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Biomedical subjects

H J Lee

Publications and source records attributed to H J Lee.

At least 19 recordsLinked to original sources

Long-term urinary toxicity after 3-dimensional conformal radiotherapy for prostate cancer in patients with prior history of transurethral resection.

PURPOSE: To report on the long-term urinary morbidity among prostate cancer patients with a prior history of a transurethral resection of the prostate (TURP) treated with high-dose 3-dimensional conformal radiotherapy (3D-CRT). METHODS AND MATERIALS: Between 1988 and 1997, 1100 patients with clinically localized prostate cancer were treated with 3D-CRT. Of these, 120 patients (8%) were identified as having had a prior TURP and are the subjects of this analysis. The median age was 71 years (range: 49-83 years). The clinical stages of the patients were T1c: 33 (28%); T2a: 38 (32%); T2b: 15 (13%); and T3: 34 (27%). Neoadjuvant androgen ablation therapy was given to 39 (33%). The median radiation dose prescribed to the planning target volume was 75.6 Gy (range: 64.8-81 Gy). The median elapsed time from TURP to initiation of 3D-CRT was 69 months (range: 4-360 months). The median follow-up time was 51 months (range: 18-109 months). RESULTS: Five patients of the 120 with a prior history of TURP (4%) developed a urethral stricture after 3D-CRT which was corrected with dilatation. The 5-year actuarial likelihood of >/= Grade 2 late urinary toxicities was 9%. No Grade 4 urinary toxicities were observed in this group of patients. Among 110 patients who were completely continent of urine prior to 3D-CRT, 10 (9%) developed stress incontinence requiring 1 pad daily for protection or experienced occasional leakage (not requiring pad protection). The 5-year incidence of >/= Grade 1 stress incontinence was 18% in patients who developed acute >/= Grade 2 GU symptoms during the course of 3D-CRT compared to 7% for patients who experienced Grade 1 or no acute urinary symptoms (p = 0.05). The radiation dose (>/=75.6 Gy vs. <75.6 Gy), the number of prior TURP procedures, or the volume of resected tissue at the time of TURP had no significant impact on the long-term urinary morbidity outcome. A multivariate analysis demonstrated that the presence of Grade 2 acute urinary symptoms was the only predictor of >/= Grade 1 stress incontinence after 3D-CRT in this group of patients. CONCLUSIONS: Despite prior TURP, the incidence of >/= Grade 3 urinary toxicities is low. Nevertheless, especially among patients with a prior history of TURP who experience Grade 2 acute urinary symptoms during radiation treatment, a higher risk of stress incontinence is observed.

Aged↗

p53 gene mutations in Bowen's disease in Koreans: clustering in exon 5 and multiple mutations.

We analyzed the p53 protein expression and gene mutations to evaluate the role of ultraviolet radiation or other carcinogens, and possible racial differences in 17 samples from 12 Korean patients with Bowen's disease. A simple microdissection technique was used to collect the tumor cells selectively. p53 protein expression was found in eight of 17 (47%) samples. Abnormalities in polymerase chain reaction (PCR)-single-strand conformation polymorphism (SSCP) analysis were observed in 16 (94%) samples. A total of 14 missense mutations were detected in eight (47%) samples; 11 were clustered in exon 5 and the remaining three were located in exon 8. UV-like mutations were seen in five of 14 (36%) mutations, but no CC to TT transitions, UV-fingerprint mutations were observed. Multiple mutations were present in two cases and double mutation in a single case. Each lesion in multiple Bowen's disease showed different mutations and was suggested to be of different clonal origins. TP53-loss of heterozygosity (LOH) was detected in four out of 15 (27%) informative samples. Clustering of mutations in exon 5 suggests the role of another carcinogen in Koreans or Asians other than the UVR. Microdissection would increase the detection rate of the p53 gene mutations and LOH not only in skin cancer but also in precancerous lesions.

Adult↗

Differential expression of nicotinamide adenine dinucleotide phosphate-diaphorase in hypothalamic areas of obese Zucker rats.

