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Takashi Ogino

Publications and source records attributed to Takashi Ogino.

At least 19 recordsLinked to original sources

[Evaluation of irradiation position in respiratory-gated radiotherapy using a phantom system simulating patient respiration].

Respiratory-gated (RG) radiotherapy is useful for minimizing the irradiated volume of normal tissues resulting from the shifting of internal structures caused by respiratory movement. The present study was conducted to evaluate the treatment field in RG radiotherapy using a phantom system simulating patient respiration. A phantom system consisting of a 3-cm ball-shaped dummy tumor and film placed in a cork lung phantom was used (THK Co., Ltd.). RG radiotherapy was employed in the expiratory phase. The phantom movement distance was set to 2 cm, and the gating signals from a respiratory-gating system (AZ-733V, Anzai Medical) were varied. The settings used for irradiation were an X-ray energy of 6 MV (PRIMUS, Toshiba Medical Systems), treatment field of 5 cm x 7 cm, and X-ray dose of 100 MU. Images were acquired using an electric portal-imaging device (EPID, OPTIVUE 500), and the X-ray dose distribution was measured by the film method. In images acquired using the EPID, the tumor margins became less clear when the gating signals were increased, and the ITVs were determined to be 3.6 cm, 3.7 cm, 4.2 cm, and 5.1 cm at gating rates of 10%, 25%, 50%, and no gate, respectively. With regard to the X-ray dose distribution measured by the film method, the dose profile in the cephalocaudal direction was shifted toward the expiratory phase, and the degree of shift became greater when the gating signals were increased. In addition, the optimal treatment fields in the cephalocaudal direction were determined to be 5.2 cm, 5.2 cm, 5.6 cm, and 7.0 cm at gating rates of 10%, 25%, 50%, and no gating, respectively. Although RG radiotherapy is useful for improving the accuracy of radiotherapy, the characteristics of the RG radiotherapy technique and the radiotherapy system must be clearly understood when this method is to be employed in clinical practice. Image-guided radiotherapy (IGRT) is now assuming a central role in radiotherapy, and properly identifying internal margins is an important issue for ensuring optimal treatment. The results of this study confirmed that it is necessary to ensure the optimal treatment field in radiotherapy of the trunk and that it is essential to confirm tumor position on the basis of image evaluation.

Humans↗

Experimental evaluation of a MOSFET dosimeter for proton dose measurements.

The metal oxide semiconductor field-effect transistor (MOSFET) dosimeter has been widely studied for use as a dosimeter for patient dose verification. The major advantage of this detector is its size, which acts as a point dosimeter, and also its ease of use. The commercially available TN502RD MOSFET dosimeter manufactured by Thomson and Nielsen has never been used for proton dosimetry. Therefore we used the MOSFET dosimeter for the first time in proton dose measurements. In this study, the MOSFET dosimeter was irradiated with 190 MeV therapeutic proton beams. We experimentally evaluated dose reproducibility, linearity, fading effect, beam intensity dependence and angular dependence for the proton beam. Furthermore, the Bragg curve and spread-out Bragg peak were also measured and the linear-energy transfer (LET) dependence of the MOSFET response was investigated. Many characteristics of the MOSFET response for proton beams were the same as those for photon beams reported in previous papers. However, the angular MOSFET responses at 45, 90, 135, 225, 270 and 315 degrees for proton beams were over-responses of about 15%, and moreover the MOSFET response depended strongly on the LET of the proton beam. This study showed that the angular dependence and LET dependence of the MOSFET response must be considered very carefully for quantitative proton dose evaluations.

Biophysical Phenomena↗

[Evaluation of absorbed dose in respiratory-gated radiotherapy using a phantom system that simulates patient respiration].

