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Skeleton undergoes constant remodeling process to maintain healthy bone mass. However, in pathological conditions, bone remodeling is deregulated, resulting in unbalanced bone resorption and formation. Abnormal osteoclast formation and activation play a key role in osteolysis, such as in rheumatoid arthritis and osteoporosis. As potential therapeutic targets or biomarkers, miRNAs have gained rapidly growing research and clinical attention. miRNA-based therapeutics is recently entering a new era for disease treatment. Such progress is emerging in treatment of skeletal diseases. In this review, we discuss miRNA biogenesis, advances in the strategies for miRNA target identification, important miRNAs involved in osteoclastogenesis and disease models, their regulated mechanisms, and translational potential and challenges in bone homeostasis and related diseases.

We propose a new objective function for optimizing a sound-absorbing material layout. The optimization seeks to reduce the average pressure of the domain in the resonance state. The properties of the sound-absorbing material were modeled as an equivalent fluid. The propagation of sound under periodic accelerations was treated using the Helmholtz equation. The energy loss through the sound-absorbing material was found and used as an objective function, which we refer to as the sound dynamic compliance. The topology optimization was implemented using the solid isotropic material with penalization (SIMP) method. The optimization problem involved maximizing the imaginary part of the sound dynamic compliance under a volume constraint. Quasi-1D and 3D numerical examples were presented to illustrate the validity and utility of the proposed method over the conventional straightforward pressure reduction optimization. Whereas no suitable solution that reduces the resonance peak was obtained using the conventional approach for some frequency inputs, the proposed approach obtained such solutions and generated optimal results for each example exhibiting high robustness against input frequency.

Objectives: The purpose of the present study was to obtain knowledge for improvement of the housing and life among radiation decontamination workers by examining the effect of housing type on anxiety over lack of privacy. Methods: This cross-sectional study comprised 544 male radiation decontamination workers in Fukushima Prefecture who anonymously answered self-administered questionnaires in 2013, including measurement of privacy anxiety, housing type, career change, social support, and sociodemographics. Chi-square tests and binary logistic regression analysis were used to evaluate the associations between these factors and anxiety over lack of privacy. Results: The number of workers who had anxiety over lack of privacy was 93 (17.1%), and the number of workers who were living in owner-occupied housing, rental housing, company dormitories, and hotels was 165 (30.3%), 177 (32.5%), 168 (30.9%), and 34 (6.3%), respectively. The presence of anxiety was significantly associated with housing type (p

Objectives: The aim of this study was to reveal the current state of preventive measures and lifestyle habits against heat illness in radiation decontamination workers and to examine whether young radiation decontamination workers take less preventive measures and have worse lifestyle habits than the elder workers. Methods: This was a cross-sectional study. Self-administered questionnaires were sent to 1,505 radiation decontamination workers in Fukushima, Japan. Five hundred fifty-eight men who replied and answered all questions were included in the statistical analysis. The questionnaire included age, duration of decontamination work, previous occupation, lifestyle habit, and preventive measures for heat illness. We classified age of the respondents into five groups

The feasibility of visible and near infrared (VIS/NIR) transmittance spectroscopy for nondestructive discrimination of healthy and diseased onion bulbs was examined. Rottenness occurring in inner scales that were hard to diagnose by the five human senses was targeted. First, VIS/NIR spectra were acquired for six bulb positions. Subsequently, the degree of rot was measured by visual inspection of vertically cut surface based on our proposed criteria and by weighing of sectioned rotted parts. Our evaluation criteria functioned as an alternative mode of the weighing method. The basal plate of onion bulb had remarkable scattering properties. Therefore, spectral features differed not only by the rot levels but also by positioning the bulb against the sensor setup. The partial least squares regression model developed from the longitudinal position, for which the basal plate did not overlap against the system optical axis, showed the best performance and classified rotted bulbs above level 1 with 98.4% accuracy. Absorbance below 736 nm was the informative region for bulb rottenness detection.

