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Biomedical subjects

Y Miki

Publications and source records attributed to Y Miki.

At least 91 records · Page 5Linked to original sources
PubMed1997

Computer-assisted quantitation of enhancing lesions in multiple sclerosis: correlation with clinical classification.

PURPOSE: To study the utility of a computer-assisted method of quantitating enhancing multiple sclerosis (MS) lesions and to correlate this quantitation with the type and duration of disease. METHODS: Forty untreated patients with MS were studied. The patients had been classified clinically as having either relapsing-remitting (n = 27) or chronic-progressive (n = 13) disease. Postcontrast contiguous 3-mm-thick MR images of the brain were obtained for up to 3 years. The computer program selected potential lesion sites automatically on the basis of the theory of "fuzzy connectedness," which was incorporated into 3DVIEWNIX software. True lesions were selected from these previously detected potential lesions by means of yes/no responses to the program query. The number of enhancing lesions and the enhancing lesions volume were subsequently computed. RESULTS: The enhancing lesion volume in patients with relapsing-remitting disease was statistically significantly higher than that of patients with chronic-progressive disease. There was a strong positive correlation between the number of enhancing lesions and the enhancing lesion volume. No significant correlation was noted between the change in score on the expanded disability status scale (EDSS) and the change in the number of enhancing lesions, or between the change in EDSS score and the change in enhancing lesion volume. A negative correlation was found between enhancing lesion volume and duration of disease, and between the number of enhancing lesions and duration of disease in the patients who had enhancing lesions. CONCLUSIONS: Our data suggest that enhancing lesion volume reflects differences in the classification of clinical MS and in the disease activity over time. Computer-assisted quantitation of enhancing lesion volume is a robust, practical, and objective measure of MS activity.

Adult↗
PubMed1997

Laparoscopic diagnosis of blunt abdominal trauma in children.

This study evaluates the safety and role of laparoscopy in the diagnosis of blunt abdominal trauma in children. Laparoscopy was performed in five patients aged 3 to 13 years because of persistent abdominal pain after blunt trauma. A laparotomy was not indicated from the physical examination, laboratory data, or radiologic findings. With the patient under general anesthesia, a 10-mm trocar was inserted through the umbilical fossa and the intra-abdominal organs were observed for 10 - 60 min under an insufflation pressure of 10 - 12 mmHg. The patients remained hemodynamically stable without pneumothorax development. Three patients underwent laparatomies: one, who had blood in the omental sac, had a duodenal injury with hemorrhagic necrosis and underwent a resection; one with ascites and high amylase levels had an injury of the main pancreatic duct and underwent resection of the pancreatic tail; and one who had fresh blood in the upper abdomen and Douglas' pouch had a splenic hemorrhage and underwent hemostasis. The other two had serous or serosanguinous ascites and recovered without surgery. In patient 1, the same amount of information might have been obtained from a barium study. In patient 2, the pancreatic transection might have been diagnosed from ascites shown on serial computed tomograms. Patient 3 might also have been treated successfully non-surgically. It hus appears that laparoscopy may be a safe diagnostic method for blunt abdominal trauma in children, however, this small series has yielded insufficient information to assess its usefulness in making the diagnosis and the decision for laparotomy. Further studies are required to ascertain whether it will make any significant difference in the form of management.

Abdominal Injuries↗
PubMed1997

[Genetic testing for cancer susceptibility: the present situation in Japan].

Genetic diagnosis of hereditary tumors has progressed extensively and contributed to the presymptomatic testing for mutation carriers. This evolution of genetic testing for cancer susceptibility leads to improved prevention and early detection of cancers. However, the benefits and limits of testing, and the range of prevention and treatment are different in each hereditary tumor. The American Society of Clinical Oncology (ASCO) made the statement on genetic testing for cancer susceptibility and showed three categories for consideration of cancer predisposition testing. They recommend that genetic testing should be offered only for the categories including well-defined tumors. We described the characteristics of hereditary tumors in the three categories and discussed the significance of genetic testing for each tumor. In conclusion, genetic testing for cancer susceptibility should be applied only for subsets of hereditary syndromes, and it is important to continue the analysis of the significance (frequency or penetrance) of mutations of cancer predisposition genes and to make clear the genotype-phenotype and other correlations.

Breast Neoplasms↗
PubMed1997

Global volumetric estimation of disease burden in multiple sclerosis based on magnetization transfer imaging.

