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Pulmonary alveolar proteinosis (PAP) is a rare disease, which is characterized by the alveolar accumulation of surfactant. A crazy-paving appearance on chest thin-section computed tomography (TSCT) is a characteristic feature of this disease. We report an unusual case of PAP, which presented as multiple localized ground glass opacites (GGOs) on TSCT in an 80-year-old female. As one of these lesions at the apex of the right lung increased in size, it was suspected to be a pulmonary adenocarcinoma. However, the others became smaller during the follow-up period. Right upper lobectomy was performed, and PAP was histologically diagnosed. In cases exhibiting multiple localized GGOs, PAP should be considered, even if GGOs with a crazy-paving-like appearance are distributed in a lobular rather than diffuse manner., (© 2024 The Authors. Published by Elsevier Inc. on behalf of University of Washington.)

Objective: The objective of this study was to determine the long-term outcomes of microendoscopic foraminotomy in treating lumbar foraminal stenosis and identify the optimal extent of decompression that yields improved results and fewer complications., Methods: A retrospective cohort study reviewed the medical records of 95 consecutive patients who underwent microendoscopic foraminotomy for lumbar foraminal stenosis. Clinical outcomes were assessed using the Japanese Orthopaedic Association scoring system and visual analog scale for low back and leg pain. Surgical success was determined by meeting significant improvement thresholds for back and leg pain at 2 years postoperatively. Multiple regression analysis identified factors associated with improved pain scores. Receiver operating characteristic curve analysis determined the cut-off values for successful surgeries., Results: Significant improvements were observed in Japanese Orthopaedic Association and visual analog scale scores for back and leg pain 2 years postoperatively compared with preoperative scores (P < 0.0001) and sustained over a ≥5-year follow-up period. Reoperation rates were low and did not significantly increase over time. Multiple regression analysis identified occupancy of the vertebral osteophytes and bulging intervertebral discs (O/D complex) as surgical success predictors. A 45.0% O/D complex occupancy cutoff value was determined, displaying high sensitivity and specificity for predicting surgical success., Conclusions: This study provides evidence supporting the long-term efficacy of microendoscopic foraminotomy for lumbar foraminal stenosis and predicting surgical success. The 45.0% O/D complex occupancy cut-off value can guide patient selection and outcome prediction. These insights contribute to informed surgical decision-making and underscore the importance of evaluating the O/D complex in preoperative planning and predicting outcomes., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: The monogenean parasite Heterobothrium okamotoi only parasitizes the gills of Takifugu rubripes. In this study, we hypothesized that the carbohydrates contribute to high host specificity of H. okamotoi., Methods: T. rubripes, T. niphobles, T. snyderi, and T. pardalis were used for UEA I staining of the gills and an in vivo challenge test against H. okamotoi. To examine the effect of l-fucose, an in vitro detachment test was conducted using the host's gills. Additionally, fucosylated proteins were isolated from the membrane proteins of T. niphobles gills., Results: The location of l-fucoside and the infection dynamics in four species were correlated to some extent; H. okamotoi detached relatively quickly from T. niphobles possessing l-fucoside both on the surface of the gills and in certain types of cells, including mucus cells, but detached slowly from T. snyderi possessing l-fucoside in only certain types of cells, including mucus cells. Under the conditions examined, H. okamotoi exhibited minimal detachment from T. rubripes and T. pardalis, and l-fucoside was not detected. The significantly higher detachment rate of H. okamotoi from the host's gills incubated in l-fucose-containing medium compared with the controls suggests that l-fucose in the non-host gills induced detachment of H. okamotoi. Four fucosylated proteins, including mucin5AC-like, were identified as potential factors for the detachment of H. okamotoi., Conclusions: Fucosylated proteins covering the surface of non-host gills might contribute to H. okamotoi detachment., General Significance: This research shows the possible involvement of oligosaccharides in the host specificity of monogenean parasites., Competing Interests: Declaration of Competing Interest The author declares no competing interests., (Copyright © 2023. Published by Elsevier B.V.)

