Biomedical subjects

T Iwai

Publications and source records attributed to T Iwai.

At least 73 records · Page 4Linked to original sources

PubMed2000

Synthesis of oligonucleotide derivatives containing a bis-pyrene residue in the main chain.

The oligonucleotide having the bis-pyrene residue in the main chain was synthesized. The preparation of the bis-pyrene was started from the conversion of 2,2-bis-(bromomethyl)-1,3-propanediol into the protected bis-amino derivative. The reaction of the bis-amino derivative with 1-pyrenebutyric acid using DCC/HOBT afforded the desired bis-pyrene. This compound was then converted to the protected phosphormidite. The oligonucleotides possessing the bis-pyrene were synthesized by using the amidite. The oligonucleotides having the bis-pyrene residue can bind to DNA sequence in an aqueous solution to give the duplex with comparable thermal stability as that of the unmodified DNA/DNA duplex. The significantly enhanced pyrene-excimer fluorescence was observed upon hybridization of the bis-pyrene modified oligonucleotides with DNA.

Base Sequence↗

PubMed2000

Reduced levels of chloroplast FtsH protein in tobacco mosaic virus-infected tobacco leaves accelerate the hypersensitive reaction.

In tobacco cultivars resistant to tobacco mosaic virus (TMV), infection results in the death of the infected cells accompanying the formation of necrotic lesions. To identify the genes involved in this hypersensitive reaction, we isolated the cDNA of tobacco DS9, the transcript of which decreases before the appearance of necrotic lesions. The DS9 gene encodes a chloroplastic homolog of bacterial FtsH protein, which serves to maintain quality control of some cytoplasmic and membrane proteins. A large quantity of DS9 protein was found in healthy leaves, whereas the quantity of DS9 protein in infected leaves decreased before the lesions appeared. In transgenic tobacco plants containing less and more DS9 protein than wild-type plants, the necrotic lesions induced by TMV were smaller and larger, respectively, than those on wild-type plants. These results suggest that a decrease in the level of DS9 protein in TMV-infected cells, resulting in a subsequent loss of function of the chloroplasts, accelerates the hypersensitive reaction.

Amino Acid Sequence↗

PubMed2000

YM-40461 improves airway clearance in guinea pigs with induced subacute bronchitis.

The effects of the surfactant secretagogue YM-40461 on the mucociliary transport (MCT) velocity were examined in guinea pigs with induced bronchitis. Guinea pigs were exposed to SO2 gas (900 ppm, 3 h/d) for 5 d. MCT velocity was measured by the movement of a 30% gelatin solution containing Evans blue dye placed on the tracheal mucosal surface. Repeated doses of YM-40461 improved the MCT guinea pigs with bronchitis within 5 d after the completion of SO2 exposure, with an ED50 value of 3.1 mg/kg p.o. At a dose of 10 mg/kg p.o., YM-40461 restored MCT to the control level (98.0% recovery). Ambroxol, bromhexine and salbutamol also improved MCT, but were far less effective than YM-40461. Airway fluid collected from bronchitic animals revealed increased disaturated phosphatidylcholine (DSPC, a major component of surfactants)-to-protein ratio and decreased surface tension produced by YM-40461 treatment (10 mg/kg). These results suggest that YM-40461 ameliorates MCT dysfunction in animals with SO2 gas-induced bronchitis by increasing the DSPC-to-protein ratio in the airway.

Animals↗

PubMed2000

YM-40461, a potent surfactant secretagogue, improves mucociliary clearance in SO2-exposed guinea pigs.

The effects of the new pulmonary surfactant secretagogue YM-40461, 1-(2-dimethylaminoethyl)-1-(3,4,5-trimethoxyphenyl) urea, on tracheal mucociliary transport (MCT) were assessed using guinea pigs with acute bronchitis. Acute bronchitis was induced by SO2 gas exposure (400 ppm for 3 h). MCT velocity was measured by means of the dye gelatin technique. YM-40461 at doses of 1-10 mg/kg, p.o. induced recovery of MCT function, with an ED50 value of 2.4 mg/kg. Maximal recovery (78.0+/-12.5%) was observed 2 h in the animals treated with 10 mg/kg of YM-40461. Ambroxol and bromhexine showed less effect on the MCT dysfunction than YM-40461. An artificial surfactant (Surfacten) also aided recovery. YM-40461 at a dose of 10 mg/kg, p.o. significantly improved surfactant production without affecting mucus secretion. These results show that YM-40461 ameliorates MCT dysfunction caused by SO2 exposure by activation of pulmonary surfactant secretion.

