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Biomedical subjects

C S Lim

Publications and source records attributed to C S Lim.

At least 19 recordsLinked to original sources

Partial anatomical and physiological characterization and dissociated cell culture of the nervous system of the marine mollusc Aplysia kurodai.

Snail nervous systems are powerful tools for neurobiological studies as the biophysical properties of the giant neurons and their neural circuits can be examined in relation to specific behaviors of animals. The marine mollusc Aplysia californica is particularly useful for analyzing the components of learning and memory at the molecular and cellular levels. Here we partially examined the nervous systems of two species (A. kurodai and A. juliana) commonly found along the Korean coast in comparison with that of A. californica, one of the American marine snails. A. kurodai appeared to be identical to A. californica in both anatomical and physiological properties of the nervous system. A. juliana could be distinguished from A. californica in certain morphological aspects of the nervous system. The hemolymph either from A. kurodai or from A. juliana was required for effectively elongating neurite outgrowth of A. kurodai neurons in dissociated cell culture. The cultured cells retained neuronal properties such as neurite outgrowth, synapse formation, and generation of action potentials. The sensory cells of A. kurodai in dissociated cultures showed a response to serotonin (5-HT) of spike broadening and enhanced membrane excitability as in intact ganglia. Therefore, the nervous system and dissociated neuronal culture of A. kurodai may be useful for studying learning and memory in the context-of well-defined neural circuits of A. californica.

Action Potentials

Sequence-independent inhibition of RNA transcription by DNA dumbbells and other decoys.

DNA dumbbells are stable, short segments of double-stranded DNA with closed nucleotide loops on each end, conferring resistance to exonucleases. Dumbbells may be designed to interact with transcription factors in a sequence-specific manner. The internal based paired sequence of DNA dumbbells in this study contains the X-box, a positive regulatory motif found in all MHC class II DRA promoters. In electrophoretic mobility shift assays (EMSAs), dumbbells and other oligonucleotides ('decoys') with the core X-box sequence were found to compete with the native strand for binding to X-box binding proteins (including RFX1). However, only the X-box dumbbell was capable of forming detectable complexes with such proteins using EMSA. In a model cell system, dumbbells were tested for their ability to block RFX1VP16 activation of a plasmid containing multiple repeats of the X-box linked to the CAT gene. While it appeared that dumbbells could block this activation, the effect was non-specific. This and further evidence suggests an inhibition of transcription, most likely via an interaction with the general transcriptional machinery.

Animals

Mutation in the phosphorylation sites of MAP kinase blocks learning-related internalization of apCAM in Aplysia sensory neurons.

The synaptic growth that accompanies 5-HT-induced long-term facilitation of the sensory to motor neuron connection in Aplysia is associated with the internalization of apCAM at the surface membrane of the sensory neuron. We have now used epitope tags to examine the fate of each of the two apCAM isoforms (membrane bound and GPI-linked) and find that only the transmembrane form is internalized. This internalization can be blocked by overexpression of transmembrane constructs with a single point mutation in the two MAPK consensus sites, as well as by injection of a specific MAPK antagonist into sensory neurons. These data suggest MAPK phosphorylation at the membrane is important for the internalization of apCAMs and, thus, may represent an early regulatory step in the growth of new synaptic connections that accompanies long-term facilitation.

Animals

Control of C. elegans larval development by neuronal expression of a TGF-beta homolog.

The Caenorhabditis elegans dauer larva is specialized for dispersal without growth and is formed under conditions of overcrowding and limited food. The daf-7 gene, required for transducing environmental cues that support continuous development with plentiful food, encodes a transforming growth factor-beta (TGF-beta) superfamily member. A daf-7 reporter construct is expressed in the ASI chemosensory neurons. Dauer-inducing pheromone inhibits daf-7 expression and promotes dauer formation, whereas food reactivates daf-7 expression and promotes recovery from the dauer state. When the food/pheromone ratio is high, the level of daf-7 mRNA peaks during the L1 larval stage, when commitment to non-dauer development is made.

Amino Acid Sequence

Colour Doppler imaging in giant cell (temporal) arteritis: serial examination and comparison with non-arteritic anterior ischaemic optic neuropathy.

