Association between BMP-2 and COL6A1 gene polymorphisms with susceptibility to ossification of the posterior longitudinal ligament of the cervical spine in Korean patients and family members.

COL6A1 and BMP-2 genes have been implicated in ossification of the posterior longitudinal ligament (OPLL) susceptibility in Japanese and Chinese Han populations. However, no study has yet investigated the DNA of unaffected family members of patients with OPLL. This study investigated differences in genetic polymorphisms of BMP-2 and COL6A1 between Korean patients with OPLL and their family members (with and without OPLL). A total of 321 subjects (110 patients with OPLL and 211 family members) were enrolled in the study. Associations between two single nucleotide polymorphisms (SNPs) of the BMP-2 gene (Ser37Ala and Ser87Ser) and two SNPs of COL6A1 [promoter (-572) and intron 33 (+20)] with susceptibility to OPLL of the cervical spine were investigated between the two groups (OPLL+ and OPLL-). Of the 321 subjects, 162 had cervical OPLL (50.4%; 110 patients, 52 family members). There was a familial tendency of OPLL in 34 of the 110 families (30.9%). Allele and haplotype frequencies of the four SNPs in the BMP-2 and COL6A1 genes did not differ significantly between the OPLL+ and OPLL- groups, even when excluding participants over 50 years of age. This is the first report identifying SNPs of COL6A1 and BMP-2 in Korean patients and family members with OPLL. Although allele and haplotype frequencies were similar with those of a previous study in Japanese and Chinese patients, unaffected family members also showed similar rates of these SNPs in the present study. These results suggest that these SNPs may not directly influence the expression of OPLL.

What is the importance of "halo" phenomenon around bone cement following vertebral augmentation for osteoporotic compression fracture?

UNLABELLED: We investigated the importance, risk factors, and clinical course of the radiolucent "halo" phenomenon around bone cement following vertebral augmentation for osteoporotic compression fracture. Preoperative osteonecrosis and a lump cement pattern were the most important risk factors for the peri-cement halo phenomenon, and it was associated with vertebral recollapse. INTRODUCTION: We observed a newly developed radiolucent area around the bone cement following vertebral augmentation for osteoporotic compression fractures. Here, we describe the importance of the peri-cement halo phenomenon, as well as any associated risk factors and long-term sequelae. METHODS: In total, 175 patients (202 treated vertebrae) were enrolled in this study. The treated vertebrae were subdivided into two groups: Group A (with halo, n = 32) and Group B (without halo, n = 170), and the groups were compared with respect to multiple preoperative (age, sex, BMD, preoperative osteonecrosis) and perioperative factors (operative approach: vertebroplasty or kyphoplasty; cement distribution pattern; cement leakage; cement volume), and postoperative results (VAS score, recollapse). Logistic regression analysis was used to evaluate the relationship between the incidence of the peri-cement halo and all of the parameters described above. RESULTS: Rates of osteonecrosis were also significantly higher in Group A than in Group B (62.5% vs. 31.2%, p < 0.05), and kyphoplasty (KP) was performed more frequently in Group A (43.8% vs. 17.6%, p < 0.05). Lump cement (93.8% vs. 30.6%, p < 0.05) and recollapse (78.1% vs. 24.7%, p < 0.05) were also more common among individuals in Group A. Logistic regression analysis also showed that preoperative osteonecrosis (OR = 3.679; 95% CI = 1.677-8.073; p = 0.001), KP (OR = 3.630; 95% CI = 1.628-8.095; p = 0.002), lump pattern (OR = 13.870; 95% CI = 2.907-66.188; p = 0.001), and vertebral recollapse (OR = 5.356; 95% CI = 1.897-15.122; p = 0.002) were significantly associated with peri-cement halo. CONCLUSIONS: The peri-cement halo was found to be associated with vertebral recollapse, this sign likely represents a poor prognostic factor after vertebral augmentation for osteoporotic compression fractures.

Suppression of putative tumour suppressor gene GLTSCR2 expression in human glioblastomas.

