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K R Lee

Publications and source records attributed to K R Lee.

At least 37 records · Page 2Linked to original sources
PubMed2001

Pulmonary small lymphocytic lymphoma (mucosa-associated lymphoid tissue type) associated with pulmonary hyalinizing granuloma.

A case of pulmonary hyalinizing granuloma (PHG) and concomitant low-grade, small lymphocytic lymphoma of the lung is presented. This is the first occurrence of pulmonary lymphoma in patients with PHG ever reported. The infiltrates around a left lower lobe nodule with left pleural effusion and thickening seen on chest CT were histologically proven to be lymphomatous infiltrates of the lung, pleura, and chest wall muscle. We believe that the lymphoma developed around the nodule and spread to the pleura and muscle in our patient. When infiltrates around the nodules, pleural effusion, or adenopathy are developed in a patient with proven PHG, close follow-up, biopsy, or careful cytology should be seriously considered to rule out a developing lymphoma.

Granuloma↗
PubMed2001

Malaria transmission potential by Anopheles sinensis in the Republic of Korea.

To evaluate the factors that determine the transmission level of vivax malaria using vectorial capacity, entomological surveys were conducted from June to August, 2000. From 6 nights of human-bait collection in Paju, the human biting rate (ma) was counted as 87.5 bites/man/night. The parity of Anopheles sinensis from human baiting collections fluctuated from 41% to 71% (average 48.8%) of which the rate gradually increased as time passed on: 35.2% in Jun.; 55.0% in July; 66.2% in Aug. From this proportion of parous, we could estimate the probability of daily survival rate of An. sinensis to be 0.79 assumed with 3 days gonotrophic cycle and the expectancy of infective life through 11 days could be defined as 0.073. Blood meal analysis was performed using ELISA to determine the blood meal source. Only 0.8% of blood meals were from human hosts. We could conclude that An. sinensis is highly zoophilic (cow 61.8%). Malaria is highly unstable (stability index < 0.5) in this area. From these data, vectorial capacity (VC) was determined to be 0.081. In spite of a high human biting rate (ma), malaria transmission potential is very low due to a low human blood index. Therefore, we could conclude that malaria transmission by An. sinensis is resulted by high population density, not by high transmission potential. For this reason, we need more effort to decrease vector population and vector-human contact to eradicate malaria in Korea.

Animals↗
PubMed2000

Suppression of inducible nitric oxide synthase expression in RAW 264. 7 macrophages by two beta-carboline alkaloids extracted from Melia azedarach.

We investigated the mechanism of suppression of inducible nitric oxide synthase (iNOS) by two beta-carboline alkaloids isolated from Melia azedarach, 4,8-dimethoxy-1-vinyl-beta-carboline (compound 1, C-1) and 4-methoxy-1-vinyl-beta-carboline (compound 2, C-2). iNOS activity in a cell-free extract of lipopolysaccharide/interferon-gamma-stimulated RAW 264.7 cells was found to be markedly increased, and this increase was prevented by C-1 and C-2, accompanied by the parallel reduction in nitrite accumulation in culture medium. However, C-1 and C-2 had no further effect on the iNOS activity prepared from fully lipopolysaccharide/interferon-gamma-stimulated RAW 264.7 cells. Treatment with C-1 or C-2 decreased the levels of iNOS protein and mRNA in a concentration-dependent manner. In addition, prostaglandin E(2) production, cyclooxygenase-2 protein and DNA binding of nuclear factor-kappaB (NF-kappaB) in lipopolysaccharide-stimulated RAW 264.7 cells were reduced by these compounds. These results indicate that C-1 and C-2 primarily inhibit iNOS and cyclooxygenase-2 activities via the suppression of de novo synthesis of these two enzymes, and that the inhibition of iNOS expression may be associated with the inhibition of NF-kappaB activation. Taken together, the results suggest that suppression of iNOS and cyclooxygenase-2 induction by lipopolysaccharide is responsible for the anti-inflammatory activity of these alkaloids through selective inhibition of the expression of genes, which play important roles in inflammatory signaling pathways.

