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T Morimoto

Publications and source records attributed to T Morimoto.

At least 163 records · Page 9Linked to original sources
PubMed1998

Novel domain-specific actions of amyloid precursor protein on developing synapses.

The effect of the secretory form of amyloid precursor protein (sAPP) on synaptic transmission was examined by using developing neuromuscular synapses in Xenopus cell cultures. The frequency of spontaneous postsynaptic currents (SSCs) was reduced by the addition of sAPP, whereas the amplitude of impulse-evoked postsynaptic currents (ESCs) was increased by sAPP. These opposing effects on spontaneous versus evoked release were separated by using the specific domain of APP. The C-terminal fragment of sAPP (CAPP) only reduced SSC frequency and did not affect ESCs. By contrast, the N-terminal fragment of sAPP (NAPP) did not affect SSC frequency but did increase ESC amplitude. The reduction of SSC frequency by sAPP appears to be mediated by activation of potassium channels through a cGMP-dependent pathway, whereas the increase of ESC amplitude is mediated by a different pathway involving activation of protein kinase(s). These results suggest the potential role of sAPP as a modulator of synaptic activity by two specific domains.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1998

Radiation Complications Following Breast Conserving Therapy.

BACKGROUND: Breast conserving therapy is being established as a standard therapeutic procedure for early breast cancer in Japan. However, the indications of radiotherapy and a standardized therapeutic procedure have not been established yet. In this study, complications following radiotherapy were evaluated in patients who had previously undergone breast conserving therapy at Tokushima University Hospital. METHODS From October 1989 to March 1996, 60 women with stage I or II breast cancer underwent radiation therapy after breast conserving surgery, and all patients were followed-up for a median of 27 months. Radiation morbidity scoring of the breast and adjacent organs was performed using the toxity criteria of the Radiation Therapy Oncology Group (RTOG) and European Organization for Research andTreatment of Cancer (EORTC). RESULTS: Only 1 patient developed local recurrence, and no distant metastasisor death was observed. The cause of recurrence in 1 case was considered to be due to extended intraductal component. Although transient dermal reaction was induced by irradiation of the breast, no side effects that may cause cosmetic problems were found. No serious radiation complications were found in the lungs, ribs, heart or other adjacent organs. CONCLUSION: The adverse reactions caused by irradiation does not reduce the merit of combined use of radiation therapy in breast conserving therapy, and therefore, are not the hesitation factor in application of radiotherapy.

Journal Article↗
PubMed1998

An essential role for the phosphatidylinositol transfer protein in the scission of coatomer-coated vesicles from the trans-Golgi network.

We identified the phosphatidylinositol transfer protein (PITP) as being responsible for a powerful latent, nucleotide-independent, Golgi-vesiculating activity that is present in the cytosol but is only manifested as an uncontrolled activity in a cytosolic protein subfraction, in which it is separated from regulatory components that appear to normally limit its action to the scission of COPI-coated buds from trans-Golgi network membranes. A specific anti-PITP antibody that recognizes the two mammalian PITP isoforms fully inhibited the capacity of the cytosol to support normal vesicle generation as well as the uncontrolled vesiculating activity manifested by the cytosolic protein subfraction. The phosphatidylinositol- (PI) loaded form of the yeast PITP, Sec14p, but not the phosphatidylcholine- (PC) loaded form of the protein, was capable of substituting for the cytosolic subfraction in promoting the scission of coated buds from the trans-Golgi network. At higher concentration, however, Sec14p, when loaded with PI, but not with PC or phosphatidylglycerol, caused by itself an indiscriminate vesiculation of uncoated Golgi membranes that could be suppressed by PC-Sec14p, which also suppresses the uncontrolled vesiculation caused by the cytosolic subfraction. We propose that, by delivering PI to specific sites in the Golgi membrane near the necks of coated buds, PITP induces local changes in the organization of the lipid bilayer, possibly involving PI metabolites, that triggers the fusion of the ectoplasmic faces of the Golgi membrane necessary for the scission of COPI-coated vesicles.

Animals↗
PubMed1998

In vitro and in vivo studies on transthyretin oligomerization.

