Effect of exogenously administered HGF activator in liver regeneration.
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Animals↗
Biomedical subjects
T Nagahama
Publications and source records attributed to T Nagahama.
Spin-polarized resonant tunneling in magnetic tunnel junctions.
Insertion of a thin nonmagnetic copper Cu(001) layer between the tunnel barrier and the ferromagnetic electrode of a magnetic tunnel junction is shown to result in the oscillation of the tunnel magnetoresistance as a function of the Cu layer thickness. The effect is interpreted in terms of the formation of spin-polarized resonant tunneling. The amplitude of the oscillation is so large that even the sign of the tunnel magnetoresistance alternates. The oscillation period depends on the applied bias voltage, reflecting the energy band structure of Cu. The results are encouraging for the development of spin-dependent resonant tunneling devices.
Journal Article↗
A novel GGNG-related neuropeptide from the polychaete Perinereis vancaurica.
The GGNG peptides are myoactive peptides so far identified from earthworms and leeches, which are the earthworm excitatory peptides (EEP) and the leech excitatory peptide (LEP), respectively. A novel GGNG peptide was isolated and structurally determined from a marine polychaete, Perinereis vancaurica, using a combination of immunological assay and high performance liquid chromatography (HPLC). The peptide was a pentadecapeptide whose amino acid sequence was similar to that of EEP and LEP, and showed myoactivity on isolated esophagus of P. vancaurica with a threshold concentration of 10(-10)M. The peptide was designated as polychaete excitatory peptide (PEP). Amidation of the alpha-carboxyl group of C-terminal residue occurred in PEP. This is the case for LEP, but not for EEP. The cDNA cloning revealed that the structure of the PEP precursor is more similar to the EEP precursor than to the LEP precursor. Immunohistochemical staining showed the presence of PEP in several neurons of central nervous system (CNS) as somata and neuropile structure, epithelial cells of the pharynx and epidermal cells throughout the body wall. Altogether these results support the physiological significance of PEP in regulation of the CNS neural activity and the peripheral myoactivity.
Amino Acid Sequence↗
New method for thyroid transplantation across major histocompatibility complex barriers using allogeneic bone marrow transplantation.
BACKGROUND: It has been shown that allogeneic bone marrow transplantation (BMT) after lethal irradiation elicits donor-specific tolerance for organ or tissue transplantation across major histocompatibility complex (MHC) barriers. Recently, we have demonstrated that the portal venous (p.v.) administration of donor bone marrow cells (BMCs) elicits donor-specific tolerance across MHC barriers by only two administrations of an immunosuppressant (CsA or FK-506). In our study, using the central and intrahepatic tolerance-inducing system, we have established a new method for thyroid transplantation with BMT that would be more applicable to humans. METHODS: In addition to sublethal (6-5 Gy) irradiation, recipient B6 (H-2b) mice received injections i.p. with the myeloablative drug busulfan (BU) on day -2 to provide a sufficient "space" for the donor hematopoietic cells to expand in the recipients. To induce the intrahepatic tolerance, donor BALB/c (H-2d) BMCs were treated with neuraminidase (Neu), which enhances the trapping of i.v. injected BMCs in the liver. After the injection of Neu-treated BMCs, the thyroid organs from the BALB/c mice were engrafted under the renal capsules. RESULTS: A 90% graft survival rate was obtained over 100 days by a combination of BU administration, 6 Gy irradiation, and i.v. injection of Neu-treated BMCs [BU+6 Gy+(Neu) i.v.], and a 70% graft survival rate was obtained by [BU+5 Gy+(Neu) i.v.]. However, the graft survival rate significantly decreased when either the BU or Neu treatment was omitted. T cells collected from the tolerant recipients suppressed the proliferative responses to donor alloantigens. CONCLUSIONS: Using both BU and Neu treatments, we have succeeded in inducing long-term tolerance and preventing the rejection of thyroid allografts by the single-day protocol.
Animals↗
Tolerance induction across Mls and minor histocompatibility complex by inhibiting activation of T helper type 1 in early period.
