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Biomedical subjects

S Chang

Publications and source records attributed to S Chang.

At least 91 records · Page 5Linked to original sources

Molecular cloning of a human dentin sialophosphoprotein gene.

Dentin sialoprotein (DSP) and dentin phosphoprotein (DPP; phosphophoryn) are two principal dentin-specific non-collagenous proteins. DPP is extremely acidic and is rich in aspartic acid and serine. By virtue of this structure, DPP may bind large amounts of calcium and may facilitate initial mineralization of dentin matrix collagen as well as regulate the size and shape of the crystals. The function of DSP is not known. DSP and DPP are encoded by a single gene in both rat and mouse, and are uniquely expressed in odontoblasts and transiently in pre-ameloblasts. Because DSP and DPP are isolated from dentin as distinct proteins and appear to be present in different amounts, the nascent dentin sialophosphoprotein (DSPP) is likely cleaved to yield DSP and DPP. However, when, where and how the DSPP is cleaved into DSP and DPP is not clear. To further elucidate the structure and function of human DSP and DPP, we have cloned DPP and DSP cDNA by reverse transcriptase-polymerase chain reaction (RT-PCR) strategies, and then cloned and initiated characterization of a human dentin sialophosphoprotein gene. The genomic organization of human DSPP is very similar to that of mouse, containing five exons and four introns, suggesting it is a homologue of mouse dentin sialophosphoprotein (DSPP). Exons 1-4 encode for DSP, while exon 5 encodes for the C-terminus of DSP and the whole DPP. A 4.6-kb RNA transcript was detected on Northern blot analyses of total RNA extracted from immature (open root apices) human teeth using either a human DPP or DSP probe.

Amino Acid Sequence↗

Telomere dysfunction impairs DNA repair and enhances sensitivity to ionizing radiation.

Telomeres are specialized nucleoprotein complexes that serve as protective caps of linear eukaryotic chromosomes. Loss of telomere function is associated with rampant genetic instability and loss of cellular viability and renewal potential. The telomere also participates in processes of chromosomal repair, as evidenced by the 'capture' or de novo synthesis of telomere repeats at double-stranded breaks and by the capacity of yeast telomeres to serve as repositories of essential components of the DNA repair machinery, particularly those involved in non-homologous end-joining (NHEJ). Here we used the telomerase-deficient mouse, null for the essential telomerase RNA gene (Terc), to assess the role of telomerase and telomere function on the cellular and organismal response to ionizing radiation. Although the loss of telomerase activity per se had no discernable impact on the response to ionizing radiation, the emergence of telomere dysfunction in late-generation Terc-/- mice imparted a radiosensitivity syndrome associated with accelerated mortality. On the cellular level, the gastrointestinal crypt stem cells and primary thymocytes showed increased rates of apoptosis, and mouse embryonic fibroblasts (MEFs) showed diminished dose-dependent clonogenic survival. The radiosensitivity of telomere dysfunctional cells correlated with delayed DNA break repair kinetics, persistent chromosomal breaks and cytogenetic profiles characterized by complex chromosomal aberrations and massive fragmentation. Our findings establish a intimate relationship between functionally intact telomeres and the genomic, cellular and organismal response to ionizing radiation.

Animals↗

Analysis of yeast protein kinases using protein chips.

We have developed a novel protein chip technology that allows the high-throughput analysis of biochemical activities, and used this approach to analyse nearly all of the protein kinases from Saccharomyces cerevisiae. Protein chips are disposable arrays of microwells in silicone elastomer sheets placed on top of microscope slides. The high density and small size of the wells allows for high-throughput batch processing and simultaneous analysis of many individual samples. Only small amounts of protein are required. Of 122 known and predicted yeast protein kinases, 119 were overexpressed and analysed using 17 different substrates and protein chips. We found many novel activities and that a large number of protein kinases are capable of phosphorylating tyrosine. The tyrosine phosphorylating enzymes often share common amino acid residues that lie near the catalytic region. Thus, our study identified a number of novel features of protein kinases and demonstrates that protein chip technology is useful for high-throughput screening of protein biochemical activity.

