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Virulent fowl adenovirus serotype 4 (FAdV-4) causes hydropericardium syndrome (HPS) with high mortality in chickens, leading to significant economic losses to the poultry industry. The development of an effective vaccine is essential for successful disease control. Here, we produced recombinant fiber-1 protein of FAdV-4, isolated from a Japanese HPS outbreak strain, JP/LVP-1/96, using a baculovirus expression system and evaluated its immunogenicity and protective efficacy. Recombinant fiber-1 protein induced high levels of neutralizing antibodies in immunized chickens, which were maintained for a minimum of 10 weeks. After being challenged with the virulent FAdV-4 strain JP/LVP-1/96, the immunized chickens did not exhibit clinical signs of infection or histopathological changes, there was a significant reduction in the viral load in various organs and total serum proteins, and albumin levels did not decline. These results suggest that the recombinant fiber-1 protein produced in this study can serve as a subunit vaccine to control HPS in chickens., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Here, we report the genomic characterization of a fowl adenovirus serotype 4 strain isolated from a chicken with hydropericardium syndrome in Japan. The viral genome of FAdV-4 strain JP/LVP-1/96 was found to be 45,688 bp long. Amino acid substitutions at position 219 (G to D) in the fiber-2 protein and at position 188 (I to R) in the hexon protein, which are commonly found in virulent FAdV-4 strains, were also found in the JP/LVP-1/96 strain. Additional specific amino acid substitutions commonly found in virulent FAdV-4 strains were found in ORFs 4 and 43, which are present only in members of the species Fowl adenovirus C. Phylogenetic analysis based on complete hexon protein gene sequences showed that strain JP/LVP-1/96 belongs to a different genetic cluster from the strains circulating in neighboring countries., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Leksell GammaPlan (LGP) software was initially designed for Gamma Knife radiosurgery, but it can be successfully applied to planning of the open neurosurgical procedures as well. We present our initial experience of delineating the cranial nerves in the vicinity of skull base tumors, combined visualization of the implanted subdural electrodes and cortical anatomy to facilitate brain mapping, and fusion of structural magnetic resonance imaging and diffusion tensor imaging performed with the use of LGP before removal of intracranial neoplasms. Such preoperative information facilitated choosing the optimal approach and general surgical strategy, and corresponded well to the intraoperative findings. Therefore, LGP may be helpful for planning open neurosurgical procedures in cases of both extraaxial and intraaxial intracranial tumors.

The availability of advanced computer-aided robotized devices for the Gamma Knife (i.e., an automatic positioning system and PerfeXion) resulted in significant changes in radiosurgical treatment strategy. The possibility of applying irradiation precisely and the significantly improved software for treatment planning led to the development of the original concept of robotic Gamma Knife microradiosurgery, which is comprised of the following: (1) precise irradiation of the lesion with regard to conformity and selectivity; (2) intentional avoidance of excessive irradiation of functionally important anatomical structures, particularly cranial nerves, located both within the target and in its vicinity; (3) delivery of sufficient radiation energy to the tumor with a goal of shrinking it while keeping the dose at the margins low enough to prevent complications. Realization of such treatment principles requires detailed evaluation of the microanatomy of the target area, which is achieved with an advanced neuroimaging protocol. From 2003, we applied the described microradiosurgical concept in our clinic for patients with benign skull base tumors. Overall, 75 % of neoplasms demonstrated shrinkage, and 47 % showed ≥50 % and more volume reduction. Treatment-related complications were encountered in only 6 % of patients and were mainly related to transient cranial nerve palsy. Just 2 % of neoplasms showed regrowth after irradiation. In conclusion, applying the microradiosurgical principles based on advanced neuroimaging and highly precise treatment planning is beneficial for patients, providing a high rate of tumor shrinkage and a low morbidity rate.

