PubMed Health⌕ Search

Biomedical subjects

T Kodama

Publications and source records attributed to T Kodama.

At least 19 recordsLinked to original sources

Functional magnetic resonance imaging is more reliable than somatosensory evoked potential or mapping for the detection of the primary motor cortex in proximity to a tumor.

The accurate localization of the primary motor cortex (M1) is critical for the preservation of motor function during resection of brain tumors in and around the M1. The goal of the present study was to determine which technique provided the most accurate localization of M1. The accuracy of preoperative functional magnetic resonance imaging (fMRI), intraoperative somatosensory evoked potential (SEP) and cortical mapping for the localization of M1 was determined in 17 patients with brain tumors in and around the M1. Because localization of the M1 is typically symmetrical in the cerebral hemispheres, the M1 on the affected side was localized by determination of the M1 location on the unaffected side using fMRI with patient hand clenching. The location of M1 was successfully determined by SEP in 5 of 11 cases. In the remainder of cases, the sulcus at which phase reversal occurred during SEP was shifted 1 or 2 gyri rostral to the central sulcus. The location of M1 was successfully determined by brain mapping in 9 of 15 cases. In the remainder of cases, stimulation failed to elicit a motor response. Finally, the location of M1 was successfully determined by fMRI in 16 of 17 cases. These data indicate that fMRI was more reliable than SEP or brain mapping for the detection of M1 in proximity to a tumor.

Adult↗

Examining the necessity to include event-by-event fluctuations in experimental evaluations of elliptical flow.

Elliptic flow at BNL RHIC is computed event by event with NeXSPheRIO. We show that when symmetry of the particle distribution in relation to the reaction plane is assumed, as usually done in the experimental extraction of elliptic flow, there is a disagreement between the true and reconstructed elliptic flows (15%-30% for eta=0, 30% for p perpendicular=0.5 GeV). We suggest a possible way to take into account the asymmetry and get good agreement between these elliptic flows.

Journal Article↗

Rheumatoid synovial endothelial cells produce macrophage colony-stimulating factor leading to osteoclastogenesis in rheumatoid arthritis.

OBJECTIVES: Periarticular osteoporosis and joint destruction are major complications in rheumatoid arthritis (RA), caused by osteoclast-mediated bone resorption. However, the mechanisms of monocyte/osteoclast maturation and role of RA endothelial cells (RAECs) in the control of osteoclastogenesis remain unclear. The present study was designed to determine the most important factors that influence monocyte accumulation and osteoclast formation among the many factors produced by RAEC. METHODS: We analysed the expression profiles of various genes in human endothelial cells from various organs (RA synovium, umbilical vein, skin, liver sinusoid, renal glomerulus and brain) using oligonucleotide microarrays. Specifically, up-regulated gene in RAECs was assessed by real-time quantitative polymerase chain reaction, enzyme-linked immunosorbent assay and immunostaining of RA synovia. Migration of monocytes was assessed by the chemotactic chamber EZ-TAXIScan. Tartrate-resistant acid phosphatase (TRAP)-positive multinucleated cell (MNC) formation was observed by microscopy. RESULTS: Among many epithelial-expressed factors, macrophage colony-stimulating factor (M-CSF) gene was abundantly expressed specifically in RAECs. Genes of fibroblast growth factor-2, interleukin-6 and osteoprotegerin were also overexpressed in RAECs. Migration of monocytes and osteoclast formation in co-cultures promoted by culture supernatants of RAECs were inhibited by M-CSF neutralizing antibody. CONCLUSIONS: M-CSF produced by RAECs is involved in osteoclastogenesis from monocytes, migration and TRAP-positive MNC formation.

Arthritis, Rheumatoid↗

Hepatocellular carcinoma in Txnip-deficient mice.

