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The histopathological distinction of lung adenocarcinoma (LADC) subtypes is subject to high inter-observer variability, which can compromise the optimal assessment of the patient prognosis. Therefore, this study developed convolutional neural networks (CNNs) capable of distinguishing LADC subtypes and predicting disease-specific survival, according to the LADC tumour grades established recently by the International Association for the Study of Lung Cancer pathology committee. Consensus LADC ground truth histopathological images were obtained from seventeen expert pulmonary pathologists and one pathologist in training. Two deep learning models (AI-1 and AI-2) were trained with EfficientNet b3 architecture to predict eight different LADC classes (lepidic, acinar, papillary, micropapillary, solid, invasive mucinous adenocarcinoma, other carcinoma types, and no carcinoma cells). Furthermore, the trained models were tested on an independent cohort of 133 patients. The models achieved high precision, recall, and F1-scores exceeding 0.90 for most of the LADC classes. Clear stratification of the three LADC grades was reached in predicting the disease-specific survival by the two models. Moreover, the grading prediction of one of the trained models was more accurate than those of 14 out of 15 pulmonary pathologists involved in the study (p=0.0003). Both trained models showed high stability in the segmentation of each pair of predicted grades with low variation in the hazard ratio across 200 bootstrapped samples. These findings indicate that the trained CNNs improve the diagnostic accuracy of the pathologist, standardise LADC subtype recognition, and refine LADC grade assessment. Thus, the trained models are promising tools that may assist in the routine evaluation of LADC subtypes and grades in clinical practice.

Primary pancreatic lymphomas (PPLs) are rare, and the histological classification of these tumors is difficult. To accurately diagnose and determine the appropriate treatment for PPLs, sufficient sample amounts are necessary. Here, we report a 73-year-old man with a primary pancreatic mantle cell lymphoma. Histological samples were obtained via endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA). The tumor cells predominantly composed of atypical small to medium round cells, with diffuse immunoreactivity of CD20 and cyclin D1. In addition, immunoglobulin gene H chain rearrangement was detected. The patient underwent chemotherapy, resulting in complete remission. Eight years after the initiation of chemotherapy, the patient was still alive. EUS-FNA could be a useful and safe diagnostic modality for PPLs by providing enough samples for testing.

Context.— The accurate identification of different lung adenocarcinoma histologic subtypes is important for determining prognosis but can be challenging because of overlaps in the diagnostic features, leading to considerable interobserver variability. Objective.— To provide an overview of the diagnostic agreement for lung adenocarcinoma subtypes among pathologists and to create a ground truth using the clustering approach for downstream computational applications. Design.— Three sets of lung adenocarcinoma histologic images with different evaluation levels (small patches, areas with relatively uniform histology, and whole slide images) were reviewed by 18 international expert lung pathologists. Each image was classified into one or several lung adenocarcinoma subtypes. Results.— Among the 4702 patches of the first set, 1742 (37%) had an overall consensus among all pathologists. The overall Fleiss κ score for the agreement of all subtypes was 0.58. Using cluster analysis, pathologists were hierarchically grouped into 2 clusters, with κ scores of 0.588 and 0.563 in clusters 1 and 2, respectively. Similar results were obtained for the second and third sets, with fair-to-moderate agreements. Patches from the first 2 sets that obtained the consensus of the 18 pathologists were retrieved to form consensus patches and were regarded as the ground truth of lung adenocarcinoma subtypes. Conclusions.— Our observations highlight discrepancies among experts when assessing lung adenocarcinoma subtypes. However, a subsequent number of consensus patches could be retrieved from each cluster, which can be used as ground truth for the downstream computational pathology applications, with minimal influence from interobserver variability.

Background Anomalous systemic arterial supply to the basal segment of the lung (ABLL) is a relatively rare congenital anomaly characterized by aberrant systemic arterial blood flow to the basal segment of the lung. We experienced a rare presentation of ABLL, in which a giant aberrant artery with the same dimensions as that of the descending aorta flowed from the celiac artery to left lower lobe. Case presentation An otherwise healthy 42-year-old man was referred to our department due to an abnormal chest X-ray. Enhanced computed tomography revealed a huge and winding aberrant artery with mural thrombus originating from the celiac artery and perfusing into the left lower lobe. We diagnosed giant ABLL and considered possible concomitant pulmonary arteriovenous fistula. The diameter of the aberrant artery was > 30 mm and high-pressure flow was assumed; therefore, we performed staged resection of the left lower lobectomy including division of the aberrant artery at the pulmonary ligament and subsequent embolization of the remnant arterial flow uneventfully. Pathologically, the aberrant artery was abundant with elastic fibers, and dissections of the tunica media and mural thrombus were observed; however, arteriovenous fistula was not confirmed. At 6 postoperative months, enhanced computed tomography showed the aberrant artery to be completely occluded without any symptoms. Conclusions We present a case of ABLL that was successfully managed by surgical resection of the left lower lobe with most of the giant aberrant artery and subsequent embolization of the remnant portion. Our study demonstrates that a staged surgical therapy is an acceptable approach for ABLL in case of complication with a giant aberrant artery.