From 1993 to 2011, a total of 3,095 patients with brain metastases underwent Gamma Knife radiosurgery (GKS) at Tokyo Women's Medical University. Follow-up information on 2,283 of these patients was available for retrospective analysis. The cases were separated into three groups according to the treatment period, the model of the Gamma Knife used, main goals of treatment, and technical nuances of radiosurgery. In the latest cohort of patients treated with the Leksell Gamma Knife model 4C with automatic positioning system, an optimized treatment strategy was applied. It was based on highly selective dose planning, with the use of multiple small isocenters located within the bulk of the mass, which was done for prevention of the excessive irradiation of the perilesional brain and avoidance of its posttreatment edema. In cases of large cystic tumors, selective coverage of the contrast-enhancing capsule with chain-like application of multiple small isocenters was done. Introduction of the new treatment strategy did not affect the 1-year tumor control rate, which was consistently >90 %. However, it did result in a statistically significant reduction of severe posttreatment peritumoral brain edema (from 15.5 % to 6.3 %; P < 0.0001). In conclusion, recent technical and methodological achievements of GKS seemingly do not affect its high efficacy in cases of brain metastasis with regard to tumor control. However, it may result in a prominent reduction of treatment-associated -morbidity, which is particularly important in patients with large and/or critically located neoplasm.

Introduction: Although Gamma Knife radiosurgery (GKS) is commonly performed under local anesthesia, general anesthesia is sometimes required. The authors previously reported a remote-controlled patient management system consisting of propofol-based general anesthesia with a target-controlled infusion (TCI) that we designed for pediatric GKS. However, a commercially available propofol TCI system has age and weight limitations (<16 years and <30 kg). We examined a manually controlled regimen of propofol appropriate for pediatric GKS., Methods: A pharmacokinetic model of the TIVA Trainer© with Paedfusor's parameter was used. A manually controlled infusion scheme to achieve a sufficient level of propofol for pediatric GKS was examined in five models ranging from 10 to 30 kg., Results: Following a loading dose of 3.0 mg/kg, the combination of continuous infusion of 14, 12, 10, and 8 mg/kg/h resulted in a target concentration of 3.0-4.0 μg/ml, the required level for pediatric GKS., Conclusion: Propofol titration is a key issue in GKS. Manual infusion is less accurate than TCI, but the combination of a small bolus and continuous infusion might be a substitute. Considering the characteristics of propofol pharmacokinetics in children, co-administration of opioids is recommended.

Objective: Results of Gamma Knife radiosurgery (GKS) were retrospectively evaluated in 16 patients with histologically confirmed atypical and anaplastic intracranial meningiomas., Materials and Methods: There were nine men and seven women (mean age 61.0 years). Atypical meningiomas were diagnosed in nine cases and anaplastic meningiomas in seven. In nine patients there was malignant transformation of a tumor that had initially proved to be benign. In total, 21 radiosurgical procedures were performed. The mean tumor volume at the time of GKS was 7.1 cm3. The mean marginal and maximum irradiation doses were 18.8 and 37.0 Gy, respectively. The mean length of follow-up after treatment was 37.1 months., Findings: Of 21 radiosurgical procedures, 6 (29 %) led to stabilization of tumor growth during the mean follow-up of 40.5 months. It was significantly associated with small lesion volume (P = 0.02), and greater marginal (P = 0.04) and maximum (P = 0.02) irradiation doses. Seven patients underwent eight surgical resections of a progressing tumor during the mean period of 26.1 months after irradiation. Five patients (31 %) died because of tumor progression within the average time period of 16.8 months after GKS. Overall, at the time of the last follow-up just two patients (13 %) had no evidence of tumor regrowth, and only three patients (19 %) maintained good activities of daily living during 12, 59, and 69 months, respectively, after radiosurgery., Conclusion: GKS has limited efficacy in cases of non-benign meningioma. Better tumor control rates can be attained for small neoplasms treated with greater marginal and maximum irradiation doses.

