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Biomedical subjects

S Ikeda

Publications and source records attributed to S Ikeda.

At least 487 records · Page 27Linked to original sources

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

Surgically resected adrenal leiomyoma: report of a case.

This report describes the case of a 48-year-old woman found to have a leiomyoma of the left adrenal gland after presenting with anemia and hypertension. An upper gastrointestinal series revealed a mass in the posterior region of the body that distorted the stomach. A computed tomography (CT) scan showed a well-circumscribed mass with a high-density outline in the left adrenal gland, and magnetic resonance imaging (MRI) revealed a homogeneous mass. Multiple catheter samplings of vena cava blood revealed a slight elevation of epinephrine and norepinephrine in the left adrenal vein and the left renal vein. Thus, asymptomatic pheochromocytoma of the left adrenal gland was highly suspected as a preoperative diagnosis and a left adrenalectomy was performed. However, histologic examination subsequently revealed findings suggestive of leiomyoma of the adrenal gland, which was confirmed by electron microscopy. The patient's postoperative course was uneventful and she has remained free from any further symptoms.

Adrenal Gland Neoplasms↗

Closure of the distal pancreatic stump with a seromuscular flap.

We describe herein our new method for transecting the pancreas and closing its stump in distal pancreatectomy, devised to decrease the risk of pancreatic fistula formation. With this technique, the pancreas is transected in such a way that a convex stump is left, whereby the pancreatic secretions from the parenchyma near the pancreatic stump are fully drained into the main pancreatic duct. A pedicled seromuscular flap of the stomach or jejunum is then used to cover the cut surface of the pancreas. This new technique provides tight closure of the pancreatic stump after distal pancreatectomy.

Humans↗

Thorn-shaped astrocytes: possibly secondarily induced tau-positive glial fibrillary tangles.

Argyrophilic and tau-positive abnormal structures occurring in glial cells are called glial fibrillary tangles. In the astrocyte, a conspicuous tau-positive structure is known to appear in progressive supranuclear palsy (PSP). In this report, another type of argyrophilic and tau-positive astrocytes is reported. The morphology of this new type is quite different from that of the previously reported tau-positive astrocyte in PSP and they are designated here as thorn-shaped astrocytes (TSA). TSA have an apparently argyrophilic cytoplasm with a few short processes and often have a small eccentric nucleus, whose appearance resembles that of a reactive astrocyte. Immunohistochemically, TSA are positive to anti-tau antibodies but are negative for ubiquitin. Simultaneous immunostaining revealed the coexistence of tau and glial fibrillary acidic protein epitopes in the same cytoplasm. Electron microscopically, bundles of 15-nm straight tubules were included in the cytoplasm together with abundant glial filaments. In the vicinity of a cluster of TSA, related structures of perivascular or subpial tau-positive linings, which correspond to astrocytic end-feet, are sometimes observed. In almost all cases, a few TSA are generally located in a confined area of subpial and subependymal regions. Although TSA appear to be intimately associated with some diseases, they are also found in a wide range of cytoskeletal disorders including the aged brain with neurofibrillary tangles. TSA are presumed to be a secondary induced product in relation to astrocytic reaction.

Aged↗

Expression rate of cytokine mRNA in the liver of chronic hepatitis C: comparison with chronic hepatitis B.

This study was carried out to test the hypothesis that, in chronic hepatitis (CH), inflammatory processes, including viral replication, host immune response, and hepatocyte destruction, are regulated by a cytokine network in the liver. Expression of the mRNA of the cytokines IL1-beta, IL2, IL4, IL5, IL6, TNF-alpha, and IFN-gamma, the lymphocyte markers CD4 and CD8, and the HLA class I molecule, beta 2-microglobulin (B2MG) in the liver tissue of 20 CH(C) cases and 9 CH(B) patients was investigated by the reverse transcription polymerase chain reaction (RT-PCR) method. TNF-alpha, CD4, and B2MG mRNA were detected in 100% of cases of in both CH(B) and CH(C). The expression rates of IL1-beta, IL2, IL4, IFN-gamma, and CD8 mRNA were 80%, 40%, 25%, 40%, and 80% in CH(C) and 88.9%, 44.5%, 30%, 55.6%, and 100% in CH(B). IL6 mRNA was detected only in CH(B), in 22.2% of cases, IL5 mRNA was not detected in either CH(B) or CH(C). IL2, IL4, and IFN-gamma mRNA were expressed significantly more frequently in patients who had high serum ALT and a high histological activity index (HAI) score. There was no difference in cytokine expression between CH(B) and CH(C), except in IL6, suggesting the existence of a common immunopathogenesis for CH(B) and CH(C). In chronic viral hepatitis, IL1-beta and TNF-alpha appear to play a major role in immune responses and IL2, IL4, and IFN-gamma seem to be associated with increased cytotoxic T cell response.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Pedicled jejunal seromuscular flap for bronchocutaneous fistula.

