Biomedical subjects

K R Lee

Publications and source records attributed to K R Lee.

At least 55 records · Page 3Linked to original sources

PubMed2000

Altered phenytoin pharmacokinetics in children with severe, acute traumatic brain injury.

The purpose of this study was to determine if phenytoin protein binding and metabolism were altered in prepubescent pediatric patients within the first 10 days following severe, acute traumatic brain injury. Patients (n = 10) received phenytoin loading doses (15-20 mg/kg) followed by a maintenance regimen (7 mg/kg/day) initiated within 12 hours of the loading dose. Phenytoin serum concentrations were measured serially on days 1, 2, 3, 5, 7, 9, and 10 at 1, 6, and 12 hours. Time-invariant and time-variant Michaelis-Menten pharmacokinetic models were fit to the unbound phenytoin concentration-time data (ADAPT II). Albumin concentrations significantly decreased over time (p < 0.001) and were predictive of the phenytoin binding ratio (r2 = 0.373, p < 0.0001). The time-variant model provided a superior fit of the data in 7 patients with no difference between models in 3 patients. Rapid inhibition of metabolism (Vmaxbaseline = 2.82 +/- 2.35 mg/kg/day) was observed initially following injury. This was followed by induction of metabolism as reflected by a Vmaxinduced of 20.79 +/- 13.71 mg/kg/day, which was approximately twofold higher than reported values for nonstressed children. Children with severe, acute neurotrauma were found to have markedly altered protein binding and phenytoin metabolism.

Anticonvulsants↗

PubMed1999

Adenocarcinoma in situ with a small cell (endometrioid) pattern in cervical smears: a test of the distinction from benign mimics using specific criteria.

BACKGROUND: Papanicolaou smears have been less effective in preventing cervical adenocarcinoma than in preventing squamous carcinoma. One reason may be a lack of awareness of certain smear patterns of adenocarcinoma in situ (AIS) such as those with crowded small cells (endometrioid pattern). METHODS: A test set of 29 smears (17 AIS with an endometrioid pattern, 12 benign mimics) was reviewed by 11 cytologists (4 experienced cytotechnologists, 3 cytopathology fellows, and 4 cytopathologists with varying levels of experience). Participants were blinded as to the actual diagnosis and the number of cases in each category and were instructed to diagnose either AIS or a benign lesion. Results of this review were not disclosed before a second review conducted after instruction in specific criteria for "endometrioid" AIS. Results were compiled using kappa statistics. RESULTS: In the first round, the ability to distinguish these lesions was poor for 8 of the 11 reviewers, and no reviewer was in excellent agreement with the actual diagnosis. In the second round, only 1 reviewer had a poor rating, and 4 of 11 were in the excellent category. Misdiagnoses in both rounds were more commonly the result of underdiagnosis of AIS than overdiagnosis of benign cases. CONCLUSIONS: The presentation of AIS in smears as groups of crowded small cells is prone to underdiagnosis. Awareness of this problem and use of criteria improves sensitivity. [See editorial on pages 243-4, this issue.] Cancer (Cancer Cytopathol)

Carcinoma, Endometrioid↗

PubMed1999

Cytologic characteristics of abnormal cells in prior "normal" cervical/vaginal Papanicolaou smears from women with a high grade squamous intraepithelial lesion.

BACKGROUND: Some cervical/vaginal Papanicolaou (Pap) smears previously diagnosed as normal in women with a high grade squamous intraepithelial lesion (HSIL) are found to contain abnormal cells on retrospective review. This study characterized and quantitated such cells in 100 Pap smears. METHODS: One hundred prior negative Pap smears from 49 women with a newly diagnosed HSIL were rescreened, as were 107 negative Pap smears from 100 women with normal subsequent smears. Cases were assorted randomly so that the rescreener was unaware of the subsequent follow-up. RESULTS: All 12 Pap smears found to contain atypical mature and immature metaplastic cells belonged to the group with a subsequent HSIL (P = 0.001). In addition, 18 of the 100 previously negative Pap smears (18%) had immature metaplastic cells without nuclear atypia compared with 4 of 107 Pap smears (4%) in the control group (P = 0.0007). CONCLUSIONS: This study supports the observations of other authors that atypical metaplastic cells, especially those of the immature type, are associated with HSIL. These cells most likely are HSIL lesional cells, which are not easily recognizable as such. Immature metaplastic cells without atypia also were shown to be associated significantly with HSIL in this study. These cells may be unrecognizable lesional cells or a marker of increased risk for HSIL and deserve further study.

