Minoru Hoshimaru

Expression of Interleukin-1β Converting Enzyme Gene Family and bcl-2 Gene Family in the Rat Brain following Permanent Occlusion of the Middle Cerebral Artery

Recent investigations have been suggesting that some neuronal subpopulations may die via programmed cell death after focal ischemic injury. To clarify the possible roles of the genes involved in the cell-death program, this study examined the expression of three members of the interleukin-1β converting enzyme (Ice) gene family (Ice, Nedd2, and Yama/CPP32) and two members of the bcl-2 gene family (bcl-2 and bcl-x) in the rat brain after permanent occlusion of the middle cerebral artery. Northern blot analysis revealed a transient induction of Nedd2 mRNA 8 h after the ischemic insult (3.8-fold) and an increase in Yama/CPP32 mRNA 16 to 24 h after the insult (5.8-fold at 24 h), whereas the expression of Ice remained constant. The expression of bcl-2 and bcl-x remained constant after the ischemic insult. Taking into account the key role of the Ice gene family in the execution of programmed cell death, the induction of Ice gene family might play a causative role in apoptotic cell death.

Results of Microsurgical Treatment for Intramedullary Spinal, Cord Ependymomas: Analysis of 36 Cases

OBJECTIVE Although intramedullary spinal cord ependymomas are amenable to surgical total resection, some ependymomas have been associated with severe surgical morbidity. The aim of this study is to determine what factors affect surgical morbidity. METHODS Thirty-six consecutive patients who underwent surgical removal of an intramedullary spinal cord ependymoma between September 1980 and June 1998 were studied retrospectively. This series includes 19 women and 17 men between the age of 12 and 67 years (mean age, 41.2 yr). The location of the tumors was cervical in 24 cases, cervicothoracic in 3 cases, thoracic in 7 cases, and conus in 2 cases. At surgery, complete removal was achieved in 34 patients and subtotal removal was performed in the remaining 2. RESULTS There has been no tumor recurrence in any patient except one who had an anaplastic ependymoma after a mean follow-up period of 56 months. The surgery improved neurological status in 14 of the 36 patients (39%). However, five patients (14%) experienced persistent deteriorations in clinical grade caused by surgery. Four of the five patients harbored benign ependymomas in the thoracic cord and characteristically demonstrated arachnoid scarring and cord atrophy at surgery, indicating that tumors had been present for a long time. CONCLUSION Surgical removal of intramedullary ependymomas is beneficial to patients. However, the thoracic cord may be susceptible to surgical manipulations for intramedullary ependymomas. In addition, intraoperative findings of arachnoid scarring and cord atrophy are ominous for surgical morbidity.

Sequence analysis of cloned cDNA for rat substance P precursor: existence of a third substance P precursor.

The sequence of the mRNA for the rat substance P precursor (preprotachykinin A) has been elucidated by molecular cloning and sequence analysis. The deduced amino acid sequence of rat preprotachykinin A indicates that it contains both substance P and substance K but differs in the sequence organization from either bovine alpha- or beta-preprotachykinin A reported previously. The existence of the bovine mRNA for the third preprotachykinin A has thus been examined and evidenced by the isolation of the corresponding cDNA clone. This mRNA, named gamma-preprotachykinin A mRNA, deletes the sequence precisely corresponding to the exon 4 sequence of the preprotachykinin A gene. Thus, alternative RNA splicing in the expression of the single preprotachykinin A gene results in the generation of three different forms of the preprotachykinin A mRNAs.

Localization of trkB and low-affinity nerve growth factor receptor mRNA in the developing rat retina

The localization of trkB and low-affinity nerve growth factor receptor (LNGFR) mRNAs in the developing rat retina was examined by in situ hybridization. TrkB mRNA was expressed in the ganglion cell layer (GCL), in the inner border of the neuroblastic layer (NBL), and the inner border of the inner nuclear layer (INL). LNGFR mRNA was expressed in the GCL, in almost full thickness of the NBL, and in the intermediate part of the INL. Although both trkB mRNA and LNGFR mRNA were expressed in the GCL, the expression pattern was different between these mRNAs; trkB mRNA was expressed in almost all cells in the GCL uniformly and the expression of LNGFR mRNA varied greatly from cell to cell. In addition, the expression of both mRNAs, especially LNGFR mRNA seemed to be down-regulated at P7, when programmed cell death of the RGCs was prominent. These observations indicate that LNGFR may modulate the function of trkB and that trkB and LNGFR play important roles in the development and maintenance of the RGCs.

Developmental expression of trkB and low-affinity NGF receptor in the rat retina

Brain-derived neurotrophic factor (BDNF) promotes the survival of retinal ganglion cells, but these effects are dependent on the developmental stages, and a number of retinal ganglion cells are eliminated during pre- and neonatal stages. We have examined the expression of BDNF receptors, trkB and low-affinity nerve growth factor receptor (LNGFR), in the rat retina during these period using Northern blot analysis. The expression of trkB and LNGFR displayed two peaks during embryonic day 17 (E17) through postnatal day 1 (P1), and during P14-P17, indicating that it may play an important role in neuronal development and neuronal cell death.

Technical improvements and results of open-door expansive laminoplasty with hydroxyapatite implants for cervical myelopathy.