Background Heat shock protein 47 (HSP47), a collagen-binding protein, has a specific role in the intracellular processing of procollagen production. HSP47 expression is associated with cancer growth and metastasis in several types of cancers. However, none of the studies have assessed whether HSP47 expression is associated with the risk of postoperative recurrence of lung cancer until now. Therefore, we aimed to assess this association. Methods The study population consisted of a cohort of consecutive patients who underwent surgery for lung cancer at Nagasaki University Hospital, Nagasaki, Japan, from January 2009 to December 2010. Patient characteristics, survival and disease-free survival (DFS), and laboratory findings were compared between patients who tested positive and negative for HSP47 expression in lung cancer cells and between those who showed high and low numbers of HSP47-positive fibroblasts in cancer stroma. Results A total of 133 patients underwent surgery for lung cancer. Sixty-seven patients (50.4%) had HSP47-positive cancer cells, and 91 patients (68.4%) had a higher number of HSP47-positive fibroblasts. The patients with a high number of HSP47-positive fibroblasts had a shorter DFS than those with a low number of HSP47-positive fibroblasts. Multivariate analysis identified only the presence of a high number of HSP47-positive fibroblasts as an independent risk factor for recurrence of lung cancer after surgery (odds ratio, 4.371; 95% confidence interval, 1.054–29.83; P = 0.042). Conclusion The present study demonstrated that the presence of a high number of HSP47-positive fibroblasts in the cancer stroma was a risk factor for recurrence of lung cancer after surgery.

The pathological T descriptor of lung invasive mucinous adenocarcinoma (IMA) is currently defined according to mucin spread, whereas that of lung non-mucinous adenocarcinoma is defined according to invasive lesion. This study aimed to evaluate and compare the prognostic impact of mucin spread, tumor cell spread, and invasive lesion in patients with lung IMA.Twenty-seven patients with completely resected pT1-4N0M0 IMA were evaluated. The radiological size (RS), mucin spread size (MS), tumor cell spread size (TS), and invasive size (IS) of the primary tumors were determined. Cox proportional hazards models were used to estimate recurrence-free survival (RFS). Because the MS, TS, and IS may be mutually confounding factors, they were evaluated using separate multivariate models including potential prognostic factors identified as significant on univariate analyses.The median postoperative follow-up time was 4.9 years. TS and IS were significantly smaller than RS by a median of 0.3 cm (p = 0.027) and 1.4 cm (p 0.0001), whereas MS and RS were not significantly different (p 0.999). Univariate analyses identified T descriptors defined by MS, TS, and IS as potentially negative prognostic factors, in addition to age75 years and carcinoembryonic antigen5 ng/mL. Multivariate analyses revealed that T factors defined by MS, TS, and IS were significant predictors of RFS (p 0.0001, p = 0.0002, and p = 0.0067, respectively).MS is a reasonable determinant of the pathological T descriptor of lung IMA. TS and IS are potential candidates, although they remain discordant with RS. If the TS or IS is to be considered a candidate for the pathological T descriptor of lung IMA, the discordance with RS should first be resolved. If IS is used to define pathological T factor, clear criteria for mucinous AIS/MIA with IMA features should be developed.

Context.—In 2013, the revised American Thoracic Society and European Respiratory Society classification of idiopathic interstitial pneumonias (IIPs) described 2 rare IIPs and 2 rare histologic patterns. Because of the rarity of the disease, there is limited evidence related to the histology. Because the rare histologic patterns are provisional criteria, no unanimous consensus on histologic diagnostic criteria has yet been reached.Objective.—To review the histologic features for rare IIPs and rare histologic patterns, and to provide diagnostic aids and discuss the differential diagnosis.Data Sources.—Published peer-reviewed literature and the authors' personal experience.Conclusions.—Following the publication of the international consensus classification, evidence regarding rare IIPs and rare histologic patterns has accumulated to some extent, although to date the amount remains insufficient and further evidence is required. Because the diagnosis is sometimes challenging, a multidisciplinary approach represents the gold standard in reaching an accurate diagnosis for these rare disorders.

This study aimed to reveal variations in Japanese early childhood education and care (ECEC) centers’ practices and thoughts regarding outdoor play and relationship between the two. A questionnaire was distributed and the answers from 1,659 centers were analyzed. First, it was revealed that the frequency and perceived importance of practice in outdoor environments are different between centers. Some outdoor practices are thought to be important in many centers while others are not. Second, a confirmatory factor analysis showed that centers varied in their practices and the perceived importance of direct or indirect guidance for children in outdoor play although indirect guidance was rated highly in many centers. This means that the varied thinking about outdoor play in Japanese centers can be seen in how they teach physical activities or make use of playgrounds. Third, it was revealed that thoughts about fostering children’s build strength and acquire athletic skills vary between centers and centers focusing on such things had high scores in direct guidance while centers focusing on children’s wonder or interests had low ones. In conclusion, we can consider ECEC’s outdoor play practices and perception together and what centers value is important in discussing the quality of outdoor environments for children’s development.

