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Biomedical subjects

S C Lee

Publications and source records attributed to S C Lee.

At least 91 records · Page 5Linked to original sources

Synthesis and biological properties of C-2, C-8, N-9 substituted 6-(3-chloroanilino)purine derivatives as cyclin-dependent kinase inhibitors. Part II.

In this study, C-2, C-8, N-9 substituted 6-(3-chloroanilino)purine derivatives were synthesized and their inhibitory effects on cyclin-dependent kinases (CDK2, 4) as well as their cytotoxicities were evaluated. The effects of substituents at the C-2, C-8, and N-9 positions of the substituted purine were investigated. Among the compounds tested, [6-(3-chloroanilino)-2-(2-hydroxymethyl-4-hydroxypyrrolidyl)-9- isopropylpurine] (4h) was the most active inhibitor of CDK2 with IC50 of 0.3 microM, i.e. a two-fold increased inhibitory activity as compared to roscovitine. Results from structure-activity relationship studies should allow the design of more potent and selective CDK2 inhibitors, which may provide an effective therapy for cancer or other CDK-dependant diseases.

Antineoplastic Agents↗

Impact of open lung biopsy for undiagnosed pulmonary infiltrates in patients with hematological malignancies.

Pulmonary complications are frequently encountered in patients with hematological malignancy. The optimal therapeutic decision including open lung biopsy (OLB) for such patients is uncertain. We herein examine the clinical impact of OLB on these patients. Seven patients with progressively diffuse pulmonary infiltrates despite aggressive medical treatment were examined. The underlying diseases, prior treatment for presumptive pneumonia, the change in therapeutic approach after operation, and clinical outcome were reviewed retrospectively. Diffuse pulmonary infiltrates were caused by infection in two patients and by noninfectious etiology such as alveolar proteinosis, idiopathic interstitial pneumonitis, leukemic involvement, and drug-induced alveolar damage in the others. Four patients who had serious underlying hematologic diseases such as myelodysplastic syndrome, acute and chronic myeloid leukemia, and T cell lymphoma died. Three patients with acute lymphoid leukemia survived. In two of these three, change of therapeutic strategies after OLB was created for the survival. OLB in patients with hematological malignancy may be useful in selected patients with a treatable hematologic disease who have treatable underlying causes of the pulmonary infiltrate.

Adolescent↗

A novel stimulation pattern improves performance during repetitive dynamic contractions.

The purpose of this study was to determine the effect of three different stimulation patterns on repetitive knee movements. Each subject's quadriceps femoris was stimulated with: (1) a constant-frequency train (CFT) with an interpulse interval (IPI) of 50 ms; (2) a variable-frequency train (VFT)-similar to the CFT, except with an initial doublet with an IPI of 5 ms; and (3) a doublet-frequency train (DFT) with multiple doublets (doublet IPI 5 ms) separated by 50 ms, while the muscle was resisted by a load equal to 10% of the muscle's maximum voluntary isometric contraction. The muscle was stimulated while the knee moved through a 50 degrees arc of motion (90 degrees to 40 degrees of flexion). Testing was stopped when the subject failed to reach the target three consecutive times. Results showed that DFTs reached the target (mean +/- SD) 36.4 +/- 14.4 times, followed by VFTs (25.4 +/- 17.9) and CFTs (17.4 +/- 11.9). The DFT was the best pattern for producing shortening contractions. The results suggest that DFTs may have significant benefits during clinical functional electrical stimulation.

Adult↗

One micrometer resolution NMR microscopy.

We obtained a magnetic resonance image of 1 microm resolution and 75 microm(3) voxel volume for a phantom filled with hydrocarbon oil within an hour at 14.1 T. For this work, a specially designed probe with a high sensitivity RF coil and gradient coils generating over 1000 G/cm was built. The optimal pulse sequence was analyzed in consideration of the bandwidth, diffusion coefficients, and T(1) and T(2) relaxations of the medium. The system was applied to the in vivo imaging of a geranium leaf stem to get the images of 2 microm resolution and 200 microm(3) voxel volume.