Excessive osteoclastic bone erosion disrupts normal bone remodeling and leads to bone loss in many skeletal diseases, including inflammatory arthritis, such as rheumatoid arthritis (RA) and psoriatic arthritis, periodontitis and peri-prosthetic loosening. Functional control of osteoclasts is critical for the maintenance of bone homeostasis. However, the mechanisms that restrain osteoclast resorptive function are not fully understood. In this study, we identify a previously unrecognized role for G-protein Gα13 in inhibition of osteoclast adhesion, fusion and bone resorptive function. Gα13 is highly expressed in mature multinucleated osteoclasts, but not during early differentiation. Deficiency of Gα13 in myeloid osteoclast lineage (Gα13ΔM/ΔM mice) leads to super spread morphology of multinucleated giant osteoclasts with elevated bone resorptive capacity, corroborated with an osteoporotic bone phenotype in the Gα13ΔM/ΔM mice. Mechanistically, Gα13 functions as a brake that restrains the c-Src, Pyk2, RhoA-Rock2 mediated signaling pathways and related gene expressions to control the ability of osteoclasts in fusion, adhesion, actin cytoskeletal remodeling and resorption. Genome wide analysis reveals cytoskeleton related genes that are suppressed by Gα13, identifying Gα13 as a critical cytoskeletal regulator in osteoclasts. We also identify a genome wide regulation of genes responsible for mitochondrial biogenesis and function by Gα13 in osteoclasts. Furthermore, the significant correlation between Gα13 expression levels, TNF activity and RA disease activity in RA patients suggests that the Gα13 mediated mechanisms represent attractive therapeutic targets for diseases associated with excessive bone resorption.

The aims of the present study were to investigate what kind of anxiety radiation decontamination workers have, and to analyze what factors are associated to presence or absence of their anxieties. A self-administered questionnaire was conducted, which included 10 anxiety items. A logistic regression model was then used to determine what factors were related to increased anxiety. Of 531 workers who completed the questionnaire, 477 (91.6%) complained of at least one of the 8 anxiety items. The most common anxiety item was job security (41.8%), and the least common item was working hours (6.0%). The logistic regression analysis revealed that the most common causes of related to presence of anxiety was heat illness and the most common causes of related to absence of anxiety was having someone available for consultation. The current study revealed the kinds of anxiety, and the factors associated with presence or absence of each anxiety among radiation decontamination workers. These results provide important implications for the improvement of educational content and occupational health management for radiation decontamination workers in the future.

Objectives: To reveal the effect of age and other factors on perceived anxiety over radiation exposure among decontamination workers in Fukushima Prefecture, Japan. Methods: A survey questionnaire was sent to 1505 workers, with questions regarding age, presence of a written employment contract, previous residence, radiation passbook ownership, presence of close persons for consultation, knowledge of how to access public assistance, and a four-point scale of radiation-related anxiety (1= "Very much," 2= "Somewhat," 3= "A little bit," and 4= "None" ). The relationships between the degree of anxiety and variables were analyzed using the chi-square test and residual analysis. Results: In all, 512 participants responded to the questionnaire. The mean age of participants was 46.2 years (SD: 13.1, range: 18-77). Of them, 50, 233, 168, and 61 workers chose "Very much," "Somewhat," "A little bit," and "None," respectively, on the anxiety scale. Chi-square test showed that participants aged 61 years and over had higher degrees of anxiety (p

Excessive osteoclastic bone erosion disrupts normal bone remodeling and leads to bone loss in many skeletal diseases, including inflammatory arthritis, such as rheumatoid arthritis (RA) and psoriatic arthritis, periodontitis and peri-prosthetic loosening. Functional control of osteoclasts is critical for the maintenance of bone homeostasis. However, the mechanisms that restrain osteoclast resorptive function are not fully understood. In this study, we identify a previously unrecognized role for G-protein Gα13 in inhibition of osteoclast adhesion, fusion and bone resorptive function. Gα13 is highly expressed in mature multinucleated osteoclasts, but not during early differentiation. Deficiency of Gα13 in myeloid osteoclast lineage (Gα13ΔM/ΔM mice) leads to super spread morphology of multinucleated giant osteoclasts with elevated bone resorptive capacity, corroborated with an osteoporotic bone phenotype in the Gα13ΔM/ΔM mice. Mechanistically, Gα13 functions as a brake that restrains the c-Src, Pyk2, RhoA-Rock2 mediated signaling pathways and related gene expressions to control the ability of osteoclasts in fusion, adhesion, actin cytoskeletal remodeling and resorption. Genome wide analysis reveals cytoskeleton related genes that are suppressed by Gα13, identifying Gα13 as a critical cytoskeletal regulator in osteoclasts. We also identify a genome wide regulation of genes responsible for mitochondrial biogenesis and function by Gα13 in osteoclasts. Furthermore, the significant correlation between Gα13 expression levels, TNF activity and RA disease activity in RA patients suggests that the Gα13 mediated mechanisms represent attractive therapeutic targets for diseases associated with excessive bone resorption.

