Biomedical subjects

M Ichikawa

Publications and source records attributed to M Ichikawa.

At least 253 records · Page 14Linked to original sources

PubMed1991

A new multiple-unit oral floating dosage system. II: In vivo evaluation of floating and sustained-release characteristics with p-aminobenzoic acid and isosorbide dinitrate as model drugs.

In a previous study, we developed a multiple-unit type of oral floating dosage system, which is a new type of floating pill composed of both an effervescent layer and a swellable membrane layer coated on sustained-release pills. The system was shown to have excellent floating ability and sustained-release characteristics in vitro, irrespective of the pH and viscosity of the medium. In the present study, the floating ability and the sustained-release characteristics of the system in the gastrointestinal tract have been evaluated in vivo. In beagle dogs and humans in the fed state, most of the new type of pills containing barium sulfate were floating in the stomach at 10 min, and they kept floating for at least 3 h after administration (observed by periodic X-ray photographs), while some control pills without the effervescent layers were already transited into the small intestine by 3 h. Moreover, in order to evaluate the sustained-release characteristics of the drug from the new type of floating pills, p-aminobenzoic acid (PABA), with a limited absorption site, and isosorbide dinitrate (ISDN), with wide absorption sites in the gastrointestinal tract, were employed as model drugs. Floating pills of the new type, with the same sustained-release rate as that of non-floating pills (control pills) were prepared. In beagle dogs in the fed state, the new type of floating pills containing PABA showed higher plasma PABA levels at 5 and 6 h after dosing and 1.61 times greater AUC than the control pills.(ABSTRACT TRUNCATED AT 250 WORDS)

4-Aminobenzoic Acid↗

PubMed1991

Anticalmodulin drugs block the sodium gating current of squid giant axons.

The effects of calmodulin (CaM) antagonists (W-7, W-5, trifluoperazine, chlorpromazine, quinacrine, diazepam, propericyazine and carmidazolium) on the sodium and potassium channels were studied on the intracellularly perfused and voltage-clamped giant axon of the squid. It was found that the drugs are more potent blockers of the sodium current than of the potassium current. The drugs also reduce the sodium gating current. The blockage of the sodium and gating current can be explained by assuming that the drugs interact with the sodium gating subunit in one of its closed states. The site of action is probably the intracellular surface of the axolemma where presumably a Ca(2+)-calmodulin complex can be formed.

Animals↗

PubMed1991

Animal model, virology and gene cloning of hepatitis E.

We have developed animal models of viral hepatitis E using cynomolgus and rhesus monkeys. They developed acute biochemical and histological hepatitis after the inoculation of virus particles with identical kinetics and magnitude for the sixth subpassage. Virus particles multiplied in hepatocytes and were excreted into feces via bile. Additionally, a transient viremia was recognized. Molecular cloning of virus gene cDNA was successfully accomplished from two separate libraries (HT3 and NE). These clones were expressed into polypeptides having immunological epitopes, which were used for antibody assay of sera of monkeys and patients with positive results.

Animals↗

PubMed1991

Impaired expression of interleukin 2 receptors in childhood acute lymphoblastic leukemia.

Peripheral blood mononuclear cells (PBMC) from acute lymphoblastic leukemia (ALL) patients were studied for the expression of interleukin 2 receptors (IL-2R). When stimulated with phytohemagglutinin (PHA) for 3 days, the percentage of p55 Tac positive cells and the number of high affinity IL-2R was decreased in on-therapy ALL patients at remission and returned to normal after cessation of the treatment. However, the percentage of p75 IL-2R positive PBMC was normal in all ALL patients at remission. It is well-known that there are several immunological abnormalities including T and natural killer (NK) cell dysfunctions in ALL patients undergoing maintenance chemotherapy. IL-2 facilitates T-cell growth and corrects defective NK activity. Taking this into account, there may be a poor utilization of autologously produced IL-2 because of the impaired expression of IL-2R, and this poor utilization of IL-2 may be related to the defective immunological functions in childhood ALL patients at remission who are receiving maintenance chemotherapy.

Adolescent↗

PubMed1991

Expression of synaptophysin during synapse formation between dissociated cortical neurons.

