Myeloid cell-specific expression of Ship1 regulates IL-12 production and immunity to helminth infection.

Helminth infection leads to the local proliferation and accumulation of macrophages in tissues. However, the function of macrophages during helminth infection remains unclear. SH2-containing inositol 5'-phosphatase 1 (Ship1, Inpp5d) is a lipid phosphatase that has been shown to play a critical role in macrophage function. Here, we identify a critical role for Ship1 in the negative regulation of interleukin (IL)-12/23p40 production by macrophages during infection with the intestinal helminth parasite Trichuris muris. Mice with myeloid cell-specific deletion of Ship1 (Ship1(ΔLysM) mice) develop a non-protective T-helper type 1 cell response and fail to expel parasites. Ship1-deficient macrophages produce heightened levels of IL-12/23p40 in vitro and in vivo and antibody blockade of IL-12/23p40 renders Ship1(ΔLysM) mice resistant to Trichuris infection. Our results identify a critical role for the negative regulation of IL-12/23p40 production by macrophages in the development of a protective T(H)2 cell response.

Response to selection for bacterial cold water disease resistance in rainbow trout.

A family-based selection program was initiated at the National Center for Cool and Cold Water Aquaculture in 2005 to improve resistance to bacterial cold water disease (BCWD) in rainbow trout. The objective of this study was to estimate response to 2 generations of selection. A total of 14,841 juvenile fish (BW = 3.1 g; SD = 1.1 g) from 230 full-sib families and 3 randomly mated control lines were challenged intraperitoneally with Flavobacterium psychrophilum, the bacterium that causes BCWD, and mortalities were observed for 21 d. Selection was applied to family EBV derived from a proportional-hazards frailty (animal) model while constraining rate of inbreeding to

Congenital pseudoarthrosis associated with venous malformation.

Congenital pseudoarthrosis is a pathologic entity that may be isolated, or may be associated with neurofibromatosis. We report the case of a 3-year-old female with congenital pseudoarthrosis involving the right tibia and fibula. Magnetic resonance imaging (MRI) and complementary magnetic resonance angiogram (MRA) revealed a lobulated mass with vivid enhancement, which led to the diagnosis of venous malformation. This is the first report of congenital pseudoarthrosis caused by the presence of a vascular malformation.

MD-1 expression regulates direct and indirect allorecognition.

Expression of the molecule MD-1 was previously described to regulate allogeneic and xenogeneic skin graft survival, as documented by the decrease in rejection seen following functional blockade of MD-1 expression in vivo, using antisense oligodeoxynucleotides (ODNs) or anti-MD-1 antibodies. It was unclear from these data whether blockade of expression of MD-1 on donor or recipient cells was crucial. We have investigated the effect on allorecognition of treating skin graft donors, and/or recipients, of either fully major histocompatibility complex (MHC)-mismatched allogeneic skin grafts (C3H with C57BL/6 grafts and vice versa) or grafts differing at only multiple minor alloantigens (C3H with B10.BR grafts; C57BL/6 with C3H.SW), with antisense ODNs to MD-1, or in some cases, following transplantation of class II-deficient cells into class I-deficient mice. Graft-specific cytotoxic T lymphocytes (CTLs) were measured in spleen cells recovered at sacrifice of recipients and following donor-specific restimulation in vitro. In the latter case, we also measured cell proliferation and (by enzyme-linked immunosorbent assay) production of interleukin-2 (IL-2)/interferon-gamma (IFN-gamma) or IL-4/IL-10 in vitro (nominal type-1 vs type-2 cytokines). CTL responses to minor-incompatible grafts were diminished, only if graft recipients were treated with ODNs. However, treatment of graft donor and/or recipient of MHC-incompatible grafts produced inhibition of CTL production. Optimal inhibition came from treating both. Specific suppression of CTL production coincided with inhibition of proliferation and preferential production of IL-4 and IL-10 at the expense of IL-2 and IFN-gamma. Our data are consistent with the hypothesis that MD-1 expression regulates both the direct and indirect pathways of allorecognition and that regulation of MD-1 expression may thus help regulate clinical graft rejection.

Preparation and functional properties of polyclonal and monoclonal antibodies to murine MD-1.

