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E26 avian leukemia oncogene 2, 3' domain (Ets2) has been implicated in various biological processes. An Ets2 mutant model (Ets2 db1/db1 ), which lacks the DNA-binding domain, was previously reported to exhibit embryonic lethality caused by a trophoblast abnormality. This phenotype could be rescued by tetraploid complementation, resulting in pups with wavy hair and curly whiskers. Here, we generated new Ets2 mutant models with a frame-shift mutation in exon 8 using the CRISPR/Cas9 method. Homozygous mutants could not be obtained by natural mating as embryonic development stopped before E8.5, as previously reported. When we rescued them by tetraploid complementation, these mice did not exhibit wavy hair or curly whisker phenotypes. Our newly generated mice exhibited exon 8 skipping, which led to in-frame mutant mRNA expression in the skin and thymus but not in E7.5 Ets2 em1/em1 embryos. This exon 8-skipped Ets2 mRNA was translated into protein, suggesting that this Ets2 mutant protein complemented the Ets2 function in the skin. Our data implies that novel splicing variants incidentally generated after genome editing may complicate the phenotypic analysis but may also give insight into the new mechanisms related to biological gene functions.

Background: Both ossification of the yellow ligament (OYL) and the ossification of the posterior longitudinal ligament are relatively rare clinical entities. We report a extremely rare case of the spinal canal stenosis because of OYL, OPLL and listhesis at the cervicothoracic junction., Case Description: A 69-year-old man had progressive pain over his bilateral axillar portion and right lower extremity for 1 year. Radiology showed cervical canal stenosis with ossification of OYL, OPLL, and listhesis at the cervicothoracic junction. Posterior decompression therapy was performed, and he recovered entirely from his symptoms., Conclusions: Triple factors of OYL, OPLL and listhesis contributed the cervical canal stenosis limited at cervicothoracic junction. Early diagnosis and surgical therapy is recommended for the good prognosis of this pathologic condition, as well as careful long-term follow-up for the early detection of its recurrence., (Copyright © 2017 Elsevier Inc. All rights reserved.)

The anesthetic effect of a combination of medetomidine, midazolam and butorphanol (Me-Mi-Bu) was evaluated in healthy cynomolgus monkeys. The Me-Mi-Bu combination was intramuscularly administered as follows: Dose 1, Me 0.015 mg/kg-Mi 0.1 mg/kg-Bu 0.15 mg/kg; Dose 2, Me 0.02 mg/kg-Mi 0.15 mg/kg-Bu 0.2 mg/kg; and Dose 3, Me 0.04 mg/kg-Mi 0.3 mg/kg-Bu 0.4 mg/kg. The combination rapidly induced immobilization, and lateral recumbency was reached within 15 min. The duration of anesthesia for each dose administered was follows: Dose 1, 47 ± 27 min; Dose 2, 113 ± 31 min; and Dose 3, 190 ± 24 min. The anesthetic effect of the combination was abolished by the α2-adrenoceptor antagonist atipamezole. No marked changes in the levels of hematologic or serum biochemical parameters were noted in cynomolgus monkeys administered the combination plus atipamezole. Taken together, these results suggest that the Me-Mi-Bu combination exhibits reversible anesthetic effect and may be useful for studies involving cynomolgus monkeys.

Here, to determine the effects of transport stress on blood parameters in dogs, we investigated the changes in hematologic and serum chemical parameters in healthy beagle dogs transported from Beijing, China, to Osaka, Japan, to obtain the background data. Only the activity of serum alkaline phosphatase increased clearly upon arrival, a change attributed to transport stress, but the activity gradually reduced afterward. No marked changes in levels of other blood parameters were noted. Our findings here suggest that alkaline phosphatase is a useful tool for studying transport stress.

