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Biomedical subjects

K Nakayama

Publications and source records attributed to K Nakayama.

At least 37 records · Page 2Linked to original sources

Association of ALDH(2) genotypes and alcohol consumption with periodontitis.

There is little information regarding the association between alcohol consumption and periodontitis risk. We assessed whether alcohol consumption and ALDH(2) genotypes were associated with periodontitis. Subjects' lifestyle was examined by a self-administered questionnaire, and the percentage of pocket depths > or = 3.5 mm was used as a periodontal parameter. ALDH(2) genotypes were determined with the use of a PCR/RFLP method. Multiple logistic analyses showed that alcohol consumption was significantly associated with periodontitis, and its odds ratio was 1.98. There was no significant relationship between periodontal status and ALDH(2) genotypes. However, ALDH(2)*1/*2 subjects who consumed > or = 33 g/day of alcohol had a significantly greater percentage of pocket depths > or = 3.5 mm than those whose daily consumption was lower, while there was no significant difference in periodontal status associated with alcohol consumption in ALDH(2)*1/*1 subjects. Our results suggest that alcohol consumption may be a risk indicator for periodontitis in ALDH(2)*1/*2 subjects who consume larger amounts of alcohol.

Adult↗

[Infected thoracoabdominal aortic aneurysm; report of a case].

A 54-year-old man complained of pain in the left upper abdomen with fever. His past medical history was significant for non-insulin-dependent diabetes mellitus and hypertension. Leucocytosis and an elevation of CRP levels were detected. Thoracoabdominal aneurysm of 69 mm in diameter was identified by enhanced computed tomography (CT). An infected thoracoabdominal aortic aneurysm was diagnosed and an emergency operation was performed. The aneurysm was treated by debridement of the infected aortic tissue and in situ prosthetic graft replacement followed by antibiotic therapy. The postoperative course was uneventful and there were no adverse neurological symptoms. After surgery, antibiotics were administered for 1 month intravenously and the patient was discharged on oral antibiotics for 2 months after the operation. The patient is doing well 7 months after the operation.

Aneurysm, Infected↗

Polarization-mode dispersion measurement by an optical time-domain reflectometer with polarimetry assuming backscattering by randomly oriented nonspherical particles.

In previous work on polarization-mode dispersion (PMD) measurement with an optical time-domain reflectometer with polarimetry (p-OTDR), scatterers were assumed to be a cloud of small spherical particles in a fiber. We have found that the p-OTDR waveforms were fitted well by modified Mueller matrices, assuming scattering by a cloud of nonspherical particles. We realized a PMD measurement based on the p-OTDR Jones matrix eigenanalysis (JME) method. The measured PMD was consistent with that of JME standard measurement with transmission-type polarimetry.

Journal Article↗

Processing of global, but not local, motion direction is deficient in schizophrenia.

Visual motion processing is compromised in a substantial proportion of schizophrenic patients, but precise neural mechanisms underlying the motion-processing deficit have not yet been elaborated. The visual motion pathway includes a local and a global processing stage, each of which has distinct neural substrates. Here, we attempt to identify the stage(s) that are implicated in impaired motion processing of schizophrenia-local, global, or both. For schizophrenia patients (n=23) and normal controls (n=26), we measured (1) the thresholds for detecting the motion direction of a random dot pattern, a task that requires global motion processing, and (2) the thresholds for detecting the motion direction of a grating, a task that requires only local motion processing, using psychophysical methods. Schizophrenia patients showed elevated thresholds for detecting the direction of coherent motion, particularly for the high dot-density target. In contrast, schizophrenia patients showed normal thresholds for detecting the direction of motion of a grating. The results indicate that the global, but not the local, processing stage of the visual motion system is compromised in schizophrenia patients, thus implicating motion-sensitive brain areas that possess large receptive fields for spatial and temporal integration, such as Middle Temporal Area/Medial Superior Temporal Area.

Adult↗

Cytotoxicity of bisphenol A glycidyl methacrylate on cytochrome P450-producing cells.

