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Biomedical subjects

L Tan

Publications and source records attributed to L Tan.

At least 109 records · Page 6Linked to original sources

[Involvement of nucleus amygdaloideus centralis, lateral hypothalamus/perifornical region and nucleus paraventricularis in insular cortex-pressor response].

In urethane-anesthetized, tubocurarine-immobilized and artificially ventilated rats, glutamate (Glu) injection into the insular cortex (INS) and substance P injection into the lateral hypothalamus-perifornical region (LH/PF) or nucleus paraventricularis (NPV) caused pressor responses. Preinjection of procaine or glutamate diethyl ester (GDEE, a glutamate antagonist) bilaterally into the nucleus amygdaloideus centralis (AC) and [D-Pro2, D-Phe7, D-Trp9]-substance P (DPDPDT, a substance P antagonist), but not GDEE, into the LH/PF markedly attenuated the pressor response induced by glutamate injection into the INS. Procaine or DPDPDT preinjection into the NPV also reduced the INS-pressor response. Since the LH/PF and NPV were found to mediate the AC-pressor response, the above results suggest that the INS-pressor response is the final outcome of activation of AC (Glu-receptor)-LH/PF and NPV (SP receptor) system.

Amygdala↗

[Role of substance P in pressor response of central amygdaloid nucleus to glutamate].

Substance P (SP)-immunoreactive cells and the axon terminals are widely distributed in the central amygdaloid nucleus (AC) and its important projection areas. The present study showed that (1) Excitation of the AC by glutamate (Glu) or injection of SP into the AC projection areas: locus coeruleus (LC), nucleus parabrachialis (NPB), periaqueductal gray matter (PAG) or lateral hypothalamus-perifornical region (LH/PF), all elicited pressor response. (2) Preinjection of DPDPDT (a SP antagonist) into bilateral LC, NPB, PAG or LH/PF could attenuate the AC pressor response to Glu. (3) Intra-RVLM (rostral ventrolateral medulla) preinjection of either phentolamine, propranolol or atropine (but not GDEE, a Glu antagonist) could also reduce the AC pressor response. Taken together with our previous findings that the alpha-, beta-, M-receptors in RVLM mediated the pressor response to LC excitation, alpha-receptors mediated the NPB pressor response, alpha- and beta-receptors mediated the PAG pressor response; these results indicate that the SPergic projections of the AC not only directly act upon the brainstem pressor areas (LC, NPB, PAG)-RVLM system, but also indirectly via the LH/PF act upon the brainstem pressor areas-RVLM system to induce the pressor response.

Amygdala↗

[Correlation between shape and direction of small articular surface in lower lumbar vertebrae and degeneration of intervertebral disc].

To assess the possible correlation between the shape and the direction of the small articular surface in the lower lumbar vertebrae and the degeneration of the intervertebral disc, we investigated with computed tomography (CT) and evaluated with statistics the small articular surface and the transverse interface-joint angle (TIFA) of the L4-5 and the L5-S1 in 152 cases who had normal or degenerative discs verified through CT, MRI or operation. The small articular surface was found arc in 69.1% of the L4-5 and in 23.0% of the L5-S1. The TIFA of the L4-5 was less than that of the L5-S1. There was no correlation between the ratio of degeneration of the intervertebral disc at the L4-5 and the TIFA of the L4-5 and the L5-S1, but the ratio of degeneration of the intervertebral disc at the L5-S1 had postive correlation with the TIFA of the L4-5, negative correlation with the TIFA of the L5-S1, and particular correlation with the TIFA of the L5-S1 and L4-5. These results suggest that the shape and direction of the lower lumbar facet joint are related to the lumbar degeneration of intervertebral disc and the causes of degeneration at the L4-5 disc differ from those at the L5-S1 disc in biomechanics.

Adolescent↗

Intramolecular disulfide bonds enhance the antimicrobial and lytic activities of protegrins at physiological sodium chloride concentrations.

