Immunogenetic analysis of gastric MALT lymphoma-like lesions induced by Helicobacter pylori infection in neonatally thymectomized mice

Most gastric mucosa-associated lymphoid tissue (MALT) lymphomas are caused by Helicobacter pylori (H. pylori) infection. We previously reported that acquired lymphoid follicles with germinal centers were induced by H. pylori infection in neonatally thymectomized (nTx) mice. In the present study, we developed gastric MALT lymphoma-like lesions in nTx mice by long-term H. pylori infection, and performed immunogenetic analyses. BALB/c mice were thymectomized on the 3rd day after birth. At 6 weeks of age, mice were orally infected with 10(8) H. pylori and serially killed 2, 4, 6, and 12 months later. Normal BALB/c and noninfected nTx mice served as controls. Follicle formation occurred after 2 months of H. pylori infection in the nTx mice. Follicle formation and infiltration of intraepithelial lymphocytes progressed in a time-dependent manner. Lymphoepithelial lesions, a characteristic feature of MALT lymphoma, also occurred in a time-dependent manner (100% at 12 months). Serum immunoelectrophoresis revealed a monoclonal band (M-protein) in 30% (3/10) of mice 6 months after infection. M-protein-positive mice had amplification of one or two IgM and/or IgG heavy-chain genes in the gastric B lymphocytes, as determined with polymerase chain reaction, suggesting mono- or oligoclonality. Overexpression of Bcl-X(L) protein was immunohistologically observed in the infiltrating B lymphocytes and in some follicular B lymphocytes in 80% (8/10) of the cases at 12 months. Thus, H. pylori infection is involved in the development of gastric MALT lymphoma-like lesions in nTx mice. Our mouse model is useful for clarifying the pathogenetic mechanism of gastric MALT lymphoma by H. pylori infection.     

Oral administration of muscle derived small molecules inhibits tumor spread while promoting normal cell growth in mice

Tumor metastases are extremely rare in striated muscles. This is surprising given the fact that this tissue constitutes 60% of body weight. The present study focuses on small molecules produced and secreted by muscle cells which possess anti-cancer activity in vivo. Recently we have shown that a low molecular weight fraction (<1000 Dalton) of skeletal muscle cell conditioned medium (muscle factor-MF), markedly inhibits the proliferation of carcinoma, sarcoma or melanoma cell lines in vitro. The MF exerts a cytostatic effect on tumor cell growth and arrests the cells in the G0/G1 of the cell cycle. However, normal cell proliferation, such as bone marrow and fibroblasts, was stimulated following incubation with MF. In this study, the effect of orally administered MF on melanoma and sarcoma growth was examined in mice. The administration of MF to mice inoculated intravenously with melanoma (B16–F10) or sarcoma (MCA-105) cells, resulted in a statistically significant inhibition of metastatic lung foci. In a different model, melanoma was induced in the foot pad and after development of a local lesion, the leg was amputated. A prolonged survival time was observed in the MF treated groups. Since the MF stimulated bone marrow cell proliferation in vitro, we decided to test its efficacy as an inhibitor of the myelotoxic effect exerted by chemotherapy, in vivo. MF, administered after chemotherapy, restored the number of white blood cells and yielded an increased percentage of neutrophils compared with the decline in these parameters after administration of chemotherapy alone. Thus, it is indicated that MF exerted a systemic anti tumor and chemoprotective effect when given orally. It can be concluded that it is bioavailable and is not biodegradable in the digestive system. MF may be considered as a potential therapy for the prevention of tumor spread. This revised version was published online in July 2006 with corrections to the Cover Date.     

Effect of IL-2-Bax, a novel interleukin-2-receptor-targeted chimeric protein, on bleomycin lung injury

The role of lymphocytes in the pathogenesis of lung fibrosis is not clear, but the weight of the evidence supports a pro-fibrotic effect for lymphocytes. The high-affinity interleukin-2 receptor (haIL-2R) is expressed on activated, but not quiescent, T lymphocytes. This selective expression of haIL-2R provides the basis for therapeutic strategies that target IL-2R-expressing cells. We hypothesized that elimination of activated lymphocytes by IL-2R-targeted chimeric proteins might ameliorate lung fibrosis. We investigated the effects of IL-2-Bax, a novel apoptosis-inducing IL-2R-targeted chimeric protein, on bleomycin-induced lung injury in mice. Treatment groups included (i) a single intratracheal instillation of bleomycin and twice-daily intraperitoneal injections of IL-2-Bax; (ii) intratracheal bleomycin and intraperitoneal IL-2-PE66(4Glu), an older-generation chimeric protein; (iii) intratracheal bleomycin/intraperitoneal PBS; (iv) intratracheal saline/intraperitoneal PBS. Lung injury was evaluated 14 days after intratracheal instillation by cell count in bronchoalveolar lavage (BAL) fluid, semi-quantitative and quantitative histomorphological measurements and by biochemical analysis of lung hydroxyproline. Bleomycin induced a BAL lymphocytosis that was significantly attenuated by IL-2-Bax and IL-2-PE66(4Glu). However, morphometric parameters and lung hydroxyproline were unaffected by the chimeric proteins. These results show that IL-2-Bax reduces the lymphocytic infiltration of the lungs in response to bleomycin, but this effect is not accompanied by a decrease in lung fibrosis.     