Magnetic Resonance Spectroscopy↗

Molecular phylogeny of gobioid fishes (Perciformes: Gobioidei) based on mitochondrial 12S rRNA sequences.

The molecular phylogeny of the gobioid fishes, comprising 33 genera and 43 valid species, was examined by use of complete mitochondrial 12S rRNA and tRNA(VAL)genes. Both parsimony and neighbor-joining analyses revealed comparable results and are generally congruent with those of morphological studies. The Odontobutis, which was always placed at the base of the phylogenetic trees, can be treated as a sister group of all other nonrhyacichthyid gobioids. Within eleotrid fishes, the monophyly of the Eleotrinae is strongly supported by molecular data. The Butinae is closer to fishes with five branchiostegal rays and should be treated as a sister group of the latter. The group with five branchiostegal rays, except for sicydiines, can be divided into two groups according to their epural counts. Fish with one epural, the Gobiinae of Pezold plus Microdesmidae, form a monophyletic group which is sister to those with two epurals, the Oxudercinae and Gobionellinae of Pezold. However, Sicydiinae, which have one epural, are closer to the Oxudercinae and Gobionellinae rather than to the Gobiinae. Since progressive reduction in epural number has been observed along this lineage, the sicydiines should be treated as a derived group within the groups with two epurals.

Animals↗

Inhibitory effects of MK-801 on contextual sensitization to climbing behavior and on development of tolerance to hypothermia induced by a single high dose of apomorphine.

A single high dose of apomorphine (10 mg x kg(-1)) produced not only contextual sensitization to and conditioning of climbing behavior, but also context-independent tolerance to hypothermia. MK-801 (0.15 and 0.3 mg x kg(-1)) inhibited contextual sensitization to and conditioning of climbing behavior. Development of tolerance to hypothermia was also inhibited by MK-801. Dopamine D1 antagonist, SCH23390 (0.5 mg x kg(-1)), but not D2 antagonist, sulpiride, inhibited sensitization to and conditioning of climbing behavior. D2 antagonist, sulpiride (50 mg x kg(-1)), but not D1 antagonist, SCH23390, inhibited development of tolerance to hypothermia. These results suggest that MK-801 inhibited contextual sensitization to climbing behavior and development of tolerance to hypothermia through glutamatergic modulation of dopaminergic functions at dopamine receptors.

Animals↗

Chiral separation of beta2-agonists by capillary electrophoresis using hydroxypropyl-alpha-cyclodextrin as a chiral selector.

Enantiomers of five racemic beta2-agonists were investigated by capillary electrophoresis employing a hydroxypropyl-beta-cyclodextrin (HP-beta-CD). The effects of the concentration of HP-beta-CD added to the background electrolyte and of the pH of the buffer on the effective mobility and resolution of the studied compounds were examined. Very good resolution was achieved for terbutaline and clenbuterol; salbutamol and bambuterol was able to be partially resolved. Enantioselectivity and resolution were influenced by the concentration of the HP-beta-CD, buffer composition and pH.

2-Hydroxypropyl-beta-cyclodextrin↗

Clinical characteristics and prognosis of patients with hepatoblastoma.

Hepatoblastoma is a rare pediatric malignancy that frequently appears in an advanced unresectable stage. Improved resectability and survival rate have been reported with the help of neoadjuvant chemotherapy. Between January 1987 and June 1995 a series of 20 patients were managed with a diagnosis of hepatoblastoma. The median age at diagnosis was 13 months (2 months to 7 years 10 months) with a male/female ratio of 13:7. Chemotherapy effectively reduced the tumor volume (with statistical significance: p = 0.008) and was able to convert seven of nine initially unresectable tumors (78%) to resectable ones. Altogether, 14 operations were done, 12 radical and 2 palliative, with or without adjuvant chemotherapy. The whole population was followed for a median duration of 33 months; and the median survival for the whole group was 26 months. The curative resection group displayed a 5-year survival rate of 61.1%, but none in the noncurative group survived more than 13 months (p = 0.0001). In the univariate analysis for prognostic factors, large tumor size at diagnosis and the absence of thrombocytopenia were associated with poor survival, but these differences were not statistically significant. Pure fetal histology was not associated with better prognosis. In this new era of neoadjuvant chemotherapy, the optimal management strategy for hepatoblastoma is still debated, with radical surgical resection at the earliest possible time being the final goal. For now an individualized approach appears to be the protocol of choice.