Adenosine Triphosphate↗

Photodynamic therapy of rat bladder and urethra: evaluation of urinary and reproductive function after inducing protoporphyrin IX with 5-aminolaevulinic acid.

OBJECTIVE: To assess the urinary and reproductive function of rats after inducing protoporphyrin IX with 5-aminolaevulinic acid (ALA) and subsequent intraurethral photodynamic therapy (PDT). Materials and methods Twelve female Wistar rats were given ALA orally or intravesically (four each), followed by intraurethral PDT through a 10-mm cylindrical fibre at 100 mW for 500 s (argon laser, 632 nm). Urinary frequency, the number of gestations and histological changes were then evaluated and compared with a group of eight control rats. RESULTS: There was only a slight increase in urinary frequency during the first 2 weeks after PDT in the group given oral ALA, while the same degree of urinary frequency was evident for up to 4 weeks in those given intravesical ALA. Despite the occurrence of urinary incontinence from undefined causes in two rats, reproductive function remained unchanged. There was no histological evidence of damage to the reproductive system adjacent to the bladder. CONCLUSIONS: PDT of the urethra with ALA is relatively safe and carries few risks of inducing permanent urological complications.

Administration, Intravesical↗

Solid-phase microextraction and headspace solid-phase microextraction for the determination of high molecular-weight polycyclic aromatic hydrocarbons in water and soil samples.

The feasibility of direct-immersion (DI) solid-phase microextraction (SPME) and headspace (HS) SPME for the determination of high-ring polycyclic aromatic hydrocarbons (PAHs) (4- to 6-ring PAHs) in water and soil samples is studied. Three SPME fibers--100- and 30-microm polydimethylsiloxane (PDMS) and 85-microm polyacrylate (PA) fibers-are compared for the effective extraction of PAHs. Parameters affecting the sorption of PAHs into the fiber such as sampling time, sampling volume, and temperature are also evaluated. The extracted amounts of high-ring PAHs decrease with the decreasing of film thickness, and the 100-microm PDMS has the highest extraction efficiency than 85-microm PA and 30-microm PDMS fibers. Also, the extraction efficiency decreases with the increasing molecular weights of PAHs. Of the 10 high-ring PAHs, only fluoranthene and pyrene can reach equilibrium within 120 min at 25 degrees C for DI-SPME in a water sample. Increasing the temperature to 60 degrees C can increase the sensitivity of PAHs and shorten the equilibrium time. A 0.7- to 25-fold increase in peak area is obtained for DI-SPME when the working temperature is increased to 60 degrees C. For HS-SPME, the extraction efficiency of PAHs decrease when the headspace volume of the sampling system increases. All high-ring PAHs can be detected in a water sample by increasing the temperature to 80 degrees C. However, only 4- and 5-ring PAHs can be quantitated in a CRM soil sample when HS-SPME is used. The addition of a surfactant with high hydrophilic property can effectively enhance the sensitivity of high-ring PAHs. HS-SPME as well as DI-SPME with 100-microm PDMS or 85-microm PA fibers are shown to be suitable methods for analyzing high-ring PAHs in a water sample; however, this technique can only apply in a soil sample for PAHs having up to 5 rings.

Chromatography, Gas↗

A preliminary study of the prognostic value of proton magnetic resonance spectroscopic imaging in gamma knife radiosurgery of recurrent malignant gliomas.