Rabbits, rats and hamsters were immunized with KLH-coupled synthetic peptide sequences of the murine MD-1 molecule. Serum from immunized animals bound in Western gels to a 25 KDa protein extracted from LPS stimulated mouse spleen cells, as did a rat hybridoma (SH1.2.47) prepared from peptide-immunized rats. CHO cells transfected with a plasmid cDNA construct encoding murine MD-1, the target antigen for the antibodies in question, were also stained (in FACS) by the same antibodies. Patching and capping of the antigen(s) detected by any one of these sera abolished binding of all antibodies in subsequent FACS analysis, consistent with the hypothesis that they all detected the same antigen. In a final study to assess the possible involvement of MD-1 in regulation of cell activation for cytokine production following allostimulation, we found that all of the antibodies inhibited IL-2 and IFNgamma production, while enhancing IL-4 and IL-10 production, in mixed leukocyte reactions (MLR) in vitro.

Regulation of gene expression of murine MD-1 regulates subsequent T cell activation and cytokine production.

The immunoadhesin (OX2:Fc) comprising the extracellular domain of murine OX2 linked to IgG2aFc, inhibits production of IL-2 and IFN-gamma by activated T cells and increases allograft and xenograft survival in vivo. Increased expression of OX2 on dendritic cells (DC) in vivo following preimmunization via the portal vein is also associated with elevated expression of MD-1. We have used antisense oligodeoxynucleotides (ODNs) to MD-1 to investigate the effect of inhibition of expression of MD-1 by DC on their function as allostimulatory cells. We also investigated by FACS analysis the cell surface expression of OX2, CD80, and CD86 on DC incubated with ODN-1 blocking MD-1 expression. Blocking MD-1 gene expression inhibits surface expression of CD80 and CD86, but not of OX2. DC incubated with ODN-1 to MD-1 did not stimulate IL-2 or IFN-gamma production, but generated cells able to suppress, in a second culture of fresh DC plus allogeneic T cells, production of IL-2 and IFN-gamma. This inhibition was blocked by anti-OX2 mAb. Infusion of DC preincubated with ODN-1 prolonged renal allograft survival, an effect also reversed by anti-OX2 mAb. By FACS, incubation of DC with anti-MD-1 Ab to promote capping eliminated cell surface expression of MD-1 and CD14 without altering DEC205, DC26, CD80, CD86, or OX2 expression. Thus OX2 and MD-1 are independent surface molecules on DC that may reciprocally regulate T cell stimulation. MD-1 is linked to CD14, a "danger receptor complex," and activation of this complex can regulate cell surface expression of CD80/CD86, which signal T cells.

The treatment of displaced supracondylar fractures of the humerus in children. A comparison of three methods.

This retrospective study compares the long-term results of the treatment of 135 children with displaced extension-type supracondylar fractures of the humerus using 3 different methods. Closed reduction and percutaneous fixation was superior with excellent and good results in 87% and had the lowest incidence of poor results (8%). Open reduction and wire fixation, and closed reduction with a plaster cast gave excellent and good results in 74% and 60% respectively. Closed reduction and wire fixation is recommended as the treatment for grades II and III supracondylar fractures.

Oral manifestations and histochemical studies of the gingiva in Down syndrome.

Down syndrome is the most frequent of the aneuploids observed in newborn infants whose major manifestations are mental and growth retardation. The purpose of this work was to study the oral manifestations, histological and histochemical changes in gingiva of Egyptian Down syndrome children and to correlate the noted histochemical changes with the intelligence quotient and the karyotype. The study comprised 29 cases (19 males and 10 females) with a mean age of (4.673 + 2.406) and 30 control children (19 males and 11 females) with a mean age of (4.632 + 2.568). 27 cases had pure trisomy 21 and 2 cases was mosaics. General clinical and orodental examination confirmed the developmental variability of Down syndrome patients. The orodental examination showed: 1--A high susceptibility to periodontal disease. 2--Bad oral hygiene. 3--High arched palate, macroglossia, hypocalcification, fissured tongue, underdeveloped maxilla delayed eruption of the primary teeth. The histological and histochemical changes were: 1--Increased inflammatory signs in the epithelium and connective tissue of the gingiva. 2--Amorphous amyloid deposits in lamina propria of Down syndrome children, while it was absent in that of control children. It was more in low I.Q. children with fair gingival index than those with better I.Q. 3--Neutral glycoprotein was stronger in Down syndrome than that in controls. 4--Reduction in the highly acidic MPS. 5--Total protein content was increased in Down syndrome children that of their controls. 6--Acid phosphatase activity was stronger in Down syndrome than of their controls. 7--Alkaline phosphatase activity was less in Down syndrome than of their controls. These changes point to a correlation which needs further investigation in a larger number of cases.

