatment of Agrp(-/-);Npy(-/-) and Mc3r(-/-);Mc4r(-/-) double knockout mice as well as Npy(-/-) and Agrp(-/-) single knockout mice with either ghrelin or an orally active nonpeptide ghrelin agonist. The data demonstrate that NPY and AgRP are required for the orexigenic effects of ghrelin, as well as the involvement of the melanocortin pathway in ghrelin signaling. Our results outline a functional interaction between the NPY and AgRP pathways. Although deletion of either NPY or AgRP caused only a modest or nondetectable effect, ablation of both ligands completely abolished the orexigenic action of ghrelin. Our results establish an in vivo orexigenic function for NPY and AgRP, mediating the effect of ghrelin.

Agouti-Related Protein↗
PubMed2001

Characterization of SH2D1A missense mutations identified in X-linked lymphoproliferative disease patients.

X-linked lymphoproliferative disease (XLP) is a primary immunodeficiency characterized by extreme susceptibility to Epstein-Barr virus. The XLP disease gene product SH2D1A (SAP) interacts via its SH2 domain with a motif (TIYXXV) present in the cytoplasmic tail of the cell-surface receptors CD150/SLAM, CD84, CD229/Ly-9, and CD244/2B4. Characteristically, the SH2D1A three-pronged interaction with Tyr(281) of CD150 can occur in absence of phosphorylation. Here we analyze the effect of SH2D1A protein missense mutations identified in 10 XLP families. Two sets of mutants were found: (i) mutants with a marked decreased protein half-life (e.g. Y7C, S28R, Q99P, P101L, V102G, and X129R) and (ii) mutants with structural changes that differently affect the interaction with the four receptors. In the second group, mutations that disrupt the interaction between the SH2D1A hydrophobic cleft and Val +3 of its binding motif (e.g. T68I) and mutations that interfere with the SH2D1A phosphotyrosine-binding pocket (e.g. C42W) abrogated SH2D1A binding to all four receptors. Surprisingly, a mutation in SH2D1A able to interfere with Thr -2 of the CD150 binding motif (mutant T53I) severely impaired non-phosphotyrosine interactions while preserving unaffected the binding of SH2D1A to phosphorylated CD150. Mutant T53I, however, did not bind to CD229 and CD224, suggesting that SH2D1A controls several critical signaling pathways in T and natural killer cells. Because no correlation is present between identified types of mutations and XLP patient clinical presentation, additional unidentified genetic or environmental factors must play a strong role in XLP disease manifestations.

Amino Acid Sequence↗
PubMed2000

A new power law for determination of total (125)I seed activity for ultrasound-guided prostate implants: clinical evaluations.

PURPOSE: The intraoperative planning with peripheral loading approach is an important technique for ultrasound-guided transperineal prostate implant. In this paper a sphero-cylindrical dose model is described to generate a new power law or a look-up table for determination of the total (125)I activity required to deliver a prescription dose to a given prostate volume. METHODS AND MATERIALS: Dose calculations were based on the new standards for (125)I seeds (model 6711) implemented by the National Institute of Standards and Technology (NIST) in 1999. Using the sphero-cylindrical dose model with peripheral loading approach, a new power law for calculating total activity of radioactive iodine required to deliver a prescribed dose for the target volume was developed. Accounting for random variation of the seed positioning in the prostate and the current air-kerma strength standard of (125)I seeds, this new power law is formulated as follows: A (mCi) = 2.15 d (cm)(2.00) where A is apparent activity in mCi, or A (U) = 1. 69 d (cm)(2.00) where A is air-kerma strength in U, required to deliver a cumulative dose of 145 Gy to a prostate gland with an average dimension, d, in centimeters. RESULTS: The efficacy of using the new power law in prostate implants was demonstrated. For clinical evaluations of this new power law, 40 patients were chosen in 1998. The average D(90) of these 40 patients was 172.0 Gy (SD +/- 29 Gy). This means that on the average, 90% of the target volume received was 172.0 Gy. The average coverage index (CI) in this study was 94.7 (SD +/- 4.7). As a result, 94.7% of the target volume received the prescription dose. The dose homogeneity index (HI) which measured the degree of the dose inhomogeneity was 0.38 (SD +/- 0.21). CONCLUSION: This new and simple power law or a new mCi-volume look-up table for (125)I seed prostate implantation has been developed and formulated for clinical use. Clinical evaluations expressed in quantitative parameters such as D(90), CI, and HI in prostate implants have been thoroughly analyzed and clearly demonstrated the efficacy of this approach.

