Successful detection of multiple communicating holes in multiple spinal extradural arachnoid cysts by using time-spatial labeling inversion pulse magnetic resonance imaging: illustrative case.

BACKGROUND: Spinal extradural arachnoid cysts (SEACs) communicate with the subarachnoid space through small communicating dural holes. The precise preoperative detection of all communicating holes, followed by minimally invasive dural closure, is the ideal treatment to prevent postoperative spinal deformities, especially in cases of multiple SEACs. However, standard imaging methods often fail to detect communicating hole locations. Although a few cases of successful single-hole detection via cinematic magnetic resonance imaging (MRI) have been reported, this modality's ability to detect multiple holes has not been demonstrated. OBSERVATIONS: The authors describe the case of a 14-year-old male with myelopathy due to multiple SEACs at T5-8 and T8-12. Myelography revealed a complete block at the T8 level; no cephalic cyst or communicating holes were identified. Time-spatial labeling inversion pulse (T-SLIP) MRI revealed cerebrospinal fluid flow into the cyst at T10 and T7. A limited laminectomy or hemilaminectomy was performed at T7 and T10, and two dural holes were closed without a total cystectomy. The patient's gait disturbance and rectal disorder disappeared. The cysts were confirmed to have completely disappeared on conventional MRI at 1 year postoperatively. LESSONS: T-SLIP MRI, a cinematic MRI, is useful for detecting multiple communicating holes in SEACs.

Prognostic Factors after Surgical Treatment for Spinal Metastases.

STUDY DESIGN: A retrospective multicenter case series was conducted. PURPOSE: This study aimed to investigate survival and prognostic factors after surgery for a metastatic spinal tumor. OVERVIEW OF LITERATURE: Prognostic factors after spinal metastasis surgery remain controversial. METHODS: A retrospective multicenter study was conducted. The study participants included 345 patients who underwent surgery for spinal metastases from 2010 to 2020 at nine referral spine centers in Japan. Data for each patient were extracted from medical records. To identify the factors predicting survival prognosis after surgery, univariate analyses were performed using a Cox proportional hazards model. RESULTS: The mean age was 65.9 years. Common primary tumors were lung (n=72), prostate (n=61), and breast (n=39), and 67.8% (n=234) presented with osteolytic lesions. The epidural spinal cord compression scale score 2 or 3 was recognized in 79.0% (n=271). Frankel grade A paralysis accounted for 1.4% (n=5), and 73.3% (n=253) were categorized as intermediate or high risk according to the new Katagiri score. The overall survival rates were -71.0% at 6 months, 57.4% at 12, and 43.3% at 24. In the univariate analysis, Frankel grade A (hazard ratio [HR], 3.59; 95% confidence interval [CI], 1.23-10.50; p<0.05), intermediate risk (HR, 3.34; 95% CI, 2.10-5.32; p<0.01), and high risk (HR, 7.77; 95% CI, 4.72-12.8; p<0.01) in the new Katagiri score were significantly associated with poor survival. On the contrary, postoperative chemotherapy (HR, 0.23; 95% CI, 0.15-0.36; p<0.01), radiation therapy (HR, 0.43; 95% CI, 0.26-0.70; p<0.01), and both adjuvant therapy (HR, 0.21; 95% CI, 0.14-0.32; p<0.01) were suggested to improve survival. CONCLUSIONS: Surgical indications for patients with Frankel grade A or intermediate or high risk in the new Katagiri score should be carefully considered because of poor survival. Chemotherapy or radiation therapy should be considered after surgery for better survival.

Reoperation for Misplaced Pedicle Screws: A Multicenter Retrospective Study.

