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Biomedical subjects

Satoshi Takeuchi

Publications and source records attributed to Satoshi Takeuchi.

At least 19 recordsLinked to original sources

Expression of the p38 MAPK, NF-kappaB and cyclin D1 in extramammary Paget's disease.

BACKGROUND: The p38 mitogen-activated protein kinase (MAPK)/nuclear factor kappaB (NF-kappaB)/cyclin D1 signaling pathway has recently been shown to play an important part in the pathogenesis of many human tumors. However, the role of this signal transduction pathway in extramammary Paget's disease (EMPD) remains unknown. OBJECTIVE: This study was designed to investigate the expression of phosphorylated p38 MAP kinasealpha (p-p38 MAPKalpha), phosphorylated NF-kappa B p65 (p-NF-kappaB p65) and cyclin D1 proteins in EMPD and to evaluate the relationship among them. METHODS: Thirty-five tissue samples from 30 primary EMPD cases were analyzed by immunohistochemical staining in formalin-fixed, paraffin-embedded tissue sections for p-p38 MAPKalpha, p-NF-kappaB p65 and cyclin D1. RESULTS: Among the 35 specimens of EMPD, p-p38 MAPKalpha, p-NF-kappaB p65 and cyclin D1 were expressed in 30, 28 and 27, respectively. Moreover, in five metastatic lymph node specimens, all were positive for p-p38 MAPKalpha and p-NF-kappaB p65, four were positive for cyclin D1. There were significant correlations between expression of p-p38 MAPKalpha, p-NF-kappaB p65, and cyclin D1 in EMPD. CONCLUSION: This study provides evidence that p-p38 MAPKalpha, p-NF-kappaB p65, and cyclin D1 was overexpressed in EMPD, suggesting that the p38 MAPK/NF-kappaB/cyclin D1 signaling pathway might participate in the oncogenesis of EMPD.

Adult↗

Expression and prognostic significance of Stat5a and E-cadherin in extramammary Paget's disease.

BACKGROUND: Stat5 has been shown to regulate the proliferation and inhibition of apoptosis in cancer cells. E-cadherin plays an important role in maintaining epithelial stability and is widely regarded as a prognostic marker in many types of human cancers. The expression of Stat5 has not been investigated in extramammary Paget's disease (EMPD). OBJECTIVES: To study the expression of Stat5a and E-cadherin protein in EMPD and to evaluate the relationships between them. METHODS: Thirty-six tissue samples from 34 cases with primary EMPD were subjected to immunohistochemical staining for Stat5a and E-cadherin. RESULTS: Twenty-nine of 30 in situ EMPD specimens were positive for Stat5a expression, and the staining pattern for Stat5a was mainly nuclear in the majority of Paget's cells. All four invasive specimens and two metastatic lymph node specimens were negative for Stat5a. Twenty-six of 30 in situ EMPD specimens expressed E-cadherin in more than 50% of tumor cells, and three of 30 in situ EMPD specimens expressed E-cadherin in less than 50% of tumor cells. One in situ EMPD specimen and one invasive specimen expressed E-cadherin in less than 25% of tumor cells. Three invasive specimens and two metastatic lymph node specimens were negative, with occasional membranous staining for E-cadherin. There is a significant correlation between the expression of Stat5a and E-cadherin. CONCLUSIONS: Our results showed that these proteins were found in in situ lesions, and it is speculated that these proteins may play some role in the prognosis/invasion of EMPD.

Aged↗

Differential induction of Th1-prone immunity by human dendritic cells activated with Sporothrix schenckii of cutaneous and visceral origins to determine their different virulence.

Sporotrichosis is caused by a thermo-dependent dimorphic fungus, Sporothrix schenckii. The major clinical manifestations occur in the skin; however, cases of visceral manifestations have also been increasingly reported with some being observed in immune compromised patients. Different virulence of individual S. schenckii strain as well as immune status of the host could contribute to form such different clinical manifestations. Thus, the purpose of the study was to investigate whether different virulence of individual S. schenckii could be a factor for such clinical difference. We investigated the interactions between human monocyte-derived dendritic cells (MoDCs) and S. schenckii, assessed by (i) morphological features, (ii) surface marker expressions, cytokine productions, (iii) signaling pathways and (iv) allostimulatory activity of the activated MoDCs. Immature MoDCs, obtained from peripheral blood monocytes supplemented with granulocyte macrophage colony-stimulating factor and IL-4, were stimulated with S. schenckii strains of both yeasts and conidia forms of different origins (cutaneous isolates: KMU4649, IFM5906 and IFM46010; visceral isolates: KMU4648, IFM41598 and ATCC26331) to be used for various assays. Through the analysis, we found that the cutaneous S. shenckii of cutaneous origins were more potent to activate MoDCs to induce strong T(h)1 response, as evidenced by abundant IFN-gamma production, while the S. shenckii of visceral origins induced only minimal dendritic cell activation and T(h)1 induction. The p38 mitogen-activated protein kinase and c-Jun N-terminal kinase signaling pathways appeared to be associated with the differential activation of the MoDCs by S. schenckii of cutaneous and the visceral origins. Overall, we concluded that the differential activation of MoDCs by S. schenckii of cutaneous and visceral origins to induce T(h)1 response, other than immune status or the host, may be a factor for their different clinical manifestations.

