Good quality of life before cardiac arrest predicts good quality of life after resuscitation.

BACKGROUND: The survival rate of cardiac arrest patients is increasing. Our aim was to compare the quality of life before and after cardiac arrest and analyse the factors associated with outcome. METHODS: All adult cardiac arrest patients admitted to the Tampere University Hospital intensive care unit between 2009 and 2011 were included in a retrospective follow-up study if surviving to discharge and were asked to return a questionnaire after 6 months. Data on patient demographics and pre-arrest quality of life were retrieved from medical records. Data are given as means (SD) or medians [Q1 , Q3 ]. We used logistic regression to identify factors associated with better quality of life after cardiac arrest. RESULTS: Six months after cardiac arrest, 36% (79/222) were alive and 70% (55/79) of those patients completed the follow-up EuroQoL (EQ-5D) quality of life questionnaire. Median values for the EQ-5D before and after cardiac arrest were 0.89 [0.63, 1] and 0.89 [0.62, 1], respectively (P = 0.75). Only the EQ-5D prior to cardiac arrest was associated with better quality of life afterwards (OR 1.2; 95% CI 1.0-1.3; P = 0.02). CONCLUSIONS: Quality of life remained good after cardiac arrest especially in those patients who had good quality of life before cardiac arrest.

The quality of manual chest compressions during transport--effect of the mattress assessed by dual accelerometers.

BACKGROUND: The quality of cardiopulmonary resuscitation (CPR) has an impact on survival. The quality may be impaired if the patient needs to be transported to the hospital with ongoing CPR. The aim of this study was to analyse whether the quality of CPR can be improved during transportation by using real-time audiovisual feedback. In addition, we sought to evaluate the real compression depths taking into account the mattress and stretcher effect. METHODS: Paramedics (n = 24) performed standard CPR on a Resusci Anne Mannequin in a moving ambulance. Participants were instructed to perform CPR according to European Resuscitation Council Resuscitation guidelines 2010. Each pair acted as their own controls performing CPR first without and then with the feedback device. Compression depth, rate and no-flow fraction and also the mattress effect were recorded by using dual accelerometers by two Philips, HeartStart MRx Q-CPR defibrillators. RESULTS: In the feedback phase, the mean compression depth increased from 51 (10) to 56 (5) mm (P < 0.001), and the percentage of compression fractions with adequate depth was 60% vs. 89% (P < 0.001). However, taking account of the mattress effect, the real depth was only 41 (8) vs. 44 (5) mm without and with feedback, respectively (P < 0.001). The values for compression rate did not differ. CONCLUSIONS: CPR quality was good during transportation in general. However, the results suggest that the feedback system improves CPR quality. Dual accelerometer measurements show, on the other hand, that the mattress effect may be a clinically relevant impediment to high quality CPR.

Association of cardio-ankle vascular index with physical fitness and cognitive symptoms in aging Finnish firefighters.

PURPOSE: Monitoring cardiovascular risk factors is important in health promotion among firefighters. The assessment of arterial stiffness (AS) may help to detect early signs of atherosclerosis. The aim of this study was to analyze associations between aerobic fitness, cognitive symptoms and cardio-ankle vascular index (CAVI) as a measure for AS among Finnish firefighters. METHODS: The data are one part of a large 13-year follow-up study of the health and physical and mental capacity of Finnish professional firefighters. The subjects in this substudy comprised 65 male firefighters of a mean age of 48.0 (42-58) years in 2009. Their maximal oxygen uptake was successfully measured in two cross-sectional studies in 1996 and 2009, and they responded to questionnaires at both sessions, and their CAVI was measured in 2009. CAVI was calculated from the pulse waveform signal and pulse wave velocity. The lifestyle habits and subjective cognitive stress-related symptoms were collected via a standardized questionnaire. Muscular fitness was measured by the routine test battery used for Finnish firefighters. RESULTS: CAVI was related to age. About one-fifth of the firefighters had a CAVI of >8. Aerobic fitness was the main physiological factor correlating with increased CAVI. Interestingly, VO(2)max and the accelerated decrease in VO(2)max during a 13-year follow-up were associated with signs of impaired vascular function. The cognitive symptoms derived from the Profile of Mood States questionnaire (POMS) were mainly associated with stress and sleeping difficulties. No clear association with physical fitness was found in this population of fit firefighters. CONCLUSIONS: Among firefighters, the decrease in aerobic fitness predicts increased arterial stiffness. The speed of the age-related decline in maximal oxygen consumption is as important as absolute level. Against expectations, the cognitive function did not correlate with vascular health parameters. The cognitive symptoms, however, were only mild.