STUDY DESIGN: A multicenter retrospective analysis. OBJECTIVE: This study aims to investigate reoperation of misplaced pedicle screws (MPSs) after posterior spinal fusion (PSF), focusing on neurological complications. SUMMARY OF BACKGROUND DATA: The management strategy for MPSs and the clinical results after reoperation are poorly defined. MATERIALS AND METHODS: Subjects were 10,754 patients (73,777 pedicle screws) who underwent PSF at 11 hospitals over 15 years. The total number of reoperations for MPS and patient clinical data were obtained from medical records at each hospital. RESULTS: The rate of reoperation for screw misplacement per screw was 0.17%. A total of 69 patients (mean age, 67.4±16.5 yr) underwent reoperation because of 82 MPS. Reasons for reoperation were neurological symptoms (58 patients), contact with vessels (5), suboptimal bone purchase (4), and misplacement recognized during operation (2). Neurological symptoms were the major reason for reoperation in cervical (5/5 screws, 100%) and lumbo-sacral (60/67 screws, 89.6%) regions. Contact with vessels was the major reason for reoperation in the thoracic spine (6/10 screws, 60.0%). We further evaluated 60 MPSs in the lumbo-sacrum necessitating reoperation because of neurological symptoms. The majority of MPSs necessitating reoperation were placed in the lower lumbar spine (43/60 screws, 71.7%). The mean pedicle breach tended to be larger in the incomplete recovery group than in the complete recovery group (6.8±2.4 vs . 5.9±2.2 mm, P =0.146), and the cutoff value resulting in incomplete resolution was 5.0 mm. Multivariate analysis revealed that medial-caudal breaches ( vs . medial breach, odds ratio: 25.8, 95% confidence interval: 2.58-258, P =0.0057) and sensory and motor disturbances ( vs . sensory only, odds ratio: 8.57, 95% confidence interval: 1.30-56.6, P =0.026) were significant factors for incomplete resolution of neurological symptoms. CONCLUSIONS: After reoperation, 70.1% of the patients achieved complete resolution of neurological symptoms. Factors associated with residual neurological symptoms included sensory and motor disturbance, medial-caudal breach, and larger pedicle breach (>5 mm).

Clinical Features and Surgical Outcomes of Lower Lumbar Osteoporotic Vertebral Collapse with Symptomatic Stenosis: A Surgical Strategy from a Multicenter Case Series.

STUDY DESIGN: A retrospective multicenter case series was conducted. PURPOSE: This study was designed to investigate the clinical features and surgical outcomes of lower lumbar osteoporotic vertebral collapse (LL-OVC) with symptomatic stenosis based on various surgical procedures and classify them using the newly developed collapse severity criteria. OVERVIEW OF LITERATURE: The surgical outcomes of LL-OVC with symptomatic stenosis remain unclear. METHODS: We investigated patients who underwent surgical intervention for LL-OVC (L3, L4, and/or L5) with symptomatic foraminal and/or central stenosis from eight spine centers. Only patients with a minimum follow-up duration of 1 year were included. We developed new criteria to grade vertebral collapse severity (grade 1, 0%-25%; grade 2, 25%-50%; grade 3, 50%-75%; and grade 4, 75%-100%). The clinical features and outcomes were compared based on the collapse grade and surgical procedures performed (i.e., decompression alone, posterior lateral fusion [PLF], lateral interbody fusion [LIF], posterior/transforaminal interbody fusion [PLIF/TLIF], or vertebral column resection [VCR]). RESULTS: In this study, 59 patients (average age, 77.4 years) were included. The average follow-up period was 24.6 months. The clinical outcome score (Japanese Orthopaedic Association score) was more favorable in the LIF and PLIF/TLIF groups than in the decompression alone, PLF, and VCR groups. The use of VCR was associated with a high rate of revision surgery (57.1%). No significant difference in clinical outcomes was observed between the collapse grades; however, grade 4 collapse was associated with a high rate of revision surgery (40.0%). CONCLUSIONS: When treating LL-OVC, appropriate instrumented reconstruction with rigid intervertebral stability is necessary. According to our newly developed criteria, LIF may be a surgical option for any collapse grade. The use of VCR for grade 4 collapse is associated with a high rate of revision.

COVID-19 Masked by Pyogenic Lumbar Discitis and Bacteremia: A Case Report.