We report a semiautomated postprocessing method based on magnetization transfer MR imaging that can quantify the extent of global disease in patients with multiple sclerosis. The technique combines segmentation and quantitative analysis of imaging data reflecting the structural integrity of white matter. Applications of this technique may include assessment of disease progress and of the efficacy of experimental therapeutic intervention. The height of the histogram peak corresponding to white matter was found to be lowered in patients with multiple sclerosis and the overall distribution of magnetization transfer ratios was shifted to lower values.

Adult↗
PubMed1996

Functional and possible physical association of scavenger receptor with cytoplasmic tyrosine kinase Lyn in monocytic THP-1-derived macrophages.

Acetyl LDL (modified low-density lipoprotein), which is thought to be taken up through scavenger receptor A (SR-A), rapidly induced the appearance of phosphotyrosine proteins in monocytic THP-1-derived macrophages in vitro. The two alternative forms of Lyn (p53 and p56) were found to be tyrosine-phosphorylated within 30 s after the stimulation with acetyl LDL. The catalytic activity of Lyn measured by an in vitro kinase assay had also increased in acetyl LDL-stimulated THP-1-derived macrophages. Furthermore, Lyn could be co-immunoprecipitated with SR-A from the cell lysate. These observations suggest a functional and possible physical association of SR-A with Lyn in THP-1-derived macrophages, and also imply a possible involvement of Lyn in SR-A signal transduction.

Amino Acid Sequence↗
PubMed1996

Determination of amikacin in human plasma by high-performance capillary electrophoresis with fluorescence detection.

A selective and reproducible high-performance capillary electrophoretic (HPCE) method for the quantification of amikacin (AMK), an aminocyclitol antibiotic, in human plasma, has been developed for use in clinical laboratory tests. The method involves ultrafiltration (UF) of plasma before derivatization with the fluorescence derivatization reagent 1-methoxy-carbonylindolizine-3, 5-dicarbaldehyde at room temperature for 15 min in the dark. An aliquot of the derivatives is directly introduced into the fused-silica capillary [75 cm (effective length) x 50 microns I.D.] at the anode side by dynamic compression injection (50 hPa for 6 s). After electrophoresis with 40 mM SDS-20 mM phosphate-borate buffer (pH 7) in the micellar electrokinetic chromatography (MEKC) mode at 30 kV, the derivative had a retention time of 16.7 min and was detected by fluorescence intensity at 482 nm (with irradiation at 414 nm). The precision (n = 5) of the method is 4.08 and 1.59% (C.V.) at the 50 and 100 micrograms AMK/ml plasma levels, respectively. Linearity (r = 0.998) was established over the concentration range 5-100 mg of AMK/ml plasma and the detection limit (at a signal-to-noise ratio of 3) is 0.5 microgram AMK/ml plasma. This assay method could potentially have wider application in the determination of other aminocyclitol antibiotics, such as arbekacin, dibekacin, kanamycin, in human plasma as well as of AMK.

Amikacin↗
PubMed1996

Mutations in the BRCA2 gene in hepatocellular carcinomas.

To investigate whether the BRCA2 gene plays a role in carcinogenesis of hepatocellular carcinomas or pancreatic cancers in view of frequent losses of heterozygosity on chromosome 13q12-13 in those tumors, we screened the entire coding region of this gene for mutations in 60 hepatocellular carcinomas and 36 pancreatic cancers. No alteration was found in any of the pancreatic cancers examined, but three mutations were identified in hepatocellular carcinomas; one was a 6-bp somatic deletion within intron 6. The other two mutations we identified in hepatocellular carcinomas were missense mutations in the germ line, although all BRCA2 mutations thus far detected in patients with familial breast cancers likewise have been deletions. None of 194 other patients with cancers or 44 normal controls exhibited either mutation. Combined with our demonstration of BRCA2 expression in adult liver tissue, the evidence implies that inactivation of BRCA2 may play some role in development or progression of hepatocellular carcinoma and might predispose carriers of mutant alleles to liver malignancies.

Carcinoma, Hepatocellular↗
PubMed1996

Generation of an integrated transcription map of the BRCA2 region on chromosome 13q12-q13.

