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Biomedical subjects

T Inoue

Publications and source records attributed to T Inoue.

At least 433 records · Page 24Linked to original sources
PubMed2000

Minimizing radial-keratotomy-induced diurnal variation in vision using contact lenses.

A 41-year-old man with 16 radial keratotomy (RK) incisions in each eye reported a paradoxical diurnal variation in vision in both eyes with low Dk/L soft contact lenses. After rk, the patient experienced the conventional diurnal change a morning-to-evening mean (right and left eyes) myopic change of -1.80 diopters (D). However, while wearing low Dk/L contact lenses, a paradoxical morning-to-evening mean hyperopic change of 2.30 D was found. The diurnal variation was minimized (0.50 D) by wearing high Dk/L contact lenses. These results suggest that contact lenses can be used to treat diurnal variation in manifest refraction after RK by inducing appropriate stress.

Adult↗
PubMed2000

Supplemental glutamine augments phagocytosis and reactive oxygen intermediate production by neutrophils and monocytes from postoperative patients in vitro.

The energy substrate for neutrophils has been believed to be glucose. However, a recent investigation has demonstrated that neutrophils use glutamine (Gln) as well as glucose. Nevertheless, little is known about the effects of Gln on neutrophil function. Thus, this study was designed to investigate the effects of Gln on phagocytosis and reactive oxygen intermediate (ROI) production by neutrophils from postoperative patients in vitro. Eleven patients who had undergone major gastrointestinal surgery were randomly selected. Peripheral blood was drawn before surgery and on postoperative days (PODs) 1, 3, and 7. The blood was washed with medium to remove plasma. Washed whole blood was incubated in RPMI 1640 medium containing neither Gln nor glucose for 24 h at 37 degrees C. The medium was supplemented with Gln at a concentration of 0, 500, 1000, or 2000 microM. Whole blood was then assessed for phagocytosis by flow cytometry using fluorescent beads. ROI production by phagocytes was measured by flow cytometry using dihydrorhodamine 123. In each assay, the neutrophil population was gated and analyzed. Serum amino acids were also measured. Postoperative serum Gln level decreased significantly until POD 7. Phagocytosis by neutrophils on PODs 3 and 7 was significantly greater at 2000 microM Gln than at other Gln concentrations. Neutrophil ROI production was significantly greater at 2000 microM Gln than at 0 microM Gln at each time point. In conclusion, supplemental Gln enhances both phagocytosis and ROI production by neutrophils from postoperative patients in vitro.

Aged↗
PubMed2000

Spontaneous regression of merkel cell carcinoma: a comparative study of TUNEL index and tumor-infiltrating lymphocytes between spontaneous regression and non-regression group.

Some Merkel cell carcinomas (MCC) have been reported to regress spontaneously. To clarify the mechanisms of spontaneous regression (SR) of MCC, we analyzed the TUNEL index, the labeling index of proliferating cell nuclear antigen (PCNA), the labeling index of bcl-2 protein, and the expression of p53 of the tumor cells. We also evaluated the number of infiltrating lymphocytes surrounding the tumor in the tissue specimens. Among seven patients with MCC (SR: n=4; non-regression (NR): n=3), the TUNEL index in the SR group was significantly higher than that in NR group (5.2 and 2.0%, respectively). In addition, the number of lymphocytes around the tumor nests was also significantly increased in the SR group compared to NR group (1576 and 663 cells/mm(2), respectively). Most of the infiltrating lymphocytes were UCHL-1 positive T-cells. There were no significant differences of the PCNA labeling index, the bcl-2 protein labeling index, and the expression p53 between SR and NR group. These results indicate that apoptosis and local T-cell mediated immune response might be involved in spontaneous regression of MCC.

Aged↗
PubMed2000

Synthesis and biological activities of novel antiallergic agents with 5-lipoxygenase inhibiting action.

Novel benzimidazole derivatives were synthesized and their pharmacological activities were examined. These compounds showed a good suppressive action on histamine release from rat peritoneal mast cells produced by antigen-antibody reaction, an antagonistic action on guinea pig ileum contraction caused by histamine, an inhibitory action on 5-lipoxygenase in rat basophilic leukemia-1 (RBL-1) cells, and a preventive action on NADPH dependent lipid peroxidation induced by Fe3+-ADP in rat liver microsomes. In addition, 1-[2-[2-(4-Hydroxy-2,3,5-trimethylphenoxy)ethoxy]-ethyl]-2-(4-meth yl-1-homopiperazino)-1H-benzimidazole difumarate (BOM1006) exhibited a dose dependent suppressive action on 48 h homologous passive cutaneous anaphylaxis (PCA) reaction in rats orally administered the drug.

