Biomedical subjects

Toshihiko Yamashita

Publications and source records attributed to Toshihiko Yamashita.

At least 19 recordsLinked to original sources

PubMed2007

Electrophysiologic changes in dorsal root ganglion neurons and behavioral changes in a lumbar radiculopathy model.

STUDY DESIGN: The DRG neuron was electrophysiologically investigated using a rat model with constriction of the proximal site of the DRG. OBJECTIVES: To investigate the pathomechanisms of lumbar radiculopathy, we established a rat model with constriction of the proximal site of the DRG. And to characterize the DRG neurons in the rat model of lumbar radiculopathy, the physiologic properties regarding action potential, Na, and K current of the DRG neurons were analyzed through the use of patch clamp recordings. SUMMARY OF BACKGROUND DATA: In lumbar root constriction models, properties of secondary afferent neurons in the dorsal horn have been investigated. However, the electrical properties of DRG neuron have not been well investigated. METHODS: To compare the excitability of DRG neurons between root constriction models and sham, we examined the threshold current, action potential (AP) threshold, resting membrane potential (RMP), afterhyperpolarization (AHP), action potential duration 50 (APD50), action potential amplitude, maximum rise time of AP, and pattern of discharges evoked by depolarizing current. We also examined the peak Na current and steady-state Na and K currents with the voltage clamp technique. RESULTS: The rats in the root constriction group demonstrated mechanical allodynia and thermal hyperalgesia. In measurement of the action potential, lower threshold current, more depolarized RMP, larger AHP, and prolonged APD50 were measured in the root constriction neurons compared with the sham group. The incidence of sustained burst was significantly higher in root constriction neurons. The Na current in root constriction neurons was markedly larger. There were no significant differences in K current density and voltage dependency. CONCLUSIONS: The constriction of lumbar root increased excitability and Na current amplitude of DRG neurons. These findings indicate that lumbar radicular pain may be associated with increased excitability of involved DRG neurons.

Action Potentials↗

PubMed2007

Plasma neuropeptides in patients undergoing lumbar discectomy.

STUDY DESIGN: A prospective analysis of patients with lumbar disc herniation (LDH). OBJECTIVES: To determine the role of neuropeptides as a biochemical signature of pain states in patients with LDH. SUMMARY OF BACKGROUND DATA: Increases in the plasma level of neuropeptides have been reported in patients suffering from a variety of painful conditions. However, there is no such report on patients with LDH. METHODS: From a total of 27 patients with a single-level LDH, blood samples were collected before and 3 weeks after lumbar discectomy. Plasma levels of alpha calcitonin gene-related peptide (CGRP), galanin, neuropeptide Y, and substance P were determined by using enzyme-linked immunosorbent assay. The association or correlation between preoperative concentration of plasma neuropeptides and gender, patients' age, and VAS were analyzed statistically. Also, the concentration of plasma neuropeptides was compared before and after lumbar discectomy. RESULTS: Preoperative plasma levels of CGRP were correlated significantly with the extent of sciatica as determined by VAS. In addition, plasma levels of CGRP and galanin significantly decreased after lumbar discectomy in line with the disappearance of pain symptoms. CONCLUSIONS: These findings indicate the role of plasma CGRP and possibly galanin as a systemic neurochemical signature of pain states in patients with LDH.

Adolescent↗

PubMed2007

Quantitative analysis of sensory functions after lumbar discectomy using current perception threshold testing.

A Neurometer device is an electrical nerve stimulator used to determine the current perception threshold (CPT) evoked by stimulating A-beta fibers at 2,000 Hz, A-delta fibers at 250 Hz and C fibers at 5 Hz. CPT evaluation is used for analyzing peripheral nerve dysfunction. In this study, the sensory disturbance of the lower-extremity was quantitatively analyzed using CPT testing before and after lumbar discectomy. In 33 patients (L4/5: 16 and L5/S: 17), as subjective evaluations, tactile sensation and leg pain were assessed before and 2 weeks after surgery. In the subjectively improved group (n = 22), significant decreases in CPT at 2,000 and 250 Hz were noted postoperatively, whereas in the unchanged group (n = 11), no significant changes in CPT at any frequencies was noted. The leg pain improved in all patients. Likewise, CPT at 5 Hz, which stimulated C fiber, decreased significantly for both improved and unchanged groups. CPT measured by a Neurometer is very useful in assessing lower-extremity sensory functions before and after surgery for lumbar disc herniation.