The Debrunner-Cech valgus osteotomy in osteoporotic four-part intertrochanteric fractures.

The main problems encountered in the management of comminuted four-part intertrochanteric fractures in the elderly are instability, severe osteoporosis and the need for early mobilization. Thirty-one patients, average age 75 years, with such fractures were operated on using a sliding blade-plate and the Debrunner-Cech valgus osteotomy. The follow-up was from 1-5 years with an average of 3.2 years. All patients were got out of bed on the first postoperative day and walked with help on the second day. The fractures united in 29 patients. The one exception occurred when the blade cut out of the neck; the operation was repeated with a good result. Two further patients died in the postoperative period. We conclude that this method is the best treatment for osteoporotic four-part intertrochanteric fractures.

Posterior interosseous nerve syndrome caused by a bursa in the vicinity of the elbow.

A case of posterior interosseous nerve syndrome presented with difficulty in extending the metacarpophalangeal joint of the little finger. Compression was caused by a bicipital bursa. Surgical decompression led to a complete recovery.

Fractures of the phalanges: results of internal fixation using 1.5mm and 2mm A. O. screws.

Thirty-six patients were treated for 38 phalangeal fractures using 1.5 mm and 2 mm A. O. screws. Plates were not used in the fingers. Oblique fractures of the condyles, shafts or bases of the proximal or middle phalanges were treated by internal fixation because of instability, displacement or rotation. 40% of fractures had associated skin wounds, were comminuted or had damage to the extensor mechanism. The mean duration of post-operative immobilization was 9 days and the mean time off work was 6 weeks. Total active movement in the involved ray was 220 degrees or greater in 24 cases, 180 degrees to 215 degrees in eight cases, and less than 180 degrees in two patients at follow up. The patients were reviewed between three and 54 months after treatment and the mean duration of follow up was 24 months. The most frequent complication was 10 degrees to 30 degrees of flexion deformity of the proximal interphalangeal joint after internal fixation of condylar fractures. Results were satisfactory in 90% of cases.

Fractures of the metacarpals: treatment by A. O. screw and plate fixation.

Twenty-two patients with 26 fractured metacarpals were treated by internal fixation using A. O. mini-fragment screws and plates. This form of internal fixation was reserved for metacarpal fractures which were multiple, unstable, displaced or rotated. Nine patients had open fractures, two had divided extensor tendons and four had multiple fractures. Fractures consistently united without infection or deformity. The mean duration of postoperative immobilization was seven days and mean time off work was six weeks. All but one patient did manual work. No patients had persistent symptoms which caused difficulty with work or sport. Fourteen patients regained full movement. Four had total active movement of 220 degrees or more in the involved ray and 6 patients had total active movement of between 180 and 220 degrees. Restricted movement was present in patients with open fractures and divided extensor tendons or intra-articular fractures of the metacarpal head. Uniformly satisfactory results were found after mini-screw and plate fixation of metacarpal fractures.

The Herbert screw for fractures of the scaphoid. A review of results and technical difficulties.

We have reviewed 22 patients with scaphoid fractures treated by internal fixation with the Herbert screw. Three patients had trans-scaphoid perilunar dislocations, one had an oblique displaced fracture of the waist of the scaphoid and 18 had fractures with delayed or non-union. Corticocancellous bone grafts were added in nine of the cases of non-union. Results were excellent or good in 80% of cases after a mean duration of postoperative immobilisation of four weeks. The technical difficulties are analysed and the problems of applying the jig and of operative exposure are discussed.

Remodeling after femoral shaft fractures in children treated by the modified blount method.

One hundred forty-one children with femoral shaft fractures in the 1-12-year age range were treated by simple skin traction without spica cast immobilization. All fractures united in an average traction period of 28 days. Clinical and radiological reevaluation 2-10 years after treatment showed that fracture location, age, and overriding significantly affected overgrowth, whereas the length of the follow-up period and the direction of angular deformity affected correction of angulation. The following conclusions were reached: Distraction should be avoided, and overriding of up to 15 mm can be compensated for by growth acceleration. Initial angular deformities of up to 20 degrees in the coronal plane and up to 30 degrees in the sagittal plane will end in a satisfactory outcome. Rotational deformity was not a problem following this method of treatment.