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Biomedical subjects

C J Lee

Publications and source records attributed to C J Lee.

At least 19 recordsLinked to original sources
PubMed1999

Development of nonionic surfactant/phospholipid o/w emulsion as a paclitaxel delivery system.

Paclitaxel is an anticancer agent with low aqueous solubility. More extensive clinical use of this drug is somewhat delayed due to lack of appropriate delivery vehicles. An attempt was made to adopt an o/w emulsion as the drug carrier which incorporated paclitaxel in the triacylglycerol stabilized by a mixed-emulsifier system. A suitable formulation was found in this study: 0.75 mg/ml paclitaxel, 10% (w/v) oil blend, 4% (w/v) EPC, 3% (w/v) Tween 80 in 2.25% (w/v) glycerol solution. The formulated emulsion has very good stability when stored at 4 degrees C, and the paclitaxel containment efficiency can be maintained above 95% and the mean emulsion diameter around 150 nm for at least 3 months. Paclitaxel-emulsion displayed cytotoxicity against HeLa cells with IC50 at 30 nM. The average life span of ascitic-tumor-bearing mice was prolonged significantly by the treatment of paclitaxel-emulsion (P<0.05). The formulated emulsion is a promising carrier for paclitaxel and other lipophilic drugs.

Animals↗
PubMed1999

Effect of alterations in extracellular norepinephrine on adrenoceptors: a microdialysis study in freely moving rats.

Chronic electroshock treatment (once daily for 12 days) increases extracellular norepinephrine in the frontal cortex and hippocampus as measured by microdialysis. This chronic treatment produced an elevation of basal norepinephrine overflow into extracellular space while both the first and the twelfth treatments produced a transient increase in norepinephrine overflow of about 40 min. Acutely, desmethylimipramine (10 mg/kg) treatment significantly increased extracellular norepinephrine. While chronic desmethylimipramine (once daily for 10 days) increased basal overflow of norepinephrine in the frontal cortex and hippocampus, the tenth daily administration of desmethylimipramine did not produce a statistically significant increase in extracellular norepinephrine. Both daily electroshock and daily desmethylimipramine produced down regulation of beta-adrenoceptors in the hippocampus and the frontal cortex. Chronic electroshock caused up regulation of alpha-adrenoceptors in the frontal cortex but not in the hippocampus while chronic desmethylimipramine administration did not alter alpha-adrenoceptors in either structure. Depletion of norepinephrine with reserpine or with 6-hydroxydopamine prevented the down regulation of beta-adrenoceptors while depletion of this neurotransmitter did not prevent the electroshock-induced up regulation of alpha-adrenoceptors in the frontal cortex. These data suggest that down regulation of beta-adrenoceptors is mediated through increases in extracellular norepinephrine. In contrast, up regulation of alpha-adrenoceptors appears to be independent of norepinephrine release and does not require the presence of noradrenergic neurons in order to be induced by electroshock.

Adrenergic Uptake Inhibitors↗
PubMed1999

Mutational and functional analysis of HPV-16 URR derived from Korean cervical neoplasia.

OBJECTIVE: The YY1 mutation has been suggested as one of the indicators that explains development of cervical neoplasia by episomal-type HPV. To extend this hypothesis, we examined whether a mutation(s) in the YY1 site is functionally related to the invasiveness of cervical neoplasia and the physical status of HPV DNA. METHODS: The URR sequences were obtained by PCR amplification of HPV-16 genome from CIN and invasive cancer patients and cloned into pUC18 for sequencing and into pBLCAT8+ for functional CAT assay. RESULTS: Our previous data classified HPV-infected patients into three groups: 3 cancer cases carrying episomal HPV DNA; 12 cancer cases carrying integrated HPV DNA; 12 CIN cases carrying episomal HPV DNA. The specific variants in HPV-16 URR were found in Korean women: G-->A transition at nt 7520 (100%, 27/27), A-->C transition at nt 7729 (70%; 19/27), and G-->A transition at nt 7841 (78%; 21/27). Selective mutations were observed at the YY1 binding sites of HPV-16 URR in the 3 patients with invasive cervical cancer who have the episomal forms of HPV-16 DNA: A-->C transition at nt 7484 and G-->A transition at nt 7488 (YY1-binding site 2; from 7481 to 7489). Additionally, C-->T transition at nt 7785 (YY1-binding site 3; from 7781 to 7790) was found in 2 of 3 patients. No YY1 site mutations were detected in the 12 CIN patients and in the HPV-integrated invasive cancer patients. To determine whether these mutations have effects on the expression of HPV E6/E7 genes driven by URR, the transient transfection assay was employed using URR-CAT reporter plasmid. The relative activities of three URR mutants from episomal HPV-16 DNA of cervical cancers were two- to fourfold higher than that of the HPV-16 URR prototype. In contrast, the URRs from integrated HPV-16 DNA in cervical cancer and from episomal HPV-16 DNA in CIN, where no mutation of the YY1 binding site was detected, showed similar levels of promoter activity to that of the URR prototype. CONCLUSIONS: Our results support the hypothesis that the mutation at the YY1 binding site is functionally related to the development of cervical neoplasia caused by episomal HPV-16 DNA in Korean cervical cancer patients. Thus, mutation in the YY1 site of episomal HPV-16 URR may play a corresponding role of HPV integration in the progression of cervical cancer.

