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In the seed production of several marine teleosts, large numbers of dead larvae are frequently observed on the water surface around the time of first feeding. We tried to prevent such “surface death” by the addition of chicken egg white (EW) into the rearing water. In the first experiment, larvae of striped bonito, Sarda orientalis , at the first feeding stage (2 and 3 days after hatching) were transferred to plastic beakers using a 5-ml pipette at a density of 10 larvae/l, in the absence or presence of EW (80 μl/l). No diet was supplied, the water was not renewed throughout the experiment, and dead larvae were removed daily. Numbers of surviving larvae of the EW-treated group were significantly higher than those of the control group. In particular, survival at the first observation (next day after transfer) was less than 30% in the control, while 100% in the EW-treated group. In a second experiment, mortality at 2 h after transfer was compared with special attention to the location of the dead larvae. Significantly ( P Dules auriga , was also higher in the presence of EW, especially during a period when dead larvae were frequently found on the water surface in the control. Thus, the addition of EW to the rearing water is suggested to prevent surface death in a variety of marine fish larvae, and the possibility of applying the method in practical rearing is discussed.

Both nitric oxide (NO) and natriuretic peptides produce apoptosis of vascular smooth muscle cells. However, there is evidence that NO induces endothelial cell proliferation, which suggests that there is a difference in the response of endothelial cells to natriuretic peptides. The purpose of this study was to investigate the effect of atrial natriuretic peptide (ANP) on human endothelial cell survival. ANP within the physiological concentration (10−11mol/l) induced a 52% increase in the number of human coronary arterial endothelial cells and a 63% increase in human umbilical vein endothelial cells at a low concentration of serum. The increase in cell numbers was blocked by pretreatment with RP8-CPT-cGMP (RP8), a cGMP-dependent protein kinase inhibitor, with wortmannin, an Akt/PKB inhibitor, and with PD-98059, an ERK1/2 inhibitor. In a Transwell migration test, ANP also increased the cell migration, and RP8, wortmannin, and PD-98059 blocked this increase. A wound healing assay was performed to examine the effects of ANP on regeneration in vitro. ANP increased both cell numbers and migration, but the effects were blocked by the above three kinase inhibitors. ANP increased the expression of phospho-Akt and of phospho-ERK1/2 within 1.5 h. These results suggest that ANP can potentiate endothelial regeneration by cGMP-dependent protein kinase stimulation and subsequent Akt and ERK1/2 activations.

A new approach for mobile storage of hydrogen has been proposed with the use of a catalytic reaction pair of decalin dehydrogenation/naphthalene hydrogenation. With the complement of the industrialized naphthalene-hydrogenation catalysis, the other endothermic catalysis for decalin dehydrogenation was now performed at around 200°C with carbon-supported platinum-based catalysts. Under liquid-film conditions, hydrogen was evolved from decalin much more efficiently than the suspended ones due to the superheated states of dehydrogenation catalysts. It was confirmed that the catalytic conversions of decalin dehydrogeno-aromatization in the liquid-film states could surpass easily the equilibrium limit, because the conditions of suppressed reactant evaporation and reactive distillation were operative here. Exergy loss in the hydrogen storage system would be reduced tremendously by adopting this catalyst-assisted decalin/naphthalene pair as the medium of hydrogen carrier.

In vivo, water diffusion displays directionality due to presence of complex microstructural barriers in tissue. The extent of directionality of water diffusion can be expressed as a fractional anisotropy (FA) value, using diffusion tensor MR imaging (DTI). The aim of this study was to determine whether FA values indicate microstructures in astrocytic tumors. We performed DTI in 31 patients with astrocytic tumor, and measured the FA values of tumor and normal brain regions prior to CT-guided stereotactic biopsy. After biopsy, FA values were compared to assess the cellularity and vascularity of tumor tissue. Although mean FA values trended to differ among histological types, all mean tumor FA values were lower than those of normal brain regions. Positive correlation was observed between FA values and both cellularity (r = 0.65, p < 0.05) and vascularity (r = 0.45, p < 0.05). We had hypothesized that the FA value of an astrocytic tumor would be determined by a balance between factors increasing the directionality of water diffusion, such as high cellularity and/or vascularity, and factors decreasing the directionality of water diffusion, such as fiber destruction. However, our results suggest that the FA values of glioblastoma, anaplastic astrocytoma, diffuse astrocytoma and pilocytic astrocytoma are largely affected by cellularity and/or vascularity, whereas that of gliomatosis cerebri are largely affected by the preservation of nerve fibers. Measurement of FA value using DTI will allow prediction of histological characteristics such as cellularity, vascularity and/or fiber structure in astrocytic tumors.

Hypoxic cells play a key role in the radioresistance of malignant glioma. Interferon-beta, ACNU as nimustine hydrochloride and radiotherapy (IAR) is a common therapy for malignant glioma in Japan. Since hyperbaric oxygenation (HBO) increases oxygen pressure in glioma tissue, we applied a modified IAR therapy, radiotherapy after HBO combined with interferon-beta and ACNU (HBO/IAR therapy), for supratentorial malignant gliomas. Daily radiation therapy was completed within 15min after HBO. We assessed HBO/IAR with respect to toxicity, response rates and the time of tumor progression (TTP). We also examined the incidence of responses by some prognostic factors before HBO/IAR, namely, age, Karnofsky performance scale (KPS), histological type, tumor size, tumor site and operation type. Of 39 patients who participated in this study, 35 underwent a complete schedule of HBO/IAR therapy in which toxicity was permissible. Thirty patients (76.9%) either maintained or increased KPS during HBO/IAR with a mean duration of 68±14 days. The response rates (CR+PR%) for glioblastoma, anaplastic astrocytoma and overall were 50%, 30% and 43%, respectively. The incidence of therapeutic responses among all prognostic factors before HBO/IAR did not significantly differ. Median TTP for patients with glioblastoma, patients with anaplastic astrocytoma, and overall were 38, 56 and 43 weeks, respectively. The present study suggested that HBO/IAR therapy could be applied to especially patients with poor prognostic factors, because of its short treatment period, its permissible toxicity and identical response to patients with good prognostic factors.