OBJECTIVES: The aim of this study was to reveal factors related to heat illness in radiation decontamination workers and determine effective preventive measures. METHODS: A self-administered questionnaire was sent to 1,505 radiation decontamination workers. The questionnaire included age, sex, duration of decontamination work, previous occupation, education provided by employers regarding heat illness, preventive action against heat illness, and subjective symptoms of heat illness during work. We included 528 men, who replied and answered all questions, in the statistical analysis. Subjective symptoms of heat illness were categorized as "no symptoms," "Grade I" and "Grade II" according to severity. A multiple linear regression model was used to determine the factors associated with the severity of heat illness. RESULTS: The mean age of the subjects was 47.6 years old (standard deviation: 13.4). Of the 528 workers, 316 (59.8%) experienced heat illness symptoms (213 at Grade I and 103 at Grade II). The results of the stepwise selection revealed that age, outdoor manual labor, adequate sleep, use of a cool vest, and salt intake were selected as preventive factors, whereas living in a company dormitory or temporary housing, wearing light clothing, and consuming breakfast were selected as risk factors for heat illness. CONCLUSIONS: Both working conditions and living environment are associated with heat illness in radiation decontamination workers. Type of housing and sleep are also strongly related to heat illness during work. Employers should consider not only the working conditions of the employee but also the employee's daily living conditions, in order to prevent heat illness. Language: en

We studied the spatial distributions of and the diurnal variations in four low molecular weight (LMW) carbonyl compounds, formaldehyde, acetaldehyde, propionaldehyde, and glyoxal, in coastal seawater. The samples were taken from the coastal areas of Hiroshima Bay, the Iyo Nada, and the Bungo Channel, western Japan. The formaldehyde, acetaldehyde, and glyoxal concentrations were higher in the northern part of Hiroshima Bay than at offshore sampling points in the Iyo Nada and the Bungo Channel. These three compounds were found at much higher concentrations in the surface water than in deeper water layers in Hiroshima Bay. It is noteworthy that propionaldehyde was not detected in any of the seawater samples, the concentrations present being lower than the detection limit (1 nanomole per liter (nM)) of the high performance liquid chromatography (HPLC) system we used. Photochemical and biological experiments were performed in the laboratory to help understand the characteristic distributions and fates of the LMW carbonyl compounds. The primary process controlling their fate in the coastal environment appears to be their biological consumption. The direct photo degradation of propionaldehyde, initiated by ultraviolet (UV) absorption, was observed, although formaldehyde and acetaldehyde were not degraded by UV irradiation. Our results suggest that the degradation of the LMW carbonyl compounds by photochemically formed hydroxyl radicals is relatively insignificant in the study area. Atmospheric deposition is a possible source of soluble carbonyl compounds in coastal surface seawater, but it may not influence the carbonyl concentrations in offshore waters.

A 65-year-old man was admitted into our hospital because of the detailed examination for abnormal Q waves in inferior leads on an electrocardiogram. Coronary angiography and 320-row area detector computed tomography (ADCT) revealed “dual left anterior descending artery (LAD)”, which was a rare anomaly of the LAD and chronic total occlusion (CTO) at segment 2 of the right coronary artery (RCA). The course of the anomalous LAD arising from the proximal portion of the RCA was specifically identified between aortic root and right ventricular outflow tract (RVOT) by 320-row ADCT. The anomalous LAD had potential risk of myocardial ischemia because of the compression from aortic root and RVOT during exercise. We performed technetium myocardial perfusion scintigram to evaluate exercise-induced ischemia in the territory of the anomalous LAD and to decide therapeutic strategies including coronary artery bypass grafting surgery to the vessel. The scintigram revealed no exercise-induced ischemia in anteroseptal wall and a constant perfusion defect in posteroinferior wall of the left ventricle. Thus, we decided to treat the patient with pharmacological treatment in the outpatient setting. This report suggests that it is important to recognize the variants of coronary arteries for optimal treatment.

