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Biomedical subjects

M Endo

Publications and source records attributed to M Endo.

At least 325 records · Page 18Linked to original sources
PubMed1997

Detection of cytokine mRNA in unfractionated peripheral blood by reverse transcriptase polymerase chain reaction.

OBJECTIVE: To detect cytokine gene expression in unfractionated peripheral blood by reverse transcriptase-polymerase chain reaction (RT-PCR). DESIGN: Prospective study. SETTING: University hospital, Japan. SUBJECTS: 3 healthy volunteers and 3 severely infected patients. INTERVENTIONS: Peripheral blood was obtained and total RNA was extracted from 0.5 ml unfractionated whole blood with a 4 M guanidinium isothiocyanate mixture, 0.2 M sodium acetate, phenol, and chloroform. The mRNA was reverse transcripted, and interleukin-1 beta (IL-1beta) and tumour necrosis factor (TNF) cDNA were selectively amplified by synthetic primers with PCR. MAIN OUTCOME MEASURES: Establishment of cytokine gene expression in unfractionated peripheral blood. RESULTS: About 10 microg of total RNA was obtained from a 0.5 ml sample of blood. IL-1beta and TNF mRNA were not detected in blood from healthy volunteers, though they were detected in patients with severe infection. CONCLUSION: This method avoids artefactual gene activation and may be applicable to monitoring cytokine gene expression in various pathophysiological states.

Adult↗
PubMed1997

[Efficacy of combination chemotherapy of cyclophosphamide and 5'-deoxy-5-fluorouridine in a mammary tumor xenograft model, MX-1].

Efficacy of long-term combination chemotherapy of cyclophosphamide (CPA) and 5'-deoxy-5-fluorouridine (5'-DFUR), both of which have been widely used as chemotherapeutics against breast cancer patients, was examined in a mammary tumor xenograft model, MX-1. 5'-DFUR suppressed the tumor growth over a long period and prolonged the survival, although it did not reduce the initial tumor burden, CPA induced the disappearance of the tumor burden temporarily. However, CPA became inaffective despite continuation of treatment, and induced the recurrence of the tumor. The combination of these two drugs dramatically reduced the tumor burden, and suppressed the recurrence of the tumor over a long period. The tumor recurring during CPA monotherapy was resistant to CPA but susceptible to 5'-DFUR, which could be a reason for the long-lasting activity of the combination therapy. These results indicate that CPA and 5'-DFUR monotherapies have different modes of antitumor activities in the long-term therapy model, and that these drugs in combination would have better therapeutic advantage than each drug given individually.

Animals↗
PubMed1997

[Operative procedures of T1 cancer of the lower thoracic esophagus].

Pathological results for 70 cases of T1 EiEa esophageal cancer resected in our department for the past 12 years, have shown 32 cases of mucosal cancer and 38 cases of submucosal cancer. Lymph node metastasis was recognized in 21 cases (30%). Moreover, positive nodes were observed only in submucosal cancer cases. Lymph node metastasis was mainly observed in the lower mediastinum and in the upper abdomen. However, it was frequently observed in the upper mediastinum (106) and sometimes in the supraclavicular area (104). The lymph node dissection should be performed in the mediastinum through the upper abdomen and neck. The subtotal esophagectomy with thoracotomy and the systematic dissection is common operative procedures, but the reduced surgery, i.e. transhiatal esophagectomy or the lower esophagectomy and proximal gastrectomy, is also indicated in some cancer patients.

Esophageal Neoplasms↗
PubMed1997

[Combination hepatic intra-arterial 5-fluorouracil and CDDP administration with oral regimen in patients with colorectal cancer metastasis to the liver].

We investigated therapeutic effectiveness and side effects of a combination weekly high-dose 5-FU plus one shot CDDP HAI (WHF + CDDP method) with oral regimen in patients with colorectal cancer metastasis to the liver. All 24 patients enrolled in this study showed 54% efficacy whereas patients combined HAI with oral regimen over one week obtained 83% efficacy for multiple liver metastasis. They showed good quality of the life during combination chemotherapy without any symptoms of metastatic lesions. The WHF + CDDP method combined with oral regimen is a promising treatment for colorectal cancer metastasis to the liver as well as extrahepatic distant organs, and this protocol may be satisfactorily accepted by most colorectal cancer laden patients because of negligible side effects.

