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Biomedical subjects

S Aoki

Publications and source records attributed to S Aoki.

At least 127 records · Page 7Linked to original sources
PubMed2000

[Pneumocystis carinii pneumonia associated with acquired immunodeficiency syndrome followed by KL-6, surfactant protein-D and beta-D-glucan in serum].

A 40-year-old man was admitted to our hospital with acute respiratory failure. The patient was given a diagnosis of Pneumocystis carinii pneumonia (PCP) associated with acquired immunodeficiency syndrome (AIDS). After treatment with trimethoprim-sulfamethoxazole and corticosteroid, the respiratory failure was improved and the abnormal shadows disappeared. The serum beta-D-glucan level, significantly elevated (76.0 pg/ml) on admission, returned to the normal range within two weeks. Serum KL-6 (max. 7580 U/ml) and surfactant protein-D (SP-D) (max. 235 ng/ml), which are produced by type II pneumocytes, increased after elevation of the beta-D-glucan level and decreased gradually following successful treatment. These findings suggest that beta-D-glucan may be a serological marker for PCP infection and KL-6 may be a serological marker for lung injury in PCP with AIDS.

AIDS-Related Opportunistic Infections↗
PubMed2000

[Respiratory failure due to diaphragmatic dysfunction in Charcot-Marie-Tooth disease: a case report].

A 56-year-woman with type 2 respiratory failure due to diaphragmatic dysfunction in Charcot-Marie-Tooth disease (CMT) is reported. The patient, who had a 50-year history of CMT, was referred to our hospital because of nocturnal dyspnea. Arterial blood gas analysis on admission showed marked hypoxia with hypercapnia, and physical examination revealed thoracoabdominal paradoxus in the supine position. Chest radiography revealed elevation of both sides of the diaphragm. The vital capacity and arterial blood gas pressure in the sitting position were markedly higher than those in the supine position. Electrical phrenic nerve stimulation failed to produce any convincing muscle action potential in the diaphragm. These findings suggested that her respiratory failure was induced by both diaphragmatic dysfunction caused by bilateral phrenic nerve palsy due to CMT. Treatment of this patient was started at home with a pressure support ventilator, resulting in satisfactory clinical improvement. In general, respiratory muscle impairment is a rare phenomenon in a patient with CMT. However when a patient with CMT complains of dyspnea or if unexpected heart failure develops, it is important to keep in mind that CMT may be associated with phrenic nerve palsy.

Charcot-Marie-Tooth Disease↗
PubMed2000

Extracellular activity in Cryptococcus neoformans strains isolated from AIDS patients and from environmental sources.

Nineteen Cryptococcus neoformans strains isolated from AIDS patients and 16 from bird droppings were tested for their extracellular activity. Typical enzymatic activity that was different from other medically important yeasts was found. The results obtained may indicate that there are new extracellular enzymatic activities that imply a relationship between C. neoformans and its virulence. A correlation among the different enzymatic activities was also investigated and according to the results obtained no relationship was observed among any of the recorded extracellular enzymatic activities. Research on C. neoformans extracellular enzymatic activity is useful not only to better understand its metabolism but in particular to establish a possible relationship between its virulence and pathogenicity.

Journal Article↗
PubMed1999

Roxithromycin and clarithromycin, 14-membered ring macrolides, potentiate the antitumor activity of cytotoxic agents against mouse B16 melanoma cells.

We previously reported antiangiogenic activity of roxithromycin and clarithromycin, 14-membered ring macrolide antibiotics. In the present study, we examined the antitumor effects of roxithromycin and clarithromycin, alone and in combination with several cytotoxic drugs, on mouse B16BL6 melanoma cells in vivo and in vitro. Both roxithromycin and clarithromycin potentiated the inhibition of tumor growth induced by cyclophosphamide, cis-diamminedichloroplatinum(II), Adriamycin and vindesine in vivo. However, neither roxithromycin nor clarithromycin, altered the cytotoxicity of 4-hydroperoxycyclophosphamide, cis-diamminedichloroplatinum(II), Adriamycin or vindesine in an in vitro cell proliferation assay. These results suggest that the antiangiogenic activity of roxithromycin and clarithromycin may provide beneficial effects in combination with cytotoxic therapies against solid tumors.

