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Biomedical subjects

H Takeda

Publications and source records attributed to H Takeda.

At least 217 records · Page 12Linked to original sources

Eradication of Helicobacter pylori using 30 mg or 60 mg lansoprazole combined with amoxicillin and metronidazole: one and two weeks of a new triple therapy.

A new triple therapy using a proton pump inhibitor and two antibiotics shows high efficiency against Helicobacter pylori infection. The aim of this study was to determine the optimal dose and duration of lansoprazole (LA) administration in combination with amoxicillin (AMPC) and metronidazole (MNZ). A total of 91 patients were enrolled in this study. They were divided into four groups: group A, 2 weeks of 30mg LA once daily, 500mg AMPC tid, and 250mg MNZ tid; group B, 2 weeks of 30mg LA bid, 500mg AMPC tid, and 250mg MNZ tid; group C, 1 week of 30mg LA once daily, 500mg AMPC tid, and 250mg MNZ tid; group D, 1 week of 30mg LA bid, 500mg AMPC tid, and 250mg MNZ tid. H. pylori status was determined by the rapid urease test, culture, histology, and 13C-urea breath test before and at least 4 weeks after the end of therapy. The cure rates in a per-protocol analysis and the incidence of adverse events in the evaluated patients were, respectively, 89.5% and 21.1% in group A, 100% and 20.0% in group B, 96.8% and 12.9% in group C, and 92.3% and 26.9% in group D. Most of the adverse events were tolerated. All four regimens in this study showed the same cure rates, and they were effective and well tolerated. One week of triple therapy using once-daily administration of 30mg LA is a good alternative.

2-Pyridinylmethylsulfinylbenzimidazoles↗

Proton magnetic resonance spectroscopy of the lenticular nuclei in bipolar I affective disorder.

Proton magnetic resonance spectroscopy (1H-NMS) was used to examine the ratio of choline-containing compound (Cho) to creatine (Cr) in the basal ganglia. Subjects comprised 10 bipolar I affective disorder patients and 10 healthy control subjects. No significant difference was found in the Cho/Cr, N-acetyl-aspartate (NAA)/Cr, or NAA/Cho ratios between bipolar patients and control subjects. Within the bipolar group, negative correlations emerged between the NAA/Cr ratio in the right lenticular nuclei and both age at onset and age at the time of study. The results suggest that a late onset of illness and older age are associated with neuronal cell loss in the right lenticular nuclei in bipolar patients.

Adult↗

Simultaneous determination of bile acids in rat liver tissue by high-performance liquid chromatography.

A method for the simultaneous determination of bile acids in rat liver tissue by high-performance liquid chromatography was developed. Without prior fractionation and alkaline hydrolysis, 30 unconjugated, glycine- and taurine-conjugated bile acids were detected by post-column enzymatic reaction and fluorescence detection. They were separated on a reversed-phase column using a linear gradient solvent system of 10 mM tribasic ammonium phosphate-acetonitrile-methanol (44:12:5, v/v/v) and 20 mM dibasic ammonium phosphate-acetonitrile-methanol (2:1:2, v/v/v). The limits of detection were 1-5 pmol, and calibration curves were linear for concentrations ranging between 10 and 4000 pmol per 10 microl injection. This rapid and reliable method is effective for measuring bile acid levels in liver tissue not only of rats but also of patients with hepatobiliary and other diseases.

Animals↗

A novel homeobox gene, dharma, can induce the organizer in a non-cell-autonomous manner.

The formation of Spemann organizer is one of the most important steps in dorsoventral axis determination in vertebrate development. However, whether the organizer forms autonomously or is induced non-cell-autonomously is controversial. In this report we have isolated a novel zebrafish homeobox gene, dharma, capable of inducing the organizer ectopically. The expression of dharma was first detected in several blastomeres at one side of the margin soon after the mid-blastula transition and continued in the dorsal side of the yolk syncytial layer (YSL) under the embryonic shield, the zebrafish organizer, until the onset of gastrulation. Furthermore, dharma expressed in the YSL induced the organizer in a non-cell-autonomous manner. These results provided the first identification of a zygotic gene to be implicated in the formation of an organizer-inducing center.

Amino Acid Sequence↗

Platelet adhesion to aortic endothelial cells in vitro after thrombin treatment: observation with video-enhanced contrast microscopy.

