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Biomedical subjects

K Park

Publications and source records attributed to K Park.

At least 397 records · Page 22Linked to original sources

[Effects of maintenance treatment after high-dose intravenous gamma-globulin for idiopathic thrombocytopenic purpura].

High-dose intravenous immunoglobulin (IVIG) for idiopathic thrombocytopenic purpura (ITP) produces a dramatic and substantial increase in platelet count, but the increased count tends to return rapidly to its pretreatment level. We studied the effects of immunosuppressive treatment aimed at the maintenance of platelet counts following the IVIG administration in ITP. Thirty-five patients with ITP were treated with IVIG, and then thirty-two of them with an immunosuppressant (azathioprine) and a glucocorticoid (prednisolone). After IVIG, the platelet count increased significantly. With immunosuppressive therapy after IVIG, most patients had a tendency to maintain the counts. In particular, this maintaining effect was remarkable in those patients who had been responsive to the standard prednisolone therapy while non-responders to the prior prednisolone failed to maintain the counts. When prednisolone was given after IVIG, the effect of maintaining platelet counts was dose-dependent. The treatment with azathioprine and prednisolone after IVIG appears to be effective in maintenance of platelet counts.

Adolescent↗

Positive effect of granulocyte-colony stimulating factor on erythropoiesis in humans.

We studied the effects of granulocyte-colony stimulating factor (G-CSF) on human erythropoiesis in vivo. Changes in the peripheral blood were analyzed in 9 subjects; 3 healthy volunteers, 3 patients with pancytopenia and hypersplenism and 3 patients with chronic renal failure and severe anemia being treated with hemodialysis. We monitored erythropoiesis according to the number of highly fluorescent cells (HFC) present in the peripheral blood after staining with Auramine 0. These cells are relatively immature reticulocytes that contain much RNA. All subjects received recombinant human G-CSF at a daily dose of 100 micrograms/m2 administered intravenously for 3 to 5 days. Plasma erythropoietin was measured in patients receiving dialysis before and several times after its administration. The number of HFC increased significantly in all subjects. In 1 of 3 patients receiving dialysis, the plasma erythropoietin increased transiently but insignificantly. These findings show that G-CSF affects human erythropoiesis in vivo, but that the mechanism of its effect did not involve an increase in plasma erythropoietin.

Adult↗

Therapy with mitoxantrone, ifosfamide, vindesine, and prednisolone for malignant lymphoma with adjustable doses and timing of courses.

Thirty-seven patients with malignant lymphoma were treated with mitoxantrone, ifosfamide, vindesine, and prednisolone. The time among courses was not fixed, being decided by the time for recovery from the leukopenia caused by the treatment. The drug dose was adjusted after the initial course. Of the 12 patients treated for the first time, eight had a complete remission and two had a partial response. Of the 18 patients who relapsed after another drug regimen, six had a complete remission and seven had a partial response. The SD of the leukocyte nadirs decreased after the first course, and time needed for recovery from leukopenia tended to shorten during treatment. Side effects seemed mild, and we can use many drugs safely in a short term without long drug-free intervals. Response rates were satisfactory, compared with other report, so this method of timing the start of courses with adjustment of the dose seems useful.

Antineoplastic Combined Chemotherapy Protocols↗

[In vitro chemosensitivity test with several antitumor agents against eight malignant brain tumor cell-lines].

We performed an in vitro chemosensitivity test with 8 malignant brain tumor cell lines, which were established in our Department. It was shown that ACNU was moderately tumoricidal against only one cell (ONS-86) line. IFN-beta (interferon-beta) was more active against 4 cell (ONS-6, -20, -76, and -81) lines. VCR (vincristine), MTX (methotrexate), and Ara-C (cytosine arabinoside) and FK 973 were most effective against all 8 cell lines. There were some difference in the drug sensitivities among the tumors with the same pathological diagnosis. Since IFN-beta was tumoricidal against to the cells, co-culture of IFN-beta and one of other antitumor agents seemed to induce more antitumor effects. With regard to the side effects of IFN-beta, the combined therapy with IFN-beta and other drugs induced more antitumor effects against malignant brain tumor cells and seemed to reduce the side effects.

