BACE inhibitor treatment of mice induces hyperactivity in a Seizure-related gene 6 family dependent manner without altering learning and memory.

BACE inhibitors, which decrease BACE1 (ß-secretase 1) cleavage of the amyloid precursor protein, are a potential treatment for Alzheimer's disease. Clinical trials using BACE inhibitors have reported a lack of positive effect on patient symptoms and, in some cases, have led to increased adverse events, cognitive worsening and hippocampal atrophy. A potential drawback of this strategy is the effect of BACE inhibition on other BACE1 substrates such as Seizure-related gene 6 (Sez6) family proteins which are known to have a role in neuronal function. Mice were treated with an in-diet BACE inhibitor for 4-8 weeks to achieve a clinically-relevant level of amyloid-ß40 reduction in the brain. Mice underwent behavioural testing and postmortem analysis of dendritic spine number and morphology with Golgi-Cox staining. Sez6 family triple knockout mice were tested alongside wild-type mice to identify whether any effects of the treatment were due to altered cleavage of Sez6 family proteins. Wild-type mice treated with BACE inhibitor displayed hyperactivity on the elevated open field, as indicated by greater distance travelled, but this effect was not observed in treated Sez6 triple knockout mice. BACE inhibitor treatment did not lead to significant changes in spatial or fear learning, reference memory, cognitive flexibility or anxiety in mice as assessed by the Morris water maze, context fear conditioning, or light-dark box tests. Chronic BACE inhibitor treatment reduced the density of mushroom-type spines in the somatosensory cortex, regardless of genotype, but did not affect steady-state dendritic spine density or morphology in the CA1 region of the hippocampus. Chronic BACE inhibition for 1-2 months in mice led to increased locomotor output but did not alter memory or cognitive flexibility. While the mechanism underlying the treatment-induced hyperactivity is unknown, the absence of this response in Sez6 triple knockout mice indicates that blocking ectodomain shedding of Sez6 family proteins is a contributing factor. In contrast, the decrease in mature spine density in cortical neurons was not attributable to lack of shed Sez6 family protein ectodomains. Therefore, other BACE1 substrates are implicated in this effect and, potentially, in the cognitive decline in longer-term chronically treated patients.

Intratumoural immune cell landscape in germinoma reveals multipotent lineages and exhibits prognostic significance.

AIMS: Alterations in microenvironments are a hallmark of cancer, and these alterations in germinomas are of particular significance. Germinoma, the most common subtype of central nervous system germ cell tumours, often exhibits massive immune cell infiltration intermingled with tumour cells. The role of these immune cells in germinoma, however, remains unknown. METHODS: We investigated the cellular constituents of immune microenvironments and their clinical impacts on prognosis in 100 germinoma cases. RESULTS: Patients with germinomas lower in tumour cell content (i.e. higher immune cell infiltration) had a significantly longer progression-free survival time than those with higher tumour cell contents (P = 0.03). Transcriptome analyses and RNA in-situ hybridization indicated that infiltrating immune cells comprised a wide variety of cell types, including lymphocytes and myelocyte-lineage cells. High expression of CD4 was significantly associated with good prognosis, whereas elevated nitric oxide synthase 2 was associated with poor prognosis. PD1 (PDCD1) was expressed by immune cells present in most germinomas (93.8%), and PD-L1 (CD274) expression was found in tumour cells in the majority of germinomas examined (73.5%). CONCLUSIONS: The collective data strongly suggest that infiltrating immune cells play an important role in predicting treatment response. Further investigation should lead to additional categorization of germinoma to safely reduce treatment intensity depending on tumour/immune cell balance and to develop possible future immunotherapies.

Usefulness of Contrast-Enhanced 3D-FLAIR MR Imaging for Differentiating Rathke Cleft Cyst from Cystic Craniopharyngioma.

