Biomedical subjects

T Horie

Publications and source records attributed to T Horie.

At least 181 records · Page 10Linked to original sources

PubMed1998

[Interferon-alpha treatment for chemotherapy-resistant primary macroglobulinemia with stomach and lung invasion].

We reported a case of primary macroglobulinemia with stomach and pulmonary invasion. The patient was 71 years-old who had cervical lymphadenopathy and abdominal pain. Biopsy material of cervical lymph node showed non-Hodgkin's lymphoma, and he was diagnosed primary macroglobulinemia by IgM immunological histo-chemical staining of materials of stomach biopsies. Combination chemotherapies were not effective for the reduction of IgM-lambda protein, and organ invasion seemed to be progressive, so we tried interferon-alpha (IFN-alpha) to control M component. Daily injection of 6 megaunits of IFN-alpha induced significant reduction of M component and pulmonary invasion. This favorable changes were observed for 1 year. However, his pulmonary invasion on X-ray films relapsed and he died of respiratory failure by reason of severe pneumonia. IFN-alpha is currently available for myeloproliferative disease, especially chronic myelogenous leukemia and multiple myeloma. This case report showed that IFN-alpha was also available for primary macroglobulinemia.

Aged↗

PubMed1998

A 5'-monophosphate form of bredinin selectively inhibits the activities of mammalian DNA polymerases in vitro.

Bredinin is an immunosuppressive drug which is used clinically in Japan. In this study, we investigated bredinin's molecular mode of action to clarify its immunosuppressive effects. We focused on the DNA polymerases in the somatic DNA synthesis which may be required in the process of lymphocyte differentiation. We found that bredinin-5'-monophosphate (breMP) could be a potent inhibitor of mammalian DNA polymerase alpha(pol.alpha) and (pol.beta) in vitro, although bredinin itself has no such effects. BreMP inhibited the pol. alpha activity at less than 7 micrograms/ml and the pol. activity at 7 micrograms/ml. Neither breMP nor bredinin influenced the activities of a plant DNA polymerase, prokaryotic DNA polymerases such as E. coli DNA polymerase I and Taq DNA polymerase, or DNA-metabolic enzymes such as DNase I, indicating that breMP selectively suppressed the activities of the mammalian DNA polymerases. For pol., beta breMP acted by competing with both the substrate and template-primer. For pol. alpha, it acted by competing only with the substrate, and non-competitively with the template-primer. The ribose of bredinin is quickly and quantitatively converted to its ribose-5'-phosphate form in vivo as soon as it is incorporated into cells. The action mode of bredinin and its use as an immunosuppressive drug are discussed based on these results.

Animals↗

PubMed1998

Salmonella penetration through eggshell associated with freshness of laid eggs and refrigeration.

Effects of egg age after laying and refrigeration on penetration of the eggshell by Salmonella enteritidis (SE) and Salmonella typhimurium (ST) were examined. Eggs 0.25 to 3 h, 3.25 to 6 h, 1 day, and 7 days old held at two temperatures were immersed in SE or ST suspensions containing 10(3) or 10(6) CFU/ml at 25 degrees C for 10 min. After holding at 25 degrees C for 2 h, the inner eggshell and egg contents were examined for Salmonella cells. The recovery rates of Salmonella cells from both the inner eggshell and egg contents of the 0.25- to 3-h-old eggs were significantly higher than those of other groups, especially at the high-exposure dose. There was no significant difference noted between SE and ST in ability to penetrate through eggshell. Salmonella penetration was significantly decreased by cooling the eggs at 4 degrees C for 15 min prior to immersing them in SE or ST suspension. The data suggested that Salmonella cells readily penetrated through the shell of freshly laid eggs, but that this penetration was suppressed by cooling the eggs before they were exposed to Salmonella suspensions.

Animals↗

PubMed1998

[Long-term effects of nasal continuous positive airway pressure on pulmonary function and blood gas data in patients with obstructive sleep apnea syndrome].