The molecular pathogenesis and the genetic aberrations that lead to the progression of hepatocellular carcinoma (HCC) are largely unknown. Here, we demonstrate that the thioredoxin interacting protein (Txnip) gene is a candidate tumor suppressor gene in vivo. We previously showed that the recombinant inbred congenic strain HcB-19 has a spontaneous mutation of the Txnip gene, and we now show that the strain has dramatically increased incidence of HCC, and that the HCC cosegregates with the Txnip mutation. Approximately 40% of the Txnip-deficient mice developed hepatic tumors with an increased prevalence in male mice. Visible tumors develop as early as 8 months of age. Histological analysis confirmed the morphology of HCC in the Txnip-deficient mice. Molecular markers of HCC, alpha-fetoprotein and p53, were increased in tumors of Txnip-deficient mice. The upregulation of p53 preceded tumor development; however, bromodeoxyuridine (BrdU) labeling of normal hepatic tissue of Txnip-deficient mice did not reveal increased cell proliferation. Finally, microarray analyses of tumor, non-tumor adjacent, and normal tissue of Txnip-deficient mice highlighted the genetic differences leading to the predisposition and onset of HCC. Our findings suggest that Txnip deficiency is sufficient to initiate HCC and suggest novel mechanisms in hepatocarcinogenesis.

Animals↗

Immunohistochemical prognostic factors in resected colorectal lung metastases using tissue microarray analysis.

AIMS: Immunohistochemical prognostic factors of pulmonary metastatic colorectal cancer lesions have not been well investigated. The study was conducted to identify the immunohistochemical prognostic factors of metastasized colorectal cancer. METHODS: We immunohistochemically investigated the expression of insulin-like growth factor-1 receptor (IGF1-R), E-cadherin, beta-catenin, and p53 using a tissue microarray in the surgical specimens of 86 metastatic lesions. RESULTS: The univariate analysis revealed E-cadherin and membrane beta-catenin positive to be prognostic factors. IGF1-R and p53 were not significantly associated with the patient's survival. In multivariate analysis, the reduced expression of E-cadherin, aerogenous spread with floating cancer cell clusters and vascular invasion were independent prognostic factors. CONCLUSIONS: The reduced expression of E-cadherin in the pulmonary metastatic lesions was an independent predictor of poor survival after pulmonary metastasectomy.

Biomarkers, Tumor↗

Dysregulated expression of P1 and P2 promoter-driven hepatocyte nuclear factor-4alpha in the pathogenesis of human cancer.

Hepatocyte nuclear factor-4alpha (HNF4alpha) exists in multiple isoforms that are generated by alternative promoter (P1 and P2) usage and splicing. Here we establish monoclonal antibodies (mAbs) for detecting P1 and P2 promoter-driven HNF4alpha, and evaluate their expression in normal adult human tissues and surgically resected carcinomas of different origins. Using immunohistochemical analysis, we demonstrate that, while P1 promoter-driven HNF4alpha is expressed in hepatocytes, small intestine, colon, kidney and epididymis, P2 promoter-driven HNF4alpha is expressed in bile duct, pancreas, stomach, small intestine, colon and epididymis. Altered expression patterns of P1 and P2 promoter-driven HNF4alpha were observed in gastric, hepatocellular and colorectal carcinomas. HNF4alpha was expressed in lung metastases from renal cell, hepatocellular and colorectal carcinoma but was not observed in lung tumours. The P1 and P2 promoter-driven HNF4alpha expression pattern of tumour metastases correlated with the primary site of origin. P1 promoter-driven HNF4alpha was also found in intestinal metaplasia of the stomach. These data provide evidence for the tissue distribution of P1 and P2 promoter-driven HNF4alpha at the protein level and suggest that HNF4alpha may be a novel diagnostic marker for metastases of unknown primary. We propose that the dysregulation of alternative promoter usage of HNF4alpha is associated with the pathogenesis of certain cancers.

Animals↗

Comparison of the immunophenotypes of signet-ring cell carcinoma, solid adenocarcinoma with mucin production, and mucinous bronchioloalveolar carcinoma of the lung characterized by the presence of cytoplasmic mucin.

