A case of multiple myeloma with metachronous chronic myeloid leukemia treated successfully with bortezomib, dexamethasone, and dasatinib.

The coexistence of multiple myeloma and chronic myeloid leukemia in a single patient is a very rare event that has been reported very infrequently in the literature. We report a case of a patient who developed chronic myeloid leukemia four years after his diagnosis with multiple myeloma. Historically, no link between the two malignancies has been identified. This synchronous existence complicates the treatment plan for these patients, and there is a lack of evidence on the best therapeutic approach. Our patient was successfully treated with a combination of bortezomib, dexamethasone, and dasatinib, which he tolerated well for eleven months until he eventually succumbed to cardiac complications and pulmonary hypertension leading to his death.

Myelofibrosis involving lymph node: a novel cytogenetic abnormality in a mimicker of mesenchymal neoplasm.

A case of primary myelofibrosis involving lymph node and with a novel cytogenetic abnormality [del (18) (p11.2-3)] is reported. The abnormalities are identical among specimens from the lymph node, peripheral blood, and bone marrow that were analyzed years apart. Additionally, we show that the infiltrate by dysplastic megakaryocytes in the lymph node morphologically mimics a metastatic mesenchymal neoplasm, even when the clinical history myelofibrosis was known.

Dialysis membrane-induced oxidative stress: role of heme oxygenase-1.

Dialysis membranes have been reported to induce monocyte apoptosis. We studied the role of oxidative stress in the induction of dialysis membrane-induced monocyte apoptosis. Superoxide dismutase, a superoxide scavenger, prevented dialysis membrane-induced monocyte apoptosis. Similarly, other antioxidants also inhibited dialysis membrane- induced apoptosis. In addition, the interaction of dialysis membranes with monocytes was associated with the generation of molecules leading to oxidative stress such as superoxide and TBARS. Interestingly, pre-induction of heme oxygenase (HO)-1 by hemin prevented dialysis membrane-induced monocyte apoptosis, whereas inhibition of HO-1 activity (treatment with tin protoporphyrin, SN-P) enhanced dialysis membrane-induced monocyte apoptosis. We suggest that oxidative injury associated with dialysis membrane and monocyte interaction plays a role in monocyte injury. Pre-induction of HO-1 may attenuate dialysis membrane-induced monocyte apoptosis.

Hepatocyte growth factor modulates H2O2-induced mesangial cell apoptosis through induction of heme oxygenase-1.

Oxidative stress plays an important role in the induction of mesangial cell (MC) injury. In the present study, we evaluated the molecular mechanism involved in hydrogen peroxide (H2O2)-induced MC apoptosis. In addition, we examined the role of heme oxygenase-1 (HO-1) in hepatocyte growth factor (HGF)-modulated, H2O2-induced MC injury. H2O2 promoted (p < 0.001) mouse MC (MMC) apoptosis. This effect of H2O2 was associated with translocation of cytochrome c from the mitochondrial to the cytosolic compartment. In addition, a caspase-9 inhibitor partially attenuated this effect of H2O2. These findings suggest that H2O2-induced MMC apoptosis is mediated through the mitochondrial pathway. HGF not only prevented H2O2-induced MMC apoptosis, but also inhibited H2O2-induced translocation of cytochrome c from the mitochondrial to the cytosolic compartment. HGF also promoted the expression of HO-1 by MMCs; interestingly, hemin inhibited (p < 0.001) H2O2-induced MMC apoptosis. On the other hand, zinc protoporphyrin inhibited the protective influence of HGF on H2O2-induced MMC apoptosis. These findings suggest that H2O2-induced apoptosis occurs through the mitochondrial pathway. HGF provides protection against H2O2-induced MMC apoptosis through induction of HO-1.

Tubular cell-Escherichia coli interaction products modulate migration of monocytes through generation of transforming growth factor-beta and macrophage-monocyte chemoattractant protein-1.

BACKGROUND: Urinary tract infection is a common occurrence often associated with renal interstitial inflammation in the form of accumulation of mononuclear cells. We hypothesized that bacteria activate tubular cells to secrete cytokines, which may promote migration of mononuclear cells at the site of interaction. MATERIALS AND METHODS: We evaluated the migration of monocytes in response to tubular cell products (TC-S) and interaction products of E. coli with proximal tubular cells (TC-EC-S; concentrations of 5%, 10%, and 25%) using a modified Boyden chamber. To determine the molecular mechanism, we evaluated the effect of antibodies against macrophage-monocyte chemoattractant protein-1 (MCP-1) and transforming growth factor-beta (TGF-beta) on E. coli-tubular cell interaction product-induced migration of monocytes. In addition, we studied the effect of free-radical scavengers on activation of tubular cells. RESULTS: The TC-EC-S enhanced (p < 0.0001) migration of monocytes compared with TC-S. Both anti-TGF-beta and anti-MCP-1 antibodies partly inhibited (p < 0.0001) TC-EC-S-induced monocyte migration. The modified TC-EC-S (produced in the presence of superoxide dismutase [SOD], dimethyl thiourea [DMTU], or catalase, all scavengers of free radicals) induced lesser monocyte migration than did TC-EC-S alone. CONCLUSIONS: These results suggest that E. coli activates tubular cells to generate cytokines such as MCP-1 and TGF-beta that promote migration of monocytes. Free radicals such as superoxide and hydrogen peroxide may be acting as second messengers in E. coli-induced tubular cell activation.

Morphine-induced macrophage apoptosis modulates migration of macrophages: use of in vitro model of urinary tract infection.

BACKGROUND: Morphine has been reported to alter immune function. Morphine-induced macrophage apoptosis has been shown to contribute to altered immune status in an opiate milieu. We studied the effect of morphine-induced macrophage apoptosis on the migration of macrophages. Because urinary tract infection (UTI) is one of the commonest infections to evoke an inflammatory response; i.e., migration of neutrophils and monocytes to the site of infection, we used an in vitro model of UTI to test our hypothesis. MATERIALS AND METHODS: We carried out both in vivo and in vitro studies. Mice of the FVB/N strain were treated with morphine for short (three doses, 24 hours) and long (11 doses, 96 hours) durations, and their bone marrow cells were isolated. In addition, apoptotic macrophages were prepared by heat treatment. To simulate the in vitro model of UTI, E. coli-activated tubular cell (TC)-conditioned medium containing transforming growth factor-beta (TGF-beta) and macrophage-monocyte chemoattractant protein-1 (MCP-1) was used to test migration of macrophages across a filter in a modified Boyden chamber. In addition, migration of macrophages into the peritoneal cavity was evaluated in both control and morphine-treated states. The effect of morphine on apoptosis as well as migration was studied in murine macrophages and bone marrow cells. RESULTS: Morphine not only promoted apoptosis of bone marrow cells (20% apoptotic cells) but also inhibited their migration across the filter. Control cells showed minimal apoptosis but displayed greater migration. Similarly, heat-treated (apoptotic) cells showed minimal migration. In peritoneal macrophage studies, morphine treatment retarded migration. CONCLUSION: Morphine inhibits macrophage migration both in vivo and in vitro. This attenuated transmigration of macrophages seems to be secondary to the apoptotic effect of morphine.