A 24-year-old male presented with headache. He had been treated with antituberculous drugs for 19 months. MRI revealed 4 intracranial Gd-DTPA enhanced lesions surrounded by massive edema in the right frontal, both occipital and left basal ganglionic regions. Digital subtraction angiography showed no tumor stain. Two procedures for tumor resection were performed for the right frontal and left occipital regions, the latter of which definitively diagnosed by the polymerase chain reaction method. The tumors were well demarcated, showed a rough surface, and were elastically hard. The two residual lesions responded differently to chemotherapy. The lesion in the right occipital region decreased in size, while the other in the left basal ganglionic region continued to grow gradually 26 months after the antituberculous chemotherapy was started. According to previous reports, treatment should be continued for as long as 12-30 months in cases showing paradoxical expansion. In this case, the left basal ganglionic lesion began to decrease in size after 28 months of administration of anti-tuberculous drugs. We report successful treatment of a case of multiple tuberculomas presenting with paradoxical expansion managed by a combination of surgery and continuous chemotherapy.

A 38-year-old male who presented with trigeminal nerve paresis was found to have a cerebellopontine angle tumor. The tumor was subtotally removed. Multiple histological sections showed no malignant changes, and the diagnosis was typical epidermoid cyst. Tumor growth recurred twice and the diagnosis after the third operation was epidermoid carcinoma. A review of the available literature yielded only 22 reported cases of malignant intracranial epidermoid cyst.

A case of neurinoma of the cauda equina which showed spinal subarachnoid hemorrhage was reported. A 39-year-old man was admitted to our hospital because of left lumboischialgia, on August 7, 1987. Myelography disclosed a round mass at L2, and cerebrospinal fluid was slightly xanthochromic. MRI demonstrated a round isointensity mass by T1 weighted image, and slightly high intensity by T2 weighted image. On August 26, 1987, the patient developed sudden onset of headache, but his headache disappeared under medication. On August 27, 1987, laminectomy L1-3 and total removal of the tumor were carried out. At operation, marked subarachnoid hemorrhage was discovered. He was discharged with slight hypesthesia of the dermatome of left S2.

Five cases of intradural arachnoid cysts were reported. Two rare cases were in cervical region, other three cases in thoracic region. Clinical and radiological findings were discussed in 67 cases including ours. All our cases with chronic clinical course except one showing spastic para- or tetraparese, sensory disturbance and gait disturbances were not much different to other reported cases in neurological findings. Plain radiography, tomography and intravenous enhanced CT were not effective. In all of the cases spinal CT was performed following metrizamide myelography. Only one cyst failed to detect during metrizamide myelography, but a metrizamide CT revealed the intradural arachnoid cyst even in this case. Vonofakos says that metrizamide myelogram failed to found the arachnoid cysts, however, we could confirm them by performing metrizamide CT about 3 hours after conventional myelography. Moreover reconstruction technique was very effective in ascertaining the shape and the extention of the tumors. Especially it is recommended to do delayed metrizamide CT with ReView technique in order to show the detailed relation between the cyst and the spinal cord. In conclusion, we emphasize the accurate neurological examination, the importance of total myelography and the improvement of fluoroscopic technique in myelography and CT scanning.

A 53-year-old woman presenting weakness in the left hand for ten years was diagnosed seven years ago as having juvenile muscular atrophy of the unilateral upper extremity. Afterwards, her left forearm and hand gradually became weaker. A neurologist pointed out syringomyelia in the film of MR imaging. However, the cause of syringomyelia was not demonstrated until gadolinium-DTPA-enhanced MR imaging disclosed a spinal tumor. Through an operation it was found that it was an intradural extramedullary tumor at C7 level. Histological diagnosis of the tumor was meningioma. Only 12 reports of syringomyelia associated with extramedullary intraspinal tumors were found. Among them each tumor in three cases was diagnosed by delayed metrizamide computed tomography, only one case by MR imaging. Though in our case myelography, postmyelographic CT, intravenous enhanced CT and MR imaging were performed, gadolinium-DTPA-enhanced MR imaging was eventually most useful in diagnosing this tumor. The pathophysiologic mechanism by which the syrinx fills, and the differentiation in MR imaging between syrinx and tumor cyst were reviewed.