BACKGROUND AND PURPOSE: Because it can be difficult to discriminate between a Rathke cleft cyst and cystic craniopharyngioma by conventional MR imaging alone, we investigated whether contrast-enhanced 3D T2-FLAIR MR imaging at 3T helps to distinguish a Rathke cleft cyst from a cystic craniopharyngioma. MATERIALS AND METHODS: We evaluated pre- and postcontrast T1-weighted and 3D T2-FLAIR images of 17 patients with pathologically confirmed Rathke cleft cyst (n = 10) or cystic craniopharyngioma (n = 7). All underwent 3T MR imaging studies before surgery. Two neuroradiologists independently recorded the enhancement grade of the lesion wall as grade 2 (most of the wall enhanced), grade 1 (some of the wall enhanced), and grade 0 (none of the wall enhanced). One neuroradiologist performed a blinded reading study of conventional MR images with/without 3D T2-FLAIR images. Interobserver agreement was determined by calculating the κ coefficient. Statistical analyses, including receiver operating characteristic curve analysis were performed. RESULTS: Interobserver agreement for postcontrast T1WI and 3D T2-FLAIR images was excellent (κ = 0.824 and κ = 0.867, respectively). Although the difference in the mean enhancement grade of Rathke cleft cysts and cystic craniopharyngiomas was not significant on postcontrast T1WIs, it was significant on postcontrast 3D T2-FLAIR images (P = .0011). The area under the receiver operating characteristic curve of the conventional MR alone and conventional MR with 3D T2-FLAIR readings was 0.879 and 1.0, respectively, though there was no significant difference in the area under the curve between the 2 readings. CONCLUSIONS: Contrast-enhanced 3D T2-FLAIR imaging at 3T helps to distinguish a Rathke cleft cyst from cystic craniopharyngioma.

Characterization of Carotid Plaque Components by Quantitative Susceptibility Mapping.

BACKGROUND AND PURPOSE: Intraplaque hemorrhage in the carotid artery is related to an increased risk of cerebrovascular ischemic events. We aimed to investigate whether quantitative susceptibility mapping can characterize carotid artery plaque components and quantify the severity of intraplaque hemorrhage. MATERIALS AND METHODS: For this ex vivo quantitative susceptibility mapping study, 9 carotid endarterectomy specimens were imaged on a 3T MR imaging scanner using a 3D multi-echo gradient-echo sequence and a microscopy coil. The samples were examined histologically using immunostains, including glycophorin A and Prussian blue. The areas of erythrocytes, iron deposits, calcification, and fibrous matrices observed on stained sections were compared with quantitative susceptibility mapping findings and their mean susceptibility values. RESULTS: Intraplaque hemorrhage and iron deposits were observed only in areas hyperintense on quantitative susceptibility mapping; calcifications and fibrous matrices were prevalent in hypointense areas. The mean susceptibility values for necrotic cores with intraplaque hemorrhage but no iron deposits, cores with iron deposits but no intraplaque hemorrhage, cores without either intraplaque hemorrhage or iron deposits, and cores with calcification were 188 ± 51, 129 ± 49, -11 ± 17, and -158 ± 78 parts per billion, respectively. There was a significant difference in the mean susceptibility values among the 4 histologic components (P < .01). The mean susceptibility values of the whole plaque positively correlated with the percentage area positive for glycophorin A (r = 0.65, P < .001) and Prussian blue (r = 0.47, P < .001). CONCLUSIONS: Our findings suggest that quantitative susceptibility mapping can characterize the composition of carotid plaques and quantify the degree of intraplaque hemorrhage and iron deposits.

Microvascular proliferation of brain metastases mimics glioblastomas in squash cytology.

