Search PubMed⌕ Search

Biomedical subjects

A Ito

Publications and source records attributed to A Ito.

At least 379 records · Page 21Linked to original sources
PubMed1996

Fluconazole monotherapy for cryptococcosis in non-AIDS patients.

Treatment with 200 to 400 mg/day fluconazole was evaluated in 44 patients without AIDS who had cryptococcosis (19 with cryptococcal meningitis, 22 with pulmonary cryptococcosis, 3 with other cryptococcal infections). For all patients, the clinical response rate was 89% (48% were clinically cured and 41% clinically improved). Of the patients with cryptococcal meningitis, 89% were mycologically cured. These rates are comparable to those obtained in the treatment of AIDS patients with cryptococcal disease. In the group of patients with cryptococcal meningitis, there was a high rate of agreement between the mycological response to therapy and cryptococcal antigen test results. The use of cryptococcal antigen testing is recommended in all patients with cryptococcosis.

Adult↗
PubMed1996

Long-term neuroleptic treatments counteract dopamine D2 agonist inhibition of adenylate cyclase but do not affect pertussis toxin ADP-ribosylation in the rat brain.

We have investigated the response of adenylate cyclase to GTP and to dopamine (DA) in striatal membranes of rats treated for 3 weeks with chlorpromazine or haloperidol, and further measured the level of Gi (an inhibitory GTP-binding protein) or Go (a similar GTP-binding protein of unknown function) in 3 areas (cerebral cortex, striatum and hippocampus) utilizing pertussis toxin-catalyzed ADP ribosylation. In saline-treated control membranes, GTP exerted a biphasic effect on basal and DA-stimulated enzyme activity--peak levels of stimulation by DA plus GTP were observed at 1 microM GTP. Conversely, dopaminergic inhibitory effects at 10-100 microM GTP were completely attenuated in chlorpromazine or haloperidol-treated membranes. D2 inhibition of adenylate cyclase by the selective D2 agonist PPHT was also attenuated due to these neuroleptic treatments, while an increase in D2 receptor binding was observed. The pertussis toxin ADP-ribosylation of G-proteins (Gi/Go) did not differ significantly in any area. This indicates that long-term neuroleptic treatments increased D2 receptor binding, but attenuated D2 inhibition of adenylate cyclase, and exercised no influence on pertussis toxin ADP-ribosylation.

Adenosine Diphosphate Ribose↗
PubMed1996

Cestocidal activity of Acacia auriculiformis.

The cestocidal activity of Acacia auriculiformis was evaluated using rats each harbouring a single adult worm of Hymenolepis diminuta. The ethanol extract (300 mg/kg/day) and the saponins (200 mg/kg/day) obtained from the funicles of A. auriculiformis, were administered orally to two groups each of 10 rats, respectively, on day 20 after oral inoculation with a single cysticercoid of H. diminuta. Adult worms were expelled within 5 days from rats treated with the ethanol extract and within 3 days from those treated with saponins. No appreciable side effects were observed in the treated rats.

Acacia↗
PubMed1996

Antibody responses against Echinococcus multilocularis antigens in naturally infected Rattus norvegicus.

Two Norway rats, Rattus norvegicus, were found to be naturally infected with Echinococcus multilocularis in Japan. One of them was simultaneously infected with at least three different sized metacestodes of Taenia taeniaeformis. These two R. norvegicus rats and another R. norvegicus naturally infected with T. taeniaeformis and Capillaria hepatica were examined to see if they showed any antibody responses against these two cestode parasites with the view to obtaining more information on the importance of rats as the intermediate host for E. multilocularis. These R. norvegicus showed very poor antibody responses against the two cestode species, although the Wistar rats, R. rattus, experimentally infected with a single smaller sized metacestode of T. taeniaeformis showed stronger responses not only against T. taeniaeformis but also against E. multilocularis. Therefore the three R. norvegicus naturally infected with E. multilocularis and/or T. taeniaeformis demonstrated virtually no immune response, at least against these cestodes.

Animals↗
PubMed1996

Measurement of soft X-ray absorption spectra and elemental analysis in local regions of mammalian cells using an electronic zooming tube.

Direct measurement of absorption spectra for minute areas (2 microns x 2 microns) in a dried mammalian cell was attempted using X-ray contact images of a whole cell. The wavelength region used ranged from 1.5 to 10nm covering the absorption edges of the major cellular elements. The measurements were achieved taking advantage of synchrotron radiation as a tuneable light source and an electronic zooming tube as an X-ray detector with a high spatial resolution. The spectra in every intracellular area exhibited marked absorption changes at the absorption edges of carbon, nitrogen and oxygen, while minor but significant changes for iron and calcium were observed, particularly in the cytoplasmic areas. These results reveal the different spatial distributions of the constituent elements in a cell.

