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Biomedical subjects

H Kim

Publications and source records attributed to H Kim.

At least 703 records · Page 39Linked to original sources

Liquid chromatographic determination of ceftibuten, a new oral cephalosporin, in human plasma and urine.

Two liquid chromatographic methods with UV detection were developed for the determination of ceftibuten in human plasma and urine. Diluted plasma samples were directly injected onto a reversed-phase column without prior protein precipitation while diluted urine samples were processed through an automated on-line sample clean-up procedure using column-switching. Both methods were linear over clinically relevant concentration ranges in plasma (from 0.1 to 50 micrograms ml-1) and urine (from 0.5 to 60 micrograms ml-1). The methods showed acceptable precision (RSD < 20%) and accuracy (bias < 15%) at the limit of quantitation (LOQ) for ceftibuten in plasma and urine. These LOQs represented the lowest concentrations of ceftibuten in plasma (0.1 micrograms ml-1) and urine (0.5 micrograms ml-1) that could be measured with acceptable precision and accuracy. RSDs for both within-day and between-day analyses were < or = 12% for plasma and < 7% for urine. These methods have been used successfully for the analysis of ceftibuten in plasma and urine following single oral doses of 200, 400 and 800 mg in man.

Administration, Oral↗

Structures of wild-type and mutant signal sequences of Escherichia coli ribose binding protein.

The structure of a chemically synthesized 25-residue-long functional signal peptide of Escherichia coli ribose binding protein was compared with that of a nonfunctional mutant-signal peptide using circular dichroism and two-dimensional 1H NMR in solvents mimicking the amphiphilic environments. The functional peptide forms an 18-residue-long alpha-helix starting from the NH2-terminal region and reaching to the hydrophobic stretch in a solvent consisting of 10% dimethylsulfoxide, 40% water, and 50% trifluoroethanol (v/v). The nonfunctional mutant peptide, which contains a Pro at position 9 instead of a Leu in the wild-type peptide, does not have any secondary structure in that solvent but forms a 12-residue-long alpha-helix within the hydrophobic stretch in water/trifluoroethanol (50:50, v/v) solvent. It seems that the Pro-9 residue in the nonfunctional peptide disturbs the helix propagation from the hydrophobic stretch to the NH2-terminal region. Because both of these peptides have stable helices within the hydrophobic stretch, it may be concluded that the additional 2 turns of the alpha-helix in the NH2-terminal region of the wild-type signal peptide is important for its function.

Amino Acid Sequence↗

Regression of lateral asymmetry scores toward the mean.

On most, if not all, laterality tasks, some subjects initially display a left sensory field advantage and others a right sensory field advantage. During the course of testing, the mean asymmetry score of those subjects who start with a left sensory field advantage decreases, whereas the mean asymmetry score of those subjects who start with a right sensory field advantage increases (asymmetry scores computed as L-R). Some previous studies (e.g., Ross-Kossak and Turkewitz, 1986) have suggested that these differential, temporal shifts in sensory field advantage reflect systematic changes in subjects' sensory field advantage (and associated hemispheric advantage) during familiarization and individual differences in those changes. Alternatively, the differential, temporal shifts may reflect unsystematic sources of changes because they are not distinguishable from statistical regression toward the mean. Consistent with this hypothesis, "time-reversed control" analyses of laterality data show that the differential trends do not reflect a factor associated with the specific direction of time passage as would be predicted in the case of increasing stimulus familiarization. Regression of asymmetry scores toward the mean, or its equivalent, imperfect reliability of asymmetry scores, may be significantly attributable to short-term fluctuations in subjects' hemispheric arousal asymmetries.

Adult↗

Electroconvulsive shock reduces inositol 1,4,5-trisphosphate 3-kinase mRNA expression in rat dentate gyrus.

