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Biomedical subjects

H Maeda

Publications and source records attributed to H Maeda.

At least 469 records · Page 26Linked to original sources

Specific growth inhibition of small-cell lung cancer cells by adenovirus vector expressing antisense c-kit transcripts.

Antisense methods to control aberrant gene expression have been investigated as therapeutic strategies. A proto-oncogene c-kit, which encodes a transmembrane tyrosine kinase, is overexpressed in some malignancies, including small-cell lung cancer (SCLC), and is thought to be involved in their pathogenesis. To test the feasibility of using adenovirus vectors for antisense strategies and to target c-kit in SCLC therapy, we constructed replication-deficient recombinant adenovirus vectors which express fragments of c-kit transcripts in antisense (Ad.kitAS) or sense orientation (Ad.kitS: control). In vitro infection of SBC-1 cells, which are c-Kit protein-producing SCLC cells, by these vectors resulted in the expression of artificial c-kit transcripts. The Ad.kitAS-infected SBC-1 cells showed reductions in the amount of c-Kit protein. As expected, at 10 days after infection (1 multiplicity of infection), Ad.kitAS-infected SBC-1 cells showed approximately 40% growth inhibition compared to uninfected or Ad.kitS-infected cells in vitro. Such a significant growth inhibition by Ad.kitAS was not induced in SBC-5 cells, which are SCLC cells producing no c-Kit protein. These results demonstrate the usefulness of adenovirus vectors in antisense strategies, and the feasibility of targeting c-kit in the therapy of c-Kit-producing SCLC.

Adenoviridae↗

Effects of caffeine on event-related potentials: comparison of oddball with single-tone paradigms.

We investigated the acute effects of caffeine (500 mg) on event-related potentials (ERP) in 10 healthy subjects using standard oddball and single-tone paradigms. Event-related potentials were recorded before oral ingestion of caffeine or placebo and 30 min and 210 min after. The oddball paradigm, but not the single-tone paradigm, showed that the P300 amplitude and the area were significantly increased 30 min after ingestion of caffeine and significantly decreased 30 min after ingestion of placebo. The effects of caffeine disappeared at 210 min. Neither the P300 latency nor the reaction time changed significantly with the oddball paradigm. However, the reaction time was shortened 30 min after ingestion of caffeine with the single-tone paradigm. These findings suggest that the caffeine-induced increase in the P300 amplitude may have resulted from the increased allocation of attentional resources to the discriminating process which was not, however, accompanied by facilitation of the process and that caffeine may specifically stimulate the discriminating process involved in the oddball paradigm. In addition, the simple psychomotor performance of buttonpressing in response to a tone signal was accelerated by caffeine.

Caffeine↗

Locally-confined signet-ring cell carcinoma of the prostate: a case report of a long-term survivor.

It is generally believed that signet-ring cell carcinoma (SRCC) of the prostate is a high-grade neoplasm with a poor prognosis. We report a case of a long-term survivor diagnosed with localized prostatic SRCC (T3N0M0), who has been alive without any clinical evidence of disease for 100 months after combination therapy which consisted of local irradiation and hormone administration. A posttreatment needle biopsy confirmed the pathological complete response.

Administration, Oral↗

Nicotinic acid transport mediated by pH-dependent anion antiporter and proton cotransporter in rabbit intestinal brush-border membrane.

In order to determine whether the vitamin nicotinic acid is absorbed via an anion antiporter, intestinal epithelial cell membrane transport mechanisms for nicotinic acid were characterized using isolated rabbit jejunal brush-border membrane vesicles. The uptake of nicotinic acid by the membrane vesicles showed an overshoot phenomenon in the presence of an outwardly directed bicarbonate gradient or an inwardly directed proton gradient and the uptakes were two times and six times greater, respectively, than that in the absence of any ion gradient. The bicarbonate-dependent initial uptake of nicotinic acid was increased at acidic pH, showing pH-dependent transport activity. An inhibitor of anion transport, 4,4'-diisothiocyanostilbene-2,2'-disulphonic acid, specifically reduced bicarbonate-dependent transport of nicotinic acid. The initial uptakes of nicotinic acid via the anion antiporter and the proton cotransporter were specifically inhibited by monocarboxylic acids such as acetic acid, benzoic acid, D- and L-lactic acid, pravastatin and valproic acid, but not by di- or tricarboxylic acids, bile acids or amino acids. Nicotinic acid uptake activity was, furthermore, expressed in a Xenopus laevis oocyte system after injection of messenger RNA (mRNA) derived from rabbit intestinal epithelial cells. These observations demonstrate that nicotinic acid is absorbed by two independent active transport mechanisms from small intestine, i.e. a proton cotransporter and an anion antiporter. The pH-dependence observed in the intestinal absorption of nicotinic acid might, therefore, be ascribed partly to pH-sensitive and partly to carrier-mediated transport mechanisms in the brush-border membrane.

