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Biomedical subjects

Seiichi Yoshida

Publications and source records attributed to Seiichi Yoshida.

14 recordsLinked to original sources

Intracranial metastatic parathyroid carcinoma: case report.

BACKGROUND: Although parathyroid carcinoma is not frequent, it is a slowly progressive disease characterized by frequent recurrences. A review of the literature revealed only 2 other cases of intracranial metastatic parathyroid carcinoma. We present here the case of cerebral metastases from parathyroid carcinoma that could be treated successfully. CASE DESCRIPTION: This 61-year-old Japanese woman presented to our institute with a complaint of right lower-extremity weakness after hemiconvulsion. She had undergone a parathyroidectomy for parathyroid carcinoma 18 years earlier. Lung metastasis was also detected 6 years earlier, and she has been dialyzed twice a month after chemotherapy. Computed tomographic scans demonstrated 2 enhancing right frontal tumors. After resection of the intracranial metastases, her right hemiparesis and secondary hyperparathyroidism resolved. CONCLUSIONS: This case report supports aggressive surgical management to eliminate all parathyroid hormone-secreting malignant tissue and prevent metabolic complications.

Brain Neoplasms↗

Expression profiles of metastatic brain tumor from lung adenocarcinomas on cDNA microarray.

Distant metastasis is one of the crucial parameters determining the type of treatment and prognosis of patients. Previous studies discovered important factors involved in multiple steps of metastasis, the precise mechanisms of metastasis still remain to be clarified. To identify genes associated with this complicated biological feature of cancer, we analyzed expression profiles of 16 metastatic brain tumors derived from primary lung adenocarcinoma (ADC) using cDNA microarray representing 23,040 genes. We applied bioinformatic algorithm to compare the expression data of these 16 brain metastatic loci with those of 37 primary NSCLCs including 22 ADCs, and found that metastatic tumor cells has very different characteristics of gene expression patterns from primary ones. Two hundred and forty-four genes that showed significantly different expression levels between the two groups included plasma membrane bounding proteins, cellular antigens, and cytoskeletal proteins that might play important roles in altering cell-cell communication, attachment, and cell motility, and enhance the metastatic ability of cancer cells. Our results provide valuable information for development of predictive markers as well as novel therapeutic target molecules for metastatic brain tumor of ADC of the lung.

Adenocarcinoma↗

Mice strain differences in effects of fetal exposure to diesel exhaust gas on male gonadal differentiation.

We have shown that in ICR pregnant mice exposed to diesel exhaust (DE), mRNA expression of mällerian inhibiting substance (MIS) and a steroid hormone transcription factor (Ad4BP/SF-1), which are essential in male gonadal differentiation, decreases in a DE concentration-dependent manner. To further investigate whether these effects differ among strains, we conducted the present study in 3 different strains: ICR mice, ddY mice, and C57BL/6J mice. The response to DE exposure differed among the 3 strains. In C57BL/6J male fetuses, only MIS mRNA expression significantly decreased, and in ddY male fetuses, there was no change in either MIS or Ad4BP/SF-1 mRNA expression. Although there was no definite correlation between mouse strain characteristics and differences in the effects of DE, our findings suggest strain-related variations in DE sensitivity with respect to gene expression regulating male gonadal differentiation.

Animals↗

In utero exposure to diesel exhaust increased accessory reproductive gland weight and serum testosterone concentration in male mice.

The effects of in utero exposure to diesel exhaust (DE) on the male mouse reproductive system were examined. Pregnant ICR mice inhaled DE at soot concentrations of 0.3, 1.0, or 3.0 mg DEP/m3 or clean air as the control, for 2-16 days postcoitum. On postnatal day (PND) 28, the weights of the testes and accessory glands and testosterone concentration in serum were significantly higher in the DE-exposed male pups. Testosterone concentration correlated significantly (P<0.01) with the expression levels of steroidogenic enzyme mRNAs, weights of the testes and male reproductive accessory glands, and daily sperm production. These findings indicate that very early stage mouse embryo exposure to DE leads to endocrine disruption after birth and acceleration of male puberty.

