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S Chang

Publications and source records attributed to S Chang.

At least 109 records · Page 6Linked to original sources
PubMed1999

Neurotransmitter secretion along growing nerve processes: comparison with synaptic vesicle exocytosis.

In mature neurons, synaptic vesicles continuously recycle within the presynaptic nerve terminal. In developing axons which are free of contact with a postsynaptic target, constitutive membrane recycling is not localized to the nerve terminal; instead, plasma membrane components undergo cycles of exoendocytosis throughout the whole axonal surface (Matteoli et al., 1992; Kraszewski et al., 1995). Moreover, in growing Xenopus spinal cord neurons in culture, acetylcholine (ACh) is spontaneously secreted in the quantal fashion along the axonal shaft (Evers et al., 1989; Antonov et al., 1998). Here we demonstrate that in Xenopus neurons ACh secretion is mediated by vesicles which recycle locally within the axon. Similar to neurotransmitter release at the presynaptic nerve terminal, ACh secretion along the axon could be elicited by the action potential or by hypertonic solutions. We found that the parameters of neurotransmitter secretion at the nerve terminal and at the middle axon were strikingly similar. These results lead us to conclude that, as in the case of the presynaptic nerve terminal, synaptic vesicles involved in neurotransmitter release along the axon contain a complement of proteins for vesicle docking and Ca2+-dependent fusion. Taken together, our results support the idea that, in developing axons, the rudimentary machinery for quantal neurotransmitter secretion is distributed throughout the whole axonal surface. Maturation of this machinery in the process of synaptic development would improve the fidelity of synaptic transmission during high-frequency stimulation of the presynaptic cell.

ADP-Ribosylation Factors↗
PubMed1999

Radiosurgery for brain metastases: is whole brain radiotherapy necessary?

PURPOSE: Because whole brain radiotherapy (WBRT) may cause dementia in long-term survivors, selected patients with brain metastases may benefit from initial treatment with radiosurgery (RS) alone reserving WBRT for salvage as needed. We reviewed results of RS +/- WBRT in patients with newly diagnosed brain metastasis to provide background for a prospective trial. METHODS AND MATERIALS: Patients with single or multiple brain metastases managed initially with RS alone vs. RS + WBRT (62 vs. 43 patients) from 1991 through February 1997 were retrospectively reviewed. The use of upfront WBRT depended on physician preference and referral patterns. Survival, freedom from progression (FFP) endpoints, and brain control allowing for successful salvage therapy were measured from the date of diagnosis of brain metastases. Actuarial curves were estimated using the Kaplan-Meier method. Analyses to adjust for known prognostic factors were performed using the Cox proportional hazards model (CPHM) stratified by primary site. RESULTS: Survival and local FFP were the same for RS alone vs. RS + WBRT (median survival 11.3 vs. 11.1 months and 1-year local FFP by patient 71% vs. 79%, respectively). Brain FFP (scoring new metastases and/or local failure) was significantly worse for RS alone vs. RS + WBRT (28% vs. 69% at 1 year; CPHM adjustedp = 0.03 and hazard ratio = 0.476). However, brain control allowing for successful salvage of a first failure was not significantly different for RS alone vs. RS + WBRT (62% vs. 73% at 1 year; CPHM adjusted p = 0.56). CONCLUSIONS: The omission of WBRT in the initial management of patients treated with RS for up to 4 brain metastases does not appear to compromise survival or intracranial control allowing for salvage therapy as indicated. A randomized trial of RS vs. RS + WBRT is needed to assess survival, quality of life, and cost in good-prognosis patients with newly diagnosed brain metastases.

Adult↗
PubMed1999

Binding of fatty acid ethyl esters to albumin for transport to cells in culture.