Adult↗

PubMed2006

Prognostic significance of HLA class I expression in osteosarcoma defined by anti-pan HLA class I monoclonal antibody, EMR8-5.

With the goal of establishing efficacious peptide-based immunotherapy for patients with bone and soft tissue sarcomas, we previously identified the cytotoxic T lymphocyte-defined osteosarcoma antigenic gene Papillomavirus binding factor. The present study was designed to determine the status of HLA class I expression in osteosarcoma and other bone and soft tissue sarcomas. Seventy-four formalin-fixed paraffin-embedded specimens of various bone and soft tissue sarcomas, including 33 osteosarcomas, were stained with the anti-HLA class I monoclonal antibody EMR8-5, which we recently generated. The expression of HLA class I was lost or downregulated in 46 of these specimens (62%). With respect to osteosarcoma, loss or downregulation of HLA class I expression was seen in 13 (52%) of 25 primary tumors and seven (88%) of eight metastatic tumors. In six of 11 HLA class I-negative osteosarcoma specimens, the expression of beta-2 microglobulin was also lost. Subsequently the prognostic significance of HLA class I expression was analyzed in 21 patients with osteosarcoma who had completed multidrug neoadjuvant chemotherapy and undergone adequate surgery. Patients with osteosarcoma highly expressing HLA class I showed significantly better overall and event-free survival than those with HLA class I-negative osteosarcoma. In contrast, such prognostic significance of HLA class I expression was not found in 15 patients with malignant fibrous histiocytoma of soft tissue. These findings suggest that the class I-restricted cytotoxic T lymphocyte pathway plays a major role in immune surveillance of patients with osteosarcoma.

Adolescent↗

PubMed2006

Piriformis syndrome resulting from a rare anatomic variation.

STUDY DESIGN: Case report. OBJECTIVES: We report a rare case of piriformis syndrome accompanying anatomic variation in the piriformis muscle and sciatic nerve. SUMMARY OF BACKGROUND DATA: Beaton classified anatomic variation in the piriformis muscle and sciatic nerve into 6 types based on cadaver studies. There has been no report in the English literature of surgical treatment for a case of piriformis syndrome accompanying Beaton type d anatomic variation. METHODS: A patient with sciatica showing no nerve root compression in lumbar MRI underwent pelvic MRI and perineurography of the sciatic nerve followed by CT. The findings in these images suggested piriformis syndrome accompanying anatomic variation of the piriformis muscle and sciatic nerve. Surgical treatment was performed. RESULTS: Surgical exploration of the piriformis muscle revealed Beaton type d anatomic variation. Both anterior and posterior lobes of the piriformis muscle were resected. The pain in the leg had completely disappeared after surgery. CONCLUSIONS: This is a very rare case of surgically treated piriformis syndrome resulting from type d anatomic variation in Beaton's classification. Pelvic MRI and perineurography of the sciatic nerve were useful for diagnosis in this case.

Buttocks↗

PubMed2006

Differential expression and subcellular localization of claudin-7, -8, -12, -13, and -15 along the mouse intestine.

