Implantation study of a novel hydroxyapatite/collagen (HAp/col) composite into weight-bearing sites of dogs

A hydroxyapatite/type I collagen (HAp/Col) composite, aligning hydroxyapatite nanocrystals along collagen molecules, has been prepared. The biocompatibility, osteoconductive activity, and efficacy as a carrier of rhBMP-2 of this novel biomaterial implanted in the weight-bearing site have been examined. The HAp/Col implants (15 mm in diameter and 20 mm in length) with a surface cross-linked layer containing rhBMP-2 (0 or 400 microg/ml) were implanted into bone defects of tibiae in three beagle dogs and fixed according to the Ilizarov method. As a control, bone defects of 20 mm in two beagle dogs did not receive implants, and the dogs were allowed to walk using an Ilizarov extraskeletal fixator. The specimens were removed from one dog in each group after 12 weeks. Also, the Ilizarov fixators in the rhBMP-treated dogs were removed after 12 weeks, after which full weight bearing started. The specimens were further taken out after 18 and 24 weeks in the rhBMP-treated and non-rhBMP-treated dogs, and after 24 weeks in the control group. The change of bone mineral density, as well as radiological and histological findings, suggest that the implants are able to induce bone remodeling units and are a superior carrier of rhBMP-2 due to the stimulation of early callus and new bone formation.     

Interhemispheric difference in emotional response without awareness

To investigate interhemispheric differences concerning unconscious human emotional responses processed, we measured human skin conductance responses (SCRs) to masked (unseen) emotional stimuli presented to left or right visual fields. Backward masking was used to preclude conscious processing of emotional stimuli. Masked negative or neutral emotional pictures from the International Affective Picture System (IAPS) were presented to 11 right-handed male volunteers. Mean SCR for negative emotional stimuli presented to the left visual field was significantly greater than mean SCRs for negative emotional stimuli to the right visual field and for neutral stimuli to the left or right visual fields. Thus, the right rather than the left hemisphere appears to respond to preattentive negative emotional stimuli.     

HIF-1 in T cells ameliorated dextran sodium sulfate-induced murine colitis

HIF-1 is active in hypoxia, such as inflamed mucosa, and HIF-1 in epithelium has been reported to control inflamed mucosa in IBD models. Although T cells play an important role for pathogenesis of IBD, the function of HIF-1 in T cells remains to be elucidated. We aimed to clarify the function of HIF-1 in T cells in IBD with focus on the balance between Treg and Teff. Double immunohistochemistry of colonic mucosa in IBD patients showed that HIF-1 was expressed in T cells infiltrating the inflamed mucosa, suggesting that HIF-1 in T cells is involved in the pathogenesis. DSS administration to T cell-specific HIF-1α KO mice showed more severe colonic inflammation than control mice with the up-regulation of Th1 and Th17. Hypoxic stimulation in vitro increased Treg activation in WT T cells but not in HIF-1-deleted T cells. In contrast, hypoxic stimulation increased Th17 activation, and the degree was higher in HIF-1-deleted cells than in control cells. These results show that hypoxia controls intestinal inflammation by regulating cytokine balance in a HIF-1-dependent manner, suggesting that strengthening HIF-1 induction in T cells at the sites of inflammation might be a therapeutic strategy for IBD regulation.     

Basophils and their effector molecules in allergic disorders

Basophils are the rarest granulocytes which represent <1% of peripheral blood leukocytes. Basophils bear several phenotypic similarities to tissue-resident mast cells and therefore had been erroneously considered as blood-circulating mast cells. However, recent researches have revealed that basophils play nonredundant roles in allergic inflammation, protective immunity against parasitic infections and regulation of innate and acquired immunity. Basophils are recruited to inflamed tissues and activated in an IgE-dependent or IgE-independent manner to release a variety of effector molecules. Such molecules, including IL-4, act on various types of cells and play versatile roles, including the induction and termination of allergic inflammation and the regulation of immune responses. Recent development of novel therapeutic agents has enabled us to gain further insights into basophil biology in human disorders. In this review, we highlight the recent advances in the field of basophil biology with a particular focus on the role of basophils in allergic inflammation. Further studies on basophils and their effector molecules will help us identify novel therapeutic targets for treating allergic disorders.     

