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Biomedical subjects

K Mitsudo

Publications and source records attributed to K Mitsudo.

At least 19 recordsLinked to original sources

Diversity-oriented synthesis of multisubstituted olefins through the sequential integration of palladium-catalyzed cross-coupling reactions. 2-pyridyldimethyl(vinyl)silane as a versatile platform for olefin synthesis.

A novel strategy for the diversity-oriented synthesis of multisubstituted olefins, where 2-pyridyldimethyl(vinyl)silane functions as a versatile platform for olefin synthesis, is described. The palladium-catalyzed Heck-type coupling of 2-pyridyldimethyl(vinyl)silanes with organic iodides took place in the presence of Pd2(dba)3/tri-2-furylphosphine catalyst to give beta-substituted vinylsilanes in excellent yields. The Heck-type coupling occurred even with alpha- and beta-substituted 2-pyridyldimethyl(vinyl)silanes. The one-pot double Heck coupling of 2-pyridyldimethyl(vinyl)silane took place with two different aryl iodides to afford beta,beta-diarylated vinylsilanes in good yields. The palladium-catalyzed Hiyama-type coupling of 2-pyridyldimethyl(vinyl)silane with organic halides took place in the presence of tetrabutylammonium fluoride to give di- and trisubstituted olefins in high yields. The sequential integration of Heck-type (or double Heck) coupling and Hiyama-type coupling produced the multisubstituted olefins in regioselective, stereoselective, and diversity-oriented fashions. Especially, the one-pot sequential Heck/Hiyama coupling reaction provides an extremely facile entry into a diverse range of stereodefined multisubstituted olefins. Mechanistic considerations of both Heck-type and Hiyama-type coupling reactions are also described.

Alkenes↗

Pyridyl group assisted deprotonation of a methyl group on silicon: complex induced proximity effect and novel hydroxymethylation.

A novel methodology for the deprotonation of a methyl group on silicon has been developed. This newly developed alpha-lithiation protocol is based on the intramolecular pyridyl group coordination to stabilize the alpha-silyl carbanion together with the inherent silicon alpha effect. It was found that the deprotonation (t-BuLi/Et(2)O/-78 degrees C) occurs with 2-pyridyltrimethylsilane but not with other related silanes such as phenyltrimethylsilane, 3-pyridyltrimethylsilane, and 4-pyridyltrimethylsilane. It seems that this deprotonation proceeded through the agency of the complex-induced proximity effect (CIPE) of a 2-pyridyl group on silicon. (1)H NMR analysis of (2-pyridyldimethylsilyl)methyllithium revealed the intramolecular coordination of a pyridyl group to lithium. (2-Pyridyldimethylsilyl)methyllithium was found to react with chlorosilanes, hydrosilanes, chlorostannanes, bromine, iodine, organic bromides, aldehydes, and ketones in good to excellent yields. The resultant adducts were further oxidized with H(2)O(2)/KF to give the corresponding alcohols in excellent yields. Thus, this two-step transformation provides an efficient method for the nucleophilic hydroxymethylation.

Journal Article↗

A case of Burkitt's lymphoma that presented initially with resorption of alveolar bone.

A 16-year-old male was evaluated for a 1-month history of alveolar bone resorption, which had been treated with endodontics by a neighborhood dentist. Intraoral examination showed slight gingival swelling and teeth mobility. However, no tumor mass was seen. The panoramic image showed resorption of alveolar bone and loss of teeth lamina dura. Because he complained of general fatigue, he was introduced to the internist. Biopsies of gingiva and bone marrow aspiration revealed a massive proliferation of lymphoblasts expressing CD10, 19, 20 and HLA-DR antigens on the surface. Their karyotypes were abnormal; 46, XY, t (8;14) (q24;q32). Accordingly, he was diagnosed as Burkitt's lymphoma, and received intensive chemotherapy which relieved his symptoms and decreased his tumor. However, his disease soon became refractory to chemotherapy, and he died 11 weeks after the onset.

Adolescent↗

Circulating hepatocyte growth factor as a marker of thrombus formation in unstable angina pectoris.