Alkaloids↗
PubMed2000

Early invasive adenocarcinoma of the cervix.

BACKGROUND: Adenocarcinoma of the cervix is increasing in frequency. There is a dearth of specific detail concerning the histomorphology, histogenesis, and associated findings in early invasive cervical adenocarcinoma. METHODS: Forty cases of cervical adenocarcinoma invasive to 5 mm or less were examined in detail. RESULTS: Mean patient age was 40.9 years. In 78% of the cases, the midpoint of the invasive focus was in the region of the squamocolumnar junction or transformation zone; more than 1 invasive focus was present in 4 cases. Eighty-five percent of cases also had adenocarcinoma in situ (AIS). In 9 of 10 minimally invasive cases, small invasive glands were present in the stroma adjacent to AIS. In some of these, the AIS had preinvasive buds that were still attached. Endometrioid adenocarcinomas were associated with AIS but were located higher in the canal than the more common endocervical type. All three adenosquamous carcinomas were associated with both squamous intraepithelial neoplasia and AIS. Vascular space invasion was observed in two cases, microglandular hyperplasia in four. CONCLUSIONS: Adenocarcinoma in situ is the precursor to most adenocarcinomas of the cervix with an average interval between clinically detected AIS and early invasion of approximately 5 years, supporting the potential for Papanicolaou test screening to prevent this disease. However, the existence of small carcinomas in the absence of AIS suggests the possibility of rapid progression in some cases. Invasion occurs by budding from or expansion of AIS glands, usually in the region of the squamocolumnar junction. Multifocal invasion is uncommon, as is vascular invasion in early lesions. The endometrioid variant has the same histogenesis as the endocervical type but may arise higher in the canal. The precursor of adenosquamous carcinoma has a similar bimorphic differentiation potential. Microglandular hyperplasia is not related to early invasive adenocarcinoma.

Adenocarcinoma↗
PubMed2000

Prospective management of stage IA(1) cervical adenocarcinoma by conization alone to preserve fertility: a preliminary report.

OBJECTIVE: Microinvasive cervical adenocarcinoma has an excellent prognosis and emerging data support the hypothesis that it should be treated in the same way as its squamous counterpart. We report our preliminary experience prospectively treating stage IA(1) cervical adenocarcinoma by conization alone in women who strongly desired to preserve their fertility. METHODS: Since May 1998, all patients with stage IA(1) cervical adenocarcinoma who expressed a strong desire to preserve fertility have been offered cold knife conization (CKC) and careful surveillance without hysterectomy. Women with lesions identifiable only microscopically, up to 3 mm invasive depth, up to 7 mm tumor width, and a conization specimen including the entire lesion with negative margins were eligible for conservative management. Postconization surveillance consisted of a Pap smear and endocervical curettage every 4 months. Medical records were reviewed for clinical data, follow-up, and disease status. RESULTS: Five women ages 26-33 elected CKC and surveillance. Four were nulliparous and one primiparous. Four tumors were endocervical cell type; one was adenosquamous. Three were grade 1, one was grade 2, and one grade 3. None had lymph-vascular space invasion. None of the patients has developed recurrent disease after 6-20 months of follow-up. CONCLUSIONS: Our preliminary data suggest that patients with FIGO stage IA(1) cervical adenocarcinoma who strongly desire to preserve their fertility may be treated by conization alone if they are fully informed of the unknown risks for disease recurrence and are carefully followed. A multicenter trial is the next logical step to test the efficacy of this approach.

Adenocarcinoma↗
PubMed2000

Conservative management of adenocarcinoma in situ of the cervix.