The ophthalmological manifestations of giant cell arteritis (GCA) present a difficult diagnostic and management problem to the ophthalmologist. The orbital circulation is frequently involved in the disease process. The effects of GCA on orbital blood flow assessed by colour Doppler imaging (CDI) were investigated in this study. Serial CDI examinations of the orbital blood vessels were performed (at presentation, 2 days, 1 week and at 1 month) on 7 patients with GCA. CDI examination at presentation was also performed on 4 patients with non-arteritic anterior ischaemic optic neuropathy (AION) for comparison. Blood flow could not be detected in up to three arteries in the affected (ipsilateral) orbit of 6 GCA patients at presentation. Five of these patients were also found to have undetectable blood flow in the posterior ciliary arteries of the contralateral orbit. Serial CDI examination revealed blood flow alterations in arteritic patients despite treatment. Return of blood flow to normal was slow, and related to the clinical features. By contrast, only 1 of the patients with non-arteritic AION showed undetectable blood flow in a posterior ciliary artery. GCA leads to widespread and prolonged alterations in orbital blood flow. CDI allows the detection and monitoring of such alterations in orbital blood flow, which correlate with the clinical features of GCA. Serial CDI examinations in GCA may be used to aid management decisions.

Aged

A simple clinical method to measure the optic disc size in glaucoma.

PURPOSE: The cup-to-disc ratio is a widely used clinical measure of optic nerve damage in the management of glaucoma patients and those suspected of having glaucoma. Knowledge of the optic disc size allows for a better assessment of the clinical significance of the cup-to-disc ratio. In this study, two optical methods-slit-lamp biomicroscopy and confocal scanning laser ophthalmoscopy-were used to measure the vertical disc diameter as an indirect measure of optic disc size. The aim was to provide a simple and clinically useful examination technique in the management of glaucoma. METHODS: The vertical optic disc diameter was measured with aspheric lenses (Volk 60, 78, and 90 D, and Nikon 60 and 90 D) using slit-lamp biomicroscopy in 25 emmetropic normal volunteers. The average of three readings was determined for each of the lenses and the measurements were correlated with the magnification-corrected diameter measured with the Heidelberg Retina Tomograph. RESULTS: The mean vertical disc diameter of the group, as measured with the Heidelberg Retina Tomograph, was 1.81 +/- 0.18 mm. Results obtained with the lower-power lenses correlated best with the Heidelberg Retina Tomograph measurements (for example, Volk 60 D: r = 0.80, p = 0.0001, 95% confidence interval 1.76-1.85 mm), whereas the 90-D correlation was the weakest (for example, Volk 90 D: r = 0.59. p = 0.002, 95% confidence interval 1.75-1.87 mm). With the Volk 60-D lens, the "best fit" equation for estimating disc diameter, in millimetres, is Y = 0.85X + 0.06, where Y is the Heidelberg Retina Tomograph value and X is the slit-lamp biomicroscopy measurement. CONCLUSION: Using these formulae, the clinician is able to estimate the optic disc diameter with sufficient accuracy to allow clinical decisions to be made in the evaluation of patients with glaucoma, without recourse to expensive technology.

Adult

Gastric stump carcinoma: a surgical challenge.

Gastric stump carcinoma is a carcinoma arising in the stomach remnant following previous gastric resection. It is a distinct disease entity with its unique aetiology and pathogenesis. We report 3 cases of gastric stump carcinoma encountered in the department over the past 5 years and review current literature pertaining to its clinical presentation, aetiology, pathogenesis, treatment strategy and the role of screening endoscopy. The disease is characterised by its late presentation and dismal prognosis and will continue to pose a surgical challenge in the years to come.

Adenocarcinoma

The Abrams-Griffiths nomogram.

The treatment of benign prostatic hyperplasia and the definition of bladder-outlet obstruction has preoccupied urologists and researchers in recent years. Bladder-outlet obstruction can be defined only by pressure-flow measurement. Various methods of analysis of pressure-flow data have been proposed. The Abrams-Griffiths nomogram is an easy method of classifying these data to distinguish between the presence or absence of obstruction. Using the values for the maximal flow and the corresponding voiding detrusor pressure a point can be plotted on the nomogram that determines whether the bladder outlet is obstructed, unobstructed, or equivocally obstructed. For those that fall in the equivocal zone, further criteria for the mean slope of the pressure-flow plot and the minimal voiding detrusor pressure are used to determine whether there is obstruction or not. The nomogram's prognostic value in predicting the outcome of prostatectomy has been studied and found to be excellent. The Abrams-Griffiths nomogram can be modified by assigning an Abrams-Griffiths number to each set of pressure-flow data. This number is easy to calculate and use and gives a continuous variable that can be used to evaluate the effects of therapy. Although the Abrams-Griffiths nomogram and number are somewhat simplistic, none of the more complex methods of pressure-flow analysis have been shown to be better predictors of treatment outcome to date.

Data Interpretation, Statistical

An unusual presentation of carcinoma of the gallbladder--case report.

Unusual modes of presentation of carcinoma of the gallbladder have been described in the literature. However, this is probably the first reported case of carcinoma of the gallbladder presenting with acute large bowel obstruction. This paper also reviews the literature pertaining to the clinical features and current treatment of carcinoma of the gallbladder. It continues to be a discouraging disease characterised by late diagnosis and a poor outcome.