Glioma tumour-suppressor candidate region gene 2 (GLTSCR2/PICT-1) is localized within the well-known 1.4 Mb tumour-suppressive region of chromosome 19q, which is frequently altered in various human tumours, including diffuse gliomas. Aside from its chromosomal localization, several lines of evidence, including PTEN-phosphorylating and cell-killing activities, suggests that GLTSCR2 participates in the suppression of tumour growth and development. However, little is known about the biological functions and molecular mechanisms of GLTSCR2 as a tumour suppressor gene. We investigated the pathological significance of GLTSCR2 expression in association with the development and progression of glioblastomas, the most common malignant brain tumour. We used real-time PCR and western blot analysis to examine the expression levels of GLTSCR2 mRNA and protein in glioblastomas, normal brain tissue and in non-glial tumour tissue of different origin, and found that GLTSCR2 expression is down-regulated in glioblastomas. In addition, direct sequencing analysis and fluorescence in situ hybridization clearly demonstrates the presence of genetic alterations, such as a nonsense mutation and deletion, in the GLTSCR2 gene in glioblastomas. Finally, our immunohistochemical study demonstrates that GLTSCR2 is sequentially down-regulated according to the histological malignant progression of the astrocytic glial tumour. Taken together, our results suggest that GLTSCR2 is involved in astrocytic glioma progression.

The putative tumor suppressor gene GLTSCR2 induces PTEN-modulated cell death.

Glioma tumor suppressor candidate region gene 2 (GLTSCR2/PICT-1) is localized within the well-known 1.4-Mb tumor suppressive region of chromosome 19q, which is frequently altered in various human tumors, including diffuse gliomas. Aside from its localization on the chromosome, several lines of evidence, such as PTEN phosphorylation, support that GLTSCR2 partakes in the suppression of tumor growth and development. However, much remains unknown about the molecular mechanisms of the tumor suppressive activity of GLTSCR2. The purpose of this study was to investigate the molecular mechanisms of GLTSCR2 in cell death pathways in association with its binding partner PTEN. In this work, we show that GLTSCR2 is a nucleus-localized protein with a discrete globular expression pattern. In addition to phosphorylating PTEN, GLTSCR2 induces caspase-independent PTEN-modulated apoptotic cell death when overexpressed. However, the cytotoxic activity of GLTSCR2 is independent of its ability to phosphorylate PTEN, suggesting that the GLTSCR2-induced cell death pathway is divergent from PTEN-induced death pathways. Our results suggest that the induction of PTEN-modulated apoptosis is one of the putative mechanisms of tumor suppressive activity by GLTSCR2.

Prevalence of osteoporosis in patients requiring spine surgery: incidence and significance of osteoporosis in spine disease.

UNLABELLED: The purpose of this study is to evaluate the incidence of osteoporosis in patients requiring spine surgery. Among patients older than 50 years, the rate of osteoporosis in males was 14.5% and the rate osteoporosis in females was 51.3%. We strongly recommend an evaluation and treatment for osteoporosis in the patients requiring spine surgery, especially in females over 50 years old. INTRODUCTION: Because lifespan is increasing, there is an increase in the incidence of osteoporosis in elderly spine surgery patients. The osteoporosis may adversely influence the fusion rate and the surgical outcome. The purpose of this study is to evaluate the incidence of osteoporosis in patients requiring spine surgery. METHODS: A total of 1,321 patients underwent spine surgeries at our institute from January 1, 2005 to December 31, 2005. Among them, there were 562 patients (42.5%) younger than 50 years old, and 759 patients (57.6%) older than 50 years old. Prior to operation, we evaluated the patients for osteoporosis on both the femur head and lumbar spine by measuring the bone mineral density (BMD) by the dual-energy X-ray absorptiometry (DXA). Based on the World Health Organization (WHO) criteria for osteoporosis, we chose the T-score to determine normal (>-1), osteopenia (-1>or=, >-2.5), and osteoporosis (

Functional recovery after human umbilical cord blood cells transplantation with brain-derived neutrophic factor into the spinal cord injured rat.

