Biomedical subjects
Publications and source records attributed to Hideaki Mori.
Choledochocele is the least common form of choledochal cyst. We report a rare bile duct cyst diagnosed in a 63-year-old woman via CT cholangiography. Although conventional sonography initially failed to reveal abnormal findings, a subsequent detailed study clearly depicted the lesion. To the best of our knowledge, this is the first report of choledochocele unambiguously demonstrated on transabdominal sonography.
PURPOSE: Perfluorocarbons have an excellent oxygen- and carbon dioxide-carrying capacity. This prompted us to investigate the feasibility of transintestinal systemic oxygenation using perfluorocarbon. METHODS: A rat hypoventilation model (room air, 20 breaths/min and a tidal volume of 10 ml/kg) was thus established, and FC-77 (Sumitomo-3M, Osaka, Japan) was used as a perfusate. Oxygenated FC-77 was perfused through the small intestine for 4 h. The rats were allocated into three groups as follows. Group 1 (n = 6): hypoventilation only; Group 2 (n = 6): saline was perfused instead of FC-77; Group 3 (n = 6): FC-77 was perfused. Arterial blood samples were drawn from the common iliac artery every 30 min until the end of perfusion. A standard blood gas analysis was performed. RESULTS: The PaO2 level in Group 3 was significantly higher than in Groups 1 or 2 (P = 0.006: at the end of perfusion, Group 1 = 58.6 +/- 14.5 mmHg, Group 2 = 65.2 +/- 29.4 mmHg, Group 3 = 84.0 +/- 35.5 mmHg). The PaCO2 level in Group 3 was significantly lower than that in Groups 1 or 2 (P = 0.014: at the end of perfusion, Group 1 = 56.8 +/- 8.5 mmHg, Group 2 = 52.6 +/- 5.7 mmHg, Group 3 = 44.4 +/- 11.1 mmHg). CONCLUSION: Our findings indicate that transintestinal systemic oxygenation is indeed possible and could therefore become a useful new modality for respiratory assist.
We have developed a simple technique for temporary shunt from the saphenous vein graft to the coronary artery during off-pump coronary anastomosis. The ends of a 2-mm diameter tube were inserted into the distal end of the saphenous vein graft in which proximal anastomosis had been established and into the right coronary artery crux. Blood flow sufficient to maintain adequate hemodynamics was obtained through the shunt tube while suturing around the tube. We successfully employed this technique in 5 patients with acute coronary syndrome. We suggest that this technique may represent an addition to the armamentarium for off-pump anastomosis to the right coronary artery.
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PURPOSE: A large animal model of hypoxia is necessary to develop a new therapeutic method for respiratory failure. METHODS: The experiments were performed on six pigs weighing from 15 to 19 kg. Under general anesthesia the left chest was opened and the left main bronchus was closed by a stapler. A Swan-Ganz catheter was inserted through the right jugular vein. The right carotid artery was cannulated and the mean arterial blood pressure was monitored, and arterial blood samples were drawn every 24 h until 96 h after the operation. The blood samples were submitted for a blood gas analysis. All data were expressed as the mean +/- standard deviation of the mean. RESULTS: The partial pressure of the oxygen of the arterial blood at baseline (104.8 +/- 24.3 mmHg) significantly decreased at 24 h after closure of the bronchus (76.7 +/- 9.9 mmHg, P < 0.001) and thereafter remained at the same level for 4 days. CONCLUSION: This hypoxic model using a pig was found to be very simple, effective, and reproducible. This model can be used for a variety of experiments to evaluate new therapeutic modalities for respiratory failure.
