Yong-Wook Park

Expression of RANKL and OPG in middle ear cholesteatoma tissue.

Objectives: The objective of this study was to investigate how the expression of the RANK‐RANKL‐OPG system mediates the formation and differentiation of osteoclasts and causes bone resorption in cholesteatoma.

Correlation of Vascular Endothelial Growth Factor-D Expression and VEGFR-3-Positive Vessel Density with Lymph Node Metastasis in Gastric Carcinoma

Lymph node metastasis is an important prognostic factor in gastric cancer. Vascular endothelial growth factor-D (VEGF-D) is a lymphangiogenic growth factor that activates VEGF receptor (VEGFR)-3, a receptor expressed in the lymphatic endothelium. We investigated the clinical value of VEGF-D expression and VEGFR-3 positive vessel density in gastric carcinoma with regard to lymphangiogenesis. Immunohistochemical staining was used to determine the expression of VEGF-D and VEGFR-3 in specimens from 104 cases of resected gastric cancer. VEGF-D expression was observed in 62.5% of the gastric cancers and in 9.6% of the non-neoplastic gastric tissue. The VEGFR-3-positive vessel density was significantly greater in the VEGFD positive group than the negative group. VEGF-D expression was significantly associated with lymph node metastasis, increased serum CEA levels, and the non-signet ring cell type. The VEGFR-3-positive vessel density was correlated with tumor size, lymphatic invasion, and lymph node metastasis. The VEGF-D expression and high VEGFR-3-positive vessel density were significant poor prognostic factors for relapse-free survival. These results suggest that VEGF-D and VEGFR-3-positive vessel density are potential molecular markers that predict lymphatic involvement in gastric carcinoma.

Actinomycin D renders cultured synovial fibroblasts susceptible to tumour necrosis factor related apoptosis‐inducing ligand (TRAIL)‐induced apoptosis

Objective: To investigate the expression of tumour necrosis factor (TNF)‐related apoptosis‐inducing ligand (TRAIL) receptors in cultured synovial fibroblasts from rheumatoid arthritis (RA) and osteoarthritis (OA) patients, and to examine their susceptibility to TRAIL‐induced apoptosis in the presence or absence of metabolic inhibitors. Methods: The expression of TRAIL receptors in synovial fibroblasts was examined by Western blot and immunohistochemistry. Expression of TRAIL‐receptor 1 (TRAIL‐R1), FLICE‐inhibitory protein (Fas‐associating protein with death domain‐like interleukin‐1‐converting enzyme), and Bcl‐2 was assessed by Western blot. Synovial cell viability was measured by 2,3‐bis(2‐methoxy‐4‐nitro‐5‐sulfophenyl)‐2H‐tetrazolium‐5‐carboxanilide assay (XTT), and apoptosis was determined both by DNA content analysis after propidium iodide staining and Annexin V stain. Results: TRAIL‐R1 was constitutively expressed on cultured synovial fibroblasts from RA and OA, however, expression of TRAIL‐R2 and TRAIL‐R3 was not observed by immunohistochemistry and Western blot. Cultured synovial fibroblasts were resistant to apoptosis by TRAIL alone, but combined treatment of TRAIL with actinomycin D (ActD: 200 ng/mL), cycloheximide (CHX: 10 μg/mL), or proteasome inhibitor (MG132: 20 μM) induced apoptosis in a dose‐dependent manner. The apoptosis was completely or partially inhibited by various caspase inhibitors, implicating an involvement of caspase pathway in TRAIL‐induced apoptosis in the presence of these metabolic inhibitors. Expression of TRAIL‐R1, FLIPL, and Bcl‐2 did not account for the apoptosis by the combined treatment of TRAIL with ActD. Conclusions: Although TRAIL‐R1 was constitutively expressed; cultured synovial fibroblasts were resistant to apoptosis by TRAIL. ActD, CHX, and MG132 rendered cultured synovial fibroblasts susceptible to TRAIL‐induced apoptosis by a caspase‐dependent mechanism. However, the exact mechanism of sensitization by these metabolic inhibitors remains to be determined.

A case of the hyperkeratotic variant of porokeratosis Mibelli

Herein, we report a case of the hyperkeratotic variant of porokeratosis Mibelli. A 58‐year‐old woman presented with two brownish verrucous plaques on the buttock for 20 years, and extremely hyperkeratotic verrucous nodules and brownish macules on the right foot for 1 year. Histopathological findings of the buttock were typical of porokeratosis. However, histopathological findings of the right foot were atypical for porokeratosis, including extreme hyperkeratosis and an increased number of and unusual sized cornoid lamellae.