OBJECTIVE: Although microvascular proliferation is a key feature in the diagnosis of high-grade glioma, the characteristics of metastatic tumour vessels in smear preparations have not been documented. In this study, the vascular changes in metastatic brain tumours, using squash cytology to examine the vascular patterns in brain metastases, were reviewed. METHODS: One hundred and forty-three squash smears of brain tissue, including 25 normal or reactive tissue, 23 malignant lymphomas, 8 grade I glioma (pilocytic astrocytoma), 23 grade II glioma (diffuse astrocytoma and oligodendroglioma), 42 grade IV glioma (glioblastoma), and 22 metastasis, were assessed. Two vascular patterns were assessed: thick and branching, and glomeruloid. The vessel density, nuclear layer and the number of vessel branches were compared. Furthermore, tumour vessels of brain metastases were analysed by histology and for immunohistochemical expression of CD34, α-smooth muscle actin (SMA) and high-molecular-weight caldesmon (h-CD). RESULTS: Among 22 metastatic tumours, thick and branching vessels were found in 17 (77%) and glomeruloid vessels in 13 (59%). These incidences of microvascular proliferation patterns were similar to those of glioblastomas or pilocytic astrocytomas. Vessel density, nuclear layer and vessel wall branches were significantly higher in metastatic tumours than malignant lymphomas, grade II gliomas or normal brain tissues. Glomeruloid vessels consisted of CD34-positive cells and α-SMA-positive cells, and α-SMA-positive cells had a low h-CD expression. These immunohistochemical patterns were similar to those of high-grade gliomas. CONCLUSIONS: The vascular features of metastatic brain tumours are similar to those of glioblastomas, suggesting that these microvascular proliferations contribute to the progression of metastatic tumours.

Permanent genetic resources added to Molecular Ecology Resources Database 1 February 2013-31 March 2013.

This article documents the addition of 142 microsatellite marker loci to the Molecular Ecology Resources database. Loci were developed for the following species: Agriophyllum squarrosum, Amazilia cyanocephala, Batillaria attramentaria, Fungal strain CTeY1 (Ascomycota), Gadopsis marmoratus, Juniperus phoenicea subsp. turbinata, Liriomyza sativae, Lupinus polyphyllus, Metschnikowia reukaufii, Puccinia striiformis and Xylocopa grisescens. These loci were cross-tested on the following species: Amazilia beryllina, Amazilia candida, Amazilia rutila, Amazilia tzacatl, Amazilia violiceps, Amazilia yucatanensis, Campylopterus curvipennis, Cynanthus sordidus, Hylocharis leucotis, Juniperus brevifolia, Juniperus cedrus, Juniperus osteosperma, Juniperus oxycedrus, Juniperus thurifera, Liriomyza bryoniae, Liriomyza chinensis, Liriomyza huidobrensis and Liriomyza trifolii.

Early-stage formation of an epigenetic field defect in a mouse colitis model, and non-essential roles of T- and B-cells in DNA methylation induction.

Epigenetic fields for cancerization are involved in development of human cancers, especially those associated with inflammation and multiple occurrences. However, it is still unclear when such field defects are formed and what component of inflammation is involved in induction of aberrant DNA methylation. Here, in a mouse colitis model induced by dextran sulfate sodium (DSS), we identified three CpG islands specifically methylated in colonic epithelial cells exposed to colitis. Their methylation levels started to increase as early as 8 weeks after DSS treatment and continued to increase until colon cancers developed at 15 weeks. In contrast to the temporal profile of DNA methylation levels, infiltration of inflammatory cells spiked immediately after the DSS treatment and then gradually decreased. Exposure of cultured colonic epithelial cells to DSS did not induce DNA methylation and it was indicated that inflammation triggered by the DSS treatment was responsible for methylation induction. To clarify components of inflammation involved, severe combined immunodeficiency (SCID) mice that lack functional T- and B-cells were similarly treated. Even in SCID mice, DNA methylation, along with colon tumors, were induced at the same levels as in their background strain of mice (C.B17). Comparative analysis of inflammation-related genes showed that Ifng, Il1b and Nos2 had expression concordant with methylation induction whereas Il2, Il6, Il10, Tnf did not. These results showed that an epigenetic field defect is formed at early stages of colitis-associated carcinogenesis and that functional T and B cells are non-essential for the formation.

Correlation with larval body size of mRNA levels of growth hormone, growth hormone receptor I and insulin-like growth factor I in larval torafugu Takifugu rubripes.