Animals↗

PubMed2000

[A case of unresectable gallbladder cancer responding to combination therapy with hyperthermia and local chemotherapy].

A 78-year-old woman was admitted to our hospital for the control of gallbladder cancer. A peritoneal metastasis, diagnosed as unresectable cancer, was detected during surgery in a previous hospital, and a biliary stent was introduced and gastrojejunostomy was performed. In our hospital she was treated weekly with local chemotherapy (PFL; cisplatin 2.5-5 mg/body ia, fluorouracil 300 mg/body ia, and calcium folinate 30 mg/body ia, via the common hepatic arterial port) at the time of hyperthermia. Hyperthermia was performed with a Thermox 500 (HEH-500 C) at the power of 500 watts for 45-60 minutes. To enhance the hyperthermia effect, mitomycin C 2-4 mg/body ia via the common hepatic arterial port and 500 ml of 7.5% glucose infusion were given. As a result of the combination therapy, the volume of the whole tumor was reduced to 60.9% on computed tomography, and diagnosed as PR. The serum level of CA19-9 decreased from 3,000 U/ml to 300 U/ml. The patient continued to receive the therapy for 1 year, and is now well. Therefore, we conclude that combination therapy with hyperthermia and local chemotherapy seems beneficial in managing unresectable advanced gallbladder cancer, especially for the elderly.

Aged↗

PubMed2000

[Barrett's esophagus].

The Barrett's esophagus showing columnar metaplasia upward to the esophagus from the esophago-gastric junction is one of the final appearance of reflux esophagitis and important as a precancerous state of esophageal adenocarcinoma. Especially the Barrett's mucosa with intestinal metaplasia has high potential risk for adenocarcinoma. Although the clinical definition of the esophago-gastric junction is not easy, the criteria of the esophago-gastric junction and the Barrett's mucosa proposed by the Japanese Society for Esophageal Diseases is useful. The gastro-esophageal reflux is important in the development of Barrett's mucosa not only in the classical Barrett's esophagus but also in the short-segment Barrett's.

Barrett Esophagus↗

PubMed2000

[Prognostic significance of chromosome analysis in childhood acute lymphoblastic leukemia. Children's Cancer and Leukemia Study Group (CCLSG)].

We analyzed the prognostic significance of chromosomal findings in children with acute lymphoblastic leukemia (ALL), treated according to the Children's Cancer and Leukemia Study Group protocols between 1987 and 1993. Patients were classified into 5 groups according to chromosome number. The patients with a hyperdiploid(> 50) karyotype(13%) had the best prognosis [4-year event-free survival (EFS): 83 +/- 6%], while those with a pseudodiploid karyotype (24%) had the worst prognosis(4-year EFS: 52 +/- 6%) (log-rank, p = 0.03). However, multivariate analysis revealed that the ploidy classification had no prognostic significance in terms of EFS. When patients were classified according to chromosome abnormalities, those with any type of translocation had a worse outcome (4-year EFS: 33 +/- 9%) than those with hyperdiploidy(> 50), normal diploidy, and other abnormalities(log-rank, p < 0.0001). Multivariate analysis revealed that chromosome abnormalities were an independent prognostic factor (relative risk 3.98; p < 0.0001). Patients with t(1; 19) had an EFS similar to that of patients with chromosome abnormalities other than translocations or normal diploidy. We conclude that chromosomal findings have prognostic significance, although some chromosome abnormalities lost their statistical significance after modern intensified chemotherapy. Childhood ALL should be further stratified according to chromosome classification.

Child↗

PubMed2000

[Hepatic arterial infusion chemotherapy for liver metastasis from esophageal squamous cell carcinoma].

