Search

Introduction Lateral radiography of the knee joint is frequently performed; however, the retake rate is high owing to positioning errors. Therefore, in this study, to reduce the required number and time of image retakes, we developed a system that can classify the tilting directions of lateral knee radiographs and evaluated the accuracy of the proposed method. Methods Using our system, the tilting directions of a lateral knee radiographs were classified into four direction categories. The system was developed by training the DCNN based on 50 cases of Raysum images and tested on three types test dataset; ten more cases of Raysum images, one case of flexed knee joint phantom images and 14 rejected knee joint radiographs. To train a deep convolutional neural network (DCNN), we employed Raysum images created via three-dimensional (3D) X-ray computed tomography (CT); 11 520 Raysum images were created from 60 cases of 3D CT data by changing the projection angles. Thereby, we obtained pseudo images attached with correct labels that are essential for training. Results The overall accuracy on each test dataset was 88.5 ± 7.0% (mean ± standard deviation), 81.4 ± 11.2%, and 73.3 ± 9.2%. The larger the tilting degree of the knee joint, the higher the classification accuracy. Conclusion DCNN could classify the tilting directions of a knee joint from lateral knee radiographs. Using Raysum images made it possible to facilitate creating dataset for training DCNN. The possibility was indicated for using support system of lateral knee radiographs. Implications for practice The system may also reduce the burden on patients and increase the work efficiency of radiological technologists.

Hypoxia has been noted as a key factor for induction and maintenance of cancer stemness thereby leading to therapy resistance. Three-dimensional (3D) spheroid models demonstrate a heterogeneity of hypoxic regions replicating the in vivo situation within tumors. Utilizing an established 3D spheroid model, we investigated whether extrinsic hypoxia reinforced chemoresistance in malignant pleural mesothelioma (MPM) spheroids.Tumor spheres were generated from Meso-1 (a typical human MPM cell line) cells having high spheroid-forming ability. To induce hypoxia condition, we utilized a hypoxia chamber with regulation of O2 and CO2 levels. Cell viability was estimated by a WST-8 assay. Real-time polymerase chain reaction and Western blot were performed to evaluate the expression at mRNA and protein levels.Compared with cells cultured in the two-dimensional monolayer model, tumor sphere cells showed elevated mRNA levels of cancer stemness markers (CD26, CD44 and ABCG2) and protein levels of the stemness and hypoxia adaptation markers (ABCG2, ALDH1A1 and HIFs). Correlating with this, 3D spheroid cells were more resistant to permetrexed and topotecan than the two-dimensional cells, indicative of their potential for hypoxic adaptation. Furthermore, significantly stronger resistance to both chemotherapeutic agents was observed in spheroid cells upon hypoxic challenge compared to spheroid cells under normoxia.From the present data, it is concluded that hypoxia adaptation of MPM cells from tumor spheres could enhance their chemoresistance.

Aim The present study aimed to propose a structural model to explain the interaction of physical, cognitive and social domains of health status in the incidence of disability in community-dwelling people aged ≥75 years. Methods We analyzed 185 older adults (mean age 79.4 years, 58.4% female) who participated in a baseline assessment from 2012 to 2013. They were followed for incident certification of care needs in the national long-term care insurance certification system during the 2 years. Baseline assessments included several measurements related to the physical, cognitive and social domains of health status. We compared the model fit index between two hypothesis models - the parallel model and the hierarchical model - using structural equation modeling. Results During the follow-up period, 15 participants (8.1%) were newly certified as requiring personal support from the long-term care insurance system. The structural equation modeling showed that the hierarchical model, indicating that cognitive and social status were indirectly associated with disability through physical status, had a better fit with the data than the parallel model, indicating that physical, cognitive and social status each were directly associated with disability. Conclusions The present results suggest that cognitive and social status might indirectly affect disability incidence through physical aging. Further research is required to examine the temporal relationship between physical, cognitive and social change using data over several time-periods. Geriatr Gerontol Int 2018; 18: 1614-1619.

Immunohistochemical and ex vivo anatomical studies have provided many glimpses of the variety, distribution, and signaling components of vertebrate retinal neurons. The beauty of numerous images published to date, and the qualitative and quantitative information they provide, indicate that these approaches are fundamentally useful. However, obtaining these images entailed tissue handling and exposure to chemical solutions that differ from normal extracellular fluid in composition, temperature, and osmolarity. Because the differences are large enough to alter intercellular and intracellular signaling in neurons, and because retinae are susceptible to crush, shear, and fray, it is natural to wonder if immunohistochemical and anatomical methods disturb or damage the cells they are designed to examine. Tissue fixation is typically incorporated to guard against this damage and is therefore critically important to the quality and significance of the harvested data. Here, we describe mechanisms of fixation; advantages and disadvantages of using formaldehyde and glutaraldehyde as fixatives during immunohistochemistry; and modifications of widely used protocols that have recently been found to improve cell shape preservation and immunostaining patterns, especially in proximal retinal neurons.

Practical methods for assessing the radiographic findings of Mycobacterium avium complex lung disease (MAC-LD) have not been established.To identify a correlation between the radiological score and semi-quantitative culture results of respiratory samples, and to assess the prognostic impact of this radiological score in MAC-LD patients.We retrospectively studied 218 MAC-LD patients. Radiographic findings were classified as nodule (N), infiltration shadow (I), cavity (C) and bronchiectasis (E), scored individually according to the area occupied on six lung field divisions, and added to give the radiological severity score.The radiological score positively correlated with the semi-quantitative culture score (P = 0.003). In univariate analysis, the radiological score was a significant negative prognostic factor for overall survival. On multivariate analysis, factors I, C and E were independent negative prognostic factors for overall survival. We compared the prognostic value of the total score of all four factors and the three significant factors (I, C and E) using receiver operating characteristic curve analysis; the corresponding areas under the curves were respectively 0.628 and 0.763 (P0.001).The radiological score correlates with prognosis. The combined score of factors I, C and E may more accurately predict prognosis in MAC-LD patients.

