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Biomedical subjects

K Yoshikawa

Publications and source records attributed to K Yoshikawa.

At least 217 records · Page 12Linked to original sources

[Nontuberculous mycobacterial disease in a general hospital].

Annual incidence of nontuberculous mycobacterial (NTM) disease has been gradually increasing in the last 10 years in Japan. It is likely to encounter this disease not only in hospitals specialized in mycobacterial diseases but also in general hospitals. NTM were isolated from 97 cases between January 1990 and June 1996 at our hospital. Out of them, 41 patients were diagnosed as NTM disease. Mycobacterium avium complex (MAC) was the most frequent pathogens (68.3%) and M. kansasii (22%) was the next. Other pathogens were M. chelonae (4.9%), M. fortuitum (2.4%) and M. szulgai (2.4%). Results obtained in our hospital were very similar to the rates which have been reported previously. Patients with MAC infection showed relatively poor prognosis (eight patients were died out of 28 patients with MAC) in this study compared with the cases reported in previous papers, and this result could be explained by the severity of illness when they were admitted to our hospital, the insufficiency of the initial treatment which should be started with the combined use of three to four antibacterial drugs including clarithromycin, and to a low dosage of clarithromycin compared with conventionally adopted dosage. Unlike tuberculosis, human to human transmission is considered to be negligible in the case of NTM disease, and general hospitals are able to provide medical care to the patients with NTM disease. Rather, if general hospitals which are located in the region near to the patients residence can play more active role in the treatment of NTM disease, it would be more beneficial to patients requiring long-term follow-up observation. Based on the result that similar therapeutic results were obtained for infections with other NTM as reported in previous papers, it is indicated that general hospitals are able to provide medical care to patients with NTM disease if therapeutic regimens recommended by specialist are sufficiently understood and applied.

Female↗

Evaluation of renal function from 99mTc-MAG3 renography without blood sampling.

UNLABELLED: To develop a camera-based method for evaluating renal function with 99mTc-mercaptoacetyltriglycine (MAG3), we examined the relationship between various renogram parameters and 99mTc-MAG3 clearance. METHODS: Twenty-one patients underwent renal scintigraphy with 99mTc-MAG3. Eighty 3-s frames were obtained after the bolus injection of 250 MBq tracer, followed by the collection of 52 30-s frames. Regions of interest were drawn for the kidneys, perirenal background areas and subrenal background areas, and background-subtracted renograms were generated. Renal accumulation at 0.5-1.5, 0.5-2, 1-2, 1-2.5 and 1.5-2.5 min after tracer arrival in the kidney was calculated as area under the background-subtracted renogram, and percent renal uptake was obtained after correction for soft-tissue attenuation and injected dose. The slope of the renogram was determined for the same segments used in calculating area under the renogram, and slope index was computed as slope corrected for attenuation and injected dose. Percent renal uptakes and slope indices were correlated by linear regression analysis with 99mTc-MAG3 clearance measured using a single blood sampling method. RESULTS: Among the values of percent renal uptake, the value obtained at 1.5-2.5 min using the perirenal background correlated best with 99mTc-MAG3 clearance. The slope index at 0.5-1.5 or 0.5-2 min using the subrenal background provided better accuracy than percent renal uptake for predicting clearance. There were no substantial differences in the relative function of the right kidney between the methods using percent renal uptake and slope index. CONCLUSION: 99mTc-MAG3 clearance can be assessed with acceptable accuracy by a camera-based method. The method based on the slope of the renogram may replace the one based on the area under the renogram in evaluating renal function from 99mTc-MAG3 renograms.

Blood Specimen Collection↗

[Influence of myopic disc shape in a classification program of the Heidelberg retina tomograph].

PURPOSE: We investigated the influence of myopic disc shape on the diagnostic capability of a glaucoma diagnostic software (classification program) of the Heidelberg retina tomograph (HRT). SUBJECTS: 66 eyes of 66 normal subjects and 78 eyes of 78 patients with open-angle glaucoma were studied. The criterion of glaucoma was a visual field defect appearing between Aulhorn classification stage II and stage V regardless of the maximum intraocular pressure value. METHODS: The subjects were divided into eyes with a myopic disc and those with a non-myopic disc on the basis of stereo disc fundus photographs without considering the refractive errors. Agreement between the classification program and the clinical diagnosis was evaluated by the calculation of sensitivity, specificity, and diagnostic precision, and the influence of the disc shape on HRT disc shape parameters was also evaluated. RESULTS: Sensitivity, specificity, and diagnostic precision of the classification program were 83%, 95%, and 89% in the eyes with a non-myopic disc, and 71%, 96%, and 83% in the eyes with a myopic disc, respectively. Rim volume, height variation contour, mean RNFL (retinal nerve fiber layer) thickness, and RNFL cross section area were significantly larger in the eyes with a myopic disc than in those with a non-myopic disc regardless of the clinical diagnosis. CONCLUSION: The classification program should be modified to adjust to a myopia-like disc shape in order to improve the capability of the glaucoma predictive diagnosis.