Introduction Nivolumab has demonstrated efficacy against metastatic NSCLC. Four programmed cell death ligand 1 (PD-L1) immunohistochemistry (IHC) assay systems are available for identification of responders among patients with NSCLC, and these assays show some differing characteristics. Accordingly, in this study, we evaluated the ability of these assays to identify responders to nivolumab therapy. Methods We retrospectively analyzed patients with previously treated advanced NSCLC, who received nivolumab between January 2016 and September 2016. Specimens were stained using four PD-L1 IHC assays (28-8, 22C3, SP142, and SP263). We classified patients as having test results that were strongly positive (tumor proportion score [TPS] ≥50%), weakly positive (TPS 1%–49%), or negative (TPS Results A total of 40 patients with NSCLC and their specimens were analyzed. Analytical comparisons demonstrated good concordance of PD-L1–stained tumor cells among the 28-8, 22C3, and SP263 assays (weighted κ coefficient 0.64–0.71), whereas the SP142 assay showed lower concordance with other assays (weighted κ coefficient 0.39–0.55). Progression-free survival in patients showing strongly positive PD-L1 staining classified by 28-8, 22C3, and SP263 assays was significantly longer than that in patients with a negative result for PD-L1 staining. Predictive performance of response to nivolumab, as assessed by receiver operating characteristic analysis, was also equivalent among the 28-8, 22C3, and SP263 assays (area under the curve 0.75–0.82), whereas the SP142 assay exhibited lower predictive performance (area under the curve 0.68). Conclusions The 28-8, 22C3, and SP263 PD-L1 IHC assays showed equivalent predictive performance, whereas the SP142 assay showed lower predictive performance.

A 67-year-old Japanese man was diagnosed with granulomatosis with polyangiitis based on the presence of right maxillary sinusitis, proteinase 3 antineutrophil cytoplasmic antibody positivity, and right scleritis. A conjunctival biopsy specimen showed neutrophil-predominant infiltration around the vessels without granuloma. Because there was a risk of blindness, pulsed methylprednisolone and intravenous cyclophosphamide pulse therapy (IVCY) were started. However, it was ineffective, and peripheral ulcerative keratitis newly emerged. We promptly switched the treatment from IVCY to rituximab, and ophthalmologists performed amniotic membrane transplantation, which avoided blindness. The close and effective working relationship between physicians and ophthalmologists improved our patient’s ocular prognosis., Internal Medicine57(12), pp.1783-1788; 2018

Selective glucose production by cellulose hydrolysis with initial or sequential water addition in the presence of solid acid catalysts in 1-butyl-3-methyl-imidazolium chloride ([bmIm][Cl]) under microwave irradiation was investigated at 120 °C and 1.2 MPa of N2 atmosphere. For revealing the effect of water on cellulose hydrolysis in [bmIm][Cl], the phase behavior during the reaction was observed. Colored compounds formed at lower amounts of water, while some amounts of cellulose precipitated at higher amounts of water. Glucose yield was highest (65 mol%) at 25 wt% water in [bmIm][Cl] for the case of initial water addition. To improve the glucose yield, sequential water addition in which water was added in steps as the reaction proceeded was examined. Glucose yields in the presence of Amberlyst-15 in [bmIm][Cl] were 68.5 and 75.0 mol% by two-step and three-step water addition, respectively. Employing three-step water addition, Dowex 50wx8-100 (ion-exchange resin), hydrothermally synthesized carbon catalyst and three types of nano-zeolites were assessed. The carbon catalyst-modified fuming sulfuric acid and H-type zeolites (mordenite and faujasite) gave comparable glucose yields as Amberlyst-15. Sequential water addition is an effective technique for improving reaction efficiency in cellulose/solid acid catalyst/ionic liquid reaction systems.

Cosmetic behavior, in which there are make-up, skin care, body painting, bath, shampoo, tooth brushing, combing, haircut, nail care and so on, historically has never broken off. And it is a fact that there is no race in the earth which doesn't have cosmetic behavior. Cosmetic behavior has universality in time and space. Human beings is an animal that can live without cosmetic behavior. What have human beings been seeking for in cosmetic behavior? What have human beings been expressing by it? Through seeing some historical episodes of cosmetical behavior, we know that fast life, which began with modernization, brought us fast beauty. Fast beauty is standardized beauty, youth is indispensable for it. Therefore the immediate effect of keeping and seeking youth is requested from cosmetics. Opposite to fast beauty I suppose slow beauty as the standard value in the next social stage. Slow beauty is diversification of beauty value, expressed “beauty of each person and each age.” The standard of beauty is not in each person but in each age of oneself. Beauty is acquired by everyday accumulation; we can realize different beauty with the accumulation of years. This is true aging.

The aim of the present study was to investigate the differences in postmortem blood biochemistry between fresh-, saltwater drowning and acute myocardial infarction/ischemia (AMI) (n=11, n=15 and n=23, respectively; postmortem interval

The aim of the present study was to review the immunohistochemical and biochemical findings with reference to the causes of death in routine casework (total, n=492). In the immunohistochemistry (n=283), an increase in intra-alveolar granular SP-A (SP-A score) was often observed in asphyxiation (n=21/34, 61.8%) and freshwater drowning (n=15/24, 62.5%), and also in fire and methamphetamine (MA) fatalities (n=22/76, 28.9% and n=5/16, 31.3%). Serum SP-A level (n=134) was elevated in acute respiratory distress syndrome and in some cases of drowning, fire and MA fatalities, hyperthermia and chest traumas. A quantitative analysis of SP-A subclass-gene expression (SP-A1/A2 mRNA) in the lung tissue specimens (n=126) revealed an increase in the SP-A1/A2 mRNA ratio in asphyxiation (n=17/21, 80.9%), freshwater drowning (n=7/9, 77.7%), fire and MA fatalities (n=20/35, 57.1% and n=8/10, 80.0%). These findings suggested the usefulness of SP-A as a marker of asphyxiation, respiratory distress and alveolar injury.