Inhibition of M-tropic HIV-1 infection by the fd phage-gene 3 protein with MIP-1α-binding activity

CCR5 is a chemokine receptor with seven transmembrane-domains. It is expressed on T cells and macrophages and functions as the principal co-receptor for macrophage (M)-tropic strains of HIV-1. The anti-CCR5 monoclonal antibody (mAb) 2D7 inhibits the binding and chemotaxis of the three natural β-chemokine ligands of CCR5, macrophage inflammatory protein (MIP)-1α, MIP-1β, and RANTES, to CCR5⁺ cells. The mAb also efficiently blocks the infectivity of several M-tropic and dual-tropic HIV-1 strains in vitro.In this study, we attempted to determine the peptide motif recognized with the 2D7 mAb. We isolated phage clones by panning a phage display library using 2D7 and identified three peptide motifs. One of these phage clones (M23) showed a marked inhibitory activity on HIV-1 infection. The unique sequence of 15 amino acids with an internal disulfide bond was inserted in the g3p of the M23 phage clone (M23-g3p). The M23-g3p was purified by fast-performance liquid chromatography (FPLC). We show here that (1) M23-g3p was specifically recognized with anti-CCR5 mAb; (2) M23-g3p showed inhibitory activity on the infectivity of M-tropic but not T-tropic HIV-1 strains; (3) M23-g3p bound to MIP-1α, MIP-1β, and RANTES but not MCP-1. These results suggested that the M23-g3p might mimic the CCR5-binding domain shared by β-chemokines, MIP-1α, MIP-1β, and RANTES as well as the HIV-1 infection.     

Intraosseous epithelioid malignant peripheral nerve sheath tumor of the phalanx. Case report

We report the first case of intraosseous epithelioid malignant peripheral nerve sheath tumor (MPNST) occurring in the phalanx. The patient was a 50-year-old Japanese man with an intramedullary lytic lesion of the proximal phalanx. Microscopically, the tumor was composed of epithelioid cells or polygonal cells, forming large cell nests with central necrosis. Most tumor cells were diffusely and strongly immunopositive for S-100 protein and vimentin, and negative for cytokeratin, epithelial membrane antigen, carcinoembryonic antigen, alpha-smooth muscle actin, and HMB-45. Laminin-positive material was discontinuously demonstrated between the individual tumor cells. Electron microscopy showed prominent external lamina. Our case indicated that laminin is useful for differentiating epithelioid MPNST from metastatic carcinoma and malignant melanoma.     

Utility of bedside artificial pancreas for postoperative glycemic control in cardiac surgery

Journal of Artificial Organs - Perioperative hyperglycemia, hypoglycemia, and high glycemic variability are independent risk factors for mortality in critically ill patients. After cardiac surgery,...     

Modified cavoatriotomy for combined PAPVC repair and maze procedure

In patients with partial anomalous pulmonary venous connection (PAPVC) to the superior cavoatrial junction, the standard right-sided left atriotomy does not allow sufficient access to the mitral valve and the left atrium. And the injury and traction of the sinus node and sinus node artery should be avoided for prevention of the cardiac rhythm disturbance after operation. We herein report a useful approach to repair the sinus venosus atrial septal defect with PAPVC of the right pulmonary veins to the superior cavoatrial junction in patients also requiring mitral valve replacement and the maze procedure.     

Emergency Pylorus-Preserving Pancreatoduodenectomy Followed by Second-Stage Pancreatojejunostomy for a Gastrointestinal Stromal Tumor of the Duodenum with an Intratumoral Gas Figure: Report of a Case

We report a case of a duodenal gastrointestinal stromal tumor (GIST) necessitating urgent surgery because of a gas figure on computed tomography (CT). A 46-year-old woman, complaining chiefly of upper abdominal pain and tarry stools, consulted a local doctor. A gastrointestinal fiberscopy revealed an ulcer in the second part of the duodenum, and the patient was admitted to our hospital where a dynamic CT scan showed a hypervascular solid tumor in the pancreatic head. A repeat CT scan done 4 days later showed a gas figure in the tumor, necessitating an emergency pylorus-preserving pancreatoduodenectomy (PpPD). First, we performed a tube pancreatostomy for complete external drainage of the pancreatic juice, and planned a second-stage pancreatojejunostomy for the near future. Histopathologically, the tumor was diagnosed as a GIST originating in the duodenum. The patient was discharged on postoperative day 23 after an uneventful postoperative recovery. Her local doctor completed the second-stage pancreatojejunostomy.     

Percutaneous radiofrequency ablation combined with previous bronchial arterial chemoembolization and followed by radiation therapy for pulmonary metastasis from hepatocellular carcinoma

A 56-year-old man had a lung metastasis from hepatocellular carcinoma 4.7 cm x 3.4 cm in size located directly adjacent to the pulmonary hilar vessels. The tumor was treated with radiofrequency ablation combined with earlier bronchial arterial chemoembolization and subsequent radiation therapy. A complete remission of the tumor has been observed for 6 months since completion of therapy. Considering that complete treatment of such an intermediate-sized tumor adjacent to the large vessels is usually difficult with radiofrequency ablation alone, this result suggests a possible role for combined therapy for pulmonary neoplasms.