Respiratory-gated (RG) radiotherapy is useful for minimizing the irradiated volume of normal tissues resulting from the shifting of internal structures caused by respiratory movement. In this technique, although improvement in the dose distribution of the target can be expected, the actual absorbed dose distribution is not clearly determined. Therefore, it is important to clarify the absorbed dose at the tumor and at the evaluation points according to the patient's respiration. We have developed a phantom system that simulates patient respiration (TNK Co., Ltd.), to evaluate the absorbed dose and ensure precise RG radiotherapy. Actual patient respiratory signals were obtained using a respiratory synchronization and gating system (AZ-733V, Anzai Medical). The acquired data were then transferred to a phantom system driven by a ball screw to simulate the shifting of internal structures caused by respiratory movement. We measured the absorbed dose using a micro-ionization chamber dosimeter and the dose distribution using the film method for RG irradiation at expiratory phase by using Linac (PRIMUS, Toshiba Medical Systems Corp.) X-rays. When the distance of phantom movement was set to the average patient respiratory movement distance of 1.5 cm, we first compared absorbed dose with RG irradiation with a gating signal of 50% or less, and without RG irradiation. The absorbed dose at the iso-center was improved by 6.0% and 4.4% at a field size of 4x4 cm2, and by 1.3% and 0.7% at a field size of 5x5 cm2 with an X-ray energy of 6 MV and 10 MV, respectively. There was, however, no dose change at a field size of 10x10 cm2 and 15x15 cm2. When the gating signal was reduced to 25% and 10%, absorbed dose was also improved. With regard to the flatness of the dose profile, no changes in dose distribution were observed in the lateral direction, e.g., beam flatness was within 1.4% and 1.6% at field sizes of 5x5 cm2 and 10x10 cm2, respectively, with an X-ray energy of 6 MV. In the cranial-caudal direction, the dose profile was relatively large even if a gating signal of 50% was applied, i.e., 8.1% and 10.4% at field sizes of 5x5 cm2 and 10x10 cm2, respectively. Beam flatness without RG was much worse, i.e., 37.8% and 38.2%, at field sizes of 5x5 cm2 and 10x10 cm2, respectively. In both cases, the dose was insufficient in the expiratory direction. Although RG radiotherapy is quite useful, the margins in the inspiratory and expiratory phases should be considered based on the level of gating signal and field size in order to formulate appropriate radiotherapy planning in terms of the shifting of internal structures. To ensure accurate radiotherapy, the characteristics of the RG irradiation technique and the radiotherapy equipment must be clearly understood when this technique is to be employed in clinical practice.

Humans↗

Development of a simple control system for uniform proton dose distribution in a dual-ring double scattering method.

In proton radiotherapy with high focusing of irradiation on the tumour, it is important to obtain treatment beams with a highly uniform dose distribution. Uniform dose distribution in the clinical irradiation field can be obtained by the dual-ring double scattering method. This method is superior to the wobbler method, which uses electromagnetic deflection of the proton beams, because of the absence of the temporal structure of irradiation distribution. However, in the dual-ring double scattering method the condition of incident proton beams entering the scatter, especially the accuracy of the position of the incident proton beams with respect to the scatter, markedly affects the uniformity of the beam distribution in the irradiation field. In this study, to ensure the uniformity of dose distribution during treatment, we developed a control system equipped with an automatic fine adjustment of the beam axis and a mechanism for moving the second dual-ring scatter of the double scatters to the optimal position. Using this system, we achieved uniform dose distribution in the irradiation field during proton radiotherapy, with symmetry within +/-1% and flatness within 2%.

Phantoms, Imaging↗

High-dose proton beam therapy for Stage I non-small-cell lung cancer.