The latest World Health Organization (WHO) classification divides adenocarcinoma mainly into adenocarcinoma mixed subtypes, acinar adenocarcinoma, papillary adenocarcinoma, bronchioloalveolar carcinoma, and solid adenocarcinoma with mucin production, and it mentions several variants, including fetal adenocarcinoma, mucinous ("colloid") adenocarcinoma, mucinous cystadenocarcinoma, signet-ring adenocarcinoma, and clear cell adenocarcinoma. In general, the mucin-producing adenocarcinoma of the lung comprises signet-ring cell carcinoma (SRCC), solid adenocarcinoma with mucin production (SA), and mucinous bronchioloalveolar carcinoma (m-BAC), mucinous ("colloid") adenocarcinomas and/or mucinous cystadenocarcinoma, and mucoepidermoid carcinoma. As SRCC, SA, and m-BAC exhibit distinct clinical features, it is important to identify differences in their immunohistochemical characteristics to better understand their histogenesis. In this study we analysed SRCC, SA, m-BAC, normal lung, and foregut-related secretory tissue for immunohistochemical differences using tissue microarrays. SRCC and SA showed high expression of MUC1 (97.4% and 100%, respectively), cytokeratin (CK) 7 (both 100%), and thyroid transcription factor-1 (TTF-1) (81.1% and 100%, respectively). They also showed low expression of MUC5AC (25.5% and 21.1%, respectively) and MUC6 (18.3% and 10.5%, respectively), whereas m-BAC showed high expression of MUC5AC (97.5%), MUC6 (75.0%), and CK7 (94.7%), but low expression of MUC1 (57.5%), and TTF-1 (27.5%). Hierarchical clustering showed that the immunophenotypes of SRCC and SA belong to the same category as alveolar lining cells, whereas m-BAC clustered onto another branch with gastric foveolar cells and bronchial goblet cells. These immunohistochemical findings support the results of our previous clinicopathological analysis of SRCC of the lung showing that SRCC occurs anatomically in the peripheral portion of the lung rather than in the bronchial gland-bearing portion.

Adenocarcinoma↗

Hepatocellular oncofetal protein, glypican 3 is a sensitive marker for alpha-fetoprotein-producing gastric carcinoma.

AIMS: Glypican 3 (GPC3) is a cell surface heparan sulphate proteoglycan expressed specifically in the fetal liver and malignant neoplasms of hepatocyte lineage. The aim was to evaluate the significance of GPC3 in alpha-fetoprotein (AFP)-producing gastric carcinoma (GC) and other forms of GC. METHODS AND RESULTS: We immunohistochemically evaluated GPC3 expression in representative cases of AFP-producing GC and in a tissue microarray of a consecutive series of GCs with other markers of hepatocyte lineage (AFP, PIVKA-II and hepatocyte antigen, HEP). In a series of 10 cases of AFP-producing GC, we observed immunohistochemical positivity for GPC3, PIVKA-II and HEP in 10, three and three cases in components with a hepatoid pattern and in nine, two and five cases in components with a non-hepatoid pattern, respectively. In a series of 118 cases of GC, we observed positivity for AFP, GPC3, PIVKA-II and HEP in one (0.8%), four (3.4%), six (5.1%) and 26 cases (22%), respectively. GPC3 was observed concurrently with AFP and discordantly with PIVKA-II and HEP. GPC3 positivity was clearly stronger in a larger area compared with immunoreactivity for AFP. CONCLUSIONS: GPC3 is a sensitive marker for AFP-producing GC and its hepatoid component and is therefore useful to identify this aggressive subgroup of GC.

Adenocarcinoma↗

Spontaneous improvement of persistent ulceration after carotid artery stenting.

BACKGROUND AND PURPOSE: Because carotid plaque ulceration is associated with an increased risk of cerebral embolism, residual carotid plaque ulceration directly around a stent (persistent ulceration) after carotid angioplasty and stent placement (CAS) could still be a risk factor for a stroke. The purpose of this study is to understand the morphologic and clinical prognosis of persistent ulceration. PATIENTS AND TECHNIQUES: CAS was attempted on 91 consecutive stenotic lesions (80 patients). Of these, 54 lesions (48 patients) had ulceration before CAS. Angiograms were evaluated immediately after the procedure. Persistent ulceration was found in 34 lesions (30 patients). The mean depth and length of persistent ulcers were 2.1 mm (range, 1-4.7 mm) and 8.9 mm (range, 1.5-22 mm), respectively. All patients with persistent ulceration were followed with antiplatelet therapy. RESULTS: No ischemic event due to the lesions occurred during the mean follow-up period of 25.5 months (range, 3-48 months). Angiography on 25 lesions (21 patients) at a mean of 5.8 months (range, 1-21 months) after CAS showed that persistent ulceration disappeared in 12 lesions (48%), improved in 11 lesions (44%), and remained unchanged in 2 lesions (8%). Nine lesions (36%) showed restenosis, which were < or =30% and did not require any additional intervention. New ischemic lesions were not detected in any of the 14 patients (17 lesions) who underwent follow-up MR imaging at a mean of 9 months (range, 1-32 months) after CAS. CONCLUSION: We conclude that persistent ulceration after CAS improves spontaneously and is not a risk factor for cerebral embolism.