To evaluate the long-term effects of nasal continuous positive airway pressure (NCPAP) on pulmonary function and blood gas levels in patients with obstructive sleep apnea syndrome (OSAS), we examined the pulmonary functions and blood gases in 25 male patients with OSAS before and after NCPAP treatment. After 22 months of treatment (titration: 13 cm H2O), no significant changes were observed in the patients' spirograms, pulmonary gas volumes, or diffusion capacity. However, PaO2 levels increased significantly (p < 0.01), from 73.8 mmHg to 79.5 mmHg; PaCO2 levels decreased significantly (p < 0.05), from 45.6 mmHg to 44.2 mmHg; and A-aDO2 levels also decreased significantly (p < 0.05), from 18.7 mmHg to 15.0 mmHg. The patients were divided into a hypoventilated group (PaCO2 > 45 mmHg; 11 cases) and normoventilated group (PaCO2 < or = 45 mmHg; 14 cases). After NCPAP treatment, increased PaO2 and decreased PaCO2 levels were observed in the hypoventilated group, and increased PaO2 and decreased A-aDO2 levels were observed in the normoventilated group. These results suggest that long-term NCPAP treatment improves gas exchange in OSAS patients without influencing the results of pulmonary function tests.

Adult↗

PubMed1998

Hepatic uptake of bromosulfophthalein-glutathione in perfused Eisai hyperbilirubinemic mutant rat liver: a multiple-indicator dilution study.

The hepatocellular uptake of the glutathione conjugate of bromosulfophthalein (BSPGSH) was examined in Eisai hyperbilirubinemic rats (EHBR; originating from Sprague-Dawley rats), which lacked the ATP-dependent canalicular transport for non-bile acid organic anions, a trend common to other mutant rat strains (TR- and GY, originating from Wistar rats). Single-pass perfused rat liver experiments were conducted with BSPGSH (26-257 microM) using the multiple indicator dilution technique. The steady-state extraction ratio of BSPGSH was close to zero due to lack of biliary excretion. After the introduction of a bolus dose containing vascular (51Cr-labeled red blood cells), interstitial (125I-labeled albumin and [14C]sucrose) and cellular space (D2O) indicators and [3H]BSPGSH into the portal vein, the outflow dilution profile of [3H]BSPGSH was found to display a protracted declining profile (tailing) at low input BSPGSH concentrations; the tail disappeared at higher BSPGSH concentrations. When data were fitted with the barrier-limited model of Goresky as used previously for BSPGSH for the Sprague-Dawley rat (SDR), model fitting was found to evoke an additional "deep pool" within the hepatocyte to account for the "tail" component. The deep pool became evident for the EHBR because biliary excretion of BSPGSH was absent and the rate of return from the deep pool was slow. The concentration of BSPGSH within the deep pool was estimated to be 12 +/- 8 times that in the cytosol. The binding of BSPGSH to EHBR S9 (effective binding concentration of 53 microM and a binding association constant KA of 2.4 x 10(4) M-1), however, was found to be lower than that of SDR S9 and could not account for the late-in-time data. The influx permeability-surface area product was concentration dependent and decreased from 0.27 to 0.01 ml.sec-1.g-1 with increasing BSPGSH concentration; the throughput component, or the portion of the dose that goes through the liver without entering the hepatocyte, increased with increasing concentration. The trends were characteristic of carrier-mediated transport and were similar to those found for the uptake of BSPGSH in SDR.

Animals↗

PubMed1998

Dihydralazine-induced inactivation of cytochrome P450 enzymes in rat liver microsomes.

