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Biomedical subjects

S Ikeda

Publications and source records attributed to S Ikeda.

At least 469 records · Page 26Linked to original sources

[T cell lymphoma presenting as recurrent bilateral pulmonary infiltrates over five years].

A 52-year-old man presented with BOOP-like recurrent bilateral pulmonary infiltrates. In 1989 a chest X-ray film showed an infiltrative shadow in the right S6 region which disappeared after administration of prednisolone. Thereafter, bilateral patchy infiltrates recurred many times, and each time they resolved rapidly with steroid therapy. Skin eruptions on the face recurred. In October 1994 the patient underwent an open-lung biopsy of the infiltrate in the left S6 region. The pathological findings were consistent with BOOP, except for the moderate-to marked infiltration of lymphocytes. A lymphoproliferative disorder was suspected, and Southern blot analysis of the specimen revealed a rearrangement of the TCR-beta gene, which led to the diagnosis of T cell lymphoma. Ten months after the diagnosis, no recurrence of the lymphoma had been detected. In this case a gene analysis of the biopsy specimen was very useful for the diagnosis of T cell lymphoma.

Cryptogenic Organizing Pneumonia↗

[Current diagnosis and treatment of early pancreatic cancer].

In the present study our current experience of early pancreatic cancer is described. The early pancreatic cancer was defined when the tumor was located within the pancreas and/or less than 2 cm in diameter. Between 1983 and 1995, 9 out of 183 cases with pancreatic cancer were fulfilled with the criteria of early pancreatic cancer. Among the diagnostic modalities including US, CT, ERP, balloon ERP-CS and EUS, the balloon ERP-CS as well as EUS appears the most valuable procedure for making diagnosis of small pancreatic cancer. Currently, 8 out of 9 patients are alive at 1-10 years after surgery.

Adult↗

[A case of so-called carcinosarcoma of the lung].

A 69-year-old male was followed at our institute for the purpose of hemo-dialization. During follow-up, a tumor shadow (phi 6.5 x 7.0 cm) was found in rt. S5 by chest X-ray. This tumor was diagnosed as squamous cell carcinoma by TBLB. Right middle lobectomy (R 2 a) was performed. Histological staging was pT 2 N 2 M 0, stage IIIa. This tumor was cystic, filled with keratin like substance. Histologically, the cyst wall was composed of well differentiated squamous cell carcinoma and sarcomatous stroma which didn't differentiate into bone, cartilage, muscle, and etc. Immunohistologically, sarcomatous stroma was positively stained by vimentin, negatively by keratin and EMA. This patient survived 7 months with recurrence.

Aged↗

Identification of a 55-KDA endonuclease in rat liver mitochondria with nucleolytic properties similar to endonuclease G.

An endonuclease was extracted from intact rat liver mitochondria with 0.4 M NaCl, and partially purified. A zymographic assay in SDS-polyacrylamide gel containing single-stranded DNA revealed that the enzyme has an apparent molecular mass of 55 kDa. It was different from the molecular mass of the major endonuclease of bovine heart mitochondria (a homodimer of a 29-kDa peptide), that was recently shown to be identical to the endonuclease G. The purified 55-kDa enzyme degraded both DNA and RNA, preferring RNA and single-stranded DNA at a weak alkaline pH, required Mg(2+) and Mn(2+) but not Ca(2+) for activity, and was strongly inhibited by monovalent cations. Nicks generated by the enzyme were resealable with T4 DNA ligase, indicating that the enzyme produces 5'-p and 3'-OH ends. The 55-kDa enzyme, like endonuclease G, displayed a strong preference to nick within a (dG)n.(dC)n sequence tract.

Animals↗

Familial amyloid polyneuropathy--clinical report of a family.

This paper reports a familial amyloid polyneuropathy (FAP) family in China. This family being investigated had 69 members of five generations. From the third generation, there have been 16 patients. The age of onset was about 3 to 5 decades. The initial symptoms were autonomic nerve symptoms, such as impotence, dyspepsia and diarrhoea, associated with the sensory loss of lower extremities. As the disease progressed, the upper extremities and motor ability were also involved. The duration of disease course was about 8-10 years, most patients died of infection and cachexia. Sural biopsy in 3 patients had showed positive Congo red staining. From the clinical view, this FAP family is similar to FAP I found in Japan. The true classification, however, should be confirmed by further genetic analysis.

Adult↗

Adjuvant activity of diesel exhaust particulates (DEP) in production of anti-IgE and anti-IgG1 antibodies to mite allergen in mice.

