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Biomedical subjects

S Nishimoto

Publications and source records attributed to S Nishimoto.

At least 37 records · Page 2Linked to original sources
PubMed1997

Licensing of DNA replication by a multi-protein complex of MCM/P1 proteins in Xenopus eggs.

In eukaryotes, chromosomal DNA is licensed for a single round of replication in each cell cycle. Xenopus MCM3 protein has been implicated in the licensing of replication in egg extract. We have cloned cDNAs encoding five immunologically distinct proteins associated with Xenopus MCM3 as members of the MCM/P1 family. Six Xenopus MCM proteins formed a physical complex in the egg extract, bound to unreplicated chromatin before the formation of nuclei, and apparently displaced from replicated chromatin. The requirement of six XMCM proteins for the replication activity of the egg extract before nuclear formation suggests that their re-association with replicated chromatin at the end of the mitotic cell cycle is a key step for the licensing of replication.

Adenosine Triphosphatases↗
PubMed1997

Prevalence of human herpesvirus-8 in skin lesions.

A putative new herpesvirus, designated Kaposi's sarcoma-associated herpesvirus (KSHV) or human herpesvirus-8 (HHV-8) was recently identified in AIDS-related Kaposi's sarcoma. The DNA sequence of the virus is homologous to the gamma-herpesviruses such as herpesvirus Saimiri or Epstein-Barr virus, both of which are tumorigenic, suggesting that this new virus may also be oncogenic. Thus, we determined whether the virus is present in other skin lesions. DNA samples from 118 skin specimens were tested for the HHV-8 sequence by polymerase chain reaction (PCR) and Southern hybridization. The sequences were detected in 13 of 21 samples from Bowen's disease, three of 11 squamous cell carcinomas, three of 11 actinic keratoses, three of seven leucoplakia, one of six from Paget's disease, one of 12 malignant melanoma, one of seven neurofibromas, two of seven chronic dermatites and one of 14 normal skin samples. On sequencing the PCR products, new mutation points were detected. These results suggest that the virus is associated with lesions other than Kaposi's sarcoma and may be more widespread than expected (with a latent level too low to be detected), like the other herpesviruses. Some lesions. e.g. in Bowen's disease or squamous cell carcinoma, may be locally immunosuppressed, allowing the virus to replicate until the copy number is sufficient for detection.

Adolescent↗
PubMed1997

Free rectus abdominis musculocutaneous flap for head and neck reconstruction.

Surgery in the head and neck often results in large and complex tissue defects. The free rectus abdominis musculocutaneous flap has many advantages for reconstruction of these defects. A good volume of tissue can be harvested with a long and large-diameter vascular pedicle. A reliable blood supply enables thinning, shaping and molding of the flap, and it can be elevated with the patient in the supine position. The harvesting technique is easy with good visualization. The authors prefer this free flap for reconstructing relatively large defects in the head and neck, and have had experience with 55 cases, which were analyzed for results and complications.

Abdominal Muscles↗
PubMed1997

A case of Paget's disease of the vulva recurring in a musculocutaneous flap.

A case of Paget's disease of the vulva which recurred in a reconstructed gracilis musculocutaneous flap without invasing adenocarcinoma is presented. The recurrent lesion was seen in the basal layer of the epidermis of the flap without invasion into the dermis. The possibility of an intraepidermal lateral invasion of Paget's cells into the epidermis of the flap is suggested.

Aged↗
PubMed1996

Kaposi's sarcoma-associated herpesvirus (KSHV) sequences in premalignant and malignant skin tumors.

The novel herpesvirus-like DNA sequences, which were identified in AIDS-related Kaposi's sarcoma (KS) and designated KS associated herpesvirus (KSHV) or human herpesvirus 8 (HHV-8), have been reported to be associated with various forms of KS. Here, we searched for the presence of KSHV sequences in various other skin lesions including premalignant or malignant skin tumors of a total of 69 clinical cases without immunodeficiency due to AIDS or following organ transplantation. Strikingly high rates of detection were obtained for premalignant Bowen's disease and malignant squamous cell carcinoma, accounting for 71.4% and 50%, respectively. A less frequent but as yet high incidence (33.3%) was scored for actinic keratosis, a premalignant epidermal disorder. In contrast, the frequency remained low (16.7%) for another type of proliferative skin lesions of extramammary Paget's disease and non-proliferative skin lesions (dermatitis, morphea, epidermal cyst and scar). These results suggest a close association of KSHV with at least some non-KS malignant and premalignant skin lesions in non-immunocompromised patients.