Brachytherapy↗
PubMed2000

Point dose variations with time during traditional brachytherapy for cervical carcinoma.

In traditional brachytherapy for carcinoma of the cervix, doses are often prescribed to specifically chosen points (A and B) and the normal tissue tolerance calculated at specific reference points in the bladder and rectum. These tolerance doses are often used to modify the brachytherapy treatment plan. It is inherently assumed that the position of the brachytherapy applicator does not change in relation to the relevant anatomical structures over the time-course of an implant. To assess the accuracy of this assumption, 2 sets of localization films were obtained for each implant in 28 patients, 1 prior to loading and another after the removal of the radioactive sources. Significant applicator movement and, consequently, significant dose variations were ob: served. Therefore, isolated one-time dose measurements to normal critical structures should not be used as the sole basis for making therapeutic decisions. The magnitude of dose variations and their clinical significant are discussed.

Brachytherapy↗
PubMed2000

Role of the melanocortin-4 receptor in metabolic rate and food intake in mice.

We evaluated the role of the melanocortin-4 receptor (MC-4R) in the control of metabolic rate and food intake in mice. Intraperitoneal administration of the non-selective MC-R agonist melanotan II (MT-II; a cyclic heptapeptide) increases metabolic rate in wildtype mice, while MC-4R knockout mice are insensitive to the effects of MT-II on metabolic rate. MC-4R knockout mice are also insensitive to the effects of MT-II on reducing food intake. We conclude that MC-4R can mediate control of both metabolic rate and food intake in mice. We infer that a role for MC-3R in mediating the acute effects of MT-II on basal metabolic rate and food intake in wildtype mice seems limited.

Animals↗
PubMed2000

Inactivation of the mouse melanocortin-3 receptor results in increased fat mass and reduced lean body mass.

Genetic and pharmacological studies have defined a role for the melanocortin-4 receptor (Mc4r) in the regulation of energy homeostasis. The physiological function of Mc3r, a melanocortin receptor expressed at high levels in the hypothalamus, has remained unknown. We evaluated the potential role of Mc3r in energy homeostasis by studying Mc3r-deficient (Mc3r(-/-)) mice and compared the functions of Mc3r and Mc4r in mice deficient for both genes. The 4-6-month Mc3r-/- mice have increased fat mass, reduced lean mass and higher feed efficiency than wild-type littermates, despite being hypophagic and maintaining normal metabolic rates. (Feed efficiency is the ratio of weight gain to food intake.) Consistent with increased fat mass, Mc3r(-/-) mice are hyperleptinaemic and male Mc3r(-/-) mice develop mild hyperinsulinaemia. Mc3r(-/-) mice did not have significantly altered corticosterone or total thyroxine (T4) levels. Mice lacking both Mc3r and Mc4r become significantly heavier than Mc4r(-/-) mice. We conclude that Mc3r and Mc4r serve non-redundant roles in the regulation of energy homeostasis.

Adipose Tissue↗
PubMed1998

Pudendal nerve latency. Does it predict outcome of anal sphincter repair?

