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Biomedical subjects

M Leung

Publications and source records attributed to M Leung.

At least 37 records · Page 2Linked to original sources
PubMed1997

Short-term effects of topical levobunolol on the human retinal circulation.

PURPOSE: The effect of topical levobunolol HCl 0.5% on the retinal circulation was studied on 15 normal volunteers aged 21-54 years (32 +/- 10 years). METHODS: In a double-masked, randomised design, one eye of each subject received a drop of levobunolol HCl 0.5% (LEV) and the fellow eye received a drop of artificial tears (TEAR). Leucocyte velocity (VBFS) and density in the retinal macular microcirculation were measured by the blue-field simulation technique. Venous diameter (D), maximum erythrocyte velocity (Vmax) and volumetric blood flow rate (Q) were measured in a major temporal vein by laser Doppler velocimetry and monochromatic fundus photography. RESULTS: The following average changes from baseline were observed 2 hours after treatment: heart rate, -4.6 +/- 8.3% (p = 0.04); intraocular pressure, -31.7 +/- 10.6% (p = 0.0001); and perfusion pressure, 15.4 +/- 14.4% (p = 0.02) in LEV eyes; no statistically significant changes in IOP and perfusion pressure were seen in TEAR eyes. When each eye was compared with its own baseline, there were no significant changes in VBFS, density, D, Vmax and Q in LEV eyes. In TEAR eyes, there were no significant changes in VBFS, density, Vmax and Q, but a significant change in D (-1.8 +/- 2.6%; p = 0.02) was observed. A significant average percentage increase in Q of 10.9 +/- 19.2% (paired t-test between the change after LEV and the change after TEAR, p = 0.044) was seen in LEV eyes when compared with TEAR eyes. Twelve of the 15 subjects demonstrated a relative increase in Q in the LEV eyes in comparison with the TEAR eyes, while 3 subjects showed the opposite. CONCLUSION: A significant difference in the effect of levobunolol between the two eyes was detected, even though there was no statistically significant effect when each eye was compared with its baseline.

Administration, Topical↗
PubMed1997

Rarity of transferable beta-lactamase production by Klebsiella species.

We report a survey of beta-lactamases and their transferability in Klebsiella spp. isolated from blood during 1992-95. beta-Lactamases were characterized by determination of isoelectric point (pI), by hybridization of plasmid DNA preparations with probes for SHV and TEM sequences and by PCR with SHV- or TEM-specific primers. There were 80 isolates of Klebsiella pneumoniae and 22 isolates of Klebsiella oxytoca. Most isolates of K. pneumoniae had a chromosomally encoded SHV-1 beta-lactamase (or a closely related enzyme); K. oxytoca also produced chromosomal beta-lactamases, but these were distinct from SHV-1. Plasmid-encoded beta-lactamases were rare in Klebsiella spp., being found in six (7.5%) isolates of K. pneumoniae and in none of the K. oxytoca. beta-Lactamase activities were relatively low (< 100 nmoles nitrocefin hydrolysed per minute per mg of protein) and ampicillin MICs were < or = 128 mg/L for most isolates of both species. However, all isolates of K. pneumoniae with plasmid-encoded beta-lactamases, three other isolates of K. pneumoniae and three isolates of K. oxytoca had high beta-lactamase activities (> 100 nmoles/mg/min) and very high ampicillin MICs (> or = 1024 mg/L).

Ampicillin↗
PubMed1997

alpha 1-Proteinase inhibitor in gingival crevicular fluid of humans with adult periodontitis: serpinolytic inhibition by doxycycline.