We have investigated postmortem serum CRP levels in 408 forensic autopsy cases consisting of 216 acute and 192 non-acute death cases having postmortem interval of less than 48 h. CRP ranged from 0.03 to 66.13 mg/dl with the median of 0.28 mg/dl. In 362 traumatic death, survival time and the presence of severe infection were the major factors contributing to CRP elevation, while postmortem interval, age, gender, hepatic injury and liver cirrhosis was not. In almost all the immediate deaths (15/16) CRP remained at a low level (

Serum uric acid (UA) and creatinine (Cr) mainly derive from skeletal muscle tissues. Although, remarkable postmortem stability of the serum levels has been reported, there appears to be very poor knowledge of the diagnostic value in investigation of death, except for uremia. The aim of the present study was to evaluate postmortem serum UA and Cr levels using 395 forensic autopsy cases, in comparison with blood urea nitrogen (BUN), for investigation of the pathophysiology of death with special regard to the causes of death involving possible skeletal muscle damage, e.g. due to hypoxia, heat or agonal convulsions. Cr and BUN showed relatively good topographic stability in the cadaveric blood, whereas, UA was often much higher in the right heart blood than in the left heart and peripheral blood, independent of postmortem intervals. Moderate to marked elevation of Cr and BUN accompanied with hyperuricemia was observed in delayed death. In the acute death cases (survival time30 min), UA, especially in the right heart blood, showed a considerable elevation in mechanical asphyxiation and drowning. The Cr level in fire victims with a lower carboxyhemoglobin (COHb) level (60%) was significantly higher than in those with the possible fatal level (60%). A similar elevation of Cr was observed in fatalities from heat stroke and methamphetamine (MA) poisoning. The observations suggested that hyperuricemia in acute death may be indicative of advanced hypoxia and that elevated Cr level may reflect the skeletal muscle damage, especially due to thermal influence.

To evaluate the significance of immunohistochemical staining of ubiquitin (heat shock protein) in the midbrain for the medico-legal diagnosis of fatal asphyxiation and drowning, we investigated forensic autopsy cases of fatal mechanical asphyxia (n = 18), manual/ligature strangulation (n = 9), hanging (n = 4), aspiration/choking (n = 5) and drowning (n = 16). These were compared to control groups (n = 30) consisting of fatalities from brainstem injury (n = 12) and acute myocardial infarction (n = 18). Ubiquitin was clearly demonstrated in the nuclei of pigmented substantia nigra neurons, showing two intranuclear staining patterns: a type of inclusion (possibly Marinesco bodies) and a diffuse staining. The diffuse staining was significantly more frequently observed in cases of drowning. The percentage of total ubiquitin positive neurons was frequently higher in strangulation (5.1– 28.4%, mean 17.0%), aspiration/choking (5.3–32.0%, mean 17.6%) and drowning (7.0–34.1%, mean 19.8%), but relatively low in hanging (5.1–12.7%, mean 8.6%), brainstem injury (0–10.4%, mean 5.0%) and acute myocardial infarction (1.5–16.9%, mean 8.3%). These observations suggest that intranuclear ubiquitin immunoreactivity of the pigmented substantia nigra neurons in the midbrain was induced by a fatal severe stress on the central nervous system in asphyxiation and drowning.

This report describes an autopsy case of a rare type of aortic sinus of Valsalva aneurysm, which caused fatal rupture from a blunt chest impact. A 51-year-old male was hit in the chest with a fist, lost consciousness after about 15 min and died after approximately 7 h. The postmortem examination revealed a large saccular aneurysm of the right coronary sinus bulging on the right atrium, which had a full laceration causing pericardial hematoma (cardiac tamponade). A related chest wall injury was observed in the right outer mammary region. A rare type of bulging onto the right atrium and subsequent sclerosis of the right coronary artery appeared to have greatly contributed to the fatal rupture.

To evaluate pathophysiological significance of post-mortem urinary myoglobin levels in determining the cause of death, we investigated 210 forensic autopsy cases, partially in comparison with serum levels. Post-mortem serum myoglobin levels were extraordinary high in most cases possibly due to post-mortem change. Urinary myoglobin levels did not correlate with the serum levels, showing possible post-mortem elevation in cases of a prolonged post-mortem period over 48h. A high (>1000 ng/ml), moderate (100-1000 ng/ml), slight (50-100 ng/ml) and not significant (

We report a case of self-decapitation by suicidal hanging from a river bridge and discuss the decapitation mechanism, reviewing the literature. The torso and the head of the victim, respectively, were found apart in a river approximately 100 m and 600 m, respectively, downstream from the bridge in two days. Morphological, serological and DNA analyses confirmed their identity. Torn ligaments between the atlas and axis accompanied by fractures in the axis at the partes interarticulares were indicative of a traction force combined with anteroflexion of the head by falling from a height, and the radial pressure due to a strong, single twisted nylon rope with a slip knot was considered to have contributed considerably to the subsequent skin laceration with wavy marginal abrasions. In the reviewed literature, cervical spine fractures were described only in two of six cases, suggesting head movement at the time of decapitation.

