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Biomedical subjects

B K Kim

Publications and source records attributed to B K Kim.

At least 109 records · Page 6Linked to original sources

Infusible platelet membrane microvesicles: a potential transfusion substitute for platelets.

BACKGROUND: Several substitutes for intact, viable platelets have been used for transfusion, both to people and in animal models, with varied success. Infusible platelet membrane (IPM) is prepared from human platelets. IPM retains the glycoprotein (GP)lb receptor and has platelet factor 3 activity (procoagulant activity). However, factor V, serotonin, a cytoplasmic marker enzyme (purine nucleotide phosphorylase), GPIIb/IIIa complex, and HLA class I and II antigens are all absent in IPM. STUDY DESIGN AND METHODS: IPM is prepared from outdated platelets. The platelets were disrupted by freezing and thawing; they were washed and heated to inactivate possible viral contaminants, and then the sonicated membrane microvesicle fraction was separated and lyophilized. The hemostatic activity of IPM was measured by its ability to reduce the prolonged bleeding time in thrombocytopenic rabbits. RESULTS: Administration of IPM at a dose of 2 mg per kg results in a substantial reduction in the bleeding time. In a series of 23 experiments, a median preinjection bleeding time of 15 minutes was reduced to 6 minutes within 4 hours after IPM administration. Administration of IPM did show a mild enhancement in the thrombogenicity index, as measured in the Wessler rabbit model. This enhancement is, however, not significant, as a thrombogenicity index value of up to 0.6 is clinically acceptable. CONCLUSION: IPM may have clinical potential as a substitute for platelets in the treatment of bleeding due to thrombocytopenia.

Animals↗

The cytotoxicity of psoralidin from Psoralea corylifolia.

A cytotoxic coumestan derivative, psoralidin (1), was isolated from the seed of Psoralea corylifolia. The IC50 values of 1 against SNU-1 and SNU-16 carcinoma cell lines were 53 and 203 micrograms/ml, respectively, indicating cytotoxic activity against stomach carcinoma cell lines.

Antineoplastic Agents, Phytogenic↗

A case of acral melanocytic hyperplasia: a unique pigmented lesion mimicking acral lentiginous melanoma in situ.

A mottled black pigmented patch on the sole of the foot is reported. Clinically, the lesion closely mimicked acral lentiginous melanoma in situ. However, the histologic findings revealed melanocytic hyperplasia with minimal cytologic atypia confined to the epidermis. Irregular pigmented patches in the acral region comprise a heterogenous group of lesions that range from benign melanocytic hyperplasia to acral lentiginous melanoma.

Biopsy, Needle↗

Cloning and sequencing of the Klebsiella K-36 astA gene, encoding an arylsulfate sulfotransferase.

A gene-encoding arylsulfate sulfotransferase (ASST) was cloned from a Klebsiella K-36 genomic library. ASST transfers a sulfate group from phenolic sulfate esters to a phenolic acceptor substrate. The gene, designated astA, was subcloned into vector pGEM3Zf(-) and sequenced. Recombinant clone-harbouring astA was directly identified using a fluorescent product. The nucleotide sequencing revealed an open reading frame (ORF) of 2,082 bp encoding a protein of 694 amino acids with a secretory signal sequence. A protein of similar size was visualized after in vitro transcription and translation using a plasmid carrying the cloned 3.1-kb fragment as a template. The N-terminal amino acid sequence of the purified processed protein was found to be identical to that predicted from the gene sequence. When searching the database for astA nucleotide or its deduced amino acid sequence, no significant homology to any sequence was found.

Amino Acid Sequence↗

Isolation and characterization of a copper-resistant methanogen from a copper-mining soil sample.

A copper-resistant methanogen for which the CuSO4 MICs were approximately 2- to 36-fold higher than those for other methanogens tested was isolated from a copper-mining area in the upper peninsula of Michigan. The rod-shaped methanogen used H2-CO2 or formate, but not acetate or methanol, as a growth substrate. Standing incubation with H2-CO2 medium resulted in a mat-like surface growth, dependent on the presence of hydrogen. The presence of 1 mM cupric salt resulted in longer filamentous and intertwined cells. Antigenic fingerprinting, 16S rRNA gene analysis, morphology, and substrate use suggest that the new isolate is a novel strain of Methanobacterium bryantii that is able to use formate.

