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Biomedical subjects

R Lim

Publications and source records attributed to R Lim.

At least 19 recordsLinked to original sources
PubMed2001

Quality of life in schizophrenia: contributions of anxiety and depression.

A number of studies have demonstrated a strong relationship between quality of life in schizophrenia and general psychopathology measures, and moreover, that the positive, negative, and disorganized symptoms are less related to quality of life. The current investigation examined the relationship between quality of life and symptomatology in 63 stabilized outpatients diagnosed with schizophrenia or schizoaffective disorder. Consistent with other findings, more severe depression, as rated on the Brief Psychiatric Rating Scale (BPRS) was associated with lower general life satisfaction and lower satisfaction with daily living, finances, health, and social life. In addition, higher anxiety ratings on the BPRS were associated with less satisfaction with global quality of life, daily activities, family, health and social relationship, even when controlling for positive symptoms, negative symptoms, or depression. No other symptoms of schizophrenia were as strongly associated with subjective quality of life. Anxiety was also significantly correlated with a number of positive and negative symptoms while depression was substantially less related. These findings, suggest that more precise analyses of general psychopathology, and anxiety in particular, may be necessary to further clarify the factors involved in quality of life in schizophrenia. In addition, these findings suggest future directions for theories of affect and treatment in schizophrenia.

Adolescent↗
PubMed2001

Effects of glia maturation factor overexpression in primary astrocytes on MAP kinase activation, transcription factor activation, and neurotrophin secretion.

Using the replication-defective adenovirus vector, we overexpressed rat glia maturation factor (GMF) in primary astrocyte cultures derived from embryonic rat brains. Among the three isoforms of MAP kinase, there was a big increase in the phosphorylation of p38, as detected with Western blotting using the phosphospecific antibody. Likewise, there was a substantial increase in the phosphorylation of the transcription factor CREB. Using the electrophoretic mobility shift assay (EMSA), we found a stimulation in the transcription factor NF-kappaB. The activations of CREB and NF-kappaB were blocked by inhibitors of either p38 (SB-203580) or MEK (PD-098059), suggesting that they were events downstream of MAK kinase. There was an increased secretion of BDNF and NGF into the conditioned medium, along with an increase in their messenger RNA. The inductions of BDNF and NGF were also blocked by inhibitors of p38 and MEK, as well as by the inhibition of NF-kappaB with a decoy DNA sequence. Taken together, the results suggest that GMF functions intracellularly in astrocytes as a modulator of MAP kinase signal transduction, leading to a series of downstream events including CREB and NF-kappaB activation, resulting in the induction and secretion of the neurotrophins.

Animals↗
PubMed2001

Acoustic transmission across a roughened fluid-fluid interface.

A set of tank experiments was performed to investigate acoustic transmission across a roughened fluid-fluid interface with the intention to test heuristic Bragg scattering predictions used to explain observations of anomalous transmission in field experiments. In the tank experiments, two immiscible fluids (vegetable oil floating on glycerin) formed the layers. Small polystyrene beads were floated at the interface to simulate roughness. An array of hydrophones placed in the bottom layer (glycerin) was used to measure the acoustic levels transmitted across the interface. This array was also employed as a beamformer to determine the apparent angle and sound speed of the scattered signals. Data were acquired at subcritical grazing angles in the frequency range of 100-200 kHz for three different bead diameters and for various configurations in which the locations of the beads floating on the interface were varied. Results of these measurements demonstrated that a significant amount of acoustic energy can be scattered into the bottom layer by beads floating at the interface. The scattered levels increased with increasing bead diameter. However, discrepancies occurred between observed propagation properties and the Bragg predictions. By comparing the processed tank data to a computer simulation of the same it was determined that these discrepancies are a consequence of near-field reception of the scattering by the bead array and ignoring the directionality of the scattering by the beads. Consequences to observations made in field experiments are discussed.

Journal Article↗
PubMed2000

Complete genome sequence of Pseudomonas aeruginosa PAO1, an opportunistic pathogen.

Pseudomonas aeruginosa is a ubiquitous environmental bacterium that is one of the top three causes of opportunistic human infections. A major factor in its prominence as a pathogen is its intrinsic resistance to antibiotics and disinfectants. Here we report the complete sequence of P. aeruginosa strain PAO1. At 6.3 million base pairs, this is the largest bacterial genome sequenced, and the sequence provides insights into the basis of the versatility and intrinsic drug resistance of P. aeruginosa. Consistent with its larger genome size and environmental adaptability, P. aeruginosa contains the highest proportion of regulatory genes observed for a bacterial genome and a large number of genes involved in the catabolism, transport and efflux of organic compounds as well as four potential chemotaxis systems. We propose that the size and complexity of the P. aeruginosa genome reflect an evolutionary adaptation permitting it to thrive in diverse environments and resist the effects of a variety of antimicrobial substances.

