Sulcus subarachnoid hemorrhage is a common stroke subtype in patients with implanted left ventricular assist devices.

BACKGROUND AND PURPOSE: Stroke is one of the major complications observed in patients with an implanted left ventricular assist device (LVAD). The purpose of this study was to clarify the types and characteristics of acute stroke in patients after LVAD implantation by using brain computed tomography (CT) findings. METHODS: Between 2005 and 2012, 110 consecutive patients who underwent LVAD implantation were reviewed. The most commonly used device was the pulsatile extracorporeal LVAD. Amongst them, 49 patients suffered from acute stroke at least once with a total of 115 stroke events. The clinical categories, lesion sites, laboratory data and CT findings of each acute stroke event were analyzed. RESULTS: Cerebral infarction (35 patients, 72 events), cerebral hemorrhage (25 patients, 31 events) and subarachnoid hemorrhage (SAH) (23 patients, 33 events) were identified. A mean of 2.3 stroke events occurred per person. Of the 72 infarction events, multiple infarctions were observed in 29 events. Of the cerebral hemorrhage events (n = 31), almost all were subcortical lesions (n = 27) and none were observed in the basal ganglia. Of the 23 patients with SAH events (n = 33), SAH localized within a single sulcus, sulcus SAH, was observed in 25 events. CONCLUSIONS: Computed tomography findings of acute stroke after implantation of an LVAD are characteristically multifocal cortical lesions, regardless of brain infarction and hemorrhage. Unexpectedly, sulcus SAH was a common stroke subtype in patients with implanted LVADs. Sulcus SAH should be carefully examined in patients after LVAD implantation, when they complain of non-specific neurological complaints.

Incidence of growth and rupture of unruptured intracranial aneurysms followed by serial MRA.

BACKGROUND: The natural history, including growth and rupture, of unruptured intracranial aneurysms (UIAs) remains unknown. Here, we present the results of serial magnetic resonance angiography (MRA) follow-up study in 111 patients with 136 UIAs. METHOD: A total of 111 patients with 136 UIAs were followed annually over the past 12 years, using 1.5-Tesla MRA. Follow-up was ended when UIAs were treated surgically, or the patients died of subarachnoid hemorrhage or other causes. Various factors influencing aneurysm rupture or growth were examined statistically. RESULTS: Aneurysm rupture and growth occurred in six and 13 of the 111 patients, respectively. Annual rupture rate was 1.8 % per year and annual growth rate was 3.9 % per year. Aneurysm size was the sole factor influencing rupture(H.R. 1.214, 95 % CI, 1.078-1.368) and multiplicity was the sole factor influencing aneurysm growth (H.R. 5.174, 95 % CI 1.81-14.80). CONCLUSIONS: Serial MRA study showed that the incidence of UIA growth was twice as high as that of UIA rupture. As four patients showed aneurysm rupture or growth within 1 year, further investigations are necessary to determine the optimum interval of radiological investigation and to identify which UIAs grow or rupture within a short time.

Radiation-induced anaplastic ependymoma with a remarkable clinical response to temozolomide: a case report.

Radiation-induced gliomas are uncommon and therapeutic options are limited due to prior exposure to radiotherapy. Meanwhile, the chemotherapeutic response of anaplastic ependymoma, another rare entity in adults, is often disappointing. We report on the first recorded case of radiation-induced anaplastic ependymoma, in which an excellent clinical response to temozolomide was demonstrated.

"Bonnet" bypass to proximal trunk of middle cerebral artery with a radial artery interposition graft: technical note.

BACKGROUND: Anastomosis of the superficial temporal artery (STA) to the middle cerebral artery (MCA) is useful for treating certain patients with internal carotid artery occlusion or MCA occlusion. However, in the case of common carotid artery (CCA) occlusion, since the blood flow in the STA is insufficient, another artery should be used as the donor artery. The cortical branches of the MCA are usually selected as recipients in the STA-MCA bypass. However, the intracranial vascular filling gradually increases over a few months after conventional cortical MCA bypass grafting, while early or even immediate vascular filling is observed after proximal MCA bypass grafting. This study aims to develop an elongation technique of the contralateral STA to reach the proximal segment of the ipsilateral MCA. METHODS: Anastomosis of the contralateral STA to the secondary trunk of the ipsilateral MCA was performed in 2 patients with occlusion of the CCA and ipsilateral vertebral artery (VA). The contralateral STA was extended with a radial artery (RA) graft in order to supply blood to the ischemic area. Elongation of the STA by using an RA interposition graft sufficiently lengthens the graft to enable its anastomosis with the contralateral M2 segment. Postoperative imaging revealed good bypass patency even at 1 year after the surgery. CONCLUSION: This novel technique of performing the "bonnet" bypass was effective in treating both CCA and ipsilateral VA occlusion; moreover, this procedure of elongation of the STA can increase candidates of the recipient, and enables one to perform a double bypass to the anterior cerebral artery (ACA) or posterior cerebral artery (PCA).