PURPOSE: Electrophysiologic evaluation has been suggested as a means of identifying prognostic factors for patients with fecal incontinence who undergo anal sphincter repair. The purpose of this study was to evaluate the results of anal sphincter repair in patients with documented pudendal neuropathy and to determine the usefulness of electrophysiologic studies for prognostication of sphincteroplasty. METHODS: A retrospective review of a series of patients undergoing electrophysiologic studies and anterior anal sphincteroplasty was performed. Data collected included age, standardized incontinence scores (preoperative, immediately postoperative, and current follow-up), and results of pudendal nerve terminal motor latency and monopolar electromyography. Outcomes of sphincteroplasty were designated as excellent, good, fair, or poor based on incontinence scores. Prolonged pudendal nerve terminal motor latency was defined as longer than 2.2 ms and elevated as unilateral or bilateral. RESULTS: During the time period of the study (1991-1996), 15 patients had electrophysiologic studies and underwent sphincteroplasty. Twelve patients (80 percent) were available for follow-up and form the basis for this study. All patients were women, with a mean age of 45 +/- 18.6 (27-75) years and a mean follow-up of 49.7 +/- 18.6 (20.4-72.6) months. Mean duration of incontinence preoperatively was 13 +/- 16.1 (range, 1-58) years. The incontinence score was 15.8 +/- 3.5 preoperatively, 5.4 +/- 4.5 postoperatively, and 5 +/- 5.1 currently for all 12 patients. There was one patient with normal pudendal nerve terminal motor latency. In the four patients with bilateral prolonged pudendal nerve terminal motor latency, the incontinence scores were 15 +/- 4.2 preoperatively, 8.5 +/- 5.3 postoperatively, and 6 +/- 6.1 (statistically significant compared with preoperation) currently. Seven patients were found to have unilateral prolonged pudendal nerve terminal motor latency with incontinence scores of 16.3 +/- 3.5 preoperatively, 4.4 +/- 3.2 (statistically significant compared with preoperation) postoperatively, and 5.1 +/- 4.9 (statistically significant compared with preoperation) currently. Based on incontinence scores, results of the sphincteroplasty at the most current follow-up were as follows: no neuropathy, excellent in one patient; unilateral neuropathy, five with good/excellent results, two with fair/poor results; bilateral neuropathy, two with good/excellent results, two with fair/poor results (P > 0.05 bilateral vs. unilateral). By monopolar electromyographic examination, external and sphincter denervation was noted in 11 patients; their incontinence scores were 15.5 +/- 3.5 preoperatively, 5.9 +/- 4.3 (statistically significant compared with preoperation) postoperatively, and 5.5 +/- 5.0 (statistically significant compared with preoperation) currently. Monopolar electromyographic results in the puborectalis included four normal examinations and six that were unobtainable. In the two patients with puborectalis denervation, the incontinence scores were 19.5 +/- 0.7 preoperatively, 8.5 +/- 4.9 postoperatively, and 2.5 +/- 3.5 (statistically significant compared with preoperation) currently. CONCLUSIONS: Anterior anal sphincteroplasty in patients with unilateral or bilateral prolonged pudendal nerve terminal motor latency can provide significant improvement in continence with minimum morbidity. Therefore, correction of the anatomic sphincter defect should still be considered, even in patients with documented pudendal neuropathy.

Adult↗
PubMed1998

VEGF gene delivery to muscle: potential role for vasculogenesis in adults.

Constitutive expression of VEGF after implantation of genetically engineered myoblasts into non-ischemic muscle led to an increase in vascular structures. Previously, effects of VEGF delivery to adult muscle have only been reported in ischemic tissues. The resulting vascular structures were reminiscent of those formed during embryonic vasculogenesis, rather than angiogenesis, sprouting from preexisting vessels. Initially, VEGF caused an accumulation of endothelial cells and macrophages, followed by networks of vascular channels and hemangiomas with locally high serum VEGF levels. No effects were evident in adjacent tissue or contralateral legs, where low serum VEGF was detected. These data suggest that the induction by VEGF of angiogenesis or vasculogenesis may be dose-dependent. Furthermore, VEGF expression must be carefully modulated, as overexpression is deleterious.

Acetyltransferases↗
PubMed1996

Evaluation of dose calculation algorithm of the peacock system for multileaf intensity modulation collimator.

