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Biomedical subjects

A Ogata

Publications and source records attributed to A Ogata.

At least 55 records · Page 3Linked to original sources
PubMed2000

IgD multiple myeloma preceding the development of extensive extramedullary disease without medullary involvement.

We present a unique case of IgD multiple myeloma (MM) preceding the development of extensive extramedullary disease without medullary involvement. A 63-year-old man was diagnosed with IgD-lambda MM when he developed anemia. After 3 months of chemotherapy, he was in complete remission as evidenced by the disappearance of bone marrow (BM) plasmacytosis, monoclonal IgD protein in his serum, and Bence Jones proteinuria. Six months after diagnosis, his disease took an unusual course with the development of plasmacytomas in the skin, without medullary involvement. He then received chemotherapy, resulting in the complete disappearance of the subcutaneous plasmacytomas. Two years after the initial diagnosis, his disease took an aggressive clinical course with retroperitoneal relapse, leading to the patient's death within 1 month. The two separate episodes of extramedullary disease were associated with elevated serum lactic dehydrogenase levels and the absence of plasma cells in the BM. This case provides evidence of two separate transformations of the original malignant MM clone.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2000

Synthesis and serotonin 2 (5-HT2) receptor antagonist activity of 5-aminoalkyl-substituted pyrrolo[3,2-c]azepines and related compounds.

A series of 5-aminoalkylpyrrolo[3,2-c]azepine derivatives was synthesized and their serotonin 2 (5-HT2) receptor antagonist and antiplatelet aggregation activities were evaluated. 5-HT2 receptor antagonist activity was largely determined by the nature of the substituent at the 8-position as well as the aminoalkyl group at the 5-position of the pyrrolo[3,2-c]azepine ring. Compound 18a, 5-[3-[4-(4-fluorophenyl)piperazin-1-yl]propyl]-8-hydroxy-1-methyl- 1,4,5,6,7,8-hexahydropyrrolo[3,2-c]azepin-4-one, was recognized as having potent 5-HT2 receptor antagonist activity with weak alpha1 adrenoceptor blocking activity and no significant D2 receptor binding affinity, while the corresponding isomeric pyrrolo[3,4-c]azepine derivative (22) displayed only weak 5-HT2 receptor antagonist activity. After racemic 18a was resolved directly via diastereomeric salt formation, each enantiomer was evaluated precisely. The 5-HT2 receptor antagonist activity of 18a was found to reside primarily in (-)-18a (which was about 14-fold more potent than (+)-18a in isolated guinea pig arteries). Consequently, (S)-(-)-18a (SUN C5174) displayed the overall best profile with potent 5-HT2 receptor antagonist activity (pA2=8.98+/-0.06) and high selectivity versus other receptors. SUN C5174 showed a marked inhibitory effect on the platelet aggregation induced by serotonin in combination with collagen and adenosine diphosphate (ADP) in canine or human platelet-rich plasma (IC50=6.5 to 16 nM). Moreover, this compound significantly inhibited the mortality rate in mouse acute pulmonary thromboembolytic death induced by collagen and serotonin at oral doses of 0.3 mg/kg or higher. SUN C5174 is currently undergoing clinical evaluation.

Adrenergic alpha-2 Receptor Antagonists↗
PubMed2000

[Development and evaluation of an individuals-oriented information-provision system for outpatients--utility of "drug Usage sheets" and "Drug Information Cards" for patient consultation].