To propose an adequate rehabilitation program for children suffering from hypoxic-ischemic encephalopathy (HIE) based on estimated outcomes.Participants were 42 children, 28 boys and 14 girls, who suffered from HIE after neonatal period. We divided them into three groups; favorable (GMFCS level 1 or 2), moderate (level 3 or 4), and unfavorable (level 5), and compared the extent of brain lesions on MRI, age of onset, and complications among the groups.The number of children in favorable, moderate, and unfavorable groups was 10, 10 and 22, respectively. All children in favorable and moderate groups showed focal cerebral lesions on MRI. In contrast, most children in unfavorable group (19/22) had diffuse brain damage and the rest were infantile onset with focal cerebral lesions. The etiology and situation of HIE did not differ among three groups. Three children in moderate group whose onsets were earlier than 5 months showed lesions similar to those in neonatal HIE; in bilateral basal ganglia, thalamus, and perirolandic cortex. In favorable group, 7 children were able to walk independently within 5 months after the insult, but 9 had moderate or severe mental retardation and 3 showed severe visual impairment. A majority of unfavorable group developed scoliosis or hip dislocation, and underwent tracheostomy or gastrostomy. Five children who had stayed acute hospitals for longer than 6 months developed irreversible complications such as joint contractures before discharge.Children with focal cerebral lesions need continual rehabilitation and education for mental retardation and visual impairment, even if they can walk within several months after HIE. Those with diffuse brain damage need sufficient rehabilitation as early as possible to avoid developing secondary complications. MR image, age of onset, and clinical course were of great prognostic value to make appropriate long-term rehabilitation and education programs.

Striped bonito Sarda orientalis larvae and juveniles were reared in a laboratory from hatching to 14 days post hatching, and the development of their digestive system was investigated histologically. On day 2 (first feeding day), the larval-type digestive system was differentiated. On day 3, a blind sac with densely distributed gastric glands developed and pyloric ceca appeared, suggesting that the digestive system was attaining adult-type structure. The yolk was completely absorbed on day 4. Bonito larvae preyed on rotifers and/or Artemia nauplii on day 2, but almost the whole gut was occupied by fish larvae from day 4. In the striped bonito, the adult-type digestive system was established right after first feeding, and this precocious development was well synchronized with the appearance of piscivory.

In this paper, the solution of a semi-infinite plane with one circular hole is presented. This solution is induced by repeatedly superposing the solution of an infinite plane with one circular hole and that of a semi-infinite plane without holes to cancel out the stresses arising on both boundaries. This procedure isrncarried out until the stresses arising on both boundaries converge. This method does not require complicated calculation procedures as does the method using stress functions defined in a bipolar coordinate system. Some numerical results are shown by graphical representations.

We examined the biochemical properties of YM-57029 ({4-[4-(4-Carbamimidoylphenyl)-3-oxopiperazin-1-yl]piperidino}acetic acid monohydrochloride trihydrate) and the pharmacodynamics and pharmacokinetics of its prodrug, YM128 (Ethyl (Z)-(4-{4-[4-(N 2 -hydroxycarbamimidoyl)phenyl]-3-oxopiperazin-1-yl}piperidino)acetate), an orally-active glycoprotein IIb/IIIa (GPIIb/IIIa) antagonist. YM-57029 strongly inhibited aggregation of human platelets induced by various agonists, with IC50 values ranging from 3.6 to 51 nM. YM-57029 specifically inhibited fibrinogen binding to purified GPIIb/IIIa about 1,000-fold more potently than Arg-Gly-Asp-Ser (RGDS). Moreover, YM-57029 effectively inhibited an Arg-Gly-Asp (RGD) peptide binding to platelets, suggesting that YM-57029 competed with the RGD sequence of ligand. YM-57029 or YM128 dose-dependently inhibited ex vivo platelet aggregation after iv bolus injection or oral administration to beagle dogs and cynomolgus monkeys. However, YM128 exerted more potent and prolonged inhibitory effects on platelet aggregation than YM-57029 after oral administration to cynomolgus monkeys. Furthermore, YM-57029 prolonged template bleeding time at a dose that inhibited ex vivo platelet aggregation during cumulative iv infusion to cynomolgus monkeys. Metabolic and pharmacokinetic studies showed that YM128 effectively converted into YM-57029 in liver microsomes from humans as well as dogs and monkeys, and that bioavailabilities of YM128 in dogs and monkeys were 32.3 and 22.2%, respectively. These results suggest that YM128, a prodrug of YM-57029, may be a valuable GPIIb/IIIa antagonist with good bioavailability in humans. Drug Dev. Res. 55:149-161, 2002. © 2002 Wiley-Liss, Inc.

Measurement of oxygen pressure (pO2) in tumor tissue is important, because pO2 is a major factor for radiosensitivity in malignant glioma treatment. We attempted to elucidate the changes in pO2 level in glioblastoma tissue of patients under various conditions. Eighteen patients with newly diagnosed glioblastoma were recruited to this study. Disposable Clark-type electrodes were inserted using CT guided stereotactic surgery under local anesthesia and left in the intra- and peritumoral regions. pO2 was measured in patients under conditions of being awake and asleep, inhaling 100% O2, being administered osmotic diuretics and following hyperbaric oxygen exposure (HBO). Peritumoral tissue had a significantly higher pO2 value in both awake and sleeping patients. O2 inhalation could not significantly increase the pO2 level, whereas administration of osmotic diuretics induced an increase in pO2 levels in peritumoral tissue alone. The pO2 levels were significantly increased in both regions after HBO, and a high pO2 level was maintained until 15 min after HBO in both regions. It is possible that the pO2 level in peritumoral tissue is affected by intracranial pressure, whereas that in the intratumoral tissue is usually low. HBO was the optimal procedure for oxygenation, but its benefit was reduced over time.

