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Biomedical subjects

Y Higuchi

Publications and source records attributed to Y Higuchi.

At least 109 records · Page 6Linked to original sources

Role of p53 and p21/WAF1 detection in patient selection for preoperative radiotherapy in rectal cancer patients.

BACKGROUND: Recent studies showed that p53 and p21 may play major roles in determining tumor radiosensitivity through the apoptosis pathway. The aim of this study was to investigate the predicting value of radiosensitivity in human rectal carcinoma. METHODS: p53 and p21/WAF1 expressions in formalin fixed, paraffin-embedded, preradiation biopsy samples from 49 patients with primary rectal carcinoma were analyzed immunohistochemically. p53 and p21 expressions and their relationships with histopathologic changes after radiation and other clinical features were evaluated. RESULTS: Expressions of p53 and p21/WAF1 were 49 and 28.6 percent, respectively. In 36.7 percent of total tumors, significant histopathologic effect can be observed. There was a significant inverse expression of p53 and p21. Most of the p53(+) or p21(-) tumors were radioresistant, and the majority of p53(-) or p21(+) tumors were radiosensitive. Tumors size in the radiosensitive, p53(-), or p21(+) group decreased more significantly than in radioresistant, p53(+), or p21(-) group (P < 0.01), and patients with radioresistant, p53(+), or p21(-) tumors had more local recurrence, more distant metastasis, and a shorter five-year survival rate than those with radiosensitive, p53(-), or p21(+) tumors, but without statistic significance. No statistically significant correlation can be observed between other tumor clinical features and radiosensitivity, p53, or p21 expressions. CONCLUSION: Immunohistochemistry detection of p53 and p21 expressions may be useful parameters for more radiosensitive patients selected for preoperative radiotherapy.

Adult↗

Steroid complications and surgery in intractable ulcerative colitis.

The major operative indication for ulcerative colitis is intractability. Although steroid side effects appear to be closely associated with surgical indications for intractable ulcerative colitis, this relationship has yet to be analyzed in detail. To elucidate this relationship, we investigated 39 surgical patients with intractable ulcerative colitis, as defined by the Research Committee for Intractable Diseases of the Ministry of Health and welfare of Japan, and 66 conservatively treated patients with ulcerative colitis, of whom 6 had intractable disease. All patients with major steroid side effects and 17/24 (71%) patients with minor side effects underwent surgery. The median number of admissions was higher in patients with major side effects than in those with less severe or no side effects in the operative series, while this value was lower in the non-operative series than in the operative series. This tendency was similar for the total duration of hospitalization and the number of relapses. In the operative series, markedly higher steroid doses were administered to patients with side effects than to those without, and lower doses were given in the non-operative series. On multivariate regression analysis, the presence of steroid side effects, disease extent, and disease duration were significantly associated with surgery. Patients without side effects had a higher postoperative complication rate than those with minor side effects. We conclude that major side effects are a surgical indication for patients with intractable ulcerative colitis, and that even minor side effects should be taken as a surgical indication in view of the patient's quality of life.

Adolescent↗

Functional magnetic resonance imaging during recognition of written words: Chinese characters for concrete objects versus abstract concepts.

An attempt was made to apply functional magnetic resonance imaging (fMRI) to reveal cortical areas activated upon presentation of two groups of Chinese characters in six normal right-handed, male, Japanese subjects. Presentation of the characters representing 'abstract concepts' activated the bilateral occipital region without a significant difference between the bilateral occipital and temporal regions. Presentation of the characters representing 'concrete objects' resulted in significantly stronger activation in the left occipital and temporal regions. These results suggest that recognition of concrete characters involves a stronger initial process in the left occipital temporal cortices than recognition of abstract characters.

Adult↗

Functional magnetic resonance imaging during recognition of written words: Chinese characters for concrete objects versus abstract concepts.

An attempt was made to apply functional magnetic resonance imaging (fMRI) to reveal cortical areas activated upon presentation of two groups of Chinese characters in six normal right-handed, male, Japanese subjects. Presentation of the characters representing 'abstract concepts' activated the bilateral occipital region without a significant difference between the bilateral occipital and temporal regions. Presentation of the characters representing 'concrete objects' resulted in significantly stronger activation in the left occipital and temporal regions. These results suggest that recognition of concrete characters involves a stronger initial process in the left occipital temporal cortices than recognition of abstract characters.

Adult↗

Phenotypic differences between T-->C and T-->G mutations at nt 8993 of mitochondrial DNA in Leigh syndrome.

