Biomedical subjects
Publications and source records attributed to H Nemoto.
Bone metabolism is regulated not only by the nutrition supplied by vessel but also by the signals from the cells in vascular tissues. Identification of such signaling molecules has been the major issue in the field of research on the relationship between bone and vasculatures. This review touches on the recent findings on the expression and functions of such signaling molecules including VEGF, MMP and non-collagenous bone matrix proteins.
A new one-pot method for the synthesis of alpha-siloxyamides is described. The three substrates, H-C(CN)(2)O-SiMe(2)t-Bu, aldehydes or ketones, and primary or secondary amines, are simply mixed in one portion in acetonitrile or ether; the alpha-siloxyamides are obtained within short peroids in excellent yields in many cases. As a demonstration of our method, the synthesis of (-)-bestatin was carried out.
[figure: see text] A reliable and rigid spacer, trans,trans,trans-perhydronaphthacene, for molecular tweezers was designed. A synthesis and molecular recognition study of its 1,14-disubstituted derivatives was carried out.
Asymmetric synthesis of a trichothecane analogue, 4-deoxyverrucarol (2), was carried out through two types of ring expansion reactions. First, synthesis of the racemate of 2 was investigated. Thus, 1-[1-(tert-butyldimethylsiloxy)-ethyl]-1-methoxycarbonyl-2-hexen-4-on e (10), prepared by Diels-Alder reaction, was converted into the cyclopropylidene 15. The cyclobutanone (+/-)-18 was obtained from 15 via dihydroxylation, followed by successive treatments with SO(2)Cl(2) in the presence of imidazole and Florisil. After transformation of (+/-)-18 into the vinylcyclobutanol (+/-)-19, the second ring expansion reaction was performed with Pd(OAc)(2) to provide the cyclopentanone (+/-)-20. The product was converted into the racemate of 4-deoxyverrucarol (2) through the cyclohexenone (+/-)-22, but the diastereoselectivity during the introduction of the double bond was unsatisfactory. The selectivity was improved in the case of the asymmetric synthesis. The optically active cyclobutanone (+)-18 was prepared via AD reaction of 15 with 73% ee. After the transformation of (+)-18 into the cyclohexanone (-)-30 through the palladium-mediated ring expansion reaction, (-)-30 was subjected to the diastereoselective deprotonation reaction using the chiral amide. The key synthetic intermediate (-)-25 of 4-deoxyverrucarol (2) was synthesized in an optically pure form by taking advantage of a kind of kinetic resolution that occurred during the deprotonation step.
The efficacy and safety of microwave coagulation therapy (MCT) in patients with hepatocellular carcinoma (HCC) and impaired hepatic reserve were studied. Preoperative background factors, postoperative results, and prognostic factors were compared in 51 patients who underwent hepatic resection (HR group) and 38 patients who underwent microwave coagulation therapy (MCT group). Before surgery, measures of hepatic function, including level of albumin (P = 0.0072), prothrombin time (P<0.0001), hepaplastin test (P = 0.0088), and the radioactivity of technetium-99m galactosyl-human serum albumin 15 min in the liver after injection divided by that in both liver and heart (P <0.0001) were significantly lower in the MCT group than in the HR group. The indocyanine green dye retention rate at 15 min was significantly greater (P<0.0001) in the MCT group than in the HR group, and a significant difference was noted in Child-Pugh grade between the groups (P<0.0001). Operative time (P = 0.0014) and blood loss during surgery (P = 0.0005) were significantly lower in the MCT group than in the HR group. In contrast, no significant differences were recognized between the groups in the changes in postoperative liver function, or in the rates of morbidity, mortality, local recurrence, and survival. Moreover, the type of treatment (HR or MCT) was not a prognostic factor. The results indicate that MCT can be used safely as an alternative to hepatic resection in patients with poor liver function without reducing the efficacy of local control.
Spider mite biology and control in Japan were reviewed. Seventy-eight spider mite species of 16 genera (Family Tetranychidae) have been recorded in Japan. Several of the species recently described were separated from a species complex comprising strains with different ecological performance such as host range. These separations were first supported by crossing experiments and then confirmed by molecular genetic studies. Spider mite control in Japan is still dependent on heavy acaricide spraying in order to attain products of extremely high quality. The commercial use of natural enemies in spider mite management has just started.