Animals↗
PubMed1996

Regulation of Bcl-2 protein expression in human neuroblastoma SH-SY5Y cells: positive and negative effects of protein kinases C and A, respectively.

The regulatory mechanism of Bcl-2 protein expression was investigated in SH-SY5Y cells, the human neuroblastoma cell line that expresses natively Bcl-2 proteins. WHen the cells were treated with 12-O-tetradecanoylphorbol 13-acetate (TPA) or retinoic acid, the level of Bcl-2 protein was increased compared with the control. These effects were inhibited by pretreatment with a protein kinase C (PKC) inhibitor, staurosporine or calphostin C. The level of Bcl-2 protein was also increased by treatment with carbachol, a muscarinic acetylcholine receptor (mAChR) agonist, and the effect were also inhibited by pretreatment with staurosporine or calphostin C. An addition, a carbachol-induced increase in Bcl-2 protein levels and a transient elevation of [Ca2+]i were inhibited by pretreatment with 4-DAMP (4-diphenylacetoxy-N-methylpiperidine), an m3 mAChR antagonist. In contrast, the level of Bcl-2 protein was decreased by treatment with dibutyryl cAMP (diBu-cAMP), forskolin, or cholera toxin, and the effects of diBu-cAMP were inhibited by pretreatment with a protein kinase A (PKA) inhibitor, H-89. From these results, we suggest that the expression of Bcl-2 proteins is regulated by PKC and PKA in positive and negative manners, respectively, in SH-SY5Y cells. Furthermore, the nucleosomal DNA fragmentation induced by serum depletion for 4 h was observed in SH-SY5Y cells when the level of Bcl-2 protein was down-regulated by treatment with 1 mM diBu-cAMP for 3 days, although the DNA fragmentation by serum depletion for 4 h was not observed in nontreatment cells, indicating that Bcl-2 proteins whose expression is regulated by PKC and PKA play important roles in serum depletion-induced apoptosis.

Apoptosis↗
PubMed1996

Changes in serum fibrogenesis markers during interferon therapy for chronic hepatitis type C.

We serially measured the levels of serum N-terminal peptide of type III procollagen (PIIINP), the 7S domain of type IV collagen (IV-7S), and hyaluronate (HA) before (0 month), at the end (6 months), and 24 weeks after the end of interferon therapy (12 months) in patients with chronic hepatitis type C to estimate the effects of interferon alfa (IFN-alpha) on serum levels of hepatic fibrogenesis markers. One hundred twenty-one patients with chronic hepatitis type C received intramuscular injection of 6 million U of natural IFN-alpha for 24 weeks. Patients were divided into three groups: sustained complete response (CR-S), complete response with rebound (CR-R), and nonresponse (NR). Serum PIIINP, IV-7S, and HA levels were significantly decreased and reached normal levels at 12 months in CR-S; only IV-7S levels were significantly decreased at 12 months in CR-R, whereas these levels remained abnormally high in the NR. These results suggest that IFN-alpha therapy could lower the levels of serum hepatic fibrogenesis markers along with improvements in hepatic inflammation.

Adult↗
PubMed1996

Mitochondrial NADH- or NADPH-linked aquacobalamin reductase activity is low in human skin fibroblasts with defects in synthesis of cobalamin coenzymes.

Mammalian livers have been reported to contain NADH- and NADPH-linked aquacobalamin reductases, which are distributed in both mitochondria and microsomes. The four aquacobalamin reductase isozymes have been purified and characterized from rat liver. It is unclear which aquacobalamin reductase among the four reductase isozymes participates in the synthesis of cobalamin coenzymes. To clarify the physiological roles of the aquacobalamin reductase isozymes, human mutant fibroblasts (cblC and cblA cells) with defects in cobalamin reductases involved in the coenzyme synthesis were used. In the cblC cells, the activity of the mitochondrial NADH-linked aquacobalamin reductase was reduced significantly, compared with normal human fibroblasts but the mitochondrial NADPH-linked enzyme was not. The reduced specific activity of the NADH-linked enzyme was not due to reduction in levels of the enzyme, but in its affinity for NADH. Although there was not a significant difference in the mitochondrial NADH-linked enzyme activity between normal and cblA cells, the activity of the mitochondrial NADPH-linked enzyme was not detectable in the mutant cells. These results indicate that the defects in the mitochondrial NADH- and NADPH-linked aquacobalamin reductases underlie cblC and cblA disorders, respectively.