Removal of a cavernous hemangioma in the orbital apex via the endoscopic transnasal approach: a case report.

INTRODUCTION: The aim of this study is to describe the case of a cavernous hemangioma extending from the orbital apex to the pterygopalatine fossa that was completely removed via an endoscopic transnasal approach. CASE REPORT: We report the case of a 48-year-old man who presented with right hemianopsia of the left eye. MRI revealed a 1.5 x 1.1 cm mass lesion extending from the infero-medial part of the left orbital apex to the pterygopalatine fossa. Removal of the lesion was performed via the endoscopic transnasal approach. Using this approach, a wide operative view of the entire extent of the lesion from the optic canal to the orbital apex and the pterygopalatine fossa was obtained, and complete removal of the lesion was performed safely. The pathological diagnosis was cavernous hemangioma. CONCLUSION: The endoscopic transnasal approach is a safe, effective, and less invasive therapeutic modality for the removal of lesions extending from the infero-medial part of the left orbital apex to the pterygopalatine fossa. With appropriate patient selection, this approach improves access and visualization, and it enables performance of operative procedures with much less risk than the conventional microscopic transcranial or transfacial approaches.

Technique for shaping microcatheter tips in coil embolization of paraclinoid aneurysms using full-scale volume rendering images of 3D rotational angiography.

INTRODUCTION: In coil embolization of paraclinoid aneurysms, it is sometimes difficult to introduce and stabilize microcatheter tips in the aneurysms. We report a new technique for shaping microcatheter tips in the coil embolization of paraclinoid aneurysms. METHODS: From May 2007 to May 2008, this new technique was applied to 10 paraclinoid aneurysms undergoing coil embolization. Before coil embolization, 3D rotational angiography was performed, and volume-rendering images were reconstructed. Vinyl-coated handicraft wire was shaped 3-dimensionally to fit full-scale volume-rendering images on the monitor, from the C5 portion of the internal carotid artery to the center of the dome of the aneurysm from various angles. The microcatheter tip was then shaped with steam to fit the vinyl-coated wire. Thereafter, the microcatheter tip was introduced into the aneurysm and coil embolization was performed. RESULTS: Microcatheter tips could be easily shaped and could be introduced smoothly into aneurysms, and were stable during coil embolization. CONCLUSION: This technique is feasible for shaping microcatheter tips precisely for coil embolization of paraclinoid aneurysms.

Stimulation of primary motor cortex for intractable deafferentation pain.

The stimulation of the primary motor cortex (M1) has proved to be an effective treatment for intractable deafferentation pain. This treatment started in 1990, and twenty-eight studies involving 271 patients have been reported so far. The patients who have been operated on were suffering from post-stroke pain (59%), trigeminal neuropathic pain, brachial plexus injury, spinal cord injury, peripheral nerve injury and phantom-limb pain. The method of stimulation was: a) epidural, b) subdural, and c) within the central sulcus. Overall, considering the difficulty in treating central neuropathic pain, trigeminal neuropathic pain and certain types of refractory peripheral pain, the electrical stimulation of M1 is a very promising technique; nearly 60% of the treated patients improved with a higher than 50% pain relief after several months of follow-up and sometimes of a few years in most reports. The mechanism of pain relief by the electrical stimulation of M1 has been under investigation. Recently, repetitive transcranial magnetic stimulation (rTMS) of M1 has been reported to be effective on deafferentation pain. In the future, rTMS may take over from electrical stimulation as a treatment for deafferentation pain.

Stimulation of primary motor cortex for intractable deafferentation pain.