Chemotherapy, Adjuvant↗

Distinguishing two types of gray mullet, Mugil cephalus L. (Mugiliformes: Mugilidae), by using glucose-6-phosphate isomerase (GPI) allozymes with special reference to enzyme activities.

The resident and migratory types of gray mullet, Mugil cephalus, on the coast of Taiwan can not be separated morphologically. Allozyme analysis was applied to estimate genetic variation between the two types of gray mullet and to test whether they belong to different populations. After starch gel electrophoresis, different allelic frequency spectra of glucose-6-phosphate isomerase-A (GPI-A) between stocks was observed. The resident stock contained Gpi-A(135) and Gpi-A(100), whereas the migratory type contained Gpi-A(100) only. In addition, GPI activities of locus A showed two distinct profiles between the two alleles. The results broadly revealed that Gpi-A allelic frequency was not regulated by temperature changes even after 6 months of thermal acclimation. This suggests that natural selection may play a role in shaping the allelic frequency change during the migratory journey. These findings suggest that the Gpi-A allelic difference can be used for population discrimination.

Acclimatization↗

A more basal approach in microvascular decompression for hemifacial spasm: the para-condylar fossa approach.

BACKGROUND: In view of the fact that a basal craniectomy in microvascular decompression (MVD) for hemifacial spasm (HFS) can minimize cerebellar retraction and expose the facial nerve root exit zone (FNREZ) directly from below without placement of tension on the seventh-eighth cranial nerve complex, we used a more basal approach in 32 patients with typical HFS. METHOD: A slightly curved skin incision 5 cm in length and 2 cm posterior and parallel to the mastoid notch was made. The basal lateral occipital plate including the lateral one-fourth of the condylar fossa and the posterior one-fourth of the jugular process were removed. For the early drainage of cerebrospinal fluid through a small dural hole, the basal occipital plate posteromedial to the condylar fossa was removed. With this basal craniectomy, minimum elevation of the cerebellar tonsil and flocculus could expose FNREZ safely. FINDINGS: Thirty one of 32 patients displayed complete disappearance of spasm following surgery. One patient showed 70% decrease of spasm. Delayed transient facial weakness occurred in one patient. Audiometries showed no postoperative hearing decrease in any patient, even though no intra-operative monitoring of the cochlear function was undertaken. INTERPRETATION: Although this basal approach, the para-condylar fossa approach, is a slightly basal modification of the conventional procedure, it may minimize complications.

Adult↗

Polymorphisms of GA/GT microsatellite loci from Anguilla japonica.

Six novel microsatellite loci, containing (GA)(15\N17) or (GT)(10\N19) perfect tandem repeats, were isolated and characterized for the catadromous eel Anguilla japonica. The allelic size of the 6 loci ranged from 79 to 226 bp in length. All loci were polymorphic with a mean number of 14.7 alleles per locus and a mean heterozygosity of 0.67, suggesting higher polymorphism than that of freshwater and anadromous fishes, but lower than that of marine fishes. Genotype diversity of the 6 loci ranged from 0.22 to 0.61 with a mean value of approximately 0.5. Cross-species amplification showed that 5 of the 6 microsatellite primers proved to be useful in addressing questions of population genetics for all Anguilla species.

Journal Article↗

Expression of inducible nitric oxide synthase and nitrotyrosine in multiple sclerosis lesions.