Protegrins are 2-kDa antimicrobial peptides that contain 16-18 amino acid residues and two intramolecular disulfide bonds. We studied the contribution of these disulfide bonds to the bactericidal activity of protegrins in physiological concentrations of NaCl by comparing protegrin PG-1 with variants that lacked one or both cysteine disulfides. Whereas the bactericidal and liposome-lytic properties of protegrin PG-1 were enhanced by adding 100 mM NaCl to the phosphate-buffered medium, NaCl addition strongly inhibited the effects of its linearized, disulfide-free variant, [A6, A8, A13, A15]protegrin-1. Whereas protegrin PG-1 manifested beta-sheet structure by CD (circular dichroism) and ATR-FTIR (attenuated-total-reflectance-Fourier-transform-infrared) spectroscopy in buffer or membrane-mimetic environments, [A6, A8, A13, A15]protegrin-1 manifested disordered structure in phosphate buffer and alpha-helical characteristics in membrane-mimetic environments. Both single-disulfide protegrin variants, [A8, A13]protegrin-1 and [A6, A15]protegrin-1, assumed beta-sheet conformations with liposomes that simulated bacterial membranes, and both retained substantial bactericidal activity when 100 mM NaCl was present. These findings demonstrate that the intramolecular disulfide bonds of protegrins are required for their antiparallel beta-sheet conformation in membrane-mimetic environments and for their potent antimicrobial activity in media containing NaCl concentrations comparable to those found in serum and extracellular fluids.

Amino Acid Sequence↗

Suppression of interleukin-1beta-induced nitric-oxide synthase promoter/enhancer activity by transforming growth factor-beta1 in vascular smooth muscle cells. Evidence for mechanisms other than NF-kappaB.

Nitric-oxide synthases (NOS) utilize L-arginine to produce NO, a potent vasodilator that contributes to the regulation of vascular tone. We demonstrated previously that transforming growth factor (TGF)-beta1 down-regulates inducible NOS after its induction by interleukin (IL)-1beta by decreasing the rate of inducible NOS gene transcription. In the present study we transfected reporter plasmids containing various lengths of the inducible NOS 5'-flanking region into primary cultured rat aortic smooth muscle cells and stimulated the cells with IL-1beta or vehicle. IL-1beta increased the activity of the plasmid containing -1485 to +31 of the inducible NOS gene by more than 10-fold, indicating the presence of IL-1beta-responsive elements. Further deletion analysis revealed that a construct containing -234 to +31 of the inducible NOS gene contained the majority of promoter/enhancer activity after IL-1beta stimulation. Mutation of the NF-kappaB site within this region partially reduced IL-1beta-inducible activity; however, a large portion of activity remained independent of the NF-kappaB site. TGF-beta1 suppressed promoter/enhancer activity after IL-1beta stimulation, and this suppression was complete in the construct with a mutated NF-kappaB site. In addition, TGF-beta1 did not decrease the binding of nuclear proteins to the NF-kappaB site. These data suggest that the ability of TGF-beta1 to suppress inducible NOS promoter/enhancer activity occurs through a site(s) other than the NF-kappaB motif in vascular smooth muscle cells.

Animals↗

An animal model for training in endoscopic nasal and sinus surgery.

An animal model has been devised to allow trainees in nasal and sinus endoscopy to develop basic instrument handling and psychomotor skills, without risk to patients. The sheep's head obtained from the abattoir was modified slightly to simulate more closely the human situation. The model permits nasendoscopy, foreign body removal, septoplasty, turbinate reduction, frontal and maxillary sinoscopy, antrostomy and an epistaxis exercise. To date the tissues have been used freshly thawed, and must be used on the day of preparation.

Animals↗

Evaluation of the Pall RC100 leucocyte removal filters and the effect of air introduction on its performance.

We evaluated the efficiency of Pall RC100 leucocyte removal filters in processing two units of concentrated red cells for transfusion. Our results show that the filter is very effective in processing the first unit. However, 32% (5/16) of the filters evaluated allowed a leak of substantial numbers of white cells towards the end of the transfusion of the second unit of blood. Air introduction experiments showed that as little as 2 ml of air in the filter may cause major deterioration of the filter function.

Air↗

A comparison of computerized tomographic staging systems in chronic sinusitis.

A number of different systems exist for staging computerized tomography (CT) scans in rhinosinusitis. The aim of this study was to determine which of four selected staging systems, currently in common use facilitated the highest level of agreement. The systems studied were those by Jorgensen (1991), May and Levine (1991), Lund and Mackay (1993) and Newman (1994). Ten observers independently assessed 10 representative films. In our assessment, the Lund and Mackay system facilitated the highest level of both inter-observer and intra-observer agreement of the four systems tested. We recommend it be adopted as the standard method of measuring the extent of disease, as depicted by CT scanning for chronic. rhinosinusitis.

