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Biomedical subjects

H Kojima

Publications and source records attributed to H Kojima.

At least 415 records · Page 23Linked to original sources
PubMed1994

[Hereditary spherocytosis associated with non-Hodgkin's lymphoma in the spleen].

A 60-year-old female was admitted complaining of anemia. We diagnosed her hereditary spherocytosis (HS) from spherocytosis and family history and found a tumor in her enlarged spleen. Splenectomy was performed and swollen paraaortic lymph nodes were found at laparotomy. The tumor in the spleen was diagnosed as Non-Hodgkin's lymphoma (follicular mixed type). After CHOP therapy she entered complete remission. Though the relationship between HS and malignant lymphoma was not clear, splenomegaly due to hemolysis inducing chronic stimulation might have resulted in malignant lymphoma.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1994

Establishment of a new natural killer (NK) cell line, TKS-1, from a patient with aggressive type of large granular lymphocyte (LGL) leukemia.

A new NK cell line, designated as TKS-1, was established from the peripheral blood of a patient with large granular lymphocyte (LGL) leukemia which showed highly aggressive clinical course. The original leukemic cells, which had a surface phenotype of CD2+, CD3-, CD16-, and CD56+, proliferated well in the presence of 200 U/ml of interleukin-2 (IL-2). Morphologically, TKS-1 cells had immature nuclei and abundant cytoplasm with fine azulophilic granules. Surface phenotype of the cell line was CD2+, CD3-, CD16-, CD57-, and CD56-, CD56 antigen disappearing during the culture. Analyses of T-cell receptor (TCR) beta- and gamma-chain genes showed germ line configurations. Functionally, TKS-1 cells showed significant cytotoxicity against K562, Raji, and Daudi target cells. We consider that TKS-1 cells originated from CD16-negative immature type of peripheral blood NK cells. This cell line will be useful not only for the investigation of NK cell leukemia, but also for that of the mechanism of cytotoxicity mediated by normal NK cells.

Adult↗
PubMed1994

[Current status and issues in clinical trials of anticancer agents].

NDA filing and government approval for drug manufacturing marketing rights are processes based on collaboration among the concerned parties; a drug manufacturer (or importer), a medical institution and a government agency. However, quality guidelines are necessary for a scientific, ethical and economically efficient clinical study to be conducted. It is more than 3 years since the Ministry of Health and Welfare of Japan introduced "The Guidelines on Clinical Evaluation for Anti-tumor Drugs" in February, 1991. However, some practical problems have been pointed out by clinicians for revision. Among them we discuss the following items for revision of the Guidelines and made suggestions and opinions from the manufacturers' point of view: Phase I: Number of institutions for clinical study, determination of MTD and study design. Phase II: Introduction of foreign data, late phase II study for plural numbers of indications at time of NDA filing and evidence of usefulness in concurrent therapy.

Antineoplastic Agents↗
PubMed1994

General pharmacological profile of the new cognition-enhancing agent nefiracetam.

