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M Yoshimoto

Publications and source records attributed to M Yoshimoto.

At least 37 records · Page 2Linked to original sources

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↗

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↗

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↗

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↗

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↗

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↗

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↗

What do breast cancer patients benefit from staging bone scintigraphy?

BACKGROUND: A review and analysis of breast cancer treatment records were conducted to establish criteria for performing disease staging by bone scintigraphy in Japanese breast cancer patients. METHODS: Records from 5538 consecutive Japanese breast cancer patients from January 1988 to December 1998 were reviewed and analyzed to determine bone metastasis status at the time of initial treatment. Correlation between metastasis to bone and factors known before and after surgery was analyzed using logistic regression. RESULTS: The overall incidence of metastasis to bone was 2.13% [95% confidence interval (CI): 1.77-2.55%, 118/5538]. Multivariate logistic analysis revealed that tumor size, nodal involvement and histopathology correlated with metastasis to bone. Patients with tumors larger than 30 mm had a significantly higher probability of metastasis to bone, as did patients with lymph node evaluation results N > or = 1. The incidence of metastasis to bone was 0% in patients with stage 0 disease, 0.08% in stage I patients, 1.09% in stage II patients, 9.96% in stage III patients and 34.04% in stage IV patients. Stage II patients were sub-classified by tumor size T (small, 21-30 mm; and large, 31-50 mm), nodal involvement N and histopathology. The incidence of metastasis to bone in stage II patients was higher in patients with large tumors, scirrhous carcinoma or invasive lobular carcinoma or both. CONCLUSION: Bone metastasis correlated with tumor size (T), lymph node involvement (N) and histopathology. Using the criteria that bone scintigraphy is not necessary in populations with a < 1% incidence of bone metastasis, but is recommended at incidence > 3%, the following conclusions were drawn. Staging by bone scintigraphy provided no benefit to patients whose disease was stage I or less, stage II with small tumors or stage II with large tumors marked by low-grade histopathology (papillotubular cancer). Bone scintigraphy is recommended in patients whose disease is stage II with large tumors marked by high-grade histopathology (scirrhous or invasive lobular cancer), stage III or stage IV. Consequently, staging by bone scintigraphy could be avoided in 71% (3943/5538) of Japanese breast cancer patients.

Adult↗

Brain structures of a medaka mutant, el (eyeless), in which eye vesicles do not evaginate.

Eye development and brain structures of a mutant teleost fish were investigated. The el (eyeless) mutation in medaka (Oryzias latipes) is recessive and affects eye formation; in the most severe cases, it results in the absence of eyes. Developmental studies revealed that normal eyeballs are not formed in the el mutant embryos, but small optic cup-like structures differentiate in situ in the walls of the prosencephalon without evagination. The anophthalmic el homozygous fish hatched normally, although they did not respond behaviorally to visual stimuli. A small fraction of these fish grew to adulthood. In the adult anophthalmic el homozygous fish, the brain exhibited abnormalities in several subdivisions. A pair of small abnormal protrusions was observed on the surface of the ventral telencephalon and preoptic area. Immunocytochemistry using a rhodopsin monoclonal antibody showed that opsin-positive cells were present in the abnormal structures. Bodian staining showed that the optic nerves were present near the abnormal structures, although the number of optic nerve fibers was extremely small. The optic tectum was extremely small, and the thickness of the stratum opticum and stratum fibrosum et griseum superficiale was reduced. These behavioral and morphological observations suggest that the adult anophthalmic el homozygous fish are functionally blind, although small retina-like structures were partially differentiated and persisted in the adult fish brain. Moreover, the adult anophthalmic el homozygous fish were infertile, and the sizes of the hypophysis and the hypothalamus were reduced. Thus, the el mutation affects not only the brain structures that are related to the visual system but also those related to the reproductive system.

Animals↗

Greater resistance and lower contribution of free radicals to hypoxic neurotoxicity in immature rat brain compared to adult brain as revealed by dynamic changes in glucose metabolism.

Seven-day-old rat brain slices were incubated at 36C in oxygenated Krebs-Ringer solution containing [(18)F]2-fluoro-2-deoxy-D-glucose ([(18)F]FDG), and serial two-dimensional time-resolved images of [(18)F]FDG uptake by the slices were obtained. The Gjedde-Patlak graphical method was applied to the image data, and the duration limit of hypoxia loading that allowed recovery of the fractional rate constant (k3*) of [(18)F]FDG (proportional to the cerebral glucose metabolic rate) after hypoxia loading to the unloaded control level was 50 min, and MK-801 as an N-methyl-D-aspartate antagonist had neuroprotective effects, but PBN as a free radical scavenger was ineffective. In our previous study in adult (7-week-old) rat brains [Murata et al., Exp Neurol 2000, 164:269-279], the limit of the hypoxia loading time was 20 min, and both MK-801 and PBN were effective. In the immature rat brains, the ratio of aerobic glucose metabolism to the total glucose metabolism was low compared with the adult rat brains, suggesting only a slight involvement of free radicals in hypoxic neurotoxicity. These data suggest that the higher resistance of immature brains to hypoxia compared to that of adult brains is attributable to a lower involvement of free radicals due to a lower aerobic glucose metabolic rate.