Animals↗
PubMed1999

Horizontal gene transfer and mutation: ngrol genes in the genome of Nicotiana glauca.

Ngrol genes (NgrolB, NgrolC, NgORF13, and NgORF14) that are similar in sequence to genes in the left transferred DNA (TL-DNA) of Agrobacterium rhizogenes have been found in the genome of untransformed plants of Nicotiana glauca. It has been suggested that a bacterial infection resulted in transformation of Ngrol genes early in the evolution of the genus Nicotiana. Although the corresponding four rol genes in TL-DNA provoked hairy-root syndrome in plants, present-day N. glauca and plants transformed with Ngrol genes did not exhibit this phenotype. Sequenced complementation analysis revealed that the NgrolB gene did not induce adventitious roots because it contained two point mutations. Single-base site-directed mutagenesis at these two positions restored the capacity for root induction to the NgrolB gene. When the NgrolB, with these two base substitutions, was positioned under the control of the cauliflower mosaic virus 35S promoter (P35S), transgenic tobacco plants exhibited morphological abnormalities that were not observed in P35S-RirolB plants. In contrast, the activity of the NgrolC gene may have been conserved after an ancient infection by bacteria. Discussed is the effect of the horizontal gene transfer of the Ngrol genes and mutations in the NgrolB gene on the phenotype of ancient plants during the evolution of N. glauca.

Amino Acid Sequence↗
PubMed1999

Cloning and sequencing of the cDNA species for mammalian dimeric dihydrodiol dehydrogenases.

Cynomolgus and Japanese monkey kidneys, dog and pig livers and rabbit lens contain dimeric dihydrodiol dehydrogenase (EC 1.3.1.20) associated with high carbonyl reductase activity. Here we have isolated cDNA species for the dimeric enzymes by reverse transcriptase-PCR from human intestine in addition to the above five animal tissues. The amino acid sequences deduced from the monkey, pig and dog cDNA species perfectly matched the partial sequences of peptides digested from the respective enzymes of these animal tissues, and active recombinant proteins were expressed in a bacterial system from the monkey and human cDNA species. Northern blot analysis revealed the existence of a single 1.3 kb mRNA species for the enzyme in these animal tissues. The human enzyme shared 94%, 85%, 84% and 82% amino acid identity with the enzymes of the two monkey strains (their sequences were identical), the dog, the pig and the rabbit respectively. The sequences of the primate enzymes consisted of 335 amino acid residues and lacked one amino acid compared with the other animal enzymes. In contrast with previous reports that other types of dihydrodiol dehydrogenase, carbonyl reductases and enzymes with either activity belong to the aldo-keto reductase family or the short-chain dehydrogenase/reductase family, dimeric dihydrodiol dehydrogenase showed no sequence similarity with the members of the two protein families. The dimeric enzyme aligned with low degrees of identity (14-25%) with several prokaryotic proteins, in which 47 residues are strictly or highly conserved. Thus dimeric dihydrodiol dehydrogenase has a primary structure distinct from the previously known mammalian enzymes and is suggested to constitute a novel protein family with the prokaryotic proteins.

Alcohol Oxidoreductases↗
PubMed1999

Dynamic MR imaging of the carotid wall.