The evaluation of the Gd-carborane complex 2 as an MR imaging and boron carrier agent was carried out in vivo using tumor-bearing Donryu rats, MRI, ICP-AES, and alpha-autoradiography. The MR imaging revealed that the carborane Gd-DTPA 2 was metabolized slower in the body than Gd-DTPA 1. The results of the ICP-AES method indicated that compound 2 was incorporated into normal tissues and metabolized quickly, whereas it was not accumulated into tumor or brain tissue. The alpha-autoradiography showed that a high level of boron was obtained in the internal organs and in the necrosis of tumor tissue.
The palladium catalyzed nucleophilic substitution of alpha-bromo-alpha,alpha-difluoroallyl derivatives turned out to be an efficient method for the preparation of several fluorinated organic molecules. Several soft carbon nucleophiles regioselectively reacted with 3-bromo-3,3-difluoropropene (BDFP) to give the 3-substituted 1,1-difluoroalkenes. Phenylzinc chloride and tributylphenyltin afforded 1-fluoro-1,3-diphenylpropene. The radical bromination of 3-substituted 1,1-difluoroalkenes provided 1-substituted BDFPs, and a 1-substituted BDFP reacted with carbon nucleophiles to give 1,3-disubstituted 3,3-difluoroalkenes. For the reaction of nitrogen nucleophiles with BDFP, an amine and the sodium salts of the carbamates reacted with BDFP at the gamma-position. However, the sodium salts of the sulfoneamide predominantly attacked at the alpha-position.
We have recently found that the infection with herpes simplex virus type-1 (HSV-1) of primary sensory neurons induces nociceptive hypersensitivity to noxious mechanical (hyperalgesia) and tactile stimulation (allodynia) in mice. In the present experiments, we determined the distribution of HSV-1 in the dorsal root ganglia and examined the effects of four analgesic agents on hyperalgesia and allodynia. HSV-1 was inoculated on the unilateral shin. HSV-antigen-positive cells were detected in the L4 and L5 dorsal root ganglia on days 5 and 7, but not day 3, post-inoculation. About 80% of the positive cells were small in size. Allodynia and hyperalgesia appeared on day 5 post-inoculation. Antinociceptive effects of analgesic agents were examined on day 6 post-inoculation. Morphine (1-5 mg/kg, subcutaneous) and gabapentin (10-100 mg/kg, peroral) dose-dependently inhibited both allodynia and hyperalgesia. Diclofenac (10-100 mg/kg, intraperitoneal) also produced antinociceptive effects, but there was a ceiling for the effect on hyperalgesia. Amitriptyline (3, 10 mg/kg, subcutaneous) did not affect allodynia and hyperalgesia. The results suggest that mechanical allodynia and hyperalgesia appeared when HSV-1 proliferated in the sensory neurons. This mouse model may be useful for studying the mechanisms of acute herpetic pain and anti-neuropathic pain agents.
In patients with accelerated (malignant) hypertension, end-organ damage is the determinant factor for prognosis. Although recent advances in antihypertensive therapy have improved the outcome of patients with accelerated hypertension, the effectiveness of antihypertensive therapy still remains less convinced. In this study, we followed 13 patients clinically diagnosed with accelerated hypertension (defined as diastolic blood pressure > 130 mmHg, retinopathy with K-W IV and accelerated renal impairment) for 3 yr. One patient died due to acute myocardial infarction arising from poor compliance with antihypertensive therapy. One patient was maintained on hemodialysis for 3 yr. One patient was introduced for continuous ambulatory peritoneal dialysis (CAPD) for a year and then lived without dialysis therapy. The remaining 10 patients were followed for 3 yr. All patients were initially treated with intravenous administration of calcium antagonist for reduction of blood pressure, followed by hemodialysis therapy if needed. After stabilization of blood pressure, combination therapy with extended release nifedipine (40 to 80 mg daily) and arotinolol (20 mg daily) was started. The targets for blood pressure control were a systolic pressure of 135 mmHg and a diastolic pressure of 80 mmHg. If blood pressure control was unsatisfactory, guanabenz (2 to 4 mg before bedtime), a central acting drug, was added. At presentation, the mean diastolic blood pressure (mDBP) among the 10 remaining patients was 134 +/- 2 mmHg, the mean serum creatinine (mScr) was 4.5 +/- 0.7 mg/dl and the left ventricular mass index (LVMi) as measured by echocardiography was 150 +/- 9 g/m2. At 1 yr, the mDBP was reduced to 90 +/- 3 mmHg, the mScr to 2.9 +/- 0.9 mg/dl and the LVMi to 140 +/- 9 g/m2. At 3 yr, the mDBP was stabilized at 79 +/- 3 mmHg, the mScr maintained at 2.2 +/- 0.4 mg/dl, and the LVMi reduced to 128 +/- 9 g/m2. These results indicate that appropriate blood pressure control is important for improvement of renal impairment and cardiac damage in patients with accelerated hypertension. Moreover, combination therapy with arotinolol and extended release nifedipine may be beneficial for this purpose.