Antineoplastic Agents↗

[Antitumor activity of FK973 for malignant gliomas and its assessment for normal brain cells].

FK973, a novel antitumor antibiotic, was obtained as a fermentation product of Streptomyces sandaensis. FK973 had excellent cytotoxic effects against in vitro cultured human glioblastomas, medulloblastomas, and murine glioma (203 glioma) cells. The antitumor effects were also well observed against ACNU resistant glioma cells. FK973 did not go through the blood-brain barrier. The median survival time (MST) of MG models treated with FK973 was 21 days. On the other hand, the MST of the control group was 15 days. In the in vitro assessment against neural disturbance, FK973 showed a little disturbance of murine brain cells but less toxic than ADM. In the in vivo neurotoxicity examination, FK973 showed no clear damage to the neural cells and myelin sheaths.

Animals↗

Effect of aggregation of histone octamers in high-salt solutions on circular dichroism spectra.

The circular dichroism (CD) of freshly prepared chicken erythrocyte core histones has been reexamined in high concentrations of ammonium sulfate and sodium chloride, conditions which cause drastic changes in the solubility and aggregative properties of these proteins. After sample clarification by ultracentrifugation, no significant net changes are detected in the secondary structure of the core histones in the range of 2.0-2.5 M ammonium sulfate. There is also no significant difference between the CD spectra of histone solutions in 2 M sodium chloride and clarified solutions of histones in high concentrations of ammonium sulfate. It was observed that sample clarification by ultracentrifugation immediately prior to taking CD spectra was necessary for signal stabilization, especially under conditions which begin to favor crystallization of the histones.

Ammonium Sulfate↗

Conformational analysis of the immunodominant epitopes of the circumsporozoite protein of Plasmodium falciparum and knowlesi.

All of the coat proteins of the sporozoite and merozoite stages of Plasmodium, determined to date, contain tandem repeats and most of these contain at least one proline residue. These tandemly repeated segments of the circumsporozite (CS) proteins of P. falciparum and P. knowlesi have been shown to constitute an immunodominant epitope. Antibodies to these peptide segments have been shown to be protective and cause the shedding of the CS protein, known as the CSP reaction. In this study, four synthetic peptides were prepared by solid-phase peptide synthesis. The first peptide corresponds to the tetrapeptide tandem repeat in the CS protein of P. falciparum, repeated eight times, (NANP)8. The second peptide is an analogue of the first in which glycine is substituted for proline, (NANG)8. The third peptide corresponds to the tandem repeat of P. knowlesi, PK(1-24), which is repeated twice (QAQGDGANAGQP)2. The fourth peptide is a tetrapeptide repeat, corresponding to the C-terminal tetrapeptide of PK(1-24) and is repeated eight times, (AGQP)8. It is shown by CD measurements that the presence of proline in these repeats induces an increase in beta-sheet (beta-turn) content in the (NANP)8 peptide relative to the repeat of (NANG)8 and PK(1-24) peptide in aqueous media. The (AGQP)8 peptide has the highest beta-sheet (beta-turn) content of all peptides studied. The Chou-Fasman predictive algorithm indicates a high beta-turn content in the synthetic peptides. It is concluded that this increase in defined structure correlates well with and hence may contribute to the increased antigenicity in these repeats.

Amino Acids↗

Assessment of bilirubin clearance capacity of a newly developed ion-exchange adsorption column and its possible use as a supportive therapy in hepatorenal syndrome.

