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Biomedical subjects

L Chang

Publications and source records attributed to L Chang.

At least 19 recordsLinked to original sources
PubMed2002

The effect of the 5-HT3 receptor antagonist, alosetron, on brain responses to visceral stimulation in irritable bowel syndrome patients.

AIM: To conduct a placebo-controlled functional brain imaging study to assess the effect of the 5-hydroxytryptamine-3 receptor antagonist, alosetron, on irritable bowel syndrome symptoms, regional brain activation by rectosigmoid distension and associated perceptual and emotional responses. METHODS: Fifty-two non-constipated irritable bowel syndrome patients (28 female) were enrolled in a randomized, placebo-controlled trial with alosetron (1-4 mg b.d.). Thirty-seven patients completed both brain scans following randomization. Rectosigmoid stimulation was performed with a computer-controlled barostat. Changes in regional cerebral blood flow were assessed using H215O positron emission tomography. Stimulus ratings and changes in gastrointestinal symptoms were assessed using verbal descriptor scales. RESULTS: Alosetron, but not placebo, treatment was associated with a decrease in symptom ratings, and reductions in emotional stimulus ratings. Compared to baseline, alosetron treatment was associated with reduced regional cerebral blood flow in bilateral frontotemporal and various limbic structures, including the amygdala. Compared to placebo, decreases in activity of the amygdala, ventral striatum, hypothalamus and infragenual cingulate gyrus were significantly greater after alosetron. CONCLUSIONS: In non-constipated irritable bowel syndrome patients, 3 weeks of treatment with a 5-hydroxytryptamine-3 receptor antagonist decreases brain activity in response to unanticipated, anticipated and delivered aversive rectal stimuli in structures of the emotional motor system, and this is associated with a decrease in gastrointestinal symptoms.

Adult↗
PubMed2002

In vivo production of interferon beta by human Tenon's fibroblasts; a possible mediator for the development of chronic conjunctival inflammation.

BACKGROUND: Chronic inflammation may develop from failure of the immune system to deactivate itself during resolution of the wound healing response, and is recognised as a major risk factor for trabeculectomy failure. Fibroblast/T cell interactions may contribute to aggressive scarring. Our previous research showed that in vitro human Tenon's fibroblast produced interferon beta was responsible for preventing T cell apoptosis, suggesting that this interaction could contribute to the development of chronic inflammation. METHODS: Immunohistological techniques were used to investigate the in vivo components of this particular fibroblast/T cell interaction in conjunctival biopsies from glaucoma patients undergoing filtration surgery. RESULTS: Fibroblast produced interferon beta and T lymphocytes were identified in human conjunctiva. CONCLUSION: The components of fibroblast mediated prevention of T cell apoptosis were identified in vivo, suggesting that the development of this interaction is possible and that it may contribute to the development of chronic inflammation and excessive scarring.

Aged↗
PubMed2001

Loss of dopamine transporters in methamphetamine abusers recovers with protracted abstinence.

Methamphetamine is a popular drug of abuse that is neurotoxic to dopamine (DA) terminals when administered to laboratory animals. Studies in methamphetamine abusers have also documented significant loss of DA transporters (used as markers of the DA terminal) that are associated with slower motor function and decreased memory. The extent to which the loss of DA transporters predisposes methamphetamine abusers to neurodegenerative disorders such as Parkinsonism is unclear and may depend in part on the degree of recovery. Here we assessed the effects of protracted abstinence on the loss of DA transporters in striatum, in methamphetamine abusers using positron emission tomography and [(11)C]d-threo-methylphenidate (DA transporter radioligand). Brain DA transporters in five methamphetamine abusers evaluated during short abstinence (<6 months) and then retested during protracted abstinence (12-17 months) showed significant increases with protracted abstinence (caudate, +19%; putamen, +16%). Although performance in some of the tests for which we observed an association with DA transporters showed some improvement, this effect was not significant. The DA transporter increases with abstinence could indicate that methamphetamine-induced DA transporter loss reflects temporary adaptive changes (i.e., downregulation), that the loss reflects DA terminal damage but that terminals can recover, or that remaining viable terminals increase synaptic arborization. Because neuropsychological tests did not improve to the same extent, this suggests that the increase of the DA transporters was not sufficient for complete function recovery. These findings have treatment implications because they suggest that protracted abstinence may reverse some of methamphetamine-induced alterations in brain DA terminals.