We have previously succeeded in inducing persistent donor-specific tolerance across Mls plus multiple minor histocompatibility barriers by portal venous (p.v.) injection of donor spleen or bone marrow cells plus cyclophosphamide (CY) treatment. Microchimerism was established in the lymph-hemopoietic organs of the tolerant recipients. However, the mechanisms, particularly the roles of CY in the tolerance induction, have not been clarified. We examined the tolerance induction using other anti-mitotic agents and evaluated the in vitro proliferative responses and cytokine expression of T cells from the recipients after stimulation with donor alloantigens. The administration of not only CY but also mitomycin C (MMC) and cytosin arabinoside (Ara C) elicited a prolongation of skin graft survival. CY induced tolerance when it was administered 2 days after the p.v. injection, but not immediately or 4 days after the p.v. injection. T cells collected from the tolerant recipients showed no proliferative responses as a result of stimulation with donor alloantigens whereas the responses of T cells from non-tolerant recipients were significantly enhanced. Interferon-gamma (IFNgamma) was extensively expressed in the non-tolerant T cells from 24 to 48 h after the stimulation with donor alloantigens. In contrast, the expression of IFNgamma was observed in the tolerant T cells from 72 h after the stimulation. Also, the tolerant T cells showed the expression of interleukin-10 (IL-10) and transforming growth factor-beta 1 (TGF-beta1) from 72 h after the stimulation whereas the non-tolerant T cells did not. These data suggest that CY, when administered 2 days after the p.v. injection, induces persistent tolerance by inhibiting T helper type 1 (Th1) activity in the early period but not the Th1 activity in the later periods.
Animals↗
Distribution and identification of red yeasts in deep-sea environments around the northwest Pacific Ocean.
We isolated 99 yeast strains, including 40 red yeasts, from benthic animals and sediments collected from the deep-sea floor in various areas in the northwest Pacific Ocean. Comparing the yeast isolates from animals and sediments collected from shallow locations, the proportion of red yeasts differed considerably, comprising 81.5% and 10.6% of the isolates from animals and sediments, respectively. All of the red yeast isolates belonged to the genera Rhodotorula and Sporobolomyces. On the basis of morphological and physiological characteristics, the isolates were identified as R. aurantiaca, R. glutinis, R. minuta and R. mucilaginosa of the genus Rhodotorula, and S. salmonicolor and S. shibatanus of the genus Sporobolomyces. Only R. glutinis and R. mucilaginosa were isolated from sediments. All of the others were isolated from animal sources. Phylogenetic analyses based on internal transcribed spacer (ITS) regions and 5.8S rRNA gene sequences allowed us to establish the precise taxonomic placement of each of the isolates and thereby investigate the intraspecific relationships among the isolates. Twenty-two strains identified as members of R. glutinis, which showed a wide distribution in the deep-sea, and five isolates identified as R. minuta, which were isolated only from benthic animals, showed substantial heterogeneity within the species. The isolates phenotypically identified as Sporobolomyces species and R. mucilaginosa phylogenetically occupied the placements corresponding to these species. Some strains assigned to known species on the basis of phenotypic features should be regarded as new species as suggested by the results of molecular analysis.
Ascomycota↗
Rhodotorula lamellibrachii sp. nov., a new yeast species from a tubeworm collected at the deep-sea floor in Sagami bay and its phylogenetic analysis.
A new species of the genus Rhodotorula was isolated from a tubeworm (Lamellibrachia sp.) collected at a depth of 1156 m in Sagami Bay, Japan. Strain SY-89 had physiological properties quite similar to R. aurantiaca. Two phylogenetic trees, one based on internal transcribed spacer (ITS) regions and 5.8S rDNA sequences and the other based on the D1/D2 region of the large subunit (26S) rDNA sequences, united strain SY-89 to the type strain of Sakaguchia dacryoides through a considerable evolutionary distance. Strain SY-89 was differentiated from S. dacryoides by the G+C content of the nuclear DNA and differences in the ability to utilize specific carbon and nitrogen compounds. The low complementarity of strain SY-89 DNA to that of the type strain of S. dacryoides confirmed that this strain was genetically unrelated to previously known species. The tubeworm isolates are described as R. lamellibrachii sp. nov. The type strain of R. lamellibrachii is strain SY-89 (= JCM 10907). R. lamellibrachii formed a cluster with Erythrobasidium hasegawianum, R. lactosa, S. dacryoides and Sporobolomyces elongatus on the ITS and 5.8S rDNA phylogenetic tree. These five species shared a signature sequence in 26S rDNA, although this relationship was not supported by phylogeny based on the D1/D2 region of 26S rDNA.
Animals↗
Pharmacodynamic effects and kinetic disposition of rabeprazole in relation to CYP2C19 genotypes.
