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Biomedical subjects

D W Kim

Publications and source records attributed to D W Kim.

At least 163 records · Page 9Linked to original sources

Esophageal aspergillosis after bone marrow transplant.

The prolonged immune suppression associated with bone marrow transplants predisposes to fungal infections including Aspergillus. Disseminated aspergillosis occurs in up to 60% of patients with invasive pulmonary aspergillosis; sites of involvement include the brain, gastrointestinal tract, kidney, liver, thyroid, heart, and spleen. There is only one report of isolated esophageal aspergillosis. A recent acute myelogenous leukemia patient had isolated esophageal aspergillosis after bone marrow transplantation which was successfully treated with amphotericin B.

Adult↗

Pre-emptive ganciclovir treatment can play a role in restoration of hematopoiesis after allogeneic bone marrow transplantation.

We performed pre-emptive ganciclovir therapy on two allogeneic bone marrow transplant (BMT) recipients with myelosuppression associated with cytomegalovirus (CMV) antigenemia after successful engraftment. During the hypoplastic phase, the nucleated cells in the bone marrow and peripheral blood were revealed to be of donor origin by DNA fingerprinting. These two patients had CMV antigen in their peripheral leukocytes. Following the pre-emptive ganciclovir treatment, both of them showed gradual recovery of granulocytes and platelets. They are still alive with stable bone marrow function. From these results, we suppose that infection or reactivation of CMV can suppress bone marrow function after bone marrow transplantation, and the pre-emptive ganciclovir therapy based on the CMV antigenemia may be beneficial if bone marrow function deteriorates after engraftment.

Adolescent↗

Interactions between mivacurium and pancuronium.

We have compared the dose-response relationships of mivacurium, pancuronium and their combination, and examined the interactions by isobolographic and fractional analyses. We studied 70 adult patients during nitrous oxide-fentanyl-propofol anaesthesia. The dose-response curves were determined by probit analysis. The ED95 and ED50 values for mivacurium were 84.2 (95% confidence interval 80.2-88.1) micrograms kg-1 and 46.2 (40.2-52.1) micrograms kg-1, respectively. Corresponding values for pancuronium were 68.5 (63.7-73.2) micrograms kg-1 and 40.7 (35.5-45.9) micrograms kg-1, respectively. Isobolographic and fractional analyses of the mivacurium-pancuronium combination demonstrated a synergistic interaction. An additional 30 patients were allocated randomly to receive either mivacurium 84.2 micrograms kg-1 (n = 15) or pancuronium 68.5 micrograms kg-1 (n = 15). When the first twitch (T1) of TOF recovered to 25%, each patient received mivacurium 46.2 micrograms kg-1. The times after administration of mivacurium until T1 25% in the mivacurium-pancuronium group were 6.4 (3.5-9.4) min and 49.8 (44.7-54.9) min, respectively (P < 0.0001). We conclude that the combination of mivacurium and pancuronium was synergistic and after pancuronium-induced neuromuscular block, mivacurium became a longer acting agent than the shorter agent.

Adult↗

Mutational analysis of the hepatitis C virus RNA helicase.

The carboxyl-terminal three-fourths of the hepatitis C virus (HCV) NS3 protein has been shown to possess an RNA helicase activity, typical of members of the DEAD box family of RNA helicases. In addition, the NS3 protein contains four amino acid motifs conserved in DEAD box proteins. In order to inspect the roles of individual amino acid residues in the four conserved motifs (AXXXXGKS, DECH, TAT, and QRRGRTGR) of the NS3 protein, mutational analysis was used in this study. Thirteen mutant proteins were constructed, and their biochemical activities were examined. Lys1235 in the AXXXXGKS motif was important for basal nucleoside triphosphatase (NTPase) activity in the absence of polynucleotide cofactor. A serine in the X position of the DEXH motif disrupted the NTPase and RNA helicase activities. Alanine substitution at His1318 of the DEXH motif made the protein possess high NTPase activity. In addition, we now report inhibition of NTPase activity of NS3 by polynucleotide cofactor. Gln1486 was indispensable for the enzyme activity, and this residue represents a distinguishing feature between DEAD box and DEXH proteins. There are four Arg residues in the QRRGRTGR motif of the HCV NS3 protein, and the second, Arg1488, was important for RNA binding and enzyme activity, even though it is less well conserved than other Arg residues. Arg1490 and Arg1493 were essential for the enzymatic activity. As the various enzymatic activities were altered by mutation, the enzyme characteristics were also changed.

Adenosine Triphosphatases↗

Increase of the protease activity of aqualysin I, a thermostable serine protease, by replacing Asn219 near the catalytic residue Ser222.