The present study indicates that diesel exhaust particulates (DEP) and pyrene contained in DEP have an adjuvant activity on IgE and IgG1 antibody productions in mice immunized intranasally with a mite allergen. The effect of pyrene on IgE and IgG1 antibody productions in mice was investigated to clarify the relation between mite allergy and adjuvancy of the chemical compounds in DEP. Der f II, one of the major allergens of house dust mite (Dermatophagoides farinae), was used as a mite allergen. Mice were grouped, and immunized with 5 micrograms of Der f II alone, 5 micrograms of Der f II plus 200 micrograms of pyrene and 5 micrograms of Der f II plus 100 micrograms of DEP intranasally seven times at two week intervals. The separate groups of mice were also immunized with 10 micrograms of Der f II plus the same dose of adjuvants in the same way. The IgE antibody responses to Der f II in mice immunized with Der f II plus pyrene or Der f II plus DEP were markedly enhanced compared with those immunized Der f II alone. The anti-Der f II IgE antibody production increased with increasing the dose of Der f II from 5 micrograms to 10 micrograms in mice immunized with Der f II plus the same dose of adjuvants. The IgG1 antibody responses to Der f II in mice immunized with 10 micrograms of Der f II plus 200 micrograms of pyrene or 10 micrograms of Der f II plus 100 micrograms of DEP were extremely higher than those immunized with 10 micrograms of Der f II alone. In addition, when the peritoneal macrophages obtained from normal mice were incubated with pyrene or DEP in vitro, an enhanced interleukin-1 alpha production of the macrophages was observed. When the spleen lymphocytes obtained from the mice immunized with 10 micrograms of Der f II plus 100 micrograms of DEP or 10 micrograms Der f II plus 200 micrograms of pyrene were stimulated with 10 micrograms of Der f II in vitro, an enhanced IL-4 production of the lymphocytes was also observed compared with those immunized with Der f II alone. These results suggest that the adjuvancy of DEP and pyrene on the production of IgE and IgG1 antibodies to Der f II may be one of the factors responsible for an incidence of asthma caused by house dust mite.

Adjuvants, Immunologic↗

Adjuvant activities of pyrene, anthracene, fluoranthene and benzo(a)pyrene in production of anti-IgE antibody to Japanese cedar pollen allergen in mice.

We have previously demonstrated that pyrene in diesel-exhaust particles (DEP) has an adjuvant activity on immunoglobulin E (IgE) antibody production in mice immunized with Japanese cedar pollen allergen (JCPA) or ovalbumin (OA) intraperitoneally. The present study is concerned with the adjuvant activity in IgE antibody production against JCPA of pyrene or DEP inoculated intranasally in mice. We show that anthracene, fluoranthene and benzo(a)pyrene in DEP have the ability to enhance anti-JCPA IgE antibody production in mice by intranasal immunization. Mice were grouped, immunized with 10 micrograms of JCPA plus 400 micrograms of pyrene, 10 micrograms of JCPA plus 100 micrograms of DEP, 10 micrograms of JCPA plus 2 mg of aluminum hydroxide and 10 micrograms of JCPA alone intranasally 7 times at 2 week intervals. Mice were also grouped, and immunized with JCPA (10 micrograms) plus 40 micrograms of anthracene, JCPA (10 micrograms) plus 400 micrograms of fluoranthene, JCPA (10 micrograms) plus 40 micrograms of benzo(a)pyrene, and JCPA (10 micrograms) plus 400 micrograms of pyrene and JCPA (10 micrograms) alone. We found that the IgE antibody responses to JCPA in mice immunized with JCPA plus pyrene, JCPA plus DEP or JCPA plus the three chemical organic compounds mentioned above were significantly enhanced compared with those immunized with JCPA alone. In addition, when the intraperitoneal macrophages obtained from the normal mice (unimmunized mice) were incubated with pyrene, anthracene, fluoranthene or benzo(a)pyrene in vitro, an enhanced chemiluminescence (CI) response and interleukin-1 alpha (IL-1 alpha) production of the macrophages was observed in each instance. These results suggest that in the production of IgE antibody to JCPA the adjuvancy of polycyclic aromatic hydrocarbons (PAHs) in DEP may be important in an attack of Japanese cedar pollinosis.

Adjuvants, Immunologic↗

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↗

Narrowing of the Hailey-Hailey disease gene region on chromosome 3q and identification of one kindred with a deletion in this region.

Hailey-Hailey disease is a cutaneous abnormality transmitted as an autosomal dominant trait in which impaired interkeratinocyte adhesion produces recurrent blisters in characteristic skin sites. We report here a confirmation of the initial mapping of the mutant gene to chromosome 3q in an additional seven kindreds, narrowing of the candidate region to the sequences flanked by D3S1589 and D3S1541, and the finding in one family of a genomic DNA deletion whose centromeric end is located between these two flanking markers.

Centromere↗

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↗

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↗

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↗

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↗

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↗

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↗