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Biomedical subjects

H Lee

Publications and source records attributed to H Lee.

At least 1,009 records · Page 56Linked to original sources

Canalographic evaluation of the external ear canal in dogs.

Canalography was performed to measure the diameter of the horizontal ear canal and to assess the clinical relevance of the measurements in identifying abnormalities of the ear canal. The diameter of the proximal and distal end of the annular cartilage in the horizontal ear canal was measured using canalography in 222 ears. The tympanic membrane could not be visualized with otoscopic examination in 70 ears even after ear cleansing. These canals were classified as being stenotic. The diameter of the proximal annular cartilage in the stenotic canals ranged from 0.8 to 3.1 mm (mean = 2.6 +/- 0.8 mm). The proximal annular cartilage was consistently smaller in diameter than the distal annular cartilage. The ratio between the diameter of the proximal and distal annular cartilage varied between dogs. In stenotic ear canals (70 ears) the ratio was less than 0.65. Total ear canal ablations and histopathological analysis were performed in 70 ear canals classified as stenotic after canalography. Hyperplasia of the epidermal layer was found in 56 stenotic canals. Stenosis of the canal due to otitis externa was found in the other 14 canals. Three canals with severe otitis externa were also diagnosed with canalography as having a ruptured tympanic membrane. The results suggest that canalography can be used to measure the diameter of the horizontal ear canal and to assess whether or not the tympanic membrane is ruptured prior to conservative or surgical therapy.

Animals↗

Behavior of murine renal carcinoma cells grown in ectopic or orthotopic sites in syngeneic mice.

We examined whether the organ microenvironment modulates the metastatic behavior and the response to doxorubicin (DXR) in murine renal carcinoma (RENCA) cells. Tumor cells were injected into kidney (orthotopic) and subcutis (ectopic) of syngeneic mice. Lung metastases developed in up to 57% (17/30) of animals having kidney tumors but not in those with skin tumors. Tumors growing in the kidney were more resistant to DXR than tumors growing in the subcutis when mice were given intravenous injections of DXR (8 mg/kg) on days 8 and 15 after implantation. In addition, tumor cells cultured from kidney tumors were initially more resistant to DXR than tumor cells cultured from subcutis tumors. After tumor cells were passaged in vitro, all cells exhibited a similar sensitivity to DXR. Additionally, we examined the expression levels of mdr1, EGFR and type IV collagenase by an in situ mRNA hybridization technique. A higher mRNA expression for type IV collagenase and EGFR was found in kidney tumors than in subcutis tumors. These results demonstrate that the organ environment influences the drug responsiveness and the expression of metastasis-related genes in murine renal carcinoma cells.

Animals↗

Methamphetamine-induced changes in AP-1 binding and dynorphin in the striatum: correlated, not causally related events?

Activation of D1 dopamine (DA) receptors in the striatum increases the expression of the opioid neuropeptide, dynorphin (DYN). While cAMP is generally accepted as a second messenger in this signal transduction pathway, the role of Fos/FRA proteins and AP-1 binding in mediating D1 receptor-induced changes in DYN expression remains uncertain. In this study, DYN peptide and mRNA levels, as well as Fos/FRA proteins and AP-1 DNA binding activity, were measured in individual animals following acute challenge with the psychostimulant drug methamphetamine (METH). METH caused an initial decrease in striatal levels of DYN A, reflecting increased peptide release. Six hours postinjection, DYN mRNA levels were significantly elevated by METH as compared to vehicle-injected controls. At the same time, these drugs increased the expression of Fos/FRA-ir proteins, in particular the 35- and 40-kDa molecular weight species, and increased binding to the AP-1 DNA element. Analyses of the time course of METH's effects revealed that DYN mRNA levels, Fos/FRA proteins and AP-1 binding activity showed variable increases by 3 h but all were significantly elevated above control levels by 6 h posttreatment. The D1-specific antagonist, SCH 23390, completely blocked the METH-induced changes in DYN peptide and mRNA levels while a D2 receptor antagonist (sulpiride) had little or no effect. These data indicate that stimulant drugs such as METH increase the expression of DYN and AP-1 factors in the striatum via a D1 receptor-mediated mechanism. However, the finding that AP-1 binding merely paralleled, but did not precede, the increase in DYN expression, as would be expected if it were mediating increased gene transcription, suggests these may be correlative, not causally related events.

Adrenergic Uptake Inhibitors↗

Spontaneous echocardiographic contrast in the descending thoracic aorta.

Spontaneous echocardiographic contrast (SEC) is an occasional finding observed in the atria in patients undergoing transesophageal echocardiographic studies, but has rarely been described in the descending thoracic aorta in the absence of an aortic dissection. The pathophysiology of SEC in the cardiac and vascular structures appears to be related to an interaction between red blood cells and plasma proteins in the setting of a low flow state. In this report we present three cases of SEC in the descending thoracic aorta, with one of the cases of SEC resolving with repair of his underlying cardiac disorder.

Aged↗

Resuspension of sediment-associated Escherichia coli in a natural stream.