Background: Gamma Knife surgery (GKS) should be considered a standard treatment option for small and medium-sized vestibular schwannomas (VSs). It results in a tumor control rate similar to that seen with microsurgery and provides better preservation of facial nerve function and hearing., Methods: From December 2002 to April 2011, a total of 260 patients with VS underwent GKS using Leksell Gamma Knife model 4C with an automatic positioning system. There were 30 Koos stage I tumors, 112 stage II, 100 stage III, and 18 stage IV. All patients were treated with the use of high-resolution magnetic resonance imaging; creation of the highly precise conformal and selective multi-isocenter dose planning with small collimators, carefully sparing adjacent cranial nerves of any excessive irradiation; and creation of a wide 80 % isodose area within the tumor while applying a low marginal dose (mean 11.9 Gy) at the 50 % isodose line., Results: Among 182 patients who were followed for more than 3 years after treatment, the tumor control and shrinkage rates were 98.4 % and 76.4 %, respectively. Volume reduction of >50 % was marked in 54.9 % of VSs. Preservation of facial nerve function and hearing at the pretreatment level was noted in 97.8 % and 87.9 %, respectively. There was marked improvement of facial nerve function and hearing after GKS in 2.2 % and 3.8 %, respectively. There was no major morbidity., Conclusion: Due to contemporary technological and methodological achievements GKS can be focused not only on growth control but on shrinking the VS, with possible reversal of the neurological deficit.

A number of intracranial tumors demonstrate some degree of enlargement after stereotactic radiosurgery (SRS). It necessitates differentiation of their regrowth and various treatment-induced effects. Introduction of low-dose standards for SRS of benign neoplasms significantly decreased the risk of the radiation-induced necrosis after -management of schwannomas and meningiomas. Although in such cases a transient increase of the mass volume within several months after irradiation is rather common, it usually followed by spontaneous shrinkage. Nevertheless, distinguishing tumor recurrence from radiation injury is often required in cases of malignant parenchymal brain neoplasms, such as metastases and gliomas. The diagnosis is frequently complicated by histopathological heterogeneity of the lesion with coexistent viable tumor and treatment-related changes. Several neuroimaging modalities, namely structural magnetic resonance imaging (MRI), diffusion-weighted imaging, diffusion tensor imaging, perfusion computed tomography (CT) and MRI, single-voxel and multivoxel proton magnetic resonance spectroscopy as well as single photon emission CT and positron emission tomography with various radioisotope tracers, may provide valuable diagnostic information. Each of these methods has advantages and limitations that may influence its usefulness and accuracy. Therefore, use of a multimodal radiological approach seems reasonable. Addition of functional and metabolic neuroimaging to regular structural MRI investigations during follow-up after SRS of parenchymal brain neoplasms may permit detailed evaluation of the treatment effects and early prediction of the response. If tissue sampling of irradiated intracranial lesions is required, it is preferably performed with the use of metabolic guidance. In conclusion, differentiation of tumor progression and radiation-induced effects after intracranial SRS is challenging. It should be based on a complex evaluation of the multiple clinical, radiosurgical, and radiological factors.

Background: Gamma Knife radiosurgery (GKS) is currently performed with 0.1 mm preciseness, which can be designated microradiosurgery. It requires advanced methods for visualizing the target, which can be effectively attained by a neuroimaging protocol based on plain and gadolinium-enhanced constructive interference in steady state (CISS) images., Methods: Since 2003, the following thin-sliced images are routinely obtained before GKS of skull base lesions in our practice: axial CISS, gadolinium-enhanced axial CISS, gadolinium-enhanced axial modified time-of-flight (TOF), and axial computed tomography (CT). Fusion of "bone window" CT and magnetic resonance imaging (MRI), and detailed three-dimensional (3D) delineation of the anatomical structures are performed with the Leksell GammaPlan (Elekta Instruments AB). Recently, a similar technique has been also applied to evaluate neuroanatomy before open microsurgical procedures., Results: Plain CISS images permit clear visualization of the cranial nerves in the subarachnoid space. Gadolinium-enhanced CISS images make the tumor "lucid" but do not affect the signal intensity of the cranial nerves, so they can be clearly delineated in the vicinity to the lesion. Gadolinium-enhanced TOF images are useful for 3D evaluation of the interrelations between the neoplasm and adjacent vessels. Fusion of "bone window" CT and MRI scans permits simultaneous assessment of both soft tissue and bone structures and allows 3D estimation and correction of MRI distortion artifacts., Conclusion: Detailed understanding of the neuroanatomy based on application of the advanced neuroimaging protocol permits performance of highly conformal and selective radiosurgical treatment. It also allows precise planning of the microsurgical procedures for skull base tumors.

