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Biomedical subjects

G H Lee

Publications and source records attributed to G H Lee.

At least 19 recordsLinked to original sources
PubMed2006

The economics of inclusion body processing.

Many recombinant proteins are often over-expressed in host cells, such as Escherichia coli, and are found as insoluble and inactive protein aggregates known as inclusion bodies (IBs). Recently, a novel process for IB extraction and solubilisation, based on chemical extraction, has been reported. While this method has the potential to radically intensify traditional IB processing, the process economics of the new technique have yet to be reported. This study focuses on the evaluation of process economics for several IB processing schemes based on chemical extraction and/or traditional techniques. Simulations and economic analysis were conducted at various processing conditions using granulocyte macrophage-colony stimulating factor, expressed as IBs in E. coli, as a model protein. In most cases, IB processing schemes based on chemical extraction having a shorter downstream cascade demonstrated a competitive economic edge over the conventional route, validating the new process as an economically more viable alternative for IB processing.

Bioreactors↗
PubMed2006

Analysis of colonoscopic findings in the differential diagnosis between intestinal tuberculosis and Crohn's disease.

BACKGROUND AND STUDY AIMS: Intestinal tuberculosis and Crohn's disease are chronic inflammatory bowel disorders that are difficult to differentiate from one another. This study aimed to evaluate the diagnostic value of various colonoscopic findings in the differential diagnosis between intestinal tuberculosis and Crohn's disease. PATIENTS AND METHODS: Colonoscopic findings on initial work-up were prospectively recorded in patients with an initial diagnosis of either intestinal tuberculosis or Crohn's disease. These findings were analyzed after a final diagnosis of intestinal tuberculosis (n = 44) or Crohn's disease (n = 44) had been made after follow-up. RESULTS: Four parameters (anorectal lesions, longitudinal ulcers, aphthous ulcers, and cobblestone appearance) were significantly more common in patients with Crohn's disease than in patients with intestinal tuberculosis. Four other parameters (involvement of fewer than four segments, a patulous ileocecal valve, transverse ulcers, and scars or pseudopolyps) were observed more frequently in patients with intestinal tuberculosis than in patients with Crohn's disease. We hypothesized that a diagnosis of Crohn's disease could be made when the number of parameters characteristic of Crohn's disease was higher than the number of parameters characteristic of intestinal tuberculosis, and vice versa. Making these assumptions, we calculated that the diagnosis of either intestinal tuberculosis or Crohn's disease would have been made made correctly in 77 of our 88 patients (87.5 %), incorrectly in seven patients (8.0 %), and would not have been made in four patients (4.5 %). CONCLUSIONS: A systematic analysis of colonoscopic findings is very useful in the differential diagnosis between intestinal tuberculosis and Crohn's disease.

Adolescent↗
PubMed2006

Segmentation of psoriasis vulgaris images using multiresolution-based orthogonal subspace techniques.

In this paper, a method is proposed for the segmentation of color images using a multiresolution-based signature subspace classifier (MSSC) with application to psoriasis images. The essential techniques consist of feature extraction and image segmentation (classification) methods. In this approach, the fuzzy texture spectrum and the two-dimensional fuzzy color histogram in the hue-saturation space are first adopted as the feature vector to locate homogeneous regions in the image. Then these regions are used to compute the signature matrices for the orthogonal subspace classifier to obtain a more accurate segmentation. To reduce the computational requirement, the MSSC has been developed. In the experiments, the method is quantitatively evaluated by using a similarity function and compared with the well-known LS-SVM method. The results show that the proposed algorithm can effectively segment psoriasis images. The proposed approach can also be applied to general color texture segmentation applications.

Algorithms↗
PubMed2006

Bridging necrosis and reticulin bridging fibrosis induced by intrahepatic involvement of acute biphenotypic leukemia.

A 47-year-old Japanese woman was diagnosed as having acute biphenotypic leukemia with association of t(9;22)(q34;q11). Cholestatic liver dysfunction arose, and she died of cachexia and intracranial hemorrhage. Autopsy showed unusual hepatic fibrosis. In the liver, bridging infiltration, bridging necrosis and bridging fibrosis by leukemic cells were seen. It seemed that the degree of fibrosis was associated with the number of aggregates of infiltrating leukemic cells. The fibrotic foci were predominantly composed of reticulin and collagen fibers, and distortion of the lobules was observed. Immunohistochemically, dense bundles of alpha-smooth muscle actin (ASMA)-positive stromal cells, namely activated hepatic stellate cells (HSCs), were observed in the immature fibrotic foci as well as along the sinusoids densely infiltrated by leukemic cells. No cells positive for TGF-beta1 or PDGF-BB were identified. In conclusion, extensive intrahepatic involvement by neoplastic cells in adult acute biphenotypic leukemia may cause the unusual "disorganized" hepatic fibrosis.