We investigated the expression of inositol 1,4,5-trisphosphate (InsP3) 3-kinase mRNA after a single electroconvulsive shock (ECS) with in situ hybridization histochemistry in rat brain. At 6 h after ECS, the expression was markedly decreased in the dentate gyrus, and the decrease was maintained until 9 h with a slight recovery. The InsP3 3-kinase mRNA content returned to basal levels after 12 h. We could not detect any apparent changes in the expression of InsP3 3-kinase mRNA in the CA1-CA3 areas of hippocampus, the striatum, and the cerebral cortex at any time point examined. In the temporal pattern, the reduction of the expression in the dentate gyrus was preceded by the induction of c-fos after ECS. These observations suggest that the InsP3 3-kinase might be one of the genes whose expression can be altered by ECS.

Animals↗

Spontaneous fragmentation of dimyristoylphosphatidylcholine vesicles into a discoidal form at low pH.

Upon prolonged incubation at low pH, the turbidity of a dimyristoylphosphatidylcholine (DMPC) small unilamellar vesicle (SUV) suspension underwent an initial increase followed by a decrease to below the starting value. Electron microscopic observation of the vesicle suspension, after the turbidity minimum was reached, revealed the formation of discoidal particles which were smaller than the original vesicles. NMR studies indicated that all the choline groups in the discoids are accessible to added chemical shift agent, corroborating the fragmentation of the vesicles. Formation of the discoids from DMPC multilamellar vesicle (MLV) was also observed but without going through the initial increase in turbidity. The DMPC was subsequently found to be hydrolyzed into lysophosphatidylcholine (lysoPC) and myristic acid under the same conditions that caused the fragmentation. That the discoidal fragment consisted of DMPC and its hydrolysis products, lysoPC and myristic acid, was verified by electron microscopic observation of discoids when these components were mixed at neutral pH. A 50% cholesterol content prevented the fragmentation of DMPC vesicles. A model for this discoidal complex, in which a patch of DMPC bilayer is surrounded at its periphery by lysoPC and myristic acid, is proposed.

Chromatography, Thin Layer↗

A randomized double-blinded comparison of the antiemetic efficacy of ondansetron and droperidol in patients receiving high-dose interleukin-2.

Emesis and nausea are common toxicities seen during high-dose interleukin-2 (IL-2) therapy (720,000 IU/kg i.v. every 8 h). A growing list of randomized studies have documented the efficacy of ondansetron, a potent antagonist of the 5-hydroxytryptamine3 receptor, in preventing acute chemotherapy-induced emesis and nausea. However, no study has evaluated the efficacy of ondansetron in preventing IL-2-induced emesis and nausea. This double-blinded, randomized trial was performed to compare the antiemetic and antinausea efficacy of ondansetron with that of droperidol, a butyrophenone, in patients receiving high-dose IL-2 on protocols at the National Cancer Institute. Ondansetron or droperidol was given intravenously, 30 min prior to the first dose of IL-2 and then every 8 h for the duration of IL-2 treatment. No significant differences were seen between the two agents in complete freedom from emesis (p2 = 0.51), level of nausea (p2 = 0.17), antiemetic treatment failure (p2 = 0.89), and time to first emetic episode (p2 = 0.44). Equivalent doses of IL-2 were administered on each arm of the study, with a similar incidence of liver dysfunction (p2 = 0.15) and diarrhea (p2 = 0.64). Finally, there was no significant difference in the response rates to metastatic disease in either arm of the antiemetic study (p2 = 0.67), and these response rates were similar to those in other patients treated under immunotherapy protocols in the Surgery Branch of the National Cancer Institute with high-dose IL-2. We conclude that droperidol is equally effective in preventing emesis and controlling nausea when compared with ondansetron for patients receiving high-dose IL-2.

Adult↗

Characterization of the major catalase from Streptomyces coelicolor ATCC 10147.