A new enzyme-linked immunosorbent assay can detect 10 pg/ml of human hepatocyte growth factor (HGF). Circulating HGF was significantly higher in patients with unstable angina (296+/-184 pg/ml, mean+/-SD, n=36) than in healthy volunteers (201+/-64 pg/ml, n=250, p<0.0001). Individual concentrations exceeded the mean control value +2 SD (329 pg/ml) in 12 of the 36 (33%) patients with unstable angina. The present study indicates that this new, sensitive HGF assay can successfully detect thrombosis in patients with unstable angina.

Adolescent↗

[Stenting for intracranial internal carotid artery stenosis with the use of a coronary stent: a case report].

A 61-year-old man was admitted to our hospital for mild left hemiparesis and speech disturbance. An initial angiogram revealed occlusion of the right internal carotid artery (ICA) but with sufficient collateral flow by compensated the contralateral carotid artery. Severe stenosis (70%) in the intracavernous (C4-5) portion was identified in the left ICA. Cerebral blood flow was remarkably decreased in both hemispheres. The patient's hemiparesis fluctuated according to the systemic blood pressure in such a manner that induced hypertension therapy was mandatory. On the 19th hospital day, we performed stenting of the left ICA stenosis using a coronary stent. A flexible coronary stent, NIR PRIMO stent 3.0 mm/16 mm (SCIMED, Boston Scientific) was deployed after the predilatation (2.5 mm/10 atm). The initial 70% stenosis was reduced to 6% after the postdilatation (3.75 mm/8 atm). The neurological status was stable after the procedure and we stopped the induced hypertension therapy the next day. We consider that intracranial artery stenting will be a common therapeutic modality in the near future.

Carotid Artery, Internal↗

[Self-expanding stent (Wallstent) supported angioplasty for carotid artery stenosis].

We reported the preliminary results of percutaneous transluminal angioplasty (PTA) supported with a self-expanding stent (Wallstent) for the cervical internal carotid artery (i.c.) stenosis in 6 patients (7 lesions). All were male aged from 60 to 79 (mean 70.8). Three patients were symptomatic and 3 were asymptomatic. The procedure was attempted in patients with severe i.c. stenosis according to criteria of NASCET, ECST or ACAS studies and with high risk if carotid endarterectomy (CEA) were performed. In all cases, vascular access was from the femoral artery and angioplasty was performed without cerebral protection. Successful angioplasty was obtained in all cases with no mortality. Stenosis was improved from 82.7% (74-90%) to 17.4% (10-33%). Perioperative complications were seen in only one case with TIA during the postdilatation period, which was supposed to be due to a distal embolism. The preliminary results of PTA supported with self-expanding stent for severe i.c. stenosis were excellent. These results suggested that some patients with severe i.c. stenosis can be treated safely and effectively by stent-supported PTA. However, it is necessary to mark the indications clear and strict, and to follow up these lesions after the procedure, because of the possibility of perioperative ischemic complications and restenosis.

Aged↗

New guiding catheter for transrad PTCA.

A new guiding catheter for PTCA is described. In our department, 302 patients (405 lesions) underwent transradial coronary angioplasty using the 6 Fr Kimny guiding catheter since January 1996. The total engagement rate using the Kimny guiding catheter was 91.3% (370/405). The engagement rate after the modified Kimny guiding catheter was introduced in May 1996 increased to 96.0% (243/253). The stent delivery success rate was 98.4%. We had two dislodged stents. PTCA for both left and right coronary arteries in a single procedure with the Kimny guiding catheter was performed via the radial artery in 27 patients. In 24 of these patients (89%) we engaged both coronaries successfully. In the remaining 3 patients we switched to another catheter. Except for 4 patients with non-Q-wave myocardial infarction, no major cardiac complications were encountered. No major entry site-related complications were seen, and no patient required vascular surgery or blood transfusions. In one patient the Kimny guiding catheter tip caused a minor dissection of the LMT, but no ischemic event occurred as a result. In conclusion, the Kimny device is a useful PTCA guiding catheter for routine angioplasty and stenting.

Aged↗

High-resolution MR cholangiopancreatography.