PURPOSE: To evaluate retrospectively the safety and efficacy of high-dose proton beam therapy (PBT) for Stage I non-small-cell lung cancer (NSCLC). METHODS AND MATERIALS: Between 1999 and 2003, 37 patients were treated in our institution. The indications for PBT were pathologically proven NSCLC, clinical Stage I, tumor size < or =5 cm, medically inoperable or refusal of surgery, and written informed consent. A total dose of 70-94 Gy(E) was delivered in 20 fractions (3.5-4.9 Gy(E) per fraction). RESULTS: Patient characteristics (number of patients) were as follows: Stage IA/IB, 17 of 20; medically inoperable/refusal of surgery, 23/14; total dose 70/80/88/94 Gy(E), 3/17/16/1. With a median follow-up period of 24 months, the 2-year local progression-free and overall survival rates were 80% and 84%, respectively. The 2-year locoregional relapse-free survival rates in Stage IA and Stage IB were 79% and 60%, respectively. No serious acute toxicity was observed. Late Grades 2 and 3 pulmonary toxicities were observed in 3 patients each. Of these 6 patients, 5 had Stage IB disease. CONCLUSIONS: Proton beam therapy is a promising treatment modality for Stage I NSCLC, though locoregional relapse and late pulmonary toxicities in Stage IB patients were substantial. Further investigation of PBT for Stage I NSCLC is warranted.

Aged↗

Dose-volume delivery guided proton therapy using beam on-line PET system.

Proton therapy is one form of radiotherapy in which the irradiation can be concentrated on a tumor using a scanned or modulated Bragg peak. Therefore, it is very important to evaluate the proton-irradiated volume accurately. The proton-irradiated volume can be confirmed by detection of pair annihilation gamma rays from positron emitter nuclei generated by the target nuclear fragment reaction of irradiated proton nuclei and nuclei in the irradiation target using a positron emission tomography (PET) apparatus, and dose-volume delivery guided proton therapy (DGPT) can thereby be achieved using PET images. In the proton treatment room, a beam ON-LINE PET system (BOLPs) was constructed so that a PET apparatus of the planar-type with a high spatial resolution of about 2 mm was mounted with the field of view covering the isocenter of the beam irradiation system. The position and intensity of activity were measured using the BOLPs immediately after the proton irradiation of a gelatinous water target containing 16O nuclei at different proton irradiation energy levels. The change of the activity-distribution range against the change of the physical range was observed within 2 mm. The experiments of proton irradiation to a rabbit and the imaging of the activity were performed. In addition, the proton beam energy used to irradiate the rabbit was changed. When the beam condition was changed, the difference between the two images acquired from the measurement of the BOLPs was confirmed to clearly identify the proton-irradiated volume.

Animals↗

[Proton beam therapy].

Proton beam therapy (PBT) has made it possible to deliver a higher concentration of radiation to the tumor by its Bragg-peak, and is easy to utilize due to the fact that its biological characteristics are identical with X-rays. PBT has a half-century history, and more than 40,000 patients have been reported as having had treatments with proton beams worldwide. The historic change to this therapy occurred in the 1990s, when the Loma Linda University Medical Center began its clinical activity as the first hospital in the world to utilize a medically dedicated proton therapy facility. Since then, similar hospital-based medically dedicated facilities have been constructed. Results from around the world have shown the therapeutic superiority of PBT over alternative treatment options for ocular melanoma, skull base sarcoma, head & neck cancer, lung cancer,esophageal cancer, hepatocellular carcinoma, and prostate cancer. PBT is expected to achieve further advancement both clinically and technologically.

Cancer Care Facilities↗

Phase II feasibility study of high-dose radiotherapy for prostate cancer using proton boost therapy: first clinical trial of proton beam therapy for prostate cancer in Japan.

OBJECTIVE: To assess the feasibility of high-dose radiotherapy for prostate cancer using proton boost therapy following photon radiotherapy. METHODS: The primary endpoint was acute grade 3 or greater genitourinary (GU) and gastrointestinal (GI) toxicities. The study included patients with clinical stage T1-3N0M0 prostate cancer. Radiotherapy consisted of 50 Gy/25 fx photon irradiation to the prostate and the bilateral seminal vesicles followed by proton boost of 26 Gy(E)/13 fx to the prostate alone. Hormonal therapy was allowed before and during the radiation therapy. RESULTS: Between January 2001 and January 2003, 30 patients were enrolled in this study. Acute grade 1/2 GU and GI toxicities were observed in 20/4 and 17/0 patients, respectively. With the median follow-up period of 30 months (range 20-45), late grade 1/2 GU and GI toxicities occurred in 2/3 and 8/3 patients, respectively. No grade 3 or greater acute or late toxicities were observed. All patients were alive, but six patients relapsed biochemically after 7-24 months. CONCLUSIONS: Proton boost therapy following photon radiotherapy for prostate cancer is feasible. To evaluate the efficacy and safety of proton beam therapy, a multi-institutional phase II trial is in progress in Japan.

