Extensive bone infarct in myeloid leukemia correlation of bone scan and magnetic resonance imaging.
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Aged↗
Biomedical subjects
W F Lau
Publications and source records attributed to W F Lau.
Differential effects of bisphosphonate on Paget's disease and metastatic prostatic carcinoma-bone scan findings.
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Aged↗
Cloning and expression of immunoreactive antigens from Mycobacterium tuberculosis.
Four immunoreactive proteins, B.4, B.6, B.10, and B.M, with molecular weights ranging from 16,000 to 58,000, were observed from immunoblots of Mycobacterium tuberculosis total lysates screened with sera from individuals with active tuberculosis. These proteins were identified from microsequence analyses, and genes of proteins with the highest homology were PCR amplified and cloned into the pQE30 vector for expression studies. In addition, a 37.5-kDa protein, designated C17, was identified from a phage expression library of M. tuberculosis genomic DNA. Preliminary immunoblot assays indicated that these five resultant recombinant proteins could detect antibodies in individuals with active pulmonary and extrapulmonary tuberculosis. The overall ranges of sensitivities, specificities, positive predictive values, and negative predictive values for the recombinant antigens were 20 to 58, 88 to 100, 69 to 100, and 56 to 71%, respectively. The B.6 antigen showed preferential reactivity to antibodies in pulmonary compared to nonpulmonary tuberculosis serum specimens. All of these recombinant antigens demonstrated potential for serodiagnosis of tuberculosis.
Antigens, Bacterial↗
A pseudopeptide incorporating the tetrahydrophthalazine nucleus, a constrained aza analog of phenylalanine.
Replacement of the alpha-carbon with a nitrogen in alpha-amino acids gives rise to azaamino acids. Most examples of azaamino acids that have been incorporated into peptides are linear analogs, in which conformational effects are restricted to the immediate vicinity of the urea bond. In contrast to the linear azaamino acids, the heterocyclic analogs might be expected to exhibit stronger conformational preferences, but examples of this class of azaamino acids are very limited. We synthesized tetrahydrophthalazine (THPhth) as a constrained phenylalanine analog and elaborated it into the model pseudotripeptide N-¿([N-alanyl]-1,2,3,4-tetrahydro-2-phthalazinyl)carbonyl)¿-L-alan ine (1). As shown by NMR studies, tetrahydrophthalazine 1A has a secondary structure in which psi THphth is fixed at 16-18 degrees and there are two equal populations of cis and trans amide bonds from the N-terminal alanine.
Magnetic Resonance Spectroscopy↗
In vitro modulation of rat adipocyte ghost membrane fluidity by cholesterol oxysterols.
The effects of cholesterol and cholesterol-derived oxysterols (cholestanone, cholestenone, coprostanone and epicoprostanol) on adipocyte ghost membrane fluidity were studied using a fluorescence depolarization method. The fluorescence anisotropy of the treated membranes was determined using 1,6-diphenyl-1,3,5-hexatriene (DPH) and 1-(4-trimethylammoniumphenyl)-6-phenyl-1,3,5-hexatriene (TMA-DPH). Cholestanone and cholesterol decreased membrane fluidity at both the concentrations tested (10 & 50 microM) while the rest of the sterols did not exert any significant effect on membrane fluidity. In the presence of epinephrine, cholestanone partitioned more towards the lipid core but cholesterol partitioning was not affected. The fusion activation energies (delta E) obtained for membranes preincubated with cholestanone (8.6 kcal/mol) and cholesterol (8.2 kcal/mol) were not significantly different from that of untreated membranes (8.3 kcal/mol). Membranes preincubated with cholestanone and cholesterol did not exhibit any change in lipid phase throughout the temperature range (10-45 degrees C) tested. The sterols were found to inhibit fisetin-induced phospholipid methylation in isolated rat adipocytes in the rank order of cholesterol > epicoprostanol > cholestanone = cholestenone = coprostanone, while basal methylation was unaffected. When adipocytes were preincubated with the sterols before the addition of fisetin, cholestanone and cholestenone showed 74% and 66% inhibition of maximal methylation respectively. These results indicated that cholesterol oxysterols interact differently with rat adipocyte membranes, with cholestanone interacting more with phospholipids located at the inner lipid bilayer (e.g. phosphatidylethanolamine) while cholesterol interacts more with phosphatidylcholine located at the outer lipid bilayer. This differential interaction may cause selective changes in membrane fluidity at different depths of the bilayer and thus may modulate the activities of membrane-bound proteins such as enzymes and receptors.