Previously, we examined the expression of C-reactive protein (CRP) in hepatic tissues in fatal injuries (injury deaths) immunohistochemically, and classified the CRP distribution into three patterns: diffuse (D-) pattern, diffuse with strong positivity in the hepatic lobules; periportal (PP-) pattern, characterized by positive cells in the periportal region of some lobules; focal (F-) pattern, showing small islands of positive cells in some lobules. There was a relationship between the CRP distribution and the survival time. In this study, we further analyzed the deaths including those due to other than fatal injuries (non-injury deaths), and a study of a total of 314 deaths from various causes was performed. Generally, non-injury deaths showed findings similar to those in injury deaths. PP- and/or F-patterns were observed in 43.7% of cases having a short survival time (6 h), but found in only 3% of those surviving longer (6 h), showing that such findings are suggestive of a short survival time. D-pattern was found more frequently in non-acute deaths (60.4%), than in acute deaths (10.9%). In acute deaths, D-pattern was found in some cases showing extensive tissue injuries, such as burns and polytrauma, and inflammative predisposition. Immunohistochemical findings also showed some correlation with the serum CRP level. Our data suggest that hepatic CRP immunohistochemistry may be a useful tool for elucidating the dying process.

To outline the recent features of child and elderly victims from the medico-legal perspective with special reference to abuse and neglect, a retrospective investigation of forensic autopsy cases over a 5 year period (1994–1998) in the southern half of Osaka city and surrounding areas (a population of 1.57 million) was undertaken. Among 646 autopsy cases, there were 53 child cases (under the age of 15 years, about 80% below 6) and 121 elderly cases (65 years old and above). Nearly half of the child deaths and more than half of the elderly deaths were described as accidental. Fire and traffic victims were much more frequent in the elderly. Child victims included those of neonaticide/infanticide ( n =6), physical abuse ( n =10), unintentional fatal infliction ( n =2), neglect ( n =2), mutual suicide ( n =2), suicide ( n =1) and murder ( n =3). Child abuse and neglect were domestic maltreatment by the parents. In this series, there was a comparable number of fatalities due to maltreatment in the elderly ( n =13) and in children, and non-domestic violence was more frequent in the elderly than domestic violence. Elderly females tended to be battered by their sons or grandsons in domestic violence cases, whereas males were predominantly attacked by younger males in non-domestic violence. The other elderly victims included those of self-neglect ( n =2), murder ( n =7) and suicide ( n =9). Non-domestic homicide of the elderly occurred mainly in the center of the city, whereas domestic maltreatment of children and the elderly was sporadic, although somewhat more frequent in the peripheral zone of the city and the surrounding areas. The above profile of child and elderly abuse suggests a substantial influence of social and familial backgrounds.

To outline the recent features of methamphetamine-related fatalities from the medico-legal point of view, a retrospective investigation of forensic autopsy cases involving methamphetamine during a 5-year period (1994-1998) in the southern half of Osaka city and surrounding areas (about 1.57 million population) was undertaken. Among 646 autopsy cases, methamphetamine was detected in 15 victims (nine males, six females; 16-71 years of age; most frequently in males in their thirties). Primary scenes of fatal events were concentrated in the middle of the city. About half of them were transferred from emergency medical centers (survival time, up to 30 h). The cause and manner of death were: methamphetamine poisoning (n=4), homicide (n=4), accidental falls and aspiration from drug abuse (n=4), fire death (n=1), myocardial infarction (n=1), and cerebral hemorrhage (n=1) under drug influence. Usually injection scars and fresh puncture sites were found. Blood methamphetamine concentrations were 2.29-17.05 micromol/dl in the fatal poisoning, 0. 44-3.80 micromol/dl in deaths from other extrinsic causes (trauma), and 1.35-2.17 micromol/dl in cardio- and cerebrovascular strokes. Common complications were cardiomyopathy, cerebral perivasculitis and liver cirrhosis/interstitial hepatitis. Fatal and nonfatal methamphetamine poisonings are separately dealt with by the administrative medical examiner's office and in emergency medical centers. Tightly cooperative approaches of clinical and medico-legal experts are required for the effective social and medical management of drug abuse.

To establish a method for the routine analysis of carboxyhemoglobin (COHb) in autopsy materials including those which have undergone postmortem changes, e.g. thermo-coagulation, putrifaction and contamination, an automated head-space gas chromatography/mass spectrometry (GC/MS) analysis was utilized. The procedure consisted of preparation of the sample in a vial and a carbon monoxide (CO) saturated sample, for estimation of hemoglobin content, in another vial, the addition of n-octanol, potassium ferricyanide and an internal standard (t-butanol), GC separation and determination of CO using a GC/MS system equipped with an automated head-space gas sampler. The method was practical not only with the blood and bone marrow aspirates to confirm the findings on the CO-oximeter system, but also with the thermo-coagulated and putrified blood.

To reassess the immunohistochemical distribution of pulmonary surfactant apoprotein A (SP-A) in relation to the causes of death, 282 forensic autopsy cases were reviewed. The most intense and dense granular immunostaining of intra-alveolar SP-A was observed in the hyaline membrane syndrome from various traumas, protracted death from drowning, and perinatal aspiration of amniotic fluid. Similar granular staining pattern was found in fatal poisoning by a muscle relaxant and organophosphate pesticides. An evident increase of intra-alveolar granular staining was noted in most fatalities from mechanical asphyxia and drowning, and some cases of fire death. SP-A staining was usually very weak or sparse in alcohol intoxication, poisoning by hypnotics and also carbon monoxide poisoning. These findings suggest that the amount of intra-alveolar granular SP-A staining may be a possible indicator of severity and duration of respiratory distress (agony) from peripheral (non-central nervous system) origin and alveolar damage.