Background: Increased signal intensity (ISI) is usually recognized at the disc level of the responsible lesion in the patients with cervical myelopathy. However, it is occasionally seen at the vertebral body level, below the level of compression. We aimed to investigate the clinical significance and the radiographic characteristics of ISI at the vertebral body level., Methods: This retrospective study included 135 patients with cervical spondylotic myelopathy who underwent surgery and with local ISI. We measured the local and C2-7 angle at flexion, neutral, and extension. We also evaluated the local range of motion (ROM) and C2-7 ROM. The patients were classified into group D (ISI at disc level) and group B (ISI at vertebral body level)., Results: The prevalence was 80.7% (109/135) and 19.3% (26/135) for groups D and B, respectively. Local angle at flexion and neutral were more kyphotic in group B than in group D. The local ROM was larger in group B than in group D. Moreover, C2-7 angle at flexion, neutral and extension were more kyphotic in group B than in group D. Two years later, local angle at flexion, neutral, and extension were also kyphotic in group B than group D; however, local and C2-7 ROM was not significantly different between the two groups. There was no significant difference of clinical outcomes 2 years postoperatively between both groups., Conclusions: Group B was associated with the kyphotic alignment and local greater ROM, compared to group D. As the spinal cord is withdrawn in flexion, the ISI lesion at vertebral body might be displaced towards the disc level, which impacted by the anterior components of the vertebrae. ISI at the vertebral body level might be related to cord compression or stretching at flexion position. This should be different from the conventionally held pincer-mechanism concept., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Introduction/background: To evaluate cases of surgically resected pulmonary adenocarcinoma (Ad) with heterogenous ground-glass nodules (HGGNs) or part-solid nodules (PSNs) and to clarify the differences between them, and between invasive adenocarcinoma (IVA) and minimally invasive adenocarcinoma (MIA) + adenocarcinoma in situ (AIS) using grayscale histogram analysis of thin-section computed tomography (TSCT)., Materials and Methods: 241 patients with pulmonary Ad were retrospectively classified into HGGNs and PSNs on TSCT by three thoracic radiologists. Sixty HGGNs were classified into 17 IVAs, 26 MIAs, and 17 AISs. 181 PSNs were classified into 114 IVAs, 55 MIAs, and 12 AISs., Results: We found significant differences in area (P = 0.0024), relative size of solid component (P <0.0001), circumference (P <0.0001), mean CT value (P <0.0001), standard deviation of the CT value (P <0.0001), maximum CT value (P <0.0001), skewness (P <0.0001), kurtosis (P <0.0001), and entropy (P <0.0001) between HGGNs and PSNs. In HGGNs, we found significant differences in relative size of solid component (P <0.0001), mean CT value (P = 0.0005), standard deviation of CT value (P = 0.0071), maximum CT value (P = 0.0237), and skewness (P = 0.0027) between IVAs and MIA+AIS lesions. In PSNs, we found significant differences in area (P = 0.0029), relative size of solid component (P = 0.0003), circumference (P = 0.0004), mean CT value (P = 0.0011), skewness (P = 0.0009), and entropy (P = 0.0002) between IVAs and the MIA+AIS lesions., Conclusion: Quantitative evaluations using grayscale histogram analysis can clearly distinguish between HGGNs and PSNs, and may be useful for estimating the pathology of such lesions., Competing Interests: Disclosure The authors have stated that they have no conflicts of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Concomitant surgical ablation for atrial fibrillation (AF) at the time of mitral valve surgery is a Society of Thoracic Surgeons Class IA recommendation with evidence from randomized trial data. We hypothesized that concomitant AF ablation rates have increased over time with implementation of this evidence-based practice., Methods: All patients (N = 7261) undergoing mitral valve operations (2011-2018) were queried from a regional Society of Thoracic Surgeons database. Patients with preoperative AF were stratified by concomitant AF ablation. Trends in concomitant ablation were evaluated over time as well as by center and surgeon mitral surgical volume. The associations between patient and center factors on implementation of concomitant ablation were assessed with multivariate regression., Results: A total of 1675 patients with preoperative AF underwent isolated mitral valve operations, with 1044 (64.6%) undergoing concomitant ablation. The utilization of concomitant ablation decreased over the study period (-2.82%/year), and was strongly associated with surgeon mitral valve volume (high 78.2% vs medium 62.5% vs low 59.0%; P < .001). Multivariate regression demonstrated age and comorbidities were strong predictors, but high volume mitral surgeons (odds ratio [OR], 2.2; P < .001) were twice as likely to perform concomitant AF ablation. Finally, patients with preoperative AF undergoing ablation were significantly less likely to be in AF at discharge (10.1% vs 53.8%; P < .001)., Conclusions: Despite increasing evidence and societal recommendations, we demonstrate a persistent underutilization of concomitant AF ablation during isolated mitral surgery across a large number of low-volume and high-volume centers. These data suggest significant variability and may represent an opportunity for improvement., (Copyright © 2021 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Objective: Osteoporotic vertebral body fractures (OVFs) represent a significant medical and socioeconomic burden. There is ongoing debate concerning the role of cement augmentation versus conservative management, but we are increasingly recognizing the longer-term effects of kyphotic vertebral alignment on functional outcomes, pain, and subsequent fracture rates. The purpose of this study was to determine the effect of timing of intervention with percutaneous balloon kyphoplasty (BKP) for OVF on clinical and radiographic outcomes., Patients and Methods: 51 patients (mean age, 75.5 years) who underwent BKP for OVF were analyzed. Patients were divided into two groups based on timing of BKP: early (<4 weeks) or late (>4 weeks). Multiple factors were assessed preoperatively and throughout follow up and compared between groups using bivariate testing, including: focal kyphosis, subsequent vertebral fracture, and low back pain., Results: This was a retrospective sub-group analysis. There were 32 patients in the early group and 19 patients in the late group. There was no significant difference in preoperative bone density between groups. Mean follow-up was 1.2 years. Local kyphosis at final follow-up was significantly greater in the late group (-28.4°) than in the early group (-9.5°; p < 0.001). There was no significant difference in local kyphosis between preoperative measurement and final follow-up in the early (p = 0.741) or late cohort (p = 0.794). Patients treated with early BKP demonstrated significantly better LBP scores (p < 0.05) and a lower rate of subsequent vertebral fracture (p < 0.05)., Conclusion: BKP is able to prevent progressive collapse and kyphosis after OVF, but not effectively restore alignment, and as a result, patients who undergo early BKP (<4 weeks) demonstrate better alignment, better LBP scores, and reduced rates of subsequent fracture at an average of 1.2 years following treatment., (Copyright © 2018 Elsevier B.V. All rights reserved.)