Aging↗

Fiber connections of the nucleus isthmi in the carp (Cyprinus carpio) and tilapia (Oreochromis niloticus).

The nucleus pretectalis (NP) is a prominent nucleus in the percomorph pretectum and has been shown to project to the nucleus isthmi in the filefish by an HRP tract-tracing method [Ito et al., 1981], but a homologous nucleus to the NP is apparently lacking in ostariophysans. The present study examined fiber connections of the nucleus isthmi in an ostariophysan teleost, the carp (Cyprinidae, Cyprinus carpio), to identify a nucleus homologous to the percomorph nucleus pretectalis. Identical studies in a percomorph tilapia (Cichlidae, Oreochromis niloticus) were also performed. Injections of biotinylated dextran amine (BDA) or biocytin to the carp nucleus isthmi labeled cells in the ipsilateral optic tectum and nucleus ruber of Goldstein [1905]. Labeled tectal neurons were located in the stratum periventriculare (SPV) and the stratum fibrosum et griseum superficiale (SFGS). The somata in the SPV were pyriform and those in the SFGS were fusiform. No labeled cells were found in the pretectum. Labeled terminals were seen in the ipsilateral nucleus pretectalis superficialis pars parvocellularis (PSp), optic tectum, and bilateral nucleus ruber. Terminals in the nucleus ruber appear to come from tectal neurons in the SFGS labeled by isthmic injections. Thus the nucleus isthmi has reciprocal fiber connections with the ipsilateral optic tectum, receives projections from the ipsilateral nucleus ruber, and projects to the ipsilateral PSp. The nucleus pretectalis homologue is apparently absent in the carp. Studies in tilapia showed that the nucleus isthmi receives bilateral projections from the NP and optic tectum. In addition, the present study revealed a previously unknown afferent from the nucleus ruber to the percomorph nucleus isthmi. The tilapia nucleus isthmi projects to the same targets as in the carp. Isthmic projection neurons in the tilapia optic tectum were located in the SPV and pyriform with a similar shape to the carp SPV neurons that project to the nucleus isthmi. No labeled cells were found in the SFGS of tilapia optic tectum. The fusiform neurons in the SFGS of the carp optic tectum possess various hodological similarities with the NP and may correspond to the NP neurons of percomorphs.

Animals↗

Modification of lipases with poly(ethylene glycol) and poly(oxyethylene) detergents and their catalytic activities in organic solvents.

The alpha-chymotrypsin-poly(ethylene glycol) complex, which was prepared by lyophilizing an aqueous solution, was found to have high catalytic activity in organic media even when the molar ratio of polymer/enzyme in its preparation stage is unity. In this study, we obtained freeze-dried complexes of lipases and poly(ethylene glycol) or poly(oxyethylene) detergents including newly synthesized gemini-type detergents, and their transesterification activity in organic solvents was evaluated. The freeze-dried lipase from Pseudomonas cepacia prepared by using each modifier showed enhanced transesterification activity, exhibiting a similar dependence on the concentration of the modifier in the preparation stage to that of the alpha-chymotrypsin-poly(ethylene glycol) complex; in contrasts, the one from Candida rugosa did not do so.

Journal Article↗

Antimutagenicity of deacylated anthocyanins in purple-fleshed sweetpotato.

The antimutagenicity of the 3-sophoroside-5-glucoside of cyanidin and 3-sophoroside-5-glucoside of peonidin, the anthocyanin derivatives deacylated from the 3-(6,6'-caffeylferulylsophoroside)-5-glucoside of cyanidin (YGM-3) and 3-(6,6'-caffeylferulylsophoroside)-5-glucoside of peonidin (YGM-6) which had been purified from the sweetpotato with purple-colored flesh, was investigated by using Salmonella typhimurium TA 98. A comparison of the antimutagenicity between YGM-3 and YGM-6 and the deacylated derivatives showed that the activity of cyanidin was stronger than that of peonidin. Deacylation of the peonidin-type pigment markedly decreased this antimutagenicity. Caffeic acid showed the strongest antimutagenicity of the constituent organic acids of the anthocyanin pigments, caffeic acid, ferulic acid, and p-hydroxybenzoic acid. These results suggest that the cathecol structure plays an important role in the strong antimutagenicity of anthocyanin pigments.