OBJECTIVE: The purpose of this study was to determine the method of treatment and outcome of women with cervical adenocarcinoma in situ (AIS). METHODS: Following institutional review board approval, all women diagnosed with cervical AIS from 1987 to 1999 were identified. Data were retrospectively collected by record review and correspondence with medical providers. RESULTS: Of 132 women treated with cone biopsy for AIS, 95 (72%) were managed conservatively after cold knife cone or loop electrical excisional procedure alone; 37 (28%) eventually underwent hysterectomy. The median age of diagnosis was 29 years (range, 17-47) in the conservative management group and 40 years (range, 25-72) in the hysterectomy group (P < 0.0001). Seventy-four percent were nulliparous in the conservative group compared with 27% in the hysterectomy group (P < 0.0001). Of the 95 conservatively managed patients, 92 obtained negative margins; three were followed despite positive or unevaluable margins. During a median follow-up of 30 months, 9 women required evaluation for follow-up abnormalities after cone biopsy with negative margins. None had pathologic evidence of recurrent AIS. Twenty-three infants were delivered. Hysterectomy was generally performed for undesired fertility or persistently positive cone margins. One woman required hysterectomy for recurrent AIS. Thirteen (62%) of twenty-one hysterectomy specimens had residual AIS following cone biopsy with positive or unevaluable margins; 1 (6%) of 16 had residual AIS following cone biopsy with negative margins (P < 0.0001). No patient developed invasive adenocarcinoma. CONCLUSIONS: Younger women with cervical AIS may be effectively treated with cone biopsy alone if negative margins can be achieved.

Adenocarcinoma↗
PubMed2000

Cytotoxic peroxides from Artemisia stolonifera.

Two sesquiterpene endoperoxides, 1S, 4R, 6R-1, 4-endoperoxy-bisabola-2, 10-diene (I), 1R, 4S, 6R-1, 4-endoperoxy-bisabola-2, 10-diene (II), and a sesquiterpene hydroperoxide, 1beta-hydroperoxygermacra-4 (15), 5, 10 (14)-triene (III) were isolated from the aerial parts of Artemisia stolonifera (Compositae). Their chemical structures were assigned by spectral evidences. Compounds I and II exhibited cytotoxicity against five human tumor cell lines with their ED50 values ranging from 0.20 to 5.43 microg/ml and from <0.1 to 0.87 microg/ml, respectively.

Antibiotics, Antineoplastic↗
PubMed2000

Validation of a peptide mapping method for a therapeutic monoclonal antibody: what could we possibly learn about a method we have run 100 times?

Peptide mapping is a key analytical method for studying the primary structure of proteins. The sensitivity of the peptide map to even the smallest change in the covalent structure of the protein makes it a valuable 'finger-print' for identity testing and process monitoring. We recently conducted a full method validation study of an optimised reverse-phase high-performance liquid chromatography (RP-HPLC) tryptic map of a therapeutic anti-CD4 IgG1 monoclonal antibody. We have used this method routinely for over 1 year to support bioprocess development and test production lots for clinical trials. Herein we summarize the precision and ruggedness of the testing procedure and the main findings with respect to 'coverage of amino acid sequence' and limits-of-detection for various hypothetical structural variants. We also describe, in more detail, two unanticipated insights into the method gained from the validation study. The first of these is a potentially troublesome side-product arising during the reduction/alkylation step. Once the cause of this side-product was identified, it was easily prevented. We also report on subtle changes to the peptide map upon extended storage of the digest in the autosampler. These findings helped us to develop a 'robust' method for implementation in a quality control laboratory.

Amino Acid Sequence↗
PubMed2000

Endocervical intraepithelial glandular atypia (dysplasia): a histopathologic, human papillomavirus, and MIB-1 analysis of 25 cases.