Animals↗

Exact renormalization group approach to a nonlinear diffusion equation.

The exact renormalization group is applied to a nonlinear diffusion equation with a discontinuous diffusion coefficient. The generating functional of the solution for the initial-value problem of nonlinear diffusion equations is first introduced, and next a regularization scheme is presented. It is shown that the renormalization of an action functional in the generating functional leads to an anomalous diffusion exponent in full order of the perturbation series with respect to a nonlinearity.

Journal Article↗

Clinical evaluation of dendritic cell vaccination for patients with recurrent glioma: results of a clinical phase I/II trial.

PURPOSE: To investigate the safety and the immunologic and clinical responses of dendritic cell therapy for patients with recurrent malignant glioma. EXPERIMENTAL DESIGN: Twenty-four patients with recurrent malignant glioma (6 grade 3 and 18 grade 4 patients) were evaluated in a phase I/II clinical study of dendritic cell therapy. All patients were resistant to the standard maximum therapy. The patient's peripheral blood dendritic cells were generated with granulocyte macrophage colony-stimulating factor, plus interleukin 4 with or without OK-432, and pulsed with an autologous tumor lysate. Dendritic cells were injected intradermally, or both intratumorally and intradermally every 3 weeks. RESULTS: The protocols were well tolerated with only local redness and swelling at the injection site in several cases. Clinical responses were as follows: 1 patient with partial response, 3 patients with minor response, 10 patients with stable disease, and 10 patients with progressive disease. The patients whose dendritic cells were matured with OK-432 had longer survival times than the dendritic cells from patients without OK-432 maturation. The patients with both intratumoral and intradermal administrations had a longer survival time than the patients with intradermal administration only. Increased ELISPOT and delayed-type hypersensitivity responses after vaccination could provide good laboratory markers to predict the clinical outcome of patients receiving dendritic cell vaccination. The overall survival of patients with grade 4 glioma was 480 days, which was significantly better than that in the control group. CONCLUSIONS: This study showed the safety and clinical response of autologous tumor lysate-pulsed dendritic cell therapy for patients with malignant glioma. Dendritic cell therapy is recommended for further clinical studies in malignant glioma patients.

Adult↗

Diesel exhaust affects immunological action in the placentas of mice.

We investigated the effect of diesel exhaust (DE) on pregnancy and fetal development in mice at day 14 postcoitum (pc) with a special focus on the placenta. The number of absorbed fetuses increased in groups exposed to DE, and congestion was observed in histological sections of placentas. During placental absorption expression of CYP1A1 mRNA decreased to undetectable levels, whereas expression of TNF alpha mRNA increased approximately twofold over that of the control. Levels of CYP1A1 mRNA in normal placentas from DE-exposed mice were unchanged. mRNA levels of inflammatory cytokines IL-2, IL-5, IL-12 alpha, IL-12 beta, and GM-CSF increased in placentas exposed to DE (0.3 and 3.0 mg diesel exhaust particles (DEP)/m3). Expression of IL-5 mRNA was markedly increased in DE-exposed placentas, although levels were barely detectable in control placentas. IL-6 mRNA expression was increased approximately 10-fold in placentas exposed to DE (3.0 mg DEP/m3). It has been reported that expression of mRNA encoding proteins involved in immune function in the placenta is increased during fetal absorption in mice. In the present study, expression of such mRNA by the placenta was increased by DE exposure. Because it is believed that expression of mRNA in the placenta also affects fetal development, DE may promote fetal absorption. These findings suggest that in mice exposure to DE affects fetal absorption and placental function by modifying expression of immune-related genes during early gestation and expression of endocrine-related genes during late gestation.

Animals↗

Asian sand dust enhances ovalbumin-induced eosinophil recruitment in the alveoli and airway of mice.