Carcinoma, Squamous Cell↗

PubMed1999

Clinical wear of 63 ultrahigh molecular weight polyethylene acetabular components: effect of starting resin and forming method.

This study compares the clinical wear rates and implant characteristics of 63 surgically retrieved acetabular components. All components were made by the same manufacturer, implanted by the same surgeon, in articulation against the same type of femoral component, and revised for the same reason; 19 were made from directly compression molded, calcium stearate free, ultrahigh molecular weight polyethylene (UHMWPE) and 44 were made from machined, ram extruded, calcium stearate containing UHMWPE. There were significant differences in wear, duration, and wear rate between the molded (type I) and machined (type II and III) components. Most importantly, the wear rates of type I (molded) components were significantly (p < 0.0001) lower than the wear rates of type II, type III, and type II and III components as a group (all machined). The machined components had wear rates 2.3 times greater than the molded components. The wear rates between the two different groups of machined components (type II and III) were not significantly different. The scanning electron microscope observations did not reveal any major differences in wear mechanisms between the three types of components, although the machined components did show more evidence of brittleness. The molded components were better consolidated (or had less fusion defects) than the ram extruded components.

Aged↗

PubMed1999

Antioxidative flavonoids from the leaves of Morus alba.

Nine flavonoids (1-9) were isolated from the leaves of Morus alba (Moraceae). The structures of compounds were determined to be kaempferol-3-O-beta-D-glucopyranoside (astragalin, 1) kaempferol-3-O-(6"-O-acetyl)-beta-D-glucopyranoside (2), quercetin-3-O-(6"-O-acetyl)-beta-D-glucopyranoside (3), quercetin-3-O-beta-D-glucopyranoside (4), kaempferol-3-O-alpha-L-rhamnopyranosyl-(1-->6)-beta-D-glucopyranoside (5), quercetin-3-O-alpha-L-rhamnopyranosyl-(1-->6)-beta-D-glucopyranoside (rutin, 6), quercetin-3-O-beta-D-glucopyranosyl-(1-->6)-beta-D-glucopyranoside (7), quercetin-3,7-di-O-beta-D-glucopyranoside (8) and quercetin (9) on the basis of spectroscopic and chemical studies. Compounds 7 and 9 exhibited significant radical scavenging effect on 1,1-diphenyl-2-picrylhydrazyl radical.

Antioxidants↗

PubMed1999

A new cytotoxic acyclic diterpene from Carpesium divaricatum.

A new acyclic diterpene (1) and a known acyclic diterpene, 12(S)-hydroxygeranylgeraniol (2) were isolated from the aerial parts of Carpesium divaricatum. The structure of 1 was determined to be (2E,10E)-1,12-dihydroxy-18-acetoxy-3,7,15-trimethylhexadeca- 2,10,14-triene (1) on the basis of spectroscopic studies. Compounds 1 and 2 exhibited cytotoxicity against cultured human tumor cell lines, A549, SK-OV-3, SK-MEL-2, XF498, and HCT15, with ED50 values ranging from 4.3-10.2 micrograms/ml and 4.1-8.3 micrograms/ml, respectively.

Antineoplastic Agents, Phytogenic↗

PubMed1999

Inducible nitric oxide synthase inhibitors from Melia azedarach var. japonica.

In bioassay-guided search for inducible nitric oxide synthase (iNOS) inhibitory compounds from higher plants of South Korea, two beta-carboline alkaloids, 4-methoxy-1-vinyl-beta-carboline (1) and 4,8-dimethoxy-l-vinyl-beta-carboline (2) have been isolated from the cortex of Melia azedarach var. japonica. The structures of these compounds were elucidated on the basis of spectroscopic data. Compounds 1 and 2 showed marked inhibitory activity of iNOS on LPS- and interferon-gamma-stimulated RAW 264.7 cells.