Objectives To elucidate the prevalence of cerebellar injury and its relationship to functional outcomes in preterm children with cerebral palsy (CP) after intraventricular hemorrhage (IVH). Participants We selected 69 children (40 males and 29 females, aged between 6 and 13 years) out of 2049 with cerebral palsy who visited Morinomiya Hospital, the regional center hospital for CP in West Japan. The inclusion criteria were (1) gestational age under 36 weeks at birth, (2) clear history of postnatal intraventricular hemorrhage, and (3) age at investigation over 6 years old. Those without sufficient imaging study or functional evaluation were excluded. Methods The participants were divided into four groups according to the presence of post-hemorrhagic hydrocephalus (PH) and cerebellar injury (CI): PH+/CI+, PH+/CI−, PH−/CI+, and PH−/CI−. Type of CP, ability to walk, verbal function, the incidence of severe visual impairment, and the complication of epilepsy were investigated and compared among the groups. Results The gestational ages of the participants were between 22 and 34 weeks, and their birth weight was between 412 and 1788 g. PH and CI were found in 39 (57%) and 40 (58%) children, respectively. Both the PH+/CI+ group ( n = 31) and the PH−/CI+ group ( n = 9) showed significantly lower walking and verbal abilities and a higher incidence of epilepsy than the PH−/CI− group ( n = 21), while the PH+/CI− group showed no significant difference from the PH−/CI− group. Severe visual impairment was found only in the PH+/CI+ group and the PH−/CI+ group. Conclusions The prevalence of CI in preterm children with CP after IVH (58%) was almost the same as that of PH. CI is one of the most significant complications in preterm infants, affecting motor and verbal functions and being associated with epilepsy more than PH.

To identify amplified oncogenes involved in hepatocellular carcinomas (HCC), we applied a genomic DNA microarray spotted with 57 oncogenes to 20 HCCs. Aberrations in DNA copy number also were analyzed by comparative genomic hybridization (CGH) using an aliquot of DNA samples. In 5 of 20 HCCs, only 6 oncogenes (CCND1, FGF3/FGF4, SAS/CDK4, TERC, MET, and MYC) were amplified, whereas in the remaining 15 tumors no oncogenes were amplified. A comparison of DNA microarray and conventional CGH analyses showed that, although 5 of 6 amplified oncogenes shown by microarray were located in chromosomal regions shown by CGH to have increased DNA copy numbers, not all genes located in such chromosomal regions were affected. One of the amplified oncogenes (SAS/CDK4) was found in a chromosomal region that was undetected by CGH. We, therefore, conclude that amplification of the oncogenes examined in this series is not directly implicated in hepatocellular carcinogenesis.

To elucidate the significance of oxidative stress in the modulation of endothelial functions, we examined the effects of H2O2on the expression of two endothelium-derived vasoactive peptides, endothelin (ET) and adrenomedullin (Am), and their interaction. H2O2dose dependently suppressed ET secretion and ET-1 mRNA expression in bovine carotid endothelial cells (ECs). Menadion sodium bisulfate, a redox cycling drug, also decreased ET secretion in a dose-dependent manner. Catalase, a H2O2reductase, and dl-α-tocopherol (vitamin E) significantly inhibited H2O2-induced suppression of ET secretion. Downregulation of ET-1 mRNA under oxidative stress was regulated at the transcriptional level. In contrast, H2O2increased Am secretion (and its mRNA expression) accompanied by the augmentation of cAMP production. Am, as well as 8-bromo-cAMP and forskolin decreased ET secretion in a dose-dependent fashion. Furthermore, an anti-Am monoclonal antibody that we developed abolished H2O2-induced suppression of ET secretion at 6–24 h after the addition of H2O2. H2O2increased the intracellular Ca2+concentration ([Ca2+]i). Moreover, treatment with ionomycin, a Ca2+ionophore, and thapsigargin, an inhibitor of endoplasmic reticulum ATPase, decreased ET secretion dose dependently for 3 h. These results suggest that the production of ET was decreased via activation of the Am-cAMP pathway and by the elevation of [Ca2+]iunder oxidative stress. These findings elucidate the coordinate expression of two local vascular hormones, ET and Am, under oxidative stress, which may protect against vascular diseases.

Background —Rho-associated kinase (ROCK), an effector of small GTPase Rho, regulates vascular tone via a calcium sensitization mechanism and plays a key role in the pathogenesis of hypertension. However, its role in vascular growth remains unclear. Methods and Results —Y-27632, a specific ROCK inhibitor, and the overexpression of dominant-negative ROCK suppressed the mitogen-induced DNA synthesis of cultured vascular smooth muscle cells (VSMCs), which indicates the essential role of ROCK in the control of VSMC proliferation in vitro. Y-27632 also suppressed the chemotaxis of VSMCs. Male Wistar rats were systemically given Y-27632 (35 to 70 mg · kg −1 · day −1 ) through an intraperitoneal infusion. The neointimal formation of balloon-injured carotid arteries was significantly suppressed in Y-27632–treated rats (intima/media ratio, 0.22±0.02) compared with vehicle-treated rats (intima/media ratio, 0.92±0.21) or hydralazine-treated rats with a similar blood pressure decrease (intima/media ratio, 1.03±0.15). The phosphorylation of myosin phosphatase and myosin light chain was elevated in injured arteries in a Y-27632–sensitive manner, indicating the augmentation of ROCK activity in neointimal formation. The downregulation of the cyclin-dependent kinase inhibitor p27 kip1 in injured vessels was reversed by Y-27632 treatment, reflecting the antiproliferative effect of ROCK inhibition in vivo. Conclusions —We conclude that ROCK plays a key role in the process of neointimal formation after balloon injury. Thus, the inhibition of ROCK may be a potential therapeutic strategy for treating vascular proliferative disorders and hypertension.