Adenocarcinoma

Gene transfer into coronary arteries of intact animals with a percutaneous balloon catheter.

Genetic manipulation of the vasculature may offer insights into the pathogenesis of coronary artery disease and may lead to gene therapy for disorders such as restenosis after percutaneous coronary angioplasty. The goal of this study was to develop a percutaneous method for gene transfer into coronary arteries of intact animals. Liposomes were used to facilitate transfection in coronary arteries with a plasmid containing the cDNA encoding luciferase. This reporter was chosen since it is not expressed in mammalian cells, and it can be quantified using a sensitive assay (light production). Mongrel dogs were catheterized, and DNA was delivered to coronary arteries via a porous perfusion balloon system. Luciferase expression was measured 3-5 days after the procedure, when the dogs were killed. Luciferase activity in control arteries (n = 12) was no higher than average background activity. Eight of 12 transfected arteries exhibited gene expression, averaging 4.3 +/- 2.1 pg luciferase (p less than 0.01, transfected versus control arteries). In addition, the ability to transfect DNA into femoral arteries without a transfection vehicle was tested. Five dogs were subjected to surgical transfection attempts in their femoral arteries with either DNA alone or DNA plus liposomes. Luciferase was expressed in all 10 femoral arteries; those treated with DNA alone expressed 35.6 +/- 8 pg luciferase, and those treated with DNA plus liposomes expressed 42.3 +/- 14 pg luciferase (p = 0.70). These results demonstrate the use of a percutaneous catheter to achieve gene transfer and expression in coronary arteries of intact dogs and suggest that the efficiency of intra-arterial gene transfer may be similar whether or not a transfection vehicle is used.

Animals

Direct in vivo gene transfer into the coronary and peripheral vasculatures of the intact dog.

Gene therapy approaches have been suggested for the treatment of cardiovascular disease. Recently, direct transfer of the gene encoding beta-galactosidase into peripheral arteries of the pig has been demonstrated. To determine whether this approach is applicable to other arterial beds and to other species, we first evaluated the use of beta-galactosidase as a marker protein in the canine model. We demonstrate that variable but substantial endogenous beta-galactosidase-like activity is induced by manipulation of canine peripheral arteries, which precludes the use of this marker protein in evaluating the efficiency of gene transfer in this model. A marker gene encoding firefly luciferase was then evaluated, and background luciferase activity was found to be low in the dog even after arterial manipulation. Using the luciferase gene, we then demonstrated lipid-mediated gene transfer directly into both coronary and peripheral arteries of the intact dog. These results indicate the feasibility of in vivo gene transfer into coronary arteries and demonstrate the use of the luciferase marker protein in quantifying recombinant protein expression following gene transfer in canine models. This simple and effective method for direct in vivo gene transfer into coronary and peripheral arteries may be applicable to the localized production of therapeutically important proteins for the treatment of cardiovascular diseases.

Animals

An investigation into the response of subjects to a plaque control programme as influenced by friends and relatives.

The aim of the present study was to assess the response of patients to a course of instruction in plaque control as influenced by friends and relatives. The subjects in the study were 41 patients who had been referred to a dental hospital for treatment. There was a major reduction in plaque and gingivitis levels in the subjects at both the 10th and 14th weeks of the study. There was a greater proportional reduction in gingivitis levels in those subjects who had a higher number of reported discussions with their friends. The effect of discussions with members of the family was less clear. Lower values for gingivitis levels at 10 weeks were associated with a higher number of discussions with parents. However the levels of gingivitis tended to be adversely affected by discussions between the subjects and their spouses. The importance of recognising the influence of family and friendship networks needs to be understood when preventive programmes are designed, especially where high levels of self-care are sought as outcomes. Further work is in progress on a group of office workers being treated in a dental practice environment. This will allow the type of advice being obtained from the various contacts to be investigated in more detail.

Adult

Rice millers' syndrome: a preliminary report.

A study was carried out to determine the health effects of rice husk dust in Malaysian rice millers. The study population consisted of 122 male Malay workers from three rice mills, with 42 controls of similar age, sex, ethnic group, and agricultural work background. Interviews using standardised questionnaires, physical examination, total and differential white cell counts, chest radiographs, and lung function tests were performed on each of the millers and the controls. Environmental dust monitoring was also carried out in the three rice mills. Clinical, haematological, and radiological findings suggest that a distinct clinical syndrome seems to be associated with exposure to rice husk dust. The manifestations of this "rice millers' syndrome" include acute and chronic irritant effects affecting the eyes, skin, and upper respiratory tract; allergic responses such as nasal catarrh, tightness of chest, asthma, and eosinophilia; and radiological opacities in the chest, probably representing early silicosis or extrinsic allergic alveolitis.

Adolescent