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Biomedical subjects

S M Lee

Publications and source records attributed to S M Lee.

At least 163 records · Page 9Linked to original sources

Chromosomal mapping of a skeletal muscle specific LIM-only protein FHL3 to the distal end of the short arm of human chromosome 1.

Four-and-a-half LIM domain proteins (FHL) possess four tandem repeats of LIM domain and an extra zinc finger. FHL family LIM proteins are unique when compared with other LIM-only proteins because they possess an odd number of zinc fingers. In this study, the tissue distribution and chromosomal mapping of skeletal muscle LIM protein FHL3 were reported. When the FHL3 cDNA probe was used to hybridize with poly-(A) RNA of various human tissues, a very strong signal was detected in skeletal muscle, and virtually no signal could be detected in heart, brain, placenta, lung, liver, kidney and pancreas. Using radiation hybrid technique, FHL3 gene was mapped to the distal end of the short arm of chromosome 1 (123.26 cR from the top of the Chr1 linkage group) and this region (near 1p34) is related to several human malignancies.

Animals↗

Recombinant human granulocyte colony-stimulating factor (filgrastim) following high-dose chemotherapy and peripheral blood progenitor cell rescue in high-grade non-Hodgkin's lymphoma: clinical benefits at no extra cost.

In order to evaluate the potential clinical and economic benefits of granulocyte colony-stimulating factor (G-CSF, filgrastim) following peripheral blood progenitor cells (PBPC) rescue after high-dose chemotherapy (HDCT), 23 consecutive patients aged less than 60 years with poor-prognosis, high-grade non-Hodgkin's lymphoma (NHL) were entered into a prospective randomized trial between May 1993 and September 1995. Patients were randomized to receive either PBPC alone (n = 12) or PBPC+G-CSF (n = 11) after HDCT with busulphan and cyclophosphamide. G-CSF (300 microg day[-1]) was given from day +5 until recovery of granulocyte count to greater than 1.0 x 10(9) l(-1) for 2 consecutive days. The mean time to achieve a granulocyte count > 0.5 x 10(9) l(-1) was significantly shorter in the G-CSF arm (9.7 vs 13.2 days; P<0.0001) as was the median duration of hospital stay (12 vs 15 days; P = 0.001). In addition the recovery periods (range 9-12 vs 11-17 days to achieve a count of 1.0 x 10(9) l[-1]) and hospital stays (range 11-14 vs 13-22 days) were significantly less variable in patients receiving G-CSF in whom the values clustered around the median. There were no statistically significant differences between the study arms in terms of days of fever, documented episodes of bacteraemia, antimicrobial drug usage and platelet/red cell transfusion requirements. Taking into account the costs of total occupied-bed days, drugs, growth factor usage and haematological support, the mean expenditure per inpatient stay was pound sterling 6500 (range pound sterling 5465-pound sterling 8101) in the G-CSF group compared with pound sterling 8316 (range pound sterling 5953-pound sterling 15,801) in the group not receiving G-CSF, with an observed mean saving of 1816 per patient (or 22% of the total cost) in the G-CSF group. This study suggests that after HDCT and PBPC rescue, the use of G-CSF leads to more rapid haematological recovery periods and is associated with a more predictable and shorter hospital stay. Furthermore, and despite the additional costs for G-CSF, these clinical benefits are not translated into increased health care expenditure.

Adult↗

A randomized phase II trial of interleukin 2 and interleukin 2-interferon alpha in advanced renal cancer.

