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Biomedical subjects

Y Aoki

Publications and source records attributed to Y Aoki.

At least 271 records · Page 15Linked to original sources

Hb Peterborough [beta 111(G13)Val-->Phe] in Japan; rapid identification by ESI/MS using proteolytic digests of oxidized globin.

A variant hemoglobin was found in a Japanese female whose hemoglobin was studied to clarify the cause of a low Hb A1c value, found during a routine medical examination. The detection and identification of the variant was performed by electrospray ionization mass spectrometry. Its structure was revealed to be the same as Hb Peterborough [beta 111(G13)Val-->Phe]. For sequence determination, oxidized globin as well as non-derivatized globin were cleaved by trypsin and lysyl endopeptidase. An abnormal peptide was found in digests of oxidized globin, as shown by electrospray ionization mass spectrometry. Cysteic acid in oxidized peptides enhanced the abundance of fragment ions in tandem mass spectrometry, which helped to quickly and accurately determine the substitution in beta T-12, a peptide in the core region. Electrospray ionization mass spectrometry analysis of the hemolysate also showed a low level of glycated hemoglobin. The patient's hemolysate showed decreased stability in the isopropanol test. An abnormal band was detected on isoelectrofocusing on the cathodic side of normal Hb A. This is the second report of Hb Peterborough and the first of its occurrence in Japan.

Adult↗

[Rbf1 (RPG-box binding factor), a transcription factor involved in yeast-hyphal transition of Candida albicans].

The major fungal pathogen for fungal diseases which have become a major medical problem in the last few years is Candida albicans, which can grow both in yeast and hyphae forms. This ability of C. albicans is thought to contribute to its colonization and dissemination within host tissues. In a recent few years, accompanying the introduction of molecular biological tools into C. albicans organism, several factors involved in the signal transduction pathway for yeast-hyphal transition have been identified. One MAP kinase pathway in C. albicans, similar to that leading to STE12 activation in Saccharomyces cerevisiae, has been reported. C. albicans strains mutant in these genes show retarded filamentous growth on a solid media but no impairment of filamentous growth in mice. These results suggest two scenarios that a kinase signaling cascade plays a part in stimulating the morphological transition in C. albicans, and that there would be another signaling pathway effective in animals. In this latter true hyphal pathway, although some candidate proteins, such as Efg1 (transcription factor), Int1 (integrin-like membrane protein), or Phr1 (pH-regulated membrane protein), have been identified, it is still too early to say that we understand the whole picture of that cascade. We have cloned a C. albicans gene encoding a novel DNA binding protein, Rbf1, that predominantly localizes in the nucleus, and shows transcriptional activation capability. Disruption of the functional RBF1 genes of C. albicans induced the filamentous growth on all solid and liquid media tested, suggesting that Rbf1 might be another candidate for the true hyphal pathway. Relationships with other factors described above, and the target (regulated) genes of Rbf1 is under investigation.

Candida albicans↗

The human poly(ADP-ribose) glycohydrolase maps to chromosome 10q11.23-21.1 by fluorescence in situ hybridization.

Poly(ADP-ribose) glycohydrolase (PARG) digests poly(ADP-ribose), which is synthesized by poly(ADP-ribose) polymerase (PARP) after DNA damage. We mapped the human poly(ADP-ribose) glycohydrolase gene to chromosome 10q11.23-21.1 by fluorescence in situ hybridization analysis. Since chromosomal rearrangements in thyroid papillary carcinoma and loss of heterozygosity in glioblastoma are frequently observed in this region, genetic alteration of PARG could be implicated in these diseases.

Base Sequence↗

[Management and delivery of radiation dose distribution images using the Internet].

Dose distribution images play important roles in the management of cancer patients. To date hard copies of these images have been stored and referred to by radiation oncologists as needed. In most cases, these images were not available to medical personnel outside the radiation oncology department. We have developed a mechanism in the hospital to access these dose distribution images via WWW (World Wide Web). A screen snapshot of a dose distribution image on the CRT of a treatment planning machine is copied to the WWW server and converted to a GIF image. Similarly, we can register dose volume histograms and digitally reconstructed radiographs on the WWW. Medical personnel throughout the hospital can access the images through the WWW browser. As a result, radiation oncologists are given detailed information on target definition in treatment planning by expert physicians. The system also helps co-medical staff in understanding dose distributions and predicting radiation injuries. At the same time, it actualizes an electronic archive of dose distribution images, which is a database for quick and reliable review, evaluation and comparison of treatment plans. This technique also furthers a close relationship among radiation oncologists, physicians, and co-medical personnel.