The purpose of this study was to determine the likelihood that intraepithelial endocervical glandular atypias that are less severe than adenocarcinoma in situ (AIS) are precursors to AIS and, if so, whether they can be recognized by morphological or other means. We first assessed the frequency of atypias found in association with either AIS or invasive adenocarcinoma (ACA) and then tested these cases and additional randomly encountered cases for the presence of human papillomavirus (HPV) and for their proliferative (Ki-67) index. Lesions not fulfilling the classic criteria for AIS were subdivided into high-grade (HGGA) and low-grade glandular atypias (LGGA). Atypias and controls were microdissected and tested for HPV by the polymerase chain reaction. Serial sections were labeled for Ki-67 by immunohistochemistry with the MIB-1 antibody. Eight cases (6.8%) containing glandular atypia were found in a search of 117 consecutive cone biopsy or hysterectomy specimens that also had either AIS, ACA, or both. An additional 17 cases were either randomly encountered or were received in consultation. In 3 cases, both HGGA and LGGA were present, yielding a total of 28 lesions for study. Of the 9 HGGA cases that were associated with either AIS, ACA, or CIN II/III, 6 were positive for HPV; MIB-1 reactivity in all 6 was present in greater than 25% of the nuclei. Of the 3 HPV-negative HGGA cases in this group, the 2 that were tested showed low MIB-1 reactivity. All 3 cases of HGGA that were not associated with a diagnostic lesion were HPV-negative and had low MIB-1 reactivity. Of the 6 LGGAs associated with either AIS, ACA, or CIN II/III, 1 was positive for HPV; MIB-1 was nonreactive in this case and was low in all of the HPV-negative cases in this group that were tested. Of 10 LGGAs not associated with a diagnostic lesion, or with a low-grade squamous lesion as the only other abnormality, 2 were positive for HPV. Of these 2, one had an MIB-1 reactivity of greater than 25% and also had intestinal differentiation. MIB-1 reactivity was elevated in 2 of the 8 HPV-negative LGGAs from this group. All 10 ciliated atypias (3 HGGA, 7 LGGA) were HPV-negative and had low MIB-1 reactivity. One HPV-positive AIS control case was focally ciliated. Six of 7 foci with apoptotic bodies (5 HGGA, 2 LGGA) were HPV-positive. The infrequent occurrence of glandular atypias with AIS and ACA and the low rate of HPV DNA positivity when they are found in isolation are evidence that most AIS lesions do not evolve through morphologically identifiable antecedents and that most isolated atypias are not AIS precursors. HGGAs associated with AIS or CIN II/III maybe either precursors to or subtle variants of AIS. However, LGGAs similarly encountered are unlikely to be either. Elevated MIB-1 reactivity may be helpful diagnostically in selected cases, but it is not reliable as an independent criterion. The presence of cilia in isolated glandular atypias favors a nonneoplastic process, whereas intestinal differentiation and apoptotic bodies each suggest neoplasia.

Adolescent↗
PubMed2000

Statistical validation of reproducibility of HPLC peptide mapping for the identity of an investigational drug compound based on principal component analysis.

Peptide mapping is a key analytical method for studying the primary structure of proteins. The sensitivity of the peptide map to even the smallest change in the covalent structure of the protein makes it a valuable "fingerprint" for identity testing and process monitoring. We recently conducted a full method validation study of an optimized reverse-phase high-performance liquid chromatography (RP-HPLC) tryptic map of a therapeutic anti-CD4 monoclonal antibody. We have used this method routinely for over a year to test production lots for clinical trials and to support bioprocess development. One of the difficulties in the validation of the peptide mapping method is the lack of proper quantitative measures of its reproducibility. A reproducibility study may include method and system precision study, ruggedness study, and robustness study. In this paper, we discuss the use of principal component analysis (PCA) to quantitate peptide maps properly using its projected scores on the reduced dimensions. This approach allowed us not only to summarize the reproducibility study properly, but also to use the method as a diagnostic tool to investigate any troubles in the reproducibility validation process.

Antibodies, Monoclonal↗
PubMed2000

Ruggedness study of HPLC peptide mapping for the identity of a drug compound: a chemometrics approach.