Carbolines↗

PubMed1999

Two new lignans from Lindera obtusiloba blume.

Two new furanolignans (3, 5), together with three known lignans (1, 2, 4), were isolated from the stem of Lindera obtusiloba (Lauraceae). The structures of the compounds were determined as actifolin (1), pluviatilol (2), 5,6-dihydroxymatairesinol (3), (+)-syringaresinol (4), and (+)-9'-O-trans-feruloyl-5,5'-dimethoxylariciresinol (5) on the basis of physicochemical and spectroscopic evidences. Compounds 1, 2, 3, and 5 showed cytotoxicity against a small panel of human tumor cell lines with ED50 values of 3.40 to approximately 19.27 microg/ml.

Antineoplastic Agents, Phytogenic↗

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

Stage IA1 cervical adenocarcinoma: definition and treatment.

OBJECTIVE: To propose a definition for stage IA1 cervical adenocarcinoma, based on the International Federation of Gynecology and Obstetrics (FIGO) staging system, and to determine if patients meeting criteria might be candidates for conservative surgery. METHODS: Two hundred women were diagnosed with early-stage cervical adenocarcinoma from 1982 to 1996. Histopathologic sections were reviewed by a gynecologic pathologist. Medical records were reviewed, and patients included in this study had microscopically identifiable lesions, up to 3 mm invasive depth, up to 7 mm tumor width, and negative margins if cone biopsy was performed. RESULTS: Twenty-one patients with microinvasive adenocarcinoma met criteria for FIGO stage IA1 carcinoma of the cervix. The median (range) follow-up was 76 (30-172) months and median (range) patient age was 38 (24-75) years. Definitive treatment included type II or III radical hysterectomy in 16 cases, simple abdominal or vaginal hysterectomy in four cases, and loop electrosurgical excision procedure in one case; one patient received adjuvant pelvic radiation. The histologic subtypes were endocervical adenocarcinoma in 18 cases, adenosquamous carcinoma in two cases, and clear-cell adenocarcinoma in one case. There was no evidence of parametrial invasion or lymph node metastases in any patient who had radical surgery, and there were no disease recurrences. CONCLUSION: Patients with microinvasive adenocarcinoma who met criteria for FIGO stage IA1 cervical carcinoma had disease limited to the cervix, and conservative surgery, such as cone biopsy or simple hysterectomy, might offer them definitive treatment.

Adenocarcinoma↗

PubMed1999

Early cervical adenocarcinoma: selection criteria for radical surgery.

OBJECTIVE: To identify selection criteria for radical surgery in early cervical adenocarcinoma based on pretreatment clinical stage and correlation with high-risk surgical-pathologic factors. METHODS: One hundred seventy-five women with International Federation of Gynecology and Obstetrics (FIGO) clinical stage IB1 (n = 132) and IB2-IIA (n = 43) cervical adenocarcinoma were treated primarily at our institutions from 1982 to 1996. Histopathologic sections were reviewed by a gynecologic pathologist. Medical records were reviewed retrospectively and clinical follow-up was done. RESULTS: The overall 5-year survival rate was 87% (95% confidence interval [CI] 81%, 93%) for stage IB1 and 61% (95% CI 46%, 77%) for stage IB2-IIA (P<.001). Adenosquamous cell type, deep cervical invasion, and lymph-vascular space invasion were significant independent high-risk surgical-pathologic factors that affected disease-free survival (each P<.002). One hundred fourteen (86%) of 132 stage IB1 patients and 19 (44%) of 43 stage IB2-IIA subjects were treated primarily with radical surgery. Lymph node metastases, lymph-vascular space invasion, adenosquamous cell type, deep cervical invasion, and positive surgical margins were more than twice as frequent in stage IB2-IIA patients who had radical surgery than in stage IB1 patients (each P <.05). Based on high-risk surgical-pathologic factors in 133 subjects who had radical surgery, postoperative radiotherapy was recommended for 18 (16%) of 114 stage IB1 patients and 18 (95%) of 19 stage IB2-IIA subjects (P<.001). CONCLUSION: Radical surgery for FIGO clinical stage IB1 cervical adenocarcinoma and primary radiotherapy for stage IB2-IIA disease would largely avoid combined-modality therapy, thereby reducing treatment-related toxicity and cost.

