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Background: Radiographic findings may provide clues to the underlying cause of neck symptoms. However, these associations remain controversial. This study investigates the association between roentgenographic findings of the cervical spine and neck symptoms in a Japanese community population., Methods: A total of 762 volunteers participated in this study. Sagittal radiographs of the cervical spine were taken and a questionnaire about the presence of and visual analog scale (VAS) for neck pain or stiff shoulder was completed. The sagittal alignment of the cervical spine (C2-C7) and the degenerative index were measured from lateral aspect radiographs. Three groups based on the sagittal alignment of C2-C7 were defined: straight-spine, lordotic-spine, and kyphotic-spine. The roentgenographic findings were examined in relation to symptoms., Results: The prevalence rate of stiff shoulder on the day of examination was significantly higher in females than males. Although the VAS for neck pain and stiff shoulder on the examination day and for stiff shoulder in the preceding 12 months were not significantly different between females and males, that for neck pain in the preceding 12 months was significantly higher in females than males. Although there was no association between the sagittal alignment of C2-C7 and neck symptoms in males or females, a significant correlation between the degenerative index and VAS for neck pain on the examination day and in the preceding 12 months was seen in females after adjusting for age. The prevalence of and VAS for neck pain and stiff shoulder were not significantly different among the three C2-C7 sagittal alignment groups., Conclusion: Although the sagittal alignment of the cervical spine was not associated with neck symptoms, degenerative changes were associated with the severity of neck pain in females.

Background: Ossification of the posterior longitudinal ligaments (OPLL) causes myelopathy with progression or trauma. Most OPLL patients visit the hospital after severe symptoms occur, and surgery did not supply complete relief in severe symptoms related to OPLL. While it is necessary to diagnose OPLL early and observe carefully, the nature of symptoms and asymptomatic OPLL have been unclear. The purposes of this study were to investigate the prevalence and symptoms of ossification of the posterior longitudinal ligaments (OPLL) of the cervical spine in the general population., Methods: The subjects were 1291 Japanese general residents. Radiographic OPLL was detected by lateral view of the cervical spine, and subjects were classified into OPLL and non-OPLL groups. Visual analog scales of neck stiffness, neck pain, arm pain, and the Japanese Orthopaedic Association Cervical Myelopathy Evaluation Questionnaire were examined. Neck and arm symptoms were compared among the presence of OPLL, and among subtypes (continuous, segmental, and mixed types) statistically., Results: Prevalence of OPLL was 3.7 % in overall participants, 3.9 % in symptomatic participants, and 2.2 % in asymptomatic participants. While 86.7 % of participants with OPLL had symptoms, the consultation rate was only 6.7 %. The female OPLL group had higher neck pain than the non-OPLL group, and neck function of JOACMEQ in the continuous type of OPLL was significantly restricted compared to those without OPLL and with the mixed type of OPLL., Conclusions: Prevalence of OPLL was 3.7 %, and most of them had neck and arm symptoms; however, they did not visit hospitals. Asymptomatic OPLL had the potential risk for spinal cord injury and myelopathy. Early detection and careful observation would prevent the severe symptoms induced by OPLL.

We investigated ascending somatosensory pathways in neonatally hemidecorticated rats. Injection of an anterograde tracer, biotinylated dextran amine (BDA), into the contralesional dorsal root ganglions revealed ipsilateral projections to the dorsal column nuclei (DCN) in hemidecorticated rats as well as in normal rats. Injection of BDA into the DCN on the same side revealed that while most axons projected to the contralateral thalamus, some axons were detected in the ipsilateral thalamus in hemidecorticated rats while such projections were rarely detected in normal rats. The results suggest that aberrant ipsilateral projections of DCN neurons contralateral to the lesion developed after the hemidecortication., (Copyright © 2013 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.)

It is well recognized that a juvenile brain is more plastic than an adult brain and often undergoes better functional recovery following cortical injury. Infants treated with hemispherectomy to cure intractable epilepsy often exhibit restored normal motor function in the extremities contralateral to the lesion. Neuronal mechanisms of functional recovery after such a large cortical damage at a young age have been studied using animals with a similar lesion, hemidecortication. In such animals, descending pathways from the undamaged sensorimotor cortex to the ipsilateral forelimb motoneurons are reorganized as restoring normal motor function of the forelimb contralateral to the injury. Similar aberrant pathways from the motor cortex to the ipsilateral motoneurons are also generated following suppression of cortical activity in the other hemisphere, suggesting the development of contralateral connections in an activity-dependent manner in normal animals. Thus, formation of ipsilateral descending pathways following neonatal hemidecortication might be due to a loss of balance in cortical activity between the two hemispheres. Studies using animal models of neonatal cortical injury can reveal mechanisms of neural development and may help to establish therapeutic strategies to facilitate recovery from human juvenile cortical injury., (Copyright © 2013 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.)

Background: A discrepancy in the incidence of anterior cruciate ligament injury in males and females appears after puberty; however, little is known about changes that occur in control of the lower limbs during jump-landing in adolescents., Methods: Twenty-five male and 29 female 5th grade students (age 10-11 years) participated at the beginning of study and were followed for 5 consecutive years. Control of the lower limbs during jump-landing was evaluated by use of a drop-jump test and 2-dimensional video analysis. The K/H ratio, which was determined by dividing the knee-separation distance by the hip-separation distance, was calculated for initial contact (IC) and for maximum knee flexion (MKF)., Results: In all grades female subjects had a significantly lower K/H ratio at both IC and MKF than male subjects. Although no statistically significant difference in K/H ratio between age categories was shown at either IC or MKF for male subjects, K/H ratio at IC and MKF decreased significantly between 5th grade and 9th grade for female subjects., Conclusion: This study suggests that adolescent females have a lower K/H ratio during jump-landing than male subjects of the same age, and that K/H ratio for females decreases with increasing age.

Frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17) is a neurodegenerative disorder caused by mutations in the tau gene. Many mutations identified in FTDP-17 have been shown to affect tau exon 10 splicing in vitro, which presumably causes pathologic imbalances in exon 10(-) [3-repeat (3R)] and exon 10(+) [4-repeat (4R)] tau expression and leads to intracellular inclusions of hyperphosphorylated tau in patient brains. However, no reports have investigated this theory using model mice with a tau intronic mutation. Herein, we generated new transgenic mice harboring the tau intron 10 +16C → T mutation. We prepared a transgene construct containing intronic sequences required for exon 10 splicing in the longest tau isoform cDNA. Although mice bearing the construct without the intronic mutation showed normal developmental changes of the tau isoform from 3R tau to equal amounts of 3R and 4R tau, mice with the mutation showed much higher levels of 4R tau at the adult stage. 4R tau was selectively recovered in insoluble brain fractions in their old age. Furthermore, these mice displayed abnormal tau phosphorylation, synapse loss and dysfunction, memory impairment, glial activation, tangle formation, and neuronal loss in an age-dependent manner. These findings provide the first evidence in a mouse model that a tau intronic mutation-induced imbalance of 3R and 4R tau could be a cause of tauopathy., (Copyright © 2013 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)

Problem: We studied the influence of adiposis on the progression of blood pressure and arteriosclerosis in the early teens., Methods: The subjects of this study were 147 boys and girls (72 boys and 75 girls) in junior high school. Height, weight, percentage body fat, blood pressure, brachial-ankle pulse wave velocity (baPWV) and exercise time were measured. All subjects were measured at two points--at 5th grade in elementary school (ages between 10 and 11 years) and 2nd grade in junior high school (8th grade, ages between 13 and 14 years). The relationship between the change values of adiposis over 3 years (from 5th grade to 8th grade) and blood pressure/baPWV at the age of 13-14 were analyzed with multiple regression analysis., Results: For boys, the change values in BMI and percentage body fat were correlated positively with systolic blood pressure. For girls, the change values in BMI and percentage body fat were correlated positively with systolic and diastolic blood pressures and baPWV., Conclusions: In conclusion, raised blood pressure was already observed in obese early teens as a result of arteriosclerosis progression regardless exercise habit, and it was more apparent in girls., (© 2012 Asian Oceanian Association for the Study of Obesity. Published by Elsevier Ltd. All rights reserved.)

Background: The purposes of this study were to reveal the prevalence of locomotive syndrome (LS) evaluated by loco-check in the Japanese general population and to analyze the relationship between radiographic knee osteoarthritis (OA) and lumbar spondylosis, metabolic syndrome and LS. Furthermore, we evaluated LS according to functional examinations., Methods: Seven hundred twenty-two volunteers aged 56.6 ± 13.6 years participated in the Iwaki Health Promotion Project in 2010 and were classified into two groups: LS (one or more disabilities) or non-LS (no disability) according to the criteria of LS proposed by the Japanese Orthopaedic Association. Radiographic knee OA and lumbar spondylosis were defined according to the Kellgren-Lawrence grade. Metabolic syndrome was defined as the presence of two or more risk factors in addition to visceral obesity. The prevalence of LS associated with knee OA, lumbar spondylosis and metabolic syndrome was compared statistically. Also, data of six functional examinations were compared between the non-LS and LS groups., Results: The prevalence of LS was 21.2 % in males and 35.6 % in females and increased with aging regardless of gender. The prevalence of LS with knee OA was 48.7 %, with lumbar spondylosis was 33.8 %, and with metabolic syndrome was 43.4 %. The non-LS group had significantly better performance in the functional reach and sit and reach tests than the LS group in males and females by age-adjusted comparison., Conclusion: The prevalence of LS in the general population was higher in females than in males. A strong risk factor for LS was radiographic knee OA. Also, those with LS had loss of skeletal muscle mass, balancing and flexibility. This study showed that evaluation by loco-check was an acceptable tool to detect the early stage of locomotive disability for LS, and interventional prevention for strength, balancing and flexibility would be helpful for those with LS.