There is ongoing controversy regarding the most appropriate surgical treatment for lumbar spinal stenosis (LSS) with concurrent degenerative lumbar scoliosis (DLS): decompression alone, decompression with limited spinal fusion, or long spinal fusion for deformity correction. The coexistence of degenerative stenosis and deformity is a common scenario; Nonetheless, selecting the appropriate surgical intervention requires thorough understanding of the patients clinical symptomatology as well as radiographic parameters. Minimally invasive (MIS) decompression surgery was performed for LSS patients with DLS. The aims of this study were (1) to investigate the clinical outcomes of MIS decompression surgery in LSS patients with DLS, and (2) to identify the predictive factors for both radiographic and clinical outcomes after MIS surgery. 438 consecutive patients were enrolled in this study. Inclusion criteria was evidence of LSS and DLS with coronal curvature measuring greater than 10°. The Japanese Orthopaedic Association (JOA) score, JOA recovery rate, low back pain (LBP), and radiographic features were evaluated preoperatively and at over 2 years postoperatively. Of the 438 patients, 122 were included in final analysis, with a mean follow-up of 2.4 years. The JOA recovery rate was 47.6%. LBP was significantly improved at final follow-up. Cobb angle was maintained for 2 years postoperatively (p = 0.159). Clinical outcomes in foraminal stenosis patients were significantly related to sex, preoperative high Cobb angle and progression of scoliosis (p = 0.008). In the severe scoliosis patients, the JOA recovery was 44%, and was significantly depended on progression of scoliosis (Cobb angle: preoperation 29.6°, 2-years follow-up 36.9°) and mismatch between the pelvic incidence (PI) and the lumbar lordosis (LL) (preoperative PI-LL 35.5 ± 21.2°) (p = 0.028). This study investigated clinical outcomes of MIS decompression surgery in LSS patients with DLS. The predictive risk factors of clinical outcomes were severe scoliosis, foramina stenosis, progressive scoliosis and large mismatch of PI-LL., (Copyright © 2016 The Japanese Orthopaedic Association. All rights reserved.)

Carboxypeptidase cleaves the C-terminal amino acid residue from proteins and peptides. Here, we report the functional and structural characterizations of carboxypeptidase belonging to the M32 family from the thermophilic bacterium Thermus thermophilus HB8 (TthCP). TthCP exhibits a relatively broad specificity for both hydrophilic (neutral and basic) and hydrophobic (aliphatic and aromatic) residues at the C-terminus and shows optimal activity in the temperature range of 75-80 °C and in the pH range of 6.8-7.2. Enzyme activity was significantly enhanced by cobalt or cadmium and was moderately inhibited by Tris at 25 °C. We also determined the crystal structure of TthCP at 2.6 Å resolution. Two dimer types of TthCP are present in the crystal. One type consists of two subunits in different states, open and closed, with a C α RMSD value of 2.2 Å; the other type consists of two subunits in the same open state. This structure enables us to compare the open and closed states of an M32 carboxypeptidase. The TthCP subunit can be divided into two domains, L and S, which are separated by a substrate-binding groove. The L and S domains in the open state are almost identical to those in the closed state, with C α RMSD values of 0.84 and 0.53 Å, respectively, suggesting that the transition between the open and closed states proceeds with a large hinge-bending motion. The superimposition between the closed states of TthCP and BsuCP, another M32 family member, revealed that most putative substrate-binding residues in the grooves are oriented in the same direction., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: The present study compared the changes in biomechanical and radiographic properties under cyclic axial loadings between the 'double-tiered subchondral support' (DSS) group (wherein two rows of screws were used) and the 'non-DSS' (NDSS) group (wherein only one row of distal screws was used) using cadaveric forearm models of radius fractures fixed with a polyaxial locking plate., Material and Methods: Fifteen fresh cadaveric forearms were surgically operated to generate an Arbeitsgemeinschaft für Osteosynthesefragen (AO) type 23-C2 fracture model with the fixation of polyaxial volar locking plates. The model specimens were randomized into two groups: DSS (n = 7) and NDSS (n = 8). Both the groups received 4 locking screws in the most distal row, as is usually applied, whereas the DSS group received 2 additional screws in the second row inserted at an inclination of about 15° to support the dorsal aspect of the dorsal subchondral bone. Cyclic axial compression test was performed (3000 cycles; 0-250 N; 60 mm/min) to measure absolute rigidity and displacement, after 1, 1000, 2000 and 3000 cycles, and values were normalized relative to cycle 1. These absolute and normalized values were compared between those two groups. Radiographic images were taken before and after the cyclic loading to measure changes in volar tilt (ΔVT) and radial inclination (ΔRI)., Results: The DSS group maintained significantly higher rigidity and lower displacement values than the NDSS group during the entire loading period. Radiographic analysis indicated that the ΔVT values of the DSS group were lower than those of the NDSS group. In contrast, the fixation design did not influence the impact of loading on the ΔRI values., Conclusions: Biomechanical and radiographic analyses demonstrated that two rows of distal locking screws in the DSS procedure conferred higher stability than one row of distal locking screws., (Copyright © 2016 The Japanese Orthopaedic Association. Published by Elsevier B.V. All rights reserved.)

