Functional and morphologic characterization of renal subcapsular islet isografts in rats treated with FK 506.
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Biomedical subjects
Publications and source records attributed to S Ikeda.
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We reported a case of opsoclonus-myoclonus syndrome. A 63-year-old man was admitted to Kenwakai Hospital with rapidly progressing symptoms, including lumbago, whole body pain, vertigo, nausea, and anorexia. He became bed-ridden because of severe vertigo and truncal ataxia. Five days after admission, he developed opsoclonus followed by myoclonus and mild disturbance of consciousness, but he showed no appendicular ataxia or pyramidal tract sign. He was treated with prednisolone, 40 mg/day, which was effective for disturbance of consciousness, but opsoclonus and myoclonus persisted. He died of liver dysfunction and ventricular fibrillation 3 weeks after onset. Blood examination revealed high LDH (1,106 IU/l), Al-P, and gamma-GTP titers. Tumor markers were normal except for increase NSE activity (129 ng/ml). The cerebrospinal fluid showed normal cell count, 63.9 mg/dl of protein, 7.3 mg/dl of IgG, and normal glucose. A cranial CT scan showed an old lacune only. Chest rentgenogram and CT scan revealed mediastinal and hilar lymph node enlargement. An abdominal CT scan showed multiple low density masses in the liver. Small cell lung cancer associated with opsoclonus-myoclonus syndrome was suspected. Western blot analysis revealed that his serum reacted with protein in the cerebellum, cerebrum, and dorsal root ganglion with a molecular weight of 77 kDa. This is the first time such an antibody was ever been detected in patients with opsoclonus-myoclonus syndrome. The molecular weights of the antigens previously found by the serum of patients with this syndrome, were 55 kDa and 80 kDa in patients with breast cancer, and 210 kDa in patients with neuroblastoma.(ABSTRACT TRUNCATED AT 250 WORDS)
The synthesis of 3-cyclopentyl-1-adamantanamines and adamantanemethanamines and some of their thioureas is described. The antiviral activity examination of these compounds indicated that some of them inhibited Respiratory Syncytial Virus (RSV) infection at concentrations that were slightly (up to 5-fold) lower than the cytotoxic concentration. Behavioral and convulsions studies of the above mentioned amines, in mice, did not show any dopaminomimetic activity and argue in favor of the existence of a glutamatergic component in the action of these derivatives.
The authors describe a case of pulmonary tuberculosis with multiple drug resistance and complicated by severe idiopathic thrombocytopenic purpura (ITP). The patient was initially treated with high-dose gamma globulin therapy and splenectomy. These procedures resulted in improvement of the patient's condition; the platelet count increased from 7,000/mm3 to 230,000/mm3 and the bleeding time fell from 15 min to 1 min 30 s. Given the significant improvement in the patient's condition, it was considered safe to carry out left pulmonary upper lobectomy and thoracoplasty. There have been no reports describing pulmonary resection performed for inflammatory lung disease in patients with ITP. High-dose gamma globulin therapy rapidly brings about an increase in the platelet count and a reduction of the bleeding time, and it thus extremely useful as preoperative treatment in surgical cases complicated by thrombocytopenia.
Familial amyloid polyneuropathy type IV (Finnish type, FAP IV) is one form of hereditary generalized amyloidosis with autosomal dominant trait and is characterized clinically by a triad of corneal lattice dystrophy, caudal cranial neuropathy and various skin changes. The vast majority of the families with this disorder originated from Finland. We carried out a clinicopathological study of a large FAP IV kindred recently found in Japan. This family consisted of 73 members in 5 generations with 17 affected individuals and 7 of them (ages 45 to 73) were examined in detail. All patients showed typical clinical manifestations, lacking significant peripheral neuropathy in the limbs. However, autonomic dysfunctions including orthostatic fainting and dysuria were seen in 2 patients. Congophilic amyloid deposits were commonly observed in an aspiration biopsy of abdominal fat tissues, and noradrenergic nerve fibers of the rectal mucosa were reduced in one patient with autonomic symptoms. DNA analysis using PCR revealed a single base change (G to A) at nucleotide position 654 of the gelsolin gene in 7 patients and one asymptomatic individual. The clinical pictures and gene abnormality in this Japanese family are very similar to those reported in Finland. Moreover, this study added that autonomic nerves might be involved in FAP IV patients at the advanced stage.