Fatty acid ethyl esters (FAEE) are non-oxidative products of ethanol metabolism that have been proposed to mediate pathological changes in various organs and tissues resulting from excessive ethanol consumption. Evidence supporting this proposal is scant, however, mainly because of the lack of adequate methods with which to solubilize the highly hydrophobic FAEE in aqueous medium for testing under physiological conditions. In this report we describe a simple and practical method for solubilizing FAEE in aqueous medium by binding them to albumin. We also report that the albumin-bound FAEE are readily taken up by rat alveolar macrophages in culture. The availability of FAEE bound to albumin, their main physiological carrier in vivo, will facilitate the investigation of the role that these metabolites may have in mediating pathological changes associated with excess ethanol consumption.

Albumins↗
PubMed1999

Mechanistic studies of the effects of the retinoid N-(4-hydroxyphenyl)retinamide on prostate cancer cell growth and apoptosis.

To explore the mechanisms underlying the chemopreventive effects of the synthetic retinoid N-(4-hydroxyphenyl)retinamide (4-HPR) in prostate cancer, we evaluated the anti-proliferative and apoptosis-inducing effects of 4-HPR in the androgen-sensitive human prostate cancer cell line LNCaP. 4-HPR decreased the number of viable LNCaP cells (as measured by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay) in a dose-dependent manner. Although 4-HPR exerted a modest G1 cell-cycle block (as determined by flow cytometry), its effect on reduced cell number appeared to result primarily from induction of apoptosis (as measured by an enzyme-linked immunosorbent assay and flow-cytometric assays). The mitogenic effects of R1881, a non-metabolizable androgen that potently induces LNCaP cell proliferation, was completely blocked by greater than 0.5 microM 4-HPR. Furthermore, increasing the R1881 concentration in the presence of 2.0 microM 4-HPR increased apoptotic cell death. 4-HPR decreased prostate-specific antigen (PSA) protein levels in conditioned medium and decreased PSA mRNA expression. 4-HPR also decreased the ratio of bcl-2 to bax mRNA expression in LNCaP cells by approximately 45%, indicating that the apoptotic effects of 4-HPR may be mediated, at least in part, by alterations in the bcl-2/bax-regulated apoptotic pathway. N-acetylcysteine (4 mM) completely blocked the anti-proliferative and apoptotic-inducing effects of 4-HPR, suggesting that an oxidative mechanism may be involved. We concluded that (i) 4-HPR exerts growth-suppressive and apoptotic effects on LNCaP cells, (ii) 4-HPR can interact with androgen to suppress proliferation and induce apoptosis, (iii) the apoptotic effects of 4-HPR may be mediated in part by the bcl-2/bax pathway, and (iv) a pro-oxidant mechanism may contribute to the anti-proliferative and apoptotic-inducing effects of 4-HPR.

Androgens↗
PubMed1999

Mechanisms of regulation of the MacMARCKS gene in macrophages by bacterial lipopolysaccharide.

Bacterial lipopolysaccharide (LPS) stably induced the protein kinase C substrate, MacMARCKS, in murine resident peritoneal macrophages; initial induction of MacMARCKS mRNA was detected within 15 min and was protein synthesis-independent. This response was observed in the macrophage cell line RAW264, and occurred also in response to plasmid DNA, a partial mimetic of other responses to LPS. In murine bone marrow-derived macrophages, MacMARCKS was expressed constitutively due to induction by macrophage colony-stimulating factor. Nuclear run-on transcription revealed that, like tumor necrosis factor alpha (TNF-alpha), MacMARCKS was transcribed constitutively in RAW264 cells. The MacMARCKS promoter was sequenced to -1.7 kb and the transcription start site determined. Transient transfections of RAW264 cells revealed that the 113-bp GC-rich proximal promoter contained all the elements required for both high basal activity and 15- to 20-fold activation by LPS.

Animals↗
PubMed1999

Kaposi's sarcoma-associated herpesvirus-positive primary effusion lymphoma arising in the subarachnoid space.