Dihydralazine is known to induce immunoallergic hepatitis, and the anti-liver microsome (anti-LM) autoantibodies found in the serum of the patients have been reported to react with cytochrome P450 1A2 (CYP1A2). It is thus suggested that a reactive metabolite of dihydralazine covalently binds to the P450 protein and triggers an immunological response as a neoantigen. We investigated the selectivity of inactivation of P450 enzymes during the metabolism of dihydralazine to evaluate the target protein of its reactive metabolite. Liver microsomes from male Wistar rats were preincubated with dihydralazine in the presence of NADPH, followed by assays of several monooxygenase activities. Preincubation of microsomes of beta-naphthoflavone-treated rats with dihydralazine resulted in time-dependent loss of phenacetin O-deethylase activity (an indicator of CYP1A2 activity), showing inactivation of CYP1A2 during the dihydralazine metabolism. The preincubation with dihydralazine was less effective on ethoxyresorufin O-deethylase activity in microsomes of beta-naphthoflavone-treated rats (CYP1A1) and pentoxyresorufin O-depentylase activity in microsomes of phenobarbital-treated rats (CYP2B). On the other hand, preincubation of microsomes of untreated rats with dihydralazine caused time-dependent loss of testosterone 2alpha-, 16alpha- (CYP2C11), and 6beta- (CYP3A) hydroxylase activities. These results demonstrated that dihydralazine was metabolically activated by CYP1A2, and the chemically reactive metabolite bound to the enzyme itself and inactivated it, as was suggested by the appearance of anti-LM antibodies in dihydralazine-hepatitis, whereas CYP2C and -3A enzymes were also suggested to be the enzymes that activate dihydralazine and lead to the target of the reactive intermediates.

Animals↗

PubMed1998

Glutathione disulfide formation during naproxen metabolism in the isolated rat hepatocytes.

As naproxen was found to induce lipid peroxidation in liver microsomes and isolated hepatocytes of rats during its oxidative metabolism, we studied changes of glutathione on its metabolism. Intracellular oxidized glutathione (GSSG) content increased in isolated rat hepatocytes during naproxen metabolism. The intracellular GSSG increased preceding the production of thiobarbituric acid reactive substances (TBARS) and the release of lactate dehydrogenase (LDH). The glutathione-depleted hepatocytes treated with diethymaleate (DEM) enhanced TBARS production and LDH release, compared to the untreated hepatocytes. The production of GSSG may possibly be an early stage of the naproxen-induced oxidative stress which leads to lipid peroxidation and lethal cell injury.

Animals↗

PubMed1998

[Sleep apnea syndrome in Japan: analysis of pathophysiology and nasal continuous positive airway pressure effectiveness].

Forty eight Japanese sleep apnea syndrome (SAS) patients, whose apnea-hypopnea index (AHI) was more than 30 times/hr. from 5 university hospitals (46 males, 2 females) were enrolled in this study to analyze the characteristics of the disorder and the effectiveness of nasal continuous positive airway pressure (nCPAP) effectiveness. Although the severity of excessive daytime sleepiness (EDS), depressive state, and ventricular premature beats caused by SAS seemed milder in Japanese than reported Caucasian patients, the prevalences of hypertension and glucose intolerance were quite high: 50 and 30% respectively. Treatment with nCPAP for 3 months was completed in 41 of 48 enrollees, a compliance rate of 85.4%, which was substantially higher than studies from Western countries. nCPAP treatment normalized about 50% of hypertensive patients and more than half of glucose intolerant patients. Moreover, EDS, driving ability, the severity of arrhythmia, and so forth were all improved with nCPAP. We, therefore, conclude that 1) SAS could differ between Japanese Caucasians in terms of clinical features resulting from SAS and 2) treatment with nCPAP is effective and should be considered as first-line treatment for patients with moderate to severe SAS, as reported in Western countries.

Adult↗

PubMed1998

[Donor leukocyte transfusion as treatment for relapsed chronic myelogenous leukemia after allogeneic bone marrow transplantation].

