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Biomedical subjects

Takayuki Yamada

Publications and source records attributed to Takayuki Yamada.

At least 19 recordsLinked to original sources

Malignant astrocytic tumors: clinical importance of apparent diffusion coefficient in prediction of grade and prognosis.

PURPOSE: To retrospectively assess the apparent diffusion coefficient (ADC) for prediction of malignancy and prognosis of malignant astrocytic tumors. MATERIALS AND METHODS: The institutional review board approved this study and did not require patient informed consent. Findings from 37 consecutive patients (21 men, 16 women; mean age, 43 years) with pathologically proved malignant astrocytic tumors that included 22 glioblastomas (GBMs) and 15 anaplastic astrocytomas (AAs) were retrospectively evaluated. The minimum ADC value of each tumor was preoperatively determined from several regions of interest defined in the tumor, preferably with avoidance of cystic or necrotic components, on ADC maps derived from isotropic diffusion-weighted images. Surgical intervention, followed by radiation therapy, was undertaken in all cases according to hospital protocol. Immunohistologically, Ki-67 labeling index (LI), indicating cell proliferation, was also determined. The patients were classified into two groups, progressive and stable, according to the 2-year observation after the initial treatment. Correlation analysis (Pearson product moment correlation), Student t test, Welch test, receiver operating characteristic analysis, and Kaplan-Meier method with log-rank test were used for statistical evaluation. RESULTS: There was a significant negative correlation between minimum ADC and Ki-67 LI (r = -0.562, P < .001). The mean minimum ADC (0.834 x 10(-3) mm2 x sec(-1)) of GBM was significantly lower than that (1.06 x 10(-3) mm2 x sec(-1)) of AA (P < .001, Student t test). The mean minimum ADC (0.80 x 10(-3) mm2 x sec(-1)) of the progressive group was significantly lower than that (1.037 x 10(-3) mm2 x sec(-1)) of the stable group (P < .001). The cutoff value of 0.90 x 10(-3) mm2 x sec(-1) for minimum ADC for differentiation of patients with a favorable prognosis from those with a poor prognosis provided the best combination of sensitivity (79%) and specificity (81%) (receiver operating characteristic analysis). The significant difference in the prognosis between two groups classified by using this cutoff value of minimum ADC was noted (P = .002, log-rank test). CONCLUSION: The minimum ADC of malignant astrocytomas can provide additional information about their clinical malignancy related to posttreatment prognosis.

Adult↗

Regulation of cytokinesis by mgcRacGAP in B lymphocytes is independent of GAP activity.

In cytokinesis, several molecules including small G proteins and their regulators are known to have important roles. One of these regulators, mgcRacGAP has GTPase activating protein (GAP) activity for Rac, Cdc42 and Rho. MgcRacGAP has also been shown to be involved in cytokinesis using various cell types. However, the requirement of mgcRacGAP for cytokinesis and survival in B lymphocytes has not been fully examined. Here, we demonstrate that normal cytokinesis in B lymphocytes requires the GAP and NH2 terminal domains but not GAP activity of mgcRacGAP. In addition, we report that apoptosis induced by conditional ablation of mgcRacGAP in the B cell line is fully rescued by the introduction of a GAP-inactive mutant, suggesting that the survival defect in mgcRacGAP-deficient B cells is also independent of GAP activity.

Animals↗

FDG PET in solitary metastastic/secondary tumor of the kidney: a report of three cases and a review of the relevant literature.

Metastatic tumors or secondary lymphoma of the kidney are rare and can often be missed on conventional computed tomography (CT) imaging. On the other hand, many types of metastatic tumor or lymphoma can be detected clearly as hotspots of elevated uptake on FDG PET. However, excreted FDG present in the urinary tract mimics these findings and interferes with image reading. Careful investigation of the renal cortex by FDG PET and review of anatomical images, such as the findings of CT and MRI, have important roles in the detection of renal tumor. Here, we present three cases of solitary metastatic/secondary tumor of the kidney, and discuss the features of the lesions on FDG PET in comparison with their appearance on CT.