Animals↗

Impairment of Kit-dependent development of interstitial cells alters contractile responses of murine intestinal tract.

We examined developmental changes in responses of the isolated segment of the ileum of BALB/c mice treated with a monoclonal antibody (ACK2) to the receptor tyrosine kinase (Kit) for 4 days postnatally to pharmacological agents in vitro. Rhythmic contraction and relaxation of the isolated ileum started to appear on day 4 postpartum, and the sensitivity to acetylcholine (ACh) decreased gradually after birth. Treatment with ACK2 induced augmentation of contractile responses and receptor sensitivity of the longitudinal muscle of the ileum to ACh, bradykinin, and prostaglandin F2 alpha. ACh induced larger depolarization in smooth muscle cells of the ileum in the ACK2-treated mice than in the control. Circular muscle responses to these substances, as measured by changes in intraluminal pressure, were not altered by ACK2 treatment. Results suggest that interstitial cells play an important role not only in the development of the pacemaking system of the small intestine but also in the functional development of the contractile properties of the intestinal smooth muscle.

Acetylcholine↗

Relationship between bronchial hyperreactivity and symptoms of cardiac asthma in patients with non-valvular left ventricular failure.

To determine whether a relationship exists between bronchial hyperreactivity and cardiac asthma, which is commonly observed in patients with left heart failure, a methacholine inhalation test was performed in 15 patients with stable left ventricular failure (LVF) and 10 normal subjects. The subjects were divided into 3 groups based on symptoms of nocturnal coughing and/or wheezing in acute exacerbation of LVF. Group A consisted of 8 patients with nocturnal coughing and/or wheezing. Group B consisted of 7 patients without such symptoms, and Group C consisted of the 10 age-matched normal controls. Eleven of the 15 patients with LVF showed a significant increase in respiratory resistance in the methacholine inhalation test, as opposed to none of the normal subjects. The median cumulative dose which produced a 35% decrease in respiratory conductance (PD35Grs) was significantly lower in Group A than in Group B (1.45 log units and 1.90 log units, respectively, p < 0.05). The results of pulmonary function tests were not significantly different between Groups A and B. The minimum cumulative dose required to initiate a decrease in respiratory conductance from the baseline, as an index of bronchial sensitivity to methacholine, was significantly correlated with DLCO/VA (r = 0.710, p < 0.01). We conclude that bronchial hyperreactivity is responsible for cardiac asthma and that it might be related to pulmonary interstitial changes in stable patients with non-valvular LVF.

Adult↗

Phylogenetic relationships in A-genome species of rice as revealed by RAPD analysis.

In order to clarify the phylogenetic relationships in A-genome species of rice, RAPD analysis was carried out using 29 accessions (8 Oryza sativa, 6 O. glaberrima, 13 O. perennis, and 2 O. breviligulata). Their total DNA was used as template for PCR with 14 decamer primers. The amplified products were electrophoresed in agarose gel, and the banding patterns were observed. Average number of total amplified bands for each accession using 14 primers was 84.6. By comparing the banding patterns, the proportion of common bands between 29 accessions was calculated and a dendrogram showing genetic relationships was constructed. Most of the accessions formed clusters corresponding to their taxonomic grouping. The Oceanian and African forms of O. perennis were substantially different from all other groups. The Asian form of O. perennis, however, formed a complex with O. sativa while O. breviligulata was clustered with O. glaberrima. This indicates that O. sativa and O. glaberrima have probably originated from the Asian form of O. perennis and from O. breviligulata, respectively.

DNA, Plant↗

Hydrolysis kinetics of okara and characterization of its water-soluble polysaccharides.

As a part of a study of reuse of waste okara, the kinetic mechanism of okara hydrolysis and the properties of the water-soluble polysaccharides (WSP) extracted were investigated. Okara was hydrolyzed by being autoclaved at pH 4.5 in two volume of water with or without a chelator such as hexametaphosphate. Okara hydrolysis proceeded by surface degradation mechanism without a chelator. Characterization of WSP suggested that the "egg-box regions" in okara were susceptible to degradation by a chelator and that the "non-egg-box regions" contained WSP linked with hydrophobic proteins. WSP with a molecular weight of more than 10(5) and the amount of protein bound to the polysaccharides seemed to govern their emulsifying characteristics.