Becaplermin↗
PubMed2006

Comparative pharmacokinetic and pharmacodynamic characteristics of amlodipine besylate and amlodipine nicotinate in healthy subjects.

BACKGROUND AND AIM: Amlodipine, a dihydropyridine calcium antagonist, is prescribed for the management of angina and hypertension, and is sold as amlodipine besylate. However, a new salt formulation, amlodipine nicotinate, has recently been developed. Here, we evaluated the comparative pharmacokinetic and pharmacodynamic characteristics of the nicotinate and besylate forms of amlodipine. SUBJECTS AND METHODS: A randomized, 2-way crossover study was conducted in 18 healthy male volunteers to compare the pharmacokinetics and pharmacodynamics of these two forms, i.e. amlodipine nicotinate (test) and amlodipine besylate (reference), after administration of a single dose of 5 mg of each drug and a washout period between doses of 4 weeks. Blood samples for the pharmacokinetic analysis of amlodipine were obtained over the 144-hour period after administration. Systolic and diastolic blood pressures and pulse rates were recorded immediately prior to each blood sampling. RESULTS: All participants completed both treatment periods, and no serious adverse events occurred during the study period. After administering a single dose of each formulation, mean AUC0-infinity and Cmax values were 190.91+/-60.49 ng x h/ml and 3.87+/-1.04 ng/ml for the test formulation and 203.15+/-52.05 ng x h/ml and 4.01+/-0.60 ng/ml for the reference formulation, respectively. The 90% confidence intervals of test/reference mean ratios for AUC0- infinity and Cmax fell within the predetermined equivalence range of 80 - 125%. Pharmacodynamic profiles including systolic and diastolic blood pressures and pulse rates exhibited no significant differences between the two formulations. CONCLUSION: The two amlodipine formulations showed similar pharmacokinetic and pharmacodynamic characteristics and the new amlodipine formulation, amlodipine nicotinate, was found to be equivalent for pharmacokinetics to the currently available amlodipine besylate with respect to the rate and extent of amlodipine absorption.

Administration, Oral↗
PubMed2004

A single institutional phase III trial of preoperative chemotherapy with hyperfractionation radiotherapy plus surgery versus surgery alone for resectable esophageal squamous cell carcinoma.

BACKGROUND: We conducted a prospective randomized controlled trial comparing surgery alone (S) with concurrent chemoradiotherapy followed by surgery (CRT-S) for resectable esophageal squamous cell carcinoma (SCC) based on our previous report. PATIENTS AND METHODS: One hundred and one patients with stage II/III esophageal SCC were randomized to receive either S (50 patients) or CRT-S (51 patients). The chemoradiotherapy (CRT) consisted of cisplatin 60 mg/m(2) intravenously (i.v.) on day 1, 5-fluorouracil (5-FU) 1000 mg/m(2) i.v. on days 2-5, cisplatin 60 mg/m(2) i.v. on day 22 combined with radiation therapy (45.6 Gy, 1.2 Gy b.i.d. on days 1-28). Surgery was performed 3-4 weeks after radiotherapy was completed. For patients with disease that was stable or responsive to CRT, three additional cycles of chemotherapy (cisplatin 60 mg/m(2) i.v. on day 1, 5-FU 1000 mg/m(2) on days 2-5 every 4 weeks) were given after surgical resection. RESULTS: The median age was 62 years. The toxicity of CRT was acceptable and did not affect the post-operative morbidity and the duration of hospital stay. Clinical response was 86% including 21% of complete response (CR) rate. Pathological CR was achieved in 43% [95% confidence interval (CI) 27-59] of the patients who underwent surgery after CRT. At a median follow-up of 25 months, median overall survival (OS) was 27.3 months in S and 28.2 months in CRT-S (P = 0.69). Event-free survival (EFS) at 2 years was 51% in S and 49% in CRT-S (P = 0.93). This trial, which was statistically powered to detect a relatively large difference in 2-year survival rate from 30% to 50% with 80% power, was discontinued at interim analysis because of the unexpectedly high drop-out rate for esophagectomy (31%) and resultant excessive locoregional failure rate in CRT-S arm (22% versus 12%, P = 0.31), though it was not statistically significant. CONCLUSION: Although preoperative CRT induced high clinical and pathological response, there was no statistically significant benefit in OS and EFS.