We have implemented an information-provision system for outpatients at the department of pharmacy, University of Tokyo Hospital, in order to comply with the revised Pharmacists' Law by which pharmacists have been obliged to provide patients with information necessary for rational usage of medicine at the time they receive dispensed drugs. This system is linked on-line with the order entry system to print "Drug Usage Sheets" containing important drug information such as therapeutic effects and adverse reactions, as well as photographic color views of drugs. We prepared the sheets by extracting and classifying the original information, and by converting medical terms into lay expressions. Moreover, we developed "Drug Information Cards" to inform each patient of severe side effects and drug interactions, which should affect drug compliance, and implemented an individuals-oriented information system using both the "Drug Usage Sheets" and "Drug Information Cards." In this study, we evaluated the usefulness of this system from the viewpoint of patients' recognition and understanding on necessary drug information. It was indicated from questionnaires to patients that the "Drug Usage Sheets" help most patients understand the names, usage, effects, and general cautions including slight adverse reactions (i.e. grade 1), and that the use of colored letters for important parts and pictograms is a useful method to attract more attention from patients as compared with a conventional method using only letters. Most patients answered that the "Drug Usage Sheets" can be utilized in many ways and valuable in taking drugs with assurance. We formulated the "Drug Information Cards" by information processing: separation of early symptoms of adverse effects into subjective and objective ones and their classification into related organs. Moreover, the brand names of drugs which may cause drug interactions have been listed on the cards so that worsening of adverse reactions and drug interactions can be avoided. Although 14% of the patients answered that they became unsecured when informed on side effects, the percentage of such patients was significantly higher with those who received caution-required drugs for the first time or who have experienced drug side effects before, suggesting the need for combining oral explanation based on each patient's background and understanding on drug adverse effects. In conclusion, an efficient provision of drug information became possible through our integration of necessary drug information in this study, and the individuals-oriented system of drug information was established, which was demonstrated to contribute to the rational usage of medicine.

Drug Information Services↗
PubMed2000

Intramammary application of ozone therapy to acute clinical mastitis in dairy cows.

The infusion of ozone into the inflamed quarter of cows with clinical mastitis was performed and the efficacy of ozone therapy was evaluated. Ozone was infused into the inflamed quarter via a teat canal using ozone gas generating equipment. Nineteen Holstein cows with acute clinical mastitis were divided into two groups: 15 cows treated with ozone therapy, and 4 cows treated with antibiotic therapy. Systemic and local clinical signs, California Mastitis Test scores, the mastitis causing pathogens, electronic conductivity of milk, and somatic cell counts in milk from ozone- and antibiotic-treated quarters, were compared between the groups. Sixty percent (9/15) of cows with acute clinical mastitis treated with ozone therapy, did not require any antibiotics for recovery. This newly developed ozone therapy method was proven to be effective, safe, and cost effective, and carries no risk of drug residues in milk.

Acute Disease↗
PubMed1999

Effect of dipotassium clorazepate on amygdaloid-kindling and comparison between amygdaloid- and hippocampal-kindled seizures in rats.

We examined the effect of dipotassium clorazepate (7-chloro-1, 3-dihydro-2-oxo-5-phenyl-1H-1, 4-benzodiazepine-3-carboxylate potassium hydroxide), an antianxiety drug, on amygdaloid kindling and compared its effects for 7 successive days on amygdaloid- versus hippocampal-kindled seizures, using the rat kindling model of epilepsy. Dipotassium clorazepate at 5 mg/kg significantly delayed amygdaloid kindling. The contralateral cortical after-discharge duration in the dipotassium clorazepate-treated group was significantly shorter than the after-discharge duration in the amygdala in the first seven stimulations, whereas it was significantly shorter only in the first three stimulations in the control group, indicating that dipotassium clorazepate suppressed the spread of seizure activity from focus to contralateral cortex. Dipotassium clorazepate suppressed amygdaloid-kindled seizures at 2 and 5 mg/kg, while 1 mg/kg or more suppressed hippocampal-kindled seizures. Thus, differences in effective dosages in both amygdaloid- and hippocampal-kindled seizures may suggest a difference in the neuronal mechanisms involved in this kindling.

Amygdala↗
PubMed1999

Effect of graft-versus-host disease (GVHD) on host hematopoietic progenitor cells is mediated by Fas-Fas ligand interactions but this does not explain the effect of GVHD on donor cells.