To treat intractable deafferentation pains, we prefer stimulation of the primary motor cortex (M1). The methods of stimulation we utilize are electrical stimulation and repetitive transcranial magnetic stimulation (rTMS). In our department, we first attempt rTMS, and if this rTMS is effective, we recommend the patient to undergo procedures for motor cortex stimulation (MCS). A 90% intensity of resting motor threshold setting is used for rTMS treatment. In this study ten trains of 5 Hz rTMS for 10 seconds (50 seconds resting interval) were applied to the M1, S1, pre-motor and supplementary motor areas. Only M1 stimulation was effective for pain reduction in 10 of 20 patients (50%). Twenty-nine MCS procedures were performed by subdural implantation of electrodes, and in the case of hand or face pain, electrodes were implanted within the central sulcus (11 cases), because the main part of M1 is located in the central sulcus in humans. The success rate of MCS was around 63%, and seemed to be higher in cases of pain with spinal cord and peripheral origins, while it was lower in cases of post-stroke pain.

MAGE-E1, a new member of the melanoma-associated antigen gene family and its expression in human glioma.

To unearth glioma-specific genes in human glioblastoma, the serial analysis of gene expression technique was applied to a primary glioblastoma, using cultured human astrocytes as a normal control. Among the top 147 most-expressed tags in glioblastoma, we found a tag, TTTTGGGTAT, that originated from an unidentified gene and which was not detected in human astrocyte cultures. Real-time quantitative reverse transcription-PCR showed that MAGE-E1 expression was 2.6-15-fold enriched in glioblastoma relative to human astrocytes. Expressed sequence tags containing this tag were homologous to the melanoma-associated antigen gene (MAGE) family, and this new cDNA, named MAGE-E1, was cloned by the 5'-rapid amplification of cDNA ends technique. Three alternatively spliced variants (MAGE-E1a-c) were found, and deduced amino acid sequence showed that MAGE-E1a and -E1b shared the MAGE-conserved region, whereas -E1c did not. This suggests that although MAGE-E1c is expressed from one of the MAGE family, it has distinct functions from other members. Tissue distribution analysis showed that MAGE-E1 was distinct from other MAGEs. MAGE-E1 expression was detected only in brain and ovary among normal tissues. Interestingly, MAGE-E1a and/or -E1b were specifically expressed in glioma cells among cancer cells. These results indicate that MAGE-E1 is a novel and glioma-specific member of MAGE family.

Diagnostic and Prognostic Value of 11C-Methionine PET for Nonenhancing Gliomas.

BACKGROUND AND PURPOSE: Noninvasive radiologic evaluation of glioma can facilitate correct diagnosis and detection of malignant transformation. Although positron-emission tomography is considered valuable in the care of patients with gliomas, (18)F-fluorodeoxyglucose and (11)C-methionine have reportedly shown ambiguous results in terms of grading and prognostication. The present study compared the diagnostic and prognostic capabilities of diffusion tensor imaging, FDG, and (11)C-methionine PET in nonenhancing gliomas. MATERIALS AND METHODS: Thirty-five consecutive newly diagnosed, histologically confirmed nonenhancing gliomas that underwent both FDG and (11)C-methionine PET were retrospectively investigated (23 grade II and 12 grade III gliomas). Apparent diffusion coefficient, fractional anisotropy, and tumor-to-normal tissue ratios of both FDG and (11)C-methionine PET were compared between grade II and III gliomas. Prognostic values of these parameters were also tested by using progression-free survival. RESULTS: Grade III gliomas showed significantly higher average tumor-to-normal tissue and maximum tumor2-to-normal tissue than grade II gliomas in (11)C-methionine (P = .013, P = .0017, respectively), but not in FDG-PET imaging. There was no significant difference in average ADC, minimum ADC, average fractional anisotropy, and maximum fractional anisotropy. (11)C-methionine PET maximum tumor-to-normal tissue ratio of 2.0 was most suitable for detecting grade III gliomas among nonenhancing gliomas (sensitivity, 83.3%; specificity, 73.9%). Among patients not receiving any adjuvant therapy, median progression-free survival was 64.2 ± 7.2 months in patients with maximum tumor-to-normal tissue ratio of <2.0 for (11)C-methionine PET and 18.6 ± 6.9 months in patients with maximum tumor-to-normal tissue ratio of >2.0 (P = .0044). CONCLUSIONS: (11)C-methionine PET holds promise for World Health Organization grading and could offer a prognostic imaging biomarker for nonenhancing gliomas.