Several studies have suggested that the activity of nitric oxide synthase (NOS) may be involved in the regulation of food intake in the genetically obese Zucker rats. In the present study, we investigated the expression of NOS in various hypothalamic regions of obese and lean Zucker rats using nicotinamide adenine dinucleotide phosphate (NADPH)-diaphorase histochemistry. Obese Zucker rats showed significantly lower staining intensities of NADPH-diaphorase-positive neurons in the paraventricular nucleus (PVN), lateral hypothalamic area (LHA) and ventromedial hypothalamic nucleus (VMH) than lean Zucker rats did. The differences in staining intensities between obese and lean Zucker rats were large in both the PVN and LHA, but such differences were relatively small in the VMH.

Animals↗

Molecular cloning and expression of aminopeptidase A isoforms from rat hippocampus.

The full-length cDNA encoding aminopeptidase A (APAL) was cloned from a rat hippocampus cDNA library. A short variant aminopeptidase A (APAS), produced by deletion, was also cloned. In the case of APAL, the longest open reading frame encodes 945 amino acid residues with a calculated molecular mass of 108 kDa, and the deduced amino acid sequence shows 76, 86 and 78% identity with its human, murine and porcine counterparts, respectively. Rat aminopeptidase A mRNAs were detected in the kidney, liver, heart and brain by Northern blot analysis. When overexpressed in COS-1 cells, APAL shows apparent aminopeptidase A activity, whereas APAS does not.

Amino Acid Sequence↗

Evidence for basolateral but not apical membrane localization of outwardly rectifying depolarization-induced Cl(-) channel in airway epithelia.

The rat primary cultured-airway monolayer had been an excellent model for deciphering the ion channel after nystatin permeabilization of its basolateral or apical membrane (Hwang et al., 1996). After apical membrane permeabilization of rat primary cultured-airway monolayer, 4,4'-diisothiocyanatostilbene-2, 2'-disulfonic acid (DIDS)-sensitive outwardly rectifying depolarization-induced Cl(-) (BORDIC) currents were observed across the basolateral membrane in symmetrical NMG-Cl solution in this study. No significant Cl(-) current induced by the application of voltage clamping was observed across the apical membrane in symmetrical NMG-Cl solution after basolateral membrane permeabilization. The halide permeability sequence for BORDIC current was Br(-) = I(-) > Cl(-). BORDIC current was not affected by basolaterally applied bumetanide (0.5 mm). Basolateral DIDS (0.2 mm) but not apical DIDS inhibited CFTR mediated short-circuit current (I(sc)) in an intact monolayer of rat airway epithelia, a T84 human colonal epithelial cell line, and a Calu-3 human airway epithelial cell line. This is the first report showing that depolarization induced Cl(-) current is present on the basolateral membrane of airway epithelia.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗

GATA-3 induces T helper cell type 2 (Th2) cytokine expression and chromatin remodeling in committed Th1 cells.

Committed T helper type 1 (Th1) and Th2 effector cells, resulting from chronic antigenic stimulation in interleukin (IL)-12 and IL-4, are implicated in the pathology of autoimmune and allergic diseases. Committed Th1 cells cannot be induced to change their cytokine profiles in response to antigenic stimulation and Th2 cytokine-inducing conditions. Here, we report that ectopic expression of GATA-3 induced Th2-specific cytokine expression not only in developing Th1 cells but also in otherwise irreversibly committed Th1 cells and a Th1 clone, HDK1. Moreover, cAMP, an inhibitor of cytokine production by Th1 cells, markedly augmented Th2 cytokine production in GATA-3-expressing Th1 cells. Ectopic expression of GATA-3 in developing Th1 cells, but not in Th1 clone HDK1, induced endogenous GATA-3, suggesting an autoregulatory mechanism for maintenance of GATA-3 expression in Th2 cells. Structure-function analyses of GATA-3 revealed that the NH(2)-terminal transactivation domain and the COOH-terminal zinc finger domain of GATA-3 were critical, whereas the NH(2)-terminal zinc finger domain was dispensable for the induction of IL-4. Both zinc fingers, however, were required for IL-5 induction. A Th2-specific DNaseI-hypersensitive site of the IL-4 locus was detected in GATA-3-expressing Th1 cells. Thus, GATA-3 can change the phenotype of committed Th1 cells, previously considered to be irreversible.