Adult↗
PubMed2001

Brain areas specific for attentional load in a motion-tracking task.

Although visual attention is known to modulate brain activity in the posterior parietal, prefrontal, and visual sensory areas, the unique roles of these areas in the control of attentional resources have remained unclear. Here, we report a dissociation in the response profiles of these areas. In a parametric functional magnetic resonance imaging (fMRI) study, subjects performed a covert motion-tracking task, in which we manipulated "attentional load" by varying the number of tracked balls. While strong effects of attention--independent of attentional load--were widespread, robust linear increases of brain activity with number of balls tracked were seen primarily in the posterior parietal areas, including the intraparietal sulcus (IPS) and superior parietal lobule (SPL). Thus, variations in attentional load revealed different response profiles in sensory areas as compared to control areas. Our results suggest a general role for posterior parietal areas in the deployment of visual of attentional resources.

Adult↗
PubMed2001

Neural correlates of attention and working memory deficits in HIV patients.

OBJECTIVES: To evaluate the neural correlates of attention and working memory deficits in patients with HIV-1. METHOD: fMRI was used to evaluate brain activity in 11 patients with HIV and 11 age-, sex-, education-, and handedness-matched seronegative subjects, while performing a battery of tasks that required different levels of attention for working memory. RESULTS: Patients with HIV showed greater brain activation (blood oxygenation level dependent signal changes) in some regions compared with control subjects while performing the same tasks. For the simpler tasks, patients with HIV showed greater activation in the parietal regions. However, with more difficult tasks, patients with HIV showed greater activation additionally in the frontal lobes. Reaction times during these tasks were slower but accuracy was similar in the patients with HIV compared with control subjects. CONCLUSION: Injury to the neural substrate caused by HIV infection may necessitate greater attentional modulation of the neural circuits, hence a greater use of the brain reserve; additional activation of the frontal lobes is required to perform the more complex tasks. The task-dependent increased frontal activation in patients with HIV suggests that the neural correlate of attentional deficits may be excessive attentional modulation as a result of frontostriatal brain injury.

AIDS Dementia Complex↗
PubMed2001

Brain metabolite concentration and dementia severity in Alzheimer's disease: a (1)H MRS study.

OBJECTIVE: (1)H-MRS studies have shown abnormalities in brain levels of myo-inositol (mI) and N-acetyl aspartate (NAA) in AD, but the relation of these abnormalities with dementia severity was not examined. The authors sought to determine whether altered brain levels of mI and other metabolites occur in mild AD and whether they change as dementia severity worsens. METHODS: The authors used (1)H-MRS with external standards to measure absolute brain concentrations of mI, NAA, total creatine (Cr), and choline (Cho)-containing compounds in 21 subjects with AD and 17 age- and sex-matched controls in occipital and left and right parietal regions. RESULTS: Concentrations of NAA were significantly decreased, whereas mI and Cr concentrations were significantly increased in all three brain regions in subjects with AD compared with controls. Higher concentrations of mI and Cr occurred even in mild AD. A discriminant analysis of the (1)H-MRS data combined with CSF volume measurements distinguished subjects with AD, ranging from mild to severe dementia, from controls with 100% correct classification. NAA concentration, though not other metabolites, was positively correlated with Mini-Mental State Examination score. CONCLUSION: The measurements with (1)H-MRS of absolute metabolite concentrations in the neocortex showed abnormal concentrations of brain metabolites in AD; these metabolite concentrations do not necessarily correlate with disease severity. Although changes in myo-inositol and creatine occur in the early stages of AD, abnormalities of N-acetyl aspartate do not occur in mild AD but progressively change with dementia severity. Further, subjects with mild AD can be differentiated from controls with (1)H-MRS.

Aged↗
PubMed2001

Local cerebral glucose utilization decreases after heatstroke onset in rats.

The quantitative autoradiographic 2-[(14)C]-deoxy-D-glucose methods were used to assess the local cerebral glucose utilization (LCGU) in 46 brain structures in rats suffering from heatstroke. Heatstroke was induced by exposing the animals to an ambient temperature of 42 degrees C. The time at which the local cerebral blood flow (CBF) and mean arterial pressure (MAP) decreased from their peak levels was taken as the onset of heatstroke. Control rats were exposed to a temperature of 24 degrees C. The values of local CBF, MAP and means of total LCGU after heatstroke onset were all significantly lower than those in control rats. However, the values of colonic temperature were greater. Thus, it appears that the decreased cerebral metabolism and perfusion can be due to secondary effect of hypertension after heatstroke onset.

