Search PubMed⌕ Search

Biomedical subjects

E S Kim

Publications and source records attributed to E S Kim.

At least 19 recordsLinked to original sources

Cloning and expression of thermophilic catechol 1,2-dioxygenase gene (catA) from Streptomyces setonii.

Streptomyces setonii (ATCC 39116) degrades various single aromatic compounds such as phenol or benzoate via an ortho-cleavage pathway using catechol 1,2-dioxygenase (C12O). A PCR using degenerate primers based on the conserved regions of known C12O-encoding genes amplified a 0.45-kbp DNA fragment from S. setonii total DNA. A Southern hybridization analysis and size-selected DNA library screening using the 0.45-kbp PCR product as a probe led to the isolation of a 6.4-kbp S. setonii DNA fragment, from which the C12O-encoding genetic locus was found to be located within a 1.4-kbp DNA fragment. A complete nucleotide sequencing analysis of the 1.4-kbp DNA fragment revealed a 0.84-kbp open reading frame, which showed a strong overall amino acid similarity to the known high-G+C Gram-positive (but significantly less to the Gram-negative) bacterial mesophilic C12Os. The heterologous expression of the cloned 1.4-kbp DNA fragment in Escherichia coli demonstrated that this C12O possessed a thermophilic activity within a broad temperature range (up to 65 degrees C) and showed a higher activity against 3-methylcatechol than catechol or 4-methylcatechol, but no activity against protocatechuate.

Amino Acid Sequence↗

Immunohistochemical expression of Smads 1-6 in the 15-day gestation mouse embryo: signaling by BMPs and TGF-betas.

The eight mammalian Smad proteins mediate cellular signaling from members of the transforming growth factor-beta (TGF-beta), bone morphogenetic protein (BMP), and activin families. Smads 1, 5, and 8 transmit signals from BMPs, while Smads 2 and 3 transmit signals from TGF-betas and activin. Smad 4 is a common mediator of both pathways, while Smads 6 and 7 inhibit signaling. Signal transduction involves translocation of Smad complexes to the nucleus and subsequent gene activation. Little is known about the expression of endogenous Smad proteins during development. We identified commercially available Smad antibodies that specifically recognize a unique Smad protein and are suitable for immunohistochemistry. Here we compare the localization of Smads 1, 2, 3, 4, 5, and 6 in tissues of the 15-day gestation mouse embryo. Immunoreactive Smad proteins are seen in many tissues with differences in the localization being dependent upon the cell type. All tissues express Smad 4 and at least one each of the BMP-specific and TGF-beta-specific Smads, while expression of Smad 6 is more restricted. Differences are observed in the nuclear versus cytoplasmic localization among the Smads in different cell types or tissues, suggesting selective activation of Smads during this stage of development.

Animals↗

Epidural naloxone reduces intestinal hypomotility but not analgesia of epidural morphine.

PURPOSE: Epidural morphine is associated with decreased bowel motility and increased transit time. Low doses of intravenous naloxone reduce morphine-induced pruritus without reversing analgesia, but the effect of epidural naloxone on bowel motility has not been studied. Therefore we evaluated bowel motility and analgesia when naloxone was co-administered with morphine into the epidural space. METHODS: Forty-three patients having combined thoracic epidural and general anesthesia for subtotal gastrectomy were randomly assigned to one of two study groups. All received a bolus dose of 3 mg epidural morphine at the beginning of surgery, followed by a continuous epidural infusion containing 3 mg morphine in 100 ml bupivacaine 0.125% with either no naloxone (control group, n = 18) or a calculated dose of 0.208 microg x kg(-1) x hr(-1) of naloxone (experimental group, n = 25) for 48 hr. We measured the time to the first postoperative passage of flatus and feces to evaluate the restoration of bowel function, and visual analog scales (VAS) for pain during rest and movement. Scores were assessed at 2, 4, 8, 16, 24, 36 and 48 hr postoperatively. RESULTS: The experimental group had a shorter time to the first postoperative passage of flatus (5 1.9 +/- 1 6.6 hr vs 87.0 +/- 19.5 hr, P < 0.001 ) and feces (95.3 +/- 25.0 hr vs 132.9 +/- 29.4 hr, P < 0.001). No differences were found in either resting or active VAS between the two groups. CONCLUSION: Epidural naloxone reduces epidural morphine-induced intestinal hypomotility without reversing its analgesic effects.