CASE: A 65-year-old man experienced backache, and 9 days later, he developed cellulitis in his left foot. On the 20th day, his body temperature was 37°C, and he had intermittent and shallow cough. On the 29th day, he was diagnosed with pyogenic lumbar discitis and bacteremia. Computed tomography examinations showed no evidence of pneumonia, but his cough persisted, and an elevated d-dimer level was observed. Finally, he tested positive for coronavirus disease 2019 (COVID-19). CONCLUSIONS: This case shows possible associations among COVID-19, venous thrombosis, cellulitis, and bacteremia. Other infections may coexist with COVID-19 and mask it.

Time-Spatial Labeling Inversion Pulse Magnetic Resonance Imaging of Cystic Lesions of the Spinal Cord.

BACKGROUND: Cystic lesions of the spinal cord such as spinal intradural arachnoid cysts (SIACs) and spinal extradural arachnoid cysts (SEACs) contain cerebrospinal fluid (CSF). The pathology of these lesions is often difficult to understand because it is difficult to detect abnormal CSF flow by conventional magnetic resonance imaging (MRI) or myelography. We preliminarily evaluated the usefulness of time-spatial labeling inversion pulse magnetic resonance imaging (T-SLIP MRI) of cystic lesions of the spinal cord. METHODS: T-SLIP MRI was applied to the following 6 consecutive cystic lesions of the spinal cord: 3 SEACs, 1 SIAC, 1 spinal intramedullary cyst associated with adhesive arachnoiditis, and 1 chronic pseudomeningocele. Information obtained by T-SLIP MRI was evaluated with regard to the following: 1) whether exclusive pathologic information was obtained, 2) whether this information affected the therapeutic strategy, and 3) the time required for T-SLIP MRI. RESULTS: Exclusive information was obtained in all 6 cases. In SEACs and the intramedullary cyst, pathologic CSF flow into the cyst was directly visualized, enabling us to narrow the therapeutic intervention targets. In SIAC, exclusive information involved detection of the cystic cranial wall and the absence of the caudal wall, enabling us to omit the exploration of the caudal wall. The examination required as long as 80 minutes for SIAC and <30 minutes for the other cases. CONCLUSIONS: T-SLIP MRI is useful for obtaining pathologic information about cystic lesions of the spinal cord.

Detection of the communicating hole(s) of spinal extradural arachnoid cysts using time-spatial labeling inversion pulse magnetic resonance imaging.

STUDY DESIGN: Report of 2 cases. OBJECTIVE: To report the usefulness of time-spatial labeling inversion pulse magnetic resonance imaging (T-SLIP MRI) for detection of the communicating hole(s) of spinal extradural arachnoid cysts (SEACs). SUMMARY OF BACKGROUND DATA: SEACs normally communicate with the subarachnoid space via small communicating hole(s) in the dura. It is necessary to identify the accurate locations of these communicating hole(s) before attempting to close them through limited laminotomy/laminectomy. Myelocomputed tomography or conventional MRI may fail to detect the locations of the hole(s) because they comprise small dural defects. METHODS: Case 1: A 33-year-old female presented with an SEAC at the T11­L2 vertebral level. Case 2: An 82-year-old female presented with an SEAC at T12­L4 vertebral level. RESULTS: Case 1: T-SLIP MR image of the left parasagittal plane (not the midsagittal or right parasagittal plane) revealed cerebrospinal fluid flow from the subarachnoid space into the cyst at L1. After limited laminotomy at T12­L1 and partial cyst resection, we identified 2 contiguous dural holes immediately medial to the left L1 pedicle; this corroborated the preoperative T-SLIP MRI findings. The holes were sutured. Postoperative conventional MR image confirmed significant cyst shrinkage. Case 2: T-SLIP MR image revealed a curved line at the L1 pedicle in the right parasagittal plane. After L1 laminectomy and partial cyst resection, a dural hole was identified L1 pedicle, which was in agreement with the preoperative T-SLIP MRI findings. After surgery, the lower extremity pain disappeared. Postoperative conventional MR image revealed significant cyst shrinkage. CONCLUSION: T-SLIP MRI is useful for detection of the communicating hole(s) of SEACs. LEVEL OF EVIDENCE: N/A.

Involvement of cancer biomarker C7orf24 in the growth of human osteosarcoma.