Quantitative EEG in occupational chronic solvent encephalopathy.

The aim of this study was to characterize the quantitative analyzed EEG (electroencephalogram) findings (qEEG) in chronic solvent encephalopathy (CSE) patients and study whether the qEEG findings associate with the duration and intensity of the solvent exposure. Also, the diagnostic value of qEEG in CSE is discussed. The EEG of 47 male CSE patients was analyzed. The laboratory's own reference EEG values of 24 healthy male subjects formed the laboratory control group. We also used an age-matched control group of 100 male blue-collar workers without occupational solvent exposure. The main finding of our study was that the power of the frontal theta band is increased in the CSE patient group compared with the laboratory control group. This suggests that the frontal cortex may be susceptible to the noxious effects of solvents. However, this difference was not seen in comparison with the matched control group, and thus, the connection with solvent effects remains uncertain. The variables indicating the level of solvent exposure did not associate with the power of the theta activity in the frontal area. Because of the small amount and unspecificity of the observed abnormalities, qEEG cannot be recommended to be used in the clinical diagnostics of solvent encephalopathy.

Middle age cognition and vocational outcome of childhood brain injury.

OBJECTIVES: In this almost four-decade follow-up we studied the cognitive performance of a cohort of 22 traumatic brain injury (TBI) patients in relation to vocational outcome. The patients had suffered a moderate to severe TBI in traffic accidents as preschoolers. METHODS: The neuropsychological assessment included the Profile of Mood States questionnaire and the Neurobehavioral Rating Scale. The cognitive performance of full-time working patients was compared with that of those not working. RESULTS: Full-time working patients had significantly better intellectual performance than the patients not at work. Memory performance was partly defective in both groups but neither group had subjective memory complaints. All patients working full time lived in a marital relationship and had less neurobehavioral problems than the patients not at work. CONCLUSIONS: Good intellectual capacity, verbal memory, and marital status were connected with a positive outcome. We suggest that as late as in middle age in spite of moderate to severe childhood TBI, it is still possible for a subgroup of patients to live a normal productive life.

High resolution deletion analysis of constitutional DNA from neurofibromatosis type 2 (NF2) patients using microarray-CGH.

Neurofibromatosis type 2 (NF2) is an autosomal dominant disorder whose hallmark is bilateral vestibular schwannoma. It displays a pronounced clinical heterogeneity with mild to severe forms. The NF2 tumor suppressor (merlin/schwannomin) has been cloned and extensively analyzed for mutations in patients with different clinical variants of the disease. Correlation between the type of the NF2 gene mutation and the patient phenotype has been suggested to exist. However, several independent studies have shown that a fraction of NF2 patients with various phenotypes have constitutional deletions that partly or entirely remove one copy of the NF2 gene. The purpose of this study was to examine a 7 Mb interval in the vicinity of the NF2 gene in a large series of NF2 patients in order to determine the frequency and extent of deletions. A total of 116 NF2 patients were analyzed using high-resolution array-comparative genomic hybridization (CGH) on an array covering at least 90% of this region of 22q around the NF2 locus. Deletions, which remove one copy of the entire gene or are predicted to truncate the schwannomin protein, were detected in 8 severe, 10 moderate and 6 mild patients. This result does not support the correlation between the type of mutation affecting the NF2 gene and the disease phenotype. This work also demonstrates the general usefulness of the array-CGH methodology for rapid and comprehensive detection of small (down to 40 kb) heterozygous and/or homozygous deletions occurring in constitutional or tumor-derived DNA.

Evidence for a cytoskeleton attachment domain at the N-terminus of the NF2 protein.

Neurofibromatosis type 2 is a hereditary cancer syndrome characterized by the development of bilateral vestibular schwannomas. Underlying the disease are inactivating mutations of the NF2 tumor suppressor gene, located on chromosome 22, encoding a 595-amino-acid protein. The NF2 protein, also known as merlin or schwannomin, is reported to act as a membrane-cytoskeleton linking protein. This assumption is based on the homology of the NF2 protein to a group of band 4.1-related proteins, ezrin, radixin, and moesin. The cytoskeletal association of the NF2 protein has in part been confirmed by its ability to resist extraction from cells by nonionic detergents. We performed detergent extraction on COS cells transfected with NF2 cDNA constructs. The extracts were analyzed by Western blotting and immunofluorescent staining with monoclonal anti-NF2 antibodies. The results provide evidence for a high-affinity cytoskeleton attachment domain at amino acids 29-131 and a putative lower affinity domain between amino acids 321 and 470.

