Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.3.1 (alkaline phosphatase)
 47,916 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In order to determine the impact of extremely large doses of methylprednisolone, naloxone, or of spinal cord injury itself, on liver enzymes, we examined the results of SGOT, SGPT, alkaline phosphatase and total bilirubin tests obtained 24 hours, 3 and 10 days after the end of the study drug infusions in spinal cord injured patients entered in the National Acute Spinal Cord Injury Study. The mean values of four liver enzymes, the amount of change between 24 hours and 3 and 10 days post infusion, and the proportion of liver enzyme levels considered to be abnormal did not appear to be affected by either drug protocol. Even when controlling for drug protocol and severity of injury (complete vs incomplete), variation in enzyme levels appeared to be the result of the spinal cord injury, not study drugs. Spinal cord injury is routinely treated with the NASCIS dose of methylprednisolone in many countries. It is reassuring to find no evidence of compromised liver function from this steroid protocol.
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PMID:The effect of methylprednisolone, naloxone, and spinal cord trauma on four liver enzymes: observations from NASCIS 2. National Acute Spinal Cord Injury Study. 802 33

Ossification of the posterior longitudinal ligament of the spine (OPLL) is a common cause of spinal canal stenosis and myelopathy in Orientals. OPLL is characterized by heterotopic new bone formation in ligamentous tissue. To investigate the pathogenesis of OPLL, human posterior longitudinal ligament cells were cultured and their in vitro morphological and biochemical characteristics were studied. Cell cultures from control subjects with normal spinal ligaments did not show any osteoblastic properties. In contrast, cell lines (OG1-OG5) obtained from an OPLL patient showed several different phenotypic characteristics for osteoblasts. OG1 cells showed typical osteoblast-like phenotypic characteristics (i.e., in vitro calcification, high alkaline phosphatase [ALP] activity, and elevation of cAMP levels by parathyroid hormone [PTH]). All cell lines (OG1-OG5) responded to PTH and PGE2 by markedly increasing cAMP levels, ALP activities varied among the cell lines. The OG1 and OG2 cells exhibited a high level of ALP activity. Compared with cell lines from the non-ossification group, the activities were higher in the OG3 and OG4 cells, but not significantly in the OG5 cells. Only in the OG3 cells, CT caused an increase in cAMP level and ALP activity, and its stimulatory effects demonstrated that CT had a direct, in vitro action on ligament cells of OPLL patients to stimulate osteoblastic differentiation. It is clear that some cells from ligaments with OPLL had several phenotypes characteristic of osteoblasts, but cells from ligaments without ossification did not show any osteoblastic properties. This observation is considered to be an important clue to understanding the pathophysiology of OPLL.
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PMID:Characterization of cultured cells derived from ossification of the posterior longitudinal ligament of the spine. 839 54

Ossification of the posterior longitudinal ligament (OPLL) of the spine is characterized by heterotopic bone formation occurring in spinal ligament, causing severe compression myelopathy. In order to investigate the mechanism of OPLL development, we isolated spinal ligament cells from OPLL patients as well as non-OPLL patients, and established 10 OPLL cell lines and 7 non-OPLL cell lines, respectively. We analyzed the effects of bone morphogenetic protein-2 (BMP-2) on these cells with respect to alkaline phosphatase (AP) activity, DNA synthesis, and collagen production. BMP-2 caused a significant increase of AP activity in 4 OPLL cell lines, whereas the activity did not change in any non-OPLL cells. Among OPLL cells, BMP-2 stimulated DNA synthesis in four cell lines and procollagen type I carboxyl-terminal peptide (PICP) synthesis in five cell lines. Some non-OPLL cells also responded to BMP-2, as there was an increase of DNA synthesis in three cell lines and PICP synthesis in one cell line. These data collectively indicate that BMP-2 preferentially induces osteogenic differentiation in OPLL cells rather than in non-OPLL cells. OPLL cells, therefore, exhibit a different response to BMP-2 than non-OPLL cells, suggesting that the expression of BMP receptor(s) and/or the signal transduction initiated by BMP-2 in the spinal ligament cells of OPLL patients somewhat deviate from those in normal spinal ligament cells. Such abnormal characteristics of OPLL cells as described here provide some clues to the clarification of the pathogenesis of OPLL.
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PMID:Bone morphogenetic protein-2 stimulates differentiation of cultured spinal ligament cells from patients with ossification of the posterior longitudinal ligament. 906 68