The full-length of insulin-like growth factor (IGF) complementary (c)DNAs encoded by igf-I and igf-II from torafugu pufferfish Takifugu rubripes were cloned in the present study. The deduced amino acid sequences of the two genes showed c. 80% identity each with those of Igf-I and Igf-II from other teleosts, respectively. Two growth hormone (GH) receptors, ghr1 and ghr2, were also cloned in silico using the T. rubripes Fugu genome database. The transcripts of T. rubripes igf-I were detected in slow muscle, heart, skin, gill, liver and intestine but not in fast muscle, spleen and testis of adult fish, whereas those of igf-II were found in all tissues examined. Subsequently, the accumulated messenger (m)RNA levels of igf-I and igf-II were investigated in an F(2) population derived from a male of an apparent fast-growing T. rubripes strain and a wild female T. rubripes together with those of other growth-related genes encoding Gh, Ghr1 and Ghr2, and with those of prolactin (Prl) and leptin (Lep) previously reported. The accumulated mRNA levels of igf-I, gh and ghr1 were significantly correlated to growth rate at larval stages in the population, but not for those of igf-II, prl, ghr2 and lep. Although it is unclear whether or not this phenotype is directly related to the heredity of the fast-growing strain, the findings suggest that the expression of igf-I, gh and ghr1 is involved in the regulation of growth rate at larval stages in T. rubripes.

Characteristics of tumour vessels in cytological squash smears of astrocytic tumours.

OBJECTIVE: Smear preparations are useful tools from which to diagnose brain tumours intraoperatively. Although vascular proliferation is histologically a key feature of high-grade astrocytoma, the characteristics of tumour vessels in smear preparations have not been determined. METHODS: We examined the density and morphological parameters (area, width, nuclear layer and branches of vessel wall) of tumour vessels in squash smears of 43 primary astrocytomas (grade II diffuse astrocytomas, n=9; grade III anaplastic astrocytomas, n=13; grade IV glioblastomas, n=21) and normal brain tissues (n=11). RESULTS: Vessel density and all morphological parameters were significantly higher in grade IV than in the other grades of tumours and in normal brain tissue. Vessel area, width and nuclear layer were greater in grade III than in normal brain tissue. The sensitivity and specificity of these vessel parameters for astrocytomas were 75-100% and 82-100%, respectively. CONCLUSIONS: Tumour vessel evaluations from squash smears provide useful information for the intraoperative diagnosis and grading of astrocytic tumours.

PERMANENT GENETIC RESOURCES: Isolation and characterization of microsatellite loci in the cichlid fish in Lake Victoria, Haplochromis chilotes.

Twelve short tandem repeat markers were successfully isolated from a cichlid, Haplochromis chilotes, in Lake Victoria, and characterized in Haplochromis pyrrhocephalus. The microsatellite regions of these markers were found to have between two and 48 alleles with heterozygosity ranging from 0.07 to 0.97. No loci showed significant departures from the Hardy-Weinberg or linkage equilibrium after the Bonferroni correction (P > 0.05). Cross-species amplification in other cichlids of Lake Victoria, Haplochromis laparogramma, Lithochromis rubripinnis, L. rufus and Haplochromis sp. 'rockkribensis', was successful.

Isolation and characterization of 15 microsatellite loci for the Japanese gudgeon Sarcocheilichthys variegatus.

A microsatellite-enriched genomic library was obtained for the Japanese gudgeon Sarcocheilichthys variegatus microoculus, and 15 dinucleotide markers were successfully isolated and characterized. These markers were also available for other Japanese congeners, Sarcocheilichthys variegatus variegatus and Sarcocheilichthys biwaensis. In three populations of Sarcocheilichthys from Lake Biwa and the Ashida River in western Japan, seven to 27 alleles were observed for each locus. Linkage equilibrium was observed among most loci, and only one locus showed significant deviation from Hardy-Weinberg equilibrium in a population. These microsatellite markers will be useful for studies of the genetic structure of the Japanese gudgeons.

Multiple prominent dilated perivascular spaces do not induce Wallerian degeneration as evaluated by diffusion tensor imaging.