Of the cytochrome P450 (CYP) family of carcinogen-activating enzymes, CYP3A is the major form found in human livers. The purpose of this study was to investigate the cytotoxic effects of dental resin monomers after being metabolized by CYP3A4 and CYP3A7, using a colony formation assay and a neutral red assay. Specimen wells were plated with transfected cells derived from the Chinese hamster lung at 100 cells well(-1). The experimental group consisted of CYP-producing 3A4-10 and 3A7-40 cells, while the control group consisted of non-CYP-producing CR-119 cells. Bisphenol A (BPA) and bisphenol A glycidyl methacrylate (Bis-GMA) and a positive control (Aflatoxine Bl) were added separately to each well and cultured for 7 days. After cultivation, the number of the colonies was counted and IC50 values were determined. The data were statistically analysed by a Student's t-test. The resultant of IC50 values indicated that the monomers were not metabolically activated by CYP3A4 or CYP3A7 as compared with the control (P < 0.05). We also confirmed that these monomers act neither as activators nor as inhibitors of CYP3A4 and CYP3A7.

Aflatoxins↗

Tentorial schwannoma: a case report.

A rare case of tentorial schwannoma in a 29-year-old male is described. The schwannoma was located within the leaves of the tentorium. MRI showed a wedge-shaped enhancing tumour. Exact nerve of origin of the tumour could not be identified. We speculate that the tumour arose from the tentorial branch of the trigeminal nerve. The literature concerning intracranial schwannoma unrelated to a major cranial nerve is reviewed.

Adult↗

Molecular genetics of Porphyromonas gingivalis: gingipains and other virulence factors.

Porphyromonas gingivalis is a black-pigmented anaerobic gram-negative bacterium that is a major pathogen of chronic adult periodontitis, an inflammatory disease of tooth-supporting tissues. P. gingivalis possesses a number of potential virulence factors. Among them, cell-surface-associated and secreted proteinases such as Arg-gingipain and Lys-gingipain have received much attention because they can degrade various host proteins and cause inflammation. Molecular genetic analysis is extremely powerful to evaluate the significance of each virulence factor in a pathogenic microorganism. This review will describe the introduction of molecular genetics to analysis of pathogenesis of P. gingivalis and the findings that have been obtained using knockout mutants of various potential virulence factors, especially proteinases.

Adhesins, Bacterial↗

Loss of heterozygosity of nucleotide excision repair factors in sporadic ovarian, colon and lung carcinomas: implication for their roles of carcinogenesis in human solid tumors.

The deficiencies of nucleotide excision repair (NER) factors are genetic diseases, xeroderma pigmentosum (XP) increasing risk of developing cancer on sun-exposed areas of the skin. However, the abnormality of NER factors in human sporadic carcinoma remains unclear. Loss of heterozygosity (LOH) analysis for the XP, XPA, XPB, XPC, XPD, XPE, XPF, XPG and the transcription-coupled repair factor, Cockayne syndrome B (CSB) revealed that NER factors were abnormal in 62.1 % of ovarian tumors (18/29), 16.7% of colon (2/12) and 22.2% lung (2/9) carcinomas. Furthermore, 13.8% of ovarian, 8.3% of colon and 22% of lung carcinomas exhibited LOH for NER factors without LOH for tumor suppressor genes such as p53, FHIT, APC, BRCAI, BRCA2 and DCC. Although both microsatellite instability and LOH of NER factors were observed in some cases, there was no strong association between them in the present study. These observations raise the possibility that alterations of NER factors may be frequent in human sporadic carcinomas. Further study should be needed to find the direct evidence of NER gene abnormalities in human sporadic carcinoma tissues.

Chromosome Aberrations↗

Inhibitory effect of M50054, a novel inhibitor of apoptosis, on anti-Fas-antibody-induced hepatitis and chemotherapy-induced alopecia.