Secondary thrombus formation following arterial occlusion is suggested to play an important role in the exacerbation of ischemic organ damage. We investigated the effect of thrombin on endothelial cells from the aspect of morphological changes and induction of platelet adhesion to the endothelial cells. Using a video-enhanced contrast microscopy, we observed human aortic endothelial cells (HAEC) following perfusion of human alpha-thrombin of 1.0 U/ml (n = 7) or vehicle (n = 7) for 30 minutes. The endothelial cells began to shrink 15 minutes after thrombin administration. Gaps between the cells were formed. The cells became rearranged orderly in the same direction 30 minutes later. In another study, following pretreatment with human alpha-thrombin 1.0 U/ml (n = 10) or vehicle (n = 7) for 20 minutes and washout, platelets were perfused over HAEC for 30 minutes. Platelets adhered directly to thrombin-treated endothelial cells and became flat on the endothelial cells. Then other platelets were observed to approach to the flattened platelets and aggregated onto it. After washout of floating platelets, adhesion of platelets was further confirmed. These results suggest that thrombin may be involved in the endothelial damage and formation of platelet thrombi on the endothelial cells after blood flow disturbance.

Aorta↗

A case of Mucinous Carcinoma of the Male Breast with Unusual Ultrasonographic Findings Mimicking Phyllodes Tumor.

Mucinous carcinoma of the male breast is a rare histological type of cancer. We describe a 35-year-old male with mucinous carcinoma of the right breast. His breast mass enlarged subacutely, and became painful over a period of 2 months. Ultrasonography demonstrated echoes of a large multilocular cystic lesion with partially heterogenic internal echoes suggesting a phyllodes tumor. A modified radical mastectomy was performed, and histopathologic examination revealed mucin-producing solid or cribriform atypical cells with fibrous granulation tissue and hemosiderin deposition. The patient recovered uneventfully, and is still free of recurrence 30 months after his operation. The prognosis for male breast cancer can be improved by early diagnosis and appropriate multidisciplinary therapy.

Journal Article↗

Lysophosphatidic acid-induced association of SHP-2 with SHPS-1: roles of RHO, FAK, and a SRC family kinase.

SHPS-1 is an approximately 120 kDa glycosylated receptor like protein that contains three immunoglobulin-like domains in its extracellular region as well as four potential tyrosine phosphorylation and SRC homology 2 (SH2) domain binding sites in its cytoplasmic region. Lysophosphatidic acid (LPA) stimulated the rapid tyrosine phosphorylation of SHPS-1 and its subsequent association with SHP-2, a protein tyrosine phosphatase containing SH2 domains in Rat-1 fibroblasts. LAP-induced tyrosine phosphorylation of SHPS-1 was inhibited by Clostridium botulinum C3 exoenzyme (which inactivates RHO) but not by pertussis toxin. The protein kinase C activator phorbol ester, 12-O-tetradecanoylphorbol 13-acetate (TPA) also stimulated tyrosine phosphorylation of SHPS-1; however, down-regulation of protein kinase C by prolonged exposure of cells to TPA did not affect LAP-induced tyrosine phosphorylation of SHPS-1. LPA-induced tyrosine phosphorylation of SHPS-1 was markedly reduced in either focal adhesion kinase (FAK)-deficient mouse cells or CHO cells overexpressing the tyrosine kinase CSK. Overexpression of a catalytically inactivate SHP-2 markedly inhibited MAP kinase activation in response to low concentrations of LPA in CHO cells, whereas overexpression of a wild-type SHPS-1 did enhance this effect of LPA. Furthermore, MAP kinase activation in response to a low concentration of LPA was inhibited by botulinum C3 exoenzyme. These results indicate that LPA-induced tyrosine phosphorylation of SHPS-1 and its association with SHP-2 may be mediated by a RHO-dependent pathway that includes FAK and a SRC family kinase. Thus, in addition to its role in receptor tyrosine kinase-mediated MAP kinase activation, the formation of a complex between SHPS-1 and SHP-2 may, in part, play an important role in the activation of MAP kinase in response to low concentrations of LPA.

ADP Ribose Transferases↗

Changes in head-dipping behavior in the hole-board test reflect the anxiogenic and/or anxiolytic state in mice.