Animals↗
PubMed2000

Flower-predominant expression of a gene encoding a novel class I chitinase in rice (Oryza sativa L.).

A flower-predominant cDNA for a gene, termed OsChia 1;175, was isolated from a cDNA library of rice pistils. Northern blot and RT-PCR analyses revealed that the OsChia 1;175 gene is highly expressed in floral organs (pistils, stamens and lodicules at the heading stage) but not or at an extremely low level in vegetative organs. OsChia 1;175 encodes a protein that consists of 340 amino acid residues, and the putative mature protein shows 52% to 63% amino acid identity to class I chitinases of rice or other plants. The phylogenetic tree shows that the OsChia 1;175 protein is a new type of plant class I chitinase in rice. The expression of OsChia 1;175 in vegetative organs is not induced by several chemicals, UV, and wounding. The soluble putative mature OsChia 1;175 protein expressed in Escherichia coli exhibited chitinase activity in the assay with colloidal chitin as a substrate. Genomic Southern analysis revealed that the OsChia 1;175 gene was organized as a low-copy gene family. The rice genomic library was screened and a genome clone corresponding to OsChia 1;175 was isolated. The transcription start sites of the OsChia 1;175 gene were mapped by primer extension analysis. The 1.2 kb putative promoter region of the OsChia 1;175 gene was fused to the GUS (beta-glucuronidase) gene, and this chimeric gene was introduced to rice by Agrobacterium-mediated transformation. The flower-predominant gene expression was identified also in the transgenic rice plants. The high promoter activity was detected in the stigmas, styles, stamens and lodicules in transgenic plants. The possible functions of OsChia 1;175 are discussed.

Amino Acid Sequence↗
PubMed2000

Mesp2 initiates somite segmentation through the Notch signalling pathway.

The Notch-signalling pathway is important in establishing metameric pattern during somitogenesis. In mice, the lack of either of two molecules involved in the Notch-signalling pathway, Mesp2 or presenilin-1 (Ps1), results in contrasting phenotypes: caudalized versus rostralized vertebra. Here we adopt a genetic approach to analyse the molecular mechanism underlying the establishment of rostro-caudal polarity in somites. By focusing on the fact that expression of a Notch ligand, Dll1, is important for prefiguring somite identity, we found that Mesp2 initiates establishment of rostro-caudal polarity by controlling two Notch-signalling pathways. Initially, Mesp2 activates a Ps1-independent Notch-signalling cascade to suppress Dll1 expression and specify the rostral half of the somite. Ps1-mediated Notch-signalling is required to induce Dll1 expression in the caudal half of the somite. Therefore, Mesp2- and Ps1-dependent activation of Notch-signalling pathways might differentially regulate Dll1 expression, resulting in the establishment of the rostro-caudal polarity of somites.

Animals↗
PubMed2000

Minimal catalytic domain of a group I self-splicing intron RNA.

The self-splicing intron ribozymes have been regarded as primitive forms of the splicing machinery for eukaryotic pre-mRNAs. The splicing activity of group I self-splicing introns is dependent on an absolutely conserved and exceptionally densely packed core region composed of two helical domains, P3-P7 and P4-P6, that are connected rigidly via base triples. Here we show that a mutant group I intron ribozyme lacking both the P4-P6 domain and the base triples can perform the phosphoester transfer reactions required for splicing at both the 5' and 3' splice sites, demonstrating that the elements required for splicing are concentrated in the stacked helical P3-P7 domain. This finding establishes that the conserved core of the intron consists of two physically and functionally separable components, and we present a model showing the architecture of a prototype of this class of intron and the course of its molecular evolution.

Base Sequence↗
PubMed2000

The in vivo pharmacological profile of CS-747, a novel antiplatelet agent with platelet ADP receptor antagonist properties.