The purpose of this study was to clarify temporal changes of carotid wall enhancement using dynamic magnetic resonance (MR) and to correlate its findings with pathological conditions. Cervical carotid arteries of 84 consecutive patients were studied with a 1.5 T MR imager using phased array coils. Axial spoiled gradient-echo (SPGR) images (30-58 second scan time) with fat saturation were repeated 4-8 times after the injection of contrast material. We evaluated the presence and thickness of hypointense inner rims and hyperintense outer rims of the carotid wall, temporal changes of outer rim enhancement, and their changes in relation to pathological conditions. Hypointense inner rims and enhanced outer rims were clearly visualized in 87% (73/84) of our subjects. Enhancement of the outer rim was minimal in early phases and gradually increased. Patient age had a significant correlation with outer rim thickness. In the portions with large atheromatous plaques, inner rims were disrupted or thickened. A marked thickening of the outer rim was observed in one patient with arteritis. The outer rims adjacent to malignant tumors were often obscured. Our study suggests that dynamic MR images of the cervical carotid artery can uniquely demonstrate angiogenesis of the wall itself. The outer rim of the artery shows relatively rapid enhancement, and its thickness correlates with age.

Adult↗
PubMed1999

Prediction of cerebral infarct sizes by cerebral blood flow SPECT performed in the early acute stage.

Cerebral infarct due to embolic stroke without recanalization was examined by cerebral blood flow (CBF) SPECT in the early acute stage, and the possibility of predicting the size it will reach in the later stages was evaluated. Twenty patients (67 +/- 13 years) were examined by CBF SPECT with 99mTc-ECD 4.5 +/- 3.1 hours after the onset of cardiogenic cerebral embolism. The ratio of the anteroposterior length of the cerebral hemisphere to that of the severe ischemic region, which was defined as an area of clear-cut severe reduction in CBF as observed by SPECT, was calculated. One week after the onset, the cerebral infarct was measured in the same manner by CT, and the relationship between the two measurements was evaluated. The CBF in the region of severe ischemia and the surrounding region was determined by the Patlak plot method, and the affected/non-affected (A/NA) ratio was calculated. In severe ischemic regions the CBF ranged from 1.7 ml/100 g/min to 20 ml/100 g/min (mean, 11 +/- 5 ml/100 g/min), whereas the A/NA ratio ranged from 4% to 45% (mean, 26 +/- 11%). On the other hand, the CBF in the surrounding regions ranged from 20 ml/100 g/min to 52 ml/100 g/min (mean, 34 +/- 8 ml/100 g/min) whereas the A/NA ratio ranged from 52% to 104% (mean, 77 +/- 11%). The coefficient of correlation between the infarct size predicted by SPECT and that measured by CT was r = 0.986, and the correlation equation was Y = 1.047X - 2.969. CBF SPECT performed in the early acute stage can be used to predict the size of cerebral infarct.

Aged↗
PubMed1999

Clonazepam in the treatment of prolonged depression.

BACKGROUND: The purpose of this paper was to examine the optimal adjunctive dose of clonazepam for the treatment of prolonged depression. METHODS: Sixty nine patients with prolonged depression were enrolled in an open trial over a 4 week period during which clonazepam was added to their medication. RESULTS: A daily dose of 3.0 mg clonazepam as augmentation was significantly more effective than doses of 1.5 mg and below. Most of the improved patients showed a rapid onset of action within 2 weeks, and side effects were not severe. CONCLUSION: A daily dose of at least 3.0 mg clonazepam as augmentation of ongoing antidepressant treatment should be considered in prolonged depressive patients with suboptimal improvement. LIMITATIONS: The effect on clonazepam alone on prolonged depression was not established, and its effect of on severe depression is unknown. High dose treatment was not carried out in this study.

Antidepressive Agents, Tricyclic↗
PubMed1999

Antiangiogenic and antitumor effects of 14-membered ring macrolides on mouse B16 melanoma cells.