The effects of treatment with anxiogenic or anxiolytic agents and exposure to acute restraint stress on emotional behavior in mice were examined using an automatic hole-board apparatus. Changes in the emotional state of mice were evaluated in terms of changes in exploratory activity, i.e., total locomotor activity, numbers and duration of rearing and head-dipping, and latency to the first head-dipping. The typical benzodiazepine anxiolytics diazepam (0.05-0.5 mg/kg, i.p.) and chlordiazepoxide (0.5-4 mg/kg, i.p.) dose-dependently increased the number and duration of head-dips at doses that did not produce sedation. In contrast with these anxiolytics, the typical anxiogenic drugs N-methyl-beta-carboline-3-carboxamide (FG7142, 0.125-10 mg/kg, i.p.) and methyl-beta-carboline-3-carboxylate (beta-CCM, 0.1-2 mg/kg, i.p.) decreased both the number and duration of head-dips, and increased the latency to head-dipping. Moreover, decreases in the number and duration of head-dips, and an increase in the latency to head-dipping, were also observed in animals that were exposed to acute restraint stress. These effects of acute restraint stress were suppressed by treatment with diazepam at a dose that alone did not produce significant behavioral effects (0.1 mg/kg, i.p.). In addition, non-benzodiazepine anxiolytic flesinoxan (0.1 mg/kg, i.p.), a 5-HT1A receptor agonist, also had an effect on the restraint stress-induced decrease in head-dipping behavior. The present study shows that the changes in several exploratory behaviors could be objectively measured using our automatic hole-board apparatus. Therefore, this system can serve as a useful tool for evaluating the changes in various emotional states of animals. Moreover, we also found that treatment with anxiolytics or anxiogenics and exposure to acute restraint stress affected head-dipping behavior. These results suggest that changes in head-dipping behavior in the hole-board test may reflect the anxiogenic and/or anxiolytic state of animals.

Animals↗

Integrin-mediated tyrosine phosphorylation of SHPS-1 and its association with SHP-2. Roles of Fak and Src family kinases.

SHPS-1 is a receptor-like glycoprotein that undergoes tyrosine phosphorylation and binds SHP-2, an Src homology 2 domain containing protein tyrosine phosphatase, in response to various mitogens. Cell adhesion to extracellular matrix proteins such as fibronectin and laminin also induced the tyrosine phosphorylation of SHPS-1 and its association with SHP-2. These responses were markedly reduced in cells overexpressing the Csk kinase or in cells that lack focal adhesion kinase or the Src family kinases Src or Fyn. However, unlike Src, focal adhesion kinase did not catalyze phosphorylation of the cytoplasmic domain of SHPS-1 in vitro. Overexpression of a catalytically inactive SHP-2 markedly inhibited activation of mitogen-activated protein (MAP) kinase in response to fibronectin stimulation without affecting the extent of tyrosine phosphorylation of focal adhesion kinase or its interaction with the docking protein Grb2. Overexpression of wild-type SHPS-1 did not enhance fibronectin-induced activation of MAP kinase. These results indicate that the binding of integrins to the extracellular matrix induces tyrosine phosphorylation of SHPS-1 and its association with SHP-2, and that such phosphorylation of SHPS-1 requires both focal adhesion kinase and an Src family kinase. In addition to its role in receptor tyrosine kinase-mediated MAP kinase activation, SHP-2 may play an important role, partly through its interaction with SHPS-1, in the activation of MAP kinase in response to the engagement of integrins by the extracellular matrix.

Animals↗

Roles of the complex formation of SHPS-1 with SHP-2 in insulin-stimulated mitogen-activated protein kinase activation.

SHPS-1 is a receptor-like protein that undergoes tyrosine phosphorylation and binds SHP-2, an SH2 domain-containing protein tyrosine phosphatase, in response to insulin and other mitogens. The overexpression of wild-type SHPS-1, but not of a mutant SHPS-1 in which all four tyrosine residues in its cytoplasmic region were mutated to phenylalanine, markedly enhanced insulin-induced activation of mitogen-activated protein kinase in Chinese hamster ovary cells that overexpress the human insulin receptor. Mutation of each tyrosine residue individually revealed that the major sites of tyrosine phosphorylation of SHPS-1 in response to insulin are Tyr449 and Tyr473. In addition, mutation of either Tyr449 or Tyr473 abolished the insulin-induced tyrosine phosphorylation of SHPS-1 and its association with SHP-2. Surface plasmon resonance analysis showed that glutathione S-transferase fusion proteins containing the NH2-terminal or COOH-terminal SH2 domains of SHP-2 bound preferentially to phosphotyrosyl peptides corresponding to the sequences surrounding Tyr449 or Tyr473, respectively, of SHPS-1. Furthermore, phosphotyrosyl peptides containing Tyr449 or Tyr473 were effective substrates for the phosphatase activity of recombinant SHP-2 in vitro. Together, these results suggest that insulin may induce phosphorylation of SHPS-1 at Tyr449 and Tyr473, to which SHP-2 then binds through its NH2-terminal and COOH-terminal SH2 domains, respectively. SHPS-1 may play a crucial role both in the recruitment of SHP-2 from the cytosol to a site near the plasma membrane and in increasing its catalytic activity, thereby positively regulating the RAS-mitogen-activated protein kinase signaling cascade in response to insulin.