Among tight-junction proteins, claudins, which play a key role in paracellular transport across epithelia, claudins 1 to 5 are expressed in the intestine, and changes in their abundance and/or distribution are considered to contribute to various gastrointestinal diseases. We investigated, by reverse transcription-PCR, immunoblot, and immunofluorescence analyses, which other claudin species were expressed in the mouse intestine, and whether they showed unique expression profiles. Rabbit polyclonal antibodies against mouse claudin-8, claudin-12, and claudin-15 were generated, and their specificity was verified by immunoblotting using COS-7 cells transfected with individual claudin cDNAs. Claudin-7, -8, -12, -13, and -15 appeared to be expressed in the duodenum, jejunum, ileum, and/or colon with remarkable variations in the expression levels along the intestinal tract, and had distinct subcellular localization in the intestinal epithelium. In addition, claudin-13 and -15 exhibited gradients along the crypt-surface axis of the colon. By contrast, claudin-6, -9, -10, -11, -14, -16, -18, and -19 were not observed in the intestine. Our results indicate that five additional species of claudins have very complex expression patterns along and within the intestine, and that this may reflect differences in paracellular permeable properties, providing valuable resources for studying the significance of these claudins in gastrointestinal disorders. This manuscript contains online supplemental material available at http://www.jhc.org. Please visit this article online to view these materials.

Animals↗

PubMed2006

CSN5/Jab1 inhibits cardiac L-type Ca2+ channel activity through protein-protein interactions.

L-type Ca(2+) channels have a wide tissue distribution and play essential roles in physiological responses. Recent studies have indicated that regulation of L-type Ca(2+) channels involves the assembly of macromolecular signaling complexes such as the beta(2)-adrenergic receptor signaling complex, the small G-protein kir/Gem and the BK channel. Here, we report the previously unidentified role of another protein in binding to the II-III linker of the alpha(1C) subunit of the L-type Ca(2+) channel. This protein is COP9 signalosome subunit 5 (CSN5)/Jun activation domain-binding protein 1 (Jab1). We have demonstrated that CSN5 interacts specifically with the II-III linker of the alpha(1C) subunit in a yeast two-hybrid system. The alpha(1C) subunit and CSN5 were coimmunoprecipitated in rat heart and both proteins were colocalized in sarcolemmal membranes and transverse tubules of cardiac myocytes. Silencing of CSN5 mRNA using siRNA decreased the endogenous protein level of CSN5 and activated L-type Ca(2+) channels expressed in COS7 cells. These data indicate that CSN5 is a protein that plays a newly defined functional role in association with the cardiac L-type Ca(2+) channel.

Animals↗

PubMed2006

HLA-restricted specific tumor cytolysis by autologous T-lymphocytes infiltrating metastatic bone malignant fibrous histiocytoma of lymph node.

Malignant fibrous histiocytoma (MFH) of the bone is a high-grade sarcoma characterized histologically by the composition of fibroblasts and pleomorphic cells with a prominent storiform pattern. Despite institution of multi-modality treatments, the prognosis for patients with this tumor remains unsatisfactory. In the present study, towards the goal of developing active immunotherapy for those affected, we established four cell lines from a 53-year-old woman who suffered from MFH of the humerus with lymph node metastases. MFH2003 and MFH2003-B7.1 were the primary lesion-derived cell line and its B7.1-transfectant, respectively. B2003-EBV and TIL2003 were a B cell line established from peripheral blood lymphocytes and a T cell line established from tumor-invaded lymph nodes, respectively. MFH2003 cells could be maintained over a period of 1 year in vitro, and could be xenotransplanted into nude mice. The phenotype of cells analyzed by immunostaining was similar to the original tumor. TIL2003 cells were all CD8+ and specifically recognized MFH2003 cells and MFH2003-B7.1 cells, but not B2003-EBV cells. An anti-HLA-class I monoclonal antibody completely blocked the anti-MFH2003 response of TILs2003. These findings indicate the existence of an anti-MFH specific immune response in the microenvironment of metastatic lymph nodes. The present autologous cell lines provide the basis for identification of novel tumor-associated antigens and may be helpful in the establishment of immunotherapy for patients with MFH of the bone.

Animals↗

PubMed2006

Scoliosis in cat cry syndrome.

