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Biomedical subjects

H Shinohara

Publications and source records attributed to H Shinohara.

At least 37 records · Page 2Linked to original sources

Photooxidation of olefins sensitized by bisazafullerene (C(59)N)(2) and hydroazafullerene C(59)HN: product analysis, emission of singlet oxygen, and transient absorption spectroscopy.

The photooxidation reactions of olefins sensitized by the excited triplet states of bisazafullerene (C(59)N)(2) and hydroazafullerene C(59)HN have been studied. Oxidation yields were compared with those of pristine C(60). The singlet oxygen yields are also determined directly from the emission intensities, which are in good agreement with the oxidation yields. The triplet states of (C(59)N)(2) and C(59)HN have been identified by the time-resolved spectroscopic method by observing the triplet-triplet absorption spectra, which decay in the presence of oxygen. It has been proven that (C(59)N)(2) and C(59)HN have the ability to sensitize the reactions via singlet oxygen in about half of the efficiency of that of pristine C(60). For both azafullerenes, the triplet lifetimes are shorter than that of pristine C(60), which may be related to the nitrogen atom embedded in the C(60) moiety.

Journal Article↗

Syntheses and biological evaluations of alpha-D-mannosyl [60]fullerenols.

[60]Fullerenols carrying mono- and bis-alpha-D-mannosyl linkages on the surface were prepared via a [3+2]-cycloaddition reaction between 2-azidoethyl alpha-D-mannoside and C(60) followed by polyhydroxylation with aqueous NaOH. Their biological activity was evaluated in terms of binding affinity to lectins by hemagglutination assay and surface plasmon resonance. [60]Fullerenols without the mannosyl linkage caused aggregation of erythrocytes and binding to a beta-D-galactopyranoside specific lectin (RCA(120)). In contrast, mono- and bis-mannosyl fullerenols were found to decrease the activity for both aggregating erythrocytes and binding to RCA(120), and mono-mannosyl fullerenols turned to binding to alpha-D-mannose specific lectin (Con A).

Carbon↗

A protective role of PKCepsilon against TNF-related apoptosis-inducing ligand (TRAIL)-induced apoptosis in glioma cells.

To elucidate the molecular mechanism(s) involved in the TRAIL-induced apoptosis sensitivity, we conducted the following experiments utilizing TRAIL-sensitive and -resistant glioma cells. We examined the expression of TRAIL receptors mRNA, but no significant differences were detected in those cells. TRAIL-resistant cells were sensitized to TRAIL-induced apoptosis by staurosporine pretreatment and preferentially expressed PKCepsilon. Since several lines of evidence suggest that PKC may play a protective role for apoptosis, we analyzed the involvement of PKCepsilon in TRAIL-induced apoptosis by an adenovirus vector expression system. We found that TRAIL susceptibility was augmented by the expression of a dominant negative PKCepsilon in TRAIL-resistant cells. Conversely, PKCepsilon introduction in TRAIL-sensitive cells resulted in the reduction of TRAIL-induced apoptosis. Taken together, these data suggest that PKCepsilon may be a regulator of susceptibility to TRAIL-induced apoptosis in gliomas and probably other malignancies.

Apoptosis↗

Expression of survivin correlates with apoptosis, proliferation, and angiogenesis during human colorectal tumorigenesis.

BACKGROUND: To identify the role of survivin, a novel inhibitor of apoptosis (IAP) in colorectal tumorigenesis, the authors investigated tissue expression of survivin in human colorectal tumors including 43 hyperplastic polyps, 171 adenomas with low dysplasia, 42 adenomas with high dysplasia, and 60 carcinomas in adenoma, and examined whether the expression of survivin correlated with tumor cell apoptosis, proliferation, and angiogenesis, which is known to initiate the imbalance between cell proliferation and apoptosis. METHODS: Immunohistochemical staining for the paraffin sections by using the monoclonal antibodies, survivin, p53, bcl-2, Ki-67, and CD34, was performed by the standard avidin-biotin-peroxidase technique. The apoptotic cells were detected by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling method, using an Apop Tag in situ detection kit. RESULTS: The immunoreactivity of survivin significantly increased in the transition from adenoma with low dysplasia to high dysplasia/carcinoma (P < 0.001). Similar changes in protein expression were observed for p53 but not for bcl-2, which was expressed throughout the colorectal tumorigenesis. This transition was associated with a significant decrease in the apoptotic index (AI) and significant increases in the Ki-67 labeling index (LI) and microvessel density (MVD; P < 0.001 for both). The expression of survivin inversely correlated with AI and was positively correlated with Ki-67 LI and MVD (P < 0.001 for both). CONCLUSIONS: These results suggest that, like p53, survivin plays an important role in transition from adenoma with low dysplasia to high dysplasia during human colorectal tumorigenesis.