Analgesia, Epidural↗

Purification and characterization of a cationic isoperoxidase from scented-geranium.

A strongly cationic isoperoxidase named PC3 was purified to homogeneity from scented-geranium (Pelargonium graveolens) callus by using DEAE-Sephacel chromatography, CM-cellulose chromatography and Sephacryl S-200 gel filtration, respectively. The enzyme was a glycoprotein with M(r) of ca. 58 kDa estimated by SDS-PAGE and Sephadex G-150 gel filtration. The pI value of the enzyme was 9.1. Kinetic studies revealed that PC3 had a very low K(m) value for scopoletin of 0.01 mM and could use ascorbate as a substrate. Interestingly, PC3 could not oxidize ferulic acid as a substrate. Chemical modification of the enzyme showed that PC3 was rapidly inactivated by His, Cys, Trp and Lys-specific reagents. The second order rate constants and reaction orders with respect to these inactivations were determined. Notably, ca. 4-7-fold activity boosting of PC3 occurred by adenine and imidazole when anilino substrates, such as o-dianisidine and o-phenylenediamine were oxidized, whereas this activity boosting did not occur when several phenolic substrates were used.

Chromatography, Gel↗

A phase II study of STEALTH cisplatin (SPI-77) in patients with advanced non-small cell lung cancer.

Cisplatin-based chemotherapy improves survival in appropriately selected patients with stage IV non-small cell lung cancer (NSCLC). However, cisplatin-based regimens have well-known dose-related toxicities, particularly renal insufficiency and neurotoxicity. On the basis of prior preclinical and phase I studies, we initiated a phase II study of SPI-77 (STEALTH) Liposomal Cisplatin) in patients with stage IIIB and IV NSCLC who failed previous treatment with platinum. Disease in all subjects had progressed during therapy, failed to respond, or progressed within 3 months after discontinuing the platinum-based chemotherapy. Between January and June 1999, 13 patients were enrolled at our institution. Patient characteristics included: seven women, six men; median age, 61 years; median Karnofsky performance status, 80%; median number of prior chemotherapy regimens, two (range, 1-3). All patients had adequate hepatic and renal function. SPI-77 was administered at a dose of 260 mg/m(2) IV every 3 weeks. A median of two cycles (range 1-6) were given; the total number of cycles was 35. Among the 12 patients evaluable for response, two had (17%) stable disease and ten (83%) had progressive disease. The median survival was 24.3 weeks, and the median follow-up was 43.9 weeks. Toxicity could be evaluated in all subjects. Moderate anemia (46% of cycles, or=grade 3) with minimal granulocytopenia and thrombocytopenia (26% of cycles grade 1; 0% of cycles, >or=grade 2) were the most notable manifestations of myelosuppression. Grade 3 nonhematological toxicities included dyspnea (8%), fatigue (8%), and pain (8%). There were no grade 4 toxicities. These data suggest that this liposomal cisplatin formulation does not have appreciable activity in this population of patients with NSCLC who had received prior platinum-based chemotherapy. The lack of encouraging results from SPI-77 use in other phase I and II studies resulted in early closure of this trial by the manufacturer.

Carcinoma, Non-Small-Cell Lung↗

Congenital abdominal aortic aneurysm causing renovascular hypertension, cardiomyopathy, and death in a 19-day-old neonate.

A full-term baby girl who was sent home day of life 2 was admitted to the hospital on day of life 7 for respiratory distress and poor feeding. The child was found to be hypertensive and in heart failure. Further workup led to the diagnosis of a suprarenal abdominal aortic aneurysm, but the infant had deteriorated clinically with heart failure, modest renal failure, renovascular hypertension, and no operative cure. The child died on day of life 20. Early diagnosis and prompt surgical resection are essential to managing this rare and lethal condition.

Aortic Aneurysm, Abdominal↗

Maternal and neonatal outcomes after uterine rupture in labor.