In this study, a tracer bacteria was used to investigate the resuspension and persistence of sediment-associated bacteria in a small alluvial stream. The study was conducted in Swan Creek, located within the Grand River watershed of Ontario, Canada. A 1.1-m2 section of the bed was seeded with a strain of Escherichia coli resistant to nalidixic acid (E. coli NAR). The survival, transport, and redistribution of the tracer bacteria within a 1.7-km river section downstream of the source cell was assessed for a 2-mo period following the introduction of the tracer bacteria. This study has illustrated that enteric bacteria can survive in bed sediments for up 6 wk and that inactivation of the tracer bacteria resembled typical first-order decay. Critical conditions for resuspension, as well as resuspension rates, of sediment-associated bacteria were determined for several storm events. The critical shear stress for E. coli NAR resuspension in Swan Creek ranged from 1.5 to 1.7 N m(-2), which is comparable with literature values for critical shear stresses for erosion of cohesive sediments. Bacteria resuspension was primarily limited to the rising limb of storm hydrographs implying that a finite supply of sediment-associated bacteria are available for resuspension during individual storm events. The information presented in this paper will further the development of representative microbial water quality models.

Escherichia coli↗

A comparison study between ragweed-specific IgG4 as measured by RAST and FAST.

A solid phase Sepharose-based RIA (IgG4 RAST) was compared to the IgG4 FAST enzyme immunoassay for measurements of Ragweed-specific IgG4. Although FAST reagents were used, a standard serum of known antibody content along with modifications in the FAST assay were necessary to attempt to develop a quantitative assay. Various assay parameters such as precision, reproducibility, sensitivity and parallelism were examined. Specificity of the monoclonal anti-IgG4 used in the FAST was not evaluated. Conditions and method of assay for the two systems differed substantially, particularly in the short incubation times for the IgG4 determinations.

Allergens↗

Enhancement of gene transfer efficiency into human cancer cells by modification of retroviral vectors and addition of chemicals.

Retroviral vectors have recently experienced limited use in cancer gene therapy mainly due to poor transduction efficiency. To overcome this drawback, we attempted to enhance the transduction efficiency by employing different retroviral packaging cell lines and chemical additives. The retrovirus from the PG13 packaging cell line gave mostly higher or similar transduction efficiencies in a variety of human cancer cell lines compared to the retrovirus from the PA317, Bing, or FLYRD18 packaging cell line. A cationic liposome, especially Lipofectamine, significantly enhanced the transduction efficiency of a retrovirus. However, the retrovirus derived from the PG13 cell line could not infect the murine cell line efficiently even after Lipofectamine treatment. Furthermore, chloroquine did not improve the transduction efficiency regardless of the presence of chemical additives. These results, therefore, suggested that the transduction efficiency of a retrovirus in human cancer cells can certainly be improved when a proper packaging cell line is chosen. In addition, this study implied that Lipofectamine is a superb additive to enhance the transduction efficiency of a retrovirus via a specific virus envelope protein-receptor interaction for virus entry, and that receptor-mediated endocytosis does not seem to be the leading route of virus delivery to liberate a virus genome.

3T3 Cells↗

Unilateral rectus resection in the treatment of undercorrected or recurrent strabismus.

BACKGROUND: When surgery is required for an undercorrection or for a recurrent strabismus that is in the same direction as the previous deviation, traditional options have included a rerecession of the previously operated muscle(s), a marginal myotomy of the previously operated muscle(s) with or without a resection of the direct antagonist, or a bilateral resection of the antagonist muscles. While many surgeons prefer to perform a bilateral resection for these reasons, a unilateral resection would be a useful approach for small to moderate deviations. METHODS: Data were collected for patients who had undergone a unilateral rectus resection: age, number of prior surgeries, the preoperative deviation, the postoperative deviation at 1 week, 6 weeks, and 6 months, and the amount of surgery performed. An acceptable postoperative result was considered to be any deviation >8 pd. RESULTS: A resection of a single rectus muscle was undergone by 11 3 patients. Complete data were available on 81 of these patients: 60 underwent a unilateral resection of the lateral rectus and 21 underwent a unilateral resection of the medial rectus. Of those patients undergoing a unilateral lateral rectus resection, 90% were acceptably aligned at the 6-month postoperative exam. Among those patients undergoing a medial rectus resection, 95.2% obtained a successful result. CONCLUSIONS: A unilateral resection of the medial or lateral rectus is an effective tool in the treatment of undercorrected or recurrent strabismus. It is predictable, stable in the immediate postoperative period, and limits surgery to 1 eye.

Adolescent↗

Effect of gamma-irradiation on peptide-containing hydrophilic poly (d,l-lactide-co-glycolide) microspheres.

