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Biomedical subjects

N Tanaka

Publications and source records attributed to N Tanaka.

At least 379 records · Page 21Linked to original sources

Serological diagnosis of idiopathic pulmonary alveolar proteinosis.

Previously, we reported the specific occurrence of neutralizing autoantibodies against granulocyte-macrophage colony-stimulating factor (GM-CSF) in the bronchoalveolar lavage fluid from 11 Japanese patients with idiopathic pulmonary alveolar proteinosis (I-PAP). The autoantibody was also detected in sera from all 5 I-PAP patients examined. To determine that the existence of the autoantibody is not limited to the Japanese patients, we examined sera from 24 I-PAP patients in five countries and showed that the autoantibody was consistently and specifically present in such patients. Thus, detection of the autoantibody in sera can be used for diagnosis of I-PAP. To establish a simple and convenient method for diagnosis of I-PAP, we developed a novel latex agglutination test using latex beads coupled with recombinant human GM-CSF. GM-CSF binding proteins isolated from the sera using the latex beads were identified as the autoantibodies of IgG(1) and IgG(2). The titer of the autoantibody determined by this test correlated with that determined by ELISA. Agglutination was positive in 300-fold diluted sera from all 24 I-PAP patients, but negative in sera from four secondary PAP patients, two congenital PAP patients, 40 patients with other lung diseases, and 38 of 40 normal subjects. These results establish that the latex agglutination test is a reliable method for serological diagnosis of I-PAP with high sensitivity (100%) and specificity (98%).

Adult↗

Extensive cell death in thymocytes in colon 26-induced cachectic mice.

Extensive atrophy has been reported to occur in the thymus in a cancer-burden state but the mechanisms of this atrophy have not been fully elucidated. We investigated changes in the thymus in tumour-bearing mice inoculated with two subclones of the murine colon 26 adenocarcinoma cell line: clone 5 (non-cachectic) and clone 20 (cachectic). In clone 20 mice, body weights and thymocyte numbers decreased significantly compared with controls. Flow cytometric analysis of the thymocytes demonstrated that the frequency of single positive cells (CD4+ CD8- and CD4- CD8+) was significantly increased and that of double positive cells (CD4+ CD8+) was significantly decreased in clone 20 mice and, to a lesser extent, in clone 5 mice compared with controls. Serum levels of interleukin 6 and granulocyte-macrophage colony-stimulating factor (GM-CSF) were significantly elevated. These results suggested that thymocyte apoptosis was accelerated in the cancer-cachectic state, and increased GM-CSF might be partly responsible for thymic atrophy.

Adenocarcinoma↗

[2-(O-Phenylalkyl)phenoxy]alkylamines III: Synthesis and selective serotonin-2 receptor binding (2).

A series of 12-(2-phenylethyl)phenoxy]ethylpyrrolidine derivatives were synthesized, and their affinity for serotonin-2 (5-HT2) and dopamine-2 (D2) receptors was examined. Among them, compound 17, (2R,4R)-4-hydroxy-2-[2-[2-[2-(3-methoxyphenyl)ethyl]phenoxylethyl] -1-methylpyrrolidine hydrochloride, showed high 5-HT2 receptor affinity in vitro. This compound was a more potent inhibitor of ex vivo 5-HT-induced platelet aggregation than compound 3, which was previously shown to be more potent than ketanserin (1) and sarpogrelate (2a). However, compound 17 produced gastric irritation in rats. Therefore, we carried out a further derivatization of 17, and compound 45 (R-102444), a lauryl ester prodrug of compound 17, was found to be a promising candidate as an antithrombotic agent. Oral administration of R-102444 produced a marked inhibition of 5-HT-induced ex vivo platelet aggregation, and R-102444 did not cause any gastric irritation. The antiaggregatory effects of R-102444 were more potent than those of sarpogrelate (2a) and its active metabolite, M-1 (2b). In addition, R-102444 exhibited more potent antithrombotic effects than sarpogrelate in a rat photochemically-induced thrombosis model.

Acylation↗

[2-(omega-phenylalkyl)phenoxy]alkylamines.II: Synthesis and selective serotonin-2 receptor binding.

