Iron deficiency anemia (IDA) and megaloblastic anemia due to vitamin B12 deficiency are well-characterized prototypes of anemia. There is no doubt that IDA is the most common hematologic disorder in Korea and worldwide as well. The diagnosis and treatment of IDA is not a difficult practice usually, however, a caution is required in detecting early-stage iron deficiency and in distinguishing IDA from anemia of chronic disorders such as chronic inflammatory disease, malignancies, chronic liver disease, and chronic renal disease. Administration of a standard iron preparation at a proper dosage over an adequate period is a prerequisite for the successful treatment of IDA, which is sometimes overlooked by both physicians and patients. Early detection and treatment as well as prevention of iron deficiency per se are also required. Pernicious anemia is the most common cause of vitamin B12 deficiency in Western populations. By contrast, the disorder is rare in Korea, although the number of cases seems to be increasing these days. The majority of patients with megaloblastic anemia reveal a history of gastrectomy. Thus, it should be reminded that vitamin B12 supplementation is important to prevent the development of overt deficiency or anemia in these susceptible individuals, since a delay in the treatment of vitamin B12 deficiency may result in an irreversible neurologic deficit.
Anemia* ; Anemia, Iron-Deficiency ; Anemia, Megaloblastic ; Anemia, Pernicious ; Diagnosis ; Gastrectomy ; Humans ; Iron ; Korea ; Liver Diseases ; Neurologic Manifestations ; Renal Insufficiency, Chronic ; Vitamin B 12 ; Vitamin B 12 Deficiency

No abstract available.
Plasmacytoma

This study investigated the production of stromal cell-derived factor-1 (SDF-1) and the expression of CXCR4 in human bone marrow endothelial cells (BMECs). Human BMEC cell line BMEC-1 cells expressed SDF-1 mRNA, and conditioned medium induced chemoattraction of CD34+ cells. Migration was not inhibited by pretreating the input cells with pertussis toxin, indicating that the chemoattractive activity was not dependent on SDF-1. Three-day culture of BMEC-1 and primary human BMEC cells produced 1,710+/-204 and 1,050+/-153 pg/mL SDF-1alpha, respectively, which was much less than primary human BM stromal cells (29,536+/-532 pg/ mL). By immuno-histochemistry, CXCR4 was detected in the endothelial cells lining sinusoids, arterioles, and venules in the bone marrow. However, cultured BMECs and BMEC-1 cells did not express CXCR4 on their surfaces. These results indicate that BMECs produce and release small amounts of SDF-1 and express CXCR4 in vivo only.
Antigens, CD34/biosynthesis ; Bone Marrow Cells/*metabolism ; Cell Movement ; Cells, Cultured ; Chemokines, CXC/*biosynthesis ; Chemotaxis ; Culture Media, Conditioned/pharmacology ; Endothelial Cells/*metabolism ; Enzyme-Linked Immunosorbent Assay ; Flow Cytometry ; Hematopoietic Stem Cells/metabolism ; Human ; Immunohistochemistry ; Pertussis Toxin/pharmacology ; RNA, Messenger/metabolism ; Receptors, CXCR4/*biosynthesis ; Reverse Transcriptase Polymerase Chain Reaction ; Support, Non-U.S. Gov't ; Time Factors ; Umbilical Veins/cytology

Multiple solitary plasmacytoma is a very rare disease entity, which occurs in up to 5% of patients with solitary plasmacytomas. We report an atypical case of multiple solitary plasmacytoma that recurred in multiple visceral organs without any evidence of bone marrow involvement. A 68-year-old male presented with voiding difficulty. Twenty months earlier, he had been placed on local radiotherapy for solitary plasmacytomas in the right 6th rib and right iliac bone. Recurrences were noted 14 and 12 months later in several ribs and the 5th cervical vertebra, respectively. These were well controlled with local radiotherapy and conventional systemic chemotherapy. He had multiple soft tissue masses in the stomach, pancreas, pelvic cavity, and right buttock. An endoscopic biopsy of the gastric mass confirmed the diagnosis of plasmacytoma. Local radiotherapy to the pelvic mass and systemic therapy consisting of bortezomib and dexamethasone were given, and he has been well for 8 months.
Aged ; Biopsy ; Bone Marrow ; Boronic Acids ; Buttocks ; Dexamethasone ; Humans ; Male ; Pancreas ; Plasmacytoma ; Pyrazines ; Rare Diseases ; Recurrence ; Ribs ; Spine ; Stomach ; Viscera ; Bortezomib