The serum protein, alpha 1-proteinase inhibitor (alpha 1-PI), defends the host against serine proteinases, e.g. PMN elastase. Using a rabbit anti-serum against human alpha 1-PI, this protein in GCF was quantified from a standard curve constructed from dot-blot analysis and characterized by Western blot. GCF was collected on filter paper strips from healthy (H), gingivitis (G) and adult periodontitis (AP) patients, then extracted with Tris/NaCl/CaCl2 buffer, pH 7.6. alpha 1-PI concentration increased with G and was highest in AP subjects. H sites only showed intact alpha 1-PI (52 kDa); no degradation fragments (48 kDa) were detected. In G and AP subjects, alpha 1-PI degradation fragments were seen in 17% and 71% of GCF samples, respectively. Both collagenase and alpha 1-PI-degrading activities in GCF increased with severity of inflammation (GCF flow). Moreover, the alpha 1-PI degrading (or serpinolytic) activity was characterized as a matrix metalloproteinase, probably collagenase, based on its in vitro response to a panel of different proteinase inhibitors including doxycycline. We propose: (1) that collagenase promotes periodontal breakdown not only by degrading collagen, but also by depleting alpha 1-PI regulation of elastase and other serine-proteinases, thereby favoring a broader attack on extracellular matrix (ECM) constituents, and (2) based on a recent longitudinal double-blind study using the techniques described above for alpha 1-PI analysis, that low-dose doxycycline administration to humans with adult periodontitis can inhibit this broad cascade of ECM degradation.

Adult↗
PubMed1996

Complementation analysis of mutants of nitric oxide synthase reveals that the active site requires two hemes.

For catalytic activity, nitric oxide synthases (NOSs) must be dimeric. Previous work revealed that the requirements for stable dimerization included binding of tetrahydrobiopterin (BH4), arginine, and heme. Here we asked what function is served by dimerization. We assessed the ability of individually inactive mutants of mouse inducible NOS (iNOS; NOS2), each deficient in binding a particular cofactor or cosubstrate, to complement each other by generating NO upon cotransfection into human epithelial cells. The ability of the mutants to homodimerize was gauged by gel filtration and/or PAGE under partially denaturing conditions, both followed by immunoblot. Their ability to heterodimerize was assessed by coimmunoprecipitation. Heterodimers that contained only one COOH-terminal hemimer and only one BH4-binding site could both form and function, even though the NADPH-, FAD-, and FMN-binding domains (in the COOH-terminal hemimer) and the BH4-binding sites (in the NH2-terminal hemimer) were contributed by opposite chains. Heterodimers that contained only one heme-binding site (Cys-194) could also form, either in cis or in trans to the nucleotide-binding domains. However, for NO production, both chains had to bind heme. Thus, NO production by iNOS requires dimerization because the active site requires two hemes.

Animals↗
PubMed1996

Occlusion of large atrial septal defects with a centering buttoned device: early clinical experience.

A feasibility clinical study was conducted for the transcatheter occlusion of large ostium secundum atrial septal defects with the centering buttoned device. The centering buttoned device is a modification of the regular buttoned device in which a centering counter-occluder is sutured at the central 40% portion of the occluder. During centering it is stretched, forming a parachute-shaped structure and pulling the occluder over the center of the defect. During buttoning, the counter-occluder forms a double figure eight, opposing the right atrial side of the atrial septum. Occlusion was performed in 12 patients aged 6 to 56 years. All had been rejected for transcatheter occlusion by the regular buttoned device, because of either their defect size or the lack of adequate septal rim. The defect size varied between 23 and 31 mm, and the device size varied between 45 and 60 mm. Nine had immediate effective occlusions of their defects and three residual shunts. One patient with unbuttoning had hemolysis at 2 weeks and underwent surgery. Early results of the transcatheter occlusion of large atrial septal defects are promising, and larger clinical trials are justified.

Adolescent↗
PubMed1995

Opioid peptides in the nervous system of Aplysia: a combined biochemical, immunocytochemical, and electrophysiological study.