Chelating Agents↗

Renal transplantation in cats with chronic renal failure.

Renal transplantation was performed on 6 cats with chronic renal failure. Clinical signs and the blood chemistry findings (BUN, Cr, IP) improved one week after renal transplantation. Renal anemia also improved 3-4 weeks after surgery. Two cases had the same complications, hydronephrosis and hydroureter within 1 or 2 weeks of surgery, evidenced by marked elevations of BUN and Cr, suggesting that ureteral obstruction at the site of ureterocystostomy is the main complication of renal transplantation in cats. As a new resolution for this problem, we transplanted the ureter with the intact ureteral opening of the bladder from the donor in the remaining 4 cats. Ureteral obstruction was not observed in them, thus the procedure was considered to be useful for avoiding this complication. Two cats died of pneumonia and other complications within 3 months. There were no acute rejections or side effects from the immunosuppressant during the observation period in the remaining four cats.

Animals↗

Pathogenic mechanisms induced by microbial proteases in microbial infections.

Most bacterial and fungal proteases excreted into infected hosts exhibit a wide range of pathogenic potentials ranging from pain, edema or even shock to translocation of bacteria from the site of infection into systemic circulation, thus resulting in septicemia. The basic mechanism or principle common to all these phenomena is explained by kinin generation, either directly from high- and/or low-molecular weight kininogens or indirectly via activation of the bradykinin generating cascade: i.e. Hageman factor-->activated Hageman factor-->prekallikrein-->kallikrein-->high-molecular weight kininogen-->bradykinin. Some bacterial proteases are also involved in activation of other host protease zymogens such as plasminogen, procollagenase (matrix metallo proteases) and proenzymes of the clotting system. Furthermore, most bacterial proteases are not only resistant to plasma protease inhibitors of the hosts, most of which belong to a group of serine protease inhibitors called serpins (serine protease inhibitors), but they also quickly inactivate serpins. Some bacterial proteases may also activate bacterial toxins thus rendering toxigenic pathogenesis. They are also capable of degrading immunoglobulins and components of the complement system and facilitate propagation of micro organisms. All in all, microbial proteases are very critical in enhancing pathogenesis of severe diseases. It is also noteworthy that bacterial cell wall components themselves, i.e. endotoxin (or lipopolysaccharide) of gram negative bacteria and teichoic/lipoteichoic acid of gram positive bacteria, are also able to activate the bradykinin generating cascade-involving activation of Hageman factor as mentioned above.

Animals↗

Clinical significance of the increased peak levels of exhaled nitric oxide in patients with bronchial asthma.

We measured exhaled nitric oxide (NO) with a chemiluminescence method to elucidate the clinical significance of the increased concentration of exhaled NO in patients with bronchial asthma. Exhaled NO was measured in 25 patients with bronchial asthma and in 10 healthy control subjects. The concentration of exhaled NO in asthmatics was significantly higher than in the controls (250.4 +/- 30.4,59.9 +/- 9.6 ppb, respectively, p < 0.01). Symptomatic patients (unstable asthmatics) had a higher exhaled NO concentration than did the asymptomatic patients (stable asthmatics) (384.2 +/- 32.5,143.6 +/- 18.8 ppb, respectively, p < 0.01). The exhaled NO concentration was significantly correlated with the peak expiratory flow rate (r = 0.671, p < 0.01) and eosinophil ratio in induced sputum (r = 0.772, p < 0.05), but it was not correlated with the parameters of bronchial hyperactivity (Dmin and PD35 Grs). We conclude that the increased concentration of exhaled NO in patients with bronchial asthma reflects the state of airway inflammation, and we suggest that the measurement of exhaled NO is a useful, non-invasive and simple method for the management of bronchial asthma.

Adult↗

Hypertriglyceridemia and fatty liver of fasting rats after administration of emeriamine.

