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Biomedical subjects

R L Lee

Publications and source records attributed to R L Lee.

At least 19 recordsLinked to original sources
PubMed2006

A novel cationic cardiolipin analogue for gene delivery.

The optically active R and S isomers of cationic cardiolipin analogues (CCA) were synthesized and evaluated as a liposome based transfection reagent. Both isomers form stable liposomes with mean diameters of about 120 nm without any additional lipid ingredients. No significant change in particle size distribution profile was observed over one-month storage at room temperature (20-25 degrees C). The gel to liquid crystalline phase transition temperature (Tm) of cationic liposomes comprised of both R and S isomers was approximately 2 degrees C, as measured by differential scanning calorimetry (DSC). Both isomers also formed stable liposomes when combined with DOPE. In vitro transfection efficiency of the CCA/DOPE liposomes complexed to plasmid DNA was evaluated using a luciferase reporter gene. Both liposomes composed of R and S isomers of the cationic cardiolipin displayed higher transfection efficiency than commercially available Lipofectin. Further in vivo studies are warranted.

Animals↗
PubMed2001

Long-term effects of glucosamine sulphate on osteoarthritis progression: a randomised, placebo-controlled clinical trial.

BACKGROUND: Treatment of osteoarthritis is usually limited to short-term symptom control. We assessed the effects of the specific drug glucosamine sulphate on the long-term progression of osteoarthritis joint structure changes and symptoms. METHODS: We did a randomised, double-blind placebo controlled trial, in which 212 patients with knee osteoarthritis were randomly assigned 1500 mg sulphate oral glucosamine or placebo once daily for 3 years. Weightbearing, anteroposterior radiographs of each knee in full extension were taken at enrolment and after 1 and 3 years. Mean joint-space width of the medial compartment of the tibiofemoral joint was assessed by digital image analysis, whereas minimum joint-space width--ie, at the narrowest point--was measured by visual inspection with a magnifying lens. Symptoms were scored by the Western Ontario and McMaster Universities (WOMAC) osteoarthritis index. FINDINGS: The 106 patients on placebo had a progressive joint-space narrowing, with a mean joint-space loss after 3 years of -0.31 mm (95% CI -0.48 to -0.13). There was no significant joint-space loss in the 106 patients on glucosamine sulphate: -0.06 mm (-0.22 to 0.09). Similar results were reported with minimum joint-space narrowing. As assessed by WOMAC scores, symptoms worsened slightly in patients on placebo compared with the improvement observed after treatment with glucosamine sulphate. There were no differences in safety or reasons for early withdrawal between the treatment and placebo groups. INTERPRETATION: The long-term combined structure-modifying and symptom-modifying effects of gluosamine sulphate suggest that it could be a disease modifying agent in osteoarthritis.

Administration, Oral↗
PubMed2001

A simplified one-pot synthesis of 9-[(3-[18F]fluoro-1-hydroxy-2-propoxy)methyl]guanine([18F]FHPG) and 9-(4-[18F]fluoro-3-hydroxymethylbutyl)guanine ([18F]FHBG) for gene therapy.

9-[(3-[18F]Fluoro-1-hydroxy-2-propoxy)methyl]guanine ([18F]FHPG, 2) has been synthesized by nucleophilic substitution of N(2)-(p-anisyldiphenylmethyl)-9-[[1-(p-anisyldiphenylmethoxy)-3-toluenesulfonyloxy-2-propoxy]methyl]guanine (1) with potassium [18F]fluoride/Kryptofix 2.2.2 followed by deprotection with 1 N HCl and purification with different methods in variable yields. When both the nucleophilic substitution and deprotection were carried out at 90 degrees C and the product was purified by HPLC (method A), the yield of compound 2 was 5-10% and the synthesis time was 90 min from EOB. However, if both the nucleophilic substitution and deprotection were carried out at 120 degrees C and the product was purified by HPLC, the yield of compound 2 decreased to 2%. When compound 2 was synthesized at 90 degrees C and purified by Silica Sep-Pak (method B), the yield increased to 10-15% and the synthesis time was 60 min from EOB. Similarly, 9-(4-[18F]fluoro-3-hydroxymethylbutyl)guanine ([18F]FHBG, 4) was synthesized with method A and method B in 9% and 10-15% yield, respectively, in a synthesis time of 90 and 60 min, respectively, from EOB. Compound 2 was relatively unstable in acidic medium at 120 degrees C while compound 4 was stable under the same condition. Both compound 2 and compound 4 had low lipid/water partition coefficient (0.126 +/- 0.022, n=5 and 0.165 +/- 0.023, n=5, respectively). Although it contains non-radioactive ganciclovir ( approximately 5-30 microg) as a chemical by-product, compound 2 synthesized by method B has a similar uptake in 9L glioma cells as that synthesized by method A, and is a potential tracer for imaging herpes simplex virus thymidine kinase gene expression in tumors using PET. Similarly, compound 4 synthesized by method B contains approximately 10-25 microg of penciclovir as a chemical by-product. Thus, the simplified one pot synthesis (method B) is a useful method for synthesizing both compound 2 and compound 4 in good yield for routine clinical use, and the method is readily amenable for automation.