BACKGROUND: S-mephenytoin 4'-hydroxylase (CYP2C19) catalyses the metabolism of rabeprazole to some extent. Based on the metabolic and pharmacokinetic differences among other proton pump inhibitors such as omeprazole, lansoprazole and pantoprazole, rabeprazole appears to be the least affected proton pump inhibitor by the CYP2C19-related genetic polymorphism. AIM: To determine whether the pharmacodynamic effects of rabeprazole on intragastric pH and serum gastrin levels, and its pharmacokinetics depend on the CYP2C19 genotype status. METHODS: Eighteen healthy subjects, whose CYP2C19 genotype status was previously determined, participated in the study. They consisted of six each of homozygous extensive metabolisers (homo EMs), heterozygous extensive metabolisers (hetero EMs), and poor metabolisers (PMs). Helicobacter pylori status was determined by serology. After a single oral dose of 10 mg or 20 mg rabeprazole or water only (baseline data), intragastric pH values were monitored for 24 h. Plasma levels of rabeprazole and serum gastrin were also measured for 24 h post-dose. RESULTS: Five homo EM, six hetero EM and four PM subjects were H. pylori-negative. After rabeprazole administration, significant differences in intragastric mean pH values, serum gastrin AUC(0-24) and plasma levels of rabeprazole were observed among the three different genotype groups. CONCLUSION: The pharmacodynamic effects of rabeprazole and its pharmacokinetics depend on the CYP2C19 genotype status.
2-Pyridinylmethylsulfinylbenzimidazoles↗
Thoracoscopically managed parathyroid adenoma in the upper anterior mediastinum.
We thoracoscopically managed parathyroid adenoma of the upper anterior mediastinum in a 29-year-old man. He had a backache and was found to have bilateral ureteric stones, hypercalcemia, and extremely increased parathyroid hormone levels. 99mTc-methoxyisobutyl isonitrile scintigraphy showed an accumulation area projected onto the right thyroid lobe and the upper mediastinum. A diagnosis of primary hyperparathyroidism secondary to double adenomas was made. The patient then underwent surgical intervention. With the patient under general anesthesia with one-lung ventilation, a reddish brown adenoma of an upper mediastinum was removed thoracoscopically with three trocars, whereas the right superior parathyroid adenoma was excised by a standard open cervical procedure. Conventionally, the mediastinal parathyroid adenoma was removed by an open approach and was associated with perioperative distress to the patient. If the exact location of the mediastinal lesion is established, thoracoscopic excision of these lesions is feasible and is strongly recommended.
Adenoma↗
Effect of T-type selective calcium antagonist on renal microcirculation: studies in the isolated perfused hydronephrotic kidney.
Although calcium antagonists exert preferential vasodilation of renal afferent arterioles, we have recently demonstrated that nilvadipine and efonidipine, possessing both L-type and T-type calcium channel blocking action, reverse the angiotensin (Ang) II-induced afferent and efferent arteriolar constriction. In the present study, we investigated the role of T-type calcium channels in mediating the Ang II-induced efferent arteriolar tone using the selective T-type calcium channel blocker mibefradil. Isolated perfused hydronephrotic rat kidneys were used for direct visualization of renal microcirculation. Administration of Ang II (0.3 nmol/L) caused marked constriction of afferent (from 13.5+/-0.6 to 9.2+/-0.6 microm, P<0.01, n=6) and efferent (from 11.5+/-1.0 to 7.4+/-0.7 microm, P<0.01, n=5) arterioles. Mibefradil (1 micromol/L) dilated both vessels, with 82+/-11% and 72+/-7% reversal of afferent and efferent arterioles, respectively. Similarly, nickel chloride (100 micromol/L) caused dilation of both arterioles, similar in magnitude in afferent (68+/-10%, n=7) and efferent (80+/-7%, n=7) arterioles. To eliminate the possibility that the mibefradil-induced dilation was mediated by L-type channel blockade, mibefradil was administered in the presence of nifedipine (1 micromol/L). Thus, nifedipine caused modest efferent arteriolar dilation (30+/-6% reversal, n=9), and subsequent addition of mibefradil elicited further dilation of this vessel (80+/-4%, P<0.01 versus nifedipine). Furthermore, mibefradil reversed the Ang II-induced efferent arteriolar constriction even in the presence of nifedipine and phentolamine. These findings demonstrate that T-type calcium antagonists markedly dilate the Ang II-induced efferent arteriolar constriction, but the action is not mediated by inhibition of catecholamine release. This potent activity would contribute to the efferent arteriolar response to nilvadipine and efonidipine and may offer benefit in light of glomerular hemodynamics.