Three patients with generalised myasthenia gravis and three with ocular myasthenia gravis received two to five courses of high dose intravenous methylprednisolone because of the failure of standard immunomodulating therapies. Changes in myasthenic signs were assessed using a four step system for grading muscle weakness and fatiguability in 10 test items. Although a brief and modest amelioration was found from day 1 to day 2 after the initial infusion in two patients with generalised myasthenia gravis, all three experienced a prolonged phase of worsening followed by improvement before the next course. Conversely, for two of the patients with ocular myasthenia gravis, a transient but dramatic improvement of ptosis and ocular immobility was noted from 90minutes to 5 hours after initiating the first infusion, followed by mild or no exacerbation. This 3 hour improvement may be related not only to possible differences in the neuromuscular junction, but also to corticosteroids unmasking the central adaptation for the peripheral ocular muscle weakness by increasing the acetylcholine release.

Very few studies on two dimensional elastic semi-infinite plane with circular hole subjected to arbitary loads at the circular hole are conducted for estimating displacement because of difficulties in treatment. This paper presents the method for estimating displacement of semi-infinite plane with circular hole subjected to arbitrary load on circular hole by using constraint-release technique which repeats superposing solutions of infinite plane with circular hole and semi-infinite plane to converge boundary conditions on both of boundaries. Some numerical results are shown by graphical representation.

Twenty-eight patients who were previously treated by aggressive surgery and radiation and were diagnosed with supratentorial malignant gliomas received a combination of nimustine hydrochloride; 1-(4-amino-2-methyl-5-pyrimidinyl) methyl-3-(2-chloroethyl)-3-nitrosourea hydrochloride (ACNU), cisplatin and etoposide (ACE therapy) as primary treatment. Cisplatin and etoposide were given at doses of 20 and 60 mg/m2/day for 5 days, respectively, ACNU doses 80 mg/m2/day on the first day. Treatment was repeated at 4-week intervals for up to 3 cycles. Seventeen patients (60.7%) complained of nausea. Grade 3 or 4 hematological toxicity occurred in 11 patients (39.3%), and grade 3 or 4 renal toxicity occurred in 2 patients. The percentage of patients who showed complete or partial response was 28.6% (8/28). The median time of tumor progression was 40 weeks, and the median survival time was 146 weeks. There were some long-surviving patients who may have benefited from ACE combination. This study demonstrated the effects of ACE combination in patients with supratentorial malignant gliomas.

We describe a case of intracranial chondrosarcoma in a 46-year-old woman. The preoperative diagnosis was meningioma as plain radiography and computed tomography of the head revealed a tumor with discrete calcifications predominantly in the right frontoparietal region and hyperostosis of the inner table of the skull overlying the tumor. However, the tumor was histologically composed of cartilaginous tissue without meningiomatous differentiation and the final diagnosis was a low-grade chondrosarcoma based on its histological appearance and size, together with the radiologic images. Intracranial chondrosarcoma occurring above the skull base is extremely rare and 19 cases were found in our literature review. Intracranial chondrosarcoma showing hyperostosis of the skull has not been reported in the cases. The discussion includes its differential diagnosis, origin, and clinical behavior.

脾外傷における脾部分切除術においては被膜の脆弱性や血管処理操作の煩雑さなどから,操作時間が短縮できてかつ安全に止血できる手術方法の開発が望まれる。今回われわれは,超音波凝固切開装置Harmonic ScalpelTM (HS)を用いて短胃動静脈,脾動静脈を凝固切離し,adjustable linear stapler (ALS)で脾実質をステイプリングして部分切除する方法を考案した。ブタにおいて日本外傷学会分類III型脾外傷モデルを作成し,A群ではHSとALSを用いて半切除術を施行した。B群では従来法(結紮切離,縫合)で半切除術を施行し比較検討すると,A群で有意な出血量の減少,操作時間の短縮を認めた。臨床応用については,HSで安全に凝固切離できる血管径やALSに取り込める実質の厚さなどの制約があるが,適応を選べば有用な手術術式になり得るのではないかと考えられた。またブタの腹腔鏡下でのHSとsurgical stapler (SS)を用いた脾臓部分切除と臨床症例についても報告した。

The purpose of this study is to analyze historically the relationship between the establishment of the ski supply system and the diffusion of skiing in Fukui Prefecture. The historical documents examined in this paper include newspapers and ″Urigenbo″, which is a price list written by the Kikukawa Ski Manufacturing Company. People who could ski represente only a small part of the entire population of Fukui Prefecture in the Taisho Era, because there was no supply system for skiing equipment. The demand for skis increased as the spread of skiing in Fukui was promoted by education associations and other groups. The Kikukawa Ski Manufacturing Company began to manufacture skis in the autumn of the last year of the Taisho Era. Kikukawa Ski supported the promotion of the spread of skiing from the side of the supply system for skiing equipment. Eight ski grounds were set up in Fukui Pref, by the 8th year of the Showa Era. In addition, ski clubs were established at each ski ground and people in those areas made use of the new infrastructure. The shops for selling Kikukawa's skis started up in places surrounding these ski grounds. Prior to the establishment of ski retailers, the conditions for the diffusion of skiing did not exist in Fukui, due to the lack of a supply system. Once Kikukawa began to supply skis, and through the activities of education associations, finally, skiing was able to spread in Fukui by the 8th year of the Showa Era.