A statistically more reliable approach than the traditional visual inspection of peptide maps to identify a drug compound is to generate a set of reference standards from a designed experiment that incorporates many possible factors that affect variation of peptide mapping. In fact, the experiment can be done for a ruggedness study as part of a high-performance liquid chromatography (HPLC) method validation. Once the ruggedness is proved with the study, those articles in the experiment may form a set of reference standards, and future articles can be compared to the set later to prove identity. A quantitative analysis of the ruggedness study can be done using a chemometrics approach, principal component analysis (PCA). The analysis is used to reduce the many channels of peptide maps to a few manageable dimensions. The scores projected onto the reduced dimensions are used to test factor effects of the ruggedness study. As a by-product, the analysis provides visual inspection of the set of articles in the experiment for any outliers and anomalies.

Antibodies, Monoclonal↗
PubMed2000

Chemometrics approach to the determination of polymorphism of a drug compound by infrared spectroscopy.

A chemometrics approach, multivariate calibration in particular, was used to determine the polymorphism of a drug compound based on Fourier transform infrared (FTIR) spectroscopy. The partial least-squares projection to latent structure makes use of all of the data, and the latent variables created by the method make use of hidden or partially separated peaks for quantitation. This paper illustrates the usefulness of the partial least-squares multivariate calibration method as an efficient tool to determine the polymorphism of a drug. Also, the analysis suggests the use of information from the modeling as diagnostic tools to gain more insight from the data. In particular, the diagnostic tools allow an analyst to assess design characteristics and any shortcomings of a calibration experiment for the polymorphism of a drug compound.

Least-Squares Analysis↗
PubMed2000

Calibration and LOD/LOQ estimation of a chemiluminescent hybridization assay for residual DNA in recombinant protein drugs expressed in E. coli using a four-parameter logistic model.

Calibration is the process of fitting a model based on reference data points (x, y), then using the model to estimate an unknown x based on a new measured response, y. In DNA assay, x is the concentration, and y is the measured signal volume. A four-parameter logistic model was used frequently for calibration of immunoassay when the response is optical density for enzyme-linked immunosorbent assay (ELISA) or adjusted radioactivity count for radioimmunoassay (RIA). Here, it is shown that the same model or a linearized version of the curve are equally useful for the calibration of a chemiluminescent hybridization assay for residual DNA in recombinant protein drugs and calculation of performance measures of the assay.

Calibration↗
PubMed2000

Mucinous tumors of the ovary: a clinicopathologic study of 196 borderline tumors (of intestinal type) and carcinomas, including an evaluation of 11 cases with 'pseudomyxoma peritonei'.

Mucinous ovarian neoplasms other than cystadenomas and adenofibromas have been classified as either borderline tumors or carcinomas for many years. Borderline tumors have been subdivided more recently into endocervical-like (mullerian) and intestinal forms. Such a distinction is rarely made in the mucinous carcinoma category. We did not encounter a pure endocervical-like carcinoma in the present series. Criteria for distinguishing an intestinal-type mucinous borderline tumor from a mucinous carcinoma have been controversial. In this study of 164 mucinous borderline tumors of intestinal type and 32 mucinous carcinomas, the former were further subdivided into 74 cases with epithelial atypia only and 90 with focal intraepithelial carcinoma. Of the 67 stage I tumors in the borderline (with atypia) category, all 49 with follow-up data were clinically benign; in the seven cases that had been designated stage III, the intraoperative appearance was that of "pseudomyxoma peritonei," which was fatal in four cases. Most of these tumors, however, were probably metastatic to the ovary rather than truly primary borderline tumors, although failure to examine the appendix in six cases compromised their interpretation. All 90 mucinous borderline tumors that had foci of intraepithelial carcinoma were recorded as stage I, but two of the 69 patients with follow-up data (3%) had fatal recurrences. Both of these tumors were incompletely staged, however, and one had ruptured intraoperatively. Thirty-two invasive carcinomas were subdivided into 12 expansile and 20 infiltrative subtypes; within the latter category seven tumors were only microinvasive. All 12 carcinomas with only expansile invasion were stage I; none of the 10 with follow-up data recurred. All seven microinvasive infiltrative carcinomas were stage I; none of the five with follow-up data recurred. One of five patients with stage I infiltrative carcinomas that were more than microinvasive and were adequately followed had a fatal recurrence, but staging had been incomplete in that case. Seven of the remaining eight infiltrative carcinomas were higher than stage I: five of the six (83%) with follow-up data persisted or recurred and were fatal. Considering all stages, increasing tumor grade in the carcinoma category correlated with an unfavorable outcome. However, grade did not influence prognosis in stage I carcinomas. Among 13 stage I cases in all categories with either preoperative or intraoperative tumor rupture and follow-up data, one recurred, a tumor in the borderline with intraepithelial carcinoma category. "Pseudomyxoma peritonei" is an ill-defined term and should not be used as a pathologic diagnosis. The presence of mucin in the abdominal cavity requires careful histologic evaluation to characterize it for prognostic purposes. Adequate and sometimes extensive sampling of mucinous ovarian tumors, the appendix and the peritoneum in cases of "pseudomyxoma peritonei" is necessary to achieve an accurate diagnosis and prognosis.

