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Biomedical subjects

C Lim

Publications and source records attributed to C Lim.

At least 73 records · Page 4Linked to original sources
PubMed1996

Gestational diabetes in Singaporean women: use of the glucose challenge test as a screening test and identification of high risk factors.

In this study, 1141 antenatal women attending 9 Government polyclinics were screened between 24 and 28 weeks of gestation for gestational diabetes mellitus (GDM) using the glucose challenge test (GCT). An attempt was made to determine whether 7.2 mmol/l or 7.8 mmol/l was an effective cut-off point as an indicator for GDM. The women with GCT levels of > or = 7.2 mmol/l had an oral glucose tolerance test (OGTT) for confirmation of GDM. The results showed that 420 (36.8%) had GCT levels > or = 7.2 mmol/l, including 299 (26.2%) with GCT levels of > or = 7.8 mmol/l. Of the 190 OGTT carried out, 8 (4.2%) were confirmed to have GDM, all of whom had GCT levels of > or = 7.8 mmol/l, indicating that a GCT level of 7.8 mmol/l was the effective cut-off point. Univariate analysis showed that epidemiological features associated with a raised GCT > or = 7.8 mmol/l were, older age that is 30 years and above, Chinese ethnic group, maternal obesity (body mass index > or = 25) and history of > or = 4 pregnancies. Multivariate analysis using stepwise logistic regression, showed that factors significantly and independently associated with raised GCT levels were older age, Chinese ethnic group and maternal obesity. All antenatal women should be screened for GDM using the GCT, and those with levels of > or = 7.8 mmol/l should be subjected to the OGTT for confirmation.

Adult↗
PubMed1995

Molecular dynamics simulation of E. coli ribonuclease H1 in solution: correlation with NMR and X-ray data and insights into biological function.

A 500 ps molecular dynamics simulation of Escherichia coli RNase H1 in the presence of explicit water molecules has been carried out to aid in the interpretation of NMR N-H backbone model free parameters and X-ray B-factor values of the free enzyme. Both experimental techniques have revealed unusual structural and dynamic features of the protein. Atomic fluctuations (B-factors) and re-orientational motions of the backbone heteronuclear bonds (order parameters) computed from the simulation are compared with results obtained from experiments. Qualitative agreement is obtained between the computed and X-ray B-factors, whereas the agreement between the computed and NMR generalized order parameters is as good as quantitative for most residues. Reasons for significant discrepancies, the physical basis and the plausible biological consequences of the observed protein dynamics are discussed.

Amino Acid Sequence↗
PubMed1995

Identifying the mechanism of protein loop closure: a molecular dynamics simulation of the Bacillus stearothermophilus LDH loop in solution.

The 'loop' involving residues 98-110 in Bacillus stearothermophilus lactate dehydrogenase (BSLDH) is of great interest as substrate-induced 'loop' closure is thought to be rate-limiting and essential in catalyzing the reaction and in determining substrate specificity. Consequently, we have explored the mechanism underlying 'loop' opening in BSLDH through a molecular dynamics simulation at high temperature (1000 K) in the presence of explicit solvent, starting from the X-ray structure of BSLDH complexed with the co-enzyme NAD+ and oxamate at 2.5 A. During the simulation, a significant conformational change occurred, as evidenced by sharp dihedral angle transitions, hydrogen bond breaking and formation and large root mean square deviations from the starting structure; these changes define the criteria for 'loop' opening. The mechanical elements responsible for 'loop' opening, i.e. 'loop' hinges and flap, are defined through a combination of order parameters, dihedral angle changes and their correlations and the dynamical cross-correlation map of atomic displacements for the 'loop' residues. The results indicate that the 'loop' consists of two flexible hinge regions on either side of a relatively rigid three-residue segment that undergoes a significant spatial displacement during 'loop' opening. 'Loop' opening is made possible through an array of correlated dihedral angle changes and intra-'loop' rearrangements of hydrogen-bond interactions. The present findings are compared to previous work related to 'loop' opening and site-directed mutagenesis experiments.