This paper presents a new form of Particle Swarm Optimization (PSO) based on the concept of tabu search (TS). In PSO, when a particle finds a local optimal solution, all of the particles gather around that one, and cannot escape from it. On the other hand, TS can escape from the local optimal solution by moving away from the best present solution. The proposed Tabu List PSO (TL-PSO) is a method for combining the strong points of PSO and TS. This method stores the history of pbest in a tabu list. When a particle has a reduced searching ability, it selects a pbest of the past from the historical values, which is used for the update. This makes each particle active, and the searching ability of the swarm makes progress. The proposed method was validated by numerical simulations with several functions that are well known as optimization benchmark problems for comparison to the conventional PSO method. © 2010 Wiley Periodicals, Inc. Electr Eng Jpn, 172(4): 31–37, 2010; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/eej.20966

Extraventricular neurocytoma (EVN) is a rare brain tumor that poses diagnostic difficulty. Described herein is a case of atypical EVN arising in a 54-year-old woman. A well-circumscribed lesion (3.0 × 3.0 × 3.0 cm) in the right parietal lobe showed diffuse proliferation of monotonous tumor cells with perinuclear clearing within a delicate fibrillary matrix similar to neuropil. Tumor also showed vascular proliferation and high mitotic activity. Immunohistochemically, these tumor cells were strongly positive for synaptophysin both in the neuropil and in the perinuclear cytoplasm, and were negative for glial fibrillary acidic protein and Olig2. Ki-67 labeling index was 13.0% in the most stained areas, but accumulation of p53 was not observed. These findings were compatible with those of EVN with histological atypia. EVN should be considered as a candidate in the differential diagnosis of parenchymal brain tumor, especially oligodendroglioma. The important features are the delicate fibrillary matrix similar to neuropil, diffuse and strong immunoreactivity for synaptophysin, and negative immunoreactivity for Olig2. High proliferative activity without accumulation of p53 suggests that other factors are involved in oncogenesis of atypical EVN.

We report two neonatal patients with high-flow intracranial or cervical arteriovenous (AV) shunts who presented with congestive heart failure and were successfully managed with endovascular treatment. One with vein of Galen malformation with body weight of only 2.0 kg is, to our knowledge, the smallest neonate successfully treated with endovascular treatment. The other neonate is, to our knowledge, the first vertebro-vertebral fistula patient presenting with heart failure and treated successfully with endovascular treatment. Even in neonates, endovascular treatment is the procedure of choice for high-flow AV shunts presenting with progressive congestive heart failure resistant to medical management. We discuss limitations and technical considerations of endovascular treatments in small neonates with high-flow AV shunts and congestive heart failure.

Hepatocyte growth factor activator inhibitor type-1 (HAI-1) is an integral-membrane proteinase inhibitor. In this study, we examined the effects of HAI-1 on human glioblastoma cells. Two glioblastoma cell lines (YKG-1, U251) were stably transfected with expression plasmid harboring mature membrane-form or truncated secreted-form HAI-1. Culture characteristics were not altered by the expression of HAI-1, whereas in vitro invasiveness of U251 was suppressed. On the other hand, the expression of membrane-form HAI-1 resulted in significantly enhanced tumorigenicity of both cell lines in vivo. In contrast, secreted-form HAI-1 did not promote the tumorigenicity. These results suggest that HAI-1 may play complex roles in progression of glioblastoma cells, and membrane-form HAI-1 may mediate an undefined important signaling in the cells.

Hepatocyte growth factor/scatter factor (HGF/SF) is a multifunctional growth factor that is involved in invasive growth of tumor cells via its receptor MET, a protein product of c-met proto-oncogene. HGF activator (HGFA) is a serine proteinase responsible for the activation of proform of HGF/SF (proHGF/SF). In our study, we examined the effects of engineered expression of HGFA on 2 human glioblastoma cell lines (YKG-1 and U251). Both cells expressed MET, while only YKG-1 expressed endogenous proHGF/SF. Enhanced MET phosphorylation and increased migratory activity were induced by the expression of HGFA in YKG-1 cells in vitro in the presence of thrombin, which is a known activator of proHGFA. In contrast, MET phosphorylation was consistently observed in U251 that lacked endogenous HGF/SF, suggesting ligand-independent activation of MET in this cell line. Consequently, the expression of HGFA in U251 did not enhance the MET phosphorylation and following cellular response even with the thrombin treatment. However, addition of exogenous proHGF/SF resulted in enhanced migratory activity of HGFA-expressing U251 cells in the presence of thrombin in vitro. The engineered HGFA expression resulted in significantly enhanced tumor growth with increased vascular density in vivo when YKG-1 cells were implanted in nude mouse brain. This effect was not observed in U251 lacking endogenous proHGF/SF. These results indicate the possible existence of multiple mechanisms of MET activation in glioblastomas and that the activation system of proHGF/SF is important in progression of glioblastomas that express endogenous proHGF/SF and require ligand-dependent MET activation. © 2005 Wiley-Liss, Inc.