Cerebral cortical cells from fetal rats (14 days) were cultured in vitro (7-104 days). Localization of synaptophysin was examined immunocytochemically using a monoclonal antibody (SY-38) against synaptophysin. Synaptophysin-immunoreactive (SP-IR) spots were distributed on the surface of the cells. Electron-microscopic observation showed that the SP-IR staining was localized at presynaptic terminals, indicating that the SP-IR spots observed will, fluorescence microscopy represent presynaptic terminals. The time-course of the distribution of SP-IR spots was examined. SP-IR spots could not be observed in cells at 7 days in vitro (DIV). At 14 DIV, SP-IR spots could be first observed on the surface of cell bodies and neurites. Thereafter, the density of SP-IR spots on the cell bodies and neurites increased with DIV. At 42 and 104 DIV, SP-IR spots were almost continued, surrounding the neurites and cell bodies of the cultured cells. These immunocytochemical studies suggest that the dissociated 14-day fetal cerebral cortical neurons make synapses by at least 14 DIV and that the density of synapses increases with time.

Animals↗

PubMed1991

Changes in serum glucocorticoid levels and thymic atrophy induced by phenytoin administration in mice.

The weights of spleen and thymus were recorded and serum glucocorticoid (GC) levels examined in mice injected intraperitoneally with 60 mg phenytoin (PHT) kg body wt. for 3, 8, and 30 days. In mice injected with PHT, the serum GCs were elevated about 4- to 5-fold in 3 days; the higher levels were maintained and accompanied thymic atrophy throughout the experiment. Moreover, dose-dependent changes in serum GC levels and thymus weight were also observed at 3 days. These results indicate that GCs may play an important role in thymic atrophy induced by PHT.

Animals↗

PubMed1991

Cloning and expression of cDNAs from enterically-transmitted non-A, non-B hepatitis virus.

The fragment gene of enterically-transmitted non-A, non-B hepatitis virus (ET-NANBHV) was cloned as a cDNA and inserted into an expression vector pUEX2. The recombinant protein was expressed in Escherichia coli HB101 as a fusion protein with beta-galactosidase (beta-Gal). The fusion protein reacted with the sera of infected cynomolgus monkeys and of patients from Myanmar. This reaction was highly related with ET-NANBHV infection, and obviously demonstrates in that the recombinant protein can be used for the detection of ET-NANBHV infection.

Amino Acid Sequence↗

PubMed1991

Primary gastric T-cell lymphoma with manifold histologic appearances.

A rare case of malignant T-cell lymphoma with manifold histologic appearances was described. The lymphoma occurred in the stomach of a 50-year-old Japanese male. Grossly, the lymphoma exhibited a deeply ulcerated mass. Histologically, in addition to diffuse infiltrate of large lymphoid cells with deeply indented nuclei, there were many epithelioid cell granulomas, remarkable tissue eosinophilia and stromal fibrosis, mimicking inflammatory disease. Immunohistochemical studies and a gene analysis demonstrated the T-cell phenotype.

Biomarkers, Tumor↗

PubMed1991

Primary malignant lymphoma of the rectum with diagnostic problems. Report of two cases with an analysis of gene rearrangement.

We present two similar cases of rectal B-cell lymphoma with diagnostic problems. Grossly, both tumors appeared as a well demarcated polypoid mass with eroded mucosa. In spite of their histologic resemblance to reactive lymphoid hyperplasia, including the presence of lymph follicles, fibrosis and polyclonal plasma cells, both cases were diagnosed as malignant lymphoma of low-grade malignancy because of the full-thickness involvement of the rectum with diffusely infiltrated small or medium-sized lymphoid cells showing rare mitoses. In one case, clonal proliferation of differentiated B cells was demonstrated by analysis of gene rearrangement. Therapeutic problems related to low-grade malignant lymphoma in the rectum are also discussed.

Adult↗

PubMed1991

Japanese encephalitis virus neurotropism is dependent on the degree of neuronal maturity.

In a study on Fischer rats, all animals infected with Japanese encephalitis virus (JEV) before the age of 13 days died, but animals infected after the age of 14 days did not die, confirming the age-dependent resistance to JEV infection in the rat brain. A study of the kinetics of JEV infection in the developing rat brain disclosed that JEV antigen disappeared in a particular pattern, i.e., from the deeper layers to the upper layers of the motor cortex, which paralleled neuronal maturation in the cortex. Fifteen-day-old rats, which were resistant to JEV infection, received intracerebral transplants of neurons taken from 19-day embryos. When these animals were infected with JEV after transplantation, viral antigen was detected only in the embryonal neurons soon after transplantation. Thus, it can be concluded that the susceptibility to JEV infection in the rat brain is closely associated with neuronal immaturity.

Aging↗

PubMed1991

Role of vasopressin in salt-induced hypertension in baroreceptor-denervated uninephrectomized rabbits.