The oligomerization of transthyretin has been studied in vitro and in vivo. The results showed that wild-type transthyretin synthesized in vitro in the absence of microsomes did not form dimers and tetramers, but in the presence of microsomes the mature transthyretin which had been translocated into the microsomal lumen formed dimers and a small amount of tetramers which could be detected only by using a cross-linking reagent. Efficiency of tetramer formation depends upon the source of microsomes; in fact the amount of tetramer formed in liver microsomes was much higher than that in pancreas microsomes. Transthyretin synthesized in HepG2 cells appeared after SDS-PAGE analysis in mostly tetrameric form, while that synthesized in transfected COS-1 cells appeared mainly as dimers. Brefeldin A treatment and pulse-chase experiments in HepG2 cells showed that transthyretin tetramer was formed in the endoplasmic reticulum. These results strongly indicate that transthyretin tetramer is formed most efficiently in the endoplasmic reticulum lumen of hepatocytes. Transthyretin without the signal peptide [S(-)] and transthyretin with a mutation that prevents processing of the signal peptide Msc failed to form dimers and tetramers in vitro. In the transfected COS-1 cells, however, S(-) transthyretin did form dimers while Msc transthyretin failed to oligomerize. These results show that the cleavage of the signal peptide and some cellular factors are required for transthyretin oligomerization.

Animals↗
PubMed1998

Prognostic value and clinical implications of disseminated cancer cells in the peritoneal cavity detected by reverse transcriptase-polymerase chain reaction and cytology.

Free cancer cells exfoliated from the cancer-invaded serosa contribute to peritoneal dissemination, the most frequent pattern of recurrence in gastric carcinoma patients. This study was designed to evaluate the prognostic relevance of such free cells in peritoneal washes detected by reverse transcriptase-polymerase chain reaction (RT-PCR) and cytology. RT-PCR analysis with primers specific for carcinoembryonic antigen and conventional cytologic examination by Papanicolaou staining were performed on peritoneal washes, collected at laparotomy from 148 gastric carcinoma patients. Prognostic analyses were performed with 1) death due to cancer recurrence and 2) peritoneal dissemination as endpoints. RT-PCR was found to be more sensitive than cytologic examination for detection of free cancer cells in the peritoneal washes, with a higher detection rate for each of the T categories in the tumor-node-metastasis (TNM) classification. Five patients with synchronous or recurrent peritoneal dissemination were found among 17 patients with positive RT-PCR and negative cytologic results. Both positive cytologic results and positive RT-PCR results had significant influences over the survival of patients with advanced gastric carcinomas (n = 75, p < .002). Detection of free cancer cells in peritoneal washes, most reliably by RT-PCR, is promising as a predictor of peritoneal dissemination in patients with gastric carcinoma.

Carcinoembryonic Antigen↗
PubMed1998

Current Status of Screening for Breast Cancer and Tasks for Introduction of Mammographic Screening in Japan.

In the United States and Europe the high mortality of breast cancer has been significantly reduced by mammographic screening of women aged over 50 years, theeffectiveness of which has been documented in many reports. In contrast, the effectiveness of such screening in women aged from 40 to 49 remains controversial.In Japan, breast cancer screening has consisted of physical examination alone, with inspection and palpation. Thus, more than half of the patients with breast cancer detected by this screening system are already aware of their lumps, the detection rate has been a little less than 0.1%, and the proportion of early-stage disease among breast cancers is only about 50%. It is difficult to detect breast cancer consisting of non-palpable tumors by physical examination, and the lowsensitivity of this screening method has been pointed out. In Japan, there is no difference in overall survival between cases detected by screening and those detected in outpatient clinics. The results of the mammographic screening trial performed in Miyagi and Tokushima, which were promising in terms of proportions of early-stage cancer and no nodal involvement, strongly suggest its usefulness in Japan as well as in other countries. However, long-term results are not yet available. It is advocated that screening for breast cancer should be performed by means of mammography to improve the screening sensitivity, and increase the proportion of early-stage breast cancers. Mammo-graphic screening, either mammography and physical examination separately or simultanously in combination, has been effective for women aged over 50 years in Japan. However, with regard to those aged under 49 years, further studies are needed.

Journal Article↗
PubMed1998

Coatomer, but not P200/myosin II, is required for the in vitro formation of trans-Golgi network-derived vesicles containing the envelope glycoprotein of vesicular stomatitis virus.