BACKGROUND: Up-regulation of the expression of the gene C7orf24, encoding γ-glutamyl cyclotransferase, is a common event in cancers derived from various tissues, but its involvement in osteosarcomas (OS) has not yet been demonstrated. MATERIALS AND METHODS: The expression of C7orf24 was analyzed in human OS cell lines and primary tumor samples. The biological effects of C7orf24 on growth, motility, and invasion in the OS cell lines were investigated using siRNA for C7orf24. Genes related to the function of C7orf24 were sought by genome-wide gene expression profiling. RESULTS: The level of C7orf24 expression was much higher in the OS cell lines and OS primary tumors than in normal osteoblasts. Down-regulation of C7orf24 expression inhibited the growth of the cell lines in association with enhancement of cell-clustering. Treatment with C7orf24-siRNA inhibited cell motility and invasion. Gene ontology suggested the function of C7orf24 to be related to cell adhesion and protein transport. CONCLUSION: C7orf24 is also involved in the growth of OS, and is a potential biomarker for this type of tumor.

Neuronal differentiation of synovial sarcoma and its therapeutic application.

Synovial sarcoma is a rare sarcoma of unknown histologic origin. We previously reported the gene expression profile of synovial sarcoma was closely related to that of malignant peripheral nerve sheath tumors, and the fibroblast growth factor (FGF) signal was one of the main growth signals in synovial sarcoma. Here we further demonstrate the neural origin of synovial sarcoma using primary tumors and cell lines. The expression of neural tissue-related genes was confirmed in synovial sarcoma tumor tissues, but the expression of some genes was absent in synovial sarcoma cell lines. Treatment of synovial sarcoma cell lines with BMP4 or FGF2 enhanced or restored the expression of neural tissue-related genes and induced a neuron-like morphology with positive Tuj-1 expression. Treatment with all-trans-retinoic acid also induced the expression of neural tissue-related genes in association with growth inhibition, which was not observed in other cell lines except a malignant peripheral nerve sheath tumor cell line. A growth-inhibitory effect of all-trans-retinoic acid was also observed for xenografted tumors in athymic mice. The simultaneous treatment with FGF signal inhibitors enhanced the growth-inhibitory effect of all-trans-retinoic acid, suggesting the combination of growth signaling inhibition and differentiation induction could be a potential molecular target for treating synovial sarcoma.

In vitro transformation of mesenchymal stem cells by oncogenic H-rasVal12.

Tissue stem cells may serve as progenitors for malignant tumors derived from the same tissue. Here, we report the establishment of immortalized human mesenchymal stem cells (ihMSC) and tested the feasibility of using ihMSC as presarcomatous cells. Immortalization was achieved by introducing the genes for human telomerase reverse transcriptase and Bmi1. ihMSC retained the potential for multi-directional differentiation of the original MSC. To transform ihMSC, we introduced an oncogenic H-ras(Val12) gene, and established the cell line ihMSC-ras. ihMSC-ras had the phenotype of fully transformed cells and retained adipogenic and chondrogenic, but not osteogenic, potential. Interestingly, ihMSC-ras demonstrated morphological features of autophagy, and inhibition of the ERK pathway suppressed the production of autophagosomes, indicating that ras/ERK signaling is responsible for the induction of autophagy. Thus ihMSC will serve as a material with which to analyze the tumorigenic and differentiation-modifying effects of candidate oncogenes involved in the development of sarcomas.

Expression of claudin7 is tightly associated with epithelial structures in synovial sarcomas and regulated by an Ets family transcription factor, ELF3.

