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Objective: The aim of this study was to clarify the predictive significance of nodal calcification in terms of the therapeutic option of (131)I therapy in papillary thyroid carcinoma (PTC) patients., Methods: We reviewed 19 computed tomography (CT) examinations of PTC patients on receiving (131)I therapy for the presence of nodal calcification, and compared the (131)I whole-body scintigraphy and (18)F-2-fluoro-2-deoxy-D-glucose (FDG) positron emission tomography (PET)/CT findings. The metastatic lymph nodes (mLNs) were divided into three groups: A, those with calcification; B, those without calcification but belonging to patients who had calcified mLNs; C, those without calcification and belonging to patients who had no calcified mLNs. The incidences of (131)I accumulation and maximum standardised uptake values (SUV max) in the three groups were compared., Results: A total of 70 mLNs were evaluated. Twelve mLNs belonged to group A, 13 to group B and 45 to group C. The incidences of (131)I accumulation were significantly higher in groups A (100%) and B (100%) than in group C (11.1%) (p < 0.0001 for both). The SUVmax was significantly lower in groups A (4.1 +/- 1.9) and B (3.9 +/- 1.4) than in group C (7.1 +/- 4.4) (p = 0.01, p = 0.002, respectively)., Conclusions: Our results indicated that calcification in mLNs related to the ability of (131)I accumulation and less dedifferentiation.

Background: If the sentinel-lymph-node (SLN) concept is valid in cervical cancer, most patients could avoid pelvic lymphadenectomy when absence of metastasis is intraoperatively confirmed in the SLN. We assessed feasibility and accuracy of SLN detection using (99m)Tc phytate in patients with cervical cancer., Methods: Eighty-two women with stage Ia-IIb cervical cancer enrolled in this study. All underwent hysterectomy or trachelectomy with accompanying total pelvic lymphadenectomy. On the day before surgery, we injected fluid containing (99m)Tc-labeled phytate subepithelially into four cervical quadrants outside the tumor. Intraoperatively, SLNs were identified as radioactive "hot nodes" by gamma probe. Systematic bilateral pelvic lymphadenectomy was performed after the hot node sampling to evaluate the predictive ability of hot nodes., Results: A total of 157 lymph nodes were detected as SLNs in 72 of 82 patients. SLN detection rate was 88%. Detection rate was 95% for the subgroups of patients with stage Ia-Ib1 disease and smaller tumor size (

Objective: The aims of this retrospective study were to evaluate the incidence of residual lymph node (LN) metastases in high-risk papillary thyroid cancer (PTC) patients receiving adjuvant I-131 therapy, especially in those without I-131 accumulation, and to evaluate the clinical usefulness of F-18 FDG PET/CT to detect those lesions., Methods: The 37 PTC patients receiving adjuvant I-131 therapy were retrospectively evaluated. We examined the incidence of residual LN metastasis and compared the accumulation of F-18 FDG and I-131 in those lesions, and compared the serum thyroglobulin (Tg) levels between patients with and without residual LN metastases., Result: A total of 33 lesions were diagnosed as residual LN metastases in 9 patients. FDG accumulated in all of the lesions, but 19 lesions (57.6%) of them had no I-131 accumulation. The SUVmax was significantly higher in lesions without I-131 accumulation than in lesions with I-131 accumulation (6.6 +/- 2.8 vs. 4.2 +/- 1.8; P = 0.007). The serum Tg levels were significantly higher in patients with residual LN metastases than in patients without it (709.9 +/- 1470.8 vs. 25.6 +/- 37.1 ng/mL; P = 0.005). The incidence of residual LN metastasis was significantly higher in patients with a detectable serum Tg level than in patients without it (35.0% vs. 0%, P = 0.03)., Conclusion: These results indicate that the residual LN metastasis was relatively common in high-risk PTC patients receiving adjuvant I-131 therapy whose serum Tg levels remained detectable, and those lesions often had no I-131 accumulation. FDG-PET/CT would be recommended for PTC patients with detectable serum Tg levels to detect residual LN metastases.

This is to report arterial spin-labeling (ASL) regional cerebral blood flow (rCBF) mapping findings in a case of corticobasal degeneration (CBD). A 68-year-old man gradually developed limb-kinetic apraxia, myoclonus, and rigidity in the left hand and was diagnosed as having CBD. Magnetic resonance imaging and single photon emission computed tomography revealed atrophy and decreased blood flow, respectively, in the right hemisphere, findings that were compatible with CBD. In addition, ASL rCBF mapping demonstrated asymmetrical hypoperfusion areas in locations typical for CBD, proving its potential usefulness for routine clinical differential diagnosis.