Animals↗

First success of catalytic epoxidation of olefins by an electron-rich iron(III) porphyrin complex and H2O2: imidazole effect on the activation of H2O2 by iron porphyrin complexes in aprotic solvent.

An electron-rich iron(III) porphyrin complex (meso-tetramesitylporphinato)iron(III) chloride [Fe(TMP)Cl], was found to catalyze the epoxidation of olefins by aqueous 30% H2O2 when the reaction was carried out in the presence of 5-chloro-1-methylimidazole (5-Cl-1-Melm) in aprotic solvent. Epoxides were the predominant products with trace amounts of allylic oxidation products, indicating that Fenton-type oxidation reactions were not involved in the olefin epoxidation reactions. cis-Stilbene was stereospecifically oxidized to cis-stilbene oxide without giving isomerized trans-stilbene oxide product, demonstrating that neither hydroperoxy radical (HOO*) nor oxoiron(IV) porphyrin [(TMP)FeIV=O] was responsible for the olefin epoxidations. We also found that the reactivities of other iron(III) porphyrin complexes such as (meso-tetrakis(2,6-dichlorophenyl)porphinato)iron(III) chloride [Fe(TDCPP)Cl], (meso-tetrakis(2,6-difluorophenyl)porphinato)iron(III) chloride [Fe(TDFPP)Cl], and (meso-tetrakis(pentafluorophenyl)porphinato)iron(III) chloride [Fe(TPFPP)CI] were significantly affected by the presence of the imidazole in the epoxidation of olefins by H2O2. These iron porphyrin complexes did not yield cyclohexene oxide in the epoxidation of cyclohexene by H2O2 in the absence of 5-Cl-1-MeIm in aprotic solvent; however, addition of 5-Cl-1-MeIm to the reaction solutions gave high yields of cyclohexene oxide with the formation of trace amounts of allylic oxidation products. We proposed, on the basis of the results of mechanistic studies, that the role of the imidazole is to decelerate the O-O bond cleavage of an iron(III) hydroperoxide porphyrin (or H2O2-iron(II) porphyrin adduct) and that the intermediate transfers its oxygen to olefins prior to the O-O bond cleavage.

Alkenes↗

Genetic diversity and molecular epidemiology of the G protein of subgroups A and B of respiratory syncytial viruses isolated over 9 consecutive epidemics in Korea.

To study genetic variation and molecular epidemiology of the G protein of respiratory syncytial virus (RSV), 253 strains from a children's hospital in Korea over 9 consecutive epidemics were analyzed. Restriction analysis of the entire G protein gene demonstrated 24 genotypes among 188 subgroup A and 6 among 65 subgroup B isolates. Two to 4 dominant genotypes of subgroup A cocirculated, and different genotypes predominated in each epidemic. Predominant genotypes were replaced with new genotypes during consecutive epidemics. One of 2 dominant genotypes among subgroup B predominated alternately or concurrently. Phylogenetic analysis revealed that there were multiple lineages, with clustering related to their location and time of isolation among strains from Korea and worldwide. Geographic and temporal distinction have been shown more clearly for subgroup B than subgroup A. These results suggest that the G protein of RSV is continuously evolving, with a distinct pattern presumably due to immune selection in a localized region over time.

Amino Acid Sequence↗

Downregulation of JNK/SAPK activity is associated with the cross-resistance to P-glycoprotein-unrelated drugs in multidrug-resistant FM3A/M cells overexpressing P-glycoprotein.