Functional role of Asn219 of aqualysin I, a thermostable serine protease from Thermus aquaticus, was investigated by using site-directed mutagenesis. Replacement of Asn219 with serine increased the catalytic efficiency (kcat/Km) for synthetic peptide substrates about twice as much as that of the wild type, while threonine replacement caused a slight decrease in the efficiency. Such replacements resulted in a significant change of kcat rather than Km, indicating that the side chain in the vicinity of the catalytic residue Ser222 affects the catalytic rate constant.

Asparagine↗

Properties of tetrahydropteroylpentaglutamate bound to 10-formyltetrahydrofolate dehydrogenase.

A new rapid procedure for purifying 10-formyltetrahydrofolate dehydrogenase results in 90 mg of pure enzyme from two rabbit livers. This abundant liver enzyme is known to bind its product tetrahydropteroylpentaglutamate (H4PteGlu5) so tightly that it does not dissociate during size exclusion chromatography. 10-Formyltetrahydrofolate dehydrogenase is also known to exhibit strong product inhibition by H4PteGlu5. There is a several-fold excess of 10-formyltetrahydrofolate dehydrogenase subunits in liver relative to the concentration of H4PteGlun, suggesting that in vivo this enzyme may bind significant amounts of this coenzyme in a nearly irreversible enzyme. H4PteGlu5 complex. How this tightly bound H4PteGlun is transferred to the other two enzymes in the cytosol, serine hydroxymethyltransferase and C1-tetrahydrofolate synthase, which use H4PteGlu5 as a substrate, is the subject of this investigation. Analysis of the product inhibition curve for 10-formyltetrahydrofolate dehydrogenase shows that H4-PteGlu5 has a dissociation constant near 15 nM which is 60-fold lower than the Ks for 10-formyl-H4PteGlu5. Fluorescence titration studies also yield a Kd of about 20 nM for H4PteGlu5. Coupling the 10-formyltetrahydrofolate dehydrogenase reaction to an excess of either serine hydroxymethyltransferase or C1-tetrahydrofolate synthase not only abolishes product inhibition but also increases the initial rate of its activity by about 2-fold. Passage of a reaction mixture of 10-formyltetrahydrofolate dehydrogenase down a size exclusion column results in enzyme with 1 equiv of H4PteGlu5 bound per subunit. However, addition of either serine hydroxymethyltransferase or C1-tetrahydrofolate synthase results in a rapid transfer of this bound folate to these enzymes. Evidence is also presented that the tightly bound folate is in equilibrium with solvent H4PteGlu5.

Aminohydrolases↗

Characterization of RNA binding activity and RNA helicase activity of the hepatitis C virus NS3 protein.

The Hepatitis C Virus (HCV) NS3 protein has RNA binding activity, RNA-stimulated NTPase activity, and RNA helicase activity. The RNA binding activity of the C-terminal domain of the HCV NS3 protein is less sensitive to pH, KCl, and MgCl2 than NTPase and the RNA helicase activity. The overall order of the binding of homoribopolymer for the NS3 protein was poly(U) > > poly(A) > poly(G), poly(C). The minimal RNA binding size of the HCV NS3 protein was determined using a gel retardation assay and is estimated between 7 nt and 20 nt. The HCV RNA helicase unwinds RNA/DNA heteroduplexes as well as RNA/RNA duplexes and it catalytically translocates in the 3' to 5' direction.

Base Sequence↗

Interactions between mivacurium, rocuronium, and vecuronium during general anesthesia.

This study was designed to examine the interactions between mivacurium and rocuronium or vecuronium when administered during a standardized anesthetic technique. Seventy healthy women undergoing abdominal hysterectomy procedures with a standardized thiopental-sufentanil-desflurane-nitrous oxide anesthetic technique were randomly assigned to one of seven treatment groups (10 patients each). After a tracheal intubating dose of vecuronium 100 micrograms/kg (Groups 1 and 2), rocuronium 600 micrograms/kg (Groups 3 and 4), or mivacurium 250 micrograms/kg (Groups 5, 6, and 7), patients received vecuronium, 25 micrograms/kg (Groups 1 and 6), rocuronium 150 micrograms/kg (Groups 3 and 7), or mivacurium 50 micrograms/kg (Groups 2, 4, and 5) for maintenance of neuromuscular blockade. Neuromuscular function was assessed using electromyography, with a train-of-four mode of stimulation at the wrist every 10 s. The clinical duration (time for T1 to return to 25% of baseline) of the maintenance dose of mivacurium was significantly longer after an intubating dose of rocuronium (40 +/- 8 min) and vecuronium (28 +/- 6 min) than after mivacurium (12 +/- 3 min). The clinical duration of maintenance doses of vecuronium (18 +/- 6 min) and rocuronium (13 +/- 2 min) were significantly shorter after an intubating dose of mivacurium than that after an intubating dose of vecuronium (30 +/- 5 min) or rocuronium (42 +/- 12 min), respectively. These data suggest that with consecutive administration of neuromuscular blocking drugs, the initial duration of action depends more on the kinetics of the first neuromuscular blocking drug than the subsequent drug. Thus, there appears to be no clinical advantage in using mivacurium for maintenance of neuromuscular blockade after initial administration of rocuronium or vecuronium.

