Expression of isotocin is male-specifically up-regulated by gonadal androgen in the medaka brain.

Oxytocin, a mammalian neuropeptide primarily synthesised in the supraoptic and paraventricular nuclei of the hypothalamus, mediates a variety of physiological and behavioural processes, ranging from parturition and lactation to affiliation and prosociality. Multiple studies in rodents have shown that the expression of the oxytocin gene (Oxt) is stimulated by oestrogen, whereas androgen has no apparent effect. However, this finding is not consistent across all studies, and no study has examined sex steroid regulation of Oxt or its orthologues in other animals. In the present study, we show that, in the teleost fish, medaka (Oryzias latipes), the expression of the isotocin gene (it), the teleost orthologue of Oxt, in the parvocellular preoptic nuclei (homologous to the mammalian supraoptic nucleus) is male-specifically up-regulated by gonadal androgen, whereas it expression in the magnocellular/gigantocellular preoptic nuclei (homologous to the mammalian paraventricular nucleus) is independent of sex steroids in both sexes. None of the it-expressing neurones appear to co-express androgen receptors, suggesting that the effect of androgen on it expression is indirect. We found that the expression of a kisspeptin gene, kiss2, in the male brain is dependent on gonadal androgen, raising the possibility that the androgen-dependent expression of it may be mediated by kiss2 neurones. Our data also show that the isotocin peptide synthesised in response to androgen is axonally transported to the posterior pituitary to act peripherally. Given that levels of it expression are higher in females than in males, androgen may serve to compensate for the female-biased it expression to ensure a role for isotocin that is equally important for both sexes. These results are unexpectedly quite different from those reported in rodents, indicating that the regulatory role of sex steroids in Oxt/it expression has diverged during evolution, possibly with accompanying changes in the role of oxytocin/isotocin.

Hairworm Infection and Seasonal Changes in Paratenic Hosts in a Mountain Stream in Japan.

For parasites with complex life cycles, the ecological traits determining host competence and seasonal changes in infection in natural habitats are often unclear, making it difficult to predict infection dynamics, including disease outbreaks. Hairworms (phylum Nematomorpha) require both aquatic and terrestrial hosts to complete their life cycle. Although hairworm host competencies have been tested in laboratory experiments, knowledge of the paratenic hosts (aquatic insect larvae) in their natural habitats is limited. This study clarified the species of aquatic insect larvae that are primarily infected by hairworms as paratenic hosts over a year in a mountain stream in central Honshu, Japan. The monthly prevalence and mean abundance of hairworm cysts were high in Ephemera japonica larvae (Ephemeridae: Ephemeroptera) throughout the study period (20.0-88.9 and 0.2-36.8%, respectively). These high prevalence and abundance values may be attributable to their filter-feeding behavior as well as their depositional habitat use. The hairworms also infected leptophlebiids (Ephemeroptera; scrapers), the perlid Calineulia sp., the chloroperlid Haploperla japonica (Plecoptera; predators), and chironomids (Diptera; filter-feeders or predators). The abundance of the cysts tended to be high in aquatic insects inhabiting pools rather than riffles, and the seasonality reflects the reproductive season of the hairworms as well as the phenology of their paratenic hosts. Filter-feeding ephemeropterans inhabiting pools were the major paratenic host of the hairworms in our study site, although their universality and effectiveness as the transporter to definitive hosts remain unclear.

Sandwich ELISA Using a Mouse/Human Chimeric CSLEX-1 Antibody.

BACKGROUND: An assay using a mouse antisialyl Lewis X (sLeX) antibody (CSLEX-1) is used clinically for screening and monitoring patients with breast cancer in Japan. However, the IgM isoform of CSLEX-1 is not preferred for the assay because the bulkiness of IgM generally causes poor accessibility to the antigen. To solve this problem, we developed an antisLeX mouse/human chimeric IgG antibody, CH-CSLEX-1, using transgenic silkworms. The performance of a homologous sandwich ELISA of CH-CSLEX1 was then evaluated. METHODS: To generate CH-CSLEX-1, we used a GAL4/UAS binary gene expression system in transgenic silkworms. The reactivities of CSLEX-1 and CH-CSLEX-1 were determined in a Biacore analysis. To confirm antigen specificity, 3 antigens [sLeX, sLeA, and Lewis Y (LeY)] were used. RESULTS: CH-CSLEX-1 formed correctly as an IgG class of immunoglobulin molecule with an isoelectric point close to the predicted value. The best combination for capturing and probing in a sandwich ELISA was determined as a homologous combination of CH-CSLEX-1. The CH-CSLEX-1 assay specifically detected sLeX, but not sLeA and LeY. A correlation analysis with 107 human samples showed good concordance between the conventional CSLEX-1 assay (homologous sandwich ELISA using CSLEX-1) and the CH-CSLEX-1 assay (r = 0.98). Moreover, the CH-CSLEX-1 assay was not affected by either human antimouse IgG antibodies (HAMA IgG) or HAMA IgM. CONCLUSIONS: The mouse/human chimeric antibody CH-CSLEX-1 allowed the establishment of a highly specific sandwich ELISA for sLeX that was not affected by HAMA.