Cells, Cultured↗
PubMed1996

Characterization of rat monoamine oxidase A with noncovalently-bound FAD expressed in yeast cells.

The FAD-binding cysteine of rat liver monoamine oxidase A (MAO A), Cys406, was converted to an alanine by site-directed mutagenesis of the cDNA. The wild-type and mutated enzymes were expressed in yeast cells and catalytic activities were assayed, using as substrates serotonin, tyramine, and kynuramine. Specific activities of the Ala-mutant for these substrates, calculated as the activities per pargyline-sensitive molecule, were about half of those of the wild-type enzyme. The Km values of the mutant enzyme for the substrates were similar to those of the wild-type enzyme. An adduct between FAD and pargyline, a mechanism-based inhibitor, was attached to the apoprotein in the wild-type enzyme, while in the Ala-mutant it was detached from the apoprotein, thereby indicating the presence of noncovalently bound FAD in the mutant enzyme. The Ala-mutant rapidly lost activity during incubation, whereas the wild-type enzyme retained the initial activity. Partial protection from inactivation occurred in the presence of FAD, but not of FMN. Recovery of the enzyme activity was nil when FAD was added after the inactivation. Thus, while the covalent attachment of FAD in MAO A is not required for the catalytic activity, it may function as a structural core for the active conformation in the membrane.

Alanine↗
PubMed1996

In situ topology of cytochrome b5 in the endoplasmic reticulum membrane.

Cytochrome b5 is tail-anchored in the ER membrane and is composed of three functionally different portions; amino-terminal heme-containing catalytic, central hydrophobic membrane-anchoring, and carboxy-terminal ER-targeting portions [Mitoma, J. and Ito, A. (1992) EMBO J. 11, 4197-4203]. In situ topology of cytochrome b5 in the ER-membrane was studied using immunofluorescence microscopy. Antibodies were raised against the hydrophilic portion (anti-b5) and the carboxy-terminal seven amino acid residues (anti-peptide) of cytochrome b5 and used for detection of the cytochrome in COS cells which expressed the rat cytochrome. Anti-b5 antibody detected the cytochrome in a reticular staining pattern characteristic of the ER, even when the cell plasma membrane was permeabilized with Streptolysin O. The anti-peptide displayed a fluorescence signal only with Triton-permeabilized cells in which the antibody was able to penetrate into the ER lumen. In a double immuno-staining of the cell using the antipeptide antibody and the antibody against protein disulfide isomerase, both antibodies showed the same staining pattern in the presence of either Triton X-100 or Streptolysin O. The results indicate that the carboxy-terminal hydrophilic stretch is exposed to the luminal side. Cytochrome b5 was tagged with c-myc peptide at the carboxy-terminal end and the topology of the c-myc peptide was analyzed by the same method. Anti c-myc monoclonal IgG detected the tagged cytochrome b5 only after Triton treatment of the fixed cells, suggesting that the addition of c-myc peptide to the carboxy-terminal end does not affect insertion or orientation of the cytochrome in the ER membrane.

Animals↗
PubMed1996

Role of basic amino acids in the cleavage of synthetic peptide substrates by mitochondrial processing peptidase.

Our recent experiments using model peptides of rat malate dehydrogenase (MDH) indicated that a proximal arginine and a distal basic amino acid are important for processing by mitochondrial processing peptidase (MPP). [Niidome, T., Kitada, S., Shimokata, K., Ogishima, T., and Ito, A. (1994) J. Biol. Chem. 269, 24719-24722]. To elucidate if the recognition elements apply to other precursor proteins, we analyzed cleavage of model peptides of human ornithine aminotransferase (OAT). Purified peptidase cleaved peptides that corresponded to N-terminal 1-25 and 3-25 at the correct site (Gly17-Val18) at nearly equal rates. Replacement of Arg16 (-2 position) with lysine or alanine reduced the processing efficiency by 95- and 380-fold, respectively. Either deletion from Met1 to Arg10 or replacement of the basic amino acids between them decreased the processing efficiency considerably. A peptide containing Arg7 in addition to Lys4 and Arg10 was more effective than the control peptide. However, a peptide with one and two consecutive basic amino acids in the distal region had a processing efficiency close to the control peptide. These results indicated that processing of OAT was enhanced by an increase in the number of basic amino acids with a suitable distance between them. In other respects, the processing signal of OAT was essentially the same as that of MDH.

Amino Acid Sequence↗
PubMed1996

Influence of paternal (252) Cf neutron exposure on abnormal sperm, embryonal lethality, and liver tumorigenesis in the F(1) offspring of mice.