We report a case of sudden death due to cardiac conduction system injury from a blunt chest impact. A 20 year old male, kicked in the precordial region, lost consciousness, and was confirmed dead on arrival at a hospital emergency care unit. According to his friends, they played a golf competition accompanied with a physical punishment. The victim, losing the game, allowed the winner to give him several kicks in the chest. Although well prepared against each kick, he fell down instantaneously after the final impact, and death was confirmed at a hospital. There was no apparent sign of injury on the body surface. At autopsy, there was no evident subcutaneous or intramuscular hemorrhages, rib or sternum fracture. Subendocardial hemorrhage in the region of the atrioventricular node and a contusion extending from the posterior wall of the left ventricle to the upper ventricular septum were observed. Histological examination revealed injury of atrioventricular node and His' bundle. Although the cardiac injury including contusion of the myocardium itself was not so extensive, it was considered that arrhythmia was induced by the cardiac conduction system failure, which was considered to be the cause of death.

We report a case of suspected fatal physical abuse in which the cause of death was proved to be pulmonary embolism. A patient with mental retardation presenting aggressive behavior was admitted to a psychiatric hospital and was treated with major tranquilizers. She suddenly died subsequent to an angina-like attack. For several days before her death, she had been confined to her bed because of very low physical and mental activity. Bruises and abrasions were observed on the extremities, suggesting the recent restraints. There was no positive evidence of physical abuse. At autopsy, the cause of death was elucidated to be pulmonary embolism originating from thrombi in the left popliteal vein. This case indicates the risk of pulmonary embolism in immobilized patients in psychiatric hospitals.

We examined blood samples of 214 forensic autopsy cases, excluding fire victims, on a CO-oximeter system in order to evaluate post-mortem oxymetric profiles with reference to the causes of death. Oxyhemoglobin (O2-Hb) levels in the left and right heart blood, respectively, ranged from 0 to 97.7% and from 0 to 92.1%, showing no apparent correlation with the post-mortem intervals or rectal temperatures. In nearly 60% of the cases, O2-Hb was lower than 10%. A high O2-Hb level (over 50%) in the left heart blood was most frequently observed in death from cold exposure and occasionally in fatalities from blunt injuries and stab/incised wounds with or without medical care. O2-Hb in the heart blood was usually very low (under 10%) in fatalities from asphyxiation, drowning, poisoning and natural diseases. A greatest oxymetric variation was observed in death from injuries, probably due to varied causal mechanisms of death. In most cases, the differences between blood O2-Hb levels in the heart and iliac vessels were within 15%; whereas O2-Hb in the cerebral venous blood was usually evidently higher than that in the right heart blood. An inverse relation of O2-Hb levels to total hemoglobin contents was observed slightly for the blood in the heart and iliac vessels, and more obviously for the cerebral venous blood. The above post-mortem oxymetric profiles were considered to at least partially reflect the final balance of oxygen uptake and consumption in dying process, possibly also affected by the circulatory status, giving an objective index to the color of cadaveric blood (hypostasis), although it should be assessed in consideration of post-mortem interference and total hemoglobin contents. In any case, however, post-mortem oxymetry seemed to have a limited value owing to severe systemic hypoxia which would be a common final state before death from various fatal traumas and diseases, maybe except for those with extremely short agony.

The effects of leptin on insulin secretion from pancreatic islets of Sprague–Dawley rats were examined in vitro. In a basal glucose medium (5.5 mM), insulin secretion from isolated islets was significantly decreased after addition of a recombinant leptin (80 nM) (3.20±0.14 nmol/10 islets/h) compared with that before the addition (4.41±0.30 nmol/10 islets/h). Although significant leptin suppression of insulin secretion was not observed under a glucose-stimulated (11.1 mM) condition, these results suggest that a negative feedback system may exist between leptin and insulin, which increases the production of leptin from adipose tissues.

To investigate whether inheritance or obesity plays a more important role in the development of non-insulin-dependent diabetes mellitus (NIDDM), female Otsuka-Long-Evans-Tokushima Fatty (OLETF) rats, which possess the diabetogenic gene, ODB-1, and Long-Evans-Tokushima-Otsuka (LETO) rats, which have no ODB-1, were compared. Neither strain becomes obese and diabetic when bred ordinarily. Female OLETF rats and male and female LETO rats were assigned to two groups of 20 rats each. Obesity was induced in one group by feeding a high-energy "cafeteria" diet (group D), and the other group was given standard chow (group C). Twenty male OLETF rats were used as NIDDM positive controls. At 25 weeks of age, the mean body weight of group D male LETO and female OLETF rats increased at a rate similar to that of male OLETF rats; female LETO rats did not show increased body weight. The incidence of diabetes mellitus in obese female OLETF rats in group D and positive control male OLETF rats was the same (80%). Only 30% of obese male LETO rats in group D developed diabetes mellitus. The insulin response to intravenous glucose in group D female OLETF rats was the highest for all groups but not sufficient to decrease blood glucose levels. In female OLETF rats, glucose infusion rate (GIR) during a euglycemic-hyperinsulinemic clamp test in group D was decreased to 50% of the group C value and tissue glucose uptake as determined by 3H-glucose infusion was significantly decreased in muscle. In male LETO rats, group D GIR was mildly decreased (80% of group C value) compared with the GIR of female OLETF rats. For obese group D female OLETF rats, abdominal fat increased more with obesity than in their male LETO counterparts. GIR was inversely correlated with the weight of abdominal fat when the data of all groups of animals were combined. The expression of GLUT4 mRNA and its protein level in adipose and muscle tissues and tumor necrosis factor alpha (TNF-alpha) protein in adipose tissue were not significantly different between group D and group C of both strains. In conclusion, the incidence of diabetes in female OLETF rats that possess the diabetogenic gene was significantly greater than in the LETO strains that do not possess the gene, in the presence of excess adiposity.