Amino Acid Sequence↗
PubMed1994

Cholinergic innervation in the human hippocampal formation including the entorhinal cortex.

The cholinergic innervation of the hippocampal formation is thought to play an important role in memory processes, but its organization in humans has not been described in detail. We studied the cholinergic innervation of the human hippocampal formation by means of immunohistochemistry with polyclonal antisera directed against acetylcholinesterase (AChE), choline acetyltransferase (ChAT), and the low-affinity (p75) nerve growth factor receptor (NGFR). The density of ChAT-like immunoreactive (ChAT-li) fibers differed substantially among the various regions, in general paralleling the pattern of AChE-li staining. One notable exception was the presence of AChE-li cell bodies. In contrast, ChAT immunoreactivity was associated only with fibers and terminals. NGFR-li staining corresponded closely to the ChAT-li fiber pattern. ChAT-li fibers in the CA fields diffusely filled the stratum pyramidale and extended into the stratum oriens and radiatum as well. The highest density was consistently observed in CA4 and CA3 subfields. Staining decreased from CA4 to CA1 and was substantially less dense in the subicular complex. In the entorhinal cortex, the ChAT- and NGFR-li fiber innervation displayed a laminar pattern, most intense over the nests of cells in layer II. There was a trend towards an age-related reduction in the density of ChAT- and AChE-li fibers and terminals. Nonetheless, we also found a surprisingly conserved NGFR-li innervation and the presence of occasional NGFR-li pyramidal cells, providing evidence of a plastic response in the brains of the elderly patients.

Acetylcholinesterase↗
PubMed1994

The double catalytic triad, Cys25-His159-Asp158 and Cys25-His159-Asn175, in papain catalysis: role of Asp158 and Asn175.

The 1.65 A X-ray structure of papain, which exhibits a Cys25-His159-Asn175 triad, does not correspond to the catalytically active ion pair state since Cys25 is oxidized to cysteic acid and His159 is predominantly neutral. Thus, stochastic boundary molecular dynamics simulations starting from the 1.65 A X-ray structure of papain have been performed for Cys25 and His159 in the SH-ImH+, SH-Im, S(-)-ImH+ and S(-)-Im states and for Asp158 mutated to Asn, Glu and Gly in the ion pair state. By comparing the resulting averaged structures and analyzing the trajectories of certain interatomic distances, important differences in the active-site geometry of papain have been found. In particular, the initial Cys25(S-)-His159(ImH+)-Asn175(C = O) triad found in the X-ray structure is retained in all the structures except the wild type and Asp158-->Asn ion pair states where there is a conformational transition to form the triad, Cys25(S-)-His159(ImH+)-Asp158(COO-). Both triads, Cys25(S-)-His159(ImH+)-Asp158(COO-) and Cys25(S-)-His159(ImH+)-Asn175(C = O) are postulated to participate in catalysis and their roles are discussed. Thus, catalysis does not take place from a single steric position but a two-state mechanism.

Amino Acid Sequence↗
PubMed1992

Effect of ethanol on prostaglandin E2 receptor in rat submandibular salivary glands.

The dose-dependent effects of acute ethanol treatment on the prostaglandin E2 (PGE2) receptor in submandibular salivary glands was investigated. Rat submandibular-gland segments were preincubated with Dulbecco's modified Eagle's medium in the absence and the presence of various concentrations of ethanol (0.1-5%). After incubation, membranes were prepared and assayed for PGE2 receptor binding using [3H]-PGE2. Ethanol had no effect on receptor binding at concentrations below 1%, but binding was stimulated by higher concentrations. A 30% increase in binding occurred with 2.5% ethanol and 50% with 5% ethanol. This increase was due to an alteration of the binding characteristics. Scatchard analysis of the data from the control and 5% ethanol groups revealed that the ethanol-induced increase in PGE2 receptor binding was mainly due to a 26 and 58% decrease in the dissociation constant (Kd) for the high- and low-affinity binding sites, respectively. A 31% decrease of binding capacity (Bmax) was also observed in the low-affinity binding sites. The results demonstrate that PGE2 receptor binding in submandibular glands is not altered by acute treatment with ethanol at physiological doses. The receptor binding is also relatively stable on pretreatment with 1% ethanol. It is suggested that the increase of receptor binding induced by high concentrations of ethanol may be a spontaneous response to the decrease of PGE2 synthesis in the tissues.

