Significance of serum Zn-α2-glycoprotein for the regulation of blood pressure.

Zn-α2-glycoprotein (ZAG) (molecular weight=41 kDa) is one component in the α2 fraction of human plasma, and is reported to be associated with several diseases, such as cancers and metabolic syndromes. ZAG is also considered to be an important modulator of lipid metabolism. However, little is known about the correlation of serum ZAG levels with indicators of metabolic syndrome. Serum ZAG concentrations analyzed by enzyme-linked immunoassay were positively correlated with systolic and diastolic blood pressure in 326 subjects (236 males and 90 females) aged 17-79 years who had an annual health examination. By luciferase reporter and electrophoretic mobility shift assays, the core promoter region to regulate the ZAG gene expression was found to exist between -110 and -101. The transcription factor Sp1 interacted with this region, and Sp1 knockdown experiments showed that Sp1 critically regulated ZAG expression. Furthermore, ZAG increased the active form of RhoA, which was determined by pull-down assay. Increased serum ZAG concentrations induced, at least partly, by Sp1 may cause an increase in vascular tone through the activation of RhoA and contribute to elevated blood pressure.

Domain 5 of high molecular weight kininogen inhibits collagen-mediated cancer cell adhesion and invasion in association with α-actinin-4.

High molecular weight kininogen (HK) is a plasma glycoprotein with multiple functions, including the regulation of coagulation. We previously demonstrated that domain 5 (D5(H)), a functional domain of HK, and its derived peptides played an important role in the vitronectin-mediated suppression of cancer cell adhesion and invasion. However, the underlying mechanisms of the D5(H)-mediated suppressive effects remain to be elucidated. Here, we showed that D5(H) and its derivatives inhibited the collagen-mediated cell adhesion and invasion of human osteosarcoma MG63 cells. Using purified D5(H) fused to glutathione-S-transferase (GST) and D5(H)-derived peptides for column chromatography, an actin-binding protein, α-actinin-4, was identified as a binding protein of D5(H) with high-affinity for P-5m, a core octapeptide of D5(H). Immunofluorescence microscopy demonstrated that D5(H) co-localized with α-actinin-4 inside MG63 cells. In addition, exogenous GST-D5(H) added to the culture media was transported into MG63 cells, although GST alone as a control was not. As α-actinin-4 regulates actin polymerization necessary for cell adhesion and is related to the integrin-dependent attachment of cells to the extracellular matrix, our results suggest that D5(H) may modulate cell adhesion and invasion together with actinin-4.

Previous vertebral compression fractures add to the deterioration of the disability and quality of life after an acute compression fracture.

Prevalent vertebral compression fracture(s) have been reported as having a negative impact on pain, disability, and quality of life. But no study has evaluated the effect of previous fracture on the course of acute compression fractures. The aim of the present study was to compare the natural course of the acute compression fracture in patients with (n = 51) and without (n = 56) previous vertebral compression fracture(s). The study is a retrospective analysis of a prospective cohort followed with postal questionnaires during a 12-month period after an acute fracture event. Eligible patients were those over 40 years of age, who were admitted to the emergency unit because of back pain and had an X-ray confirmed acute vertebral body fracture. A total of 107 patients were included in the study. The pain, disability (von Korff pain and disability scores), ADL (Hannover ADL score), and quality of life (QoL) (EQ-5D) were measured after 3 weeks, and 3, 6, and 12 months. The X-rays from the first visit to the emergency unit were evaluated. The difference of the scores between the groups with and without previous fracture was statistically significant (P < 0.05) at 3 weeks, 6 and 12 months for von Korff disability score, at all occasions for EQ-5D and at 3-12 months for Hannover ADL score, but only at 12 months for the von Korff pain intensity score. In both the groups all scores had improved in a statistically significant way at 3 months. The number of previous fractures was related to all the outcome scores in a statistically significant way (P < 0.05) except von Korff pain intensity score at 3 weeks and 3 months and von Korff disability score at 3 months. In conclusion, disability, ADL, and QoL scores, but not pain intensity score, were significantly worse in the patients with previous fracture from the fracture episode through the first 12 months. However, the improvements during the follow-up year seen in both groups were of a similar magnitude. The presence or absence of a previous fracture in an acutely fractured patient will influence the prognosis and thus possibly also the indications for treatments.

