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T Honda

Publications and source records attributed to T Honda.

At least 289 records · Page 16Linked to original sources
PubMed1997

Different effects of Alzheimer-associated mutations of presenilin 1 on its processing.

Presenilin 1 (PS 1) shows missense mutations in most early-onset familial Alzheimer's disease (FAD). Transfection of cDNA for wild type PS 1 into rat pheochromocytoma PC12 cells generated a 47 kDa full-size PS 1 protein, which was processed into a 28 kDa N-terminal fragment and a 19 kDa C-terminal fragment. We prepared selected Alzheimer-associated mutations (Gly384Ala, Leu392Val, and Cys410Tyr) of PS 1, which localized after a possible cleavage site. By transient expression in PC12 cells and rat glioma cell line, C6, we examined their influence on the processing of PS 1. Cys410Tyr inhibited proteolytic processing of PS 1, while Gly384Ala and Leu392Val did not. Thus, the Alzheimer related mutations can be divided into two groups in terms of their effect on the proteolytic cleavage of PS 1.

Alzheimer Disease↗
PubMed1997

A mutant cell line resistant to Vibrio parahaemolyticus thermostable direct hemolysin (TDH): its potential in identification of putative receptor for TDH.

Thermostable direct hemolysin (TDH), a pore-forming toxin produced by Vibrio parahaemolyticus, is cytotoxic to Rat-1, a fibroblast cell line derived from rat embryo. Through mutagenesis of Rat-1 with nitrosoguanidine, we established a mutant cell line, MR-T1. MR-T1 was over 200 times more resistant to the cytotoxic activity of TDH than Rat-1. TDH increased membrane permeability of Rat-1 but not of MR-T1. Binding analysis showed that, while being able to bind to Rat-1. TDH failed to bind to MR-T1, indicating that MR-T1 is deficient in the putative receptor for TDH. Somatic hybrid cells between Rat-1 and MR-T1 were similarly sensitive to TDH as Rat-1. Moreover, TDH could bind to the hybrid cells as well as to Rat-1 cells. These results indicate that MR-T1 is promising for complementation cloning of a gene related to the putative receptor for TDH.

Animals↗
PubMed1997

Analysis of functional domains of Vibrio parahaemolyticus thermostable direct hemolysin using monoclonal antibodies.

Neutralizing monoclonal antibodies (mAbs) against Vibrio parahaemolyticus thermostable direct hemolysin (TDH) were used in probing the functional domains of this toxin. While pre-incubation of TDH with mAb 2A-13C inhibited further binding of TDH to erythrocytes, pre-incubation with another mAb 1-24 did not, indicating that mAb 1-24 epitope resides in a domain which is not involved in binding of TDH to erythrocytes. On the other hand after binding to erythrocytes, TDH could react with mAb 1-24 but poorly with mAb 2A-13C, indicating that the mAb 2A-13C epitope is masked, possibly by erythrocyte surface. As both antibodies are TDH-specific and do not react with TRH (TDH-related hemolysin), we used TDH/ TRH chimeric proteins to identify location of the epitopes for mAbs by inhibition ELISA as well as Western blotting. The results showed that the mAb 1-24 epitope resides on a region near the C-terminal of TDH (residues 99-139), while the mAb 2A-13C epitope resides on the N-terminal (residues 1-31). All these results suggested that, in TDH, the N-terminal region may be involved in binding process while the region near C-terminal may be involved in postbinding process.

Animals↗
PubMed1997

Intramolecular chaperone activity of the pro-region of Vibrio cholerae El Tor cytolysin.

Vibrio cholerae synthesizes a toxin named El Tor cytolysin/hemolysin, which lyses erythrocytes and other mammalian cells. This toxin is encoded by the hlyA gene and is synthesized as a precursor form, prepro-HlyA. Prepro-HlyA consists of, from the amino terminus of this protein, a signal peptide, a pro-region, and a mature region. The pro-region is cleaved off extracellularly resulting in activation. To analyze the role of the pro-region, we substituted the native hlyA gene with the pro-region-deleted hlyA gene (hlyA delta pro). The hemolytic activity of the mutant organism was markedly decreased; the product of the hlyA delta pro gene, secreted in the periplasm, was degraded. To compare their abilities to form tertiary structure, the purified mature- and pro-HlyA were denatured and then renatured by reducing the concentration of denaturant; the denatured pro-HlyA recovered almost all activity while the mature-HlyA was not renatured. The sequences of the pro-region and a molecular chaperone, Hsp90, were similar. The pro-region expressed in Escherichia coli containing the hlyA delta pro gene increased the cytolytic activity. The purified pro-region peptide also facilitated renaturation of the denatured mature HlyA. These results suggest that the pro-region possibly guides the folding of the cytolysin similar to a molecular chaperone; the pro-region and molecular chaperones share common function and structure.