Female↗

Reduction of BRCA1 protein expression in Japanese sporadic breast carcinomas and its frequent loss in BRCA1-associated cases.

BRCA1 is a tumor suppressor gene that is responsible for hereditary breast and ovarian cancer syndrome. To clarify the possible involvement of the BRCA1 protein in mammary carcinogenesis in sporadic and hereditary forms, we have analyzed the BRCA1 protein expression pattern in five breast epithelial cell lines, including a BRCA1-deficient cell line, and 162 breast cancer tissue samples [including 108 sporadic, 35 hereditary (BRCA1 status unknown), and 19 BRCA1-associated cases] from Japanese women. Twelve anti-BRCA1 antibodies were tested by fixation conditions, in which nuclear localization of BRCA1 protein was preserved, and by specificity of the antibodies, which was evaluated in BRCA1-deficient cancer cells. Using monoclonal antibodies applicable to immunohistochemical analysis of paraffin-embedded tissue sections, we found high-level expression of BRCA1 protein in normal mammary epithelium and various degrees of reduced expression in breast cancer cells. Of the 19 BRCA1-associated breast cancer tissues, 15 (79%) showed reduction (8 cases) or complete loss (7 cases) of nuclear expression. Thirty (28%) of 108 sporadic and 6 (17%) of 35 hereditary carcinomas showed reduced BRCA1 protein expression. Reduction of BRCA1 protein expression in sporadic carcinomas was associated with solid-tubular phenotype, with poor tubular differentiation, and with an overexpression of c-erbB-2 protein, which is one of the prognostic factors in breast cancer. Our data suggest that reduced expression of BRCA1 protein may play an important role in mammary carcinogenesis, not only in BRCA1-associated breast carcinomas, but also in sporadic carcinomas, and also suggest that mechanisms other than mutation may be involved in its reduced expression.

Animals↗

[Stereometry of temporal peripapillary atrophy in early-stage open-angle glaucoma].

PURPOSE: To study the significance of temporal peripapillary atrophy in the pathogenesis of open-angle glaucoma in its early stage. CASES AND METHOD: Sterometry of temporal peripapillary atrophy was performed in 46 eyes of 46 patients with early-stage open-angle glaucoma and in 38 eyes of 38 healthy persons using a Heidelberg Retina Tomograph. RESULTS: The area of peripapillary atrophy averaged 0.78 +/- 0.46 mm2 in glaucoma eyes and 0.55 +/- 0.33 mm2 in controls. The difference was significant (p < 0.002). Its volume averaged 0.04 +/- 0.04 mm3 in glaucoma eyes and 0.02 +/- 0.02 mm3 in controls. The difference was significant (p < 0.001). Both the area and volume of disc cupping were significantly greater in glaucoma eyes than in controls (p < 0.001). The volume of rim of the disc was significantly smaller in eyes with symmetrical cupping than asymmetrical one (p < 0.001). Both the area and volume of peripapillary atrophy were significantly greater in eyes with asymmetrical cupping than symmetrical one (p < 0.001 each). CONCLUSION: The presence, shape and size of temporal peripapillary atrophy are closely associated with the pathogenesis of open-angle glaucoma in its early stage.

Adult↗

[Effects of gadobenate dimeglumine on MRI of mouse liver metastasis model constructed by orthotopic transplantation of highly metastatic murine colon carcinoma (C38-OT7): comparison with gadopentetate dimeglumine].

Twelve mice with metastatic liver tumors were divided into two groups of six, with one group administered contrast medium at 0.1 mmol/kg, and the other at 0.2 mmol/kg. Contrast medium, gadobenate dimeglumine (GD) or gadopentetate dimeglumine (GP), was administered at 0.1 or 0.2 mmol/kg via the tail vein to each animal in each group. Using a Signa Horizon 1.5-Tesla MRI unit, spin-echo transverse and coronal T1-weighted sections were obtained every 15 minutes until 2 hours after administration. The numbers of liver tumors detected on films were counted before and after the administration of contrast medium, and the liver/tumor contrast-to-noise ratio (CNR) was calculated. After the completion of MRI, livers were removed, and the number of metastatic nodules on the liver surface were counted as the number of tumors. Liver/tumor CNR rose after administration in both of the GD groups. In the GP group, liver/tumor CNR remained almost constant throughout the observation period. Relative to the number of tumors detected at optical microscopy, approximately 80% and 100% of tumors were detected at MRI after the administration of GD at 0.1 and 0.2 mmol/kg, respectively. On the other hand, approximately similar numbers of tumors were detected at MRI before and after the administration of GP. These results suggest that GD administered by intravenous injection was transported promptly to the liver, increased liver/tumor CNR, and enhanced detection performance for metastatic liver tumor.