A series of [2-(omega-phenylalkyl)phenoxy]alkylamines was synthesized and their receptor binding affinity was examined in vitro. These compounds showed an affinity for serotonin-2 (5-HT2) and dopamine-2 (D2) receptors. [2-(2-phenylethyl)phenoxy]alkylamine derivatives with a pyrrolidine or piperidine moiety in the structure showed higher affinity for 5-HT2 receptors but lower affinity for D2 receptors. Among these compounds, (S)-2-[2- [2-[2-(3-methoxyphenyl)ethyl]phenoxy]ethyl]-1-methylpyrrolidine, (S)-27, exhibited the most potent and selective affinity for 5-HT2 receptors. Furthermore, (S)-27 was effective in inhibiting 5-HT-induced vasoconstriction in vitro and platelet aggregation both in vitro and ex vivo.

Animals↗

Usefulness of transesophageal echocardiographic monitoring in transluminal endovascular stent-graft repair for thoracic aortic aneurysm.

The endovascular stent-graft has been devised for the treatment of thoracic aortic aneurysm (TAA) to reduce complications associated with conventional surgical repair. The present study assessed the usefulness of transesophageal echocardiography (TEE) for intra- and post-operative examinations in patients treated with transluminal endovascular stent-graft repair for TAA. Nine patients with TAA and 2 with chronic type B aortic dissection were studied. Immediately after stent-graft deployment, perigraft leakage was evaluated with both intraoperative TEE and aortography. In 9 of 11 patients, TEE and aortography immediately after stent-graft deployment revealed the same perigraft leakage results. TEE might therefore be useful for evaluating perigraft leakage and thrombus formation after stent-graft repair for TAA and could be an alternative to aortography, especially for patients with renal dysfunction who have the possibility of contrast agent-induced complications.

Aged↗

Liver involvement in hereditary haemorrhagic telangiectasia: assessment with 99Tcm-phytate radionuclide angiography and 123I-IMP transrectal portal scintigraphy.

Abnormal hepatic haemodynamics and function in a 43-year-old woman with hereditary haemorrhagic telangiectasia (HHT) were evaluated using 99Tcm-phytate angiography and iodine-123-iodoamphetamine transrectal portal scintigraphy. Radionuclide angiography demonstrated hyperdynamic perfusion of the liver owing to intrahepatic arteriovenous fistulae (AVF), entry of tracer into the systemic circulation through intrahepatic portosystemic shunts and an increase in recirculating blood flow caused by these vascular disorders. Heterogeneous distribution of tracer also suggested the presence of chronic hepatic injury. Transrectal portal scintigraphy showed large portosystemic shunts. Other imaging techniques confirmed the presence of the AVF but failed to identify the portosystemic shunts. Non-invasive radionuclide studies are helpful in the evaluation of hepatic involvement of HHT.

Adult↗

Effect of cobalamin on the allergic response in mice.

Cyanocobalamin, deoxyadenosylcobalamin and methylcobalamin were separately administered to mice sensitized with the ovalbumin antigen to investigate the allergic response. The serum IgE and pulmonary histamine concentrations were significantly lower in all cobalamin (Cbl)-administered groups. The production of interleukin (IL)-2 and IL-4 in splenocytes was also lower in all Cbl-administered groups. These results show that Cbls were effective in mitigating allergic reactions and IL-2 production. CD3+ CD28+ (CD28 is an accessory molecule related to IL-2 production) and CD4+ CD28+ in splenocytes were higher in all the Cbl-administered groups. However, CD3+ CD28-, CD4+ CD28- and CD5+ CD25- (CD25: IL-2 R alpha/p55) were lower in the Cbl-administered groups. In addition, Cbl specifically inhibited the cellular phosphorylation of tyrosine induced by ovalbumin sensitization. These results indicate that the signal in a cell by CD 28 was restrained by Cbl. We infer that Cbl administration significantly reduced the IL-2 concentration, and secondarily the IL-4, IgE and histamine concentrations.

Animals↗

Proliferating cell nuclear antigen and p53 protein expression in submucosal invasive colorectal carcinoma.

In some cases of early colorectal carcinoma, radical surgical resection might be required because of vessel invasion, distant metastasis, or inadequate surgical margin. To characterize submucosal invasive colorectal carcinoma, we investigated expression of PCNA and p53 protein. Sixty-seven patients who underwent curative resection of submucosal invasive colorectal carcinoma participated in this study. The PCNA labeling index (PCNA-LI) is determined at the deepest lesion of carcinoma. The expression of PCNA and p53 protein were analyzed according to clinicopathological factors. 1) The PCNA-LI was correlated to histological grade, depth of invasion or vessel invasion in polypoid type. 2) The flat type had significantly higher PCNA-LI (65.1+/-8.2%) and p53 protein expression (69.6%) than the polypoid type. 3) The PCNA-LI was higher in cases with lymph node metastasis than in these without lymph node metastasis. 4) Overexpression of the p53 protein was detected in all cases with liver metastasis. Our results suggest that in order to determine the treatment for the patients with submucosal invasive colorectal carcinoma, the expression of PCNA and p53 protein may be a useful biologic marker.