Nitric oxide generated by the inducible form of nitric oxide synthase (iNOS) may contribute to the pathogenesis of multiple sclerosis (MS). In this report, we studied postmortem tissues of MS patients for the expression of iNOS by in situ hybridization and immunocytochemistry. Immunocytochemistry for nitrotyrosine, a putative footprint for peroxynitrite formation was also performed. In acute MS lesions, intense reactivity for iNOS mRNA and protein was detected in reactive astrocytes throughout the lesion and in adjacent normal appearing white matter. Staining of macrophages, inflammatory cell infiltrates, and endothelial cells was variable from case to case, but generally detected only in acute lesions. In chronic MS lesions reactive astrocytes at the lesion edge were positive for iNOS whereas the lesion center was nonreactive. Normal appearing white matter demonstrated little reactivity, as did tissues from noninflamed control brains. Staining for nitrotyrosine was also detected in acute but not chronic MS lesions, and displayed a diffuse parenchymal, membranous, and perivascular pattern of immunoreactivity. These results support the conclusion that iNOS is induced in multiple cell types in MS lesions and that astrocyte-derived nitric oxide could be important in orchestrating inflammatory responses in MS, particularly at the blood-brain barrier.

Adult↗

Elevated levels of plasma homocyst(e)ine and asymmetric dimethylarginine in elderly patients with stroke.

Cerebrovascular risk factors, including hypertension, smoking, diabetes mellitus, aging, dyslipidemia, and hyperhomocyst(e)inemia are linked to endothelial dysfunction. Endothelial-derived nitric oxide (NO) has inhibitory effects on key processes in atherothrombosis. Although asymmetric dimethylarginine (ADMA), an endogenous inhibitor of NO synthase, is associated with atherosclerotic disease, there has been no report on association of ADMA with ischemic stroke. Here we investigated the relation of plasma ADMA, stroke, and homocyst(e)inemia in the elderly. Plasma ADMA and homocyst(e)ine concentration was determined using high-performance liquid chromatography and fluorescence detection. Patients with ischemic stroke had significantly higher concentrations of plasma ADMA than controls (1.85+/-1.32 vs. 0.93+/-0.32 micromol/l, P=0.0001). After adjustment for risk factors, elevated ADMA levels, above 90th percentile of normal controls (> or =1.43 micromol/l) was associated with stroke (OR=6.05, 95% CI; 2.77-13.3, P=0.02). ADMA plasma levels were positively correlated to homocyst(e)ine levels (r=0.43, P=0.01). Multiple logistic regression analysis revealed that hyperhomocyst(e)inemia (plasma homocyst(e)ine concentration > or =15.0 micromol/l) was a significant predictor of elevated ADMA level. Altogether, findings indicate that elevated ADMA concentrations are at increased risk for ischemic stroke in the elderly, and may account for increased risk of stroke in patients with hyperhomocyst(e)inemia.

Aged↗

Complete nucleotide sequence and cell-line multiplication pattern of the attenuated variant CH2195LA of Japanese encephalitis virus.

Strain-specific determinant of Japanese encephalitis virus (JEV) can be different among each virulence phenotype. We reported previously that the attenuated variant CH2195LA compared with the non-attenuated variant CH2195SA had four amino acid differences in E protein (E-85, E-306, E-331, and E-387) (Wu, S.-C., Lian, W.-C., Hsu, L.-C., Liau, M., 1997. Japanese encephalitis virus antigenic variants with characteristic differences in neutralization resistance and mouse virulence. Virus Res. 51, 173-181). Our present study determined the complete nucleotide sequences of these two variants and found another five amino acid changes in the nonstructural gene regions, including NS2A-215, NS3-350, NS4B-196, NS4B-197, and NS4B-198. The complete nucleotide sequences of the attenuated variant CH2195LA were compared with the non-attenuated variant CH2195SA and other 13 JEV strains. CH2195LA was mostly close to CH2195SA and JaOArS982, and phylogenetically distant to SA14-14-2, SA14-2-8, and RP-2ms of the attenuated JEV strains. The multiplication patterns for CH2195LA compared with CH2195SA in other seven cell lines were different from Vero cells. Relative fitness vector analysis based on a mixture of both variants during cell passage indicated the attenuated variant CH2195LA showed increased viral fitness in Vero cell adaptation. These results revealed that the attenuated variant CH2195LA was unique to culture in Vero cells.