A rare case of extramedullary-intradural hemangioblastoma in the thoracic spine.

STUDY DESIGN.: Case report. OBJECTIVE.: To present a rare case of extramedullary-intradural hemangioblastoma in the thoracic spine and to review the literature on this condition. SUMMARY OF BACKGROUND DATA.: Spinal hemangioblastoma is rare, and moreover, there is seldom purely extramedullary-intradural hemangioblastoma of the spinal cord and there are few reports on histopathological features of spinal hemangioblastoma. METHODS.: A 65-year-old Japanese woman presented with gait disturbance and numbness below the trunk that had gradually worsened, and finally she was unable to walk by herself. Physiologic and neurologic examinations at admission revealed severe transverse neurologic defects, with no sign of von Hippel-Lindau's disease. Radiologic methods showed an extramedullary-intradural mass at Th4-5. A diagnosis of extramedullary-intradural spinal tumor was done, total tumorectomy was performed with recapped laminoplasty. RESULTS.: The patient's neurologic condition gradually improved after the operation. The immunohistopathological findings revealed the diagnosis of hemangioblastoma. CONCLUSION.: A rare case of extramedullary-intradural spinal hemangioblastoma was reported. The immunohistopathological findings were helpful for making a final diagnosis.

The prognosis for pain, disability, activities of daily living and quality of life after an acute osteoporotic vertebral body fracture: its relation to fracture level, type of fracture and grade of fracture deformation.

The level of the acute osteoporotic vertebral fracture, fracture type and grade of fracture deformation were determined in 107 consecutive patients and related to pain, disability, activities of daily living (ADL) and quality of life (QoL) after 3 weeks, 3, 6 and 12 months. Two-thirds of the fractured patients were women and with a similar average age, around 75 years, as the men. Fifty-eight of the acute fractures were located in the thoracic spine and 49 in the lumbar spine and predominantly at the Th12 and L1 levels. Sixty-nine percent of the fractures were wedge, 19% concave and 12% crush fractures. There were 22 mildly, 50 moderately and 35 severely deformed vertebrae. The grade of fracture deformation was not related to gender, age or fracture location. Severely deformed vertebrae predominantly (92%) occurred among the crush fracture type. One year after the fracture, irrespective of fracture level, fracture type or grade of fracture deformation, 4/5 still had pronounced pain and deteriorated QoL. Initial severe fracture deformation by far was the worst prognostic factor for severe lasting pain and disability, and deterioration of ADL and QoL. Factors like fracture level, lumbar fractures tended to improve steadily while thoracic deteriorated, type of fracture, the wedge and concave resulting in less pain and better QoL than the crush fracture type and gender influenced to a lesser extent the outcomes during the year after the acute fracture.

The course of the acute vertebral body fragility fracture: its effect on pain, disability and quality of life during 12 months.

The vertebral body fracture is the most frequent bone fragility fracture. In spite of this there is considerable uncertainty about the frequency, extent and severity of the acute pain and even more about the duration of pain, the magnitude of disability and how much daily life is disturbed in the post-fracture period. The aim of the present study was to follow the course of pain, disability, ADL and QoL in patients during the year after an acute low energy vertebral body fracture. The study design was a longitudinal cohort study with prospective data collection. All the patients over 40 years admitted to the emergency unit because of back pain with a radiologically acute vertebral body fracture were eligible. A total of 107 patients were followed for a year. The pain, disability (von Korff pain and disability scores), ADL (Hannover ADL score), and QoL (EQ-5D) were measured after 3 weeks, 3, 6 and 12 months. Two-thirds of the patients were women, and were similar in average age, as the men around 75 years. A total of 65.4% of the fractures were due to a level fall or a minor trauma, whereas 34.6% had no recollection of trauma or a specific event as the cause of the fracture. A total of 76.6% of the fractured patients were immediately mobilized and allowed to return home while the remaining were hospitalized. The average pain intensity score after 3 weeks was 70.9 (SD 19.3), the disability score 68.9 (SD 23.6), the ADL score 37.7 (SD 22.1) and EQ-5D score of 0.37 (SD 0.37). The largest improvements, 10-15%, occurred between the initial visit and the 3 months follow-up and were quite similar for all the measures. From 3 months, all the outcome measures leveled out or tended to deteriorate resulting in a mean pain intensity score of 60.5, disability score of 53.9, ADL score of 47.6, and EQ-5D score 0.52 after 12 months. After a whole year the fractured patients' condition was similar to the preoperative condition of patients with a herniated lumbar disc, central lumbar spinal stenosis or in patients 100% work disabled due to back or neck problems. Instead of the generally believed good prognosis for the greater majority of those fractured, the acute vertebral body fracture was the beginning of a long-lasting severe deterioration of their health.