BACKGROUND: Cat cry syndrome is an autosomal disease accompanying abnormal deletion of chromosome 5 and occurs in only 1 of 50,000 neonates. Scoliosis has been reported as a skeletal complication in cat cry syndrome. The characteristics and causes of scoliosis in this rare syndrome are unknown. The purpose of this study was to present the characteristics of scoliosis in cat cry syndrome and to speculate on its causative mechanisms. METHODS: We report on 11 cases (5 boys and 6 girls) of cat cry syndrome. Detailed investigations of scoliosis, as well as physical and imaging examinations, were performed to characterize scoliosis and its causes. Average age at initial diagnosis of scoliosis was 4.3 years, and average age at final examination was 11.8 years. RESULTS: The incidence of scoliosis was as high as 73% (8/11). Most cases show a single right thoracic curve. Of the 8 patients with scoliosis, 3 patients who had increased muscular tone showed marked progression of scoliosis with growth. CONCLUSIONS: Muscular hypertonia may play a key role in the progression of scoliosis in cat cry syndrome.

Child↗

PubMed2006

Underutilization of antiosteoporotic drugs by orthopedic surgeons for prevention of a secondary osteoporotic fracture.

BACKGROUND: Despite the availability of effective treatment and well-publicized treatment guidelines for preventing osteoporotic fractures, there are significant gaps in implementing the recommendations, and it is unknown how many patients are treated for prevention of secondary osteoporotic fractures. In this study, we investigate what percentage of osteoporosis patients were treated with antiosteoporotic drugs after osteoporotic fractures of the hip, wrist, and proximal humerus, and we discuss here the need for improvement in the treatment of osteoporosis following fracture. METHODS: We studied 422 patients with osteoporotic fractures, 91 men and 331 women, with an average age of 77.1 years (range, 52-102 years). The 422 cases consisted of 299 hip fractures, 97 distal radius fractures, and 26 proximal humerus fractures. All patients underwent surgical intervention. The variables were examined to ascertain whether osteoporosis patients were medicated with antiosteoporotic drugs at postfracture. RESULTS: Fifty-five (13%) of the 422 patients received antiosteoporotic medication at postfracture. Pharmaceutical treatment was given in 44 cases (14.7%) of hip fractures, 8 cases (8.2%) of distal radius fractures, and 3 cases (11.5%) of proximal humerus fractures. Thirty-one (7.3% of total) of the 55 patients were taking the same medication pre- and postfracture. Seven (1.7%) of the 55 were administered a different drug compared to before the fracture, and 17 (4%) started to take an antiosteoporotic drug for the first time subsequent to the fracture. CONCLUSIONS: The present rate of treatment is insufficient given the high risk of secondary fractures and the availability of appropriate drugs that would reduce that risk.

Aged↗

PubMed2006

Intraoperative measurement of pressure adjacent to the ulnar nerve in patients with cubital tunnel syndrome.

PURPOSE: Little is known about whether the pressure adjacent to the ulnar nerve actually is increased in patients with cubital tunnel syndrome or if it is a causative factor. We measured the pressure adjacent to the ulnar nerve in patients with cubital tunnel syndrome during surgery and verified whether or not there was an association with patient age, duration of the disease, motor nerve conduction velocity, and severity of the ulnar nerve neuropathy. METHODS: Eight elbows in 8 patients with an average age of 62 years were treated surgically and the extraneural pressures within the cubital tunnel were measured during surgery by using a fiberoptic microtransducer. Pressure was measured 3 times with the elbow fully extended and then 3 times with the elbow flexed 130 degrees. The transducers were placed at 1, 2, and 3 cm distal to the proximal edge of the Osborne ligament. The severity of the neuropathy was evaluated according to Akahori's classification. The ulnar nerve palsy was graded as stage III in 5 patients and as stage IV in 3 patients. RESULTS: The average pressures within the cubital tunnel at 1, 2, and 3 cm distal to the proximal edge of the cubital tunnel retinaculum with the elbow flexed were 105, 29, and 18 mm Hg, respectively. The pressures at 1 and 2 cm distal to the proximal edge of the cubital tunnel retinaculum were significantly higher in elbow flexion than in elbow extension. There was also a positive correlation between the pressure and patient age but this was not significant The pressures correlated significantly with the stage of ulnar nerve neuropathy, motor nerve conduction velocity, and disease duration. CONCLUSIONS: The extraneural pressure within the cubital tunnel actually was increased in the patients and compression of the ulnar nerve might be a causative factor of cubital tunnel syndrome.