We assessed the bilirubin reduction capacity of three different types of devices in vitro: a high-permeable membrane column for double-filtration plasmapheresis (DFP) (Evaflux 2A, Kuraray, Japan), and non-coated charcoal column for hemoperfusion (HP) (N-180, Asahi Medical, Japan), and ion-exchange columns for plasma adsorption (PA) (BR-350, Asahi Medical, Japan, and B-001, Kuraray, Japan). A column for DFP reduced the concentration of low-molecular proteins effectively such as plasma bilirubin and bile acids in an albumin-dependent manner. A charcoal column adsorbed low-molecular substances preferentially. But in these two columns, the loss of fibrinogen is a limiting factor for determining the processing plasma volume. Ion-exchange columns for PA adsorbed bile acids, disconjugated bilirubin, and monoconjugated bilirubin more efficiently compared with delta-bilirubin and unconjugated bilirubin. Pretreatment of the column with heparin reduced the loss of fibrinogen to less than 10%. We applied the BR-350 ion-exchange column in vivo for treatment of three patients with hyperbilirubinemia. After treatment, an alcoholic hepatitis patient with the hepatorenal syndrome (HRS) recovered from acute renal failure. However, in a patient with primary biliary cirrhosis and in a patient with fulminant hepatitis, the decrease of serum bilirubin was transient and no obvious beneficial responses were noted. The capacity and ability of the BR-350 column to adsorb plasma bilirubin was shown sufficient to treat deeply jaundiced patients, because 4 liters of the plasma of a patient with 108 mg/dl of initial total bilirubin concentration was able to be processed continuously without an obvious decrease in bilirubin adsorption capacity.(ABSTRACT TRUNCATED AT 250 WORDS)

Adsorption↗

Active HSV-1 immunization prevents the cocarcinogenic activity of HSV-1 in the oral cavity of hamsters.

Previous investigations have demonstrated that herpes simplex virus (HSV) increased the oral carcinogenic activity of 7,12-dimethylbenz[a]anthracene (DMBA) probably by enhancing the DMBA-induced amplification and overexpression of c-erb-B-1 proto-oncogene in hamster buccal pouch epithelium. The present study investigated the effect of active type 1 HSV (HSV-1) immunization on the development of oral cancer induced by HSV-1 and DMBA, alone or in combination, in the hamster buccal pouch. The results were similar to our previous report in that HSV-1 significantly enhanced the oncogenic effect of DMBA, and the numbers of pouches harboring tumor nodules and the numbers and sizes of tumors developed by topical DMBA were significantly increased by HSV-1 inoculation to the site of the DMBA application. Although HSV-1 immunization did not alter the carcinogenic activity of DMBA in animals receiving topical DMBA in combination with mock inoculation, it prevented the cocarcinogenic effect of HSV-1 in animals receiving topical DMBA in conjunction with HSV-1 inoculation. These data indicate that active HSV-1 immunization completely obstructs the co-oncogenic effect of HSV-1 in the oral cavity of hamsters.

9,10-Dimethyl-1,2-benzanthracene↗

Morphological characterization of surface-induced platelet activation.

Morphological changes of platelets activated on glass and dimethyldichlorosilane-treated glass were investigated using video microscopy. The platelet morphological changes were quantified by measuring the area and circularity of spreading platelets. In addition, re-organization of cytoskeletal structures of spread platelets was examined. The effects of precoated albumin and fibrinogen on the platelet spreading kinetics were examined as a function of surface protein concentrations. Results showed that platelet shape changes were very sensitive to the surface concentration of precoated proteins. In general, platelets on fibrinogen-precoated surfaces spread fully to a circular shape and developed an extensive inner filamentous zone. In the presence of albumin on the surface, however, platelets could not spread fully and the development of the inner filamentous zone was very poor. For both albumin and fibrinogen, the maximum effects of precoated proteins on platelet shape changes were observed when the surface protein concentration reached the monolayer concentration.

Adsorption↗

Interleukin-2 induces motility of human lymphocytes, but not their mobility.

Interleukin-2 induces cytotoxic and antitumor activities of human lymphocytes. For the expression of these activities, the cytoskeletal system is probably activated. This study was do;ne to find if interleukin-2 causes cell movement. Lymphocytes were incubated with interleukin-2, and their morphology and motile activities were studied. After 72 hr of incubation, some 29% of lymphocytes were larger than before; nucleoli had formed and the microvilli were well-developed. The membrane potential of the lymphocytes increased during incubation. Motility under agar after 3 days of incubation with interleukin-2 was examined. Cells aggregated in clumps in the incubation well, and migration was not observed. When mobility was examined with Boyden's method, fewer cells incubated with interleukin-2 migrated than in control preparations. Cells incubated with interleukin-2 were extracted with Triton X-100. The extract obtained had three more bands on sodium dodecyl sulfate-polyacrylamide gel electrophoresis than the controls. The band were at the positions for the molecular weights of 270,000-300,000. We concluded that interleukin-2 activated the motility of lymphocytes, but not their mobility.