1. We have used biochemical, immunocytochemical, and electrophysiological techniques to evaluate the role of opioid peptides in the central nervous system of the marine mollusc, Aplysia californica. 2. Binding studies using 3H-D-Ala2, met-enkephalinamide (3H-DAMA) showed a single class of high-affinity binding sites with a Kd of 1.3 nM and a binding density of 45 pmol/g. 3. HPLC extracts of ganglia revealed multiple peaks with immunoreactivity for either leu (LEU-IR)- or met-enkephalin (MET-IR), but the amounts were not uniformly distributed in all ganglia. 4. LEU-IR and MET-IR neurons were demonstrated immunocytochemically in all ganglia, but MET-IR neurons were more frequent and were concentrated in pedal and pleural ganglia. While absorption control studies abolished MET-IR, LEU-IR was only partially abolished in the neuropil. 5. In electrophysiological studies, both depolarizing and hyperpolarizing responses were found to D-Ala2-leu-enkephalin (DALEU) and D-Ala2-met enkephalin (DAMET) on some and different neurons. 6. HPLC fractions from regions with retention times corresponding to authentic leu- or met-enkephalin showed physiologic responses similar to those of DALEU and DAMET, respectively. 7. These studies suggest that a variety of endogeneous opioid peptides play physiologically important roles in the nervous system of Aplysia, including but not necessarily limited to leu- and met-enkephalin.

Analgesics, Opioid↗
PubMed1995

Evaluation of myocardial infarction therapy at a Canadian tertiary referral hospital.

OBJECTIVE: To evaluate the appropriateness of acute and postmyocardial infarction (MI) treatment. DESIGN: A retrospective chart review. SETTING: Tertiary care teaching hospital. PATIENTS: All patients admitted with a potential MI or who experienced an MI during their hospital stay from November 18, 1991 to September 20, 1992. RESULTS: For acute treatment, thrombolytics, acetylsalicylic acid (ASA) and intravenous beta-blockers were used in 82%, 96% and 39% of eligible patients with a median time delay of 1.4, 4.4 and 1.8 h, respectively. For post-MI treatment, ASA, oral beta-blockers, warfarin and angiotensin-converting enzyme inhibitors were used in 93%, 68%, 50% and 71% of eligible patients, respectively. CONCLUSIONS: ASA use was considered acceptable while the other therapies were underused. The time delays in the initiation of therapies were also considered longer than desirable. Ongoing audit may aid in improving the quality of care in future patients with an MI.

Adrenergic beta-Antagonists↗
PubMed1994

Differential structural requirements for specific binding of nonpeptide and peptide antagonists to the AT1 angiotensin receptor. Identification of amino acid residues that determine binding of the antihypertensive drug losartan.

The biphenylimidazole derivative losartan exemplifies a novel class of nonpeptide antagonists that selectively inhibit angiotensin II binding to the mammalian AT1 receptor and have potentially wide application as anti-hypertensive agents. In contrast to mammalian AT1 receptors, which have high affinity for both peptide antagonists and losartan, amphibian and avian angiotensin II receptors are pharmacologically distinct and recognize peptide but not nonpeptide antagonists. Mutant rat AT1 receptors in which non-conserved amino acids were replaced by the corresponding amphibian residues were constructed to identify specific sites in the AT1 receptor that determine losartan binding. Only minor changes in binding affinity for peptide antagonists were observed in COS-7 cells transiently expressing mutant receptors, indicating that the structural integrity of the receptor was maintained. However, analysis of receptors with single point and combined mutations revealed that specific residues in transmembrane domains III, IV, V, VI, and VII are involved in binding of the nonpeptide antagonist to the mammalian AT1 receptor. The most marked attenuation of losartan binding (IC50 > 50 microM) was observed in a mutant receptor containing amino acid substitutions at Val108, Ala163, Thr198, Ser252, Leu300, and Phe301. These results have demonstrated that the binding site of a potent nonpeptide antagonist of the AT1 receptor is defined by epitopes located within the membrane-spanning regions of the receptor and is distinct from the site at which peptide antagonists bind to the AT1 receptor.

