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Biomedical subjects

M Yoshimoto

Publications and source records attributed to M Yoshimoto.

At least 19 recordsLinked to original sources
PubMed2003

Comparison between solitary and multiple skeletal metastatic lesions of breast cancer patients.

BACKGROUND: Breast cancer has been the subject of many recent studies because it is a significant cause of death in women. This study was performed to clarify whether solitary skeletal metastasis has clinical significance compared with multiple skeletal metastasis. PATIENTS AND METHODS: Seven hundred and three patients who developed metastatic bone lesions up to September 2002 after beginning treatment for breast cancer from 1988 to 1998 were included. The lesions were classified first as solitary or multiple based on bone scan results and then according to anatomical distribution. Next, solitary-to-multiple conversion was investigated in patients with solitary skeletal metastasis. Then factors related to solitary or multiple skeletal metastasis were analyzed. The prognosis of skeletal metastasis was compared between patients with solitary or multiple metastatic bone lesions. A Cox proportional hazards model was used to test whether solitary skeletal metastasis compared with multiple skeletal metastasis was an independent factor of survival. RESULTS: Two hundred and eighty-nine patients (41%) had solitary skeletal metastasis and 414 patients (59%) showed multiple skeletal metastasis. The sternum was a frequent site for solitary skeletal metastasis (98 of 289, 34%), while other skeletal sites were more frequent in patients with multiple metastatic bone lesions (P <0.001). Solitary sternal metastatic lesions remained solitary longer than solitary metastatic bone lesions to places other than the sternum (P <0.001), but did not lengthen patient survival times (P = 0.871). The factors related to solitary skeletal metastasis are TNM stage (tumor-node-metastasis) and histology. The patients with earlier stage and favorable histology tend to have solitary skeletal metastasis. The patients with solitary skeletal metastasis lived longer than those with multiple metastatic bone lesions (P <0.001). Multivariate analysis revealed that a solitary metastatic bone lesion (P = 0.002) is an independent favorable prognostic factor in patients with skeletal metastasis. CONCLUSIONS: Solitary skeletal metastasis has a different anatomical distribution and is an independent prognostic factor in patients with skeletal metastasis.

Adult↗
PubMed2003

Sentinel node detection using 99mTc-rhenium sulphide colloid in breast cancer patients: evaluation of 1 day and 2 day protocols, and a dose-finding study.

Sentinel node (SN) biopsy is a promising replacement for standard axillary lymph node dissection for the staging of early breast cancer, and various techniques have been studied to identify SNs with dye or radioactive colloid. This study assesses the effect of the dose of radioactivity and the time before biopsy in order to set standards for the use of 99mTc-rhenium sulphide for the detection of SNs in breast cancer patients. Sixty patients with stage T1-2 N0 M0 breast cancer underwent SN biopsy, which was immediately followed by standard axillary dissection to confirm the SN results. For SN biopsy, 99mTc-rhenium colloid was injected peritumorally. A 1 day (morning injection and afternoon surgery) or 2 day (day before afternoon injection and morning surgery) protocol was applied. A dose-finding study was performed simultaneously using 7.4-37 MBq for the 1 day protocol and 37-74 MBq for the 2 day protocol. A scintigram was taken at 2 h for the 1 day protocol and 16 h for the 2 day protocol. After the injection of blue dye, SN biopsy was performed with a gamma probe, followed by standard axillary node dissection. The radiation exposure received by the surgical team during the operation was monitored. Histopathological comparison between SNs and axillary nodes was performed. Patient characteristics that might affect the radiocolloid uptake by SNs were assessed. SNs were identified in all patients regardless of the dose or administration protocol used. Two patients showed false negative pathological SN results, and the negative predictive value was 96% and the positive predictive value was 100%. In addition, radiation exposure to the surgical team and the amount of radioactive surgical waste were low, especially at lower doses. Two groups of patient characteristics were related to SN uptake. One was the body mass index (BMI) and the other was the age or menopausal status. Patients with a larger BMI tended to take up a smaller amount of 99mTc colloid. Older or post-menopausal patients showed lower SN uptake. 99mTc-rhenium sulphide colloid is an efficient radiopharmaceutical for SN detection. Both 1 day and 2 day protocols have equally good efficacy, and the recommended dose is 7.4 MBq for the 1 day protocol and 37 MBq for the 2 day protocol. Patients with larger BMI and older or post-menopausal patients tend to take up less 99mTc colloid.