The mouse obese (ob) gene product (leptin), expressed specifically in adipose cells, regulates energy balance in mice. Both mouse diabetes (db) and rat fatty (fa) gene products are thought to play major roles in leptin signaling pathways in the hypothalamic area. Mutations of these genes in murines result in marked obesity and type II diabetes as part of a syndrome that resembles morbid obesity in humans. Reported herein are the cloning and sequencing of one of spliced variant forms of rat leptin receptor (OB-R) cDNA with a short intracellular domain. In the Zucker (fa/fa) rat, no changes in either the gene structure or the expression levels were observed. However phenotype-linked nucleotide alteration exists in the cDNA from Zucker (fa/fa) rat, which results in an amino acid substitution.

Non-steroidal anti-inflammatory drugs, such as piroxicam and sulindac, are known to inhibit development of aberrant crypt foci (ACF) and cancer in the colon. However, these agents cause gastrointestinal side-effects. Nimesulide is a selective inhibitor of cyclooxygenase 2 and has been shown to have a more potent anti-inflammatory action than piroxicam, but be less ulcerogenic and, therefore, a potentially more useful chemopreventive agent. To assess this possibility the inhibitory effects of nimesulide on the formation of ACF induced by azoxymethane in rat colon were investigated, and compared with those of piroxicam and sulindac. Male F344 rats were treated s.c. with 15 mg/kg body weight azoxymethane once a week for 2 weeks and given 50, 100 or 200 ppm nimesulide, 200 ppm piroxicam, or 200 ppm sulindac in their diet from the day before the first carcinogen treatment until the end of the experiment at week 4. At this time, nimesulide at doses of 50, 100 and 200 ppm had reduced the numbers of azoxymethane-induced ACF to 75%, 71% and 65% respectively compared to the control. The number of azoxymethane-induced ACF per colon in the group given 200 ppm nimesulide was almost the same as in those given 200 ppm piroxicam, and lower than that in the group given 200 ppm sulindac. These results suggest that nimesulide, a selective cyclooxygenase 2 inhibitor, warrants attention as a candidate for chemopreventive agent with low toxicity, active against colon carcinogenesis.

Morphological changes of the pancreas and impairment of pancreatic B-cell function in a model rat (Otsuka Long Evans Tokushima Fatty [OLETF]) with non-insulin dependent diabetes mellitus might be the result of over-activity of B-cells to compensate for insulin insensitivity. To test this possibility, we studied whether the histological and functional alterations in the pancreas of male OLETF rats were improved by treatment with insulin for a certain period, which might reduce the burden to B-cells. Groups of 6 male OLETF rats and 5 or 4 male non-diabetic control Long Evans Tokushima Otsuka (LETO) rats received injections of insulin (Ultralente MC; 10 U/kg/day to OLETF rats, 5 U/kg/day to LETO rats) or saline subcutaneously, once a day for 3 weeks from 24 weeks of age. Then their insulin responses to glucose (200 mg/dl) and arginine (10 mmol/l) were examined by perfusion of the pancreas. The morphological features of their pancreata were also examined. The insulin response to glucose in OLETF rats treated with insulin was significantly higher than that of OLETF rats treated with saline (sigma IRI 142.5 +/- 27.0 vs. 37.4 +/- 6.3 ng/ml.20 min, p < 0.05) and unlike in the latter showed the normal two phases. The morphological changes of the pancreas in the insulin-treated OLETF rats were remarkably ameliorated, animals showing no enlargement and only slight fibrosis of islets. Thus treatment with insulin was effective for preventing B-cell dysfunction and morphological changes of the pancreas in NIDDM model rats.

Exercise training every day has been shown to be effective in preventing the development of non-insulin-dependent diabetes mellitus (NIDDM) in a model rat (Otsuka Long Evans Tokushima Fatty (OLETF)). For determination of whether less vigorous exercise training also has a protective effect against the development of NIDDM in this model, seven male OLETF rats each were assigned to training every other day, every 3 days and every 7 days from 6 to 30 weeks of age. At 30 weeks of age, rats trained every other day, 3 days, 7 days and sedentary rats weighed averages of 547, 548, 603 and 695 g and had abdominal fat deposits of 28, 24, 32 and 72 g, respectively. The mean meterages of running of rats trained every other day, 3 days and 7 days over the whole experimental period were 9630, 5166 and 1685 m/week, respectively. At 30 weeks of age, the cumulative incidence of NIDDM in sedentary rats was 85.7% ( 6 7 ), while none of the trained rats became diabetic except for one of rats trained every 7 days. The glucose infusion rate (GIR), an index of insulin sensitivity, in the group trained every 7 days, 60.6 ± 5.0 μmol · kg−1 · min−1, was significantly greater than that in the sedentary group, 21.7 ± 1.7 μmol · kg−1 · min−1. Morphological studies on the pancreas of rats trained every other day and every 3 days showed minimal changes of islets, whereas sections of islets from rats trained every 7 days appeared enlarged and fibrotic, though significantly less so than the islets of sedentary rats. These results demonstrate that less vigorous exercise, such as once a week, is effective for reducing the incidence of NIDDM in this model.