Using a cytosol and nucleotide dependent assay that we previously developed, we have investigated the requirement for coat proteins in the in vitro production of trans-Golgi network (TGN)-derived vesicles from a Madin-Darby canine kidney (MDCK) cell Golgi fraction that contains the 35S-labeled, terminally glycosylated, envelope glycoprotein of vesicular stomatitis virus (VSV-G) accumulated in the TGN. We found that the TGN-derived vesicles, like those involved in intra-Golgi transport and in retrograde transport to the endoplasmic reticulum, contain a coatomer coat and that coatomer is required for their formation. Thus, after they are produced with GTPgammaS, the coated vesicles could be captured on beads containing anticoatomer antibody. Moreover, a cytosolic protein fraction depleted of coatomer could not support vesicle formation but it did so after purified coatomer was added. We also determined that P200/myosin II does not play an essential role in the in vitro generation of TGN-derived vesicles. Thus, removal of this protein from the cytosol, by differential salt precipitation or binding to phalloidin-induced actin filaments, had no effect on vesicle generation. Nevertheless, immunodepletion of cytosol using the anti-P200/myosin II AD7 antibody abolished vesicle generation and that antibody was capable of effectively immunocapturing coated vesicles, even when these were generated in the absence of P200/myosin II. These effects, however, are explained by the unexpected finding that the AD7 antibody interacts with undenatured coatomer.

Animals↗
PubMed1998

Involvement of amyloid precursor protein in functional synapse formation in cultured hippocampal neurons.

Amyloid precursor protein (APP) is known to be widely expressed in neuronal cells, and enriched in the central and peripheral synaptic sites. Although it has been proposed that APP functions in synaptogenesis, no direct evidence has yet been reported. In this study we investigated the involvement of APP in functional synapse formation by monitoring spontaneous oscillations of intracellular Ca2+ concentration ([Ca2+]i) in cultured hippocampal neurons. As more and more neurons form synapses with each other during the culture period, increasing numbers of neuronal cells show synchronized spontaneous oscillations of [Ca2+]i. The number of neurons that showed synchronized spontaneous oscillations of [Ca2+]i was significantly lower when cultured in the presence of monoclonal antibody 22C11 against the N-terminal portion of APP. Moreover, incubation with excess amounts of the secretory form of APP or the N-terminal fragment of APP also inhibited the increase in number of neurons with synchronized spontaneous oscillations of [Ca2+]i. The addition of monoclonal antibody 22C11 or secretory form of APP did not, however, affect MAP-2-positive neurite outgrowth. These findings suggest that APP play a role in functional synapse formation during CNS development.

Amyloid beta-Protein Precursor↗
PubMed1998

Lymph node status assessment for gastric carcinoma: is the number of metastatic lymph nodes really practical as a parameter for N categories in the TNM Classification? Tumor Node Metastasis.

BACKGROUND AND OBJECTIVES: The anatomical extent of nodal metastasis has been replaced by the number of metastatic nodes as a key indicator of prognosis (pN categories) in the fifth edition of Tumor Node Metastasis Classification for gastric carcinoma by the International Union Against Cancer. The rate of metastatic nodes among all the nodes harvested is also a good prognostic factor. The object of this study is to evaluate which of the three parameters for the assessment of nodal status is the most appropriate for use in the stage classification. METHODS: Retrospective survival analyses were performed in 656 consecutive patients with advanced gastric carcinoma who underwent D2 lymphadenectomy and for whom histopathologic data of more than 20 lymph nodes were available. RESULTS: Although all three systems served well to classify the patients into distinct groups in terms of survival curves, stratification by the number of metastatic nodes was vulnerable to stage migration because of differences in the number of lymph nodes harvested. Such stage migration was not evident for the other two parameters. CONCLUSIONS: Lymph node metastatic rate can be recommended as an internationally applicable parameter for lymph node involvement of gastric carcinoma.

Adult↗
PubMed1998

[Removal of the endocardial pacemaker leads--experience with 16 leads in 10 patients].

Recent advances in pacemaker leads have contributed to the improvement of their stability at the anchored sites. However, we sometimes have difficulty in removing them. We have experienced the removal of 16 leads in 10 patients (male: 7, female: 3) in the last 5 years. The age of patients ranged from 48 to 87 years, and the average was 60. The reasons for the removal were as follows; pocket infection in 6 cases, sepsis in 1 case, ischemic skin erosion in 1 case, retained fractured ventricular lead in 1 case, fracture of Accufix atrial lead in 1 case. The methods of removal consisted of using the removal kit, the snare or the basket snare transvenously, direct surgical approach or a combination of them. We used the removal kit alone in 12 electrodes (6 atrial, 6 ventricular), and removal of 5 atrial and 3 ventricular leads were successfully by this method only. The removal of 4 leads by kits alone failed, so that 2 ventricular leads were removed transvenously, one atrial and one ventricular lead were removed surgically, and 1 ventricular lead was left untreated. Finally, we were able to remove 15 of 16 leads (93.3%) successfully. This experience indicates that these interventions should be performed as less invasively as possible, yet we should give an explanation to the patients as to the options we may employ when we have failed in the intended procedure.