Objective We sought to evaluate from a behavioral and histological viewpoint the effect of local administration of glial cell line-derived neurotrophic factor (GDNF) on neonatal preganglionic Erb's palsy in rats. Methods The Erb's palsy model was produced by transecting the anterior and posterior roots of the left C5-C7 nerves of 7-day-old rats. The rats were divided into GDNF-treated (n = 10) and vehicle-treated groups (n = 11). After we transected the roots, contact in the proximal and distal stumps of the transected nerves was maintained, and the transected point and the entire intraspinal portion of the transected roots were enclosed by Gelfoam soaked with 10 micro g GDNF or saline. The behavioral evaluation consisted of a foot-fault test and a forepaw muscle strength test, all of which were performed from the third to the seventh weeks after the operation. Seven weeks after the operation, all rats were killed, the number of anterior horn cells was counted at C5-C7, and the differences on each side were compared. Results In the vehicle-treated group, the foot-fault test indicated an abnormality in forelimb function on the root transection side. In the GDNF-treated group, however, significant improvement in forelimb function was observed on the basis of the foot-fault test results obtained in the third to sixth weeks after the operation. In the histological evaluation, the number of anterior horn cells from the side in which the operation took place in the vehicle-treated group was significantly less than that taken from the contralateral side at each segment. In the GDNF-treated group, however, there was no difference in any of the segments, regardless of the side from which they were taken. Conclusion Local administration of GDNF in a neonatal preganglionic Erb's palsy model resulted in significant improvement in deficits on the basis of behavioral and histological evaluations.

✓ SThe authors devised a paramedian transmuscular approach to the C2–3 facet joint that enabled total removal of C-3 dumbbell-type neurofibroma; dissection of the paravertebral muscles from the spinous process was not required and the facet joint was preserved. Only splitting or retraction of the paravertebral muscles was necessary. The anatomical features and procedures involved in muscle splitting are described.

In a previous study, we demonstrated that the expression levels in tumor cells of emmprin (CD147) correlated with the grade of astrocytic tumors. Also, we found that emmprin was expressed in vascular endothelial cells of the non-neoplastic brain and hypothesized that emmprin expression could be associated with normal blood-brain-barrier (BBB) function of vascular endothelial cells. In this study, this possibility was examined in non-neoplastic brain, glioma and metastatic carcinoma tissues by comparing emmprin immunohistochemistry with gadolinium diethylenetriaminepentaacetic acid (Gd-DTPA) enhancement of magnetic resonance imaging (MRI), which is a clinical indicator of the BBB function. This study included 10 cases of non-neoplastic brain tissues, 7 of metastatic carcinoma, 7 of diffuse astrocytoma, 4 of anaplastic astrocytoma and 13 of glioblastoma multiforme. In all the cases, MRI with administration of Gd-DTPA was performed. The lesions were resected using the microdissection method with the help of ultrasonography and a neuronavigator. The tissues from Gd-DTPA-enhanced or non-enhanced areas were processed into frozen sections and subjected to immunohistochemistry with anti-emmprin antibody. The expression of emmprin in brain vascular endothelial cells inversely correlated with Gd-DTPA-enhancement of MRI: emmprin was positive in tissues not enhanced by Gd-DTPA and was negative in DTPA-enhanced tissues. Since BBB function presumably remains unimpaired in regions in which MR images are not Gd-DTPA-enhanced, emmprin expression appears to be associated with unimpaired BBB function. This is the first report to demonstrate a possible correlation between emmprin expression and BBB function in humans.