Aged↗

Direct carotid puncture for the endovascular treatment of anterior circulation aneurysms.

We report the usefulness of Guglielmi detachable coil (GDC) embolization by direct carotid puncture for anterior circulation aneurysms. For all 27 patients, GDC embolization by direct carotid puncture was safely performed by using a 5F sheath introducer 5 cm long and a Tracker-38 catheter. Neurologic deficits and hemorrhage were not found in any patient during the follow-up period. If the transfemoral approach cannot be applied, GDC embolization should be considered as an alternative method.

Aged↗

The significance of incomplete stent apposition in patients undergoing stenting of internal carotid artery stenosis.

BACKGROUND AND PURPOSE: Incomplete stent apposition after carotid angioplasty and stent placement (CAS) is often seen but little is known about how the incomplete attachment goes after stent placement. For example, some may change into restenosis around the stent edge and some may remain unchanged. The purpose of this study is to clarify the morphologic prognosis of an incomplete stent apposition at the stent edge. METHODS: CAS was attempted on 135 consecutive stenotic lesions (124 patients). Angiograms were then evaluated immediately after the procedure. An incomplete stent apposition at stent edge was found in 15 patients, and all of them were followed up by angiography and MR imaging with antiplatelet therapy. RESULTS: No ischemic event caused by the lesions occurred during the mean follow-up period of 11 months (from 4 to 32 months). The angiography findings of 15 lesions at a mean of 8.8 months (from 2 to 28 months) after CAS showed that all remained unchanged. No patients required any additional intervention. No new ischemic lesions were detected in any of the 15 patients who underwent follow-up MR imaging at a mean of 10 months (from 2 to 32 months) after CAS. CONCLUSION: In this study, the existence of a segment of incomplete stent apposition had no adverse morphologic or clinical effect.

Aged↗

Nitric oxide from the laterodorsal tegmental neurons: its possible retrograde modulation on norepinephrine release from the axon terminal of the locus coeruleus neurons.

Nitric oxide released from the cholinergic neurons in the pons may play important roles in sleep-wake regulation. However, there are few reports demonstrating the mechanisms of nitric oxide release in the cholinergic neurons in the pons. The present study investigated the effects of drug delivery of N-methyl-D-aspartic acid on nitric oxide and the neurotransmitters released in the laterodorsal tegmental nucleus (LDT), one of the major cholinergic cell groups in the pons, in rats by in vivo microdialysis with a view to clarifying nitric oxide functions in the cholinergic system. The application of N-methyl-D-aspartic acid (1 mM) into the LDT induced a significant increase in NO(2)and NO(3) for 40 min (P<0.001). Furthermore the same dose of N-methyl-D-aspartic acid induced a significant increase in cyclic GMP for 30 min (P<0.05), as well as in acetylcholine (P<0.001) and norepinephrine for 15 min (P<0.001). 3-(4-Morpholinyl)-sydonone imine hydrochloride (a nitric oxide donor, 5 mM) also induced significant increase in norepinephrine (P<0.05). Pretreatment with 1 mM 2-amino-5-phosphonopentanoic acid (an antagonist of N-methyl-D-aspartic acid receptor) prevented the N-methyl-D-aspartic acid-induced increase in cyclic GMP (P<0.01), acetylcholine and norepinephrine (P<0.01), while that with 1 mM N(G)-nitro-L-arginine (an inhibitor of nitric oxide synthase) prevented the increase in cyclic GMP (P<0.01) and norepinephrine (P<0.01) but not in acetylcholine. These results suggested that nitric oxide release in the LDT induced by activation of the N-methyl-D-aspartic acid receptor on the cholinergic neurons of the LDT, then through the cyclic GMP system, facilitates norepinephrine release from the terminals of noradrenergic neurons in the locus coeruleus. Based on these findings, we propose a possible role of nitric oxide in the LDT is as a retrograde regulator of norepinephrine release from the locus coeruleus.