1. High-resolution MRCP is a noninvasive imaging modality for depicting the pancreatobiliary tree. The imaging quality of high-resolution MRCP is satisfactory. MRCP can demonstrate dilation, stenosis, and intraductal filling defects of both the biliary tract and the pancreatic duct, which meets the clinical demand for pancreatobiliary imaging. 2. MRCP was successful in almost all the patients. However, the causes of MRCP failure were patient motion, irregular respiratory rhythm, severe pneumobilia, and massive ascitic fluid. 3. When only MIP reconstructed images were used for interpretation, small intraductal filling defects such as a gallstone can be missed. In combination with coronal source images, the ability to detect intraductal stones can be increased. 4. Ferrite ammonium citrate (FAC) is useful in suppressing the background signal intensity of gastrointestinal contents so that the ducts can be clearly visualized. The other technique for decreasing the background signal intensity is target MIP postprocessing, which works well for better visualization of the ducts. 5. The degree of ductal narrowing tends to be overestimated with MRCP because of MIP reconstruction artifact and lower spatial resolution of MRCP than ERCP. 6. MRCP has a diagnostic pitfall of a pseudostenosis of extrahepatic ducts, which may lead to a false-positive diagnosis of ductal narrowing. This pitfall may be caused not only by MIP postprocessing artifacts but by gas, surgical metal, and vascular compression of right hepatic artery. There is another diagnostic pitfall that it is difficult to differentiate intraductal mucin from pancreatic fluid in dilate pancreatic ducts, although ERCP identifies mucin as intraductal filling defects.

Biliary Tract↗

[MR dynamic subtraction angiography (MRDSA)].

We have developed magnetic resonance dynamic subtraction angiography (MRDSA), which depicts the long segments of arteries from the upper abdomen to the lower leg by using a small dose of Gd-DTPA. The lower half of the body was divided into three imaging regions, abdomen, thigh and lower leg, in the order of scanning. The contrast-enhanced three-dimensional breath-hold fast field echo technique with half Fourier acquisition was performed in 3 normal volunteers and 12 patients with vascular diseases (4: abdominal aortic aneurysm, 8: atherosclerotic occlusive disease). The images were reconstructed into composite images by using maximum-intensity-projection postprocessing after the subtraction of precontrast images. A bolus intravenous injection of a small dose of Gd-DTPA (0.02-0.05 mmol/kg) was given, followed by the five sets of scans. The acquisition time of each set was 8 to 16 seconds, and the total dose used in MRDSA was 0.1 to 0.15 mmol/kg. The image quality of MRDSA was satisfactory in 3 normal volunteers and 12 patients with vascular diseases. MRDSA demonstrated aortic aneurysm and atherosclerotic obstruction as clearly as conventional angiography. MRDSA can replace conventional angiography.

Angiography, Digital Subtraction↗

[Usefulness of directional coronary atherectomy as a bail-out device for acute closure after coronary angioplasty].

The usefulness of directional coronary atherectomy (DCA) as a bail-out device for acute closure (reclosure) after percutaneous transluminal coronary angioplasty (PTCA) was evaluated. PTCA was performed in 1,023 patients (182 with acute myocardial infarction) between January 1993 and January 1994 in our hospital. Thirty-one patients (11 with acute myocardial infarction) suffered acute closure (reclosure) after PTCA. In six patients (five with acute myocardial infarction), DCA was performed as a rescue treatment for acute closure (reclosure). In three of these patients, angioscopy was performed before DCA, which demonstrated intimal tear and some thrombi although coronary angiography showed no evidence of thrombus. Bail-out DCA was successful in all six patients without complications. DCA is useful as a bail-out device for acute closure (reclosure) after PTCA when the thrombus is not massive.

Angioplasty, Balloon, Coronary↗

Thermochemotherapy for cancer of the tongue using magnetic induction hyperthermia (implant heating system: IHS).

A 55-year-old patient with cancer of the tongue (T2N0M0) was treated by thermochemotherapy using interstitial magnetic induction hyperthermia (Implant Heating System: IHS). The patient received 2 courses of hyperthermia, each of which was 45 minutes long. At the same time, the patient received 2 courses of chemotherapy, which included intra-arterial infusion of 100 mg of cisplatin (CDDP) and 25 mg of peplomycin (PEP). The patient showed complete response (CR) to this therapy. To date, 1.5 years after completion of treatment, the patient has shown no recurrence. This therapy, which makes surgery and radiotherapy unnecessary, is promising, because it is expected to improve the quality of life (QOL) of cancer patients.