OBJECTIVE: A new, modified technique of cervical open-door laminoplasty with hydroxyapatite implants was developed to enlarge the spinal canal in stable fashion yet preserve the architecture of the cervical spine and surrounding tissues. To assess the efficacy of this technique, a retrospective review of neurological and radiological outcomes after cervical laminoplasty was conducted. METHODS: Clinical charts and cervical x-rays of 151 patients with cervical stenotic myelopathy were reviewed. Patients were treated with the cervical laminoplasty between May 2001 and January 2002. The patient group comprised 69 women and 82 men ranging in age from 30 to 86 years (mean, 63 yr). Neurological outcomes were evaluated according to the Japanese Orthopaedic Association grade. To assess alignment and mobility of the cervical spine, the C2–C7 angle was used. RESULTS: The average Japanese Orthopaedic Association grade was 8.1 ± 2.5 before surgery and 15.2 ± 1.5 at 1 year after surgery (P < 0.01). No neurological complications were observed. The average C2–C7 angle at the neutral position increased from 8.3 ± 11.7 degrees before surgery to 14.9 ± 11.6 degrees at 1 year after surgery (P < 0.01). The range of motion between C2 and C7 was 36.9 ± 12.5 degrees and 29.1 ± 10.8 degrees before and 1 year after surgery, respectively. CONCLUSION: A new modified technique of cervical open-door laminoplasty described herein offers some solutions to the problems associated with conventional techniques of cervical laminoplasty.

Immunohistochemical Reactions for Fibroblast Growth Factor Receptor in Arteries of Patients with Moyamoya Disease

The cause of moyamoya disease remains unknown, and pathophysiological mechanisms remain uncertain. Basic fibroblast growth factor (FGF) is a pluripotent polypeptide that has been shown to play roles in angiogenesis, tumorigenesis and many other processes. In a previous study, we demonstrated immunohistochemically that the amount of basic FGF was increased above normal in the superficial temporal artery (STA) of patients with moyamoya disease. To clarify the function of basic FGF in moyamoya disease, we have performed an immunohistochemical study of the STA using a polyclonal antihuman FGF receptor antibody and also have tested immunohistochemical reactions for basic FGF. Twelve surgical specimens of the STA from patients with moyamoya disease were studied. Twelve specimens of the STA from skin flaps of patients with other neurological diseases were also investigated for comparison. The sections of the STA from patients with moyamoya disease showed dense and strong FGF receptor and basic FGF immunoreactivity in endothelial cells, in cells scattered in the thickened intima, and in smooth muscle cells in the media. In contrast, the sections of the STA of control patients showed faint basic FGF immunoreactivity. The statistical analysis revealed a significant difference of basic FGF immunoreactivity between moyamoya disease and other neurological diseases (chi 2 = 23; P = 0.0001). Moderately intense FGF receptor immunoreactivity was observed in most control patients. However, the statistical analysis revealed a significant difference of FGF receptor immunoreactivity between moyamoya disease and other neurological diseases (chi 2 = 13.382; P = 0.0012).(ABSTRACT TRUNCATED AT 250 WORDS)

Expression of heat shock proteins in the developing rat retina

Expression of three heat shock proteins (HSPs), HSP70, HSP90, and immunoglobulin heavy chain binding protein (Bip) was examined in the developing rat retina using Northern blot analysis. The expression of the inducible form of HSP70 remained uniformly low throughout the perinatal period until P5 and increased rapidly at P7. On the other hand, the constitutive form of HSP70, HSP90, and Bip were expressed constitutively in the rat retina throughout the developmental stage except P3-P5, at which a transient decrease of the expression was observed. The increase of inducible HSP70 mRNA at P7 may correspond to the functional maturation of photoreception in the visual nervous system and may be one of the stress responses to photostimulation. The potential roles of each HSP during development of the rat visual system are discussed.

Central diabetes insipidus resulting from a nonneoplastic tiny mass lesion localized in the neurohypophyseal system.

With the advent of magnetic resonance imaging (MRI), the neurohypophyseal system can be clearly delineated and its functional integrity can be predicted. The authors describe seven cases of central diabetes insipidus (DI) that occurred spontaneously. MRI revealed that the normal hyperintensity of the pituitary posterior lobe, which has been thought to be the neurosecretory material containing antidiuretic hormone, was absent in all cases. In addition, enlargement of a part of the neurohypophyseal system was recognized in five of seven cases on MRI. Three of the five patients with enlargement of a part of the neurohypophyseal tract underwent biopsy and were demonstrated to have chronic inflammation of the neurohypophyseal system. It was demonstrated that the enlarged parts of the neurohypophyseal system had shrunk either spontaneously or after the biopsy in four of the five cases. All patients are alive and have not experienced progression or remission of the disease. This study indicates that some cases of idiopathic DI result from a tiny mass lesion, usually nonneoplastic, localized in the neurohypophyseal system.

Regulated expression of neurogenic basic helix-loop-helix transcription factors during differentiation of the immortalized neuronal progenitor cell line HC2S2 into neurons

Abstract Expression of nine neurogenic basic helix-loop-helix (bHLH) transcription factors was examined in an immortalized neuronal progenitor cell line HC2S2, which differentiates into neurons after suppression of the v-myc expression with tetracycline. Expression of MASH-1, NeuroD, NeuroD-related factor (NDRF) and HES-1 was demonstrated in HC2S2 cells by Northern blot analysis using total RNA. Expression of MASH-1 mRNA was downregulated upon differentiation of HC2S2 cells into mature neurons. In contrast, NeuroD and NDRF mRNA expression was maintained all through the differentiation. The expression of HES-1, a negative regulator of the neuronal differentiation, was upregulated temporarily in accordance with the suppression of the v-myc expression and was downregulated upon the differentiation of HC2S2 cells into neurons. The reduced expression of HES-1 mRNA in undifferentiated HC2S2 cells may be explained by the transcriptional suppression of HES-1 by the myc oncoprotein. The above data imply that both HES-1 and MASH-1 need to be downregulated at the time of accomplishment of the terminal differentiation into mature neurons and that NeuroD and NDRF participate in the regulatory process of the terminal differentiation in combination.