Bacterial Proteins↗
PubMed2000

GABA mediates presynaptic inhibition at glycinergic synapses in a rat auditory brainstem nucleus.

Many inhibitory nerve terminals in the mammalian anteroventral cochlear nucleus (AVCN) contain both glycine and GABA, but the reason for the co-localization of these two inhibitory neurotransmitters in the AVCN is unknown. We have investigated the roles of glycine and GABA at synapses on bushy cells in the rat AVCN, using receptor immunohistochemistry and electrophysiology. Our immunohistochemical results show prominent punctate labelling of postsynaptic clusters of glycine receptors and of the receptor clustering protein gephyrin over the surface of bushy cells. In contrast, weak diffuse membrane immunolabelling of GABAA receptors was observed. Whole-cell recordings from bushy cells in AVCN slices demonstrated that evoked inhibitory postsynaptic currents (IPSCs) were predominantly (81 %) glycinergic, based on the decrease in amplitude of the IPSCs in bicuculline (10 microM). This observation was supported by the effect of strychnine (1 microM), which was to decrease the evoked IPSC (to 10 % of control IPSC amplitude) and to produce a greater than 90 % block of spontaneous miniature IPSCs. These results suggest a minor role for postsynaptic GABAA receptors in bushy cells, despite a high proportion of GABA-containing terminals on these cells. Therefore, a role for metabotropic GABAB receptors was investigated. Activation of GABAB receptors with baclofen revealed a significant attenuation of evoked glycinergic IPSCs. The effect of baclofen was presynaptic, as indicated by a lack of change in the mean amplitude of spontaneous IPSCs. Significantly, the decrease in the amplitude of evoked glycinergic IPSCs observed following repetitive nerve stimulation was reduced in the presence of the GABAB antagonist, CGP 35348. This indicates that synaptically released GABA can activate presynaptic GABAB receptors to reduce transmitter release at glycinergic synapses. Our results suggest specific pre- versus postsynaptic physiological roles for GABA and glycine in the AVCN.

Animals↗
PubMed2000

Transfection of C6 glioma cells with glia maturation factor upregulates brain-derived neurotrophic factor and nerve growth factor: trophic effects and protection against ethanol toxicity in cerebellar granule cells.

Glial cells play active roles in neuronal survival, as well as neuroprotection against toxic insult. Recent studies suggest that the brain protein glia maturation factor (GMF) is involved in intracellular signaling in glia. This study investigated whether or not GMF plays a role in the survival-promoting and neuroprotective functions of glia. C6 glioma cells were transfected in vitro with GMF utilizing an adenovirus vector. The transfected cells overexpressed GMF intracellularly, but did not secrete the protein. The conditioned medium (CM) was obtained from the GMF-transfected cells (CM-GMF) and tested on primary neuronal cultures, consisting of cerebellar granule cells (CGC). The CGC cultures were utilized because these cultures have a background level of cell death, and the survival-promoting, i.e. neurotrophic effect, of the CM could be tested. In addition, since CGC cultures are ethanol-sensitive (ethanol enhances neuronal death), the neuroprotective effect of the CM against ethanol-induced cell death was tested also. We demonstrated that the CM-GMF had an enhanced neurotrophic effect as well as an increased neuroprotective effect against ethanol-induced cell death compared to control CM obtained from untransfected C6 cells (CM-Mock) or CM obtained from cells transfected with an unrelated gene (CM-LacZ). Because neurotrophins have trophic and protective effects, we investigated whether GMF-transfection upregulated the expression of neurotrophins in C6 cells. RT-PCR verified that GMF-transfected C6 cells had increased mRNA levels for BDNF and NGF. Immunoblotting corroborated the RT-PCR results and indicated that CM-GMF contained greater concentrations of BDNF and NGF protein compared to CM-Mock and CM-LacZ. A soluble TrkB-IgG fusion protein, which selectively binds BDNF and prevents its binding to the neuronal TrkB receptor, eliminated the neurotrophic effect of CM-GMF; whereas anti-NGF antibody was ineffective in preventing this effect, suggesting that the neurotrophic effect was due to BDNF. On the other hand, both the TrkB-IgG fusion protein and anti-NGF reduced neuroprotection, suggesting that BDNF and NGF both contribute to the neuroprotective effect of CM-GMF. In conclusion, GMF upregulates the expression of BDNF and NGF in C6 cells, and these factors exert neurotrophic and neuroprotective functions on primary neurons.