The effect of emeriamine, a potent inhibitor of the entry of fatty acids into mitochondria on lipid metabolism, was examined. Emeriamine (10 mg/kg body weight) was orally administered to rats under the two different physiological conditions of a 2-day fast or refeeding with a high-carbohydrate diet after a 2-day fast. When rats were refed with a high-carbohydrate diet, serum and hepatic ketone bodies and the levels of free fatty acids decreased, and triglycerides significantly increased compared with fasting rats. However, no significant effect of emeriamine on serum and hepatic lipids was observed between two refeeding groups with or without emeriamine. Conversely, when emeriamine was administered to fasting rats, the levels of serum and hepatic triglycerides increased about 11- and 5-fold, respectively. However, the increased level of hepatic triglycerides was not accompanied by the activities of fatty acid synthetase and NADPH-generating enzymes. The analysis of serum lipoprotein revealed that very low-density lipoprotein consisted of triglyceride-rich particles and there were less apolipoproteins in the fasting rat given emeriamine. We also determined the 120-kDA protein content, which was probably dependent on lipogenesis. The level of 120-kDa protein was greatly increased with or without the administration of emeriamine after refeeding with a high-carbohydrate diet, but the concentration of 120-kDa protein was slight in the fasting rat with emeriamine. These results suggest that specific inhibition of fatty acid oxidation by emeriamine diverted the exogenous fatty acid to the esterification pathway, and induced fatty liver and hypertriglyceridemia under fasting conditions.

Animals↗

Effects of refeeding diets on emeriamine-induced fatty liver in fasting rats.

We recently reported that fatty liver and hypertriglyceridemia are easily induced by the administration of an inhibitor of fatty acid oxidation (emeriamine; (R)-3-amino-4-trimethylaminobutyric acid) to fasting rats, and that these conditions are not accompanied by the increased de novo synthesis of fatty acid [J. Nutr. Sci. Vitaminol., 42, 111-120, (1996)]. To study whether emeriamine-induced fatty liver is affected by nutrients during recovery from fatty acid oxidation inhibition, we fed rats with either a high-carbohydrate (HCHO) diet or a high-fat (HFAT) diet. Rats fed an HCHO diet following the administration of emeriamine showed a marked decrease in serum and hepatic triglycerides, and a marked increase in hepatic glycogen. The lower levels of serum and hepatic triglycerides were accompanied by decreased activities of the NADPH-generating enzymes such as malic enzyme and glucose-6-phosphate dehydrogenase. By contrast, rats fed an HFAT diet showed less significant changes in hepatic triglyceride and glycogen levels. These results suggest a reciprocal relationship between the triglyceride level and glycogen accumulation caused by HCHO diet during recovery from emeriamine.

Animals↗

Potentiation of nitric oxide-mediated vasorelaxation by xanthine oxidase inhibitors.

Nitric oxide (NO), now almost synonymous with endothelium-derived relaxing factor (EDRF), reacts with superoxide anion radical (O2-) and forms a potentially toxic molecular species, peroxynitrite (ONOO-). Because xanthine oxidase (XO) seems to be a major O2- -producing enzyme in the vascular system, it is important to clarify the mechanism of XO regulation of NO/EDRF. We first characterized the inhibition of XO in vitro by three types of pyrazolopyrimidine derivatives. Kinetic studies indicated that 4-amino-6-hydroxpyrazolo[3,4-d]pyrimidine (AHPP) and allopurinol competitively inhibited the conversion of xanthine to uric acid catalyzed by XO, with apparent Ki values of 0.17 +/- 0.02 and 0.50 +/- 0.03 micro M respectively; alloxanthine inhibited this conversion in a noncompetitive manner with an apparent Ki value of 3.54 +/- 1.12 microM. O2- generation in the xanthine/XO system assayed by lucigenin-dependent chemiluminescence was suppressed most strongly by AHPP in a dose-dependent fashion; allopurinol itself appears to reduce the enzyme by transfer of an electron to O2, thus generating O(2-). AHPP significantly augmented EDRF-mediated relaxation of aortic rings from both rabbits and spontaneously hypertensive rats (SHR) in a dose-dependent manner, whereas allopurinol did not affect the relaxation and only marginal potentiation of the vasorelaxation was observed with alloxanthine. Finally, iv injection of AHPP (50.4 mg/kg; 100 micromol/300 g rat) reduced the blood pressure of SHR rats to 70% of the initial pressure; this pressure is almost the blood pressure of normal rats. Allopurinol (100 micromol/300 g rat; iv) showed transient decrease in blood pressure and moderate reduction of hypertension of SHR (10%) was observed with iv injection of alloxanthine (100 mumol/300 g rat). On the basis of these results, it seems that XO regulates EDRF/NO via production of O2-.

Allopurinol↗

Disinfection of removable dentures using ozone.