Aims: Hypercholesterolemia is known to be a risk factor for Alzheimer's disease (AD), and diet-induced hypercholesterolemia has been shown to accelerate amyloid pathology in animals. While growing evidence has shown that synaptic and cognitive dysfunction in AD is associated with intraneuronal accumulation of Aβ, the relationships between hypercholesterolemia, memory impairment, and intraneuronal Aβ remains unclear. The present study aims to clarify this association., Main Methods: Transgenic mice expressing amyloid precursor protein (APP) harboring the Osaka (E693∆) mutation (APP(OSK)-Tg mice) were used. These mice exhibit intraneuronal Aβ oligomers and memory impairment from 8months of age. Five-month-old male APP(OSK)-Tg mice and non-Tg littermates were fed a high-cholesterol diet for 1 month to induce hypercholesterolemia. At 6 months of age, their cognitive function was evaluated by the Morris water maze. Intraneuronal Aβ, synaptic density, and tau phosphorylation were examined by immunohistochemistry., Key Findings: Serum and brain cholesterol levels were significantly higher in APP(OSK)-Tg mice and non-Tg littermates that were fed a high-cholesterol diet than in control mice that were fed normal chow, indicating that hypercholesterolemia was successfully induced. Hypercholesterolemic APP(OSK)-Tg mice, but not control APP(OSK)-Tg mice or hypercholesterolemic non-Tg littermates, exhibited impaired spatial reference memory, which was accompanied with intraneuronal accumulation of Aβ oligomers, reduced synaptophysin immunoreactivity, and abnormal tau phosphorylation in the hippocampus. Hypercholesterolemia-accelerated accumulation of intraneuronal Aβ oligomers was also observed in another model mouse, Tg2576., Significance: Our findings suggest that hypercholesterolemia accelerates intraneuronal accumulation of Aβ oligomers and subsequent synapse loss, resulting in memory impairment., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Infected aortic aneurysm and inflammatory aortic aneurysm each account for a minor fraction of the total incidence of aortic aneurysm and are associated with periaortic inflammation. Despite the similarity, infected aortic aneurysm generally shows a more rapid change in clinical condition, leading to a fatal outcome; in addition, delayed diagnosis and misuse of corticosteroid or immunosuppressing drugs may lead to uncontrolled growth of microorganisms. Therefore, it is mandatory that detection of aortic aneurysm is followed by accurate differential diagnosis. In general, infected aortic aneurysm appears usually as a saccular form aneurysm with nodularity, irregular configuration; however, the differential diagnosis may not be easy sometimes for the following reasons: (1) symptoms, such as abdominal and/or back pain and fever, and blood test abnormalities, such as elevated C-reactive protein and enhanced erythrocyte sedimentation rate, are common in infected aortic aneurysm, but they are not found infrequently in inflammatory aortic aneurysm; (2) some inflammatory aortic aneurysms are immunoglobulin (Ig) G4-related, but not all of them; (3) the prevalence of IgG4 positivity in infected aortic aneurysm has not been well investigated; (4) enhanced uptake of 18F-fluorodeoxyglucose (FDG) by 18F-FDG-positron emission tomography may not distinguish between inflammation mediated by autoimmunity and that mediated by microorganism infection. Here we discuss the characteristics of these two forms of aortic aneurysm and the points of which we have to be aware before reaching a final diagnosis., (Copyright © 2011 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.)

Background: The objectives of this study were to investigate the prevalence rate of metabolic syndrome (MetS) among knee osteoarthritis (OA) patients in the Japanese general population, and to analyze the relationship between MetS and knee OA., Methods: A total of 795 volunteers participated in this study. Based on the Kellgren-Lawrence (K-L) grade, participants were classified into two groups: the non-knee OA (non-KOA) group (K-L grade 0 or 1) or knee OA (KOA) group (grade 2-4). MetS was defined according to the Japanese Committee for the Diagnostic Criteria of MetS with a slight modification. The presence of hyperlipidemia, hypertension, diabetes mellitus and MetS were compared between the non-KOA and KOA groups. Furthermore, risk factors for MetS were analyzed by logistic regression analysis., Results: The prevalence rate of hypertension in the KOA group was significantly higher than in the non-KOA group (P = 0.025) in males. Those of hypertension (P < 0.001), hyperlipidemia (P < 0.001) and diabetes mellitus (P = 0.019) in the KOA group were significantly higher than in the non-KOA group in females. Aging was significantly associated with MetS in males; the odds ratio (OR) for age was 1.033 (P = 0.020), suggesting that a 1-year increase in age raised the risk of MetS. In females, the presence of KOA was significantly associated with MetS; the risk of MetS in the KOA group was 2.196 (P = 0.034) fold the risk in the non-KOA group., Conclusion: The prevalence rates of MetS and knee OA tended to increase with age in males; however, there was no association between MetS and knee OA. On the other hand, knee OA was significantly associated with MetS in females. Knee OA patients must be provided the best treatment approach because of their high risk for MetS, which promotes cardiovascular diseases.

Objective: The notion that late evening meal promotes weight gain is popular, and it may also elicit postprandial hyperglycemia, since glucose tolerance decreases during midnight. Diabetic patients with night-eating symptoms, compared with patients without night-eating behaviors, are more likely to be obese and to have elevated A1c. However, epidemiological analysis adjusted for difference in total energy intake did not identify nighttime eating as the risk of obesity. The present study evaluated the effect of a single loading of late evening meal on diurnal variation of blood glucose and 24-h energy expenditure., Methods: Ten young adults stayed twice in a room-size respiratory chamber for 24 h, in a randomized repeated-measures design. After the entrance to the chamber at 1700 h, the subjects took normal (1900 h) or late (2230 h) evening meal, breakfast and lunch, and remained in the chamber until 1700 h. Time course of blood glucose was measured by continuous glucose monitoring system., Results: Late evening meal enhanced postprandial blood glucose response to the evening meal and the subsequent breakfast. Overall 24 h average blood glucose level was also elevated by late evening meal. Late evening meal shifted postprandial increase in energy expenditure toward late at night, but overall 24 h energy expenditure remained almost identical in the two dietary conditions., Conclusions: The present study under controlled sedentary condition supports the notion that a single loading of late evening meal enhances average blood glucose over 24 h, but does not support that late evening meal reduces 24 h energy expenditure., (© 2011 Asian Oceanian Association for the Study of Obesity . Published by Elsevier Ltd. All rights reserved.)