The firing squad synchronization problem on cellular automata has been studied extensively for more than forty years, and a rich variety of synchronization algorithms have been proposed for two-dimensional cellular arrays. In the present paper, we reconstruct a real-coded transition rule set for an optimum-time synchronization algorithm proposed by Shinahr [11], known as the first optimum-time synchronization algorithm for two-dimensional rectangle arrays. Based on our computer simulation, it is shown that the proposed rule set consists of 28-state, 12849 transition rules and has a validity for the synchronization for any rectangle arrays of size m ×n such that 2 ≤ m, n ≤ 500.

In the present study, to investigate the effect of glucosamine, a component of glycosaminoglycans with a chondroprotective action, on articular cartilage in athletes, we looked at soccer players, who expose their joints to excessive motion and loading, and compared the levels of biomarkers for type II collagen degradation (CTX-II) and type II collagen synthesis (CPII) between soccer players and non-athlete controls, and in soccer players before and after glucosamine-administration. CTX-II (P

Recently, the decline in the use of make-up has stood out. High school girls wearing make-up was seen daily and junior high school girls and even elementary school girls wearing it was not unusual either. Many adults oppose the use of make-up for children and school girls. But there is no guide, no advice, no discussion about it both in school and at home. To advice them and to discuss about it we should have standard of beauty value, but we have no criteria. In this paper we will grasp the current state of girl children and the school girls' make-up and toiletries in Japan with various questionnaires to make proposal of the education of make-up and toiletries. The proposal is based on the ideal beauty value which we should take. This paper is the first step of this plan. The decrease of the make-up beginning age started in the latter half of 1990's. Then it happened the "high school girls' boom". High school girls brought us in our daily life heavy eye make-up, for example mascara and eyebrow make-up, lip gloss, and hair color. High school girls' make-up and beauty expression has spreaded out to other stage, including junior high and elementary girls. A toy maker, which is one of the leading companies in Japan, was the first maker to sell a school girls' own cosmetic bland. It was in 1998. In 2004 "The cosmetic parlor" was open in Shibuya 109-2, in this building there is many fashion brand shops for school girls. Now we can get cosmetics for children and school girls at toy shops, in big discount electrical appliance stores, fancy stationary corner in department stores and super markets. The conscious to make-up of girl children and school girls is the same as it of female adults in Japan. They underestimate their face and body in beauty. Make-up is an indispensable way to live with "normal" body and face for them. Make-up releases Japanese female adults from their faults in beauty, it is the same as girls. This is negative make-up. Not only adults but also girls have fear to have aged. The grasp of the current state of the make-up of girl children and school girls in Japan is the grasp of the issue in beauty culture and beauty value in Japan. So the proposal of education of make-up and toiletries for girl children and the school girls is the proposal of education for all people in our society.

Extracts of Ginkgo biloba (EGB) are a complex product prepared from green leaves of the Ginkgo biloba tree. In the present study, the antidepressant effect of EGB was examined using two behavioral models, the forced swimming test (FST) in rats and tail suspension test (TST) in mice. EGB significantly reduced immobility time in the FST at a dosage of 10 and 50 mg/kg body weight after repeated oral treatment for 14 d, although no change of motor dysfunction was observed with the same dosage in the open field test. These results indicate that EGB might possess an antidepressant activity. In addition, EGB markedly shortened immobility time in the TST after acute inter-peritoneal treatment at a dosage of 50 and 100 mg/kg body weight. The present study clearly demonstrated that EGB exerts an antidepressant effect in these two behavioral models.

Men's Beauty Culture in Japan has more and more popular for these 10years. The genre and the concept "Metrosexual" came in Japan from Western World last year, which has get many sympathy among men and which has become one of the strongest goal of men's smart self -expression in Japan. Will "Metrosexual" release men from the fixed idea of manliness or drive in the competition of appearance, which is goodlooking for goodlooking's sake? For it should not become the latter case, I propose now to men "Slow Beauty" the same as to women. In beauty culture we have the time, when we can face to ourselves. It is precious time in our everyday life. But in the fact beauty culture make us to compare our real body and facial state with the standardized beauty value, which exists out of ourselves. We must look over ourselves in beauty culture, find out what we should be, and express it by our face and body. To do so is necessary for us to live to be ourselves. Without variety of values in our society we cannot realize "Slow Beauty".

In this paper we will make evidently the issue of the modernization of body usage and will try to propose a solution of it. The modernization in Meiji Restoration was westernization and modernization of the structure of society and of our way of life. The modernization requested us standardization of our body and body usage. We have been carried out this in education, march symbolizes it. To solve issues caused by modern value standard it is necessary to realize the new value, which we have proposed in last three papers, that is "The Beauty of Each Person and Each Age", based on "Slow Beauty". In modernization and westernization we successfully introduced material elements but we could get acquired only few body usage. At this result we have double stratum in our body usage, the traditional one and the modern western one. The action of modern Japanese is far from perfect and beautiful in western style clothes, but also in Kimono we don't know how to move our hands and legs. Therefore we can make ourselves conscious making use of this gap between two stratum in our body usage. I have been trying it at one of my university's class for five years. At first, students learn knowledge of Kimono by lecture, aim to learn traditional sense of beauty. After that they learn how to wear and fold up Kimono by using Yukata (a kind of Kimono, which is the most simple and the most informal). And the next they actually move themselves in Yukata, stand-up, sit down, walk, stand still, bow and so on. At last they learn a short peace of Kabuki Dance for two months. Aiming to be beautiful our consciousness of our own action is one way to realize the new value in coming society. I hope that such trial in my university class is spread and many people will do their own action in consciousness on their body usage.