We report a case of perforated Meckel's diverticulum with aseptic peritonitis in a 17-day-old neonate. The baby had been brought to the hospital with fever and abdominal distention. Abdominal computed tomography showed a 5-cm abscess in the lower abdomen, and emergency laparotomy was performed for suspected perforated appendicitis. However, we found a perforated Meckel's diverticulum. No bacteria were detected in the purulent ascites from the peritoneal cavity. We speculate that the narrow lumen between the small intestine and the diverticulum, accompanied by poor self-emptying had caused acute inflammation resulting in perforation of Meckel's diverticulum. The anatomic limitations in "walling off" the perforated Meckel's diverticulum by the surrounding loops of small intestine prevented the bowel contents from spreading within the peritoneal cavity.

A 14-year-old boy presented with a very rare meningioma in the posterior cranial fossa without dural attachment. Magnetic resonance imaging revealed a 3-cm, well-circumscribed, heterogeneously enhanced, round mass without dural tail sign in the right side of the posterior fossa. Right vertebral angiography revealed very faint tumor staining supplied by the right posterior inferior cerebellar artery. Total removal of the tumor was performed. Intraoperatively, the mass exhibited no attachment to the dura mater, cerebellar parenchyma, or choroid plexus, but was firmly attached to the arachnoid tissue near the foramen of Luschka. Histological and immunohistochemical studies established the diagnosis of meningothelial meningioma (World Health Organization grade I).

Comparative genomic hybridization (CGH) is a technique that allows the detection of losses and gains in DNA copy number across the entire genome. We used CGH to study the genetic alterations that occur in primary astrocytomas, including 14 glioblastomas (GBM), 12 anaplastic astrocytomas (AA), and 7 low-grade astrocytomas (LGA). The average numbers of total aberrations in GBM, AA, and LGA were 9.7, 5.4, and 4.0, respectively. The average number of DNA sequence losses in GBM was significantly higher than that in AA or LGA (P eight cases) observed in all grades of astrocytoma were 7p13-p12 (gain), 7q31 (gain), 8q24.1-q24.2 (gain), 9p21 (loss), 10p12-p11 (loss), 10q22-qter (loss), 13q21-q22 (loss), and 20q13.1-q13.2 (gain). Loss of 9p, 10p, or 10q, and the gain or amplification of 7p, were observed frequently in GBM (64%, 57%, 64%, and 50% of cases, respectively). Frequent alterations found in AA were losses of 9p, 10q, and 13q, and gains of 1q, chromosome 7, 11q, and Xq. Whereas 7p13-p11 amplification occurred exclusively in cases with the loss of all or part of chromosome 10, this change never occurred in cases having an increase in copy number of 8q, which was the most frequent change observed in LGA (four of seven cases). These results may indicate that an increase in copy number of 8q is an important event in GBM, with a genetic pathway, which is distinct from that in GBM with 7p amplification. Genes Chromosomes Cancer 21:340–346, 1998. © 1998 Wiley-Liss, Inc.

We investigated factors of the early recurrence and malignant transformation of histologically benign meningiomas using immunohistochemistry for MIB-1 positive indices (PI) and p53 protein expression, a flow cytometric DNA analysis, and the examination of numerical chromosomal aberrations detected by fluorescence in situ hybridization using an alpha-satellite DNA probe and a bcr gene locus-specific probe. Twenty-six meningiomas of 23 patients were classified into two groups: the 3 patients in whom a recurrence was defined within two years after initial surgery and who showed histologically malignant features were classified as the early recurrent group, and the other 20 patients in whom recurrence did not develop during the same period were classified as the nonrecurrent group. DNA aneuploidy was observed in 40% of the nonrecurrent patients and in 67% of the early recurrent patients. Loss of chromosome 22 was the most common numerical aberration, but the aberrations characteristic of early recurrent meningiomas were not detected. The MIB-1 PI values of the early recurrent meningiomas were higher than those of nonrecurrent meningiomas, suggesting that MIB-1 PI is very important for biological and histopathological analyses and prediction of the future recurrence of meningiomas.

Persons with severe motor and intellectual disabilities (SMID) caused by injury to the developing brain sometimes present generalized hypertonia in a specific position with extreme muscle overactivity persisting for most of the time during wakefulness. This "persistent generalized muscle contraction" is often associated with bad humor, sleep disturbance, hyperhidrosis, wasting, elevation of serum creatine kinase levels, regular daytime use of hypnotic or sedative medication, and the necessity to maintain the neck or hip in a flexed position manually. The aim of this study is to elucidate the clinical profile of this condition.We retrospectively examined the medical records and brain imaging data of 66 SMID patients in the state of persistent generalized muscle contraction.Most patients could be classified into 2 major categories on the basis of clinical presentation and brain imaging: (A) those with premature birth and bilateral lesion of globus pallidus interna (kernicterus) (n = 16), and (B) those with various widespread bilateral basal ganglia/thalamic and/or cerebral lesions such as hypoxia-ischemia, acute encephalopathy, malformation, etc (n = 50). Group A assumed an asymmetrical tonic-neck-reflex-like position, torsion of the trunk, fluctuation of hypertonia, and better mental development. Three of them exhibited extreme hypertonia resembling status dystonicus. Group B often exhibited persistent and fixed retroflexion of the neck and trunk or opisthotonus. Drugs such as oral muscular relaxants were ineffective in both groups. Injection of botulinum toxin into the cervical and paravertebral muscles partially alleviated symptoms.Persistent generalized muscle contraction in SMID has at least two different types. Group A has characteristics of severe dystonic hypertonia that could lead to status dystonicus. Group B might have peculiar characteristics of muscle overactivity triggered by wakefulness or discomfort, which probably results from inability to achieve spontaneous muscle relaxation.

We investigated the effect of Fas/APO1-ligand (CD95L) gene transfer on allogeneic immune responses in vivo. A colon carcinoma cell line from BALB/c mice, CT26, was stably transfected with a vector encoding mouse CD95L and was inoculated into C57BL/6 mice. CD95L expression markedly reduced allogeneic cytotoxic T lymphocyte and helper T lymphocyte activity directed toward CT26. Strikingly, expression of CD95L on these allogeneic tumors completely inhibited the generation of alloantibodies of both IgM and IgG subclasses. Thus, CD95L inhibited alloantibody production and conferred localized immune suppression through this mechanism. These results provide insight into the role of CD95L in regulating the alloantibody response and the generation of local immune responses.