Animals↗

Pulmonary nodule mimicking lung cancer in a human immunodeficiency virus type-1 infected patient.

We reported a human immunodeficiency virus type 1-infected patient with a small solitary pulmonary nodule mimicking adenocarcinoma, who was treated successfully with antituberculosis therapy. We believe that high-resolution CT scans of thorax are important examinations to detect pulmonary inflammatory findings, such as ectasis of the bronchi leading to the nodules and calcifications in the nodules, and also as follow-up tests for evaluating effectiveness of treatment on pulmonary inflammatory nodules in human immunodeficiency virus type 1-infected patients.

Acquired Immunodeficiency Syndrome↗

[Vitamin and dermatology].

Vitamin A, B1, B2, B6, B12, biotin, nicotinic acid, panthotenic acid, vitamin C, E and K have been used for various skin disorders. The use is mostly based on the similarity of the skin manifestations seen in their deficiencies, except for the rare cases of clear deficiency like pellagra. Recent introduction of vitamin A and D analogues for psoriasis and keratinization disorders resulted in significant progress in clinical dermatology. Application of vitamin C, E and beta-carotene++ for UV-induced skin damages are being studied, and the vitamins will be more important in dermatology in the future.

Avitaminosis↗

Direct laser trapping of single DNA molecules in the globular state.

A sharply focused laser is able to trap small particles at the laser focal point due to the difference in refractive index of the particles and that of the surrounding medium. This technique, called laser trapping, can be used to manipulate animal or bacterial cells without any contact and has been widely applied in biological research. However, it has been difficult to trap biological macromolecules such as DNA molecules, because these molecules give a low difference in refractive index and cannot overcome Brownian motion. DNA molecules can be transformed to a condensed globular state. This transformation results in a higher refractive index of DNA due to its increased density. We demonstrate in this paper that a single DNA molecule can be optically trapped using a Nd:YAG laser (1064 nm wavelength) upon transformation from the coiled state to the globular state.

Animals↗

Mutation at histidine 338 of gp91(phox) depletes FAD and affects expression of cytochrome b558 of the human NADPH oxidase.

Defective NADPH oxidase components prevent superoxide (O-2) generation, causing chronic granulomatous disease (CGD). X-linked CGD patients have mutations in the gene encoding the gp91(phox) subunit of cytochrome b558 and usually lack gp91(phox) protein completely (X91(0)). gp91(phox) is considered to be a flavocytochrome that contains binding sites for NADPH, FAD, as well as heme. We here report a rare X-linked CGD patient whose neutrophils entirely failed to produce O-2, but presented a diminished expression of gp91(phox) containing about one-third of the heme present in normal individuals by Soret absorption. Translocation of cytosolic factors p67(phox) and p47(phox) was normal. However, the FAD content in his neutrophil membranes was as low as that of X91(0) patients, suggesting complete depletion of FAD in his gp91(phox). This was in agreement with the finding that a single base substitution (C1024 to T) changed His-338 to Tyr in gp91(phox) in a predicted FAD-binding domain of the flavocytochrome model. The loss of FAD could not be corrected even after addition of reagent FAD or a FAD-rich dehydrogenase fraction isolated from normal neutrophils to the patient's membranes, in a reconstitution in vitro with normal cytosol. These results indicate that His-338 is a very critical residue for FAD incorporation into the NADPH oxidase system. This is the first such mutation found in CGD.

Amino Acid Sequence↗

Increased production of amyloid precursor protein provides a substrate for caspase-3 in dying motoneurons.

Biochemical and molecular mechanisms of neuronal cell death are currently an area of intense research. It is well documented that the lumbar spinal motoneurons of the chick embryo undergo a period of naturally occurring programmed cell death (PCD) requiring new gene expression and activation of caspases. To identify genes that exhibit changed expression levels in dying motoneurons, we used a PCR-based subtractive hybridization protocol to identify messages uniquely expressed in motoneurons deprived of trophic support as compared with their healthy counterparts. We report that one upregulated message in developing motoneurons undergoing cell death is the mRNA for amyloid precursor protein (APP). Increased levels of APP and beta-amyloid protein are also detected within dying motoneurons. The predicted peptide sequence of APP indicates two potential cleavage sites for caspase-3 (CPP-32), a caspase activated in dying motoneurons. When peptide inhibitors of caspase-3 are administered to motoneurons destined to undergo PCD, decreased levels of APP protein and greatly reduced beta-amyloid production are observed. Furthermore, we show that APP is cleaved by caspase-3. Our results suggest that differential gene expression results in increased levels of APP, providing a potential substrate for one of the cell death-activated caspases that may ultimately cause the demise of the cell. These results, combined with information on the toxic role of APP and its proteolytic by-product beta-amyloid, in the neurodegenerative disease Alzheimer's, suggest that events of developmental PCD may be reactivated in early stages of pathological neurodegeneration.