Adult↗
PubMed2002

Breast conserving treatment without radiotherapy.

Radiotherapy (RT) is not always necessary for the prevention of ipsilateral breast recurrence in cases where cancer is not detected in the remaining breast tissue after breast conserving surgery. In addition, under these circumstances, the rate of a second primary cancer of the remaining breast is theoretically equal to the rate of contralateral breast cancer. In performing breast conserving treatment (BCT) at our institution we do not treat with RT if a strict serial pathological examination of the specimen (every 5 mm) reveals that the case has been safely resected (negative surgical margins). From 1986 to 1998, 827 patients (157 were ductal carcinoma in situ, and 670 were invasive) underwent BCT without RT at the Cancer Institute Hospital. Ipsilateral breast cancer was observed in 46 cases or 5.6% (0.85% annually) during a median observation period of 67 months. Of these 46 cases, 19 (2.3%) were diagnosed as a recurrence and 27 cases (3.3%) were second primary cancers. This recurrence rate is equivalent to the rate observed in 406 cases of BCT (1.7%) that were treated with RT. Most of these cases had shown positive surgical margins. Furthermore, the rate of occurrence of second cancers is not significantly different from the rate of occurrence of contralateral breast cancers. These results suggest that, by selecting irradiation cases based on careful pathological examinations, BCT can be safely performed.

Breast Neoplasms↗
PubMed2002

[Rice-wheat rotational FACE platform. I. System structure and control].

A Free Air CO2 Enrichment (FACE) system for rice and winter wheat rotation was established, elevated CO2 concentration was controlled to 200 mumol.mol-1 above ambient by computer system platform according to ambient CO2 concentration variation, wind direction, wind speed, canopy height and day-night changing. Experiments showed that the main factors affecting control precision are wind speed, crop and soil respiration and thickness of diffuse layer. After parameters adjustment, in daytime the time fraction for control precision achieve 80% is 83%, in night is 68%. The CO2 concentrations distribution in FACE rings are uniformity. The set CO2 is 557 mol.mol-1 in daytime and 608 mol.mol-1 in night. In 2001 rice season the target achievement ratios (TAR) were 1.03 after sunrise and 1.09 after sunset, respectively.

Agriculture↗
PubMed2002

[Rice-wheat rotational FACE platform. II. Data processing software package].

A large amount data are brought from daily control, data collection and processing of FACE platform. A FACE system control, data collection and processing software package written in Visual BASIC including OLE to support office functions can finish the platform control, data collection, original data save and backup, daily data processing, monthly data processing and whole time FACE system control status analysis functions, so FACE system controllers can observe FACE system control status and keep control precision timely, and the researchers can get the data they want at any moment and convenient.

Air↗
PubMed2001

Expression of beta-synuclein in normal human astrocytes.

Although alpha- and beta-synucleins are expressed predominantly in presynaptic nerve terminals, recent studies have demonstrated that alpha-synuclein is also expressed in cultured astrocytes and oligodendrocytes. We determined whether beta-synuclein might be expressed in astrocytes. Beta-synuclein mRNA and protein were detected in normal human astrocytes in culture, and immunofluorescent staining showed that beta-synuclein protein was expressed within the cytoplasm and nucleus. Furthermore, beta-synuclein immunoreactivity was present in astrocytes, but not in oligodendrocytes, in normal human brain tissues. Ultrastructurally, beta-synuclein immunoreactivity was found in the cytoplasm of astrocytes, in association with the plasma membrane, ribosomes, rough endoplasmic reticulum and the nuclear outer membrane. The novel expression of beta-synuclein in astrocytes may provide an important insight about the role of this protein.

Astrocytes↗
PubMed2001

Expression of alpha-synuclein in a human glioma cell line and its up-regulation by interleukin-1beta.