There have been many efforts to recover neuronal function from spinal cord injuries, but there are some limitations in the treatment of spinal cord injuries. The neural stem cell has been noted for its pluripotency to differentiate into various neural cell types. The human umbilical cord blood cells (HUCBs) are more pluripotent and genetically flexible than bone marrow neural stem cells. The HUCBs could be more frequently used for spinal cord injury treatment in the future. Moderate degree spinal cord injured rats were classified into 3 subgroups, group A: media was injected into the cord injury site, group B: HUCBs were transplanted into the cord injury site, and group C: HUCBs with BDNF (Brain-derived neutrophic factor) were transplanted into the cord injury site. We checked the BBB scores to evaluate the functional recovery in each group at 8 weeks after transplantation. We then, finally checked the neural cell differentiation with double immunofluorescence staining, and we also analyzed the axonal regeneration with retrograde labelling of brain stem neurons by using fluorogold. The HUCBs transplanted group improved, more than the control group at every week after transplantation, and also, the BDNF enabled an improvement of the BBB locomotion scores since the 1 week after its application (P<0.05). 8 weeks after transplantation, the HUCBs with BDNF transplanted group had more greatly improved BBB scores, than the other groups (P<0.001). The transplanted HUCBs were differentiated into various neural cells, which were confirmed by double immunofluorescence staining of BrdU and GFAP & MAP-2 staining. The HUCBs and BDNF each have individual positive effects on axonal regeneration. The HUCBs can differentiate into neural cells and induce motor function improvement in the cord injured rat models. Especially, the BDNF has effectiveness for neurological function improvement due to axonal regeneration in the early cord injury stage. Thus the HUCBs and BDNF have recovery effects of a moderate degree for cord injured rats.

Reinduced expression of developmental proteins (nestin, small heat shock protein) in and around cerebral arteriovenous malformations.

Intermediate filament (IF) nestin and small heat shock protein (sHSP) are developmentally regulated proteins. Nestin is highly expressed on proliferating neuroepithelial stem cells of the developing central nervous system (CNS). During the developmental neurulation stage, nestin is replaced by mature neuronal (neurofilament) or glial cell-specific IFs (glial fibrillary acidic protein, GFAP). Several pathologic states induce astrocytes to synthesize nestin transiently in the mature brain. However, the exact nature of the embryonic conversion from nestin to mature cytoskelton is unclear. In an attempt to define the effect of ischemic hemodynamic stress caused by cerebral arteriovenous malformation (AVM) on the brain parenchyma, we examined the synthesis and cellular distribution of sHSP and nestin in vascular elements of AVMs and in the gliotic area surrounding AVMs. Ten consecutively collected surgical specimens meeting the histological criteria for AVM were immunohistochemically stained using primary antibodies for nestin, HSP27 and alphaB-crystallin. Nestin, HSP27 and alphaB-crystallin mRNA expressions were examined by reverse transcriptase-polymerase chain reaction (RT-PCR). Nestin expression is reinduced not only in reactive astrocytes, but also in endothelial cells in the surrounding gliotic tissue of the cerebral AVM. These cells also expressed sHSP (HSP27, alphaB-crystallin) that maintain the integrity of the IF network and prevent unfolding of cellular proteins induced by various stresses. RT-PCR showed the increased expression of sHSP and nestin mRNA in the AVM specimens. These results indicate that embryonic reversion of the mature cytoskeleton to nestin and the increased expression of sHSP in response to cerebral injury are associated with increased wall tension caused by dilating AVM vessels and with the hemodynamic stress that surrounds AVMs.

Intermediate filament nestin expressions in human cord blood monocytes (HCMNCs).

OBJECTS: Nestin is an intermediate protein and a well-known specific neural stem cell antigen. Some bone marrow stem cells can generate not only blood cells but also neurons and glial cells under specific culture conditions. Furthermore, in vitro cultured bone marrow stem cells also express nestin antigen. However, it is unclear whether cord blood cells also differentiate into neural cells or not. In this study, we investigated the expression of nestin on human cord blood monocytes (HCMNCs) and we discuss the relevance of this finding upon future therapeutic applications of HCMNCs in neurological diseases. METHODS: HCMNCs were prepared from normal placenta after full-term normal delivery. Immunocytochemical staining and reverse transcriptase polymerase chain reaction (RT-PCR) for nestin and CD133 antigen were performed to confirm nestin and CD133 antigen expression in the HCMNCs. RESULTS: Some nestin expressing HCMNCs were found. Immunocytochemical staining showed that some of the blood stem cell marker CD133 expressing cells co-expressed nestin. RT-PCR demonstrated nestin and CD133 mRNA in HCMNCs, but not in adult blood monocytes. Approximately, 60 +/- 8% of CD133 expressing cells expressed nestin. CONCLUSION: In the present study, we found that more than 60% of CD133 expressing HCMNCs also express nestin antigen in their cytoplasm, which supports the idea that cord blood stem cells can adopt a neuronal fate.