Since 1993, we have treated 9 patients with liver metastases from esophageal squamous cell carcinoma using hepatic arterial infusion chemotherapy (HAI). These patients underwent esophagectomy and reconstruction with a stomach roll, and without preoperative chemotherapy and/or radiotherapy, HAI was effective in 5 patients (56%) with a CR in 2 patients. Preceding systemic chemotherapy was done with 7 patients, and was effective in 3 of them. HAI was also effective in all of them. In 3 patients with hepatic arterial anomalies, the right gastroepiploic artery and right gastric artery feeding the stomach roll could be preserved after changing the hepatic arterial flow. Two stomach roll ulcers and one hepatic arterial stenosis were experienced due to the toxicity of HAI. However, the nausea, vomiting, diarrhea, and/or myelosuppression seen with the preceding systemic chemotherapy were not experienced. In spite of the technical difficulties in catheterization and toxicities to stomach roll, HAI is considered to be more effective and feasible than systemic chemotherapy.

Aged↗

PubMed2000

[A complication with hepatic arterial infusion chemotherapy--a case of sepsis related to catheter tip dislocation to the duodenal bulb].

Extra-arterial dislocation of a catheter is one of the complications with hepatic arterial infusion chemotherapy. The authors report a case of sepsis related to catheter tip dislocation to the duodenal bulb. A 69-year-old man underwent sigmoidectomy for sigmoid colon cancer and partial hepatectomy for synchronous metastasis to the liver. We performed hepatic arterial catheterization via the femoral artery, and the patient underwent prophylactic hepatic arterial infusion chemotherapy with 5-FU. Thirty months later, computed tomography during arteriography (CTA) using a port system revealed the dislocation of catheter tip to the duodenal bulb. He showed no symptoms, so we kept him under observation. Sepsis occurred because of the dislocated catheter 39 months later. After removal of the catheter, the symptoms of sepsis disappeared.

Aged↗

PubMed2000

Hand-assisted laparoscopic surgery for the abdominal phase in endoscopic esophagectomy for esophageal cancer: an alteration on the site of minilaparotomy.

The authors present an alteration at the site of a minilaparotomy in the abdominal phase of endoscopic esophagectomy and reconstruction by means of hand-assisted laparoscopic surgery. In the first case, a minilaparotomy was performed in the lower right side of the abdomen during laparoscopic construction of a gastric tube using hand-assisted laparoscopic surgery. However, this technique was not always feasible because an elaborate technique was necessary, even with the use of the surgeon's hand, which was inserted in the abdomen through the mini-incision. After the second case, the authors performed a minilaparotomy slightly above the stomach. The upper abdominal incision allowed easier and safer management of the gastric tube. This technique was also helpful in the Kocher maneuver and in the construction of the retrosternal route. The site of the minilaparotomy in the upper abdomen reduced the stress of this procedure, and, therefore, became the standard procedure for select patients at the First Department of Surgery, Tokyo Medical and Dental University.

Biopsy↗

PubMed2000

[Development of Hodgkin's disease four years after autologous peripheral blood stem cell transplantation for multiple myeloma].

We report a case of Hodgkin's disease that developed 4 years after autologous peripheral blood stem cell transplantation (PBSCT). The patient, a 67-year-old Japanese male, underwent PBSCT for multiple myeloma (IgA-lambda type) under a conditioning regimen of carboplatin, etoposide and cyclophosphamide in June 1994 and obtained partial remission. In January 1995, he underwent a second PBSCT under a conditioning regimen of high-dose melphalan and obtained complete remission. In December 1998, he noticed swelling of the left cervical lymph nodes, and Hodgkin's disease of the mixed cellularity subtype was diagnosed from a lymph node biopsy sample. Immunohistochemistry studies showed that the Hodgkin's and Reed-Sternberg cells were CD30-positive. In situ hybridization using EBER probes showed that these cells expressed EBER RNA transcripts, indicating that the tumor was associated with Epstein-Barr virus. One noteworthy feature was the absence of both M-component in the serum and urine, as revealed by immunoelectrofixation, and plasmacytosis in the bone marrow, which would have indicated relapse of the multiple myeloma. After chemotherapy with MOPP and ABVD, the Hodgkin's disease was eradicated and the patient obtained complete remission in May 1999.