Cell Differentiation↗

Adjuvant chemotherapy with irinotecan hydrochloride and cisplatin for clear cell carcinoma of the ovary.

Clear cell carcinoma (CCC) of the ovary has distinct characteristics showing resistance to conventional platinum-based regimen. Our aim was to evaluate the effects of combination therapy with irinotecan hydrochloride and cisplatin (CPT-P), comparing to regimen with paclitaxel and platinum (TP). We retrospective reviewed 172 patients with complete surgical staging procedures including lymphadenenctomy. Forty-six patients received CPT-P and 126 patients were treated with TP. Survival of the two groups was compared. Between CPT-P group and TP group, there was no significant difference in median age, performance status, FIGO stage, rate of optimal cytoreduction, and follow-up period. There was no significant difference in progression-free survival of patients with stage I tumors (p=0.95) and suboptimally debulked stage II-IV tumors (p=0.92). Although there was no significant difference of overall survival, progression-free survival of CPT-P group was significantly better than that of TP group in optimally debulked stage II-IV (p=0.03). Multiple regression survival analysis revealed CPT-P regimen (p=0.02) and residual tumor diameter (p<0.01) were both independent prognostic factors in stage II-IV tumors. The combination of CPT-P was shown to have a potential therapeutic benefit for advanced CCC of the ovary, especially for cases with optimal debulking surgery. However, this is a limited retrospective study, therefore we recommend that the CPT-P regimen be evaluated in a larger prospective study.

Adenocarcinoma, Clear Cell↗

Coherent nuclear wavepacket motions in ultrafast excited-state intramolecular proton transfer: sub-30-fs resolved pump-probe absorption spectroscopy of 10-hydroxybenzo[h]quinoline in solution.

The dynamics of the excited-state intramolecular proton transfer of 10-hydroxybenzo[h]quinoline (10-HBQ) and the associated coherent nuclear motion were investigated in solution by femtosecond absorption spectroscopy. Sub-picosecond transient absorption measurements revealed spectral features of the stimulated emission and absorption of the keto excited state (the product of the reaction). The stimulated emission band appeared in the 600-800-nm region, corresponding to the wavelength region of the steady-state keto fluorescence. It showed successive temporal changes with time constants of 350 fs and 8.3 ps and then disappeared with the lifetime of the keto excited state (260 ps). The spectral feature of the stimulated emission changed in the 350-fs dynamics, which was likely assignable to the intramolecular vibrational energy redistribution in the keto excited state. The 8.3-ps change caused a spectral blue shift and was attributed to the vibrational cooling process. The excited-state absorption was observed in the 400-600-nm region, and it also showed temporal changes characterized by the 350-fs and 8.3-ps components. To examine the coherent nuclear dynamics (nuclear wavepacket motion) in excited-state 10-HBQ, we carried out pump-probe measurements of the stimulated emission and absorption signals with time resolution as good as 27 fs. The obtained data showed substantially modulated signals due to the excited-state vibrational coherence up to a delay time of several picoseconds after photoexcitation. This means that the vibrational coherence created by photoexcitation in the enol excited state is transferred to the product. Fourier transform analysis indicated that four frequency components in the 200-700-cm(-1) region contribute to the oscillatory signal, corresponding to the coherent nuclear motions in excited-state 10-HBQ. Especially, the lowest-frequency mode at 242 cm(-1) is dephased significantly faster than the other three modes. This observation was regarded as a manifestation that the nuclear motion of the 242-cm(-1) mode is correlated with the structural change of the molecule associated with the reaction (the reaction coordinate). The 242-cm(-1) mode observed in excited-state 10-HBQ was assigned to a vibration corresponding to the ground-state vibration at 243 cm(-1) by referring to the results of resonance Raman measurements and density functional calculations. It was found that the nuclear motion of this lowest-frequency mode involves a large displacement of the OH group toward the nitrogen site as well as in-plane skeletal deformation that assists the oxygen and nitrogen atoms to come closer to each other. We discuss the importance of the nuclear wavepacket motion on a multidimensional potential-energy surface including the vibrational coordinate of the low-frequency modes.