The impact of spinal cord injury (SCI) on later bone mineral status was studied in 35 adults who had sustained their injury in childhood. The median age of the patients was 31 years, the median age at injury 12.9 years and the median time period from injury was 19 years. The methods used in the study were clinical interview and examination, measurement of bone mineral density (BMD) of the lumbar spine and the proximal femur with dual energy X-ray absorptiometry (DEXA) and estimation of bone turnover with biochemical markers. The densitometric examination revealed that the BMD at the lumbar spine was within the normal range but grossly decreased in the femoral region. Moreover, there was a significant difference in BMD between patients with high (C2-T6) and low (below T6) lesions in the lumbar spine as well as in the femoral region. Patients with lower lesions had higher BMD values. The markers of bone turnover which were studied were serum and urinary calcium and phosphate serum alkaline phosphatase and its isoenzymes, osteocalcin, carboxyterminal propeptide of human type I procollagen (PICP), carboxyterminal telopeptide of type I collagen (ICTP) and urinary deoxypyridinoline. These markers of bone metabolism showed no signs of ongoing accelerated bone formation or resorption. The present study suggests that caution should be observed in weight bearing training or mobilisation of patients with pediatric SCI or perhaps with long standing SCI because of increased fracture risk. The prevention of dissociated osteoporosis should be investigated further in order to avoid fractures of weakened bones. The modes of prevention might be found in the use of modern pharmacotherapy of osteoporosis and from correctly dosage physical training.
Spinal Cord 1998 Sep
PMID:Bone mineral status after pediatric spinal cord injury. 977 50

Immobilisation secondary to spinal cord injury (SCI) is associated with marked and rapid atrophy of trabecular bone. The purpose of this study was to evaluate bone mineral density (BMD) in both the upper and lower extremities following SCI sustained for various lengths of time and to correlate the BMD to the level of the lesion, time from injury, spasticity and serum calcium, phosphorus and alkaline phosphatase (ALP) levels. A study was undertaken in 41 SCI patients with a mean age of 35.8 +/- 12.7 years. A significant difference in BMD between upper and lower extremities of the paraplegics were found. BMD of upper and lower extremities were similar in tetraplegies. The BMD values were significantly different when the upper extremity scores of paraplegics and tetraplegics were compared but BMD scores of the lower extremities were similar in the two groups. The decrease in BMD was less in the spastic patients when compared to the flaccid group. There was a positive correlation between time from injury and the degree of BMD deficit in the paralysed areas. In the whole group of patients a significant positive correlation was found between the duration of SCI and serum ALP levels.
Spinal Cord 1998 Dec
PMID:Osteoporosis after spinal cord injury. 988 30

Heterotopic ossification (HO) is an important complication of spinal cord and brain injuries but is rarely reported among patients with non-traumatic myelopathies. In a prospective study on medical problems seven (6.04%) among the 114 subjects with non-traumatic myelopathies had heterotopic ossification. All of them had involvement of hip joints. The co-morbid conditions were: urinary tract infection, seven; spasticity, three; pressure sores, five; and deep venous thrombosis, one. The initial diagnosis was often other than heterotopic ossification. Erythrocyte sedimentation rate and serum alkaline phosphatase levels were elevated in all subjects. Following rest and non-steroidal anti-inflammatory drugs, the range of motion improved in two patients. Heterotopic ossification can occur in patients with non-traumatic myelopathies and has risk factors and clinical features similar to patients with traumatic spinal cord injury. A high index of suspicion about this complication is necessary for early diagnosis and prompt intervention.
Spinal Cord 1999 Jan
PMID:Heterotopic ossification in non-traumatic myelopathies. 1002 95

Heterotopic ossification (HO) is an important cause of restriction in range of movements and secondary motor disability following neurotrauma, orthopaedic interventions and burns. It has not received focussed attention in non-traumatic neurological disorders. In a prospective study of 377 patients, on medical problems in neurological rehabilitation setting, 15 subjects (3.97%) had neurogenic heterotopic ossification. Their clinical diagnosis was: transverse myelitis (7), neurotuberculosis (4), traumatic myelopathy (2) and stroke (2). Hip (10), knee (4) and elbow joints (1) were involved. The risk factors included urinary tract infection (15), spasticity (6), pressure sores (13) and deep venous thrombosis (DVT) (6). The initial diagnosis was often other than HO and included DVT (3), haematoma (2) and arthritis (2). ESR and serum alkaline phosphatase levels were elevated in all but one subject. The diagnosis of HO was established using X-rays, CT Scan and three-phase bone scan. Following treatment with non-steroidal anti-inflammatory drugs, the range of motion improved in only four patients. HO resulted in significant loss of therapy time during rehabilitation. High index of suspicion about this complication is necessary for early diagnosis and prompt intervention.
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PMID:Neurogenic heterotopic ossification : a diagnostic and therapeutic challenge in neurorehabilitation. 1130 39