Chronic Disease↗

A novel serine/threonine kinase binding the Ras-related RhoA GTPase which translocates the kinase to peripheral membranes.

We previously reported the cloning of a serine/threonine kinase, PAK (for p21 (Cdc42/Rac)-activated kinase), which binds to the Ras-related GTPases Cdc42Hs and Rac1 (Manser, E., Leung, T., Salihuddin, H., Zhao, Z-s., and Lim, L. (1994) Nature 367, 40-46). These p21 proteins together with RhoA comprise the Rho subfamily of proteins that are involved in morphological events. We now report the isolation of a rat cDNA encoding a 150-kDa protein, which specifically binds RhoA in its GTP form and contains an N-terminal serine/threonine kinase domain highly related to the human myotonic dystrophy kinase and a cysteine-rich domain toward the C terminus. The RhoA binding domain is unrelated to other p21 binding domains. Antibody raised against the kinase domain of the predicted protein, termed ROK alpha (for ROK alpha, RhoA-binding kinase), recognized a ubiquitous 150-kDa protein. The brain p150 purified by affinity chromatography with RhoA exhibited serine/threonine kinase activity. In cultured cells, immunoreactive p150 was recruited to membranes upon transfection with dominant positive RhoAV14 mutant and was localized with actin microfilaments at the cell periphery. These results are consistent with a role for the kinase ROK alpha as an effector for RhoA.

3T3 Cells↗

Peptide anchor residue glycosylation: effect on class I major histocompatibility complex binding and cytotoxic T lymphocyte recognition.

This study extends our previous observation that glycopeptides bind to class I major histocompatibility complex (MHC) molecules and elicit carbohydrate-specific CTL responses. The Sendai virus nucleoprotein wild-type (WT) peptide (FAPGNYPAL) binds H-2Db using the P5-Asn as an anchor. The peptide K2 carrying a P5 serine substitution did not bind Db. Surprisingly, glycosylation of the serine (K2-O-GlcNAc) with N-acetylglucosamine (GlcNAc), a novel cytosolic O-linked glycosylation, partially restored peptide binding to Db. We argue that the N-acetyl group of GlcNAc may fulfil the hydrogen bonding requirements of the Db pocket which normally accomodates P5-Asn. Glycosylation of the P5-Asn residue itself abrogated binding similar to K2, probably for steric reasons. The peptide K2-O-GlcNAc readily elicited Db-restricted cytotoxic T lymphocytes (CTL), which did not cross-react with K2 or WT. However, all Db-restricted CTL raised against K2-O-GlcNAc cross-reacted strongly with another glycopeptide, K3-O-GlcNAc, where the GlcNAc substitution is on a neighboring P4-Ser. Furthermore, Db-restricted CTL clones raised against K2-O-GlcNAc or K3-O-GlcNAc displayed a striking TCR conservation. Our interpretation is that the carbohydrate of K2-O-GlcNAc not only mediates binding to Db, but also interacts with the TCR in such a way as to mimic K3-O-GlcNAc. This unusual example of molecular mimicry extends the known effects of peptide glycosylation from what we and others have previously reported: glycosylation may create a T cell neo-epitope, or, conversely, abrogate recognition. Alternatively, glycosylation may block peptide binding to MHC class I and finally, as reported here, restore binding, presumably through direct interaction of the carbohydrate with the MHC molecule.

Acetylglucosamine↗

Comparison of palmolein and olive oil: effects on plasma lipids and vitamin E in young adults.

Twenty-one healthy normocholesterolemic young adults, men and women, completed a randomized 30-d/30-d crossover comparison of the effect of palmolein and olive oil on plasma lipids. The subjects were free-living volunteers who changed to low-fat diets to which one of the test oils was added (used as a spread, for baking, or for frying) in turn. Complete food records were kept throughout: the test oils were compared at 17% of total dietary energy. Under the conditions of this experiment plasma total and low-density-lipoprotein (LDL) cholesterol were almost identical with the two oils, so that when the palmitic acid (16:0) in palm oil replaced oleic acid (18:1) in olive oil the expected increase in LDL cholesterol was not seen. These results indicate that 16:0, though saturated, is not always a plasma cholesterol-raising fatty acid. Palmolein is rich in vitamin E, alpha-tocopherol, and especially tocotrienols, but the latter were barely detectable in plasma.

Adult↗

Impact of culture on pain management: an Australian nursing perspective.

