Neuroimaging in Pineal Tumors

BACKGROUND AND PURPOSE: The authors report radiological findings in 11 tumors in the pineal region, which were histologically diagnosed as germinomas, pineocytomas pineoblastomas, ependymomas, teratomas, and astrocytomas. METHODS: Computed tomography (CT) was performed in seven patients and magnetic resonance imaging (MRI) was performed in all patients. RESULTS: CT showed a solid or solid/cystic mass with variable contrast enhancement. MRI showed a heterogeneous mass, with hypointense signal on T1 and iso/hyperintense signal on T2-weighted images (WI) and gadolinium enhancement. Extension to adjacent structures occurred in five patients and spread through the cerebral spinal fluid (CSF) in two. CONCLUSIONS: Pineal region tumors have no pathognomonic imaging pattern. MRI and CT are complementary in diagnosis and are important to determine localization, extension, and meningeal spread.     

Labial Adhesion with Acute Urinary Retention Secondary to Bartholin's Abscess

Labial adhesions are usually seen in early childhood or in the postmenopausal years, but this clinical entity is rarely seen in the reproductive years. We report a case of labial adhesion with acute urinary retention secondary to Bartholin's abscess in a reproductive‐aged woman with normal menstrual periods. We emphasize the possible occurrence of labial adhesion following Bartholin's abscess in the reproductive years with normal estrogen levels.     

Sera from patients with heparin-induced thrombocytopenia generate platelet-derived microparticles with procoagulant activity: an explanation for the thrombotic complications of heparin-induced thrombocytopenia

Heparin-induced thrombocytopenia is characterized by moderate thrombocytopenia and thrombotic complications, whereas quinine/quinidine-induced thrombocytopenia usually presents with severe thrombocytopenia and bleeding. Using flow cytometry and assays of procoagulant activity, we investigated whether sera from patients with these immune drug reactions could stimulate normal platelets to generate platelet-derived microparticles with procoagulant activity. Sera or purified IgG from patients with heparin-induced thrombocytopenia stimulated the formation of platelet-derived microparticles in a heparin-dependent fashion. Further studies showed that heparin-induced thrombocytopenia sera also produced a marked increase in procoagulant activity. In contrast, sera from patients with quinine- or quinidine-induced thrombocytopenia did not generate platelet-derived microparticles nor generate increased procoagulant activity. However, quinine/quinidine-induced thrombocytopenia sera produced a significant increase in the binding of IgG to platelets in a drug-dependent fashion, whereas sera from patients with heparin-induced thrombocytopenia demonstrated no drug-dependent binding of IgG to platelets. We also observed increased levels of circulating microparticles in patients with acute heparin-induced thrombocytopenia compared with control patients. Our observations indicate that the generation of procoagulant platelet-derived microparticles in vivo is a plausible explanation for the thrombotic complications observed in some patients with heparin-induced thrombocytopenia.     

A humanised tissue‐engineered bone model allows species‐specific breast cancer‐related bone metastasis in vivo

Bone metastases frequently occur in the advanced stages of breast cancer. At this stage, the disease is deemed incurable. To date, the mechanisms of breast cancer‐related metastasis to bone are poorly understood. This may be attributed to the lack of appropriate animal models to investigate the complex cancer cell–bone interactions. In this study, two established tissue‐engineered bone constructs (TEBCs) were applied to a breast cancer‐related metastasis model. A cylindrical medical‐grade polycaprolactone‐tricalcium phosphate scaffold produced by fused deposition modelling (scaffold 1) was compared with a tubular calcium phosphate‐coated polycaprolactone scaffold fabricated by solution electrospinning (scaffold 2) for their potential to generate ectopic humanised bone in NOD/SCID mice. While scaffold 1 was found not suitable to generate a sufficient amount of ectopic bone tissue due to poor ectopic integration, scaffold 2 showed excellent integration into the host tissue, leading to bone formation. To mimic breast cancer cell colonisation to the bone, MDA‐MB‐231, SUM1315, and MDA‐MB‐231BO breast cancer cells were cultured in polyethylene glycol‐based hydrogels and implanted adjacent to the TEBCs. Histological analysis indicated that the breast cancer cells induced an osteoclastic reaction in the TEBCs, demonstrating analogies to breast cancer‐related bone metastasis seen in patients.     

Tissue reactions to modern suturing material in colorectal surgery

Morphological changes in the wall of the large intestine were studied after its manual suturing by a double-row interrupted suture with modern suture threads. Light and scanning electron microscopy showed “fuse properties” and “sawing effect” of polyfilament twisted threads (e.g. vicryl). Monofilament threads were free from these drawbacks and therefore were preferable. Metal elastic threads on the basis of titanium-nickelide alloys caused no inflammatory changes in tissues. __________ Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 143, No. 6, pp. 714–717, June, 2007     

Molecular characterization of a high A2 beta thalassemia by direct sequencing of single strand enriched amplified genomic DNA

Two families, one of Anglo-Saxon-Dutch descent, and the other, West Indian black, have an atypical beta thalassemia characterized by an unusually high level of Hb A2 in the heterozygous state. Restriction endonuclease mapping showed a deletion of about 1.35 kilobase (kb) in the 5' region of the beta globin gene. Direct sequencing of a specific region of genomic DNA amplified by a new modification of the polymerase chain reaction defined the deletion to be 1,393 base pairs (bp) and to be the same in both families. The deletion extends from 485 bp 5' to the mRNA CAP site to the middle of the second intervening sequence. This deletion, together with three others previously described that remove the 5' end of the beta gene but leave the delta gene intact, are all associated with unusually high levels of Hb A2 in the heterozygous state.     

