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Biomedical subjects

Tomomi Kusumi

Publications and source records attributed to Tomomi Kusumi.

13 recordsLinked to original sources

Utility of immunohistochemical analysis for cyclo-oxygenase 2 in the differential diagnosis of osteoblastoma and osteosarcoma.

AIMS: To study the immunoexpression of cyclo-oxygenase (COX) 2 in osteoblastomas (OBs) and osteosarcomas (OSs), and to assess the utility of immunohistochemical analysis for COX 2 in the differential diagnosis of the two tumour forms. METHODS: The immunohistochemical features of COX 2 were studied in 11 OBs and 30 OSs, including 26 high-grade OSs (16 osteoblastic, 7 chondroblastic, and 3 fibroblastic) and 4 low-grade OSs. RESULTS: Tumour cells from all 11 OBs unequivocally showed diffuse, intense and cytoplasmic immunoreactivity for COX 2. Strong cytoplasmic expression of COX 2 was observed in 5 of 26 (19%) high-grade OSs, all chondroblastic. In one osteoblastic-type OS, COX 2 was expressed in the chondroblastic component, but this tumour was considered to be COX 2 negative. No COX 2 expression was noted in atypical osteoblastic cells. Staining in the four low-grade OSs was negative. CONCLUSION: The results of immunohistochemical analysis of COX 2 suggest that in addition to the routine histopathological evaluation, COX 2 is a valuable diagnostic marker in the distinction between OB and OS.

Adolescent↗

Pretibial cyst formation after anterior cruciate ligament reconstruction with a hamstring tendon autograft.

We report a case of pretibial cyst formation, which is a rare complication, after anterior cruciate ligament (ACL) reconstruction. The patient had undergone ACL reconstruction at age 18 and complained of pain and swelling localized on the anteromedial aspect of the ipsilateral proximal tibia 2 years postoperatively. Magnetic resonance imaging showed a multilocular fluid-filled cyst arising from the outlet of the tibial bone tunnel. Open resection of the cyst was performed and communication between the tibial tunnel and the joint space was confirmed arthroscopically. The cavity of the tibial tunnel was packed with cancellous bone to seal off a water channel. The laboratory examination revealed slightly concentrated chondroitin sulfate in the cyst fluid compared with the articular fluid, despite histologic observation of no glycosaminoglycan synthesis in the cells of the cyst wall. These findings indicated that leakage of the articular fluid via the tibial tunnel might have caused the pretibial cyst after ACL reconstruction.

Absorbable Implants↗

Co-localization of beta-peptide and phosphorylated tau in astrocytes in a patient with corticobasal degeneration.

The co-localization of amyloid beta (Abeta) and phosphorylated tau in astrocytes in a patient with corticobasal degeneration is described. At autopsy, the present case exhibited neuropathological findings compatible with those of corticobasal degeneration, including atrophy of the frontal and temporal lobes, neuronal loss and gliosis in the cortical and subcortical regions, and presence of cortical ballooned neurons and astrocytic plaques. Moreover, many senile plaques were found in the cerebral cortex. There were also clusters of Abeta-positive granules associated with astrocytic cytoplasm and processes in the subiculum and entorhinal cortex. In the entorhinal cortex, the Abeta-positive granules were occasionally co-localized with phosphorylated tau-positive fibrillary structures in the astrocytic cytoplasm. To our knowledge, this is the first demonstration of co-localization of Abeta and phosphorylated tau in astrocytes. This phenomenon implies that phagocytosis of Abeta coincides with production of phosphorylated tau in the same reactive astrocytes.

Amyloid beta-Peptides↗

Osteochondritis dissecans of the elbow: histopathological assessment of the articular cartilage and subchondral bone with emphasis on their damage and repair.

Osteochondritis dissecans (OCD) of the elbow is a localized injury of the articular cartilage and subchondral bone that is commonly seen in the young athlete. In the present study, the extent of damage and repair on the articular cartilage and subchondral bone was examined histologically using specimens of 25 osteochondral cylinders and seven loose bodies obtained from 25 young athletes who had undergone osteochondral autograft surgery. Terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling (TUNEL) assays for detecting apoptotic cells and immunohistochemistry of matrix metalloproteinases (MMP) were performed on the osteochondral cylinder specimens. The histological findings of the OCD of the elbow showed that the articular cartilage exhibited degenerative change, mimicking osteoarthritis, and was markedly damaged as the lesion progressed. TUNEL-positive cells and MMP-3- and -13-expressing cells were distributed in the degenerative articular cartilage and reparative fibrocartilage tissue. Separation occurred at either the deep articular cartilage or the subchondral bone, with the former being dominant in the early OCD lesions. The present results suggest that the primary pathological changes in OCD of the elbow were due to damage of articular cartilage induced by repeated stress following degenerative and reparative process of articular cartilage and subchondral fracturing, and separation subsequently occurred on the cartilage and developed onto the subchondral bone in its advanced stages.