1. CS-747 is a novel antiplatelet agent that generates an active metabolite, R-99224, in vivo. CS-747 itself was totally inactive in vitro. This study examined in vivo pharmacological profiles of CS-747 after single oral administration to rats. 2. Orally administered CS-747 (0.3 - 10 mg kg(-1)) partially but significantly decreased [(3)H]-2-methylthio-ADP binding to rat platelets. CS-747 (3 mg kg(-1), p.o.) treatment neutralized ADP-induced decreases of cyclic AMP concentrations induced by prostaglandin E(1), suggesting that metabolites of CS-747 interfere with G(i)-linked P2T receptor. 3. CS-747 (0.3 and 3 mg kg(-1), p.o.) markedly inhibited ex vivo washed platelet aggregation in response to ADP but not to thrombin. CS-747 also exhibited a marked inhibition of ADP-induced ex vivo platelet aggregation in PRP with a rapid onset (<0.5 h) and long duration (>3 days) of action (ED(50) at 4 h=1.2 mg kg(-1)). 4. R-99224 (IC(50)=45 microM) inhibited in vitro PRP aggregation in a concentration-related manner. 5. CS-747 prevented thrombus formation in a dose-related manner with an ED(50) value of 0.68 mg kg(-1). CS-747 was more potent than clopidogrel (6.2 mg kg(-1)) and ticlopidine (>300 mg kg(-1)). 6. CS-747, clopidogrel, and ticlopidine prolonged the bleeding time. The order of potency of these agents in this activity was the same as that in antiaggregatory and antithrombotic activities. 7. These findings indicate that CS-747 is an orally active and a potent antiplatelet and antithrombotic agent with a rapid onset and long duration of action, and warrants clinical evaluations of the agent.

Adenosine Diphosphate↗
PubMed2000

Adsorption and pharmacokinetics of cyclosporin A in relation to mode of infusion in bone marrow transplant patients.

Two main factors that affect the pharmacokinetics of cyclosporin A (CsA) during 24-h durable intravenous (DIV) administration have been reported, namely physiological changes after bone marrow transplantation, and blood sampling through indwelling lines. In addition, it has been found that infusion sets made of polyvinyl chloride (PVC) markedly adsorb CsA. We conducted in vitro adsorption studies of CsA on infusion sets, and the administration routes that are used in the treatment of patients with bone marrow transplantation. We also examined the effects of administration route on CsA pharmacokinetics in clinical practice. The in vitro adsorption study using 30-mm segments of lumen from commercially available infusion sets showed that the degree of CsA adsorption per area of lumen made of PVC was significantly higher than that in those made of polyethylene (PE) or polybutadiene (PB), which showed no adsorption of CsA. Due to its adsorption, use of infusion sets made of PVC resulted in about a 40-50% loss of CsA dose, which affected the pharmacokinetic parameters during 24-h DIV, while those made of PE and PB did not. The use of non-PVC infusion sets should allow for accurate monitoring of CsA results, and provide cost benefit in the treatment of bone marrow transplantation.

Adsorption↗
PubMed2000

Pharmacokinetics and adverse events following 5-day repeated administration of lenograstim, a recombinant human granulocyte colony-stimulating factor, in healthy subjects.

Recombinant human granulocyte colony-stimulating factor (rhG-CSF) (lenograstim) was administered to healthy subjects at doses of 2, 5 and 10 micrograms/kg/day for 5 days (twice a day subcutaneously) to examine the optimal dose and schedule of lenograstim in mobilizing peripheral blood progenitor cells (PBSC) for allogeneic transplantation. Lenograstim administration significantly increased CD34+ cells in a dose-related manner. A significant correlation was observed between the maximal post-dosing counts and the pre-dosing baseline counts of CD34+ cells. Peripheral neutrophils increased markedly by seven to 13 times from the baseline to a peak of approximately 40,000/microliter on day 5 for the 5 and 10 micrograms/kg/day doses. After peak serum concentration (Cmax) was attained 4 h following administration, serum G-CSF declined with time in a log-linear fashion. The Cmax and 12 h area-under-the-curve increased dose dependently, but minimum drug level increased up to day 2 and then decreased until day 5. Clearance decreased with increasing dosage at the first dose, and increased significantly at the last dose. We found a highly significant correlation between absolute neutrophil counts and clearance for each dose. Adverse events most frequently occurred on day 6, with increases of alkaline phosphatase and lactate dehydrogenase and onset of bone pain. Increases of aspartate aminotransferase and alanine aminotransferase occurred as delayed events. Platelet count gradually decreased after the end of drug administration to 57% of the pre-dosing count on day 10, but was still within the normal range. These preliminary results suggest that repeated doses of lenograstim induce mobilization of PBSC in a dose-dependent manner and the pre-dosing baseline count of PBSC may predict the post-dosing maximal mobilization. The drug treatment may cause delayed-onset moderate thrombocytopenia and increased transaminase, and the drug clearance changes in a complex manner during repeated dosing.

Adult↗
PubMed2000

MIDA1 is a sequence specific DNA binding protein with novel DNA binding properties.