Synovial sarcoma, a soft tissue sarcoma that develops in adults, is pathologically subclassified into monophasic spindle synovial sarcoma and biphasic synovial sarcoma with epithelial components. The molecular mechanism building the epithelial components in biphasic synovial sarcoma is totally unknown. Here we investigated claudins, critical molecules in the tight junction, in biphasic synovial sarcoma. Expression profiles of 21 claudins in 17 synovial sarcoma tumor samples, including 9 biphasic tumors, identified claudin4, claudin7, and claudin10 as biphasic tumor-related claudins, and immunohistochemical analyses demonstrated the localization of these claudins in the epithelial component in biphasic tumors, with claudin7 the most closely associated with the epithelial component. The mRNA expression and protein localization of claudin7 coincided with those of the ELF3, an epithelia-specific member of the Ets family of transcription factors. Luciferase reporter assays demonstrated that the presence of the Ets-binding site at -150 in the promoter region of the claudin7 gene was critical for the transcriptional activity, and gel shift and chromatin immunoprecipitation assays confirmed the binding of ELF3 to the Ets site at -150. Inhibition of ELF3 expression by small interfering RNA simultaneously down-regulated the mRNA expression of the claudin7 gene, and the introduction of ELF3 expression in claudin7-negative cell lines induced mRNA expression of the claudin7 gene. Therefore, the induction of claudin7 expression by ELF3 appears critical to the formation of the epithelial structures in biphasic synovial sarcoma.

Regeneration of osteonecrosis of canine scapho-lunate using bone marrow stromal cells: possible therapeutic approach for Kienböck disease.

We evaluated the ability of canine bone marrow stromal cells (cBMSCs) to regenerate bone in a cavity of the scapholunate created by curretage and freeze-thawing with liquid nitrogen (LN). Autologous BMSCs were harvested from the iliac crest and expanded in vitro. Their potential to differentiate into osteo-, chondro-, and adipogenic lineages was confirmed using a standard differentiation induction assay. LN-treated scapholunates showed no regeneration of bone tissue when the cavity was left alone, demonstrating severe collapse and deformity as observed in human Kienböck disease. A combination of beta-tri-calcium phosphate and a vascularized bone graft with autologous fibroblasts failed to regenerate bone in the LN-treated cavity. When the same procedure was performed using BMSCs, however, LN-treated scapholunates showed no collapse and deformity, and the cavity was completely filled with normal cancerous bone within 4 weeks. These results suggested the potential of using BMSCs to treat Kienböck disease.

A variant of the SYT-SSX2 fusion gene in a case of synovial sarcoma.

Synovial sarcoma is a malignant soft tissue tumor harboring a tumor-specific fusion gene, SYT-SSX, of which exon 10 of the SYT gene is fused to exon 6 of the SSX gene is the common form. Here we report a case of synovial sarcoma with a novel form of the SYT-SSX2 fusion transcript, in which 75 bases were inserted at the common fusion junction. Computer analyses revealed that 15 bases were from intron 10 of the SYT gene, and 10 from the end of intron 4, and 50 from exon 5 of the SSX2 gene. Precise analyses of genomic breakpoints in SYT and SSX2 loci revealed that the reciprocal translocation creating the fusion gene was associated with a large deletion in both loci. The structure of SYT-SSX2 suggests that the fusion transcript in this case was created using a cryptic splicing acceptor site 15 bases upstream of the genomic fusion point, incorporating intronic sequences in mature mRNA. Reexamination of two variant SYT-SSX2 genes reported previously revealed that unknown sequences inserted at the common junction points were derived from intron sequences, as in the present case.

Disruption of fibroblast growth factor signal pathway inhibits the growth of synovial sarcomas: potential application of signal inhibitors to molecular target therapy.

PURPOSE: Synovial sarcoma is a soft tissue sarcoma, the growth regulatory mechanisms of which are unknown. We investigated the involvement of fibroblast growth factor (FGF) signals in synovial sarcoma and evaluated the therapeutic effect of inhibiting the FGF signal. EXPERIMENTAL DESIGN: The expression of 22 FGF and 4 FGF receptor (FGFR) genes in 18 primary tumors and five cell lines of synovial sarcoma were analyzed by reverse transcription-PCR. Effects of recombinant FGF2, FGF8, and FGF18 for the activation of mitogen-activated protein kinase (MAPK) and the growth of synovial sarcoma cell lines were analyzed. Growth inhibitory effects of FGFR inhibitors on synovial sarcoma cell lines were investigated in vitro and in vivo. RESULTS: Synovial sarcoma cell lines expressed multiple FGF genes especially those expressed in neural tissues, among which FGF8 showed growth stimulatory effects in all synovial sarcoma cell lines. FGF signals in synovial sarcoma induced the phosphorylation of extracellular signal-regulated kinase (ERK1/2) and p38MAPK but not c-Jun NH2-terminal kinase. Disruption of the FGF signaling pathway in synovial sarcoma by specific inhibitors of FGFR caused cell cycle arrest leading to significant growth inhibition both in vitro and in vivo. Growth inhibition by the FGFR inhibitor was associated with a down-regulation of phosphorylated ERK1/2 but not p38MAPK, and an ERK kinase inhibitor also showed growth inhibitory effects for synovial sarcoma, indicating that the growth stimulatory effect of FGF was transmitted through the ERK1/2. CONCLUSIONS: FGF signals have an important role in the growth of synovial sarcoma, and inhibitory molecules will be of potential use for molecular target therapy in synovial sarcoma.