Adenocarcinoma↗

Clinical impact of criteria for complete response (CR) of primary site to treatment of esophageal cancer.

BACKGROUND: With the development of chemoradiotherapy for esophageal cancer, the complete response (CR) rate would become an important surrogate end-point. However, the Response Evaluation Criteria in Solid Tumors (RECIST) do not provide criteria for a response at the primary site of esophageal cancer. The objective of this study was to assess the validity of the endoscopic CR criteria for the primary site of esophageal cancer treated with chemoradiotherapy. METHODS: We reviewed 139 patients with T1-T4, N0-1, M0-1a esophageal cancer treated with definitive chemoradiotherapy from August 1992 to April 1999. CR was tentatively defined upon endoscopic observation of the entire esophagus as: (i) disappearance of the tumor lesion; (ii) disappearance of ulceration (slough); and (iii) absence of cancer cells in biopsy specimens. RESULTS: CR at the primary site (primary-CR) was achieved in 80 patients (58%). Of these, 71 (89%) were evaluated as having primary-CR within 6 months from the start of therapy. With a median follow-up of 53 months, a remarkable difference in the 5-year survival rate was observed between patients evaluated as having primary-CR and having non-CR (46 and 6%, P < 0.0001). Local failure was observed in 15 patients and the local control rate in patients with primary-CR was 78% at 5 years. CONCLUSIONS: These criteria appear to represent an appropriate surrogate end-point because they are convenient to apply, require only a short time before a primary-CR can be declared and their fulfillment can predict long-term survival. It is recommended that RECIST include precise endoscopic findings for primary lesions in esophageal cancer in the CR criteria.

Adult↗

Phase II study of radiotherapy employing proton beam for hepatocellular carcinoma.

PURPOSE: To evaluate the safety and efficacy of proton beam radiotherapy (PRT) for hepatocellular carcinoma. PATIENTS AND METHODS: Eligibility criteria for this study were: solitary hepatocellular carcinoma (HCC); no indication for surgery or local ablation therapy; no ascites; age >/= 20 years; Zubrod performance status of 0 to 2; no serious comorbidities other than liver cirrhosis; written informed consent. PRT was administered in doses of 76 cobalt gray equivalent in 20 fractions for 5 weeks. No patients received transarterial chemoembolization or local ablation in combination with PRT. RESULTS: Thirty patients were enrolled between May 1999 and February 2003. There were 20 male and 10 female patients, with a median age of 70 years. Maximum tumor diameter ranged from 25 to 82 mm (median, 45 mm). All patients had liver cirrhosis, the degree of which was Child-Pugh class A in 20, and class B in 10 patients. Acute reactions of PRT were well tolerated, and PRT was completed as planned in all patients. Four patients died of hepatic insufficiency without tumor recurrence at 6 to 9 months. Three of these four patients had pretreatment indocyanine green retention rate at 15 minutes of more than 50%. After a median follow-up period of 31 months (16 to 54 months), only one patient experienced recurrence of the primary tumor, and 2-year actuarial local progression-free rate was 96% (95% CI, 88% to 100%). Actuarial overall survival rate at 2 years was 66% (48% to 84%). CONCLUSION: PRT showed excellent control of the primary tumor, with minimal acute toxicity. Further study is warranted to scrutinize adequate patient selection in order to maximize survival benefit of this promising modality.