Animals↗
PubMed1992

Visual field differences for clockwise and counterclockwise mental rotation.

Geometric line drawings were presented to normal subjects in the left visual field (LVF) or right visual field (RVF) at various degrees of rotation from a centrally presented vertical standard. The task of the subject was to indicate with a reaction time (RT) response whether the laterally presented stimulus could be rotated into the vertical standard or if it was a rotated mirror image of the standard. In Study 1, an overall right hemisphere superiority was found for RT and accuracy on match trials. Most interestingly, interactions between Visual Field and Rotation Angle for the match accuracy data and between Visual Field and Direction of Rotation (clockwise or counterclockwise) for the match RT slopes were found. These interactions suggested that clockwise rotations were more readily performed in the LVF and counterclockwise rotations in the RVF, consistent with other literature for mental rotation. The purpose of Study 2 was to replicate this finding of visual field differences for rotation direction using a design in which direction and degree of rotation were varied orthogonally. No main effect of Visual Field was found. However, significant interactions between Visual Field and Rotation Angle were found for both RT and accuracy, confirming the presence of visual field differences for rotation direction in a new sample of subjects. These differences were discussed in terms of the possibly greater relevance of medially directed stimuli and a possible hemispheric bias for rotation direction, and in terms of interhemispheric transmission factors.

Adolescent↗
PubMed1992

Cigarette smoking reduces human salivary eicosanoids.

The effect of cigarette smoking on salivary eicosanoid levels was investigated in 10 smoker and 10 non-smoker volunteers. The smokers consumed an average of 20 cigarettes/day for the past 5 years or longer. The smoking status was validated by salivary cotinine level. Eicosanoids were extracted from saliva with ethanol, and the radioimmunoassay was performed to determine the concentrations of four major eicosanoids, i.e. prostaglandin E2 (PGE2), PGF2 alpha, 6-sulphidopeptide-containing leukotrienes (LTs) and 12-hydroxyeicosatetraenoic acid (12-HETE). The levels of PGE2, PGF2 alpha, and LTs were significantly lower in the saliva of smokers as compared to that of the non-smokers (1.74 +/- 0.32 vs 2.41 +/- 0.64, p = 0.006; 0.36 +/- 0.12 vs 0.54 +/- 0.18, p = 0.04; 2.24 +/- 0.96 vs 4.92 +/- 1.29, p = 0.006; mean +/- SD, ng/ml saliva). No significant differences were found in the levels of 12-HETE between the two groups. The results suggest that cigarette smoking reduces the concentrations of both the cyclooxygenase and 5-lipoxygenase products in saliva.

Cotinine↗
PubMed1992

Hemodynamic effects of carvedilol after acute oral administration in hypertensive and normal subjects.

Forearm hemodynamics using pulsed Doppler flowmetry were studied in nine healthy volunteers and 12 patients with mild-to-moderate hypertension before and after acute oral administration of the beta-blocking and vasodilating agent carvedilol. Both the 25- and the 50-mg dose produced a significant blood pressure reduction by comparison with placebo in normotensive and hypertensive subjects. Only the 50-mg dose caused a decrease in forearm vascular resistance in hypertensive subjects. The decrease disappeared after wrist occlusion. Although brachial artery diameter did not change, a significant decrease in tangential tension was observed. This study provides evidence that carvedilol produced arteriolar dilation within the forearm of hypertensive subjects in association with a decrease in brachial artery tangential tension.