Adenoma↗

Regulatory domain of protein stability of human P51/TAP63, a P53 homologue.

The amino terminal of human P51/TAp63, a P53 homologue, possesses a transactivation domain involved in the activation of its target genes by binding to DNA elements responsive to the p53 protein family. Using a series of amino terminal deletions, the transactivation domain was mapped between amino acid residues 50 to 69. This domain also regulates protein stability in a proteasome-dependent manner, and Ser51 and Ser68 were found to be essential for this stability. Our results suggest that P51 activity is greatly affected by protein stability.

Amino Acid Sequence↗

XAFS study on metal endohedral fullerenes.

Structure of metal endohedral fullerenes is studied by XAFS and XANES. The Sc-Sc distance of 2.23(1) A determined from Sc K-edge XAFS supports the formation of a triangular Sc3 cluster in Sc3@C82 as is found by MEM analysis for the X-ray diffraction. Gd L(III)-edge XAFS of Gd@C82 shows that the first and the second neigboring Gd-C distances are 2.51(2) and 2.85(4) A, respectively. The La-La distance of La2@C80 has been determined to be 3.90(1) A at 40 K. This value does not change when increasing temperature [3.90(2) A at 240 K]. The position and the valenece of the Eu atom in Eu@C60 are also discussed based on Eu L(III)-edge XAFS and XANES.

Journal Article↗

Pentagonal-dodecahedral la2 charge density in [80-ih ]fullerene: la2 @c80.

A double shell of Platonic solids: A trajectory that connects the six-membered rings of Ih -C80 is followed by the two La atoms of La2 @C80 according to maximum entropy/Rietveld analysis of the synchrotron powder-diffraction data. The result is a pentagonal-dodecahedral charge-density distribution for La2 (brown in the picture) inside the icosahedral C80 cage (green).

X-ray diffraction↗

The lacrimal fascia redefined.

It has been commonly accepted that the lacrimal fascia is an intact septum, composed of connective tissue, that separates the orbital cavity into a large compartment, which contains the eyeball, and a small compartment, which contains the lacrimal sac and nasolacrimal duct. the septum, however, is not necessarily always intact. We found a circular or oval opening in the lacrimal fascia in 37 of 52 specimens (71.2%) examined. The opening, which we shall refer to as the lacrimal fascial foramen, was located at variable levels in the lacrimal fossa. The lacrimal fascial foramen was buried in fatty tissue through which passed a branch of either the inferior palpebral artery or the infraorbital artery and a vein of the nasolacrimal duct. The clinical implications of the lacrimal fascial foramen in obstruction of the nasolacrimal duct are discussed.

Aged↗

Efficacy of intraperitoneal and intravenous chemotherapy and left upper abdominal evisceration for advanced gastric cancer.

BACKGROUND: The study was carried out to evaluate the efficacy of intraperitoneal (i.p.) and intravenous (i.v.) chemotherapy, as well as left upper abdominal evisceration (LUAE), for patients with advanced gastric cancer. METHODS: We carried out a retrospective study of 348 patients who underwent gastrectomy for advanced gastric carcinoma between 1978 and 1998 at our institution and who had macroscopic type 3 or 4 cancer (Japanese classification) with depth of invasion to the serosal surface, but no liver metastasis or lymph node metastasis around the abdominal aorta. Cumulative survival rates were compared in patients who underwent gastrectomy together with: (1) intraoperative i.p. chemotherapy alone, (2) postoperative i.v. chemotherapy alone, (3) both i.p. and i.v., or (4) no chemotherapy. Then patients were stratified according to the presence of peritoneal dissemination (P+) and its absence (P-). In P+ patients, survival was compared between those who received i.v. chemotherapy and those who did not, and between those who received i.p. chemotherapy and those who did not. Then, survival was compared between patients with high and low immunosuppressive acidic protein (IAP) levels. Finally, we compared cumulative survival rates in patients (stratified as P+ and P-) who underwent LUAE with cumulative survival rates in those who underwent total gastrectomy combined with resection of the pancreatic body, tail, and spleen (PS). RESULTS: For P- patients, there was no survival advantage with adjuvant i.p. or i.v. therapy when compared with surgery alone. For P+ patients, however, there was an improvement in survival when patients received both i.p. and i.v., compared with survival with surgery alone (P < 0.05). In P+ patients aged less than 60 years, there was improvement in survival for those who underwent i.p. therapy together with surgery (P < 0.05), but not for those who had i.v. chemotherapy after surgery. When LUAE was examined, there was a survival advantage for this procedure when there was no peritoneal dissemination. Four long-term survivors (surviving for more than 5 years) were identified in our study. Three of the 4 patients were aged less than 60 years, and all 4 had macroscopic type 4 gastric cancers. CONCLUSION: Although the prognosis for patients with invasive type gastric cancer remains poor, there have been a few long-term survivors, in whom this survival was associated with aggressive combination therapy, including surgery, i.p., and i.v. therapy. P+ patients aged less than 60 years and patients with type 4 gastric cancer may stand to benefit most from such therapy. For P- patients, the role of adjuvant i.p. or i.v. therapy continues to be ambiguous, although LUAE in this population may be superior to PS.