Adult↗

PubMed2006

Pisotriquetral arthrosis after triquetral malunion: a case report.

We report a patient with chronic ulnar palmar wrist pain caused by malunion after isolated fracture of the triquetrum. Intra-articular malunion of the triquetrum body resulted in posttraumatic pisotriquetral arthrosis. The diagnosis was made by magnetic resonance imaging, computed tomography, bone scintigraphy, and wrist arthroscopy 5 months after the injury. The patient's symptoms were relieved by excision of the pisiform.

Adult↗

PubMed2006

Distal fibular length needed for ankle stability.

BACKGROUND: The fibula is commonly used for bone grafts. Previous clinical and biomechanical studies have suggested that the length of the residual portion of the distal part of the fibula has an important effect on the long-term stability of the ankle joint. However, we cannot find clear-cut guidelines for the amount of bone that can be harvested safely. METHODS: Using six normal fresh-frozen cadaver legs, motions of the tibia, talus and calcaneus were measured. The fibula was cut sequentially 3 cm from the proximal tip of the fibula and distally 10 cm, 6 cm, and 4 cm from the distal tip of the lateral malleolus. The angular motion of each bone was measured while a medial and lateral traction force of 19.6 N was applied to the proximal tibia. Angles of the tibia, talus, and calcaneus were measured. RESULTS: Sequential resection of the fibula increased the inversion angles of the ankle joint. The proximal 3-cm cut increased the inversion angle from 42.1 +/- 6.2 degrees to 49.6 +/- 3.6 degrees, and the distal 4-cm cut increased the angle from 57.6 +/- 6.6 degrees to 67.4 +/- 5.9 degrees. The rotational angles were almost constant with sequential resections of the fibula; however, the distal 4-cm cut increased the rotational angle from 11.3 +/- 25.1 degrees to 78.7 +/- 37.5 degrees. CONCLUSIONS: The whole fibula including the head is essential for the stability of the ankle joint complex, and the distal fibula is responsible for stabilizing the ankle mortise during external rotation and inversion. We recommend fixation of the syndesmosis or bracing to prevent ankle joint instability with rotation of the talus in the mortise, especially when the distal fibula is shortened 6 cm or more.

Aged↗

PubMed2006

[Bone and bone related biochemical examinations. Bone and collagen related metabolites. DPD (total, free)].

Urinary deoxypyridinoline (DPD) shows a high specificity for bone, and the measurement of DPD is not influenced by newly collagens and dietary intake. The measurement of free DPD is available by Japanese health insurance. Free DPD excretion above the upper limit of the premenopausal range was associated with increased hip fracture and osteoporotic fracture risk with approximately 2-folds. Total DPD is good predictor of change bone mineral density (BMD) in bone antiresorptive drugs, however, free DPD is inferior to type I -collagen N-telopeptide (NTX).

Amino Acids↗

PubMed2006

[Prospects of treatment using interferon for bone diseases].