Although alpha-synuclein is expressed primarily in neurons, it is a major component of oligodendroglial and astrocytic inclusions in several neurodegenerative diseases. Recent study has further demonstrated that alpha-synuclein is expressed in cultured rat oligodendrocytes. We determined whether alpha-synuclein might be expressed in astrocytic cells. alpha-Synuclein mRNA and protein were detected in U251 human astrocytic glioma cells and normal human astrocytes, and the levels were increased in the former, but not in the latter, by stimulation with interleukin-1beta in a time- and concentration-dependent manner. Serum deprivation also led to an increase of alpha-synuclein mRNA and protein in U251 cells. Immunofluorescent staining confirmed the cell-associated alpha-synuclein. These findings suggest that human astrocytes can produce alpha-synuclein in culture and that certain inflammatory cytokines and cell stress increase alpha-synuclein expression.

Astrocytes↗
PubMed2001

Dynamic changes in glucose metabolism accompanying the expression of the neural phenotype after differentiation in PC12 cells.

To assess what properties of glucose metabolism are most closely related to expression of the neural phenotype, some parameters of glucose metabolism in PC12 cells before (tumor-type) and after differentiation (neuron-type) were investigated. Neuron-type cells exhibited a 2.7-fold higher level of [3H]DG retention than tumor-type cells, accompanied by a higher glucose transport rate and higher levels of hexokinase activity. [14C]CO2 production from [U-14C]glucose in neuron-type was also more than four-times greater than that in tumor-type cells. The levels of [14C]carbon in macromolecules from [14C]glucose in neuron-type cells were also much higher (10.6-fold) than those in tumor-type cells, and the levels of incorporation of [14C]carbon were almost as high as those of [14C]CO2. From the metabolite analysis, amino acids appeared to be the major compounds converted from glucose. On the other hand, the uptakes of [35S]methionine-[35S]cysteine and [3H]uridine in neuron-type cells were lower than those in tumor-type cells. Following depolarization with 50 mM potassium, [14C]CO2 production increased, but the retention of [14C]carbon was not changed in neuron-type cells. The largest change accompanied by acquisition of the neural phenotype was carbon incorporation into the macromolecules derived from glucose. This property may be important for the expression of the neural phenotype as well as the higher levels of both glucose uptake and oxygen consumption.

Animals↗
PubMed2001

Gene expression profile in Alzheimer's brain screened by molecular indexing.

Gene expression in the Alzheimer brain and normal brain was compared by molecular indexing, an advanced version of differential display. Using this technique, each gene was represented by a 3'-end cDNA fragment generated by class IIS restriction enzymes. The fragments were divided into 384 groups, and each group was separated by denaturing polyacrylamide gel electrophoresis. Comparison of gel patterns revealed 70 genes exhibiting marked differences in gene expression between AD and normal brain. A similarity search revealed 22 genes already reported, including those considered to be related to the pathogenesis such as G protein, G protein-related, and mitochondrial components. Detailed analysis of one from those only matched to EST sequences revealed a novel protein with leucine-zipper and SH3-binding motifs. Its expression was suppressed in a subpopulation of cortical pyramidal neurons in the AD brain, suggesting a possible relation to the pathogenesis. Thus, genome-scale analysis of gene expression of neurodegeneration is a potentially powerful approach to listing genes related to the pathogenesis.

Aged↗
PubMed2001

Absence of endothelial cells, central necrosis, and fibrosis are associated with aggressive inflammatory breast cancer.

We recently established a new human inflammatory breast cancer (IBC) xenograft (WIBC-9) originating from a patient with IBC. The graft was transplantable in BALB/c nude and severe combined immunodeficient (SCID) mice. WIBC-9 was frequently accompanied by lung metastasis and exhibited erythema of the overlying skin, reflecting its human counterpart. Histological study of the original tumor and WIBC-9 revealed invasive ductal carcinoma with a hypervascular structure of solid nests and marked lymphatic permeation in the overlying dermis. In the central part of the solid nests, absence of endothelial cells, central necrosis, and fibrosis were observed. In vitro, WIBC-9 formed tube-like structures and loops, reflecting its in vivo feature and its human counterpart. WIBC-9 exhibited aneuploidy, ErbB-2 gene amplification, and an absence of estrogen receptor and progesterone receptor, which is consistent with IBC. Comparative studies of WIBC-9, three established non-IBC xenografts, and a human breast cancer cell line (SK-BR3) by reverse transcription-PCR, ELISA, and immunohistochemistry indicated that certain human genes (interleukin 8, vascular epidermal growth factor, basic fibroblast growth factor, angiopoietin 13, Flt-1, Tie-2, and Tie-1) and certain murine genes (integrin alpha(v)beta3, flt-1, tie-2, vascular epidermal growth factor, and CD31) were overexpressed in exposure to tumor cells. The molecular basis and these unique histological features may be associated with aggressive IBC on angiogenic and nonangiogenic pathways.