We experienced 19 histologically verified intracranial malignant lymphomas during the period of 15 years from April 1, 1965 to August 31, 1979. From the analysis of cases of our own and from the literature, the following are considered to be the clinical characteristics of intracranial malignant lymphomas. 1) Males were more affected than females. 2) The highest frequency was observed in the 5th to 7th decades. 3) Increased intracranial pressure, motor disturbance, and psychic or consciouness disturbance were 3 cardinal symptoms. 4) Tumors were localized frequently in the paraventricular region. 5) Angiography revealed hypovascular lesion in many cases, while CT scan showed homogenous, slightly high density lesion which was remarkably enhanced by contrast material. 6) Long survival was rare irrespective of all kinds of treatments. 7) Immunological classification was thought to be useful in prospecting survival time.

The computed tomography (CT) in examination of the spine and spinal cord has rapidly advanced and its diagnostic value has been well documented. It is widely accepted that CT is very useful for the diagnosis of the spinal neurinomas, especially of dumb-bell tumors. In the last two years we have experienced with 11 cases of spinal neurinomas. These include 1 accessory neurinoma, 7 cervical neurinomas of dumb-bell type, 2 thoracic dumb-bell neurinomas, 1 intradural neurinoma in the conus medullaris and multiple neurofibromas in the cauda equina in one patient. The age distributed from 24 to 52 years, with an average of 41.5. In all of these patients except one, metrizamide CT was performed following a total myelography. In most of the cases, CT with and without an intravenous contrast medium injection was also carried out. The conventional radiologic examinations including plain radiography, tomography and angiography were done in most of the patients. Comparing with the results of those examinations, we reached the following conclusions: (1) metrizamide CT can disclose the superior border of the tumor which is often not visualized by conventional ascending myelography. The reconstruction CT clearly outlines the whole extent of the tumor. (2) The bony changes associated with a dumb-bell neurinoma, for example, the widening of the intervertebral foramen, can be found by plain CT in much earlier stage than by the plain roentgenogram. The findings can be more clearly using a "ReView" software program. (3) The extraspinal part of the dumb-bell tumor is shown in CT by an intravenous enhancement as a slightly high-dense, homogeneous mass with CT-number of approximately 70 HU. The capsule of the tumor is a little more enhanced in the most cases. (4) It is recommended to do a metrizamide CT with "ReView" technique when a tumor in the cauda equina is suspected on conventional myelography. (5) A tumor near the foramen magnum or in the upper cervical region is often overlOoked on metrizamide myelography. When a tumor in these regions is highly suspected on neurological examinations, it is also recommended to perform a metrizamide CT about 3 hours after conventional myelography.

A rare case of intrasacral perineurial cyst is presented. Findings on metrizamide myelography and computed tomography scan are described, and their usefulness in the diagnosis of this rare condition is emphasized. The literature is reviewed, and the clinical and pathological features of the 17 reported cases including our own are summarized. Indication for operation and surgical approach are briefly discussed.

Several kinds of the lumbosacral nerve root anomalies have already been recognized, and the conjoined nerve roots is the most common among them. It does not make symptoms by itself, but if there is a causation of neural entrapment, for example, disc herniation, lateral recessus stenosis, spondylolisthesis, etc., so called "biradicular syndrome" should occur. Anomalies of the lumbosacral nerve roots, if not properly recognized, may lead to injury of these nerves during operation of the lumbar spine. Recently, the chance of finding these anomalous roots has been increased more and more with the use of metrizamide myelography and metrizamide CT, because of the improvement of the opacification of nerve roots. We describe the findings of the anomalous roots as revealed by these two methods. They demonstrate two nerve roots running parallel and the asymmetrical wide root sleeve. Under such circumstances, it is important to distinguish the anomalous roots from the normal ventral and dorsal roots.