Primary effusion lymphoma (PEL) is a rare and distinctive type of B-cell non-Hodgkin's lymphoma (NHL) that occurs primarily, although not exclusively, in patients with AIDS. It usually develops as a lymphomatous effusion in the absence of a tumor mass, characteristically contains the Kaposi's sarcoma-associated herpesvirus/human herpesvirus 8 (KSHV/HHV-8), usually also contains the Epstein-Barr virus (EBV), displays a characteristic cytomorphology bridging immunoblastic and anaplastic large cell lymphoma, often expresses an indeterminate immunophenotype, and a B-cell genotype. Thus far, PEL has been limited almost entirely to the pleural, peritoneal, and pericardial cavities. We describe a NHL occurring in a gay man with AIDS that is typical of PEL in that it arose in a body cavity or space without an associated tumor mass, displays the cytomorphology typical of PEL, is a clonal B-cell neoplasm, and contains KSHV as well as EBV. This case is singularly distinctive in that it is the first case of PEL reported to arise in the subarachnoid space. This unique case further supports the strong association between KSHV and malignant lymphoma arising in body cavities and growing as an effusion.

Adult↗
PubMed1999

Distribution of neurotransmitter secretion in growing axons.

Neurotransmitter secretion from the nerve terminal is mediated by the fusion of synaptic vesicles with the plasma membrane. It is generally believed that neurotransmitter release in mature synapses is localized to the presynaptic nerve terminals. To probe the topology of neurotransmitter secretion along developing axons in culture, we recorded membrane currents from myocytes manipulated into contact with axons. At the early stages of growth, exocytotic events were detected along the axon as well as at the growth cone. At the later stages of growth, neurotransmitter secretion adopted the form of a smooth proximodistal gradient, with the highest level of activity at the growth cone region. Our results reveal the existence of a previously undetected early stage of axonal growth and suggest developmental regulation in the pattern of neurotransmitter secretion along the growing nerve processes.

Acetylcholine↗
PubMed1999

Lennox-Gastaut syndrome after a further attenuated live measles vaccination.

We reported a 2-year-old boy with Lennox-Gastaut syndrome, of which the cause could be an adverse effect of further attenuated live (FL) measles vaccine. The pre- and peri-natal histories of the patient were uneventful, except that he was one of monozygotic twins. He had developed normally until 24 months of life, when tonic seizures began on postvaccination day 14 without a preceding episode of continuous fever or any neurologic symptoms. The tonic seizures and atypical absence have been intractable as to various antiepileptic drugs, while his twin brother has experienced no epileptic seizures.

Child, Preschool↗
PubMed1999

Speckle microscopic evaluation of microtubule transport in growing nerve processes.

Assembly of microtubules is fundamental to neuronal morphogenesis. Microtubules typically form crosslinked bundles in nerve processes, precluding resolution of single microtubules at the light microscopic level. Therefore, previous studies of microtubule transport in neurites have had to rely on indirect approaches. Here we show that individual microtubules can be visualized directly in the axonal shafts of Xenopus embryo neurons by using digital fluorescence microscopy. We find that, although the array of axonal microtubules is dynamic, microtubules are stationary relative to the substrate. These results argue against a model in which newly synthesized tubulin is transported down the axon in the form of microtubules.

Animals↗
PubMed1999

Netilmicin pharmacokinetics in Hong Kong Chinese cancer patients.

OBJECTIVES: To study the pharmacokinetics of netilmicin in Chinese haematology-oncology patients and to determine the pharmacokinetic differences, if any, between this patient subpopulation of Chinese and Caucasians. METHODS: A prospective study was carried out in the adult oncology unit of a major hospital in Hong Kong. During a 6 week period in 1997, all patients commencing on netilmicin therapy were monitored; the patients' demographics, clinical status, netilmicin dose and regimen, and drug administration/blood sampling time were collected. Pharmacokinetic parameters were generated using the USC*PACK package based on specifics of the patients themselves and Caucasians matched for the same patients' parameters using the Bayesian alogrithms. RESULTS: A total of 22 patients were enrolled into the study. Twenty-nine sets of levels were drawn, but only 25 sets from 18 patients (86%) were interpretable. The predicted peak (7.47+/-1.46 microg ml-1 ) and trough levels (1.39+/-0.96 microg ml-1 ) generated by USC*PACK were found to be significantly higher than the levels observed (6.01+/-1.14 microg ml-1 and 0.93+/-0.71 microg ml-1, respectively). Netilmicin clearance, volume of distribution and rate of elimination were all significantly higher in this Chinese subpopulation than those predicted for matched Caucasians. Conclusion Alterations in the netilmicin pharmacokinetics observed in our study population might be related to the disease state and/or ethics of the study patient population. Direct application of Caucasian based population pharmacokinetic parameters to this subgroup of Chinese patients may not be appropriate and may result in underdose.