The therapeutic efficacy of a regimen consisting of intravenous injection of Cardiocrome, containing cytochrome c, flavin mononucleotide and thiamine diphosphate for mitochondrial encephalomyopathy (MEM) was examined. This combined therapy was applied to nine patients with MEM, including four with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes. For the standard regimen, Cardiocrome was first injected daily, usually for 4 weeks, and later by means of intermittent injections for maintenance treatment. Clinical improvement was obtained in eight of the patients. Improvement was observed in the muscle symptoms of easy fatigability, motor disability and severity of stroke-like episodes, as well as in various other symptoms such as phosphate, tinnitus, headache, corneal edema, chilblains, thalamic pain, respiratory failure, and nystagmus. This clinical improvement was maintained for more than 1 year by additional intermittent injections. In conclusion, this therapy was fairly effective for the management of patients with MEM.

The purpose of this study is to explain the manufacturing and marketing activities of the Kaneda Ski Manufacturing Factory in Toyama Prefecture from the end of the Taisho Era to the early years of the Showa Era. This study uses historical data from Toyama Prefecture during the Taisho and Showa Eras.The following conclusions are deduced ; 1) Johana Town had Tatenogahara ski ground and was a good environment forskiing. The "Take" ski was popular in Johana Town from the middle of the Taisho Era. Kaneda took interest in skis from that time, as he enjoyed skiing and was a carpenter. He started to manufacture skis from the latter half of the Taisho Era and to sell skis from the fifteenth year of that era. 2) The trend in ski goods in this period was from Austrian to Norwegian type, but as Kaneda did not manufacture bindings, the biggest obstacle for him in manufacturing was to achieve the proper curvature of the ski. 3) Kaneda was willingly coached about manufacturing by Tomesaburo Sakur aba. Kaneda was coached from the fourth year of the Showa Era for ten years. Because of the superior help he received, Kaneda was able to succeed in both the manufacturing and marketing of the product.

頸動脈疾患におけるドプラ超音波を用いた無症候性の塞栓シグナル (ES) の検出の頻度は高く, 疾患の活動性のマーカーとなり, 卒中リスクの高い患者の選択を可能にする.しかし報告によって無症候性ESの検出頻度が異なっており, ESの同定に違ったクライテリアが用いられているのではないかという懸念がある.前回の二つのセンターの間の再現性調査では良好な一致を見たが多数のセンター問の調査は行われていない.ES検出について最近報告を出している九つのセンターの間で国際的な再現性調査が行われた.各センターは症候性頸動脈狭搾のある六人の患者の中大脳動脈TCD記録のオーデイオドプラ信号をブラインドで解析した.ESを検出した正確な時間を記録した.六つのセンターでは各ESの強度の増加も記録した.観察者間の一致は特別な協定に基づく方法で決められた.七つのセンターは39-55の信号を記録した.しかし一つのセンターは142のESを報告した.観察者間の一致確率は.678であるが, 最多のESを報告したセンターを除くと.791であった.デシベル閾値を導入すると一致確率は著明に上昇した.>7dBのデシベル閾値にすると.902の一致確率となった.大概のセンター問での強度測定は良い相関を示したが必ずしも常にそうではない.15の相関のうち3は有意ではなかった.測定された強度の絶対値はセンター間で40%も違っていた.結論: 研究報告によってESの頻度が違うのは少なくともある程度はESの同定に異なるクライテリアが用いられていることを反映している.以前に提唱されていたES同定のコンセンサスクライテリアは異なるセンターにおけるES同定の再現性には十分に精確とはいえない.デシベル閾値を用いると再現性が向上し観察者間の一致率の著明な改善が得られる.しかし, 一つのセンターで開発された強度閾値をそのまま他の施設で使うことは出来ない.測定方法が違うので同じ装置が用いられていても同じESで違った強度の値が得られるのである.

Although it is known that osteoclasts are multinucleated cells that are responsible for bone resorption, the mechanism by which their size is regulated is unclear. We previously reported that an actin-rich superstructure, termed the zipper-like structure, specifically appears during the fusion of large osteoclast-like cells (OCLs). Actin cytoskeleton reorganization in osteoclasts is regulated by a signaling network that includes the macrophage colony-stimulating factor (M-CSF) receptor, a proto-oncogene, Src, and small GTPases. Here, we examined the role of actin reorganization in the multinucleation of OCLs differentiated from RAW 264.7 cells using various pharmacological agents. Jasplakinolide, which stabilizes actin stress fibers, induced the development of small OCLs, and the Src inhibitor SU6656 and the dynamin inhibitor dynasore impaired the maintenance of the podosome belt and the zipper-like structure. These inhibitors decreased the formation of large OCLs but increased the number of small OCLs. M-CSF is known to stimulate osteoclast fusion. M-CSF signaling via Src up-regulated Rac1 activity but down-regulated Rho activity. Rac1 and Rho localized to the center of the zipper-like structure. Rho activator II promoted the formation of small OCLs, whereas the Rho inhibitor Y27632 promoted the generation of large OCLs. These results suggest that the status of the actin cytoskeleton signaling network determines the size of OCLs during cell fusion.

To date, several small molecules of CD4 mimics, which can suppress competitively the interaction between an HIV-1 envelope glycoprotein gp120 and a cellular surface protein CD4, have been reported as viral entry inhibitors. A lead compound 2 (YYA-021) with relatively high potency and low cytotoxicity has been identified previously by SAR studies. In the present study, the pharmacokinetics of the intravenous administration of compound 2 in rats and rhesus macaques is reported. The half-lives of compound 2 in blood in rats and rhesus macaques suggest that compound 2 shows wide tissue distribution and relatively high distribution volumes. A few hours after the injection, both plasma concentrations of compound 2 maintained micromolar levels, indicating it might have promise for intravenous administration when used combinatorially with anti-gp120 monoclonal antibodies.