OBJECTIVE: There is significant controversy about the risks related to attempted vaginal birth after cesarean and the implications for informed consent of the patient. Recent data suggest that women who deliver in hospitals with high attempted vaginal birth after cesarean rates are more likely to experience successful vaginal birth after cesarean, as well as uterine ruptures. We conducted a study to evaluate maternal and neonatal morbidity and mortality after uterine rupture at a tertiary care center. STUDY DESIGN: We performed a retrospective chart review of cases of uterine rupture from 1976 to 1998. All women who had a history of uterine rupture were identified with International Classification of Diseases, Ninth Revision, identifiers with hospital discharge data cross-referenced with a separate obstetric database. We abstracted demographic information, fetal heart rate patterns, maternal pain and bleeding patterns, umbilical cord gas values, and Apgar scores from the medical record. Outcome variables were uterine rupture events and major and minor maternal and neonatal complications. RESULTS: During the study period there were 38,027 deliveries. The attempted vaginal birth after cesarean rate was 61.3%, of which 65.3% were successful. We identified 21 cases of uterine rupture or scar dehiscence. Seventeen women had prior cesarean deliveries (10 with primary low transverse cesarean delivery, 3 with unknown scars, 1 with classic cesarean delivery, 2 with two prior cesarean deliveries, and 1 with four prior cesarean deliveries). Of the 4 women who had no history of previous uterine surgery, one had a bicornuate uterus whereas the others had no factors increasing the risk for uterine rupture. We confirmed uterine rupture and scar dehiscence in 19 women. Specific details were not available for 2 patients. Uterine rupture or scar dehiscence was clinically suspected in 16 women with 3 cases identified at delivery or after delivery. Sixteen women had symptoms of increased abdominal pain, vaginal bleeding, or altered hemodynamic status. There were 2 patients who required hysterectomies and 3 women who received blood transfusions; there were no maternal deaths related to uterine rupture. The fetal heart rate pattern in 13 cases showed bradycardia and repetitive variable or late decelerations. Thirteen neonates had umbilical artery pH >7.0. Two cases of fetal or neonatal death occurred, one in a 23-week-old fetus whose mother had presented to an outlying hospital and the second in a 25-week-old fetus with Potter's syndrome. All live-born infants were without evidence of neurologic abnormalities at the time of discharge. CONCLUSION: Our data confirm the relatively small risk of uterine rupture during vaginal birth after cesarean that has been demonstrated in previous studies. In an institution that has in-house obstetric, anesthesia, and surgical staff in which close monitoring of fetal and maternal well-being is available, uterine rupture does not result in major maternal morbidity and mortality or in neonatal mortality.

Adult↗

Platelet concentration and its effect on bone formation in calvarial defects: an experimental study in rabbits.

STATEMENT OF PROBLEM: The use of the platelet concentration technique is widespread in dental implant surgery. However, its effect or mechanism is not clearly understood. PURPOSE: This study introduced an animal model for the platelet concentration technique and evaluated its effect on bone formation with natural cancellous bovine bone mineral. MATERIAL AND METHODS: Adult New Zealand white rabbits were used as the animal model. A density gradient medium was used to obtain a constant platelet count for the preparation of platelet concentrates. In the experimental group, natural cancellous bovine bone mineral with added platelet concentrates was grafted onto critically sized bony defects of the rabbit calvarium. Bone formation in the tissue sections was evaluated with soft x-ray imaging and computer tomography. RESULTS: The average platelet count of the rabbit platelet concentrates was 1487 x 10(3)/microL (287% concentrated). In all the tested parameters, greater bone densities were obtained in grafts that were combined with platelet concentrates. CONCLUSION: This study showed that the rabbit is a useful animal model for studying the platelet concentration technique. When combined with grafts of natural cancellous bovine bone mineral, the technique increased bone formation.

Anatomy, Cross-Sectional↗

Epidermal growth factor receptor biology (IMC-C225).

Treatment of solid tumors despite improved techniques in detection, surgery, radiation therapy, and chemotherapy remains difficult. Therefore, strategies to improve efficacy in accord with safety are needed. Many epithelial cancers have been found to overexpress the receptor to epidermal growth factor (EGFR), including head and neck, breast, colon, lung, prostate, kidney, ovary, brain, pancreas, and bladder. Because overexpression of EGFR has been associated with an overall poor prognosis in patients with cancer, a number of strategies to block or downregulate EGFR have been developed to inhibit tumor proliferation and improve overall clinical outcome. These include monoclonal antibodies to the EGFR, tyrosine kinase inhibitors, ligand-linked toxins, and antisense approaches. Antibodies such as IMC-C225 specifically target EGF receptors, whereas tyrosine kinase inhibition by many small molecules is less specific. Ultimately, IMC-C225 may prove to become a valuable contributor in the treatment of cancer. This report will focus on IMC-C225, a novel monoclonal antibody that targets the EGFR.