Aged↗

A phase II study of hyperfractionated accelerated radiotherapy (HART) after induction cisplatin (CDDP) and vinorelbine (VNR) for stage III non-small-cell lung cancer (NSCLC).

PURPOSE: The purpose was to assess the feasibility and efficacy of hyperfractionated accelerated radiotherapy (HART) after induction chemotherapy for Stage III non-small-cell lung cancer. METHODS AND MATERIALS: Treatment consisted of 2 cycles of cisplatin 80 mg/m(2) on Day 1 and vinorelbine 25 mg/m(2) on Days 1 and 8 every 3 weeks followed by HART, 3 times a day (1.5, 1.8, 1.5 Gy, 4-h interval) for a total dose of 57.6 Gy. RESULTS: Thirty patients were eligible. Their median age was 64 years (range, 46-73 years), 24 were male, 6 were female, 8 had performance status (PS) 0, 22 had PS 1, 9 had Stage IIIA, and 21 had Stage IIIB. All but 1 patient completed the treatment. Common grade > or =3 toxicities during the treatment included neutropenia, 25; infection, 5; esophagitis, 5; and radiation pneumonitis, 3. The overall response rate was 83%. The median survival was 24 months (95% confidence interval [CI], 13-34 months), and the 2-year overall survival was 50% (95% CI, 32-68%). The median progression-free survival was 10 months (95% CI, 8-20 months). CONCLUSION: Hyperfractionated accelerated radiotherapy after induction of cisplatin and vinorelbine was feasible and promising. Future investigation employing dose-intensified radiotherapy in combination with chemotherapy is needed.

Aged↗

Adverse hepatic events caused by radiotherapy for advanced hepatocellular carcinoma.

BACKGROUND: Radiotherapy is often used to treat patients with unresectable advanced hepatocellular carcinoma (HCC). The present study examines the nature and frequency of adverse events with respect to liver function in such patients after radiotherapy. METHODS: Forty-six patients with HCC who underwent radiotherapy were retrospectively examined. Radiotherapy was applied using coplanar 2-3-beam arrangements to a target dose of 50 Gy/5 weeks. The adverse hepatic events were evaluated according to the National Cancer Institute Common Toxicity Criteria and the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer Late Radiation Morbidity Scoring Scheme during the acute phase and the late phase by following the patients for up to 1 year. The influence on survival by adverse hepatic events and other factors was analyzed. RESULTS: The full irradiation dose of 50 Gy was given to 40 patients (87.0%). Grade 3 or 4 toxicity was observed in 18 (39.1%) within 3 months after radiotherapy and in 11 (33.3%) of 33 thereafter, respectively. The most frequent and serious adverse events were hyperbilirubinemia, hypoalbuminemia, and ascites. The independent adverse prognostic factors for survival were portal vein tumor thrombus (P = 0.0012), tumor response (P = 0.011), acute adverse hepatic event (P = 0.012), and late adverse hepatic event (P = 0.015). CONCLUSIONS: Hypoalbuminemia, hyperbilirubinemia, and ascites were important hepatic adverse events that developed after applying radiotherapy to treat advanced HCC. These adverse events seriously affected survival.

Adult↗

In vitro 1H NMR spectroscopy shows an increase in N-acetylaspartylglutamate and glutamine content in the hippocampus of amygdaloid-kindled rats.

We examined energy metabolism and amino acid content in the hippocampus of amygdaloid-kindled rats using (1)H NMR spectroscopy. Three weeks after the last stage 5 seizure, kindled rats were killed by microwave irradiation. The hippocampus was dissected out and subjected to MeOH/CHCl(3) extraction. All (1)H spectra were analyzed to quantify absolute concentrations using a non-linear least squares method, combined with a prior knowledge of chemical shifts. Saturation effects were compensated for by the T1 measurement of each component. Levels of energy metabolism-related compounds, phosphocreatine, creatine, glucose and succinate were the same in both kindled rats and sham controls. Lactate concentration had a tendency to increase, although this was not statistically significant. When compared with sham controls, levels of aspartate, glutamate, glycine and glutamine, as well as GABA and inositol, were increased in the ipsilateral but not the contralateral hippocampus. In contrast, levels of taurine, alanine and threonine were unchanged. Finally, N-acetylaspartylglutamate content was elevated, whereas N-acetyl-l-aspartate content was unaltered in the ipsilateral hippocampus of kindled animals. Our results suggest that amygdala kindling may affects amino acid metabolism, but not energy metabolism.