Adenocarcinoma↗

PubMed1999

Subclassifying atypical squamous cells in Thin-Prep cervical cytology correlates with detection of high-risk human papillomavirus DNA.

Recent studies have proposed subclassifying ASCUS into "favor reactive" (ASFR), "not otherwise specified" (ASNOS), and "favor squamous intraepithelial lesion (SIL)" (ASFS). This study explored the reproducibility of these diagnoses with Thin-Prep cytology and their association with high-risk human papillomavirus DNA (HRHPV). Three pathologists and 1 cytotechnologist with 2 to 25 years of experience reviewed 144 Thin-Prep (Cytyc, Boxborough, MA) specimens previously diagnosed as normal, ASFR, ASNOS, ASFS, and SIL. Interobserver reproducibility was computed with the kappa statistic. The original laboratory diagnosis was compared with the presence of HRHPV types. Interobserver reproducibility for a normal or SIL diagnosis was very good (kappa = .68 and .63). Reproducibility for ASFR, ASNOS, and ASFS ranged from poor to fair (kappa = .21, .19, and .32). In a weighted analysis, kappa values for ASFR/ASNOS and ASFS/SIL were .36 and .62, respectively. HRHPV-positivity for preparations originally diagnosed as N, ASFR, ASNOS, ASFS, and SIL were 5.7%, 8.8%, 17.4%, 47.8%, and 54.5%, respectively. The difference in index of HRHPV for either N or ASFR and ASFS or SIL was significant (P < .001). Reproducibility for ASCUS is generally poor, but better reproducibility is obtained by combining ASFS with SIL and, to a lesser degree, ASNOS with ASFR. ASFS and SIL confer a similar index of HRHPV and merit similar management. ASFR may be managed with cytologic follow-up; but this may depend upon the individual laboratory. HPV testing, in conjunction with cytologic and biopsy follow-up, appears useful for estimating the significance of ASCUS subgroups in laboratory practice.

DNA, Viral↗

PubMed1999

A hemorrhagic factor (Apicidin) produced by toxic Fusarium isolates from soybean seeds.

Fifty-two isolates of Fusarium species were obtained from soybean seeds from various parts of Korea and identified as Fusarium oxysporum, F. moniliforme, F. semitectum, F. solani, F. graminearum, or F. lateritium. These isolates were grown on autoclaved wheat grains and examined for toxicity in a rat-feeding test. Nine cultures were toxic to rats. One of these, a culture of Fusarium sp. strain KCTC 16677, produced apicidin, an antiprotozoal agent that caused toxic effects in rats (including body weight loss; hemorrhage in the stomach, intestines, and bladder; and finally death) when rats were fed diets supplemented with 0.05 and 0.1% apicidin. The toxin was toxic to brine shrimp (the 50% lethal concentration was 40 microg/ml) and was weakly cytotoxic to human and mouse tumor cell lines.

Animals↗

PubMed1998

Matching for private or public HLA epitopes reduces acute rejection episodes and improves two-year renal allograft function.

BACKGROUND: The current role of HLA matching in renal transplantation is controversial. Public HLA epitope matching has been suggested to be as advantageous as private HLA matching, with the added benefit of increasing recipients' access to well-matched grafts. METHODS: In this single-center study of 105 renal transplant recipients, we examined the association of HLA matching with early (0-3 months) and late (4-6 months) rejection episodes (RE), as well as renal allograft function up to 2 years after transplant. RESULTS: Poor HLA-DR, but not HLA-A or -B, matching was associated with early RE (0 DR matches, RE=2.7+/-0.19, 1 DR match, RE=2.37+/-0.18, vs. 2 DR matches, RE=1.5+/-0.38; P < 0.01). In contrast, poor HLA-B, but not HLA-A or -DR, matching was associated with late rejections (0 HLA-B matches, RE=1.1+/-0.51 vs. 1-2 HLA-B matches, RE=0.51+/-0.1; P < 0.004). HLA-B matching was also associated with a significantly lower serum creatinine (SCr) level at 24 months (0 HLA-B matches, SCr=178+/-20 micromol/L vs. SCr=132+/-6 micromol/L for 1-2 HLA-B matches; P < 0.025). Matching for 10 supertypic HLA-A and -B cross-reactive groups was associated with reduced late graft rejection (0-2 residue matches, RE=1.15+/-0.18 vs. RE=0.62+/-0.12 for 3 to 7 residue matches; P < 0.013) as well as a significantly lower SCr level at 24 months (0-2 residue matches, SCr=205+/-29 micromol/L vs SCr=131+/-6 micromol/L for 3 to 7 residue matches; P < 0.001) after transplantation. CONCLUSIONS: HLA-DR matching was associated with a reduced frequency of early rejection episodes, whereas HLA-B or residue/cross-reactive group matching was associated with a reduced frequency of late rejection episodes and improved graft function at 2 years.