Amino Acid Sequence↗

Neoadjuvant concurrent chemoradiotherapy followed by definitive high-dose radiotherapy or surgery for operable thoracic esophageal carcinoma.

PURPOSE: A prospective clinical trial was undertaken to investigate the feasibility of concurrent chemoradiotherapy for esophageal carcinomas. MATERIALS AND METHODS: Between June 1989 and May 1996, forty patients with operable squamous cell carcinoma of the thoracic esophagus (Stage 0 to III: UICC 1987), ages 45 to 78 years (mean: 64), were enrolled in a study of neoadjuvant concurrent chemoradiotherapy followed by definitive high-dose radiotherapy (CRT group) or surgery (CRT-S group). Neoadjuvant chemoradiotherapy consisted of 44 Gy in 40 fractions for 4 weeks (2.2 Gy/2 Fr/day) through 10-MVX rays, with 2 courses of cisplatin (80-100 mg/body, mean: 60 mg/m2, Day 1, bolus injection) and 5-fluorouracil (500-1000 mg/body/day, mean: 400 mg/m2, Days 1-4, continuous infusion). After completion of neoadjuvant chemoradiotherapy, an intermediate clinical response was assessed by barium swallow, esophagoscopy with/without biopsy, EUS in most cases, thoracic and upper abdominal CT scan, and cervical US. Definitive chemoradiotherapy was performed in patients when regression of more than 75% was evident (CRT Group), and esophageal resection was indicated in those who remained at less than 75% (CRT-S Group). In CRT Group, a cumulative dose of 60-70 Gy for Tis, T1 and 65-75 Gy for T2-T4 tumor with high-dose-rate intraluminal brachytherapy and a total of 3 courses of chemotherapy were planned. In CRT-S Group, intraoperative radiotherapy for abdominal lymphatic system and postoperative supraclavicular irradiation were added. RESULTS: At the time of intermediate assessment, complete response (CR) was observed in 16 patients, a partial response (PR) in 22, and no change (NC) in 2. Thirty responding patients (CR, 16; PR, 14) entered the CRT Group, and 10 nonresponding patients (PR, 8; NC, 2) were followed by surgery (CRT-S Group). Radiotherapy was completed satisfactorily, but chemotherapy was suspended in 26 patients (65%) because of acute toxicity. Clinical CR rate at the completion of treatment showed 90% in CRT Group, and pathologic CR rate 10% in CRT-S Group. The overall median survival was 45 months, survival at 1, 2, and 3 years being 100%, 72%, and 56%, respectively. Local-regional failure was observed in 7 patients (all in CRT Group), distant failure in 6 (3 in CRT Group, 3 in CRT-S Group) and local-regional with distant failure in 1 (CRT Group). Four patients with local-regional recurrence in the CRT Group were salvaged by surgery. Overall survival at 2 and 3 years for CRT vs. CRT-S Group was 72%, 64% vs. 75%, 38%, respectively. No treatment-related mortality was observed. The rate of the 'esophagus conservation' was 65% (Stage 0: 1 of 1, 100%; Stage I: 11 of 12, 92%; Stage II: 8 of 17, 47%; Stage III: 6 of 10, 60%). CONCLUSION: Our results demonstrated that almost all early disease (Stage 0-I) and about half of advanced disease (Stage II-III) could be conserved, their esophagus treated by the multidisciplinary approach centering on high-dose radiotherapy and concurrent chemotherapy.

Aged↗

Sphingomyelinase and ceramide inhibit formation of F-actin ring in and bone resorption by rabbit mature osteoclasts.

Recent studies have demonstrated that ceramide plays an important role as a second messenger in many kinds of cells. However, it is not known whether apoptosis of and bone resorption by mature osteoclasts are mediated via sphingomyelinase (SMase) and ceramide. Thus, we examined the possible involvement of SMase and ceramide in the induction of apoptosis in and bone resorption by rabbit mature osteoclasts. SMase and C2-ceramide inhibited strongly F-actin ring formation of and bone resorption by the osteoclasts. However, the osteoclast apoptosis was not induced by C2-ceramide. The ceramide inhibition of the bone resorption was suppressed by DL-threodihydrosphingosine, an inhibitor of sphingosine kinase. In addition, we observed that sphingosine-1-phosphate is able to inhibit bone resorption by the osteoclasts. These results suggest an important role of the sphingomyelin pathway in bone resorption by rabbit mature osteoclasts.

Actins↗

Hydrogen peroxide enhances phagocytic activity of ameboid microglia.