Esophageal endoscopic submucosal dissection enables en bloc resection of large superficial esophageal cancer; however, this procedure may induce severe stricture. Intralesional steroid injection is an effective treatment for prevention of stricture after endoscopic resection; however, there have been no studies assessing the duration of such treatment. The aim of this study was to reduce treatment duration and to evaluate the effectiveness of weekly and biweekly steroid injections in preventing esophageal stricture after endoscopic resection.We performed a randomized controlled trial comparing patients receiving weekly or biweekly intralesional triamcinolone injections. Patients with a mucosal defect greater than 75% (3/4) of the luminal circumference after esophageal endoscopic submucosal dissection for superficial esophageal cancers were enrolled. The primary endpoint was the duration of steroid injection treatment.The median duration of treatment was 37.0 days in the weekly group and 34.2 days in the biweekly group (P = 0.059). Among patients with a mucosal defect larger than 50 mm, there was a significant difference in the median duration of treatment between the weekly and biweekly groups (42.5 days vs 29.0 days, P = 0.013).Biweekly steroid injection of triamcinolone reduces treatment duration, particularly in those with mucosal defects larger than 50 mm. (Acta gastro-enterol. belg., 2016, 79, 315-320).

Generally the main component of fishy flavor is considered to be trimethylamine. On the other hand, carbonyl compounds, produced from oxidation of polyunsaturated fatty acid by lipoxygenase or by autoxidation, might have some contribution to the fishy flavor. Since sardine skin contains high levels of polyunsaturated fatty acids and lipoxygenase, carbonyl compounds may be generated more easily than trimethylamine. In this study, volatile flavor compounds of sardine were analyzed by gas chromatograph-mass spectrometry and gas chromatograph-olfactometry combined with solid phase microextraction. Then, the flavor components that contribute to fishy flavor were identified. At normal pH (6.2), trimethylamine was not detected or sensed from the fresh sardines. When the pH was raised, the amount of trimethylamine became higher. Trimethylamine flavor was weak at pH 9 and strongly sensed at pH 11 or higher. On the other hand, 33 other compounds were positively or tentatively identified, including 8 hydrocarbons, 5 ketones, 1 furan, 1 sulfur compound, 12 aldehydes, and 6 alcohols in fresh sardines. Among them, 2,3-pentanedione, hexanal, and 1-penten-3-ol were the main components. Forty-seven flavors were detected by gas chromatograph-olfactometry. Among them, paint-like (1-penten-3-one), caramel-like (2,3-pentanedione), green-like (hexanal), shore-like ((Z)-4-heptenal), citrus note (octanal), mushroom-like (1-octen-3-one), potato-like (methional), insect-like ((E,Z)-2,6-nonadienal), and bloody note (not identified) were strongly sensed. From the aforementioned results, it can be concluded that these compounds rather than trimethylamine contributed to fresh sardine flavor.

Background Frequent use of emergency rooms by injection drug users (IDUs) has been attributed to a lack of access to primary care and barriers to health services. Using a community-based sample of IDUs, we examined rates of primary care and emergency room use among IDUs and identified correlates of frequent emergency department use. Methods From January to November 2003, we enrolled IDUs into a prospective cohort study involving a baseline questionnaire, comprehensive retrospective and prospective health record linkages. We examined rates of primary care and emergency department utilization, and diagnoses upon arrival in the emergency room. Logistic regression was used to determine factors independently associated with frequent emergency room use. Results Of the 883 IDUs included in this analysis, 687 (78 per cent) accessed a primary care clinic in the previous year, while 528 (60 per cent) participants accessed the emergency room (ER) during the years 2002 and 2003. Abscesses, cellulitis and other skin infections accounted for the greatest proportion of ER use. Factors independently associated with frequent ER use included: frequent crystal methamphetamine injection (AOR = 2.4, 95 per cent CI: 1.0–5.6); non-fatal overdose (AOR = 2.1, 95 per cent CI: 1.4–3.3); HIV-positive status (AOR = 1.5, 95 per cent CI: 1.1–2.1), having been physically assaulted (AOR = 1.5, 95 per cent CI: 1.1–2.1); and primary care utilization (AOR = 1.5, 95 per cent CI: 1.0–2.1). Discussion High rates of ER use were observed among IDUs, despite high rates of primary care use among this same population. ER use was due primarily to preventable injection-related complications that are less amenable to primary care interventions, and therefore educational and prevention efforts that encourage and enable sterile injection practices should be promoted.

Viral respiratory infections are the most frequent cause of hospital admission for infants and young children during winter. However, the mechanisms of illness that are associated with viral lower-respiratory-tract infection (LRI) are unclear. A widely accepted hypothesis attributes the pathogenesis of viral LRI in infants to the induction of innate inflammatory responses. This theory is supported by studies showing that Toll-like receptor 4 is activated by respiratory syncytial virus (RSV), leading to production of inflammatory cytokines. We prospectively examined previously naive infants in Buenos Aires, Argentina, who had either upper- or lower-respiratory-tract symptoms. Infection with human metapneumovirus (hMPV) was second only to RSV in frequency. Both viruses were associated with rhinorrhea, cough, and wheezing; however, hMPV elicited significantly lower levels of respiratory inflammatory cytokines than did RSV. Symptoms in infants infected with influenza virus were different from those in infants infected with RSV, but cytokine responses were similar. These findings suggest that hMPV and RSV either cause disease via different mechanisms or share a common mechanism that is distinct from innate immune activation.

The purpose of the present study was to clarify the relationship between the flow of a bolus and occlusal condition during mastication. First, the characteristics of a bolus under mastication was measured in subjects having different occlusal conditions. Secondly, the flow of a bolus between the upper and lower first molars under mastication was simulated using finite element non-linear dynamic analysis. Measurement of the elasticity of the bolus clarified the phenomenon of its communition. The measurement of the viscosity of the bolus clarified the phenomenon of its mixing with saliva. In addition, a relationship between the elasticity and the viscosity of the bolus at the point of just before swallowing was investigated. The flow of the bolus under mastication was revealed to vary according to the occlusal condition. These results suggest a close relationship between the occlusal condition, the flow of the bolus and its characteristics.