Background: Not all lumbar intra- and/or extra-foraminal stenosis (LIEFS) on MRI is symptomatic. Therefore, the establishment of clinical diagnostic tools that can identify patients with symptomatic LIEFS is crucial in the clinical setting. The aim of this study was to develop a support tool for clinical diagnosis of LIEFS., Methods: Patients with L5 radiculopathy alone were prospectively enrolled. Fifty-one patients with lumbar spinal canal stenosis only at the L4-5 level and 49 patients with LIEFS only at the L5-S1 level were extracted from this cohort. We compared the two groups with regard to 12 variables--three subjective and three objective items from the Japanese Orthopaedic Association (JOA) score; Kemp's sign; results of the lumbar flexion test, Bonnet test, and Freiberg test; pain on sitting; and pain when recumbent--to determine which factors were associated with a high index of clinical suspicion of LIEFS., Results: The significant predictors of a final diagnosis of LIEFS were identified as follows: pain when recumbent, Freiberg and Bonnet test results, and pain on sitting. To develop a diagnostic tool, a scoring system (0-20 points) was formulated on the basis of the contribution ratios of these risk factors. To determine the contribution ratio, an integer score was assigned to the identified risk factors as follows: pain when recumbent = 9 points, Freiberg = 5 points, Bonnet = 3 points, and pain on sitting = 3 points. The Hosmer-Lemeshow statistic for this scoring system was p = 0.063, and confirmed that it was a good model. Receiver operating characteristic (ROC) curve analysis demonstrated a cut-off value of 5 points, an area under the ROC curve of 0.87435, sensitivity of 75.5 %, and specificity of 82.3 %., Conclusions: We believe that the use of this tool in the clinical setting will improve the accuracy of diagnosing symptomatic LIEFS, which will lead to improved quality of patient care.

Objectives: The risk of postoperative neurological impairment mandates the use of intraoperative spinal cord monitoring (IOM) during intramedullary spinal cord tumor (IMSCT) surgery. We have used spinal cord evoked potential after electrical stimulation of the cord(Sp-SCEP) to monitor the sensory tract, and SCEP after electrical stimulation to the brain (Br-SCEP) to monitor the motor tract. Both Sp-SCEP and Br-SCEP are stable under general anesthesia. We assessed the clinical utility of these multimodal spinal cord monitoring methods in a retrospective study of a cohort of patients undergoing IMSCT surgery., Methods: Thirteen patients with IMSCTs underwent tumor resection using Sp-SCEP and/or Br-SCEP., Results: Four patients underwent surgery using only Sp-SCEP monitoring, resulting in two false negatives. Nine patients underwent surgery monitored by Br-SCEP and Sp-SCEP. In three of the nine cases, Br-SCEP amplitude fell by 50% from control levels, despite there being no change in Sp-SCEP. In one of the nine cases, Sp-SCEP amplitude fell to 50% of control levels, but Br-SCEP amplitude was stable., Conclusions: During IMSCT surgery, localized regions of the cord may be damaged. Multimodal monitoring should be used to monitor.Combining Sp-SCEP and Br-SCEP is a useful means of monitoring the sensory and motor tracts.