Protons↗

Use of interleukin 7 receptor-alpha knockout donor cells demonstrates the lymphoid independence of dendritic cells.

The precise lineage of dendritic cells (DCs), including skin Langerhans cells (LCs), is unclear. Interleukin 7 (IL-7) and its receptor (IL-7R alpha) are known to mediate lymphopoiesis, and IL-7 is also known to be essential for the generation of DCs from lymphoid-committed precursors in vitro. Thus, to determine the developmental lymphoid (or IL-7R alpha) dependency of various DCs and to examine the importance of IL-7/IL-7R alpha for DC development in vivo, we used IL-7R alpha knockout (KO) donor cells to reconstitute DCs/LCs in sublethally irradiated recipients and compared the results to those obtained using wild-type (WT) donor cells. We found that lymphoid lineage cells (except natural killer [NK] cells), including thymocytes, were less efficiently reconstituted by IL-7R alpha KO donor cells, whereas myeloid lineage cells and DCs/LCs were equally well reconstituted by both the IL-7R alpha KO and WT donor cells. Overall, we conclude that IL-7R alpha is not required for the development of DCs/LC in vivo.

Animals↗

Tripartite relationship among P300, clinical features and brain structure in neuroleptic-naive schizophrenia.

Auditory P300 abnormalities in schizophrenia patients have been repeatedly reported by many studies. However, reported relationships among P300 abnormalities, clinical features and other biological variables, such as abnormalities in structural brain imaging, are notably discrepant. This is partially due to the inclusion of patients who have had long-term administration of neuroleptics and those from whom this treatment has been withdrawn. The present study measures event-related potentials in 13 neuroleptic-naive schizophrenia patients using an auditory oddball paradigm to clarify the relationships among P300 amplitude, clinical features and brain structure. All patients underwent computed tomography to estimate the area of the right and left frontal cortical sulci and Sylvian fissures. Clinical symptoms were assessed using the Positive And Negative Syndrome Scale. The high correlation coefficients were obtained between P300 amplitude and the anxiety/depression factor score (r = -0.77), the positive factor score (r = -0.58) and between P300 amplitude and the area ratios of the fronto-temporal region (r = -0.66). These findings show that fronto-temporal region and P300 amplitude are closely related to the earliest stage of illness even in neuroleptic-naive patients.

Adult↗

Activation of medial prefrontal cortex by phencyclidine is mediated via a hippocampo-prefrontal pathway.

Phencyclidine (PCP) is a psychotomimetic drug that elicits schizophrenia-like symptoms in healthy persons, and administration of PCP to animals is used as a pharmacological model of schizophrenia. We recently demonstrated that systemic administration of PCP to rats produces long-lasting activation of medial prefrontal cortex (mPFC) neurons with augmentation of locomotor activity, whereas direct application of PCP to mPFC neurons has little effect on their firing activity. These findings suggest that PCP-induced activation of mPFC neurons is elicited mainly via excitatory inputs from regions outside the mPFC. In the present study, we examined effects of local application of PCP to the ventral hippocampus (vHIP) on firing activity of PFC neurons in freely moving rats. PCP locally perfused into the vHIP increased spontaneous discharges of PFC neurons during perfusion with augmentation of locomotor activity. Local application of a more selective NMDA receptor antagonist, MK801, to vHIP neurons under anesthesia increased the spontaneous firing rates of most neurons directly projecting to the mPFC, whereas local application of MK801 to mPFC neurons did not induce excitatory responses in any of those neurons. The present results indicate that tonic excitatory inputs from the vHIP to the PFC may trigger development of behavioral abnormalities.

Animals↗

Femtosecond absorption study of photodissociation of diphenylcyclopropenone in solution: reaction dynamics and coherent nuclear motion.