SUMMARYIn this study we have tested the concept of using wild-type p53 gene for immunotherapy of cancer. Dendritic cells (DC) were transduced with a human wild-type p53 containing recombinant adenovirus (Ad-p53). About a half of DC transduced with this virus expressed p53 protein by FACS analysis 48 h after infection. Mice immunized twice with Ad-p53 DC developed substantial cytotoxic T lymphocyte (CTL) responses against tumour cells expressing wild-type and different mutant human and murine p53 genes. Very low CTL responses were observed against target cells infected with control adenovirus (Ad-c). Immunization with Ad-p53 provided complete tumour protection in 85% of mice challenged with tumour cells expressing human mutant p53 and in 72.7% of mice challenged with tumour cells with murine mutant p53. Treatment with Ad-p53-transduced DC significantly slowed the growth of established tumours. Thus, DC transduced with wild-type p53 may be a promising new tool for the immunotherapy of cancer.

The ATP-dependent glutathione S-conjugate export pump (GS-X pump) has been suggested to play a role in the mechanism of cisplatin resistance. The purpose of this study was to determine the relationship between intracellular glutathione (GSH) levels and GS-X pump activity and whether GS-X pump overexpression results in cisplatin resistance. We transfected the human gamma-glutamylcysteine synthetase (gamma-GCS) gene into a human small-cell lung cancer cell line, SBC-3, producing SBC-3/GCS. The intracellular GSH content of SBC-3/GCS was twice that of the parental line, its GS-X pump activity was significantly enhanced and cellular cisplatin accumulation decreased. SBC-3/GCS showed higher resistance (relative resistance value of 7.4) to cisplatin than the parental line SBC-3. These data indicate that gamma-GCS gene overexpression induces cellular cisplatin resistance associated with increases in both the GSH content and GS-X pump activity, resulting in reduced cisplatin accumulation. In conclusion, GS-X pump expression is related to cellular GSH metabolism and involved in cisplatin resistance.

We have already proposed a model for the lethal effects of heat on cells. In the model, a three-step process for cellular inactivation was hypothesized: 1) heating produces sublethal damage; 2) the damage is repaired in a certain time period; 3) the cell is inactivated when it undergoes cumulative sublethal damage to the extent that it cannot be repaired. Using the previous model, we investigated the modifications of the survival curve in 1) continuous heating, 2) step-down heating, 3) step-up heating, and 4) recovery from the thermal injury by split heating. These four phenomena were explained well with the mathematical model.

BACKGROUND--Susceptibility to the development of sarcoidosis has been demonstrated to be associated with HLA-DR5, -DR6, and -DR8 encoded by the DRB1 gene. However, involvement of the DRB3 (HLA-DR52) gene in the development of sarcoidosis remains unclear. METHODS--HLA-DRB3 genotyping was performed using the PCR-RFLP method and the clinical features of the patients with and without the DR3, 5, 6, 8 group antigens were compared. RESULTS--HLA-DRB3 genotyping indicated an association between DRB3*0101 and sarcoidosis. The DR8 haplotype lacking the DRB3 gene has been found to be increased significantly in sarcoidosis, suggesting that the HLA-DRB3 gene is not a primary determinant of predisposition to sarcoidosis. The association of DRB3*0101 with sarcoidosis is attributable to linkage disequilibrium with DR5- and DR6-associated alleles. There were significant decreases in the DR3, 5, 6, 8 group (DR5, DR6, or DR8) antigen frequencies in patients with retinal perivasculitis, high intraocular pressure (or secondary glaucoma), and optic nerve and/or macular lesion. Correlations were observed among the DR3, 5, 6, 8 group antigens, early onset sarcoidosis and disease with fewer intraocular lesions. CONCLUSION--This established a molecular basis for some of the clinical heterogeneity observed in sarcoidosis.

This report describes FHR patterns of monozygotic twins, one of whom was anencephalic. The recording were made from 20 to 36 weeks of gestation. Differences were observed in the FHR patterns after week 28.

Ubiquilin-1 acts as an adaptor protein that mediates the translocation of polyubiquitinated proteins to the proteasome for degradation. Although previous studies suggested a key role of ubiquilin-1 in the pathogenesis of Alzheimer's disease (AD), a direct relationship between ubiquilin-1 and Hirano bodies in AD brains remains unknown.By immunohistochemistry, we studied ubiquilin-1 and ubiquilin-2 expression in the frontal cortex and the hippocampus of six AD and 13 control cases.Numerous Hirano bodies, accumulated in the hippocampal CA1 region of AD brains, expressed intense immunoreactivity for ubiquilin-1. They were much less frequently found in control brains. However, Hirano bodies did not express a panel of markers for proteasome, autophagosome or pathogenic proteins, such as ubiquilin-2, ubiquitin, p62, LC3, beclin-1, HDAC6, paired helical filament (PHF)-tau, protein-disulphide isomerase (PDI) and phosphorylated TDP-43, but some of them expressed C9orf72. Ubiquilin-1-immunoreactive deposits were classified into four distinct morphologies, such as rod-shaped structures characteristic of Hirano bodies, dystrophic neurites contacting senile plaques, fragmented structures accumulated in the lesions affected with severe neuronal loss, and thread-shaped structures located mainly in the molecular layer of the hippocampus.Ubiquilin-1 immunoreactivity is concentrated on Hirano bodies and dystrophic neurites in AD brains, suggesting that aberrant expression of ubiquilin-1 serves as one of pathological hallmarks of AD.