There is a controversy on the surgical treatment for the so-called cervical herniated disc. Recently operators choosing the anterior approach have increased in more and more. However, considering the historical view of the treatment of disc disease, it is obvious that the posterior approach is also an important method, especially in the cases combined with the stenotic cervical spinal canal. During the past five years 200 patients of cervical herniated disc disease were operated in our clinic by using our newly devised instruments and new materials. We studied the relation between the operative approach, the extent of interbody fusion and the surgical results. The social adaptation of the operated patients was also examined especially by comparing the short follow-up with the long one. Regardless of surgical approach, the percentage of the good recovery is higher (10% at the most) in the short follow-up than that in the long observation. The consequence is thought to show that the social adaptation deteriorates as the time goes on. Based on these results, the historical aspects and the technical problems of anterior and posterior approach were reviewed, focusing especially the controversial points. On the other hand, presenting our opinion on the surgical approach, we showed how the surgical problems have been solved and other complications lowered by introducing our new technique. Consequently, we stress that it is insignificant to discuss whether we should choose the anterior approach or the posterior approach. Finally, in case of criticizing the surgical results, it is reemphasized that we should think over not only the simple operative results, but also the aspect of social adaptation.

A case of spinal epidural AVM with unusual clinical course was presented. A 28-year-old male had repeated episodes of paraparesis and complete recovery in several hours. Metrizamide myelography revealed the dorsal epidural mass at the level of L2 and L3. Accidental epidurogram during the procedure indicated extradural angioma. Surgical intervention proved solitary spinal epidural AVM. Ninety-nine cases in literature were reviewed. Among them, 14 cases of spinal epidural hematoma were due to ruptured angioma which were verified histologically. Others were unknown causes. Age distribution was discussed. It was suggested that the younger patients in the group of unknown causes might have angiomas. It was emphasized that it should not be overlooked even the insignificant transient symptoms and should schedule the extensive radiological examination in such cases.

A case is reported of recurring or multiple spinal meningioma and focuses again on the incomplete information at present available regarding this class of meningioma. Repeated operations were performed earlier in the extradural space at C2 and an intradural tumour at the same level was completely removed. After a six year interval, we diagnosed an intramedullary meningioma once again at C2, which was subtotally removed. Histological examination indicated an angioblastic tumour, the same type of meningioma as was previously found. Postoperative recovery was satisfactory. Two years later, an intradural extramedullary tumour at T2-3 level was totally removed. Again postoperative recovery went well. In view of the rare occurrence of this meningioma, and the reports on it, we envisaged the pathogenesis of our case as an invasion from the extradural into the intradural space and into the spinal cord. Its appearance in the thoracic region might have been by dissemination via the cerebrospinal fluid pathways or it may have occurred independently.

The occurrence of a novel and specific inhibitor of Ca2+-dependent neutral protease in rat liver has been demonstrated. The partially purified product is a heat-stable and acid-stable protein of an approximate molecular weight of 3x10(5), and readily inactivated by tryptic digestion. The inhibition of Ca2+-dependent protease is not a result of the binding of Ca2+ by the inhibitor.

Three cases of haemangiolipoma are described. Two of them were in the thoracic region and one in the lumbar region. All of them were subtotally removed, positively diagnosed histologically and good recovery was obtained. In reviewing 16 previous cases, the clinical characteristics, neurological features and neuroradiological findings were noted. Spinal extradural haemangiolipomas show a high incidence in middle-aged people and at the mid-thoracic level. Usually they show the signs of an extradural space-occupying lesion. Sometimes, worsening and improving are found particularly in female cases. Reviewing the existing literature, our diagnosis and procedures stress the importance of technical aspects in performing myelography and the findings of CT scanning.

Spinal epidural lymphoma is rarely found in Japan, comparing with Europe and America. We experienced two cases, who were suffered from intractable pain and gait disturbance. In both cases, a wide laminectomy and partial removal of the epidural tumor were performed because of the deteriorated paraparesis. After that, they were able to walk without support. These epidural tumors were supposed to be primary spinal epidural lymphomas, judging from the clinical course and some other examinations, that is, Gallium scintigram and CT scan, etc. There were few reports that mentioned CT findings of spinal lymphomas. In our two cases, we got the characteristic CT findings of spinal lymphomas. In case 1, plain CT demonstrated a high density mass at epidural space extending into the intra- and extra-foraminal region. CT scan following intravenous injection showed the tumor enhancement remarkably and homogeneously. Bone erosion was not found even on plain CT, in both cases. These findings were thought to be different from those of metastatic tumors. It may be possible to diagnose and decide the therapeutic planning preoperatively, when we get these characteristic CT findings of spinal lymphomas.