Amino Acid Sequence↗
PubMed1997

Controlling the capsular shape in lens refilling.

OBJECTIVES: To investigate control of the capsular shape by determining the ability of the lens capsule to mold injected silicone and to evaluate the relationship among the volume of silicone injected, refraction, and the amplitude of accommodation. METHODS: After endocapsular phacoemulsification following an upper, minicircular capsulorhexis, the lens capsule of a pig eye was refilled with a silicone mixture that polymerizes in vitro in 2 hours. The minicircular capsulorhexis opening was sealed by a small silicone plug to prevent leakage. The anterior capsule curvature and refraction of the lens were measured by a Scheimpflug camera and lensometer, respectively, with and without zonular tension. Zonular tension was created using a ciliary ring sutured to the ciliary bodies and expanded. RESULTS: The mean (+/- SD) anterior curvature of the lenses without zonular tension was 6.50 +/- 0.07 mm after 17 hours and 6.54 +/- 0.04 mm after 42 hours; with zonular tension it was 7.01 +/- 0.11 mm and 7.23 +/- 0.24 mm, respectively. The curvature became flatter when zonular tension was applied or steeper when zonular tension was abolished momentarily during measurements after 17 hours, but after 42 hours the curvature was unaffected by the application or removal of zonular pressure. The mean (+/- SD) amplitude of accommodation (the difference between refraction without zonular tension and that with it) was 3.2 +/- 0.5 diopters (D), 6.1 +/- 1.8 D, 4.8 +/- 0.8 D, and 2.8 +/- 1.3 D, when the lens was refilled with a silicone volume corresponding to 45%, 55%, 75%, and 95%, respectively, of the mean normal lens volume. CONCLUSIONS: The lens capsule possesses some ability to mold the injected silicone during its polymerization. When the eye is atropinized, the lens capsule may conform to its nonaccommodated state. Accommodation could be obtained by various degrees of refilling. Moderate refilling yields a greater amplitude of accommodation than does more complete refilling. Using a silicone plug to seal the capsular opening facilitates lens refilling with excellent reproducibility and seems to be useful in research.

Accommodation, Ocular↗
PubMed1997

Bacterial invasion induces interleukin-7 receptor expression in colonic epithelial cell line, T84.

The intestinal epithelial layer forms the interface between the external and the internal environments of a host. Since the interleukin-7 (IL-7) and IL-7 receptor (IL-7R) signaling pathway has been shown to play an important role in the mucosal immune system, we studied the expression of IL-7R in T84, a colonic epithelial cell line, after cells were infected with several types of enteropathogenic bacteria, including Salmonella typhimurium, enteropathogenic Escherichia coli and enteroinvasive Escherichia coli. Bacterial invasion induced IL-7R expression in T84 assessed by a semi-quantitative reverse transcription-polymerase chain reaction technique and flow cytometry. The inhibition of bacterial invasion by cytochalasin D, a specific inhibitor of actin polymerization, led to a reduction in the expression of IL-7R. These data indicate that bacterial invasion into intestinal epithelial cells is likely to be an essential process in the induction of IL-7R. The communication between the epithelium and mucosal lymphocytes which is mediated via IL-7 and IL-7R may be involved in the modulation of the mucosal inflammation which occurs in bacterial infection.

Antigens, CD↗
PubMed1997

Population-based investigation of relative clearance of digoxin in Japanese patients by multiple trough screen analysis: an update.

The steady-state concentrations of digoxin at trough levels were studied to reestablish the role of patient characteristics in estimating doses for digoxin using routine therapeutic drug-monitoring data. The data (n = 548) showing steady-state serum concentrations of digoxin after repetitive oral administration in 385 hospitalized patients were analyzed using NONMEM, a computer program designed to analyze pharmacokinetics in study populations by allowing pooling of data. Analysis of the pharmacokinetics of digoxin was accomplished with a simple steady-state pharmacokinetic model. The effect of a variety of developmental and demographic factors on the clearance of digoxin was investigated. Estimates generated by NONMEM indicated that clearance of digoxin was influenced by the demographic variables of age, total body weight, serum creatinine, estimated creatinine clearance, gender, the coadministration of spironolactone, the presence or absence of congestive heart failure, and the administration of a half-tablet. The interindividual variability in the clearance of digoxin was modeled with proportional error with an estimated coefficient of variation of approximately 22%; the residual variability was approximately 25.0%. An a priori method, based on the value for clearance of digoxin obtained by NONMEM analysis, was proposed as a useful adjunct for the prediction of the steady-state concentration of digoxin at trough level as a function of the maintenance dose of digoxin.