PURPOSE: To evaluate the dose calculation algorithm used in the inverse treatment planning computer system for the intensity modulation multileaf collimator. METHODS AND MATERIALS: The inverse treatment-planning computer system calculates the intensities of multiple pencil beams to achieve an optimal distribution and modulates the beam intensity through the special multileaf collimator. The system's dose calculation algorithm made the two basic assumptions: (a) The tissue-maximum ratios (TMRs) of a single pencil beam have the same values as TMRs for raylines through each pencil beam that are determined from percentage depth dose isodose curves along the long axis of the 2 x 20 cm2 field with all leaves open; and (b) the relative output factors (ROF) of each pencil beam also have the same values as the rayline TMR at d(max) of the 2 x 20 cm2 field. To verify these two assumptions, a special multileaf collimator was installed to our linear accelerator which produces 4 MV x-rays. The TMRs and ROFs for the single leaves 1 through 10 were measured using an ion chamber and TLD dosimeter in either a water or a polystyrene phantom. The values of rayline TMRs were calculated from the measured crossplane isodose curves of the 2 x 20 cm2 field. Comparisons were made between these two sets of data. RESULTS: Based on our measurements, we found that the ROFs of a pencil beam obtained from the rayline TMRs at d(max) are as much as 7.6% greater than that of single pencil beams. The ROF of the 1 x 1 cm2 pencil beam is 4 and 6.5% less than that of a cluster of four neighboring pencil beams forming a 2 x 2 cm2, and a 2 x 20 cm2 field respectively. However, the rayline TMRs are generally larger than the TMRs of a single pencil beam. At a depth of 8 cm, the average depth in the middle of intracranial space, the rayline TMRs of the pencil beams of leaves 1 and 10 are 5.4 and 9% higher than a single pencil beam TMR at the same depth, respectively. Also interesting is to note that the TMRs of each of the single pencil beams were found to be equal. CONCLUSIONS: In our article, evaluations and comparisons of TMRs and ROFs were made for two extreme conditions. The measured values of TMRs and ROFs of a single beam have been shown to be significantly different from those used in the calculations. Because both the TMR and ROF are influenced by the scattering radiation in the same direction, the deviations for these two factors would be expected to be magnified. Thus, for the two extreme situations we have investigated, dose deviations would be on the order of 15%. In real patient treatment; of course, these deviations may be somewhat less, but still significant. Our results, however, show that further investigations are warranted.

Algorithms↗
PubMed1995

Node-positive cervical cancer: impact of pelvic irradiation and patterns of failure.

PURPOSE: The roles of postoperative pelvic and prophylactic paraaortic irradiation in pelvic node positive cervical cancer are currently controversial. A retrospective study was undertaken to examine the effect of pelvic irradiation on pelvic control and survival and to analyze the patterns of recurrence to determine whether indications exist for prophylactic paraaortic irradiation. METHODS AND MATERIALS: From 1964 to 1991, 143 cases of FIGO Stage I and II cervical cancer undergoing exploratory laparotomy, pelvic lymph node dissection, and radical hysterectomy had positive pelvic lymph nodes. Postoperatively, 108 cases were treated with whole pelvic irradiation while 35 patients were observed. Prophylactic paraaortic irradiation was not given. RESULTS: Patients who received postoperative whole pelvic irradiation compared with those treated with radical hysterectomy alone had a significantly improved pelvic control rate, disease-free survival (DFS), and overall survival. The 5-year actuarial pelvic control rate was 78% vs. 45% (p = < 0.0001), respectively. The 5-year actuarial DFS was 65% vs. 41% (p = 0.0004). The 5-year actuarial overall survival was 58% vs. 46% (p = 0.02). In multivariate analysis, pelvic irradiation continued to show a positive effect on DFS (p = 0.0001) and overall survival (p = 0.0035). Lymphatic invasion and the total number of positive lymph nodes were the only other independent predictors of overall survival and DFS. The actuarial 5-year pelvic, paraaortic, and distant failure rates were 30%, 10%, and 28%, respectively. An isolated first recurrence in the paraaortic nodes occurred in only three cases. CONCLUSION: Postoperative pelvic irradiation significantly improves pelvic control, DFS, and overall survival, and should be used in patients with early stage cervical cancer and pathologically proven pelvic nodal metastases. The low incidence of isolated paraaortic nodal failure calls into question the value of routine prophylactic paraaortic irradiation in these patients.

Adult↗
PubMed1995

A 30-year experience in the management of primary carcinoma of the vagina: analysis of prognostic factors and treatment modalities.

This retrospective study of 100 cases of primary carcinoma of the vagina treated at Magee-Women's Hospital of the University of Pittsburgh from 1962 to 1992 analyzes disease and treatment-related prognostic factors and treatment results. Fifty percent of patients had previous hysterectomies prior to the diagnosis of vaginal cancer. The tumor was limited to one-third of the vaginal canal in 64 patients, but involved more than one-third of the canal in 36 patients. Treatment consisted of surgery in 40 patients, radiation therapy in 47 patients, and surgery plus radiation therapy in 13 patients. With a median follow-up of 11.2 years, the 5-year actuarial disease-free survival (DFS) was 67% for Stage I (23 patients), 53% for Stage II (58 patients), 0% for Stage III (9 patients), and 15% for Stage IV (10 patients). Using univariate and multivariate analysis, treatment with surgery, disease limited to one-third of the vaginal canal, and FIGO Stage I and II disease were significantly favorable prognostic factors for DFS. Treatment with surgery was superior to radiation therapy alone in Stage II patients (P = 0.00004). There appeared to be a selection bias in Stage II patients, as the more unfavorable cases were treated with radiation therapy. Although radiation therapy will often be the treatment of choice, excellent results and limited morbidity accompany selected cases surgically resected.