The general pharmacological properties of a novel cognition-enhancing agent, nefiracetam (N-(2,6-dimethylphenyl)-2-(2-oxo-1-pyrrolidinyl)acetamide, DM-9384, CAS 77191-36-7) were investigated, and the following results were obtained. 1. Central nervous system: Nefiracetam showed depressant activities (such as ataxia) on general behavior (mice), and inhibited spontaneous locomotor activity, rota-rod and traction performances (mice) and polysynaptic potential of the spinal reflex (rats), and potentiated pentobarbital anesthesia (mice). The drug inhibited electroshock-induced seizure at relatively low doses, but did not affect chemoshock-induced seizure (mice). Nefiracetam failed to show analgesic activity in the tail pinch test, but inhibited the acetic acid-induced writhing syndrome (mice). An inhibitory pattern in the electroencephalogram was observed (cats). Nefiracetam had little or no effect on body temperature (rats). 2. Respiratory and cardiovascular systems: Nefiracetam induced transient decreases in blood pressure, left ventricular pressure and LV dp/dt max at higher doses (dogs). 3. Autonomic nervous system: Nefiracetam had no influence on pupil size (rabbits). The drug induced no significant effect on the pressor response to norepinephrine or depressor response to acetylcholine, but inhibited the contractile response of the nictitating membrane to preganglionic cervical sympathetic nerve stimulation at the highest dose (dogs). 4. Gastrointestinal system: Nefiracetam inhibited gastrointestinal propulsion (mice), gastric emptying rate and gastric secretion (rats) at higher doses. Nefiracetam produced no apparent damage in the gastric mucosa, and had no effect on bile secretion (rats). 5. Isolated smooth muscle: Nefiracetam had no effect on the resting tonus of isolated ileum, whereas it inhibited the contractile response to acetylcholine, histamine, serotonin, nicotine and BaCl2 at higher concentrations (guinea pigs). Nefiracetam had no effect on the resting tonus or the serotonin-induced contraction of stomach fundus (rats). The drug had no effect on the resting tonus or the norepinephrine-induced contraction of vas deferens, but tended to inhibit the contraction induced by nerve stimulation (guinea pigs). Nefiracetam had little or no effect on the resting tonus or oxytocin-induced contraction of virgin uterus, or on spontaneous contraction of pregnant uterus (rats). Nefiracetam did not affect the resting tonus of trachea, whereas it inhibited isoproterenol-induced relaxation at the highest concentration (guinea pigs). Nefiracetam had no chronotropic effect in isolated atria, but showed a slight negative inotropic effect at the highest concentration (guinea pigs). 6. Miscellaneous: Nefiracetam slightly decreased urinary volume, whereas it did not affect urinary electrolyte excretion (rats).(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1994

[Salvage chemotherapy for relapsed/refractory aggressive non-Hodgkin's lymphoma with a combination of dexamethasone, etoposide, ifosfamide and carboplatin].

Seventeen patients with refractory or relapsed, intermediate or high grade non-Hodgkin's lymphoma (NHL) were treated with the combination of dexamethasone (40 mg/body x 3d, iv) (DeVIC) between January and December 1992. The treatments were repeated every three weeks for a minimum of two courses unless the patient had PD. G-CSF (2 micrograms/kg, sc) was given during leukopenia in most cases. Of 16 evaluable patients 6 (38%) achieved a complete remission (CR) and 4 showed a partial remission. With median follow up of 15 (7-26) months (mos.) all CR patients were alive in CR, except for 1 patient who died of secondary AML. The actuarial 50% survival duration after DeVIC was 15+ mos. One patient died of sepsis but myelosuppression was generally moderate and no other serious toxicity was observed. Although this is a preliminary study, DeVIC regimen seems to be an effective salvage therapy for patients with refractory or relapsed NHL with acceptable toxicity.

Adolescent↗
PubMed1993

Successful treatment of a patient with adult T-cell leukemia by daily oral administration of low-dose etoposide. Decrease in the amount of HTLV-I proviral DNA revealed by the polymerase chain reaction method.

BACKGROUND: Oral administration of low-dose etoposide is known to be effective against various malignancies, including malignant lymphoma. However, the effectiveness of low-dose etoposide as a treatment for adult T-cell leukemia (ATL) has not been established. METHODS: A 74-year-old woman with ATL in acute phase was treated by daily oral administration of low-dose etoposide (25 mg/m2). The authors assayed changes in the surface markers and the amount of human T-cell lymphotropic virus type I (HTLV-I) proviral DNA in peripheral blood mononuclear cells (PBMC) by using flow cytometry and the polymerase chain reaction (PCR) method, respectively. RESULTS: Before treatment, generalized lymphadenopathy and hepatomegaly were observed. In laboratory examination, the leukocyte count was 13.7 x 10(3)/microliters, with 65% abnormal lymphocytes. The percentages of CD3-, CD4-, and CD25-positive cells in PBMC were 84.4%, 84.4%, and 76.5%, respectively. The serum lactic dehydrogenase (LDH) level was 1376 IU/l (normal range, less than 520 IU/l). After the initiation of treatment, lymph-adenopathy and hepatomegaly disappeared, and the serum LDH level was reduced to the normal level before the 20th day of the treatment. On the 55th day of the treatment, CD25-positive cells had virtually disappeared. In addition, the amount of the proviral DNA in PBMC was reduced to approximately one-tenth by this treatment. Subsequently, the patient was in remission for more than 16 months. No side effects were observed. CONCLUSIONS: Daily oral administration of low-dose etoposide can be a safe and effective treatment for patients with ATL. The authors believe this to be the first report of a patient with ATL in whom complete remission (CR) was achieved by this treatment.