Clinicopathological study of cellular proliferation and invasion in gliomatosis cerebri: important role of neural cell adhesion molecule L1 in tumour invasion.

BACKGROUND/AIMS: In patients with gliomatosis cerebri (GC), glial fibrillary acidic protein (GFAP) positive cells invade the entire brain, particularly the white matter. Because the nosological definition and histogenesis of GC remain controversial, the morphology and immunohistochemical staining patterns of neoplastic GC cells were compared with those of other gliomas. METHODS: An immunohistochemical analysis of neoplastic cells from four patients with GC and 20 with astrocytic tumours using antibodies against Ki-67, GFAP, and L1, the last of which is a neural cell adhesion molecule putatively related to glioma invasion. RESULTS: GC tumour cells can be divided into two types, those mainly composed of strongly GFAP and L1 positive gemistocytic cells, the other composed of small, GFAP and L1 negative spindle shaped cells. The two types did not differ with respect to Ki-67 positivity. Cells from patients with other gliomas were positive for GFAP but concurrent L1 expression was negative or weakly positive. CONCLUSION: The strong expression of L1 in patients with GC and its poor expression in the 20 patients with other types of glioma, including those with GFAP positive gemistocytic astrocytomas, suggest that L1 expression may play a role in the histogenesis of GC.

Pituitary-Targeted Dynamic Contrast-Enhanced Multisection CT for Detecting MR Imaging-Occult Functional Pituitary Microadenoma.

BACKGROUND AND PURPOSE: Although resection of a tumor by trans-sphenoidal surgery is considered the criterion standard for successful surgical treatment of functional pituitary microadenoma, MR imaging occasionally fails to visualize and identify the tumor and supplementary imaging modalities are necessary. We tested the possibility of dynamic contrast-enhanced multisection CT of the pituitary gland accompanying image reconstruction of contrast agent dynamics to identify the localizations of microadenomas and compared the diagnostic performance with conventional pituitary-targeted MR imaging. MATERIALS AND METHODS: Twenty-eight patients with surgically confirmed functional pituitary microadenomas (including growth hormone-, adrenocorticotropic hormone-, and prolactin-secreting adenomas) who underwent pituitary-targeted dynamic contrast-enhanced multisection CT were retrospectively investigated. We undertook image reconstruction of the dynamics of the contrast agent around the pituitary gland in a voxelwise manner, visualizing any abnormality and enabling qualification of contrast dynamics within the tumor. RESULTS: Fifteen cases were correctly diagnosed by MR imaging, while dynamic contrast-enhanced multisection CT correctly diagnosed 26 cases. The accuracy of localization was markedly better for adrenocorticotropic hormone-secreting microadenomas, increasing from 32% on MR imaging to 85% by dynamic contrast-enhanced multisection CT. Compared with the normal pituitary gland, adrenocorticotropic hormone-secreting adenoma showed the least difference in contrast enhancement of the different functional microadenomas. Images acquired at 45-60 seconds after contrast agent injection showed the largest difference in contrast enhancement between an adenoma and the normal pituitary gland. CONCLUSIONS: Dynamic contrast-enhanced multisection CT combined with image reconstruction of the contrast-enhanced dynamics holds promise in detecting MR imaging-occult pituitary microadenomas.

Immunohistochemical investigation of cerebral ischemia in gerbils.

Experimental cerebral ischemia was produced in gerbils by occlusion of the right common carotid artery in the neck. The evolution of the ischemic lesions was followed from five minutes to six hours by using the immunohistochemical techniques for tubulin and creatine kinase BB-isoenzyme. The earliest lesion was found in the subiculum-CA1 and CA2 regions of the hippocampus in five minutes. There was loss of staining in the apical dendrites and perikarya of the pyramidal cells. The earliest lesion in the cerebral cortex, visible in ten minutes, was a laminar loss of staining for tubulin. Evolution of the ischemic lesions in the thalamus and caudoputamen was delayed. However, in two hours widespread ischemic lesions were seen there. Evolution of the ischemic lesions was slightly slower with the reaction for creatine kinase BB-isoenzyme as compared to the reaction for tubulin, but was far more sensitive than hematoxylin-eosin staining. The distribution of ischemic lesions detected by the immunohistochemical method compared to ischemic areas detected by an India ink perfusion study suggested that both the extent of regional ischemia and regional difference in tissue vulnerability were contributing factors for the emergence of early ischemic lesions. The mechanism for prompt disappearance of the immunohistochemical reaction for tubulin is not clear, but the present investigation demonstrates the usefulness of the immunohistochemical technique for detecting early ischemic lesions and provides a possible biochemical mechanism for cellular damage after ischemic insults.