Experiments were conducted to determine whether neutron-induced genetic damage in parental germline cells can lead to development of cancer in the offspring. Seven-week-old C3H male mice were irradiated with (252) Cf neutrons at a dose of 0, 50, 100, or 200 cGy. Two weeks or three months after irradiation, the male mice were mated with virgin 9-week-old C57BL females. Two weeks after irradiation, the irradiated male mice showed an increased incidence of sperm abnormalities, which led to embryo lethalities in a dose-dependent manner when they were mated with unirradiated female mice. Furthermore, liver tumors in male offspring of male mice in the 50 cGy group were significantly increased in 19 of 44 (43.2%) animals, in clear contrast to the unirradiated group (1 of 31; 3.2%) (P < 0.01). In the 100 cGy group, 6 of 39 (15%) mice had lesions. At 3 months after irradiation abnormal sperm and embryonal lethality were not significantly increased. The incidences of liver tumors in male offspring from the 50 cGy, 100 and 200 cGy groups were 6 of 20 (30%), 5 of 22 (23%) and 1 of 19 (5%), respectively, which are not significantly increased compared with the control. It is concluded that increased hepatic tumor risk in the F(1) generation may be caused by genetic transmission of hepatoma-associated trait(s) induced by (252) Cf neutron irradiation.

Animals↗
PubMed1996

Gastric tumorigenicity of 1,2-dimethylhydrazine on the background of gastric intestinal metaplasia induced by X-irradiation in CD (SD) rats.

Five-week-old male CD (SD) rats were X-irradiated with a total of 20 Gy in 2 equal fractions with a 3-day interval. After the second irradiation, rats were fed normal diet supplemented with 1% sodium chloride, which is known to increase intestinal metaplasia. 1,2-Dimethylhydrazine (DMH) solution was injected i.m. into the back musculature at a dose of 20 mg/kg body weight weekly for 10 weeks, beginning 20 weeks after the final irradiation. Twelve months after the initial carcinogen treatment, gastric tumors in the glandular stomach were observed in 2 (3 lesions) of 30 animals in the X-irradiated and DMH-treated group fed diet supplemented with 1% sodium chloride. No gastric tumors were observed in the group which excluded X-irradiation from the experimental protocol.

1,2-Dimethylhydrazine↗
PubMed1996

Differential diagnosis of gall-bladder masses using colour Doppler ultrasonography.

To evaluate the diagnostic accuracy of colour Doppler ultrasonography in the differential diagnosis of gall-bladder lesions, we studied colour Doppler flow imaging of gall-bladder masses in 75 patients with gall-bladder masses, including 26 patients with cancer, 18 with benign polyps, 10 with adenomyomatosis and 21 with pseudo-tumorous sludge and 28 healthy subjects as controls. The presence of a colour signal, pattern of the colour signal, blood flow velocity and resistive index (RI) within lesions were assessed using colour Doppler ultrasonography. In cancerous lesions, the colour signal pattern was diffuse or arborizing (sensitivity 90.5% (19/21); specificity 62.5% (10/16)) and the velocity and RI were (mean +/- s.d.) 39.0 +/- 12.4 cm/s and 0.62 +/- 0.12, respectively, which was significantly different (P < 0.01) compared with controls (11.4 +/- 2.5 and 0.75 +/- 0.03, respectively). The colour signal pattern obtained from polyps was linear at their base in 62.5% (10/16) of cases, but the velocity (13.6 +/- 5.5) and RI (0.74 +/- 0.08) did not differ from those of the controls. Lesions other than cancer and polyp had no colour signal. There were overlaps in the values of velocity and RI between malignant and benign lesions. When 20 cm/s for velocity and 0.65 for RI were used as the respective cut-off values, the sensitivity and specificity of this method in the diagnosis of malignant lesions was 95.2% (20/21) and 87.5% (14/16) for velocity and 66.7% (14/21) and 87.5% (14/16) for RI, respectively. In a prospective study consisting of 10 patients with cancer and 21 patients with polyps, the sensitivity and specificity were 90 and 66.7% for the colour signal, 100 and 100% for velocity and 80 and 90.4% for RI, respectively. In conclusion, colour Doppler ultrasonography can be useful in the diagnosis of gall-bladder masses in combination with conventional ultrasonographic findings of gall-bladder masses, especially in the differentiation of cancers from benign lesions.

Blood Flow Velocity↗
PubMed1996

[Hansenula anomala fungemia in a patient undergoing IVH-treatment with ascending colon carcinoma].