An integrated approach involving physical mapping, identification of transcribed sequences, and computational analysis of genomic sequence was used to generate a detailed transcription map of the 1. 0-Mb region containing the breast cancer susceptibility locus BRCA2 on chromosome 13q12-q13. This region is included in the genetic interval bounded by D13S1444 and D13S310. Retrieved sequences from exon amplification or hybrid selection procedures were grouped into physical intervals and subsequently grouped into transcription units by clone overlap. Overlap was established by direct hybridization, cDNA library screening, PCR cDNA linking (island hopping), and/or sequence alignment. Extensive genomic sequencing was performed in an effort to understand transcription unit organization. In total, approximately 500 kb of genomic sequence was completed. The transcription units were further characterized by hybridization to RNA from a series of human tissues. Evidence for seven genes, two putative pseudogenes, and nine additional putative transcription units was obtained. One of the transcription units was recently identified as BRCA2 but all others are novel genes of unknown function as only limited alignment to sequences in public databases was observed. One large gene with a transcript size of 10.7 kb showed significant similarity to a gene predicted by the Caenorhabditis elegans genome and the Saccharomyces cerevisiae genome sequencing efforts, while another contained a motif sequence similar to the human 2',3' cyclic nucleotide 3' phosphodiesterase gene. Several retrieved transcribed sequences were not aligned into transcription units because no corresponding cDNAs were obtained when screening libraries or because of a lack of definitive evidence for splicing signals or putative coding sequence based on computational analysis. However, the presence of additional genes in the BRCA2 interval is suggested as groups of putative exons and hybrid selected clones that were transcribed in consistent orientations could be localized to common physical intervals.

BRCA2 Protein↗
PubMed1996

Inhibitory mechanisms of H(+)-ATPase inhibitor bafilomycin A1 and carbonic anhydrase II inhibitor acetazolamide on experimental bone resorption.

The effects of the vacuolar-type H(+)-ATPase inhibitor bafilomycin A1 (baf.A1) and the carbonic anhydrase II inhibitor acetazolamide (AZ) on bone resorption and procathepsin L secretion of rat osteoclasts were investigated using the bone slice assay method, pit formation test. Baf.A1 completely suppressed osteoclastic bone resorption stimulated by parathyroid hormone (PTH), but did not affect procathepsin L secretion, while AZ suppressed both bone resorption and procathepsin L secretion. These findings suggest that bone resorption by procathepsin L secretion and its processing are regulated by proton production and proton secretion.

Acetazolamide↗
PubMed1996

Mutations in the BRCA1 gene in Japanese breast cancer patients.

Predisposing germline mutations in the BRCA1 gene were identified recently in families with 17 q-linked breast and ovarian cancers. Using single-strand conformation polymorphism (SSCP) analysis, we examined primary breast cancers for mutations in coding exons of BRCA1 in a panel of 103 patients, of whom all either represented early-onset cases (< 35 of age), were members of multiply-affected families, and/or had developed bilateral breast cancers. Mutations were detected in tumors from four patients, all of whom had developed breast cancers bilaterally: a frame-shift due to a 2-bp deletion at codon 797; a nonsense mutation at codon 1214; and two missense mutations, one at codon 271 leading to Val-->Met substitution, and the other at codon 1150 leading to Pro-->Ser substitution. In each case the same mutation was present in constitutional DNA. The mean age of onset was 49 years among the Japanese carriers of BRCA1 mutations identified in this study, in contrast to the mean age of 35 observed among carriers of BRCA1 mutations in a similar U.S. study (Futreal et al., 1994). The evidence reported here supports a rather limited role of BRCA1 in breast carcinogenesis.

Adult↗
PubMed1996

Congenital multiple intestinal atresia successfully treated with multiple anastomoses in a premature neonate: report of a case.

We report herein the case of a 2080-g premature male infant born at 34 weeks' gestation with multiple intestinal atresia, for whom multiple anastomoses were successfully performed. A total of 11 atresias were found in the small bowel, and five anastomoses were performed to preserve 59 cm of small bowel and the ileocecal valve. Postoperatively, he developed several episodes of sepsis caused by persistent enterostasis, but was able to be weaned from total parenteral nutrition (TPN) by postoperative day (POD) 106. Thus, multiple anastomoses may be the appropriate procedure to prevent short-gut syndrome for congenital multiple intestinal atresia, even in premature infants.

Abnormalities, Multiple↗
PubMed1996

Development of a quantitative sampling method for periapical exudates from human root canals.

A quantitative method for collection of periapical exudates on endodontic paper points is described. In a pilot study, it was revealed that the relationship between fluid volume and wetted length of paper points had a highly significant curvilinear relationship (p < 0.0001), and a highly significant positive linear relationship was found to describe eluted and absorbed interleukin (IL)-1 beta activities from paper points. Periapical exudates from 29 root canals with apical periodontitis were collected using this method, and IL-1 beta activities in clinical specimens were measured. Periapical exudates (0.15 to 26.7 microliters) were recovered, and the range of IL-1 beta concentration was 0.1 to 179.5 ng/ml. These results showed that this sampling method was useful to analyze immunological changes in periapical lesions.