For the purpose to assess tumor-selectivity of doxifluridine (5'-DFUR), an anticancer drug of fluorinated pyrimidine class, the authors conducted a clinical-pharmacological study with the drug. The subjects in the present study, 26 patients with colorectal cancer received surgeries, were preoperatively administered 5'-DFUR orally at either doses of 800 or 1,200 mg/day for 3 days followed by oral administration of the drug at a dose of 400 mg 4-6 hrs before operation. The tissues were collected from specimens removed at operations and we measured both the activities of pyrimidine nucleoside phosphorylase (PyNPase), an activating enzyme for 5'-DFUR, and 5-FU concentrations in the tissue samples. The PyNPase activities showed higher levels in tumor tissues and regional lymph nodes than in normal tissues adjacent to the tumors. The 5-FU concentrations were: 102.7 ng/g in tumor tissues, 12.5 ng/g in normal tissues adjacent to the tumors, 97.6 ng/g in metastatic lymph nodes, and 7.3 ng/g in normal lymph nodes. In other words, the 5-FU concentrations were significantly (p < 0.01) higher in either of tumor tissues and metastatic lymph nodes than in the rests. The 5-FU concentrations in the sera were also extremely low. The results above clearly indicate that 5'-DFUR has a high selectivity for tumors.
A 46-year-old woman who noticed tightness of the skin in September, 1993, was admitted to a local hospital due to hypertension, congestive heart failure and renal dysfunction on the 2nd of November. After admission, renal function deteriorated progressively. A diagnosis of scleroderma renal crisis (SRC) was suspected from her skin biopsy and clinical course. She was referred to our hospital for further evaluation and maintenance of hemodialysis. Her blood pressure was kept normal by anti-hypertensive drugs including cilazapril. Acute interstitial pneumonia, microangiopathic hemolytic anemia and thrombocytopenia appeared during her clinical course. Corticosteroid therapy was effective for acute interstitial pneumonia, but in-effective for thrombocytopenia. Plasma exchange was not effective for thrombocytopenia, which was successfully treated with intravenous gamma-globulin therapy. She died of cytomegaloviral encephalitis, which might have resulted from immunodeficiency caused by prolonged corticosteroid therapy and uremia. Complications other than SRC might have appeared during the clinical course based on the immune disorder of progressive systemic sclerosis itself. In order to improve the prognosis of patients with SRC such complications should be detected promptly and treated correctly.
In 105 patients with primary lung cancer who were operated on, the rate of diagnosis of mediastinal lymph node metastasis was determined, and the results of CT scanning and mediastinoscopy were compared. The rate of accuracy of mediastinoscopy was 93.8%, considerably higher than that of CT, which was less than 85%. For the lymph nodes other than #7, which indicate contralateral metastasis, the rate of accuracy of mediastinoscopy was even better and reached 96.3%. In the 9 patients who were proved by mediastinoscopy to have contralateral lymph node metastasis, the rate of accuracy of CT was only 44%. Mediastinoscopy was very effective in the diagnosis of mediastinal lymph node metastases from primary lung cancers.
A 24-day-old female newborn with persistent jaundice and acholic stool was diagnosed by laparoscopic cholecystcholangiogram. A catheter was inserted through a small incision at the fundus of the gallbladder. With definitive diagnosis of biliary atresia, laparotomy was performed, and Kasai's operation was carried out successfully.
The significance of preoperative N factor assessment in T1 lung cancer and the need for mediastinal node dissection in T1 N0 M0 cases were investigated. The results of mediastinoscopy were evaluated in patients with T1 adenocarcinoma or squamous cell carcinoma who underwent preoperative mediastinoscopy and thoracotomy from 1971 to 1991 (n = 164). Mediastinoscopy gave true negative results in 90% of patients, false negative in 1%, and true positive in 9%. The 5-year survival was 90% for patients with T1 N0 M0 disease who underwent nonradical dissection (n = 64) and 70% for those who underwent radical dissection (n = 61), indicating that the prognosis was significantly better (p < 0.05) with nonradical dissection. Distant metastasis was a common cause of death, and no death was related to local recurrence, whether nonradical or radical dissection had been performed. The results strongly suggest that preoperative mediastinoscopy and intraoperative node sampling are sufficient for assessment of N factors in T1 lung cancer. The possible relation between immunologic functional changes associated with mediastinal lymph node dissection and the prognosis in patients without evidence of positive lymph nodes should be clarified by a prospective randomized study.