RGMa is a repulsive guidance molecule that induces the collapse of axonal growth cones by interacting with the receptor neogenin in the central nervous system during development. It remains unknown whether RGMa plays a role in the neurodegenerative process of Alzheimer's disease (AD). We hypothesize that RGMa, if it is concentrated on amyloid plaques, might contribute to a regenerative failure of degenerating axons in AD brains.By immunohistochemistry, we studied RGMa and neogenin (NEO1) expression in the frontal cortex and the hippocampus of 6 AD and 12 control cases. The levels of RGMa expression were determined by qRT-PCR and Western blot in cultured human astrocytes following exposure to cytokines and amyloid beta (Aβ) peptides.In AD brains, an intense RGMa immunoreactivity was identified on amyloid plaques and in the glial scar. In the control brains, the glial scar and vascular foot processes of astrocytes expressed RGMa immunoreactivity, while oligodendrocytes and microglia were negative for RGMa. In AD brains, a small subset of amyloid plaques expressed a weak NEO1 immunoreactivity, while some reactive astrocytes in both AD and control brains showed an intense NEO1 immunoreactivity. In human astrocytes, transforming growth factor beta-1 (TGFβ1 ), Aβ 1-40 or Aβ 1-42 markedly elevated the levels of RGMa, and TGFβ1 also increased its own levels. Coimmunoprecipitation analysis validated the molecular interaction between RGMa and the C-terminal fragment β of amyloid beta precursor protein (APP). Furthermore, recombinant RGMa protein interacted with amyloid plaques in situ.RGMa, produced by TGFβ-activated astrocytes and accumulated in amyloid plaques and the glial scar, could contribute to the regenerative failure of degenerating axons in AD brains.

We present a case report about bilateral multicystic dysplastic kidneys (MCDKs). Pregnancy was terminated at 21 weeks' gestation and the fetus was examined by autopsy. The kidneys were replaced by many cysts and there was no parenchyma. However, on histological examination, there was normal nephrogenesis amid the cystic/dysplastic tissue. This suggests that normal nephrogenesis occurs before the secondary changes leading to MCDKs.

A recent study showed that γ-secretase activating protein (GSAP), derived from a C-terminal fragment of pigeon homolog (PION), increases amyloid-β (Aβ) production by interacting with presenilin-1 (PS1) and the β-secretase-cleaved C-terminal fragment of amyloid precursor protein (APP-CTF). In the study, knockdown of GSAP reduces production of Aβ and plaque formation in the brain of APPswe and PS1ΔE9 double transgenic mice without affecting the Notch-dependent pathway. Therefore, GSAP is an ideal target for designing γ-secretase modulators with least side effects in Alzheimer's disease (AD). However, at present, the precise distribution of GSAP in AD brains remains to be characterized.By immunohistochemistry, we studied GSAP expression in the frontal cortex and the hippocampus of 11 aged AD and 17 age-matched control cases.GSAP immunoreactivity exhibited distinct morphological features, such as fine granular cytoplasmic deposits, dense nodular and patchy deposits, beads and string-like deposits, and diffuse dot-like deposits. In both AD and control brains, a fairly small subset of cerebral cortical and hippocampal neurones expressed fine granular cytoplasmic deposits, while diffuse dot-like deposits were more frequently found in the neuropil and neuronal processes, particularly enriched in the hippocampal CA2 and CA3 regions. Among GSAP-immunoreactive deposits, dense nodular and patchy deposits, located in the neuropil and closely associated with PS1 expression and Aβ deposition, indicated the most distinguishing features of AD pathology.Aberrant regulation of GSAP expression plays a key role in acceleration of γ-cleavage of APP-CTF and accumulation of Aβ in AD brains.

To achieve hyperthermia using electromagnetic energy, RF of under 100 MHz is basically suitable for the external heating of the deep portions of the body. For applicators using such RF, the following types are considered: capacitive, inductive, radiative and hybrid. With radiative applicators, the intensity of the EM waves radiated from the applicator decreases with propagation into the material to be heated, but the phased annular array of radiative applicators potentially increases the intensity of the EM energy in the deep portion owing to the interference of the waves. Using this method, the focusing of EM energy depends on the dielectric properties of the material to be heated. With respect to RF heating at a lower frequency than the RF used for the annular phased array, some devices have been said to concentrate EM energy in the deep portions, where the characteristics of 'wave' are not utilised. To this end, some methods using capacitive electrodes, an inductive coil, or a combination of both, are being designed. The results of using such methods have shown that it is possible to supply sufficient EM energy to the muscle layers deep in the material to be heated, without heating the fat layers excessively.

The c-erbA alpha gene encodes the alpha type thyroid hormone receptor. This gene is expressed in various types of cells, its expression being relatively high in the central nervous system. A genomic clone that contains the 5'-terminal portion of the human c-erbA alpha gene was isolated. The 615 base pair (bp) 5'-flanking sequence of the c-erbA alpha gene showed promoter activity when placed upstream of the bacterial chloramphenicol acetyltransferase gene and transfected into HeLa cells. Nine transcriptional initiation sites were detected within this sequence by S1 nuclease protection analysis. DNA sequence analysis showed that the promoter region contains ten putative binding sites for transcriptional factor Sp1 in the GC rich region (86%). Three putative cAMP responsive elements (CRE) and one putative TPA responsive element (TRE) were identified upstream of the GC rich region. The c-erbA alpha promoter sequence also contains a putative binding site for the Krox-20 transcriptional factor, which is thought to play a role in early development of the mouse central nervous system.

A method for concentrating electromagnetic (EM) energy of a low frequency in hyperthermia is proposed. The phantom together with boli are placed between a pair of inductive aperture-type applicators. The calculated results show that the method can heat the deep portion of the phantom without overheating the fat layers excessively. >

Vascular degeneration appears to play crucial roles in producing many vascular mulfunctions (1-3). In order to identify specific inducers of programmed death in vascular endothelial cells (VEC), examinations were made of the effects of substances that are known to affect the vascular system by using VEC in culture (4,5). We found that hemorrhagic snake venoms induced apoptotic cell death or programmed cell death of VEC. By contrast, neurotoxic snake venoms did not induce programmed cell death but caused necrosis at much higher doses of the venoms. No effect of hemorrhagic venom was observed with many types of cultured cells other than VEC. Thus, hemorrhagic snake venom appears to be a useful tool for studies of the molecular mechanisms of vascular apoptosis. The results also suggest a possible mechanism of action of hemorrhagic snake venom on the vascular system.