The acute graft-versus-host disease (GVHD) generated in BDF1 mice by the injection of spleen cells from the C57BL/6 parental strain induces a direct cell-mediated attack on host lymphohematopoietic populations, resulting in the reconstitution of the host with donor hematopoietic stem cells. We examined the effect of GVHD on the donor and host hematopoiesis in parental-induced acute GVHD. The bone marrow was hypoplastic and the number of hematopoietic progenitor cells significantly decreased at 4 weeks after GVHD induction. However, extramedullary splenic hematopoiesis was present and the number of hematopoietic progenitor cells in the spleen significantly increased at this time. Fas expression on the host spleen cells and bone marrow cells significantly increased during weeks 2 to 8 of GVHD. Host cell incubation with anti-Fas Ab induced apoptosis, and the number of hematopoietic progenitor cells decreased during these weeks. A significant correlation between the augmented Fas expression on host bone marrow cells and the decreased number of host bone marrow cells by acute GVHD was observed. Furthermore, the injection of Fas ligand (FasL)-deficient B6/gld spleen cells failed to affect host bone marrow cells. Although Fas expression on repopulating donor cells also increased, Fas-induced apoptosis by the repopulating donor cells was not remarkable until 12 weeks, when more than 90% of the cells were donor cells. The number of hematopoietic progenitor cells in the bone marrow and the spleen by the repopulating donor cells, however, decreased over an extended time during acute GVHD. This suggests that Fas-FasL interactions may regulate suppression of host hematopoietic cells but not of donor hematopoietic cells. Hematopoietic dysfunctions caused by the reconstituted donor cells are independent to Fas-FasL interactions and persisted for a long time during parental-induced acute GVHD.

Animals↗
PubMed1999

Muc-1 core protein is expressed on multiple myeloma cells and is induced by dexamethasone.

Monoclonal antibodies (MoAbs) that selectively identify Muc-1 core protein (MoAbs DF3-P, VU-4H5) determinants were used to identify the Muc-1 glycoform present on 7 multiple myeloma (MM) cell lines, 5 MM patient plasma cells, 12 MM patient B cells, as well as 32 non-MM cell lines and normal hematopoietic cells. Flow cytometry studies demonstrated that all MM cell lines, MM patient plasma cells, and MM patient B cells expressed Muc-1 core protein epitopes. Circulating B cells from 4 normal donors also expressed Muc-1 core protein. In contrast, Muc-1 core protein was absent on 28 of 32 non-MM neoplastic cell lines, 17 of which expressed Muc-1. Splenic and tonsillar B cells, CD34(+) stem cells, resting T cells, and bone marrow plasma cells obtained from normal donors both lacked Muc-1 glycoforms. We next studied the effects of estrogen, progesterone, and glucocorticoid receptor agonists and antagonists on Muc-1 expression, because consensus sequences for the response elements of these steroids are present on the Muc-1 gene promoter. These studies showed that dexamethasone (Dex) induced Muc-1 expression on MM cell lines, as determined by both flow cytometry and Western blot analyses. Dex also induced upregulation of Muc-1 on prostate and ovarian cancer cell lines. Time and dose-response studies demonstrated that Dex induced maximal cell surface Muc-1 expression by 24 hours at concentrations of 10(-8) mol/L. Dex induced Muc-1 upregulation could be blocked with a 10-fold excess of the glucocorticoid receptor antagonist RU486, confirming that Dex was acting via the glucocorticoid receptor. No changes in Muc-1 expression were observed on MM cells treated with estrogen and progesterone receptor agonists and antagonists or with RU486. These studies provide the framework for targeting Muc-1 core protein in vaccination and serotherapy trials in MM. In addition, the finding that Muc-1 expression on MM cells can be augmented by Dex at pharmacologically achievable levels suggests their potential utility in enhancing treatments targeting Muc-1 in MM.

Dexamethasone↗
PubMed1999

Augmented expression of macrophage migration inhibitory factor (MIF) in the telencephalon of the developing rat brain.

