Protective effects of nicotinamide on renal subcapsular islet isografts with a marginal mass from sustained hyperglycemia in the streptozotocin-induced diabetic rats.
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Animals↗
Biomedical subjects
S Ikeda
Publications and source records attributed to S Ikeda.
A potential solution for the shortage of donors in islet transplantation using a novel oral antidiabetic agent, troglitazone.
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Administration, Oral↗
[Reevaluation of precancerous lesions of the skin].
Precancerous skin lesions are categorized into three groups; (1) carcinoma in situ, (2) hereditary precancerous lesions, and (3) non-hereditary precancerous lesions. Carcinoma in situ includes Bowen's disease, actinic keratosis and leukoplakia as squamous cell carcinoma in situ, Paget's disease as adenocarcinoma in situ, and melanoma in situ. Hereditary precancerous lesions include xeroderma pigmentosum, epidermodysplasia verruciformis and porokeratosis. The mechanisms of carcinogenesis in these diseases are investigated intensively. Chronic radiodermatitis and other scars are treated as non-hereditary precancerous lesions.
Humans↗
[A patient with Kennedy-Alter-Sung syndrome showing cardiomyopathy].
A 31-year-old man with a history of progressive muscular atrophy and weakness from around 22 years of age, recently experienced arrhythmia. On examination he showed gynecomastia and slight proximal weakness in both upper and lower extremities. Androgen receptor gene analysis showed an increased number of tandem CAG repeats in exon 1, thus leading to a diagnosis of Kennedy-Alter-Sung (KAS) syndrome. Cardiological investigations including echocardiography, scintigraphy and catheterization disclosed dilated cardiomyopathy. Cardiac muscle biopsy showed myocardial cell degeneration. KAS syndrome is causatively related to androgen receptor gene abnormality. This receptor is widely distributed throughout human body, including the genital tract, spinal cord, liver, and heart. Androgen receptor dysfunction may induce cardiac muscle involvement in patients with KAS syndrome, producing the previously unknown pathophysiology of cardiomyopathy.
Adult↗
Characterization of human proteins that bind the repeated sequences in the squirrel monkey retrovirus enhancer.
We have recently identified two different human DNA-binding proteins, SMBP1 (35 kDa) and SMBP2 (17 kDa), that specifically interact with the direct repeats of the enhancer sequence in the squirrel monkey retrovirus long terminal repeat. Herein, we report several biochemical properties of the human DNA-binding proteins. SMBP1 and 2 recognized an overlapped sequence of the 5' region of the repeat which contains a palindrome of CCAATGG. Both proteins required divalent cations such as Mg2+ and Ca2+ for their specific DNA binding at the optimum concentration of 1 mM. SMBP2 is a thermostable protein that binds tightly to the DNA sequence even by treatment at 80 degrees C for 15 min. The SMBP2-DNA complex was also stable in the presence of 300 mM NaCl. The resistance of SMBP2 to heat and salt treatment is a prominent character distinguishable from SMBP1 and other known transcriptional factors. SMBP1 and 2 can be easily separated by heparin-agarose chromatography. These DNA-binding proteins were found to be present in nuclear extracts from several human cell lines including T cell, B cell, and epithelial cell.
Animals↗
[Variable clinical manifestations of familial amyloid polyneuropathy and living related liver transplantation].
Familial amyloid polyneuropathy (FAP) is clinically characterized by polyneuropathy and autonomic failure but it shows diverse clinical pictures in different families. We presented clinical and molecular biological findings for a peculiar family in which type I FAP and spinocerebellar ataxia type 1 (SCA-1) coexist. Type IV FAP which is also called familial amyloidosis, Finnish type (FAF), shows the triad of corneal lattice dystrophy, cranial neuropathy and various skin changes. Recently, 3 FAF families were reported in our country, and their clinical pictures and gene abnormalities closely resembled those seen in Finnish patients with this disease. FAP had long been considered to be a genetically determined incurable disorder. Since it has been shown that the precursors of amyloid fibrils (variant forms of transthyretin) in this disorder are produced mainly in the liver, successful results of liver transplantation (LT) were reported in several countries. In our country there are many FAP patients, but LT from a cadaveric donor is still not possible. We, therefore, performed a partial LT for 3 FAP patients using a graft taken from healthy family members, resulting in good outcomes. It seems likely that this partial LT is a very promising therapeutic approach for FAP patients.