DNA Mutational Analysis↗
PubMed1999

Subpopulations of GABAergic and non-GABAergic rat dorsal horn neurons express Ca2+-permeable AMPA receptors.

Subpopulations of alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptors that are either permeable or impermeable to Ca2+ are expressed on dorsal horn neurons in culture. While both mediate synaptic transmission, the Ca2+ -permeable AMPA receptors provide a Ca2+ signal that may result in a transient change in synaptic strength [Gu, J.G., Albuquerque, C., Lee, C.J. & MacDermott, A.B. (1996) Nature, 381, 793]. To appreciate the relevance of these receptors to dorsal horn physiology, we have investigated whether they show selective expression in identified subpopulations of dorsal horn neurons. Expression of Ca2+-permeable AMPA receptors was assayed using the kainate-induced cobalt loading technique first developed by Pruss et al. [Pruss, R.M., Akeson, R.L., Racke, M.M. & Wilburn, J.L. (1991) Neuron, 7, 509]. Subpopulations of dorsal horn neurons were identified using immunocytochemistry for gamma-aminobutyric acid (GABA), glycine, substance P receptor (NK1 receptor) and the Ca2+-binding proteins, calretinin and calbindin D28K. We demonstrate that, in dorsal horn neurons in culture, kainate-induced cobalt uptake is selectively mediated by Ca2+-permeable AMPA receptors, and that a majority of GABA and NK1 receptor-expressing neurons express Ca2+-permeable AMPA receptors. GABAergic dorsal horn neurons are important in local inhibition as well as in the regulation of transmitter release from primary afferent terminals. NK1 receptor-expressing dorsal horn neurons include many of the projection neurons in the nociceptive spino-thalamic pathway. Thus, we have identified two populations of dorsal horn neurons representing important components of dorsal horn function that express Ca2+-permeable AMPA receptors. Furthermore, we show that several subpopulations of putative excitatory interneurons defined by calretinin and calbindin expression do not express Ca2+-permeable AMPA receptors.

Aging↗
PubMed1999

The merit of sintered PDLLA/TCP composites in management of bone fracture internal fixation.

Polyesters based on lactic acid have been reported in terms of safety and biodegradation in human beings for 2 decades. The greatest advantage of such material is its degradation conducted only by hydrolysis, whereby the ester backbones are supposed to be unchained in the aqueous condition. The final degradable products are carbon dioxide and water which can be metabolized and digested in the physiological environment. The goal of this study was aimed at developing a composite sintered with poly-DL-lactide (PDLLA) and tricalcium phosphate (TCP) ceramic particles for orthopedic application. The TCP particles in a range of 30-60 wt% with 5 wt% increments were doped into the PDLLA matrix which was prepared by melting and hot pressing techniques for the reinforcement. The basic mechanical strength, biodegradable behavior, and biological response of the composites were investigated in the study. Various techniques such as pH meter, UV, Fourier-transform infrared, and x-ray diffractometer were used to examine and record the degradable process of the composites soaked in saline for 1-16 weeks. The rabbit femur condyle fracture fixation test was used to evaluate tissue compatibility and the effects of bone fracture fixation on the composites. Histological observation and x-ray photography were used for investigating assistance. The mechanical strength of the composites initially increased with TCP additions up to 50wt%, but thereafter they showed no significant difference (p < 0.05). The composite with 50 wt% TCP addition showed greater mechanical strength and had good agreement with cortical bone in terms of its elastic modulus of 30-40 GPa. The weight loss of the pure PDLLA soaked in the saline started at 4 weeks and reached 95% after 16 weeks. The composites compared with pure PDLLA, however, showed no apparent evidence of degradation after soaked for 12 weeks. The possible mechanisms for the delayed degradation of the composites in saline might have been solution penetration retardation by the ceramic particles and chemical bonds formed between the interface of the TCP particles and the PDLLA matrix. In the histological evaluation of the rabbit femur condyle fracture fixation test, the surface of the composite with 50 wt% TCP addition was attached by the newly generated bone without fibrous tissue around 8 weeks after implantation. The fractured bone was gradually healed and the composite firmly and properly fixed on the fracture area during the implanted period, which provided a breeding environment for normal bone remodeling. The developed composite was thought to be an alternative material for orthopedic application in the future, especially for bone screws and bone plates.