Streptomyces coelicolor ATCC 10147 produced catalases whose electrophoretic mobility varied depending on the growth phase in liquid culture. Polyacrylamide gel electrophoresis of cell extracts resulted in six catalase activity bands, which were designated Cat1 to Ca6. Of these, Cat4 appeared during all growth phases, whereas Cat1 appeared only during the stationary phase. Catalase-deficient mutants were screened by the H2O2 bubbling test following NTG mutagenesis. In all the non-bubbling mutants tested, the Cat4 activity band significantly decreased or disappeared, suggesting that Cat4 is the major catalase. Cat4 was purified to electrophoretic homogeneity and some of its properties analysed. The enzyme has a native molecular mass of 225 kDa, as determined by gel permeation column chromatography, and consists of four identical subunits of 57 kDa, as determined by SDS-PAGE. The enzyme contains 2.6 molecules of protohaem IX per tetramer, as indicated by the absorption spectrum. It was not reducible by sodium dithionite and exhibited no peroxidase activity with o-dianisidine as the substrate. All these characteristics, as well as inhibitor studies, indicate that the major vegetative catalase in S. coelicolor, unlike E. coli vegetative catalase, is a member of the typical monofunctional catalases found in eukaryotes and some bacteria.

Catalase↗

Reversible topology of a bifunctional transmembrane protein depends upon the charge balance around its transmembrane domain.

Hybrid genes were constructed to express bifunctional hybrid proteins in which staphyloccal nuclease A with or without an amino-terminal OmpA signal sequence was fused with TEM beta-lactamase (at the carboxyl terminal side) using the signal peptide of the major outer membrane lipoprotein of Escherichia coli as an internal linker. The hybrid proteins were found to be inserted in the membrane. Orientation of the hybrid protein with the OmpA signal peptide showed that the nuclease was translocated into the periplasm and the beta-lactamase remained in the cytoplasm. This indicates that the cleavable OmpA signal peptide served as a secretory signal for nuclease and the internal lipoprotein signal served as the transmembrane anchor. In the absence of the OmpA signal sequence the topology of the hybrid protein was reversed indicating that the internal lipoprotein signal peptide initially served as the signal peptide for the secretion of the carboxy terminal beta-lactamase domain across the membrane and subsequently as a membrane anchoring signal. The role of charged amino acids in the translocation and transmembrane orientation of membrane proteins was also analysed by introducing charged amino acids to either or both sides of the internal lipoprotein signal sequence in the bifunctional hybrid proteins in the absence of the amino-terminal signal sequence. Introduction of two lysine residues at the carboxy-terminal side of the internal signal sequence reversed the topology of the transmembrane protein by translocating the amino-terminal nuclease domain across the membrane, leaving the carboxyl terminal beta-lactamase domain in the cytoplasm. When three more lysine residues were added to the amino-terminal side of the internal signal sequence of the same construct the membrane topology flipped back to the original orientation. A similar reversion of the topology could be obtained by introducing negatively charged residues at the amino-terminal side of the internal signal sequence. Present results demonstrate for the first time that a bifunctional transmembrane protein can be engineered to assume either of the two opposite orientations and that charge balance around the transmembrane domain is a major factor in controlling the topology of a transmembrane protein.

Amino Acid Sequence↗

Antagonistic effects of antipamezole on medetomidine-midazolam induced sedation in dogs.

Antagonistic effect of atipamezole (80 micrograms/kg) on medetomidine (20 micrograms/kg)-midazolam (0.3 mg/kg) induced sedation was evaluated in dogs. Atipamezole effectively reversed sedation and significantly shortened arousal time and total recovery time without apparent side effects. Atipamezole also effectively reversed changes in heart rate, respiratory rate and body temperature produced by medetomidine-midazolam. The possible use of atipamezole as a reversal agent might enhance the value and availability of medetomidine-midazolam for a chemical restraint agent in dogs.

Adrenergic alpha-Agonists↗

Comparison of sedative effects induced by medetomidine, medetomidine-midazolam and medetomidine-butorphanol in dogs.

Sedative effects of combinations of medetomidine at 20 micrograms/kg--midazolam at 0.3 mg/kg (Me-Mi) and medetomidine at 20 micrograms/kg--butorphanol at 0.1 mg/kg (Me-B) were evaluated comparing with those of medetomidine alone (20, 40 and 80 mu/kg). All dogs given Me-Mi or Me-B were smoothly and rapidly induced to more profound and longer sedation than those by medetomidine alone. Especially, Me-Mi produced desirable sedation with moderate reflex depression, analgesia, excellent muscle relaxation and immobilization without further side effects. This potent effect of this combination seemed to be induced by a synergistic interaction between medetomidine and midazolam. This combination is available and valuable as a chemical restraint agent in dogs for various diagnostic or therapeutic procedures accompanied by light pain.