Ultrasound-guided single shot caudal block anesthesia reduces postoperative urinary catheter-induced discomfort.

BACKGROUND: Urinary catheter-induced discomfort during the postoperative period can be distressing, and sometimes results in severe restlessness and agitation, especially in middle-aged and elderly male patients. Recent advances in ultrasound technology have increased the consistency, safety, and ease of a caudal block even in older patients. We speculated that an ultrasound-guided caudal block would be reliable and safe as treatment for such postoperative discomfort. METHODS: Adult male patients (ASA I-II) undergoing cervical laminoplasty were allocated to either the caudal block (CB, N.=24) or non-block (NB, N.=24) group. Following anesthesia induction, urinary catheterization was performed using a 16 French Foley catheter. Thereafter, an ultrasound-guided caudal block was performed with 8 ml of 0.3% ropivacaine and 100 µg of fentanyl for patients in group CB, while group NB did not receive a caudal block. We assessed urinary catheter-induced discomfort as mild, moderate, or severe at 0, 2, 6, 10, and 18 hours after surgery, and compared the incidence and severity of discomfort between the groups using a randomized double-blind design. RESULTS: All caudal blocks were successfully performed with 1 or 2 needle insertions. The incidence of urinary catheter-induced discomfort was significantly reduced in group CB as compared to NB at 0, 2, and 6 hours, while severity was also reduced at 0 and 2 hours. No patient required re-catheterization due to urinary retention after catheter removal. There were no other complications related to the caudal block. CONCLUSION: Preoperative ultrasound-guided single shot caudal block anesthesia safely reduced postoperative urinary catheter-induced discomfort in our male patients.

Serum epidermal growth factor receptor levels in patients with malignant melanoma.

BACKGROUND: Epidermal growth factor receptor (EGFR) is known to be abnormally expressed in many human carcinomas, suggesting that there may be an increase in serum EGFR levels in patients with malignant melanoma (MM) and that this might be a possible new tumour marker. AIM: To assess whether serum EGFR levels might be a marker of MM. METHODS: Serum samples were obtained from 66 patients with MM and 12 healthy controls, and EGFR levels were measured by double-determinant ELISA. RESULTS: Patients with in situ or stage I MM had significantly higher serum EGFR levels compared with healthy controls. Interestingly, serum EGFR levels decreased gradually with the stage of the tumour, being highest at stage I and lowest at stage IV. There was also a trend towards a reverse correlation between tumour thickness and serum EGFR levels. Moreover, a longitudinal study identified a trend for serum EGFR levels in patients with preoperative MM to decrease compared with patients with recurrent MM. CONCLUSIONS: To our knowledge, this is the first report investigating the serum EGFR levels of patients with MM, and gives new insight into the relationship between EGFR and MM. We found that serum EGFR levels were significantly increased in patients with early-stage MM such as in situ and stage I tumours. Measurements of serum EGFR levels might be of clinical value in the detection of early-stage MM.

Effect of κ-opioid receptor agonist on the growth of non-small cell lung cancer (NSCLC) cells.