Antibodies, Monoclonal↗

Pseudonocardia kongjuensis sp. nov., isolated from a gold mine cave.

The taxonomic position of an isolate that was recovered from a gold mine cave near Kongju, Republic of Korea, was determined by 16S rDNA sequence studies and chemotaxonomic characterization. Comparative studies of 16S rDNA sequences indicated that this organism was phylogenetically related to members of the genus Pseudonocardia, branching outside a cluster encompassing Pseudonocardia autotrophica and Pseudonocardia compacta. The affiliation to the genus was also supported by the cell chemistry, which was represented by a type IV cell wall, MK-8(H4) as the major menaquinone, a phospholipid type PIII pattern (phosphatidylcholine as a diagnostic phospholipid) and a DNA G+C content of 71 mol%. The fatty acid profile contained saturated, unsaturated and 10-methyl branched fatty acids, but tuberculostearic acid and hydroxy fatty acids were not present. The isolate differed from its phylogenetic neighbours in the presence of phosphatidylethanolamine, dodecanoate, 16-methylheptadecenoate and 16-methylheptadecanoate and the absence of phosphatidylinositol mannoside and phosphatidylmethylethanolamine. The unique combination of physiological properties, the cellular fatty acid profile and DNA-DNA hybridization data indicates that this organism is readily differentiated from the type strains of all of the validly published species of the genus Pseudonocardia. The name Pseudonocardia kongjuensis sp. nov. is proposed for the type strain, LM 157T (= IMSNU 50583T = KCTC 9990T = DSM 44525T).

Actinomycetales↗

Modulation of actinorhodin biosynthesis in Streptomyces lividans by glucose repression of afsR2 gene transcription.

While the biosynthetic gene cluster encoding the pigmented antibiotic actinorhodin (ACT) is present in the two closely related bacterial species, Streptomyces lividans and Streptomyces coelicolor, it normally is expressed only in S. coelicolor-generating the deep-blue colonies responsible for the S. coelicolor name. However, multiple copies of the two regulatory genes, afsR and afsR2, activate ACT production in S. lividans, indicating that this streptomycete encodes a functional ACT biosynthetic pathway. Here we report that the occurrence of ACT biosynthesis in S. lividans is determined conditionally by the carbon source used for culture. We found that the growth of S. lividans on solid media containing glucose prevents ACT production in this species by repressing the synthesis of afsR2 mRNA; a shift to glycerol as the sole carbon source dramatically relieved this repression, leading to extensive ACT synthesis and obliterating this phenotypic distinction between S. lividans and S. coelicolor. Transcription from the afsR2 promoter during growth in glycerol was dependent on afsR gene function and was developmentally regulated, occurring specifically at the time of aerial mycelium formation and coinciding temporally with the onset of ACT production. In liquid media, where morphological differentiation does not occur, ACT production in the absence of glucose increased as S. lividans cells entered stationary phase, but unlike ACT biosynthesis on solid media, occurred by a mechanism that did not require either afsR or afsR2. Our results identify parallel medium-dependent pathways that regulate ACT biosynthesis in S. lividans and further demonstrate that the production of this antibiotic in S. lividans grown on agar can be modulated by carbon source through the regulation of afsR2 mRNA synthesis.

Anthraquinones↗

Aortic dissection: percutaneous management with a separating stent-graft--preliminary results.

The authors used a separating stent-graft to treat Stanford type B aortic dissection. The separating stent-graft consists of two stents: a stent-graft and an inner bare stent. The separating stent-graft has three parts: a proximal stent, a graft made of synthetic polyester textile fiber, and a distal stent. A 12-F introducing sheath was used. After the separating stent-graft was placed, false-lumen thrombosis was evident in all six patients during a follow-up period of 206 days. The major advantages of this technique are that a cutdown and blood pressure control are not required.

Adult↗

IMC-C225, an anti-epidermal growth factor receptor monoclonal antibody, for treatment of head and neck cancer.