Genetic aberrations in sporadic and neurofibromatosis 2 (NF2)-associated schwannomas studied by comparative genomic hybridization (CGH).

BACKGROUND: Schwannomas occur sporadically or in association with neurofibromatosis 2 (NF2), an autosomal dominant disorder, which predisposes to multiple schwannomas, meningiomas and spinal ependymomas, with bilateral vestibular schwannomas as the classic hallmark. As NF2 and sporadic schwannomas differ in some respect in their clinical and biological behavior we evaluated whether there are any differences in the distribution of genetic aberrations between NF2 and sporadic schwannomas. Our interest was also to verify whether secondary genetic alterations besides the loss of 22q could be detected in schwannomas. METHODS: We investigated DNA copy number changes in 25 schwannomas (12 NF2 and 13 sporadic schwannomas) using the comparative genomic hybridization (CGH) technique. Some chromosomal regions were further studied by LOH or FISH analysis. FINDINGS: CGH detected genomic abnormalities in 15 of 25 schwannomas (60%). The most common alteration was loss on 22q, found in 32% (8/25) of schwannomas. No consistent changes were detected in other chromosomal regions. The overall number of genetic aberrations was similar in NF2 and in sporadic schwannomas. INTERPRETATION: Our results support the present view that loss of chromosome 22q harboring the NF2 gene plays a universal role in the pathogenesis of schwannomas without consistent involvement of other chromosomal regions.

Hemangioblastomas of the retina: impact of von Hippel-Lindau disease.

PURPOSE: To assess the prevalence of von Hippel-Lindau (VHL) disease and prognosis of vision in patients with retinal hemangioblastomas (HBs). METHODS: Thirty-six consecutive patients with retinal HBs were treated at Helsinki University Hospital between 1974 and 1998. Detailed neurologic, ophthalmologic, and radiologic examinations; pedigree; mutation analyses; and collection of all relevant clinical, imaging, operative, and autopsy data were performed to identify VHL. RESULTS: The median follow-up time was 10 years. No patient was lost to follow-up. There were three patient groups: 1) 11 patients with clinically definite VHL; 2) 10 patients with clinically suspected VHL with more than one retinal HB (5/10) or visceral cysts (5/10), but with no family history, no detected germ-line mutations, and no VHL-related neoplasms; and 3) 15 patients without VHL with a single retinal HB but no other data suggestive of VHL. In the 11 patients with definite VHL, retinal HBs were detected at a median age of 27 years versus 40 years in the 15 non-VHL patients, and 21 of the 22 eyes were affected. Two VHL patients were totally blind at the end of follow-up compared with one legally blind patient with suspected VHL, but none of the non-VHL patients was blind. The clinical appearance of HBs did not differ among the patient groups. CONCLUSIONS: The prevalence of VHL among patients with retinal HBs was 30% to 58% (11-21 of 36). Visual prognosis was more favorable in non-VHL than VHL patients. All patients with retinal HB should undergo thorough VHL exclusion.

Mild familial neurofibromatosis 2 associates with expression of merlin with altered COOH-terminus.

OBJECTIVE: To understand molecular details of the pathogenesis of a very mild and homogenous form of neurofibromatosis 2 (NF2). BACKGROUND: Inactivation of the NF2 tumor suppressor gene leads to the development of multiple nervous system tumors, accompanied by loss of the NF2 gene product, merlin, or schwannomin. The severity of disease varies between patients, and the biologic basis of this variation is poorly understood. METHODS: We studied the genotype-phenotype correlation in a large pedigree with extremely mild and uniform disease manifesting as slowly growing bilateral vestibular nerve schwannomas of late onset. RESULTS: The tumors demonstrated a low proliferation rate and loss of the wild-type NF2 allele. The disease is caused by a novel mutation in the NF2 gene at intron 15 splice donor site (1737 + 3 a --> t), which was identified in all carriers by the minisequencing method. The mutation resulted in splicing out of exon 15 and production of two transcripts: a novel mutant transcript with exon 16 and overexpression of isoform III, normally detected at a low level. Both transcripts encode for the COOH-terminus of isoform III. Immunoblotting of patient fibroblasts and tumor tissue demonstrated variant merlin with altered COOH-terminus. CONCLUSIONS: The mutational skip of exon 15 and the expression of a protein with the COOH-terminus of isoform III correlates with the exceptionally mild NF2, and suggests tumor suppressor activity for isoform III. The detection of expressed mutant proteins may provide useful information for prediction of the clinical outcome of individual mutations.