Neural phenotype expression of cultured human cord blood cells in vitro.

Neural stem cells have been proposed as useful vectors for treating diseases in the CNS, but their utility is severely limited by lack of accessibility. Brain development is ongoing extensively in early postnatal life. However, it is unclear whether stem cells that differentiate into neurons exist in the blood during early postnatal life. We showed in this experiment that neural markers (NeuN, neurofilament, MAP2, GFAP) are expressed and long cytoplasmic processes are elaborated in the cultured human cord blood monocytes prepared from newborn umbilical blood. These results suggest that stem cells in human cord blood may be potential sources of neurons in early postnatal life. We suggest that the neonatal blood system functions as a circulating pool of different types of stem cell.

Thermatomal changes in cervical disc herniations.

Subjective symptoms of a cool or warm sensation in the arm could be shown objectively by using of thermography with the detection of thermal change in the case of radiculopathy, including cervical disc herniation (CDH). However, the precise location of each thermal change at CDH has not been established in humans. This study used digital infrared thermographic imaging (DITI) for 50 controls and 115 CDH patients, analyzed the data statistically with t-test, and defined the areas of thermatomal change in CDH C3/4, C4/5, C5/6, C6/7 and C7/T1. The temperature of the upper trunk and upper extremities of the control group ranged from 29.8 degrees C to 32.8 degrees C. The minimal abnormal thermal difference in the right and left upper extremities ranged from 0.1 degree C to 0.3 degree C in 99% confidence interval. If delta T was more than 0.1 degree C, the anterior middle shoulder sector was considered abnormal (p < 0.01). If delta T was more than 0.3 degree C, the medial upper aspect of the forearm and dorsal aspect of the arm, some areas of the palm and anterior part of the fourth finger, and their opposite side sectors and all dorsal aspects of fingers were considered abnormal (p < 0.01). Other areas except those mentioned above were considered abnormal if delta T was more than 0.2 degree C (p < 0.01). In p < 0.05, thermal change in CDH C3/4 included the posterior upper back and shoulder and the anterior shoulder. Thermal change in CDH C4/5 included the middle and lateral aspect of the triceps muscle, proximal radial region, the posterior medial aspect of the forearm and distal lateral forearm. Thermal change in CDH C5/6 included the anterior aspects of the thenar, thumb and second finger and the anterior aspects of the radial region and posterior aspects of the pararadial region. Thermal change in CDH C6/7 included the posterior aspect of the ulnar and palmar region and the anterior aspects of the ulnar region and some fingers. Thermal change in CDH C7/T1 included the scapula and posterior medial aspect of the arm and the anterior medial aspect of the arm. The areas of thermal change in each CDH included wider sensory dermatome and sympathetic dermatome. There was a statistically significant change of temperature in the areas of thermal change in all CDH patients. In conclusion, the areas of thermal change in CDH can be helpful in diagnosing the level of disc protrusion and in detecting the symptomatic level in multiple CDH patients.

Digital infrared thermographic imaging in patients with gastroesophageal reflux disease.

We performed a thermographic study to observe any possible interaction between the esophageal acid perfusion and the temperature changes of skin surface in patients with gastroesophageal reflux disease (GERD). Twenty-seven patients with GERD were categorized as group I(globus symptoms with posterior laryngitis) and group II (heartburn and/or regurgitation symptoms). Patients and 6 healthy volunteers underwent Bernstein test (BT) and digital infrared thermographic imaging (DITI) simultaneously. The positive rate for BT in group I and group II was 22.2% and 55.6%, respectively, and the DITI positive rate was 55.6% for group I and 50.0% for group II. None of healthy control were positive in BT or DITI. All subjects with DITI positive were hypothermic. The overall accordance rate between DITI and BT was 69.7%. All group I patients showed a diffuse type, while in group 11, 4 patients showed diffuse type and 5 patients showed localized type (p<0.05). In patients with DITI (+)/BT (-), 83.3% showed diffuse type, whereas equal numbers of diffuse and localized type were noted in patients with DITI (+)/BT (+). In conclusion, add contact with a sensitive mucosa leads to an activation of the sympathetic nervous system in some patients with GERD, inducing skin surface hypothermia.