The progressive growth of tumors in mice is accompanied by down-regulation of specific T cell responses. The factors involved in this suppression are not completely understood. Here, we have developed a model to examine the role of host immune effector cells in the inhibition of T cell function. In this model, progressive growth of a colon carcinoma line, CT26, is accompanied by loss of T cell response to alloantigens in both cytolytic and proliferation assays. The CT26 tumor was inoculated into BALB/c syngeneic mice. Tumor growth, cytolytic T cell responses, lymphocyte proliferation, and flow cytometric analysis was performed in tumor-bearing animals 7 or 28 days after tumor inoculation. Spleen cells from tumor-bearing mice were found to suppress the proliferative response of spleen cells from normal mice to alloantigens. Examination of the spleen cell population by FACS analysis revealed an increase in the percentage of monocytes as defined by expression of CD1 1b, the Mac-1 antigen. Removal of the Mac-1-positive cells from the tumor-bearing hosts spleen relieved suppression of the tumor-bearing mouse spleen cell proliferative response to alloantigens, and addition of the Mac-1-positive enriched cells suppressed proliferation of normal T cells in response to alloantigens. Cell contact was required for this inhibition. Tumor induction of suppressive monocytes plays an important role in the general immunosuppression noted in animals bearing CT26 tumors. Identification of the mechanisms responsible for this effect and reversal of tumor-induced macrophage suppression may facilitate efforts to develop effective immunotherapy for malignancy.

In order to evaluate the roles of the RET proto-oncogene in normal human tissues and tumors derived from the neural crest cells, we examined the expression of RET in a variety of adult human tissues, pheochromocytomas, medullary thyroid carcinomas (MTCs), ganglioneuromas, and a neurinoma. Northern blot analysis demonstrated that RET is normally expressed in the adrenal medulla and cerebellum among adult human tissues. RET transcripts were detected in all of 11 sporadic and one familial pheochromocytomas. The levels of RET mRNA were higher in 8 of 12 pheochromocytomas than in the normal adrenal medulla, indicating that RET is overexpressed in the majority of sporadic pheochromocytomas. There was a considerable difference in the level of RET expression in each pheochromocytoma ranging from 0.2 to 10 times the transcripts found in the normal adrenal medulla. The sizes of the transcripts of 7.0, 6.0, 4.5, and 3.9 kb were the same as those found in the adrenal medulla, suggesting no rearrangements of the RET gene in pheochromocytomas. Southern blot analysis revealed neither amplification nor gross structural changes in the RET gene. RET was also expressed at high levels in four MTCs examined, whereas its transcripts were detected at low abundance in only one of three ganglioneuromas. RET was not expressed in a neurinoma. These results suggest that RET may play some roles in a limited range of adult human tissues, and that its high levels of expression may have relevance to development or growth of pheochromocytomas and MTCs.

The effects of lead nitrate on the induction of hepatic cytochrome P450IA (CYP1A) isoforms, mainly CYP1A2, by aromatic amines (2-methoxy-4-aminoazobenzene, 2-amino-3-methyl-9H-pyrido [2,3-b]indole and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine) and aryl hydrocarbons (3-methylcholanthrene, benzo[a]pyrene and beta-naphthoflavone) in male F344 rats were examined at the levels of mRNA, protein and activity of the enzymes. Pretreatment of rats with lead nitrate suppressed the expression of hepatic CYP1A enzyme(s), especially CYP1A2, at both levels of protein and activity of the enzyme(s) by treatment with an aromatic amine or an aryl hydrocarbon. On the other hand, the lead nitrate pretreatment suppressed the induction of CYP1A mRNA(s) by an aromatic amine but not by an aryl hydrocarbon. These findings indicate that lead nitrate suppresses the expression of CYP1A enzymes at both stages of post-translation of mRNAs and transcriptional activation of the genes, and further suggest that the pathway for the transcriptional activation of the CYP1A genes by the aromatic amines is different from that by the aryl hydrocarbons.

We conducted a quantitative study of an animal community associated with clumps of submerged drifting algae on a sand/mud bottom at Fildes Bay, King George Island. The algae clumps were found at depths between 5 and 20 m in the inner part of the bay. The clumps mainly consisted of Desmarestia anceps covering about 5% of the bottom. A large number of a nemertinean (0-220 individuals/m^2), Nacella concinna (0-65 individuals/m^2), Glyptonotus antarcticus (adults 0-8 individuals/m^2, juvenile 0-80 individuals/m^2) and gammaridean amphipods (490-25020 individuals/m^2) were found associated with the clumps. Schools of Trematomus newnesi young (0-18 individuals/m^2) hovered over the clumps. Stomach contents of T. newnesi consisted mainly of gammaridean amphipods. The algae clump seemed to be an important habitat as a nursery ground for G. antarcticus and T. newnesi.

From 1991 to 1993 we conducted underwater observations on communities of fish and epibenthic invertebrates four times during the austral summer in Fildes Bay, King George Island Antarctica. We defined eight distinctive habitat types in the inshore areas (depths between 0 and 40 m), each having a characteristic community of fish and epibenthic invertebrates. Species compositions of animal communities varied according to the bottom substrates, depths and the presence or absence of macroalgal colonies. The habitat types of the major animal species are described, and characteristics of each habitat type and its faunal composition are noted.