Chemical Phenomena↗
PubMed2001

Colorimetric and spectroradiometric characteristics of narrow-field-of-view clear skylight in Granada, Spain.

As part of our ongoing research into the clear daytime sky's visible structure, we analyze over 1,500 skylight spectra measured during a seven-month period in Granada, Spain. We use spectral radiances measured within 3 degrees fields of view (FOV's) to define colorimetric characteristics along four sky meridians: the solar meridian and three meridians at azimuths of 45 degrees, 90 degrees, and 315 degrees relative to it. The resulting clear-sky chromaticities in 44 different view directions (1) are close to but do not coincide with the CIE daylight locus, (2) form V-shaped meridional chromaticity curves along it (as expected from theory), and (3) have correlated color temperatures (CCT's) ranging from 3,800 K to infinity K. We also routinely observe that sky color and luminance are asymmetric about the solar meridian, usually perceptibly so. A principal-components analysis shows that three vectors are required for accurate clear-sky colorimetry, whereas six are needed for spectral analyses.

Journal Article↗
PubMed2001

Color and spectral analysis of daylight in southern Europe.

We have analyzed the colorimetric and spectral characteristics of 2600 daylight spectra (global spectral irradiances on a horizontal surface) measured for all sky states during a 2-year period at Granada, Spain. We describe in detail the chromaticity coordinates, correlated color temperatures (CCT), luminous efficacies, and relative UV and IR contents of Granada daylight. The chromaticity coordinates of Granada daylight lie far above the CIE locus at high CCTs (>9,000 K), and a CCT of 5,700 K best typifies this daylight. Our principal-components analysis shows that Granada daylight spectra can be adequately represented by using six-dimensional linear models in the visible, whereas seven-dimensional models are required if we include the UV or near-IR. Yet on average only three-dimensional models are needed to reconstruct spectra that are colorimetrically indistinguishable from the original spectra.

Journal Article↗
PubMed2000

Standardized head position and reference planes for dento-facial aesthetics.

The angulations of the anterior teeth in the sagittal view are important for diagnosing lip support for pleasing smiles and proper facial profiles (Figure 19). In Figure 20, the slant of the occlusal plane (incisal-canine line), the off-center tilted midline, and the asymmetry of the gingival line (contours) of this patient in the frontal view are now obvious. A diagnosis can now be made for possible correction using the horizontal and vertical frames of the articulator as a bioesthetic guide.

Cephalometry↗
PubMed1999

Receptor-targeted gene delivery via folate-conjugated polyethylenimine.

A novel synthetic gene transfer vector was evaluated for tumor cell-specific targeted gene delivery. The folate receptor is a tumor marker overexpressed in more than 90% of ovarian carcinomas and large percentages of other human tumors. Folic acid is a high affinity ligand for the folate receptor that retains its binding affinity upon derivatization via its gamma carboxyl. Folate conjugation, therefore, presents a potential strategy for tumor-selective targeted gene delivery. In the current study, we investigated a series of folate conjugates of the cationic polymer polyethylenimine (PEI) for potential use in gene delivery. A plasmid containing a luciferase reporter gene (pCMV-Luc) and the folate receptor expressing human oral cancer KB cells were used to monitor gene transfer efficiency in vitro. Transfection activity of polyplexes containing unmodified polyethylenimine was highly dependent on the positive to negative charge (or the N/P) ratio. Folate directly attached to PEI did not significantly alter the transfection activity of its DNA complexes compared to unmodified PEI. Modification of PEI by polyethyleneglycol (PEG) led to a partial inhibition of gene delivery compared to unmodified PEI. Attaching folates to the distal termini of PEG-modified PEI greatly enhanced the transfection activity of the corresponding DNA complexes over the polyplexes containing PEG-modified PEI. The enhancements were observed at all N/P ratios tested and could be blocked partially by co-incubation with 200 microM free folic acid, which suggested the involvement of folate receptor in gene transfer. Targeted vectors based on the folate-PEG-PEI conjugate are potentially useful as simple tumor-specific vehicles of therapeutic genes.