We report a 62-year-old woman with multiple myeloma associated with cryoglobulinemia accompanied by gangrene of the digits. She presented with generalized purplish net-like discoloration (livedo reticularis), which was more prominent in the lower extremities. Multiple small shallow ulcers with crusts were found in places. In addition, gangrene was observed in both ear helices, both index fingers, and several toes. The patient had monoclonal gammopathy consisting of IgG and kappa (3.95 g/dL), cryoglobulinemia, and bone marrow plasmacytosis (42%). A biopsy of a discolored skin patch on the lower leg revealed leukocytoclastic vasculitis. She was diagnosed with multiple myeloma associated with cryoglobulinemia. Immediate plasmapheresis halted the progression of the skin lesions and digital gangrene. Two cycles of thalidomide plus dexamethasone therapy led to a partial response. This case highlights the need to search for cryoglobulinemia and multiple myeloma when we see livedo reticularis or multiple skin ulcers with obscure causes.
Biopsy ; Bone Marrow ; Cryoglobulinemia ; Dexamethasone ; Ear ; Female ; Fingers ; Gangrene ; Humans ; Immunoglobulin G ; Leg ; Livedo Reticularis ; Lower Extremity ; Middle Aged ; Multiple Myeloma* ; Paraproteinemias ; Plasmapheresis ; Skin ; Skin Ulcer ; Thalidomide ; Toes ; Ulcer ; Vasculitis*

PURPOSE: The chemokine receptor CXCR4 plays a role in the metastasis and progression of a broad range of malignant tumors; however, its influence on hepatocellular carcinoma (HCC) is not well defined. Thus, we analyzed the expression of CXCR4 and its functions in HCC cell lines in vitro. MATERIALS AND METHODS: Five HCC cell lines (HepG2, Hep3B, SK-HEP-1, NCI-H630 and PLC/PRF5) were investigated. The CXCR4 expression was analyzed by RT-PCR, Western blotting, flow cytometry and immunofluorescence staining. In addition, the effects of stromal cell-derived factor-1 (SDF-1) on the migration, proliferation and survival of the cells were investigated, as well as the SDF-1-induced phosphorylation of signaling molecules. RESULTS: All five cell lines had abundant CXCR4 in their cytoplasm, whereas a cell surface CXCR4 expression was only detected in a very small population of PLC/ PRF5 cells. In contrast, SDF-1 bound to all the cells. SDF-1 induced the phosphorylation of AKT and ERK1/2 in the PLC/PRF5 cells and the phosphorylation of Stat3, AKT and ERK1/2 in the Hep3B cells. Nonetheless, SDF-1 did not induce migration or proliferation in any of the cells, nor did it rescue the cells from serum deprivation-induced apoptosis. Recruitment of CXCR4 from the cytoplasm to the cell surface was not elicited by dexamethasone, proinflammatory cytokines or VEGF. Hypoxia increased both the cytoplasmic and cell surface expressions of CXCR4 in only the PLC/PRF5 cells. CONCLUSIONS: CXCR4 is trapped in the cytoplasm and it is not recruited to the cell surface by standard extrinsic stimuli in the majority of HCC cell lines, and the result of this is a negligible response to SDF-1.
Anoxia ; Apoptosis ; Blotting, Western ; Carcinoma, Hepatocellular ; Cell Line ; Cytokines ; Cytoplasm ; Dexamethasone ; Flow Cytometry ; Fluorescent Antibody Technique ; Neoplasm Metastasis ; Phosphorylation ; Vascular Endothelial Growth Factor A