Reaction dynamics and coherent nuclear motions in the photodissociation of diphenylcyclopropenone (DPCP) were studied in solution by time-resolved absorption spectroscopy. Subpicosecond transient absorption spectra were measured in the visible region with excitation at the second absorption band of DPCP. The obtained spectra showed a new short-lived band around 480 nm immediately after photoexcitation, which is assignable to the initially populated S(2) state of DPCP before the dissociation. The dissociation takes place from this excited state (the precursor of the reaction) with a time constant of 0.2 ps, and the excited state of diphenylacetylene (DPA) is generated as the reaction product. The transient absorption after the dissociation decayed with a time constant of 8 ps that is very close to the S(2)-state lifetime of DPA, but the spectrum of this 8-ps component was different from the S(2) absorption observed with direct photoexcitation of DPA. We conclude that the dissociation of DPCP generates the S(2) state of DPA that probably has a cis-bent structure. At later delay times (>30 ps), the transient absorption signals are very similar to those obtained by direct photoexcitation of DPA. This confirmed that the electronic relaxation from the S(2) state of the product DPA occurs in a similar manner to that of DPA itself, i.e., the internal conversion to the S(1) state and subsequent intersystem crossing to the T(1) state. In order to examine the coherent nuclear dynamics in this dissociation reaction, we carried out time-resolved absorption measurements for the 480-nm band with 70 fs resolution. It was found that an underdamped oscillatory modulation with a 0.1-ps period is superposed on the decay of the precursor absorption. This indicates that DPCP exhibits a coherent nuclear motion having a approximately 330-cm(-1) frequency in the dissociative excited state. Based on a comparison with the measured and calculated Raman spectra of ground-state DPCP, we discuss the assignment of the "330-cm(-1) vibration" and attribute it to a vibration involving the displacement of the CO group as well as the deformation of the Ph-C[Double Bond]C-Ph skeleton. We consider that this motion is closely related to the reaction coordinate of the photodissociation of DPCP.

Journal Article↗

Time-wavelength two-dimensional femtosecond fluorescence imaging.

We report a new femtosecond time-resolved fluorescence spectrometer that enables us to observe fluorescence intensity as a time-wavelength two-dimensional image in a single measurement. This method utilizes a time-to-space conversion technique and fluorescence sum-frequency mixing with a femtosecond gate pulse. It provides a fluorescence image covering temporal and spectral spans of approximately 2 ps and approximately 60 nm, respectively. Calibration of the time and intensity axes of the image is made by use of a long-lived dye fluorescence. The two-dimensional fluorescence image of beta-carotene obtained demonstrates the high potential of this method for quantitative studies of ultrafast excited-state dynamics.

Journal Article↗

Malignant melanoma of nasal cavity: report of 16 Japanese patients.

BACKGROUND: Primary malignant melanoma of the nasal cavity is a rare disease that has a poor prognosis. There are significant racial differences in the incidence of melanomas in the nasal cavity. METHODS: Sixteen Japanese patients treated at the Hospital of Tokyo University were reviewed retrospectively. RESULTS: Fourteen patients were treated with surgery. Two patients received treatment with radiotherapy alone. Seven patients had microscopically negative surgical margins and seven patients had positive surgical margins. The 2- and 5-year actuarial survival rates for all patients were 63.6 and 31.8%, respectively. No statistically significant difference could be shown in the overall survival rate between patients with positive surgical margins and those with negative surgical margins. CONCLUSIONS: Clinical features of nasal melanoma in Japanese are not different from nasal melanoma in Caucasians. The negative surgical margins were not predictive of a better prognosis.

Aged↗

Absorption of short wavelengths of endoillumination in indocyanine green solution: implications for internal limiting membrane removal.

PURPOSE: To measure the absorption coefficients of short wavelengths, irradiated by a light source used for vitreous surgery, in indocyanine green (ICG) solution and balanced salt solution (BSS), and to determine the implications of these absorption coefficients on retinal phototoxicity caused by ICG-assisted internal limiting membrane removal. METHODS: The absorption coefficients of short wavelengths irradiated by a commercially available light source used for vitreous surgery were measured in ICG solution and BSS using a dual-beam spectroradiometer. RESULTS: The absorption coefficient of wavelengths irradiated by the endoillumination light source in ICG solution was almost the same as that obtained in BSS. The absorbance coefficients of the ICG solutions were 0.18 cm(-1) at 400 nm and 0.03 cm(-1) at 450 nm. In BSS, the absorption coefficients were 0.17 cm(-1) at 400 nm and 0.015 cm(-1) at 450 nm. No significant difference in absorbance was seen between 400 nm and 450 nm ( P>0.05). CONCLUSIONS: The absorption of wavelengths is not greater in ICG solution than in BSS. ICG solution during intravitreal use probably does not enhance retinal photochemical injury during ICG-assisted internal limiting membrane removal.

Absorption↗

Genomic convergence: identifying candidate genes for Parkinson's disease by combining serial analysis of gene expression and genetic linkage.