Adult↗

A case-control study on the risk factors of hepatitis C virus infection among Koreans.

In order to identify the risk factors for hepatitis C virus (HCV) infections, a case-control study was conducted from September 1993 to April 1994. HCV infection was confirmed by the second generation of recombinant immunoblot assay. Sixty-four cases and 128 controls matched for age and sex with a 1:2 ratio of cases to controls were enrolled. Exposure data were obtained from all participants by self-administered questionnaire and the odds ratios of possible risk factors of HCV infection analysed. Sixty-four cases consisted of forty-two patients with chronic hepatitis, nine with cirrhosis, one with hepatocellular carcinoma, and twelve with normal liver function. History of acute hepatitis (OR 3.9) and transfusion (OR 2.4) were associated with an increased risk of HCV infection. Operation, acupuncture, endoscopy, tooth extraction, tattooing, ear piercing, needle sharing and family history of hepatitis were not associated with an increased risk of HCV infection. In conclusion, transfusion remains the major route of transmission of HCV in Korea.

Adult↗

A case of disseminated coccidioidomycosis--autopsy report.

Disseminated coccidioidomycosis is a systemic fungal infection that is occurring more commonly and causes high mortality in patients with compromised host defense or debilitated. It is endemic in certain areas of North, Central, and South America. Increasingly, cases are being recognized outside the endemic area, due to travelers who have visited an endemic area. We experienced a case of disseminated coccidioidomycosis, as a reactivation of infection acquired earlier in a patient, who was a former resident of an endemic area.

Amphotericin B↗

An Epstein-Barr virus-associated lymphoproliferative lesion of the skin presenting as recurrent necrotic papulovesicles of the face.

We describe four patients with lymphoproliferative lesions confined to the skin for several years. They presented with recurrent necrotic papulovesicles of the face. Latent Epstein-Barr virus (EBV) infection was detected in the lymphoid cells from the skin lesions by in situ hybridization. The disease in three patients progressed to T-cell lymphoma. We believe that these patients represent a subset of peripheral T-cell lymphoma with a tendency to localize in the skin.

Adolescent↗

Induction chemotherapy with idarubicin plus N4-behenoyl-1-beta-D-arabinofuranosylcytosine in acute myelogenous leukemia: a newly designed induction regimen--a prospective, cooperative multicenter study.

This report describes the results of induction chemotherapy with idarubicin (IDA) plus N4-behenoyl-1-beta-D-arabinofuranosylcytosine (BH-AC), a newly designed induction regimen, in cases of previously untreated acute myelogenous leukemia (AML). The study was conducted by the Multicenter Clinical Study Group of the Korean Biologic Response Modifier Society (KBRMS). From March 1994 through January 1995, 40 patients were treated. The median age was 30 years (range, 15 months to 65 years), with a distribution according to the French-American-British (FAB) classification of one MO, nine MI, 15 M2, six M3, four M4, and five M5 patients. Remission induction therapy consisted of IDA 12 mg/m2 intravenously (i.v.) over 30 minutes daily on days 1 to 3, in combination with BH-AC 300 mg/m2 over 4 hours daily on days 1 to 7 (in patients aged 41 to 65 years, BH-AC dosage was decreased to 200 mg/m2/d). Complete remission (CR) was achieved in 30 patients (75%), 22 by the first induction therapy and eight by the second induction therapy. Ten patients (25%) failed to respond to therapy, six due to resistant disease and four due to death caused by aplasia. The time to CR was 30 days, the median granulocytopenic period was 19 days, and the thrombocytopenic period was 24 days. All nonhematologic side effects such as nausea, vomiting, mucositis, skin eruption, liver and cardiac dysfunction, and neurotoxicity, were transient and tolerable. These data indicate an efficacy comparable to that of other combinations of IDA (or other anthracyclines) with cytosine arabinoside (Ara-C) for remission induction in AML.

Adolescent↗

C-terminal domain of the hepatitis C virus NS3 protein contains an RNA helicase activity.

