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Biomedical subjects

S Ikeda

Publications and source records attributed to S Ikeda.

At least 19 recordsLinked to original sources
PubMed1996

Determining the origin of hematuria by immunocytochemical staining of erythrocytes in urine for Tamm-Horsfall protein.

PURPOSE: We analyzed the feasibility of immunocytochemical staining of urinary erythrocytes for Tamm-Horsfall protein to differentiate renal from nonrenal hematuria. MATERIALS AND METHODS: Urine samples collected from 74 patients with hematuria were evaluated. Erythrocytes in urine were inspected morphologically and the same samples were immunocytochemically stained with antibody against human Tamm-Horsfall protein. RESULTS: Erythrocytes in urine were clearly stained for Tamm-Horsfall protein in renal hematuria. Tamm-Horsfall protein immunocytochemistry was more consistent with clinical diagnosis than morphology. CONCLUSIONS: Immunocytochemical staining of urine erythrocytes for Tamm-Horsfall protein appears to be a reliable tool to differentiate renal from nonrenal hematuria.

Diabetic Nephropathies↗
PubMed1995

Metalloproteinase-mediated release of human Fas ligand.

Fas ligand (FasL) is a type II integral membrane protein homologous with tumor necrosis factor (TNF). Recent studies indicate that TNF is processed to yield the soluble cytokine by metalloproteinases at the cell surface of activated macrophages and T cells. In the present study, we investigated whether FasL is also released by metalloproteinases. Treatment with hydroxamic acid inhibitors of matrix metalloproteinases specifically led to accumulation of membrane-type FasL (p40) on the surface of human FasL cDNA transfectants and activated human T cells, as estimated by surface immunofluorescence and immunoprecipitation with newly established anti-human FasL monoclonal antibodies. This surface accumulation of mFasL was associated with the decrease of soluble FasL (p27) in the supernatant as estimated by quantitative ELISA and immunoprecipitation with anti-human FasL monoclonal antibodies. These results indicate that human FasL is efficiently released from the cell surface by metalloproteinases like TNF.

Animals↗
PubMed1995

Structure-function relationship of the eukaryotic DNA replication factor, proliferating cell nuclear antigen.

Proliferating cell nuclear antigen (PCNA) is essential for eukaryotic DNA replication and functions as a processivity factor of DNA polymerase delta (pol delta). Due to the functional and structural similarity with the beta-subunit of Escherichia coli DNA polymerase III, it has been proposed that PCNA would act as a molecular clamp during DNA synthesis. By site-directed mutagenesis and biochemical analyses, we have studied the functional domains of human PCNA required for stimulation of replication factor C (RF-C) ATPase and DNA synthesis by pol delta. Short deletions from either the N or C termini caused drastic changes in extraction and chromatographic behaviors, suggesting that both of these terminal regions are crucial to fold the tertiary structure of PCNA. The short C-terminal stretch from Lys254 to Glu256 is necessary for stimulation of RF-C ATPase activity, but not for stimulation of DNA synthesis by pol delta. Nine basic amino acids that are essential for activating DNA synthesis by pol delta are positioned at the internal alpha-helices of PCNA. This result is in good agreement with the observation that PCNA has a ring structure similar to the beta-subunit and clamps a template DNA through this positively charged internal surface. Several other charged amino acids are also required to stimulate either RF-C ATPase or pol delta DNA synthesis. Some of them are positioned at loops which are exposed on one of the side surface of PCNA adjacent to the C-terminal loop. In addition, the beta-sheets composing the intermolecular interface of the trimeric PCNA are important for interaction with pol delta. Therefore, the outer surface of PCNA has multiple functional surfaces which are responsible for the interaction with multiple factors. Furthermore, the two side surfaces seem to be functionally distinguishable, and this may determine the orientation of tracking PCNA along the DNA.

Adenosine Triphosphatases↗
PubMed1995

Secretion kinetics of Alzheimer's amyloid beta-protein differs from secreted beta-amyloid precursor protein.

Amyloid beta-protein (A beta) and secreted beta-amyloid precursor protein (sAPP), derived from beta-amyloid precursor protein (APP), are normally released by cultured mammalian cells. We investigated by pulse-chase analysis the secretion kinetics of these two APP derivatives using mouse cholinergic SN49 cell lines stably transfected with mouse APP695 cDNA. After both A beta and sAPP peaked at about the second hour, sAPP decreased with a half-life of approximately 5 hours, but A beta remained almost unchanged for at least 14 hours. These results indicate that A beta is more stable than sAPP in the SN49 conditioned medium.