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Recombinant mitochondrial transcription factor 1 (r-mtTF1) was overproduced in Escherichia coli, and purified to near homogeneity by DNA affinity chromatography. Binding affinities of r-mtTF1 to the light strand promoter (LSP) and heavy strand promoter (HSP) of human mitochondrial DNA and a non-promoter fragment derived from pUC vector were quantitatively measured by electrophoretic mobility shift assay. The order of the affinities for these DNAs estimated by competition experiments was LSP > HSP = pUC, which was essentially the same as that of transcriptional activity from each promoter in vitro. Recombinant mtTF1 bound more tightly to supercoiled or relaxed DNA than to linear DNA, moreover to single-stranded DNA with the same affinity for linear DNA. The results suggest that the mechanism of activation of HSP by mtTF1 is different from that of LSP, and that multiple binding of mtTF1 to mitochondrial DNA, in a non-specific manner, may significantly participate in activation of transcription from HSP and replication of mitochondrial DNA.
The present study describes the pharmacological profile of an endothelin (ET) receptor antagonist, TAK-044, in anesthetized rats. TAK-044 given 10 min before administration of ET-1 (0.3 nmol/kg i.v.) partially inhibited the ET-1-induced pressor response at 0.1 and 1 mg/kg i.v. and almost completely inhibited the response at a dose of 10 mg/kg. The transient depressor response induced by ET-1 was also inhibited by 1 and 10 mg/kg TAK-044. BQ-123 partially inhibited the pressor response at 0.1-10 mg/kg i.v., whereas it did not inhibit the depressor response except at a dose of 10 mg/kg. These inhibitory effects of TAK-044 were longer lasting than those of BQ-123: 3 hr for TAK-044 and 1 hr for BQ-123 at 10 mg/kg. A selective ETB agonist, sarafotoxin S6c (0.3 nmol/kg i.v.), induced both depressor and pressor responses similar to ET-1. The initial depressor response was inhibited by TAK-044 in a dose-dependent manner (0.1-10 mg/kg i.v.) and by BQ-123 at the highest dose, whereas the sustained pressor response was inhibited only by TAK-044 at a dose of 10 mg/kg. Similar differences between TAK-044 and BQ-123 were observed for sarafotoxin S6c-induced renal vasoconstriction: TAK-044 but not BQ-123 inhibited the response at a dose of 3 mg/kg i.v. We conclude that TAK-044 inhibited both ETA- and ETB-mediated blood pressure responses and that these effects were longer lasting than those of BQ-123. In addition, the ETB-mediated vasoconstriction and pressor responses were inhibited by TAK-044 and not by BQ-123.
Effect of heparin and low-molecular-weight heparin (LMWH) were evaluated on 15 patients with proliferative glomerulonephritis with various degrees of sclerosing legion. Five cases were subcutaneously administered with 7000 to 11000 units of heparin for 4 weeks. Ten cases were administered with 60 unit/kg of LMWH by drip infusion for 4 weeks. Eleven cases were treated with prednisolone and all cases were treated with anti-platelet agent as well. Urinary protein excretion reduced from 3.0 +/- 1.8 to 1.8 +/- 0.6 g/day in the heparin-treated group and from 2.4 +/- 1.9 to 1.8 +/- 1.4 g/day in the LMWH-treated group, respectively. There were no remarkable changes in the renal functions of both groups. In one case, both heparin and LMWH brought about reduction of proteinuria. Therefore, LMWH reduced urinary protein excretion by the same mechanism as heparin. The LMWH has an advantage over heparin in that the former has less risk of causing bleeding. We conclude that heparin and LMWH reduce proteinuria in some patients with proliferative glomerulonephritis. The LMWH is beneficial in the treatment of proliferative glomerulonephritis with a sclerosing lesion.
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A 58-year-old man with a solitary plasmacytoma of the chest wall is reported. He was admitted because of a painless tumor on the right lateral chest wall. The chest CT scan showed a chest wall tumor surrounding the 7th and 8th ribs without rib destruction. A transcutaneous needle biopsy of the tumor with a Sure-Cut-Needle revealed a plasmacytoma. The bone marrow biopsy findings were normal. Under a diagnosis of solitary plasmacytoma, the chest wall tumor was resected. The tumor was an extramedullary plasmacytoma. Southern blot analysis of the immunoglobulin light chain gene of the tumor cells detected a rearrangement of genes in the lambda chain, while no rearrangements of immunoglobulin genes were detected in the bone marrow specimen. Seven months later another solitary plasmacytoma was found at the left radius, and was resected. Southern blot analysis of the immunoglobulin light chain gene was useful in the differential diagnosis from systemic myeloma and in determining the monoclonality of the tumor.
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