We examined the effects of macrolide antibiotics on tumor angiogenesis, tumor growth and metastasis in the B 16BL6 mouse melanoma and C57BL mouse system. Two 14-membered ring macrolide antibiotics, roxithromycin and clarithromycin, significantly reduced the dense capillary network area in a mouse dorsal air sac angiogenesis model, whereas a 15-membered ring macrolide, azithromycin, and a 16-membered ring macrolide, josamycin, did not show any inhibitory effect on angiogenesis at the same dose. Intraperitoneal administration of roxithromycin and clarithromycin at 50 mg/kg/day reduced the tumor size of B 16BL6 melanoma to about 41% and 56%, respectively, of that of the control, and significantly suppressed pulmonary metastasis of B16BL6 cells in a spontaneous system. Azithromycin and josamycin, on the other hand, did not inhibit tumor growth or pulmonary metastasis of B16BL6 cells. Immunohistochemistry revealed that roxithromycin and clarithromycin reduced the tumor vascularity and increased apoptosis of the tumor cells in vivo. These results suggest that 14-membered ring macrolides have antiangiogenic and antitumor effects and might have possible therapeutic applications.

Angiogenesis Inhibitors↗
PubMed1999

Genetic alterations on chromosome 17p associated with response to radiotherapy in bulky cervical cancer.

Chromosome 17 alterations are found in more cancers than those of any other chromosome, and frequently involve the p53 gene on 17p13. The aim of this study was to identify the correlations between the presence of loss of heterozygosity (LOH) and microsatellite instability (MI) on chromosome 17p13 in patients with cervical cancer and the patients' response to radiotherapy. A total of 50 patients were treated with definitive radiotherapy. We performed biopsies and took specimens from the tumour and venous blood of all patients. Tumour and normal DNAs were analysed by polymerase chain reaction for genetic losses and instability at three polymorphic microsatellite loci mapped to 17p13. Nineteen of the 50 tumours (38%) displayed a genetic alteration (GA) on 17p13, 16 (32%) were found to have LOH, and three (6%) showed MI. The sizes of the tumours of the GA-positive patients were significantly greater than those of the GA-negative patients (P = 0.009). The mean tumour diameter of all patients was 6 +/- 2.4 cm. We divided the patients into those with tumours smaller than 6 cm in diameter (n = 26) and those with tumours equal to or greater than 6 cm in diameter (n = 24). The former group survived significantly longer compared to the latter group (P = 0.0002). Among the patients with < 6 cm tumours, all six GA-positive patients are alive with no evidence of disease (NED), whereas of the 20 GA-negative patients, 18 have NED and two are alive with disease (AWD) or suffered cancer-caused death (CD). Thus, there was no correlation between GA and radiotherapy response in the tumours smaller than 6 cm. However, among the patients with > or = 6 cm tumours, two of the GA-positive patients have NED and 11 are AWD/CD, whereas seven of the GA-negative patients have NED and four are AWD/CD. Among the patients with > or = 6 cm tumours, the response to radiotherapy of the GA-positive patients were significantly poorer than those of the GA-negative patients (P = 0.02). In addition, the GA-negative patients survived significantly longer compared to the GA-positive patients (P = 0.026). The results of this study suggest that GA increases with tumour growth. Improved success in the management of bulky cervical cancer requires a better understanding of its biological behaviour.

Aged↗
PubMed1999

Generation of bcr-abl specific cytotoxic T-lymphocytes by using dendritic cells pulsed with bcr-abl (b3a2) peptide: its applicability for donor leukocyte transfusions in marrow grafted CML patients.