Amyloid beta-Peptides↗
PubMed1995

Differential antiviral activity of derivatized dextrans.

The antiviral activity of water-soluble dextrans derivatized with varying percentages of carboxymethyl, benzylamide, and sulfonate groups was evaluated. Several of the polymers exhibited potent antiviral activity against a variety of enveloped viruses, but not against non-enveloped viruses, and only when present during virus adsorption. The mechanism of activity against retroviruses [i.e. human immunodeficiency virus (HIV)] and herpes viruses (i.e. human cytomegalovirus) could be ascribed to inhibition of virus binding to the cells. An absolute requirement for anti-HSV activity appeared to be a sufficiently high percentage of benzylamide and benzylamide sulfonate groups. This did not, however, apply for human cytomegalovirus, respiratory syncytial virus, and HIV. The sensitivity of the latter viruses appeared to be influenced by factors other than the global chemical composition, which leads us to assume that physical factors such as the distribution and sequence of the substituents on the sugar backbone play an important role in the antiviral activity of the derivatized dextrans.

Antiviral Agents↗
PubMed1995

Bilirubin is oxidized in rats treated with endotoxin and acts as a physiological antioxidant synergistically with ascorbic acid in vivo.

We examined the possibility that bilirubin physiologically acts as an antioxidant by using scurvy-prone ODS-od/od rats treated with endotoxin (lipopolysaccharide: LPS). Recently, bilirubin oxidative metabolites were isolated from human urine and named biotripyrrin-a and biotripyrrin-b. The LPS injection markedly increased bilirubin oxidative metabolites in urine of rats fed an ascorbic acid-free diet. This increase was supressed by feeding an adequate amount of ascorbic acid, a physiological antioxidant. the concentrations of biotripyrrin-a and -b in urine collected 6.5-10 h after the LPS injection were lower in rats fed an ascorbic acid-supplemented diet than in rats fed an ascorbic acid-free diet. Moreover, feeding with ascorbic acid suppressed the elevation of hepatic mRNA level of heme oxygenase-1, the rate-limiting enzyme of bilirubin biosynthesis, in rats injected with LPS. These findings suggest that bilirubin is oxidized in rats treated with LPS and acts as a physiological antioxidant synergistically with ascorbic acid in vivo.

Animals↗
PubMed1995

Synthesis and antiviral activity of benzyl-substituted imidazo [1,5-a]-1,3,5-triazine (5,8-diaza-7,9-dideazapurine) derivatives.

A variety of imidazo[1,5-a]-1,3,5-triazine derivatives carrying C-, O-, and S-benzyl and/or 4-methylbenzyl groups were synthesized and examined for their inhibitory effects on the replication of ortho- and paramyxoviruses. The key compounds 8-R-2-thioxo-2,3-dihydroimidazo [1,5-a]-1,3,5-triazin-4(1H)-ones 3a,b,d were synthesized by chlorotrimethylsilane/HMDS-effected cyclization--rearrangement of the corresponding 6-amino-5-(formylamino)-5-R-2-mercaptopyrimidin-4(5H)-ones 2a,b,d (R = benzyl, 4-methylbenzyl and 5-(benzyloxy)pentyl). Compounds 3a,b were further transformed into 4-thiones 5a,b and 4-dimethylamino derivatives 7a,b. Preparation of S-methyl, S-benzyl, and S-(4-methylbenzyl) derivatives 12-19 was carried out by the treatment of thioxo compounds 3b,d, 5b, and 8b in an alcohol/potassium carbonate system with methyl iodide or the appropriate aralkyl bromide. Simultaneous presence of the benzyl and thio structural units was found to be indispensable for any selective biological activity. Some 2-thio substituted compounds were specifically inhibitory to some viruses, e.g., 8-(4-methylbenzyl)-2-[(4-methylbenzyl) thio]imidazo[1,5-a]-1,3,5-triazin-4-one (13) and 8-[5-(benzyloxy)pentyl]-2-[(4-methylbenzyl)thio]imidazo [1,5-a]-1,3,5-triazin-4-one (15) inhibited influenza A virus at a concentration of 4.1 and 5.3 microM, and 2-(benzylthio)-6, 8-dimethylimidazo[1,5-a]-1,3,5-triazin-4-one (16) and 6, 8-dimethyl-2-[(4-methylbenzyl)thio]imidazo[1,5-a]1,3, 5-triazin-4-one (17) inhibited respiratory syncytial virus at a concentration of 21.9 and 15.7 microM, respectively, that is, at concentrations that were 20-50-fold lower than the cytotoxic concentrations. Compound 13 was inhibitory to respiratory syncytial virus at a concentration of 1.4 microM, that is, at a concentration that was 180-fold lower than the cytotoxic concentration to MDCK or Vero cells but only 7-fold lower than the cytotoxic concentration to HeLa cells. The 4-thiones 5a,b were nonselectively inhibitory to ortho-and paramyxoviruses at concentrations that coincided with their cytotoxic concentrations.