Amyloid Neuropathies↗
[Correlative study of the brain CT and clinical features of patients with Down's syndrome in three clinical stages of Alzheimer type dementia].
Patients with Down's syndrome often develop Alzheimer type neuropathological changes as well as dementia of the Alzheimer type after the age of 40. We studied brain CT findings in relation to three clinical stages of Alzheimer type dementia in 11 patients with Down's syndrome aged from 17 to 55 years. In addition, 123I-IMP-SPECT was studied in 4 of these patients. Dementia of the Alzheimer type was present in 9 patients; 5 patients were in the early stage, 2 were in the progressive stage, and the other 2 were in the end stage. The earliest CT finding was enlargement of the suprasellar cistern, which indicated atrophy of the medial temporal lobe including the hippocampus and amygdala. This finding was not present in non-demented individuals with Down's syndrome. Moreover, CT scans showed that brain atrophy progressed to the temporal, frontal lobe, and then generalized cerebral cortices, which correlated clinically with the severity of dementia. Studies of 123I-IMP-SPECT in two patients with mild dementia revealed abnormally decreased isotope uptake in the temporal and posterior parietal regions. We suggest to measure the size of the suprasellar cistern in CT and SPECT scans for early detection and diagnosis of mild dementia of the Alzheimer type in patients with Down's syndrome.
Adolescent↗
[The inferior epigastric artery as a coronary artery bypass graft].
From January 1992 through December 1993, 31 patients underwent myocardial revascularization with the inferior epigastric artery (IEA) graft. There were one emergency case and four coronary reoperation cases. IEA grafts were taken down through the left side paramedian incision and dilated with papaverine hydrochloride solution. The distal anastomoses were made to left anterior descending (3 cases), diagonal (14 cases), obtuse marginal (9 cases), postero-lateral (I case) and right coronary artery (4 cases). The proximal anastomoses were made to the aorta (22 cases), the hood of a new vein graft (4 cases) and the hood of an old vein graft (4 cases). When IEA was not long enough to reach the ascending aorta, it was anastomosed to the internal thoracic artery (2 cases) or the gastroepiploic artery (1 case) graft. There was one hospital death, and early patency rate (within one month) was 90% (19/21). The postoperative angiography performed at 1.3 years or 2 years showed excellent IEA graft patency. These results suggested that the IEA is suitable as a coronary artery bypass graft. Further long-term patency must be evaluated.
Adult↗
[Positive expression of c-myc and p53 products in two cases of pulmonary sclerosing hemangioma].
The c-myc and p53 genes are thought to be an oncogene and a tumor suppressor gene, respectively. These genes' products are characteristic of malignant tumors. We quantitatively analyzed the c-myc and p53 products by flow cytometry in two cases of pulmonary sclerosing hemangioma. In case 1, 32.3% of the tumor cells were found to have the c-myc product, and 8.9% were found to have the p53 product. In case 2, 6.7% of the tumor cells were found to have the c-myc product and 15.5% were found to have the p53 product. The percentages in both cases were twice as high as those in a negative control lymphocytes stained with c-myc and p53 products. Therefore, these two cases showed positive expression of the c-myc and p53 products. In addition DNA from six other patients with sclerosing hemangioma was analyzed with paraffin-embedded sections. All six had DNA diploidy, with DNA indexes ranging from 0.91 to 1.03 and coefficients of variation ranging from 3.0 to 5.5. We suggest that pulmonary sclerosing hemangioma is a very weakly malignant tumor.
Adult↗
Setting of a low price CCD camera on the view window of TEM for printing out electron diffraction patterns.
In order to print out electron diffraction patterns quickly, an industrial CCD camera is conveniently set on the view window of an electron microscope. Although the observed pattern on the camera is distorted since the view direction has an angle of 41.5 degrees from the normal of the screen, however, the printed pattern is successfully restored to the correct one by varying the aspect ratio from 3:4 for the CCD camera to 1:1 for the printer. Note that cos(41.5) = 3/4. The camera used has a sensitivity of 1 lux. The aperture ratio of the lens is F 1.4, and the focal length is 50 mm.
Costs and Cost Analysis↗
Heterodimeric deoxyguanosine kinase/deoxyadenosine kinase of Lactobacillus acidophilus R-26: heterotropic activation of deoxyadenosine kinase subunit implicated by limited proteolysis and affinity labeling.