Objective: The Clock Drawing Test (CDT) is commonly used for cognitive screening, but there are few studies that compare performance on the CDT among schizophrenic patients of different ages. The objective of this study was to investigate the influence of schizophrenia and aging on performance in the CDT., Method: Schizophrenic patients (N = 244) and a comparison group (N = 875) were recruited as subjects. Freedman's CDT was completed by all subjects, and the influences of disease and aging on performance in the CDT were examined. Multiple comparisons of the CDT scores between patients and the comparison group and within three age subgroups (young: less than 40 years, middle aged: 40-59 years, elderly: more than 60 years) were performed., Results: There was a significant interaction of diagnosis and age, and the education significantly influenced the total score for all CDT conditions. For almost all age subgroups of patients, individuals with schizophrenia had significantly lower scores on all the CDT conditions than did the comparison group subjects. For patients and the comparison group, the elderly subgroup performed significantly worse than the young and middle-aged subgroups on almost all conditions of the CDT. Qualitative analysis of the clocks drawn revealed that the number of CDT categories in which schizophrenic patients scored significantly lower than the comparison group tended to increase with aging across both groups., Conclusions: This study suggests that performance on the CDT was impaired not only by disease but also by aging. The study confirms that the CDT is sensitive enough to screen for cognitive impairments in schizophrenia.

Carbazole 1,9a-dioxygenase (CARDO) consists of terminal oxygenase (Oxy), ferredoxin (Fd), and ferredoxin reductase (Red) components and is a member of the Rieske nonheme iron oxygenases. Rieske nonheme iron oxygenases are divided into five subclasses (IA, IB, IIA, IIB, and III) based on the number of constituents and the nature of their redox centers. Each component of a class IIB CARDO from Nocardioides aromaticivorans IC177 was purified, and the interchangeability of the electron transfer reactions with each component from the class III CARDOs was investigated. Despite the fact that the Fds of both classes are Rieske-type, strict specificities between the Oxy and Fd components were observed. On the other hand, the Fd and Red components were interchangeable, even though the Red components differ in cofactor composition; the class IIB Red contains flavin-adenine-dinucleotide (FAD)- and NADH-binding domains, whereas the class III Red has a chloroplast-type [2Fe-2S] cluster in addition to the FAD- and NADH-binding domains. The crystal structures of the class IIB Oxy and Fd components were compared to the previously reported Fd:Oxy complex structure of class III CARDO. This comparison suggested residues in common between class IIB and class III CARDOs that are important for interactions between Fd and Oxy. In the class IIB CARDOs, these included His75 and Glu71 in Fd and Lys20 and Glu357 in Oxy for electrostatic interactions, and Phe74 and Pro90 in Fd and Trp21, Leu359, and Val367 in Oxy for hydrophobic interactions. The residues that formed the interacting surface but were not conserved between classes were thought to be necessary to form the appropriate geometry and to determine electron transfer specificity between Fd and Oxy.

Objectives: The prevalence of cigarette smoking among Japanese men has been consistently high compared with males in Western countries over the past 30 years. However, during the same period, the incidence and mortality rates for lung cancer have been consistently lower in Japan than in Western countries, which has been termed the 'Japanese smoking paradox'. The odds ratio/relative risk of cigarette smoking for lung cancer mortality and incidence for the same number of cigarettes smoked per capita in Japan have been lower than those in Western countries. This difference in the odds ratio/relative risk is likely to be the main reason for the Japanese smoking paradox. The aim of this study was to clarify the reason for the difference in the odds ratio/relative risk between Japan and the USA., Study Design: Literature review to compare environmental, hereditary and other factors that may be related to lung cancer in Japan and the USA., Results and Conclusions: The main factors likely to have brought about the difference in the odds ratio/relative risk between Japan and the USA (and perhaps other Western countries as well) are: lower alcohol consumption by Japanese males; lower fat intake by Japanese males; higher efficiency of filters on Japanese cigarettes; lower levels of carcinogenic ingredients in Japanese cigarettes; and lung-cancer-resistant hereditary factors among Japanese males.

Background: The present study was undertaken to examine whether antibiotic-impregnated calcium phosphate cement (CPC) would provide a valid means of treating osteomyelitis., Methods: The antibiotic used for the impregnation was dideoxy-kanamycin B (DKB), which is available in two forms (powder and liquid). Columnar test specimens (diameter 7 mm, height 14 mm) were prepared by adding the liquid or powdered DKB. Group A: Three types (6.25-titer, 12.5-titer, 25-titer) of test specimen were prepared by mixing the setting solution and DKB solutions into cement. Group B: Three types (25-titer, 50-titer, 100-titer) of test specimen were prepared by mixing the setting solution and DKB powder into cement. Group C: A control specimen was prepared by mixing the setting solution into the cement. The study included a consistency test, setting-time test, compressive strength test, porosity test, and elution test., Results: The value for the consistency test was >23 mm in all test groups. The results of the setting-time test showed that the setting time became significantly longer as the DKB content increased for groups A group B. Compressive strength decreased as the antibiotic content increased, although all specimens remained sufficiently strong for clinical application. In group A the porosity did not differ significantly depending on the antibiotic content, whereas in group B the porosity increased significantly as the antibiotic content increased. In the elution test using specimens with the same titer (25 titer), the elution efficiency was higher in group A than in group B, and the duration of elution was longer in group A., Conclusions: Although polymethylmethacrylate (PMMA) has been conventionally used as a drug-delivery system (DDS), the results of the present study indicate that CPC shows better elution efficiency than PMMA. It is thus a promising DDS for the treatment of osteomyelitis.