The effect of gamma-irradiation on the physicochemical properties of peptide-containing hydrophilic poly (d,l-lactide-co-glycolide) (PLGA) microspheres was evaluated. PLGA (50/50, Mw: 8,600) with free carboxylic end groups was used to make drug-loaded and placebo microspheres by a solvent extraction evaporation method. Both formulated and non-formulated microspheres were gamma-irradiated at 0, 1, 1.5, and 2.5 Mrad doses. HPLC analysis based on extraction of peptide from the microspheres showed that peptide content of the microspheres was lowered upon irradiation and the reduction was more pronounced in formulated microspheres. The in-vitro release in 0.033M phosphate buffer, pH 7.0 at 37 degrees C (based on extraction of residual peptide) showed that the initial and subsequent release of peptide was higher in gamma-irradiated microspheres during the first 20 days. The difference became insignificant during the erosional controlled release of the peptide. There was no difference in release between the formulated and non-formulated microspheres of the nonirradiated or irradiated forms. Molecular weights (Mw and Mn), determined by size exclusion chromatography, were reduced by gamma-irradiation for both formulated and non-formulated placebo microspheres. Differential scanning calorimetry showed a gradual reduction in Tg of placebo microspheres but no reduction in peptide-loaded microspheres. In-vivo evaluation of the nonirradiated and the 1.5 Mrad irradiated microspheres showed no marked differences through 28 days. Since irradiation caused a lowering of Mw and Mn with the appearance of a low amount of unidentified substances, seemingly catalyzed by the polymer and the formulation excipients, gamma-irradiation sterilization of these parenteral delivery systems requires careful investigation on an individual product basis.

Gamma Rays↗

Detection of p53 mutations in sputum smears precedes diagnosis of non-small cell lung carcinoma.

Little progress has been made in reducing lung cancer mortality by applying conventional methods to early diagnosis and screening. Recent advances in molecular oncology, however, have provided tools which may be of use in this area. p53 gene mutation is the most common gene alteration in the development of lung cancer. Conventional cytologic analysis of sputum is an insensitive test for the diagnosis of lung cancer. In this study, we attempted to establish a polymerase chain reaction (PCR)-based assay for assessing the possibility of early detection of p53 mutation in archival Papanicolaou-stained cytologic sputum smears. Ten sputum smear slides were collected prior to clinical diagnosis from 10 lung cancer patients who had been confirmed to have p53 mutations in surgically resected lung tumors. We successfully obtained sufficient amounts of RNA from each sputum smear specimen for amplification of PCR and direct sequencing. Only one patient was found to have p53 mutation at codon 286; the other nine patients had wild type p53 genes. This result supports the possibility that detection of p53 mutations in cytologic sputum smears is an available strategy for the early diagnosis of lung cancer.

Aged↗

Preventing sexual transmission of HIV: anti-HIV bioregulatory and homeostatic components of commercial sexual lubricants.

Certain safe over-the-counter (OTC) sexual lubricants such as Astroglide, KY Liquid, Replens, Vagisil, ViAmor, and Wet Stuff inhibit both cell-free HIV and the production of HIV by infected leukocytes in vitro even in the presence of seminal fluid. To identify which components of the lubricants were active against HIV, we tested five components (glycerin, methylparaben, propylparaben, polyquaternium-32, and propylene glycol). The paraben preservatives and propylene glycol in the lubricants did not inhibit HIV, while the common natural homeostatic metabolite, glycerin, and the thickener polyquaternium-32 did strongly inactivate infectious HIV and HIV-infected leukocytes. Activity against HIV and HIV-infected cells by glycerin was stable through 24 hours at 37 degrees C. Glycerin and polyquaternium-32 were active at minimum concentrations of approximately 2% and 0.01%, respectively--well within the highest FDA safety guidelines. Both active components disrupted infected leukocytes within 5 minutes which resulted in inhibition of infectious HIV production by infected leukocytes of greater than 25 to 100-fold. These components do not disrupt vaginal epithelial cells in vivo. These components also rapidly inactivate cell-free HIV by 10- to 30-fold. Thus, we may conclude that the active components of the OTC lubricants are glycerin and polyquaternium-32. Using these components, OTC sexual lubricants could be reformulated to optimize their anti-HIV activity. Furthermore, clinical trials of these lubricants and components seem to be indicated because of their FDA safety level, wide availability, and low cost.

Anti-Infective Agents, Local↗

In vivo metabolism of isoxicam in rats, dogs, and monkeys.

Isoxicam is a long half-life nonsteroidal anti-inflammatory agent which undergoes extensive metabolism prior to elimination in animals and man. The major route of isoxicam transformation is hydroxylation of the methylisoxazole functionality to form hydroxymethylisoxicam, and cleavage of its benzothiazine moiety to give an oxoacetic acid metabolite. The metabolic pathway for scission of the benzothiazine moiety to the oxoacetic acid metabolite and to other potential metabolites is not known. To gain additional information on the metabolic fate of isoxicam, 14C-isoxicam labeled on the N-methyl group was administered to rats, dogs, and monkeys with urine and feces collected for metabolic profiling and identification. Identified as new metabolites of isoxicam were an open-ring sulfonamide, N-methylsaccharin, and saccharin. The formation of these metabolites suggests that isoxicam undergoes direct oxidative scission of its benzothiazine ring at carbon atom 3 to generate the observed open-ring sulfonamide, N-methylsaccharin, and oxoacetic acid metabolites.

Animals↗