Acetylation↗

Brain metastases of malignant melanoma showing unbalanced whole arm chromosomal translocations der (8; 14) (q10; q10) and der (11; 15) (q10; q10) in a Japanese patient.

Since malignant melanoma is a rare malignancy in Japan, little is known about the cytogenetic abnormalities in Japanese patients. We report a case of malignant melanoma showing complex chromosomal abnormalities. A 70-year-old woman was admitted to our hospital because of anorexia, delirium, and right hemiplegia. Cranial CT disclosed several metastatic brain tumors. Multiple subcutaneous and intra-abdominal metastases were also found. A diagnosis of metastatic malignant melanoma was made by biopsy of a subcutaneous tumor. Chromosomal analysis of the tumor cells disclosed complex karyotypic abnormalities including novel unbalanced whole arm translocations der (8; 14) (q10; q10) and der (11; 15) (q10; q10).

Aged↗

[Brain abscess developed five years after splenectomy in a patient with idiopathic thrombocytopenic purpura].

The increased susceptibility to infection following splenectomy has been well documented. We report here, a case of brain abscess developed five years after splenectomy in a patient with idiopathic thrombocytopenic purpura (ITP). A 65-year-old woman was admitted to our hospital because of fever, mental disorientation, and weakness in August, 1999. She had been followed with diagnoses of essential hypertension and type 2 diabetes mellitus (DM) since 1988. The patient was diagnosed as having ITP in 1992, and then underwent splenectomy in 1994. Monoclonal gammopathy of undetermined significance (MGUS) of IgG, lambda type was found in February 1999. Though high grade fever persisted after admission, blood cultures were negative. Antibiotics were given without a satisfactory effect. Right hemiparesis and worsening of consciousness developed subsequently. Contrast enhanced cranial computed tomography (CT) disclosed a ringed enhanced low density mass in the left parieto-occipital lobe compatible with a diagnosis of brain abscess. Surgical drainage was performed and 20 ml of pus was obtained. No primary infectious focus of the brain abscess was detected with intensive examinations.

Aged↗

[Association of idiopathic thrombocytopenic purpura and type 1 diabetes mellitus in a patient with sarcoidosis].

Occurrence of autoimmune diseases with sarcoidosis is well known. However, a case in which more than one of these diseases coexist with sarcoidosis is rare. We present a young man with suspected sarcoidosis, complicated by idiopathic thrombocytopenic purpura (ITP) and type 1 A diabetes mellitus (DM). A 21-year-old man was admitted to our hospital because of thrombocytopenia, hyperglycemia, and bilateral hilar lymphadenopathy (BHL). Although a histological proof could not be obtained, the patient was considered to have sarcoidosis because 67-gallium scintigraphy disclosed "Lambda" and "Panda" signs which are highly specific for sarcoidosis. Type 1 A DM was also diagnosed as the patient had antiglutamic acid decarboxylase antibodies. The patient disclosed no hepatosplenomegaly or no lymphadenopathy and diagnosis of ITP was confirmed by bone marrow examination. High dose steroid was started as the thrombocytopenia progressed. The platelet number increased satisfactorily and shrinkage of BHL was also observed with the therapy.

Adult↗

[A case of central retinal vein occlusion followed by branch retinal artery occlusion].

BACKGROUND: The influence of retinal artery circulation on central retinal vein occlusion (CRVO) is not well known. CASE: A 73-year-old man with hypertension complained of transient visual loss in his left eye. At initial examination, ophthalmoscopy of his left eye showed mild dilatation and tortuosity of the retinal vein and a few dot hemorrhages. Fluorescein angiography disclosed normal arm-to-retina circulation time and no leakage of dye, but delayed retinal circulation time. These findings indicated venous stasis retinopathy of CRVO. In spite of intravenous infusion of prostaglandin E1 and vasodilative treatment, four days after initial examination, the patient's left eyeground showed complication of branch retinal artery occlusion (BRAO). A fibrinolytic agent was given intravenously, but four weeks later, his left eyeground developed typical hemorrhagic retinopathy. The hemodynamics of retrobulbar arterial circulation were investigated by color Doppler imaging. CONCLUSION: We report a case of venous stasis retinopathy of CRVO associated with BRAO, that developed hemorrhagic retinopathy despite treatment with prostaglandin E1 and other vasodilative agents. We think that arterial insufficiency might be responsible for the conversion from venous stasis retinopathy to hemorrhagic retinopathy of CRVO.

Aged↗