A randomized phase II trial was performed to compare the efficacy and toxicity of interleukin 2 (IL-2) with an IL-2 and interferon alpha (IFN-alpha) regimen for the treatment of metastatic renal carcinoma. Sixty patients with recurrent renal cell carcinoma (RCC) who had previously undergone a nephrectomy were randomized to receive three cycles of IL-2 or IL-2 with IFN-alpha2b. Eighteen MU of IL-2 were administered subcutaneously on Mondays-Fridays for 3 weeks out of 4. Those patients randomized to receive the combination received the same regimen of IL-2 with 9 MU of IFN-alpha2b subcutaneously on Mondays, Wednesdays and Fridays for 3 weeks out of 4. Thirty patients were randomized to receive each arm. Twenty-nine were evaluable in each arm. Twenty-two patients received three cycles of IL-2 but only 14 patients received three cycles of IL-2/IFN-alpha because of the greater toxicity of the combination. The principal toxicities included nausea, fatigue and fever. There were no complete responses in either arm and only two patients who were treated with IL-2 attained a partial response. Twelve patients in each arm had stable disease and 15 patients in the IL-2 arm and 16 patients in the IL-2/IFN-alpha arm progressed through treatment. There were no significant differences in survival. Ten patients who received IL-2 are alive with a median follow-up of 266 days, whereas six patients who received IL-2/IFN-alpha are alive after a median of 278 days. The median survival from the time of identification of metastatic disease is 444 days in the IL-2 arm and 381 days in the IL-2/IFN-alpha arm. The IL-2/IFN-alpha combination is more toxic than IL-2 alone and this resulted in a reduced number of cycles of treatment. However, the median survival of the two groups was the same, suggesting that further evaluation of the IL-2/IFN-alpha combination should be confined to large prospective randomized clinical trials.

Adult↗

O6-methylguanine-DNA methyltransferase in pretreatment tumour biopsies as a predictor of response to temozolomide in melanoma.

Resistance of tumour cells to methylating and monochloroethylating agents in vitro and in vivo has been linked to levels of the DNA repair protein O6-methylguanine-DNA methyltransferase (MGMT). In a clinical trial of temozolomide in advanced malignant melanoma, the relationship between pretreatment MGMT levels in biopsies of cutaneous tumours and involved lymph nodes and clinical response to the drug has been studied. Among 50 evaluable patients, there were three complete responses (CR), four partial responses (PR), six with stable disease (SD) and 37 with progressive disease (PD), with an overall response rate of 14%. In 33 patients in whom MGMT level and clinical response could be evaluated, the tumour MGMT levels (fmol mg(-1) protein) were: CR, 158 +/- 119; PR, 607 +/- 481; NC, 171 +/- 101; PD, 185 +/- 42.3. Thus, measurements of pretreatment levels of MGMT in melanoma did not predict for response to temozolomide.

Adult↗

Enhancement by copper, zinc superoxide dismutase of DNA damage and mutagenicity with hydrogen peroxide.

Oxidative DNA damage caused by hydrogen peroxide was enhanced by copper, zinc superoxide dismutase (CuZnSOD) in a concentration-dependent manner, as reflected by the formation of 8-hydroxy-2'-deoxyguanosine (8-OH-dG) and strand breaks. Hydroxyl radical scavengers such as sodium azide, mannitol and 5,5-dimethyl-1-pyrroline N-oxide (DMPO), a metal chelator, diethylenetriamine-pentaacetic acid, and catalase decreased strand breaks and 8-OH-dG formation in DNA. The deoxyribose assay showed that hydroxyl free radicals were generated in the reaction of CuZnSOD with H2O2. CuZnSOD also caused enhancement of mutation in the pUC18 lacZ' gene in the presence of H2O2 when measured as a loss of alpha-complementation. Based on these results, we interpret the effects of CuZnSOD on hydrogen peroxide induced DNA damage and mutation as due to reactive oxygen species, probably hydroxyl free radicals, formed predominantly by the reaction of hydrogen peroxide and free Cu2+ released from oxidatively damaged CuZnSOD.

8-Hydroxy-2'-Deoxyguanosine↗

Possible target components for the inhibitory effect of N-ethylmaleimide on the activation of neutrophil NADPH oxidase.