This study investigated the usefulness of perfusion computed tomography (CT) for the evaluation of patients with chronic internal carotid artery (ICA) occlusion by comparing the findings with those of iodine-123 iodoamphetamine ([(123)I]IMP) single photon emission computed tomography (SPECT). Twenty five patients with chronic ICA occlusion were investigated on the same day by perfusion CT to measure the cerebral blood flow (CBF), cerebral blood volume (CBV), and mean transient time (MTT), and [(123)I]IMP SPECT to measure the regional CBF, significant correlations were observed between regional CBF measured by SPECT and CBF measured by perfusion CT (r = 0.659, R(2) = 0.434, p < 0.001), regional CBF and CBV (r = -0.406, R(2) = 0.165, p < 0.001) and regional CBF and MTT (r = -0.592, R(2) = 0.350, p < 0.001). Significant correlations were also observed between CBF and CBV (r = -0.153, R(2) = 0.023, p < 0.001), CBF and MTT (r = -0.580, R(2) = 0.337, p < 0.001) and MTT and CBV (r = 0.763, R(2) = 0.582, p < 0.001). Perfusion CT is useful to evaluate the hemodynamic state of patients with chronic major cerebral artery occlusive disorders.

Doxorubicin and ifosfamide are the two most active agents used to treat soft tissue sarcomas. However, because of their overlapping side effects, concurrent administration to achieve optimal doses of each agent is difficult. We therefore conducted a Phase II trial to investigate the efficacy and feasibility of a novel alternating sequential chemotherapy regimen consisting of high dose ifosfamide and doxorubicin/cyclophosphamide in advanced adult non-small round cell soft tissue sarcomas. Adult patients with non-small round cell soft tissue sarcomas were enrolled. The treatment consisted of four sequential courses of chemotherapy that was planned for every 3 weeks. Cycles 1 and 3 consisted of ifosfamide (14 g/m(2)), and cycles 2 and 4 consisted of doxorubicin (60 mg/m(2)) and cyclophosphamide (1200 mg/m(2)). Forty-two patients (median age 47 years) were enrolled. Of the 36 assessable patients, 1 complete response and 16 partial responses were observed, for a response rate of 47.2%. Responses were observed in 57% of patients who had received no previous chemotherapy and 13% of those who had previously undergone chemotherapy. Grade 3-4 neutropenia was observed during 70% of all cycles. Sequential administration of high-dose ifosfamide and doxorubicin/cyclophosphamide has promising activity with manageable side effects in patients with advanced adult non-small round cell soft tissue sarcomas.

In the slug stage of the cellular slime mold Dictyostelium discoideum, prespore cells and four types of prestalk cells show a well-defined spatial distribution in a migrating slug. We have developed a continuous mathematical model for the distribution pattern of these cell types based on the balance of force in individual cells. In the model, cell types are assumed to have different properties in cell motility, i.e. different motive force, the rate of resistance against cell movement, and diffusion coefficient. Analysis of the stationary solution of the model shows that combination of these parameters and slug speed determines the three-dimensional shape of a slug and cell distribution pattern within it. Based on experimental data of slug motive force and velocity measurements, appropriate sets of parameters were chosen so that the cell-type distribution at stationary state matches the distribution in real slugs. With these parameters, we performed numerical calculation of the model in two-dimensional space using a moving particle method. The results reproduced many of the basic features of slug morphogenesis, i.e. cell sorting, translocation of the prestalk region, elongation of the slug, and its steady migration.

An anterolateral thigh flap is very useful in head and neck reconstruction because of its long and large-caliber vascular pedicle, large skin territory and elevation simultaneous with tumour resection. However, the number and locations of cutaneous perforators vary individually, and thus, it is not widely used because flap elevation is often complicated and time-consuming owing to unexpected anatomical variations. To overcome this disadvantage, we assessed the number and locations of cutaneous perforators preoperatively by colour Doppler flowmetry. These data were compared with the intraoperative anatomical findings and their reliability evaluated. A total of 48 cutaneous perforators were found by preoperative colour Doppler flowmetry scanning of 17 anterolateral thigh flaps. All the perforators except two were found intraoperatively. Doppler scanning failed to detect four perforators. Colour Doppler flowmetry assessment therefore has a 92% true-positive rate and a 95.8% positive predictive value. All the flaps except one included multiple perforators, and sufficient blood circulation was observed in all cases. No flaps were unexpectedly changed to anteromedial thigh flaps or contralateral anterolateral thigh flaps because of inappropriate cutaneous perforators or the absence of perforators. Though this investigation is relatively time-consuming (30-40 min) and requires skill, it is very useful for preoperative flap planning and increases the reliability and safety of elevating an anterolateral thigh flap.

After aggregation by chemotaxis, cells of the cellular slime mold Dictyostelium discoideum form a multicellular structure and show coherent motion such as vortices. Here, we present a mathematical model to explain both aggregation and coherent motion of cells in two-dimensional space. The model incorporates chemotactic response of cells and the cell's property, called "contact following", to follow the other cells with which they are in contact. Analytical study and computer simulation using the model show that with contact following, cells form circular clusters within which cell rotation occurs. Unidirectional cell motion in a long belt of cells is another type of solution of the model. Besides, contact following has an effect to accelerate cell cluster merging. By considering the mechanism of cell movement, possible explanations of contact following are proposed.