Administration, Oral↗
PubMed1993

Enrichment of interleukin-2-responsive natural killer progenitors in human bone marrow.

Natural killer (NK) cells can be cultured in interleukin-2 (IL-2)-containing medium from selected human bone marrow (BM) cells obtained after the elimination of mature T and NK cells. To isolate and characterize IL-2-responsive NK progenitors in the selected BM cells, we investigated the expression of IL-2 receptors (IL-2R) on these cells. Neither CD25 (IL-2R alpha) nor IL-2R beta antigen was observed on the selected BM cells before culture. However, CD25+ cells without detectable levels of IL-2R beta antigen appeared 24 hours after culture in IL-2-containing medium. Cells were sorted from each fraction of the selected BM cells 24 hours after culture after staining with anti-CD33, anti-CD34, and anti-CD25 monoclonal antibodies. The generation of NK cells (CD3- CD56+ cells) and NK activity were observed only from the CD33-/CD34-/CD25+ cell fraction after culture in IL-2-containing medium. The frequency of IL-2-responsive NK progenitors relative to the fraction was 1/231 (95% confidence range, 1/156 to 1/289), which corresponded to the frequency relative to the total number of selected BM cells when the frequency relative to the CD33-/CD34-/CD25+ cell-fraction was converted according to the percentage of these cells in the total number of selected BM cells. These results indicated that IL-2-responsive NK progenitors were enriched in the CD33-/CD34-/CD25+ cell fraction.

Bone Marrow↗
PubMed1993

Charge-reversion mutagenesis of Dictyostelium actin to map the surface recognized by myosin during ATP-driven sliding motion.

Amino acid residues D24/D25, E99/E100, E360/E361, and D363/E364 in subdomain 1 of Dictyostelium actin were replaced with histidine residues by site-directed mutagenesis. Mutant actins were expressed in Dictyostelium cells and purified to homogeneity. The sliding movement of mutant actin filaments on heavy meromyosin attached to a glass surface was measured to assess the effect of the mutation on the motility of actin. For two C-terminal mutants, force generated by a single actin filament and myosin was also measured. These measurements indicated that both D24/D25 and E99/E100 are involved in ATP-driven sliding, whereas E360/E361/D363/E364 are not essential for ATP-driven sliding and force generation.

Actins↗
PubMed1993

Anticus-lateralis muscle suturing. Treatment of recurrent nerve paralysis.

We have devised a new surgical method that sutures the cricothyroid (anticus) muscle to the paralyzed lateral cricoarytenoid (lateralis) muscle for the dynamic reconstruction of the larynx. Because this method achieved remobilization of the paralyzed vocal cord in dogs, we applied it to seven patients with unilateral recurrent laryngeal nerve paralysis (four patients had postsurgical paralysis and three patients had idiopathic paralysis). We obtained the following satisfactory results: (1) vocal cord tension and voice quality improved in all patients, and (2) in four patients, remobilization of the paralyzed vocal cord was obtained. We believe that this surgical method could serve as a new dynamic method of reconstruction for the treatment of unilateral recurrent laryngeal nerve paralysis.

Anastomosis, Surgical↗
PubMed1993

Remobilization of paralyzed vocal cord by anticus-lateralis muscle suturing.

A new method of dynamic reconstruction by suturing the cricothyroid (anticus) and the lateral cricoarytenoid (lateralis) muscles was devised for the treatment of unilateral recurrent laryngeal nerve paralysis. Eighteen adult dogs underwent this surgical procedure after sectioning a recurrent laryngeal nerve. Immediate postoperative observations revealed a marked increase in tension of the paralyzed vocal cords and remobilization to the median line of 17 of 18 dogs. More than 4 months later, fiberscopic examination revealed a satisfactory adduction of the cords. Electrophysiologic and histologic examination showed reinnervation of the affected lateralis muscle by the external branch of the superior laryngeal nerve. The clinical applications of this surgery may serve as a dynamic reconstruction for unilateral recurrent laryngeal nerve paralysis.