Aged↗

Anterior tributaries of the portal vein at the superior margin of the pancreas: is "tunneling" procedure safe during pancreatic surgery?

BACKGROUND: It is widely believed that using the "tunneling" procedure during pancreatoduodenectomy is a safe maneuver because the anterior tributaries of the portal vein (PV) are absent or very rare. METHODS: The head of the pancreas with the duodenum and the common bile duct (CBD) was obtained from 22 autopsy cases. Three colors of silicon-polymerase dyes were injected into the pancreatic artery, PV, and bile duct. The tributaries of the PV at the superior margin of the pancreas were studied. RESULTS: There was no anterior branch of the intrapancreatic PV. The anterior superior pancreaticoduodenal vein (ASPDV) gave a definite branch to the anterior aspect of the PV at the superior margin of the pancreas in 4 of 22 cases. When the posterior superior pancreaticoduodenal vein (PSPDV) was located in front of the CBD (5 of 22 cases), the ASPDV and PSPDV had a thick common trunk at the right side of the PV. In these 5 cases, no individual branch from the ASPDV was found at the anterior aspect of the PV. CONCLUSION: PV sometimes has a definite anterior tributary at the superior margin of the pancreas; this must be kept in mind to perform the tunneling procedure during pancreatic surgery.

Adult↗

A case of rectal Dieulafoy's ulcer and successful endoscopic sclerotherapy.

A 54-year-old woman presented a massive hematochezia 7 days after sigmoidectomy. Repeated colonoscopy and angiography failed to locate the site of bleeding and Hartman's operation was performed. Rebleeding from the rectum on the day of operation occurred and pulsate arterial bleeding with minimal surrounding ulcer 1 cm above the pectinate line was observed. Screlotherapy with ethanol and electro coagulation was successfully performed to achieve permanent hemostasis. The importance of detailed rectal examination and an awareness of this clinical entity in life-threatening lower intestinal bleeding is discussed.

Electrocoagulation↗

Rat small intestinal transplantation: a comparison of the cuff and hand-suture methods.

The rat model is ideal for investigating various reactions to small intestinal transplantation (SIT). The conventional surgical model (hand-suture method), however, requires microsurgical techniques and remains difficult for beginners to perform at a high success rate. We have employed the SIT model using the cuff method, by which the vessels are anastomosed without sutures. All of the fellows who used the hand-suture models needed over 8 +/- 5.8 months until they achieved a 70% success rate. In contrast, the fellows employing the cuff method mastered SIT models after 6 weeks' practice. The cuff technique is a simplified and quickly mastered alternative to the hand-suture method that may be desirable for researchers who wish to apply the method to SIT experiments and whose primary purpose is not microsurgery.

Animals↗

Creation and use of a composite polyurethane-expanded polytetrafluoroethylene graft for hemodialysis access.

The Thoratec (Vectra) polyurethane vascular access graft (TPVA) is among the most recent additions to the list of materials used to construct prosthetic grafts for vascular access during hemodialysis. We give the TPVA very high marks, and recognize the utility of such a graft for use in hemodialysis. However, the strong elasticity of this graft can lead to unexpected complications after suturing. We devised a new surgical method using a TPVA-ePTFE (expanded polytetrafluoroethylene) composite graft, substituting the anastomosis section of the TPVA with a portion of ePTFE graft material, and have been able to overcome most of the TPVA's potential problems. We herein describe the technique.

Aged↗

Endoscopic submucosal tumor biopsy using Stiegmann-Goff endoscopic ligator.

Endoscopic biopsy is an important tool for histological diagnosis of lesions residing in gastrointestinal tracts. However, it is less useful in submucosal lesions due to the existence of normal overlying mucosa. We developed a new and safe technique for the diagnosis of submucosal tumor using Stiegmann-Goff endoscopic ligator. After removing surface mucosa to expose submucosal tissue by this method, conventional secured histological diagnosis could be performed. To determine definitive histological diagnosis, this technique is useful as well as Endoscopic Ultrasound (EUS) with fine needle aspiration biopsy and other modalities.

