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Biomedical subjects

K C Lee

Publications and source records attributed to K C Lee.

At least 109 records · Page 6Linked to original sources
PubMed2000

Giant cisterna chyli: MRI depiction with gadolinium-DTPA enhancement.

AIM: To demonstrate the use of MRI with Gadolinium-DTPA enhancement in the diagnosis of giant cisterna chyli. MATERIALS AND METHODS: The study consisted of contrast enhanced MRI with ultrasound and CT correlation in three patients with a giant cisterna chyli. An analysis of the morphology, location and post-contrast MR signal characteristics in relation to time was performed. RESULTS: Cisterna chyli has a characteristic lobulated morphology and location but the unenhanced MRI appearances are not specific. The post-Gadolinium-DTPA MRI appearances are critically dependent on the time elapsed after injection of contrast medium. Within the first 5 min, there is no enhancement at all, but by 10 min there is early layering of contrast medium evident, which by 30 min produces a clear fluid-fluid level. Delayed images at 4-5 h demonstrate a uniform enhancement of the cisternal contents producing a homogeneous intermediate signal. All of these features are best visualized on T1 fast saturation sequences. CONCLUSION: MRI with Gadolinium-DTPA enhancement is valuable in confirming the nature of the lymphatic ducts in the retroperitoneal space and helps to differentiate these normal structures from alternative lesions such as lymphadenopathy and tumour recurrence.

Adolescent↗
PubMed2000

Emergency surgical recanalisation of A1 segment occluded by a Guglielmi detachable coil.

We describe a case of A1 segment occlusion caused by a tangled Guglielmi detachable coil (GDC) during an endovascular treatment for a ruptured anterior communicating aneurysm. Immediate surgical recanalisation of the occluded artery and clipping of the aneurysm rescued the patient. This case demonstrates that an emergency surgical team, as well as an operating room, should be available during any complicated intra-aneurysmal procedure, so that timely surgical intervention could be carried out without delay.

Cerebral Angiography↗
PubMed2000

Selection of treatment modalities for cerebral arteriovenous malformations: a retrospective analysis of 348 consecutive cases.

The objective was to establish the selection criteria for the optimal management modalities for cerebral arteriovenous malformations. We analysed the complications and late outcomes in 348 consecutive cases (132 microsurgical resections, 202 stereotactic radiosurgeries, 8 embolisations only, 6 combined treatments) managed at Yonsei University Hospital from 1988 to 1997. Files for all patients were analysed. The outcome was classified into good for the patients who returned to their previous job with or without neurological deficits, fair for the patients who were unable to return to work but performed daily activities independently with minor deficits, and poor for the patients who were performing dependent daily activities with major deficits. The outcome of microsurgery was considered good in 108 patients (81.8%), fair in 18 (13.6%), poor in 4 (3.1%), and 2 (1.5%) patients died. Initial insults and haemodynamic complications were the major cause of an unfavourable outcome. The cumulative occlusion rate of the nidus after radiosurgery was 10.2% within 12 months, 75.3% within 24 months, and 89.8% within 36 months. Perilesional imaging changes with neurological deficits (4 permanent and 6 transient, 4.8%) and haemorrhage (16 patients, 7.7%) during the latent interval were the major cause of an unfavourable outcome (1 poor, 4 dead after radiosurgery). Postradiosurgery bleeding occurred frequently within 6 months (6 patients), and between 13 and 24 months (8 patients). In conclusion, selection of treatment modality for cerebral AVMs depends on the preoperative evaluation of the risk/benefit ratio in each case. Microsurgical removal, which eliminates the risk of bleeding immediately, is preferred for lesions in non-eloquent areas. Radiosurgery is an effective treatment modality for small lesions in eloquent areas, but has a substantial risk of haemorrhage during the latency period. Results of this study suggest that microsurgical removal should be considered for lesions in eloquent areas with high haemorrhage risk, such as prior haemorrhage, medium to large size lesion, and single deep venous drainage.

Adolescent↗
PubMed2000

Janibacter terrae sp. nov., a bacterium isolated from soil around a wastewater treatment plant.