Squamous cell carcinoma (SCC) of the head and neck (H&N) remains a clinical challenge due to its high rate of locoregional disease recurrence. The importance of the epidermal growth factor receptor (EGFR) in the development and progression of many solid tumours (including SCC of the H&N) is well understood; increased expression is associated with enhanced tumour invasion, resistance to chemotherapy and decreased patient survival. Several approaches have been developed to achieve EGFR blockade as an anticancer treatment strategy, including an anti-EGFR monoclonal antibody (mAb), IMC-C225, which competitively binds to the extracellular receptor site to prevent binding by natural EGFR ligands (EGF and TGF-alpha). Preclinical studies evaluating this chimeric mAb in human cancer cell lines in vitro and human tumour xenografts in vivo have demonstrated its potent antitumour activity. The clinical efficacy of IMC-C225 appears to involve multiple anticancer mechanisms, including inhibition of cell cycle progression, induction of apoptosis, anti-angiogenesis, inhibition of metastasis and its ability to enhance the response to chemotherapy and radiation therapy. Phase I studies of IMC-C225 combined with chemotherapy or radiation for SCC of the H&N demonstrate excellent response rates in patients with recurrent or refractory disease. Phase II and III trials examining the efficacy and safety of these combinations are currently underway. To date, IMC-C225 has been well-tolerated, with skin rashes and allergic reactions being the most clinically important adverse events reported. IMC-C225 displays dose-dependent elimination characteristics and a half-life of approximately 7 days. Current recommendations for dosing include a 400 mg/m2 loading dose, followed by weekly infusions of 250 mg/m2.

Animals↗

Potential role of caspase-3 and -9 in arsenic trioxide-mediated apoptosis in PCI-1 head and neck cancer cells.

Arsenic trioxide (As2O3) has been shown to inhibit the proliferation of hematologic malignant cells. Previously, we reported that As2O3 had an antitumoral effect in head and neck cancer. Here, we investigated the induction of apoptosis and its mechanism in PCI-1 head and neck squamous carcinoma cells, after treatment with As2O3. Treatment with 2 microM of As2O3 caused apoptosis in PCI-1 cells following 3 days of exposure, which was detected by the annexin V-PI and DAPI staining methods. The cell death population was markedly increased, being 88% larger than the As2O3-untreated control cells. To address the mechanism of apoptosis, a Western blot assay was performed, showing that Bax was up-regulated without a change in Bcl-2. Activation of caspase-9 during As2O3-induced apoptosis was substantiated by monitoring the proteolysis of the caspase-9, which was associated with an increase of Apaf-1 and cytochrome c protein. PCI-1 cells rapidly changed the mitochondria membrane potential (DeltaPsim) after addition of As2O3. Furthermore, activation of caspase-3 was demonstrated by monitoring the proteolysis of the caspase-3 and by measuring caspase-3 activity with a fluorogenic substrate, which was associated with the cleavage of poly(ADP-ribose) polymerase. To examine the in vivo effect of As2O3, C3H mouse inoculated with syngenic SCC7 cells was treated by intratumoral injection of As2O3 (300 microg) every day, demonstrating that tumor mass was dramatically reduced on day 4, and revealed induction of apoptosis by TUNEL assay. These results suggest that apoptosis of PCI-1 cells by As2O3 is induced by activation of caspase-3 via cytochrome c, caspase-9 and Apaf-1 complex.

Animals↗

The impact of smoking status, disease stage, and index tumor site on second primary tumor incidence and tumor recurrence in the head and neck retinoid chemoprevention trial.