In the present study, cross-drug resistance in multidrug-resistant (MDR) cells, which overexpress P-glycoprotein (Pgp), a mdr1 gene product, against Pgp-unrelated drugs, and its relevance to c-Jun N-terminal kinase (JNK)/stress-activated protein kinase (SAPK) activity were examined. The multidrug-resistant FM3A/M cells overexpressing Pgp were resistant to apoptotic cell death induced either by Pgp-related drugs including vincristine and vinblastine, which are pumped out by Pgp, or by the Pgp-unrelated drugs including 5'-fluorouracil (5-FU) and bleomycin, which are not targets for Pgp, compared with the parental FM3A cells. Verapamil reversed the resistance of FM3A/M cells to apoptosis induced by the Pgp-related drugs but not that induced by the Pgp-unrelated drugs. Interestingly, FM3A/M cells have shown significantly lower basal and drug-stimulated JNK/SAPK activities than FM3A cells. After transfection with pEBG-SEK or pEBG-SAPK constructs, FM3A/M cells recovered the basal and Pgp-unrelated drug-stimulated activities of JNK/SAPK and the susceptibility to Pgp-unrelated drug-induced apoptotic cell death comparable to those of FM3A cells. Furthermore, FM3A cells became resistant to apoptotic cell death induced by vincristine and 5-FU after transfection with pEBG-SEK(K --> R), a dominant negative inhibitory mutant of SEK. These results suggest that downregulation of JNK/SAPK activity appears to confer on Pgp-associated FM3A/M cells a cross-resistance to Pgp-unrelated drugs.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Pressure-derived fractional collateral blood flow: a primary determinant of left ventricular recovery after reperfused acute myocardial infarction.

OBJECTIVES: We evaluated the relation between pressure-derived fractional collateral flow (PDCF) and left ventricular (LV) recovery after reperfused acute myocardial infarction (AMI). BACKGROUND: The functional significance of collateral flow remains uncertain in AMI. METHODS: The PDCF was measured in 70 patients with first AMI (pain onset <12 h) treated with primary angioplasty (PA), being determined by simultaneous measurement of mean aorta pressure (Pa), distal coronary pressure during the balloon occlusion (Poc), and central venous pressure (CVP): (Poc - CVP)/(Pa - CVP)*100. Sufficient collateral (group I) was defined as PDCF index >24% and insufficient collateral (group II) as PDCF index <24%. Echocardiography was performed before, and on day 3, day 7, and day 30 after PA. Wall-motion recovery index (RI) was obtained by dividing the number of improved wall-motion segments (>grade 1) at follow-up by the number of abnormal wall-motion segments within the infarct zone at baseline. RESULTS: Baseline characteristics were similar between both groups. Peak levels of creatine kinase were lower in group I than in group II (2,600+/-1,900 U/liter vs. 4,100+/-3,000, p < 0.05). At one month, infarct zone wall-motion score index (1.65+/-0.54 vs. 2.31+/-0.46, p < 0.01) and LV volume indexes were smaller in group I than in group II, whereas, LV ejection fraction was higher in group I than in group II (52.8+/-8.3 vs. 45.9+/-9.0, p < 0.01). The PDCF index was the strongest predictor of RI at one month (r = 0.61, p < 0.01). Time to reperfusion was not related to RI at one month. However, it was significantly related to RI in group II (r = -0.34, p < 0.05). CONCLUSIONS: The LV recovery after reperfused AMI is primarily determined by PDCF and is less dependent on time to reperfusion in patients with sufficient collaterals.

Adult↗

The difference between electroacupuncture only and electroacupuncture with manipulation on analgesia in rats.

Plain acupuncture uses manipulation (rotation or varying the depth of insertion of the needle) to increase its effect. However, in commonly used electroacupunture (EA), variable manipulations have not been used. This study was performed to investigate the possibility of an increase in analgesic effect by adding manipulation to EA. The pain index used was the Tail-Flick latency (TFL) of the rat, which was lightly anesthetized with thiopental sodium (intraperitoneally). Four types of manipulation were used. Rotation and varying the depth of the needle (RN and VN) was employed using two different types of manipulation during each 20 min stimulation of EA. Each manipulation persisted for 1 min out of every 5 min (long - duration and long - interval: LDLI) or 12 s every 1 min (short - duration and short interval: SDSI). EA produced an increase in TFL; peak value was 49.7+/-12.2% of the pre - EA and occurred immediately after cessation of 20 min of EA stimulation. Performing RN or VN combined with EA also increased TFL more than just EA and a greater peak increase in TFL was observed with a SDSI - RN and SDSI - VN as compared to a LDLI - RN and LDLI - VN (77.5+/-13.8, 79.2+/-19.8 and 67.3+/-14.0%, 65.6+/-23.7% of the pre - EA, respectively). These results indicate that manipulation combined with EA produces a more potent antinociception than when only EA is applied.