Background and Purpose: Velocity-coded colour magnetic resonance angiography (VCCMRA) and perfusion magnetic resonance imaging (pMRI) were evaluated as methods for investigating the efficacy of extracranial-to-intracranial arterial bypass (EC-IC bypass) by comparing the findings of VCCMRA and those of cerebral angiography and by measuring the improvement ratio after EC-IC bypass by pMRI compared to that by single photon emission computed tomography (SPECT) using the autoradiographic technique., Methods: Thirteen patients who underwent VCCMRA, angiography, SPECT, and pMRI before and after surgery were analyzed. Findings of VCCMRA were compared to those of angiography. Improvement ratio was calculated compared to the cerebellum for cerebral blood volume, mean transit time (MTT), and regional cerebral blood flow (rCBF) as measured by pMRI and quantitative SPECT., Results: Findings of VCCMRA were in good agreement with those of angiography and clearly showed the direction of bypass flow. No statistically significant correlation was observed between the improvement ratios in CBF in the hemisphere and middle cerebral artery territory on the surgical and non-surgical sides and in rCBF in the same regions of interest (ROIs) (r=-0.574, 0.09). However, a statistically significant correlation was observed between the cerebrovascular reserve capacity (CVRC) in the hemisphere on the surgical side and in MTT in the same ROIs (r=0.955, P<0.001)., Conclusion: VCCMRA may clearly show the direction of flow in the EC-IC bypass. MIT measured by pMRI may indicate the postoperative state of CVRC. These techniques could replace angiography and positron emission tomography or SPECT in patients undergoing EC-IC bypass.

The potential risks to human health and reproduction from the xenoestrogen bisphenol A (BPA) have not been well established. This is due in part to the absence of accurate analytical methods to quantify BPA in biological samples. In this study we establish an accurate, sensitive and selective analytical method for the quantification of BPA in human semen. To quantify BPA we compared the techniques of liquid chromatography-mass spectrometry (LC-MS) and enzyme-linked immunosorbent assay (ELISA). In addition we have taken steps to eliminate BPA contamination during sample extraction and preparation. Results show that the ELISA method gives an over-estimate of BPA concentration, which may be due, at least in part, to non-specific interactions with the BPA-antibodies. LC-MS gave much more accurate results and proved to be more sensitive with a detection limit of 0.5 ng ml(-1) compared to 2.0 ng ml(-1) by ELISA.

The formation and maintenance of synaptic connections are critical in the development and plasticity of the central nervous system (CNS). Until recently, there have been few studies that followed the molecular sequences of the CNS synapse formation and maintenance. This situation changed dramatically after the introduction of green fluorescent protein (GFP)-based fluorescent probes and the development of lipophilic tracers of endocytotic membranes. These techniques enabled us to visualize presynaptic and postsynaptic structures in living neurons and illustrated active transport and remodeling of synaptic components. Furthermore, recent attempts to identify correlation between presynaptic and postsynaptic morphogenesis suggested very rapid time course of synapse formation at the individual axo-dendritic contact sites. These recent works clearly demonstrated the power of real-time imaging studies. Development of a wide variety of fluorescent probes and advances in the imaging techniques in future will further extend our knowledge on the molecular events that take place in the process of the development and maturation of synaptic junctions.

We investigated the relation between coffee drinking and serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) concentrations among 7313 Japanese men receiving a health examination, excluding former alcohol drinkers and men with a history of chronic liver disease. Serum AST > 40 and/or ALT > 40 U/L was defined as liver inflammation. Adjustment was made for alcohol use, smoking, body mass index, serum marker for hepatitis virus infection, and other possible confounders. Adjusted odds ratios of liver inflammation were 1.00 (reference), 0.80, 0.69, and 0.61 for men drinking < 1, 1-2, 3-4, and > or = 5 cups of coffee daily, respectively. Among 6898 men without liver inflammation, serum AST and ALT were inversely associated with coffee consumption, and alcohol-related rise in AST was attenuated with coffee drinking. These findings suggest coffee may have an effect of suppressing the rise of serum aminotransferase, partly by inhibiting the alcohol-related elevation. Studies regarding biological mechanism are warranted.

Multidimensional HPLC systems with coupled anion-exchange, cation-exchange, and reversed-phase columns, and ultraviolet and electrochemical detectors were developed for the determination of cefmatilen and its seven metabolites in the plasma and urine of humans and animals. These target compounds with a wide range of polarities were efficiently separated and determined by HPLC assay methods with simple pretreatments, deproteinization of plasma and dilution of urine. The assay methods showed good linearity, precision and accuracy. The methods were successfully applied to pharmacokinetic and metabolic studies of cefmatilen hydrochloride hydrate administered orally to humans and animals.

Three olean-12-ene type triterpenoid saponins, named TR-saponins A, B and C, were isolated as methyl esters from tea roots (Camellia sinesis var. assamica) after treatment with diazomethane. Their structures were established as the methyl esters of 3-O-alpha-L-arabinopyranosyl (1-->3)-beta-D-glucuronopyranosyl-21, 22-di-O-angeloyl-R1-barrigenol-23-oic acid, 3-O-alpha-L-arabinopyranosyl (1-->3)-beta-D-glucuronopyranosyl-21-O-angeloyl-22-O-2-me thylbutanoyl-R1- barrigenol-23-oic acid and 3-O-alpha-L-arabinopyranosyl (1-->3)-beta-D-glucuronopyranosyl-16 alpha-O-acetyl-21-O-angeloyl-22-O-2-methylbutanoyl-R1-bar rigenol-23-oic acid, by extensive 1D and 2D-NMR as well as FABMS and HR-MS analyses.