PGE2 signal through EP2 promotes the growth of articular chondrocytes.

UNLABELLED: EP2 was identified as the major PGE2 receptor expressed in articular cartilage. An EP2 agonist increased intracellular cAMP in articular chondrocytes, stimulating DNA synthesis in both monolayer and 3D cultures. Hence, the EP2 agonist may be a potent therapeutic agent for degenerative cartilage diseases. INTRODUCTION: Prostaglandin E2 (PGE2) exhibits pleiotropic effects in various types of tissue through four types of receptors, EP1-4. We examined the expression of EPs and effects of agonists for each EP on articular chondrocytes. MATERIALS AND METHODS: The expression of each EP in articular chondrocytes was examined by immunohistochemistry and RT-PCR. A chondrocyte cell line, MMA2, was established from articular cartilage of p53(-/-) mice and used to analyze the effects of agonists for each EP. A search for molecules downstream of the PGE2 signal through the EP2 agonist was made by cDNA microarray analysis. The growth-promoting effect of the EP2 agonist on chondrocytes surrounded by cartilage matrix was examined in an organ culture of rat femora. RESULTS AND CONCLUSION: EP2 was identified as the major EP expressed in articular cartilage. Treatment of MMA2 cells with specific agonists for each EP showed that only the EP2 agonist significantly increased intracellular cAMP levels in a dose-dependent manner. Gene expression profiling of MMA2 revealed a set of genes upregulated by the EP2 agonist, including several growth-promoting and apoptosis-protecting genes such as the cyclin D1, fibronectin, integrin alpha5, AP2alpha, and 14-3-3gamma genes. The upregulation of these genes by the EP2 agonist was confirmed in human articular chondrocytes by quantitative mRNA analysis. On treatment with the EP2 agonist, human articular chondrocytes showed an increase in the incorporation of 5-bromo-2-deoxyuracil (BrdU), and the organ culture of rat femora showed an increase of proliferating cell nuclear antigen (PCNA) staining in articular chondrocytes surrounded by cartilage matrix, suggesting growth-promoting effects of the PGE2 signal through EP2 in articular cartilage. These results suggested that the PGE2 signal through EP2 enhances the growth of articular chondrocytes, and the EP2 agonist is a candidate for a new therapeutic compound for the treatment of degenerative cartilage diseases.

Mutation analysis of the RECQL4 gene in sporadic osteosarcomas.

Osteosarcoma (OS) is the most prevalent malignant tumor among cases of Rothmund-Thomson syndrome (RTS) with germline mutations of the RECQL4 gene, a member of the RecQ helicase family. We investigated the involvement of the RECQL4 gene in the development of OS unrelated to RTS. RECQL4 mRNA was detected in 9 of 9 OS cell lines by Northern blotting and 26 of 26 OS tumors by RT-PCR. Direct sequencing of the entire coding region along with flanking splice junctions and 13 small (< 100 bp) introns in 71 OS tumors revealed 2 sites with a single-base change causing an amino acid change (G1814A for R355Q and C2474T for P441S) and one site with a 6 bp inframe deletion (4837-42delTGCACC for CT857-8del). Identical genotypes were found in corresponding normal tissues in all cases, and the frequency of each allele was not significantly different between OS and control populations. Our data indicate that the RECQL4 gene is not a frequent target for somatic mutations in sporadic OS unrelated to RTS.