We describe the prevalence of community-acquired M. pneumoniae pneumonia diagnosed by culture methods in a single institute in Japan from January 1979 to December 1999. Cultures were performed in 2971 pneumonia cases and yielded M. Pneumoniae in 508 cases. The epidemic peaks recurred regularly at 4-year intervals (1980, 84, 88 and 91–2). Although a large epidemic has not occurred since 1992, traces of epidemic periodicity have still persisted from 1992 to 1999 at 3-year intervals.

MicroRNAs (miRNAs) are small non-coding RNAs that regulate translational repression of target mRNAs. Accumulating evidence indicates that various miRNAs, expressed in a spatially and temporally controlled that manner in the brain plays a key role in neuronal development. However, at present, the pathological implication of aberrant miRNA expression in neurodegenerative events remains largely unknown. To identify miRNAs closely associated with neurodegeneration, we performed miRNA expression profiling of brain tissues of various neurodegenerative diseases.We initially studied the frontal cortex derived from three amyotrophic lateral sclerosis patients by using a microarray of 723 human miRNAs. This was followed by enlargement of study population with quantitative RT-PCR analysis (n = 21).By microarray analysis, we identified up-regulation of miR-29a, miR-29b and miR-338-3p in amyotrophic lateral sclerosis brains, but due to a great interindividual variation, we could not validate these results by quantitative RT-PCR. However, we found significant down-regulation of miR-29a in Alzheimer disease (AD) brains. The database search on TargetScan, PicTar and miRBase Target identified neurone navigator 3 (NAV3), a regulator of axon guidance, as a principal target of miR-29a, and actually NAV3 mRNA levels were elevated in AD brains. MiR-29a-mediated down-regulation of NAV3 was verified by the luciferase reporter assay. By immunohistochemistry, NAV3 expression was most evidently enhanced in degenerating pyramidal neurones in the cerebral cortex of AD.These observations suggest the hypothesis that underexpression of miR-29a affects neurodegenerative processes by enhancing neuronal NAV3 expression in AD brains.

We examined the usefulness of MRI in differentiating post-radiation scar tissue from the residual tumour. Ten consecutive patients who underwent MR imaging before and after radiation therapy were assessed prospectively. T1- and T2-weighted images using a 1.5 unit were obtained in 10 patients (3 T1, 6 T2, 1 T3) at 1 week before irradiation, and 2 weeks, 2 months, 4 months, 6 months and every 6 months thereafter following completion of radiation. Although all T2 and T3 tumours demonstrated high signal intensity compared to muscle on T2-weighted images, the T1 tumour could be demonstrated in only one of three patients. Six patients in whom the primary tumour clinically disappeared demonstrated low signal intensity on T2-weighted images until 4 months after completion of radiation therapy (range 1 week to 4 months). This study suggests that MRI can detect primary tumours larger than T2 (2 cm), and may be useful in assessing the effectiveness of therapy for tongue cancer.

A total of 141 Streptococcus pneumoniae isolates from patients with community-acquired pneumonia were collected from May 2003 through October 2004. The strains were tested for antimicrobial agent susceptibility, serotype and genotype by multilocus sequence typing (MLST) and the presence of the pilus rlrA islet. MLST analysis identified 49 sequence types (STs), of which 19 were novel. eBURST analysis using the MLST database (3773 STs) grouped the isolates into 27 clonal complexes and three singletons. A total of 92 (65.2%) isolates were related to ten of the 43 international Pneumococcal Molecular Epidemiology Network (PMEN) clones; major clones found were multidrug-resistant Netherlands3-31 [clonal complex (CC) 180], Taiwan19F-14 (CC271), Taiwan23F-15 (CC242), and Colombia23F-26 (CC138) (the latter new to Asia). We adopted univariate and multiple logistic regression models to identify factors associated with PMEN CCs. Multivariate analysis showed that multidrug resistance (OR 6.3; 95% CI 2.0–22.9), carriage serogroups (OR 7.2; 95% CI 2.5–23.7), prevalence of rlrA (OR 12.6; 95% CI 3.6–59.7) and central nervous system-related disorders (OR 7.7; 95% CI 1.8–48.4) were independently associated with PMEN CCs. Our data indicate that multidrug-resistant PMEN clones are highly prevalent, contributing to the high frequency of resistance to antimicrobial agents in Japan, and suggest that certain predisposing factors in patients contribute to the high frequency of these clones.

We established the distribution of amino acid alterations in quinolone resistance-determining regions (QRDRs) of Streptococcus pneumoniae isolates in Japan and described the correlation of these alterations with serotypes determined by multilocus sequencing typing. Among 141 S. pneumoniae isolates, five levofloxacin-resistant isolates harbored mutations in both gyrA and parC and/or parE and were clonally unrelated. Among 136 levofloxacin-susceptible isolates, one isolate (MIC = 2 mg/l) had a first-step parC mutation at Asp78. Twenty isolates had Lys137Asp in parC and Ile460Val in parE and contained nine serotypes and eight clonal complexes (CCs), including all eight Colombia(23F)-26 (CC138) isolates. Eighty-one isolates had Ile460Val in parE alone and contained 14 serotypes and 16 CCs, including 36 of 37 Netherlands(3)-31 (CC180) isolates and all 22 Taiwan(19F)-14 (CC271) isolates. In contrast, seven of ten Taiwan(23F)-15 (CC242) isolates were wild-type. Although each QRDR genotype contained various serotypes and CCs, prevalent clones were mostly associated with a single QRDR genotype.