We present a multifactorial, multistep approach called genomic convergence that combines gene expression with genomic linkage analysis to identify and prioritize candidate susceptibility genes for Parkinson's disease (PD). To initiate this process, we used serial analysis of gene expression (SAGE) to identify genes expressed in two normal substantia nigras (SN) and adjacent midbrain tissue. This identified over 3700 transcripts, including the three most abundant SAGE tags, which did not correspond to any known genes or ESTs. We developed high-throughput bioinformatics methods to map the genes corresponding to these tags and identified 402 SN genes that lay within five large genomic linkage regions, previously identified in 174 multiplex PD families. These genes represent excellent candidates for PD susceptibility alleles and further genomic convergence and analyses.

Alleles↗

Different effects of phencyclidine and methamphetamine on firing activity of medial prefrontal cortex neurons in freely moving rats.

The purpose of this study was to compare the effects of systemically administered MAP with those of phencyclidine (PCP), both of which induced comparable locomotor activity, on firing activity of medial prefrontal cortex (mPFC) neurons in freely moving rats. The results show that, unlike PCP, acutely administered MAP produced little changes in firing activity of mPFC neurons.

Animals↗

Indications for surgical repair of funnel chest based on indices of chest wall deformity and psychological state.

PURPOSE: We examined the surgical indications for funnel chest, taking psychological factors into consideration. METHODS: We assessed 36 young people with funnel chest who were seen as outpatients, including 31 boys and 5 girls aged from 1 to 22 years old. Respondents were asked whether they suffered psychological distress, and if they wanted surgery. The severity of the deformity was evaluated using the Vertebral Index (VI) and the Frontosagittal Index (FSI) calculated from chest roentgenograms. RESULTS: The VI in 11 patients without distress (23.7 +/- 4.1) was lower than that in 25 patients with distress (32.8 +/- 8.2), and the FSI in the patients without distress (33.5 +/- 5.3) was higher than that in the patients with distress (23.6 +/- 8.6). The VI in 19 patients who did not want surgery (26.9 +/- 7.9) was lower than that in 17 patients who did (33.5 +/- 7.5), and the FSI in the patients who did not want surgery (30.4 +/- 8.1) was higher than that in the patients who did (22.4 +/- 8.1). The distressed patients suffered many psychological problems, such as being the object of bullying. CONCLUSION: The severity of the deformity affected the patient's psychological state. We consider that a VI >28 or an FSI <28 are indications for surgery, based on the mean VI + SD and the mean FSI-SD of patients not suffering distress.

Adolescent↗

Paradoxically abundant expression of Bcl-2 and adrenomedullin in invasive cervical squamous carcinoma.

BACKGROUND: The purpose of this study was to identify the role of Bcl-2 protein and adrenomedullin (AM) expression in relation to apoptosis in the neoplastic changes of squamous epithelium of the uterine cervix. METHODS: Apoptosis in sections of normal cervical epithelium, cervical intraepithelial neoplasia (CIN), and invasive squamous cell carcinoma was determined by terminal deoxynucleotidyl transferase-mediated 2'-deoxyuridine 5'-triphosphate nick-end labeling (TUNEL) assay. Bcl-2 protein and AM expression were analyzed using the avidin-biotin immunoperoxidase method. RESULTS: On the basis of the TUNEL assay, the apoptosis positive rate of the nuclei in early invasive squamous carcinoma and in bulky invasive squamous carcinoma was significantly higher than that in normal cervical epithelium, but no such increase in the apoptosis-positive rate was noted in the nuclei in CIN. Immunohistochemical staining revealed that Bcl-2 protein and AM were immunolocalized in the cytoplasm of invasive squamous carcinoma cells, but not in either CIN lesions or normal cervical epithelium. Bcl-2 protein expression was more prominent in bulky invasive squamous carcinoma cells than in early invasive squamous carcinoma cells. AM expression was also more abundant in bulky invasive squamous carcinoma compared with that in early invasive squamous carcinoma. CONCLUSION: The present results suggest that the expression of Bcl-2 protein and AM in invasive squamous carcinoma may play crucial roles in selecting carcinoma cells resistant to apoptosis and in promoting malignant progression.

Adrenomedullin↗

Relativistic E x B acceleration.

The relativistic motion of charged particles is analyzed theoretically in electric and magnetic fields that are constant, uniform, and mutually perpendicular. In the relativistic regime where the magnitude of the electric field E is equal to or greater than that of the magnetic field B, i.e., |E| > or =|B|, the particle is effectively accelerated and gains energy indefinitely. This is quite different from the E x B drift motion in the nonrelativistic regime.

Journal Article↗