Microglia are considered to serve as a guardian of the brain. In achieving this task, they have been observed to transform into a reactive form and then an ameboid form. Several substances are implicated in the control of such behavior. We examined the effect of hydrogen peroxide on cultured microglia of ameboid form obtained from the fetal rat brain employing video-enhanced contrast-differential interference contrast microscopy. Microglia harvested from the culture bottle were observed to float in a spherical shape with abundant filopodia on the surface. However, on coming into contact with the glass surface of a cover slip, they immediately transformed into an ameboid form. The microglia spread themselves out, surrounded by thin transparent lammellipodia, which would not be clearly observable by either light microscopy or electron microscopy. In a concentration-dependent fashion, 10(-3)-10(-1) M hydrogen peroxide solution enhanced the ruffling process of the lamellipodia and formation of vesicles (phagosomes), which displayed a typical phagocytotic form. It is concluded that an increase in free radicals in ischemic tissue tends to facilitate the phagocytosis of ameboid microglia as macrophages.

Animals↗

The effect of short-term continuous epidural morphine on postoperative pain after laparoscopic cholecystectomy.

This study was undertaken to determine whether short-term continuous epidural analgesia using morphine would relieve pain after laparoscopic cholecystectomy. The authors retrospectively reviewed the clinical data of 182 cases who had undergone a laparoscopic cholecystectomy. These cases were divided into four groups according to their anesthetic modes as follows: a control group with general anesthesia only (n = 37); group I, general anesthesia combined with one shot of epidural morphine (n = 78); and group II, general anesthesia combined with continuous epidural analgesia using morphine (IIa for 12 h (n = 33); IIb for 8 h (n = 34)). The pain score on a four-category verbal scale and the frequency of analgesic use were investigated. There were no differences in the background characteristics of the patients among the groups, except for the duration of surgery (I vs IIa; P = 0.006). The pain scores were significantly different between the control group and the other groups. The frequency of analgesic use in the control group was also significantly higher than in the other groups. A tendency toward a higher frequency of analgesic use in group I, compared with that in groups IIa and IIb, was observed. These findings thus suggest that short-term continuous epidural analgesia using morphine can effectively relieve postoperative pain after a laparoscopic cholecystectomy.

Analgesia, Epidural↗

A prospective analysis of the factors influencing pancreaticojejunostomy performed using a single method, in 100 consecutive pancreaticoduodenectomies.

The factors influencing the healing process of pancreaticojejunostomy (P-J) following pancreaticoduodenectomy (PD) are still ill defined, allowing the recommendation of various anastomotic methods. We conducted a prospective study to determine the risk factors influencing the protracted healing of P-J, examining 100 consecutive patients who underwent PD followed by P-J, performed as an end-to-side "mucosa-to-mucosa" anastomosis using vertical mattress sutures (VMS method). Protracted healing of P-J was classified as either peripancreatic sepsis (PPS), defined as prolonged suppurative discharge of less than 50 ml a day from the drain beneath the P-J for more than 1 week; or a pancreatic fistula (PF), defined as prolonged discharge of more than 50 ml a day with a high amylase content (> 1000 IU) for more than 1 week. There were 80 patients with a malignant neoplasm, and 20 with benign disease. The overall incidence of healing problems following P-J was 9%, which included 6 patients (6%) with PPS and 3 (3%) with PF. Apart from an advanced age of more than 70 years, none of the patients' characteristics or postoperative complications influenced the healing of P-J. The type of reconstruction, an anastomotic stent, the duct size, and a "soft" pancreas were not risk factors either. In conclusion, no factors, apart from the age or any special problem of an individual patient, influenced the dehiscence of P-J when the VMS method was used after PD.

Adult↗

Modified Bankart procedure for recurrent anterior dislocation and subluxation of the shoulder in athletes.

Thirty-four athletes (34 shoulders) with recurrent anterior glenohumeral instability were treated with a modified Bankart procedure, using a T-shaped capsular incision in the anterior capsule. The inferior flap was advanced medially and/or superiorly and rigidly fixed at the point of the Bankart lesion by a small cancellous screw and a spike-washer. The superior flap was advanced inferiority and sutured over the inferior flap. Twenty-five athletes (median age: 22) were evaluated over a mean period of follow-up of 65 months. The clinical results were graded, according to Rowe, as 22 (88%) excellent, 3 (12%) good, and none as fair or poor. The mean postoperative range of movement was 92 degrees of external rotation in 90 degrees of abduction. Elevation and internal rotation was symmetrical with the opposite side. Twenty-four patients returned to active sport, 22 at their previous level. This modified Bankart procedure is an effective treatment for athletes with recurrent anterior glenohumeral instability.

Adolescent↗