Osteoblasts and osteoclasts produce a variety of cytokines to maintain bone homeostasis. One of the most important cytokines, receptor activator of nuclear factor-IkappaB ligand (RANKL), is essential for osteoclastogenesis. Recently, it was shown that activated T cells promote osteoclastogenesis through RANKL expression and also negatively affect osteoclastogenesis through interferon (IFN)-gamma production. Additionally, it was revealed that IFN-beta was involved in osteoclast regulation by signaling cross-talk with RANKL and that it contributed to the maintenance of normal bone mass. These studies indicate that there are complex regulatory interactions between bone-remodeling cells and immune cells, which depend on the balance between RANKL and IFN. Thus, the interaction between T cells and bone cells could be physiologically critical for the maintenance of normal bone metabolism, and IFN might be an attractive cytokine for use in therapy for bone disease in pathological bone resorptive conditions such as rheumatoid arthritis, osteoporosis, osteomyelitis and bone metastasis of cancers.

Bone Diseases, Metabolic↗

PubMed2006

[Adequate treatment with bisphosphonates for senile osteoporosis].

The characteristics of senile osteoporosis are as follows. (1) Bone turnover is not always decrease in senile osteoporosis. (2) Senile patients have urgent fracture risk, such as aging, prevalent fracture(s), low bone mass, and increasing bone turnover. (3) Most of patients are insufficient of calcium and vitamin D. The important things of the treatment for senile osteoporosis with bisphosphonates are (1) to take calcium and vitamin D sufficiently to avoid the excess secretion of parathyroid hormone, (2) to pay attention gastro-esophageal reflux disease, especially the patients with spinal deformity, and (3) to adhere the patient with treatment.

Adult↗

PubMed2005

A quest for therapeutic antigens in bone and soft tissue sarcoma.

Over the past three decades, there have been remarkable advances in the treatment of bone and soft tissue sarcomas. These include the introduction of adjuvant chemotherapy, establishment of guidelines for adequate surgical margins, and the development of post-excision reconstruction. There have also been advances in the field of immunotherapy against bone and soft tissue sarcomas, which, unfortunately, have received less attention. However, lack of progress in chemotherapy-based treatments for bone and soft tissue sarcomas has reignited interest in immunotherapeutic approaches. Here we summarize current progress in the immunotherapy of bone and soft tissue sarcomas including the strategies utilized to identify tumor-associated antigens, and the design of clinical trials.

Journal Article↗

PubMed2005

Expression of epidermal growth factor receptor, ERBB2 and KIT in adult soft tissue sarcomas: a clinicopathologic study of 281 cases.

BACKGROUND: Little is known about the expression of receptor tyrosine kinases in adult soft tissue sarcomas (STS). In the current study, the authors analyzed the expression of epidermal growth factor receptor (EGFR), ERBB2, and KIT in 281 patients with STS who were treated in a single institution. Verification of the presence of an association with prognosis was performed. METHODS: The current study included 281 adult patients with STS of the extremity and trunk who were diagnosed and treated in the National Cancer Center, Tokyo. Expression was assessed using immunohistochemical stains for EGFR, ERBB2, and KIT on formalin-fixed, paraffin-embedded tissue sections by standard avidin-biotin peroxidase complex technique and EGFR detection system. RESULTS: Positive staining of EGFR was observed in 168 of 281 (60%) patients. Positive staining was common in pleomorphic malignant fibrous histiocytomas (89%), myxofibrosarcomas (89%), synovial sarcomas (76%), malignant peripheral nerve sheath tumors (89%), and leiomyosarcomas (73%). It was less common in well differentiated liposarcomas (38%), fibrosarcomas (36%), and myxoid liposarcomas (6%). In contrast, positive staining of ERBB2 and KIT was very limited. Increased levels of EGFR were significantly associated with a decreased probability of overall survival (P = 0.01), although by univariate analysis; probability of overall survival at 5 years was 64% in patients with increased levels of EGFR and 79% in patients without such overexpression. The overexpression of EGFR was significantly associated with histologic grade (P < 0.001). Moreover, stratified log-rank test revealed that there is an interrelation between EGFR overexpression and histologic grade. CONCLUSIONS: EGFR overexpression was found to be a negative prognostic factor of adult STS, which is strongly associated with histologic grade. STS patients with EGFR overexpression may benefit from treatment with currently available biospecific inhibitors for EGFR.

Adult↗