Background: The 2-[18F]-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) has recently become an important non-invasive tool for the diagnosis and staging in several cancers. The standardized uptake value (SUV) of primary tumor has been reported to relate to cancer progression and prognosis, however, biological mechanism is still unclear., Method: Seventy-nine patients with non-small cell lung cancer (NSCLC) who had undergone preoperative FDG-PET and a surgical resection were enrolled in this study. NSCLC tissue samples prepared from the surgical specimens were subjected to an immunohistochemical analysis for the expression of Ki-67 and vascular endothelial growth factor (VEGF) proteins. The relationships between the expression status of these proteins and SUV(max) of primary tumors were evaluated., Result: Concerning the relationship with various clinicopathological findings, SUV(max) of primary tumors was associated with histology, tumor proliferation, pleural or vascular invasion, and pathological stage. A significant correlation was observed between the SUV(max) and either the Ki-67 or VEGF expression (P < 0.001, P = 0.006), respectively. Cases with both Ki-67-negative and VEGF-negative findings exhibited a significantly lower SUV(max) than those with single positive or double positive cases (P = 0.006, P < 0.001)., Conclusion: The SUV(max) was associated with the expression of Ki-67 and VEGF in NSCLC. These findings indicated that the SUV(max) of primary tumors might therefore reflect the biological malignant potential in NSCLC., (Copyright 2009 Wiley-Liss, Inc.)

Phospholipase C gamma isozymes (PLC gamma 1 and PLC gamma 2) have a crucial role in the regulation of a variety of cellular functions. Both enzymes have also been implicated in signaling events underlying aberrant cellular responses. Using N-ethyl-N-nitrosourea (ENU) mutagenesis, we have recently identified single point mutations in murine PLC gamma 2 that lead to spontaneous inflammation and autoimmunity. Here we describe further, mechanistic characterization of two gain-of-function mutations, D993G and Y495C, designated as ALI5 and ALI14. The residue Asp-993, mutated in ALI5, is a conserved residue in the catalytic domain of PLC enzymes. Analysis of PLC gamma 1 and PLC gamma 2 with point mutations of this residue showed that removal of the negative charge enhanced PLC activity in response to EGF stimulation or activation by Rac. Measurements of PLC activity in vitro and analysis of membrane binding have suggested that ALI5-type mutations facilitate membrane interactions without compromising substrate binding and hydrolysis. The residue mutated in ALI14 (Tyr-495) is within the spPH domain. Replacement of this residue had no effect on folding of the domain and enhanced Rac activation of PLC gamma 2 without increasing Rac binding. Importantly, the activation of the ALI14-PLC gamma 2 and corresponding PLC gamma 1 variants was enhanced in response to EGF stimulation and bypassed the requirement for phosphorylation of critical tyrosine residues. ALI5- and ALI14-type mutations affected basal activity only slightly; however, their combination resulted in a constitutively active PLC. Based on these data, we suggest that each mutation could compromise auto-inhibition in the inactive PLC, facilitating the activation process; in addition, ALI5-type mutations could enhance membrane interaction in the activated state.

A large cis-regulatory landscape is a common feature of vertebrate genomes, particularly at key developmental gene loci with finely tuned expression patterns. Existing genetic tools for surveying large genomic regions of interest spanning over hundreds of kilobases are limited. Here we propose a chromosomal engineering strategy exploiting the local hopping trait of the Sleeping Beauty transposon in the mouse genome. We generated embryonic stem cells with a targeted integration of the transposon vector, carrying an enhancer-detecting lacZ reporter and loxP cassette, into the developmentally critical Pax1 gene locus, followed by efficient local transpositions, nested deletion formation and derivation of embryos by tetraploid complementation. Comparative reporter expression analysis among different insertion/deletion embryos substantially facilitated long-range cis-regulatory element mapping in the genomic neighborhood and demonstrated the potential of the transposon-based approach as a versatile tool for exploration of defined genomic intervals of functional or clinical relevance, such as disease-associated microdeletions.

Objective: This study examined the influence of linearization correction (LC) on brain perfusion single-photon emission computed tomography (SPECT) for the diagnosis of Alzheimer's disease (AD)., Methods: The early onset group (<65 years old) consisted of 10 patients with AD, and the late onset group (>/=65 years old) of 13 patients with AD. Age-matched controls included seven younger and seven older normal volunteers. Tc-99m hexamethyl propyleneamine oxine (HMPAO) SPECT images were reconstructed with or without LC [LC (+) or LC (-)] and a statistical analysis was performed using a three-dimensional stereotactic surface projection (3D-SSP). In addition, a fully automatic diagnostic system was developed, which calculated the proportion of the number of abnormal pixels in the superior and inferior parietal lobule, as well as in the precuneus and posterior cingulate gyrus., Results: The areas under the receiver-operating characteristic curve (AUCs) of the early onset group for conventional axial SPECT images, SPECT + 3D-SSP images and the fully automatic diagnostic system were 0.71, 0.88, and 0.92 in LC (-) and 0.67, 0.85, and 0.91 in LC (+), respectively. The AUCs of the late onset group were 0.50, 0.61, and 0.79 in LC (-) and 0.49, 0.67, and 0.85 in LC (+), respectively., Conclusion: LC on Tc-99m HMPAO SPECT did not significantly influence the diagnostic performance for differentiating between AD and normal controls in either early or late onset AD. Further examination with individuals suffering from very mild dementia is, therefore, expected to elucidate the effect of LC on minimally hypoperfused areas.

