Toru Fujimoto

The effect of a local application of fibroblast growth factor-2 on tendon-to-bone remodeling in rats with acute injury and repair of the supraspinatus tendon

METHODS We investigated the effect of application of fibroblast growth factor (FGF)-2 on the tendon-to-bone remodeling of repaired supraspinatus tendon in rats subjected to bilateral detachment. FGF-2 (100 mg/kg) in a fibrin sealant or sealant alone was applied on the right and left shoulders, respectively. Twelve animals each at 2, 4, and 6 weeks after surgery were sacrificed for histological analysis (n = 5) and biomechanical Q1 testing (n = 7). RESULTS Histologically, at 2 weeks, FGF-treated specimens had significantly higher tendon-to-bone insertion maturing scores then untreated specimens (P < .002). At 4 and 6 weeks, the scores of FGF-treated and untreated specimens were similar (P > .05). Biomechanically, FGF-treated specimens were stronger at 2 weeks (P = .001); at 4 and 6 weeks, both specimens exhibited similar strength (P > .05). CONCLUSIONS The initial tendon-to-bone remodeling was accelerated by a local application of FGF-2. This may represent a clinically important improvement in rotator cuff repair.

Potent Protective Effects of Melatonin on Experimental Spinal Cord Injury

STUDY DESIGN Experimental biochemical, behavioral, and histologic investigations of spinal cord injury in rats. OBJECTIVE To investigate the effects of melatonin, a pineal hormone, in compression ischemic-induced spinal cord injury. SUMMARY OF BACKGROUND DATA The implication of activated neutrophils in the worsening of spinal cord injury has been shown. Melatonin was shown to play an important role in protecting animal cells from neutrophil-induced toxicity and damage by free radicals. There is no report on using melatonin for spinal cord injury. METHODS Spinal cord injury was induced by placing 25 g of weight extradurally on the rat spinal cord at T12 for 20 minutes. The rats were randomly divided into three groups. Sham rats had only laminectomy. Melatonin rats were injected with melatonin (2.5 mg/kg) intraperitoneally (intraperitoneal) five times: at 5 minutes, then 1, 2, 3, and 4 hours after the injury. Correspondingly, the control rats were injected with saline. Measured levels of lipid peroxidation estimated thiobarbituric acid reactive substances (TBARS) and the accumulation of leukocytes at the site of trauma, which were evaluated by measuring tissue myeloperoxidase activity. The recovery was assessed by using three clinical scoring systems, and histologic changes of the damaged spinal cord were examined. RESULTS The thiobarbituric acid reactive substances content in the spinal cord increased after the injury, with two peaks (at 1 and 4 hours), and nitrogen mustard-induced leukocytopenia significantly attenuated the thiobarbituric acid reactive substances content in four 4 after injury. Also in these 4 hours, myeloperoxidase activity increased and melatonin injection reduced thiobarbituric acid reactive substances content and myeloperoxidase activity, which attenuated the motor deficits as well. Histologic findings showed that the melatonin group had less cavity formation than the control group. CONCLUSION Results showed that injection of melatonin reduced thiobarbituric acid reactive substances content and myeloperoxidase activity, facilitating recovery of the damaged spinal cord.

Usefulness of diffusion-weighted imaging for differentiating between desmoid tumors and malignant soft tissue tumors

To evaluate the usefulness of diffusion‐weighted imaging (DWI) for differentiating between desmoid tumors and malignant soft tissue tumors.

Characterization of chondroblastic osteosarcoma: gadolinium-enhanced versus diffusion-weighted MR imaging.

To detect differences in magnetic resonance imaging (MRI) between chondroblastic osteosarcoma and the other types of osteosarcomas or chondrosarcomas using gadolinium‐enhanced versus diffusion‐weighted sequences.