Animals↗
PubMed1995

The amelioration of hyperglycemia in streptozotocin-induced diabetic rats after the intraportal transplantation of an insufficient number of islets by nicotinamide treatment.

The purpose of the present study was to determine whether or not hyperglycemia in streptozotocin (STZ)-induced diabetic rats after the intraportal transplantation of an insufficient number of isogenic islets can be ameliorated by nicotinamide treatment. WKA/Qdj (RT 1u) rats were used both as donors and recipients. Islets were isolated by the collagenase technique. A total of 350 islets was transplanted into the liver via the portal vein of the STZ-induced diabetic rats. Either nicotinamide (NA, 0.5 g/kg) or a vehicle (saline) was administered ip once a day for 60 days after transplantation. All the diabetic rats without islet transplantation remained hyperglycemic irrespective of the NA treatment. All the recipients (n = 12) bearing the islet grafts and treated with saline remained hyperglycemic (> 400 mg/dl) at 60 days after transplantation. In marked contrast, all the recipients (n = 18) with islet grafts and treated with NA became normoglycemic (< 200 mg/dl) at 16.2 +/- 7.1 days (mean +/- SD) after transplantation. Morphologically, islets were easily found in the liver of the recipients. Aldehyde-fuchsin stain revealed that the beta cells in the islet grafts of the NA treated recipients were well granulated, whereas those treated with saline were degranulated. The insulin content of the liver bearing the grafts treated with either NA or saline was 116.3 +/- 26.0 micrograms/liver (n = 4) or 5.7 +/- 2.2 micrograms (n = 4), respectively, while that of 350 donor islets was 29.4 +/- 2.5 micrograms (n = 5). The insulin content of the pancreas in the NA- or saline-treated recipients was 27.3 +/- 10.6 micrograms/pancreas (n = 4) or 2.7 +/- 1.2 micrograms (n = 4), respectively, while those of the pancreas from the diabetic rats without transplantation was 1.9 +/- 0.7 micrograms (n = 4) or 1.6 +/- 0.8 micrograms (n = 5), respectively. These findings clearly demonstrate that the hyperglycemia in the STZ-diabetic recipients after transplantation of an insufficient number of islets can be ameliorated while, in addition, the islet mass in the liver as well as the endogenous pancreas both increase in size with nicotinamide treatment.

Animals↗
PubMed1995

Identification of two human sequence-specific DNA-binding proteins which interact with the direct repeats in the squirrel monkey retrovirus long terminal repeat.

Squirrel monkey retrovirus (SMRV) is a xenotropic endogenous virus of the squirrel monkey. The long terminal repeat of the SMRV contains four direct repeats (43 or 42 bp) with different degrees of perfection in the U3 region. Herein, we found two human nuclear proteins (SMBP1 and SMBP2) which bind specifically to the direct repeats with different affinities. The binding proteins recognize overlapped sequences in the 5' region of the repeats. SMBP1 and 2 are monomeric proteins of 35 and 17 kDa, respectively.

Animals↗
PubMed1995

3-deaza- and 7-deaza-5'-noraristeromycin and their antiviral properties.