A 65-year-old woman was referred to our hospital for investigation of increased opacity in the right lower lung field of the chest X-ray. Chest CT demonstrated a large tumor in the right thoracic cavity. A preoperative needle biopsy was performed. The microscopic appearance revealed many spindle cells. An immunohistochemical study was positive for CD34 and vimentin. Solitary fibrous tumor of the pleura was strongly suspected and the operation was performed. The tumor arose from the visceral pleura and was pedunculated. The resected specimen was positive for CD34 and vimentin. The tumor was diagnosed as solitary fibrous tumor of the pleura. Although this case was diagnosed 11 years after detection, the tumor was completely resected. Solitary fibrous tumors are usually cured with complete resection, but long-term clinical follow up is needed because of the possibility of recurrence and metastasis.

Many of inflammatory diseases, including inflammatory arthritis, are multifactorial bases. The Ali18 semidominant mutation induced by N-ethyl-N-nitrosourea in the C3HeB/FeJ (C3H) genome causes spontaneous inflammation of peripheral limbs and elevated immunoglobulin E (IgE) levels in mice. Although the Ali18 locus was mapped to a single locus on chromosome 4, the arthritic phenotype of Ali18/+ mice was completely suppressed in F1 hybrid genetic backgrounds. To determine the chromosomal locations of the modifier loci affecting the severity of arthritis, an autosomal genome scan of 22 affected Ali18/+ F2 mice was conducted using C57BL/6J as a partner strain. Interestingly, regions on chromosomes 1 and 3 in C3H showed significant genetic interactions. Moreover, 174 N2 (backcross to Ali18/Ali18) and 267 F2 animals were used for measurement of arthritis scores and plasma IgE levels, and also for genotyping with 153 genome-wide single nucleotide polymorphism (SNP) markers. In N2 populations, two significant trait loci for arthritis scores on chromosomes 1 and 15 were detected. Although no significant scores were detected in F2 mice besides chromosome 4, a suggestive score was detected on chromosome 3. In addition, a two-dimensional genome scan using F2 identified five suggestive scores of chromosomal combinations, chromosomes 1 x 10, 2 x 6, 3 x 4, 4 x 9, and 6 x 15. No significant trait loci affecting IgE levels were detected in both N2 and F2 populations. Identification of the Ali18 modifier genes by further detailed analyses such as congenic strains and expression profiling may dissect molecular complexity in inflammatory diseases.

Purpose: The aim of this study was to address the efficacy of 2-[F-18]-Fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) in the staging of non-small cell lung cancer (NSCLC) and in prognostic prediction in patients with NSCLC., Methods: Forty-four patients (26 males, 18 females) were analyzed., Results: Accurate staging was obtained by addition of FDG-PET. Multivariate analysis indicated that the standardized uptake value of the primary tumor was the most significant prognostic factor for disease-free survival (P=.0073)., Conclusion: FDG-PET is useful for the diagnosis of NSCLC and for prognostic prediction in patients with NSCLC.

Pulmonary tumor thrombotic microangiopathy (PTTM) is histopathologically characterized by proliferation of intimal myofibroblasts in the small pulmonary arterioles, induced by tumor microemboli. Patients develop rapidly progressive and severe cardiopulmonary failure, and the clinical course of this disease is fatal. Conventional radiologic findings are often minimal or nonspecific, making diagnosis difficult before death. We report 2-(F-18)-fluoro-2-deoxy-d-glucose positron emission tomography (FDG-PET) images of PTTM, which illustrate the characteristic findings of this clinical entity. FDG-PET can be helpful for the diagnosis of PTTM.

One of the upcoming next quests in the field of genetics might be molecular dissection of the genetic and environmental components of human complex diseases. In humans, however, there are certain experimental limitations for identification of a single component of the complex interactions by genetic analyses. Experimental animals offer simplified models for genetic and environmental interactions in human complex diseases. In particular, mice are the best mammalian models because of a long history and ample experience for genetic analyses. Forward genetics, which includes genetic screen and subsequent positional cloning of the causative genes, is a powerful strategy to dissect a complex phenomenon without preliminarily molecular knowledge of the process. In this review, first, we describe a general scheme of positional cloning in mice. Next, recent accomplishments on the patho-mechanisms of inflammatory arthritis by forward genetics approaches are introduced; Positional cloning effort for skg, Ali5, Ali18, cmo, and lupo mutants are provided as examples for the application to human complex diseases. As seen in the examples, the identification of genetic factors by positional cloning in the mouse have potential in solving molecular complexity of gene-environment interactions in human complex diseases.