Patient was an 18-year-old female student. After she had symptoms of common cold for 3 days, she developed somnolence, diplopia, dysarthria, urinary disturbance and ataxia. On admission neurological examination revealed coma with mydriasis, ophthalmoplegia, ptosis and weakness of the upper limbs. Light reflex, corneal reflex and oculocephalic test were all negative. Deep tendon reflexes were brisk and extensor toe signs were positive bilaterally. She did not have nuchal rigidity. Laboratory test revealed normal cerebrospinal fluid with negative myelin basic protein. Brain MRI, brainstem evoked potentials presented no abnormality. EMG revealed normal conduction velocity and no conduction block. EEG had diffuse theta and delta slowing. Culture of the stool represented no Campylobacter jejuni. At the fifth day of admission consciousness level improved, and other neurological findings disappeared in about 6 weeks. She had anti GQ 1 b, GT 1 a(IgG, IgM) and anti GM 1(IgM) antibodies in the serum. We made a diagnosis of Bickerstaff's brainstem encephalitis from these neurological symptoms and clinical course. The main lesion was present in the brainstem from midbrain to medulla oblongata in the midline. High titer of anti GT 1a antibody may be related to the ophthalmoplegia as noted in Miller Fisher syndrome. As a result of EMG and stool culture, it denied the complication of Guillain-Barré syndrome. We had no proof of the reason of the presentation of anti GM 1 antibody.
The beta-cholestane derivatives 1a-c bearing a cascade-type polyol, were newly synthesized. The release of fluorescent marker 6-CF [5(6)-carboxyfluorescein] encapsulated in the modified liposomes prepared from 1 was dramatically faster than that in the conventional liposomes prepared from cholesterol.
The effects of a combined therapy with a calcium channel antagonist and alphabeta-blocker in patients with accelerated-malignant hypertension on blood pressure and renal function were examined. Thirteen patients presented with the clinical features of malignant hypertension (diastolic blood pressure >130 mmHg, retinal damage and progressive renal failure) at our hospital, over the 3 yr period from 1995 to 1997. These patients were treated with both a calcium antagonist, 60-80 mg/d dose of long acting nifedipine, and an alphabeta-blocker, 20 mg/d dose of arotinolol, for over 12 mo. At admission, the average blood pressure of the patients was 233+/-8/144+/-3 mmHg. The level of serum creatinine in these patients was 6.2+/-1.0 mg/dl. Intermittent hemodialysis therapy was introduced in 7 patients. Three days after treatment, blood pressure decreased to 162+/-4/102+/-4 mmHg. A month later, blood pressure decreased to 148+/-3/89+/-2 mmHg and serum creatinine levels were 3.6+/-0.4 mg/dl. Renal function in these patients improved, and they completely recovered from renal dysfunction, allowing withdrawal of haemodialysis therapy. One year later, the blood pressure in all of these patients was well controlled and no further renal deterioration was observed, except in one patient. Despite the reduction in blood pressure, one patient was on hemodialysis three times a week after 8 mo of treatment. From these finding, it is concluded that combination therapy with a calcium antagonist and alphabeta-blocker is effective in both the reduction of highly elevated blood pressure and protection of the kidneys, resulting in amelioration of accelerated-malignant hypertension.