Cervical compressive myelopathy patients sometimes show localized girdle sensation in the mid trunk (so-called false localizing sign). This symptom often confuses physicians, but the clinical features and mechanism of this symptom are still unclear. We investigated the clinical features and possible mechanism. In each of five cases of cervical compressive myelopathy disease with and without mid-truncal girdle sensation, the clinical features, degree and shape of cord compression were analysed. The girdle sensation was expressed as a vague or burning sensation, and was localized with a width of 3 or 4 dermatomes from the T3 to T11 level. There was no correlation between the appearance of the girdle sensation and etiology and level of cervical cord compression. Pyramidal tract signs and disturbance of superficial sensation were observed in all cases. Furthermore, on axial MRI, the midline ventral surface of the cervical cord was remarkably compressed in cases with girdle sensation, as if the compressive lesion entered the anterior medial fissure of the cervical cord. From these findings, this false localizing sign may be caused by severe compression of midline ventral structure of the cervical cord. Ischemia of the thoracic watershed zone of the anterior spinal artery from the compression of the anterior spinal artery at the cervical level might also be considered to be a possible cause.

A 59-year-old male presented with a large cholesterol granuloma arising from the frontal sinus manifesting as a large, fluctuated, soft mass in his brow, compressing left eye. Skull radiography showed dilation of the frontal sinus. Computed tomography and magnetic resonance imaging revealed a cystic mass extending into the left orbit and anterior cranial fossa. Gross inspection at the frontal craniotomy showed mucinous, dark green fluid intermingled with shining material. The histological diagnosis was cholesterol granuloma with epithelial lining. Large cholesterol granuloma with facial deformity is always associated with bone and cosmetic problems. Wide opening of the frontal sinus followed by cyst wall removal and plastic repair of the skull is necessary.

AIM: To investigate the correlation between angiographic cerebral circulation time (CCT) and cerebral blood flow (CBF) evaluated by single photon emission computed tomography (SPECT) before and after endovascular treatment for symptomatic vasospasm. MATERIALS AND METHODS: Seven patients with unilateral vasospasm as demonstrated by catheter angiography who underwent pre- and post-treatment SPECT were selected. All patients had angiographic vasospasm of unilateral middle cerebral artery (MCA). Eight vessels in seven patients underwent intra-arterial papaverine infusion and three vessels underwent percutaneous transluminal angioplasty. Angiographic CCT was defined as the interval from the first image in which contrast medium was visible at the origin of MCA to its disappearance from the cortical arteries in the MCA territory. In SPECT studies, the ischaemic degree in MCA territory was analysed by side to side comparison with calculating the asymmetry index (AI). RESULTS: The pre-treatment mean CCT was 4.1 ± 0.8 s. The mean CCT immediately after treatment was 2.7 ± 0.5 s. In the control subjects (n = 15) with unruptured aneurysm, mean CCT was 3.5 ± 0.2 s. The pre-treatment mean CCT was significantly prolonged compared with that in the control subjects (P = 0.02). The post-treatment mean CCT was significantly shortened compared with that in the control subjects (P = 0.001). The pre-treatment mean AI was 71.2 ± 7.4%, and that immediately after treatment was 90.5 ± 3.6%. AI increased in all territories treated with endovascular treatment; the mean change was 19.3%. Angiographic CCT was closely correlated with AI in both pre- (r = − 0.95) and post-treatment (r = − 0.79). CONCLUSION: Measurement of CCT is useful in evaluating cerebral haemodynamics of endovascular treatments in patients with cerebral vasospasm.Iseda, T., (2000). Clinical Radiology55, 679–683.