TNF plays diverse and contrasting roles in cancer, promoting skin carcinogenesis and metastasis, but also possessing potent antitumor effects in mice. TNF via TNFR1 axis induces NFkappaB, and may contribute to inflammation-facilitated neoplasia. On the other hand, lymphomas are cited as rare complications of anti-TNF therapy in humans. In order to address possible modulating role of TNF and of a related cytokine, LTalpha, in spontaneous tumorigenesis, we compared mice with p53-TNF, p53-LTalpha, p53-TNFR1 and p53-TNF-LT combined deficiencies. Unexpectedly, neither of these mice showed significant modulation of their survival or shift in the spectrum of emerging tumors, as compared to p53-deficient mice, arguing against direct link between TNF blockade and lymphoma development.

Osteogenesis imperfecta is an inherited disorder characterized by increased bone fragility, fractures, and osteoporosis, and most cases are caused by mutations affecting the type I collagen genes. Here, we describe a new mouse model for Osteogenesis imperfecta termed Aga2 (abnormal gait 2) that was isolated from the Munich N-ethyl-N-nitrosourea mutagenesis program and exhibited phenotypic variability, including reduced bone mass, multiple fractures, and early lethality. The causal gene was mapped to Chromosome 11 by linkage analysis, and a C-terminal frameshift mutation was identified in the Col1a1 (procollagen type I, alpha 1) gene as the cause of the disorder. Aga2 heterozygous animals had markedly increased bone turnover and a disrupted native collagen network. Further studies showed that abnormal proalpha1(I) chains accumulated intracellularly in Aga2/+ dermal fibroblasts and were poorly secreted extracellularly. This was associated with the induction of an endoplasmic reticulum stress-specific unfolded protein response involving upregulation of BiP, Hsp47, and Gadd153 with caspases-12 and -3 activation and apoptosis of osteoblasts both in vitro and in vivo. These studies resulted in the identification of a new model for Osteogenesis imperfecta, and identified a role for intracellular modulation of the endoplasmic reticulum stress-associated unfolded protein response machinery toward osteoblast apoptosis during the pathogenesis of disease., Competing Interests: Competing interests. The authors have declared that no competing interests exist.

Objectives: To explore the cerebral hemodynamics in subclavian steal syndrome, we examined the cerebral perfusion of seven patients with subclavian steal (one symptomatic and six asymptomatic) using single-photon emission computed tomography (SPECT) during resting, arm exercise, and acetazolamide-activated conditions., Methods: The regional CBF (rCBF) was measured with SPECT under all conditions, and region of interest (ROI) analysis was performed using a three-dimensional stereotaxic ROI template (3DSRT). We evaluated the relationship between arm exercise-induced rCBF change and (1) presence of subclavian artery stenosis, (2) vertebral reverse flow severity, (3) presence of vertebro-basilar insufficiency (VBI) symptoms, and (4) cerebrovascular reactivity (CVR) to acetazolamide., Results: Overall, no arm exercise-induced rCBF reduction was observed on either the affected or the unaffected side, even in patients with severe vertebral reverse flow. One patient with VBI symptoms showed an arm exercise-induced global rCBF reduction in the cerebrum and cerebellum, whereas the other asymptomatic patients did not. The %rCBF changes in segments with severely impaired CVR (-8.6%+/-10.7%, mean+/-SD) were significantly lower than those in other segments with less impaired CVR (P<0.01)., Conclusions: Our results suggest that subclavian steal is a benign condition in asymptomatic patients. On the other hand, arm exercise-induced rCBF reduction can occur in the cerebrum and cerebellum in patients with VBI symptoms possibly related to low CVR.

Objective: To evaluate the efficacy of (123)I-IMP single photon emission computed tomography (SPECT) for the diagnosis of ocular malignant melanoma (MM)., Methods: Thirty-eight patients (18 males, 20 females) clinically suspected of having ocular MM were retrospectively examined in this study. The age of patients ranged from 8 to 81 years (mean 55.6 years). Twelve patients were finally diagnosed as having ocular MM. Orbital SPECT images were taken 15 min, 4 h, 24 h and 48 h after intravenous injection of 111-222 MBq (3-6 mCi) (123)I-IMP. (123)I-IMP uptake in the orbital tumor was visually evaluated as-(negative),+/-(equivocal), or+(positive). The uptake index (UI) and increase ratios (IRs) were calculated., Results: For visual evaluation, the accuracy of (123)I-IMP for the diagnosis of MM was 73.7% (15 min), 81.6% (4 h), 81.6% (24 h) and 86.8% (48 h). When UI and IR were calculated on both the MM and non-MM groups, the UI and IR of the MM group were significantly higher than those of the non-MM group (P<0.001). Moreover, the highest sensitivity (100%) and accuracy (94.7%) were obtained 48 h after (123)I-IMP administration when the cut-off value of UI was defined as 1.90., Conclusions: This study shows that (123)I-IMP SPECT is useful for the diagnosis of ocular MM. The UI values 48 h after the injection were efficient for the differentiation between MM and non-MM lesions.