Acetylcholine↗

Intraoperative cortical mapping has low sensitivity for the detection of motor function in proximity to a tumor in the primary motor area.

Six patients with brain tumors within or near the primary motor cortex underwent preoperative functional magnetic resonance imaging (fMRI) and intraoperative cortical mapping, and the accuracy of those techniques for localization of the primary motor cortex and motor function beside the tumor were determined by comparison against neuroanatomical correlates from pre-, intra- and postoperative neurological observations. The location of the primary motor cortex was detected by intraoperative cortical mapping in 5 of 6 cases and by fMRI in all 6 cases. Brain mapping provided equivocal information on the cortical representation of motor territories, and with the technique used in close proximity to the tumor, the motor territories were not detected in all but 1 case. In contrast, the areas controlling motor function in close proximity to the tumor were detected by fMRI in 4 of 6 cases. These data indicate that intraoperative cortical mapping has a low sensitivity for the detection of motor function in the area beside the tumor. Therefore, this technique may not be sufficient to prevent compromise of motor areas during tumor resection.

Aged↗

Effects of single and long-term administration of wheat albumin on blood glucose control: randomized controlled clinical trials.

OBJECTIVE: To examine the effects of single and long-term administration of wheat albumin (WA) on blood glucose levels and blood glucose control, respectively. DESIGN: Randomly arranged crossover trial for single administration in healthy subjects and double-blinded randomized controlled trial for long-term administration (3 months) in diabetic patients. In vitro alpha-amylase inhibitory activity of WA was also determined. SETTING: Central Research Laboratories of Nisshin Flour Milling Co. Ltd. (Saitama, Japan) for single administration and Aiwa Clinic (Saitama, Japan) for long-term administration. SUBJECTS: A total of 12 healthy adult male volunteers for the single administration and 24 type II outpatient diabetics with mild hyperglycemia for the long-term administration. INTERVENTIONS: Subjects took soups containing 0, 0.25, 0.5, and 1.0 g WA before test meals for single administration, and patients took soups with or without 0.5 g WA before every meal for the long-term (3 months) administration. RESULTS: In vitro alpha-amylase inhibitory activity of WA was 150 times that of wheat flour. In the single administration experiment, WA suppressed peak postprandial blood glucose levels in a dose-dependent manner: 31, 47, and 50% reduction after 0.25, 0.5, and 1.0 g administrations, respectively. In the long-term administration, 0.5 g of WA did not affect fasting blood glucose levels, whereas it reduced hemoglobin A1c levels. No significant adverse effects such as hypoglycemia or gastrointestinal disturbances were observed in the two experiments. CONCLUSION: In the treatment of type II diabetic patients, WA might be a useful functional food, which, with diet and exercise, could help to improve blood glucose control without any critical adverse effects.

Administration, Oral↗

Preoperative fMRI, tractography and continuous task during awake surgery for maintenance of motor function following surgical resection of metastatic tumor spread to the primary motor area.

The goal of the present study was to determine the efficacy of preoperative fMRI, tractography, and intraoperative continuous task during awake surgery in preserving postoperative motor function in patients undergoing resection of metastatic brain tumors in or near the primary motor area. Three patients with metastatic brain tumors in the primary motor area elected to undergo surgical treatment. Preoperative fMRI and tractography were performed, and various primary motor areas (e. g., hand, arm, face and leg) were identified and confirmed by cortical mapping or by the outcome of awake surgery. Cortical mapping and continuous appropriate task were performed during awake surgery. Preoperative fMRI and tractography correctly identified the primary motor area. In contrast, cortical mapping identified the gyrus of the primary motor area but was unable to identify specific primary motor areas, such as those for the hand or arm, which were compressed by the tumor. Tumor resection was terminated when any deterioration in continuous task performance was observed during awake surgery. Paresis was transient and resolved within one week in all cases. The combination of preoperative fMRI, tractography and continuous task during awake surgery helped to maintain motor function following surgical management of metastatic brain tumors of the primary motor cortex.

Brain Mapping↗

Association of motor deficits with head position during awake surgery for resection of medial motor area brain tumors.