Macrophage migration inhibitory factor (MIF) has been characterized as a proinflammatory cytokine, hormone, and immunomodulator. We previously demonstrated the distribution of MIF in the adult rat brain and revealed its expression in neurons as well as glial cells. In this study, we investigated the localization of MIF in the developing rat brain from embryonic day (ED) 13 to ED19, and after birth from postnatal day (PD) 1 to PD28 using both immunohistochemistry and in situ hybridization. On ED16, the signals of MIF mRNA were high in the ventricular, subventricular, and intermediate zones of the telencephalon, in which 'neuropoietic' progenitor cells proliferate and migrate from the ventricular zone to the superficial layer in the cerebral cortex. The mRNA expression was detected throughout the postnatal period, and intense signals of the transcript were seen in the ventricle and in layers I, II and III of the cerebral cortex at PD5. Similarly, positive staining of MIF protein was seen in the ventricular zone by immunohistochemical analysis, although the positively stained area appeared to be smaller than the mRNA expression. Taken together, these results suggest that the increase in MIF mRNA in the developing brain reflects the growth and maturation of neurons and glial cells.

Animals↗
PubMed1999

Teratogenicity of thujaplicin in ICR mice.

Beta-thujaplicin (TP) was studied by in vitro and in vivo tests for teratogenicity using ICR mice. In the in vitro study, TP (0, 3.125, 6.25, 12.5 microg/ml medium) dissolved in dimethyl sulfoxide (DMSO) was administered to cultured embryos on 9 day of gestation. After 24 hr of exposure to TP, the embryos were examined for developmental parameters and external anomalies. Growth retardation and embryos with facial dysplasia or hydrocyst of the tail tip were observed among the embryos given 12.5 microg/ml. In the in vivo study, TP (0, 420, 560, 750 or 1000 mg/kg) dissolved in olive oil was administered orally to pregnant mice on day 9 of gestation. All foetuses were removed from the uterus on day 18 of gestation, and were examined for external and skeletal anomalies. Various types of malformations were observed in the mice given 560 mg/kg or more. The number of litters having foetuses with external or skeletal anomalies increased in proportion to the dose of TP. The regression lines of Y (probit response) on X (log dose) for external anomalies was Y = 4.87X-8.43 . The 1% effective dose (ED1) for the malformation was 190 mg/kg. The present study shows that TP has teratogenic effects on mice.

Abnormalities, Drug-Induced↗
PubMed1999

A method for detection of a cytokine and its mRNA in the central nervous system of the developing rat.

We report here an effective and concise method to determine the localization of macrophage migration inhibitory factor (MIF), a proinflammatory cytokine, and its mRNA in the central nervous system of pre- and postnatal rats. This method allows for double staining to demonstrate localization of different molecules on the same tissue specimen at the levels of mRNA and proteins by in situ hybridization and immunohistochemistry, respectively. Additionally, the present method gives results more quickly than the conventional isotopic techniques. By use of this method, we carried out immunohistochemistry with an anti-rat MIF polyclonal antibody and demonstrated positive staining using the avidin-biotin complex method (ABC method). To detect its mRNA, we performed nonradioactive in situ hybridization using a digoxigenin (DIG)-labeled RNA probe prepared from a full length fragment of rat MIF cDNA. MIF was strongly expressed in the telencephalon on embryonic day 16. Non-radioactive in situ hybridization with a DIG-labeled RNA probe as well as the immunohistochemistry described here could be applicable to characterize localization of mRNA and proteins of different molecules on the same tissue specimen.

Animals↗
PubMed1999

Stress distribution and abutment tooth mobility of distal-extension removable partial dentures with different retainers: an in vivo study.

Three types of retainers (wrought wire clasp, Aker's cast clasp, and conical crown telescopic retainer) designed for distal-extension removable partial dentures (RPDs) were assessed in two Kennedy class I patients' mouths. The assessment, included the ratio of denture base shearing load and mobility of the terminal abutments when loaded on a free-end RPD occlusal surface. The mean values of denture base shearing ratios of wrought wire clasp, Aker's clasp and conical crown telescope were 60, 42 and 20%, respectively. The abutment mobility of the three types of retainers were all within the 'mobile ability area' except the wrought wire clasp for patient A's right side. The greatest tooth mobility was observed with the wrought wire clasps, followed by Aker's clasp and the conical crown telescopic retainer. From the analysis the following was concluded: (i) different retainers do influence the occlusal load distribution; (ii) the occlusal load distributed to the free-end saddle is closely related to the connecting rigidity of the retainer; (iii) mucosal support has an indispensable role in sharing the occlusal load with various retainers, even the rigid telescopic retainer.