Amino Acids↗

Distributions of beta+ decayed nuclei generated in the CH2 and H2O targets by the target nuclear fragment reaction using therapeutic MONO and SOBP proton beam.

In proton radiotherapy, the irradiation dose can be concentrated on a tumor. To use this radiotherapy efficiently in the clinical field, it is necessary to evaluate the proton-irradiated area and condition. The proton-irradiated area can be confirmed by coincidence detection of pair annihilation gamma rays from beta+ decayed nuclei generated by target nuclear fragment reaction of irradiated proton nuclei and nuclei in the irradiation target. In this study, we performed experiments of proton irradiation to a polyethylene (PE:CH2) target containing 12C nuclei, which is a major component of the human body, and a gelatinous water (H2O) target containing 16O nuclei at different proton irradiation energy levels under different beam conditions of mono-energetic Bragg peak and spread-out Bragg peak. The distribution of the activity in the target after proton irradiation was measured by a positron emission tomography (PET) apparatus, and compared with the calculated distribution. The temporal dependence of the activity distribution during the period between the completion of proton irradiation and the start of measurement by the PET apparatus was examined. The activity by clinical proton irradiation was 3 kB/cc in the PE target and 13 kB/cc in the water target, indicating that the intensity was sufficient for the evaluation of the distribution. The range of the activity distribution against the physical range was short (several millimeter water equivalent length), indicating the presence of target dependence. The range difference in the water target was slightly large with time dependence until the start of measurement. The difference of the lateral widths with full width half at maximum in the distributions of the measured irradiated dose and activity was within 1 mm.

Algorithms↗

Sequence of forebrain activation induced by intraventricular injection of hypertonic NaCl detected by Mn2+ contrasted T1-weighted MRI.

In order to define the sequence of forebrain activation involved in osmoregulation, central activation in response to intracerebroventricular injection of NaCl solution (10 microl of 0.15, 0.5, or 1.5 M) was detected using manganese-contrasted magnetic resonance imaging (MRI) in anesthetized rats. Changes in renal sympathetic nerve activity (RNA) were also measured, and the time courses of forebrain activation and RNA changes compared. NaCl injection resulted in rapid activation of the subfornical organ (SFO), organum vasculosum lamina terminalis (OVLT), and periventricular regions and the lateral hypothalamic area (LHA), then of the paraventricular hypothalamic nucleus (PVN) and supraoptic nucleus (SON). The delay in activation in the PVN and SON showed a wide variation from 0 to 5.78 min, and the average delay in the PVN (2.88+/-0.34 min) and SON (2.90+/-0.39 min) was significantly greater than that in the SFO (0.40+/-0.10 min) and OVLT (0.74+/-0.13 min). NaCl (1.5 M) injection elicited a rapid, large increase in RNA, which consisted of two components, an early rapid increase at 99 s after injection (160+/-27%) and a slower increase at 9 min after injection (209+/-34%). These results suggest that the PVN and SON are activated not only by the afferent input from the SFO and OVLT but also by diffusion of the hypertonic stimulus to these regions and probably by their intrinsic osmosensitivity. The PVN might be responsible for the second slower component of the RNA response, but cannot be responsible for the first component.

Animals↗

Senescence-associated decline of lymphocyte migration in gut-associated lymphoid tissues of rat small intestine.