We report a 33-year-old woman who had a 60-mm thoracic aneurysm of the ascending aorta with Marfan syndrome and effort angina due to compression of the right coronary artery (RCA) by the aneurysm. Surgery was performed using the Bentall procedure and a coronary artery bypass graft to the RCA. Postoperatively, coronary angiography showed that the coronary flow of the RCA was restored by removing the aneurysmal compression. The patient was discharged without angina on postoperative day 21.

The Notch signaling pathway is an evolutionarily conserved transduction pathway involved in embryonic patterning and regulation of cell fates during development. Recent studies have demonstrated that this pathway is integral to a complex system of interactions, which are also involved in distinct human diseases. Delta1 is one of the known ligands of the Notch receptors. Mice homozygous for a loss-of-function allele of the Delta1 gene Dll1(lacZ/lacZ) die during embryonic development. Here, we present the results of two phenotype-driven modifier screens. Heterozygous Dll1(lacZ) knockout animals were crossed with ENU-mutagenized mice and screened for dysmorphological, clinical chemical, and immunological variants that are dependent on the Delta1 loss-of-function allele. First, we show that mutagenized heterozygous Dll1(lacZ) offspring have reduced body weight and altered specific clinical chemical parameters, including changes in metabolites and electrolytes relevant for kidney function. In our mutagenesis screen we have successfully generated 35 new mutant lines. Of major interest are 7 mutant lines that exhibit a Dll1(lacZ/+)-dependent phenotype. These mutant mouse lines provide excellent in vivo tools for studying the role of Notch signaling in kidney and liver function, cholesterol and iron metabolism, cell-fate decisions, and during maturation of T cells in the immune system.

Objectives: The aim of this study was to evaluate the usefulness of (123)I-iomazenil (IMZ) single photon emission computed tomography (SPECT) for the pre-surgical identification of epileptogenic areas in patients with temporal lobe epilepsy and to compare the results with those of (123)I-IMP SPECT and (18)Fluorodeoxyglucose positron emission tomography (FDG PET)., Methods: We examined seven patients with medically refractory temporal lobe epilepsy (five men and two women; mean age, 28 years) with no remarkable findings on magnetic resonance imaging. Before surgery, IMZ SPECT, IMP SPECT and FDG PET were all performed in the interictal state. Then, visual assessment and region-of-interest (ROI) analysis were performed on each image. Final definitions of the epileptogenic areas were made by electrocorticography and histopathology., Results: By IMZ SPECT, a decreased IMZ uptake in the ipsilateral temporal lobe was found in all patients, while a similar decrease in the contralateral temporal lobe was also found in one patient. In comparison to IMP SPECT, the extent of the abnormal area on IMZ SPECT was equal to that on IMP SPECT in one patient while it was more restricted to the epileptogenic area in five patients. In comparison to FDG PET, the extent of the abnormal area on IMZ SPECT was equal to that on FDG PET in three patients while it was more restricted in the epileptogenic area in four patients. In ROI analysis, decreases of IMZ, IMP and FDG uptake were observed in the epileptogenic area, although they were not statistically significant., Conclusions: IMZ SPECT was considered to be useful for pre-surgical determination of the epileptogenic areas in temporal lobe epilepsy with no remarkable MRI findings, and it was also found to be superior to IMP SPECT and FDG PET for this purpose.

Inflammation is a complex cellular and humoral response against trauma and infection, and its presence leads to destruction of tissue in humans. The mechanisms that initiate inflammatory diseases remain largely unknown because of complex interactions between multiple genetic and environmental factors during pathogenesis. Animal models for human diseases offer dissection of complex pathogenesis by inbred genetic backgrounds and controlled circumstances. In this article we report a chemically induced new mutation, Ali18 (Abnormal limb), as a mouse model for inflammatory arthritis and dermatitis. Ali18/+ mice exhibit rubor and swelling of footpads in hindlimbs in adults. In Ali18/Ali18 mice, the digits in forelimbs and hindlimbs and tails were necrotic and/or deformed by severe swelling. Histologic analysis revealed infiltration of mixed populations of inflammatory cells into bone marrow, peripheral joints, and skin in the affected areas of Ali18/Ali18 mice. In addition, generalized osteoporosis-like phenotypes were confirmed by dual energy X-ray absorptiometry (DXA), microcomputed tomography (muCT), and peripheral quantitative computed tomography (pQCT) in homozygous animals. Whereas the Ali18 mutation was mapped to a single locus, the phenotype presentation was altered by complex modifier effects from other inbred genetic backgrounds. Detailed analysis of the Ali18 phenotype and identification of the mutation and its modifier genes may provide molecular insights into the complex nature of inflammatory diseases and the relationship between inflammation and bone metabolism.