Adenocarcinoma, Mucinous↗
PubMed2000

A new caffeoyl quinic acid from aster scaber and its inhibitory activity against human immunodeficiency virus-1 (HIV-1) integrase.

The phytochemical study of the aerial parts of Aster scaber Thunb. (Asteraceae) yielded a new caffeoyl quinic acid, (-) 3,5-dicaffeoyl-muco-quinic acid (2) and three known compounds, (-) 3,5-dicaffeoyl quinic acid (1), (-) 4,5-dicaffeoyl quinic acid (3), (-) 5-caffeoyl quinic acid (4). The structures were established by high resolution spectroscopic methods. The antiviral effects against HIV-1 integrase of the compounds was evaluated. (-) 3,5-Dicaffeoyl-muco-quinic acid (2) exhibited potent antiviral activity with an IC50 value of 7.0 +/- 1.3 microg/ml.

Asteraceae↗
PubMed2000

New cytotoxic butanolides from Lindera obtusiloba BLUME.

Three new butanolides, 2-(1-methoxy-11-dodecenyl)-penta-2,4-dien-4-olide (1), (2Z,3S,4S)-2-(11-dodecenylidene)-3-hydroxy-4-methylbutano lide (2) and (2E,3R,4R)-2-(11-dodecenylidene)-3-hydroxy-4-methoxy-4-methylbu tanolide (3), were isolated from the stems of Lindera obtusiloba BLUME. Their chemical structures were assigned by spectroscopic evidence. They exhibited cytotoxicity against cultured human tumor cell lines with their ED50 values ranging from 3.19 to 14.63 microg/ml.

4-Butyrolactone↗
PubMed2000

Total hip arthroplasty in young patients. 8- to 13-year results using an uncemented stem.

One hundred eight uncemented total hip arthroplasties were performed in 91 patients who were 50 years of age or younger using the Taperloc femoral component. The average age of the patients at time of surgery was 37 years (range, 20-50 years). The mean followup was 10.2 years (range, 8-13 years). No patient was lost to followup. Seven patients (eight hips) died before obtaining the minimum time of 8 years for inclusion in this study. All seven died with their femoral components in place. Of the remaining 100 total hip arthroplasties, no femoral component required revision for aseptic loosening. One femoral component was revised to correct a leg length discrepancy, and one well-fixed femoral component was revised for sepsis. In the 98 total hip arthroplasties that had not undergone femoral component revision, complete radiographic and clinical followup was obtained. Radiographically, 96 (98%) femoral components were determined to have fixation by bone ingrowth, two (2%) femoral components showed stable fibrous ingrowth, and no femoral component was unstable. Femoral cortical osteolysis occurred in seven (7%) hips; major lysis was present in only one (1%). Clinically, 91 (93%) total hip arthroplasties were rated good or excellent; six (6%) were rated fair, and one (1%) was rated poor. Thirty-nine patients with 47 total hip arthroplasties (48%) were engaged in moderate to strenuous manual labor. These results indicate that excellent fixation and minimal lysis can be achieved with an uncemented femoral component in young and active patients at 10 years.

Adult↗