Potential target components for the inhibitory effect of covalent sulfhydryl-modifying reagent N-ethylmaleimide (NEM) on the activation of NADPH oxidase in human neutrophils was studied in a cell-free system. The capacity of both cytosol and membrane fractions to induce the translocation of cytosolic components and O2-generation in the cell-free activation system was affected by NEM. The phosphorylation of p47phox, which mediates the translocation of cytosolic complex, by protein kinase C was not inhibited by NEM and NEM-treated p47phox was as effective as untreated p47phox both in the kinase-dependent and in the amphiphile-dependent cell-free activation systems. In addition, phosphatidic acid-dependent phosphorylation of cytosol including p47phox was not affected by NEM. The inhibition of cytosol's capacity to activate NADPH oxidase was partially reversed by an addition of the fraction containing G-protein rac. Taken together, the data suggest that membrane component cytochrome b558 and cytosolic component rac may be the potential targets for the NEM effect on the activation of NADPH oxidase.

Cell-Free System↗

Cloning and expression of human adenylate kinase 2 isozymes: differential expression of adenylate kinase 1 and 2 in human muscle tissues.

A cDNA clone coding for adenylate kinase 2B was isolated from fetal liver, and the expression of AK2 was investigated in human tissues. The ORF in the cDNA clone for human AK2B predicted a protein comprising 232 amino acids (25.6 kDa). The features of AK2A and AK2B sequences in human were the same as those in the bovine system. Each of the recombinant proteins, AK2A and AK2B, was expressed in Escherichia coli cells, and the purified recombinant proteins were enzymatically active. The distribution of AK2 transcripts in various human tissues was examined by Northern analysis. Unlike in the bovine system, it was found that the AK2A transcript was the major form of AK2 mRNA species in all human tissues. The transcripts of AK2 isozymes were relatively abundant in heart, liver, and also in skeletal muscle, where the expression level of AK2 was known to be low. Western blot analysis of AK isozymes in human heart and skeletal muscle revealed that AK2 protein was found only in heart, whereas AK1 was detected in both tissues. These tissue-specific expressions of the AK isozymes in human might suggest the presence of organ-specific regulation of the AK2 gene including a post-transcriptional control in skeletal muscle.

Adenylate Kinase↗

An active noise control algorithm for controlling multiple sinusoids.

The filtered-x LMS algorithm and its modified versions have been successfully applied in suppressing acoustic noise such as single and multiple tones and broadband random noise. This paper presents an adaptive algorithm based on the filtered-x LMS algorithm which may be applied in attenuating tonal acoustic noise. In the proposed method, the weights of the adaptive filter and estimation of the phase shift due to the acoustic path from a loudspeaker to a microphone are computed simultaneously for optimal control. The algorithm possesses advantages over other filtered-x LMS approaches in three aspects: (1) each frequency component is processed separately using an adaptive filter with two coefficients, (2) the convergence parameter for each sinusoid can be selected independently, and (3) the computational load can be reduced by eliminating the convolution process required to obtain the filtered reference signal. Simulation results for a single-input/single-output (SISO) environment demonstrate that the proposed method is robust to the changes of the acoustic path between the actuator and the microphone and outperforms the filtered-x LMS algorithm in simplicity and convergence speed.

Acoustics↗

Human syngamosis: the first case in Korea.

Parasites of the genus Mammomonogamus affect the respiratory tract of domestic mammals but have only rarely been reported in humans. In this case report the diagnosis of human syngamosis is described following bronchoscopic examination of a patient whose initial symptoms were simply of community acquired pneumonia. The patient had a persistent and productive cough with intermittent fever during 10 days of observation. After bronchoscopic extraction of the parasites and treatment with albendazole he recovered fully. This is one of the first recognised cases of human syngamosis in Korea.

Animals↗

Effect of melatonin on cadmium-induced hepatotoxicity in male Sprague-Dawley rats.

Effect of melatonin on toxicity of cadmium (Cd) was studied in male SD rats co-administered daily Cd (1 mg/kg b.w., s.c.) with melatonin (10 mg/kg b.w., i.p.) for 15 days. Cd alone injection decreased GSH concentrations in the liver and RBC by 35% and 43% compared with those in saline-treatment group, but not in the kidney and whole brain. The activity of GSSG-reductase was significantly decreased in the liver of Cd alone injected rats, while melatonin given in combination with Cd failed to prevent the Cd-induced decreased activity of hepatic GSSG-reductase. However, the hepatic GSH concentration decreased by Cd alone was restored by melatonin treatment, and the melatonin also ameliorated Cd-induced histopathological changes in the liver. Therefore, data indicate that melatonin restores the reduction of hepatic GSH level induced with Cd regardless of GSSG-reductase activity, and suggests that melatonin may ameliorate Cd-induced hepatotoxicity.