Purpose: The purpose of this study was to evaluate the reliability of left ventricular ejection fraction (LVEF) measured by quantitative gated SPECT (QGS). We compared the efficacy of LVEF assessment among Tc-99m tetrofosmin gated SPECT imaging, contrast left ventriculography (LVG), and first-pass radionuclide angiography (FP)., Patients: One-hundred and seven patients with ischemic heart disease underwent QGS and LVG simultaneously within 3 months, and 92 of the 107 patients also underwent FP at the same time., Results: QGS progressively overestimated LVEF at the lower range of end-systolic volume (ESV), especially in patients with small hearts. Moreover, the QGS technique systemically tended to underestimate LVEF in comparison with LVG. However, linear regression analysis demonstrated a good correlation between the LVEF values measured by QGS and those measured by both LVG (p<0.0001) and FP (p<0.0001)., Conclusion: Although QGS has a tendency to overestimate LVEF in patients with small hearts, and to systemically underestimate LVEF compared with LVG, this technique is still a reliable clinical tool for measurement of LVEF.

Objective: Bone is one of the most common sites of metastasis in breast cancer patients. Although bone scintigraphy is widely used to detect metastatic breast cancer, the usefulness of 18FDG-PET for detecting bone metastasis has not been clearly evaluated. The purpose of this study was to compare the diagnostic accuracy of 18FDG-PET with bone scintigraphy in detecting bone metastasis in breast cancer patients., Methods: Forty-four women aged 35 to 81 years (mean, 56 years) with breast cancer were examined in this study. Both 18FDG-PET and bone scintigraphy were performed for each patient with 0-69 day intervals (mean, 11.5 days). The results of each image interpretation were compared retrospectively. Whole-body bones were classified into 9 anatomical regions. Metastases were confirmed at 45/187 regions in 14 patients by bone biopsy or clinical follow-up including other imaging techniques for a period of at least 6 months afterwards., Results: On a region basis, the sensitivity, specificity, and accuracy of 18FDG-PET were 84%, 99% and 95%, respectively. Although these results were comparable to those of bone scintigraphy, the combination of 18FDG-PET and bone scintigraphy improved the sensitivity (98%) and accuracy (97%) of detection. False negative lesions of bone scintigraphy were mostly bone marrow metastases and those of 18FDG-PET were mostly osteoblastic metastases. 18FDG-PET was superior to bone scintigraphy in the detection of osteolytic lesions (92% vs. 73%), but inferior in the detection of osteoblastic lesions (74% vs. 95%)., Conclusions: This study shows that 18FDG-PET tends to be superior to bone scintigraphy in the detection of osteolytic lesions, but inferior in the detection of osteoblastic lesions. 18FDG-PET should play a complementary role in detecting bone metastasis with bone scintigraphy.

1. In the [(13)C]-octanoic acid breath test, the time versus pulmonary [(13)CO(2)] excretion rate curve is analysed using mathematical curve-fitting techniques to calculate gastric emptying parameters. Thus, the goodness-of-fit highly influences the accuracy of the breath test. However, a double-peaked [(13)CO(2)] excretion curve, which occasionally develops owing to the presence of an interval of quiescent gastric emptying (the plateau phase), is likely to be fitted poorly. 2. In pharmacokinetics, the Wagner-Nelson method has been used to describe precisely the absorption kinetics of orally administered drugs and its reliability is independent of the nature of gastric emptying. A recent study has shown the potential of the Wagner-Nelson method to generate a realistic gastric emptying flow curve from [(13)CO(2)] excretion data. In the present report, we have demonstrated that the Wagner-Nelson method can visualize the plateau emptying phase responsible for the cases of double peaks. 3. Wagner-Nelson analysis applied to the breath test described precisely the characteristic emptying pattern of the two emptying phases being interrupted by the plateau phase. Conventional analysis for the breath test failed to detect the plateau phase. 4. The Wagner-Nelson method is a useful tool for analysing atypical double-peaking [(13)CO(2)] excretion curves.

Background: Cigarette smoking is associated with an increased risk of peptic ulcer and gastroesophageal reflux disease. Gastric emptying disorders may play a role in the development of these upper gastrointestinal diseases. Thus, studies examining a link between smoking and gastric emptying disorders have clinical relevance. This study was conducted to investigate the effect of smoking on gastric emptying of solids in Japanese smokers., Methods: The (13)C-octanoic acid breath test was performed in eight male habitual smokers on two randomized occasions (either sham smoking or actively smoking). The time vs (13)CO(2) excretion rate curve was mathematically fitted to a conventional formula of y (t) = m*k*beta*e(-k*t)*(1 - e(-k*t))(beta-1), and the parameters of k and beta were determined: under the crossover protocol, a larger (smaller) beta indicates slower (faster) emptying in the early phase, and a larger (smaller) k indicates faster (slower) emptying in the later phase. The half (13)CO(2) excretion time (t(1/2b) = -[ln(1 - 2(-1/beta))]/k) and the time of maximal (13)CO(2) excretion rate (t(max) = [lnbeta]/k) were also calculated. Between the two occasions, k, beta, t(1/2b), and t(max) were compared by the Wilcoxon signed-rank test., Results: After smoking, k was significantly increased. No significant differences were found in beta, t(1/2), and t(max) between the two occasions., Conclusions: The increase in k suggests the acceleration of gastric emptying in the later phase. For the first time, this study has revealed that acute smoking speeds the gastric emptying of solids in Japanese habitual smokers.