Second primary tumors (SPTs) develop at an annual rate of 3-7% in patients with head and neck squamous cell cancer (HNSCC). In a previous Phase III study, we observed that high doses of 13-cis-retinoic acid reduced the SPT rate in this disease. In 1991, we launched an intergroup, placebo-controlled, double-blind study to evaluate the efficacy of low-dose 13-cis-retinoic acid in the prevention of SPTs in patients with stage I or II squamous cell carcinoma of the larynx, oral cavity, or pharynx who had been previously successfully treated with surgery, radiotherapy, or both, and whose diagnoses had been established within 36 months of study entry. As of September 16, 1999, the Retinoid Head and Neck Second Primary (HNSP) Trial had completed accrual with 1384 registered patients and 1191 patients randomized and eligible. All of the patients were followed for survival, SPT development, and index cancer recurrence. Smoking status was assessed at study entry and during study. Smoking cessation was confirmed biochemically by measurement of serum cotinine levels. The annual rate of SPT development was analyzed in terms of smoking status and tumor stage. As of May 1, 2000, SPTs have developed in 172 patients. Of these, 121 (70.3%) were tobacco-related SPTs, including 113 in the aerodigestive tract (57 lung SPTs, 50 HNSCC SPTs, and 6 esophageal SPTs) and 8 bladder SPTs. The remaining 51 cases included 23 prostate adenocarcinomas, 8 gastrointestinal malignancies, 6 breast cancers, 3 melanomas, and 11 other cancers. The annual rate of SPT development observed in our study has been 5.1%. SPT development related to smoking status was marginally significant (active versus never, 5.7% versus 3.5%; P = 0.053). Significantly different smoking-related SPT development rates were observed in current, former, and never smokers (annual rate = 4.2%, 3.2%, and 1.9%, respectively, overall P = 0.034; current versus never smokers, P = 0.018). Stage II HNSCC had a higher overall annual rate of SPT development (6.4%) than did stage I disease (4.3%; P = 0.004). When evaluating the development of smoking-related SPTs, stage was also highly significant (4.8% for stage II versus 2.7% for stage I; P = 0.001). Smoking-related SPT incidence was significant for site as well (larynx versus oral cavity, P = 0.015; larynx versus pharynx, P = 0.011). Primary tumors recurred at an annual rate of 2.8% in a total of 97 patients. The rate of recurrence was higher in patients with stage II disease (4.1% versus 2.2%, P = 0.004) as well as oral cavity site when compared with larynx (P = 0.002). This is the first large-scale prospective chemoprevention study evaluating smoking status and its impact on SPT development and recurrence rate in HNSCC. The results indicate significantly higher SPT rates in active smokers versus never smokers and significantly higher smoking-related SPT rates in active smokers versus never smokers, with intermediate rates for former smokers.

Adult↗

Prevalence of hepatitis B and C virus infection among women in Jeju Island, Republic of Korea.

Hepatitis B and C virus infection prevalence was investigated in the Island of Jeju (formerly Cheju), the Republic of Korea, by means of a small-scale sero-epidemiological survey in 2000. Adult women in the city of Jeju (the provincial capital) and two fishing-farming villages A and B were invited to offer venous blood samples for immunological examination for infection markers of two virus and serum biochemistry for liver function. In practice, 66 married women (33, 16 and 17 women from the city, Village A and Village B, respectively) volunteered. Sera were separated on site and were assayed for HBsAg, anti-HBs, anti-HBc, and anti-HCV positivities and liver function markers including AST, ALT and gamma-GTP. The serum assay showed that the prevalence of HbsAg+ or anti-HCV+ cases was low (5 and 2%, respectively), whereas that of anti-HBs+ and anti-HBc+ cases were high (71 and 62%) so that the over-all HBV positivity was 82%. There were essentially no urban-rural difference or age-dependent changes in the positivity. Comparison with the prevalence reported in literature shows that prevalence of HBsAg+ and anti-HCV+ is in general agreement with the values reported for the populations in general, but HBV+ prevalence might be somewhat higher than the levels reported for the general populations.

Adult↗

Early development of the secretory cavity of peltate glands in Humulus lupulus L. (Cannabaceae).

Early development of the secretory cavity of chemically fixed peltate glands in Humulus lupulus L. showed secretions with different densities, light, gray and dark, in the cytoplasm of disc cells and in the periplasmic space adjacent to the developing secretory cavity. Secretions were detected in the disc cell wall and subsequently in the developing secretory cavity under the subcuticular wall of the sheath. Light and gray secretions in the cavity possessed a membrane-like surface feature. Secretions were in contact with the irregular inner surface of the cuticle. Secretions contributed to the thickening of the cuticle, whereas the membrane-like surface feature contributed to a network of Cannabis striae distributed throughout the cuticle. This study supports an early development and organization of the secretory cavity in H. lupulus, parallel to those in Cannabis, and may represent common features for lipophilic glands in angiosperms.

Cannabis↗