Scenescence-induced changes in gut-associated lymphoid tissues may contribute largely to the impaired immune responses during aging. Age-related changes in lymphocyte recirculations were investigated in Peyer's patches of rat small intestine. Cell dynamics of labeled T lymphocytes were observed under an intravital fluorescence microscope and compared between young and aged rats. Lymphocyte transport through intestinal lymph was decreased in aged rats. The lymphocyte rolling and adherence in postcapillary venules (PCV) of Peyer's patches was also significantly impaired in aged rats, with decreased expression of L-selectin on lymphocyte surfaces. Immunohistochemical analysis revealed a significant decrease in the CD8-positive cell population in Peyer's patches of the aged group, although mucosal addressin cell adhesion molecule-1 (MAdCAM-1) expression in postcapillary venules was unaltered. Lymphocyte adoptive-transfer studies indicated that although both the donor and recipient factors influence the adherence of T cells, the former may play a predominant role in the age-related change. This study clearly demonstrated in situ that T cell migration into Peyer's patches is significantly decreased in the aged intestine, which may reflect the impaired immune responses in the aging process.

Adoptive Transfer↗

In vivo 31P NMR spectroscopy shows an increase in glycerophosphorylcholine concentration without alterations in mitochondrial function in the prefrontal cortex of medicated schizophrenic patients at rest.

The (31)P NMR localised method was used to study the metabolism of phospholipid and high energy phosphate in the prefrontal cortex. The spectra were taken from patients with schizophrenia (11 males) receiving neuroleptic medication, and were compared to normal controls (15 males). Their spectral intensities were analysed using a non-linear least-squares method with a prior knowledge of the fixed chemical shifts and linewidths, leading to further resolution into resonances of glycerophosphorylethanolamine (GPE), glycerophosphorylcholine (GPC), phosphorylethanolamine (PE) and phosphorylcholine (PC). The metabolite concentrations were calculated referring to the spectral intensities of phosphate phantoms with known concentrations. T1 values of phantom and cerebrum were estimated from a series of localised inversion recovery spectra to correct for the signal saturation effects. The schizophrenic patients showed an increased concentration of GPC but not GPE, PE or PC. Furthermore, no difference was observed regarding the concentration of high-energy phosphates such as phosphocreatine, inorganic phosphate and ATP. The patients did not show any differences in mitochondrial function such as phosphorylation potential and the ratio of the rate of ATP synthesis. Thus, an increase in GPC concentration in the prefrontal cortex could be characteristic of the pathophysiology of schizophrenia with mild negative symptoms.

Adult↗

In situ demonstration of dendritic cell migration from rat intestine to mesenteric lymph nodes: relationships to maturation and role of chemokines.

Dendritic cells (DCs) are continuously transported from the intestine to mesenteric lymph nodes (MLNs). The objective of this study was to determine the migration kinetics of DCs via intestinal lymph and to investigate regulatory factors affecting their migration in vivo. DCs were obtained from spleen or thoracic duct lymph of mesenteric lymphadenectomized rats. The DCs were fluorescently labeled and injected into the subserosa of the small intestine near the cecum, and their migration patterns into MLNs were determined. Isolated DCs from intestinal lymph express intercellular adhesion molecule-1 (ICAM-1), CD11b/c, CD80/86, and major histocompatibility complex class II but maintain their ability to phagocytize latex particles, suggesting the presence of immature DCs. The isolated DCs accumulated in MLNs in a time-dependent manner with maximal accumulation at 48 h. Cytokine-induced maturation of lymph DCs did not cause a change in cell number but accelerated their transport into MLNs with a maximum at 24 h. Splenic DCs showed an intermediate level of maturation and a migration pattern similar to mature DCs. Inhibition of ICAM-1 or CD11b/c did not affect DC migration. Migration of mature DCs to MLNs was specifically blocked by desensitization of CCR7 with CCL21. In contrast, freshly isolated lymph DCs were not chemotactic for CCL21, but their migration to MLNs was mainly inhibited by desensitization of CCR6 with CCL20. The migratory ability of DCs correlates well with their degree of maturation, and different chemokine/chemokine receptor use may be the main regulator of DC migration kinetics through intestinal lymph.

Animals↗