Background: Contemporary technological developments revolutionized management of brain tumors. The experience with information-guided surgery of gliomas, based on the integration of the various intraoperative anatomical, functional, and histological data, is reported., Methods: From 2000 to 2009, 574 surgeries for intracranial gliomas were performed in our clinic with the use of intraoperative MRI (ioMRI) with magnetic field strength of 0.3T, updated neuronavigation, neurochemical navigation with 5-aminolevulinic acid, serial intraoperative histopathological investigations of the resected tissue, and comprehensive neurophysiological monitoring. Nearly half of patients (263 cases; 45.8%) were followed more than 2 years after surgery., Findings: Maximal possible tumor resection, defined as radiologically complete tumor removal or subtotal removal leaving the residual neoplasm within the vital functionally-important brain areas, was attained in 569 cases (99.1%). The median resection rate constituted 95%, 95%, and 98%, for WHO grade II, III, and IV gliomas, respectively. Actuarial 5-year survival was significantly worse in WHO grade IV gliomas (19%), but did not differ significantly between WHO grade III and II tumors (69% vs. 87%)., Conclusions: Information-guided management of gliomas using low-field-strength ioMRI provides a good opportunity for maximal possible tumor resection, and may result in survival advantage, particularly in patients with WHO grade III neoplasms.

Agenesis of the corpus callosum (ACC) is a congenital abnormality of the brain structure. We have produced transgenic mice expressing both reverse tetracycline-controlled transactivator (rtTA) and transcriptional silencer (tTS) ubiquitously. Although the transgene products do not affect development of the mouse brain, one of the founder lines, TAS, showed ACC, suggesting transgenic disruption of endogenous gene(s). To identify the causative gene and its role in ACC, we performed pathological investigations of the brain and chromosomal mapping of foreign genes in TAS mice. Sixty-two percent of the heterozygous TAS mice showed ACC accompanied with formation of Probst bundles, as seen in human. Complete penetrance of ACC was observed in homozygous TAS mice. Furthermore, homozygous TAS fetuses revealed that ACC is a congenital anomaly. Moreover, axons of the corpus callosum were not repelled by the midline glial structures in TAS mice. These findings suggested that the causative gene for ACC is involved in critical steps in corpus callosum development. Multiple FISH analyses were performed to determine the site of transgene insertion. On 1-color FISH analyses, rtTA and tTS were detected on the A/B region of chromosome 18, suggesting cointegration of the transgenes. On 2-color FISH analyses, tTS signal was observed in a region from 9.3 to 16.9 Mb on chromosome 18. The TAS mice may serve as a useful model to identify a novel gene regulating corpus callosum development and to gain a new insight into molecular genetics of ACC.

Introduction: The present study was done for evaluation of the possible influence of the oral administration of choline on metabolic characteristics of gliomas detected with proton magnetic resonance spectroscopy ((1)H-MRS)., Materials and Methods: Thirty patients (22 men and eight women; mean age 38 +/- 15 years) with suspicious intracranial gliomas underwent single-voxel long-echo (TR 2,000 ms, TE 136 ms, 128-256 acquisitions) (1)H-MRS of the tumor, peritumoral brain tissue, and distant normal-appearing white matter before and several hours (median, 3 h; range, 1.2-3.7 h) after ingestion of choline with prescribed dose of 50 mg/kg (median actual dose, 52 mg/kg; range, 48-78 mg/kg). Investigations were done using 1.5 T clinical magnetic resonance imager. The volume of the rectangular (1)H-MRS voxel was either 3.4 or 8 cm(3). At the time of both spectroscopic examinations, similar voxels' positioning and size and technical parameters of (1)H-MRS were used. Surgery was done in 27 patients within 1 to 68 days thereafter. In all cases, more than 80% resection of the neoplasm was attained., Results: There were 12 low-grade gliomas and 15 high-grade gliomas. MIB-1 index varied from 0% to 51.7% (median, 13.8%). Statistical analysis did not disclose significant differences of any investigated metabolic parameter of the tumor, peritumoral brain tissue and distant normal-appearing white matter between two spectroscopic examinations., Conclusion: Single-voxel (1)H-MRS at 1.5 T could not detect significant changes of the metabolic characteristics of gliomas, peritumoral brain tissue, and distant normal-appearing white matter after oral administration of choline.