A bacterial strain, CS12T, which was isolated from soil around a wastewater treatment plant, was subjected to a polyphasic taxonomic study using phenotypic characterizations and genetic methods. The cell wall of strain CS12T contains meso-diaminopimelic acid as the diamino acid but no arabinose and galactose. The predominant menaquinone is MK-8(H4). Mycolic acids are absent. Strain CS12T has a cellular fatty acid profile containing saturated, unsaturated, branched and 10-methyl fatty acids. The major fatty acids are iso-C16:0, C18:1 omega9c and anteiso-C17:0, The G+C content is 69 mol%. A phylogenetic tree based on 16S rDNA sequences showed that strain CS12T forms an evolutionary lineage within the radiation enclosing the members of the family Intrasporangiaceae and, in particular, a coherent cluster with Janibacter limosus DSM 11140T. The level of 16S rDNA similarity between strain CS12T and J. limosus DSM 11140T is 98.7%. The phenotypic characteristics and DNA-DNA relatedness data indicate that strain CS12T should be distinguished from J. limosus DSM 11140T. Therefore, on the basis of the data presented, a new species of the genus Janibacter, Janibacter terrae, is proposed. The type strain of the new species is strain CS12T (= KCCM 80001T = JCM 10705T).

Actinomycetales↗
PubMed2000

Pharmacokinetic disposition of polyethylene glycol-modified salmon calcitonins in rats.

This study first reports the pharmacokinetic disposition of polyethylene glycol (PEG)-modified salmon calcitonin (sCT) based on the number of attached PEG molecules. PEG-modified sCT was prepared by covalent linkage with succinimidyl carbonate monomethoxy polyethylene glycol. Mono- and di-PEG-sCTs were separated by size exclusion and reverse phase HPLC, and radioiodinated by the chloramine-T method with Na125I. 125I-mono-PEG sCT, 125I-di-PEG-sCT and unmodified 125I-sCT were administered to rats by i.v. injection. Serial blood samples, urine and various tissue samples were taken for the determination of radioactivity. Di-PEG-sCT exhibited significantly reduced systemic clearance (2.3 vs. 11.1 ml/min/kg) and steady-state volume of distribution (229.9 vs. 603.1 ml/kg), while mono-PEG-sCT showed a prolonged elimination half-life (189.1 min vs. 59.8 min) compared with unmodified sCT. The extent of urinary excretion of the PEG-modified sCTs was higher than for the unmodified sCT, but all these chemicals were excreted in urine in small quantities (< or = 0.6%). There was a tendency toward reduced accumulation of PEGylated sCTs in tissues, with its reduction being inversely proportional to the molecular size. Accumulation of the total radioactivity of the unmodified and PEG-modified sCTs was highest in the liver, followed by kidneys, lungs, spleen, heart and thyroid. When expressed per tissue gram weight, however, the highest radioactivity was found in the kidneys. PEGylated sCTs may have greater therapeutic potential via reduced systemic clearance and prolonged elimination half-life over unmodified sCT.

Animals↗
PubMed2000

Absorption, first-pass metabolism, and disposition of itraconazole in rats.

This study examined the pharmacokinetic disposition, oral absorption and hepatic extraction of itraconazole and its active metabolite, hydroxyitraconazole, in rats. After i.v. injection, serum itraconazole concentrations decreased biexponentially, with an average terminal elimination half-life, volume of distribution and systemic clearance of 4.9 h, 6.0 l/kg and 14.2 ml/min/kg, respectively. When given orally, its absorption was low, with a mean absolute bioavailability of 16.6%. The metabolite to parent drug area under the curve (AUC) ratio was higher after oral administration compared with i.v. injection (mean ratio, 2.7 vs. 0.9). The hepatic drug extraction ratio determined after femoral and portal vein administration averaged 18.5%. When hydroxyitraconazole was injected i.v., the elimination half-life, volume of distribution and systemic clearance of itraconazole averaged 10.0 h, 2.4 l/kg and 3.4 ml/min/kg, respectively. The fraction of the systemically available itraconazole that was metabolized to hydroxyitraconazole was 21.0% and 76.0% after i.v. and oral administration, respectively. In summary, this study is the first reporting the hepatic extraction of itraconazole and the i.v. disposition characteristics of hydroxyitraconazole in rats. Itraconazole is a drug with a low hepatic extraction ratio and its systemic clearance appears to be largely accounted for by hepatic metabolism.