Adult↗
PubMed2003

Idiopathic thrombocytopenic purpura: better therapeutic responses of patients with B- or T-cell clonality than patients without clonality.

Results of recent studies of the pathogenesis of idiopathic thrombocytopenic purpura (ITP) have suggested activated helper T-cells drive B-lymphocytes to produce antibodies. Twenty-eight children and 85 adults with ITP entered this study. We performed polymerase chain reaction (PCR) using framework III variable region (V(H) FRIII)- and joining region (J(H))-specific primers to analyze immunoglobulin heavy-chain gene rearrangement (IgH GR) for B-cell clonality. We used multiplex PCR to analyze T-cell receptor (TCR) gamma-chain gene rearrangement (TCRgamma GR) for T-cell clonality. We diagnosed 10 cases as acute ITP and 97 cases as chronic ITP. The IgH GR result was positive in 77.8% of the acute-form cases and in 58.8% of the chronic-form cases. The TCRgamma GR result was positive in 11.1% of the acute cases and in 10.6% of the chronic cases. There was no difference in frequency of clonality between the acute and chronic forms. After treatment the platelet count normalized in 81.8% (36/44) of the chronic ITP cases with B-cell clonality and in 88.9% (8/9) of the chronic ITP cases with T-cell clonality, compared with a normalized platelet count in 46.2% (12/26) of the chronic ITP cases without clonality. The patients with T- or B-cell clonality appeared to have better therapeutic responses than patients without clonality. In conclusion, T- and B-cell clonality may play a positive role in determining therapeutic response.

Adolescent↗
PubMed2001

Fine chromosomal localization of the mouse Par2 gene that confers resistance against urethane-induction of pulmonary adenomas.

BALB/cByJ mice are 14 times more resistant to urethane-induction of pulmonary adenomas than the susceptible A/J strain. Our previous linkage analysis of (A/J x BALB/cByJ)F1 x A/J backcross mice provided statistical evidence that a major resistance locus of BALB/cByJ with a dominant effect, designated Par2 (Pulmonary adenoma resistance 2), exists within an approximately 25 cM section of distal chromosome 18. To facilitate molecular identification of the Par2 locus, the present study was conducted to finely localize its chromosomal position utilizing Par2-congenic mice. Male BALB/cByJ mice were mated with female C57BL/6J mice carrying recessive Par2 alleles and their male F1 progeny were backcrossed to female BALB/cByJ mice. A male backcross mouse heterozygous within the Par2 interval of 25 cM was randomly selected and again backcrossed to female BALB/cByJ mice. This backcross-selection cycle was simply repeated to produce semi-congenic mice with a general BALB/cByJ genetic background except for the Par2 interval, where the mice were heterozygous with paternal C57BL/6J alleles and maternal BALB/cByJ alleles. After the 6th or 7th backcross, nine male mice possessing a recombination within the paternal Par2 interval were retained and crossed to female A/J mice. Resultant progeny were treated with urethane and examined for lung tumor development in order to deduce the Par2 genotypes of the recombinants through linkage analysis. By comparing the deduced Par2 genotype of each recombinant with its recombinational breakpoint, the Par2 locus was confined to an approximately 0.5 cM region flanked by D18Mit103 and D18Mit188 loci. Our results indicate that fully congenic mice conventionally established by at least nine simple backcrosses or by the speed congenic method are not necessarily required for fine mapping of quantitative trait loci. In the case of the Par2 locus, we found that semi-congenic mice after as few as four simple backcrosses were useful for this purpose. The map information obtained in this study should enable subsequent positional cloning of the Par2 gene.

Adenomatosis, Pulmonary↗
PubMed2001

Syntheses, reactivity, and pi-donating ligand metathesis reaction of five-coordinate sixteen-electron manganese(I) complexes: crystal structures of [Mn(CO(3)(-TeC(6)H(4)-o-NH-)](-), [(Mn(CO)(3))2(mu-SC(6)H(4)-o-S--S--C(6)H(4)-o-mu-S--)], [(CO)(3)Mn(mu-SC(6)H(4)-o-NH(2)-)]2, and [(CO)(3)Mn(mu-SC(8)N(2)H(4)-o-S-)](2)(2-).