OBJECTIVE: Resection of tumors involving the motor area frequently results in postoperative motor deficits. In an attempt to prevent poor motor outcomes, our institution has utilized preoperative fMRI and tractography as well as intraoperative cortical mapping and continuous motor tasks during awake surgery in patients with motor area tumors. In one case, a patient demonstrated deterioration in continuous motor task performance before initiation of tumor resection. Thus, the goal of this study was to evaluate the relationship between head position and development of intraoperative or postoperative motor deficits in five patients with motor area tumors. CLINICAL PRESENTATION: In four cases, the patient's head was rotated 60 degrees from the supine position. In two cases, in which the tumor was located relatively medially, deterioration in continuous motor task function was noted prior to resection of the tumor. In the two other cases, in which the tumor was located relatively laterally, there was no deterioration of continuous motor task performance until resection of the tumor. Another patient, in whom the tumor was located relatively medially, underwent surgery with the head positioned straight and with the patient in a half-sitting position. This patient did not experience deterioration of continuous motor task performance during the surgery. CONCLUSION: These data suggest that head positioning can have a significant impact on motor function in patients with motor area tumors. Furthermore, the straight head position may be the preferred positioning, particularly for patients with tumors located on the medial side of motor area.

Aged↗

Lymphomatous polyposis of the gastrointestinal tract, including mantle cell lymphoma, follicular lymphoma and mucosa-associated lymphoid tissue lymphoma.

AIMS: Lymphomatous polyposis (LP) is considered to represent mantle cell lymphoma (MCL) of the gastrointestinal (GI) tract. However, a few reports have suggested that some are follicular lymphoma (FL) or mucosa-associated lymphoid tissue (MALT) lymphomas. In this study, we analysed 35 patients and clarified the clinicopathological features of LP. METHODS AND RESULTS: Paraffin-embedded tissue samples were stained immunohistochemically and analysed by tissue-fluorescence in situ hybridization (T-FISH) for IGH/CCND1 (cyclin D1) and IGH/BCL2. The average age of the patients was 58.3 years. Over half of the cases showed gastric, duodenal, small intestinal, ileocaecal and sigmoid colonic lesions (15, 19, 15, 16 and 16 cases, respectively). Phenotypically, cases were classified into three types of MCL (cyclin D1+ CD5+ CD10-) (n=12), FL (cyclin D1- CD5- CD10+) (n=14) and MALT (cyclin D1- CD5- CD10-) (n=9). T-FISH identified 11 of the 11 examined cases with MCLs to have IGH/CCND1, while seven of 10 cases with FL had IGH/BCL2, and none of the MALT cases were positive for IGH/CCND1 or IGH/BCL2. At the study endpoint, five of 12 patients with MCL were dead, two of 14 with FL and one of nine with MALT were dead of other disease. Event-free survival analysis showed significantly poorest outcome in MCL, followed by FL, while MALT was associated with a favourable outcome (P=0.0040). CONCLUSIONS: Our study emphasizes the importance of differentiating MCL, FL and MALT of LP in evaluating prognosis and hence the most suitable therapeutic regimen.

Aged↗

S-carboxymethylcysteine normalises airway responsiveness in sensitised and challenged mice.

S-carboxymethylcysteine (S-CMC) has been used as a mucoregulator in respiratory diseases. However, the mechanism of action of S-CMC on allergic airway inflammation has not yet been defined. In the present study, BALB/c mice were initially sensitised and challenged to ovalbumin (OVA) and, weeks later, re-challenged with OVA (secondary challenge). S-CMC (5-100 mg.kg-1) was administered from 2 days before the secondary challenge through to the day of assay. Mice developed airway hyperresponsiveness (AHR) 6 h after the secondary challenge and increased numbers of neutrophils were present in the bronchoalveolar lavage (BAL) fluid. At 72 h after secondary challenge, mice again developed AHR, but the BAL fluid contained large numbers of eosinophils. S-CMC treatment was found to reduce AHR and neutrophilia at 6 h, as well as eosinophilia and AHR at 72 h. These effects appeared to be dose dependent. Goblet cell hyperplasia, observed at 72 h, was reduced by S-CMC. In BAL fluid, increased levels of interferon-gamma, interleukin (IL)-12 and IL-10 and decreased levels of IL-5 and IL-13 were detected. In conclusion, the data indicate that S-carboxymethylcysteine is effective in reducing airway hyperresponsiveness and airway inflammation at two distinct phases of the response to the secondary allergen challenge in sensitised mice.

Allergens↗