BACKGROUND: It is becoming increasingly recognised that opioids are responsible for tumour growth. However, the effects of opioids on tumour growth have been controversial. METHODS: The effects of κ-opioid receptor (KOR) agonist on the growth of non-small cell lung cancer (NSCLC) cells were assessed by a cell proliferation assay. Western blotting was performed to ascertain the mechanism by which treatment with KOR agonist suppresses tumour growth. RESULTS: Addition of the selective KOR agonist U50,488H to gefitinib-sensitive (HCC827) and gefitinib-resistant (H1975) NSCLC cells produced a concentration-dependent decrease in their growth. These effects were abolished by co-treatment with the selective KOR antagonist nor-BNI. Furthermore, the growth-inhibitory effect of gefitinib in HCC827 cells was further enhanced by co-treatment with U50,488H. With regard to the inhibition of tumour growth, the addition of U50, 488H to H1975 cells produced a concentration-dependent decrease in phosphorylated-glycogen synthase kinase 3ß (p-GSK3ß). CONCLUSION: The present results showed that stimulation of KOR reduces the growth of gefitinib-resistant NSCLC cells through the activation of GSK3ß.

The role of microRNA-150 as a tumor suppressor in malignant lymphoma.

MicroRNA (miRNA; miR) is a class of small regulatory RNA molecules, the aberrant expression of which can lead to the development of cancer. We recently reported that overexpression of miR-21 and/or miR-155 leads to activation of the phosphoinositide 3-kinase (PI3K)-AKT pathway in malignant lymphomas expressing CD3(-)CD56(+) natural killer (NK) cell antigen. Through expression analysis, we show in this study that in both NK/T-cell lymphoma lines and samples of primary lymphoma, levels of miR-150 expression are significantly lower than in normal NK cells. To examine its role in lymphomagenesis, we transduced miR-150 into NK/T-cell lymphoma cells, which increased the incidence of apoptosis and reduced cell proliferation. Moreover, the miR-150 transductants appeared senescent and showed lower telomerase activity, resulting in shortened telomeric DNA. We also found that miR-150 directly downregulated expression of DKC1 and AKT2, reduced levels of phosphorylated AKT(ser473/4) and increased levels of tumor suppressors such as Bim and p53. Collectively, these results suggest that miR-150 functions as a tumor suppressor, and that its aberrant downregulation induces continuous activation of the PI3K-AKT pathway, leading to telomerase activation and immortalization of cancer cells. These findings provide new insight into the pathogenesis of malignant lymphoma.

Skewed T cell receptor repertoire of Vdelta1(+) gammadelta T lymphocytes after human allogeneic haematopoietic stem cell transplantation and the potential role for Epstein-Barr virus-infected B cells in clonal restriction.

The proliferation of Vdelta1(+) gammadelta T lymphocytes has been described in various infections including human immunodeficiency virus (HIV), cytomegalovirus (CMV) and malaria. However, the antigen specificity and functions of the human Vdelta1(+) T cells remain obscure. We sought to explore the biological role for this T cell subset by investigating the reconstitution of T cell receptor (TCR) repertoires of Vdelta1(+) gammadelta T lymphocytes after human allogeneic haematopoietic stem cell transplantation (HSCT). We observed skewed TCR repertoires of the Vdelta1(+) T cells in 27 of 44 post-transplant patients. Only one patient developed EBV-associated post-transplant lymphoproliferative disorder in the present patient cohort. The -WGI- amino acid motif was observed in CDR3 of clonally expanded Vdelta1(+) T cells in half the patients. A skew was also detected in certain healthy donors, and the Vdelta1(+) T cell clone derived from the donor mature T cell pool persisted in the recipient's blood even 10 years after transplant. This T cell clone expanded in vitro against stimulation with autologous EBV-lymphoblastoid cell lines (LCL), and the Vdelta1(+) T cell line expanded in vitro from the same patient showed cytotoxicity against autologous EBV-LCL. EBV-infected cells could also induce in vitro oligoclonal expansions of autologous Vdelta1(+) T cells from healthy EBV-seropositive individuals. These results suggest that human Vdelta1(+) T cells have a TCR repertoire against EBV-infected B cells and may play a role in protecting recipients of allogeneic HSCT from EBV-associated disease.

Geldanamycin-induced degradation of Chk1 is mediated by proteasome.