Three patients with relapse (two molecular and one cytogenetic relapse) after allogeneic bone marrow transplantation (BMT) for chronic myelogenous leukemia (CML) were treated with donor leukocyte transfusion (DLT). Two had complete molecular remission, which persisted 16 and 20 months after treatment. The performance status of all patients was 90-100%. Mild chronic GVHD was observed in one patient as a side effect of DLT. One patient with cytogenetic relapse required three infusions to attain molecular remission and this suggests the importance of cell numbers to infuse in DLT. Positive anti-nuclear antibody was observed in the effective cases and elevation of IgE in all cases after DLT. These abnormal laboratory findings may suggest a relationship between GVHD and GVL. DLT may be effective therapy for patients with CML who relapse after BMT. Further controlled studies are necessary to determine the optimal number of cells to infuse, interval and frequency of DLT.

Adult↗

PubMed1998

Salicylic acid-induced lipid peroxidation in rat liver microsomes.

Rat liver microsomes (1 mg protein/ml) were incubated at 37 degrees C with non-steroidal anti-inflammatory drug, salicylic acid (5 mM) in the presence of 0.2 mM NADPH. The amounts of thiobarbituric acid reactive-substances (TBARS) were increased remarkably by the incubation for 30 min. TBARS formation was dependent on salicylic acid concentration. Salicylic acid-induced lipid peroxidation was not observed in the absence of NADPH. It was also inhibited by the presence of cytochrome P450 inhibitor, SKF-525A. The singlet oxygen's scavengers such as histidine suppressed salicylic acid-induced lipid peroxidation. These results suggested that salicylic acid-induced lipid peroxidation was coupled with the metabolism through cytochrome P450 in rat liver microsomes. The singlet oxygen may be involved in the reaction.

Animals↗

PubMed1998

[Plasma cell leukemia (IgG kappa) presenting bilateral neurosensory hearing loss and left sixth cranial nerve plasy].

A 30-year-old man who had been given a diagnosis of IgG-kappa multiple myeloma by another hospital and treated with melphalan, prednisone, and cyclophosphamide 6 months earlier, was admitted to our hospitaly in July 1994 because of progressively impaired hearing in both ears, vertigo, and worsening fatigue. Peripheral blood examination showed a white blood cell count 25,000/microliter, with 77.5% atypical plasma cells. Examination at the time of hospitalization also revealed retinal hemorrhages and serum hyperviscosity. The diagnosis was plasma cell leukemia with hyperviscosity syndrome. Subsequent treatment consisted of vincristine, doxorubicine, and prednisone and repeated plasmapheresis. This resulted in a partial response and a reduction of serum viscosity but no reversal of hearing loss. One month after admission, left sixth cranial nerve plasy was demonstrated. Cranial computed tomography studies disclosed a tumoral mass in the sphenoid sinus. The patient received local radiotherapy and intensive chemotherapy, but exhibited no notable alleviation of his cranial nerve palsy. He died of septicemia and progressive disease in August 1994. This case was rare in that it involved plasma cell leukemia and bilateral neurosensory hearing loss associated with serum hyperviscosity and sixth cranial nerve plasy due to plasmacytoma within the sphenoid sinus.

Abducens Nerve↗

PubMed1998

Structural requirements for the hepatotoxicity of nonsteroidal anti-inflammatory drugs in isolated rat hepatocytes.