Neurofibromatosis type 2.

Neurofibromatosis type 2 is an often devastating autosomal dominant disorder which, until relatively recently, was confused with its more common namesake neurofibromatosis type 1. Subjects who inherit a mutated allele of the NF2 gene inevitably develop schwannomas, affecting particularly the superior vestibular branch of the 8th cranial nerve, usually bilaterally. Meningiomas and other benign central nervous system tumours such as ependymomas are other common features. Much of the morbidity from these tumours results from their treatment. It is now possible to identify the NF2 mutation in most families, although about 20% of apparently sporadic cases are actually mosaic for their mutation. As a classical tumour suppressor, inactivation of the NF2 gene product, merlin/schwannomin, leads to the development of both NF2 associated and sporadic tumours. Merlin/schwannomin associates with proteins at the cell cytoskeleton near the plasma membrane and it inhibits cell proliferation, adhesion, and migration.

Population-based analysis of sporadic and type 2 neurofibromatosis-associated meningiomas and schwannomas.

OBJECTIVE: To estimate the incidence of meningiomatosis and schwannomatosis, and their familial occurrences and relation to type 2 neurofibromatosis (NF2) in a well-defined population. METHODS: Patients with histologically verified intracranial, spinal, or peripheral schwannomas or meningiomas, who were residents of the Helsinki University Hospital catchment area (population, 1,713,000) from January 1, 1985, to December 31, 1995, were included in the study. The Population Register Center was used to identify relatives of all the patients, and their data were linked further to the Finnish Cancer Registry to find NF2-related tumors. Detailed pedigrees were constructed for the patients with NF2, schwannomatosis, meningiomatosis, patients with relatives with histologically verified schwannomas or meningiomas, and patients younger than 25 years of age at the time of diagnosis. RESULTS: Approximately 3% (12 of 455) of the schwannoma patients had multiple schwannomas in association with NF2, and 2% (11 of 455) had schwannomatosis without NF2. Two of the patients with schwannomatosis (2 of 11) had familial schwannomatosis. Approximately 1% (7 of 823) of the patients with meningioma had multiple meningiomas in association with NF2, and 4% (29 of 823) had meningiomatosis without NF2. No families with meningiomatosis were found among the 823 patients with meningioma studied. The birth occurrence of NF2 was 1 in 87,410. CONCLUSIONS: The current diagnostic criteria of type 2 neurofibromatosis (NF2) seem valid because NF2 patients were differentiated rather easily from patients with sporadic schwannomatosis and meningiomatosis. Familial meningiomatosis, if it truly exists, is very rare, and familial schwannomatosis is uncommon.

Long-term prognosis of haemangioblastoma of the CNS: impact of von Hippel-Lindau disease.

The aim was to assess the frequency of von Hippel-Lindau disease (VHL) and the long-term prognosis of VHL and non-VHL patients among 110 consecutive patients with haemangioblastoma (HB) of the CNS treated between 1953 and 1993 at one neurosurgical unit. To reveal VHL manifestations we performed a detailed clinical and radiological examination (neuraxis and abdomen) (61/110), VHL-gene mutation analysis (40/110), and collection of all available clinical, imaging, operative and autopsy data from the hospitals involved. All patients were followed-up with a median of 14 years (excluding 14 operative deaths), and no patient was lost to follow-up. Altogether 49 patients died during the follow-up. In the 14 VHL patients (13%), HB(s) of the CNS were detected at a median age of 33 years, retinal HB(s) at 39 years, and renal cell carcinoma (RCC) at 43 years. The frequency of VHL in patients operated on for HB(s) was 29% before the age of 25 years, 19% between 25 and 45 years, and only 2% after 45 years. HB patients not meeting the VHL criteria had internal organ cysts in 14%. One non-VHL patient (4%) had two adjacent HBs in the same cyst wall. The growth rates of non-VHL and VHL-related HBs were similar as indicated by the median time to recurrence and the proliferation indices (MIB-1). Recurrence of the HB in patients whose primary operation was considered radical developed in four of the 10 VHL patients at a median of 19 years, and in nine of the 74 non-VHL patients at a median of 11 years. The median length of life of all VHL and non-VHL patients was 46 and 63 years, respectively. In VHL, RCC and HBs were equal causes of death.