Amino Acid Substitution↗

Diabetes mellitus--a special medical challenge from a Chinese perspective.

As we enter the new millennium, Asia is being hit by an epidemic of diabetes and its related diseases. The rising prevalence of young onset diabetes which is closely associated with obesity and genetic factors as well as the increased propensity to develop kidney disease are special challenges in the management of Chinese diabetic patients. Although diabetic patients have earlier mortality and increased risks for micro and macrovascular complications, there is strong evidence that these devastating complications can be largely prevented by patient education, periodic assessments and use of appropriate therapeutic agents to optimize metabolic control and improve cardiovascular risk factors. However, a multidisciplinary approach is often required to deliver these complex disease management protocols. Hence, it is not surprising that large scale studies often revealed substandard diabetes management in both the hospital and community settings. This is often due to a combination of factors such as non-adherence to recommended guidelines both by patients and doctors as well as the 'non-urgent' and 'silent nature' of diabetes and its complications. To minimize the impacts of diabetes on quality of life, society productivity and utilization of health care resources, concerted efforts between health care professionals and public bodies are urgently needed to increase awareness, improve standards of care and develop better diagnostics and treatment modalities.

Asia↗

Determination of the optical purity of (R)-terbutaline by 1H-NMR and RP-LC using chiral derivatizing agent, (S)-(-)-alpha-methylbenzyl isocyanate.

A simple, convenient and precise 1H-NMR and indirect HPLC methods were used for the determination of (S)-terbutaline in (R)-terbutaline. The enantiomers were converted to diastereomeric derivatives using (S)-(-)-alpha-methylbenzyl isocyanate and were successfully separated on an ODS column within 40 min with RS=1.41 and alpha=1.09. Interaction between chiral solutes by the formation of the diastereomeric complexes also led to differentiations of the 1H-NMR spectra of enantiomers and optical purities were determined on the basis of the peak area of the enantiomeric amine proton resonance. The effect of various experimental parameter, such as reaction time, reaction temperature and concentration of chiral derivatizing agent on the derivatization reaction and composition of mobile phase on the ODS column is discussed. Validation data such as recovery, linearity and detection limit are also presented. The results from 1H-NMR and RP-HPLC methods were compared with those from chiral HPLC method and no racemization was found during the experiments. NMR results had agreed with those obtained by indirect HPLC method and two methods could be used as a quality control method for the enantiomeric purity determination of (R)-terbutaline.

Adrenergic beta-Agonists↗

Slipknot for scleral fixation of intraocular lenses.

We describe a simple, quick technique to construct a slipknot that can be snared around the haptic of an intraocular lens (IOL) during transscleral fixation of a posterior chamber IOL or repositioning of a dislocated IOL. An in vitro experiment showed that the time required for the slipknot method was significantly less than that for the traditional triple-knot method. An additional advantage is that the slipknot technique can be performed by a single surgeon using standard ophthalmic instrumentation. In addition, the slipknot is as secure as a triple knot.

Humans↗

Clinical significance of oral urease in diagnosis of Helicobacter pylori infection by [13C]urea breath test.

This study was performed to evaluate the effect of oral flora on [13C]urea breath test in detecting H. pylori infection and find an optimal method and timing for sample collection. Forty-five volunteers were included in this study. The [13C]urea breath test was performed using mouthwash, endoscopic administration, and conventional methods. According to the receiver-operating characteristic curves, the earliest optimal time for discriminating H. pylori-positive and H. pylori-negative patients was at 25 min with the mouthwash method with 78% sensitivity and 82% specificity, at 2 min with the endoscopic administration method with 100% sensitivity and 100% specificity, and at 6 min with the conventional method with 100% sensitivity and 95% specificity. The study shows a significant effect of oral urease on the results of the [13C]urea breath test. The timing of sampling collection can be shortened to 6 min with the conventional method or to 2 min through endoscopic administration.

Adult↗