OBJECTIVE: Perfluorocarbons are structurally similar to hydrocarbons but with the hydrogen atoms replaced by fluorine. In general, perfluorocarbons have an excellent oxygen and carbon dioxide carrying capacity. We studied the suitability of oxygenated perfluorocarbon as an agent for transintestinal oxygenation and measured its perfusion rates under different conditions. SUBJECTS AND METHODS: We used FC-77 (Sumitomo 3M, Tokyo, Japan) perfluorocarbon and a rat hypoventilation model (room air, 20 breaths/min, a tidal volume of 10 ml/kg). Oxygenated FC-77 was perfused through the small intestine for 4 hours. Rats were allocated to 3 experimental groups according to the perfusion rate and a control group: Group 1 (n=6), 10 ml/min; Group 2 (n=6), 2.5 ml/min; Group 3 (n=6), 0.75 ml/min; Group 4 (n=6) served as a control (hypoventilation only). Arterial blood samples were drawn every 30 minutes. Standard blood gas analysis was performed. RESULTS: After four hours of perfusion, the PaO2 levels in Groups 1 to 3 were significantly better than Group 4 (p<0.01, Group 1: 141.7 +/- 18.0 mmHg, Group 2: 145.2 +/- 25.1 mmHg, Group 3: 120.5 +/- 21.2 mmHg, Group 4: 67.4 +/- 7.2 mmHg). PaCO2 levels in Groups 1 and 2 were significantly better than Groups 3 and 4 (p<0.01, Group 1: 42.6 +/- 7.2 mmHg, Group 2: 52.1 +/- 7.7 mmHg, Group 3: 78.2 +/- 22.8 mmHg, Group 4: 75.3 +/- 10.3 mmHg). CONCLUSION: In the present settings, 8 ml/kg/min was adequate for oxygenation and CO2 clearance. This approach promises to become another modality for respiratory assistance.
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Severe mitral annular calcification is frequently encountered in patients with chronic renal failure requiring dialysis. The procedures are described for the implantation of mitral prostheses in two dialysis patients with mitral stenosis who exhibited heavily calcified mitral annuli. In both cases the calcifications extended around the entire mitral annulus as well as the valve leaflets, papillary muscle, atrial wall and ventricular myocardium, making it impossible to secure prosthetic valves to the mitral annuli. Before implantation, the calcification was partially debrided ultrasonically, and an 'atrioventricular channel' created. A mechanical valve with a polyester fabric collar was fixed on the atrial side of the calcified annulus using double sutures and gelatin-resorcin-formol glue. Perivalvular leakage, obstruction of valve opening or tortuous movements of prosthetic valve ring were not observed, and neither patient developed heart failure after surgery. This technique represents a potentially useful approach in the surgical treatment of patients with severely calcified mitral annuli.
Brachiocephalic artery aneurysm with concomitant coronary artery aneurysm is rare. We describe a case of a patient with a history of prosthetic graft placement following resection of an abdominal aortic aneurysm and was subsequently found to have a brachiocephalic artery aneurysm. After surgical correction of the brachiocephalic aneurysm, postoperative coronary arteriography demonstrated coronary artery aneurysms, and the patient subsequently underwent coronary artery bypass grafting (CABG).
BACKGROUND: In the final step of production of adrenomedullin (AM), an inactive intermediate form of glycine-extended AM (AM-glycine) is converted to the active mature form of adrenomedullin (AM-mature) by enzymatic amidation. Recent studies have revealed that AM-mature and AM-glycine circulate in human plasma. In this study, we investigated the differences of the concentrations of cardiac AM between pressure-overloaded (PO) heart failure (HF) and volume-overloaded (VO)-HF in humans. METHODS AND RESULTS: We measured AM-mature and AM-glycine by immunoradiometric assays in pericardial fluid and plasma in 38 patients who underwent valve replacement surgery (PO-HF: aortic stenosis, n=14; VO-HF: aortic or mitral regurgitation, n=24). Stable coronary artery disease with normal left ventricular function served as the control (n=24). Plasma AM-mature (VO-HF: +59%, PO-HF: +65%, P<.05) and AM-glycine (VO-HF: +43%, PO-HF: +50%, P<0.05) were similarly higher in the 2 HF groups than in the control group. Interestingly, pericardial fluid AM-mature was markedly higher than that in plasma (control: +789%, VO-HF: +1050%, PO-HF: +1745%, all P<.001). Pericardial fluid AM-mature was higher in VO-HF (+106%, P<.01) than in controls and they were further increased in PO-HF (+243%, P<.05). Pericardial fluid molecular forms of AM correlated with left ventricular systolic pressure, but not with left ventricular end-diastolic volume index in PO-HF. In contrast, they correlated with left ventricular end-diastolic volume index, but not with left ventricular systolic pressure in VO-HF. CONCLUSION: These results suggest that cardiac AM is differently regulated from plasma AM and that cardiac AM production is upregulated in both types of HF in response to each different stimulus.