Dental Pulp Cavity↗
PubMed1996

Relationship between prostaglandin E2 concentrations in periapical exudates from root canals and clinical findings of periapical periodontitis.

In this study the relationship of prostaglandin E2 (PGE2) concentrations in periapical exudates with clinical findings of teeth with periapical periodontitis is discussed. Periapical exudate samples were obtained from root canals of 77 endodontically involved teeth during routine root canal treatment by the quantitative sampling method using paper points. PGE2 concentrations in periapical exudates (PE-PGE2) were determined by radioimmunoassay. Significantly higher levels of PGE2 were found in periapical exudates from teeth with radiolucent areas than from teeth without radiolucent areas (236.8 +/- 521.3 pg/microliter vs. 14.9 +/- 23.1 pg/microliter, respectively). The elevated PE-PGE2 levels were associated with the presence of clinical symptoms that reflected an acute inflammation in the periapical lesion. In contrast, a significantly negative association of decreased PE-PGE2 levels with increasing size of radiolucent areas was demonstrated. These results suggested that PGE2 was produced locally in periapical lesions and that the PGE2 concentration in periapical exudate could reflect the state of the disease activity in periapical periodontitis.

Chi-Square Distribution↗
PubMed1996

Mutation analysis in the BRCA2 gene in primary breast cancers.

Breast cancer, one of the most common and deleterious of all diseases affecting women, occurs in hereditary and sporadic forms. Hereditary breast cancers are genetically heterogeneous; susceptibility is variously attributable to germline mutations in the BRCA1 (ref. 1), BRCA2 (ref. 2), TP53 (ref. 3) or ataxia telangiectasia (ATM) genes, each of which is considered to be a tumour suppressor. Recently a number of germline mutations in the BRCA2 gene have been identified in families prone to breast cancer. We screened 100 primary breast cancers from Japanese patients for BRCA2 mutations, using PCR-SSCP. We found two germline mutations and one somatic mutation in our patient group. One of the germline mutations was an insertion of an Alu element into exon 22, which resulted in alternative splicing that skipped exon 22. The presence of a 64-bp polyadenylate tract and evidence for an 8-bp target-site duplication of the inserted DNA implied that the retrotransposal insertion of a transcriptionally active Alu element caused this event. Our results indicate that somatic BRCA2 mutations, like somatic mutations in the BRCA1 gene, are very rare in primary breast cancers.

BRCA2 Protein↗
PubMed1995

Extracellular calcium causes the release of calcium from intracellular stores in chick osteocytes.

We have recently demonstrated that a rise in the extracellular divalent cation concentration induces a rapid elevation of cytosolic calcium in chick osteocytes. Here, we demonstrate that cytosolic calcium elevation that occurs in osteocytes on exposure to elevated extracellular calcium is independent of membrane voltage and is insensitive to modulation by organic calcium channel modulators, namely, BAY K 8644, nicardipine, and nifedipine. However, the calcium elevation was sensitive to modulation by an intracellular calcium antagonist, TMB-8, suggesting that the cytosolic calcium elevation was due to mobilization of this cation from an intracellular store.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1995

Remarkable activity enhancement of thermolysin mutants.

Most attempts to modify the properties of enzymes by amino acid substitution around the active sites have resulted in suppression of the biological activity, suggesting that the structure of natural enzymes should be almost optimized evolutionally to show the highest activity. In contrast, we found an interesting site of a well-known metalloendopeptidase, thermolysin (EC.3.4.24.4), where almost all the amino acid replacement causes a remarkable increase in the hydrolytic activity. Negative correlation between the activity and the thermal stability was observed. The flexibility around the substrate binding site is suggested to be a key to the correlation. Nature may have selected the amino acid at this site, which suppresses the flexibility of the molecule, to get the highest thermal stability at the expense of the activity.

Enzyme Activation↗
PubMed1995

A physical map encompassing GP2B, EPB3, D17S183, D17S78, D17S1183, and D17S1184.

The q21 region of chromosome 17 contains the gene BRCA1, which is involved in familial early-onset breast and ovarian cancers. A physical map of a region that extends from a distal boundary of the BRCA1 region, D17S78, to GP2B has been constructed. The map consists of 30 STSs, including 2 new short tandem repeat polymorphic markers. The contig is composed of a mixture of 7 YACs, 5 P1 plasmids, and 14 cosmids and was ordered by STS-content mapping.

BRCA1 Protein↗