To elucidate the contributions of renal, humoral, and arterial baroreceptor reflex components to salt-induced hypertension, we administered 10% NaCl intravenously for 10 days to sinoaortic-denervated rabbits with unilateral nephrectomy (n = 7), sinoaortic-denervated rabbits with intact kidneys (n = 7), and sham-operated sinoaortic-denervated rabbits with unilateral nephrectomy (n = 7). Serial changes in mean arterial pressure (MAP), heart rate, and blood pressure variability were recorded. In sinoaortic-denervated rabbits with unilateral nephrectomy, MAP increased significantly from 109 +/- 2 to 124 +/- 3 mm Hg (day 4) and remained elevated for the rest of the experiment. This elevation of MAP was accompanied by a reduction in the standard deviation of MAP, with significant elevations in plasma vasopressin, norepinephrine, and atrial natriuretic peptide concentrations and in sodium retention. In the other groups, there were no significant changes in these vasoactive hormones. In the sham-operated sinoaortic-denervated rabbits with unilateral nephrectomy, sodium retention was similar to that of sinoaortic-denervated rabbits with unilateral nephrectomy. Continuous infusion (1 microgram/kg/hr) of a V1 antagonist prevented the elevation of blood pressure and plasma norepinephrine, the accumulation of sodium, and the reduction of blood pressure lability, whereas a bolus injection (10 micrograms/kg) on day 4 reduced blood pressure from 128 +/- 3 to 115 +/- 2 mm Hg (p less than 0.005). These results imply that vasopressin plays a crucial role in the expression of salt-induced hypertension in rabbits with compromised baroreceptor and renal function.

Animals↗

PubMed1991

Localization of cephalosporinase in Enterobacter cloacae by immunocytochemical examination.

Enterobacter cloacae NUH10 was isolated at Nagasaki University Hospital in 1987. E. cloacae NUH10 is a mutant strain which produces high levels of cephalosporinase. E. cloacae ATCC 23355 is known to be sensitive to so-called third generation cephems and produces an inducible cephalosporinase. The polyclonal antibody to cephalosporinase extracted from E. cloacae NUH10 was utilized in post-embedding immunogold labeling in order to localize this protein in E. cloacae ATCC 23355 and E. cloacae NUH10. Immunocytochemical localization of the cephalosporinase in both strains was observed with and without incubation with an inducer. Cephalosporinase was detected in both the cytoplasm and periplasmic space of E. cloacae ATCC 23355 and E. cloacae NUH10 incubated in medium including cefoxitin as an inducer. In the case of incubation without the inducer, a small quantity of cephalosporinase was located in the periplasmic space in either strain of bacteria. Western blot analysis showed that cephalosporinase was predominantly localized in the periplasmic space rather than in the cytoplasmic space.

Anti-Bacterial Agents↗

PubMed1991

[Superior vena cava syndrome as initial symptom of Vasculo-Behçet's disease--case report].

A 26-year-old woman with a history of recurrent spontaneous abortion was admitted because of superior vena cava syndrome. Chest computed tomography and digital subtraction angiography revealed obstruction of the superior vena cava by a thrombus. After admission she also developed oral aphthous ulceration, erythema nodosum, and positive cutaneous hypersensitivity reaction to intradermal injection of saline. Laboratory investigations revealed HLA-B51 and positive lupus anticoagulant. We made the diagnosis of Vasculo-Behçet's disease and treated her with heparin and urokinase with no clinical improvement. The fever subsided after prednisolone administration. Two years later, superior vena cava syndrome had slightly improved, although RI venography showed complete obstruction of the superior vena cava with development of collateral circulation. Endoscopic examination showed downhill esophageal varices. It is of note that the initial symptom in this case of Vasculo-Behçet's disease was superior vena cava syndrome, and that lupus anticoagulant may have contributed to the thrombus formation.

Adult↗

PubMed1990

Gonadotropin-releasing hormone (GnRH) immunoreactive system in the brain of the dwarf gourami (Colisa lalia) as revealed by light microscopic immunocytochemistry using a monoclonal antibody to common amino acid sequence of GnRH.