Methylation in the core-promoter region of the chondromodulin-I gene determines the cell-specific expression by regulating the binding of transcriptional activator Sp3.

Transcriptional regulation of cell- and stage-specific genes is a crucial process in the development of mesenchymal tissues. Here we have investigated the regulatory mechanism of the expression of the chondromodulin-I (ChM-I) gene, one of the chondrocyte-specific genes, in osteogenic cells using osteosarcoma (OS) cells as a model. Methylation-specific sequence analyses revealed that the extent of methylation in the core-promoter region of the ChM-I gene was correlated inversely with the expression of the ChM-I gene in OS primary tumors and cell lines. 5-Aza-deoxycytidine treatment induced the expression of the ChM-I gene in ChM-I-negative OS cell lines, and the induction of expression was associated tightly with the demethylation of cytosine at -52 (C(-52)) in the middle of an Sp1/3 binding site to which the Sp3, but not Sp1, bound. The replacement of C(-52) with methyl-cytosine or thymine abrogated Sp3 binding and also the transcription activity of the genomic fragment including C(-52). The inhibition of Sp3 expression by small interfering RNA reduced the expression of the ChM-I gene in ChM-I-positive normal chondrocytes, indicating Sp3 as a physiological transcriptional activator of the ChM-I gene. These results suggest that the methylation status of the core-promoter region is one of the mechanisms to determine the cell-specific expression of the ChM-I gene through the regulation of the binding of Sp3.

Expression of the chondromodulin-I gene in chondrosarcomas.

We investigated the expression of the Chondromodulin-I (ChM-I) gene, a putative tumor suppressor gene in cartilaginous tumors, by quantitative RT-PCR in 15 chondrosarcomas (CSs). Eight CSs expressed the ChM-I gene at the level higher than those in articular cartilage (positive cases), whereas the expression of the ChM-I gene in the remaining seven CSs was lower than those in articular cartilage (negative cases). All of five peripheral CS were positive, and the ChM-I positive tumors shared expression profiles of cartilage-related genes with articular cartilage cells. On the other hand, all of four central CSs without extramedullary lesions were negative, and the ChM-I negative tumors expressed the parathyroid hormone-related peptide gene at the lower level and the COL10A1 genes at the higher level than articular cartilage cells. Neither the histological grade nor the rate of recurrence showed clear association with the level of ChM-I gene expression. These results suggested that the expression of ChM-I gene in CS has no direct role in tumorigenesis but rather reflects the site of tumor development and therefore precursor of tumor cells.

Respiratory dysfunction in patients with chronic-onset cervical myelopathy.

STUDY DESIGN: A retrospective study. OBJECTIVE To clarify the characteristics of respiratory dysfunction associated with chronic-onset cervical myelopathy. SUMMARY OF BACKGROUND DATA: In acute cervical cord injury, respiratory dysfunction, especially vital capacity (VC), is impaired, which causes respiratory complications. No comprehensive study has been published about respiratory dysfunction in patients with chronic-onset myelopathy. METHODS: Eighty-four consecutive patients without history of respiratory disease who underwent surgery for cervical myelopathy were studied. The control group consisted of 84 age-matched patients with lumbar degenerative diseases. Parameters of spirometry, arterial blood gas, height of the diaphragm, and the score for neurologic impairment were analyzed before and after surgery. RESULTS: Percent VC (%VC) was significantly lower in the study group than in the control group. In patients with cranial cord lesions and multilevel cord lesions, %VC was lower than in those with a caudal lesion and a single-level lesion, respectively. Percent VC correlated with the preoperative neurologic score in the study group. In patients having the lesion at or above C4, %VC improved after surgery, whereas in those with a lower lesion, %VC had not decreased before surgery, and no further improvement was obtained. CONCLUSIONS: In patients with chronic-onset cervical myelopathy, %VC significantly decreases when they have more cranial or multilevel lesions. Percent VC also correlates with the preoperative neurologic score and improves with surgical treatment in patients with more cranial cord lesions. Respiratory dysfunction should be taken into consideration as a part of neurologic impairment in chronic-onset cervical myelopathy.