Acquired Immunodeficiency Syndrome↗
PubMed1996

A rare case of burn scar malignancy.

Malignant changes in burn scars have long been reported in the literature. Most cases are squamous cell carcinomas and some other epithelial cell carcinomas. Soft tissue tumours are considered rare. A rare case of sarcoma arising in a scar on the sole of the foot in a 64-year-old male is reported. He had suffered fire burns 25 years previously. Histological findings indicated that the tumour was a pleomorphic liposarcoma. Amputation was performed, but he died 3 months after the operation. To our knowledge, this is only the second case of liposarcoma developing in a burn scar.

Burns↗
PubMed1995

Identification of the yeast MCM3-related protein as a component of Xenopus DNA replication licensing factor.

Replication licensing factor is thought to be involved in the strict control of the initiation of DNA replication in eukaryotes. We identified a 100 kDa protein as a candidate for the licensing factor in Xenopus egg extracts. This protein was required for replication; it bound to sperm DNA before the formation of nuclei and apparently dissociated from the nuclear DNA during the progression of replication without being transported into the nuclei. An immunologically homologous protein in HeLa cells behaved similarly to the Xenopus protein during the cell cycle. Cloning and sequencing of the cDNAs encoding the Xenopus and human proteins revealed that they are homologs of yeast Mcm3, a putative yeast DNA replication licensing factor.

Amino Acid Sequence↗
PubMed1995

Effect of donor age on the phosphorylation of the retinoblastoma gene product in cultured human keratinocytes.

The retinoblastoma gene product (pRB) is a tumor suppressor protein. Recently, it has been shown that the phosphorylation of pRB is necessary for progression from G1 to S phase in a variety of cells. In a word, the phosphorylation of pRB accelerates cell growth. In this study, we examined the phosphorylation status of pRB in normal human keratinocytes obtained from donors aged from 1 year to 71 years. The cells of old donors (61-71 years old) presented the more dense hypophosphorylated pRB band than cells of young donors (1-19 years old). Densitometric measurement showed that 42.3% +/- 4.8% of the total pRB was hypophosphorylated in cells of young donors, while 58.1% +/- 6.9% was hypophosphorylated in those of old donors. Results indicate that more pRB is hypophosphorylated in cells of old donors. The phosphorylated status of pRB might be related to the loss of growth fraction in human keratinocytes of old donors.

Adult↗
PubMed1995

Electron-affinic radiosensitizers possessing NPSH-reactive side chains: cytotoxicity and radiosensitizing activity towards hypoxic EMT6 cells in vitro.