Biogenesis of HDL by SAA is dependent on ABCA1 in the liver in vivo.

Serum amyloid A (SAA) was markedly increased in the plasma and in the liver upon acute inflammation induced by intraperitoneal injection of lipopolysaccharide (LPS) in mice, and SAA in the plasma was exclusively associated with HDL. In contrast, no HDL was present in the plasma and only a small amount of SAA was found in the VLDL/LDL fraction (d < 1.063 g/ml) after the induction of inflammation in ABCA1-knockout (KO) mice, although SAA increased in the liver. Primary hepatocytes isolated from LPS-treated wild-type (WT) and ABCA1-KO mice both secreted SAA into the medium. SAA secreted from WT hepatocytes was associated with HDL, whereas SAA from ABCA1-KO hepatocytes was recovered in the fraction that was >1.21 g/ml. The behavior of apolipoprotein A-I (apoA-I) was the same as that of SAA in HDL biogenesis by WT and ABCA1-KO mouse hepatocytes. Lipid-free SAA and apoA-I both stabilized ABCA1 and caused cellular lipid release in WT mouse-derived fibroblasts, but not in ABCA1-KO mouse-derived fibroblasts, in vitro when added exogenously. We conclude that both SAA and apoA-I generate HDL largely in hepatocytes only in the presence of ABCA1, likely being secreted in a lipid-free form to interact with cellular ABCA1. In the absence of ABCA1, nonlipidated SAA is seemingly removed rapidly from the extracellular space.

The relationship between the cross-sectional area of the cauda equina and the preoperative symptoms in central lumbar spinal stenosis.

STUDY DESIGN: A cross-sectional registry and imaging cohort study. OBJECTIVES: To study the association between typical symptoms and signs of central spinal stenosis and the minimum cross-sectional area (mCSA) of the cauda equina in patients subsequently undergoing surgery. SUMMARY OF BACKGROUND DATA: Relations between mCSA and the symptoms of spinal stenosis have not been studied before. SUBJECTS AND METHODS: The preoperative walking ability, pain in the leg(s) and back, duration of symptoms and quality of life in 82 men and women subsequently operated for spinal stenosis were related to the digitally determined CSA of the single most constricted level, mCSA of their lumbar spines. RESULTS: A smaller mCSA was directly related to a shorter walking distance before claudication. A small mCSA meant more leg and back pain and a lower health-related quality of life. For those with a walking ability <100 m, the average mCSA was around 53 mm; whereas it was just <69 mm for those able to walk >500 m. The average mCSA did not differ depending on gender, age, or vertebral level. CONCLUSIONS: The mCSA was a strong predictor of the preoperative walking ability, leg and back pain, and was directly related to the quality of life of patients with central spinal stenosis.

Primary structure and properties of Mn-superoxide dismutase from scallop adductor muscle.