Dendritic cells (DC), the most potent 'professional' antigen-presenting cells, hold promise for improving the immunotherapy of cancer. In this study, we investigated the ability of normal donor DC pulsed ex vivo with 12 mer bcr-abl (b3a2) peptide to generate b3a2-specific autologous or HLA-identical sibling donor's cytotoxic T-lymphocytes (CTL). DC that were grown from normal peripheral blood adherent cells or purified DC precursors in the presence of GM-CSF and IL-4, were pulsed with b3a2-peptide then were induced to become mature and functional cells by the addition of TNF-alpha. These peptide-pulsed mature DC elicited a potent b3a2-specific CTL response in vitro. The b3a2-peptide pulsed DC-primed peripheral blood lymphocytes (PBL) displayed significantly higher cytotoxic activity compared with peptide non-pulsed DC-primed PBL against target cells, which are b3a2 positive marrow cells derived from HLA-identical sibling chronic myelogenous leukemia (CML) patient, or peptide-pulsed autologous macrophages (P < 0.001). In addition, the b3a2 peptide-pulsed DC-primed and non-pulsed DC-primed PBL showed no cytotoxic response against peptide non-pulsed autologous macrophages. These findings revealed that normal donor PBL pre-immunized with b3a2-peptide pulsed autologous DC could increase the graft-versus-leukemia effect without exaggerating graft-versus-host-disease. Both CD8+ and CD4+ T lymphocytes were shown to be involved in the effector cell populations. The b3a2 peptide-pulsed DC-primed T cells were significantly superior in their production of GM-CSF and TNF-alpha compared with peptide non-pulsed DC-primed T cells. These intriguing preclinical results imply the feasibility of developing b3a2 peptide-DC based protocol for in vitro sensitization of normal donor leukocytes before donor leukocyte transfusions for patients with CML, who relapsed after HLA-matched sibling bone marrow transplantation.

Blood Donors↗
PubMed1999

Oxidative stress sensitivity and superoxide dismutase of a wild-type parent strain and a respiratory mutant of Candida albicans.

It is important to know responses of the pathogenic fungi to reactive oxygen species by which hosts protect themselves against fungal infection. In the present study, sensitivities to the superoxide radical (O2-) and superoxide dismutase (SOD) were compared between a wild-type parent strain and a respiration-deficient mutant of Candida albicans. When their survival was examined on an agar medium containing an intracellular O2- generator, paraquat (PQ), the parent strain was selectively killed by increasing the PQ concentration. In contrast, when cells of both strains were illuminated in a riboflavin solution, they exhibited similar sensitivity to O2- generated extracellularly by photo-reduced riboflavin. There were no large differences in sensitivity to hydrogen peroxide in the two strains. Thus, the high tolerance of the mutant to PQ was suggested to result from low intracellular O2- generation by PQ due to the respiratory deficiency. It is generally accepted that fungal cells contain manganese (Mn)-SOD in the mitochondria and copper and zinc (CuZn)-SOD in the cytoplasm. Cyanide-insensitive SOD activity (attributable to Mn-SOD) was dominant in the parent strain throughout growth phases, whereas cyanide-sensitive activity (attributable to CuZn-SOD) occurred in the mutant. The activity bands of Mn- and CuZn-SODs were clearly separated by electrophoresis of the cell extracts of both strains on non-denaturing polyacrylamide gels. The electrophoretic profiles obtained were consistent with the results of the activity assay. These results showed that the respiratory deficiency affected oxidative stress sensitivity and SOD in C. albicans.

Candida albicans↗
PubMed1999

Different effect of desipramine on protein kinase C in platelets between bipolar and major depressive disorders.

Protein kinase C (PKC) activity was investigated in platelets from affective disorder subjects and healthy volunteers. The PKC activity of platelets incubated with desipramine was determined in vitro. The PKC activity of the major depressive disorder subjects and healthy volunteers was inhibited by desipramine, whereas that of the bipolar disorder subjects showed both inhibition and activation. In addition, the base PKC activity incubation with antidepressants of the major depressive disorder patients was significantly higher than of the bipolar disorder patients. These preliminary results suggest that the function of PKC may, at least in part, be associated with the mechanism of affective disorder.

Adult↗
PubMed1999

Nitric oxide synthesis is increased after dehydroepiandrosterone sulphate administration in term human pregnancy.