Adolescent↗
PubMed1999

Development of a database for assessing dietary phytoestrogen intake.

For the past two decades, epidemiologists have observed lower risks of lung, breast, prostate, colon, and other cancers in populations that frequently consume fruits and vegetables. Numerous phytoestrogens have been shown to be anticarcinogenic under experimental conditions and may account for at least part of the cancer-prevention effects of fruit and vegetable consumption. These plant constituents include isoflavonoids, coumestans, lignans, phytosterols, and flavonoids. DietSys, the nutrient analysis program associated with the National Cancer Institute Health Habits and History Questionnaire (HHHQ), and other nationally available nutrient analysis databases do not fully assess these constituents. Therefore, we modified DietSys to include these components in foods on the basis of published values. In addition, as part of an epidemiological study of prostate cancer, we modified the food-frequency component of the HHHQ to include the main foods contributing to phytoestrogen intake. Although there are limitations to the consistency and quality of many of the values because they were gathered from a variety of sources, our approach should provide a useful first tool for assessing the epidemiological association between phytoestrogen consumption and cancer risk. Furthermore, this work has already facilitated the identification of the major dietary contributors with phytoestrogen activity and prioritized future laboratory analyses of specific foods toward the development of a more complete and accurate database.

Anticarcinogenic Agents↗
PubMed1999

Immunity to cross-reactive serotypes induced by pneumococcal conjugate vaccines in infants.

Infants were immunized with 1 of the 3 experimental pneumococcal conjugate vaccines that contain 6B and 19F but not 6A or 19A serotypes. Their sera were studied for the capacity to opsonize Streptococcus pneumoniae 6A, 6B, 19A, and 19F serotypes and the level of IgG antibody to the 4 serotypes. Significant increases were observed in the number of infants with detectable opsonophagocytic titers with 3 conjugate vaccines for 6B (vaccine) serotype but with only 2 vaccines for 6A (cross-reactive) serotype. Significant increases were observed with 2 conjugate vaccines for 19F serotype but with only 1 vaccine for 19A serotype. Thus, some conjugate vaccines may elicit cross-protection better than others. In addition, correlations between opsonophagocytic titers and IgG antibody levels by ELISA were high for 6B and 19F serotypes but low for 6A and 19A serotypes. Thus, ELISA may be an inadequate surrogate assay of vaccine response for cross-reactive serotypes.

Adult↗
PubMed1999

Identification of electrically stimulated quadriceps muscles in paraplegic subjects.

This work establishes a method for the noninvasive in vivo identification of parametric models of electrically stimulated muscle in paralyzed individuals, when significant inertial loads and/or load transitions are present. The method used differs from earlier work, in that both the pulse width and stimulus period (interpulse interval) modulation are considered. A Hill-type time series model, in which the output is the product of two factors (activation and torque-angle) is used. In this coupled model, the activation dynamics depend upon velocity. Sequential nonlinear least squares methods are used in the parameter identification. The ability of the model, using identified time-varying parameters, to accurately predict muscle torque outputs is evaluated, along with the variability of the identified parameters. This technique can be used to determine muscle parameter models for biomechanical computer simulations, and for real-time adaptive control and monitoring of muscle response variations such as fatigue.

Algorithms↗
PubMed1999

Behaviour and development of stunted and nonstunted Jamaican children.