Computer Communication Networks↗

[C-MOS flat-panel sensor for real time X-ray imaging].

Flat-panel, self-scanning, solid state diagnostic x-ray imaging devices using complementary metal-oxide-semiconductor (C-MOS) arrays are under investigation. A unit device with a 5 cm by 5 cm sensor area was developed and tested. The device consists of a CsI scintillator and C-MOS detector arrays. The detector arrays are composed of a regular arrangement of pixels (256 x 256), each of which is made of a C-MOS photodiode sensor coupled to a C-MOS FET (field effect transistor). A common FET gate line is connected to all the FET gates along each column. A common date line is connected to all the FET drains of each row. The source contact of each FET is connected to that of its corresponding photodiode. A positive gate pulse applied to a gate turns on all FETs connected to the date lines. The readout continues column by column. Correlated double sampling circuits and an offset variance compensation circuit were installed to reduce noise. A sampling speed of 15 frames per second and spatial resolution of 2.5 line per mm were achieved. Noise level and maximum signal were 1.5 mV rms and 1.8 V, respectively. Image quality was considered acceptable for clinical use. It is also discussed how to fabricate a large area sensor with the unit device.

Humans↗

[A collision tumor between squamous cell carcinoma and malignant lymphoma of urinary bladder: a case report].

A 68-year-old-male was admitted to our hospital with the chief complaint of macrohematuria. He was diagnosed with malignant lymphoma at 63 years old. Cystoscopy and computerized tomography revealed a non-papillary and broad based tumor at the anterior wall of the urinary bladder and partial cystectomy was done. Pathological diagnosis was collision tumor between squamous cell carcinoma and malignant lymphoma. To our knowledge, this is the 13th case of collision tumor associated with genitourinary organs in the literature.

Aged↗

Detection of ABH blood group antigens from minute human hairs using polyvinylidene difluoride membrane with elution--ELISA method.

A sensitive and simple method for ABH blood grouping of human hairs using a polyvinylidene difluoride (PVDF) membrane was described. The hairs sensitized with monoclonal antibodies were applied onto the membrane and heated at 60 degrees C on a hot plate. When the membrane was examined with ELISA using a peroxidase-conjugated anti-IgM antibody, group-specific streaky stains were perceived on the membrane, because the eluates directly bound to the membrane. The present method could be available to the detection of minute antigens of short hairs.

ABO Blood-Group System↗

[Three-dimensional CT angiography for cerebral aneurysm using a multi-angle reconstruction plan method].

The purpose of this study was to evaluate the clinical usefulness of three-dimensional CT angiography (3D-CTA) for the diagnosis of cerebral aneurysm using a new reconstruction method called Multi-Angle Reconstruction Plan (MARP). The threshold values, region of interest and six angles of view were preset for the MARP method on the basis of our experience with cerebral 3D-CTA. Spiral CT angiography was performed in 27 patients with 29 aneurysms. The six images reconstructed with the MARP method were generated from the volumetric CT data. Two radiologists independently reviewed the six 3D-CT images for the presence of aneurysm. It took about five minutes to semiautomatically reconstruct the six 3D-CT images with the MARP method. There were no discrepancies in the evaluation of the 3D-CT images. Twenty-six aneurysms of 24 patients were demonstrated on the six 3D-CT images. Three aneurysms in 3 patients were not depicted on the 3D-CT images by the MARP method. In them, the additional 3D-CT images which were generated after evaluating the 2D-CT images clearly showed the aneurysms. The MARP method is considered to be a useful three-dimensional reconstruction technique for the diagnosis of cerebral aneurysm.

Adult↗

Free-to-total prostate specific antigen ratio in clinical staging of prostate cancer.