A new class of dual-function nitroazole derivatives that are composed of electron-affinic nitroazole rings and a thiol-reactive alpha, beta-unsaturated carbonyl side chain were synthesized to evaluate their physico-chemical properties, reactivity with glutathione (GSH), and cytotoxicity and radiosensitizing activity towards EMT6/KU cells in vitro. Among this class of nitroazole compounds, 2-nitroimidazole-derivative (1), 3-nitro-1,2,4-triazole derivative (2), and 2-methyl-4-nitroimidazole derivative (3) with a common side-chain structure of trans CH2CH = CHCO2CH3 readily reacted with GSH in phosphate-buffer solution (pH 7.2, 310 K). These compounds showed higher cytotoxicities to both aerobic and hypoxic EMT6/KU cells than the corresponding alpha, beta-saturated counterparts (6-8) with a side-chain structure of CH2CH2CH2CO2CH2CH3. The hypoxic cytotoxicity of 1 and 2 with similar electron affinities to that of misonidazole (9) was potentiated by the combined effects of depletion of non-protein thiols (NPSH) by the alpha, beta-unsaturated carbonyl side chains and bioreduction of the nitroazole rings. The sensitizer enhancement ratios in vitro (SERvitro) of 1 (2.80 +/- 0.20) and 2 (2.63 +/- 0.27) at a dose of 1.0 mmol dm-3 are comparable with the oxygen enhancement ratio (OER = 2.90 +/- 0.10) and are significantly larger than those of their respective counterparts 6 (1.28 +/- 0.06) and 7 (1.22 +/- 0.09). A less electron-affinic compound, 3, also gave a large SERvitro = 1.80 +/- 0.18, whereas the counterpart 8 was not effective (1.10) in radiosensitizing hypoxic cells. Compounds 1-3 not only altered the slope, but also reduced the shoulder of the dose-survival curve. These 'dual-function' nitroazole radiosensitizers show much lower levels of in vitro radiosensitization, as measured by the C1-6, than the previously reported 'anomalous' radiosensitizers such as 5-substituted 4-nitroimidazole radiosensitizers.

Azoles↗
PubMed1994

Fluorinated 2-nitroimidazole derivative hypoxic cell radiosensitizers: radiosensitizing activities and pharmacokinetics.

PURPOSE: To assess the effects of incorporation of a CF2 group into the side chain of a 2-nitroimidazole derivative, we evaluated the in vitro and in vivo radiosensitizing activities of KU-2285 (a 2-nitroimidazole derivative with an N1-substituent of -CH2CF2CONH(CH2)nOH, n = 2) and its related compounds in comparison with those of comparable nonfluorinated compounds. The pharmacokinetics of these compounds in murine tumors was also tested. METHODS AND MATERIALS: KU-2285, KU-3202 (n = 3) and KU-3207 (n = 4) are fluorinated 2-nitroimidazole derivative compounds with similar structures. Etanidazole (a 2-nitroimidazole derivative with an N1-substituent of -CH2CONH(CH2)nOH, n = 2) and its related compounds, KU-3205 (n = 3) and KU-3206 (n = 4) were also tested. The in vitro radiosensitizing activities of each compound for hypoxic cells was evaluated with a standard colony formation method. The in vivo radiosensitizing activities of these compounds were tested in female C3H/He mice bearing SCCVII tumors using an in vivo/in vitro clonogenic assay. The pharmacokinetic studies were performed in C3H/He mice bearing the SCCVII tumor. Samples were analyzed by reverse-phase high-performance liquid chromatography. RESULTS: The in vitro radiosensitizing activities of fluorinated 2-nitroimidazoles were higher than those of the nonfluorinated compounds. Although the in vivo radiosensitizing activity of KU-2285 was higher than that of etanidazole (p < 0.05), other fluorinated 2-nitroimidazoles showed less radiosensitizing activity than the comparable nonfluorinated compounds. The compound was eliminated from serum more rapidly with the increase in the number of CH2 group in the side chain of the compound in each series. CONCLUSION: Although the in vitro sensitizing activity of the fluorinated compounds was higher than that of the comparable nonfluorinated compounds, the in vivo radiosensitizing activity of all fluorinated compounds but KU-2285 was lower than that of comparable etanidazole group compounds, probably due to their lower molecular concentrations in tumor and rapid elimination.

Animals↗
PubMed1994

Dynamic structures of intact chicken erythrocyte chromatins as studied by 1H-31P cross-polarization NMR.

The dynamic properties of DNA in intact chicken erythrocyte cells, nuclei, nondigested chromatins, digested soluble chromatins, H1, H5-depleted soluble chromatins and nucleosome cores were investigated by means of single-pulse and 1H-31P cross-polarization NMR. The temperature dependence of the phosphorus chemical shift anisotropy was identical for the former three in the presence of 3 mM MgCl2, suggesting that the local higher order structure is identical for these chromatins. The intrinsic phosphorus chemical shift anisotropy of the nucleosome cores was -159 ppm. The chemical shift anisotropy of DNA in the chromatins can be further averaged by the motion of the linker DNA. The spin-lattice relaxation time in the rotating frame of the proton spins (T1p) of the nondigested chromatins was measured at various locking fields. The result was analyzed on the assumption of the isotropic motion to get a rough value of the correlation time of the motion efficient for the relaxation, which was eventually ascribed to the segmental motion of the linker DNA with restricted amplitude. The 30 nm filament structure induced by NaCl was shown to be dynamically different from that induced by MgCl2. Side-by-side compaction of 30-nm filaments was suggested to be induced in the MgCl2 concentration range higher than 0.3 mM. Biological significance of the dynamic structure was discussed in connection with the results obtained.