Antigens, Bacterial↗

Tuberculosis-associated hemophagocytic syndrome in a hemodialysis patient: case report and review of the literature.

We present an unusual hematologic manifestation of tuberculosis in a hemodialysis patient. A 37-year-old man was admitted because of fever, anorexia, and weight loss which developed 3 months earlier. He previously received a renal transplant and commenced hemodialysis 1 year ago. Physical examination revealed hepatomegaly, and peripheral blood counts revealed pancytopenia. The delayed bone marrow biopsy demonstrated marked hemophagocytosis, granuloma and tubercle bacilli by the acid-fast stain. The clinical course was fatal and he died without definite treatment. Through this case, we would like to recommend early bone marrow biopsy and antituberculosis therapy if fever of unknown origin, anorexia, weight loss, hepatomegaly and pancytopenia develop in patients undergoing dialysis.

Adult↗

Increased inhibitory effect of phorbol ester on cytosolic Ca2+ level and contraction in rat myometrium after gestation.

Activation of voltage-dependent Ca2+ channels by high K+ (40 mM) increased the cytosolic Ca2+ level ([Ca2+]i) (estimated by fura-PE3 fluorescence ratio) and force in myometrium isolated from pregnant (21 days after gestation) and non-pregnant (estrus) rats. 12-Deoxyphorbol 13-isobutyrate (DPB, 1 mM) decreased the high (K+)-stimulated [Ca2+]i and force in a concentration-dependent manner. The inhibitory effect was stronger in the pregnant myometrium than in the non-pregnant myometrium. In the pregnant myometrium, the increase in Ca2+ permeability by ionomycin (1 microM) greatly increased [Ca2+]i and force, which were only partially inhibited by verapamil (10 microM). DPB (1 microM) inhibited the verapamil-insensitive component of the increases in [Ca2+]i and muscle tension. Oxytocin (100 nM) and thapsigargin (1 microM) also induced a verapamil-insensitive increase in [Ca2+]i and force, and DPB (1 microM) inhibited these increments. Ca2+ sensitivity of contractile elements, estimated from the relationships between Ca2+ and muscle force in intact and alpha-toxin permeabilized muscle, was not significantly changed by DPB (1 microM). In summary, DPB inhibits the increase in [Ca2+]i more strongly in myometrium isolated from pregnant rats than that from non-pregnant rats without any change in the [Ca2+]i/tension relationship. Since DPB decreased [Ca2+]i-rise induced by three different mechanisms, DPB may activate Ca2+ extrusion, rather than to inhibit a specific influx pathway, to decrease [Ca2+]i.

Animals↗

Efficacy of in vitro treatment of chronic myelogenous leukemia cell line, K562 cells, using 4-hydroperoxycyclophosphamide, alpha-interferon and gamma-interferon.

Alpha-interferon (alpha-IFN) and gamma-interferon (gamma-IFN) are highly effective biologic agents in the treatment of chronic myelogenous leukemia (CML). 4-hydroperoxycyclophosphamide (4-HC) is the most commonly used chemotherapeutic drug when purging bone marrow contaminated with malignant cells. To investigate the efficacy of alpha-IFN, gamma-IFN and 4-HC as purging agents in CML patients, K562 cells, a human CML cell line, were treated in vitro with these drugs singly or in combination. The cytotoxic effect was evaluated by MTT assay. Data were analyzed for synergism by the median effect principle of Chou and Talalay. Using Southern blot analysis, the effect of purging on the suppression of bcr gene rearrangement was also evaluated. Alpha-IFN, gamma-IFN and 4-HC all showed good concentration-dependent cytotoxic effect. Median cytotoxic doses of alpha-IFN gamma-IFN and 4-HC were 0.03 microM 0.20 microM and 1.97 microM respectively, and molar ratios of median doses of alpha-IFN to 4-HC, gamma-IFN to 4-HC and alpha-IFN to gamma-IFN were 1:80, 1:10 and 1:8, respectively. The combination treatment of alpha-IFN and 4-HC, and gamma-IFN and 4-HC showed significant synergistic cytotoxic activities, but combination of alpha-IFN and gamma-IFN was antagonistic. Status of bcr gene rearrangements in K562 cells was not changed after the treatments. Our results appear to provide an efficient method for removing CML cells from the bone marrow of CML patients.