In order to examine the mechanism whereby stunted children have poor developmental levels, we compared the behaviour of stunted (N = 78) and nonstunted (N = 26) children aged 12 to 24 months, and examined the relationship of their behaviour to their developmental levels. The effect of nutritional supplementation with or without psychosocial stimulation on the stunted children's behaviour was also examined. The children were observed at home during 4 days over a period of 6 months. The stunted children showed significantly more apathy, and less enthusiasm and variety in exploring, were less happy and more fussy. Caretakers' vocalisations to them were less warm or instructive. Stunted children's activity level, exploratory and happy behaviours were predictive of change in developmental levels measured on the Griffiths Scales, from enrolment to 12 and 24 months later. Supplementation predicted mental age at 12 and 24 months after enrolment, however, it had no significant effect on behaviour.

Child↗
PubMed1999

A case-control study of diet and testicular carcinoma.

No risk factor other than cryptorchidism has been consistently associated with testicular cancer, and the influence of diet on testicular cancer risk has not been extensively explored. A few studies have found increased testicular cancer risk in men whose diets are high in fat, red meats, and milk or low in fruits and vegetables. We evaluated the relationship of dietary factors and risk of testicular cancer and also examined whether this risk varied by type of testicular cancer. We conducted a hospital-based case-control study at The University of Texas M. D. Anderson Cancer Center (Houston, TX) of 160 testicular cancer cases diagnosed between 1990 and 1996 and 136 friend-matched controls. The results of multivariable logistic regression analysis showed that after adjustment for age, education, income, ethnicity, cryptorchidism, and total daily calories, increasing total fat, saturated fat, and cholesterol consumption were associated with increasing risk of nonseminoma testicular cancer, with odds ratios (ORs) for the highest vs. the lowest quartiles of 6.3, 5.3, and 4.6, respectively. The risk for seminoma testicular cancer marginally increased with increasing intake of total fat and saturated fat, with ORs for the highest vs. lowest quartiles of 1.9 and 2.1, respectively. Higher total fat consumption was nearly significantly related to increased mixed germ cell tumor risk, with an OR for highest vs. lowest quartile of 4.2. This study supports the hypothesis that diet (particularly high fat consumption) increases testicular cancer risk in young men. However, the small sample size and the possibility that these observations may be due to bias indicate that the relationship of diet and testicular cancer risk needs to be further examined within a prospective or incident case-control study.

Adolescent↗
PubMed1999

Possible influences of ginseng on the pharmacokinetics and pharmacodynamics of warfarin in rats.

We evaluated the significance of a reported clinical case of drug-drug interaction between ginseng and warfarin using a robust pharmacokinetic/pharmacodynamic approach in a rat model. The influence of ginseng on the pharmacokinetics and pharmacodynamics of oral warfarin after a single dose (2 mg kg(-1)) and at steady state (0.2 mg kg(-1) daily x 6 days) was studied in male Sprague-Dawley rats. Prothrombin time was employed as a pharmacodynamic index. Warfarin plasma concentration and vitamin K content in the ginseng extract were assessed by validated HPLC assays. The pharmacokinetics of warfarin after a single dose were not altered in the presence of ginseng; peak plasma concentration (control 7.8+/-0.5; ginseng 7.3+/-2.5 microg mL(-1)), time to peak (control 2.6+/-1.0; ginseng 3.1+/-1.1 h), elimination half-life (control 14.3+/-5.8; ginseng 10.6+/-3.1 h), and oral clearance (control 17.5+/-3.3; ginseng 20.2+/-5.5 mL h(-1)) were not significantly different (P>0.05). Similarly, alterations in the pharmacokinetics of warfarin were not detected under the multiple dosing paradigm. Under both dosing conditions, ginseng also showed no significant impact on the pharmacodynamics of warfarin as assessed by the area under the prothrombin time vs time curve (multiple dosing; control 3776+/-619, ginseng 3830+/-362 sh) and maximum prothrombin time (control 57.2+/-11.8, ginseng 63.3+/-9.1 s). Furthermore, the content of vitamin K was undetectable in the ginseng decoction. In conclusion, current data obtained in the rat showed no significant impact of ginseng on the pharmacokinetics/pharmacodynamics of warfarin when they are concomitantly administered.

Animals↗