The preparation of the varieties of five-coordinate sixteen-electron manganese(I) complexes [Mn(CO)(3)(-EC(6)H(4)-o-E'-)](-) (E = Te, Se, S, O; E' = NH, S, O) by (a) oxidative addition of 2-aminophenyl dichalcogenides to anionic manganese(0)-carbonyl, (b) pi-donating ligand metathesis reaction of complex [Mn(CO)(3)(-TeC(6)H(4)-o-NH-)](-), and (c) reduction /deprotonation of the neutral dimetallic [(Mn(CO)(3))(2)(mu-SC(6)H(4)-o-S-S-C(6)H(4)-o-mu-S-)]/[(CO)(3)Mn(mu-SC(6)H(4)-o-NH(2)-)](2) proved successful approaches in this direction. The IR nu(CO) data of the coordinatively and electronically unsaturated [Mn(CO)(3)(-EC(6)H(4)-o-E'-)](-) (E = Te, Se, S, O; E' = NH, S, O) complexes suggest the relative order of pi-donating ability of the series of bidentate ligands being [TeC(6)H(4)-o-NH](2)(-) > [SeC(6)H(4)-o-NH](2)(-) > [SC(6)H(4)-o-NH](2)(-) > [SC(6)H(4)-o-S](2)(-) > [SC(6)H(4)-o-O](2)(-) > [OC(6)H(4)-o-O](2)(-). Proton NMR spectra of the [Mn(CO)(3)(-EC(6)H(4)-o-NH-)](-) (E = Te, Se, S) derivatives show the low-field shift of the amide proton ((1)H NMR (C(4)D(8)O): delta 9.66 (br) ppm (E = Te), 9.32 (br) ppm (E = Se), 8.98 (br) ppm (E = S)). The formation of the dimetallic [(CO)(3)Mn(mu-SC(8)N(2)H(4)-o-S-)](2)(2-) can be interpreted as coordinative association of two units of unstable mononuclear [(CO)(3)Mn(-SC(8)N(2)H(4)-o-S-)](-) and reflects the pi-donating ability of the bidentate ligand is responsible for the formation of pentacoordinate, sixteen-electron manganese(I) carbonyl complexes. The neutral bimetallic manganese(I)-bismercaptophenyl disulfide complex [(Mn(CO)(3))(2)(mu-SC(6)H(4)-o-S-S-C(6)H(4)-o-mu-S-)] with internal S-S bond length of 2.222(1) A and the five-coordinate sixteen-electron complex [Mn(CO)(3)(-SC(6)H(4)-o-S-)](-) are chemically interconvertible. In a similar fashion, treatment of complex [Mn(CO)(3)(-SC(6)H(4)-o-NH-)](-) with HBF(4) yielded neutral dinuclear complex [(CO)(3)Mn(mu-SC(6)H(4)-o-NH(2)-)](2) and showed that the amine deprotonation is reversible. Investigations of pi-donating ligand metathesis reactions of complex [Mn(CO)(3)(-TeC(6)H(4)-o-NH-)](-) revealed that the stable intermediate, not the pi-donating ability of bidentate ligands, is responsible for the final protonation/oxidation product. This argument is demonstrated by reaction of [Mn(CO)(3)(-TeC(6)H(4)-o-NH-)](-) with 1,2-benzenedithiol, hydroxythiophenol, and catechol, respectively leading to the formation of [Mn(CO)(3)(-EC(6)H(4)-o-E'-)](-) (E = S, O; E' = S, O), although any pi-donor containing the amido group is a more effective donor than any other pi-donor lacking an amido group. Also, the reactions of [Mn(CO)(3)(-TeC(6)H(4)-o-NH-)](-) with electrophiles occurring at the more electron-rich amide site support that the more electron-rich amide donor of the chelating 2-tellurolatophenylamido occupies an equatorial site as indicated by a shorter Mn(I)-N bond length of the distorted trigonal bipyramidal [Mn(CO)(3)(-TeC(6)H(4)-o-NH-)](-).

Journal Article↗
PubMed2001

Proton-lithium binding behavior of tris(2-((pyrid-2-ylmethyl)uredio)ethyl)amine.

Tris(2-((pyrid-2-ylmethyl)uredio)ethyl)amine (2) and its perchlorate salt, 2.HClO(4), bind with Li+ in nitromethane in a 1:1 fashion. The stability constants of K(Li+) and K(H)(Li+) were found to be 112 +/- 25 and 130 +/- 30 M(-)(1) in CD(3)NO(2), respectively. Formation of the 1:1 complexes were further evidenced by electrospray ionization mass spectrometry (ESI-MS). The slight increase, or at least the same order of magnitude, of K(H)(Li+) compared to K(Li+) points to a remarkable preorganization of the protonated podand in 2.HClO(4), that essentially overcomes the increased Columbic repulsion occurring on complexation to Li+.