Antineoplastic Agents↗

Hemangiopericytoma of renal sinus expanding to the renal hilum: an unusual presentation causes misinterpretation as transitional cell carcinoma.

We report a case of renal hemangiopericytoma occurring in renal sinus and expanding to the renal hilum. This unusual presentation caused misinterpretation of this tumor as transitional cell carcinoma of the renal pelvis clinically. The patient who was a 30-year-old woman had a relatively well demarcated solid tumor, 8 x 6 cm, in the renal sinus of the left kidney.

Adult↗

Interphase cytogenetics of non-Hodgkin's lymphoma using non-fluorescent in situ hybridization in paraffin embedded tissue.

Paraffin-embedded tissue samples from 30 cases of non-Hodgkin's lymphoma(NHL) and 10 of reactive hyperplasia, were processed for interphase cytogenetic chromosomal study. We performed non-fluorescent in situ hybridization(NFISH) using the enzymatic method with digoxigenin-labeled DNA centromeric probes for chromosome 7,12,18 and X, and a painting probe for chromosome 18. Chromosomal aberrations were observed in 27(90%) out of 30 cases of NHL. The most commonly observed numerical aberration was extracopy of X chromosome. There were some characteristic aberrations corresponding to each grade and group of NHL by International Working Formulation: In low grade NHL(9 cases), a third were associated with extracopy of chromosome 12, and disomy X was frequently found in small lymphocytic lymphoma(75%). With intermediate grade(16 cases), tetraploidy(25%), translocation of chromosome 18(25%), and extracopy of chromosome 18(19%) were characteristically associated. These results suggest that interphase NFISH is an easily performable method in retrograde cytogenetic study of archival materials. Some specifically correlated chromosomal aberrations corresponding to the histopathologic grades and groups could provide us more valuable information for determining pathologic diagnosis and assessing the clinical outcome of NHL.

Chromosome Aberrations↗

Bone marrow scintigraphy using technetium-99m-antigranulocyte antibody in hematologic disorders.

UNLABELLED: Bone marrow is the primary site for many hematologic disorders. To date, however, no suitable bone marrow imaging method has been found. The present study investigates the usefulness of bone marrow immunoscintigraphy using 99mTc-labeled antigranulocyte antibody (anti-NCA-95) in 31 patients with hematologic disorders. METHODS: One milligram of antibody labeled with 259-370 MBq 99mTc was injected intravenously, and bone marrow images were taken 4 hr later. We also calculated the uptake ratios of lumbar bone marrow-to-background (L/B) and ilium-to-background (I/B). RESULTS: Of 15 patients with aplastic anemia, 7 showed diffusely decreased antibody uptake (L/B = 2.3 +/- 0.8, I/B = 3.0 +/- 0.8) compared to control patients (n = 21, L/B = 8.2 +/- 2.5, I/B = 10.3 +/- 3.1) Six patients had both decreased and increased uptake areas and two had normal to slightly increased uptake. Of those patients receiving various types of therapy for aplastic anemia, all but one showed increased or irregular uptake. The degree of antibody uptake in the bone marrow correlated with peripheral blood analyses (hemoglobin, white blood cells, platelets). Of six patients with myelodysplastic syndrome, four had irregular uptake and two diffusely decreased uptake. Four patients with myelogenous leukemia showed normal uptake, whereas two with lymphocytic leukemia had decreased uptake. Patients with iron deficiency anemia, pure red cell aplasia or thalassemia minor exhibited normal uptake with bone marrow expansion. CONCLUSION: Immunoscintigraphy with antigranulocyte antibody is a useful method for evaluating the bone marrow status of patients with various hematologic disorders.

Adolescent↗

Effect of a vitamin D3 analog, EB1089, on hematopoietic stem cells from normal and myeloid leukemic blasts.