Adolescent↗

57Arg in the bHLH transcription factor DEC2 is essential for the suppression of CLOCK/BMAL2-mediated transactivation.

The basic helix-loop-helix (bHLH) transcription factors, DEC2 and DEC1, play critical roles in the circadian rhythm of the suprachiasmatic nucleus (SCN). It is known that mammalian circadian rhythms are regulated by molecular clockwork systems based on a negative-feedback loop, and CLOCK/BMAL1 and CLOCK/BMAL2 enhance DEC2 transcription via CACGTG E-boxes. To understand the role of arginine 57 ((57)Arg) within the basic region of DEC2, we examined the effect of substituting this residue into DEC2 on CLOCK/BMAL2-mediated transactivation. A luciferase assay showed that substituting (57)Arg for Ala or Lys in DEC2 diminished the suppressive activity of wild-type DEC2 on CLOCK/ BMAL2-mediated transactivation, while substituting (48)Pro for Ala in DEC2 did not alter it, and the same was true for wild-type DEC2. We also showed that proteins which were wild-type and substitution mutants of DEC2 were expressed at nearly equivalent levels by Western blotting. These findings demonstrate that (57)Arg in the basic region of DEC2 is essential for its activity in suppressing CLOCK/BMAL2-mediated transactivation.

ARNTL Transcription Factors↗

[Pathology of bone diseases in elderly subjects].

In elderly persons, structural changes occur in bone tissue. The bone histology and histomorphometry demonstrate that the trabecular volume and thickness are reduced and trabecular connection is disrupted in cancellous bone, and that the cortical layer becomes thinner and the bone lacuna is enlarged in compact bone. These features become more serious in osteoporotic patients. Even weak forces can cause fragility fractures in osteoporotic patients. However, a prolonged period is not always required for fracture healing in elderly patients. Elderly persons can suffer from many disorders, such as osteomalacia, bone diseases associated with joint diseases and bone tumors.

Aged↗

Regulation of synthesis of osteoprotegerin and soluble receptor activator of nuclear factor-kappaB ligand in normal human osteoblasts via the p38 mitogen-activated protein kinase pathway by the application of cyclic tensile strain.

Mechanical stress is thought to play an important role in bone remodeling. However, the correlation between mechanical stress and bone remodeling is poorly understood. In this context, using a model of cyclic tensile strain (CTS) toward human osteoblasts, synthesis of osteoprotegerin (OPG) and soluble receptor activator of nuclear factor-kappaB ligand (sRANKL), and the activation of mitogen-activated protein kinases (MAPKs) were examined. The application of 7%, 0.25-Hz CTS once a day for 4 h for 3 successive days simultaneously caused an increase of OPG synthesis and a decrease of sRANKL release and RANKL mRNA expression in osteoblasts. As for MAPKs activation in osteoblasts with the application of CTS, p38 MAPK was activated 10-20 min after the application of CTS, but extracellular signal-regulated kinase (ERK1/2) and c-Jun NH2-terminal kinase (JNK) were not activated by such application. Furthermore, when CTS was applied once a day for 4 h for 1, 2, or 3 successive days to osteoblasts, p38 MAPK activation was maintained during the 3-day period but ERK1/2 activation was downregulated from day to day, simultaneously. Then, when CTS was applied once a day for 4 h for 3 successive days to osteoblasts pretreated with the p38 MAPK inhibitor SB203580 for 1 h, OPG synthesis was dose-dependently suppressed and inhibition of sRANKL release and RANKL mRNA expression was abrogated. These results indicate that biological responses of OPG and sRANKL synthesis in osteoblasts to the application of CTS are regulated via the p38 MAPK pathway and suggest that CTS might modulate and regulate bone metabolism.

Blotting, Western↗

Low-grade fibromyxoid sarcoma arising in the big toe.

Low-grade fibromyxoid sarcoma (LGFMS) is a rare tumor. Reported herein is a case of LGFMS arising in the big toe. The patient was a 58-year-old man who underwent excision of the tumor. The tumor was well-demarcated. Histologically, there were proliferating spindle-shaped tumor cells arranged in a whorled growth pattern, and the stroma showed hyalinized collagen bundles and a myxoid matrix. Nuclear mitotic figures were conspicuous in part. A large rosette-like structure with hyalinized stroma was found, which is characteristic of LGFMS. The differential diagnosis included tumor occurrence in adults; tending to arise in distal extremities; and having bland fibromyxoid histological features, such as fibroma of tendon sheath, low-grade myxofibrosarcoma and acral myxoinflammatory fibroblastic sarcoma. It was not possible to detect the FUS/CREB3L2 and FUS/CREB3L1 fusion genes from the formalin-fixed and paraffin-embedded tissue, although the histological features of the present case were typical of LGFMS. LGFMS may become more common with time, and unique cases may accumulate.