Animals↗

The regulation and biological activity of interleukin 12.

Interleukin 12 (IL-12) is a pleiotropic cytokine and mediates several biological activities on human T and natural killer (NK) cells, including induction of IFN-gamma production, enhancement of cell-mediated cytotoxicity and comitogenic effects on resting T-cells. The major cellular sources producing IL-12 are antigen-stimulated monocytes, macrophages, and B-cells isolated from peripheral blood mononuclear cells (PBMC). Our laboratory has investigated the regulation of IL-12 gene expression in both cord blood and adult PBMC, and the effects of IL-12 on induction of IFN-gamma production, NK, and lymphokine-activated killer (LAK) cytotoxicity. IL-12 mRNA expression and protein production in LPS-stimulated cord blood MNC were 3-4 fold decreased when compared with adult PBMC. There were no differences between cord blood and adult PBMC in both basal levels of transcription or the degree of transcriptional activation of the IL-12 gene. Additionally, the half-life of IL-12 p40 mRNA was 3-fold lower in activated cord blood compared to adult PBMC. Exogenous IL-12 induced a significant increase of IFN-gamma from both cord and adult PBMC. Cord MNC has significantly reduced levels of NK activity, and IL-12 significantly enhanced cord blood NK cytotoxicity up to similar levels in adult PBMC. IL-12 also significantly enhanced cord blood NK and LAK activities against a broad range of neuroblastoma, leukemia, and lymphoma cell lines. Lower doses of IL-12 and IL-15 concomitantly generated either synergistic or additive effects on cord blood NK and LAK cytotoxicities. In light of the important biological functions of IL-12, reduced expression and production of IL-12 from activated cord blood may contribute to the immaturity of cord blood cellular immunity and contribute, in part, to decreased severe graft vs. host disease following unrelated cord blood stem cell transplantation. IL-12 enhancement of IFN-gamma, NK, and LAK activity in activated cord blood MNC up to comparable levels in adult PBMC suggests that exogenous IL-12 stimulation can compensate for the immaturity in cord blood cellular immunity. These characteristics of IL-12 biological activity strongly suggest its potential usefulness in future cancer immunotherapy.

Adult↗

Giant-cell interstitial pneumonia in a gas station worker.

Giant-cell interstitial Pneumonia (GIP) is a very uncommon respiratory disease. The majority of cases of GIP are caused by exposure to cobalt, tungsten and other hard metals. In this report, we describe GIP in a patient who worked in gas station and dealt in propane gas vessels. He presented with clinical features of chronic interstitial lung disease and underwent an open lung biopsy that showed DIP-like reaction with large numbers of intra-alveolar macrophages and numerous large, multinucleated histiocytes which were admixed with the macrophages. Analysis of lung tissue for hard metals was done. Cobalt was the main component of detected hard metals. Corticosteroid therapy was started and he recovered fully.

Giant Cells↗

Immunodiagnosis of clonorchiasis using a recombinant antigen.

A cDNA expression library of Clonorchis sinensis adult worm was constructed, and screened out immunologically. One clone, pBCs31, was selected in view of its predominant reactivity with an experimentally infected rabbit serum. Recombinant C. sinensis antigen with 28 kDa as a beta-galactosidase fusion protein produced in Escherichia coli was identified by immunoblot analysis. The cloned gene was composed of 16 copies of a 30 base pair repeat and an additional 320 bases. The deduced amino acid sequence of the tandem repeat was AQPPKSGDGG. On RNA slot blot analysis. C. sinensis adult worm RNA showed a positive reaction with the cloned gene. Enzyme-linked immunosorbent assay using a purified recombinant antigen of pBCs31 showed high specificity for diagnosis of clonorchiasis.