Fusion genes have been identified as chromosomal rearrangements in certain cancers, such as leukaemia, lymphoma, and sarcoma. The EML4–ALK (EML4: echinoderm microtubule-associated-protein-like 4; ALK: anaplastic lymphoma kinase) fusion gene has been identified as an oncogene in non-small-cell lung cancer (NSCLC). This study examined the presence of this fusion transcript in gastrointestinal and breast cancers. We evaluated the expression of the EML4–ALK transcript in 104 lung cancer cases and in 645 gastrointestinal and breast cancer samples. Only one of the lung cancer samples tested positive for the EML4–ALK fusion transcript, whereas none were detected in 555 gastrointestinal and 90 breast cancer cases. Our data suggest that the EML4–ALK fusion transcript is not present in gastrointestinal or breast cancers and is specific to NSCLC.

We assessed pneumococcal surface protein A (PspA) family types of 141 isolates of Streptococcus pneumoniae from community-acquired pneumonia patients in Japan. Families 1 and 2 were expressed in 78 (55.3%) and 58 (41.1%) isolates, respectively. Five isolates were not typed either as family 1 or 2. PspA family types were not associated with age, sex, or pneumonia severity. Penicillin-resistant S. pneumoniae was more likely to belong to family 2 whereas organisms highly resistant to erythromycin and positive for ermB were more prevalent in family 1. The association of PspA type with antimicrobial resistance was possibly affected by prevalent serotypes or resistance clones. It would therefore be necessary to include both family 1 and 2 proteins in a PspA-containing vaccine to cover the major PspA families and to reduce antimicrobial resistance.

This essay looks at the historical significance of three APS classic papers that are freely available online: Naka K-I and Nye PW. Role of horizontal cells in organization of the catfish retinal receptive field. J. Neurophysiol 34:785–801, 1971. Marmarelis PZ and Naka K-I. Nonlinear analysis and synthesis of receptive-field responses in the catfish retina. II. One-input white-noise analysis. J. Neurophysiol 36: 619–633, 1973. Naka K-I, Marmarelis PZ, and Chan RY. Morphological and functional identifications of catfish retinal neurons. III. Functional identification. J. Neurophysiol 38: 92–131, 1975.

The association between congenital pseudoarthrosis and osteofibrous dysplasia of the tibia and fibula is a rare entity that has been recently recognized. We report a male newborn who was found to have swelling and deformity of the left lower leg. Radiographs and magnetic resonance imaging showed an extensive destructive lesion of the tibial shaft, with dysplastic congenital pseudoarthrosis of the lower fibula. Histopathological examination confirmed the diagnosis of congenital pseudoarthrosis of the tibia and fibula with underlying osteofibrous dysplasia involving both bones. Immunohistochemical stains showed cytokeratin positivity.

To examine patterns of high resolution computed tomography (HRCT) of lungs of adults with disseminated tuberculosis (TB).Disseminated TB was defined as radiological involvement of all lung lobes.The case series illustrated wide variation in HRCT of disseminated TB. Patterns identified on HRCT included (1) miliary TB (haematogenous dissemination), (2) miliary TB with exudative reaction, (3) bronchogenic spread, (4) miliary TB mixed with bronchogenic spread, and (5) bronchogenic spread with multiple cavity formation.The HRCT patterns described allow classification of disseminated TB according to the mechanism of spread (haematogenous and/or bronchogenic) and the degree of local lung involvement (reaction or cavitation).

We report the first case of glossal necrotizing myositis by group A beta-hemolytic Streptococcus in an 8-year-old girl on chronic nonsteroidal anti-inflammatory drugs, immunomodulators, and steroids for juvenile rheumatoid arthritis. Treatment included partial glossectomy and parenteral antibiotics. After a critical course, full recovery ensued. The subject of necrotizing myositis is reviewed.

Ever since it was proposed that reactive oxygen species (ROS) are involved in the pathogeneses of various diseases, superoxide dismutase (SOD)-mimetic complexes have been intensively studied. We prepared copper(II) aspirinate [Cu2(asp)4] from Cu(II) and aspirin, which has been in use for many years as an antipyretic, an analgesic, and an anti-inflammatory agent. However, Cu2(asp)4 has been found to have additional activities, including anti-inflammatory, antiulcer, anti-ischemic/reperfusion agent, anticancer, antimutagenic, and antimicrobial activities. The activity of copper salicylate [Cu(sal)2] was also compared with that of Cu2(asp)4. The structure of the Cu2(asp)4 was determined using X-ray structure analysis. Its SOD-mimetic activity was determined using cytochrome c, electron spin resonance (ESR) spectroscopy, and ESR spin trap methods. The activity of Cu2(asp)4 was slightly greater than CuSO4 and copper acetate [Cu(ace)2] and slightly less than that of Cu(sal)2. The in vitro antioxidant activity, evaluated in human epithelial or transformed neoplastic keratinocyte cells, HaCaT, and normal dermal fibroblasts in terms of cell survival following ultraviolet B (UVB) irradiation, was significantly increased in the presence of Cu2(asp)4, Cu(sal)2, and CuSO4. Further, ROS generation following UVA irradiation in the skin of hairless mice following oral treatment with Cu2(asp)4 for three consecutive days was significantly suppressed compared to the vehicle- or Cu(ace)2-treated mice. On the basis of these results, Cu2(asp)4 was observed to be a potent antioxidative compound possessing antioxidative activity in biological systems. In conclusion, Cu2(asp)4 is a potent antioxidative agent that may be useful for future treatment of diseases resulting from ROS.