Aged↗
PubMed1999

[Effects of isatin, an endogenous MAO inhibitor, on dopamine (DA) and acetylcholine (ACh) concentrations in rats].

Isatin (indole-2,3-dione), an endogenous inhibitor of monoamine oxidase (MAO), has several physiological properties for stress and anxiety. We previously identified isatin in the brain of stroke-prone spontaneously hypertensive rats (SHRSP) using gas-chromatography mass spectrometry. This study elucidated the effects of isatin on the ACh and DA levels of brain tissues in rats. Furthermore, we evaluated the effect of isatin on DA levels in a rat model of Parkinson's disease induced by Japanese encephalitis virus. Striatal ACh and DA levels significantly increased at 2 hours after isatin (50-200 mg/kg, i.p.) administration. Perfused through a microdialysis probe, isatin (10(-6)-10(-4) M) also produced a significant and concentration-dependent increase in the ACh and DA concentrations in the perfusate from the rat striatum. Furthermore, urinary isatin concentrations in patients with Parkinson's disease tend to increase according to the severity of disease. Isatin (100 mg/kg, i.p.) significantly increased striatal DA levels in a rat model of Parkinson's disease. These results suggest that urinary isatin may become a diagnostic marker for the clinical severity of Parkinson's disease and that endogenous isatin, a new biological modulator, may play a role in the regulation of the brain levels of ACh by increasing the level of DA under stress.

Acetylcholine↗
PubMed1999

Successful treatment of a patient with febrile, lobular panniculitis (Weber-Christian disease) with oral cyclosporin A: implications for pathogenesis and therapy.

We report a 15-year-old Japanese girl with severe systemic Weber-Christian disease (WCD) who presented with acute onset of high fever associated with tender subcutaneous nodules. Laboratory tests showed an elevated serum concentration of lactate dehydrogenase (LDH), leukopenia, and coagulation abnormalities. The anti-nuclear and anti-DNA antibodies were negative, and the serum pancreatic enzymes and alpha 1-antitrypsin levels were normal. Pulse steroid therapy was not effective, and eventually cerebellar hemorrhage occurred. After initiation of oral cyclosporin A (CyA) therapy, fever came down and her clinical condition improved markedly. Extremely high serum concentrations of interferon-gamma (IFN-gamma) and soluble interleukin-2 receptor (sIL-2R) in this patient returned to normal with CyA therapy. These findings suggest that T-cell immune responses are involved in the pathogenesis of WCD, and that CyA is effective against the disease via suppression of T-cell reactions.

Administration, Oral↗
PubMed1999

[Clinical examination to screen for laryngeal cancer: results, problems and prospects].

The Yokohama Municipal Cancer Detection Center, established as an affiliate of the Yokohama Municipal Citizen's Hospital in June, 1981, has performed clinical examinations to screen for laryngeal cancer in a total of 26,377 patients (12,205 men and 14,172 women) 40 years of age or older, in the past 15 years. Approximately 9.3% (2,398) of the patients required further examination, surgery, or observation. Thirty-one cases of malignant tumor were found, 26 of laryngeal cancer, 2 of hypopharyngeal cancer, and 1 each of thyroid cancer, tonsillar cancer and acute lymphoid leukemia. In addition, 51 cases of vocal fold leukoplakia and approximately 700 cases of vocal fold polyp and polypoid vocal fold were diagnosed. As mentioned in previous reports, examinations of this type present both definite benefits and deficiencies. Many problems still remain. Examples of these are the small absolute numbers of examinees, the rather heavy burden placed upon the examining doctor, and the low incidence of laryngeal cancer in female patients. Laryngeal cancer is predominantly a male disease, but female patients should not be excluded from receiving screening examinations. In recent years, many thyroid tumors have been detected in female patients. In the future, laryngeal cancer examination may develop into a head and neck cancer examination that includes screening for thyroid cancer.

Adult↗
PubMed1999

[Advances in interleukin-6 therapy].