Checkpoint kinase 1 (Chk1) is a cell cycle regulator and a heat shock protein 90 (Hsp90) client. It is essential for cell proliferation and survival. In this report, we analyzed the mechanisms of Chk1 regulation in U87MG glioblastoma cells using Geldanamycin (GA), which interferes with the function of Hsp90. GA reduced Chk1 protein level but not its mRNA level in glioblastoma cells. Co-treatment with GA and cycloheximide (CHX), a protein synthesis inhibitor, induced a decrease of half-life of the Chk1 protein to 3h and resulted in Chk1 down-regulation. CHX alone induced only 32% reduction of Chk1 protein even after 24h. These findings indicated that reduction of Chk1 by GA was due to destabilization and degradation of the protein. In addition, GA-induced down-regulation of Chk1 was reversed by MG132, a specific proteasome inhibitor. And it was revealed that Chk1 was ubiquitinated by GA. These results have indicated that degradation of Chk1 by GA was mediated by the ubiquitin-proteasome pathway in U87MG glioblastoma cells.

Surgical pathology of spinal schwannoma: has the nerve of its origin been preserved or already degenerated during tumor growth?

OBJECTIVE: This study was aimed to understand ultrastructural pathology of nerves of tumor origin of spinal schwannomas, which has not been reported so far, in order to understand the mechanism of the postoperative functional restoration after the nerve transection. METHODS: From 13 patients who underwent sacrifice of an affected nerve root at total removal of spinal schwannomas (C2 conus), the proximal (spinal cord side, n = 12) and distal (dorsal root ganglion side, n = 10) stumps of the nerves of the tumor origin were collected and examined by light and electron microscope, followed by morphometric analysis (n = 9). RESULTS: Almost all of affected nerves at both proximal and distal to the lesion were composed of well-preserved myelin sheath and axons with mild disturbance of endo- and perineurial structures at light microscopic level except one case, which showed severe fibrosis. Electron-microscopically, regenerated axons with thin myelin were found in part in the proximal and distal nerves with few macrophages in three cases. The area of nerves (mm2), density of myelinated axons (axons/mm2) and total number of myelinated axons in the proximal stump (0.552 +/- 0.430, 10,400 +/- 5,240 and 5,480 +/- 4,790) was approximately 70%, 80% and 60%, respectively, of those in the distal stump (0.765 +/- 0.333, 12,400 +/- 5,180 and 9,970 +/- 8,630). CONCLUSIONS: This data combined with no permanent deficits after nerve transection suggest that the nerves of tumor origin are in the processes of slowly progressed deterioration with repeated degeneration and regeneration/remyelination, and the postoperative rapid recovery from the transient neurological deficit may be explained by functional compensation by the adjacent non-affected nerves with slow tumor growth.

IgM and IgG antibody response to Paracoccidioides brasiliensis in naturally infected wild armadillos (Dasypus novemcinctus).

We studied the extent to which wild nine-banded armadillos, Dasypus novemcinctus, produce immune humoral responses specifically directed against characteristic Paracoccidioides brasiliensis antigens. Such antibody production might reflect direct contact with the ecological microniche of P. brasiliensis, or might merely reflect inhalation of widely distributed airborne propagules. An enzyme-linked immunosorbent assay (ELISA) was designed containing purified glycoprotein gp43 and gp70 antigens from P. brasiliensis as well as cross-reactive antisera originally targeted against human IgM (mu chain) and armadillo anti-IgG (gamma-chain). It was used to detect and classify IgM and IgG antibodies to P. brasiliensis in the armadillo. In a serological survey of 47 wild armadillos, IgM antibodies to gp43 were detected in seven animals (14.8%), and IgG antibodies were detected in 20 (42.5%). IgM antibodies to gp70 were detected in 10 (21.3%) animals and IgG antibodies were detected in 18 (38.3%). These results, showing a pattern consistent with infection, suggest that P. brasiliensis is enzootic in armadillos. How the animals became exposed could not be determined.

Recurrent intracranial esthesioneuroblastoma outside the initial field of radiation with progressive dural and intra-orbital invasion.

A 55-year-old man presented with esthesioneuroblastoma in the right paranasal sinuses and orbita, extending into the right anterior and middle cranial fossa. He received a partial resection of tumour and post-operative radiotherapy, which was set with a central focus on the right orbit. Five years later, he came to our hospital with a complaint of left exophthalmos. Neuro-imaging revealed that the tumour recurred on the opposite side of the primary lesion, which was out side the irradiated field, with progressive invasion of the left temporal dura. The residual tumour in the irradiated field had reduced in size. He received gross total resection and post-operative radiotherapy. We would like to emphasize that radiotherapy is an important adjuvant therapy for esthesioneuroblastoma, and that the field setting for radiation therapy is extremely important.