Administration, Oral↗
PubMed1997

[Comparison between intraperitoneal and intravenous 5-fluorouracil administration using pancreatic cancer model of nude mouse].

Carcinoma of the pancreas is a virulent malignancy. The purpose of this study was to evaluate the efficiency of 5-FU intraperitoneal administration for this malignancy. We developed a pancreatic cancer model whereby a human pancreatic cell line, MIA PaCa-2, was orthotopically transplanted to the pancreas of nude mice as cell suspension (1 x 10(6) cells). IP group (n = 6) received 5 times IP administration (4, 7, 12, 16, 20 days after implantation) of 5-FU 50 mg/kg, 1.5 ml. IV group (n = 6) received 5 times IV therapy (the same dates as IP group) of 5-FU 50 mg/kg, 0.2 ml. Control group (n = 6) received no treatment. The mice were sacrificed 42 days after implantation. The weight of the tumors of IP, IV and Control group was 0.332 +/- 0.143 g, 0.138 +/- 0.047 g and 0.329 +/- 0.085 g. Significant differences were found between IP and IV, and control. There was no difference between IP and control. This experiment demonstrated that 5 FUIP therapy for primary pancreatic cancer showed no effect and 5 FUIV therapy was much more effective.

Animals↗
PubMed1997

[Experimental study on intraperitoneal sequential MTX/5-FU therapy for peritoneal seeding in comparison with intravenous administration].

Sequential MTX/5-FU therapy (intravenous route) is powerful chemotherapy especially for poorly differentiated adenocarcinoma of the stomach and its peritoneal metastases. The authors had proposed the idea of intraperitoneal sequential MTX/5-FU chemotherapy for potential peritoneal metastases and micrometastases from advanced gastric carcinoma. This experimental study was planned to confirm this experimentally. Peritoneal seeding model of nude mice was made by the intraperitoneal inoculation of human gastric cancer cell line MKN-45. Control group (n = 5) had no treatment. The intraperitoneal (i.p.) group and intravenous (i.v.) group underwent the treatments on the 7th, 14th, and 21st day after cell implantation. Experimental chemotherapies consisted of intraperitoneal injection of MTX (15 mg/kg, 1.5 ml saline) and 5-FU (50 mg/kg, 1.0 ml saline) for i.p. group and intravenous injection of MTX (15 mg/kg, 0.2 ml saline) and 5-FU (50 mg/kg, 0.2 ml saline) for i.v. group. Interval time between MTX and 5-FU administration was 2 hours. On the 35th day after the cell implantation necropsies were performed. Counting of peritoneal metastatic nodules revealed the number of nodules of control group. (14.2 +/- 6.7) > i.v. group (5.3 +/- 4.1) > i.p. group (0.41 +/- 0.7) (p < 0.05). Weight of omental tumors showed Control group (0.246 +/- 0.136 g) > i.v. group (0.140 +/- 0.068 g) > i.p. group (0.051 +/- 0.017 g) (i.v.-i.p., p < 0.01). The mouse body weight decrease less in the i.p. group than in the i.v. group (p < 0.05) throughout this experiment. The results of this experiment demonstrated intraperitoneal sequential MTX/5-FU therapy was more effective than intravenous sequential MTX/5-FU therapy for potential peritoneal seeding and peritoneal micrometastases from the gastric cancer. Moreover, the side effect of intraperitoneal administration was milder than by the intravenous route.

Adenocarcinoma↗
PubMed1997

[Radiation therapy for adrenal metastases].

PURPOSE: To evaluate the role of radiation therapy for adrenal metastases. MATERIALS AND METHODS: Fourteen patients, 13 with primary lung carcinoma and one with primary unknown carcinoma, received radiation therapy for adrenal metastases from 1984 to 1995 at the Hyogo Medical Center for Adults. Total dose ranged from 16 Gy to 60 Gy, and fractional dose from 1.6 Gy/ Fr to 3 Gy/Fr. RESULTS: Partial response of the local tumor was recognized in 2 of 7 patients by CT imaging. Pain relief was obtained in 7 of 8 patients. Median survival was 3 months, and 6-month survival was 28.6% in all patients. Among patients in the symptomatic group, who had complaints of pain due to adrenal mass, survival was even worse (12.5% at 6 months). There were no severe complications, but 4 patients (29%) had gastrointestinal symptoms. CONCLUSION: Radiation therapy is useful for the purpose of pain relief in adrenal metastases.