Aged↗
PubMed1998

[Coronary artery bypass graft surgery in dialysis patient].

To determine the operative outcome of coronary artery bypass graft surgery (CABG) for severe coronary artery disease in long-term hemodialysis patients, we analyzed a group of 16 patients who underwent CABG over a ten-year period in our institution. Hospital mortality was 12.5% (2 of 16 patients). These two patients died of ischemic colitis and perioperative myocardial infarction, respectively. There were five late deaths: one patient died from myocardial infarction, one from uremia, one from gastro-intestinal bleeding, one from gastric cancer and one from unknown cause. There were four significant postoperative complications (morbidity 25%), consisted of one pulmonary tuberculosis, one sternal dehiscence secondary to mediastinitis, one mediastinal hematoma secondary to late bleeding from the LITA dissection area and one A-V shunt trouble. Graft patency rate within the first two months was 93% (30 to 42 in 13 patients). Hospital survivors experienced complete relief from angina. Actuarial survival was 68.8% at 3 years, 57.3% at 5 years and 28.6% at 7 years. This rate is not significantly different from the survival of all dialysis patients, but seems to be better than that of dialysis patients with not operated coronary artery disease. We concluded that CABG in dialysis patients can be accomplished with acceptable morbidity and mortality and effective relief of symptoms.

Cause of Death↗
PubMed1998

Value of mass screening for thyroid cancer.

This study aims to clarify the presently uncertain value of mass screening for thyroid cancer, which has been performed by physical examination along with mass screening for breast cancer in Zentsuji, Japan since 1983. Among 18,619 subjects, 36 individuals with thyroid cancer (0.19%) were found. The detection rate was 0.40% at the initial screening and 0.10% during subsequent periodic screening. All thyroid cancers were confirmed histologically as well differentiated carcinoma. The tumor size in the mass-screening group (14 +/- 6 mm) was significantly smaller than in patients presenting at an outpatient clinic during the same period (19 +/- 13 mm) (p < 0.05). The incidence of nodal metastases in the mass-screening group (38%) was significantly lower than in the outpatient group (68%) (p < 0.05). Thus mass screening seemed to find thyroid cancers in a relatively early stage. Mass screening for thyroid cancer was economic in this instance because it was performed together with screening for other cancers, such as breast cancer. Thyroid cancer screening required less than one additional minute per subject. The ultimate aim of mass screening is to reduce mortality. No improvement in prognosis from enforced mass screening for thyroid cancer was detected in this study. It cannot be demonstrated that there is sufficient value of mass screening for thyroid cancer to perform it independently despite early cancer detection.

Adult↗
PubMed1998

Induction of heat shock response: effect on the rat liver with carbon tetrachloride-induced fibrosis from ischemia-reperfusion injury.

The role of heat shock pretreatment in the induction of tolerance for ischemia-reperfusion injury was investigated in rat livers with fibrosis produced by carbon tetrachloride (CCI4) injected subcutaneously. The control group (group C, n = 56) received no pretreatment except anesthesia, and the heat shock group (group HS, n = 56) were exposed to heat shock (42 degrees C) for 15 minutes. After a 48-hour recovery all rats were subjected to 30 minutes of warm ischemia. Western blotting analysis was employed for heat shock protein (HSP) 72 detection. The adenine nucleotide levels in liver tissue and the liver enzyme levels in serum were measured before and after ischemic intervention (seven animals were used at each of six time point measurements in both groups). HSP72 was induced in group HS at greater intensity than in group C. The survival rate on postoperative day 7 in group C (3/14) was significantly poorer than that in group HS (14/14) (p < 0.01). The higher survival rate in group HS was accompanied by more rapid recovery of the adenosine triphosphate level and lower serum levels of liver enzymes after reperfusion (p < 0.01 vs. group C). Heat shock preconditioning induces HSP72 in the rat liver with fibrosis and provides significantly increased tolerance of warm-ischemia reperfusion injury.