It is unknown whether dilated perivascular spaces can affect the adjacent neuronal fibers. We describe conventional MR and diffusion tensor imaging findings of a case with multiple, prominent dilated perivascular spaces in the left cerebral hemisphere. Diffusion tensor imaging showed no alterations in the fractional anisotropy and apparent diffusion coefficient values for the corona radiata, posterior rim of the internal capsule, and the cerebral peduncle, indicating no wallerian degeneration associated with dilated perivascular spaces.

External Manual Carotid Compression is Effective in Patients with Cavernous Sinus Dural Arteriovenous Fistulae.

SUMMARY: External manual carotid compression is a non-invasive method to treat patients with cavernous sinus dural arteriovenous fistulae (CSDAVF). We studied a group of patients with CSDAVF to identify factors that made cure by compression therapy possible. We treated 23 patients with CS-DAVF without cortical venous drainage or a recent decline in visual acuity by compression therapy. All were followed up by magnetic resonance angiography (MRA) at one, three, six, and 12 months after treatment and the characteristics of the imaging findings, their neurological symptoms, and the patterns of symptom improvement were examined. In group A (n=8), cure was achieved by manual carotid compression; in the other 15 patients (group B), cure was not obtained. Group B manifested significantly higher ocular pressure and a significantly longer interval between symptom onset and treatment by manual carotid compression. In group A, venous drainage was via the superior orbital vein (SOV) with/without involvement of the inferior petrosal sinus (IPS); closure of the CS-DAVF occurred within 4.1 months after the start of treatment. In three patients symptom improvement progressed steadily and gradually. The other five cured patients experienced transient worsening of their symptoms at two to four months after the start of treatment, these resolved within four to seven months. Manual carotid compression was effective in patients without retrograde venous CS-DAVF drainage or a severe decline in visual acuity. The factors that rendered cure by compression therapy possible were lower ocular pressure and a shorter interval between symptom onset and the start of treatment. Venous drainage in those patients was exclusively via the SOV without involvement of the IPS.

Clinical evaluation of cellulose porous beads for the therapeutic embolization of meningiomas.

BACKGROUND AND PURPOSE: Cellulose porous beads (CPBs) are a new, exceptionally uniformly sized, nonabsorbable embolic agent. We evaluated their efficacy in the preoperative embolization of meningiomas. METHODS: In 141 consecutive patients, we used CPBs (200-microm diameter) for the preoperative embolization of meningiomas. We selected patients whose tumors were > or =4 cm with 50% of blood to the tumor supplied by the external carotid artery (ECA). All patients underwent a provocation test before embolization. The percentage of blood supplied to the tumor by the internal carotid artery and ECA was determined angiographically. Nonenhanced areas on postembolization MR imaging were calculated. Intraoperative blood loss, units of blood transfusion, and hemostasis at the time of surgery were recorded for each patient. The interval between embolization and surgery was intentionally longer than 7 days. RESULTS: Of the 141 patients, 128 underwent CBP embolization. Eleven patients had positive provocation test results, and 2 had vasospasm; they were not CBP embolized. In 72% of the patients CBP embolization achieved reduction in the flow of the feeding artery by more than 50%. The nonenhanced area on MR imaging was not significantly correlated with the degree of ECA supply or devascularization. The interval between embolization and surgery was 8-26 days (mean, 9.9 days). The longer this interval, the greater was the tumor-softening effect and the rate of tumor removal. CONCLUSIONS: CPBs may be useful for the preoperative embolization of meningiomas. To increase the efficacy of CPB embolization, the interval to surgery should be at least 7 days.

Nociceptin system does not affect MAC of volatile anaesthetics.