M50054, 2,2'-methylenebis (1,3-cyclohexanedione), was identified as a novel inhibitor of apoptosis (programmed cell death) using an in vitro cell death assay system induced in human Fas-expressing WC8 cells by soluble human Fas ligand. Furthermore, M50054 inhibited the apoptotic cell death of U937, a human monocytic leukemic cell line, induced by anticancer agents such as etoposide; it was also confirmed that M50054 inhibited apoptotic features such as DNA fragmentation and phosphatidylserine exposure in these cells. These anti-apoptotic effects were attributable to inhibition of caspase-3 activation. Additionally, M50054 significantly inhibited anti-Fas-antibody-induced elevation of plasma alanine aminotransferase and aspartate aminotransferase. Alopecia (hair loss) symptoms were also significantly improved with topical treatment with M50054. In conclusion, M50054 inhibits apoptosis induced by a variety of stimuli via inhibition of caspase-3 activation, and may thus be effective for hepatitis and chemotherapy-induced alopecia.

Alopecia↗

Essential role of the prosurvival bcl-2 homologue A1 in mast cell survival after allergic activation.

Mast cells reside in tissues, where upon activation through the high-affinity-IgE-receptor (FcepsilonRI) they degranulate and orchestrate the allergic reaction. Mast cells survive this activation and can thus be reactivated. In this study we demonstrate that this process depends on the pro-survival gene A1. Activation of mast cells through FcepsilonRI resulted in degranulation, strong induction of A1 mRNA and protein, and cell survival. In contrast, A1-deficient mast cells released granule mediators similar to the wild-type control, but the cells did not survive an allergic activation. Furthermore, A1(-/-) mice that had been sensitized and provoked with allergen exhibited a lower number of mast cell compared with littermate controls. The induction of A1 was dependent on calcium, as EDTA prevented A1 expression. The calcium ionophore, ionomycin, induced A1 expression and mast cell survival, whereas compound 48/80, a well-known mast cell secretagogue, did not. This study uncovers the importance of A1 for mast cell survival in allergic reactions, and it proposes A1 as a potential target for the treatment of allergic diseases.

Animals↗

Novel peptidomimetics of the antifungal cyclic peptide Rhodopeptin: design of mimetics utilizing scaffolding methodology.

[reaction: see text]. Novel nonpeptide peptidomimetics of the antifungal cyclic peptide Rhodopeptin were designed utilizing hydantoin, benzimidazole, D-glucosamine, quinolone, and benzodiazepine units as scaffolds. The scaffolds were chosen on the basis of their potential to improve the physiochemical properties of the peptidomimetics as well as their ability to bear the requisite Rhodopeptin side-chain moieties with the proper three-dimensional orientation.

Antifungal Agents↗

Novel peptidomimetics of the antifungal cyclic peptide Rhodopeptin: synthesis of mimetics and their antifungal activity.

[reaction: see text]. Novel peptidomimetics of the antifungal cyclic peptide Rhodopeptin were synthesized. As with the cyclic peptides, the presence of all three Rhodopeptin side chains was found to be indispensable for peptidomimetic activity. We discovered new compounds exhibiting greater antifungal activity and improved physiochemical properties in comparison to the parent compounds.

Alkanes↗

Degradation of p27(Kip1) at the G(0)-G(1) transition mediated by a Skp2-independent ubiquitination pathway.

Targeting of the cyclin-dependent kinase inhibitor p27(Kip1) for proteolysis has been thought to be mediated by Skp2, the F-box protein component of an SCF ubiquitin ligase complex. Degradation of p27(Kip1) at the G(0)-G(1) transition of the cell cycle has now been shown to proceed normally in Skp2(-/-) lymphocytes, whereas p27(Kip1) proteolysis during S-G(2) phases is impaired in these Skp2-deficient cells. Degradation of p27(Kip1) at the G(0)-G(1) transition was blocked by lactacystin, a specific proteasome inhibitor, suggesting that it is mediated by the ubiquitin-proteasome pathway. The first cell cycle of stimulated Skp2(-/-) lymphocytes appeared normal, but the second cycle was markedly inhibited, presumably as a result of p27(Kip1) accumulation during S-G(2) phases of the first cell cycle. Polyubiquitination of p27(Kip1) in the nucleus is dependent on Skp2 and phosphorylation of p27(Kip1) on threonine 187. However, polyubiquitination activity was also detected in the cytoplasm of Skp2(-/-) cells, even with a threonine 187 --> alanine mutant of p27(Kip1) as substrate. These results suggest that a polyubiquitination activity in the cytoplasm contributes to the early phase of p27(Kip1) degradation in a Skp2-independent manner, thereby promoting cell cycle progression from G(0) to G(1).