Effects of EPC-K1 on lipid peroxidation in experimental spinal cord injury

Study Design. A study in which levels of lipid peroxidation were measured, the thiobarbituric acid–reactive substances were estimated in an experimental rat model, and the recovery was assessed. Objective. To ascertain the occurrence of thiobarbituric acid–reactive substances in the damaged spinal cord, and to investigate the effectiveness of a hydroxyl radical scavenger EPC-K1, a phosphate diester linkage of vitamins E and C, in attenuating the severity of spinal cord injury. Summary of Background Data. Lipid peroxidation has been reported to play an important role in spinal cord injury. There is no report on the use of EPC-K1 to attenuate the severity of spinal cord injury in either animal or human studies. Methods. Spinal cord injury was induced by placing a 25-g weight on T12, and the animals were divided into six groups. Group 1 (sham) received only laminectomy. Group 2 (control) received spinal cord injury. Group 3 received EPC-K1 5 minutes before injury. Group 4 received it 5 minutes after injury. Group 5 received it 3 hours after injury. Group 6 received it five times, respectively: at 5 minutes, then 1, 2, 3, and 4 hours after injury. The levels of thiobarbituric acid–reactive substances were measured in the spinal cord, and the recovery was assessed. Results. The thiobarbituric acid–reactive substances content increased after injury, with two peaks, at 1 and 4 hours. Concentration at the 4-hour peak was lower in nitrogen mustard–induced leukocytopenia rats than in the control rats. The EPC-K1 injection reduced thiobarbituric acid–reactive substances content at 1 and 4 hours after injury in Group 3 (respectively, 34.3% and 42.7%vs. control) and only that at 4 hours in Group 6 (24.9%vs. control). Motor function recovery and histologic findings were better in these two groups than in Group 2. Conclusion. Repeated injection of EPC-K1 attenuated the severity of spinal cord injury.

Angiopoietin-like protein 2 induced by mechanical stress accelerates degeneration and hypertrophy of the ligamentum flavum in lumbar spinal canal stenosis

Chronic inflammation and subsequent fibrosis induced by mechanical stress play an important role in ligamentum flavum (LF) hypertrophy and degeneration in patients with lumbar spinal canal stenosis (LSCS). Angiopoietin-like protein 2 (Angptl2) is a chronic inflammatory mediator induced under various pathological conditions and increases the expression of TGF-β1, which is a well-characterized mediator in LF hypertrophy. We investigated whether Angptl2 is induced by mechanical stress, and whether it contributes to LF hypertrophy and degeneration by activating the TGF-β1 signaling cascade. In this study, we investigated human LF tissue and LF fibroblasts isolated from patients who underwent lumbar surgery. We found that Angptl2 was abundantly expressed in fibroblasts of hypertrophied LF tissues at both the mRNA and protein levels. This expression was not only positively correlated with LF thickness and degeneration but also positively correlated with lumbar segmental motion. Our in vitro experiments with fibroblasts from hypertrophied LF tissue revealed that mechanical stretching stress increases the expression and secretion of Angptl2 via activation of calcineurin/NFAT pathways. In hypertrophied LF tissue, expression of TGF-β1 mRNA was also increased and TGF-β1/Smad signaling was activated. Angptl2 expression in LF tissue was positively correlated with the expression of TGF-β1 mRNA, suggesting cooperation between Angptl2 and TGF-β1 in the pathogenesis of LF hypertrophy. In vitro experiments revealed that Angptl2 increased levels of TGF-β1 and its receptors, and also activated TGF-β1/Smad signaling. Mechanical stretching stress increased TGF-β1 mRNA expression, which was partially attenuated by treatment with a calcineurin/NFAT inhibitor or Angptl2 siRNA, indicating that induction of TGF-β1 expression by mechanical stretching stress is partially mediated by Angptl2. We conclude that expression of Angptl2 induced by mechanical stress in LF fibroblasts promotes LF tissue degeneration by activation of TGF-β1/Smad signaling, which results in LF hypertrophy in patients with LSCS.

Amyloid deposits derived from transthyretin in the ligamentum flavum as related to lumbar spinal canal stenosis

Amyloidosis is a protein conformational disorder with the distinctive feature of extracellular accumulation of amyloid fibrils that come from different proteins. In the ligamentum flavum of the lumbar spine, amyloid deposits were frequently found in elderly patients with lumbar spinal canal stenosis and were at least partially formed by wild-type transthyretin. However, how amyloid deposits in the ligamentum flavum affect lumbar spinal canal stenosis has remained unclear. In this study, we analyzed clinical, pathologic, and radiologic findings of patients with lumbar spinal canal stenosis who had amyloid deposits in the ligamentum flavum. We studied 95 ligamentum flavum specimens obtained from 56 patients with lumbar spinal canal stenosis and 21 ligamentum flavum specimens obtained from 19 patients with lumbar disk herniation. We evaluated histopathologic findings and clinicoradiologic manifestations, such as thickness of the ligamentum flavum and lumbar spinal segmental instability. We found that all 95 ligamentum flavum specimens resected from patients with lumbar spinal canal stenosis had amyloid deposits, which we classified into two types, transthyretin-positive and transthyretin-negative, and that transthyretin amyloid formation in the ligamentum flavum of patients with lumbar spinal canal stenosis was an age-associated phenomenon. The amount of amyloid in the ligamentum flavum was related to clinical manifestations of lumbar spinal canal stenosis, such as thickness of the ligamentum flavum and lumbar spinal segmental instability, in the patients with lumbar spinal canal stenosis with transthyretin-positive amyloid deposits. To our knowledge, this report is the first to show clinicopathologic correlations in transthyretin amyloid deposits of the ligamentum flavum. In conclusion, transthyretin amyloid deposits in the ligamentum flavum may be related to the pathogenesis of lumbar spinal canal stenosis in elderly patients.