Interleukin-6 (IL-6) exhibits multiple biologic activities such as regulation of immunological responses and hematopoiesis, promotion of acute inflammation, and stimulation of some malignant and non-malignant cell growth. The IL-6 receptor system consists of an IL-6 specific binding molecule, IL-6R and a signal transducer, gp130. Following gp130 dimerization, IL-6 activates multiple signaling pathways (Ras dependent MAPk cascade, STAT1-STAT3 heterodimer pathway, and STAT3 homodimer pathway). Several other cytokines including oncostatin M, IL-11, leukemia inhibitory factor (LIF), ciliary neurotrophic factor (CNTF) and cardiotropin-1 (CT-1) use gp130 as a common signal transducing molecule and therefore have similar biological activities. Two major in vivo functions of IL-6 are reported. Firstly, IL-6 acts as a growth factor of some malignant and non-malignant cells such as malignant plasma cells in multiple myeloma, mesangial cells in the kidney, and keratinocytes. Secondly, IL-6 mediates inflammatory and immune responses in rheumatoid arthritis, Castleman disease, psoriasis, cardiac myxoma, cachexia, and other inflammatory conditions. Recently, a humanized anti-IL-6 receptor antibody was developed. Neutralization of IL-6 activity by the humanized anti-IL-6 receptor antibody may be a new therapeutic approach for IL-6 related diseases such as multiple myeloma, Castleman disease and rheumatoid arthritis.

Antibodies↗
PubMed1999

Clinical significance of interleukin-6 gene expression in the bone marrow of patients with multiple myeloma.

The proliferation and differentiation of multiple myeloma (MM) cells has been suggested to be induced by continuous stimulation of interleukin (IL)-6 in the bone marrow (BM) microenvironment. We investigated the production and gene expression of this cytokine in bone marrow mononuclear cells (BMMC) of 31 untreated patients with MM. The IL-6 gene was expressed in 20/31 patients in whom increased IL-6 production in vitro was observed, suggesting that IL-6 gene expression correlates with IL-6 production by BMMC. A significant correlation was found between the presence of bone lesions and IL-6 gene expression; however, the percentage of MM cells infiltrating the BM did not correlate with IL-6 gene expression. This IL-6 gene expression was assigned to adherent cells of the BM microenvironment. Furthermore, serial measurement of IL-6 gene expression along with the clinical course revealed increased expression of IL-6 gene during the progressive phase of MM and decreased expression after remission at the individual level. These results suggest that IL-6 gene expression in BMMC reflects disease severity in MM.

Biomarkers, Tumor↗
PubMed1998

Adenovirus vector-based purging of multiple myeloma cells.

Adenoviruses are efficient gene delivery agents for a variety of neoplasms. In the present study, we have investigated the use of adenoviruses for the delivery of the thymidine kinase (tk) gene into multiple myeloma (MM) cells. We first demonstrated that MM cell lines and MM patient cells express both adenovirus receptors as well as the DF3/MUC1 protein, thus providing a rationale for using adenoviruses to selectively deliver genes under the control of the DF3 promoter. By using an adenoviral construct containing beta-galactosidase (beta-gal) gene driven by the DF3 promoter (Ad. DF3-betagal), we demonstrate greater than 80% transduction efficiency in OCI-My5 and RPMI 8226 MM cell lines at a multiplicity of infection of 1 to 100. Importantly, transduction with the tk gene driven by the DF3 promoter (Ad.DF3-tk) followed by treatment with 50 micromol/L ganciclovir (GCV) purged >/=6 log of contaminating OCI-My5 and RPMI 8226 MM cells within bone marrow mononuclear cells. In contrast, normal human hematopoietic progenitor cell number was unaffected under these conditions. Selectivity of DF3/MUC1 promoter was further confirmed, because Ad.DF3-betagal or Ad.DF3-tk did not transduce MUC1-negative HeLa cervical carcinoma cells. In addition, GCV treatment of Ad.DF3-tk-transduced RPMI 8226 MM cells did not induce a significant bystander effect. These findings demonstrate that transduction with Ad vectors using a tumor-selective promoter provides a highly efficient and selective approach for the ex vivo purging of MM cells.

Adenoviridae↗