Expression of bone-related protein messenger RNA in human meningiomas: possible involvement of osteopontin in development of psammoma bodies.

Meningiomas often contain concentric calcified foci, referred to as psammoma bodies. Since calcium phosphate deposits in both psammoma bodies and bone tissues, we examined whether messenger (m) RNA of bone-related extracellular matrix proteins and bone morphogenetic proteins (BMP) were expressed in human meningioma tissues. Northern blotting demonstrated the expression of osteopontin (OPN), matrix Gla protein (MGP), osteonectin (ON) and BMP-4 mRNA but not bone sialoprotein, osteocalcin and BMP-2 mRNA. In situ hybridization revealed that most OPN mRNA-expressing cells were located around the psammoma bodies in meningothelial whorls. Moreover, combination of in situ hybridization and immunohistochemistry on serial sections showed that the OPN mRNA-expressing cells were CD68-positive, suggesting they were macrophages. Immunohistochemistry with anti-OPN antibody and von Kossa staining on the adjacent section showed that the deposition site of OPN protein was consistent with that of calcium phosphate. Neither MGP nor ON mRNA expression appeared to correlate with the calcification. The present result suggests that OPN produced by CD68-positive macrophages may play a significant role for development of psammoma bodies in meningiomas.

Cerebral ischemia in rabbit: a new experimental model with immunohistochemical investigation.

Regional cerebral ischemia was produced in the rabbit by unilateral transorbital occlusion of the middle cerebral artery (procedure I); the middle cerebral and azygos anterior cerebral or anterior communicating artery (procedure II); or the middle cerebral, azygos anterior cerebral or anterior communicating, and internal carotid artery (procedure III). Evolution of ischemic lesions was examined with the immunohistochemical reaction for tubulin. With procedure I, ischemic lesions did not become constantly visible for 6 h in the basal ganglia and for 8 h in the frontoparietal region of the cerebral cortex. With procedure II, it was shortened to 3 h in the basal ganglia and to 6 h in the cerebral cortex. With procedure III, the ischemic lesions were observed in 1 h both in the basal ganglia and in the cerebral cortex as loss of the reaction for tubulin in the neuropil, nerve cell bodies, and dendrites. The evidence of neuronal damage became apparent in the same areas later by staining with hematoxylin-eosin. The experimental model presented here may be suitable for investigation of the mechanism that shifts reversible ischemia to cerebral infarction and for evaluation of the effectiveness of pharmacological intervention.

Elevation of plasma nitric oxide end products during focal cerebral ischemia and reperfusion in the rat.

We investigated the alterations in the stable end products of nitric oxide, i.e., nitrate and nitrite, in the plasma during and after rat focal cerebral ischemia by an automated procedure based on the Griess reaction. At 2 h of middle cerebral artery (MCA) occlusion, plasma nitrate/nitrite levels were significantly higher (53 +/- 8 microM, mean +/- SD, n = 5, p < 0.05) than in rats with sham operation (36 +/- 9 microM, n = 5), and were mildly elevated at 4 h of MCA occlusion (42 +/- 9 microM, n = 5, n.s.). At 30 min of reperfusion after 2 h of MCA occlusion, plasma nitrate/nitrite levels were more markedly elevated (72 +/- 7 microM, n = 5, p < 0.01 vs. sham operation), but were moderately elevated at 2 h of reperfusion after 2 h of MCA occlusion (61 +/- 10 microM, n = 5, p < 0.05). Plasma nitrite levels were not changed during these experimental periods. Administration of 20 mg/kg of NG-nitro-L-arginine methyl ester (L-NAME) significantly decreased plasma nitrate/nitrite as well as nitrite at 30 min of reperfusion after 2 h of MCA occlusion (n = 5), but 2 mg/kg of L-NAME did not (n = 3). The effect of 20 mg/kg of L-NAME on plasma nitric oxide end products was reversed by the simultaneous administration of 200 mg/kg of L-arginine (n = 3), but not D-arginine (n = 3). The present study suggests that the L-arginine-nitric oxide pathway is activated during acute cerebral ischemia and reperfusion.