Adipose Tissue↗
Structure of a retro-binding peptide inhibitor complexed with human alpha-thrombin.
The crystallographic structure of the ternary complex between human alpha-thrombin, hirugen and the peptidyl inhibitor Phe-alloThr-Phe-O-CH3, which is acylated at its N terminus with 4-guanidino butanoic acid (BMS-183507), has been determined at 2.6 A resolution. The structure reveals a unique "retro-binding" mode for this tripeptide active site inhibitor. The inhibitor binds with its alkyl-guanidine moiety in the primary specificity pocket and its two phenyl rings occupying the hydrophobic proximal and distal pockets of the thrombin active site. In this arrangement the backbone of the tripeptide forms a parallel beta-strand to the thrombin main-chain at the binding site. This is opposite to the orientation of the natural substrate, fibrinogen, and all the small active site-directed thrombin inhibitors whose bound structures have been previously reported. BMS-183507 is the first synthetic inhibitor proved to bind in a retro-binding fashion to thrombin, in a fashion similar to that of the N-terminal residues of the natural inhibitor hirudin. Furthermore, this new potent thrombin inhibitor (Ki = 17.2 nM) is selective for thrombin over other serine proteases tested and may be a template to be considered in designing hirudin-based thrombin inhibitors with interactions at the specificity pocket.
Amino Acid Sequence↗
Molecular modeling studies of novel retro-binding tripeptide active-site inhibitors of thrombin.
A novel series of retro-binding tripeptide thrombin active-site inhibitors was recently developed (Iwanowicz, E. I. et al. J. Med. Chem. 1994, 37, 2111(1)). It was hypothesized that the binding mode for these inhibitors is similar to that of the first three N-terminal residues of hirudin. This binding hypothesis was subsequently verified when the crystal structure of a member of this series, BMS-183,507 (N-[N-[N-[4-(Aminoiminomethyl)amino[-1-oxobutyl]-L- phenylalanyl]-L-allo-threonyl]-L-phenylalanine, methyl ester), was determined (Taberno, L.J. Mol. Biol. 1995, 246, 14). The methodology for developing the binding models of these inhibitors, the structure-activity relationships (SAR) and modeling studies that led to the elucidation of the proposed binding mode is described. The crystal structure of BMS-183,507/human alpha-thrombin is compared with the crystal structure of hirudin/human alpha-thrombin (Rydel, T.J. et al. Science 1990, 249,227; Rydel, T.J. et al. J. Mol Biol. 1991, 221, 583; Grutter, M.G. et al. EMBO J. 1990, 9, 2361) and with the computational binding model of BMS-183,507.
Amino Acid Sequence↗
Potentiation of beta-adrenoceptor agonist mediated-lipolysis by cholesterol-derived oxysterols.
Cholesterol-derived oxysterols such as cholestanol, cholestanone and coprostanone were able to potentiate epinephrine-induced lipolysis in intact rat adipocytes but not cholesterol. The relative potency of the oxysterols followed the sequence: cholestanone > or = coprostanone > cholestanol. Cholestanone was selected to study its mode of action on epinephrine-induced lipolysis. A sustained increase in the level of cAMP was observed in adipocytes incubated with both cholestanone and epinephrine compared to a transient peaking of cAMP in adipocytes incubated with epinephrine alone. Binding assays using [125I]cyanopindolol (beta-adrenergic receptor antagonist) showed that cholestanone could increase the binding affinity of [125I]-cyanopindolol to beta-adrenergic receptors on rat adipocyte ghost membranes without affecting the total number of binding sites. The results suggest that cholestanone exerts its potentiation effect by facilitating the binding of beta-adrenergic agonist to its receptor.
Adipocytes↗
Retro-binding tripeptide thrombin active-site inhibitors: discovery, synthesis, and molecular modeling.