Acupuncture Analgesia↗

Inhibition of LPS-induced NO production and NF-kappaB activation by a sesquiterpene from Saussurea lappa.

To elucidate the molecular mechanisms for the suppression of LPS-induced nitric oxide (NO) production by a dehydrocostus lactone (DL) from Saussurea lappa, we examined the preventive effect of this compound on NF-kappaB activation in LPS-treated RAW 264.7 macrophages and U937 human monocytic cells. The results suggest that the suppression of NO production is mediated by the inhibitory action on the i-NOS gene expression through the inactivation of NF-kappaB and this sesquiterpene lactone can act as a pharmacological inhibitor of the NF-kappaB activation.

Animals↗

Expression pattern of germ cell-specific genes in the testis of patients with nonobstructive azoospermia: usefulness as a molecular marker to predict the presence of testicular sperm.

OBJECTIVE: To analyze the expression pattern of testis-specific genes of patients with various spermatogenic defects and their usefulness as a molecular marker to predict the presence of testicular spermatozoa in patients with nonobstructive azoospermia undergoing IVF. DESIGN: Prospective, controlled study. SETTING: Hospital-based infertility research laboratory. PATIENT(S): Fifty-eight men with azoospermia or severe oligozoospermia. INTERVENTION(S): Testicular biopsy was done in the patients with obstructive or nonobstructive azoospermia, including Sertoli cell-only syndrome, maturation arrest, severe hypospermatogenesis, and normal spermatogenesis. MAIN OUTCOME MEASURE(S): Reverse transcriptase polymerase chain reaction was performed using 1 microgram of total RNA extracted from testicular tissues. Three pairs of primers were used for amplification of male germ cell-specific genes (DAZ, transcribed in male germ cells; PGK2, in late spermatocytes and spermatids; protamine-2, in spermatids) as molecular markers. Testicular sperm was obtained by multiple testicular sperm extraction. RESULT(S): The DAZ, PGK2, and protamine-2 genes were expressed in 38, 30, and 21 of the 43 patients with nonobstructive azoospermia, respectively. Testicular spermatozoa were successfully extracted in 4 of 43 patients with nonobstructive azoospermia with the use of multiple testicular sperm extraction. Detection of protamine-2 transcripts predicted the presence or absence of spermatozoa in the testicular tissue in 39 of 43 patients (91%). CONCLUSION(S): Expression of the protamine-2 gene may be a useful molecular marker to predict the presence of testicular sperm in patients with nonobstructive azoospermia.

Adult↗

Novel steroid spiro enones: condensation of prednisolone derivatives with diethyl oxalate.

In a continuing effort to discover potent anti-inflammatory steroids without systemic side effects, diethyl oxalate was condensed with the 17beta-ketol side chain of prednisolone derivatives. Prednisolone gave the most interesting result in forming a novel spiro enone with alpha-hydroxy and beta-carboxylic ester substitutions, and a facile one-pot procedure has been established for the synthesis of this highly functionalized spiro enone structure. The spiro products were tested for their binding potency to the RAW 264.7 macrophage glucocorticoid receptor, for their effect on LPS-induced nitric oxide generation in RAW 264.7 cells, and for their inhibition of rats ear edema induced by croton oil. The new compounds showed weak activities in all of the bioassays. Because the corresponding acid metabolites of two representative spiro enone esters gave no activity in either the binding assay or the nitric oxide generation test, the novel steroids are probably antedrugs. The reduced potency as compared to their parent compounds suggests that the rigid spiro structure is unfavorable to anti-inflammatory activities. Molecular modeling studies confirm that the spiro enones adopt a rigid planar geometry with the ester group in the plane.

Animals↗

New steroidal anti-inflammatory antedrugs: methyl 21-desoxy-21-chloro-11beta,17alpha-dihydroxy-3,20-dioxo-1, 4-pregnadiene-16alpha-carboxylate, methyl 21-desoxy-21-chloro-11beta-hydroxy-3,20-dioxo-1, 4-pregnadiene-16alpha-carboxylate, and their 9alpha-fluoro derivatives*.