We report the successful closure of a complicated bronchocutaneous fistula using a pedicled jejunal flap. The fistula, secondary to tuberculosis and irradiation, previously had been closed with a latissimus dorsi musculocutaneous flap. This initial repair failed. The recurrent fistulas were closed again using a jejunal seromuscular flap, and the chest wall defect was reconstructed with a rectus abdominis musculocutaneous flap.

Aged↗

Reappraisal of safety of endoscopic sphincterotomy for common bile duct stones in the elderly.

BACKGROUND: Endoscopic sphincterotomy is the method of choice for elderly patients with common bile duct stones, even though these patients are poor operative risks. We undertook this study to analyze the operative risk factors for this age group. METHODS: We compared specific problems of 182 patients aged 80 years or older and 921 younger patients who underwent endoscopic sphincterotomy for common bile duct stones. RESULTS: Despite a higher frequency of periampullary diverticula in the elderly than in the younger patients (54% versus 36%, P < 0.001), the success rates of sphincterotomy were not different. The elderly patients required lithotripsy more often than did the younger ones (15% versus 4%, P < 0.001), and the necessity of stenting or nasobiliary drainage was greater in this group (9%) than in the younger group (5%, P < 0.05). This difference in the tactics between the older and younger groups was due to the greater number and size of stones, longer period of time for complete clearance of the common bile duct (13.5 versus 6.0 days, P < 0.01), and a greater percentage of patients with operative risks (55% versus 36%, P < 0.001). The elderly also had significantly greater overall morbidity compared with the younger patients (13% versus 7%, P < 0.005), frequency of acute cholangitis (8% versus 2%, P < 0.001), and mortality (1% versus 0%). CONCLUSION: These results suggest that frequent stenting or nasobiliary drainage to prevent cholangitis or prompt stone removal by lithotripsy would be necessary in this group of patients.

Adolescent↗

A mutation in the ceruloplasmin gene is associated with systemic hemosiderosis in humans.

We identified a mutation in the ceruloplasmin (Cp) gene in a Japanese family with aceruloplasminemia, some of whose members showed extrapyramidal disorders, cerebellar ataxia, and diabetes mellitus. A post-mortem study of the proband revealed excessive iron deposition mainly in the brain, liver and pancreas. The G to A transition at the splice acceptor site introduces a premature termination codon at the amino acid position 991 by defective splicing, thereby truncating the carboxyl terminus of Cp in affected individuals. We conclude that the mutation in the Cp gene is associated with systemic hemosiderosis in humans.

Alternative Splicing↗

Adult T-cell leukemia with multiple lymphomatous polyposis of the gastrointestinal tract.

A rare case of adult T-cell leukemia (ATL) in which multiple lymphomatous polyposis (MLP) was revealed throughout the entire gastrointestinal tract is reported here. The polypectomy specimens taken from the rectum revealed infiltration of neoplastic T-cells, the integration of HTLV-1 proviral DNA, and increased CD4 (OKT4) and CD25 (IL-2R) cells. The analysis of surface markers of the lymphocytes from polypoid lesions may be useful for elucidating cell tropism and homing properties in the gastrointestinal tract. Although MLP has always been associated with B-cell lymphoma in the Western world, it is important for clinicians and pathologists to be aware that MLP may be caused by the infiltration of ATL cells.

Adult↗