Biopsy↗

Calcineurin antagonists inhibit interferon-gamma production by downregulation of interleukin-18 in human mixed lymphocyte reactions.

Tacrolimus (FK-506) and cyclosporin A (CsA) are calcineurin antagonists used widely as T-cell immunosuppressants; however, their relative efficacy on the production of interleukin-18 (IL-18) remains undefined. We have examined the effects of FK-506 and CsA on the cytokine generation of human peripheral blood mononuclear cells (PBMCs) in mixed lymphocyte reaction (MLR) with lipopolysaccharide (LPS). We studied the levels of interleukin-18 (IL-18), IL-12, IL-10, IL-6, IL-2 and interferon-gamma (IFN-gamma) in the supernatant in allo-MLR by ELISA assay. Supernatant levels of IFN-gamma, IL-2, IL-6, IL-10 and IL-12 were detected 12 h after MLR and markedly increased thereafter. In contrast, production of IL-18 was detected at 12 h, reached a near maximum level at 24 h and decreased at 72 h. These results suggested that IFN-gamma production depended on IL-18, IL-12 and IL-2 in the early phase of MLR and depended mainly on IL-12 and IL-2 in the late phase. Both calcineurin antagonists inhibit the generation of IL-18, which plays a large role in allogeneic cell interactions, in macrophages and they also promote an equivalent down-regulation of T helper 1 (Th1) and Th2 responses in a concentration-dependent manner. About 90% of IFN-gamma production induced by MLR was inhibited by an anti-IL-18 antibody, showing that IL-18 can trigger IFN-gamma production in MLR. These results suggest that dual signaling consisting of antigen-driven nuclear factor of activated T cells (NFAT) activation and LPS-mediated NF-kappaB activation is crucial for IL-18 production in macrophages, and that IL-18 can trigger IFN-gamma production in T-cells by MLR.

Calcineurin Inhibitors↗

Biochemical modulation of 5-fluorouracil with a streptococcal preparation, OK-432, against murine colon-26 carcinoma.

Conventional therapy for colorectal carcinoma using 5-fluorouracil (5-FU) has shown limited antitumor action. The purpose of our study was to investigate synergistic antitumor effects of the streptococcal preparation of OK-432 and 5-FU, and to elucidate the mechanisms of interaction between the 2 agents in mice. Biochemical modulation of OK-432 and 5-FU were determined in vivo against colon-26 carcinoma. The concentration of 5-FU and its metabolites, and the activity of thymidylate synthase and thymidine kinase, respectively, were measured using cytosolic extracts of the tumors. Combination treatment with OK-432 produced a significant increase in intratumor 5-FU and 5-FU in RNA (F-RNA) concentrations, increased the thymidylate synthetase inhibition rate, and decreased thymidine kinase activity, as compared with the results observed in the control mice. These additive antitumor effects are obtained by use of the 2 agents; the mechanism of action is considered to be the suppression of both the de novo and the salvage pathway for DNA synthesis, along with the suppression of RNA synthesis.

Animals↗

[Ability to avoid falls among aged residents in a barrier-free welfare institution].

This study was carried out to investigate the physical functions of the elderly, living in a barrier-free home for the aged and to obtain basic data for giving appropriate guidance on exercise and daily life. A total of 38 women were tested. These included 18 persons (aged 72-87: mean: 80.7) who were living in the home for the aged, and 20 (aged 75-86: mean: 78.3) who voluntarily participated in the "fall prevention school", established in Tokyo Kosei-Nenkin Hospital. The following examinations were done: 1) BMI, Waist/Hip ratio; 2) good walker's index consisting of 10 m walking times, maximum length of steps, and 40 cm-staircase climbing; and 3) equilibrium examination done by gravinography. Statistical analysis was carried out using a paired t-test (p < 0.01). Values for the "good-walker's index" were significantly lower in, the "home" group than in the "school" group (p < 0.01). This was especially obvious with 40 cm-staircase climbing. Many of the subjects from the institution group required assistance and there was a significant difference in the chi-squire square distribution between the two groups. Furthermore, on gravinography, the "home" group had significantly inferior values in total length (cm) and Romberg's ratio (p < 0.01). It was clear that residents in the barrier-free home had a significant reduction in good-walker's index, indicating an apparent weakening of physical function.

Accidental Falls↗