Cell Aggregation↗

Biochemical and mechanical characterization of enzyme-digestible hydrogels.

Albumin-cross-linked hydrogels were prepared by free radical polymerization using 1-vinyl-2-pyrrolidinone as a monomer and functionalized albumin as a crosslinking agent. The degree of chemical cross-linking was controlled by varying the degree of albumin functionality and the concentration of albumin. With emphasis placed on the potential use of these hydrogels for long-term oral drug delivery, gel characterization studies examined both the swelling and the mechanical properties in the absence and presence of pepsin. In the absence of pepsin, the equilibrium swelling ratio in simulated gastric fluid ranged from 17 to 55, depending on the degree of albumin functionality and the albumin concentration. Swelling was pH dependent at pH's greater than 7. The uptake of solvent into the dried hydrogels was determined to be Fickian. The integrity of swelling gels was dependent on the concentration of the functionalized albumin as well as on the degree of albumin functionality. In the presence of pepsin, a predominance of either surface or bulk degradation was observed, depending on the functionality of the albumin used as a cross-linker. Gel integrity during pepsin degradation also showed a marked dependence on the albumin functionality.

Drug Carriers↗

Goblet cell carcinoid of the appendix.

We have reviewed all cases of goblet cell carcinoid in the Department of Pathology, Edinburgh University. Of the 10 cases identified, two had died as a result of the tumour. This would suggest a poorer prognosis than is generally recognized. Those patients who subsequently had progression of their disease were not predicted by histological criteria. Because of the unpredictable behaviour of these tumours we recommend that such patients should correctly be treated by a right hemicolectomy.

Adult↗

Protein adsorption on polymer surfaces: calculation of adsorption energies.

In an attempt to understand the mechanisms of protein adsorption at the solid-liquid interface, we have calculated the interaction potential energy between the protein and the polymer surface by a computer simulation approach. The adsorption of four proteins--lysozyme, trypsin, immunoglobulin Fab, and hemoglobin--on five polymer surfaces was examined. The model polymers used for the calculation were polystyrene, polyethylene, polypropylene, poly(hydroxyethyl methacrylate), and poly(vinyl alcohol). All possible orientations of the protein on the polymer surfaces were simulated and the corresponding interaction energies for the initial contact stage of protein adsorption were calculated. In the calculation of interaction energies, the hydrophobic interaction was not treated explicitly owing to the difficulty in the theoretical treatment. The results showed that the interaction energy was dependent on the orientation of the protein on the polymer surfaces. The energy varied from -850 to +600 kJ/mol with an average of about -155 kJ/mol. The interaction energy was also dependent on the type of polymer. The average interaction energies of the four proteins with poly(vinyl alcohol) were always lower than those with the other polymers. The interaction energy was not dependent on the protein size. It was found that the dispersion attraction played the major role in protein adsorption on neutral polymer surfaces.

Adsorption↗

[Expression of major histocompatibility complex on human medulloblastoma cells].

Medulloblastoma is one of the most common malignant brain tumors in childhood. These cells are immature bipotential cells that could differentiate into both neuronal and glial cells. The authors established two human medulloblastoma cell lines. One was derived from a 2-year-old girl with cerebellar tumor (designated as ONS-76) and another was from a 9-year-old girl with metastatic tumor in the right frontal lobe (ONS-81). Immunohistochemical studies showed that both cell lines possessed 145 and 200 kDa neurofilament proteins and neuron-specific enolase, without glial fibrillary acidic protein and S-100 protein. It was shown that interferon gamma could enhance or induce the expression of the major histocompatibility complex (MHC) antigens which play a major role in immune response. Also shown for the first time was the expression of MHC class II antigens on human medulloblastoma (ONS-76 and 81) with neuronal differentiation.