Animals↗

Estimation of the geometric means and the reference values of blood lead levels among Koreans.

Blood lead concentrations of Koreans who have not been exposed to lead occupationally, show a wide range of variation. Despite the fact that blood lead concentration reveals a long-normal distribution, geometric means and standard deviations have not been presented in almost all studies on blood lead levels in Koreans. A new meta-analytical method was applied to estimate the theoretical geometric means, the standard deviations of the logarithm, and the reference values of blood lead concentrations among Koreans based on arithmetic means and standard deviations reported, and to compare them to those of other countries. Estimated geometric means of Korean men, women, and men and women, were 18.03, 13.13, and 15.80 micrograms/dl, respectively. Values of 90, 95, and 99 percentile for Korean men were 31.81, 37.36, and 50.52 micrograms/dl, for women, 28.41, 35.34, and 53.24 micrograms/dl, and for men and women, 31.42 micrograms/dl, 38.17 micrograms/dl, and 54.95 micrograms/dl, respectively. These values are higher than those of neighboring countries, such as China and Japan.

Environmental Exposure↗

Incidence estimation of female breast cancer among Koreans.

The authors conducted a nationwide survey to estimate the incidence rates of female breast cancer among Korean women in 1990-1991. We identified potential breast cancer cases based on the claims sent by medical care institutions throughout Korea to the Korea Medical Insurance Corporation (KMIC) from January 1988 to December 1989, whose diagnoses in the claims included one of the following diagnostic codes; ICD-9 174-175 (malignant neoplasms of the breast), 217 (benign neoplasms of the breast), 610-611 (benign mammary dysplasia and other disorders of the breast), 233 (carcinoma in situ of the breast and genito-urinary system), or 195-199 (malignant neoplasms with uncoded sites). In order to collect the final diagnosis of the potential cases, abstracting medical records was performed through visiting or mailing an abstracting format to the corresponding medical institutions. Thereafter oncologists reviewed the abstracting formats and confirmed the incident cases of female breast cancer among the potential breast cancer cases. Using these data from the KMIC, the incidence patterns of female breast cancer among Korean women were estimated as of July 1, 1988 to June 30, 1989. The incidence rate of female breast cancer adjusted for the Korean population was estimated to be 9.9 (95% confidence interval: 9.5-10.4). The cumulative rates for the ages 0-64 and 0-74 were 0.85% and 1.0%, respectively. The standardized rate for the world population was 10.9, which was lower than those of any other Asian country including China and Japan in 1983-1987.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Hepatitis B virus carrier with low titer of antibody to hepatitis B core antigen.

Of 798 hepatitis B virus (HBV) carriers, 22 had low titers (lower than 80% inhibition in 200- or 400-fold diluted serum) of antibody to hepatitis B core antigen (anti-HBc). Among these 22 patients, there were 12 (1.50%) with viremia who were positive for hepatitis B e antigen and had a high titer of HBV-associated DNA polymerase activity. Among these 12 patients, four showed no significant change in the anti-HBc titer, while four others showed significant increases in the anti-HBc titer during the follow-up periods. The former all remained asymptomatic carriers (ASCs), while the latter all developed chronic hepatitis (CH). The liver histology of four patients (ASC: 2, CH: 2) showed mild inflammation, and the localization of hepatitis B core antigen (HBcAg) in the liver specimens showed a nuclear pattern in the two ASCs, but a nuclear plus cytoplasmic pattern in the two CH cases. In HBV carriers, the increase in anti-HBc titer seems to be closely correlated to the change in HBcAg localization from the nucleus to the cytoplasm in the liver. Therefore, rising titers of anti-HBc were assumed to be associated with increased expression of HBcAg on the hepatocyte, and hence increased immune-mediated hepatic damage and the onset of hepatitis in ASC with low titer of anti-HBc.

Adolescent↗

Clinical and pathological characteristics of sporadic colorectal carcinomas with DNA replication errors in microsatellite sequences.