An enantiospecific synthesis of 3-deaza-5'-noraristeromycin as its dihydrochloride ((-)-6) has been accomplished in six steps beginning with the reaction of (+)-(1R,4S)-4-hydroxy-2-cyclopenten-1-yl acetate with 4-chloro-1H-imidazo[4,5-c]pyridine. The preparation of 7-deaza-5'-noraristeromycin ((-)-7) was described previously. Compounds (-)-6 and (-)-7 were evaluated for antiviral activity against a large number of viruses. Compound (-)-6 produced an antiviral activity pattern similar to 5'-noraristeromycin but was less potent. Compound (-)-6 inhibited CEM cell proliferation at a 50% inhibitory concentration of 27 micrograms/mL but proved not inhibitory to HEL cell proliferation and not toxic to E6SM, HeLa, Vero, and MDCK cells at concentrations up to 200 micrograms/mL. While (-)-6 showed inhibition of S-adenosyl-L-homocysteine (AdoHcy) hydrolase, it was less inhibitory than 5'-noraristeromycin. Compound (-)-7 displayed no antiviral properties or inhibitory effects toward AdoHcy hydrolase.

Adenosine↗
PubMed1995

Molecular detection of pre-ATL state among healthy HTLV-1 carriers in an endemic area of Japan.

Adult T-cell leukemia/lymphoma (ATL) usually develops after age 40 in Japan, suggesting a long latency since HTLV-I is considered to be transmitted mainly from mothers to babies via breast milk. Our previous studies had suggested that HTLV-I carriers who have a monoclonal integration of HTLV-I proviral DNA in the peripheral blood cells, designated pre-ATL, account for about 2% of healthy carriers and are at high risk of developing ATL. Their ages ranged from 32 to 80 (median 57). Nevertheless, many cases of pre-ATL showed a long-lasting carrier state (10-year probability around 90%). In the present investigation we conducted a large-scale molecular detection of monoclonal integration in a population (481 cases) of healthy carriers with ages ranging from 16 to 82 (median 49) for the purpose of clarifying the earliest onset of this pre-ATL state. Southern-blot analysis of DNA extracted from peripheral blood mononuclear cells revealed 6 cases (1.2%) with a monoclonal band. All of these 6 were older than 40; no single positive case was found in 220 carriers under age 40. These results indicate that the molecularly detectable pre-ATL state also develops after a long latency. Thus the pre-ATL state seems to be a subtype of ATL showing an extremely indolent course of disease development, but not merely an early phase of all subtypes of ATL. We propose that, in order to reveal a promoter(s) responsible for the development of ATL from the pre-ATL state, intensive epidemiological investigation of life style, eating habits, occupation and exposure to carcinogens must be conducted on this unique group prone to ATL. It is also important to perform such an epidemiological study on the general population of carriers by paying special attention to the first 3-4 decades of each carrier's life in Japan and by comparing the data with those from carriers in different geographical areas of the world.

Adolescent↗
PubMed1995

Secretory cleavage of beta-amyloid precursor protein in the cerebral white matter produces amyloidogenic carboxyl-terminal fragments.

To elucidate the metabolic process generating amyloid-beta protein (A beta) from beta-amyloid precursor protein (APP) in human brain, we partially purified secretory forms and carboxyl-terminal fragments (CTFs) of APP from the white matter of a Down's syndrome brain. We obtained secretory forms of APP which lack the entire A beta sequence and CTFs which contain the full-length A beta from the cerebral white matter. Some A beta-lacking secretory APP isoforms in the white matter were derived from APP695. These results suggest that amyloidogenic CTFs can be produced by secretory cleavage of APP which is anterogradely transported through the axon in human brain.

Amyloid beta-Peptides↗
PubMed1995

Acute nephrotoxicity of a carcinogenic iron chelate. Selective inhibition of a proteolytic conversion of alpha 2U-globulin to the kidney fatty acid-binding protein.

The mechanism of acute nephrotoxicity of an iron chelate in vivo has been investigated. Administration of a renal carcinogen ferric nitrilotriacetate (Fe-NTA) (15 mg Fe/kg body weight, intraperitoneally) led to selective loss of a renal protein with an apparent molecular mass of 17 kDa. Analysis of the 17 kDa protein by NH2-terminal sequence demonstrated its identity over 16 NH2-terminal residues as a kidney fatty acid-binding protein (k-FABP) that is a proteolytically modified form of alpha 2U-globulin, a major urinary protein of adult male rats. An immunochemical study using anti-alpha 2U-globulin polyclonal antibodies confirmed that a single injection of Fe-NTA led to a decrease in k-FABP levels. However, a 19-kDa protein identical to the alpha 2U-globulin progressively appeared in the kidney, suggesting that the proteolytic processing of alpha 2U-globulin in the renal proximal tubules was suppressed by the treatment with Fe-NTA. By monitoring k-FABP and its precursor alpha 2U-globulin, it was determined that repeated exposure to Fe-NTA caused suppression of both proteolytic and endocytotic activity of the kidney. The implications of these data in relation to the nephrotoxicity of Fe-NTA are discussed.