Journal Article↗
PubMed2001

Structural correlation of catecholase-like activities of oxy-bridged dinuclear copper(II) complexes.

Eight oxy-bridged dinuclear copper(II) complexes with catecholase-like sites, [Cu(L1)X]2 (HL1 = 1-diethylaminopropan-2-ol, X=N3- 1, NCO- 2, and NO2- 3), [Cu(L2)X]2 (HL2=N-ethylsalicylaldimine, X=NO3- 4, Cl- 5, N3- 6, NCS- 7), and [Cu(L3)]2(ClO4)2, 8 (HL3=N-(salicylidene)-N'-(2-pyridylaldene)propanediamine) have been prepared and characterized. The single crystal X-ray analysis show that the structures of complexes 6 and 8 are dimeric with two adjacent copper(II) atoms bridged by pairs of micro-oxy atoms from the L2 and L3 ligands. Magnetic susceptibility measurements in the temperature range 4-300 K indicate significant antiferromagnetic coupling for 4, 5 and 7 and ferromagnetic coupling for 6 between the copper(II) atoms. The catecholase activity of complexes for the oxidation of 3,5-di-tert-butylcatechol by O2 was studied and it was found that the complexes with the bond distance of Cu(II)...Cu(II) located at 2.9-3.0 A show higher catecholase activity.

Catalytic Domain↗
PubMed2001

Aroma components of cooked tail meat of American lobster (Homarus americanus).

Key aroma components of cooked tail meat of American lobster (Homarus americanus) were studied by gas chromatography-olfactometry (GCO) techniques. Components of low and intermediate volatility were evaluated by aroma extract dilution analysis of solvent extracts prepared by direct solvent extraction-high vacuum distillation and vacuum steam distillation-solvent extraction, whereas headspace volatile components were assessed by GCO of decreasing headspace (static and dynamic modes) samples. Forty-seven odorants were detected by all techniques. 3-Methylbutanal (chocolate, malty), 2,3-butanedione (buttery), 3-(methylthio)propanal (cooked potato), 1-octen-3-one (mushroom), 2-acetyl-1-pyrroline (popcorn), and (E,Z)-2,6-nonadienal (cucumber), were identified as predominant odorants by all four isolation methods. The highly volatile compounds methanethiol (rotten, sulfurous) and dimethyl sulfide (canned corn) were detected by headspace methods only. These eight odorants along with three unknown compounds with crabby, amine, fishy odors were found to predominate in the overall aroma of cooked lobster tail meat.

Animals↗
PubMed2001

Cytotoxic and novel compounds from Solanum indicum.

Solavetivone (1), cytotoxic to OVCAR-3 cells with an IC(50) value of 0.1 mM, has been isolated from Solanum indicum. In addition, a novel solafuranone (2) and three known compounds, scopoletin, N-(p-trans-coumaroyl)tyramine, and N-trans-feruloyltyramine, were isolated for the first time from this plant. The structures of the above compounds were established by means of spectroscopic and X-ray analyses.

Antineoplastic Agents, Phytogenic↗
PubMed2001

Growth-suppressive function of human connexin32 in a conditional immortalized mouse hepatocyte cell line.

Mouse hepatocytes immortalized with a temperature-sensitive allele of the SV40 large T-antigen (CHST8 cells) were found to lack the high expression of the gap junction proteins Cx26 and Cx32 that characterizes normal mouse hepatocytes, expressing instead Cx43 and Cx45 at minimal levels. In order to examine the growth suppressive function of Cx32 on hepatocytes, we transfected these CHST8 cells with human Cx32 complementary deoxyribonucleic acid and measured the growth rates at 33, 37, and 39 degrees C. Expression of human Cx32 and its messenger ribonucleic acid in the stable cell lines was confirmed by immunocytochemistry and by Western and Northern blots analyses. Dye transfer following lucifer yellow injection into the transfectants was extensive; Cx32 channels displayed unitary conductances of about 70 pS and were moderately voltage sensitive. When cultured at 33 and 39 degrees C, growth rates of both parental cells and transfectants were of the same level. When examined at 37 degrees C, growth rate of the transfectant, which highly expressed Cx32 at the membranes, was significantly decreased compared to the parental cells. However, no changes in the expression of Cx32 protein in the transfectants were observed between 33 and 37 degrees C. These results suggest that Cx32 expression could inhibit hepatocyte growth in vitro using the conditional immortalized cells. Cx32 transfectants using a conditional immortalized mouse hepatocyte may be useful for examining the mechanisms of growth and differentiation in hepatocytes by gap junction expression.

Animals↗