Several CD4 mimics have been reported as HIV-1 entry inhibitors that can intervene in the interaction between a viral envelope glycoprotein gp120 and a cell surface protein CD4. Our previous SAR studies led to a finding of a highly potent analogue 3 with bulky hydrophobic groups on a piperidine moiety. In the present study, the aromatic ring of 3 was modified systematically in an attempt to improve its antiviral activity and CD4 mimicry which induces the conformational changes in gp120 that can render the envelope more sensitive to neutralizing antibodies. Biological assays of the synthetic compounds revealed that the introduction of a fluorine group as a meta-substituent of the aromatic ring caused an increase of anti-HIV activity and an enhancement of a CD4 mimicry, and led to a novel compound 13a that showed twice as potent anti-HIV activity compared to 3 and a substantial increase in a CD4 mimicry even at lower concentrations.

Objective: Recently, COL4A1 mutations have been reported in porencephaly and other cerebral vascular diseases, often associated with ocular, renal, and muscular features. In this study, we aimed to clarify the phenotypic spectrum and incidence of COL4A1 mutations. Methods: We screened for COL4A1 mutations in 61 patients with porencephaly and 10 patients with schizencephaly, which may be similarly caused by disturbed vascular supply leading to cerebral degeneration, but can be distinguished depending on time of insult. Results: COL4A1 mutations were identified in 15 patients (21%, 10 mutations in porencephaly and 5 mutations in schizencephaly), who showed a variety of associated findings, including intracranial calcification, focal cortical dysplasia, pontocerebellar atrophy, ocular abnormalities, myopathy, elevated serum creatine kinase levels, and hemolytic anemia. Mutations include 10 missense, a nonsense, a frameshift, and 3 splice site mutations. Five mutations were confirmed as de novo events. One mutation was cosegregated with familial porencephaly, and 2 mutations were inherited from asymptomatic parents. Aberrant splicing was demonstrated by reverse transcriptase polymerase chain reaction analyses in 2 patients with splice site mutations. Interpretation: Our study first confirmed that COL4A1 mutations are associated with schizencephaly and hemolytic anemia. Based on the finding that COL4A1 mutations were frequent in patients with porencephaly and schizencephaly, genetic testing for COL4A1 should be considered for children with these conditions. ANN NEUROL 2013.

Heterozygous loss of function mutations of CASK at Xp11.4 in females cause severe intellectual disability (ID) and microcephaly with pontine and cerebellar hypoplasia (MICPCH). However, the longitudinal clinical and radiological course of affected patients, including patterns of postnatal growth, has not been described. Neurodevelopmental and imaging information was retrospectively accrued for 16 Japanese (15 female and 1 male) patients with ID and MICPCH associated with CASK mutations. All records were analyzed; patient age ranged from 2 to 16 years at the time of the most recent examinations. The growth pattern, neurological development, neurological signs/symptoms, and facial features were similar in the 15 female patients. Their head circumference at birth was within the normal range in about half, and their height and weight were frequently normal. This was followed by early development of severe microcephaly and postnatal growth retardation. The patients acquired head control almost normally between 3 and 6 months, followed by motor delay. More than half of the female patients had epilepsy. Their MRIs showed microcephaly, brainstem, and cerebellar hypoplasia in early infancy, and a normal or large appearing corpus callosum. The male patient showed a more severe clinical phenotype. These uniform clinical and radiological features should facilitate an early diagnosis and be useful for medical care of females with ID and MICPCH associated with CASK mutations.

Purpose Congenital tracheal stenosis is a rare condition and can be difficult to manage. One source of difficulty is postoperative tracheomalacia requiring long-term tracheal stenting. To prevent symptomatic postoperative tracheomalacia, we have been adding aortopexy to tracheal reconstruction since 2008. The aim of this study was to evaluate efficacy of aortopexy for preventing postoperative tracheomalacia after reconstruction of congenital tracheal stenosis. Methods Retrospective chart review was conducted. From October 2003 to March 2011, 24 had tracheal reconstruction without aortopexy (group A) and 8 with aortopexy (group B). Statistical analysis was performed using Fisher's Exact test. Results One had anastomotic leakage in group A, and 1, in group B ( P = .44). Eleven patients required tracheostomy because of postoperative tracheomalacia confirmed by postoperative bronchoscopy in group A vs none in group B ( P = .029). Conclusions We found that aortopexy with tracheal reconstruction reduced the need for postoperative tracheostomy in this patient group. Although there is a potential risk of anastomotic leakage because of the suspension suture on the anterior tracheal wall to aorta, we did not detect an increased incidence after aortopexy. Thus, aortic suspension may be a useful adjunct to prevent symptoms of tracheomalacia in these patients.

Brain and atrial natriuretic peptides (BNP and ANP) are cardiac hormones with diuretic, natriuretic, and vasodilatory activities. Cardiomyopathic hamsters are widely used animal models of heart failure. Due to the structural divergence of BNP among species, examination on pathophysiological roles of BNP using cardiomyopathic hamsters is so far impossible. We therefore isolated hamster BNP and ANP cDNAs, and investigated synthesis and secretion of these peptides in normal and cardiomyopathic hamsters. The COOH-terminal 32-residue peptide of cloned hamster preproBNP with 122 amino acids, preceded by a single arginine residue, supposedly represents hamster BNP showing < 50% homology to rat BNP. Alpha-hamster ANP, 28-residue peptide, is identical to alpha-rat ANP. In hamsters, BNP and ANP occur mainly in the ventricle and the atrium, respectively. The 32-wk-old hypertrophic cardiomyopathic BIO14.6 strain exhibited ventricular hypertrophy. The 32-wk-old dilated cardiomyopathic BIO53.58 strain remained at the stage without apparent heart failure. In BIO14.6 and BIO53.58 strains at this age, ventricular BNP and ANP gene expressions are augmented, and the plasma BNP concentration is elevated to 136 and 108 fmol/ml, respectively, three times greater than the elevated plasma ANP concentration, which well mimics changes of the plasma BNP and ANP concentrations in human heart failure. Cardiomyopathic hamsters, therefore, are useful models to investigate the implication of BNP in human cardiovascular diseases.