The deoxyguanosine (dGuo) kinase/deoxyadenosine (dAdo) kinase complex of Lactobacillus has been purified to homogeneity by using a newly constructed dATP-Sepharose column as a final step (2700-fold purification). A heterodimeric structure for the complex has recently been established [Ikeda et al. (1994) Biochemistry 33, 5328-5334]. On the basis of the kinetic and structural data accumulated so far, a model for the heterotropic activation of the dAdo kinase subunit by dGuo or dGTP is proposed: (1) there is an intrinsic difference in the enzyme conformation of the two subunits, with the dAdo kinase subunit being in a constrained (closed) state and the counterpart dGuo kinase subunit being in a relaxed (open) state, as reflected in their relative Vmax values and in the presence or absence of heterotropic activation, and (2) the conformational change induced by the binding of dGuo or dGTP to the active site of the dGuo kinase subunit causes the activation of the dAdo kinase subunit through subunit--subunit interactions. These proposed mechanisms are strongly supported by the following new findings made in this work: (1) low concentrations of chaotropic agents such as guanidine--HCl were found to increase the Vmax of dAdo kinase up to 2-fold--in the same kinetic fashion, apparently, as the activation by dGuo--while showing no effect on dGuo kinase; (2) the proteolytic inactivation of dAdo kinase by trypsin is significantly slower than that of dGuo kinase, but its rate of inactivation is stimulated by dGTP to the same level as for dGuo kinase; (3) the activating effect of dGuo on dAdo kinase was abolished in the course of differential proteolytic inactivation of the dGuo kinase by trypsin in the presence of dATP; and (4) photoaffinity labeling with [8-14C]-8-azido-Ade produces a new species of kinase heterodimer in which the dAdo kinase subunit is permanently activated as a result of specific labeling of the dGuo kinase active site.
Enzyme Activation↗
Binding of [3H](+)-PN200-110 to aortic membranes from normotensive and spontaneously hypertensive rats.
We report here the quantitative evaluation of binding density (Bmax) of [3H](+)-PN200-110 in aortic membranes obtained from spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) rats. At both 4 and 13 weeks of age, there were no significant differences in Bmax and the dissociation constants (Kd) of [3H](+)-PN200-110 binding between SHR and WKY rat aortas. Irrespective of strain, the Kd increased and the Bmax decreased with age. These results suggest that the number of Ca2+ channels in aortas of SHR and WKY rats are not significantly different, even when hypertension is established in SHR.
Aging↗
Secretory cleavage site of Alzheimer amyloid precursor protein is heterogeneous in Down's syndrome brain.
A beta (beta/A4) is the major constituent of brain amyloid in Alzheimer's disease (AD), Down's syndrome (DS) and normal aged persons. This protein is presumably derived by normal proteolysis from a precursor protein (APP). In this study, C-terminal fragments of APP in a Tris/Triton soluble fraction were partially purified from DS brain by heparin-affinity and reverse phase chromatography, and analyzed by N-terminal amino acid sequencing after SDS polyacrylamide gel electrophoresis and Western blotting. We found at least six different C-terminal fragments including those with the entire A beta region. These results suggest that secretory processing of APP is heterogeneous and generates amyloidogenic C-terminal fragments.
Alzheimer Disease↗
Synthesis and antiviral activity evaluation of some aminoadamantane derivatives.
The synthesis of some spiro[cyclopropane-1,2'-adamantan]-2-amines and methanamines and some spiro[pyrrolidine-2,2'-adamantanes] is described. The title compounds were evaluated against a wide range of viruses (influenza A, influenza B, parainfluenza 3, RSV, HSV-1, TK- HSV-1, HSV-2, vaccinia, vesicular stomatitis, polio 1, coxsackie B4, sindbis, semliki forest, Reo 1, HIV-1, and HIV-2), and some of them (compounds 6b, 6c, 9a, 16a, 16b, and 17) inhibited the cytopathicity of influenza A virus at a concentration significantly lower than that of amantadine and also significantly lower than the concentrations at which they proved cytotoxic to the host cells. None of the new aminoadamantane derivatives was active against influenza B virus or any of the other viruses tested, which points to their specificity as anti-influenza A virus agents.