Adolescent↗
PubMed1997

Treatment of primary multiple early gastric cancer: from the viewpoint of clinicopathologic features.

The treatment of multiple early gastric cancer was investigated through the clinicopathologic assessment of 61 cases of primary multiple early gastric cancer (82 accessory lesions) treated by surgical resection over a 15-year period. These cases accounted for 11.7% of all cases of early gastric cancer resected during the same period. The 61 patients included 48 men (mean age 64 years) and 13 women (61 years). Of the 82 accessory lesions, 41 (50%) were located in the same region as the main lesion. The most frequent combination of macroscopic types of the main lesion and the accessory lesion was depressed type/depressed type (28 cases). The main lesion was of the well differentiated type in 39 (64%) of the 61 cases; the accessory lesion was also well differentiated in 37 of the 39 cases. Of the 82 accessory lesions, 29 (35%) had been overlooked preoperatively; most of them were located in the middle third of the stomach and included 17 depressed and 10 flat lesions, most of which measured no more than 1 cm. Cases of multiple early gastric cancer are characterized by the predominance of male patients of advanced age (> 60 years), a combination of the same macroscopic type of the main and accessory lesions, and well differentiated carcinoma. Lymph node metastasis and vascular invasion are equally or less frequent than in cases of solitary early gastric cancer. The postoperative crude survival rate in patients with multiple gastric cancer is similar to that in those with solitary gastric cancer. Therefore we believe that multiple early gastric cancer does not require extended operative procedures. Endoscopic treatment may be indicated if each lesion fits the criteria for treatment and careful follow-up is ensured.

Adult↗
PubMed1997

Proximal gastrectomy and jejunal pouch interposition for the treatment of early cancer in the upper third of the stomach: surgical techniques and evaluation of postoperative function.

BACKGROUND: Limited surgery for the treatment of early gastric cancer located in the upper third of the stomach should be based on a well-balanced reduction in the extent of lymph node dissection and gastric resection while assuring a favorable quality of life and prognosis after operation. METHODS: We have used interposition of a double jejunal pouch between the esophagus and the remnant stomach after performing proximal gastrectomy. To assure anastomosis and hemostasis during this operation, we currently use a surgical stapler with a vaginoscope and our new edge clamps. This method has been used in 12 patients to date. RESULTS: On histopathologic examination the 12 cases comprised 11 early cancers (seven mucosal and four submucosal cancers) and one subserosal cancer. There was no evidence of lymph node metastasis of postoperative complications such as anastomotic leakages or hemorrhage, demonstrating the low-risk nature of this procedure. CONCLUSIONS: The evaluation of postoperative quality of life, in terms of clinical signs and symptoms and dietary status, yielded favorable results. Thus our method has the important advantage of allowing good organ preservation.

Adult↗
PubMed1997

Two-step repositioning of the maxilla in bimaxillary orthognathic surgery.

A two-step repositioning system in bimaxillary osteotomies, a combination of a modified face-bow transfer and the use of an occlusal plane indicator is described. With this system, the risks involved in depending solely on reproduction of the model-constructed position can be avoided.

Acrylic Resins↗
PubMed1997

The stimulating effect of fosfomycin, an antibiotic in common use in Japan, on the production/release of verotoxin-1 from enterohaemorrhagic Escherichia coli O157:H7 in vitro.

In 1996 Japan had a big outbreak of enterohaemorrhagic Escherichia coli (EHEC) O157:H7, especially in Osaka prefecture where about 6000 patients (mainly schoolchildren) suffered from diarrhoea, haemorrhagic colitis and haemolytic uraemic syndrome (HUS) due to EHEC infection via school lunch. Our survey of doctors who took care of those patients showed that most patients had received antibiotics, especially fosfomycin which comprised 84% of the prescribed treatment. Since the administration of antibiotics for EHEC infection is under discussion, we analysed the effect of fosfomycin on production/release of verotoxins (VTs). Addition of fosfomycin into EHEC culture in CAYE broth at 2 and 5 h after start of incubation caused marked increase of VT1 release. This observation warns of the possibility of fosfomycin treatment making the disease worse.

Anti-Bacterial Agents↗
PubMed1997

Report on the nationwide epidemiological survey of exudative age-related macular degeneration in Japan.