Scanning electron microscopic study of the cleaning ability of chlorhexidine as a root-canal irrigant.

AIM: To evaluate in vitro the cleaning of root-canal walls after irrigation with different irrigants. METHODOLOGY: A total of 36 recently extracted human teeth were divided into four experimental groups according to the irrigating solution used: saline; 2% chlorhexidine; 2.5% sodium hypochlorite; and 2.5% sodium hypochlorite + EDTA. The cleaning of the apical, middle and coronal thirds of the root canals was evaluated by scanning electron microscope examination using a 4-point scoring system. RESULTS: The best cleaning was obtained using 2.5% sodium hypochlorite and EDTA, followed by 2.5% sodium hypochlorite only (P < 0.05), whose cleaning was similar to chlorhexidine only in the cervical third. Cleaning by saline and 2% chlorhexidine was worse than the other two groups and was similar in all thirds. Better cleaning was found in the cervical and middle thirds for all groups with the worst results in the apical third. CONCLUSIONS: The apical third of the root canals was not cleaned as well as the middle and coronal thirds. Cleaning by chlorhexidine and saline was inferior compared to the cleaning by sodium hypochlorite with and without EDTA.

Congenital arachnoid cyst mimicking meningocele.

The subject of this report is a rare case of a 5-year-old girl who developed an arachnoid cyst with a bony and dural defect in the parietal convexity. She had no history of head trauma or infection. Surgical exploration revealed the bulging lesion to consist of cerebrospinal fluid-containing spongy subcutaneous tissue and to extend into the bony and dural defect. The arachnoid cyst cavity was found beneath the subcutaneous lesion and was not connected to the adjacent subarachnoid space. Histologically, the subcutaneous tissue contained a complex of sinusoidal channels formed by an abundance of migrating arachnoidal cells, thus mimicking meningocele.

Accelerated reendothelialization with suppressed thrombogenic property and neointimal hyperplasia of rabbit jugular vein grafts by adenovirus-mediated gene transfer of C-type natriuretic peptide.

BACKGROUND: Vein graft disease limits the late results of coronary revascularization. C-type natriuretic peptide (CNP) inhibits the growth of vascular smooth muscle cells. Given the effects of CNP on cGMP cascade, we hypothesized that transfected CNP genes modulate endothelial repair and thrombogenicity in the vein graft. METHODS AND RESULTS: Autologous rabbit jugular vein grafts were incubated ex vivo in a solution of adenovirus vectors containing CNP gene (Ad.CNP) or Escherichia coli lac Z gene (Ad.LacZ) and then interposed in the carotid artery. Reendothelialization, mural thrombi formation, and intima/media ratio were evaluated on the 14th and 28th postoperative days. More reendothelialization was seen in Ad.CNP-infected grafts than in Ad.LacZ-infected grafts both at 14 days (0.81+/-0.05 versus 0.30+/-0.14, P<0.01) and at 28 days (0.96+/-0.01 versus 0.45+/-0.08, P<0.001). The mural thrombus area was smaller in Ad.CNP-infected grafts than in Ad.LacZ-infected grafts. Neointimal thickening was significantly suppressed in the Ad.CNP group. The in vitro wound assay with human coronary artery endothelial cells revealed significant potentiation of the wound repair process by CNP and atrial natriuretic peptide administration. CONCLUSIONS: Infected Ad.CNP accelerated reendothelialization and suppressed thrombosis and neointimal hyperplasia. The method may potentially prevent vein graft disease in patients undergoing coronary artery revascularization.

Expression of E-cadherin-catenin complex in human benign schwannomas.

The Ca2+-dependent cell adhesion molecule E-cadherin has been known to express in normal and reactive Schwann cells in rodents, and to play an important role in Schwann cell-Schwann cell adhesion and maintenance of peripheral nervous tissue architecture. However, little is known about expression of E-cadherin in schwannomas. The aim of the present study was to investigate the cellular expression and localization of E-cadherin, and its associated protein, alpha E-, alpha N- and beta-catenins in human schwannomas, which are supposed to derive from Schwann cells. We tested the hypothesis that these proteins might show an altered expression/distribution in schwannoma cells which correlates with their neoplastic behavior, including sparse cell-cell contact, as seen those in meningiomas and various carcinomas. In human schwannomas, however, E-cadherin, alpha E-catenin, and beta-catenin were detected by western blotting and immunohistochemistry, whereas alpha N-catenin was not. Immunoprecipitation using anti-E-cadherin antibody resulted in alpha E-catenin forming a complex with E-cadherin. SSCP analysis revealed no mutations in the transmembrane domain or in intracellular catenin-binding site of E-cadherin. These data suggest that the E-cadherin-alpha E-catenin complex is well preserved in human schwannoma cells, which is compatible with its benign behavior, and these molecules might be used as additional cell markers of Schwann cell-derived tumors.