Homotypic and heterotypic interaction of the neurofibromatosis 2 tumor suppressor protein merlin and the ERM protein ezrin.

Ezrin, radixin and moesin (ERM) are homologous proteins, which are linkers between plasma membrane components and the actin-containing cytoskeleton. The ERM protein family members associate with each other in a homotypic and heterotypic manner. The neurofibromatosis 2 (NF2) tumor suppressor protein merlin (schwannomin) is structurally related to ERM members. Merlin is involved in tumorigenesis of NF2-associated and sporadic schwannomas and meningiomas, but the tumor suppressor mechanism is poorly understood. We have studied the ability of merlin to self-associate and bind ezrin. Ezrin was coimmunoprecipitated with merlin from lysates of human U251 glioma cells and from COS-1 cells transfected with cDNA encoding for merlin isoform I. The interaction was further studied and the association domains were mapped with the yeast two-hybrid system and with blot overlay and affinity precipitation experiments. The heterotypic binding of merlin and ezrin and the homotypic association of merlin involves interaction between the amino- and carboxy-termini. The amino-terminal association domain of merlin involves residues 1-339 and has similar features with the amino-terminal association domain of ezrin. The carboxy-terminal association domain cannot be mapped as precisely as in ezrin, but it requires residues 585-595 and a more amino-terminal segment. Unlike ezrin, merlin does not require activation for self-association but native merlin molecules can interact with each other. Heterodimerization between merlin and ezrin, however, occurs only following conformational alterations in both proteins. These results biochemically connect merlin to the cortical cytoskeleton and indicate differential regulation of merlin from ERM proteins.

Structure-function relationships in the ezrin family and the effect of tumor-associated point mutations in neurofibromatosis 2 protein.

Ezrin, radixin and moesin (ERM proteins) link cell adhesion molecules to the cytoskeleton, modulate cell morphology and cell growth and are involved in Rho-mediated signal transduction. Merlin, the tumor suppressor in neurofibromatosis 2, is a diverged member of the ezrin family, but its function is at least partially similar to the ERM proteins. In the N-domain, the ezrin family belongs to the band 4.1 superfamily. Secondary structure predictions made separately for the ezrin and band 4.1-tyrosine phosphatase families give a similar pattern for the homologous N-domains, indicating that both families have a similar binding site for the integral membrane proteins. The alpha-domain shows a strong coiled-coil prediction, that can be involved in the protein dimerization. The C-terminal actin-binding site in the ERM proteins and the actin-binding helix in the villin headpiece have a common amino acid motif. In merlin, the published tumor-associated single amino acid mutations in the N-domain are located in the conserved sites, and they affect mainly the predicted helices and strands, indicating that these mutations cause the disease primarily by disturbing the protein structure. In the alpha- and C-domains, some of the mutations break the helical structures. Some known mutations are observed at a site potentially interacting with cell adhesion molecules. We will also discuss the implications of the evolutionary information and the actin-binding models in the ezrin family.

Multiple schwannomas: schwannomatosis or neurofibromatosis type 2?

OBJECT: The aim of this study was to clarify the clinical outcome of schwannomatosis, a rare condition characterized by multiple nonvestibular schwannomas in the absence of meningiomas, intraspinal ependymomas, and other clinical signs of neurofibromatosis type 2 (NF2). METHODS: Nine patients with schwannomatosis treated at one institution are presented and their clinical course during a median follow-up time of 9.9 years is discussed. The patients were typically middle-aged at the time of their first operation (median 43.5 years), none had a positive family history of schwannomatosis or NF2, and none showed cutaneous or ocular signs of NF2. On histopathological examination the tumors from the patients with schwannomatosis showed a lobular appearance and frequent Verocay bodies, signs indicating NF2, more often than 20 sporadic schwannomas that were investigated as controls. Two patients died of unrelated causes at 3.2 and 9.9 years, respectively, of follow up. Magnetic resonance images of the head and spine were obtained in seven patients at the end of the follow-up period. New spinal schwannomas were detected in one patient and a residual schwannoma in three. No germline mutations of the NF2 gene were found in these seven patients. Two additional patients originally included in the schwannomatosis group who were 8.6 and 11.7 years old at initial surgery had NF2. One was diagnosed at follow-up review and the other developed a fulminant disease that led to death in 4 years. CONCLUSIONS: The clinical course, long-term outcome, and genetic mechanism of schwannomatosis differ from that of NF2.