Administration, Oral↗
PubMed2000

Somatotropin and adipose tissue metabolism: substrate and temporal effects.

The purpose of these studies was to determine the time course for changes in feed intake, blood metabolites, and lipogenic activity in adipose tissue in response to the initiation of porcine somatotropin (pST) treatment and following withdrawal from treatment in barrows. An initial study was conducted to determine the impact of chronic pST treatment (4 wk of daily injection; 0 vs 4 mg/d) on adipose tissue lipid metabolism in barrows (initial weight 67 kg). Feed efficiency was improved 27%, backfat thickness was decreased 43%, and glucose and lactate oxidation and incorporation into lipid in adipose tissue was reduced 70 to 86% in pST-treated pigs. Palmitate esterification was decreased 44%, whereas palmitate oxidation was unaffected. In vitro metabolism of lactate, glucose, and palmitate in liver slices was not affected by pST treatment. The time-course for changes in intake and adipose tissue metabolism in response to 7 d of pST (0 vs 4 mg/d) treatment and 7 d of withdrawal was examined in subsequent studies in barrows (initial weight 75 kg). Feed intake during pST treatment was significantly (P < .05) less than in control pigs within 24 h of the initiation of treatment and remained low through 3 d after withdrawal. Adipose tissue biopsies were obtained on d 0, 1, 2, 4, and 7 of the treatment phase and on d 2, 4, and 7 after withdrawal from 7 d of treatment. Maximal inhibition of lipogenesis by pST treatment in adipose tissue in vitro was observed on d 4 (-68%) and d 7 (-69%). Similarly, fatty acid synthase activity declined during the treatment period, with the greatest change noted on d 7 (-26%). After withdrawal from treatment, lipogenesis gradually increased, returning to control values 7 d after withdrawal. Levels of IGF-I began to increase from d 1 to d 7 of treatment, continually decreased during withdrawal, and were normalized by the end of the withdrawal period. Plasma urea nitrogen concentrations decreased during treatment, increased during the withdrawal phase, and were normalized 4 d after the last pST treatment. Overall results indicate that most of the metabolic changes in response to pST occur within 1 wk of treatment and return to pretreatment values after 7 d of withdrawal from treatment.

Adipose Tissue↗
PubMed2000

The C282Y mutation of the HFE gene is not found in Chinese haemochromatotic patients: multicentre retrospective study.

OBJECTIVE: To detect two novel mutations (C282Y and H63D) of the HFE gene in Chinese patients with hepatic iron overload. DESIGN: Multicentre retrospective study. SETTING: Four public hospitals, Hong Kong. PARTICIPANTS: Fifty Chinese patients who presented from January 1987 through December 1999 with hepatic iron overload from various causes. MAIN OUTCOME MEASURES: The DNA from liver biopsy samples was tested for HFE mutations by restriction fragment length polymorphism analysis. RESULTS: The sample DNA quality was unsatisfactory for analysis of the C282Y mutation in one case and the H63D mutation in nine cases. The C282Y mutation was not detected in any of the 49 satisfactory samples. Three of the 41 samples were heterozygous for the H63D mutation and only one was homozygous, giving an allele frequency of 6.1%. Of the three H63D-heterozygotes, one had beta-thalassaemia major, one had beta-thalassaemia minor, and one had hereditary spherocytosis. None of the 12 patients who were presumed to have primary haemochromatosis were positive for either mutation. CONCLUSIONS: The classical form of human leukocyte antigen-linked hereditary haemochromatosis appears to be absent form this locality. The H63D mutation is found in a minority (9.8%) of the patients, in whom it may act synergistically with an erythropoietic factor.

Adolescent↗
PubMed1999

Hepatocyte nuclear factor 3 relieves chromatin-mediated repression of the alpha-fetoprotein gene.