The prognosis for malignant pelvic bone tumors is worse than that for malignant bone tumors of the extremities because definitive surgery in the pelvis is often difficult to accomplish. The results for eight patients who were treated consecutively with a multidisciplinary approach, from 1990, were analyzed. The histologic diagnosis was osteosarcoma in five patients, chondrosarcoma in two, and Ewing's sarcoma in one. Five lesions arose in the ilium and three in the pubis. The extraosseous tumors decreased in size and/or were encapsulated as a result of preoperative chemotherapy in six patients, four of these achieving a wide surgical margin. With respect to tumor location and surgical margin, all five lesions in the ilium involved the sacrum, four of these being resected with an inadequate margin. The three lesions in the pubis were resected with an adequate margin. Local recurrence was observed in two patients who had been treated with an inappropriate margin. During the period between 18 and 57 months after the first operation, five patients were continuously free of disease and one was still alive but had lung metastases. Our results indicate that a patient's chances of definitive surgery may be enhanced by a multidisciplinary approach, although the management of sacroiliac involvement remains challenging.

The migration of Langerhans cells is an initial event in the sensitization phase of contact sensitivity. Langerhans cells travel from the epidermis to the regional lymph node, and can be variously modulated in the skin where many cytokines are released from epidermal cells, dermal cells, T helper (Th) cells, and other inflammatory cells during the sensitization and elicitation phase of contact dermatitis, and thus induce an altered inflammatory skin reaction. The modulatory effect of the cytokines released in the skin, such as IL-1beta, GM-CSF, and TNF-alpha as epidermal cytokines, IL-2, IL-12, and IFN-gamma as Th1 type cytokines, and IL-4 and IL-10 as Th2 type cytokines, was analyzed using the chemotactic chamber method in this study. Both GM-CSF and TNF-alpha induced the migration of human Langerhans cells in vitro, whereas IL-1beta, IL-2, IL-10, IL-12, and IFN-gamma had no effect on Langerhans cell migration. In contrast, IL-4 inhibited Langerhans cell migration in a dose dependent manner. The inhibitory activity of IL-4 was reversed by both anti-human IL-4 monoclonal antibody and anti-human IL-4 receptor monoclonal antibody. IL-4 inhibited the Langerhans cell migration induced by both TNF-alpha and GM-CSF. Furthermore, anti-TNF-RII monoclonal antibody inhibited both random migration and the migration induced by TNF-alpha, but not that induced by GM-CSF. A reverse-transcriptase-polymerase chain reaction and fluorescence-activated cell sorter analysis revealed that TNF-alpha up-regulated and IL-4 downregulated the TNF receptor II (TNF-RII) expression of Langerhans cells at both the mRNA and the protein levels. The pretreatment of Langerhans cells with TNF-alpha enhanced the migration of Langerhans cells and the expression of TNF-RII. After pretreating Langerhans cells with TNF-alpha, IL-4 inhibited both the migration of Langerhans cells and the expression of TNF-RII in a time dependent manner. These results indicate that IL-4 inhibits the migratory activity of Langerhans cells by downregulating the expression of TNF-RII in human Langerhans cells and thereby modulates the immune response in the skin.

Purpose: To examine the effect of coffee drinking on serum gamma-glutamyltransferase (GGT) level in relation to alcohol drinking, smoking, and degree of obesity in middle-aged Japanese men., Methods: From 1986 to 1994, a total of 7,637 male officials of the Self-Defense Forces of Japan aged 48-59 years received a preretirement health examination. Coffee drinking was ascertained by a self-administered questionnaire, and serum GGT level was measured. After excluding 1,360 men with a possible pathologic condition influencing liver enzyme levels and 182 former alcohol drinkers, effect of coffee drinking on serum GGT was examined by a multiple linear regression model and analysis of variance adjusting for alcohol drinking, smoking, and body mass index (BMI)., Results: The adjusted percentage of difference in serum GGT was -4.3 (95% CI = -5.0; -3.5) per cup of coffee. The inverse coffee-GGT relation was most prominent among men drinking > or = 30 ml of ethanol and smoking > or = 15 cigarettes daily; and positive associations of alcohol and smoking with GGT were attenuated by coffee drinking, more clearly among men with BMI > or = 25.00 kg/m2. Adjusted percentages of difference in serum GGT were -2.6% (p = 0.0003) per cup of brewed coffee, and -5.1% (p = 0.0001) per cup of instant coffee, independently of each other., Conclusions: The present study suggests that coffee consumption may weaken GGT-induction by alcohol, and possibly by smoking. These effect modifications by coffee may differ according to the degree of obesity.

Direct injection high-performance liquid chromatographic (HPLC) methods with column switching and UV detection were developed for the rapid and accurate determination of S-1090 in human plasma and urine. An internal-surface reversed-phase pre-column and a C18 analytical column were used for the plasma assay. Two pre-columns packed with cyano and phenyl materials and a C18 analytical column were used for the urine assay. The calibration curves for plasma and urine assays were linear in the ranges 0.09-9 microg/ml and 0.5-100 microg/ml of S-1090, respectively. The relative standard deviations for plasma and urine assays were less than 6% with low relative errors. The established HPLC methods were demonstrated to be useful for clinical pharmacokinetic studies after oral administration of S-1090.