Carrier Proteins↗
PubMed1997

Image processing assessment of femoral osteopenia.

Visual assessment of femoral osteopenia (the radiographic presentation of osteoporosis) is unreliable. Many of the short-comings of observer grading can be overcome by digital image analysis. Our group has developed algorithms to make automatic assessment of osteopenia from clinical radiographs. Texture Analysis Models (TA) commonly used in image analysis were investigated as measures of osteopenia. Unlike densitometric methods, TA characterizes properties of the structure of the image (ie, trabecular patterns). A group of women were analyzed whose subjects ranged from those at risk of osteoporosis (n = 24) to normal (n = 40). Using an IBM PC, frame-grabber, camera, and light-box, we appraised five statistical TA algorithms for assessment of the femoral neck in standard pelvic radiographs: (1) Fractal Signature (FS) describes the image's fractal nature. (2) Auto-Correlation of unaltered and Sobel Edge Transformed images (ACSE) measures image spatial self-similarity. (3) Co-occurrence Matrices (CM) gives the joint probability of greylevels with distance/direction and describes statistical relationships of image variation. (4) Textural Spectrum (TS) neighborhood pixel relationships measure regional directional and pixel-inversion properties. (5) Eular Numbers (EN) describe texture by properties (such as connectivity) of binary images. Good reproducibility from repeated analysis of radiographs was shown using both paired t-tests and Altman-Bland's methods. We have shown a correlation between femoral neck bone mineral density (BMD-the "gold standard" of osteoporosis assessment) and textural measures for all five algorithms. Significant measures of osteopenia were: ACSE (r = 0.6, P < .001), CM (r = -0.69, P < .001), FS (r = 0.35, P < .01), TS (r = 0.52, P < .001) and EN (r = -0.39, P < .01). Relationships were also found between textural characteristics and age/weight. TA techniques characterize the radiographic changes of bone in osteoporosis. Technology based on these ideas may have a place alongside BMD measurements in the assessment of this condition.

Absorptiometry, Photon↗
PubMed1996

Isolation and chromosomal mapping of a mouse homolog of the Batten disease gene CLN3.

We describe the isolation and chromosomal mapping of a mouse homolog of the Batten disease gene, CLN3. Like its human counterpart, the mouse cDNA contains an open reading frame of 1314 bp encoding a predicted protein product of 438 amino acids. The mouse and human coding regions are 82 and 85% identical at the nucleic acid and amino acid levels, respectively. The mouse gene maps to distal Chromosome 7, in a region containing genes whose homologs are on human chromosome 16p12, where CLN3 maps. Isolation of a mouse CLN3 homolog will facilitate the creation of a mouse model of Batten disease.

Amino Acid Sequence↗
PubMed1992

Population genetics of colonic cancer.

BACKGROUND: There are several well known but rare syndromes of inherited colonic cancer. Genetic epidemiologic studies also have demonstrated that relatives of individuals with colonic cancer in general exhibit an excess risk for this malignancy. METHODS: This report reviews the literature pertinent to genetic and familial risk for colonic cancer with emphasis on the recent work that suggests that inherited susceptibility to colonic neoplasms is common. RESULTS: The adenomatous polyposis syndromes are rare inherited colonic cancer conditions caused by a mutant gene which recently has been characterized. Hereditary nonpolyposis colorectal cancer is likewise inherited and may account for up to 5% of cases. The molecular genetics of this disease remain to be clarified. The majority of colonic cancer cases are considered sporadic but are known to often cluster in families. Recent work suggests that inherited susceptibility may be the basis of this familial occurrence. Screening strategies based on inherited and familial risk are suggested. CONCLUSIONS: Knowledge of the familial and inherited risk for colonic cancer is leading to a better understanding of this disease and is suggesting more directed preventive strategies.

Adenomatous Polyposis Coli↗
PubMed1992

Hereditary aspects of colorectal adenomas.