Administration, Oral↗
PubMed1991

Effect of electroconvulsive therapy on serum concentration of alpha-1-acid glycoprotein.

Recent studies have shown significant alterations in serum alpha-1-acid glycoprotein (AGP) concentration in epileptic patients, the major protein to which basic drugs bind in serum. To date, there have been no reports in the literature investigating the effects of generalized seizures as a result of repeatedly administered electroconvulsive therapy (ECT) on this serum protein. As the cyclic antidepressants are basic drugs that bind avidly to AGP, an alteration of AGP concentration by ECT could represent a mechanism of interaction between two somatic treatments for depression. We therefore determined the serial AGP concentrations of 10 patients undergoing repeated ECT. AGP concentrations were determined by radial immunodiffusion on serum samples obtained at each treatment session (course of treatment ranged from 4 to 12 sessions over 8 to 32 days). The mean (SD) AGP concentrations prior to and at the end of ECT were 88.7 (18.3) mg/dl and 97.8 (24.8) mg/dl, respectively. Variability in AGP concentration was observed over the course of treatments with no consistent trend (intrapatient coefficients of variation averaged 11.5%). These data suggest that serial ECT does not produce consistent, significant changes in serum AGP concentrations and should have limited effects on altering the serum protein binding and, therefore, pharmacological effects of concurrently administered cyclic antidepressants.

Adolescent↗
PubMed1991

Hippocampus and the blood supply to TE: parahippocampal pial section impairs visual discrimination learning in monkeys.

In the base of each temporal lobe in 4 monkeys (Macaca fascicularis) we sectioned the pia mater in an antero-posterior line along the most medial part of the inferior temporal visual association cortex (area TE), lateral to the parahippocampal cortex. This pial section interrupts the blood flow in branches of the posterior cerebral artery which cross the parahippocampal gyrus en route to area TE. Histologically, the brains of 2 of these animals did not show any abnormalities in cresyl violet stained material, apart from the small cortical damage along the line of the pial section itself. Of the remaining two animals, one had a small unilateral infarct in TE and one had bilateral infarcts in TE. All of these animals were impaired in visual discrimination learning, and the severity of impairment was correlated only imperfectly with the severity of infarction. These results show that pial section along the medial boundary of area TE can affect visual discrimination learning without producing large infarcts. Further, since aspiration lesions of the hippocampal formation require the pia mater to be sectioned in a similar way to that reported here, the effects of such aspiration lesions on visual learning and memory may be mediated in part by effects on TE.

Animals↗
PubMed1991

Impairment by ethanol of prostaglandin production in rat salivary glands.

Sublingual salivary acini and submandibular tissue were incubated in DMEM medium in the presence of various concentrations (0-5%) of ethanol and the content of the three major prostaglandins, PGE2, PGF2 alpha and 6-keto-PGF1 alpha, were determined by radioimmunoassay. In In the sublingual gland, ethanol caused a decrease in PGE2 and PGF2 alpha levels, but had no effect on 6-keto-PGF1 alpha, while all three prostaglandins were affected in the submandibular gland. At 2.5% ethanol, the production of PGF2 alpha and PGE2 in sublingual gland decreased by 10% and reached maximum inhibition at 5% ethanol, at which concentration there was a 20 and 30% decrease in their levels. In submandibular gland, 2.5% ethanol caused a 20% decrease in PGE2, 30% in PGF2 alpha and 50% in 6-keto-PGF1 alpha; 40% inhibition in PGE2, 57% in 6-keto-PGF1 alpha and 65% in PGF2 alpha occurred in the presence of 5% ethanol. These findings suggest that alcohol impairs the function of salivary glands by inhibiting prostaglandin production.

6-Ketoprostaglandin F1 alpha↗
PubMed1990

Stereoselective protection of exogenous and endogenous atrial natriuretic factor by enkephalinase inhibitors in mice and humans.