Adolescent↗

Evaluation of the relationship between physiological FDG uptake in the heart and age, blood glucose level, fasting period, and hospitalization.

OBJECTIVE: Positron emission tomography (PET) with fluorodeoxyglucose (FDG) is widely used for evaluation of cancer and ischemic heart disease. Recently, increased myocardial FDG uptake has been reported to be related to some types of heart disease, such as sarcoidosis. However, the physiological increased FDG uptake in the heart often mimics the abnormal high uptake in these cases. In this study, we investigated the relationships between myocardial uptake and age, blood glucose level, fasting period, and hospitalization status (inpatient vs. outpatient). METHODS: A total of 159 non-diabetic patients were enrolled in the present study. Patients were imaged on a PET/CT scanner, and a three-dimensional region of interest (ROI) was drawn on the fused PET/CT image to measure the maximum standardized uptake value (SUV(max)) of the whole left ventricle. RESULTS: No significant relationships were observed between myocardial uptake and age or fasting period. Blood glucose level showed a significant relationship (p = 0.025) with myocardial uptake, but the R-square was extremely small (r2 = 0.03). With an SUV(max) threshold of 3.0, there was no significant difference between inpatients and outpatients. However, outpatients showed a significantly higher frequency of myocardial uptake over SUV(max) of 5.0 (chi2 test: p = 0.046). CONCLUSION: It is difficult to predict the degree of physiological uptake in the heart from data regarding age, fasting period, or blood glucose level. Outpatients tend to show higher myocardial uptake than inpatients, which may make it difficult to detect abnormally increased uptake in the heart. A long fasting period, such as overnight fasting, is an inadequate means to reduce the physiological uptake of FDG in the heart.

Adolescent↗

Atlantoaxial osteoarthritis in rheumatoid arthritis: FDG PET/CT findings.

The cervical spine is a common focus of destruction in patients with rheumatoid arthritis, and the resultant instability and neural compression represent severe complications in these patients. Evaluation of disease activity at the level of the atlantoaxial joint is important in such cases. Here, we report a 47-year-old man with a 3-year history of rheumatoid arthritis. FDG PET/CT clearly demonstrated a hot spot in the atlantoaxial area, suggesting high metabolic activity of synovitis.

Arthritis, Rheumatoid↗

Comparison of MDCT and MRI for evaluating the intraductal component of breast cancer.

OBJECTIVE: The purpose of our study was to compare the accuracy of MDCT and MRI for evaluating the intraductal component of breast cancer. MATERIALS AND METHODS: Sixty-nine patients with histologically proven invasive carcinoma underwent MDCT and MRI. Retrospectively, two radiologists performed a blinded review of the MDCT and MRI. Cases with intraductal component enhancement were classified into two morphologic types: ductal extension and segmental distribution. The lengths of the main tumor and of the intraductal component were measured in cases with ductal extension. For cases with segmental distribution, only the maximum length of the tumor was measured. RESULTS: The sensitivity, specificity, and accuracy in detecting the intraductal component were 61%, 88%, and 71%, respectively, using MDCT; and 75%, 88%, and 80%, respectively, using MRI. MRI revealed the presence of the intraductal component with significantly higher sensitivity than did MDCT (p = 0.031). In the analysis of the length of the intraductal component in cases with ductal extension, which had relatively small intraductal components, underestimation by 15 mm or more was significantly less frequent with MRI than with MDCT (p = 0.008). There was no significant difference between MDCT and MRI in the evaluation of the maximum length of tumors in cases with segmental distribution, which had relatively large intraductal components. CONCLUSION: Compared with MDCT, MRI revealed the presence of the intraductal component with higher sensitivity and equivalent specificity. In cases with ductal extension, MRI is more precise than MDCT for determination of the margin for surgical removal, with less underestimation of the extent of the intraductal component.

Adult↗

Ascorbic acid promotes osteoclastogenesis from embryonic stem cells.