Adenoviridae↗
PubMed2000

Iris color and cataract: the Blue Mountains Eye Study.

PURPOSE: To investigate the relationship between eye color and cataract. METHODS: A population-based cross-sectional study (N = 3654) was conducted near Sydney, Australia. Lens photographs were graded for cortical, nuclear, and posterior subcapsular cataract. Iris color was assessed at slit-lamp examination by comparison with four photographic standards. RESULTS: Eyes with dark brown irises were more likely to have nuclear (adjusted odds ratio, 1.59; 95% confidence interval [CI], 1.03 to 2.28) or posterior subcapsular cataract (adjusted odds ratio, 2.50; 95% CI, 1.57 to 3.98) than eyes with lighter-colored irises. CONCLUSIONS: People with dark brown eyes are at increased risk of cataract and should be encouraged to protect their eyes from direct exposure to sunlight.

Cataract↗
PubMed2000

Activation of nuclear factor-kappaB in C6 rat glioma cells after transfection with glia maturation factor.

The 17-kDa endogenous brain protein glia maturation factor (GMF) was transfected into C6 rat glioma cells using a replication-defective human adenovirus vector. The cells overexpressed GMF but did not secrete the protein into the medium. Transfection with GMF led to the activation of the transcription factor nuclear factor-kappaB (NF-kappaB), as evidenced by electrophoretic mobility shift assay of the nuclear extract, using a double-stranded oligonucleotide probe containing the consensus binding sequence for NF-kappaB. The specificity of binding was demonstrated by competition with unlabeled probe and by the nonbinding of the mutant probe. Binding was detectable as early as 3 h after transfection, peaked at 6 and 12 h, and gradually declined thereafter. The observed NF-kappaB activation was reduced by cotransfection with catalase and by the presence of high concentrations of pyruvate in the medium, suggesting the involvement of H2O2. The p38 mitogen-activated protein kinase inhibitor SB-203580 also suppressed the GMF-activated NF-kappaB, suggesting the involvement of the p38 signal transduction cascade. On the other hand, the phorbol ester phorbol 12-myristate 13-acetate activated NF-kappaB whether or not GMF was overexpressed. Along with NF-kappaB activation was an enhanced expression of superoxide dismutase (SOD), which was suppressed if NF-kappaB nuclear translocation was blocked by its specific decoy DNA, implicating NF-kappaB as an upstream mediator of this antioxidant enzyme. The p38 inhibitor SB-203580 also blocked the GMF-activated SOD. As NF-kappaB and SOD are both pro-survival signals, the results suggest a cytoprotective role for endogenous GMF in glial cells.

Animals↗
PubMed2000

Acoustic scattering by a three-dimensional elastic object near a rough surface

The ensemble-averaged field scattered by a smooth, bounded, elastic object near a penetrable surface with small-scale random roughness is formulated. The formulation consists of combining a perturbative solution for modeling propagation through the rough surface with a transition (T-) matrix solution for scattering by the object near a planar surface. All media bounding the rough surface are assumed to be fluids. By applying the results to a spherical steel shell buried within a rough sediment bottom, it is demonstrated that the ensemble-averaged "incoherent" intensity backscattered by buried objects illuminated with shallow-grazing-angle acoustic sources can be well enhanced at high frequencies over field predictions based on scattering models where all environmental surfaces are planar. However, this intensity must compete with the incoherent intensity scattered back from the interface itself, which can defeat detection attempts. The averaged "coherent" component of the field maintains the strong evanescent spectral decay exhibited by flat interface predictions of shallow-angle measurements but with small deviations. Nevertheless, bistatic calculations of the coherent field suggest useful strategies for improving long-range detection and identification of buried objects.

Journal Article↗
PubMed1999

Enhanced expression of neurotrophic factors by C6 rat glioma cells after transfection with glia maturation factor.

Glia maturation factor (GMF) is a 17-kDa protein unique to the nervous system. Although GMF was initially characterized as a growth/differentiation factor, the absence of a leader sequence and its intracellular localization in normal brain suggest an intracellularfunction as well. In this paper we transfected the C6 glioma cells with GMF cDNA by infecting the cells with a GMF/adenovirus construct. The transfected cells overexpressed GMF but did not secret the protein into the culture medium. However, the transfected cells showed an increased expression of the neurotrophic factors including nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF). The increase in neurotrophic activity of the C6 cell conditioned medium was demonstrable by its ability to promote neurite outgrowth in PC12 cells.

Adenoviridae↗
PubMed1999

Quantal size is correlated with receptor cluster area at glycinergic synapses in the rat brainstem.

