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Biomedical subjects

R Kim

Publications and source records attributed to R Kim.

At least 145 records · Page 8Linked to original sources

Quantifying the extent of osteonecrosis of the femoral head. A new method using MRI.

In a randomised trial comparing core decompression with conservative treatment we tested the hypothesis that the extent of necrosis at the initial MRI predicts the subsequent risk of collapse of the femoral head. After the initial clinical evaluation, including plain radiography and MRI, 37 hips with early-stage osteonecrosis (ON) in 33 patients were randomly assigned to a core-decompression group or a conservatively-treated group. All were followed regularly by clinical evaluation, plain radiography and MRI at intervals of three months. The extent of ON was estimated on the basis of abnormal signal intensity in the weight-bearing portion of the femoral head as determined from a combination of coronal and sagittal MRIs. The arc of the necrotic portion in the mid-coronal image (A) and that in the mid-sagittal image (B) were used to quantify the extent of necrosis by the formula: (A/180) x (B/180) x 100. There was a strong correlation between this index and the risk of collapse before and after adjustment for age, gender, stage and treatment group. We conclude that the extent of the necrotic portion ascertain by this method is a major predictor of future collapse. We propose a systematic method of determining the index of the necrotic portion which may be clinically useful in the management of early-stage ON of the femoral head.

Femur Head↗

Automated reconstruction of endoscopic images of the esophagus.

Endoscopic devices distort the image of a region under examination. Previous work has shown that there are computational methods which can precisely reconstruct planar structures in a model of the esophagus and that reconstruction in human subjects is operator independent. The purpose of this report is to show that much of the process can be automated and to provide additional evidence that the reconstruction is both accurate and reproducible.

Esophagoscopy↗

Differences between drug-sensitive and -resistant human leukemic CEM cells in c-jun expression, AP-1 DNA-binding activity, and formation of Jun/Fos family dimers, and their association with internucleosomal DNA ladders after treatment with VM-26.

Although the DNA topoisomerases are critical intracellular targets of a number of clinically important anticancer drugs, the mechanism(s) by which inhibition of these enzymes causes cell death are poorly understood. We found that treatment of human leukemic lymphoblasts (CCRF-CEM) with teniposide (VM-26), under conditions that stabilize DNA-topoisomerase II complexes, caused the formation of internucleosomal DNA ladders. However, it appeared unlikely that the VM-26-stabilized DNA-topoisomerase II-cleavable complexes directly produce these internucleosomal DNA ladders, since similar nucleosomal DNA ladders were observed following either continuous or a short (1 h) exposure of cells to VM-26. Under continuous exposure to VM-26, the internucleosomal DNA ladders were associated with the transient induction of c-jun mRNA in a dose-dependent fashion, reaching maximum expression at 6 h after treatment with VM-26 and being down-regulated to basal levels by 12 h. The induction of c-jun mRNA by VM-26 apparently preceded DNA ladder formation. However, in CEM sublines selected for resistance to VM-26 (CEM/VM-1 and CEM/VM-1-5; approximately 50- and 140-fold resistant, respectively) and which display the phenotype of multidrug resistance associated with altered DNA topoisomerase II (at-MDR), we found that the induction of c-jun mRNA by VM-26 and subsequent DNA ladder formation were progressively attenuated in proportion to the resistance of the cells, apparently due in part to decreased stabilization of DNA-topoisomerase II-cleavable complexes. Further, the attenuated induction of c-jun in the at-MDR cells was found to be associated with a decreased rate of c-jun transcription and an increase in the instability of its mRNA following VM-26 treatment. The attenuation of c-jun mRNA induction was also reflected in decreased production of c-Jun protein in the at-MDR cells. Of interest was the fact that no significant induction of c-fos mRNA by VM-26 was observed in either CEM or at-MDR cells. Furthermore, the induction of c-jun was related to the activation of AP-1 DNA-binding activity in a time- and dose-dependent manner in CEM cells, whereas the activation of AP-1 binding was attenuated in at-MDR cells in proportion to their resistance to VM-26. Using Jun and Fos family member antibody inhibition experiments in gel-mobility shift assays, we found that AP-1-binding activity appeared to be preferentially mediated by c-Jun/Fra-1 heterodimers in both CEM and at-MDR cells.(ABSTRACT TRUNCATED AT 400 WORDS)

Base Sequence↗

High-resolution crystals and preliminary X-ray diffraction studies of a catalytic RNA.

High-resolution single crystals of a catalytic RNA molecule derived from the sequence of the satellite RNA of tobacco ringspot virus have been obtained. The unit-cell volumes of the RNA crystals vary depending on the crystallization conditions and temperature. The best crystal form, when flash frozen, has space group P1 with unit-cell dimensions a = 53.08, b = 71.81, c = 28.03 A, alpha = 98.43, beta = 104.32 and gamma = 74.54 degrees. This form diffracts to a resolution of 2.4 A. A heavy-atom derivative search is in progress.

Journal Article↗

Novel actions of inhibitors of DNA topoisomerase II in drug-resistant tumor cells.