OBJECTIVE: The goal of this study was to investigate the use of proton magnetic resonance spectroscopic imaging as a prognostic indicator in gamma knife radiosurgery of recurrent gliomas. METHODS: Thirty-six patients with recurrent gliomas were studied with proton magnetic resonance spectroscopic imaging at the time of radiosurgery, and with conventional magnetic resonance imaging examinations at regular time intervals until the initiation of a new treatment strategy. Patients were categorized on the basis of their initial spectroscopic results, and their performance was assessed in terms of change in contrast-enhancing volume, time to further treatment, and survival. RESULTS: The trends in the overall population were toward more extensive increase in the percent contrast-enhancing volume, a decreased time to further treatment, and a reduced survival time for patients with more extensive initial metabolic abnormalities. Statistical analysis of the subpopulation of patients with glioblastoma multiforme found a significant increase in relative contrast-enhancing volume (P < 0.01, Wilcoxon signed-rank test), a decrease in time to further treatment (P < 0.01, log-rank test), and a reduction in survival time (P < 0.01, log-rank test) for patients with regions containing tumor-suggestive spectra outside the gamma knife target, compared with patients exhibiting spectral abnormalities restricted to the gamma knife target. Further studies are needed to establish statistical significance for patients with lower-grade lesions and to confirm the results observed in this study. CONCLUSION: The pretreatment spectroscopic results provided information that was predictive of outcome for this patient pool, both in local control (change in contrast-enhancing volume) and global outcome (time to further treatment and survival). This modality may have an important role in improving the selection, planning, and treatment process for glioma patients.

Adult↗

Pars plana vitrectomy for persistent, visually significant vitreous opacities.

PURPOSE: To evaluate the role of vitrectomy in patients with persistent, visually disabling vitreous opacities. METHODS: Six consecutive eyes of five men (age 58-66 years) with pseudophakia or aphakia and vitreous opacities resulting in visual symptoms for more than 1 year that underwent vitrectomy were retrospectively reviewed. Postoperative questionnaires regarding functional performance and quality-of-life issues were completed by the participants to assess subjective patient satisfaction. RESULTS: Postoperative Snellen visual acuity was improved or equal to preoperative acuity in all cases (8-44 month follow-up) and there were no surgical complications. All patients expressed high satisfaction with overall visual function. Analysis of the National Eye Institute Visual Function Questionnaire-39 indicated that general vision, near activities, distance activities, mental health, role difficulties, and peripheral vision were significantly improved (P < 0.05) following surgical intervention. CONCLUSIONS: Vitrectomy may be indicated in a select group of patients with visually disabling vitreous floaters, although objective assessment of visual dysfunction from vitreous floaters requires further evaluation.

Aged↗

Transition from amplified spontaneous emission to laser action in strongly scattering media

In an active random medium, the combination of multiple scattering with light amplification may lead to random laser action. However, it is crucial but sometimes difficult to distinguish between amplified spontaneous emission and lasing. By varying the amount of scattering in an amplifying random medium, we have observed the transition from amplified spontaneous emission to lasing with coherent feedback. We have found out when the transition occurs through the measurement of the scattering mean free path. Our numerical simulation based on the direct solution to Maxwell equations clearly illustrates the transition from light amplification to laser oscillation due to an increase of the amount of scattering in active random medium.

Journal Article↗

Studies of detrusor-sphincter synergia and dyssynergia during micturition in rats via fractional Brownian motion.

In normal humans, the bladder is supposed to empty by a synergistic contraction of the detrusor and relaxation of the sphincter during micturition. By contrast, suprasacral spinal cord injury (SCI) patients usually will have both of them contract simultaneously and result in the so-called detrusor-sphincter dyssynergia. In this study, the cystometrograms of the detrusor and the electromyograms of external urethral sphincter of intact and SCI female Wistar rats are used to investigate the detrusor-sphincter synergia and dyssynergia during micturition. Due to the statistical self-similarity of the waveforms, the cystometrogram is modeled as discrete-time fractional Brownian motion and the electromyogram as discrete-time fractional Gaussian noise. Fractal dimensions of both of them are calculated and used as indices in the investigation of synergia. Results indicate that, for intact rats, the sphincter muscle is not only active but also recruited in a synchronous fashion with the detrusor. Furthermore, clear-cut measure using the fractal dimensions can be used to diagnose detrusor-sphincter synergia and dyssynergia.

Algorithms↗

The effect of glucocorticosteroid treatment on dentine formation in the Lewis rat, a histological study.