The alpha-fetoprotein gene (AFP) is tightly regulated at the tissue-specific level, with expression confined to endoderm-derived cells. We have reconstituted AFP transcription on chromatin-assembled DNA templates in vitro. Our studies show that chromatin assembly is essential for hepatic-specific expression of the AFP gene. While nucleosome-free AFP DNA is robustly transcribed in vitro by both cervical (HeLa) and hepatocellular (HepG2) carcinoma extracts, the general transcription factors and transactivators present in HeLa extract cannot relieve chromatin-mediated repression of AFP. In contrast, preincubation with either HepG2 extract or HeLa extract supplemented with recombinant hepatocyte nuclear factor 3 alpha (HNF3alpha), a hepatic-enriched factor expressed very early during liver development, is sufficient to confer transcriptional activation on a chromatin-repressed AFP template. Transient transfection studies illustrate that HNF3alpha can activate AFP expression in a non-liver cellular environment, confirming a pivotal role for HNF3alpha in establishing hepatic-specific gene expression. Restriction enzyme accessibility assays reveal that HNF3alpha promotes the assembly of an open chromatin structure at the AFP promoter. Combined, these functional and structural data suggest that chromatin assembly establishes a barrier to block inappropriate expression of AFP in non-hepatic tissues and that tissue-specific factors, such as HNF3alpha, are required to alleviate the chromatin-mediated repression.

Animals↗
PubMed1999

VAMP-7 mediates vesicular transport from endosomes to lysosomes.

A more complete picture of the molecules that are critical for the organization of membrane compartments is beginning to emerge through the characterization of proteins in the vesicle-associated membrane protein (also called synaptobrevin) family of membrane trafficking proteins. To better understand the mechanisms of membrane trafficking within the endocytic pathway, we generated a series of monoclonal and polyclonal antibodies against the cytoplasmic domain of vesicle-associated membrane protein 7 (VAMP-7). The antibodies recognize a 25-kD membrane-associated protein in multiple tissues and cell lines. Immunohistochemical analysis reveals colocalization with a marker of late endosomes and lysosomes, lysosome-associated membrane protein 1 (LAMP-1), but not with other membrane markers, including p115 and transferrin receptor. Treatment with nocodozole or brefeldin A does not disrupt the colocalization of VAMP-7 and LAMP-1. Immunoelectron microscopy analysis shows that VAMP-7 is most concentrated in the trans-Golgi network region of the cell as well as late endosomes and transport vesicles that do not contain the mannose-6 phosphate receptor. In streptolysin- O-permeabilized cells, antibodies against VAMP-7 inhibit the breakdown of epidermal growth factor but not the recycling of transferrin. These data are consistent with a role for VAMP-7 in the vesicular transport of proteins from the early endosome to the lysosome.

Animals↗
PubMed1999

Microbore high-performance liquid chromatographic determination of cisapride in rat serum samples using column switching.

For the determination of cisapride from serum samples, an automated microbore high-performance liquid chromatographic method with column switching has been developed. After serum samples (100 microl) were directly injected onto a Capcell Pak MF Ph-1 pre-column (10 x 4 mm I.D.), the deproteinization and concentration were carried out by acetonitrile-phosphate buffer (20 mM, pH 7.0) (2:8, v/v) at valve position A. At 2.6 min, the valve was switched to position B and the concentrated analytes were transferred from MF Ph-1 pre-column to a C18 intermediate column (35x2 mm I.D.) using washing solvent. By valve switching to position A at 4.3 min, the analytes were separated on a Capcell Pak C18 UG 120 column (250 x 1.5 mm I.D.) with acetonitrile-phosphate buffer (20 mM, pH 7.0) (5:5, v/v) at a flow-rate of 0.1 ml/min. Total analysis time per sample was 18 min. The linearity of response was good (r=0.999) over the concentration range of 5-200 ng/ml. The within-day and day-to-day precision (CV) and inaccuracy were less than 3.7% and 3.8%, respectively. The mean recovery was 96.5+/-2.4% with the detection limit of 2 ng/ml.

Animals↗
PubMed1999

A frequent activated smoothened mutation in sporadic basal cell carcinomas.