We compared the relative potencies of sinorphan and retorphan, the S- and R-enantiomers of acetorphan a potent inhibitor of enkephalinase (EC 3.4.34.11), to inhibit membrane metalloendopeptidase in vivo and to protect exogenous and endogenous ANF after oral administration. In mice, sinorphan was 2-3 fold as potent as retorphan in inhibiting the specific in vivo binding of [3H]acetorphan to kidney enkephalinase. The same potency ratio was found for the enhancement of trichloroacetic acid-precipitated radioactivity in kidneys of mice that had received 125I-ANF, which is used as a test for the protection of the hormone against inactivation in vivo. In nine healthy human volunteers who had received a low oral dosage of sinorphan or retorphan in a double-blind, placebo-controlled, randomized trial, sinorphan was also 2-3 fold more potent than retorphan in inhibiting plasma enkephalinase activity. These effects were accompanied by a related rise in plasma ANF immunoreactivity, which also reflected the difference in the effectiveness of the two compounds. Sinorphan was also more potent than retorphan in enhancing urinary cyclic GMP excretion and sodium excretion in five of these subjects. These data indicate that, in humans as in rodents, enkephalinase plays a crucial role in the inactivation of ANF, its partial inhibition in vivo being accompanied by a significant protection of the exogenous or endogenous hormone as well as by typical ANF-like responses. Thus orally administered sinorphan appears to be a promising compound for therapeutic use in cardiovascular and renal diseases in which ANF has been postulated to exert beneficial effects.

Administration, Oral↗
PubMed1987

Hangman's fracture: radiologic assessment in 27 cases.

Traumatic spondylolisthesis of C-2, frequently referred to as the hangman's fracture, is typically regarded as a hyperextension injury with rare neurologic sequelae by virtue of decompression of the neural canal. The authors retrospectively evaluated their radiographic experience with this injury in 27 patients over a 24-month period. Lateral cervical spine studies and computed tomography (CT) scans (21 patients) were analyzed. CT studies provided better delineation of the fracture in all 21 patients and significant additional information in five patients (24%). Seven patients (26%) suffered initial neurologic sequelae in association with the C-2 injury. Nine patients had additional sites of fracture, including seven with associated C-1 ring disruption (26%). Extension of the fracture line into the transverse vertebral artery foramen led to vertebral artery injury and cerebellar embolization in one patient. Angiography may be necessary to detect intimal injury to the vertebral arteries when the fracture extends through the transverse foramina and to indicate the need for anticoagulation when clinically feasible.

Adolescent↗
PubMed1986

Changing patterns of transfusion practice in a tertiary care hospital from 1977 to 1984.

Patterns of blood transfusion practice over an eight-year-period (1977-1984) are described. Use of blood and blood products increased annually as did the number of patients crossmatched and transfused. Programs such as the "Blood Group & Antibody Screen" and the "Maximum Surgical Blood Order Schedule" were important in improving transfusion practices. There was improvement in blood use by all subspecialties; the overall C:T (crossmatched:transfused blood) ratio declined from 4.4 to 2.8. Approximately a quarter of both crossmatches performed and transfusions of red cells were associated with cardiac surgery. Incidence of outdated units of blood declined markedly (2.6 per cent in 1984), as did requests for and administration of single unit transfusions. Seven per cent of patients received one unit of blood during hospitalization; since 85 per cent of these were associated with surgery (57 per cent cardiac surgery), it is suggested that single unit transfusions may sometimes be more appropriate than inappropriate. Two per cent of patients had clinically significant alloantibodies. About two per cent of patients had positive direct antiglobulin tests; nine per cent of the sera of these patients contained both auto and alloantibodies. Such data are important for transfusion quality assurance as well as for optimal logistical use of facilities both at hospital Blood Bank and blood collection agency levels.

Antibodies↗