Amino Acid Sequence↗

Trends in Asian American racial/ethnic intermarriage: a comparison of 1980 and 1990 census data.

"In this paper, we use data from the 1990 [U.S.] census to compare patterns of Asian American intermarriage with those reported by Lee and Yamanaka (1990).... Our main findings show that: (i) the overall outmarriage rate has declined; (ii) Asian American inter-ethnic marriages (that is, marriages between two Asian Americans of different Asian ethnicities) have increased; and (iii) social distance, measured by an Index of Intermarriage Distance, between Asian Americans and other racial and ethnic groups has widened. We conclude by discussing some implications of the findings for the role of racial and ethnic intermarriage as an indicator of intergroup relations."

Americas↗

Body temperature and thermoregulation during submaximal exercise after 115-day spaceflight.

BACKGROUND: Altered thermoregulation has been reported following spaceflight simulations (bed rest and water immersion) but has never been examined after actual spaceflight. HYPOTHESIS: We tested the null hypothesis that body temperatures and heat loss responses during exercise would be similar before and after spaceflight. METHODS: Two male crewmembers of the 115-d Mir 18 mission performed supine submaximal cycle exercise (20 min at 40% and 20 min at 65% of preflight VO2peak) once at 145-146 d preflight and once at 5 d postflight (R + 5). RESULTS: After flight neither crewmember could complete the exercise protocol, stopping after 28-29 min. The core temperature (Tin, ingestible telemetry pill) at test termination was similar (37.8 degrees C for both subjects) pre- and postflight despite shorter postflight test duration. The slopes of the skin blood flow (laser Doppler)/Tin relationship (subject 1: 396 vs. 214; subject 2: 704 vs. 143% change Perfusion Unit/degree C), and the sweating rate (dew point hygrometry)/Tin relationship (subject 1: 6.3 vs. 2.0; subject 2: 4.6 vs. 0.7 mg.min-1.cm-2.degree C-1), were both reduced postflight without appreciable change in the Tin thresholds for sweating or skin blood flow. CONCLUSION: In this preliminary report for two crewmembers, the sensitivity of the heat loss responses were reduced after long-duration spaceflight, resulting in a faster rate of rise in core temperature.

Adult↗

Glaucoma following congenital cataract surgery.

BACKGROUND: Glaucoma is a well known complication that arises after congenital cataract surgery. The purpose of this research was to study eyes that manifested glaucoma after congenital cataract surgery and to identify associated factors. METHODS: A retrospective review of patients who received cataract surgery before the age of five was conducted. The chi-squared test for association was used to evaluate risk factors. RESULTS: One hundred and forty eyes of 85 patients were studied. Nineteen eyes of 12 patients had glaucoma, among which 79% was open angle. Patients who underwent secondary membranectomy for visual axis occlusion had a higher risk of glaucoma, especially when secondary membranectomy was performed within one year of primary surgery. Of eight eyes with microcornea, none developed glaucoma after surgery. No significant difference in outcome was found among the surgical methods of cataract removal. CONCLUSIONS: Aggressive clearance of lens cortex during surgery is important. Secondary membranectomy for clearing the visual axis occlusion is associated with post operative glaucoma. Frequent and long-term patient follow-up is mandatory since glaucoma may manifest many years after congenital cataract surgery.

Cataract↗

Dose intensity in small cell lung cancer.

Evidence from preclinical models and from clinical trials describing the importance of dose intensity in securing a better treatment outcome is reviewed. Recent randomized trials have shown statistically significant survival benefits with higher-dose, accelerated chemotherapy regimens with and without granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor. The novel use of peripheral blood progenitor cells contained in whole blood autotransfusions, which allow a marked increase in dose intensity of an ifosfamide/carboplatin/etoposide regimen, could provide a much easier method of delivering dose-intensive chemotherapy than previously available.

Antineoplastic Combined Chemotherapy Protocols↗