Over time, removable dentures tend to become unsanitary and emit unpleasant odors, and oral mucosa sometimes becomes inflamed or denture stomatitis is caused by denture plaque. Recently, various cleaning products designed to keep removable dentures sanitary have appeared on the market. It is known that denture plaque is mainly composed of Candida albicans (C. albicans), and that ozone seems to inhibit these micro-organisms. Accordingly, a denture cleaner using ozone bubbles (ozone concentration of about 10 ppm) was considered as clinically appropriate because of its strong disinfecting and deodorizing power, and high biological safeness. The effectiveness of this cleaner against C. albicans was investigated using. Results showed that C. albicans decreased to about 1/10 after 30 min and to 1/10(3) after 60 min.

Candida albicans↗

[HLA class II alleles and leprosy (Hansen's disease) classified by WHO-MDT criteria].

Human leukocyte antigens (HLA) class II alleles were analyzed in Japanese leprosy patients to ascertain whether immunogenetic differences exist among the forms of leprosy in classification of World Health Organization-recommended multidrug therapy (WHO-MDT). The subjects were 86 unrelated Japanese leprosy patients, including 62 multibacillary leprosy (MBL), 24 paucibacillary leprosy (PBL). Controls were 114 unrelated healthy subjects. Genotyping of HLA class II alleles was performed by using the polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) and PCR-restriction fragment length polymorphism (RFLP) methods. The frequencies of HLA-DRB1* 1501, * 1502 and DRB5* 0101,* 0102 and DQA1* 0102 and DQB1* 0602 were significantly increased in the whole patients (44.2%, 34.9%, 44.2%, 34.9%, 53.4% and 41.9%, respectively) as compared with the control subjects (14.0%, 21.1%, 14.0%, 21.1%, 27.2% and 13.2%, respectively). On the other hand, the frequencies of HLA-DRB1* 0405, * 0803, * 0901 and DQA1* 03 and DQB1* 0401 were significantly decreased in the whole patients (10.5%, 5.8%, 16.3%, 41.9% and 9.3%, respectively) as compared with the control subjects (29.8%, 17.5%, 30.7%, 78.1% and 29.8%, respectively). When MBL and PBL patients were compared, the frequencies of HLA-DRB1* 1501, DRB5* 0101 and DQB1* 0602 were significantly increased in the MBL patients (51.6%, 51.6% and 48.4%, respectively) as compared with the PBL patients (25.0%, respectively). Our results suggest that HLA-DRB1* 1501, DRB5* 0101 and DQB1* 0602 contribute to the susceptibility to the Japanese MBL.

Aged↗

[Mesonephric adenocarcinoma arising in the female urethral diverticulum].

A forty four-year-old house-wife presented with gross hematuria and difficulty on urination of a year and 3 months duration. Transvaginal examination showed a hen egg-sized soft mass on the anterior vaginal wall. Urine cytology revealed many clusters of malignant cells suggestive of adenocarcinoma. Cystourethrography revealed two urethral diverticula, whose orifices were cystoscopically located at the proximal and distal side of urethral sphincter, respectively. By vaginal digital pressing, a soy-bean sized papillary tumor came out of the proximal diverticulum. Histopathological examination of the biopsied tumor suggested poorly differentiated transitional cell carcinoma with inverted growth. Under the diagnosis of carcinoma arising in the urethral diverticulum, anterior pelvic exenteration with formation of Indiana pouch was carried out. The tumor in the proximal diverticulum was histologically composed of a variety of adenocarcinomatous pattern, such as tubular, papillary and cystic structure with a distinctive pattern of tubules lined by a superficial layer of hobnail cells, leading to the diagnosis of mesonephric adenocarcinoma of urethral diverticulum. Postoperative radiation therapy was given because the diverticulum was adherent to the pubic bone, though lymph node metastasis was negative. She has been well with no evidence of the disease for 1 year and 4 months after the operation. Although the histogenesis of female urethral mesonephric adenocarcinoma was still controversial, this case seems to be the forty fourth case in the world literature.

Adult↗

Leustroduscin B, a new cytokine inducer derived from an actinomycetes, induces thrombocytosis in mice.

Leustroduscin B (LSN-B), a novel colony-stimulating factor (CSF) inducer produced by an actinomycetes, has previously been shown to induce CSF production in bone marrow stromal cells. To determine the biological activity of LSN-B on hematopoiesis in vivo, LSN-B was administered intraperitoneally to mice every day for three to six days. Peripheral platelet counts were markedly elevated on days 4 through 6 compared with the control mice injected with vehicle. Serum II/6 levels were low (0.8 ng/ml) or virtually undetectable in the drug treated groups. This cytokine profile suggests that LSN-B induction of thrombocytosis is mechanistically distinct from other cytokine inducers such as IL-1 or FK-565.

Animals↗