Ossification of spinal ligaments (OSL) is a common form of myelopathy characterized by heterotopic bone formation in the spinal ligaments, predominantly in men. Although the etiology of OSL is not fully understood, previous studies have strongly suggested the involvement of genetic factors in this disease. To investigate the possible involvement of vitamin D receptor (VDR) gene polymorphism in Japanese male patients with OSL, we analyzed: (a) the VDR genotype defined by BsmI polymorphism in patients with obvious OSL and controls; and (b) the effect of 1,25-dihydroxyvitamin D3 on alkaline phosphatase (ALP) activity of spinal ligament cells derived from patients without OSL. With regard to the VDR genotype, of the patients with OSL (n = 27), none had the BB genotype (0%), one had the Bb genotype (4%), and 26 had the bb genotype (96%). In the control group (n = 97) three had the BB genotype (3%), 18 had the Bb genotype (19%), and 76 had the bb genotype (78%). As a result, the B allele frequency in patients with OSL (2%) was significantly lower than in controls (12%). 1,25-Dihydroxyvitamin D3, at concentrations of 10-9 and 10-8 M, significantly increased ALP activity of the ligament cells (n = 8), suggesting that 1,25-dihydroxyvitamin D3 is able to promote osteogenic differentiation of normal ligament cells. Among the Japanese, sensitivity to vitamin D has been reported to vary between the alleles of the VDR; i.e., bone mineral density (BMD) in patients without the B allele is increased by vitamin D treatment, whereas patients with the B allele do not show such an increase in BMD. The present investigation is a small preliminary study, but the findings suggest, for the first time, that the B allele of the VDR acts as an inhibitor in the pathogenesis of human male OSL.
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PMID:Possible involvement of vitamin D receptor gene polymorphism in male patients with ossification of spinal ligaments. 1149 33

Ossification of the posterior longitudinal ligament of the spine (OPLL) is the leading cause of myelopathy in Japan and is diagnosed by ectopic bone formation in the paravertebral ligament. OPLL is a systemic high bone mass disease with a strong genetic background. To detect genes relevant to the pathogenesis of OPLL, we performed a cDNA microarray analysis of systematic gene expression profiles during the osteoblastic differentiation of ligament cells from OPLL patients (OPLL cells), patients with a disorder called ossification of yellow ligament (OYL), and non-OPLL controls together with human mesenchymal stem cells (hMSCs) after stimulating them with osteogenic differentiation medium (OS). Twenty-four genes were up-regulated during osteoblastic differentiation in OPLL cells. Zinc finger protein 145 (promyelotic leukemia zinc finger or PLZF) was one of the highly expressed genes during osteoblastic differentiation in all the cells examined. We investigated the roles of PLZF in the regulation of osteoblastic differentiation of hMSCs and C2C12 cells. Small interfering RNA-mediated gene silencing of PLZF resulted in a reduction in the expression of osteoblast-specific genes such as the alkaline phosphatase, collagen 1A1 (Col1a1), Runx2/core-binding factor 1 (Cbfa1), and osteocalcin genes, even in the presence of OS in hMSCs. The expression of PLZF was unaffected by the addition of bone morphogenetic protein 2 (BMP-2), and the expression of BMP-2 was not affected by PLZF in hMSCs. In C2C12 cells, overexpression of PLZF increased the expression of Cbfa1 and Col1a1; on the other hand, the overexpression of CBFA1 did not affect the expression of Plzf. These findings indicate that PLZF plays important roles in early osteoblastic differentiation as an upstream regulator of CBFA1 and thereby might participate in promoting the ossification of spinal ligament cells in OPLL patients.
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PMID:The promyelotic leukemia zinc finger promotes osteoblastic differentiation of human mesenchymal stem cells as an upstream regulator of CBFA1. 1562 33

To reveal the involvement of extracellular nucleotides in the ossification process in ossification of the posterior longitudinal ligament of the spine (OPLL), the mRNA expression profiles of P2 purinoceptors, mechanical stress-induced ATP release, and ATP-stimulated expression of osteogenic genes were analyzed in ligament cells derived from the spinal ligament of OPLL patients (OPLL cells) and non-OPLL cells derived from the spinal ligaments of cervical spondylotic myelopathy patients as a control. The extracellular ATP concentrations of OPLL cells in static culture were significantly higher than those of non-OPLL cells, and this difference was diminished in the presence of ARL67156, an ecto-nuclease inhibitor. Cyclic stretch markedly increased the extracellular ATP concentrations of both cell types to almost the same level. P2Y1 purinoceptor subtypes were intensively expressed in OPLL cells, but only weakly expressed in non-OPLL cells. Not only ATP addition but also cyclic stretch raised the mRNA levels of alkaline phosphatase and osteopontin in OPLL cells, which were blocked by MRS2179, a selective P2Y1 antagonist. These increases in the expression of osteogenic genes were not observed in non-OPLL cells. These results suggest an important role of P2Y1 and extracellular ATP in the progression of OPLL stimulated by mechanical stress.
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PMID:Possible role of extracellular nucleotides in ectopic ossification of human spinal ligaments. 1818 32


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