A case of catheter-related fungemia due to Hansenula anomala is reported. A 61-year-old male was diagnosed as having stage 3 ascending colon carcinoma stenosing the colon severely and was admitted to our hospital to receive an operation of the carcinoma. Just after admission, an intravenous hyperalimentation (IVH) catheter was inserted and IVH was started to prevent development of ileus and to prepare for laparotomy. Nine days later, he developed a fever. On the next day, the IVH catheter was removed and cultures of blood and the catheter revealed the presence of yeast-like organisms that were identified as H. anomala. Laboratory data showed hypogranulocytemia, slight disturbances of liver and kidney, a prolongation of PT, an increase of FDP and positive reaction of candida antigen by CAND-TEC. He improved after the removal of the catheter, and treatment with intravenous infusion of fluconazole 2 days after the removal was thought to be useful for recovery and to prevent the reappearance of infection though susceptibility to fluconazole was not good. Human infections due to H. anomala are rare and this is the 8th case of H. anomala fungemia in Japan. From this report and a review of the literature, risk factors for developing this fungemia include the use and abuse of central venous catheters such as IVH-catheter. It appears that H. anomala has recently emerged as a potential pathogen in the immunocompromised hosts and patients after insertion of central venous catheters and that these organisms should be added to the growing list of unusual fungal pathogens in these patients.

Colonic Neoplasms↗
PubMed1996

Translational augmentation of pro-matrix metalloproteinase 3 (prostromelysin 1) and a tissue inhibitor of metalloproteinases (TIMP)-1 mRNAs by epidermal growth factor and transforming growth factor alpha, but not by interleukin 1 alpha or 12-O-tetradecanoylphorbol 13-acetate in human uterine cervical fibroblasts: the possible involvement of an atypical protein kinase C.

We have previously reported that epidermal growth factor (EGF) augments the translation of pro-matrix metalloproteinase 3 (proMMP-3/prostromelysin 1) and tissue inhibitor of metalloproteinases (TIMP)-1 mRNAs during the first 1-h treatment of human uterine cervical fibroblasts (Hosono, T. et al., FEBS Lett., 381, 115-118, (1996)). In this report, we have investigated the effect of interleukin 1 alpha (IL-1 alpha) and 12-O-tetradecanoylphorbol 13-acetate (TPA), potent stimulators of proMMPs and TIMP-1 production, on the translation of proMMP-3 and TIMP-1 mRNAs. When human uterine cervical fibroblasts were treated with IL-1 alpha or TPA for 2h, their translations were not augmented, whereas the steady-state levels of proMMP-3 and TIMP-1 mRNAs in the cells treated with these stimuli for 24 h were increased 13.3- and 1.3-fold by IL-1 alpha and 52.5- and 5.7-fold by TPA, respectively. By contrast, transforming growth factor alpha(TGF alpha), which also binds to EGF-receptor, enhanced their production as early as 2 h after treatment, indicating that growth factors that bind to EGF-receptor are likely to be involved in the translational enhancement of proMMP-3 and TIMP-1 mRNAs. EGF partially translocated cytoplasmic protein kinase C (PKC) to plasma membrane, but the PKC down-regulation induced by 100nM TPA did not diminish the EGF-mediated translational augmentation of proMMP-3 and TIMP-1 mRNAs. In contrast, the PKC inhibitor of 1-(5-isoquinolinesulfonyl)-2-methylpiperazine dihydrochloride (H-7) effectively suppressed the translational regulation of proMMP-3 and TIMP-1 in a dose-dependent manner during the first 2-h treatment with EGF. These results suggest that EGF and TGF alpha, but not IL-1 alpha and TPA, specifically augment the translation of proMMP-3 and TIMP-1 mRNAs and accelerate their accumulation without modifying their transcripts during the first 1-2 h treatment of human uterine cervical fibroblasts. This translational augmentation is suggested to be mediated by a TPA-insensitive atypical PKC subclass in the PKC family.

Cervix Uteri↗
PubMed1996

Development of oral dosage form for elderly patients: use of agar as base of rapidly disintegrating oral tablets.

Rapidly disintegrating tablets as an oral dosage form for elderly patients with impaired swallowing were investigated using agar powders (AG) or treated agar powders (TAG). When the compression pressure was changed from 0.4 to 2.0 ton/cm2, the disintegration time of AG tablets increased from about 60 to about 160s, and the hardness significantly increased from 3 to 13 kgw. The disintegration time and hardness of the TAG tablets were scarcely affected by the compression pressure: the disintegration time was 5--6s, and the hardness was 2--3 kgw. The rapid disintegration of the TAG tablets seemed due to the rapid water penetration into the tablet resulting from the large pore size and large overall pore volume. It was found that rapidly disintegrating oral tablets with proper hardness can be prepared using TAG.

Absorption↗