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Amino Acid Sequence↗
Parapharyngeal teratoma in the newborn.
A parapharyngeal teratoma in a newborn was the cause of acute respiratory distress, which was relieved by tracheostomy. Subsequent investigations by soft tissue x-rays of the neck, computed tomography, and examination under anesthesia defined the anatomic location of the tumor, its extent, and its likely nature. The tumor was removed completely by the transcervical approach. Mandibulotomy was not required. Histological examination showed the presence of a large amount of mature brain tissue, a moderate amount of collagenous fibers and smooth muscle cells, and a minute amount of cartilage and epithelial structures. The postoperative course was satisfactory. No recurrence was seen 6 years after surgery. The computed tomography scan was found to be the most useful investigative method. To the authors' knowledge, this is the first comprehensive report of a teratoma occupying the parapharyngeal space in a newborn.
Female↗
Effects of retinoic acid on cartilage differentiation in a chondrogenic cell line.
Previously we have isolated the monopotential chondrogenic cell line RCJ 3.1 C5.18 from the multipotential mesenchymal cell line RCJ 3.1 [Grigoriadis et al.: Endocrinology, 125:2103-2110, 1989]. When cultured for approximately 20 days under appropriate conditions, these cells from cartilage nodules. In the present investigation, we have used this cell line to study the effects of all-trans retinoic acid (RA) on chondroblast differentiation, cartilage formation, and cartilage degradation. Continuous exposure of cultures to RA (0.01-100 nM) inhibited chondroblast differentiation and glycosaminoglycan (GAG) accumulation in a dose-dependent manner, without comparable effects on cell growth. Pulse treatment with RA for various 4 day periods during a 17-24 day culture period established that RA inhibited differentiation of chondroprogenitors at all periods tested. These effects were reversible, except for part of the effect on early chondroprogenitors. Treatment with RA on days 13-17 in 17 day cultures not only resulted in cessation of cartilage formation, but also in disappearance of pre-existing cartilage nodules. We demonstrated that this was associated with RA-induced downregulation of GAG synthesis and increased degradation of cartilage proteoglycans. Hence, the inhibitory effects of RA on cartilage formation consist of inhibition of chondroblast differentiation, inhibition of GAG synthesis by differentiated chondroblasts, and stimulation of cartilage proteoglycan degradation by differentiated chondroblasts and/or chondrocytes. These results indicate that the clonal monopotential chondrogenic cell line RCJ 3.1 C5.18 forms a good model system to study the effects of retinoids on cartilage differentiation, formation, and degradation.
Animals↗
Treatment of neck nodes in oral cancer.
In a review of 98 patients who were operated upon for squamous oral cancer, a high proportion of them (48%) developed recurrence after a minimum follow-up of 2 years. Nodal status significantly affected the nodal recurrence rate and survival. For N0, N1, N3 tumours, the 2-year nodal recurrence-free rates were 79, 83, 18%, and the 2-year survival rates were 58, 59 and 10%. For small tumours with N0 neck, the group with elective neck dissection and the observed group did not have statistically different nodal recurrence-free rate and overall survival. The 2-year nodal recurrence-free rate was 92% versus 77% (P value > 0.3) and the 2-year survival rate was 56% versus 72% (P value > 0.6). In patients with N1 neck, radical neck dissection was reasonably effective in controlling neck metastasis. Radical neck dissection in an attempt to treat fixed neck nodes (N3) was not successful in controlling the neck disease.
Adult↗
Tracheostomal stenosis after immediate tracheoesophageal puncture.
The incidence of tracheostomal stenosis in a group of patients after total laryngectomy with or without pharyngectomy plus immediate tracheoesophageal or tracheogastric puncture was compared with that of a control group without puncture. The stenosis rate of the puncture group was significantly higher than that of the control group (19% vs 6%). The other probable etiologic factors for stomal stricture were similar in both groups. Analysis of the risk factors in the puncture group suggested a higher tendency of stenosis in females (43% vs 16%) and in patients receiving postoperative radiotherapy (29% vs 14%), although the difference failed to reach statistical significance.
Adult↗
Flexibility of tripeptides in solution: free energy molecular mechanics.