The Hepatitis C Virus (HCV) NS3 protein contains amino acid motifs of a serine proteinase, a nucleotide triphosphatase (NTPase), and an RNA helicase based on amino acid sequence analysis. Proteinase and NTPase activities of the HCV NS3 protein were reported by several investigators. Here, we show that the recombinant HCV NS3 protein purified from a T7 promoter and His-tag expression system possesses an RNA helicase activity. The recombinant HCV NS3 protein consists of 466 amino acids from the carboxy terminal of a HCV NS3 open reading frame and 25 additional residues from the vector. The recombinant HCV NS3 protein was purified by metal-binding chromatography. The helicase activity requires ATP and divalent cations such as Mg2+ and Mn2+. The helicase activity was abolished by monoclonal antibody specific to the HCV NS3 protein.

Adenosine Triphosphate↗

Characterization of an established human hepatoma cell line constitutively expressing non-structural proteins of hepatitis C virus by transfection of viral cDNA.

A human hepatoma cell line constitutively expressing proteins of hepatitis C virus (HCV) was established by transfection with cDNA encoding part of the virus nonstructural (NS) genome region. Proteins consistent with authentic processing at NS3/NS4A, NS4A/NS4B and NS4B/NS5A were identified. Pulse-chase experiments indicated that the cleavage between NS3 and NS4A occurred first and cleavage at other sites followed. Expression of specific surface antigens in response to the presence of HCV proteins was analysed by flow cytometry. A significant increase in CD26 expression was observed in cells expressing the HCV proteins. CD26 plays an important role in cellular signal transduction. Its upregulation in response to the presence of HCV proteins may play a role in viral pathology.

Base Sequence↗

Immune suppression therapy in aplastic anemia: influencing factors on response and survival.

OBJECTIVES: Immune suppression (IS) therapy has provided another opportunity of cure or improvement in the aplastic anemia patients who cannot receive bone marrow transplantation due to many causes. There are a few reports regarding the factors that affect response, survival and prognosis after IS therapy, including antilymphocyte globulin (ALG) in aplastic anemia. Therefore, we analysed our experience to determine the prognostic factors. METHODS: Statistically analysed were 172 patients, from April 1982 to July 1992, who were diagnosed as severe aplastic anemia and treated with IS therapy, including ALG, at Catholic University Medical College, St. Mary's Hospital. RESULTS: Among 172 severe aplastic anemia (SAA) patients who entered the study from April 1982 to July 1992, 144 patients were analysed for response and 122 patient for survival. 58.4% (84/144) responded after the first course of IS therapy. Among those who did not respond on the first course an additional 44% (11/25) responded after the second course of IS therapy. Prognostic factors that might affect the response to the treatment and survival were analysed. In a univariate analysis of patients with no previous history of treatment before is therapy, and a shorter interval between diagnosis and treatment, higher hemoglobin levels before IS therapy, and higher granulocyte counts and combined use use of cyclosporin A(CSA) were positively associated with response (p < 0.05). The combined use of CSA during IS therapy, younger age, lower monthly requirement of platelets transfusion before IS therapy, higher leukocyte counts, higher percent of polymorphonuclear leukocytes, lower percent of lymphocyte, higher bone marrow cellularity and response were positively associated with survival (p < 0.05). In a multivariate analysis, shorter interval between diagnosis and treatment, no combined use of hemopoietic stimulants, such as androgen, and lesser total amount of transfusion were positively associated with Response (p < 0.05). Higher leukocyte counts before IS therapy and the combined use of CSA during IS therapy were significantly associated with longer survival (p < 0.05). Patients with complete or partial response had excellent prognosis (96.7%-100% of 5 year survival rates). In contrast, patients with no response after IS therapy had 45.1% of 5 year survival rates. CONCLUSIONS: With these results from the retrospective study of IS therapy, we find many valuable factors that have an influence on response or survival. IS therapy improves the survival of responded patients with SAA, and we confirmed that IS therapy is an important therapeutic tool for the SAA patients who are not feasible candidates for bone marrow transplantation.

Adolescent↗

Discoid lateral meniscus associated with anomalous insertion of the medial meniscus.

Discoid lateral meniscus in the knee joint is common. From July 1990 through September 1992, the authors performed arthroscopy on 534 symptomatic knee joints. Seventy-seven knees of 72 patients had discoid lateral meniscus. Of the 77 knees treated, 4 (5.5%) had discoid lateral meniscus associated with anomalous insertion of the anterior horn of the medial meniscus into the anterior cruciate ligament. The discoid lateral meniscus was reshaped in the 4 knees, and followup was done from 12 to 24 months (average, 20 months) after surgery. The results were satisfactory, except for 1 patient who damaged his knee in a traffic accident. The authors concluded that this anatomic variant of the medial meniscus was not related to the patients' symptoms, but that reshaping the discoid lateral meniscus did relieve their symptoms.

Adolescent↗