Animals↗
PubMed1994

Dynamic properties of nucleic acids in biosupramolecular systems, as studied by 31P NMR.

The dynamic properties of nucleic acids in five different types of intact supramolecular systems, namely, chicken erythrocyte chromatin, the wild type and a deletion mutant of the lambda phage, lipid-containing phage PM2, and Alteromonas espejiana ribosomes, were investigated by means of 31P solid-state NMR. The nucleic acids in the different supramolecular systems showed unique dynamic properties, which are closely connected with their functions. The total anisotropy of the phosphorus chemical shift (delta sigma = sigma 33-sigma 11) of the ribosomes was 210 ppm at 5 degrees C. This anisotropy was much larger than those of any DNA complexes, suggesting the highly rigid structure of ribosomal RNA. In contrast, 160 ppm was the largest chemical shift anisotropy at 5 degrees C for B-form DNA in the supramolecular systems. This flexibility would be essential for DNAs to exert their functions. The involvement of a condensation protein in the PM2 phage was supported by the chemical shift anisotropy. The spin-lattice relaxation time in the proton rotating frame [T1 rho(H)] of the nucleic acids became shorter with the increase in the effective field in the rotating frame for all systems examined, showing that the motions of the nucleic acids effective for the relaxation are in the slow motional regime or in the range of omega 1 tau c = 1 at 5 degrees C. The motional state of DNA of the lambda phage was found to change at about 20 degrees C on the basis of the temperature dependence of the spin-lattice relaxation time of phosphorus (T1).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Isolated lateral traumatic dislocation of the radial head in a boy: case report.

Lateral traumatic dislocation of the radial head occurred in a 9-year-old boy with cubitus varus. Reduction of the dislocation and immobilization of the arm in flexion and supination in a plaster cast for 4 weeks were done and after 6 months the boy returned to school, with no problems in daily living.

Biomechanical Phenomena↗
PubMed1993

Intracaval and intracardiac extension of malignant thymoma.

A case of malignant thymoma presenting as the superior vena cava syndrome is reported. A 56-year old male was admitted with superior vena cava syndrome. CT and NMR-CT scan showed a solid homogenous superior mediastinal mass; which filled the lumen of the superior vena cava and the right atrium. A biopsy of the right atrial mass showed myxoma, and operation was performed. Histopathologically the tumor was diagnosed as thymoma. Intracaval and intracardiac extension of a thymoma is very rare.

Diagnosis, Differential↗
PubMed1992

Metabolic rate modification of nitrotriazole radiosensitizers by sulfur substitution of side chain.

The pharmacokinetic properties and radiosensitizing activities in vitro and in vivo of a series of 3-nitro-1,2,4-triazole (NTA) derivatives with a -CH2(C = Y)NH(CH2)nZCH3 (Y, Z = O or S; n = 2 or 3) group in the side chain at N-1 position of NTA were investigated with respect, particularly, to the effects of sulfur substitution in the side chain of NTA. The sulfur substitution for an oxygen atom in the side chain NTA radiosensitizers increased the rho value, but gave rise to little effect on the one-electron reduction potential. The derivatives bearing a thioether group (-CH2SCH3) in the side chain were slightly less effective both in vitro on hypoxic EMT6/KU cells and in vivo on SCCVII tumors than their oxygen analogs (-CH2OCH3). The thioether compounds tended to metabolize rapidly. The thioamide compound showed high sensitizing activity in vitro, but metabolized very slow.

Animals↗