Angiotensin II↗
Major histocompatibility complex restriction between hematopoietic stem cells and stromal cells in vitro.
We have previously found that a significant number of hematopoietic progenitors accumulate in engrafted bones with the same major histocompatibility complex (MHC) as the transplanted bone marrow cells. In the present study, to further clarify the MHC restriction between hematopoietic stem cells (HSC) and microenvironment, we carried out cobblestone colony formation assays by culturing HSCs with MHC-matched or -mismatched stromal cell monolayers. The formation of cobblestone colonies under MHC-mismatched stromal cells significantly decreased in comparison with MHC-matched stromal cells. However, the decrease in cobblestone colony formation under MHC-mismatched stromal cells was not significant when using MHC class I-deficient HSC or stromal cells. Taken together with the results using B10 congenic strains, it is suggested that the MHC preference is restricted by MHC class Ia molecules. Treatment with monoclonal antibodies (mAbs) against MHC class Ia molecules of stromal cell phenotypes significantly enhanced the cobblestone colony formation, whereas treatment with mAbs against HSC phenotypes significantly inhibited it. The expression of cytokines to promote hematopoiesis was enhanced by the mAbs against stromal cell phenotypes. The enhancement of cytokine expression was also observed when stromal cells and HSCs were MHC-matched. These results suggest that signaling via the MHC molecules augments stromal cell activity and elicits the MHC restriction.
Animals↗
A new method for tolerance induction: busulfan administration followed by intravenous injection of neuraminidase-treated donor bone marrow.
The portal venous (p.v.) administration of foreign cells induces donor-specific tolerance. Recently, we have demonstrated that the p.v. administration of donor cells elicits donor-specific tolerance across major histocompatibility complex barriers. In the present study, utilizing the intrahepatic tolerance-inducing system, we have established a new method for organ transplantation using both busulfan ([Bu] to provide a sufficient "space" for the donor hematopoietic cells to expand in the recipient) and neuraminidase ([Neu] to enhance the trapping of i.v.-injected cells in the liver). Radiolabeled bone marrow cells (BMCs) were found to exclusively accumulate in the livers of the recipients as a result of the Neu treatment. Furthermore, hematopoietic progenitors (forming hematopoietic foci) in the accumulated BMCs were retained in the recipient livers for at least 18 days. C57BL/6 (B6) mice that had been transplanted with skins of BALB/c mice immediately after the injection of BALB/c BMCs showed a 90% skin graft survival rate over 400 days as a result of using the combination of injecting 50 mg/kg Bu into the B6 mice and treatment of the BALB/c BMCs with 0.25 U/ml Neu (50 Bu + 0.25 Neu). However, the survival rate significantly decreased when either the Bu or Neu treatment was omitted. In tolerant recipients, microchimerism was observed in the various hematolymphoid organs. T cells collected from the tolerant recipients suppressed proliferative responses to the donor-alloantigens but enhanced the production of Th2 and Th3 cytokines. These findings suggest that the enhanced retention of donor BMCs in the recipient livers as a result of the Bu and Neu treatments efficiently induces tolerance induction. Therefore, this "single-day protocol" would be of great advantage for human organ transplantation.
Animals↗
[Preoperative chemotherapy for advanced colorectal carcinomas--comparison of histological effect between 5'-DFUR + leucovorin tablet and 5'-DFUR alone].
The authors analyzed the histological effect of preoperative chemotherapy for 62 advanced colorectal cancer patients using resected specimens. Thirty-one patients in the 5'-DFUR + LV group received 800 mg/day of 5'-DFUR and 30 mg/day of leucovorin for 10-14 days just before the operations. Thirty-one patients in the 5'-DFUR group received 5'-DFUR 800 mg/day during the same period. None of the patients in either group developed any side effects. The results of the histological examination showed the number of Grade 1a and 1b cases in the 5'-DFUR + LV group was 22 (66.7%) and 5 (15.2%), respectively, and in the 5'-DFUR group 21 (65.6%) and 5 (15.6%). In the 5'-DFUR + LV group, 3 lesions showed Grade 2 histological degeneration, while there were no such lesions in the 5'-DFUR group. However, our results did not demonstrate any statistical difference between the two groups (p = 0.25, U test).
Administration, Oral↗
[Drug administration for enteral nutrition].
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Dosage Forms↗
[Pharmacokinetic study of the intraperitoneal administration of CPT-11 for patients with peritoneal seedings of gastric and colonic cancers].