OBJECTIVE This study investigated the cerebral blood flow (CBF) thresholds of ischemic cortices that were salvageable with intravenous tissue plasminogen activator (t-PA) infusion therapy. METHODS We retrospectively reviewed data for 20 patients who were treated with intravenous low-dose (7.2 mg) native t-PA infusion therapy for distal embolic occlusions of middle cerebral artery divisions or branches, without early computed tomographic ischemic changes. All patients underwent pretreatment single-photon emission computed tomographic CBF measurements using (99m)Tc-N,N'-(1,2-ethylenediyl)bis-L-cysteine diethylester. Intravenous t-PA infusion was initiated within 6 hours (average, 3 h) after symptom onset for 14 patients and 6 to 14 hours (average, 8.8 h) after the last time the patient was noted to be in normal condition for the other 6 patients. Pretreatment single-photon emission computed tomographic and 3-month post-treatment computed tomographic scans were compared using computerized coregistration. Ischemic cortices in single-photon emission computed tomographic scans were divided into areas of reversible and irreversible ischemia. The degree of hypoperfusion was analyzed with an asymmetry index (AI). The AI was calculated as C(a)/C(b) x 100%, where C(a) represents the mean reconstructed counts for the ipsilateral ischemic area and C(b) represents the mean reconstructed counts for the corresponding contralateral area. RESULTS Partial recanalization, with clinical improvement, at 60 minutes was confirmed by angiography for 14 of the 20 patients (70%). Seventeen of the 20 patients (85%) exhibited major neurological improvements (defined as decreases in National Institutes of Health Stroke Scale scores of > or =4 points) at 24 hours, suggesting that recanalization occurred within 24 hours for almost all patients. AIs for the 25 irreversible lesions ranged from 15.0 to 53.4% (37.3 +/- 11.6%), whereas AIs for the 38 reversible lesions ranged from 45.0 to 83.1% (69.3 +/- 8.6%). There was a significant difference in the AIs for these two groups (P < 0.0001). The ischemia in tissue with AIs of more than 53.4% was reversible. In contrast, ischemic tissue with AIs of less than 45.0% could not escape cerebral infarction with our treatment. The ischemia in tissue with AIs between 45.0 and 53.4% was reversible in some patients and irreversible in others. CONCLUSION To save ischemic tissue with our intravenous t-PA infusion therapy, residual CBF should be at least 45% of the contralateral presumed normal CBF value. CBF thresholds for ischemia that would be surely salvageable with our intravenous t-PA infusion therapy might be approximately 50 to 55% of the contralateral presumed normal CBF values.

We prospectively evaluated the safety and efficacy of an intravenous infusion of low-dose native tissue plasminogen activator for distal embolisms in the middle cerebral artery divisions or branches.Twenty patients were selected according to the following computed tomographic and angiographic criteria and treated with intravenous infusion of 7.2 mg of tisokinase: 1) no early ischemic changes on the initial computed tomographic scan, and 2) embolic occlusion of the middle cerebral artery divisions or branches without the involvement of the lenticulostriate arteries. For comparison, the records of 12 patients from previous years who met the above inclusion criteria but underwent no thrombolytic therapy were reviewed retrospectively. The degree of neurological recovery was assessed using the National Institutes of Health Stroke Scale at 24 hours after admission. Major neurological improvement was defined as a decrease in the stroke score by 4 points or more.There was no significant difference in stroke scores at the time of admission between the treatment group (mean +/- standard deviation, 12.8 +/- 2.8) and the untreated group (14.0 +/- 2.4). In the treatment group, major neurological improvement was seen in 17 (85%) of 20 patients, whereas in the untreated group only 5 (41.7%) of 12 patients showed major neurological improvement (P0.05). The mean score at 24 hours in the treatment group (3.6 +/- 3.5) was significantly lower than that in the untreated group (9.4 +/- 7.3) (P0.05). There was no hemorrhagic complication with neurological exacerbation in the treatment group.Even with delayed initiation (3 h after symptom onset), intravenous infusion of low-dose tisokinase may be safe and effective for small distal emboli in the middle cerebral artery divisions or branches, when early ischemic changes on computed tomographic scans and involvement of the lenticulostriate arteries are absent.

BACKGROUND We describe techniques combining wrapping and clipping using a collagen-impregnated Dacron knitted fabric (Hemashield) for accidental arterial perforations and broad-based aneurysms. The results of these techniques in seven patients are presented. METHODS Clip-reinforced wrapping was performed to obtain hemostasis in two patients with arterial perforations and in a patient with a ruptured broad-based aneurysm in the internal carotid artery. Clipping of the broad neck of the aneurysm and wrapping with Hemashield (wrap-clipping) was performed in four patients with unruptured aneurysms (one internal carotid artery, two middle cerebral artery, one basilar artery). RESULTS In the three patients treated with clip-reinforced wrapping, complete hemostasis was obtained just after clip application. In the patient with a ruptured broad-based aneurysm, postoperative angiography demonstrated that the dome of the aneurysm was well compressed. In the four patients treated with wrap-clipping, postoperative angiography revealed successful clipping of the broad neck of the aneurysm. CONCLUSION In this early experience, there were no problems in the use of Hemashield for clip-reinforced wrapping or wrap-clipping.