Absorption↗
PubMed1999

The removal of beta-2-microglobulin by an immunoadsorption wall.

The accumulation of beta-2-microglobulin (beta2M) in collagen-rich tissues has been proven to be the main cause of dialysis related amyloidosis. However, it remains uncertain which technique for the removal of beta2M can be used without compromising the advantages of other dialysis strategies. A new concept, an immunoadsorption wall, which combines the principles of immunoisolation and immunoadsorption is proposed to remove beta2M. The present investigations suggested that the application of the concept to clinical use is feasible and worthwhile. The concept, if validated, will help shape a novel multitask type of artificial kidney based on the combination of different separation technologies.

Antibodies↗
PubMed1999

Suicide under the age of eighteen: a 10-year retrospective study.

The number of suicides in the pediatric age group is rising, and death investigators need to be aware of the common scenarios, risk factors, and victims as they investigate such cases to properly assign the cause and manner of death. We reviewed all pediatric cases referred to the Medical University of South Carolina, Forensic Section, from January 1988 through January 1998. Thirty-one cases of pediatric suicide were analyzed with regards to age, gender, race, cause of death, surrounding circumstances, and past history. Sixty-eight percent of victims were aged 16 or 17 years, 84% were male, 68% were white, 78% used firearms to commit suicide, 81% were found within close vicinity of their home, and 26% had a documented history of mental illness. Suicide is a manner of death that is often difficult for the public to accept, especially in pediatric cases. We report our findings in this 10-year retrospective study to better understand this entity and work toward the prevention of future cases.

Adolescent↗
PubMed1999

Inhibition of mucin release from airway goblet cells by polycationic peptides.

In the present study, we investigated whether polycationic peptides affect mucin release from cultured airway goblet cells. Confluent primary hamster tracheal surface epithelial cells were metabolically radiolabeled with [(3)H]glucosamine for 24 h and chased for 30 min in the presence of varying concentrations of either poly-L-arginine (PLA) or poly-L-lysine (PLL) to assess the effects on [(3)H]mucin release. Possible cytotoxicity by the polycations was assessed by measuring lactate dehydrogenase release, (51)Cr release, and cell exfoliation. The results were as follows: 1) both PLA and PLL inhibited mucin release in a dose-dependent fashion; 2) there was no significant difference in either lactate dehydrogenase release, (51)Cr release, or the number of floating cells between control and treatment groups; 3) the effects of both PLA and PLL on mucin release were completely blocked by neutralizing the positive charges either by pretreatment with heparin or by N-acetylation of the polycations; and 4) both PLA and PLL completely masked the stimulatory effect of ATP on mucin release. We conclude that these polycationic peptides can inhibit mucin release from airway goblet cells without any apparent cytotoxicity, and the inhibitory effect seems to be attributable to their positive charges. These are the first nonsteroidal agents, to the best of our knowledge, that have been shown to inhibit mucin release from airway goblet cells.

Acetylation↗
PubMed1998

Topographic localization of neuropeptide Y mRNA in the monkey brainstem.

Neuropeptide Y (NPY) modulates cardiovascular, feeding and reproductive functions. Peripheral neurohumoral inputs from these systems are integrated and transformed into efferent signals in the brainstem. Detailed mapping of NPY-expressing cells in the brainstem has not been established in primates. In this report we utilized the in situ hybridization (ISH) method to identify brainstem areas that contain NPY mRNA in four ovariectomized rhesus macaques treated with estradiol-17beta. A 35S-labeled human NPY cRNA probe was used for ISH in paraformaldehyde-fixed brainstem blocks that were sectioned at 20 microm thickness. In the upper cervical spinal cord, NPY mRNA signals were confined to the substantia gelatinosa along the spinal tract of the trigeminal nerve. In the medulla, NPY images were found in the nucleus of solitary tract, dorsal motor nucleus of vagus nerve, nucleus of the spinal tract of trigeminal nerve, lateral reticular nucleus and the reticular formation. In the pons, NPY mRNA was confined to cells in the locus coeruleus and the nucleus of raphe. NPY signals were observed in the ventral portion of the periaqueductal grey, the dorsal nucleus of raphe and the reticular formation of mesencephalon in the midbrain. Whereas the brainstem distribution of NPY-containing cells in the rhesus macaque overlap those regions that are rich in catecholamines, NPY perikarya were also present in 'noncatecholaminergic' areas. For example, the reticular formation of both the medulla and mesencephalon abundantly expressed NPY mRNA. The functional significance of, and the effects of estrogen on, these patterns in NPY expression is unknown.

Animals↗