Animals↗
PubMed1993

Rabbit eye irritation caused by wearing toxic contact lenses and their cytotoxicities: in vivo/in vitro correlation study using standard reference materials.

To clarify the relationship between eye irritancy and cytotoxic potential induced by irritant materials, we made lenses coated with standard reference materials (SRMs) prepared from various amounts of zinc diethyldithiocarbamate (ZDEC) and polyurethane (PU). Zinc diethyldithiocarbamate was classified as a mild irritant by the Draize eye irritation test. When ZDEC-SRM coated contact lenses were applied to rabbit eyes, Draize scores increased in proportion to both the ZDEC and PU concentrations used for coating. Furthermore, correlation with the cytotoxic potential (gamma = -0.93) was better than with lactate dehydrogenase (LDH) activities of tears from rabbit eyes wearing these coated lenses (gamma = 0.78). In conclusion, in vivo eye irritancy induced by wearing lenses could be estimated quantitatively with the cytotoxic potentials using a colony assay. Furthermore, we could compare different sensitivities caused by the same set of SRMs among three different sites of tissue. As a result, the order of sensitivity was eye > muscle >> skin.

3T3 Cells↗
PubMed1993

Isolation of a subclonal cell line of PC12 transfected with dexamethasone-regulated ras oncogene: morphological differentiation, biochemical properties, and tumorigenicity.

We have isolated and characterized a new subclonal cell line designated as MR31, which was obtained by transfection of PC12 cells with a glucocorticoid-regulated ras oncogene. The mRNA derived from the c-Ha-ras gene was proved to be expressed on exposure of the MR31 cells to dexamethasone, the highest value being attained at 8 h. MR31 cells rapidly extended neurite-like processes within 24 h in response to dexamethasone as well as nerve growth factor (NGF). The time of onset of neurite outgrowth induced by dexamethasone corresponded to the time when the highest ras mRNA level was observed. The catecholamine content of MR31 cells was found to be twice that of PC12 cells. A time course study on the effects of dexamethasone or NGF on cells showed that the former caused an increase in dopamine, a major catecholamine, to twofold the control level at 48 h after the treatment, while the latter caused a decrease in the dopamine level. These effects on catecholamines were almost the same in MR31 and PC12 cells. The acetylcholinesterase activity of MR31 cells was enhanced by both dexamethasone and NGF, whereas that of PC12 cells was enhanced by NGF, but not by dexamethasone. The changes in acetylcholinesterase activity were correlated with neurite outgrowth. Electron-microscopically, MR31 cells were not different from PC12 cells. MR31 cells exhibited extremely decreased tumorigenicity as compared with PC12 cells. The morphological and biochemical properties of MR31 cells remained constant, even after repeated passages.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

A novel fucosylated glycosphingolipid with a Gal beta 1-4Glc beta 1-3Gal sequence in plerocercoids of the parasite, Spirometra erinacei.

A novel glycosphingolipid (SEGLx) has been isolated from the plerocercoids of a tapeworm, Spirometra erinacei. From the results of compositional analysis, methylation analysis, exoglycosidase hydrolysis, acid hydrolysis, fast atom bombardment mass spectrometry, and proton nuclear magnetic resonance (NMR) analysis, its structure was concluded to be [formula: see text] This is the first report of a glycosphingolipid with a novel carbohydrate structure which is characterized by i) the occurrence of a penultimate glucose molecule attached to the reducing end galactose through a beta 1-3 linkage and ii) the presence of a fucose attached to a glucose through an alpha 1-3 linkage. The ceramide contained sphinganine or 4-D-hydroxy-sphinganine, and either a nonhydroxy fatty acid with 16, 18, 26, or 28 carbon atoms, or hydroxystearic acid. Proton NMR analysis revealed that the chemical species of both the long chain base and fatty acid moieties affect the chemical shifts of the anomeric proton resonances of not only the reducing terminal galactose but also the penultimate glucose.

Animals↗