Background: The purposes of this study were to assess the reliability of 3-dimensional magnetic resonance (MR) imaging (3D MRI) and conventional MRI (CMRI) for detection of lumbar intra and/or extra-foraminal stenosis (LIEFS) and to compare the diagnostic accuracy of the 2 imaging modalities., Methods: A total of 60 sets of 3D MR and CMR images from 20 healthy volunteers and 40 LIEFS patients were qualitatively rated according to defined criteria by 3 independent, blinded readers. Kappa statistics were used to characterize intra and inter-reader reliability for qualitative rating of data. Multireader, multicase analysis was used to compare lumbar foraminal stenosis detection between the 2 modalities., Results: Intra-reader agreement for 3D MRI was excellent, with kappa = 0.90; that for CMRI was good, with kappa = 0.78. Average inter-reader agreement for 3D MRI was good, with kappa = 0.79, whereas that for CMRI was moderate, with kappa = 0.41. Average area under the ROC curve values (1st reading/2nd reading) for detection of lumbar foraminal stenosis using 3D MRI and CMRI were 0.99/0.99 and 0.94/0.92, respectively. Detection of LIEFS with 3D MRI was significantly better than with CMRI (P = 0.0408/0.0294)., Conclusions: These results suggest that CMRI was of limited use for detection of the presence of LIEFS. Isolated imaging with CMRI may risk overlooking the presence of LIEFS. In contrast, reliability of 3D MRI for detection of LIEFS was good. Furthermore, readers' performance in the diagnosis of LIEFS can be improved by use of 3D MRI. Therefore, 3D MRI is recommended when using imaging for diagnosis of LIEFS.

We herein report an unusual case of invasive thymoma with venous intraluminal extension. The thymoma extended into the superior vena cava, the left brachiocephalic vein, and the proximal portion of the left jugular and subclavian veins intraluminally. It was suggested that the tumor had a discrete intravascular growth via the thymic vein into the left brachiocephalic vein and extended into the proximal portion of the left jugular and subclavian veins in the opposite direction of the venous stream., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Background: Little information is available on the prevalence, incidence, and risk factors associated with curve progression in de-novo degenerative lumbar scoliosis (DNDLS) in the general population. Development of treatment guidelines requires further knowledge about the etiology and natural history of DNDLS in the elderly., Methods: To identify the cumulative incidence and radiographic features of DNDLS in the elderly, the authors reanalyzed the results of lumbar radiographic examinations from the Miyama study, which was originally conducted in a Japanese rural community to determine the prevalence of vertebral fractures in Japanese people. DNDLS was defined as a coronal curvature greater than 10° in the Cobb angle in the second survey and progression of greater than 5° compared with curve magnitude in the initial survey. The radiological features of the new curves were documented. The DNDLS group was recruited to compare the risk of curve progression with that in a control group of participants who had no scoliosis during a 15-year follow-up. Ten radiographic features were measured for statistical analysis to determine the prognostic factors of curve progression., Results: The cumulative incidence of DNDLS was 33/194 (17.0%) in this cohort. There was a tendency for female predominance and frequency increased with age. However, the severity of these curves was relatively low and no curves developed a Cobb angle of greater than 30°, with most in the range 10°-20°. The 2 groups differed significantly in lateral spondylolisthesis and vertebral rotation only at the L3 level., Conclusions: The radiographic features of DNDLS revealed mild scoliosis with minimal rotatory deformity. Spinal decompensation by the upper lumbar segments of the asymmetric anatomical deformity in the lower lumbar segments may induce de-novo lumbar scoliosis. Rotatory deformity and lateral spondylolisthesis of the L3 vertebra may be a prognostic factor for DNDLS in the elderly.

Plasma adiponectin levels are reduced in obese people, and hypoadiponectinemia is recently reported to associate with cholesterol gallstone formation in human. The aim of this study was to examine the role of adiponectin in gallstone formation using adiponectin knockout mice. We analyzed male knockout and C57BL6J mice fed normal or lithogenic diet for 6 weeks. On lithogenic diet, the prevalence rate of gallstone was significantly greater in knockout mice than C57BL6J mice. The molar percentages of beta and omega-muricholic acid were significantly higher and hepatic sterol 12 alpha-hydroxylase expression (cyp8b1) was significantly lower in knockout mice than C57BL6J mice fed normal diet. The bile apolipoprotein A-I protein levels were decreased in knockout mice. Histological examination showed gallbladder wall thickening and accumulation of glycoprotein in the gallbladder of knockout mice. Gallbladder phospholipase A2-IVA expression was significantly higher in knockout mice than in C57BL6J mice fed lithogenic diet. Our results indicate that lack of adiponectin promotes gallstone formation in mice., (Copyright 2010 Elsevier Inc. All rights reserved.)