Is there a need for lumbar orthosis in mild compression fractures of the thoracolumbar spine?: A retrospective study comparing the radiographic results between early ambulation with and without lumbar orthosis

Compression fractures of the thoracolumbar spine are common in spinal trauma. Most patients are treated with early ambulation. Bracing is an option not always recommended by the treating team. There are no definite recommendations so far regarding the need for lumbar orthosis in this type of injury. The authors retrospectively compared two methods for treating patients with compression as great as 30%: early ambulation with and without lumbar orthosis. The results show that although demographic variables, type of injury, and cause of injury were similar between the groups, neither treatment emerged as superior. Thoracolumbar fractures with compression as much as 30% can be treated with early ambulation and no external support. Close clinical and radiographic follow-up is essential.     

The effect of halofuginone, an inhibitor of collagen type i synthesis, on urethral stricture formation: in vivo and in vitro study in a rat model

PURPOSE: Urethral strictures are narrowing of the urethra caused by fibrosis due to excessive collagen production in response to an insult. We evaluated the effects of halofuginone, a potent inhibitor of collagen alpha1(I) gene expression, on experimentally induced urethral strictures in vivo and on rat urethral fibroblasts in vitro. MATERIALS AND METHODS: Applying coagulation current to the male rat urethra produced urethral strictures. Halofuginone was given to the animals for 7 days, starting on the day of stricture formation, either orally at 1 and 5 ppm in the diet or by injection of 0.03% halofuginone solution into the urethra. All rats were sacrificed on day 21. Collagen alpha1(I) gene expression was evaluated by in situ hybridization, collagen content by sirius red staining and urethral morphology by urethrogram. RESULTS: Coagulation current produced reproducible strictures with a typical urethrogram appearance, which were associated with increases in collagen alpha1(I) gene expression and collagen content at the stricture site. Halofuginone injected into the urethra or orally at 5 ppm normalized the urethrogram and prevented increases in collagen alpha1(I) gene expression and collagen content. Halofuginone at a concentration of 10-8 M. inhibited the collagen secreted by fibroblasts derived from the rat male urethra, which was due to inhibition of the collagen alpha1(I) gene expression. CONCLUSIONS: Halofuginone prevented stricture formation and may become an important mode of therapy in the prevention of restenosis during urethral stricture formation.     

Mutation of Vav1 adaptor region reveals a new oncogenic activation

Vav family members function as remarkable scaffold proteins that exhibit both GDP/GTP exchange activity for Rho/Rac GTPases and numerous protein-protein interactions via three adaptor Src-homology domains. The exchange activity is under the unique regulation by phosphorylation of tyrosine residues hidden by intra-molecular interactions. Deletion of the autoinhibitory N-terminal region results in an oncogenic protein, onco-Vav, leading to a potent activation of Rac GTPases whereas the proto-oncogene barely leads to transformation. Substitution of conserved residues of the SH2-SH3 adaptor region in onco-Vav reverses oncogenicity. While a unique substitution D797N did not affect transformation induced by onco-Vav, we demonstrate that this single substitution leads to transformation in the Vav1 proto-oncogene highlighting the pivotal role of the adaptor region. Moreover, we identified the cell junction protein β-catenin as a new Vav1 interacting partner. We show that the oncogenicity of activated Vav1 proto-oncogene is associated with a non-degradative phosphorylation of β-catenin at residues important for its functions and its redistribution along the cell membrane in fibroblasts. In addition, a similar interaction is evidenced in epithelial lung cancer cells expressing ectopically Vav1. In these cells, Vav1 is also involved in the modulation of β-catenin phosphorylation. Altogether, our data highlight that only a single mutation in the proto-oncogene Vav1 enhances tumorigenicity.     

“Habitual Adnexal Torsions”—Recurrence after Two Oophoropexies in a Prepubertal Girl: A Case Report and Review of the Literature

BackgroundRecurrent adnexal torsion rarely affects girls. Various surgical techniques for its prevention are available. We describe a case of recurrent asynchronous bilateral torsions in a prepubertal patient.CaseAn 8-year-old girl first presented with a right adnexal torsion and underwent a laparoscopic untwisting. During the following 3 years, 4 additional laparoscopies were required for treatment of left adnexal torsions. Although undergoing bilateral utero-ovarian ligament plication twice, torsion recurred. After examining the various options, we fixated the left ovary to the sidewall just below the pelvic brim.Summary and ConclusionIn the absence of clear evidence, treatment should be flexible and dependent on the individual case. Thorough patient education is imperative in order to prevent a delay in diagnosis and treatment of recurrent adnexal torsion.     

Ultra-low-dose unenhanced chest CT: Prospective comparison of high kV/low mA versus low kV/high mA protocols

Purpose

To qualitatively and quantitatively compare unenhanced ultra-low-dose chest computed tomography (ULD-CT) acquired at 80 kVp and 135 kVp.

Quantifying continuous-flow dielectrophoretic trapping of cells and micro-particles on micro-electrode array

An interdigitated electrode array embedded within a micro-channel with forced flow is shown to enable dielectrophoretic (DEP) characterization of particles and/or cells based on measurements of their trapping percentage over a continuous frequency range. A simplified model of the trapping percentage, using spatial averaging of the convective and DEP force, linearly correlated it to the effective DEP force (in its positive mode). Thus, the Clausius–Mossotti factor was fitted to the experimental data, yielding effective electrical characteristics of the particles and/or cells. Also, the generated trapping percentage curve response over a continuous range of frequencies facilitates sorting and detection based on differences other than just the cross-over frequencies.