Cerebellar Neoplasms↗

Experimental intraocular fibrovascular proliferation through sclerotomy wound.

In the process of closing scleral wounds caused by various conditions, incarceration of conjunctiva, Tenon's capsule, or vitreous in the wound can occur unexpectedly. We created such conditions experimentally in order to discover their intraocular complications. The experimental materials consisted of 12 albino rabbits (24 eyes) divided into two groups (Groups I & II). Vitrectomy was performed in the Group I rabbits (12 eyes) but not in the Group II rabbits (12 eyes). Flaps of conjunctiva and Tenon's capsule were made and inserted into the vitreous cavity through the sclerotomy site, which was soon closed. Fundal examination of the rabbits was carried out using an indirect ophthalmoscope at intervals after the procedure; first at 3 days, then at 1, 3, and 6 weeks, and then at 3 months and 6 months, respectively. Enucleation of the rabbits' eyes 4 from two different rabbits at each of these intervals was carried out, and the extracted eyes were examined under a light microscope at each interval. The results are summarized as follows: 1. All rabbit eyes studied showed intraocular fibrovascular proliferation. 2. The extent of tissue proliferation, which was proportional to the amount of vitreous hemorrhage, was greater in Group II than in Group I. 3. The proliferated tissue developed to "band" by three weeks postexperiment, after which it gradually regressed. 4. The fibrovascular band was made of fibroblasts, stromal matrix, and capillaries.

Animals↗

A high density cell culture system for generation of human lymphokine-activated killer (LAK) cells for clinical use in adoptive immunotherapy.

A high density cell culture system has been developed for large-scale production of lymphokine-activated killer (LAK) cells from peripheral blood lymphocytes (PBLs) of malignant tumor patients. The system consists of a culture bag, which has two compartments separated by a semipermeable membrane, and an external rotator. The system allows for a long-term, at least 4 weeks, culture of LAK cells at high cell density in the inner compartment. The collected PBLs were first divided between the two culture bags and cultured without harvesting for 7-10 days to obtain LAK cells. Half of the LAK cells from each bag was administered to patients twice a week for clinical trials. Culture of the remaining half was continued following addition of a fresh culture medium. LAK cells were transferred to patients alternatively from each bag for the following 2-3 weeks. The total number of LAK cells administered amounted to 3.9-9.8 (mean 5.8) times more than the PBLs collected by leukapheresis (n = 10). The 5 x 10(6)/ml of PBLS of the initial concentration reached a maximum of 2 x 10(7)/ml. Our system does not need for a CO2 incubator. Cytotoxicity of the LAK cells was evaluated in 4 hr 51Cr release assays. Mean cytotoxicity at maximum cell density was 95.4 +/- 3.2% against ONS-12 (a human glioma cell) and 84.8 +/- 3.0% against Daudi cells (n = 10), but gradually decreased to about 50% at the end of fourth week of the culture period. Cell viability of the LAK cells was normally over 80% through the entire culture period.(ABSTRACT TRUNCATED AT 250 WORDS)

Antigens, CD↗

Evaluation of serum sialyl Lewisx-i in hematologic disorders.

Sialyl Lewisx-i (SLX) was found in more than 40% of patients with acute leukemia or chronic myelogenous leukemia, and in about 20% of those with myelodysplastic syndrome or malignant lymphoma. This tumor marker was absent in all patients with polycythemia vera, essential thrombocythemia, primary myelofibrosis, chronic lymphatic leukemia, multiple myeloma, and those with acute leukemia or malignant lymphoma in remission. The marker was found in 8% and of the patients with idiopathic thrombocytopenic purpura and 33% of those with autoimmune hemolytic anemia but in no patient with aplastic anemia or megaloblastic anemia. Immunostaining with SLX antibody showed that tumor cells of the patients with high levels of serum SLX were producing the SLX antigen. The detection of this marker in the serum is thought to be useful not only in the diagnosis but also in the observation of the recurrence of the diseases.

Antigens↗