Animals↗
PubMed1998

Nine-year survivor after resection of cholangiocellular carcinoma with tumor thrombi in the main portal trunk.

We report a patient with cholangiocellular carcinoma with tumor thrombi in the main portal trunk who has survived for 9.5 years after hepatic resection. A 57-year-old woman underwent an extended left lobectomy, and resection of the caudate lobe plus the main portal trunk for a liver tumor that had a portal tumor thrombus in the main portal trunk. The portal vein was reconstructed with an autologous vein graft obtained from the external iliac vein. Histological examination of the resected specimen revealed moderately differentiated tubular adenocarcinoma compatible with cholangiocellular carcinoma. Factors contributing to the patient's long-term survival are discussed. Aggressive surgical resection can be effective even for such an advanced case of cholangiocellular carcinoma.

Bile Duct Neoplasms↗
PubMed1998

Increased urinary excretion of bilirubin metabolites in association with hyperbilirubinemia after esophagectomy.

This study was conducted to investigate the rationale for postoperative hyperbilirubinemia after major surgery. The serum bilirubin values and urinary excretion of bilirubin metabolites (BM) were monitored in 11 patients who underwent esophagectomy via right thoracotomy for esophageal cancer. Both the serum bilirubin values and the urinary excretion of BM increased postoperatively in all patients. The maximum serum bilirubin level in four patients with septic complications, two of whom developed pneumonia and two, anastomotic leakage (group A), was significantly higher at 5.25+/-4.16 mg/dl than in the remaining patients without septic complications (group B), at 2.11+/-0.07 mg/dl. The peak value of urinary BM was 99.5+/-88.2 micromol/day in group A and 23.5 +/-26.7 micromol/day in group B. The correlation between the level of serum bilirubin and urinary BM excretion was found to be significant. Thus, the metabolism of bilirubin was increased by extensive surgical stress and septic insult.

Aged↗
PubMed1998

Two-stage skull base surgery for tumours extending to the sub- and epidural spaces.

The surgical management of extensive skull base neoplasms, which often extend to both the sub- and epidural spaces, is still a great challenge with considerable risk. The authors report 12 cases in which a two-stage operation was performed for such nonmalignant tumours. The series consisted of four cavernous sinus meningiomas, one sphenoid-ridge meningioma, one cerebello-pontine angle meningioma, three pituitary adenomas, two chordomas, and one fibroma. Our operative strategy involved removal of the epidural part of the tumour and extensive skull base reforming during the first stage. After approximately one month, the second stage operation was performed by removing the residual subdural parts and the affected dura, which were less vascular, with dural plasty and subsequent spinal drainage. No complications such as cerebrospinal fluid (CSF) leakage or infection were observed. During the long-term follow-up (1.4 to 4.6 years, with a mean of 2.7 years), tumour recurrence was observed in a single case. In conclusion, the major advantages of this procedure were as follows: [1] improvement of the total removal rate, [2] prevention of postoperative CSF leak and infection, [3] residual tumours were avascular, necrotic, and dwindling, and also shifted outwards resulting in less adhesions to the brain. Although it may counter the trend toward less invasive procedures, the two-staged skull base surgery warrants serious consideration as an option for the management of patients with such extensive cranial base tumours.

Adenoma↗
PubMed1998

Regulation of albumin mRNA and its promoter-binding nuclear factors under different perioperative nutritional methods in hepatectomized rats.

BACKGROUND: Regulation of perioperative albumin synthesis under parenteral (PN) and enteral (EN) nutrition was investigated. METHODS: Rats were divided into PN and EN groups. Both groups received the same regimen of artificial nutrition for 7 days and then underwent 70% hepatectomy. Serum albumin and mRNA levels of albumin and its promoter-binding nuclear factors (C/EBPalpha, beta, and DBP) were measured. RESULTS: Serum albumin and albumin mRNA in the PN group were significantly lower than those in the EN group at 72 hours after hepatectomy. Preoperative and postoperative DBP and C/EBPalpha mRNA levels in the EN group were significantly higher than those in the PN group. CONCLUSION: Serum albumin was well maintained by EN after hepatectomy owing to an early recovery of albumin mRNA level and its nuclear factor mRNA levels (C/EBPalpha and DBP). Compared with PN, EN is a more advantageous from of perioperative nutrition as pertains to albumin synthesis.

Animals↗