Asian sand dust (ASD) containing sulfate (SO4(2-)) reportedly causes adverse respiratory health effects but there is no experimental study showing the effect of ASD toward allergic respiratory diseases. The effects of ASD and ASD plus SO4(2-) toward allergic lung inflammation induced by ovalbumin (OVA) were investigated in this study. ICR mice were administered intratracheally with saline; ASD alone (sample from Shapotou desert); and ASD plus SO4(2-) (ASD-SO4); OVA+ASD; OVA+ASD-SO4. ASD or ASD-SO4 alone caused mild nutrophilic inflammation in the bronchi and alveoli. ASD and ASD-SO4 increased pro-inflammatory mediators, such as Keratinocyte chemoattractant (KC) and macrophage inflammatory protein (MIP)-1 alpha, in bronchoalveolar lavage fluids (BALF). ASD and ASD-SO4 enhanced eosinophil recruitment induced by OVA in the alveoli and in the submucosa of the airway, which has a goblet cell proliferation in the bronchial epithelium. However, a further increase of eosinophils by addition of SO4(2-) was not observed. The two sand dusts synergistically increased interleukin-5 (IL-5) and monocyte chemotactic protein-1 (MCP-1), which were associated with OVA, in BALF. However, the increased levels of IL-5 were lower in the OVA+ASD-SO4 group than in the OVA+ASD group. ASD caused the adjuvant effects to specific-IgG1 production by OVA, but not to specific-IgE. These results suggest that the enhancement of eosinophil recruitment in the lung is mediated by synergistically increased IL-5 and MCP-1. IgG1 antibodies may play an important role in the enhancement of allergic reaction caused by OVA and sand dust. However, extra sulfate may not contribute to an increase of eosinophils.

Animals↗

Intrathecal chemotherapy for patients with meningeal carcinomatosis.

BACKGROUND: Meningeal carcinomatosis (MC) is increasing, and these patients have a poor prognosis. We analyzed the effects of intrathecal (IT) chemotherapy for these patients. METHODS: Patients received both methotrexate (MTX) (15 mg/m(2)) and prednisolone (10 mg/m(2)) 6 times in 2 weeks by Ommaya reservoir, along with cytosine arabinoside (10 mg/m(2)) for 4 doses of MTX. A cycle consisted of a 2-week period during which patients received these drugs and then 2 weeks off. Treatments were repeated 3 to 6 cycles depending on the clinical status. Cerebrospinal fluid (CSF) samples were also analyzed for cytology and a few markers. RESULTS: Of the 58 patients treated the most common tumor was lymphoma (30 patients), followed by lung and breast. Elevated soluble IL-2 receptor levels were observed in 23 of 30 patients with lymphomatous meningitis. Median survival of MC patients with malignant lymphoma, lung cancer, and breast cancer was 32.8 +/- 9.8, 13.0 +/- 4.1, and 18.4 +/- 7.4 months, respectively. Thus, the patients with lymphoma responded best, both by clearing the CSF and clinically. CONCLUSIONS: Our treatment regimen can improve the neurologic status of patients with MC. In particular, early IT chemotherapy can be effective for patients with lymphoma.

Adult↗

Generation of a human leukocyte antigen-A24-restricted antitumor cell with the use of SART-1 peptide and dendritic cells in patients with malignant brain tumors.

Dendritic cells (DCs) can be the principal initiators of antigen-specific immune responses. In this study, we attempted to generate cytotoxic T-lymphocytes (CTLs) using DCs pulsed with SART-1(254) peptide. Peripheral-blood mononuclear cells (PBMCs) and tumor-infiltrating mononuclear cells (TIMCs) were obtained from 11 patients with brain tumors expressing human leukocyte antigen (HLA)-A24. After stimulation with SART-1(254) peptide, CTLs showing over 15% were observed in one of 4 patients with gliomas and in 4 of 7 patients with metastatic brain tumors. Furthermore, exposure to DCs pulsed with SART-1(254) peptide increased the killing activity of these CTLs by 28.7% and 37.5%, respectively. We conclude that DCs pulsed with SART-1(254) peptide are effective in generating HLA-A24-restricted antitumor cells.

Antigens, Neoplasm↗

Endocrine-disrupting activity of chemicals in diesel exhaust and diesel exhaust particles.