This study reports on a patient with Leigh syndrome with a T-to-C mutation at nucleotide 8993 of mitochondrial deoxyribonucleic acid (T8993C). The authors reviewed 10 Leigh syndrome patients, including ours, with T8993C. Compared with 18 reported patients with Leigh syndrome caused by a T-to-G mutation at nucleotide 8993 (T8993G), Leigh syndrome with T8993C was characterized by a significantly higher frequency of ataxia (P < 0.01). None of the reviewed T8993C-associated Leigh syndrome patients had retinitis pigmentosa, which is one of the characteristic findings in Leigh syndrome with T8993G. The milder symptoms of T8993C-Leigh syndrome can be explained by the milder complex V dysfunction; however, the higher frequency of ataxia in T8993C-Leigh syndrome requires more study.

Child, Preschool↗

Active oxygen-mediated chromosomal 1-2 Mbp giant DNA fragmentation into internucleosomal DNA fragmentation in apoptosis of glioma cells induced by glutamate.

C6 glioma cells treated with 10 mM glutamate reduced intracellular GSH to one-seventh of the initial level, and induced cytolysis accompanied by apoptosis. The treated cells produced extracellular H2O2. The cytolysis of the C6 cells induced by glutamate was prevented by antioxidants such as N-acetylcysteine (NAC), ascorbic acid (ASC), catalase, and NaN3, iron chelators such as deferoxamine and 1,10-phenanthroline, and oxygen radical scavengers such as 5,5'-dimethyl-1-pyrroline-N-oxide (DMPO) and alpha-phenyl-tert-butyl nitrone (PBN). The effect of these antioxidants, iron chelators, and oxygen radical scavengers on the cytolysis of C6 cells was dependent on the dose and the intracellular GSH level. Furthermore, 1-2 Mbp chromosomal DNA (giant DNA) fragments were observed during cytolysis. The giant DNA fragments were further cleaved into smaller DNA fragments of 200-800 kbp, and then to fragments of less than 300 kbp in size including chromosomal ladder DNA fragments. Such serial chromosomal DNA degradations induced by glutamate were also inhibited by addition of these antioxidants, iron chelators, and oxygen radical scavengers. These findings suggest that glutamate induces GSH depletion, and consequently, apoptosis through endogenously produced active oxygen species in C6 glioma cells and that the apoptosis is accompanied by 1-2 Mbp giant DNA fragmentation prior to the internucleosomal DNA fragmentation.

Acetylcysteine↗

Enhancement of XPG mRNA expression by human interferon-beta in Cockayne syndrome cells.

Using PCR-differential display, we have searched for genes expressed specially in human interferon (HuIFn)-beta-treated Cockayne syndrome (CS) fibroblast cells. Eighteen expressed genes induced by HuIFN-beta were identified, the sequences of seven of which were highly homologous to previously cloned sequences. The cDNAs of six of these seven clones were similar to expression tagged sequences from unknown genes in databases and the remaining one was identical to the cDNA of the xeroderma pigmentosum XPG gene. These results, together with our previous finding of increased resistance to ultraviolet (UV) cell-killing of CS cells pretreated with HuIFN-beta prior to UV irradiation suggest that XPG might be one of the genes possibly involved in the HuIFN-beta-induced UV-resistance.

Cells, Cultured↗

Syntheses and preventive effects of analogues related to 1alpha,25-dihydroxy-2beta-(3-hydroxypropoxy)vitamin D3 (ED-71) on bone mineral loss in ovariectomized rats.

Analogues related to 1alpha,25-dihydroxy-2beta-(3-hydroxypropoxy)vitamin D3 (ED-71) (2), 26,27-dimethyl ED-71 (3) and 26,27-diethyl ED-71 (4), were synthesized from lithocholic acid (5). In the study of the preventive effects of these analogues and ED-71 (2) on bone mineral loss in ovariectomized rats, 26,27-dimethyl ED-71 (3) showed the most potent activity.

Animals↗

Computed tomographic features of calcifying odontogenic cysts.

OBJECTIVES: To describe the CT appearances of 4 cases of the calcifying odontogenic cyst (COC) with particular reference to the effect of varying the window settings. METHODS: Conventional radiographs and CT scans of 4 calcifying odontogenic cysts were analyzed with respect to the presence of an impacted tooth, root resorption and calcification. In addition, increased attenuation by desquamated keratin was examined by varying the window settings on CT. RESULTS: All lesions were located in the maxilla and on conventional radiographs, had unilocular radiolucency with a well-defined margin. Calcifications and inclusion of an impacted tooth were seen in all cases. Root resorption was observed in two cases, but was not prominent. On CT, calcification was detected at the periphery of the lesion and/or around the impacted tooth in all cases. Varying the window setting revealed an increased attenuation area due to desquamated keratin. CONCLUSIONS: Varying the window setting on CT is useful as a means of identifying both desquamated keratin and peripheral calcification in COC.