Angiogenesis Inducing Agents↗
PubMed2001

Identification of an inhibitor for interleukin 4-induced epsilon germline transcription and antigen-specific IgE production in vivo.

IgE plays a key role in the pathogenesis of allergic disease. Interleukin (IL) 4 is a potent and critical stimulator of immunoglobulin class switching from IgM to IgE in B cells. IL-4 induces the expression of epsilon germline transcript (epsilonGT), which is critical to initiate IgE production. While searching for molecules that inhibit epsilonGT expression induced by IL-4, we found that polyphenol strictinin, which was isolated from tea leaves, was able to inhibit the IL-4-induced epsilonGT expression in the human B cell line DND39. Strictinin also acted on human peripheral blood mononuclear cells obtained from healthy donors to inhibit IL-4-induced epsilonGT expression. Strictinin demonstrated similar inhibitory activity in peripheral blood mononuclear cells obtained from atopic donors. Interestingly, strictinin decreased ovalbumin-induced IgE production in mice, whereas the production of IgG and IgM was not affected. Furthermore, we found that the IL-4-induced STAT6 tyrosine phosphorylation, which is essential for IL-4-induced epsilonGT expression, was inhibited in DND39 cells upon treatment with strictinin. Taken together, these results suggest that strictinin can inhibit IgE production through the inhibition of IL-4-mediated signaling in B cells.

Animals↗
PubMed2001

Analysis of a non-functional HNF-1alpha (TCF1) mutation in Japanese subjects with familial type 1 diabetes.

Mutations in the transcription factor hepatocyte nuclear factor-1alpha (HNF-1alpha; gene symbol TCF1) cause maturity-onset diabetes of the young type 3 (MODY3), a form of diabetes mellitus characterized by autosomal dominant inheritance, early onset, and pancreatic beta-cell dysfunction. Recent genetic studies, however, also found mutations in patients diagnosed with idiopathic (non-autoimmune based) type 1 diabetes. We identified a novel frameshift mutation (142delG) in the TCF1 gene in a family with a strong family history of type 1 diabetes and examined the functional properties of the mutant HNF 1alpha. The expression of the mutant protein was not detected in COS-7 cells by Western blot analysis after transfection of the mutant cDNA. This is the first case of an unstable mutant HNF-1alpha protein. Reporter gene analysis indicated that the mutant HNF-1alpha had no transactivation activity in HeLa and MIN6 cells. Haploinsufficiency for HNF-1alpha may lead to severe forms of diabetes like type 1 diabetes.

Adolescent↗
PubMed2001

Myelodysplastic syndrome progresses rapidly into erythroleukemia associated with synchronous double cancers of the stomach and the papilla of Vater.

Patients with myelodysplastic syndrome (MDS) show a relatively high incidence of developing cancers. However, it is extremely rare that synchronous double cancers develop in an MDS patient. We report a case of MDS that progressed rapidly into erythroleukemia (M6 by French-American-British classification) complicated by gastric cancer and carcinoma of the papilla of Vater. A 66-year-old man was admitted because of pancytopenia with peripheral blasts. A diagnosis of MDS (with refractory anemia with excess of blasts in transformation [RAEB-T]) was made by bone marrow examination. Chromosome analysis revealed 46,XY. An early gastric cancer was also diagnosed by endoscopic examination. The peripheral blasts gradually proliferated and the disease progressed to M6. A chromosome abnormality 46,XY,del(1)(q42) was detected at the leukemic transformation. A CAG (low-dose cytarabine and aclarubicin in combination with granulocyte colony-stimulating factor) regimen was started as a remission-induction therapy. However, obstructive jaundice developed and a marked dilatation of bile ducts was observed by abdominal computed tomography (CT). A carcinoma of the papilla of Vater was detected by endoscopy. As remission was achieved and the pancytopenia improved, the patient subsequently underwent a surgical jejuno-choledochostomy to manage the jaundice. However, the leukemia relapsed thereafter and additional chromosome abnormalities including der(5)t(5;10)(p15:q11) were observed.