Synthetic di-sulfated iduronic acid attenuates asthmatic response by blocking T-cell recruitment to inflammatory sites

Identification of carbohydrate sequences that determine affinity to specific chemokines is a critical step for strategies to interfere with chemokine-mediated leukocyte trafficking. Here, we first characterized the development of allergic asthma in Tie2-dependent and inducible Ext1-knockout (Tie2-Ext1^iKO) mice. We showed that heparan sulfate is essential for leukocyte recruitment in the peribronchial region and bronchoalveolar lavage fluid (BALF), and is crucial for induction of airway hyperresponsiveness. Our glycan microarray showed a unique affinity profile of chemokine CCL20 to substructures of heparin and heparin-like oligo/di/monosaccharides. Among them, we identified a synthetic and not naturally occurring monosaccharide, 2,4-O-di-sulfated iduronic acid (Di-S-IdoA), as a potential inhibitor for CCL20–heparan sulfate interaction. Mice injected with Di-S-IdoA via tail vain or nasal inhalation showed attenuated leukocyte recruitment into inflammatory sites and BALF. These results demonstrate a critical role of chemokine–heparan sulfate interaction in the asthma development and Di-S-IdoA as a potential drug for asthma treatment.Asthma is a common allergic disease characterized by chronic airway inflammation, mucus hypersecretion, and airway hyperreactivity to inhaled allergens (1). Despite the importance of T lymphocytes in adaptive immunity and host defense, their accumulation in airway in allergic asthma causes Th2-mediated pulmonary inflammation. The asthmatic inflammatory response is orchestrated by T-cell trafficking network among lung, blood circulation, secondary lymphoid organ, and peripheral tissue (2). Of note, the significant increase of T cells in the airway in asthma is mostly due to T-cell recruitment from regional lymph nodes rather than their proliferation at the inflamed site (3). Therefore, a therapeutic approach that shuts off the trafficking pathway of pathogenic T cells should significantly inhibit the Th2-mediated inflammation in allergic asthma.It is well known that the destination of T-cell trafficking pathway is tightly restricted by the profile of chemokines, lipid chemoattractants, and T-cell chemokine receptors. As a part of immune surveillance, naïve T cells and central memory T cells constantly access secondary lymphoid organs from blood circulation via specialized high endothelial venules (HEVs). The interaction between T cells and HEV cells includes in a stepwise manner (4, 5), L-selectin–dependent tethering and rolling, activation, firm arrest, and transendothelial migration. Besides 6-sulfo sialyl Lewis X as a L-selectin ligand, HEVs constitutively express chemokine CCL21 and CCL19 and attract T cells that express its cognate receptor CCR7 (5). In contrast to this homeostatic homing, circulating T cells interact with inflamed blood vessels in lung after asthmatic exposure to an inhaled allergen. Among numerous combinations of chemokines and their receptors, there is considerable evidence that CCL20 and its cognate receptor CCR6 may contribute to the pathogenesis of asthma (6). CCL20-CCR6 plays a key role in the recruitment of Th17 (7) cells and Th2 cells (8). Indeed, CCL20 is highly enriched on inflammatory epithelium (9) and CCR6 is expressed on memory T cells infiltrated in the lung during allergic inflammation (7). In addition, CCR6-deficient mice have decreased airway responsiveness, and reduced recruitment of eosinophils into lung (10, 11). These findings suggest that CCL20-CCR6 axis is a putative target for the treatment of asthma.Cumulative evidence in vivo and in vitro indicates that chemokines cannot be functionally active in HEVs and inflamed sites without their interaction with heparan sulfate (12). Heparan sulfate protects chemokines from proteolysis, immobilizes them on the endothelium surface and produces chemokine gradients in the vasculature. Heparan sulfate is composed of repeating disaccharide units of uronic acid [glucuronic acid (GlcA) or iduronic acid (IdoA)] and N-acetylglucosamine (GlcNAc) carbohydrates. Some of GlcA (or IdoA) carbohydrates are subsequently O-sulfated, and GlcNAc carbohydrates are partially modified with N-deacetylation and N-sulfation (13). Previous reports have indicated that the sulfation patterns in heparan sulfate are more restricted than expected (14), and the sulfation is associated with respiratory distress (15) and asthma (16). It is believed that there are specific interactions between heparan sulfate and chemokines (17). Nevertheless, the nontemplate nature of long carbohydrate chains (<25,000 disaccharide units) and conformational plasticity still make it difficult to identify the common sequences of heparan sulfate that display affinity to specific chemokines. In this regard, our previously established glycan microarray system (18, 19) is a powerful tool to define the selectivity in heparan sulfate–chemokine interactions.Recently, we established the exostoses-1 (Ext1) gene conditional knockout Tie2-Ext1^iKO mouse model, in which GlcA/IdoA-GlcNAc repeat of heparan sulfate can be abrogated in endothelial cells in a tetracycline-inducible manner (20). In this study, Tie2-Ext1^iKO mouse showed significant reduction of both leukocyte recruitment to lung tissues and of airway hyperresponsiveness in ovalbumin (OVA) asthma model. Moreover, glycan microarray analysis surprisingly identified that an unnatural and synthetic monosaccharide, 2,4-O-di-sulfated iduronic acid (Di-S-IdoA) has a high affinity to recombinant CCL20. Intravenous and inhalation challenges of Di-S-IdoA significantly inhibited the leukocyte infiltration in bronchoalveolar lavage fluid (BALF). Our finding that even a monosaccharide can attenuate airway inflammation suggests its potential use as an antiasthma therapy that can be administered by inhalation.