Acetylcysteine↗

Characteristic changes of stress protein expression in streptozotocin-induced diabetic rats.

Stress proteins (heat shock proteins, HSP) play essential roles in folding, assembly and translocation of polypeptides and also in maintenance of the integrity of polypeptides as molecular chaperones. Since long-lasting hyperglycemia causes modification of cellular proteins, it is possible that expression of molecular chaperones may be altered during the course of diabetes. Here, we examined the cellular levels of stress proteins such as HSP105, HSP90 and HSC70/HSP70 in various tissues of streptozotocin-induced diabetic rats. In comparison to controls, the levels of HSC70 were markedly decreased in the liver but not in the brain, adrenal gland and pancreas of diabetic rats. The levels of HSP105 and HSP90 were not significantly changed in these tissues of diabetic rats. Furthermore, the induction of HSP70 as well as HSC70 by hyperthermia was significantly reduced in the liver and adrenal gland of diabetic rats. These results suggested that the expression and induction of HSC70/HSP70 may be altered during the course of diabetic disease and may result in impairment of the cytoprotective ability of diabetic rats.

Animals↗

Studies on transcriptional regulation of Cyp3a16 gene in mouse livers by application of direct DNA injection method.

CYP3A16 is expressed in the mouse liver specifically during a fetal and puberty life. Functional regions responsible for the transcriptional regulation of the Cyp3a16 gene were identified by an in vivo direct DNA injection into mouse livers followed by a luciferase assay. The results of the deletion analysis of a 5'-flanking sequence suggested the existence of an adult-specific repressor(s) interacting with the Cyp3a16 gene. In addition, a positive regulatory element was assumed to be present in a region from -146 to -56 of the Cyp3a16 gene. A hepatocyte nuclear factor 4 (HNF-4)-binding consensus sequence was found in this region. In fact, HNF-4alpha bound to this sequence as evidenced by a gel mobility shift assay. The role of the HNF-4-binding sequence was further examined by an introduction of mutations in this sequence. The introduction of the mutations resulted in a reduced activity of a luciferase in the assay. These results obtained by an application of the direct DNA injection method suggest that the HNF-4alpha activates the transcription of the Cyp3a16 gene in vivo.

Aging↗

Different features of angiogenesis between ovarian and breast carcinoma.

Angiogenesis assessed by immunohistochemical staining for endothelial cells has been widely accepted as an independent prognostic factor in human breast carcinoma. However, the clinicopathologic significance of angiogenesis is still being argued in ovarian carcinoma. Therefore, we retrospectively analyzed the clinicopathologic significance of angiogenesis in ovarian carcinoma compared with that in breast carcinoma. After vessels were stained with CD34-monoclonal antibody, the areas with the highest number of intratumoral microvessels were assessed in a 200x field in 42 ovarian carcinoma and 41 breast carcinoma. Intratumoral microvessel density (IMD) in ovarian carcinoma was significantly lower than that in breast carcinoma. Further, the difference of IMD from tumor to tumor in ovarian carcinoma was smaller than that in breast carcinoma. IMD was correlated with tumor grade, but not with other clinicopathologic variables in ovarian carcinoma. Although the patients with high-IMD tumor revealed a poorer prognosis than those with low-IMD tumor in breast carcinoma, IMD had no influential effects on the survival of the patients with ovarian carcinoma. Our comparative analysis of IMD in ovarian carcinoma with that in breast carcinoma indicates that angiogenesis may play an important role in the transient of ovarian neoplasms, but not in the progression of ovarian carcinomas, and that the biological roles of angiogenesis might be different, depending on histologic subtype.

Adult↗