Antineoplastic Combined Chemotherapy Protocols↗

Intravenous dopexamine in the treatment of acute congestive heart failure: results of a multicenter, double-blind, placebo-controlled withdrawal study.

Acute hemodynamic effects of intravenous infusion of dopexamine were evaluated by a placebo-controlled withdrawal study in patients with acute congestive heart failure. Twenty patients were enrolled at 10 centers in Japan. All patients had a pulmonary capillary or diastolic pressure of 15 mmHg or greater and a cardiac index of 2.5 l/min/m2 or less. Phase I: Intravenous dopexamine was introduced in a single-blind, uncontrolled fashion at the rate of 0.5 micrograms/kg/min and was titrated up to achieve a 30% or more increase in the cardiac index. Two patients withdrew from the study due to sinus tachycardia and ventricular ectopy or exacerbation of heart failure. Phase II: The remaining 18 responders who were free of limiting side effects were randomized in double-blind fashion to continue dopexamine or to switch to placebo for an additional 60 minutes. At the end of phase II, the hemodynamic improvement obtained in phase I of the study disappeared completely after substitution of placebo but was maintained in dopexamine-treated patients. Our findings suggest that dopexamine, when given in appropriate doses to selected patients, shows balanced vasodilator action suitable for the treatment of acute congestive heart failure.

Acute Disease↗

Electron-microscopic and immunohistochemical studies of Langerhans cells and Thy-1-positive cells in mouse tongue epithelium subjected to local hyperthermia.

Local hyperthermia via skin has been used to treat cancer but may suppress local immune responses as a side-effect. To examine effects of heat on immunologically responsive cells in oral mucosa, mouse tongues were heated by an implant system at 43 degrees C for 20 min. The densities of Langerhans cells and Thy-1-positive cells rapidly increased within 3 h after the treatment, then returned to a normal level after 7 days. Electron microscopy confirmed that Langerhans cells in the tongue epithelium formed clusters with lymphocytic cells, suggesting an active response to the hyperthermia.

Adenosine Triphosphatases↗

The clinical and histopathological effects of combined chemotherapy using cisplatin and peplomycin to treat cancer of the tongue.

Combined chemotherapy (PP therapy) using cisplatin (CDDP) and peplomycin (PEP) was performed as induction chemotherapy for 31 patients with cancer of the tongue, and the clinical and histopathological effects were investigated. As the primary clinical effect, complete response (CR) was observed in three cases, partial response (PR) in 20 cases, minor response (MR) in six cases and no change (NC) in two cases, with a clinical response rate of 74.2%. The histopathological effects of the chemotherapy in the following cases showed these histological Grades: 0 or I in four cases, IIa in 12 cases, IIb in eight cases, III in six cases and IV in one case. Fifteen of the 31 patients who received PP therapy showed a histological Grade of IIb or better, representing 48.4% of the histopathological response rate. With regard to the mode of invasion of the tumor, the histopathological response rate was 90.0% in patients with invasive Grades 1 and 2, 41.7% in those with invasive Grade 3 and 16.7% in those with invasive Grade 4C. There were no patients with invasive Grade 4D in whom the therapy was histopathologically effective. In other words, the histopathological effect significantly decreased as the invasive Grade increased. With regard to the relationship between clinical effects and histopathological effects, there was one CR patient who showed a histological Grade of IIa. Thus, it is noteworthy that clinical effects were not necessarily consistent with post-chemotherapeutic histopathological effects.

Adult↗

Langerhans cells closely associated with Thy-1-positive dendritic cells in the stratified squamous mucosal epithelium of mice.

An immunohistochemical study was carried out on two types of dendritic immune cells, Langerhans cells and Thy-1-positive cells, in the epithelium of the forestomach of 1-, 2-, 3-, 4- and 8-week-old mice. Investigation focused on how both types of cells were distributed and might interact in the mucosal epithelium. Langerhans cells and Thy-1-positive dendritic cells appeared in mucosal epithelium at 3 weeks of age, while in the epidermis they were first observed just after birth. In contrast with the epidermal Thy-1-positive cells, mucosal Thy-1-positive cells were closely associated with Langerhans cells. Electron microscopy also confirmed that two types of immune cells interact directly in the stratified squamous mucosal epithelium of mice.

Animals↗