Adrenal Gland Neoplasms↗
PubMed1997

[A case of mediastinal angiomyolipoma].

A 53-year-old woman was referred to our hospital for further evaluation of a mediastinal tumor. The tumor was diagnosed as a mediastinal angiomyolipoma by computed tomography and angiographic findings. Transarterial embolization was performed three times, then the tumor was completely organized. Although angiomyolipomas are often found in the kidney, those in the mediastinum are very rare. Angiomyolipoma is a benign tumor, then small asymptomatic tumor may be conserved. When the tumor is large in size and has a high risk of spontaneous rupture, arterial embolization is valuable for treatment of the tumor.

Angiomyolipoma↗
PubMed1996

Subtype specificity of the ryanodine receptor for Ca2+ signal amplification in excitation-contraction coupling.

In excitable cells membrane depolarization is translated into intracellular Ca2+ signals. The ryanodine receptor (RyR) amplifies the Ca2+ signal by releasing Ca2+ from the intracellular Ca2+ store upon receipt of a message from the dihydropyridine receptor (DHPR) on the plasma membrane in striated muscle. There are two distinct mechanisms for the amplification of Ca2+ signalling. In cardiac cells depolarization-dependent Ca2+ influx through DHPR triggers Ca2+-induced Ca2+ release via RyR, while in skeletal muscle cells a voltage-induced change in DHPR is thought to be mechanically transmitted, without a requirement for Ca2+ influx, to RyR to cause it to open. In expression experiments using mutant skeletal myocytes lacking an intrinsic subtype of RyR (RyR-1), we demonstrate that RyR-1, but not the cardiac subtype (RyR-2), is capable of supporting skeletal muscle-type coupling. Furthermore, when RyR-2 was expressed in skeletal myocytes, we observed depolarization-independent spontaneous Ca2+ waves and oscillations, which suggests that RyR-2 is prone to regenerative Ca2+ release responses. These results demonstrate functional diversity among RyR subtypes and indicate that the subtype of RyR is the key to Ca2+ signal amplification.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1996

Generation and characterization of mutant mice lacking ryanodine receptor type 3.

The ryanodine receptor type 3 (RyR-3) functions as a Ca2+-induced Ca2+ release (CICR) channel and is distributed in a wide variety of cell types including skeletal muscle and smooth muscle cells, neurons, and certain non-excitable cells. However, the physiological roles of RyR-3 are totally unclear. To gain an insight into the function of RyR-3 in vivo, we have generated mice lacking RyR-3 by means of the gene targeting technique. The mutant mice thus obtained showed apparently normal growth and reproduction. Although Ca2+-induced Ca2+ release from intracellular Ca2+ stores of the mutant skeletal muscle differed in Ca2+ sensitivity from that of wild-type muscle, excitation-contraction coupling of the mutant muscle seemed to be normal. Moreover, we could not find any significant disturbance in the smooth muscle and lymphocytes from the mutant mice. On the other hand, the mutant mice showed increased locomotor activity, which was about 2-fold greater than that of the control mice. These results indicate that the loss of RyR-3 causes no gross abnormalities and suggest that the lack of RyR-3-mediated Ca2+ signaling results in abnormalities of certain neurons in the central nervous system.

Animals↗
PubMed1996

Syngeneic bone marrow transplantation without conditioning in a patient with paroxysmal nocturnal hemoglobinuria: in vivo evidence that the mutant stem cells have a survival advantage.

A 10-year-old girl with paroxysmal nocturnal hemoglobinuria (PNH) received an infusion of syngeneic bone marrow without preparative marrow ablation or immunosuppression. Following transplant, the patient became asymptomatic in concordance with an increase in the percentage of peripheral blood cells with normal expression of glycosyl phosphatidylinositol-anchored proteins (GPI-AP). However, molecular analysis suggested engraftment of a relatively small number of donor stem cells and persistence of an abnormal stem cell with mutant PIG-A. During 17 months of observation, the percentage of cells with normal GPI-AP expression gradually decreased, while intravascular hemolysis progressively increased. Approximately 16.5 months post-transplant, the patient once again became symptomatic. Together, these results indicate that syngeneic marrow infusion provided a clinical benefit by increasing the proportion of erythrocytes with normal expression of GPI-anchored complement regulatory proteins without supplanting the abnormal stem cells. However, evidence of insidious disease progression following the marrow infusion implies that the abnormal stem cells have a survival advantage relative to the transplanted stem cells. Thus, these studies contribute in vivo data in support of the hypothesis that PNH arises as a consequence of a pathological process that selects for hematopoietic stem cells that are GPI-AP-deficient.