Absence of Clinical Prognostic Value of Vascular Endothelial Growth Factor and Microvessel Density in Multiple Myeloma

Vascular endothelial growth factor (VEGF) is considered a potent stimulator of angiogenesis. In multiple myeloma (MM), it has been reported that bone marrow angiogenesis parallels tumor progression and correlates with a poor prognosis. To investigate the role of angiogenesis in MM, we investigated VEGF expression and microvessel density (MVD) in the bone marrow of 75 MM patients by immunohistochemical methods. VEGF expression was observed in 87.3% (62 of 71) of patients. MVD was 69.42 ± 9.67 (mean ± SE) compared with the normal control values of 26.81 ± 2.85. MVD values were 73.98 ± 11.27 and 36.04 ± 6.99 in the VEGF-positive and VEGF-negative groups, respectively. The MVD of patients in the VEGF-positive group was significantly higher than in the VEGF-negative group (P = .045). However, there were no significant differences in various clinical parameters, such as age, sex, hemoglobin, platelet count, serum levels of albumin, calcium, creatinine, and β2-microglobulin, and bone marrow plasma cell percentage, between the VEGF-positive and VEGF-negative groups. Multivariate analysis revealed that age, hemoglobin, platelet count, serum levels of albumin and creatinine, and bone marrow plasma cell percentage were correlated with overall survival, whereas VEGF expression or MVD was not. In conclusion, our results suggest that VEGF is highly expressed and that MVD is increased in MM, indicating that angiogenesis may play a role in MM. Although MVD in the bone marrow of the VEGF-positive group is significantly higher compared with the VEGF-negative group (P = .045), VEGF is not correlated with overall survival. Further studies that include other angiogenic factors are needed to determine the functional role of angiogenesis in MM. Int J Hematol. 2002;76:460-464.

A Case of Erythema Nodosum and Serositis Associated with Myelodysplastic Syndrome

Myelodysplastic syndrome (MDS) is a heterogenous group of stem cell disorders usually characterized by progressive refractory cytopenias, which could progress to acute myeloid leukemia. MDS may be associated with a wide spectrum of skin lesions, including neoplastic cell infiltration, Sweets syndrome, pyoderma gangrenosum, erythema elevatum diutinum, vasculitis, and panniculitis. However, erythema nodosum is rarely associated with MDS. Unusual rheumatologic manifestations in patients with MDS also have been reported, which range from asymptomatic serological abnormalities to classic connective tissue disorders such as Sjogrens syndrome, relapsing polychondritis, systemic lupus erythematosus, rheumatoid arthritis and mixed connective tissue disease. However, concurrent erythema nodosum and serositis has rarely been reported. We describe a case of MDS with erythema nodosum and immune-mediated pericardial effusion in a 34-year-old woman.

Macrophagic myofasciitis unrelated to vaccination

Macrophagic myofasciitis (MMF) is known to be closely associated to vaccination containing aluminium as an adjuvant. Here we describe a case of MMF unrelated to vaccination, and presented as focal tender muscle in a 59‐year‐old woman. Magnetic resonance imaging showed evidence of unilateral myofasciitis involving muscles and fascias of the vastus lateralis. Open biopsy showed a unique pathological pattern of MMF. Our case suggests that other causes unrelated to vaccination need to be investigated in the pathogenesis of MMF, and MMF could be considered in the differential diagnosis of patients with focal muscle tenderness.

A Case of Childhood Generalized Pustular Psoriasis Treated with Dapsone

Acute generalized pustular psoriasis (GPP) is a rare, sometimes fatal, exudative form of psoriasis characterized by acute febrile pustular psoriasis. Unlike the adult forms, GPP in childhood tends to undergo a more benign course. It may resolve spontaneously with only supportive treatment, but may sometimes be life threatening and resistant to therapy. We report a case of GPP in 7‐year‐old girl treated successfully with dapsone.

Angiotensin-Converting Enzyme Gene Insertion/Deletion Polymorphism in Korean Patients with Systemic Sclerosis

To determine whether angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism is associated with the development and clinical features of systemic sclerosis (SSc) in Korean, we studied seventy two Korean patients with SSc fulfilling the ACR preliminary classification criteria. The controls were 114 healthy, disease free Koreans. ACE I/D genotypes were determined by PCR method using oligonucleotides. Sixty eight patients (94.4%) were women and age at diagnosis was 43.5±12.6 yr old (mean±SD). Thirty nine patients (54.2%) had a diffuse type of SSc. There were no statistical differences in the frequencies of all ACE I/D genotypes and D allele between patients and controls, and neither between diffuse and limited types of SSc. ACE I/D gene polymorphism was not associated with the development of SSc in Korea. The investigation for the pathogenesis of SSc requires more studies about the role of other candidate genes such as endothelin, TGF-β, nitric oxide, or angiotensin II receptor in addition to the ACE genes.

Retained surgical sponge presenting as a pelvic tumor after 25 years

A surgical sponge left in the abdominal cavity may remain asymptomatic for a long period. When a foreign granuloma reaction is reactivated, it can cause the clinical symptoms and signs of a rapidly growing pelvic tumor. A 63-year-old diabetic woman was referred from a private clinic because of a rapidly growing pelvic mass and intermittent abdominal pain for several months. She had a history of right salpingectomy for tubal pregnancy 25 years before. Sonography showed an echogenic solid pelvic tumor with no cystic component. Pelvic CT revealed a welldemarcated mass with homogenous internal echo. Within the mass, a focally enhanced small area was noted (Fig. 1). At operation, the tumor was removed with segmental resection of the ileum due to severe bowel adhesions. On gross examination, the tumor had a well-developed glistening capsule and most of the internal content was filled with amorphous necrotic materials and cotton fibers of gauze were noted in the central area (Fig. 2). Microscopically, eosinophilic amorphous necrotic material with an area of foreign body