Glucocorticosteroids are widely used in the treatment of chronic illnesses and have been reported to cause premature obliteration of the pulp space. During the active stages of dentinogenesis, odontoblasts are growth hormone receptor (GHr) positive. The aims of this study were to determine if the glucocorticosteroid, prednisone, affected the rate of dentine deposition and odontoblast expression of GHr in the rat molar. Following subcutaneous injection of 0.05 mg/kg, 1.0 mg/kg or 5.0 mg/kg prednisone for 20 days, immature and mature molars from rats aged 3 and 6 weeks respectively, were examined histologically. Distribution of GHr expression was determined immunohistochemically. No morphological differences were observed in molars from prednisone treated animals. Prednisone did not appear to enhance dentine deposition in immature molars but in mature molars significantly increased dentine deposition on the roof of the pulp chamber at a dosage of 5.0 mg/kg (p < 0.001). In all immature molars, odontoblasts and pulp cells expressed GHr immunoreactivity. In mature molars, odontoblasts and pulpal cells from controls did not show GHr immunoreactivity. However, odontoblasts and pulp cells were GHr immunoreactive in mature molars from animals treated with prednisone.

Animals↗

Medication continuation and compliance: a comparison of patients treated with clozapine and haloperidol.

BACKGROUND: This study compares medication continuation and regimen compliance with the atypical antipsychotic medication clozapine versus the conventional antipsychotic haloperidol. METHOD: Data from a 15-site double-blind, randomized clinical trial (N = 423) were used to compare patients with DSM-III-R schizophrenia assigned to clozapine or haloperidol in terms of duration of participation while taking the randomly assigned study drug (continuation) and the proportion of prescribed pills that were taken (compliance). Multiple regression analysis was used to determine the relationship of baseline characteristics and measures of clinical change to continuation for the entire sample and for patients assigned to each medication. RESULTS: Patients assigned to clozapine continued taking the study drug for a mean of 35.5 weeks as compared with only 27.2 among patients assigned to haloperidol (F = 4.45, df = 1,422; p = .0001). No differences were found between the groups in the proportion of prescribed pills that were returned at any timepoint. Among patients assigned to haloperidol, poorer continuation was associated with being older and greater continuation with receiving public support. Among patients on clozapine treatment, continuation was poorer among African American patients and greater among patients who showed reduced clinical symptoms and akathisia. Continuation with clozapine was greater even after adjusting for these factors. CONCLUSION: Continuation with medication is greater with clozapine than haloperidol and is partly explained by greater symptom improvement and reduced side effects. No differences were found in regimen compliance.

Adult↗

[Current situation and trend of child growth in China].

Data of Food and Nutrition Surveillance in 1990, 1995 and 1998 was analyzed; it indicated the evident improvement of weight and height of children under 5 in the past eight years. The prevalence of underweight were reduced from 8.0% in 1990 to 2.7% in 1998 in the urban, and in the rural, the prevalence were 22.0% and 12.6% respectively. The reduction of prevalence of stunting in the urban decreased from 9.4% to 4.1%, and in the rural from 41.4% to 22.0% in the same period. During 1990-1995, weight of children under 5 went up evidently, but linear growth improvement was very slow and did not match the weigh gain. Height of children increased in a higher speed during 1995-1998. Height and weigh of age groups indicated that 6-18 month was the critical period for prevention of malnutrition of children under 5. The paper further analyzed the favorable changes of the attributable factors of malnutrition, such as diarrhea, safe drinking water, breastfeeding, education level of mothers, household diet and income during this period. The conclusion is the remarkable nutrition improvement of children under 5 in 1990s is the consequence of the rapid socio-economic development of China.

Adult↗

[Exclusive breastfeeding and growth of infants under 4 months in China].

Data collected at the 40 CFNSS sites in 1998 was analyzed on the relationship of exclusive breastfeeding and the growth, diseases of infant aged under 4 months. The results showed that the exclusive breastfeeding rates (EBF) of children under 4 months were 53.7% in urban and 76.6% in general rural, but was 64.6% in the poor rural. EBF rate of the stunted children was 57.3% that was significantly lower than the infants with normal length. 73.0%. The infants EBF under 4 months were 0.36 kg heavier, 1.2 cm longer, and WAZ 0.4 and HAZ 1.53 higher than the non-EBF infants. Prevalence of diarrhea were 13.1% among EBF and 29% in non-EBF infants. Logistic regression analysis showed that odds ratio (OR) of stunting for non-EBF infants was 2.19, OR of diarrhea was 2.74.