Aclarubicin↗
PubMed2001

Co-localization of alpha-synuclein and phosphorylated tau in neuronal and glial cytoplasmic inclusions in a patient with multiple system atrophy of long duration.

Neuronal and glial cytoplasmic inclusions (NCIs and GCIs), which contain alpha-synuclein as a major component, are characteristic cytopathological features of multiple system atrophy (MSA). We report MSA of 19 years' duration in a 73-year-old woman. Her initial symptom was parkinsonism, with dementia appearing about 8 years later. Postmortem examination showed marked atrophy of the frontal and temporal white matter and limbic system, in addition to the pathology typical of MSA. In the limbic system, severe neuronal loss and astrocytosis were observed, and the remaining neurons often had lightly eosinophilic, spherical cytoplasmic inclusions. Interestingly, a double-labeling immunofluorescence study revealed that the NCIs in the dentate gyrus and amygdaloid nucleus, and the GCIs in the frontal and temporal white matter often expressed both alpha-synuclein NACP-5 and phosphorylated tau AT8 epitopes. Double-immunolabeling electron microscopy of the NCIs in the dentate gyrus and the GCIs in the temporal white matter clearly revealed labeling of their constituent granule-associated filaments with NACP-5, and some of them were also labeled with AT8. These findings strongly suggested that some alpha-synuclein filaments were decorated with phosphorylated tau without formation of fibrils such as paired helical filaments. Immunoblotting of sarkosyl-insoluble tau indicated that the accumulated tau consisted mainly of four-repeat tau isoforms of 383 amino acids and 412 amino acids. We consider that the limbic system can be a major site of neurodegeneration in MSA of long duration. The mechanisms of such abnormal tau accumulation in the NCIs and GCIs are unknown.

Aged↗
PubMed2001

An ocular cat-scratch disease patient positive for cytoplasmic anti-neutrophil cytoplasmic antibody.

BACKGROUND: We report a case of ocular cat-scratch disease with permanent vision reduction in a patient who was cytoplasmic anti-neutrophil cytoplasmic antibody (C-ANCA) positive. METHODS: Case report and review of the literature. RESULTS: While taking steroids and antibiotics, a 52-year-old man with uveitis associated with cat-scratch disease developed retinal vein occlusion and a macular exudate. His final visual acuity was poor because of residual macular degeneration and optic atrophy. Serum C-ANCA increased and decreased in parallel with ocular inflammatory activity. CONCLUSION: C-ANCA is an indicator of vasculitis and may be useful as an indicator of severe cat-scratch disease.

Ampicillin↗
PubMed2001

Characterization of acetate metabolism in tumor cells in relation to cell proliferation: acetate metabolism in tumor cells.

To reveal the metabolic fate of acetate in neoplasms that may characterize the accumulation patterns of [1-(11)C]acetate in tumors depicted by positron emission tomography. Four tumor cell lines (LS174T, RPMI2650, A2780, and A375) and fibroblasts in growing and resting states were used. In uptake experiments, cells were incubated with[1-(14)C]acetate for 40 min. [(14)C]CO(2) was measured in the tight-air chamber, and the metabolites in cells were identified by thin layer chromatography and paper chromatography. The glucose metabolic rate of each cell line was measured with [2,6-(3)H]2-deoxy-glucose (DG), and the growth activity of each cell line was estimated by measuring the incorporation of [(3)H]methyl thymidine into DNA. Compared with resting fibroblasts, all four tumor cell lines showed higher accumulation of (14)C activity from [1-(14)C]acetate. These tumor-to-normal ratios of [1-(14)C]acetate were larger than those of DG. Tumor cells incorporated (14)C activity into the lipid-soluble fraction, mostly of phosphatidylcholine and neutral lipids, more prominently than did fibroblasts. The lipid-soluble fraction of (14)C accumulation in cells showed a positive correlation with growth activity, whereas the water-soluble and CO(2) fractions did not. These findings suggest that the high tumor-to-normal ratio of [1-(14)C]acetate is mainly due to the enhanced lipid synthesis, which reflects the high growth activity of neoplasms. This in vitro study suggests that [1-(11)C]acetate is appropriate for estimating the growth activity of tumor cells.

Acetates↗