Suppression of membrane-type 1 matrix metalloproteinase (MMP)-mediated MMP-2 activation and tumor invasion by testican 3 and its splicing variant gene product, N-Tes.

Using expression cloning to screen a human fetal kidney cDNA library for regulator(s) of pro-matrix metalloproteinase (MMP)-2 processing mediated by membrane-type (MT) 1 MMP, we isolated a cDNA whose product interfered with pro-MMP-2 activation. It encodes the NH(2)-terminal 313-amino acid region of a calcium-binding proteoglycan, testican 3, with a 3-amino acid substitution at the COOH terminus and thus was named N-Tes. N-Tes comprises a signal peptide, a unique domain, a follistatin-like domain, and a Ca(2+)-binding domain but lacks a COOH-terminal thyroglobulin domain and two putative glycosaminoglycan attachment sites of testican 3. Pro-MMP-2 activation by MT3-MMP was also inhibited by the coexpression of N-Tes. Immunoprecipitation analysis demonstrated direct interaction of N-Tes with either MT1-MMP or MT3-MMP. Expression of testican 1 or testican 3 but not testican 2 also inhibited pro-MMP-2 activation by either MT1-MMP or MT3-MMP. Deletion and substitution of amino acids residues in N-Tes revealed that the unique NH(2)-terminal domain of N-Tes is responsible for the inhibition of pro-MMP-2 activation by MT-MMPs. Expression of N-Tes and testican 3 was detected in normal brain but down-regulated in glioma tissues. Transfection of either the N-Tes or testican 3 gene into U251 glioma cells or Madin-Darby canine kidney cells transformed by erbB2 suppressed their invasive growth in collagen gel. These results suggest that both N-Tes and testican 3 would interfere with tumor invasion by inhibiting MT-MMPs.

Calpain-dependent proteolysis of merlin occurs by oxidative stress in meningiomas: a novel hypothesis of tumorigenesis.

BACKGROUND: The purpose of this study is to indicate that oxidative stress may contribute to occurrence of meningiomas. Recently, it was reported that aside from the neurofibromatosis type 2 (NF2) gene mutations, the calpain-dependent proteolysis of the NF2 gene product, merlin might be closely related to the development of certain NF2-related tumors. Although meningiomas are well known to occur more frequently in aged persons, it still remains unknown why calpain activation occurs predominantly in them. Because the production of free radicals with aging might be one of the causes of calpain activation especially in leptomeningeal cells being devoid of blood supply, the authors examined the relations between mu-calpain activation and merlin proteolysis induced by the oxidative stress. METHODS: The authors examined 12 patient-derived sporadic meningiomas and their primary cultured cells. Malignant glioma cell line (U-251MG), which had no relation to NF2, was used as a control. They were exposed to hydrogen peroxide (H2O2) for 1 hour. After oxidative stress, they were examined by Western blot and immunofluorescence microscopic analyses. RESULTS: Despite the consistent expressions of activated mu-calpain in 11 of 12 meningioma tissues, this calpain activation completely disappeared after culture; instead the full-length merlin appeared again in 8 of 11 cases. The treatment of cultured cells with hydrogen peroxide induced both mu-calpain-dependent cleavage of merlin and reduction of an intrinsic calpain inhibitor calpastatin. Such proteolysis was significantly blocked by a specific calpain inhibitor, Z-LLal. The full-length merlin was immunocytochemically colocalized with activated mu-calpain at the plasma membrane, and, after mu-calpain activation, the fragment of merlin translocated to the perinuclear cytoplasm or into the nucleus. CONCLUSIONS: These findings suggest that oxidative stress-induced activation of mu-calpain causes proteolysis of merlin conceivably to impair cell adhesion and/or contact inhibition of meningioma cells.