Aged↗

PubMed2000

Ileosigmoid anastomosis with exclusion of transected ileal loop for intestinal fistula following total cystectomy of bladder cancer. Report of a case.

We report in this article a new technique of surgical treatment of enterocutaneous or enterovaginal fistula after total cystectomy for three cases of bladder cancer. The surgical outcome was successful in these patients, showing good performance status after this operation. It would seem that this technique is a good indication for enteric fistulas in the bottom of the pelvic cavity, which were difficult to be managed even under the control of total parenteral nutrition.

Abscess↗

PubMed1999

Failure of preventive effects of 2-deoxy-D-glucose on ischemia-induced gerbil hippocampal neuronal damage by induced hyperthermia.

Post-ischemic administration of 2-deoxy-D-glucose (2-DG), a glucose antimetabolite, markedly reduces the occurrence of ischemia-induced delayed neuronal death (DND) in the gerbil hippocampus. This means that the reduction of energy dependent metabolism after ischemia prevents ischemia-induced damages of hippocampal neurons. In the present study, we demonstrated hyperthermia during ischemia fails to preserve neurons in hippocampal CA1 of 2-DG treated gerbil following transient forebrain ischemia.

Animals↗

PubMed1999

Predominant germ-line mutation of the hMSH2 gene in Japanese hereditary non-polyposis colorectal cancer kindreds.

By means of PCR-SSCP and direct sequencing, we detected 12 germ-line mutations of hMSH2 or hMLH1 in 37 Japanese hereditary non-polyposis colorectal cancer (HNPCC) kindreds, of whom 15 satisfied the Amsterdam and 22 the Japanese criteria. The germ-line mutation detection rate of hMSH2 was much higher than that of hMLH1 (11/37 vs. 1/37). The total mutation detection rate of hMSH2 and hMLH1 in the Amsterdam criteria group was significantly higher than that in the Japanese criteria group (9/15 vs. 3/22). Furthermore, the mean age of the HNPCC patients in the mutation-positive group was lower than that in the mutation-negative one; the rates of both vertical transmission and multiplicity of tumors in the mutation-positive group were higher than those in the mutation-negative one. In addition, the number of patients with microsatellite instability-positive cancers in the mutation-positive group was higher than that in the mutation-negative one. Our results suggest firstly that the hMSH2 gene plays a much more important role than hMLH1 in the carcinogenesis of Japanese HNPCC patients, secondly that the rate of hMSH2 and hMLH1 mutations is high in the kindreds satisfying the Amsterdam criteria and thirdly that both the clinical phenotypes (early onset, vertical transmission and multiplicity of tumors) and the microsatellite instability status are important for the genetic screening of HNPCC.

Colorectal Neoplasms, Hereditary Nonpolyposis↗

PubMed1999

Efficacy of the mobilization of peripheral blood stem cells by granulocyte colony-stimulating factor in pediatric donors.

The advantages/disadvantages of the use of peripheral blood stem cells (PBSCs) for allogeneic transplantation still need to be clarified, particularly in children. We compared the kinetics, efficacy, and safety of PBSC mobilization by granulocyte colony-stimulating factor (G-CSF) and collection by apheresis between healthy pediatric and adult donors. A total of 19 pediatric (median age, 6 years) and 25 adult healthy donors (median age, 37 years) were given 10 micro/kg/day of G-CSF for 5 consecutive days for PBSC mobilization, which were harvested by apheresis on days 5 and/or 6. All of the donors tolerated the whole procedures. Serum trough levels of G-CSF determined by ELISA were significantly lower in the 16 pediatric donors evaluated than in adults (n = 16) on days 3 and 4 (P < 0.05). Although the WBC counts on days 4 and 5 were significantly higher in adults than in children (P = 0.006 and 0.004, respectively), the numbers of circulating CD34+ cells/unit of blood were identical. The number of blood CD34+ cells collected per unit of blood processed was identical in both donor populations. We propose that PBSCs could be effectively mobilized and collected in small children so that they could be donors for adult patients.