九州・沖縄地区の平成9年度の脳梗塞急性期再灌流療法の実態調査のために,脳神経外科,神経内科のある195施設にアンケート調査を行い,117施設(60.0%)より回答を得た.そのうち脳梗塞急性期医療を行っている109施設について検討した。CTで異常がない急性期脳梗塞に対して血管閉塞部位診断を行う施設は全体の67.0%で,大部分がdigital subtraction angiography (DSA)あるいはmagnetic resonance angiography (MRA)を行っており,ultrasonography (US)やcomputed tomographic angiography (CTA)を行う施設は全体の2～3割であった.何らかの再灌流療法を試みる施設は全体の58.7%で,神経内科の53.3%,脳神経外科の28.1%の施設が再灌流療法は考慮しないという結果であった.再灌流療法として最も多くの施設で行われていたのはウロキナーゼの点滴静注で(51.6%),次いでマイクロカテーテルを用いた局所線溶療法(50.0%),血管造影用カテーテルからの血栓溶解薬の動注(46.9%)の順であった.

S-genotypes, isozyme phenotypes, and RAPD markers were investigated to identify the parenthood of the Japanese pear cultivar 'Kuratsuki', which is a chance seedling found in a mixed planting of 'Shinsui', 'Kosui', 'Hosui' and 'Chojuro'. The S-genotype of 'Kuratsuki' was judged to be S3S5, the same as that of 'Hosui', in that the pollen of 'Kuratsuki' was cross-incompatible, and it exhibited the same PCR-RFLP pattern of the S-RNase genes with 'Hosui'. Analyses of seven loci in five isozymes among the parental candidates showed that 'Kuratsuki' had the common a allele at POD-1 locus as 'Shinsui' and 'Chojuro', and the common b allele at PGM-3 locus comparable only to 'Hosui'. The common RAPD markers specific with 'Kuratsuki' were detected only in 'Shinsui' and 'Hosui' which suggest that 'Kuratsuki' is a hybrid seedling between 'Shinsui' and 'Hosui'.

Cleavase® fragment length polymorphism (CFLP) is a newly developed method used for the detection of gene mutation. This study evaluates the usefulness of this method. Thirty-three human glioma specimens obtained at surgery were analyzed for human p53 gene mutation using radiolabeled polymerase chain reaction (PCR)-based CFLP analysis and the results were compared with results of direct sequencing. Three (one of five anaplastic astrocytomas and two of 24 glioblastomas) and five (one of four low-grade gliomas, one of five anaplastic astrocytomas and three of 24 glioblastomas) samples were suspected as being mutations in exon 5–6 and 7–8 of the p53 gene, respectively. Further, two of three (one anaplastic astrocytoma and one glioblastoma) and two of five (both glioblastoma) samples were confirmed as having mutations in direct sequence (their positive rates were 66.7 and 40%, respectively). However, the false-negative rate of CFLP analysis was very low (0%, 0/60). Therefore, it was concluded that although PCR-CFLP using a radioisotope might be too sensitive given its superior false-negative rate, it offers an alternative protocol for the screening of the mutation of human p53 gene.

Several lines of evidence indicate that hepatocyte growth factor/scatter factor (HGF/SF) and its receptor, c-Met, may play an important role in progression of human glioma. In this study, effects of HGF/SF on urokinase- type plasminogen activator (uPA)-mediated proteolysis network were examined in c-Met-positive human glioma cell lines. Treatment of the glioma cells with various concentrations of HGF/SF resulted in an enhanced secretion of uPA proteins accompanying increased transcription of uPA mRNA in a dose dependent fashion. The levels of uPA receptor (uPAR) mRNAs were also elevated simultaneously upon HGF/SF stimulation, and the cell-surface associated uPA activity was also elevated by the treatment. Since concomitant expression of HGF and its receptor c-Met are frequently observed in malignant gliomas, these results suggest that HGF/SF participates in invasive process of malignant glioma cells not only by its motility-stimulating activity but also through enhanced degradation of the extracellular matrix induced by autocrine activation of uPA proteolysis network.