The value of the free-to-total serum prostate-specific antigen (f/t PSA) ratio was compared with that of the total prostate specific antigen (tPSA) value for the prediction of clinical stage in patients with prostate cancer. The f/t PSA ratio was obtained from the frozen sera of 56 untreated patients with histologically proven BPH and 78 patients with prostate cancer. The clinical stage was organ-confined in 36, locally advanced in 20 and metastatic in 22 patients. Serum levels of free PSA (fPSA) and tPSA were determined using a chemiluminescent enzyme immunoassay. The f/t PSA ratio was calculated by dividing the fPSA value by the tPSA value and was compared with tPSA and fPSA in the correlation with clinical stage via the Spearman rank correlation test. Patients with prostate cancer had a significantly lower f/t PSA ratio than patients with BPH. The f/t PSA ratio did not differ between patients with clinically localized and metastatic cancer. tPSA and fPSA reflected the clinical stage and the extent of bone metastasis more accurately than the f/t PSA ratio. The extent of bone metastasis had no effect on the PSA ratio. The f/t PSA ratio had no additional value in clinical staging compared to tPSA. Our study suggests that the f/t PSA ratio does not reflect tumor load.

Aged↗

[Clinical usefulness of "optimal threshold setting plan" for reconstruction of three-dimensional CT imaging: preliminary clinical study on hepatic tumors and hepatic parenchymal disease].

Clinical application of three-dimensional CT (3D-CT) angiography using the volumetric acquisition capabilities inherent in spiral CT has provided 3D-CT images of vascular structures as well as visceral organs. However, the standard method for deciding the threshold, which is an important process for defining regions of interest, has not yet been established. The setting of an inappropriate threshold may result in reconstruction of a 3D-CT image, leading to misdiagnosis. To simplify the determination of the optimal threshold in a way consistent with the purpose of reconstructing a 3D-CT image, we developed an Optimal Threshold Setting Plan (OPT Plan). With this method, an optimal 3D-CT image could be selected from among those multiple 3D-CT images that were reconstructed on the basis of the multiple thresholds input in advance by referring to attenuation values in both the hepatic lesion and its background on two-dimensional CT images. Clinical usefulness of the OPT Plan for the reconstruction of 3D-CT images was evaluated in 10 patients with hepatic tumors and hepatic parenchymal disease. We obtained 13 3D-CT images (on average) with threshold changes every 5 Hounsfield units, with a mean reconstruction time of 2 minutes 49 seconds, and easily selected an adequate 3D-CT image. Based upon this preliminary experience, the OPT Plan may resolve the difficulty encountered in the setting of thresholds for achieving 3D-CT images, and is considered to be useful for three-dimensional qualitative evaluation of hepatic lesions and hepatic parenchymal disease.

Adult↗

[Quality of life after radical prostatectomy].

In the past, radical prostatectomy commonly led to urinary incontinence and erectile dysfunction. In the last decade, new operative techniques have greatly reduced the complication rate and the operation has gained increasing popularity as treatment of choice for localized prostate cancer. Success or failure of radical prostatectomy has been reported not only in terms of disease-free survival, but in terms of patient attitudes to treatment and side effects. As physicians, we must remember that in presenting treatment options to patients it is important to emphasize both the quality and quantity of life that may result. With richer information on QOL in addition to duration of survival, patients will be able to make more informed decisions. Therefore, the QOL study will contribute patient self-report data to current treatment decision models that rely solely on physician estimates of patients' QOL and side effects following radical prostatectomy. We herein report the results of our recent QOL survey in men treated with radical prostatectomy, and briefly discuss QOL methodology.

Erectile Dysfunction↗

Simple methods of forced oral opening for cadavers oriented to causes of fixed jaw.

Forensic dentistry plays an essential role in personal identification procedures. An adequate interincisal space of relatively fresh cadavers would be required to obtain detailed dental findings. We developed novel and simple procedures of oral opening which are oriented to the causes of the fixed jaw and conscious of facial damage. Preliminary inspection disclosed three causes of the difficulty of oral opening, namely exceptional drying or parchmenting, rigor mortis and loss of extensibility of the temporalis muscles. Tenotomy on the temporalis muscles for cases with the last two factors, and/or mandibular periosteal stripping for those with the first one were employed to approach the oral cavity of cadavers, and a desired degree of interincisal opening was attained. Single or combinational operation of these methods is definitely effective to obtain odontological data without altering facial configuration.

Autopsy↗

[Desquamative interstitial pneumonitis accompanied by a variety of autoimmune abnormalities in an individual with a history of asbestos exposure].