To a series of 21-desoxy-21-chloro-corticosteroids, a metabolically labile methoxycarbonyl group at C-16 has been incorporated. The approach is to synthesize locally active compounds that are hydrolyzed to inactive and readily excretable acid metabolites upon entry into the systemic circulation. Novel antedrugs were evaluated for anti-inflammatory activity and their adverse effects in an acute and semichronic croton oil-induced ear edema bioassay. Binding affinity to glucocorticoid receptors and induction of L-tyrosine-2-oxoglutarate aminotransferase were studied in hepatoma tissue culture cells. After a single topical application in the croton oil-induced ear edema bioassay, treatment with all the compounds resulted in dose-dependent inhibition of edema. From these dose-response profiles, the following ID(50) values (nmol/ear resulting in a 50% reduction of edema) were calculated: 540, 618, 454, and 346 nmol for prednisolone (P), methyl 21-desoxy-21-chloro-11beta,17alpha-dihydroxy-3,20-dioxo-1, 4-pregnadien-16alpha-carboxylate (PClCM), methyl 21-desoxy-21-chloro-11beta,17alpha-dihydroxy-9alpha-fl uoro-3, 20-dioxo-1,4-pregnadien-16alpha-carboxylate (FPClCM), and methyl 21-desoxy-21-chloro-9alpha-fluoro-11beta-hydroxy-3,20-dioxo- 1, 4-pregnadien-16alpha-carboxylate (FDPClCM), respectively. Results of the 5-day rat croton oil ear edema bioassay indicated that, in contrast with the parent compound P, the novel steroidal antedrugs did not significantly alter body weight gain, thymus weights, or plasma corticosterone levels. The binding affinities for cytosolic hepatoma tissue culture glucocorticoid receptors were 33, 201, 471, 5304, and 3765 nM for P, PClCM, FPClCM, methyl 21-desoxy-21-chloro-11beta-hydroxy-3,20-dioxo-1, 4-pregnadien-16alpha-carboxylate (DPClCM), and FDPClCM, respectively. Collectively, results of these investigations suggest that modifications of P, which included replacement of 21-hydroxyl group with chlorine and addition of 16-methoxycarbonyl group with or without 17-hydroxyl moiety, retained the topical anti-inflammatory activity of the parent compound P without significant adverse systemic effects.

Animals↗

Clinical experience with intensity modulated radiation therapy (IMRT) in prostate cancer.

PURPOSE: To compare acute and late toxicities of high-dose radiation for prostate cancer delivered by either conventional three-dimensional conformal radiation therapy (3D-CRT) or intensity modulated radiation therapy (IMRT). MATERIALS AND METHODS: Between September 1992 and February 1998, 61 patients with clinical stage T1c- T3 prostate cancer were treated with 3D-CRT and 171 with IMRT to a prescribed dose of 81 Gy. To quantitatively evaluate the differences between conventional 3D-CRT and IMRT, 20 randomly selected patients were planned concomitantly by both techniques and the resulting treatment plans were compared. Acute and late radiation-induced morbidity was evaluated in all patients and graded according to the Radiation Therapy Oncology Group toxicity scale. RESULTS: Compared with conventional 3D-CRT, IMRT improved the coverage of the clinical target volume (CTV) by the prescription dose and reduced the volumes of the rectal and bladder walls carried to high dose levels (P<0.01), indicating improved conformality with IMRT. Acute and late urinary toxicities were not significantly different for the two methods. However, the combined rates of acute grade 1 and 2 rectal toxicities and the risk of late grade 2 rectal bleeding were significantly lower in the IMRT patients. The 2-year actuarial risk of grade 2 bleeding was 2% for IMRT and 10% for conventional 3D-CRT (P<0.001). CONCLUSIONS: The data demonstrate the feasibility and safety of high-dose IMRT for patients with localized prostate cancer and provide a proof-of-principle that this method improves dose conformality relative to tumor coverage and exposure to normal tissues.

Aged↗