BACKGROUND: Id proteins not only regulate cell differentiation negatively, but they also promote growth and apoptosis. To know the mechanism of how Id regulates cell fate, we previously isolated an Id-associating protein, MIDA1, which positively regulates cell growth. Its predicted amino acid sequence contains tryptophan-mediated repeats (Tryp-med repeats) similar to the DNA binding region of the c-Myb oncoprotein. We determined whether MIDA1 can bind to DNA in a sequence specific manner by PCR-assisted binding site selection. RESULTS: We identified a 7-base sequence (GTCAAGC) surrounded by a 1-3 bp palindromic sequence as the DNA sequence recognized by the Tryp-med repeats of MIDA1. This motif is located within the 5'-flanking sequence of several growth regulating genes. Gel shift assays revealed that this sequence and a certain length of flanking DNA are necessary for MIDA1 to bind DNA in a stable manner. Methylation interference and DNase I footprint analysis suggested that the DNA binding of MIDA1 is resistant to DNA methylation and that MIDA1 does not specifically localize on this particular motif. CONCLUSIONS: We concluded that MIDA1 is a novel sequence-specific DNA binding protein with some different properties from the usual transcription factors and that MIDA1 may act as a mediator of Id-mediated growth-promoting function through its DNA binding activity.

Base Sequence↗
PubMed2000

Primary choriocarcinoma and human chorionic gonadotrophin-producing giant cell carcinoma of the lung: are they independent entities?

AIMS: Human chorionic gonadotrophin (hCG) is a useful marker for chorionic proliferative disorders, such as choriocarcinoma. Although hCG synthesis in lung cancers is frequent, primary pulmonary choriocarcinoma (PCC) is rare. To clarify the differences between primary choriocarcinoma and hCG-producing giant cell carcinoma (GCC) of the lung, we compared the clinicopathological and immunohistochemical findings of these tumours. METHODS AND RESULTS: Three patients, one with PCC and two with hCG-producing GCC, were included in this study. They were all middle-aged men and habitual smokers. The growth of these tumours and the progression of the clinical courses were extremely rapid, and the patients all died within 8 months after the pulmonary tumours were found. Haemorrhagic appearance was a common macroscopic feature of the specimens obtained. Microscopically, both types of tumours mainly consisted of atypical polygonal cells. While PCC contained many syncytial trophoblast-like multinucleated cells that had strong immunoreactivity for anti-hCG, such cells were relatively few in hCG-producing GCC. These histological and immunohistochemical findings reflected the serum test result for hCG, which was higher in the case of PCC. CONCLUSIONS: There are a few differences between PCC and hCG-producing GCC, as described above. Reliable distinction between them seems to be difficult for pathologists and worthless for clinicians.

Carcinoembryonic Antigen↗
PubMed2000

Use of oligotrophic bacteria for the biological monitoring of heavy metals.

Oligotrophic bacteria exhibited active growth even in nutritionally deficient medium made with nutrient broth that had been diluted with distilled water, 1 : 10 000. The oligotrophic bacteria, Sphingomonas paucimobilis KPS01 and Burkholderia cepacia KPC01 and KPC02 were found to be highly susceptible to heavy metals and to be potentially useful as sensors for the assessment of toxicity. The susceptibility of the bacteria to metals was measured by incubating the bacteria with metals of varying concentrations in the nutritionally deficient medium at 30 degrees C for 24 h. Bacteria were considered susceptible when the growth inhibition rate (EC50 was more than 50% of the control. The EC50 value of Ag+, Pb2+ and Cd2+ was 10(5)mmol l(-1) and Zn2+, Cr3+, Cr6+, Cu2+ and Hg2+ was 10(-4) mmol l(-1) in S. paucimobilis KPS01. Other strains also showed similar results. No difference in the EC50 was found using either the chloride or sulphate forms of these metals. The optimum incubation time was 24 h and a longer incubation time did not necessarily lead to more inhibition. The EC50 value rose in proportion to the concentration of nutrition in media. Environmental samples were tested and 14 out of 88 samples inhibited the growth of S. paucimobilis KPS01.

Burkholderia cepacia↗
PubMed2000

Nitric oxide production and hepatic dysfunction in patients with postoperative sepsis.