The effects of leucine- and methionine-enkephalin, opiate peptides, on Ca2+ efflux from cultured bovine adrenal chromaffin cells were examined. These enkephalins stimulated the efflux of 45Ca2+ from cells in a concentration-dependent manner (10(-8) M-10(-6) M). Leucine-enkephalin did not increase the intracellular free Ca2+ level, 45Ca2+ uptake, catecholamine secretion, cAMP level or cGMP level. The peptide-stimulated 45Ca2+ efflux was not inhibited by incubation in Ca2+-free medium, but was inhibited by incubation in Na+-free medium. These results indicate that enkephalins stimulate extracellular Na+-dependent 45Ca2+ efflux from cultured bovine adrenal chromaffin cells, probably by stimulating membrane Na+/Ca2+ exchange.

A new method was developed for the determination of 7alpha-hydroxycholesterol (7-HC) in dog plasma by means of high-performance liquid chromatography (HPLC) with fluorescence detection. 7-HC extracted with organic solvent from plasma was purified with Bond Elut 2OH and converted to a sensitive fluorescent derivative containing double coumarin groups at the C-3 and C-7 positions of the steroid nucleus with 7-methoxycoumarin-3-carbonyl azide. After removal of the excess reagent with Bond Elut NH2, the 7-HC derivative was separated by reverse-phase HPLC method. The detection limit of the authentic 7-HC-3,7-coumarin derivative was 4 pg (S/N = 5), approximately four times less than that of the 7-HC-3-anthroyl derivative yielded by reaction of 7-HC with 1-anthroylcyanide. The newly developed method was used to investigate the effects of consecutive oral administrations of cholestyramine (CA) on 7-HC levels in dog plasma. The plasma 7-HC levels of the CA-treated group were two times greater than those of the control group., (Copyright 1998 Academic Press.)

A nonradioisotopic method has been developed for the determination of all-trans-farnesyl pyrophosphate (FPP), the common intermediate at the branch point of the biosynthesis of cholesterol and nonsterol end products, in dog and human plasma. FPP was cleaved to the parent alcohol, farnesol, by the direct addition of alkaline phosphatase to plasma. Farnesol extracted from plasma was converted into a fluorescent derivative with 9-anthroylcyanide. After the excess reagent was removed using an NH2-bonded phase cartridge, the derivative was separated by a column-switching high-performance liquid chromatographic system, followed by fluorescence detection. A linear response was obtained over the range of 2-18 ng/ml, when FPP was added to dog plasma in which the endogenous FPP concentrations had been lowered to undetectable levels by treatment with an HMG-CoA reductase inhibitor. The endogenous plasma FPP levels in the morning in dog and human detected for the first time by our method were 5.2 and 6.6 ng/ml, respectively. The method was utilized to examine the circadian rhythm of FPP in dog plasma, and different rhythms were observed between feeding and fasting dogs.

Colonies of bacteria, Bacillus subtilis, that grow on the surface of thin agar plates show various morphological patterns in response to environmental conditions, such as the nutrient concentration, the solidity of an agar medium and temperature. For instance, the colony pattern shows a dense-branching morphology with a smooth circular envelope (DBM-like) in a nutrient-poor semi-solid agar medium, and it turns to a simple disk-like colony as both the nutrient concentration and the agar's softness increase. These patterns have been shown to involve cell movement inside colonies. In a DBM-like colony, individual cells actively move, particularly in the expanding periphery of the colony, while they become immotile at the inner region of the colony where nutrient is very low. In a disk-like colony, cells are highly active in the whole region of the colony. Based on such experimental observations, we develop a diffusion-reaction model, in which density dependent cell movements are incorporated by the level of nutrient concentration available for the cell. Numerical simulations of the model under different environmental conditions closely reproduce various colony patterns ranging from DBM-like pattern to the homogeneous disk-like one in a unifying manner. The analysis also predicts the growth velocity of a colony as a function of the nutrient concentration., (Copyright 1997 Academic Press Limited.)

An achiral/chiral coupled high-performance liquid chromatographic method with electrochemical detection was developed for the determination of the enantiomers of a new dihydropyridine calcium blocker, methyl (+-)-4,7-dihydro-3-isobutyl-6-methyl-4-(3-nitrophenyl)- thieno[2,3-b]pyridine-5-carboxylate (1), in dog plasma. The assay showed linearity over the range 1-200 ng/mL for the two enantiomers. The limit of determination was 1 ng/mL for each analyte. The assay precision was < 9%, with relative errors of -5.7 to +6.9% at 3 and 30 ng/mL levels of both the enantiomers. The method was applied to a pharmacokinetic study of the enantiomers of 1 in beagle dogs after oral administration of racemic 1.

In order to verify the clinical usefulness of saliva in assessing the adrenocortical function, we measured saliva cortisol levels by a radioimmunoassay after extraction with dichloromethane, and compared the results with the levels of serum unbound cortisol determined by the method of equilibrium dialysis. Paired samples of saliva and serum were obtained from 10 healthy male volunteers. Morning levels of saliva cortisol and serum unbound cortisol were 0.99 +/- 0.42 and 1.56 +/- 0.54 microgram/100 ml, respectively, where serum total cortisol was 19.28 +/- 3.56 microgram/100 ml. A well-defined diurnal rhythm and a greater response to ACTH stimulation were observed in saliva cortisol than in serum total cortisol. Kinetic study of injected cortisol revealed almost identical values for the compartments of saliva cortisol and serum unbound cortisol. The correlation coefficient (r) between the levels of saliva cortisol and serum unbound cortisol was 0.893 (p less than 0.001, n = 150). From these results we concluded that the measurement of saliva cortisol can be used sufficiently to monitor unbound free concentrations in serum.