Acute Disease↗

PubMed1998

Cytologic correlates of papillary immature metaplasia (immature condyloma) of the cervix.

Papillary immature metaplasia (PIM) of the cervix (immature condyloma) is a variant of low-grade squamous intraepithelial lesions (LSIL). It is frequently associated with human papillomavirus (HPV) types 6 and 11. The purpose of this study was to characterize the cytologic changes associated with this lesion. We analyzed 10 cases of PIM from our files and reviewed the Papanicolaou smears taken proximate to the time of the biopsy. Four cases had either reactive epithelial changes (2 cases) or cytologic findings typical of low-grade SIL, with koilocytosis (2 cases). Six cases displayed a spectrum of metaplastic cells with varying maturation that ranged from atypical reactive cells to atypical immature metaplastic cells. Binucleation was common. Some cells exhibited features characteristic of SIL, although the degree of nuclear atypia generally was less than that associated with high-grade SIL. Papanicolaou smears from all cases were interpreted as atypical (ASCUS) metaplasia or low-grade SIL. Follow-up biopsy in one case revealed a PIM in association with a high-grade SIL, the latter undiagnosed by smear alone. PIM is a distinct histologic entity that can present with a spectrum of cytologic findings. Its recognition histologically can resolve some cytologic/histologic discrepancies. Confusion with an immature HSIL or atypical immature metaplasia can occur in some instances and the diagnosis of PIM by cytology alone is not recommended, unless the diagnosis is qualified.

Cervix Uteri↗

PubMed1998

A new epoxynaphthoquinol from Rumex japonicus.

A new epoxynaphthoquinol derivative, 3-acetyl-2-methyl-1, 5-dihydroxy-2,3-epoxynaphthoquinol (I), was isolated from the root of Rumex japonicus. The structure was elucidated by high field 1D and 2D NMR techniques.

Magnetic Resonance Spectroscopy↗

PubMed1998

Isolation of a multidrug resistance inhibitor from Aconitum pseudo-laeve var. erectum.

To overcome multidrug resistance (MDR) in cancer chemotherapy, we prepared various plant extracts and searched for a component which is effective for inhibition of MDR. MDR inhibition activity was determined by measuring cytotoxicity to MDR cells using multidrug resistant human fibrocarcinoma KB V20C, which is resistant to 20 nM vincristine and expresses high level of mdr1 gene. Of various plant extracts, the MeOH extract of the root of Aconitum pseudo-laeve var. erectum was found to have potent inhibitory activity on MDR. The bioassay-guided fractionation of the MeOH extract of the plant led to the isolation of an alkaloid, lycaconitine, as an active principle. And the IC50 of lycaconitine for KB V20C cells was 74 micrograms/ml.

Alkaloids↗

PubMed1998

Thymol derivatives from Carpesium divaricatum.

Four thymol derivatives, 2,5-dimethoxythymol (1), 2-methoxythymol isobutyrate (2), 10-isobutyloxy-8,9-epoxythymolisobutyrate (3) and 10-(2-methylbutyloxy)-8,9-epoxythymolisobutyrate (4) were isolated from the aerial parts of Carpesium divaricatum. The structures were elucidated by high field 1D and 2D NMR techniques.

Asteraceae↗