1. Although hepatic function is well known to deteriorate following bacterial infection, the underlying mechanisms remain poorly understood. We have previously reported that nitric oxide (NO) radical leads to a decrease in the ketone body ratio (KBR) and in ATP content due to the inhibition of mitochondrial electron transport in primary cultured rat hepatocytes. 2. To evaluate the effects of NO radical on the liver in patients with postoperative sepsis, we analysed both the stable end-product of nitric oxide radical (NOx) as well as the arterial KBR (AKBR), which reflects liver tissue NAD+/NADH. 3. Twenty patients who had undergone general abdominal surgery and who developed postoperative sepsis were divided into two groups: (i) surviving; and (ii) non-surviving. Blood samples were collected before the development of postoperative sepsis and every 3 days until the patient either died or was discharged from hospital. 4. Plasma NOx levels in seven patients who subsequently died became progressively higher than those in the 13 surviving patients over the clinical course of postoperative sepsis. 5. In the non-surviving group, the AKBR was significantly lower than in surviving patients, indicating impaired hepatic function. In contrast, plasma NOx levels in non-surviving patients were significantly higher than in surviving patients. 6. Decreases in AKBR to levels below 0.7 in non-surviving patients followed high NOx levels. Moreover, plasma NOx levels were closely correlated with the AKBR, indicating that NO radical is associated with mitochondrial dysfunction in the liver. 7. It is likely that the overproduction of NO radical plays an important role in causing fatal metabolic disorders in patients with postoperative sepsis.

Aged↗
PubMed2000

Mucinous carcinoma of the breast with neuroendocrine differentiation.

A case of mucinous carcinoma of the breast with neuroendocrine differentiation in an 89-year-old woman is presented. The patient presented with a rapidly growing right breast mass, which she had had for 2-3 years. The tumor, 15 x 8 x 5 cm, was located mainly in the upper outer quadrant. Light microscopy revealed a pure mucinous carcinoma of type B. Neuroendocrine differentiation was demonstrated by Grimelius stain and chromogranin A, as well as the presence of neurosecretory granules. The breast cancer cells were of luminal origin and had dedifferentiated to attain neuroendocrine properties.

Adenocarcinoma, Mucinous↗
PubMed2000

Larynx preservation in surgical treatment of cervical esophageal cancer--combined procedure of laryngeal suspension and cricopharyngeal myotomy.

From July 1994 to July 1998, a larynx-preserving procedure was performed on 10 out of 22 (45%) patients in the surgical treatment of hypopharyngeal and cervical esophageal cancer. At first, all 10 patients were treated with concurrent radiochemotherapy with cisplatin (10 mg/m2/day), 5-fluorouracil (500 mg/m2/day) and radiation (2 Gy/day) five times per week for 4 weeks. After preoperative radiochemotherapy, the larynx-preserving procedure, combining laryngeal suspension and cricopharyngeal myotomy, was performed. The operative and hospital mortality rate was 0%. The incidence of post-operative morbidity with minor complications was 70% in the present study. Laryngeal speech and oral food intake were preserved in all patients after this procedure. The new larynx-preserving procedure combining laryngeal suspension and cricopharyngeal myotomy for cervical esophageal cancer is a favorable operative method for retaining intelligible laryngeal speech and good food intake.

Adult↗
PubMed2000

Evaluation of the histologic effect of chemoradiation therapy for squamous cell carcinomas of the esophagus by assessing morphologic features of surgical specimens.

The histologic effects of chemoradiation therapy (CRT) for esophageal cancer, which determine the benefit obtained from a salvage operation, are difficult to evaluate preoperatively. We therefore investigated whether or not the morphologic features of esophageal cancer tissue after CRT can be correlated with the histologic features of the tissue. Seventy-six patients with advanced esophageal squamous cell carcinoma underwent CRT followed by esophagectomy. The effects of CRT were evaluated by histologic examination of the residual tumors in the surgical specimen and correlated with clinicopathologic factors, including postoperative prognosis. The histologic effects of CRT were used to classify tumors as grade 1 (CRT poorly effective; 23 cases, 30.3%); grade 2 (CRT moderately effective; 31 cases, 40.8%); or grade 3 (CRT completely effective with no residual tumors; 22 cases, 28.9%). Among the gross findings of the removed esophagus, significant correlation with the CRT effects was observed in the case of wall thickness and ulceration but not in the case of longitudinal tumor length. Tumors with no wall thickening or ulceration were never classified as grade 1, whereas tumors with both wall thickening and ulceration were frequently rated as grade 1 (18/30, 60%). Microscopic examination of grade 2 tumors (23/31, 74.1%) revealed residual tumor cells growing below the mucosal layer, whereas tumor cells were exposed to the esophageal surface in 22 out of 23 patients with grade 1 tumors. The morphologic features after CRT can be used to evaluate its histologic effect, especially in the case of grade 1 tumors. However, the detection and prediction of grade 2 tumors remains difficult because of the presence of small amounts of residual tumor underneath the mucosa.

Antineoplastic Combined Chemotherapy Protocols↗