Objective: The aim of this study is to clarify the period of extraosseous accumulation of (99m)Tc-hydroxymethylenediphosphonate (HMDP) to radiation nephropathy mimicking recurrent or remnant neuroblastoma in the pararenal region., Methods: We reviewed five neuroblastoma and one ganglioneuroblastoma patients (2 boys and 4 girls aged 1-9 years) who underwent (99m)Tc-HMDP bone scintigraphies periodically before and after radiation therapy., Results: Increased renal uptake coincident with the radiation port appeared in 5 of 6 patients from 0 to 3 months (mean 1.7 months), and persisted up to 7 months after the completion of radiotherapy. Renal uptake of (99m)Tc-HMDP was gradually decreased, and eventually became accumulation defects in 5 of 6 patients from 6 to 17 months (mean 8.9 months) after radiotherapy., Conclusion: When extraosseous accumulation is found after radiation therapy in neuroblastoma patients, radiation nephropathy would be a candidate in the differential diagnosis besides recurrent or remnant tumor.

Background: We evaluated the quantitative accuracy of the post-injection transmission-based segmented attenuation correction (SAC) technique and transmissionless calculated attenuation correction (CAC) technique in both 2D and 3D scanning for the brain, and compared the results with those obtained using the pre-injection transmission-based measured attenuation correction (MAC) technique, which is generally accepted as the 'gold standard'., Methods: We examined [18F]fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) on both a cylindrical phantom and in 10 patients with epilepsy. The statistical analyses were performed using both the region of interest (ROI) method and statistical parametric mapping (SPM)., Results: In the ROI analysis, [18F] activity concentration values obtained by the SAC technique were well correlated with those obtained by the MAC technique (2D, R2=0.94; 3D, R2=0.98; P<0.001), although these values were underestimated over the entire brain. The CAC technique was also found to have significant correlation with the MAC technique (2D, R2=0.84; 3D, R2=0.86; P<0.001), but this technique showed apparent overestimation or underestimation in several parts of the brain. In the SPM analysis, there were no significant differences between the SAC and MAC technique, while those values obtained by the CAC technique were significantly lower in the parieto-occipital region and higher in the lower frontal region (P<0.001, uncorrected)., Conclusion: The SAC technique was superior to the CAC technique in both 2D and 3D scanning, although we found that both the SAC and CAC techniques had some problems in quantitative evaluation. We considered that the SAC technique may yield adequate qualitative measurements of the [18F] activity concentration value after global normalization.

Tumour necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is a member of the TNF superfamily, which is capable of inducing apoptosis in many cell types, including tumour and virus-infected cells, but rarely in normal cells. Expression of TRAIL mRNA and TRAIL receptors has previously been detected in neutrophils; however, the expression of TRAIL protein and the regulation of TRAIL and TRAIL receptor expression in these cells remain unknown. Here we report, for the first time, that neutrophils constitutively express TRAIL protein on their cell surface and that the TRAIL protein is shed during culture. TNF-alpha is a down-regulator of TRAIL expression, whereas IFN-gamma up-regulates the expression of TRAIL. Neutrophils did not express a detectable level of TRAIL-R1 or -R4, but constitutively expressed a low, but substantial, level of TRAIL-R2 and a high level of TRAIL-R3. Although the level of TRAIL-R2 was not significantly altered during culture under different experimental conditions, approximately 30% of TNF-alpha-treated cells rapidly lost their high-level TRAIL-R3 expression, whereas the majority of IFN-gamma-treated cells retained a high level of TRAIL-R3 expression. Anti-TRAIL neutralizing antibody significantly inhibited neutrophil apoptosis during cultures in medium alone, or in the presence of TNF-alpha or IFN-gamma. Thus, our study identified human neutrophils as a cellular source of TRAIL and suggests that neutrophil-derived TRAIL may play a role in immune surveillance. Our results also suggest a role for the TRAIL/TRAIL receptor system in neutrophil apoptosis.

The purpose of this study was to clarify the normal gastric FDG uptake pattern to provide basic information to make an accurate diagnosis of gastric lesions by FDG PET. We examined 22 cases, including 9 of malignant lymphoma, 8 of lung cancer, 2 of esophageal cancer, and 3 of other malignancies. No gastric lesions were observed in any of the 22 cases on upper gastrointestinal examinations using either barium meal or endoscopic techniques. The intervals between FDG PET and the gastrointestinal examination were within one week in all cases. The stomach regions were classified into the following three areas: U (upper)-area, M (middle)-area, and L (lower)-area. The degree of FDG uptake in these three gastric regions was qualitatively evaluated by visual grading into 4 degrees, and then a semiquantitative evaluation was carried out using the standardized uptake value (SUV). Based on a visual grading evaluation, the mean FDG uptake score in the U-, M-, and L-areas was 1.14 +/- 0.96, 0.82 +/- 0.96, and 0.36 +/- 0.49 (mean +/- S.D.), respectively. The FDG uptake scores obtained in the three areas were significantly different (Friedman test, p < 0.05). Furthermore, the rank order of the FDG uptake score in each case (U > or = M > or = L) was found to be statistically significant (Cochran-Armitage trend test, p < 0.05). The mean SUVs of 11 cases in the three areas were 2.38 +/- 1.03, 1.91 +/- 0.71, and 1.34 +/- 0.44 (mean +/- S.D.), respectively. The SUV in the U-area was significantly higher than that in the L-area (Friedman test, p < 0.05). A significant difference in FDG uptake was observed among the three gastric areas, and the FDG uptake extent in all cases was U > M > L. In conclusion, the physiological gastric FDG uptake was significantly higher at the oral end. A stronger gastric FDG uptake at the anal end may therefore be suggestive of a pathological uptake.