The seco-steroid 1,25 dihydroxyvitamin D3 (1,25(OH)2D3) induces differentiation and inhibits clonal proliferation of HL-60 cells. We analyzed the effect of a novel vitamin D3 analog, EB1089, on normal myeloid and leukemic cells as well as CD34+ cells. EB1089 showed an extraordinary inhibition of clonal growth of HL-60 cells (ED50 = 5 x 10(-11) M) and AML blast cells (ED50 = 9 x 10(-10) M) compared to 1,25(OH)2D3 without suppression of growth of normal human bone marrow CFU-GM. The CD34+ cells from acute myeloid leukemia (AML) blasts were inhibited in a dose-dependent fashion by 1,25(OH)2D3 with an ED50 of 1.2 x 10(-9) M; and even more strikingly, 10(-10) M of EB1089 inhibited all clonal growth of human CD34+ leukemic colony-forming cells. In contrast, both EB1089 and 1,25(OH)2D3 (10(-8) M) showed little or only mild inhibition of CD34+ clongenic hematopoietic cells from normal human peripheral blood (PB); and in liquid culture, EB1089 stimulated the proliferation of normal human CD34+ cells about 2.5 times as compared to control cultures. In order to evaluate the potential use of EB1089 for purging leukemic cells from normal CD34+ progenitor cells for PB stem cell transplantation (PBSCT), normal human PB mononuclear cells (PBMNC) were contaminated with HL-60 cells, and then CD34+ cells purified and treated with EB1089. We found that CD34+ purification and EB1089 purging was able to eliminate approximately 100% of HL-60 leukemic cells with no toxicity to normal CD34+ hematopoietic progenitor cells. These data suggested that purification of CD34+ cells and ex vivo treatment with EB1089 might provide an effective therapeutic approach for PBSCT.

Antigens, CD34↗

[Spontaneously thrombosed aneurysm of the vein of Galen: a case report].

A 13-year-old girl was admitted with headache of sudden onset. Neurological examination did not reveal any abnormalities on admission. Her growth and development were normal. CT scan showed a high density mass in the pineal region without contrast enhancement. It was a spontaneously thrombosed aneurysm of the vein of Galen associated with thrombosis of the straight and the transverse sinuses on MRI. Moreover, there were an interhemispheric lipoma and a right temporal arachnoid cyst. The superior sagittal, bilateral transverse, sigmoid and straight sinuses were not opacified but unusual pathways of various venous channels were demonstrated on angiograms. Persistent fetal drainage remained as the collateral venous pathways such as the ventral diencephalic and striate veins and the paired longitudinal head sinuses. There were two types of unusual deep venous pathways. The left internal cerebral vein drained into the left ventral diencephalic vein. The left ventral diencephalic vein drained through the left lateral mesencephalic and ponto-medullary veins into the spinal venous plexi. The dilated striate veins drained into the deep middle cerebral veins through the cerebral parenchyma. Mainly, there were three types of superficial venous pathways. The paired longitudinal head sinuses drained into the emissary veins at the ethmoid sinus in retrograde fashion, and finally into the nasal mucosa. The superficial cerebral veins drained into the cavernous sinus which communicated with the nasal mucosa and the pterygoid plexi. The veins of the posterior fossa drained into the occipital emissary veins. After being admitted, the patient had remarkable nasal bleeding which was difficult to stop. This symptom seemed to be related to the collateral venous drainage to the nasal mucosa shown on angiograms. Finally, she became completely asymptomatic three weeks after admission.

Adolescent↗

A novel T-cell differentiation antigen expressed in immature human thymocytes and neuroglial cells.

We report a novel human thymocyte differentiation antigen ICT-1 with a molecular weight of 49 kDa that is noncovalently associated with another 12-kDa protein. The ICT-1 antigen is expressed in 50-70% of total thymocytes, but not in resting or PHA-activated peripheral blood T-cells and bone marrow cells. The thymocytes expressing ICT-1 antigen appear after the 18th week of gestation during fetal development. Since the distribution pattern of the ICT-1 antigen within thymus partly overlaps with that of the CD1 antigens, we investigated whether ICT-1 was one of the CD1 antigen family. However, the failure of anti-ICT-1 antibody to react with mouse L cells transfected with cDNA of CD1a, -b, and -c and the different histologic distribution patterns from that of CD1d strongly suggest that the anti-ICT-1 antibody recognizes an antigen distinct from CD1. Furthermore, ICT-1 is also expressed in human neuroglial cells such as oligodendroglioma, glioblastoma multiforme, Ewing's sarcoma, and cerebellar astrocyte. Hence we believe that the ICT-1 antigen may be a novel thymus-leukemia (TL) antigen or a nonclassical MHC class I antigen.