The research Committee on Chorioretinal Degeneration, in cooperation with the Research Committee on the Epidemiology of Intractable Diseases, performed the second nationwide epidemiological survey of exudative age-related macular degeneration (AMD) in 1993. The number of exudative AMD patients in all ophthalmology departments throughout Japan was estimated to be 14,400 in 1993. This number was estimated to have almost doubled over the six year period since the initial survey in 1987. The number of people visiting ophthalmology departments due to exudative AMD was 53 males and 20 females per 100,000 population aged 50 years or over. The percentage of patients with bilateral disease increased with age and accounted for nearly 50% of those aged 80 years or over.

Age Distribution↗
PubMed1997

Identification of oncocytic lesions of salivary glands by anti-mitochondrial immunohistochemistry.

AIMS: To evaluate the immunohistochemistry using an anti-mitochondria antibody in the investigation of various oncocytic lesions of the salivary glands. METHODS AND RESULTS: Ten cases of adenolymphoma (Warthin's tumour) and one case each of benign oncocytoma and oncocytic carcinoma of the salivary glands were examined. Normal salivary glands were also tested. They were investigated immunohistochemically using mouse monoclonal antibody against human mitochondria. In normal salivary glands, epithelial cells of the striated ducts showed a thick linear immunoreactivity, which corresponded well to the intracytoplasmic distribution pattern of mitochondria. In addition, a small number of swollen epithelial cells showing an intense, finely granular immunoreactivity in the cytoplasm were scattered in the ductal system and acini ('oncocytic metaplasia'). Almost all neoplastic cells involved in adenolymphoma, benign oncocytoma, and oncocytic carcinoma showed an intense, finely granular immunoreactivity in the cytoplasm. CONCLUSIONS: Immunohistochemistry using the anti-mitochondria antibody proved to be a highly sensitive and specific method for light microscopic identification of mitochondria and superior to routine H & E or PTAH stain especially in the detection of isolated oncocytic cells.

Adenocarcinoma↗
PubMed1997

Biliary excretion and microfloral transformation of major conjugated metabolites of 2,4-dinitrotoluene and 2,6-dinitrotoluene in the male Wistar rat.

1. Major biliary conjugates of the male Wistar rat dosed orally with 2,4-dinitrotoluene (2,4-DNT) or 2,6-dinitrotoluene (2,6-DNT) were examined by hplc using potassium 2,4-dinitrobenzyl glucuronide (potassium 2,4-DNB-G), potassium 2,6-dinitrobenzyl glucuronide (potassium 2,6-DNB-G), pyridinium 2,4-dinitrobenzyl sulphate (pyridinium 2,4-DNB-S) and pyridinium 2,6-dinitrobenzyl sulphate (pyridinium 2,6-DNB-S) as authentic compounds. Other metabolites were also examined by hplc. In addition, metabolites formed by incubation of potassium 2,4-DNB-G and potassium 2,6-DNB-G with rat intestinal microflora under nitrogen were examined by hplc. 2. Conjugates detected directly from bile following administration of 2,4-DNT and 2,6-DNT were 2,4-DNB-G and 2,6-DNB-G, which accounted for 35.0 and 51.5% of the administered dose respectively. No peaks corresponding to pyridinium 2,4-DNB-S and pyridinium 2,6-DNB-S were detected in bile samples. 3. 2-Amino-4-nitrotoluene, 4-amino-2-nitrotoluene, 2,4-diaminotoluene and 4-acetylamino-2-nitrobenzoic acid (0.02-0.12% of the dose excreted in 24 h), in addition to the known metabolites 2,4-dinitrobenzyl alcohol (2,4-DNB), 2,4-dinitrobenzaldehyde and 2,4-dinitrobenzoic acid (0.09-0.14%), were detected in ether extracts of bile of rat given 2,4-DNT. 2,6-Dinitrobenzyl alcohol (2,6-DNB), 2-amino-6-nitrotoluene and 2,6-dinitrobenzaldehyde (0.02-0.03%), which are known metabolites, were detected in ether extracts of bile from rat given 2,6-DNT. 4. Potassium 2,4-DNB-G was transformed by the anaerobic incubation of rat intestinal microflora into 2,4-DNB, 4-amino-2-nitrobenzyl alcohol and 2-amino-4-nitrobenzyl alcohol. Potassium 2,6-DNB-G was transformed into 2,6-DNB and 2-amino-6-nitrobenzyl alcohol by the anaerobic incubation. Time-course studies showed that 2,4-DNB, 4-amino-2-nitrobenzyl alcohol, 2-amino-4-nitrobenzyl alcohol and 2,6-DNB, 2-amino-6-nitrobenzyl alcohol peaked at 30, 75, 120 and 10, 50 min respectively. 5. These results, together with previous findings, show that 2,4-dinitrobenzaldehyde and 2,6-dinitrobenzaldehyde, which are potent mutagens, are formed either by the hepatic metabolism of 2,4-DNB and 2,6-DNB formed by the intestinal metabolism of 2,4-DNB-G and 2,6-DNB-G excreted in bile or by the direct hepatic metabolism of 2,4-DNT and 2,6-DNT.