Adult↗

Mitoses of existing corticotrophs contribute to their proliferation in the rat pituitary during the late fetal period.

We studied the proliferation of pituitary corticotrophs quantitatively by labeling the proliferating cells with bromodeoxyuridine (BrdU) and carrying out immunocytochemistry for ACTH in rat fetuses at 19.5 days of gestation. In addition to labeling proliferating cells with a single injection of BrdU, we used double BrdU administrations at 9:00 and 19:00 for a more sensitive detection of proliferating cells. With this double administration, the number of cells labeled with either BrdU or both BrdU and ACTH increased by 1.75 and 2.3 times, respectively, compared with the single BrdU injection. The labeled cells further increased when the sections were stained for the proliferating cell nuclear antigen (PCNA) instead of BrdU. The number of cells labeled with PCNA or both PCNA and ACTH was 1.37 and 1.68 times that of the cells labeled with either BrdU or both BrdU and ACTH, respectively. The ratio of BrdU/ACTH-labeled cells or PCNA/ACTH-labeled cells to all corticotrophs was 13.6% and 24.3%, respectively, much higher than the ratios in fetuses having a single BrdU injection (6.6%). These results indicate that the mitosis of existing corticotrophs contributes greatly to their increase during the late fetal period.

Adrenocorticotropic Hormone↗

Proliferation and differentiation of thyrotrophs in the pars distalis of the rat pituitary gland during the fetal and postnatal period.

Pituitary glands from rat fetuses (gestational age 17.5-21.5 days) and rat pups (3, 7, 10, 14, 28 days old) were labeled with bromodeoxyuridine (BrdU) 2 h prior to sacrifice and embedded in paraffin. Sections were consecutively immunostained with anti-BrdU and anti-rat TSH. The number of cells stained with anti-BrdU, anti-rTSH, or both of them were counted. The area of the section and the volume of the pituitary were measured and the number of immunostained cells per mm3 or per pituitary was calculated. Thyrotrophs were few in 17.5 day-fetuses but increased thereafter, with a rapid increase during the 2nd week after birth. The number of cells labeled with both BrdU and TSH peaked at 7 days after birth. It was estimated that about 1/5 of the thyrotrophs increased during this period was derived from the mitosis of existing thyrotrophs.

Aging↗

Regression of lymph node metastases by immunotherapy using autologous breast tumor-lysate pulsed dendritic cells: report of a case.

A 50-year-old woman was diagnosed as having stage IV breast cancer with bilateral supraclavicular lymph node metastasis resistant to CAF therapy. She received immunotherapy using autologous tumor lysate-pulsed dendritic cells (DCs). Four cycles of DC injection into the right supraclavicular lymph nodes resulted in regression of bilateral supraclavicular lymphogenous metastasis. Histological studies revealed an accumulation of CD45+ T lymphcytes in the regressive lymph nodes. This case suggests that immunotherapy with DCs may be a safe and promising approach for the treatment of advanced breast cancer.

Adjuvants, Immunologic↗

Proliferation and differentiation of pituitary somatotrophs and mammotrophs during late fetal and postnatal periods.

Proliferation of somatotrophs and mammotrophs in the rat pituitary during late fetal and postnatal periods up to 4 weeks after birth was quantitatively studied with the double immunostaining of bromodeoxyuridine and the hormones produced by them. Somatotrophs were first detected in 18.5-day fetuses and rapidly increased in number throughout the periods studied. The cells labeled with both anti-BrdU and anti-GH were few in number until shortly before birth and then increased conspicuously during the first 10 days after birth. Mammotrophs were detected at gestational day 19.5 but they were few until the second week after birth, when their number began to increase rapidly. The percentage of the number of the cells double-labeled with both anti-BrdU and anti-GH to all somatotrophs was 8.3% at the most. This was about the same as that of corticotrophs during the late fetal period and that of thyrotrophs in the early postnatal period. In contrast, the percentage of double-labeled cells to all mammotrophs was 3.8% as a maximum, which is lower than the values for somatotrophs, corticotrophs, or thyrotrophs, indicating a smaller contribution of mitosis to mammotroph proliferation. It is possible that this smaller contribution is compensated for by transdifferentiation of cells committed to become the somatotroph lineage. However, coexistence of GH and PRL was not observed in the present material.

Animals↗