Ascorbic acid (AA) is known to regulate cell differentiation; however, the effects of AA on osteoclastogenesis, especially on its early stages, remain unclear. To examine the effects of AA throughout the process of osteoclast development, we established a culture system in which tartrate-resistant acid phosphate (TRAP)-positive osteoclasts were induced from embryonic stem cells without stromal cell lines. In this culture system, the number of TRAP-positive cells was strongly increased by the addition of AA during the development of osteoclast precursors, and reducing agents, 2-mercaptoethanol, monothioglycerol, and dithiothreitol, failed to substitute for AA. The effect of AA was stronger when it was added during the initial 4 days during the development of mesodermal cells than when it was added during the last 4 days. On day 4 of the culture period, AA increased the total cell recovery and frequency of osteoclast precursors. Magnetic cell sorting using anti-Flk-1 antibody enriched osteoclast precursors on day 4, and the proportion of Flk-1-positive cells but not that of platelet-derived growth factor receptor alpha-positive cells was increased by the addition of AA. These results suggest that AA might promote osteoclastogenesis of ES cells through increasing Flk-1-positive cells, which then give rise to osteoclast precursors.

Animals↗

Time-related changes in computed tomographic appearance and pathologic findings after radiofrequency ablation of the rabbit lung: preliminary experimental study.

PURPOSE: To evaluate correlations between computed tomographic (CT) appearance and pathologic findings after radiofrequency (RF) ablation of lungs and to determine whether CT appearance could predict the extent of the effective therapeutic area. MATERIALS AND METHODS: The lungs of 14 rabbits were subjected to RF ablation and CT scans were obtained immediately and at various intervals thereafter. Four rabbits were killed immediately after the initial CT imaging (n = 4). The remaining 10 rabbits were killed after additional CT scans at intervals of 3 days (n = 2), 1 week (n = 4), 2 weeks (n = 2), and 3 weeks (n = 2) after RF ablation. Pathologic findings were correlated with CT appearance. RESULTS: Immediately after RF ablation, a restricted area of central dense opacity enclosed by an extensive area of ground-glass opacity was noted in the ablated region on CT images. Pathologically, the former corresponded to destructive tissue and the latter corresponded to tissue with some degree of injury. After 1 week, the entire ablated region appeared as a well-demarcated homogeneous dense opacity on CT that corresponded to necrotic tissue and its surrounding rim of granulation tissue on histopathologic examination, indicating that the enclosing extensive area of ground-glass opacity on the initial CT scan represented an ongoing necrosis. Within 2-3 weeks, the ablated region gradually contracted on the CT images, representing a tissue repairing process in which the granulation tissue was encroaching on the inner necrotic tissue. CONCLUSION: Ground-glass opacity of the ablated region on CT immediately after RF ablation represents an ongoing necrosis.

Animals↗

Systemic to pulmonary venous shunt in lung cancer with obstruction of superior vena cava: case report with review of the literature.

We describe the CT features of an unusual collateral pathway of systemic to pulmonary venous shunt in a patient with lung cancer that obstructed the superior vena cava (SVC). Spiral CT scan with rapid injection of contrast medium from a right arm vein revealed a systemic to pulmonary venous shunt (SPVS), passing through thick pleural effusion, which was the direct transpleural communication between right upper chest wall veins and right superior pulmonary veins. Three-dimensional CT angiography revealed the entire shunt. We consider that the shunt was formed in association with radiation therapy, and was not injured with the subsequent collapse of the lung and accumulation of massive pleural effusion. We review the reports that have dealt with the shunt in patients with lung cancer, and discuss the conditions related to the development of SPVS in such patients.

Heart Defects, Congenital↗

Long-term outcome of breast-conserving therapy for breast cancer.