Bone Marrow Transplantation↗
PubMed1996

AUR1, a novel gene conferring aureobasidin resistance on Saccharomyces cerevisiae: a study of defective morphologies in Aur1p-depleted cells.

Aureobasidin A (AbA), a cyclic depsipeptide produced by Aureobasidium pullulans R106, is highly toxic to fungi including Saccharomyces cerevisiae. We isolated several dominant mutants of S. cerevisiae which are resistant to more than 25 micrograms/ml of AbA. From a genomic library of one such AUR1 mutant, the AUR1R (for aureobasidin resistant) mutant gene was isolated as a gene that confers resistance to AbA on wild-type cells. Its nucleotide sequence showed that the predicted polypeptide is a hydrophobic protein composed of 401 amino acids, which contains several possible transmembrane domains and at least one predicted N-linked glycosylation site. Comparison of the mutant gene with the wild-type aur1+ gene revealed that the substitution of Phe at position 158 by Tyr is responsible for acquisition of AbA resistance. We suggest that the gene product of the wild-type aur1+ is a target for AbA on the basis of following results. Firstly, cells that overexpress the wild-type aur1+ gene become resistant to AbA, just as cells with an AUR1R mutation do. Secondly, disruption of the aur1+ gene demonstrated that it is essential for growth. Thirdly, in the cells with a disrupted aur1 locus, pleiotropic morphological changes including disappearance of microtubules, degradation of tubulin and abnormal deposition of chitin were observed. Some of these abnormalities are also observed when wild-type cells are treated with AbA. The abnormality in microtubules suggests that the Aur1 protein is involved in microtubule organization and stabilization.

Amino Acid Sequence↗
PubMed1996

Effect of serum protein binding on real-time trafficking of liposomes with different charges analyzed by positron emission tomography.

Liposomes have been used as carriers of various materials and as tools for gene transfer: for the latter purpose, positively charged liposomes are usually used. To evaluate the stability in the presence of serum and the in vivo behavior of such liposomes as well as those aspects of neutral and negatively charged liposomes, we investigated liposomal agglutinability in the presence of serum, serum protein binding to these liposomes, and real-time liposomal trafficking by a non-invasive method using positron emission tomography (PET). Liposomes composed of dipalmitoylphosphatidylcholine, cholesterol without or with charged lipid were prepared in the presence of mannitol, and the turbidity change in the presence of serum was determined. Turbidity increase was not observed for so-called long-circulating liposomes, i.e., liposomes modified with glucuronic acid or with poly(ethylene glycol), or for negatively charged liposomes containing dicetyl phosphate (DCP), phosphatidylglycerol, or phosphatidylserine. On the contrary, a significant turbidity increase was observed when positively charged liposomes modified with stearylamine, stearyltrimethylammonium chloride or 1,2-dimyristyloxypropyl-3-dimethylhydroxyethyl bromide (DMRIE), which is known as a component of liposomes for gene transfer, were used. These liposomes were found to have bound a high amount of serum proteins after separation of unbound serum proteins by use of a spin column. The liposomal trafficking in vivo was determined for three kinds of liposomes, i.e., liposomes with DMRIE, those with DCP, and those without charged lipids. These liposomes were prepared in the presence of 2-[18F]fluoro-2-deoxy-D-glucose ([2-18F]FDG), and the [2-18F]FDG-labeled liposomes were administered to mice to perform PET scans. Positively charged liposomes containing DMRIE showed high accumulation in the liver compared with neutral and negatively charged liposomes. Since DMRIE-liposomes tended to aggregate in the presence of serum, and to be associated with serum protein, these characteristics may lead to the high uptake of DMRIE-liposomes by the liver.

1,2-Dipalmitoylphosphatidylcholine↗