BACKGROUND: Nociceptin is the endogenous agonist of the opioid receptor-like (ORL) 1 receptor (NOP), and both nociceptin and NOP are widely expressed in the brain and spinal cord, which are target organs of general anaesthetics. As nociceptin has been reported to be involved in modulating pain mechanisms and stress responses, it is possible that the activity of the nociceptin system affects the anaesthetic potency of general anaesthetics. To address this possibility, we investigated the minimum alveolar concentrations (MACs) of various volatile anaesthetics in nociceptin receptor knockout mice (NOP-/-) and wild-type mice (NOP+/+). METHODS: We used male NOP-/- mice and NOP+/+ mice. MACs for halothane, isoflurane and sevoflurane were determined by the tail-clamp method. RESULTS: MACs for halothane, isoflurane and sevoflurane in NOP-/- mice were 1.60 (SD 0.06), 1.68 (0.08) and 3.36 (0.07)%, respectively. In NOP+/+ mice, MACs for halothane, isoflurane and sevoflurane were 1.59 (SD 0.07), 1.72 (0.07) and 3.38 (0.09)%, respectively. CONCLUSION: MACs in NOP-/- mice did not significantly differ from those in NOP+/+ mice for halothane, isoflurane and sevoflurane. This result suggests that the nociceptin system does not affect the anaesthetic potency of volatile anaesthetics.

Expression of lymphocyte-specific chemokines in human malignant glioma: Essential role of LARC in cellular immunity of malignant glioma.

Lymphocytes are frequently observed in human malignant glioma, the mechanism(s) underlying their appearance is not fully understood. To clarify tumor immunity in malignant gliomas, we analyzed the expression of 8 novel lymphocyte-specific chemokines in human glioma cell lines and glioma tissues by RT-PCR, Northern blot, immunoblot and immunohistochemistry, and examined the correlation with the infiltration of various subsets of lymphocytes. For the 8 chemokines examined (LARC, TARC, ELC, SLC, PARC, LEC, HCC-2, and SCM-1alpha), expression of LARC was clearly detectable in all 12 glioma cell lines by RT-PCR. Additionally, expression of TARC and SCM-1alpha was detectable in the majority of glioma cell lines. However, the expression level of most chemokines was low, so that Northern blot analysis could not demonstrate their expression with the exception of LARC in 2 cell lines. Expression of LARC mRNA and LARC protein was strongly induced by phorbol myristate ester in U87 MG cells. The production of LARC protein was demonstrated in 4 of 8 glioblastoma tissues by immunoblotting, and 9 of 33 samples (27.3%) by immunohistochemistry. Interestingly, the positivity of LARC staining was significantly correlated with the infiltration of CD8-, CD4-, and CD45R0-positive cells (p<0.001). Although the constitutive expression level of LARC is low, certain stimulations could strongly induce its expression, and play a crucial role in the tumor immunity of human malignant glioma.

Store-operated Ca2+ entry uncoupled with ryanodine receptor and junctional membrane complex in heart muscle cells.

Store-operated Ca2+ entry (SOCE) is the Ca2+ influx that is activated on depletion of intracellular Ca2+ stores. Although SOCE is found in a variety of cell types, its activation mechanism and molecular identity remain to be clarified. Current experimental results suggest that SOCE channels are activated by direct coupling with Ca2+ release channels on depleted stores. Here we report SOCE in cardiac myocytes, that was prominently sensitive to Zn2+ but resistant to inhibitors for voltage-dependent Ca2+ channels and Na+/Ca2+ exchangers. The SOCE activity may be developmentally regulated, because the SOCE was easily detected during embryonic and neonatal stages but not in mature myocytes from adult hearts. In cardiac myocytes, ryanodine receptor type 2 (RyR-2) is thought to be the sole Ca2+ release channel on the intracellular store, and junctophilin type 2 (JP-2) contributes to formation of the junctional complex between the cell surface and store membranes. Using the knockout mice, we also examined possible involvement of the Ca2+ release channel and junctional membrane complex in cardiac SOCE. Apparently normal SOCE activities were retained in mutant myocytes lacking RyR-2 or JP-2, suggesting that neither the Ca2+ release channel nor junctional membrane complex is involved in activation of cardiac SOCE.

A combined pharmacological and genetic approach to investigate the role of orphanin FQ in learning and memory.