The progression of renal disease is reported to be more rapid in male patients than in premenopausal females. However, few studies compare the difference in dialysis therapy between males and females. We compared the efficacy of peritoneal dialysis capacity, using measurements of retention volume and pelvic cavity by helical section of computed tomography (CT) in 6 male and 6 female patients. The patients did not differ significantly in age (males: 54 +/- 3 years; female: 56 +/- 4 years). Males were heavier than females (p < 0.05). Retention volume in the visceral cavity was significantly larger in males (1787 +/- 43 mL) than in females (1580 +/- 59 mL) (p < 0.05). Peritoneal dialysis capacity was evaluated by peritoneal equilibration test (PET). Although no significant differences were observed in the PET data, when the PET results at 4 hours were divided by body weight in kilograms, a significant difference between males and females was seen (p < 0.05). There was a mild, but not significant, correlation between the volume of the pelvis as measured by helical CT and the PET data per kilogram body weight (p = 0.07). These results suggest that gender differences in peritoneal dialysis capacity relate partially to the difference in pelvic cavity volume.
Laparoscopic cholecystectomy (LC) and endoscopic sphincterotomy (EST) are widely accepted procedures for cholecysto-choledocholithiasis in adults. However, their use in infants has not been reported. An 8-month-old girl presented with high fever and obstructive jaundice. Ultrasound scan showed acute cholecystitis with stones in the bile duct. After 2-week-long antibiotic therapy the acute cholecystitis and hepatic impairment resolved. An endoscopic retrograde cholangiopancreatography (ERCP) confirmed choledocholithiasis and cholecystolithiasis. Risk factors for the development of biliary calculi were not detected. One month after the restoration of her liver function, she underwent EST using a side-viewing endoscope with a small sphincterotome. A common bile duct stone was extracted using a basket catheter. LC was then carried out. The time interval between the EST and LC was 34 days. No complications have been noted for 6 months.
A one-year-and-ten-months-old male infant with Arima syndrome, a very rare genetic disorder, underwent urgent insertion of a catheter for continuous ambulatory peritoneal dialysis (CAPD) under general anaesthesia. During the procedure he showed QRS-interval changes caused by hyperkalaemia which was successfully treated with calcium gluconate. The management and intraoperative complications of this syndrome are reported and available literature reviewed.
A 41-year-old female was admitted to our hospital with acute renal failure. The renal biopsy showed focal necrotizing crescentic glomerulonephritis, and her serology revealed a high titer of MPO-ANCA. The diagnosis of MPO-ANCA-associated microscopic polyarteritis was made, and her basic illness proved to be systemic lupus erythematosus (SLE) because of renal injury, polyarteritis, pancytopenia, anti-double-strand DNA antibody, and anti-nuclear antibodies. After treatment with prednisolone (PSL) and cyclophosphamide, her renal function improved and her MOP ANCA titer was lowered. After 2 years, she was readmitted due to dyspnea. Chest X-ray and echocardiography revealed pericarditis and bilateral pleural effusion. Renal biopsy was carried out again because of an increase in MPO-ANCA, which showed minor abnormalities. PSL therapy led to remission of pericarditis, resulting in a decrease in MPO-ANCA. In this case, MPO-ANCA is likely to be associated not with the activity of polyarteritis, but with that of SLE, and care should be taken in evaluating the clinical usefulness of MPO-ANCA in cases with SLE.
Hydroxylforms of boronophenylalanine (BPA) were synthesized by conjugation with a cascade of polyols to decrease the BPA uptake of normal parenchyma without affecting uptake into the tumor. We determined their tumor cell killing effect on boron neutron capture therapy (BNCT) against BPA using the human glioma cell line T98G. The thermal neutron doses yielding the D37 (dose used to inhibit 63% colony formation) values of dl-p-BPA(OH)n were 1.45 x 10(12)nvt (n = 1), 1.33 x 10(12)nvt (n = 2), 3.37 x 10(12)nvt (n = 4), and 1.72 x 10(12)nvt (n = 0). The relative tumor cell killing effect on BNCT of dl-p-BPA(OH)n against dl-p-BPA, which was defined as the ratio of D37-BPA to D37-BPA(OH)n, was 1.18 (n = 1) 1.29 (n = 2), and 0.51 (n = 4). The tumor:normal brain ratio of dl-p-BPA(OH)n in 9L rat brain tumor models was improved 1.2- (n = 1) and 1.4-fold (n = 2) against that of dl-p-BPA without a decrease of its uptake into the tumor. The water solubility of BPA(OH)n increased against BPA, and the toxicity represented as the IC50 value of dl-p-BPA(OH)2 was nearly one half that of dl-p-BPA, being established in our previous works. Hydroxylforms of BPA, especially dl-p-BPA(OH)2, might be more suitable boron carriers of BNCT to malignant brain tumors since the radiation injury to the normal parenchyma surrounding the tumor is reduced.