Adolescent↗

PubMed1999

Differential effects of angiotensin II receptor blockade on pressure-induced left ventricular hypertrophy and fibrosis in rats.

The effects of the angiotensin II receptor type 1 (AT1) antagonist losartan on pressure overload-induced left ventricular (LV) hypertrophy were studied in female Sprague-Dawley rats. Starting on the day of surgery, losartan (L, 12 mg/kg/day) was administered as continuous intraperitoneal infusion for 2 weeks by using alzet mini-osmotic-pumps (model 2002). This dose of losartan shifted the in vivo dose-response curve of the angiotensin II-induced elevation of left ventricular systolic pressure (LVSP) to the right. Pressure overload was achieved by placing a band around the aortic arch. This caused an aortic stenosis (AS) with an outer diameter of 1.0 mm. The hemodynamic effects were measured in the intact, anesthetized rats (n = 15). The hearts were excised, and the weights of the left (LV) and right ventricle (RV) were determined. Some of these hearts (n = 7) were perfused with collagenase to obtain isolated cardiac myocytes for the measurement of cell volume. Other hearts (n = 8) were examined for morphological changes. In the animals with AS, LVSP was markedly elevated. Furthermore, LV weight and LV myocyte cell volume were increased in this group, while RV weight and RV myocyte cell volume remained stable in all the groups. L had no significant effect on the AS-induced increase in LVSP and cell size parameters, nor on the weight gain of the LV. Histological analysis revealed that the AS-induced enlargement of the mean myocyte diameter was not affected by L. The interstitial collagen fraction was increased in the AS rats and became normalized by L. These data suggest that the renin-angiotensin system might not be involved in the development of pressure-induced cardiac hypertrophy within the time-frame of these experiments, but that it does play a major role in the genesis of the interstitial fibrosis which is a typical feature of this pathophysiological condition.

Angiotensin Receptor Antagonists↗

PubMed1999

A new, simple method for measuring mucociliary clearance in guinea-pigs.

Airway mucociliary transport (MCT), which continuously removes inhaled particles and cellular debris from deep in the lung, is impaired in a number of diseases such as bronchitis and asthma. In order to determine the effects of candidate drugs on MCT function in the airway, a new in situ method to measure MCT function was established. MCT function is represented by the distance a gelatin solution containing Evans blue as a marker moves after injection into the trachea. The basal rate of dye transport in non-treated guinea-pigs was 4.4+/-0.2 mm/min. The beta2-adrenoceptor agonist salbutamol (2, 6, 10, 20 mg/kg, po), dose-dependently accelerated the basal MCT rate. However, its effect was completely inhibited by pretreatment with the non-selective beta -adrenoceptor antagonist, propranolol (1 mg/kg, iv). MCT function in guinea-pigs was significantly attenuated to 2.6+/-0.3 mm/min by SO2 gas exposure. Salbutamol failed to prevent MCT dysfunction in SO2-exposed animals at doses previously shown to accelerate basal MCT rate. This simple method is useful for estimating MCT function in several airway disease models and for examining new drugs designed to improve MCT function in airway diseases.

Adrenergic beta-Antagonists↗

PubMed1999

Celiac artery aneurysm: report of two surgical cases.

Celiac artery aneurysms are uncommon and only 21 cases have been reported in Japan. We present herein two cases of celiac artery aneurysm treated by aneurysmectomy and vascular reconstruction, and review the Japanese literature documented between 1969 and 1997. Our two patients were asymptomatic, and their aneurysms were detected incidentally by abdominal computed tomography (CT) and ultrasonography during investigations of other disorders. The celiac trunk was imaged well by three-dimensional CT angiography, which proved very effective for determining the best surgical approach and type of operation. Aneurysmectomy and reconstruction of the common hepatic and splenic arteries with direct end-to-end anastomosis was performed successfully in both patients. Pathological examination revealed medial degeneration with loss of elastic fibers and atherosclerotic changes that were probably secondary. In Japan, 13 patients (61.9%) have been surgically treated and several methods of vascular reconstruction with grafting have been reported; however, there have been no previous reports of an end-to-end anastomosis without grafting as described herein.

Anastomosis, Surgical↗