The present paper aims to give a morphological basis for the study of the terminal nerve system and its relation to the whole gonadotropin-releasing hormone (GnRH) immunoreactive (ir) neuronal system. We examined the GnRH-ir neuronal system of a tropical fish, the dwarf gourami, by using a recently developed monoclonal antibody against GnRH (LRH13) which recognizes the amino acid sequence common to all known variants of GnRH (Park and Wakabayashi, Endocrinol. Jpn. 33:257-272, '86). The ganglion cells of the terminal nerve (TN-ggl cells) in the transitional area between the olfactory bulb and the telencephalon reacted strongly with the LRH13. A distinct bundle of axons emanating from the TN-ggl cells ran caudally through the ventral telencephalon and the preoptic area. Some of these axons entered the optic nerve and innervated the retina. The remaining axons continued caudally to enter the hypothalamus and the midbrain. A second group of GnRH-ir cell bodies was found in the preoptic area. A distinct bundle of GnRH-ir fibers originating from these cell bodies innervated the pituitary. This pathway is equivalent to the preoptico-infundibular pathway of other vertebrates, and the GnRH in this pathway is presumed to function as hypophysiotrophic hormone to facilitate the release of gonadotropins from the pituitary. The distribution of GnRH-ir fibers in the brain was extensive. Most fibers apparently originated from the TN-ggl cells and covered various brain regions from the olfactory bulb to the spinal cord. They were especially abundant in the olfactory bulb, ventral telencephalon, preoptic area, optic tectum, and some hypothalamic areas. Thus, GnRH might function as a neuromodulator and/or neurotransmitter in these areas. The abundant GnRH-ir fibers in the ventral telencephalon and the preoptic area might affect some aspects of sexual behavior, since these areas have been suggested to be involved in the control of sexual behavior in teleosts.

Animals↗

PubMed1990

Novel screening method for agents that overcome classical multidrug resistance in a human cell line.

P-glycoprotein (P-gp) is involved in the transport of a wide variety of organic compounds including a fluorescent dye, rhodamine 6G (RG), as well as anti-cancer drugs. Agents that overcome classical multidrug-resistance (MDR) increased the accumulation of RG in a MDR cell line, KB-C1. The effect of agents on RG-accumulation in KB-C1 cells was highly correlated with their effect on the reversion of vincristine-resistance in KB-C1 cells. RG was detected on a fluorescence microplate reader with a rhodamine channel. This assay may become a useful method for the screening of agents that overcome classical MBR, since it is quick and simple.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed1990

Modulators of the multidrug-transporter, P-glycoprotein, exist in the human plasma.

P-glycoprotein (P-gp) is thought to mediate the transport of anticancer drugs and to be responsible for the multidrug-resistant (MDR) phenotype. P-gp is also expressed in normal human tissues, such as the adrenal gland, kidney, liver, colon and capillary endothelium of the brain. However, the function and transporting substrates of P-gp in normal tissues are still not understood. This paper explains that some compounds in the human plasma can modulate the transporting activity of P-gp. A partially purified fraction from the human plasma enhanced the accumulation of anti-cancer agents in MDR cells. This fraction inhibited the efflux of vinblastine from MDR cells, and also inhibited the photoaffinity labeling of P-gp with azidopine as effectively as vinblastine, quinidine and cepharanthine. The compounds in this purified fraction may be physiological substrates of P-gp and can probably overcome MDR.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed1990

Birth of normal calves resulting from bovine oocytes matured, fertilized, and cultured with cumulus cells in vitro up to the blastocyst stage.

Bovine oocytes matured in vitro were fertilized in high proportions (92% of matured oocytes) by sperm capacitated with Ca ionophore A23187. Eight percent of inseminated oocytes that were denuded 96 h after insemination developed to the morula stage when cultured for 6-120 h after insemination with cumulus cells from the original oocytes. Inseminated oocytes denuded 96 h after insemination developed to the blastocyst stage when cultured with or without cumulus cells or in the conditioned medium from 96 h to 168-216 h after insemination (9.0%, 8.1%, and 6.8% of inseminated oocytes respectively). Six frozen-thawed blastocysts were transferred nonsurgically to 3 recipients (2 embryos/recipient). Two of the 3 recipients became pregnant, with one delivering live twins at term. Seven fresh blastocysts were transferred nonsurgically to 6 recipients (1-2 embryos/recipient). Three of the 6 recipients became pregnant, with 2 delivering live calves.

Animals↗

PubMed1990

Expression of the multidrug transporter, P-glycoprotein, in chronic myelogenous leukaemia cells in blast crisis.

The overexpression of a cell-surface glycoprotein termed P-glycoprotein (P-gp) is frequently associated with multidrug resistance (MDR) in cell lines in vitro. To evaluate the implications of P-gp expression in clinical drug-resistance, we examined the expression of P-gp in fresh leukaemia cells from chronic myelogenous leukaemia (CML) patients in blast crisis. By using immunoblotting with a monoclonal antibody against P-gp, C219, we showed that leukaemia cells from three CML patients in blast crisis were P-gp negative at the stage when these patients were in complete remission, and that the cells showed high levels of P-gp expression at times when the same patients had relapsed and had not responded to chemotherapy. Six out of 11 patients (nine in the refractory state) were P-gp positive and they rarely responded to chemotherapy. These data suggest that the expression of P-gp is closely associated with drug-resistance in CML.

ATP Binding Cassette Transporter, Subfamily B, Mem↗