Pain assessment and pain management are complex tasks. Knowledge and beliefs of patients, physicians, and nurses about pain are key determinants of clinical decision making. Despite new theoretical insights, routine approaches to pain assessment and management persist in practice. Culture is a potent force in shaping beliefs, behavior, and meaning about pain. In health care contexts, there may be conflict between care and cure and differing perceptions about the role and status of nurses that impinge on the provision of pain relief. The article explores aspects of culture, knowledge, and belief and their influence on pain management from an Australian perspective.

Attitude of Health Personnel↗

Absorption of cyclosporin from conventional and new microemulsion oral formulations in liver transplant recipients with external biliary diversion.

1. Less than 5% of a dose of the conventional oral formulation of cyclosporin, Sandimmun, is absorbed in liver transplant recipients with external biliary drainage, necessitating intravenous administration of the drug and exposing the patient to increased risk of severe side-effects. 2. We compared the pharmacokinetics of the conventional oral formulation of cyclosporin with that of the new microemulsion formulation, Neoral, in eight liver transplant recipients with external biliary diversion. Patients were maintained on a continuous infusion of cyclosporin until steady-state conditions had been achieved. They were then given a test dose (10 mg kg-1) of either the conventional or microemulsion formulation (randomised order) followed by the same dose of the other formulation. Parent cyclosporin concentrations were measured in whole blood samples collected at timed intervals over the 24 h after the oral doses and pharmacokinetic parameters calculated. 3. The bioavailability of cyclosporin from the microemulsion formulation was, on average, 6.5-fold (95% C.I. 1.9 to 11.1-fold) greater than that of the conventional formulation, indicating the improved absorption characteristics of the new oral microemulsion formulation during external bile drainage. 4. A significant negative correlation was found between the external bile drainage volume and bioavailability of cyclosporin from the microemulsion formulation (r = -0.8; P = 0.016), suggesting that variability in cyclosporin absorption from the microemulsion formulation may still be at least partly attributable to bile- dependence.(ABSTRACT TRUNCATED AT 250 WORDS)

Absorption↗

Benign and malignant breast lesions: differentiation with echo-planar MR imaging.

PURPOSE: To quantify dynamic enhancement of breast lesions with echo-planar and conventional magnetic resonance (MR) imaging, to correlate these data with histologic findings and vessel density, and to evaluate MATERIALS AND METHODS: Twenty female patients with 22 breast lesions underwent conventional and MR echo-planar imaging T1 values, change in gadopentetate dimeglumine concentration, and extraction-flow products were calculated with echo-planar imaging data and were correlated with histologic findings and microvessel density. RESULTS: T1 values of cancers were not statistically significantly shorter. Cancers had more rapid uptake and higher extraction-flow products (P < .02). Sensitivity was 86% and specificity was 93% for diagnosis of malignancy. Microvessel density was higher for malignant lesions (P < .02) with an overall positive (not statistically significant) correlation between extraction-flow product and microvessel density. CONCLUSION: Echo-planar imaging appears promising for quantification of breast lesion enhancement. Microvessel data indicate that tumor angiogenesis affects enhancement.

Adolescent↗

Bactericidal properties of murine intestinal phospholipase A2.

We purified a molecule from the murine small intestine that killed both Escherichia coli and Listeria monocytogenes, and identified it as intestinal phospholipase A2 (iPLA2) by NH2-terminal sequencing and enzymatic measurements. The ability of iPLA2 to kill. L. monocytogenes was greatly enhanced by 5 mM calcium, inhibited by EGTA and abolished after reduction and alkylation, suggesting that enzymatic activity was required for iPLA2-mediated bactericidal activity. A mouse-avirulent phoP mutant, S. typhimurium 7953S, was 3.5-fold more susceptible to iPLA2 than its isogenic virulent parent, S. typhimurium 14028S (estimated minimal bactericidal concentrations 12.7 +/- 0.5 micrograms/ml vs. 43.9 +/- 4.5 micrograms/ml P < 0.001). Overall, these findings identify iPLA2 as part of the antimicrobial arsenal that equips Paneth cells to protect the small intestinal crypts from microbial invasion. Because iPLA2 is identical to Type 2 phospholipase A2 molecules found in other sites, including spleen, platelets and inflammatory exudate cells, this enzyme may also contribute to antibacterial defenses elsewhere in the body.

Amino Acid Sequence↗