We review herein current work on the cytotoxic and cellular actions of two classes of inhibitors of DNA topoisomerase II: one represented by etoposide and teniposide, which stabilize DNA-protein complexes, and another represented by merbarone and aclarubicin, which do not stabilize such complexes. We discuss current concepts of protooncogene activation and cell cycle perturbations by some of these inhibitors and summarize recent findings of novel actions of the latter compounds in tumor cells that express a mutant topoisomerase II.

Animals↗

Asbestos hazard evaluation in South Korean textile production.

The manufacture and use of asbestos-containing products has become the object of restrictive environmental and occupational health regulation in the United States and many European countries. World production, however, has not declined, but rather shifted to developing countries. Our knowledge of the working conditions in these countries is limited. This article describes an investigation conducted in 1991 into the conditions and work practices in asbestos textile manufacturing in South Korea. The findings are based on site visits to several asbestos textile manufacturing facilities, meetings with industrial safety experts, and labor and industry representatives. The authors describe the current status of exposure control technology and industrial hygiene practices, and the results of personal asbestos dust monitoring at five representative textile production workstations. In general, manufacturers and regulatory agencies have not taken the precautions necessary to adequately protect employee health and meet international standards. Worker exposure to asbestos dust well above U.S. and German standards is commonplace in South Korea. International cooperation of health and safety experts with experience in asbestos-related problems should be promoted to improve the level of industrial safety in developing countries.

Air Pollutants, Occupational↗

Angiography, scintigraphy, intraosseous pressure, and histologic findings in high-risk osteonecrotic femoral heads with negative magnetic resonance images.

One hundred twenty-six hips of 68 patients who were suspected of having osteonecrosis or being at risk for osteonecrosis were studied with magnetic resonance (MR) imaging. Abnormal patterns on MR imaging characteristic of osteonecrosis were observed in 98 hips. The remaining 28 hips (22 patients) with negative MR images underwent superselective angiography of the medial femoral circumflex artery. Angiography showed interruption of the superior retinacular arteries in 13 hips (12 patients), including 6 of 7 symptomatic hips. Bone scans were performed on 8 of 13 hips angiographically positive for osteonecrosis. Decrease of radionuclide uptake (cold lesions) was observed in all 8 of these femoral heads. Thirteen femoral heads with interruption of superior retinacular arteries underwent intraosseous pressure measurement and core biopsy. Intraosseous pressure was elevated in 11 hips. The results of histologic study showed evidence of early necrosis in 10 femoral heads. This study indicates that there are a considerable number of femoral heads at high risk, even when they have negative MR images. They do, however, show positive findings on angiography, scintigraphy (cold lesions), intraosseous pressure measurement, and histologic study.

Adolescent↗

Anaphylaxis to protamine masquerading as an insulin allergy.

This is the case of a 62-year-old man referred for the evaluation of insulin allergy. This patient had reacted to the subcutaneous injection of Novolin 70/30 (Squibb, Princeton, N.J.) and Humulin NPH (Eli Lilly, Indianapolis, Ind.). These reactions were characterized by the immediate onset of diffuse pruritic urticaria and angioedema with progression to hypotension as well as a local reaction. Past history also included anaphylactic shock after intravenous administration of protamine sulfate used for heparin reversal during arterial bypass surgery. Immediate hypersensitivty skin testing to protamine containing (NPH) insulin and protamine sulfate USP were strongly positive, while Lente insulin (Eli Lilly, Indianapolis, Ind.) and controls were negative. RAST tests revealed the titers > 24 ng/ml of protamine specific IgE with 98 percent inhibition and 1163 ng/ml of protamine specific IgG with 29 percent inhibition, while levels of insulin specific antibodies were negligible. Subsequently, the patient was treated with non-protamine containing insulin preparation, Lente insulin, without further incident. This study confirms the diagnosis of Type I hypersensitivity to protamine sulfate masquerading as insulin allergy.

Anaphylaxis↗

Experimental studies on biochemical modulation targeting topoisomerase I and II in human tumor xenografts in nude mice.

Topoisomerase (topo) I and II are nuclear enzymes which are novel targets of cancer chemotherapy. A new camptothecin (CPT) analog, 7-ethyl-10-[4-(1-piperidino)-1-piperidino]carbonyl-oxy-CPT (CPT-11), is a topo-I inhibitor with a higher activity and less toxicity than CPT. To investigate topo-I and -II-targeting chemotherapy in an in vivo model, we studied the effect of sequential or co-treatment using CPT-11 and adriamycin (ADR) a topo-II inhibitor, in 6 human tumor xenografts (2 esophageal, 2 gastric and 2 colon tumor lines). In sequential treatment, adriamycin was administered i.v. 24 hr after CPT-11 treatment, and no antagonistic effect of this treatment schedule was observed. ADR cytotoxicity was potentiated significantly by CPT-11 pretreatment in the case of 2 esophageal and 2 gastric tumor lines and 1 colon tumor line. On the other hand, co-treatment abolished the sensitivity to CPT-11 and ADR in all 6 tumor lines. Moreover, CPT-11 did not significantly enhance the cytotoxicity of other agents tested, including mitomycin C (MMC) and cisplatin (CDDP). Flow cytometry and dot-blot analyses showed that CPT-11 pretreatment induced an increase in the S-phase cell population with an increase of topo-II mRNA expression after 24 and 48 hr, respectively, in the esophageal and colon tumor lines. These results suggest that CPT-11 can modulate topo-11 levels to enhance the effect of topo-II inhibitors in some human tumors, and this suggests a new clinical method of topo-I and -II targeting chemotherapy for human solid tumors.