Biosynthesis and intracellular targeting of the CLN3 protein defective in Batten disease.

Batten disease (juvenile-onset neuronal ceroid lipofuscinosis, JNCL), the most common neurodegenerative disorder of childhood, is caused by mutations in a recently identified gene ( CLN3 ) localized to chromosome 16p11.2-12.1. To elucidate the biosynthesis and localization of the CLN3 protein, we expressed CLN3 cDNA in COS-1 and HeLa cell lines. In vitro translation, immunoprecipitation and Western blotting analyses detected an approximately 43 kDa polypeptide. Pulse-chase experiments indicated that the CLN3 protein is synthesized as an N -glycosylated single-chain polypeptide, which was not detected in growth medium. Confocal immunofluorescence microscopy revealed that the CLN3 protein is localized to the lysosomal compartment. These results provide evidence that Batten disease can be classified as a member of lysosomal diseases.

Genomic structure of the human ezrin gene.

The ERM proteins, ezrin, radixin, and moesin, act as linkers between the plasma membrane and actin cytoskeleton. They are involved in a variety of cellular functions, such as cell adhesion, migration, and the organization of cell surface structures, and are highly homologous, both in protein sequence and in functional activity, with merlin/schwannomin, a neurofibromatosis-2-associated tumor-suppressor protein. We report here the genomic structure and intron junction sequences of the human ezrin gene. Ezrin consists of 13 exons and spans approximately 24 kb genomic DNA. The coding parts of the exons range in size from 12 bp to 275 bp and the introns from 182 bp to 7 kb. The genomic structures of ezrin and moesin are highly conserved, suggesting their recent divergence. Radiation hybrid mapping has refined the location of ezrin to the interval between D6S442 and D6S281.

Proliferation potential and histological features in neurofibromatosis 2-associated and sporadic meningiomas.

The authors compared the histological appearance and proliferation potential of 35 meningiomas in patients with neurofibromatosis 2 (NF2) and 30 sporadic meningiomas in age- and gender-matched patients without NF2. The NF2 meningiomas showed more mitotic figures (p < 0.001) and nuclear pleomorphism (p = 0.003) than the sporadic meningiomas; however, the incidence of meningothelial, fibroblastic, and transitional subtypes occurred equally in both groups. The proliferation potential was significantly higher in the 35 meningiomas removed from 23 patients with NF2 than in the 30 sporadic meningiomas removed in the 30 patients without NF2 (mean MIB-1 labeling indices: 2.5 vs. 1.75, p = 0.0147). The higher proliferation potential of the NF2 meningiomas may reflect differences in molecular biology between sporadic and NF2 meningiomas and may be related to an earlier onset, multiplicity, and more aggressive behavior of NF2 tumors.

Neurofibromatosis 2 tumor suppressor protein colocalizes with ezrin and CD44 and associates with actin-containing cytoskeleton.

Neurofibromatosis 2 (NF2) protein (merlin; schwannomin) is a tumor suppressor involved in tumorigenesis of NF2-associated and sporadic schwannomas and meningiomas. The protein shares the domain structure of three homologous proteins: ezrin, radixin and moesin (ERM). ERM proteins function as membrane organizers and may act as linkers between plasma membrane molecules, such as CD44 and ICAM-2, and the cytoskeleton. We analyzed the distribution and effects of transfected NF2 protein in COS-1, CHO and 293 cells, and endogenous NF2 protein in U251 glioma cells. The distribution was compared to ezrin, CD44 and F-actin. Both transfected and endogenous NF2 protein localized underneath the plasma membrane in a pattern typical of an ERM protein. In COS-1 transfectants, NF2 protein typically codistributed with ezrin but, in cells with poorly developed actin cytoskeleton, it replaced ezrin in filopodia and ruffling edges. NF2 protein colocalized with CD44, which in transfected cells accumulated into restructured cell membrane protrusions. The association of CD44 and NF2 protein was further suggested by binding of CD44 from cellular lysates to recombinant NF2 protein. Interaction between NF2 protein and the actin-containing cytoskeleton was indicated by partial colocalization, by cytochalasin B-induced coclustering, and by retention of NF2 protein in the detergent-insoluble fraction. Transfected NF2 protein induced morphogenic changes. The cells contained restructured membrane extensions and blebs, and CHO cells expressing NF2 protein were more elongated than control transfectants. In conclusion, NF2 protein possesses functional properties of an ERM family member.