Animals↗
PubMed1997

Invasive phenotype of Vibrio parahaemolyticus.

Many studies have been done on the virulence factors of Vibrio parahaemolyticus, which causes acute gastroenteritis. Invasion by this bacterium of culture cells in vitro, however, has not been clearly demonstrated. To assess the invasive ability of V. parahaemolyticus, quantitative studies using antibiotic survival assays were done. Of 21 isolates examined, 4 could invade Caco-2 cells, a human colon carcinoma-derived cell line. Invasion of an isolate, AQ4023, was inhibited by cytochalasin D, nocodazole, and genistein. This indicates that active processes in cells, such as signal transduction by tyrosine protein kinase, may be involved in the internalization of this bacterium by Caco-2 cells and that actin filaments and cytoskeletal structure may have important roles in this process. These results suggested that the disease caused by some isolates of V. parahaemolyticus is attributable not only to toxin production but also to invasion into intestinal epithelium.

Caco-2 Cells↗
PubMed1997

Integrin alpha5 is expressed on human luteinizing granulosa cells during corpus luteum formation, and its expression is enhanced by human chorionic gonadotrophin in vitro.

We previously reported that human granulosa cells (GC) express integrin alpha6beta1, in large follicles and early corpus luteum (CL). In this study, we examined the expression of integrin alpha5 and fibronectin (FN) by immunohistochemistry. Integrin alpha5 was undetectable on human GC in preovulatory follicles, but it was intensely expressed on luteinizing GC of CL in the early luteal phase, and it was weakly expressed on large luteal cells (LL) in the midluteal phase. FN was similarly expressed between GC/LL. Thus, integrin alpha5 and FN were stage-specifically expressed on/between luteinizing GC in the early luteal phase. Next we examined the effect of human chorionic gonadotrophin (HCG) on expression of integrin alpha5 on luteinizing GC in vitro. GC obtained from preovulatory follicles were cultured for 3 days without (control) or with HCG (1 IU/ml), and expression of integrin alpha5 was examined by flow cytometry. Although the positivity rate did not differ, the mean relative fluorescence intensity was 3.4-fold higher in the HCG-treated group (n = 8, P < 0.01). These findings indicate that integrin alpha5 is rapidly expressed on GC during luteinization, probably under LH stimulation, and suggest that integrin alpha5 is involved in CL formation via interaction with its ligand FN.

Antigens, CD↗
PubMed1997

Immunohistochemical localization of the LH/HCG receptor in human ovary: HCG enhances cell surface expression of LH/HCG receptor on luteinizing granulosa cells in vitro.

We examined the immunohistochemical localization of luteinizing hormone (LH)/human chorionic gonadotrophin (HCG) receptor (LH-R) in the human ovary using the anti-human LH-R monoclonal antibody, 3B5. In the antral follicles, LH-R was detected on theca interna cells. In pre-ovulatory follicles, granulosa cells also expressed LH-R. During corpus luteum formation, granulosa cells seemed to increase the expression of LH-R, and in corpus luteum of mid-luteal phase, large luteal cells expressed LH-R more intensely than small luteal cells. In the regressing corpus luteum, LH-R was almost undetectable on both luteal cells, whereas in the corpus luteum of early pregnancy, LH-R continued to be expressed on large luteal cells. The granulosa cells obtained from the patients undergoing in-vitro fertilization therapy were cultured for 3 days in serum-free medium, without or with HCG (10 IU/ml) and tumour necrosis factor (TNF)alpha (10 ng/ml). Flow cytometry showed that the expression of LH-R on the cell surface of luteinizing granulosa cells was enhanced by HCG, but was unaffected by TNFalpha. These results suggest that the main target cells for LH/HCG change from theca interna cells/small luteal cells to granulosa cells/large luteal cells during ovulation, corpus luteum formation, and differentiation into the corpus luteum of pregnancy, probably under the influence of LH/HCG.

Adolescent↗