Breast Feeding↗

Fractal geometry in urodynamics of lower urinary tract.

The physiological signals are usually extremely complicated and difficult to analyze. Recently, investigators have tried the fractal dimension that can characterize roughness and self-similarity of them. It turns out that it is also suitable for obtaining the modalities of lower urinary tract during normal micturition. In this investigation, the external urethral sphincter electromyogram (EUS EMG) and the cystometrogram (CMG) of the Wistar rats under both room temperature and cold water stimulation of the bladder are studied. The modified relative differential box-counting (RDBC) method is used to calculate the fractal dimensions of EMG and CMG time series. According to the experimental results, the modalities of micturition for the Wistar rats can be characterized as normal if both the fractal dimensions of EMG and CMG are of low values during voiding. Furthermore, the technique is validated in identifying the dyssynergia of the bladder and EUS under cold water stimulation.

Animals↗

Long-range signaling within growing neurites mediated by neurotrophin-3.

In addition to well established trophic functions, neurotrophins acutely affect neurotransmitter secretion from the presynaptic nerve terminal, influence synaptic development, and may serve as selective retrograde messengers that regulate synaptic efficacy. The crucial question related to the mechanisms of neurotrophin-mediated signaling is whether acute effects of neurotrophins are spatially restricted to the activated synapses. Here we have used a local perfusion technique for local delivery of neurotrophin-3 (NT-3) to various regions of developing Xenopus embryo neurons in culture. Within minutes after a focal exposure of a soma or a small ( approximately 30 micrometer in length) axonal segment to NT-3, we observed an increase in the spontaneous neurotransmitter secretion from the presynaptic nerve terminals located approximately 300-400 micrometer away from the site of NT-3 application. Secretory activity along the axonal shaft was not affected. Our findings suggest that the NT-3-mediated signal may rapidly travel through neuronal cytoplasm over unexpectedly long distances and modulate neurotransmitter release specifically at the presynaptic nerve terminals.

Acetylcholine↗

Longevity, stress response, and cancer in aging telomerase-deficient mice.

Telomere maintenance is thought to play a role in signaling cellular senescence; however, a link with organismal aging processes has not been established. The telomerase null mouse provides an opportunity to understand the effects associated with critical telomere shortening at the organismal level. We studied a variety of physiological processes in an aging cohort of mTR-/- mice. Loss of telomere function did not elicit a full spectrum of classical pathophysiological symptoms of aging. However, age-dependent telomere shortening and accompanying genetic instability were associated with shortened life span as well as a reduced capacity to respond to stresses such as wound healing and hematopoietic ablation. In addition, we found an increased incidence of spontaneous malignancies. These findings demonstrate a critical role for telomere length in the overall fitness, reserve, and well being of the aging organism.

Aging↗

Chemical bonding effects in the determination of protein structures by electron crystallography.

Scattering of electrons is affected by the distribution of valence electrons that participate in chemical bonding and thus change the electrostatic shielding of the nucleus. This effect is particularly significant for low-angle scattering. Thus, while chemical bonding effects are difficult to measure with small-unit cell materials, they can be substantial in the study of proteins by electron crystallography. This work investigates the magnitude of chemical bonding effects for a representative collection of protein fragments and a model ligand for nucleotide-binding proteins within the resolution range generally used in determining protein structures by electron crystallography. Electrostatic potentials were calculated by ab initio methods for both the test molecules and for superpositions of their free atoms. Differences in scattering amplitudes can be well over 10% in the resolution range below 5 A and are especially large in the case of ionized side chains and ligands. We conclude that the use of molecule-based scattering factors can provide a much more accurate representation of the low-resolution data obtained in electron crystallographic studies. The comparison of neutral and ionic structure factors at resolutions below 5 A can also provide a sensitive determination of charge states, important for biological function, that is not accessible from X-ray crystallographic measurements.

Crystallography↗