Using a combination of the selective opioid receptor-like1 (ORL1) receptor agonist, Ro 64-6198, and orphanin FQ/nociceptin (OFQ/N) peptide knockout (KO) mice, the influence of OFQ/N on cognition has been studied in the rodent. In wild type, C57BL/6J mice, Ro 64-6198 (0.3-1 mg/kg i.p.) impaired the acquisition of spatial learning in the Morris water maze, although a mild neurological impairment was evident which complicated precise interpretation. In Lister hooded rats, Ro 64-6198 (6 mg/kg i.p.) produced delay dependent impairments in rats performing either a delayed matching or a delayed nonmatching to position task with only a modest (< 20%) effect on omissions - an effect consistent with a short-term memory impairment. Electrophysiological studies demonstrated an inhibitory effect of OFQ/N on LTP recorded from the CA1 region of wild type mice, but not in ORL1 receptor knockout mice. In contrast to the ORL1 agonist, mice deficient in the OFQ/N peptide showed some evidence of improved spatial learning, fear conditioning and passive avoidance retention. However, CA1 LTP was similar between OFQ/N peptide KO mice and wild type controls. Subsequent receptor radioautography studies demonstrated the presence of ORL1 receptors within various regions of the medial temporal lobe system: i.e. CA1, dentate gyrus molecular layer, subiculum, perirhinal cortex. Taken together, these results suggest a bi-directional effect of OFQ/N containing systems on aspects of cognitive behaviour, particularly those elements associated with hippocampal function. This is consistent with a likely modulatory role of OFQ/N on hippocampal and associated cortical circuitry.

Abnormal formation of sarcoplasmic reticulum networks and triads during early development of skeletal muscle cells in mitsugumin29-deficient mice.

Recently, we detected a novel membrane protein, mitsugumin29 (MG29), in the triads in rabbit skeletal muscle cells and suggested important roles for this membrane protein in the formation of the sarcoplasmic reticulum (SR) networks and triads in muscle cells. In the present study, we examined the development of skeletal muscle cells in MG29-deficient mice to try to determine the roles played by MG29 in the formation of the SR networks and triads. Ultrastructural observations revealed some morphological abnormalities in these mice, such as incomplete formation of the SR networks, an irregular running of the transverse tubule and a partial defect in the triads at the A-I junctional region. These ultrastructural abnormalities occurred during early myogenesis and were preserved until the adult stage. The possible roles for MG29 in the formation of SR networks and triads in skeletal muscle cells are discussed in the light of these observations.

Trends in the incidence of primary intracranial tumors in Kumamoto, Japan.

BACKGROUND: The introduction of modern neuro-imaging techniques, as well as various environmental factors, have been changing the incidence and the proportions of the types of clinically diagnosed intracranial tumors. The aim of this study was to determine recent trends in the occurrence of primary intracranial tumors in the residents of Kumamoto Prefecture, Japan. METHODS: We surveyed 2129 patients who were diagnosed with primary intracranial tumors between 1989 and 1998, with histological diagnosis being obtained in 71% of the patients. RESULTS: Of the 2129 patients, 710 (33.3%) had meningiomas, 390 (18.3%) had pituitary adenomas, 315 (14.8%) had malignant gliomas, and 208 (9.8%) had schwannomas. The overall age-adjusted incidence rates were 10.97/100,000/year (males, 9.70; females, 11.86). One hundred and nine patients (5.1%) were younger than 15 years, and 480 patients (22.5%) were older than 70 years. The most common tumors in children were astrocytomas (37.6%), followed by germ-cell tumors (16.5%) and craniopharyngiomas (11.9%), medulloblastomas (11.0%), and ependymomas (4.6%). Meanwhile, the most common tumors in elderly residents were meningioma (51.7%), followed by malignant glioma (13.7%), pituitary adenoma (11.4%), schwannoma (7.7%), malignant lymphoma (4.6%), and astrocytoma (2.7%). The proportion of asymptomatic tumors increased, from 24.6% in 1989-1994 to 33.0% in 1995-1998; 169 (62.8%) were meningiomas, followed by pituitary adenomas (14.1%).