We studied the pharmacokinetics of the intraperitoneal administration of CPT-11 for four patients with peritoneal metastasis (2 gastric cancer cases, 2 colon cancer cases). CPT-11 was administrated in a dose of 40-60 mg and the intraperitoneal and serum levels of CPT-11, SN-38 and SN-38 glucuronized (SN-38 Glu) were measured periodically. Intraperitoneal therapy with CPT-11 was effective for the control of malignant ascites. No serious side effects were observed. The levels of CPT-11, SN-38 were no different 30 min afterwards the administration of CPT-11 either intraperitoneally or intravenously. The high concentration of CPT-11 was achieved with intraperitoneal therapy and a small fraction of CPT-11 changed into SN-38 in the abdominal cavity.
Aged↗
[Adjuvant short-term continuous hepatoarterial infusion of 5-FU for advanced colorectal cancer using a removable hepatoarterial catheter].
We devised a removable hepatoarterial catheter which we then implanted in patients during colorectal operations, after first making sure this system worked well in an experiment with rabbits. We have applied this devise in 21 advanced colorectal cancer patients. The procedure to place the hepatoarterial catheter followed the resection of the colorectal cancer. A 16 G 30 cm TPN catheter was inserted into the gastroduodenal artery. This artery was ligated at two points with a double loop of elastic rubber threads (Elastik, Matsuda Suture, Tokyo). The catheter was fixed with Vicryl RAIDE (4-0). After the operation, 5-FU was continuously infused through the catheter for 2 weeks. We could remove the arterial catheter without any complications or bleeding after the chemotherapy was completed.
Adenocarcinoma↗
[A patient with small-cell carcinoma of the esophagus with synchronous liver metastasis surviving 48 months after surgery].
Small-cell carcinoma of the esophagus is regarded as having a poor prognosis with frequent and early systemic metastasis. Recently, several reports have described small-cell carcinoma satisfactorily treated by chemotherapy and radiation therapy combined with surgery. We herein report a patient with small-cell carcinoma of esophagus with synchronous multiple liver metastasis who survived 44 months after surgery. A 70-year-old man was found to have a polypoid lesion at the abdominal esophagus by upper gastrointestinal endoscopy. A biopsy specimen of the lower esophagus demonstrated undifferentiated carcinoma of the esophagus. Ultrasonographic investigation demonstrated solitary SOL in the liver. The patient underwent a total gastrectomy and lower esophagectomy by an abdominal approach. As ultrasonographic evaluation during laparotomy revealed multiple liver metastases, a hepatic artery infusion catheter was inserted into the proper hepatic artery. A pathological study of the resected esophagus and a biopsy specimen of the liver revealed undifferentiated cell carcinoma of the esophagus (small-cell type). During hospitalization, hepatic artery infusion therapy (CDDP 20 mg/4 h and 5-FU 750 mg/5 h) was given for 4 days starting on days 14 and 28. After chemotherapy, liver metastasis could not be detected by ultrasonographic investigation. At the outpatient clinic bi-weekly hepatic artery infusion of 5-FU (1,500 mg/body/5 h) was continued for 30 months. The patient is alive 48 months after surgery without any evidence of recurrence.
Aged↗
[A case of advanced gastric cancer with multiple liver metastases partially responding to combination intra-arterial chemotherapy via the hepatic artery and abdominal aorta].
A 57-year-old female diagnosed with advanced gastric cancer with multiple organ metastases was treated by various intra-arterial chemotherapies. After surgical resection of the tumor, adjuvant chemotherapy was carried out. Continuously administered 5-fluorouracil of 250 mg/day made it possible to control the growth of the liver metastases. Extrahepatic metastases were kept under control by administering 30 mg of methotrexate, 750 mg of 5-fluorouracil and 30 mg of Leucovorin per/day/week, and 60 mg/day biweekly of cisplatinum via an abdominal artery infusion port. Owing to this multiple infusion route and chemotherapy regimen, the patient lived for 18 months after her first diagnosis of gastric cancer with multiple liver metastases. Although liver metastases may respond to hepatic arterial infusion chemotherapy, extrahepatic metastases lead to poor prognosis. Given the above results, intra-abdominal aorta chemotherapy may be effective for extrahepatic metastases since this method gives high concentration of the anticancer agents at tumor sites with a low incidence of side effects.
Antineoplastic Combined Chemotherapy Protocols↗