Hepatotoxicity is one of the common side effects of nonsteroidal anti-inflammatory drugs (NSAIDs). We investigated the cytotoxicity of 18 acidic NSAIDs (3 salicylic acids, 3 anthranilic acids, 6 arylacetic acids, 6 arylpropionic acids) to freshly isolated rat hepatocytes as assessed by the NSAID-induced leakage of lactate dehydrogenase (LDH) in order to determine structural requirements for the direct hepatotoxicity of the NSAIDs. Diflunisal (salicylic acids), flufenamic acid, mefenamic acid, tolfenamic acid (anthranilic acids), diclofenac, indomethacin, acemetacin (arylacetic acids) and flurbiprofen (arylpropionic acids) caused significant LDH leakage, indicating that substituent position of a carboxyl group does not relate to the hepatotoxicity of the NSAIDs. Because the cytotoxic NSAIDs were of two types as classified by their "skeleton," diphenyl and diphenylamine, we tested the cytotoxicity of the compounds. Diphenyl did not cause LDH leakage, but diflunisal, which has the diphenyl structure, was cytotoxic. On the other hand, diphenylamine induced LDH leakage to the same degree as diclofenac, which has the diphenylamine structure. Therefore, diphenylamine itself was suggested to be responsible for the cytotoxicity of diclofenac and anthranilic acids, whereas a substituted group(s) in addition to diphenyl structure seems to be important for diflunisal cytotoxicity. All of the cytotoxic NSAIDs and diphenylamine extensively decreased hepatocellular ATP content, whereas the noncytotoxic NSAID did not, indicating that the NSAID-induced decrease in ATP, probably by their uncoupling effects on mitochondrial oxidative phosphorylation, is involved in the hepatotoxicity of the NSAIDs.

Adenosine Triphosphate↗

PubMed1998

[Pulmonary function at the early stage after bone marrow transplantation].

Twenty-one patients, aged 16-41 years, were prospectively followed for pulmonary function prior to and up to nine months after bone marrow transplantation (BMT). All patients had normal radiographs and no clinical signs of pulmonary disease. The FEV1.0%, V25, and of V50/V25 were within the normal ranges for all patients. Percent vital capacity (%VC) and percent diffusing capacity of lung for CO (% DLco) dropped progressively in most of the patients up to 9 months following BMT. Pulmonary function decreased earlier in patients with GVHD as well as patients who received total body irradiation either at a high dose rate (10 cGy/min) or a high lung dose (12 Gy). These asymptomatic declines in pulmonary function were measured by frequent tests of lung function.

Adolescent↗

PubMed1998

[Severe hemolytic anemia with tear drop red cells as initial manifestation of Wilson's disease].

A 16-year-old girl was admitted for a detailed examination of hemolytic anemia in November 1995. Initial laboratory findings included a total bilirubin concentration of 1.46 mg/dl, hemoglobin of 9.1 g/dl, and a reticulocyte count of 89/1000 percent. The plasma haptoglobin concentration was below 10 mg/dl. A blood smear showed many dacryocytes and a few echinocytes and codocytes. GOT was 71 IU/l; GPT, 44 IU/l; and LDH, 812 IU/l; the results of a hepaplastin test were 45% of normal. On further investigation, the level of serum ceruloplasmin was found to be 4 mg/dl, and of serum copper, 43 micrograms/dl. Urinary copper excretion was markedly increased, at 345 micrograms per day. Slit-lamp examination of both corneas revealed obvious Kayser-Fleischer rings. A liver biopsy sample showed fibrosis histologically and an elevated copper concentration of 535 micrograms/g dry weight and 183 micrograms/g wet weight. In family studies, the patient's asymptomatic 5-year-old sister was observed to have metabolic abnormalities consistent with Wilson's disease. These findings suggested that the patient's hemolytic anemia with red cell deformities was due to abnormal copper metabolism associated with Wilson's disease.

Adolescent↗

PubMed1997

Curcumin inhibition of Dermatophagoides farinea-induced interleukin-5 (IL-5) and granulocyte macrophage-colony stimulating factor (GM-CSF) production by lymphocytes from bronchial asthmatics.

Curcumin, a dietary pigment responsible for the yellow color of curry, has been used for the treatment of inflammatory diseases and exhibits a variety of pharmacological effects such as anti-inflammatory, anti-tumor, anti-oxidant, and anti-viral activity. However, it has not been determined whether the effect of curcumin on the production of cytokine affects eosinophil functions and IgE synthesis. In the present study, we examined the effect of curcumin on the production of interleukin (IL)-2, IL-5, granulocyte macrophage-colony stimulating factor (GM-CSF), and IL-4 by lymphocytes from atopic asthmatics in response to house dust mites (Dermatophagoides farinea: Df) in order to clarify a potential application for allergic diseases. Curcumin inhibited Df-induced lymphocyte proliferation and production of IL-2. Exogenous IL-2 reconstituted the proliferative responsiveness of lymphocytes to Df in the presence of curcumin. Furthermore, curcumin inhibited IL-5, GM-CSF, and IL-4 production in a concentration-dependent manner. These results indicate that curcumin may have a potential effect on controlling allergic diseases through inhibiting the production of cytokines affecting eosinophil function and IgE synthesis.