Amino Acid Sequence↗
PubMed1994

Treating periodontal diseases by blocking tissue-destructive enzymes.

A new therapeutic approach involves the discovery by the "Stony Brook group," that tetracyclines, but not other antibiotics, can inhibit host-derived collagen-destructive enzymes. This newly discovered property of tetracyclines is unrelated to the antimicrobial activity of these drugs. Examples support the hypothesis that this unexpected property of tetracyclines provides a new approach to treating periodontal diseases as well as a variety of medical disorders.

Gingival Crevicular Fluid↗
PubMed1993

Chemically-modified tetracycline normalizes collagen metabolism in diabetic rats: a dose-response study.

An earlier study indicated that a chemically-modified non-antimicrobial tetracycline (4-de-dimethylaminotetracycline; CMT-1) can inhibit excess collagenase activity in the connective tissues of diabetic rats, however, the optimum oral dose and resulting serum concentration were not determined. In the current study, adult male Sprague-Dawley rats (body weight approx. 350 g) were made diabetic by streptozotocin injection and administered by oral gavage either 0, 1, 2, 5, or 10 mg CMT-1 per day. After 3 weeks of drug therapy, the rats were killed and gingiva, skin, and serum collected. The tissues were 1) extracted, partially purified and analyzed for collagenase activity using [3H-methyl] collagen as substrate and SDS-PAGE/fluorography; 2) extracted in neutral salt and dilute acid solutions (4 degrees C) to assess collagen solubility; and 3) analyzed for hydroxyproline to determine tissue (skin) collagen mass. Serum was analyzed for glucose and CMT-1 concentration, the latter by HPLC. Inducing diabetes dramatically increased both gingival and skin collagenase activity and reduced skin collagen mass by 69.8%. Increasing the oral dose of CMT-1 progressively increased the serum concentration of the drug from 0.6-6.5 micrograms/ml and progressively decreased the excessive collagenase activity in gingiva and skin (p < 0.01 vs untreated diabetics). Although skin collagen mass tended to be increased at all oral doses of CMT-1, only the 5 mg dose effect was statistically significant (p < 0.01). The diabetes-induced reduction in collagen solubility, a classic abnormality (reflecting excessive collagen crosslinking) of this disease, was also normalized by CMT-1 therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1992

Tissue concentration and localization of tetracycline following site-specific tetracycline fiber therapy.

The primary objective of this study was to evaluate the concentration and location of tetracycline hydrochloride in tissue adjacent to periodontal pockets treated with a tetracycline impregnated fiber. A secondary objective was to determine if the presurgical placement of fibers had any adverse effects on healing following periodontal surgery. The study population consisted of 10 patients with at least 2 pockets in both maxillary quadrants of > or = 5 mm in depth and exhibiting bleeding on probing. After an initial scaling and root planing, placebo or tetracycline fibers were randomly assigned by quadrant to 2 non-adjacent pockets. Fibers were removed at the time of surgery; i.e., day 8, and periodontal surgery was performed utilizing a flap incision that allowed biopsy of 1 interdental papilla from each of the 2 test sites in each quadrant. One biopsy was analyzed for tetracycline concentrations by high performance liquid chromatography (HPLC). The second biopsy was examined by both light and ultraviolet fluorescence microscopy to determine the location of residual tetracycline and the intensity of inflammatory cell infiltrates. Results showed that the tissue concentration of the antibiotic in tetracycline treated sites was 64.4 +/- 7.01 ng/mg (ng of tetracycline/mg tissue weight) which corresponds to 43 micrograms of tetracycline and was below levels of accurate measurement in placebo treated sites. Tetracycline tissue concentrations corresponded to the ultraviolet fluorescence microscopy with a Pearson correlation coefficient of r = 0.92. Tetracycline fluorescence was noted in the soft tissue wall ranging from 1 to 20 microns.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