Basal-cell carcinomas (BCCs) are the most common cancer in Caucasians. It has been reported that the patched gene is inactivated in 30-40% sporadic BCCs and 20% sporadic medulloblastomas via loss of heterozygosity and nonsense mutations. Recently, two activating smoothened mutations have been found in the sporadic basal cell carcinomas. One, at base pair 1604 (G-to-T transversion) of exon 9, changes codon 535 from tryptophan to leucine, and the other, at base pair 1685 (G-to-A transition) of exon 10, changes codon 562 from arginine to glutamine (Xie et al., 1998). In our study, 1604G-->T was found in 20 out of 97 (20.6%) sporadic BCCs. The high prevalence indicates that 1604G is the mutation hot spot in our tumor samples. This mutation was detected in all three histological subtypes of BCCs, suggesting that smoothened mutation is an early event during the development of the tumor. Our finding of a high smoothened mutation rate, together with high frequent patched gene mutations reported recently, indicates that activation of the hedgehog signal transduction pathway is the most common and early event in the development of sporadic BCCs. Additionally, to determine whether smoothened, like patched, is also involved in the carcinogenesis of medulloblastomas, we screened medulloblastoma samples for these two mutations by restriction analysis. We have found the 1604G-->T mutation in 1 out of 21 medulloblastomas. This result confirmed smoothened gene involvement in the carcinogenesis of medulloblastoma.

Basal Cell Carcinoma↗
PubMed1999

Stability and cytotoxicity of Fab-ricin A immunotoxins prepared with water soluble long chain heterobifunctional crosslinking agents.

The effects of the hindered and non-hindered water soluble long-chain disulfide bonds on the stability and cytotoxicity of the ricin A chain (RTA) immunotoxin were examined. The RTA immunotoxins were prepared with the Fab fragments of anti-common acute lymphoblastic leukemia antigen (CALLA) monoclonal antibody (Fab-RTA) using sulfosuccinimidyl-6-[(-methyl-(-(2-pyridyldithio)toluamido]hexanoate (S-LC-SMPT) and sulfosuccinimidyl-6-[3-(2-pyridyldithio)-propionamido]hexanoate (S-LC-SPDP). The prepared Fab-RTA immunotoxins were evaluated for their conjugation yield, immunoreactivity, thermal and disulfide bond stability and cytotoxicity. The conjugation yield of the Fab-RTA immunotoxin from the water soluble long chain crosslinking agents, S-LC-SMPT and S-LC-SPDP, were comparable. Both Fab-RTA immunotoxins exhibited a similar immunoreactivity and thermal stability in aqueous solution. However, S-LC-SMPT -mediated Fab-RTA, sterically hindered, showed an enhanced disulfide bond stability in vitro over S-LC-SPDP mediated one. In the cytotoxicity against antigenic cell Daudi, the S-LC-SMPT -mediated RTA immunotoxin maintained a comparable cytotoxicity, compared with S-LC-SPDP mediated Fab-RTA immunotoxin.

Animals↗
PubMed1999

Isolation and characterization of biologically active lectin from Korean mistletoe, Viscum album var. Coloratum.

A mistletoe lectin was isolated from water extracts of Korean mistletoe, a subspecies of Viscum album, grown on Quercus mongolica using CM-Sepharose chromatography followed by an affinity chromatography on a concanavalin A-Sepharose column. The compound proved to be a mistletoe lectin II with D-galactose and N-acetyl-D-galactosamine specificity. Matrix-assisted laser desorption time-of-flight mass spectroscopy showed it to have an average molecular mass of 62.7 kDa and to consist of two subunits of 30.6 kDa and 32.5 kDa. It was a basic protein with isoelectric points of 9.4 and 9.6 by capillary isoelectric focusing and was cytotoxic to Molt4 cell.

Humans↗
PubMed1999

Recanalization of completely thrombosed giant aneurysm: case report.

BACKGROUND: Spontaneous recanalization in a completely thrombosed giant aneurysm is a very rare condition. CASE DESCRIPTION: An 18-year-old woman presented with a serpentine variety giant aneurysm of the posterior cerebral artery, in which spontaneous recanalization of a completely thrombosed lumen was demonstrated on magnetic resonance imaging and angiography. The patient was treated by trapping of the parent artery and aneurysmectomy. CONCLUSION: This case will provide insight into the potential for spontaneous recanalization in completely thrombosed giant aneurysms.

Adult↗