PURPOSE: We present a retrospective analysis of long-term therapeutic results for patients treated in our institution to evaluate the efficacy of breast-conserving therapy (BCT). PATIENTS AND METHODS: The study population was 99 patients (102 breasts) with stage 0, I, and II breast cancer who underwent breast conservation therapy between April 1990 and November 1997. The entire breast was irradiated to a median dose of 50 Gy (range, 50-60 Gy) in 25-30 fractions. An additional 10 Gy in five fractions with 6-12 MeV electrons was given to 23 breasts (23%) with positive surgical margins. RESULTS: The 5-/10-year overall survival, cause-specific survival, relapse-free rate, local recurrence, and regional recurrence rates were 94.6/93.3%, 95.7/94.5%, 88.2/77.5%, 4.2/8.5%, and 2.0/6.3%, respectively. In both uni- and multivariate analyses, age < 40 years was a significant prognostic factor for local recurrence. No severe morbidity was observed. CONCLUSION: The long-term clinical outcome of BCT for early breast carcinoma patients in our department was favorable. Patient age <40 was the most important factor associated with an increased risk of local recurrence in the ipsilateral breast.

Adult↗

Lipopolysaccharide-induced osteoclastogenesis in Src homology 2-domain phosphatase-1-deficient viable motheaten mice.

Osteoclasts are hemopoietic cells that participate in bone resorption and remodeling. Receptor activator of nuclear factor-kappaB ligand (RANKL) and macrophage colony-stimulating factor (M-CSF) are critical for development of osteoclasts. The Toll-like receptor (TLR) family shares some of the downstream signaling with RANK. The TLR4 ligand, lipopolysaccharide (LPS), is reported to accelerate bone lysis; however, signaling via TLRs has never been reported to induce osteoclastogenesis without RANKL. In this study we showed that significant numbers of mature osteoclasts were generated from protein tyrosine phosphatase Src homology 2-domain phosphatase-1-defective Hcph(me-v)/Hcph(me-v) (me(v)/me(v)) bone marrow cells in the presence of M-CSF and LPS without addition of RANKL in culture. This M-CSF plus LPS-induced osteoclastogenesis was not inhibited by an anti-TNFalpha antagonistic antibody or by osteoprotegerin, a decoy receptor for RANKL. The replacement of RANKL by TLR ligands only occurred with LPS. Other ligands, a peptidoglycan for TLR2 or an unmethylated CpG oligonucleotide for TLR9, did not support osteoclast generation. The osteoclast precursors as well as RANKL-responsive osteoclast precursors were present in the Kit-positive cell-enriched fraction of bone marrow cells. Although me(v)/me(v) bone marrow cells required a comparable concentration of RANKL or TNFalpha as wild-type cells for the initiation of osteoclastogenesis, the numbers of multinucleated osteoclasts in me(v)/me(v) bone marrow cultures were significantly increased by the equivalent dose of RANKL or TNFalpha in the presence of M-CSF. These results indicate that a defect of Src homology 2-domain phosphatase-1 function not only accelerates physiological osteoclast development by RANKL/RANK, but also acquires a novel pathway for osteoclastogenesis by LPS.

Animals↗

Low-dose CT of the thorax in cancer follow-up.

PURPOSE: To evaluate the quality of low-dose computed tomography (CT) images in the follow-up of cancer patients. MATERIALS AND METHODS: We selected patients with urogenital (n = 7) or esophageal cancer (n = 13) who were attending routine follow-up between April and July 2001. After water and chest phantom studies to decide the scan parameters, postcontrast low-dose CT scans were obtained at 60 mA (45 mA s) with a smoothing kernel. Three radiologists reviewed the CT scans of the thorax independently for overall image quality and anatomic detail in both mediastinal and lung windows. They subjectively rated the images on a four-point scale (0: poor, 1: fair, 2: good, 3: excellent) according to graininess and sharpness. RESULTS: The average score of the low-dose CT for the lung window was 2.85, which was equivalent to control images. The average score for the mediastinal window was 1.77, which was lower than that of the control CT scan (2.62, P < 0.001) and almost identical to that of the chest phantom experiment. Nine of the 20 cases had abnormal findings; low-dose CT scans depicted them well and offered sufficient information for diagnosis. The radiation exposure was reduced by about half. CONCLUSION: The image quality of low-dose thoracic CT was satisfactory for both mediastinal and lung windows in the follow-up of cancer patients.

Aged↗

Lysophosphatidic acid (LPA) in malignant ascites stimulates motility of human pancreatic cancer cells through LPA1.