The purpose of this study was to evaluate the role of nitric oxide in the vasodilative effect of dehydroepiandrosterone sulphate (DHEA-S) in term pregnant women. Circulating nitrite, nitrate and oestradiol concentrations were measured on 10 normal full-term pregnant women before (-30 min) and after (10, 30, 60, 90 and 120 min) administration of a 200 mg i.v. dose of DHEA-S dissolved in 20 ml of 5% dextrose (DHEA-S group). Ten normal full-term pregnant women received 20 ml of 5% dextrose as controls (control group). Maternal blood pressure and heart rate were also recorded. The median oestradiol concentration increased significantly after the infusion in DHEA-S group (P < 0.001), whereas there was no significant change in plasma oestradiol in the control group. In the DHEA-S group, plasma circulating nitrate and nitrite increased significantly at 10 and 30 min after DHEA-S administration respectively (P < 0.05). In the control group, there was no change in plasma nitric oxide (NO) metabolites. No change was found in heart rate or mean arterial blood pressure in the control or DHEA-S groups. These results suggest there may be a link between increased NO and increased oestrogen after DHEA-S injection but their peak values did not coincide. Both may be associated with vasodilation in term pregnant women.

Blood Pressure↗
PubMed1999

Effect of multidrug resistance-reversing agents on transporting activity of human canalicular multispecific organic anion transporter.

The canalicular multispecific organic anion transporter (cMOAT), also termed MRP2, is a recently identified ATP-binding cassette transporter. We previously established stable human cMOAT cDNA-transfected cells, LLC/cMOAT-1 from LLC-PK1 cells, and LLC/CMV cells that were transfected with an empty vector. We found that LLC/cMOAT-1 cells have increased resistance to vincristine (VCR), 7-ethyl-10-hydroxy-camptothecin, and cisplatin but not to etoposide. The multidrug resistance-reversing agents cyclosporin A (CsA) and 2-[4-(diphenylmethyl)-1-piperazinyl]-5-(trans-4,6-dimethyl-1,3, 2-dioxaphosphorinan-2-yl)-2, 6-dimethyl-4-(3-nitrophenyl)-3-pyridinecarboxylate P-oxide (PAK-104P) almost completely reversed the resistance to VCR, 7-ethyl-10-hydroxy-camptothecin, and cisplatin of LLC/cMOAT-1 cells; and DL-buthionine-(S,R)-sulfoximine, (3'-oxo-4-butenyl-4-methyl-threonine(1), (valine(2)) cyclosporin (PSC833), and 3-([(3-(2-[7-chloro-2-quinolinyl]ethenyl)phenyl)-((3-dimethylamino-3- oxopropyl)-thio)-methyl]thio)propanoic acid (MK571) partially reversed the resistance to these drugs. CsA and PAK-104P at 10 microM enhanced the accumulation of VCR in LLC/cMOAT-1 cells almost to the level in LLC/CMV cells without the agents. The efflux of VCR from LLC/cMOAT-1 cells was enhanced compared with LLC/CMV cells and inhibited by CsA and PAK-104P. Transport of leukotriene C(4) (LTC(4)) and S-(2, 4-dinitrophenyl)glutathione also was studied with membrane vesicles prepared from these cells. LTC(4) and S-(2, 4-dinitrophenyl)glutathione were actively transported into membrane vesicles prepared from LLC/cMOAT-1 cells. The K(m) and V(max) values for the uptake of LTC(4) by the LLC/cMOAT-1 membrane vesicles were 0. 26 +/- 0.05 microM and 7.48 +/- 0.67 pmol/min/mg protein, respectively. LTC(4) transport was competitively inhibited by PAK-104P, CsA, MK571, and PSC833, with K(i) values of 3.7, 4.7, 13.1, and 28.9 microM, respectively. These findings demonstrate that cMOAT confers a novel drug-resistance phenotype. CsA and PAK-104P may be useful for reversing cMOAT-mediated drug resistance in tumors.

Adenosine Triphosphate↗