Twelve cases of benign extramedullary tumors in the high cervical region and at the foramen magnum were experienced during past five years among eighty all spinal and paraspinal tumors. The diagnosis of masses in this region is very difficult because of the variety of clinical course, symptoms and neurological findings as pointed out by many reporters. Also in our cases, 70% of the patients complained of the deteriorated motor weakness of the upper or lower extremities on admission, though they had noticed the onset of slight neck or occipital pain a few years ago. Neurological examination on admission clearly showed the symptom of myelopathy except in two cases with a tumor at the foramen magnum and C1 level. The percentage of positive findings of plain X-rays was 50%, that of metrizamide myelography was 92% and that of IV. e. CT and met. e. CT was 100%. NMR-CT was performed in 2 cases, and in one of them it was useful in confirming the tumor configuration and extension. Five interesting cases were described mainly from the neuroradiological aspects. Finally the differentiation between meningioma and neurinoma was discussed from the aspects of myelogram, CT and NMR-CT. As already pointed out, it is most important not to forget the existence of tumors in this region when one comes across the confused symptoms, afterwards not to overlook the slight positive neurological and neuroradiological findings.

A 58-year-old female was admitted because of lumbago and dysesthesia on the lateral aspect of the left leg. She had myelographies and spinal operations 4 years ago. Metrizamide myelogram on admission revealed the findings of adhesive arachnoiditis. During operation, four plaques involving the cauda equina were found, removed and histologically proved to be osseous tissue. In reviewing the previously published cases of arachnoiditis ossificans, it is divided into two forms. One is incidentally found in the arachnoid membrane at the time of an autopsy or spinal operation. The other is a progressive form causing impairment of the spinal cord and cauda equina. Compared with the former, the latter is extremely rare. At present, there appears to be a general agreement about the pathological process to ossification in the latter. The ossified plaque has its origin in meningothelial cell clumps located at the junction of the arachnoid sheet and the trabecula. The ossification occurs secondarily as a result of degenerative change in these clumps after myelography, spinal operation, subarachnoid hemorrhage, spinal trauma and spinal anesthesia. In our case, it is presumed that repeated spinal operations or myelographies played a role as a trigger toward ossification.

Spinal meningiomas are common as intradural-extramedullary neoplasm, but solitaly epidural spinal meningiomas are extremely rare. They may often be misdiagnosed as malignant neoplasms which are much more common in this location. Furthermore, at the time of operation, it is often difficult to distinguish the epidural meningioma from malignant tumors, even by the microscopic examination of the fresh frozen section. We present a case of spinal epidural meningioma, and emphasize the importance of preoperative neuroradiological examinations. A 26-year-old woman was referred to us from a neurologist of another hospital under the diagnosis of thoracic spinal tumor. She noticed sensory numbness in the lower extremities and thermal hypesthesia below the breasts about one year previously, and progressive gait disturbance about half a year prior to admission. Neurological examination revealed spastic paraparesis with hypesthesia of all modalities below T3. Plain films of the thoracic spine showed scalloping of the posterior margine of the T3 vertebral body. Metrizamide myelography showed a complete block at T3/4, and metrizamide CT revealed marked dural compression by an epidural mass which occupied the left side of the spinal canal from T2 to T4. The subarachnoid space all around the spinal cord was preserved comparatively well. The tumor was homogeneously enhanced by intravenous contrast enhanced CT scan, and the extracanalicular extension was not revealed. MRI [SE (400/25)] showed an iso-intensity signal tumor. Neither extracanalicular nor intrathecal extension of the tumor was showed. In addition to the possibility of the malignant tumors, we considered the possibility of spinal epidural meningioma. At operation, of highly vascularized, moderately firm epidural tumor was found invading the surrounding epidural fat.(ABSTRACT TRUNCATED AT 250 WORDS)