Cytokines and growth factors in malignant ascites are thought to modulate a variety of cellular activities of cancer cells and normal host cells. The motility of cancer cells is an especially important activity for invasion and metastasis. Here, we examined the components in ascites, which are responsible for cell motility, from patients and cancer cell-injected mice. Ascites remarkably stimulated the migration of pancreatic cancer cells. This response was inhibited or abolished by pertussis toxin, monoglyceride lipase, an enzyme hydrolyzing lysophosphatidic acid (LPA), and Ki16425 and VPC12249, antagonists for LPA receptors (LPA1 and LPA3), but not by an LPA3-selective antagonist. These agents also inhibited the response to LPA but not to the epidermal growth factor. In malignant ascites, LPA is present at a high level, which can explain the migration activity, and the fractionation study of ascites by lipid extraction and subsequent thin-layer chromatography indicated LPA as an active component. A significant level of LPA1 receptor mRNA is expressed in pancreatic cancer cells with high migration activity to ascites but not in cells with low migration activity. Small interfering RNA against LPA1 receptors specifically inhibited the receptor mRNA expression and abolished the migration response to ascites. These results suggest that LPA is a critical component of ascites for the motility of pancreatic cancer cells and LPA1 receptors may mediate this activity. LPA receptor antagonists including Ki16425 are potential therapeutic drugs against the migration and invasion of cancer cells.

Adult↗

Distinct osteoclast precursors in the bone marrow and extramedullary organs characterized by responsiveness to Toll-like receptor ligands and TNF-alpha.

Osteoclasts are derived from hemopoietic stem cells and play critical roles in bone resorption and remodeling. Multinucleated osteoclasts are attached tightly to bone matrix, whereas precursor cells with the potential to differentiate into osteoclasts in culture are widely distributed. In this study, we assessed the characteristics of osteoclast precursors in bone marrow (BM) and in extramedullary organs as indicated by their responsiveness to ligands for Toll-like receptors (TLRs) and to TNF-alpha. Development of osteoclasts from precursor cells in the BM was inhibited by CpG oligonucleotides, a ligand for TLR9, but not by LPS, a ligand for TLR4. BM osteoclasts were induced by TNF-alpha as well as receptor activator of NF-kappaB ligand in the presence of M-CSF. Splenic osteoclast precursors, even in osteoclast-deficient osteopetrotic mice, differentiated into mature osteoclasts following exposure to TNF-alpha or receptor activator of NF-kappaB ligand. However, splenic osteoclastogenesis was inhibited by both LPS and CpG. Osteoclastogenesis from peritoneal precursors was inhibited by not only these TLR ligands but also TNF-alpha. The effects of peptidoglycan, a ligand for TLR2, were similar to those of LPS. BM cells precultured with M-CSF were characterized with intermediate characteristics between those of splenic and peritoneal cavity precursors. Taken together, these findings demonstrate that osteoclast precursors are not identical in the tissues examined. To address the question of why mature osteoclasts occur only in association with bone, we may characterize not only the microenvironment for osteoclastogenesis, but also the osteoclast precursor itself in intramedullary and extramedullary tissues.

Animals↗

Compound heterozygosity for two novel mutations in a severe factor XI deficiency.

We identified two novel mutations in an asymptomatic 25-year-old Japanese patient with severe factor XI deficiency. Direct sequencing analysis of PCR products from his factor XI gene revealed a G to T transversion in exon 12, resulting in the nonsense mutation (Glu447Stop) and a G insertion in five consecutive guanine nucleotides ((501)Trp(TGG)-(502)Gly(GGG)) in exon 13 that is expected to lead to the substitution of the last 105 amino acids ((503)Tyr-(607)Val) with 32 abnormal amino acid residues ((503)Val-(534)Thr) followed by stop codon. We also demonstrated that two mutations are associated with the separate alleles in this patient, indicating compound heterozygosity for these mutations. Both mutations lead to the disruption of the catalytic domain structure of the FXI molecule and thus are responsible for his deficiency of factor XI.

Adult↗