Although the physiological roles of the cellular prion protein (PrP C) remain to be fully elucidated, PrP C has been proposed to represent a potential regulator of cellular immunity. To test this hypothesis, we evaluated the consequences of PrP C deficiency on the course of experimental autoimmune encephalomyelitis induced by immunization with myelin oligodendrocyte glycoprotein peptide. Consistent with augmented proliferative responses and increased cytokine gene expression by myelin oligodendrocyte glycoprotein-primed Prnp-/- T cells, PrP C-deficient mice demonstrated more aggressive disease onset and a lack of clinical improvement during the chronic phase of experimental autoimmune encephalomyelitis. Acutely, Prnp-/- spinal cord, cerebellum, and forebrain exhibited higher levels of leukocytic infiltrates and pro-inflammatory cytokine gene expression, as well as increased spinal cord myelin basic protein and axonal loss. During the chronic phase, a remarkable persistence of leukocytic infiltrates was present in the forebrain and cerebellum, accompanied by an increase in interferon-gamma and interleukin-17 transcripts. Attenuation of T cell-dependent neuroinflammation thus represents a potential novel function of PrP C.

The Pten tumor suppressor gene is critical for normal intrathymic development of T cells; however, its role in mature antigen-activated T cells is less well defined. A genetically crossed mouse line, Pten(fl/fl) GBC, in which Pten gene deletions could be primarily confined to antigen-activated CD8+ T cells, enabled us to evaluate the consequences of Pten loss on the course of experimental autoimmune encephalomyelitis. Compared with Pten(fl/fl) controls, myelin oligodendrocyte glycoprotein (MOG) peptide-immunized Pten(fl/fl) GBC mice developed more severe and protracted disease. This was accompanied by increased spinal cord white matter myelin basic protein depletion and axonal damage, as well as a striking persistence of macrophage and granzyme B-expressing cellular neuroinfiltrates in the chronic phase of the disease. This persistence may be explained by the observation that anti-CD3 activated Pten(fl/fl) GBC T cells were more resistant to proapoptotic stimuli. Consistent with the predicted consequences of Pten loss, purified CD8+ T cells from Pten(fl/fl) GBC mice displayed augmented proliferative responses to anti-T-cell receptor stimulation, and MOG-primed Pten(fl/fl) GBC T cells exhibited a reduced activation threshold to MOG peptide. Pten(fl/fl) GBC mice also developed atypical central nervous system disease, manifested by prominent cervical cord and forebrain involvement. Collectively, our findings indicate that the phosphatidylinositol 3-kinase signaling pathway is an essential regulator of CD8+ T-cell effector function in experimental autoimmune encephalomyelitis.

In earlier work, we identified a novel mannose-specific lectin, termed pufflectin-s, from the skin mucus of torafugu, Takifugu rubripes. We here make a brief review on the lectin. The amino acid sequence of pufflectin-s shares sequence homology with mannose-binding lectins of monocotyledonous plants, and has conserved two of three carbohydrate recognition domains, QDNVY motifs, of these plant lectins. By site-directed mutagenesis, we verified that the QDNVY motif in the N-terminal region was critical to the mannose-binding function of pufflectin-s. RT-PCR and Northern blot analyses indicated that the pufflectin-s gene is expressed in the gill, oral cavity wall, esophagus, and skin. In addition, an isoform, pufflectin-i, which shares 91.4% amino acid identity with pufflectin-s, was isolated from the intestine. Using immunohistochemistry, pufflectin-s could be detected exclusively in the epithelial cells of the skin, gill, oral cavity wall and esophagus, whereas pufflectin-i was observed in both mucous and epithelial cells in the intestine. Nevertheless, mRNAs for both pufflectins were detected only in epithelial cells of these tissues with in situ hybridization. Pufflectin-s agglutinated some bacteria isolated from rearing water and from fish skin. This lectin also bound to a parasite, Heterobothrium okamotoi, suggesting that it may play an important role in the self-defense system of fugu.

Two lactose-binding lectins (PFL-1 and -2) were identified in the skin mucus of ponyfish, Leiognathus nuchalis. The molecular masses of PFL-1 and -2 were estimated to be 24 and 30kDa, respectively. Cloning of the PFL-1 cDNA demonstrated its unique tandem repeat structure composed of two homologous domains with 41.7% internal identity. Furthermore, PFL-1 exhibited homology with L-rhamnose-binding lectins previously purified from the eggs of fish and sea urchins. The N-terminal amino acid sequence of PFL-2 was similar to that of PFL-1, suggesting that this protein is an isotype of PFL-1. The PFL-1 gene was expressed in the skin, an important line of defense against pathogens in fish, but was not expressed in any of the other tissues tested here. PFL-1 is the fourth type of fish skin mucus lectin to be identified, suggesting that different species of fish express different types of lectin in their skin mucus.