Adolescent↗

Plasminogen Kanagawa-I, a novel missense mutation, is caused by the amino acid substitution G732R.

A new dysplasminogen, plasminogen Kanagawa-I, was identified in a healthy male with no previous thrombotic episodes. His plasma plasminogen (PLG) activity was 51.4% of that of normal pooled plasma (reference interval 70-130%) and the antigen level was 94.2% of that of normal pooled plasma (reference interval 80-150%). Nucleotide sequencing revealed a heterozygous G to A transition in exon 18, which resulted in an amino acid substitution of G732R. Both the proband's father and paternal grandfather were heterozygous for this mutation. Interestingly, the grandfather was found to be a compound heterozygote for plasminogen Kanagawa-I and Tochigi (A601T), so that his plasminogen activity and antigen level was 7.7% and 87.2% of that of normal pooled plasma, respectively. However, he has never been affected by significant thrombosis.

Adult↗

Range of motion of the temporomandibular joint in rheumatoid arthritis: relationship to the severity of disease.

The purpose of this study was to determine the frequency and nature of temporomandibular joint (TMJ) involvement in rheumatoid arthritis (RA) patients with symptoms in this joint, and to investigate the relationship of symptoms to the C-reactive protein (CRP), erythrocyte sedimentation rate (ESR) and Steinbrocker stage. Clinical examination of the range of motion of the TMJ was performed in 218 RA patients. In addition, correlations between the maximal mouth opening and the severity of RA were studied. Restriction in opening the mouth (defined as < or = 30 mm movement in the central incisor region from the fully occluded to maximally open positions) was observed in 12.8% of the RA patients (28/218). The CRP, ESR and Steinbrocker stage were all correlated with maximal opening (p < 0.05). There was a positive correlation between the severity of RA and the range of motion of the jaw.

Adult↗

Establishment of ameloblastoma cell line, AM-1.

Ameloblastomas are slowly growing, locally invasive neoplasms with a potentially destructive behaviour. The molecular mechanisms that regulate the cell growth and invasion of ameloblastoma cells are unknown. Because ameloblastoma cells placed in culture have a very limited lifespan, the establishment of immortalized clones of ameloblastoma cells would aid its study. We produced an immortalized ameloblastoma cell line (AM-1) using human papillomavirus type-16. This cell line maintains epithelial cell morphology and expresses cytokeratins K8, K14, K18, K19. Furthermore, bcl-2 protein, which prevents apoptosis, is expressed. We investigated the behaviour of these cells on a collagen matrix in vitro. These cells grew in a monolayer over foci of collagen degradation and could invade the collagen gel at such sites. Since the behavior of cell line AM-1 mimics the behavior of ameloblastoma in vivo, it may be a valuable model for the study of these neoplasms.

Ameloblastoma↗

Preventive effects of Shichimotsu-koka-to on renal lesions in stroke-prone spontaneously hypertensive rats.

Shichimotsu-koka-to (SKT) has been prescribed to treat patients with essential and renal hypertension. We investigated the effects of SKT on renal lesions in stroke-prone spontaneously hypertensive rats (SHRSPs). SHRSPs were given an extract of SKT by mixing it with drinking water, from 8 through 29 weeks of age, so that the average intake of SKT extract was about 1.5 g/kg/d. At 29 weeks of age, the kidneys of SHRSPs exhibited proliferative arteritis characterized by the proliferation of smooth muscle cells in the interlobular arteries, dilation and degeneration of renal tubules, infiltration of inflammatory cells and hemorrhage, with partial swelling or necrotizing of glomeruli. In particular, arteritis and periarteritis were noted. The treatment of SHRSPs with SKT ameliorated this morphological damage in the kidney and significantly decreased urea nitrogen in the serum. Treatment with SKT also strongly decreased the xanthine oxidase (XOD) activity and significantly increased the superoxide dismutase (SOD) activity in the kidney of SHRSPs; consequently, these values became close to those in normotensive Wistar Kyoto rats (WKYs). These results indicate that treatment with SKT ameliorated the histopathological damage and change in activity of enzymes related to free radicals in the kidney of SHRSPs, which may be important mechanisms for SKT for protecting SHRSPs from renal dysfunction.

Animals↗

MaMi, a human endometrial stromal sarcoma cell line that constitutively produces interleukin-6, interleukin-8, and monocyte chemoattractant protein-1.