Adamantane↗
Secretory form of beta-amyloid precursor protein is much abundantly contained in the cerebral white matter in human brain.
To elucidate the metabolic process of beta-amyloid precursor proteins (APP) in cerebral gray and white matter of the human brain, we compared the content and characteristics of secretory APP between these two parts. The white matter contained much more secretory APP than the gray matter in both a control and a Down's syndrome brain, but no difference in the characteristics of the APP isoforms was detected. Our results suggest that, in the human brain, a considerable amount of APP is carried by axonal transport, during which some of the APP isoforms are processed to their secretory forms.
Aged↗
Antiviral activity of a sulphated polysaccharide from the red seaweed Nothogenia fastigiata.
The antiviral activity of polysaccharide fractions obtained from water extracts of the red seaweed Nothogenia fastigiata was investigated. Fraction F6, corresponding to a sulphated xylomannan, was found to inhibit efficiently the replication of herpes simplex virus type 1 (HSV-1). Furthermore, F6 selectively inhibited the replication of several other enveloped viruses including herpes simplex virus type 2, human cytomegalovirus (HCMV), respiratory syncytial virus, influenza A and B virus, Junin and Tacaribe virus and simian immunodeficiency virus. F6 was only weakly active against human immunodeficiency virus type 1 and 2. The mode of action of F6 against HSV-1 and HCMV could be ascribed to an inhibitory effect on virus adsorption.
Antiviral Agents↗
Heterodimeric deoxynucleoside kinases of Lactobacillus acidophilus R-26: functional assignment of subunits using limited proteolysis controlled by end-product inhibitors.
Heterodimeric quaternary structures for two enzyme complexes from Lactobacillus acidophilus R-26 exhibiting deoxycytidine kinase/deoxyadenosine kinase (I) and deoxyguanosine kinase/deoxyadenosine kinase(II) activities have been proven by the following steps: (1) separation of each complex into two components on SDS-PAGE at pH 6.6; (2) N-terminal amino acid sequencing of each component; (3) functional assignment of each component by differential limited proteolysis. The third step was facilitated by the finding that the binding of a specific end-product inhibitor dNTP, to each kinase active site makes the corresponding kinase subunit resistant to trypsin, while leaving the heterologous kinase subunit susceptible to proteolysis. Analysis on SDS-PAGE has revealed only two fragments (15.8 and 11.0 kDa) following proteolysis of dCyd kinase/dAdo kinase (I) with trypsin in the presence of dATP. This may indicate that the kinase polypeptide chain (27.2 kDa) not protected by dNTP is cut by trypsin at a single specific site, with concomitant loss of activity. Thus, this work presents a unique approach to the clarification of structure and function of enzymes composed of heterologous subunits.
Amino Acid Sequence↗
Synthesis and antiviral activities of 8-alkynyl-, 8-alkenyl-, and 8-alkyl-2'-deoxyadenosine analogues.
Palladium-catalyzed cross-coupling of 8-bromo-2'-deoxyadenosine with terminal alkynes in the presence of copper(I) iodide in dimethylformamide resulted in a series of 8-(1-alkyn-1-yl)-2'-deoxyadenosines. Hydrogenation of alkynyl derivatives over 10% Pd/C under atmospheric pressure gave 8-n-alkyl analogues in nearly quantitative yields. On partial saturation of heptynyl, pentynyl, and propynyl derivatives over Lindlar catalyst, the corresponding cis-olefins were obtained along with minor amounts of trans isomers. Of the analogues tested, the following showed some activity, i.e. they were found to be active at concentrations that were at least 3-fold lower than the cytotoxic concentrations: the 8-heptynyl derivative against vaccinia virus (VV), vesicular stomatitis virus (VSV), cytomegalovirus (CMV), and respiratory syncytial virus (RSV); the 8-propyl derivative against varicella-zoster virus (VZV) and CMV; the 8-pentyl derivative against CMV; the 8-heptyl derivative against VV, CMV, RSV, and influenza A; and the 8-heptenyl derivative against VV, RSV, and influenza A. The unsubstituted 2'-deoxyadenosine did not show any antiviral effect, except against RSV. Except for 8-propyl-dA, the antivirally active dA analogues were rather inhibitory to the growth of human embryonic lung cells. The most cytotoxic was the 8-ethynyl derivative.
Adenosylhomocysteinase↗