Objective: Compound muscle action potentials (CMAPs) evoked by transcranial electrical stimulation have been widely introduced to monitor motor function during spinal surgery. They may reflect segmental injuries as well as injuries to motor-related tracts in the spinal cord. However, we have experience with some patients who developed postoperative segmental motor weakness without any potential changes during surgery. To evaluate the efficacy of this method, we used a cat model to observe the relationships between potential changes and selective injuries to the white and gray matters of the spinal cord and spinal nerve roots., Methods: Ten CMAPs were obtained before and after injury to the spinal cord and spinal nerve roots in 20 cats. Changes in the amplitude, latency, and duration of CMAPs were analyzed., Results: CMAPs decreased in amplitude significantly after the insult to the motor-related tracts in the spinal cord in all cats, while the potentials did not always change when the insult was restricted to a limited area in the anterior horn of the spinal cord or to the single spinal nerve root., Conclusions: CMAPs may not exactly reflect segmental injury, and careful attention should be paid to the interpretation of CMAPs.

The purpose of this study was to evaluate the efficacy and reliability of intraoperative spinal monitoring using spinal cord-evoked and compound muscle action potentials. We reviewed 716 cases of spinal monitoring performed over 15 years. The series contained 672 patients with spinal functions that could be monitored intraoperatively; 44 (6.1%) were impossible to record. Based on the 21 impossible-to-record patients, it is evident that missing a serious case such as a Frankel B type spinal cord injury indicates the limitations of the current monitoring methods for stimulating and recording. The monitoring outcomes were true-negative in 652 patients, true-positive in 12, false-negative in four, and false-positive in four. In two of the patients with false-negative results, postoperative myelomere motor paralysis was observed temporarily even though it was possible to record the muscle-evoked potential after electrical stimulation to the brain [Br(E)-MsEP] at the end of the operation. In cases in which the spinal parenchyma or spinal nerve root might be selectively damaged, Br(E)-MsEPs may not diagnose the disorder accurately. By employing multimodal monitoring, it should be possible to eliminate patients with false-negative results and to detect spinal disorders during the early stages, as well as to examine whether the abnormality that had been recorded by a single method is false-positive.

Aims: Various biological parameters are now being evaluated as predictors for the response of chemohormonal therapy for breast cancer. Few studies compare these parameters between the primary lesions and metastatic regional lymph nodes of breast cancer., Methods: Immunohistochemical analyses for epidermal growth factor receptor (EGFR), c-erbB2 and p53 protein were performed on the primary lesions and matching metastatic regional lymph nodes of 107 breast cancers. The intensity of the immunoreactivity was graded for heterogeneous or 10-50% staining, and diffuse or >50% staining., Results: EGFR, c-erbB2 and p53 protein showed a concordance between the primary lesions and matching regional lymph nodes in terms of a negative or positive finding (+ and ++) in 98 (92%) of 106 cases, 76 (100%) of 76 cases and 79 (93%) of 85 cases respectively, while EGFR, c-erbB2 and p53 protein also showed a concordance in the intensity of the immunoreactivity in 24 (89%) of 27 cases 14 (74%) of 19 cases and 30 (94%) of 32 cases respectively. In 21 of 24 cases which showed a disconcordance in the positivity or the intensity of the positivity of EGFR, c-erbB2 and p53 protein, one of the primary lesions and matching regional lymph nodes showed heterogeneous or 10-50% immunostaining., Conclusions: The immunoreactivity of EGFR, c-erbB2 and p53 protein shows a concordance between the primary lesions and matching metastatic regional lymph nodes in a majority of breast cancers., (Copyright 2002 Elsevier Science Ltd. All rights reserved.)

Calphostin C, a secondary metabolite of the fungus Cladosporium cladosporioides, is generally used as a specific inhibitor of protein kinase C. It is known that 12-O-tetradecanoyl-13-phorbol acetate (TPA), a protein kinase C activator, induces expression of mRNA for amphiregulin (AR), a member of EGF-related polypeptides, in mammalian epithelial cells. In this work, we determined the effect of calphostin C on AR mRNA expression in IEC-6 cells, a rat intestinal epithelial cell line, and unexpectedly found that this compound enhanced the TPA-induced expression of AR mRNA. Moreover, calphostin C alone induced expression of AR mRNA in a light-dependent manner, and this effect was abrogated by pretreatment with N-acetylcysteine. These results suggest that calphostin C can upregulate expression of AR mRNA via reactive oxygen species.