Diesel exhaust (DE) is known as the main cause of air pollution. DE is a complex mixture of particulate and vapor-phase compounds. The soluble organic fraction of the particulate materials in DE contains thousands of compounds including a variety of polycyclic aromatic hydrocarbons and heavy metals. To clarify the endocrine-disrupting activities of DE, we have reviewed the reports about the effects of DE on the reproductive and brain-nervous systems, and the endocrine-disrupting action of diesel exhaust particles (DEP). In utero exposure to low levels (0.1 mg DEP/m3) of DE from day 2 postcoitum (p.c.) until day 13 p.c. reduced the expression level of Ad4BP/SF-1 mRNA and thereby might affect the development of gonads. Low levels of DE also reduced the expression of several genes known to play key roles in gonadal development, including an enzyme necessary for testosterone synthesis. Mature male rats exposed to DE during the fetal period showed an irreversible decrease in daily sperm production due to an insufficient number of Sertoli cells. DE exposure during the fetal period influenced the brain tissue in newborn mice. In the 3 mg DEP/m3 exposure group at 10 weeks of age, a significant reduction in performance was observed in the passive avoidance learning test in both male and female mice. In addition, the fetal exposure of mice to DE affected the emotional behaviors associated with the serotonergic and dopaminergic systems in the mouse brain. In toluidine blue-stained specimens from the DE-exposed group, edema around the vessels where fluorescent granular perithelial (FGP) cells exist and degenerated granules within the FGP cytoplasm were observed; similar findings were obtained by electron microscopic examination. DEP contain many substances that stimulate Ah receptors, such as the polycyclic aromatic hydrocarbon containing benzo[a]pyrene. DEP also contain substances with estrogenic, antiestrogenic and antiandrogenic activities. The neutral substance fraction of DEP has the causal substance that reduces estrogen receptor mRNA expression. Evaluating the influence of these chemicals present in the environment on human health is an important task.

Animals↗

Tumor mRNA-loaded dendritic cells elicit tumor-specific CD8(+) cytotoxic T cells in patients with malignant glioma.

In this study, we demonstrate that tumor mRNA-loaded dendritic cells can elicit a specific CD8(+) cytotoxic T-lymphocyte (CTL) response against autologous tumor cells in patients with malignant glioma. CTLs from three patients expressed strong cytolytic activity against autologous glioma cells, did not lyse autologous lymphoblasts or EBV-transformed cell lines, and were variably cytotoxic against the NK-sensitive cell line K-562. Also, DCs-pulsed normal brain mRNA failed to induce cytolytic activity against autologous glioma cells, suggesting the lack of autoimmune response. Two patients' CD8(+) T cells expressed a modest cytotoxicity against autologous glioma cells. CD8(+) T cells isolated during these ineffective primings secreted large amounts of IL-10 and smaller amounts of IFN-gamma as detected by ELISA. Type 2 bias in the CD8(+) T-cell response accounts for the lack of cytotoxic effector function from these patients. Cytotoxicity against autologous glioma cells could be significantly inhibited by anti-HLA class I antibody. These data demonstrate that tumor mRNA-loaded DC can be an effective tool in inducing glioma-specific CD8(+) CTLs able to kill autologous glioma cells in vitro. However, high levels of tumor-specific tolerance in some patients may account for a significant barrier to therapeutic vaccination. These results may have important implications for the treatment of malignant glioma patients with immunotherapy. DCs transfected with total tumor RNA may represent a method for inducing immune responses against the entire repertoire of glioma antigens.

Adult↗

Generation of dendritic cells from the ventricular fluid in patients with meningeal carcinomatosis.

Mononuclear cells were obtained from the ventricular fluid and peripheral blood in 10 patients with meningeal carcinomatosis (MC). Using GM-CSF, IL-4, tumor necrotizing factor (TNF)-alpha, and CD40L, we could induce mature dendritic cells (DC) (positive for CD45, CD80, CD83, and CD86) from the ventricular fluid in all MC patients. Their DC could enhance the proliferation of the autologous lymphocytes remarkably. Expression of the IL12 p40 was observed in DC generated from seven cases who showed good response to our intrathecal (IT) chemotherapy. These DC also could produce p70 IL-12 over the concentration 20 pg/ml. Thus, DC generated from the ventricular fluid seemed to be useful in the treatments of the MC patients.

Body Fluids↗