1. Whole-cell patch electrode recordings of glycinergic miniature inhibitory postsynaptic currents (mIPSCs) were obtained in neurons of the rat anteroventral cochlear nucleus (AVCN). Mean mIPSC peak amplitude was found to vary considerably between AVCN neurons (range, -19.1 to -317.9 pA; mean +/- s.d., -159.1 +/- 100.7 pA; 14 cells). 2. Immunolabelling of glycinergic receptor clusters in AVCN neurons was performed using antibodies against the glycine receptor clustering protein gephyrin. Measurements of the area of gephyrin immunoreactive clusters were obtained using confocal fluorescence microscopy. These measurements showed a large variability in cluster area, not only in the same cell (mean coefficient of variation, c.v., 0.66 +/- 0.18; 16 cells), but also in mean cluster area between cells (range, 0.21-0.84 microm2; 16 cells). 3. A possible relationship between mIPSC amplitude and receptor cluster area was investigated in a further series of experiments, in which mIPSCs recordings and immunolabelling of glycine receptor clusters were obtained for the same cells. In these experiments, AVCN neurons were identified using intracellular labelling with neurobiotin. Successful results using a combination of whole-cell recordings, neurobiotin identification and immunolabelling were obtained for a total of 10 AVCN neurons. Analysis of the results revealed a positive, statistically significant correlation between mean receptor cluster size and mean mIPSC amplitude (P < 0.05, 10 cells, Spearman's correlation test). 4. These results provide direct experimental evidence supporting a hypothesis of central glycinergic transmission in which synaptic strength may be regulated by changes in the size of the postsynaptic receptor region.

Animals↗
PubMed1999

Male breast carcinoma: a review of 229 patients who presented to the Princess Margaret Hospital during 40 years: 1955-1996.

BACKGROUND: A single-institution review of clinical presentation, treatment, and outcome of male breast carcinoma was conducted. METHODS: Data obtained by chart review of 229 cases were analyzed with respect to clinical presentation, treatment choice, significant prognostic factors, and survival. The patients were analyzed both as a single cohort and as four cohorts grouped according to decade of diagnosis. RESULTS: Presentation occurred at a median age of 63 years, most often with a self-detected lump. Pathology consisted of subtypes similar to those of female breast carcinoma. The majority of tumors were larger than 2 cm in greatest dimension. Lymph node status, hormone receptors, and histologic and nuclear grade were underreported. Primary, adjuvant, and advanced disease treatment practices were reviewed over time. The 5-year disease free survival (DFS), overall survival (OS), and local control were 47%, 53%, and 91%, respectively. No difference in outcome by decade of diagnosis was observed. Negative lymph nodes and adjuvant hormone treatment predicted for better DFS and OS. Younger age and Stage 0 also predicted for better OS. CONCLUSIONS: Compared with data from female breast carcinoma patients, 5-year OS for this series was low; however, when these patients were separated by lymph node status, survival was similar for those with axillary lymph node metastases. Despite a change in standard primary surgical treatment and an increased use of chemotherapy and hormone therapy over the study period, no difference in outcome was observed among these males. In the absence of prospective, randomized clinical trials, collection of comprehensive data on the presentation and management of male breast carcinoma may help to optimize clinical care.

Adult↗
PubMed1999

Effects of local heparin administration on coronary thrombin activity during percutaneous transluminal coronary angioplasty.

Simultaneously obtained blood samples from the coronary sinus and systemic arterial circulation were analyzed for antithrombin III (ATIII) activity and fibrinopeptide A (FpA) concentration in nine patients undergoing elective PTCA in order to determine the effects of locally delivered heparin. Samples were obtained at the following designated times: prior to the administration of systemic heparin (period I); 5 min following a loading dose of systemic heparin (period II); 5 min following the final balloon inflation but prior to local delivery (period III); and 5 min following the administration of 4,000 units of unfractionated heparin using a local delivery catheter system (period IV). We found consistent increases in both systemic arterial (P = 0.006) and coronary sinus (P = 0.0002) ATIII activity with systemic heparinization designed to prolong the activated clotting time to 300 sec. However, local delivery of heparin further increased coronary sinus ATIII activity (P = 0.003, period III vs. period IV). FpA concentration decreased in both systemic arterial (P < 0.0001) and coronary sinus (P < 0. 0001) samples following systemic heparinization. Moreover, local delivery of heparin further decreased coronary sinus FpA concentration (P = 0.04). Thus, on a background of intense anticoagulation during PTCA, the local delivery of 4,000 units of unfractionated heparin confers incremental antithrombotic activity. Cathet. Cardiovasc. Intervent. 48:84-88, 1999.

Angioplasty, Balloon, Coronary↗