Diagnosis, Differential↗

Split lesions of the peroneus brevis tendon in the Japanese population: an anatomic and histologic study of 112 cadaveric ankles.

Split lesions of the peroneus brevis tendon are believed to be rare and have received little attention in populations of Asian countries. The purpose of this study was to investigate the incidence of split lesions in the Japanese population. The peroneus tendons of 112 ankles from 30 male and 26 female adult human embalmed cadavers with an average age of 76.9 years (range, 55-93) were dissected. The presence of split lesions, determined by either thinning or longitudinal splitting of the peroneus brevis tendon, was examined. Forty-two ankles (37.5%) had split lesions, of which 21 (50%) showed a thinning appearance without splitting, and 12 (28.6%) had well-defined, full-thickness longitudinal tears. The incidence of split lesions of the peroneus brevis tendon in the Japanese population was similar to that in studies of the U.S. population, but the condition of the lesions was less severe. Although the clinical presence is expected to be extremely rare, we must consider a neglected split lesion of the peroneus brevis tendon when residual pain is observed in the retrofibular location.

Aged↗

An immunohistochemical evaluation of extracellular matrix components in the spinal posterior longitudinal ligament and intervertebral disc of the tiptoe walking mouse.

Ossification of the posterior longitudinal ligament (OPLL) in the spine is caused by systemic and/or regional factors affecting the regulation of osteocartilaginous formation and maintenance. The aims of this study were to elucidate the relationship between the degeneration of the intervertebral discs and changes in the posterior longitudinal ligament (PLL) in the tiptoe walking (ttw) mouse, an animal model of OPLL, and to analyze the sequential changes of the cells producing extracellular matrix components using immunohistochemical methods. At 6 weeks of age, the discs degenerated and the chondrocytes in the nucleus pulposus were positive for chondroitin-6-sulfate in the ttw mice. The fibroblasts in the PLL at the disc level were positively stained with type II and XI collagens. At 14 weeks, the discs herniated into the thickened PLL, and chondrocyte-like cells appeared in the PLL at vertebral endplate level. At 18 and 22 weeks, the number of chondrocyte-like cells increased in the PLL and expressed type I collagen. A potent regional factor causing OPLL in the ttw mice appears to be the initial degeneration and subsequent herniation of the nucleus pulposus. These sequential changes in the ttw mice were accelerated by administration of etidronate. It was suggested that etidronate stimulated the cartilaginous hyperplasia in the PLL of the ttw mice. It appeared as if the PLL transformed itself into cartilaginous tissue to repair the degeneration of the intervertebral disc.

Animals↗

Induction of differentiation and peroxisome proliferator-activated receptor gamma expression in colon cancer cell lines by troglitazone.

PURPOSE: We investigated the relationship between the effects of troglitazone (TGZ) on cellular growth, differentiation and apoptosis induction, and the induction of peroxisome proliferator-activated receptor (PPAR) gamma in three human colon cancer cell lines, HCT-15, DLD-1and LoVo. METHODS: Viable cell number was evaluated by the Alamar blue assay and apoptotic cell death by TUNEL methods. Expression of PPARgamma mRNA and protein was examined by reverse transcription-polymerase chain reaction (RT-PCR) and Western blot, respectively. The differentiation markers of colonic mucosa, villin and MUC2 mRNAs, were analyzed by real-time RT-PCR. RESULTS: HCT-15 and DLD-1 cells proliferated rapidly while LoVo cells grew slowly. TGZ dose-dependently inhibited the proliferation of all the cell lines, and also induced apoptotic cell death. High expression of PPARgamma mRNA and protein was demonstrated in DLD-1 and LoVo cells before TGZ treatment. After the treatment, PPARgamma mRNA and protein levels were increased in HCT-15 and LoVo cells. Villin and MUC2 mRNAs were increased by TGZ treatment in HCT-15 cells while villin mRNA was repressed in LoVo cells. Changes in expression of PPARgamma, villin or MUC2 mRNAs were not observed in DLD-1 cells. CONCLUSIONS: These results suggest that PPARgamma levels are not correlated with the rates of cell proliferation. Differentiation induction by TGZ was only observed in the cell lines with enhanced PPARgamma expression.

Apoptosis↗