Amiodarone is an amphiphilic, iodinated, benzofuran derivative that is known to be effective for refractory ventricular tachyarrhythmia. Amiodarone also is known to cause a variety of side effects, related to its accumulation in multiple organs. The deposition of amiodarone and its metabolite, desethylamiodarone (DA), in liver elevates liver function tests and increases liver attenuation on computed tomography (CT). Although several groups have reported increased liver attenuation in patients receiving chronic amiodarone therapy, there is still no clear statistically significant relationship between liver CT attenuation and the cumulative dose of amiodarone, or between plasma levels of amiodarone and DA. CT scans were originally performed for the evaluation of pulmonary fibrosis in 13 patients (7 men and 6 women; mean age, 69.9 years, range 35 to 86 years) receiving chronic amiodarone therapy. Liver CT attenuation tended to increase in these patients. We found no significant correlation between liver CT attenuation and the cumulative dose of amiodarone. However, the CT attenuation of the liver was correlated significantly with the plasma level of amiodarone and DA. It was also suggested that liver CT scan is a useful means of evaluating the plasma levels of amiodarone and DA, and for estimating their deposition in liver.

TNF/LTalpha/LTbeta (tumor necrosis factor/lymphotoxin-alpha/lymphotoxin-beta) triple knockout (KO) mice show a significant reduction of dendritic cell (DC) number in the spleen, presumably due to defective recruitment and/or production. To distinguish between these possibilities, DCs were generated from bone marrow (BM) cultures prepared from wild-type (wt) and mutant mice in the presence of granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-4 (IL-4). The yield of CD11c(+) major histocompatibility complex (MHC) class II(+) DCs generated from TNF/LTalpha/LTbeta(-/-) BM culture was significantly reduced compared with wt BM culture. In order to further dissect the individual pathways responsible for defective DC properties observed in TNF/LTalpha/LTbeta(-/-) mice, the panel of TNF/LT ligand and receptor single KO mice were used. The production of DCs from BM culture was significantly reduced in TNF(-/-) and TNF receptor (TNFR) p55(-/-) mice, but normal in LTalpha(-/-), LTbeta(-/-), LTbetaR(-/-) mice. Recombinant TNF (rTNF) exogenously added to TNF/LTalpha/LTbeta(-/-) BM cultures could reverse this defect, and blocking antibodies showed partial effect on BM cultures of wt mice. Conversely, numbers of mature DCs in spleen were significantly decreased in LTalpha(-/-), LTbeta(-/-), LTbetaR(-/-) mice, but not in TNF(-/-) and TNFRp55(-/-) mice. These results reveal 2 distinct contributions of TNF/LT cytokines. First, TNF acting through TNF receptor is involved in the development/maturation of DCs in BM progenitor cultures, but this function appears to be redundant in vivo. Second, the microenvironment in peripheral lymphoid organs associated with LTalpha/LTbeta-LTbetaR signaling and chemokine production is critical for recruitment efficiency of DCs, and this pathway is indispensable.

In order to definitively ascertain the functional contribution of lymphotoxin (LT) expressed by B cells, we produced mice with the LTbeta gene deleted from B cells (B-LTbeta KO mice). In contrast to systemic LTbeta deletion, in B-LTbeta KO mice only splenic microarchitecture was affected, while lymph nodes and Peyer's patches (PP) were normal, except for PP's reduced size. Even though B-LTbeta KO spleens retained a small number of follicular dendritic cells (FDC) which appeared to be dependent on LTbeta produced by T cells, IgG responses to sheep red blood cells were markedly reduced. Thus, the organogenic function of B-LTbeta is almost entirely restricted to spleen, where it supports the correct lymphoid architecture that is critical for an effective humoral immune response.

The gene expression patterns of primordial germ cells (PGCs) and embryonic stem cells were analyzed by a modified serial analysis of gene expression. During the process, we cloned a novel gene, PGC7, which was preferentially expressed in PGCs. Immunohistochemical analysis revealed that PGC7 was specifically expressed in early pre-implantation embryos, PGCs and oocytes. These results suggest that PGC7 might play an important role in the development of PGCs and oocytes.