Adult↗

PubMed1997

Stereoselective determination of a new antidepressant, E2011, and its diastereoisomer as a metabolite by high-performance liquid chromatography.

A stereoselective HPLC method has been developed for the determination of E2011 (compound I) and one of its metabolites and diastereoisomers, ER-20593 (compound II), in plasma. The two substances and the internal standard were extracted from plasma, followed by two purification steps. In the first step, a minicolumn, Bond Elut C18, was used and in the second step, another minicolumn, Bond Elut Si, was used for purification of the compounds. After the purification, the compounds were analyzed by HPLC with two Chiralpak AD columns. In this procedure, compounds I and II were stable and there was no chiral inversion. The within-day and the between-day assays were performed in rat plasma, where compounds I and II existed simultaneously. The within-day and the between-day precisions of compound I were 2.0 approximately 10.1% and 1.3 approximately 7.1%, and the within-day and the between-day accuracies were -8.2 approximately +3.0% and -6.6 approximately +4.0% in the concentration range 0.003-10 microg ml(-1). The within-day and the between-day precisions of compound II were 1.7 approximately 16.9% and 0.9 approximately 4.5% and the within-day and the between-day accuracies were -9.0 approximately +2.4% and -5.6 approximately +3.8% in the concentration range of 0.005-0.5 microg ml(-1). QC samples for compound I and II were stable for at least 3 months. The method was applied to measure the levels of compound I and II in the rat plasma after oral administration of compound I.

Animals↗

PubMed1997

Elevation of soluble CD23 in sera from patients with infectious mononucleosis.

CD23 is induced in B cells upon infection by Epstein-Barr virus (EBV) and a soluble form (soluble CD23: sCD23) is found in culture supernatants from EBV-transformed B cell lines. Based on these observations, we measured serum sCD23 levels in patients with infectious mononucleosis (IM) caused by EBV infection. Sera from patients with IM at the time of diagnosis contained more sCD23 than sera from normal control subjects. Changes in serum sCD23 levels during the course of disease showed that serum sCD23 levels were elevated at the time of diagnosis and they decreased to the normal levels during the convalescent phase defined by the improvement of symptoms of IM. These results indicate that the elevated levels of sCD23 were observed at the acute phase of IM and may be useful in diagnosing IM.

Adolescent↗

PubMed1997

Mutations in a hydrophilic part of the core gene of hepatitis C virus in patients with hepatocellular carcinoma in China.

We investigated the association between hepatocellular carcinoma (HCC) and the genomic characteristics of the hepatitis C virus (HCV) isolated from residents of the inshore region of the Yangtze River, an area that has one of the highest incidence of HCC in China. We determined the genomic heterogeneity of HCV, and the sequence divergence of the HCV core gene in individuals with chronic hepatitis and HCC. HCV genotype II was predominant among these isolates, which were homologous to other Chinese and Japanese HCV isolates. The rate of nucleotide substitutions in the core gene was significantly greater for isolates from HCC patients than for those from individuals with chronic hepatitis. The nucleotide substitutions were unevenly scattered along the core gene; a cluster of missense mutations was apparent in the region encoding the second hydrophilic domain of the core protein. The rate of occurrence of missense mutations per nucleotide substitution was significantly greater in this clustering variable region (CVR) of the core gene than in the remaining core gene sequence. These observations suggest that mutations in the CVR may be involved in the pathogenesis of chronic HCV infection during hepatocellular carcinogenesis.

Base Sequence↗