L5 radiculopathy caused by a ganglion cyst of the posterior longitudinal ligament in a teenager

BACKGROUND CONTEXT There is no previous report on the intraspinal ganglion cyst of the posterior longitudinal ligament in a teenager. PURPOSE To report a case of radiculopathy caused by a ganglion cyst of the posterior longitudinal ligament in a teenager. STUDY DESIGN Case report. METHODS A 17-year-old male with a 4-month history of left L5 radicular pain was found to have an intraspinal cystic lesion causing radicular compression. Magnetic resonance imaging showed a cystic lesion located in the ventral side of the dura. The patient suffered from severe leg pain. As a result, a surgical operation was therefore performed. RESULTS The cyst containing jelly-like components and a hemorrhage was punctured and then extirpated. It originated from the posterior longitudinal ligament. A histological study revealed the cyst to be without any synovial layers. CONCLUSIONS This is the first report to describe a ganglion cyst originating from the posterior longitudinal ligament in a teenager. This possible etiology should be kept in mind for any other individuals displaying symptoms of spinal nerve root compression as well as disc herniation.

Effects of the water‐holding capability of polyvinyl formal sponges on osteogenic ability in in vivo experiments

In this study, dextran-coated polyvinyl formal (PVF) sponges with high water-holding capability were developed to increase the osteogenic response in the PVF sponge. The study aimed to estimate the effect of the increased water-holding capability of the sponges on osteogenic capacity at a bone defect site in the rabbit femur epiphysis. Bone formation was evaluated using radiography, microcomputed tomography (CT), and histological analysis at 2, 4, and 6 weeks after implantation. As shown by radiography and micro-CT findings, the dextran-coated PVF sponge without water-holding capability showed little bone formation at all evaluated time points. However, the dextran-coated PVF sponge with high water-holding capability showed increasing bone formation around the implant at 4 and 6 weeks after implantation. Furthermore, as shown by micro-CT quantitative analysis, the grafted PVF sponge with high water-holding capability showed significantly greater values for percentage of bone volume per total volume and mean bone mineral density compared with the grafted PVF sponge without water-holding capability at 4 and 6 weeks after implantation. These results suggest that the dextran-coated PVF sponge with high water-holding capability promoted osteogenesis in vivo. The PVF sponge might be a new biomaterial to be used as a fill material for bone defects.

Corresponding scapular pain with the nerve root involved in cervical radiculopathy.

Purpose. To correspond scapular pain with the nerve root involved in cervical radiculopathy. Methods. In the anatomic study, 11 Japanese adult cadavers were dissected to examine the numbers and courses of the cutaneous nerves from C3 to C8 dorsal rami. In the clinical study, 14 men and 11 women aged 34 to 77 years who presented with scapular pain as well as pain, numbness or motor weakness in the upper limbs secondary to cervical radiculopathy were assessed. The involved nerve roots were identified based on the symptoms and signs in the arm and/or fingers, the radiological diagnosis, and the pain response to cervical nerve root blocks. The sites and characteristics of radicular pain were assessed. Results. In the anatomic study of 22 cutaneous nerves from medial branches of dorsal rami, 18 involved the C5 nerve root, 0 the C6 root, one the C7 root, and 8 the C8 root. In the clinical study, the radicular pain often occurred in the suprascapular region involving the C5 root, in the suprascapular to posterior deltoid region involving the C6 root, in the interscapular region involving the C7 root, and in the interscapular and scapular regions involving the C8 root. All patients with C5 or C8 radiculopathy had both superficial and deep pain, whereas almost all patients with C6 or C7 radiculopathy had deep pain only. No patient had superficial pain only. Conclusion. Cervical radiculopathy can cause scapular pain. Pain sites and characteristics are related to the affected nerve root.