Animals↗
PubMed2001

Brain proton magnetic resonance spectroscopy in children exposed to methamphetamine in utero.

OBJECTIVE: To examine the possible neurotoxic effects of prenatal methamphetamine exposure on the developing brain using 1H-MRS. METHODS: Methamphetamine-exposed children (n = 12) and age-matched unexposed control subjects (n = 14) were evaluated with MRI, localized 1H-MRS, and a Child Behavior Checklist. Metabolite concentrations of N-acetyl-containing compounds (NA), total creatine (Cr), choline-containing compounds, myoinositol, and glutamate + glutamine were measured in the frontal white matter and striatum. RESULTS: Despite an absence of visible structural abnormalities in either group, children exposed to methamphetamine in utero had higher [Cr] (+10%, p = 0.02) in the striatum. [NA], primarily a measure of N-acetylaspartate, was normal in both regions, which suggests no significant neuronal loss or damage in the two brain regions examined. There were no differences in reported behavior problems among the methamphetamine-exposed children relative to the unexposed group. CONCLUSIONS: The authors found increased [Cr] in the striatum with relatively normal [NA] in children exposed to methamphetamine. These findings suggest an abnormality in energy metabolism in the brains of children exposed to methamphetamine in utero.

Brain↗
PubMed2001

Fragmented condensate ground state of trapped weakly interacting bosons in two dimensions.

The ground state and its structure for a rotating, harmonically trapped N-boson system with a weak repulsive contact interaction are studied as the angular momentum L increases up to 3N. We show that the ground state is generally a fragmented condensate due to angular momentum conservation. In response to an (arbitrarily weak) asymmetric perturbation of the trap, however, the fragmented ground state can be transformed into a single condensate state. We manifest this intrinsic instability by calculating the conditional probability distributions, which show patterns analogous to the boson density distributions predicted by mean-field theory.

Journal Article↗
PubMed2001

c-Jun N-terminal kinase activation is required for the inhibition of neovascularization by thrombospondin-1.

Thrombospondin-1 (TSP-1) is a potent inhibitor of angiogenesis that acts directly on endothelial cells via the CD36 surface receptor molecule to halt their migration, proliferation, and morphogenesis in vitro and to block neovascularization in vivo. Here we show that inhibitory signals elicited by TSP-1 did not alter the ability of inducers of angiogenesis to activate p42 and p44 mitogen-activated protein kinase (MAPK). Rather, TSP-1 induced a rapid and transient activation of c-Jun N-terminal kinases (JNK). JNK activation by TSP-1 required engagement of CD36, as it was blocked by antagonistic CD36 antibodies and stimulated by short anti-angiogenic peptides derived from TSP-1 that act exclusively via CD36. TSP-1 inhibition of corneal neovascularization induced by bFGF was severely impaired in mice null for JNK-1, pointing to a critical role for this stress-activated kinase in the inhibition of neovascularization by TSP-1.

Angiogenesis Inhibitors↗
PubMed2001

Purification and characterization of a chymotrypsin inhibitor from the venom of Ophiophagus hannah (King Cobra).

A chymotrypsin inhibitor from the venom of Ophiophagus hannah was isolated by a combination of ion-exchange chromatography and reverse phase HPLC. Amino acid sequence analysis revealed that this protein consists of 58 amino acids, six of these being cysteine residues and is highly homologous to Kunitz-type protease inhibitors. ESI-mass spectrum showed that the protein had a mass of 6493, which is in agreement with that predicted from its primary structure. In contrast to P1 Leu, Met, Phe, Trp, and Tyr appearing in other chymotrypsin inhibitors, a P1 Asn in the novel inhibitor may cause a weak binding (Ki = 3.52 microM) with chymotrypsin. Phylogenetic analysis suggests that the functional variations of the chymotrypsin inhibitor and other Kunitz-type inhibitors probably distinguish from dendrotoxins by accelerated evolution.

Amino Acid Sequence↗
PubMed2001

Prostate cancer risk and serum levels of insulin and leptin: a population-based study.