Regional cerebral ischemia in the gerbil: measurement of regional cerebral blood flow by quantitative autoradiography.

Alterations in the regional CBF after occlusion of the posterior communicating, middle cerebral, or common carotid artery were investigated in the gerbil with a quantitative autoradiographic technique using [14C]iodoantipyrine. Occlusion of the posterior communicating artery produced severe ischemia in the ipsilateral hippocampus, thalamus, and dorsal mesencephalon. Occlusion of the middle cerebral artery produced severe ischemia in the ipsilateral rostral and central cerebral cortex and lateral caudate-putamen. Occlusion of the common carotid artery produced ipsilateral hemispheric ischemia of variable degrees. The distribution and degree of cerebral ischemia produced by occlusion of one of these arteries correlated closely to the arterial territory and the extent of collateral blood supply. Since the areas affected after occlusion of the posterior communicating or middle cerebral artery differ, those models will be useful for the comparative investigation of the ischemia-related cerebral pathophysiology associated with different sites of primary lesion.

Autoradiographic study of regional protein synthesis in focal cerebral ischemia with TCA wash and image subtraction techniques.

The standard biochemical method of trichloracetic acid (TCA) wash and the image processing technique were combined to differentiate and visualize the distributions of polypeptide-incorporated and unincorporated tracers in an autoradiographic study of regional protein synthesis. The validity of applying TCA wash procedures to cryostat sections was considered by histologic and chemical evaluations. For the autoradiographic study of in vivo protein synthesis, a tracer dose of L-[14C]valine was administered 30 min after occlusion of the posterior communicating artery in gerbils. Images of total (polypeptide-incorporated and unincorporated) radioactivity and of polypeptide-incorporated radioactivity were obtained from an identical cryostat section before and after TCA wash. The polypeptide-unincorporated radioactivity image was produced with an image processing system by subtracting pixel by pixel the polypeptide-incorporated radioactivity from the total radioactivity. The present study clearly demonstrated that in spite of the sufficient delivery of tracer amino acids, the polypeptide synthesis was completely lost in the ischemic focus. Free tracer was markedly accumulated in the brain adjacent to the ischemic focus. This kind of autoradiographic technique seems to be indispensible in studying the topographical complexity of the altered protein metabolism in the pathologic brain.

Structural characterization and chromosomal localization of the MAGE-E1 gene.

Genes of the melanoma-associated antigen (MAGE) family are characterized by the expression of tumor antigens on a malignant melanoma recognized by autologous cytolytic T lymphocytes. We have previously identified novel members of the MAGE gene family expressed in human glioma and named them MAGE-E1a-c. In the present study, we have revealed the genomic structure of MAGE-E1 by sequence analysis of a human chromosome bacterial artificial chromosome clone containing the MAGE-E1 gene. The MAGE-E1 gene is composed of 13 exons, and three of these (exon 2, exon 3 and exon 12) are alternatively spliced in each variant (E1a-c). The open reading frame encoding the MAGE-E1 peptides initiates in exon 2 and ends in exon 13. We have also demonstrated that the MAGE-E1 gene is located in Xp11 through the analysis of radiation hybrid panels. The genomic structure of MAGE-E1 is markedly similar to that of MAGE-D and its chromosomal locus is also identical to that of MAGE-D, but these features contrast with those of other MAGEs. These results suggest that MAGE-D and -E1 may be evolutionarily distant from other members of the MAGE family, and the two may be ancestral genes for the others.

Isolation and expression analysis of a novel human homologue of the Drosophila glial cells missing (gcm) gene.

A novel human homologue (GCMB) of the Drosophila glial cells missing gene (dGCM) was isolated using RACE. GCMB contained a gcm motif sequence and a nuclear targeting sequence similar to that of dGCM and mouse GCMb. Homology searches indicated that GCMB was located within chromosome 6p24.2. Transcripts of GCMB were detected by means of RT-PCR in fetal brain, normal adult kidney, 3/3 medulloblastomas, 1/3 gliomas and 4/8 non-neuroepithelial tumor cell lines. Our data suggest that humans have two homologues of gcm like mice and that human gcm genes form a novel family which may function not only during fetal development but also in the postnatal or pathological stage.