BACKGROUND: Inheritance is important to the development of colonic adenomatous polyps and colon cancer. Current knowledge of inherited susceptibility to colonic neoplasms suggests that colon cancer screening strategies should consider familial and genetic risk. METHODS: This report reviews the literature pertinent to adenomatous polyp and colon cancer inheritance and suggests polyp-cancer screening procedures based on inherited or familial risk. RESULTS: Colorectal adenomas and cancer occur in several rare inherited syndromes and more commonly as sporadic cases. Intensive screening protocols have been suggested for the inherited syndromes because of the high associated cancer risk. Recent evidence suggests that inherited susceptibility also may be important in a large fraction of the so-called sporadic cases. Preliminary screening guidelines are suggested for this category based on the number of first-degree relatives affected with colon cancer. CONCLUSIONS: Inherited susceptibility appears to be more important to the pathogenesis of colorectal adenomas and cancer than previously recognized. Screening strategies which consider inherited risk may increase the effectiveness of cancer detection and prevention.

Adenoma↗
PubMed1990

Effects of intrathecal administration of 8-OH-DPAT on genital reflexes and mating behavior in male rats.

Systemic administration of the 5HT1A receptor agonist, 8-OH-DPAT, consistently decreases the threshold of ejaculatory behavior and enhances some aspects of arousal. Previous findings by others demonstrated the in copula ejaculatory behavior effect using intrathecal (IT) injection at the level of the lumbosacral spinal cord, but the dose used was in the range that produced results systemically. This study aimed at a) a more comprehensive study of the sexual effects of 8-OH-DPAT and b) use of IT doses of 8-OH-DPAT below those effective when administered systemically. The ex copula genital reflex test showed severe inhibition. At doses of 5 micrograms or more, significant inhibition of the percentage of rats displaying ejaculation occurred, and the two highest doses also significantly reduced the percentage of rats displaying erection. In the in copula mating test, 20 and 80 micrograms IT 8-OH-DPAT, significantly reduced ejaculation latency, intromission frequency and intercopulatory interval. Copulatory plugs, collected at the highest dose only, showed a trend towards weight reduction. We conclude that the facilitation of ejaculatory behavior and some measure of arousal by 8-OH-DPAT can be mediated directly via the lumbosacral spinal cord. An hypothesis for explaining the inhibitory effect on ejaculation ex copula is presented, but the inhibitory effect on erectile reflexes is without interpretation.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1989

The relationship between cholecystectomy and colon cancer: an Iowa study.

The relationship between cholecystectomy and subsequent development of colon cancer was investigated in a case-control study of 165 patients with histologically proven adenocarcinoma of the colon. These patients were from a community in Iowa where incidence of colon cancer was considered to be higher than average in the United States. The relative risk of developing colon cancer after cholecystectomy was shown to be 2.11 (P = .009) for the entire series and 2.91 (P = .002) for the female group. There was a difference of frequency in developing colon cancer after cholecystectomy between the right- and left-sided colons; the relative risk of the right versus the left colon cancer was 2.31 (P = .019). The other factors, including blood group, red cell indices, obesity, serum cholesterol, colonic diverticula, and co-existence of hyperplastic or adenomatous polyp disclosed no significant relation to colon cancer developed after cholecystectomy.

Adenocarcinoma↗
PubMed1989

A component analysis of the effects of DPAT on male rat sexual behavior.

Male rat sexual behavior was examined in a variety of tests following a single acute IP injection of the serotonin1A (5-HT1A) receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (DPAT). The objective was to determine the effects of 5-HT1A receptor stimulation on the components of sexual behavior (arousal/motivation, erection and ejaculation) using this prototypical 5-HT1A ligand. In the ex copula genital reflex test, DPAT dramatically inhibited ejaculation and the display of penile erections. When examined in the mating behavior test, DPAT caused a significant reduction in intromission frequency (IF), ejaculation latency (EL), intercopulatory intervals (ICI) and postejaculatory interval (PEI). The decrease in IF and EL indicated a lowering of the behavioral-ejaculatory threshold, while the reduction in ICI and PEI indicated a stimulation of two aspects of sexual arousal. Further tests, however, revealed complexities. Using the mounting test (with genital anesthesia) as an assessment of sexual arousal, no effect of DPAT was found. Collection and examination of the coagulated ejaculates resulting from mating (copulatory plugs) provided evidence of an impairment in ejaculation, as a result of DPAT treatment. The data suggests that 5-HT1A receptor stimulation lowers the behavioral-ejaculatory threshold despite inhibition of ejaculation in and ex copula; as well as stimulating specific aspects of sexual arousal. It remains to be determined whether the effects on arousal were either due to nonselectivity as currently believed or because 5-HT1A receptor stimulation affects alpha 2-adrenoceptor activity by some as yet undefined mechanism; and as a result modulates sexual arousal.

8-Hydroxy-2-(di-n-propylamino)tetralin↗