BACKGROUND: In a previous study of Chinese men, we found that men with a higher waist-to-hip ratio (WHR) have a higher prostate cancer risk. Because leptin and insulin are related to body fat distribution, we examined whether leptin and insulin were associated with prostate cancer risk. METHODS: Blood samples were collected from 128 case patients with incident prostate cancer and from 306 healthy control subjects randomly selected from residents of Shanghai, CHINA: Epidemiologic information and anthropometric measurements were collected in personal interviews. Serum leptin, insulin, and sex hormone levels were measured by radioimmunoassay, and insulin-like growth factor-I (IGF-I) was measured by enzyme-linked immunosorbent assay. Multiple logistic regression analyses were used to estimate odds ratios for prostate cancer in relation to serum insulin and leptin levels. All statistical tests were two-sided. RESULTS: After adjustment for body mass index, WHR, IGF-I, and sex hormone levels, higher serum insulin levels were associated with a statistically significantly elevated risk of prostate cancer (P<.001). Men in the highest tertile of insulin levels had a 2.56-fold (95% confidence interval [CI] = 1.38 to 4.75) risk of prostate cancer compared with men in the lowest tertile. Regardless of the tertile level of WHR, higher serum insulin levels were associated with an increased risk of prostate cancer: Men in the highest tertiles of WHR (>0.900) and insulin (>8.83 microU/mL) had 8.55 times (95% CI = 2.80 to 26.10) the prostate cancer risk of men in the lowest tertiles of both, and those in the lowest tertile of WHR (<0.873) and highest tertile of insulin had 4.30 times (95% CI = 1.17 to 15.70) the risk. By contrast, the association between leptin levels and prostate cancer risk was not statistically significant. CONCLUSION: Our results suggest that serum insulin levels may influence the risk of prostate cancer in Chinese men. Further research, especially prospective studies, is needed to confirm these findings in high-risk populations and to clarify the underlying mechanisms involved.

Age Factors↗
PubMed2001

Mammalian MAP kinase signalling cascades.

Mitogen-activated protein kinases (MAPKs) are important signal transducing enzymes, unique to eukaryotes, that are involved in many facets of cellular regulation. Initial research concentrated on defining the components and organization of MAPK signalling cascades, but recent studies have begun to shed light on the physiological functions of these cascades in the control of gene expression, cell proliferation and programmed cell death.

Animals↗
PubMed2001

Kinetic analyses of stability of simple and complex retroviral vectors.

Simple and complex retroviral vectors derived from Moloney murine leukemia virus (MLV) and human immunodeficiency virus type 1 (HIV-1), respectively, are useful tools for gene transfer studies. However, factors affecting the stability of these vectors have not been carefully investigated. Here we studied the stability factors on vesicular stomatitis viral envelope glycoprotein (VSV-G)-pseudotyped MLV- and HIV-1-derived vectors. Analysis of the ratio of defective particles versus infectious units using electron microscopy and a functional transduction assay revealed that both vectors consisted of high numbers of defective particles ( approximately 100-350:1), which could be reduced ( approximately 10-20:1) by centrifugation. Frequent freeze-and-thaw rapidly decreased vector titer in the first three to five cycles and stabilized thereafter. Both viral vectors were sensitive to temperatures above 37 degrees C but more stable at temperatures below 37 degrees C, exhibiting a two-phase inactivation kinetic starting with a steep inactivation phase, followed by a more leveled phase. Interestingly, HIV-1-derived vectors were significantly more stable than MLV-derived vectors at higher temperatures (>37 degrees C). Both vectors were rapidly destabilized at pH either below or above 7.0. Incubation with human or mouse serum significantly inhibited VSV-G-pseudotyped vector activities. Preheated human serum still reduced vector half-lives to approximately 50% (150 min), suggesting that certain inactivation factors are not heat-labile. Analyses of these stability factors may improve future production and applications of retroviral and lentiviral vectors.

Animals↗
PubMed2001

Automatic scan prescription for brain MRI.