A 75-year-old-man who had been occupationally exposed to asbestos over several decades was admitted complaining of dry cough and mild exertional dyspnea. Chest X-ray films revealed the presence of bilateral infiltrates. An open biopsy showed the lung pathology to be desquamative interstitial pneumonitis (DIP), and detected a calcified plaque of the left parietal pleura at cost-phrenic sulcus, which on microscopic inspection demonstrated thin needle-like structures suggestive of asbestos particles. A hormonal examination showed decreased levels of tri-iodothyronine and tetraiodothyronine and an increased level of thyroid stimulating hormone. Additionally, a positive microsome test indicated autoimmune hypothyroidism. A serological study was positive for anti-nuclear antibody and direct Coombs, and showed heightened levels of IgG. The patient was placed on oral prednisolone therapy; one month later, his symptoms had subsided, and his lung function and chest x-ray findings had improved significantly. In addition, the abnormal values for autoimmune and thyroid function eventually returned to normal ranges. These findings suggest that DIP and humoral immune dysfunction were caused by asbestos exposure, and responded well to steroid treatment.

Aged↗

Arotinoid mofarotene (RO40-8757) up-regulates p21 and p27 during growth inhibition of pancreatic cancer cell lines.

Effective chemotherapy for pancreatic cancer is urgently needed. The anti-proliferative activity of a new retinoid, mofarotene (RO40-8757), was compared with that of other retinoids, such as all trans-retinoic acid, 13-cis retinoic acid and 9-cis retinoic acid, on 9 pancreatic cancer cell lines in relation to the effects on various cell cycle-regulating factors. After treatment with each retinoid, anti-proliferative effect was determined by the MTT method and expression of cell cycle-regulating factors, such as cyclins (D1, E and A), cyclin-dependent kinases (2 and 4), cyclin-dependent kinase inhibitors (p21 and p27) and retinoblastoma protein, was analyzed by Western blotting. Mofarotene showed half-maximal inhibition of cell proliferation at concentrations between 0.14 x 10(-6) and 3.8 x 10(-6) mol/l with little cytotoxicity. In contrast, the other retinoids did not inhibit the growth of all cell lines by over 50% compared to controls. A marked increase in the fraction of cells in G1 phase of the cell cycle was observed after mofarotene treatment; this was associated with marked up-regulation of p21/p27 and a shift of retinoblastoma protein into the hypophosphorylated form. In conclusion, mofarotene inhibits the growth of pancreatic cancer cells by inducing G1-phase cell cycle-inhibitory factors (p21, p27 and hypophosphorylated form of Rb protein) and is considered to be a useful agent for pancreatic cancer treatment.

Alitretinoin↗

A solid-phase assay to screen monoclonal antibodies against DNA-binding protein.

A method is described for selecting monoclonal antibodies (mAb) against DNA-binding protein. The protocol involves a non-radioactive solid-phase DNA binding assay using a 96-well plate. Because the solid-phase assay is highly specific and sensitive, partially purified antigen is sufficient for the immunization, and mAb screening can be performed with crude cell extract as the antigen. MAbs obtained by this method could supershift the DNA-protein complex in the electromobility shift assay, and were sufficient for immunoscreening of a cDNA expression library.

Animals↗

Non-genomic mechanisms of glucocorticoid inhibition of adrenocorticotropin secretion: possible involvement of GTP-binding protein.

We investigated non-genomic mechanisms of glucocorticoid negative feedback regulation on pituitary corticotroph cells using the AtT20 mouse corticotroph tumor cell line. A synthetic glucocorticoid dexamethasone (100 nM) potently suppressed forskolin-induced cAMP generation, adrenocorticotropin (ACTH) secretion, and proopiomelanocortin gene expression. When de novo gene expression was inhibited by actinomycin D (1 microM), dexamethasone still suppressed cAMP efflux and ACTH release, although less potently. Interestingly, under the same conditions, pretreatment of the cells with pertussis toxin (50 ng/ml) completely abolished the suppressive effect of dexamethasone on both parameters. These results suggest that non-genomic and genomic mechanisms are involved in the glucocorticoid negative regulation of ACTH expression, and a pertussis toxin-sensitive GTP-binding protein might, at least partly, participate in the non-genomic effect.

8-Bromo Cyclic Adenosine Monophosphate↗