Introduction: The physiological mechanisms of deep brain stimulation (DBS) are not completely clear. Our understanding of them may be facilitated with the use of proton magnetic resonance spectroscopy ((1)H-MRS)., Methods: Serial (1)H-MRS of both thalami was performed during the course of DBS of bilateral globus pallidus internus in a patient with primary generalized dystonia., Results: Two days after microelectrode implantation, a pulse frequency of 185 Hz was applied for stimulation. It resulted in relief of symptoms and a decrease of Burke-Fahn-Marsden dystonia rating scale (BFMDRS) scores, and was accompanied by a prominent increase of N-acetylaspartate (NAA)/choline-containing compounds (Cho) ratio, a mild increase of NAA/creatine (Cr) ratio, and a moderate decrease of Cho/Cr ratio. Two weeks later, for a search of the optimal stimulation mode, the pulse frequency was switched to 60 Hz, which resulted in clinical deterioration and significant increase of BFMDRS scores. At that time, all investigated (1)H-MRS-detected metabolic parameters had nearly returned to the pretreatment levels., Conclusion: Use of serial (1)H-MRS investigations of various brain structures during DBS in cases of movement disorders permits detailed evaluation of the treatment response, has a potential for its possible prediction, and may facilitate understanding of the physiological mechanisms of stimulation.

Background: Radical resection of gliomas can increase patient's survival. There is known concern, however, that aggressive tumour removal can result in neurological morbidity. The objective of the present study was to evaluate the usefulness of low magnetic field strength (0.3 Tesla) open intraoperative magnetic resonance imaging (iMRI) for complete resection of glioma with emphasis on functional outcome., Methods: From 2000 to 2004, 96 patients with intracranial gliomas underwent tumour resection with the use of iMRI in Tokyo Women's Medical University. There were 50 men and 46 women; mean age was 39 years. Tumour volume varied from 1.2 ml to 198 ml (median: 36.5 mL). Resection rate and postoperative neurological status were compared between control group (46 cases, operated on during the initial period after installation of iMRI), and study group (50 most recent cases, in whom surgery was done using established treatment algorithm and improved image quality)., Findings: Overall, mean resection rate was 93%, and medial residual tumour volume was 0.17 ml. Total tumour removal was achieved in 44 cases (46%). Compared to control group, resection rate in the study group was significantly higher (91%, vs. 95%; P < 0.05), whereas residual tumour volume was significantly smaller (1.7 mL vs. 0.025 mL; P < 0.001). Nine patients in the control group (20%) and 24 in the study group (48%) experienced temporary postoperative neurological deterioration (P < 0.01), however, the rate of permanent morbidity evaluated 3 months after surgery did not differ significantly between the groups investigated (13% vs. 14%)., Conclusions: Use of iMRI during surgery for intracranial gliomas permits to attain aggressive tumour resection with good functional outcome. Nevertheless, surgical experience with the iMRI system, establishment of treatment algorithm, and improvement of image quality are of paramount importance for optimal results.

We investigated the short-term effects of an intrathecal bolus injection of baclofen on central pain due to stroke or spinal cord injury. Pain relief was obtained in 64% of the patients. The effects developed 1-2 hours after the injection and continued for 10-24 hours. Both spinal segmental and supraspinal mechanisms may be involved in the production of baclofen-analgesia.

The histochemical activity of adenosine triphosphatase (ATPase) was studied at light and electron microscopic levels in larval tail musculature of Rana catesbeiana and Rana ornativentris during late metamorphic stages. The presence of low, moderate or dark reaction of K2-EDTA-preincubated Ca++-ATPase was correlated with the variable degree of degeneration of white fibres even at the late stage of tail resorption. The reasons for an increase in this ATPase activity in degenerating white muscle fibres are discussed. Irrespective of the degree of degeneration, all red fibres showed high ATPase reaction. During myocytolysis, it is shown that the SR vesicles accumulate electron dense amorphous material. The degree of myofibrillar disintegration correlated with decrease in ultrastructural reaction product for Mg++-ATPase. Although grouped atrophy of muscle fibres (as seen in Xenopus laevis, den Hartog Jager et al., 1973, 1975) was absent in musculature of resorptive tails, ultrastructural characteristics including proliferation of SR and dilation of its vesicles represent alteration of the normal neural influence on the skeletal muscle fibres.