Alpha-Globulins↗
PubMed1995

Hereditary ceruloplasmin deficiency with hemosiderosis: a clinicopathological study of a Japanese family.

A hereditary ceruloplasmin deficiency associated with severe iron deposition in visceral organ and brain tissues found on histopathological examination at autopsy is discussed. Three siblings of consanguineous Japanese parents were studied. Their clinical symptoms were progressive dementia, extrapyramidal disorders, cerebellar ataxia, and diabetes mellitus, all of which appeared when they were between 30 and 50 years old. All had serum ceruloplasmin deficiencies and increased serum ferritin concentrations. The dentate nucleus, thalamus, putamen, caudate nucleus, and liver of each one showed low signal intensities on T1- and T2-weighted magnetic resonance images. Examination of the central nervous system revealed severe destruction of the basal ganglia and dentate nucleus, with considerable iron deposition in neuronal and glial cells, whereas the cerebral cortex showed mild iron deposition in glial cells without neuronal involvement. An electron microscopic study with energy-dispersive x-ray analysis showed iron depositions in the hepatocytes, of both the neural and glial cells of the brain. We consider this a new disease entity because of the primary ceruloplasmin deficiency.

Adult↗
PubMed1995

Haplotype analysis in gelsolin-related amyloidosis reveals independent origin of identical mutation (G654A) of gelsolin in Finland and Japan.

Familial amyloidosis, Finnish type (FAF) (gelsolin-related amyloidosis) is an autosomal dominant form of systemic amyloidosis characterized by corneal lattice dystrophy and peripheral polyneuropathy. The accumulating protein in FAF consists of fragments of gelsolin, an actin-modulating protein. The gelsolin mutation G654A has been found in both Finnish and Japanese patients. To study the origin of the gelsolin mutation in these patients we performed haplotype analysis in 10 Finnish and 2 Japanese FAF families. Poymorphic DNA markers GSN, D9S103, AFMa061xd9, and AFMa139xb9 revealed a uniform disease haplotype in all the disease-associated chromosomes of the Finnish FAF families, which was different from the one observed in the Japanese families. The present results and the previously detected gelsolin mutation G654T in Czech and Danish FAF patients suggest that nucleotide 654 may represent a mutation hot spot in the gelsolin gene. The DNA markers studied here will be useful in future genealogical analyses of FAF.

Amyloid Neuropathies↗
PubMed1995

Multiple mitochondrial DNA deletions in a patient with mitochondrial myopathy and cardiomyopathy but no ophthalmoplegia.

Deletions of muscle mitochondrial DNA are known in mitochondrial myopathy patients who have chronic progressive external ophthalmoplegia (CPEO). A 41-year-old patient with no apparent family history of this condition suffers from hypertrophic cardiomyopathy, slight muscle atrophy, and weakness of the extremities, but not from CPEO. A muscle biopsy showed the presence of ragged-red fibers, and Southern blot analysis disclosed multiple deletions of muscle mitochondrial DNA. This combination of clinical features in our patient is atypical in mitochondrial myopathy with demonstrable deleted muscle mitochondrial DNA. Pleomorphic clinical expression is suggested.

Adult↗
PubMed1995

Malposition of a totally implantable venous access catheter in the azygous vein: report of a case.

We report herein the case of a 2-year-old girl with short bowel syndrome who developed chest pain 2 weeks after a totally implantable central venous access catheter had been surgically placed to facilitate total parenteral nutrition. A lateral chest X-ray and contrast flow study subsequently revealed that the catheter tip had been inserted into the azygous vein. Although this complication is very rare, it may be encountered more commonly with the increasing use of this type of venous access. Thus, we believe that a lateral chest X-ray should be routinely performed on all patients following catheter insertion to check for possible malposition of the tip in the azygous vein.

Catheters, Indwelling↗