Amino Acid Sequence↗

A Case of Breast Cancer Coexisting with Florid Papillomatosis of the Nipple.

We report a 47 year-old woman with a unique breast cancer coexisting with florid papillomatosis (FP) of the left nipple. The diseased nipple was enlarged and reddened. There was an area of erosion on the surface. Incisional biopsy revealed FP of the nipple. Under the nipple, there was an elastic hard tumor with an unclear border and irregular surface. Aspiration biopsy cytology of the tumor revealed carcinoma. Modified radical mastectomy was performed. Histological examination showed that the superior portion of the tumor was FP, and most of the tumor in and under the nipple was breast cancer. To the best of our knowledge, only 16 cases of FP of the nipple have been reported in the Japanese literature. FP of the nipple coexisting with carcinoma in the same nipple has never been reported. This is thought to be the first case in Japan of mammary carcinoma coexisting with FP in the same nipple.

Journal Article↗

Hovetrichosides C-G, five new glycosides of two auronols, two neolignans, and a phenylpropanoid from the bark of Hovenia trichocarea.

Two 2-hydroxy-2-benzylcoumaranone glycosides, 2,4, 6-trihydroxy-2-[(4'-hydroxyphenyl) methyl]-3(2H)-benzofuranone-4-yl-beta-D-glucopyranoside (maesopsin 4-O-glucoside) (1) and 2,4,6-trihydroxy-2-[(4'-hydroxyphenyl) methyl]-3(2H)-benzofuranone-4-yl-beta-D-glucopyranosido-4'-y l-alpha-L -rhamnopyranoside (maesopsin 4-O-glucosido 4'-O-rhamnoside) (2), two neolignan glycosides, 2R-(E)-2, 3-dihydro-2-(4'-hydroxy-3'-methoxylphenyl)-5-(3"-hydroxy-1"-pro pen yl) -7-methoxy-3-benzofuranmethanol-4'-yl-beta-D-glucopyranosyl-(1-->3 )-[ beta-D-glucopyranosyl-(l-->2)]-beta-d-glucopyranoside (3) and (threo) 1-(4'-hydroxy-3'-methoxy)-2-(4"-hydroxymethyl-2", 6"-dimethoxyphenoxy)-propane-1,3-diol-4'-yl-beta-d-glucopynosid e (4), and a phenylpropanoid glycoside, 3-methoxy-5-(2'-propenyl)-1, 2-benzenediol-1-yl-beta-D-apiofuranosyl-(1-->6)-beta-D- glucopyransodie (5) were isolated from the bark of Hovenia trichocarea. Compounds 1-5 were named hovetricosides C-G, respectively, and their structures were established by extensive NMR experiments and chemical methods. Also obtained in this investigation were the known compounds acanthoside B, kelampayoside A, shashenoside I, and 3,4, 5-trimethoxyphenol-1-O-beta-D-xylopyranosyl-(1-->6)-beta-D- glucopyranoside.

Carbohydrate Sequence↗

The human chromosomal gene for necdin, a neuronal growth suppressor, in the Prader-Willi syndrome deletion region.

Necdin is a growth suppressor expressed in virtually all postmitotic neurons in the brain. The human necdin gene, NDN, is maternally imprinted and deleted in the Prader-Willi syndrome, a neurobehavioral contiguous gene disorder. Here, we isolated and characterized the human chromosomal necdin gene and its promoter region. The necdin gene is intronless, and it encodes a protein of 321 amino acid residues, four residues shorter than mouse Necdin. By fluorescence in-situ hybridization analysis, the necdin gene was localized to chromosome 15q11.2-q12 within the Prader-Willi syndrome deletion region. CpG islands were found in a region extending from the proximal 5'-flanking sequence to the protein coding region. The 5'-flanking sequence, which lacks canonical TATA and CAAT boxes, possessed a promoter activity in postmitotic neurons derived from murine embryonal carcinoma P19 cells. Methylation in vitro of HhaI CpG sites in the promoter region reduced the transcriptional activity. These results suggest that the necdin gene is silenced through methylation of the CpG island encompassing its promoter region.

Amino Acid Sequence↗