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(1S,2R)-2-Acylamino-1-methyl-2-phenylethyl phosphate derivatives 2a, 2b, 3a, and 5a, which are conformationally restricted and metabolically stable analogues of (2R)-2-acylamino-2-phenylethyl phosphate derivatives 1a and 1b, are a new class of inhibitors of TNF-alpha production. More efficient alternative synthesis of a key intermediate, (1R,2S)-1-amino-1-(3-methoxyphenyl)propan-2-ol hydrochloride (9), was achieved using one-step, three-component coupling of 3-methoxyphenyl boronic acid (13), (5S)-2,2,5-trimethyl-1,3-dioxolan-4-ol (14), and amino diphenyl methane (15), [as reported in J. Am. Chem. Soc. 1998, 120, 11798]. Evaluation of the hypotensive activity of these compounds was done to assess one of their side effects. Among the compounds tested, the above-mentioned four compounds (2a, 2b, 3a, and 5a) were identified as inhibitors with both sufficient potency and an acceptable safety margin regarding their hypotensive activity. The pharmacodynamics of these compounds were also investigated. Single-dose pharmacokinetic data for compounds 2a, 2b, 3a, and 5a are displayed. These compounds were estimated to be mainly metabolized by the liver in the species tested based on their in vitro stability in tissue homogenates and plasma. A representative compound, 2a, showed good linearity of its plasma concentration after intravenous injection.
We used left common carotid artery cannulation for repair of type A aortic dissection in 2 patients for whom both femoral artery and axillary artery cannulation were thought to be more dangerous, due to dissection of the brachiocephalic trunk and left subclavian artery in association with abdominal stenosis. Before performing end-to-side anastomosis, we attached a small partial clamp to the left common carotid artery, thereby maintaining adequate cerebral blood flow during perfusion. To date, neither of our patients has experienced neurologic complications related to this procedure. We believe that left common carotid artery cannulation for type A dissections is useful when dissection of the brachiocephalic trunk and left subclavian artery is found in association with abdominal or femoral artery stenosis. To the best of our knowledge, these 2 cases are the 1st described in the medical literature.
Metabolic stabilization of the chemical lead 1, which is a structurally novel inhibitor of TNF-alpha production, was accomplished by introducing a (1S)-methyl group into the optically active backbone. As a result, 2, 3 and 4 were identified as drug candidates and evaluated pharmacologically. The analysis of an active conformer was also carried out.
Design and synthesis of metabolically stabilized inhibitors of TNF-alpha production, which could be new drug candidates, are reported. Conformational analysis of an active diastereoisomer was performed based on biological evaluations of the conformationally fixed indane derivatives 17 and 18. Structure-activity relationships (SARs) based on biological evaluations of the optically active derivatives are also discussed. Full details including chemistry are reported.
Discovery of new chemical leads of inhibitors for TNF-alpha production starting from the chemical modification of 1 is reported. Further biological studies of 1 to disclose the site of its action strongly suggested that 1 inhibits LPS-induced TNF-alpha expression in the liver and spleen of mice. Structure-activity relationships (SARs) are also discussed and full details including the chemistry are reported.
The ETS-domain transcription factor family can be divided into a series of subfamilies. Elk-1 represents the founding member of the ternary complex factor (TCF) subfamily. By focusing on the TCF subfamily, we can demonstrate the complexities that exist in the function and regulation of ETS-domain transcription factors. This article focuses on Elk-1 in detail and summarizes the functions of other TCFs. The key themes covered include the domain structure of the TCFs, the mechanisms of complex formation with serum response factor, regulation of TCFs by mitogen-activated protein kinase cascades, and transcriptional regulatory properties of the TCFs. Finally, the emerging role of the TCFs in vivo is discussed. A picture is developing indicating that, while these proteins exhibit significant sequence and functional conservation, key differences in their structure and regulation are being identified which may relate to unique functions of these proteins in vivo.