BACKGROUND: Uterine endometrial stromal sarcoma is a rare neoplasm with a morphology that closely resembles that of the proliferative endometrial stroma. To understand its pathologic characteristics, we established a novel cell line, MaMi, from a primary culture of an endometrial stromal sarcoma obtained from a 65-year-old Japanese woman. METHODS: We observed the morphology of MaMi cells and performed immunohistochemical analysis on the primary tumor and transplants in nude mice. Prolactin, insulin-like growth factor-binding protein-1, interleukin (IL)-6, IL-8, monocyte chemoattractant protein-1, intercellular adhesion molecule-1, E-selectin, vascular cell adhesion molecule-1, and fibronectin production in the culture medium of MaMi cells were also examined. RESULTS: MaMi cells were shown to exhibit a fibroblast-like morphology in vitro, and they adopted a more elongated appearance in response to 12-O-tetradecanoyl phorbol-13-acetate (TPA). On injection into nude mice, the cells gave rise to subcutaneous tumors. Immunohistologically, both the primary tumor and MaMi cell-induced tumors stained positively with antibodies to neuron-specific enolase or vimentin. MaMi cells constitutively produced IL-6, IL-8, and monocyte chemoattractant protein-1 in vitro. Interleukin-1beta, (100 pmol/L), tumor necrosis factor-alpha (1 nmol/L), and lipopolysaccharide (1 microg/mL) each increased the release of IL-6, IL-8, and monocyte chemoattractant protein-1 by MaMi cells. TPA (10 nmol/L) also stimulated the production of IL-6 and IL-8 by these cells, but inhibited that of monocyte chemoattractant protein-1. CONCLUSIONS: We demonstrated that MaMi cells closely resemble proliferative endometrial stromal cells not only morphologically, but also functionally. This cell line may prove valuable in understanding the role of cytokines produced by tumor cells in the pathogenesis of endometrial stromal sarcoma and may also be useful as an in vitro model of functioning endometrial stromal cells.

Aged↗

Unusual ligand structure in Ni-Fe active center and an additional Mg site in hydrogenase revealed by high resolution X-ray structure analysis.

BACKGROUND: The hydrogenase of Desulfovibrio sp. catalyzes the reversible oxidoreduction of molecular hydrogen, in conjunction with a specific electron acceptor, cytochrome c3. The Ni-Fe active center of Desulfovibrio hydrogenase has an unusual ligand structure with non-protein ligands. An atomic model at high resolution is required to make concrete assignment of the ligands which coordinate the Ni-Fe center. These in turn will provide insight into the mechanism of electron transfer, during the reaction catalysed by hydrogenase. RESULTS: The X-ray structure of the hydrogenase from Desulfovibrio vulgaris Miyazaki has been solved at 1.8 A resolution and refined to a crystallographic R factor of 0.229. The overall folding pattern and the spatial arrangement of the metal centers are very similar to those found in Desulfovibrio gigas hydrogenase. This high resolution crystal structure enabled us to assign the non-protein ligands to the Fe atom in the Ni-Fe site and revealed the presence of a Mg center, located approximately 13 A from the Ni-Fe active center. CONCLUSIONS: From the nature of the electron-density map, stereochemical geometry and atomic parameters of the refined structure, the most probable candidates for the four ligands, coordinating the Ni-Fe center, have been proposed to be diatomic S=O, C triple bond O and C triple bond N molecules and one sulfur atom. The assignment was supported by pyrolysis mass spectrometry measurements. These ligands may have a role as an electron sink during the electron transfer reaction between the hydrogenase and its biological counterparts, and they could stabilize the redox state of Fe(II), which may not change during the catalytic cycle and is independent of the redox transition of the Ni. The hydrogen-bonding system between the Ni-Fe and the Mg centers suggests the possible.

Binding Sites↗

Structure of cytochrome c' from Rhodobacter capsulatus strain St Louis: an unusual molecular association induced by bridging Zn ions.

Rhodobacter capsulatus strain St Louis cytochrome c' (RCCP-SL) has been crystallized and the structure solved by molecular replacement. It was refined at 2.1 A resolution to an R value of 18.4%, and compared with Rhodobacter capsulatus strain M110 cytochrome c' (RCCP-M110). Although these two proteins are very similar in sequence and structure, the intermolecular interaction is largely different. In RCCP-M110, the molecules dimerize through interaction of helix B to form an antiparallel arrangement. When crystallized in the presence of Zn ions, molecules of RCCP-SL were found to be arranged as linear polymers connected by the bridging Zn ions. The changes in conformation of the side chains induced by binding of the Zn ions, by the substitution of Glu90 for Asp90, and by the different arrangement of the molecules, are discussed in detail.

Journal Article↗