Animals↗

Biochemical and biological activity of phosphorylated and non-phosphorylated ras p21 mutants.

In contrast to all cellular ras oncogenes which carry a single activating mutation at codon 12, 13 or 61, all known retroviral ras oncogenes have two mutations at codons 12 and 59. To understand the role of the mutation at codon 59, we have constructed plasmids containing genes for Harvey ras: p21(Gly-12,Thr-59) and p21(Val-12,Thr-59). Escherichia coli expressed proteins and their respective phosphorylated (Pi) and non-phosphorylated (non-Pi) proteins were purified to 95% homogeneity by ion-exchange chromatography and gel filtration. GTPase, autophosphorylation and nucleotide exchange activities of the mutants were studied. When the mutants were microinjected into Xenopus oocytes, the non-phosphorylated forms of p21(Gly-12,Thr-59) and p21(Val-12,Thr-59) showed high activity. Surprisingly, their phosphorylated forms were inactive. These results suggest that threonine at position 59 endows the protein with transforming activity but that phosphorylation of the residue inhibits biological activity. A structural interpretation of the observation is presented.

Animals↗

Local and systemic influenza haemagglutinin-specific antibody responses following aerosol and subcutaneous administration of inactivated split influenza vaccine.

An easily administered and safe vaccine is required to produce the herd immunity necessary to control influenza epidemics worldwide. A commercial quadrivalent inactivated split influenza vaccine was administered intranasally in aerosol form to a group of 46 volunteers; other groups were given the same vaccine subcutaneously and saline intranasally. The results show that mucosal stimulation via intranasal vaccination resulted in a marked increase in local HA-specific IgA antibodies, and that this stimulation was necessary for serum HA-specific IgA responses. Serum HA-specific IgA antibody levels can be used as indicators of local antigenic stimulation, providing a method for evaluating potency and antigenicity in humans of intranasal influenza vaccine. This vaccination route shows much promise for the future.

Adult↗

A simple and sensitive ELISA of antibodies to pertussis antigens.

A precise method for quantifying serum antibody levels to antigens of Bordetella pertussis is required to evaluate pertussis vaccines, to diagnose pertussis infections, and to detect transplacentally transmitted maternal antibodies. The purpose of this paper is to report a rapid, sensitive, easy and standardized ELISA method using polystyrene balls for the assay of serum antibodies against pertussis toxin (PT) and filamentous haemagglutinin (FHA), which are protective antigens of B. pertussis. By the polystyrene ball method, a clear-cut difference was observed between values of pre- and postvaccination serum samples while by the conventional plate method those values overlapped. It was concluded that the PS ball method is one of the most sensitive and simple methods for detecting antibodies against PT and FHA.

Adhesins, Bacterial↗

Fatal cerebral hemorrhage due to autonomic dysreflexia in a tetraplegic patient: case report and review.

Autonomic dysreflexia is the most important specific complication of high level spinal cord injury both in tetraplegic and in paraplegic patients above the midthoracic neural segment. It is a life threatening emergency that may lead to apoplexy. We present a case of fatal cerebral hemorrhage due to autonomic dysreflexia in order to demonstrate the gravity of this particular syndrome.

Adult↗

Risk of human immunodeficiency virus in surgeons, anesthesiologists, and medical students.

We postulated that three factors determined the occupational risk of infection from the human immunodeficiency virus (HIV) for surgeons, anesthesiologists, and medical students: first, the risk of needlestick exposure per year (range for surgeons 3.8-6.2, weighted average 4.2; range for anesthesiologists 0.86-2.5, weighted average 1.3; range for third-year medical students 0-5, best estimate 5); second, the risk of seroconversion from a needlestick exposure (0.42%-0.50%); and third, prevalence of HIV in the population served (0.32%-23.6%, depending on geographic location). Thus, the calculated range for occupational risk of HIV infection for a surgeon over a 30-yr period (assuming no change in HIV prevalence or benefit from protective measures) was 0.17%-13.9%; for an anesthesiologist, 0.05%-4.50%. The corresponding range of occupational risk for a medical student during the third year was 0.007%-0.59%. The range of risk is large because the variation in prevalence of HIV infection from one area to another is great. The authors validated the methodology first by using an equation, with estimates from the literature for factors in the equation, to calculate the risk of infection for hepatitis B and then by comparing the results with known rates of infection in the prevaccine era. Calculated occupational risk of hepatitis B infection for anesthesiologists was in the lower range of actual prevalence of infection (calculated range 2.32%-20.6%; known range 6%-26%). Calculated risk versus prevalence for surgeons was fairly close (7.31%-53.4% versus 24.4%).(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesiology↗