Animals↗

Development of bone marrow immunoscintigraphy using a Tc-99m labeled anti-NCA-95 monoclonal antibody.

We evaluated the monoclonal antibody CEA-79.4 against carcinoembryonic antigen as an immunoscintigraphic agent for assessing the state of the bone marrow. Western blotting of human granulocyte extracts with the antibody could confirm that the binding was with the epitope of NCA-95. Immunocytochemical staining of bone marrow aspirates revealed specific uptake of this antibody by granulopoietic cells. The affinity constant was 2-9 x 10(9) L/mol. Immunoscintigraphy using 99mTc-labeled CEA-79.4 in a normal volunteer revealed high uptake in the bone marrow as compared to other organs.

Antibodies, Monoclonal↗

Structural integrity of the cyclin-dependent kinase inhibitor genes, p15, p16 and p18 in myeloid leukaemias.

The cyclin-dependent kinase inhibitors known as p15, p16 and p18 have been suggested as candidates for tumour suppressor genes. We examined these genes for their alterations in 46 myeloid leukaemias and 15 myeloid leukaemia cell lines. p16 mRNA expression was studied in 41 myeloid leukaemias. The p15 and p16 genes were either deleted or mutated in myeloid leukaemia lines at a high frequency [6/15 (40%) for p15; 8/15 (53%) for p16] but alterations in primary myeloid leukaemias are much less frequent [2/46 (4%) for p15; 3/46 (6%) for p16]. Alterations of p18 were not found in any of the samples. 13 primary myeloid leukaemia samples had negligible levels of p16 mRNA. In summary, the deletions of p15 and p16 genes identified in the myeloid leukaemia cell lines probably occurred during their in vitro immortalization. Alterations of the p16 or p15 gene only occurred in primary acute myeloid leukaemia samples that were of mixed myeloid/lymphoid lineage (CD19/CD20-positive acute myeloid leukaemia [AML], CD2/CD19-positive AML, and lymphoid blastic crisis of chronic myeloid leukaemia). Further studies are required to determine if the absence of mRNA expression results from inactivation of the p16 gene.

Blotting, Northern↗

Increased sensitivity of rat myometrium to the contractile effect of platelet activating factor before delivery.

1. The contractile effects of platelet activating factor (PAF) were compared in the myometrium isolated from non-pregnant and pregnant rats. 2. In the non-pregnant myometrium, PAF, at a concentration of 0.1 microM, did not change muscle tension and induced only a small transient contraction at 10 microM. 3. The contractile responses to PAF increased with the progress of gestation. In the late pregnant myometrium (21 day after gestation), PAF (0.1 nM-10 microM) induced large and relatively sustained contractions. The threshold concentration of PAF was decreased by approximately 10,000 times and the maximum contraction was increased 5 times by day 21 of gestation. 4. PAF (10 microM) increased the cytosolic Ca2+ concentration ([Ca2+]i) and muscle contraction to levels higher than those induced by high K+ in the pregnant rat myometrium (day 21). Verapamil (10 microM), a voltage-dependent Ca2+ channel blocker, decreased the stimulated [Ca2+]i and muscle tension to 49.6% and 22.7%, respectively, while the same concentration of verapamil completely inhibited the high K(+)-induced responses. 5. PAF (10 microM) induced a transient increase in [Ca2+]i with no contraction in the absence of external Ca2+ in the pregnant myometrium (day 21). 6. These results suggest that PAF induces contraction in rat myometrium by increasing Ca2+ influx. Although PAF released Ca2+ from stored sites, this Ca2+ does not seem to contribute to the PAF-induced contraction. Our major finding is that the sensitivity of the myometrium to PAF increased after gestation and that this may play a role in delivery.

Animals↗