A full theory of the conformations of biopolymers requires a method for treating the effects of solvent on the induced structures. This is especially critical in aqueous solvent where hydrogen-bonding and dielectric shielding play major roles in determining the relative stability of conformers. Calculations of peptide conformations on a free energy surface are contrasted with the traditional sort of calculations which employs a simple potential energy function (in vacuo). The method employs a pairwise decomposable free energy surface determined by approximate analytical statistical mechanical theory. Applications are presented for tripeptides of alanine and glycine in water. This method, with precomputed free energy functions, takes the same amount of time and effort as traditional molecular mechanics in vacuo.
Alanine↗
Modified jet ventilation during total laryngectomy: a prospective study using pulse oximetry and a pressure regulator.
A method of jet ventilation during total laryngectomy is described. During the construction of the terminal tracheostomy, a small metal tube is used, instead of the traditional tracheostomy tube, to provide intermittent jet ventilation down the distal trachea. A pressure regulator is also employed to choose a driving pressure best suited to the chest and lung compliance of each patient. Excellent surgical access for tracheo-cutaneous anastomosis is achieved. Satisfactory ventilation during the jet period is also confirmed by unaltered PaCO2 and increased PaO2 levels. The use of pulse oximetry as a non-invasive and continuous monitor of arterial oxygenation is a simple alternative to arterial blood sampling.
Adult↗
Fate of skin element of pectoralis major flap in intraoral reconstruction.
A skin island carried by pectoralis major muscle has been used to reconstruct an intraoral defect created after resection of a tumor. To our knowledge, what happens to the skin after its mobilization from the chest wall into the mouth has not been documented. To answer this, a wedge biopsy of the intraoral skin island on the pectoralis muscle was performed in 14 patients under local anesthesia. The skin biopsy specimen was subjected to scanning electron microscopic and histologic examination. The interval between the reconstructive surgery and the biopsy ranged from ten to 66 months (mean, 32 months). The results revealed desquamation of the epidermis and loss of appendages. The degree of desquamation was maximal when the skin island was used to replace the whole of the floor of the mouth and least when it was used for the lateral portion.
Adult↗
Immediate reconstruction of pharyngoesophageal defects. Preference or reference.
In this era of development in reconstruction, interest in searching for the most appropriate procedure for replacing the pharyngoesophageal defect is intense. The type of defect, depending on the level of invasion by the cancer, should be classified as partial pharyngeal, circumferential pharyngeal, or pharyngoesophageal. Within each class, the surgeon can have his preference for a reconstructive procedure according to available expertise and familiarity. In our series of 97 patients with pharyngoesophageal defects resulting from resection of laryngeal, hypopharyngeal, and cervical esophageal cancers, the patch-on pectoralis major myocutaneous flap, the tubed pectoralis major myocutaneous flap, and the stomach were used for the three types of defects, respectively. Mortality and morbidity, while kept at an acceptable level, appear to rise as the complexity of the procedure increases. This supports the argument that the reconstructive method should be selected with reference to the type of defect, which is in turn dependent on the site and behavior of the tumor. The reconstructive procedure is to fit the defect, and not vice versa.
Adult↗
Selective elimination of interactions: a method for assessing thermodynamic contributions to ligand binding with application to rhinovirus antivirals.
A new method for evaluating the free energy of various physical interactions, such as hydrogen-bond, electrostatic, or van der Waals interactions, is presented. Rather than destroying or creating whole groups, selective (pairwise) interactions are eliminated from the total potential energy and the energy difference with the fully interacting system is evaluated. The exponential ensemble average of such an energy difference is then directly related to the corresponding free energy difference. This procedure is then applied to a rather large protein-ligand system involving the coat proteins of a human rhinovirus and an antiviral ligand. The results seem to indicate that a particular bent hydrogen bond between the ligand and protein system may not be favorable for binding. The method presented gives an estimate of the hydrogen bond free energy contribution with an available trajectory that was previously computed without the expenditure of sizeable computational resources such as recomputing a trajectory. This procedure is effective and efficient for computing the free energy for a given type of physical interaction. It can be used for calculating the binding energy differences for various interactions which can be used to guide the search for isosoluble synthetic targets.
Antiviral Agents↗