Streptococcus pneumoniae (Sp) and Haemophilus influenzae (Hi) are the leading bacterial cause of acute otitis media (AOM), having the nasopharynx (NP) as their reservoir. In October 2001 we began a prospective, multicenter, randomized, evaluator blind study, comparing the efficacy of amoxicillin-sulbactam (Ax/S) and amoxicillin-clavulanic acid (Ax/C) for the treatment of non-recurrent AOM (nr-AOM). Both antimicrobial susceptibility (AS) to Ax/S and Ax/C from Sp and Hi carried by study children (aged 6-48 months with nr-AOM) and, clinical outcome after treatment with high dose of either Ax/C (7:1) or Ax/S (4:1) (amoxicillin dose: 80 mg/(kg day), b.i.d. for 10 days) were assessed. Nasal cultures (NCs) were taken at Day 0. Follow-up NCs, were done only for Sp carriers. On final analysis 247/289 pts (85.5%) were fully evaluable (120 Ax/S and 127 Ax/C). NP carriage rate of Hi and Sp at Day 0 was 32.2% (93/289 pts) and 28.7% (83/289 pts), respectively. Persistent Sp carriage was detected only in 2 pts. Hi betalactamase positive rate was 13% (12/93). MICs for Ax/S and Ax/C were identical when tested against Sp and Hi isolates (range < or = 0.016-1.0 and < or = 0.016-0.25 mg/L, respectively). Clinical efficacy at Days 12-14 and 28-42 were 98.3% (115/117) and 94.2% (97/103) for Ax/S; and 98.3% (115/117) and 95.1% (98/103) for Ax/C, respectively (pNS). We conclude, that Sp and Hi isolated from NCs of nr-AOM pts were highly sensitive to both drugs and correlated with high clinical efficacy rate.

Mitral regurgitation (MR) due to only punched out lesion is extremely rare in infective endocarditis. A 31-year-old male was admitted to our hospital due to unusual cause of MR. Echocardiography showed MR due to punched out lesion of the mitral anterior leaflet, which is extremely rare. A round shape punched out lesion (about 16 mm in size) was found intraoperatively in the anterior leaflet of the mitral valve. The surface around the punched out lesion was smooth, and the leaflet displayed good movability. Neither vegetation nor calcification was found. Punched out lesion was successfully closed with autologous pericardial patch and annuloplasty was performed.

In picture archiving and communication systems (PACS), the information on the body parts included in radiographs is often not or incorrectly recorded in an image header. In order to apply the computer-aided diagnosis (CAD) system in the PACS environment, the body parts in radiographs need to be recognized correctly by computer. The purpose of this study is to develop a computerized method for correctly classifying the body parts in digital radiographs based on a template matching technique.The image database used in this study was 1032 digital radiographs (14 x 17 inches) obtained with a computed radiography, and included 505 chest of postetroanterior view, 39 chest of lateral view, 241 abdomen, 108 pelvis, 10 upper limbs, 125 lower limbs, and 4 thoracic spine. In this method, test images were classified into four body parts, i.e., (1) chest, (2) abdomen, (3) pelvis, and (4) upper/lower limbs and thoracic spine. This computerized method was tested with 852 images, since 180 images were employed for creation of 98 templates, which represented the average radiographs for various body parts. Our approach was to examine the similarity of a given test image with templates by use of the cross-correlation values as the similarity measures. The body part of the test image was identified as the body part in the template yielding the maximum correlation value. Our method consisted of the following five steps. First, test images were classified into one of three groups; i.e. 1) chest and abdomen, 2) pelvis, and 3) upper/lower limbs and thoracic spine by using the templates obtained from images with the average size and position. Second, the remaining uncertain images were classified by using additional templates in various directions. Third, the chest and abdomen group was separated into two subgroups; i.e.chest and abdomen. Fourth, in order to classify some uncertain images, templates were shifted horizontally and vertically. Fifth, outer pixels of templates were eliminated to avoid the misclassification due to x-ray collimation.Our preliminary results indicated that the body parts for 850 cases (99.8%) were correctly classified with our method.This method would be useful for automated identification of the body parts in radiographs when various CAD systems would be implemented in the PACS environment.

To clarify the etiology of community-acquired pneumonia (CAP) in Japan, the causative pathogens were prospectively investigated in adult patients admitted to Kurashiki Central Hospital. The microbiological diagnosis was based on the results of quantitative sputum culture, blood culture, and other invasive procedures, including transthoracic needle aspiration or bronchoscopic examination. Five hundred fifty-two episodes of CAP in 540 patients were admitted between July 1994 and June 1999. Causative pathogens were identified in 353 episodes (63.9%). Several characteristics about the etiology of CAP in Japan were recognized: 1) Streptococcus pneumoniae is the most common pathogen followed by Haemophilus influenzae; 2) Mycoplasma pneumonia is dominant among young patients; 3) Chlomydia pneumoniae is one of the significant pathogens in Japan as well as in western countries; 4) Streptococcus milleri group and anaerobes are important pathogens in patients with suppurative pulmonary diseases; 5) The incidence of Legionella pneumonia is far lower than in western countries; 6) The prevalence of tuberculosis in CAP is still high in Japan; etc. Recognition of these results will lead us to treat patients with prompt antimicrobial therapy.

Dendritic cells (DCs) are the most important antigen-presenting cells. Many recent studies have compared the function of immature DCs (iDCs) and mature DCs (mDCs), but there have been few reports of the molecular changes that occur in DCs during maturation. Here, we report on differential gene expression in iDCs generated from peripheral blood monocytes compared with mDCs. Gene expression was evaluated using the differential display method after activation of iDCs with a low concentration of lipopolysaccharide (LPS) to induce maturation. Proteasome subunit alpha type 3 (PSMA3), transcription factor EC (TFEC) isoform and BTK region clone 2f10-rpi were transiently upregulated. Tryptophanyl-tRNA synthetase and CD63 antigen were upregulated for at least 24 h. Neuronal apoptosis inhibitory protein (NAIP) and transforming growth factor-beta-induced 68 kDa protein were downregulated. This is the first report of NAIP expression in human DCs. By comparing the expression of NAIP with that of other members of the inhibitor of apoptosis protein (IAP) family and the Bcl-2 family, only NAIP was found to be strongly expressed in iDCs before stimulation by LPS. PSMA3 was also induced in the DCs stimulated with immune complex. These findings might contribute to our understanding of DC maturation and the effectiveness of DC-based vaccines.