Adolescent↗
PubMed1995

Managing diabetic retinopathy: the partnership between ophthalmologist and primary care physician.

Diabetic retinopathy (DR), an ocular complication of diabetes mellitus, is the leading cause of blindness in Americans age 20 to 74 today. The more severe stage of the disease, proliferative diabetic retinopathy, affects an estimated 700,000 Americans. Based on clinical findings, the disease is generally classified as nonproliferative DR or proliferative DR. While the former often begins as a symptomatically silent disease, it nevertheless may be progressing to itself cause significant visual loss. Based principally on evidence from several studies sponsored by the National Eye Institute, current treatment consists of regular observation by an ophthalmologist, laser photocoagulation, and vitrectomy. In addition, preventive methods such as tight glycemic control and ophthalmic screening of diabetics appear beneficial. While the ophthalmologist can provide specialized services for the DR patient, prevention and control lie largely in the hands of the primary care physician. Thus, only when primary and specialized care have established a strong partnership can they save the sight of the thousands at risk for diabetic retinopathy.

Adult↗
PubMed1994

Aberrant splicing in adult onset glycogen storage disease type II (GSDII): molecular identification of an IVS1 (-13T-->G) mutation in a majority of patients and a novel IVS10 (+1GT-->CT) mutation.

Two newly identified splice site mutations (IVS1 -13T-->G and IVS10 +1GT-->CT) were found in a patient with adult onset of the autosomal recessive disorder glycogen storage disease type II (GSDII). The IVS1 -13T-->G transversion in the acceptor splice site was found on one allele in over two thirds of adult onset GSDII patients studied (28/41), but was not seen in 58 normal or 12 infantile onset GSDII chromosomes. Molecular analysis of cDNA from the index patient and four additional, ethnically different, individuals carrying the IVS1 -13T-->G transversion showed splicing out of the first coding exon as well as rare utilization of a cryptic splice site in the exon. An IVS10 +1GT-->CT transversion, unique to the index patient, was detected on the second chromosome. The IVS10 +1GT-->CT results in splicing out of exon 10 including part of the enzyme catalytic site. Additionally, a large deletion encompassing exon 18, previously described in four unrelated patients, was also detected in three unrelated adult GSDII patients, two of whom carried the IVS1 -13T-->G transversion. The frequency of the IVS1 splice site mutation suggests that detection of this mutation could potentially aid in the diagnosis of the phenotypically variable syndrome of adult onset GSDII. The finding that the -13T-->G mutation is a very common mutation in adult onset GSDII patients of varying ethnic and racial backgrounds, suggests that it is either an ancient mutation or confers a selective advantage. Although to our knowledge these are the first splice site mutations to be reported for GSDII, additional splice site mutations are likely and could provide the basis for later onset disease in GSDII.

Adult↗
PubMed1994

A de novo 13 nt deletion, a newly identified C647W missense mutation and a deletion of exon 18 in infantile onset glycogen storage disease type II (GSDII).

We identified the presumably rare event of de novo mutation in an autosomal recessive disorder, glycogen storage disease type II (GSDII). GSDII results from inherited deficiency of acid alpha-glucosidase (acid maltase) and both the expressed and structural gene (designated GAA) have been isolated. The mutation was a deletion of 13 nt of coding sequence (delta nt 1456-1468) on the paternally derived allele of the proband. The delta nt 1456-1468 results in a reading frameshift and a premature termination signal upstream of the enzyme catalytic site. Paternity was confirmed by presence of two downstream, uncommon amino acid substitutions (E689K, W746C) in both proband and father and by comparison of nine short tandem repeats. The maternal allele carried a newly identified deleterious C647W missense mutation in a highly conserved area of the protein. The C647W mutation was also found in a second unrelated proband, heteroallelic with a deletion extending from IVS17 to IVS18.

Alleles↗