The present study was designed to investigate whether heparin-binding epidermal growth factor-like growth factor and its related peptides are expressed in response to gastrin in rat stomach. Rat gastrin-17I (2.5 nmol/kg/hour) or gastrin-17I plus gastrin receptor antagonist, L-740,093 (2.0 mg/kg/hour), was injected intravenously into male Sprague-Dawley rats. RNA was extracted from oxyntic mucosa, and heparin-binding epidermal growth factor-like growth factor and related peptide gene expression was estimated using a ribonuclease protection assay. The level of transforming growth factor-alpha mRNA did not change at any time point during the experiment. In contrast, the levels of heparin-binding epidermal growth factor-like growth factor and amphiregulin mRNA were significantly increased within 3 hours following gastrin infusion and reached maximum levels 6 and 12 hours later, respectively. Continuous infusion of gastrin significantly increased oxyntic mucosal proliferation. Gastrin receptor antagonist significantly inhibited gastrin-induced heparin-binding epidermal growth factor-like growth factor and amphiregulin gene expression and gastrin-induced oxyntic mucosal proliferation. These findings indicate that heparin-binding epidermal growth factor-like growth factor and amphiregulin genes are induced by gastrin and that they play a role in the trophic action of gastrin on oxyntic mucosa.

We investigated the effects of oxidative stress on mRNA levels of heparin-binding epidermal growth factor-like growth factor (HB-EGF) and amphiregulin (AR) in rat gastric epithelial RGM1 cells. In response to stimulation with hydrogen peroxide (100-400 microM), gene expression of HB-EGF and AR increased in a dose-dependent manner, peaked at 3 h, and returned to the base line at 7 h. Hydrogen peroxide-induced HB-EGF and AR gene expression was blocked by pretreatment with an antioxidant N-acetyl-cysteine. In addition, it was significantly inhibited by pretreatment with EGF receptor-specific tyrphostin AG1478, but not by depletion of protein kinase C. These data indicate that oxidative stress upregulates expression of EGF-related polypeptides and the possible involvement of EGF receptor in this process.

We examined the biological action and expression of heparin-binding EGF-like growth factor (HB-EGF) in a rat gastric mucosal cell line, RGM1. HB-EGF stimulated DNA synthesis of RGM1 cells in a dose-dependent manner. Mitogenic effect of HB-EGF was as potent as that of other known mitogens for gastric epithelial cells, such as hepatocyte growth factor (HGF) and transforming growth factor (TGF)-alpha. Northern blot analysis showed that RGM1 cells as well as rat gastric mucosal tissue expressed a 2.5-kilobase transcript of HB-EGF. Not only HB-EGF and TGF-alpha but also HGF caused a rapid induction of HB-EGF mRNA in the cells. Treatment with heparitinase which destroys heparan sulfate proteoglycan (HSPG) or with chlorate which inhibits sulfation of HSPG diminished [3H]thymidine incorporation of RGM1 cells in serum-free medium. In addition, a synthetic peptide corresponding to the heparin-binding domain of HB-EGF inhibits the DNA synthesis of RGM1 cells in serum-free medium in a dose-dependent manner. These results suggest that HB-EGF is an autocrine and paracrine growth factor for gastric epithelial cells and may play significant roles in mucosal repair of the stomach in cooperation with other growth factors.

To determine the contributing factors for eight postoperative complications after esophagectomy through a right thoracoabdominal approach, a multivariate analysis was carried out on preoperative and intraoperative variables in 141 patients with thoracic esophageal cancer. Although postoperative complications occurred in 125 patients, only 7 died of such complications. The multivariate analysis indicated that the retrosternal route was a significant factor predisposing to postoperative atelectasis. Age, preoperative arterial oxygen tension, and volume transfused were significant factors predisposing to postoperative hypoxemia, whereas age, routes other than the intrathoracic route, and volume transfused were significant factors predisposing to prolonged respiratory support. In addition, preoperative total serum bilirubin level and volume transfused were significant factors predisposing to postoperative hyperbilirubinemia; preoperative serum creatinine level was a significant contributing factor for postoperative renal insufficiency; and sex, antesternal route, and substituted colon were significant contributing factors for anastomotic leakage. There were no significant factors predisposing to postoperative pneumonia and liver dysfunction. These significant factors should be taken into consideration not only during perioperative management but also when choosing the operative procedures and extending the surgical indication for esophagectomy through a right thoracoabdominal approach.

The clinicopathological features of esophageal carcinoma were examined from the viewpoint of age differences in a study of 364 consecutively treated patients. The three groups studied were: group I, aged less than 49 years; group II, aged between 50 and 69 years; and group III, aged more than 70 years. There were no significant differences among the three groups with regard to sex ratio, site and length of the lesion, gross types, histological grade, depth of tumor invasion, vessel permeation, lymph node metastasis, TNM classification, incidence of incomplete resection, or crude actuarial 5-year survival curves. The malignant potentiality of the esophageal carcinoma in young patients did not differ from that in older patients in terms of deoxyribonucleic acid distribution pattern. The only difference clearly evident between young and older patients was the number of hospital deaths due to complications: That of the young patients was significantly lower than that of the older patients (p less than 0.05). Esophageal carcinoma in persons aged less than 50 years appeared to behave biologically like the same neoplasm in older people, whereas gastric and colorectal carcinomas behave differently in various age groups.