In cardiac surgery, several studies have shown bacterial contamination rates of intraoperative salvaged blood ranging from 12.7 to 96.8%. We evaluated the relation between intraoperative salvaged blood transfusion produced by the Cell Saver 5 device (Haemonetics Corp., Braintree, MA, USA) and postoperative infection determined by bacteriological study and the postoperative clinical course after cardiac surgery. Seven cases of cardiac surgery were investigated by bacteriological study. Although bacteria were cultured from all salvaged blood, no bacteria were cultured from the patients' blood 24 hours after salvaged blood infusion. Another 26 patients who underwent cardiac surgery, were divided into groups: group CS (n = 15) with salvaged blood transfusion after operation and group N (n = 11) without salvaged blood transfusion, and were evaluated in relation to the postoperative clinical course. There were no statistically significant differences between group CS and group N in the data of WBC, CRP and maximum body temperature. One case of deep sternal wound infection and 2 cases of local wound infection were observed in group CS, but none in group N (p = 0.18). These complications were treated by primary closure without muscle flaps. We conclude that salvaged blood autotransfusion was not related to postoperative infections in cardiac surgery.

SUMMARY It has been suggested that the humoral immune system plays a role in the pathogenesis of non-specific interstitial pneumonia (NSIP). Although some circulating autoantibodies to cytoskeletal protein(s) have been suggested, the antimyofibroblast antibody has not been investigated in patients with idiopathic pulmonary fibrosis (IPF) and NSIP. The purpose of this study is to evaluate the existence of antimyofibroblast antibody in the sera of patients with IPF and NSIP. The MRC5 cell line was used as a model of myofibroblast. The anti-MRC5 cell antibody was characterized in a patient with NSIP using Western blotting. Since we found that one of the anti-MRC5 antibodies was an antivimentin antibody, we established an enzyme-linked immunosorbent assay (ELISA) to measure the levels of antivimentin antibody in the sera of patients with IPF (n = 12) and NSIP (n = 23). Initially, two anti-MRC5 cell antibodies were detected in the sera of patients with NSIP, one of which was characterized as the antivimentin antibody by Western blotting. The other was characterized as an antivimentin fragment antibody. We established an ELISA to measure the antivimentin antibody and found significantly higher levels in patients with IPF and NSIP than in normal volunteers. One of the anti-MRC5 cell antibodies in the serum of a patient with NSIP was against vimentin. The serum levels of antivimentin antibody were increased in patients with IPF and NSIP compared with that of normal volunteers. These results suggest that the antivimentin antibody may be involved in the process of lung injury in IPF and NSIP.

Recently, the clinical features of non-specific interstitial pneumonia (NSIP) have been described. We hypothesize that recurrent infection caused by Chlamydia pneumoniae may play a role in the pathogenesis of NSIP. To prove this, we quantified serum IgA and IgG antibodies against C. pneumoniae using the enzyme linked-immunosorbent assay kit. The study included 15 patients diagnosed with NSIP, 20 patients with chronic obstructive pulmonary diseases (COPD) as disease group, and 27 control subjects. IgA antibody against C. pneumoniae was positive in 12 of 15 patients with NSIP, in 16 of 20 patients with COPD, and in 14 of 27 control subjects. IgG antibody against C. pneumoniae was positive in 14 of 15 patients with NSIP, in 17 of 20 patients with COPD, and in 16 of 27 control subjects. If the cut off value (mean +/- 2SD, index more than 3.0) was introduced, IgA and/or IgG antibodies against C. pneumoniae were positive in 8 of 15 patients with NSIP (53.3%), in 9 of 20 patients with COPD (45%), and in 2 of 27 control subjects (7.4%). These results suggest that infection of C. pneumoniae might play a role in the pathogenesis of NSIP.

RANTES, a member of C-C chemokine, is known to be produced at sites of granulomatous reactions in the lung of sarcoidosis. RANTES is a potent eosinophil and lymphocyte attractant with particular preference for CD45RO+ T cells and eosinophils. Polymorphism of the RANTES promoter has recently been shown to be related to allergic and infectious diseases; atopic dermatitis, asthma, and polymyalgia rheumatica. Considering that this might affect sarcoidosis, we studied polymorphism of the RANTES gene in 114 patients with sarcoidosis and 136 healthy control subjects. Their genotypes were determined using polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP). Although no difference in the genotype distribution between healthy control subjects and sarcoidosis patients was identified, the difference in the frequencies of the patients with three or more organ involvement was significant (P0.01) with the frequency of those in AA genotype being elevated (P0.05). BAL findings in 48 out of 114 patients who underwent bronchoscopy were reviewed. The CD4/8 ratio of lymphocytes in bronchoalveolar lavage fluid in the patients with AA genotype was significantly increased (P0.05). From the results, we suggest that in RANTES gene polymorphism the homozygous A allele might be a genetic risk factor for extent disease of sarcoidosis.

An 18-year-old girl with a 5-year history of neurofibromatosis type 2, consisting of bilateral acoustic tumors and a meningioma at the planum sphenoidale, presented with an intramedullary mass at the T-1 level, and underwent total removal of the tumor. Histological examination showed that the tumor consisted of markedly elongated spindle-shaped cells, which were immunopositive for S-100 protein and glial fibrillary acidic protein. Ultrastructural examination showed microvilli-lined lumina and prominent intercellular junctions, which were characteristic ependymal features. These findings were compatible with the diagnosis of tanycytic ependymoma. This rare subtype of ependymoma appears to arise through inactivation of NF2, in addition to some typical ependymomas.

We analyzed methods and clinicopathological factors for multiple (or = 5) bilobar liver metastases (H3) from colorectal cancer and evaluated the indication of surgical and microwave coagulation therapy (MCT) for them. Twenty-four patients with H3 underwent surgical therapy and were divided into two groups. Group a: 9 patients with a prognosis of more than 700 days. Group b: the remaining 15 patients. There was no significant difference in prognosis between those receiving MCT and resection + MCT as a surgical therapy. The number and maximum diameter of tumors tended to be smaller in Group a. The number of tumors was less than or equal to 9 and the maximum size of the tumors was 38 mm. Moreover, the tumor could be controlled by MCT alone if the tumor size was less than 30 mm. MCT is a useful therapy for these cases and the indication for surgical therapy may depend on the number and maximum size of tumors.