Manganese-superoxide dismutase was purified to homogeneity from scallop adductor muscle using DEAE-Sephacel, Buthyl-Cellulofine and Superdex 200 pg column chromatographies. The molecular weights of the purified enzyme were calculated to be 22,321.4 according to time-of-flight mass spectrometry, and to be approximately 95,000 and 93,000 on Superdex 200 pg column chromatography and non-denatured PAGE, respectively, and were calculated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis to be 24,000 and 25,000 in the absence and 25,000 in the presence of beta-mercaptoethanol. These findings suggested that the native enzyme is composed of four identical subunits. Other properties of scallop adductor muscle manganese-superoxide dismutase, including pH stability and heat stability, were also determined. We determined the partial amino acid sequences of purified manganese-superoxide dismutase using digestions by bromocyan and lysyl endopeptidase and also determined the manganese-superoxide dismutase cDNA structure. The amino acid sequence of the enzyme obtained using both methods showed homology to those of vertebrates such as human, bovine, chicken, Xenopus and zebrafish manganese-superoxide dismutases (64.91, 65.35, 64.47, 63.27 and 64.60%, respectively). We also predicted the 3D structure of scallop adductor muscle manganese-superoxide dismutase using molecular operating environment and compared its structure with those of other manganese-superoxide dismutases. The overall structure of scallop adductor muscle manganese-superoxide dismutase was very similar to those of other species, including human and Aspergillus.

Inhibition of recombinant dipeptidyl peptidase III by synthetic hemorphin-like peptides.

In order to find the most effective antagonist for dipeptidyl peptidase III degrading enkephalin, we synthesized hemorphin-like pentapeptides with aliphatic or aromatic amino acids at the N-termini, such as VVYPW, LVYPW, IVYPW, YVYPW, FVYPW and WVYPW. Among those pentapeptides, IVYPW and WVYPW showed the strongest inhibitory activity toward rDPP III. The K(i) values of IVYPW and WVYPW were 0.100+/-0.011 and 0.126+/-0.015 microM (mean+/-S.E.), respectively. The order of K(i) values was Ile> or =Trp>Phe> or =Tyr>Leu>Ala>Val>Ser>Gly. rDPP III activity is inhibited in a non-competitive manner by these peptides. The peptide VYPW did not inhibit rDPP III activity, but the sequence is essential for the expression of inhibitory activity.

Anterior decompression for myelopathy resulting from thoracic ossification of the posterior longitudinal ligament.

STUDY DESIGN: A retrospective study was conducted to investigate the anterior decompression and fusion of 12 patients with thoracic ossification of the posterior longitudinal ligament. OBJECTIVE: To evaluate the effect of myelopathy management in which the thoracic ossification of the posterior longitudinal ligament is removed. SUMMARY AND BACKGROUND DATA: Very few reports have described operative treatments for thoracic ossification of the posterior longitudinal ligament. The condition is extremely rare, even in Japan. Consequently, operative procedures for myelopathy resulting this disorder have not been established. METHODS: This study involved 12 patients with thoracic ossification of the posterior longitudinal ligament. All the patients underwent direct removal of the ossification and spinal fusion using an anterior approach. A scapula-releasing technique was used in five patients who had major ossification of the posterior longitudinal ligament at Th4. The follow-up period ranged from 2.5 to 10 years (mean, 6.5 years). The clinical effect of the decompression was evaluated with a Japanese Orthopedic Association score for cervical myelopathy. The efficacy of the decompression was determined by postoperative computed tomography scan. RESULTS: Complete removal of the ossification was achieved in eight patients. In four patients, however, residual ossification was noted. The Japanese Orthopedic Association score before the operation ranged from 4 to 7 points (mean, 5.3 +/- 0.4 points). It showed a change 3 months after the operation, ranging from 1 to 8 points (mean, 6.9 +/- 0.5 points). At 1 year after the operation, it had changed to a range of 1 to 10 points (mean, 7.2 +/- 0.6 points). At the final consultation, it had changed further to a range of 1 to 10 points (mean, 6.9 +/- 0.5 points). Patients whose ossification was not completely removed showed severe or minor postoperative deterioration. CONCLUSIONS: Total removal of the ossification might be required to manage severe myelopathy in patients with thoracic ossification of the posterior longitudinal ligament. Complete removal of the ossification gave good results in eight patients. Patients whose ossification of the posterior longitudinal ligament had not been completely removed, however, had a poor outcome.