PURPOSE: The aim of this study is to determine the diagnostic and prognostic role of baseline spinal magnetic resonance imaging (MRI) in patients with multiple myeloma. MATERIALS AND METHODS: We enrolled patients newly diagnosed with multiple myeloma from 2004-2011 at a single center. Abnormal MRI findings that were not detected in radiographs have been analyzed and categorized as malignant compression fractures or extramedullary plasmacytoma. The bone marrow (BM) infiltration patterns on MRI have been classified into five categories. RESULTS: A total of 113 patients with a median age of 65 years (range, 40 to 89 years) were enrolled in the study. Malignant compression fractures not detected in the bone survey were found in 26 patients (23.0%), including three patients (2.6%) with no related symptoms or signs. Extramedullary plasmacytoma was detected in 22 patients (19.5%), including 15 (13.3%) with epidural extension of the tumor. Of these 22 patients, 11 (50.0%) had no relevant symptoms or signs. The presence of malignant compression fractures did not influence overall survival; whereas non-epidural extramedullary plasmacytoma was associated with poor overall survival in the multivariate analysis (hazard ratio, 3.205; 95% confidence interval [CI], 1.430 to 9.845; p=0.042). During the follow-up for a median of 21 months (range, 1 to 91 months), overall survival with the mixed BM infiltrative pattern (median, 24.0 months; 95% CI, 22.9 to 25.1 months) was shorter than those with other patterns (median 56 months; 95% CI, 48.9 to 63.1 months; p=0.030). CONCLUSION: These results indicate that spine MRI at the time of diagnosis is useful for detecting skeletal lesions and predicting the prognosis in patients with multiple myeloma.
Bone Marrow ; Diagnosis* ; Follow-Up Studies ; Fractures, Compression ; Humans ; Magnetic Resonance Imaging* ; Multiple Myeloma* ; Multivariate Analysis ; Plasmacytoma ; Prognosis ; Spine*

Plasmacytoma in patients with multiple myeloma usually develops in the advanced stage of the disease. We report herein an atypical case of extramedullary relapse of multiple myeloma that presented as mechanical obstruction of the small bowel in a patient who had achieved complete remission after chemotherapy. A 75-year-old man was diagnosed with multiple myeloma 25 months previously and treated with a bortezomib-containing chemotherapy regimen. He presented for evaluation of abdominal pain. A circumferential mass resulting in mechanical ileus was observed by abdominal computed tomography. Biopsy after surgical resection confirmed the diagnosis of plasmacytoma. The patient was subsequently treated with thalidomide-containing chemotherapy, but he died of disease progression after 6 months. We suggest careful observation of unusual relapses of multiple myeloma in patients who have achieved complete remission after antimyeloma therapy.
Abdominal Pain ; Aged ; Biopsy ; Diagnosis ; Disease Progression ; Drug Therapy ; Humans ; Ileus ; Intestinal Obstruction ; Multiple Myeloma* ; Plasmacytoma ; Recurrence*

PURPOSE: AMD3100, an antagonist of the CXCR4 chemokine receptor is soon to be used clinically for the peripheral mobilization of hematopoietic stem cells (HSCs) in patients with multiple myeloma. AMD3100 has been shown to activate a G protein coupled with CXCR4 and thus acts as a partial CXCR4 agonist in vitro. Thus, we explored whether AMD3100 affected the survival and proliferation of myeloma cells in vitro. MATERIALS AND METHODS: The effects of AMD3100 on survival and proliferation of two myeloma cell lines (RPMI8226 and U266) as well as CD138+ cells obtained from several patients with multiple myeloma were analyzed by flow cytometry using annexin V and a colorimetric cell proliferation assay (CCK-8 assay). RESULTS: AMD3100, but not T140, another CXCR4 antagonist, stimulated the proliferation of myeloma cell lines and CD138+ primary human myeloma cells (-2-fold increase) in a dose-dependent manner in serum-free culture for up to 5 days, which was inhibited by pretreating the cells with pertussis toxin. AMD3100 enhanced the proliferation of U266 cells induced by interleukin-6 and partially reversed AG490-mediated growth inhibition and apoptosis induced by serum deprivation in RPMI8226 cells. AMD3100 induced the phosphorylation of Akt and MAPK p44/p42 in U266 cells and MAPK p44/p42 in RPMI8226 cells. In contrast, AMD3100 markedly increased the cell apoptosis and reduced the number of RPMI8226 cells after 5 to 7 days of culture under serum-free conditions. CONCLUSION: AMD3100 exerts dual effects, initially enhancing and subsequently inhibiting the survival and proliferation of myeloma cells, signaling via CXCR4 in vitro.
Annexin A5 ; Apoptosis ; Cell Line ; Cell Proliferation ; Flow Cytometry ; GTP-Binding Proteins ; Hematopoietic Stem Cells ; Heterocyclic Compounds ; Humans ; Interleukin-6 ; Multiple Myeloma ; Oligopeptides ; Pertussis Toxin ; Phosphorylation

No abstract available.
Hemoglobinuria, Paroxysmal* ; Humans ; Prednisolone*