DNA replication errors (RERs) in repeated nucleotide sequences due to defective mismatch repair genes have been reported in a subset of sporadic colorectal carcinomas and in the majority of tumors from patients with hereditary nonpolyposis colorectal cancer syndrome (HNPCC). We detected RER in 18 cases (13%) in a prospective series of 137 sporadic stage II and III (Dukes' B and C) colorectal carcinomas. The clinical and pathological features of the RER-positive cases differed from those without RER. The patients with RER-positive cancers tended to be somewhat younger (60 +/- 5 years, range 22-83, versus 66 +/- 1, range 27-90, P = 0.2 with unequal variances) and had a marked preponderance of tumors proximal to the splenic flexure (17/18, 94%, versus 41/119, 34%, P < 0.0001). Only two RER-positive patients (11%) had a family history of colorectal cancer. In comparison to the 41 RER-negative proximal colonic cancers, RER-positive cancers had more frequent exophytic growth (P = 0.04), large size (P = 0.03), poor differentiation (P = 0.0004), extracellular mucin production (P = 0.003) and Crohn's-like lymphoid reaction (P = 0.003), and a trend toward less frequent p53 gene product overexpression by immunohistochemistry (3/17, 18%, versus 18/41, 44%, P = 0.06). We conclude that a subset of sporadic colorectal carcinomas has unique biological features that may indicate inherited germline mutation, de novo germline mutation, or somatic mutations of the mismatch repair genes involved in HNPCC.

Adult↗

Semen preparation with the Sperm Select System versus a washing technique.

OBJECTIVE: To compare sperm migration through sodium hyaluronate with simple washing as methods for preparing sperm for IUI. DESIGN: Ten normal semen specimens were prospectively collected and samples were prepared by simple washing and by migration into sodium hyaluronate using the Sperm Select System (Select Medical Systems, Williston, VT). The semen and each treatment group were evaluated for sperm concentration, percent motile, viability, acrosomal status, longevity, and computer-aided semen analysis (CASA) parameters. SETTING: University reproductive endocrinology facility. RESULTS: The recovery of motile sperm was significantly higher for the washing method (mean +/- SEM 75% +/- 7%) than for the hyaluronate method (10% +/- 1%). The number of motile sperm recovered by migration into hyaluronate was independent of the percentage of motile sperm in the semen specimen and positively correlated with sperm concentration. The hyaluronate method produced greater percentages of motile, viable, and morphologically normal sperm, with lower proportions of premature acrosome reactions, higher sperm velocity, and greater linearity. CONCLUSIONS: The Sperm Select System method of sperm separation provides a highly uniform specimen with improved sperm quality. However, the recovery of motile sperm is considerably lower than for simple washing methods.

Adult↗

Alterations of the p53 tumor-suppressor gene in transformed mouse liver cells.

Mutational inactivation of p53, a potential tumor-suppressor gene, has been found in many tumors of humans as well as rodents. The p53 status in normal and transformed mouse liver cell lines has, however, not been investigated. We examined possible point mutations and compared mRNA and protein expression of the p53 gene in normal vs. transformed mouse liver cells. The transformed cells studied included lines spontaneously transformed by sub-culture, virally transformed by simian virus 40 (SV40), and chemically transformed by N-methyl-N-nitro-N-nitrosoguanidine (MNNG) or methylcholanthrene epoxide (MC). A heterozygous G-->A point mutation at codon 241, position 1, of p53 was detected in MNNG-transformed cells after screening of 5 evolutionarily conserved regions where mutation hot-spots are clustered. The mutation causes a gly-->arg substitution. No mutations were found in normal or other transformed cells. The steady-state levels of p53 mRNA were decreased in chemically transformed (both MNNG- and MC-transformed) cells. Elevated levels of p53 protein were found in spontaneously transformed and SV40-transformed cells, an observation that may reflect a longer half-life of the protein, as has been shown in other transformed lines. The low level of the p53 protein in MC-transformed cells may result from transcriptional depression of the p53 gene. We conclude from these data that abnormal p53 status, such as point mutation or altered expression, may play a role during the malignant transformation of mouse liver cells.

Animals↗