Diagnostic brain MRI scans are usually performed by trained medical technologists who manually prescribe the position and orientation of a scanning volume. In this study, a fully automatic computer algorithm is described which compensates for variable patient positioning and acquires brain MRI scans in a predefined reference orientation. The method involves acquiring a rapid water-only pilot scan, segmenting the brain surface, and matching it to a reference surface. The inverse matching transformation is then used to adapt a geometric description of the desired scanning volume, defined relative to the reference surface, to the current patient. Both pilot scan and processing are performed within 30 sec. The method was tested in 25 subjects, and consistently recovered orientation differences between the reference and each subject to within +/-5 degrees. Compared to manual prescription, automatic scan prescription promises many potential benefits, including reduced scan times, reproducible scan orientations along anatomically preferable orientations, and better reproducibility for longitudinal studies. Magn Reson Med 45:486-494, 2001.

Algorithms↗
PubMed2001

Biexponential modeling of multigradient-echo MRI data of the brain.

Functional MRI (fMRI) using fast multigradient-echo acquisition methods allows the quantitative determination of the relevant parameter T2*. Previously, the TE-dependent signal decay has been modeled with a monoexponential function despite the complex composition of the brain. In this study, biexponential modeling was used to evaluate the relaxation of brain parenchyma and blood separate from that of cerebrospinal fluid. Single-shot multigradient-echo data acquired with spiral or EPI techniques were analyzed. In phantom experiments the biexponential method proved to be accurate. Compared to the biexponential procedure, the monoexponential model overestimated T2* (72.2 msec vs. 65.3 msec) and underestimated DeltaT2* (2.96 msec vs. 3.19 msec) during visual stimulation. The biexponential method may allow intrinsic correction for partial volume effects due to cerebrospinal fluid. The activation-induced parameter changes are detected with a sensitivity equal to that of a monoexponential method. The resulting T2* and DeltaT2* values describe the experimental data more accurately.

Brain↗
PubMed2001

The role of nitric oxide in hyperoxic lung injury in premature rats.

To investigate the role of nitric oxide (NO) in hyperoxic lung injury, the 3-day-old preterm rats were randomly assigned to four groups: group I (hyperoxia group), group II (hyperoxia + Nw-nitro-L-arginine methyl ester (L-NAME) group), group III (air group), and group IV (air + L-NAME) group. Group I and II were exposed to > or = 90% O2 for 3 or 7 days. Group II and IV received subcutaneous L-NAMEy on daily basis (20 mg/kg). After 3 day or 7 day exposure, the lung wet weight/dry weight ratio (W/D), total protein and malondialdehyde (MDA) in bronchoalveolar lavage fluid (BALF) and lung pathology were examined in all groups. NO content, expression of endothelial NOS (eNOS) and inducible NOS (iNOS) in lungs were measured in group I and III. Our results showed that after 3 day exposure, group I appeared acute lung injury characterized by the increase of MDA content (P < 0.01) and the presence of hyperaemia, red cell extravasation and inflammatory infiltration; after 7 day exposure, except MDA, total protein and W/D were also increased in comparison with group III (P < 0.01, 0.05), pathological changes were more severe than those after 3 day exposure. After 3 and 7 day exposure, total protein in group II was significantly increased as compared with group I (P < 0.01 for both). The pulmonary acute inflammatory changes were more obvious in group II than in group I. Occasionally, mild hemorrhage was detected in the lungs of group IV. BALF protein content in group IV was higher than that in group III after 7 day exposure (P < 0.01). After 3 and 7 day exposure, NO content in BALF were all significantly elevated in group I as compared with group III (P < 0.01 for all). In the lungs of group I, strong immunostaining for iNOS was observed in airway and alveolar epithelia, inflammatory cells, which were stronger than those in group III. Expression of iNOS in rats after 7 day hyperoxic exposure was stronger than that after 3 day exposure. Shortly after 7 day exposure, stronger immunostaining for eNOS in airway epithelia in group I than that in group III was seen. Our study suggested that treatment with L-NAME worsened acute hyperoxic lung injury in preterm rats and also had a deleterious effect on the rats exposed to air, indicating that endogenous nitric oxide may play a protective role in rats under both physiological and hyperoxic status. Hyperoxia can significantly upregulate the expression of iNOS and eNOS in inflammatory cells, epithelia in the lungs of preterm rats, promote NO generation, which suggests that endogenous NO may mediate the hyperoxic pulmonary damage. Over-stimulation of iNOS may contribute to the pathogenesis of hyperoxic lung injury. NO may have dual roles in pulmonary oxygen toxicity.

Animals↗