Acquisition of Involuntary Spinal Locomotion (Spinal Walking) in Dogs with Irreversible Thoracolumbar Spinal Cord Lesion: 81 Dogs.

BACKGROUND: Spinal walking (SW) is described as the acquisition of an involuntary motor function in paraplegic dogs and cats without pain perception affected by a thoracolumbar lesion. Whereas spinal locomotion is well described in cats that underwent training trials after experimental spinal cord resection, less consistent information is available for dogs. HYPOTHESIS: Paraplegic dogs affected by a thoracolumbar complete spinal cord lesion undergoing intensive physical rehabilitation could acquire an autonomous SW gait under field conditions. ANIMALS: Eighty-one acute paraplegic thoracolumbar dogs without pelvic limb pain perception. METHODS: Retrospective study of medical records of dogs selected for intensive rehabilitation treatment in paraplegic dogs with absence of pain perception on admission and during the whole treatment. Binary regression and multivariate logistic regression were used to analyze potential associations with the development of SW. RESULTS: Autonomous SW was achieved in 48 dogs (59%). Median time to achieve SW was of 75.5 days (range: 16-350 days). On univariate analysis, SW gait was associated with younger age (P = .002) and early start of physiotherapy (P = .024). Multivariate logistic regression showed that younger age (≤60 months) and lightweight (≤7.8 kg) were positively associated with development of SW (P = .012 and P < .001, respectively). BCS, full-time hospitalization, and type and site of the lesion were not significantly associated with development of SW. CONCLUSIONS: Dogs with irreversible thoracolumbar lesion undergoing intensive physiotherapic treatment can acquire SW. Younger age and lightweight are positively associated with the development of SW gait.

PTPRC (CD45) is not associated with the development of multiple sclerosis in U.S. patients.

A C-->G nucleotide transition in exon 4 of PTPRC (encoding protein-tyrosine phosphatase receptor-type C, also known as CD45) was recently reported to be genetically associated with the development of multiple sclerosis (MS). We performed an extensive evaluation of this polymorphism using large family-based and case-control comparisons. Overall, we observed no evidence of genetic association between the PTPRC polymorphism and MS susceptibility or disease course.

Expression of mouse CD43 in the B cell lineage of transgenic mice causes impaired immune responses to T-independent antigens.

CD43 (leukosialin), a sialylated glycoprotein expressed on the surface of most hematopoietic cells, has been implicated in cell adhesion and signaling. However, its precise physiological function remains unclear. We used mouse CD43 (mCD43)-immunoglobulin enhancer-transgenic (TG) mice to study the role of mCD43 in vivo. Previous work revealed that mCD43 expression on mature B cells in these mice resulted in immunodeficiency to T-dependent (TD) antigens (Ag), possibly by impairing B-T cell interactions. In the present study we have immunized the TG mice with the T-independent (TI) Ag fluorescein-(Fl) lipopolysaccharide (LPS) (TI type 1 Ag) and Fl-Ficoll (TI type 2 Ag). Surprisingly, the mCD43-Ig enhancer expressing mice were impaired in their ability to mount humoral responses to both Fl-LPS and Fl-Ficoll, and had decreased numbers of cells responding to Ag in vivo. Flow cytometric analysis was performed on peritoneal B-1 cells, a population which often plays a major role in humoral responses to TI Ag such as bacterial Ag. This analysis revealed similar B220, IgM and CD5 expression patterns for the TG and nontransgenic (NTG) B-1 cells. In addition, purified peritoneal B-1 cells from TG and NTG mice were able to respond to LPS. Stimulation of splenic B cells in vitro with Fl-LPS and Fl-Ficoll revealed that, in contrast to NTG B cell responses, TG B cell responses could not be enhanced by co-culture with T cells. However, soluble T cell factor enhancement of the TG B cell responses was normal. These data suggest that the mCD43 expression on B cells may inhibit cell interactions that are important for enhanced TI Ag responses. The anti-adhesive forces of mucins in general may thus be critical in regulating both TD and TI humoral responses.

Disregulated expression of CD43 (leukosialin, sialophorin) in the B cell lineage leads to immunodeficiency.

Leukosialin (CD43 or sialophorin) is a cell surface sialoglycoprotein implicated in cell adhesion and proliferation whose tightly regulated expression in B lymphocytes is likely important for their normal development and/or function. To examine the physiologic role of mouse CD43 (mCD43) in vivo, we exploited transgenic (TG) mice whose developmental expression of mCD43 was extended during B cell differentiation so that mCD43 was now expressed on peripheral B cells. Despite having increased B cells, localization of lymphocytes in the TG spleens appeared normal by immunocytochemistry with anti-CD4, anti-CD8, and anti-B220 mAbs. However, the numbers of splenic germinal centers and the resting sera Ig levels were decreased in the TG mice compared with littermate controls. TG mice had decreased humoral responses to the T-dependent Ags keyhole limpet hemocyanin and OVA, as well as reduced Ag-specific B cell numbers. In contrast, in vitro LPS stimulation of purified TG or control B cells resulted in similar proliferation and IgM responses. Thus, the alteration of B cell mCD43 expression that resulted in profound immunodeficiency in vivo was not due to absolute defects in B cell development or Ab production. However, TG B cells had a decreased ability to homotypically aggregate and to present Ag to the T cell hybridoma B3Z. These data suggest that the immunodeficiency seen in vivo is due to the anti-adhesive forces of mCD43 preventing normal T-B cell interaction. This likely reflects a general property of mucins in regulating cell interactions.

Disregulation of leukosialin (CD43, Ly48, sialophorin) expression in the B-cell lineage of transgenic mice increases splenic B-cell number and survival.

Leukosialin (also known as Ly48, CD43, and sialophorin) is a major cell surface sialoglycoprotein found on a variety of hematopoietically derived cells. The precise function of this molecule is poorly understood but it has been implicated in cell proliferation and intercellular adhesion. We developed a transgenic mouse model to assess leukosialin's function in vivo. Our approach was to alter mouse CD43 (mCD43) expression in the B-cell lineage where it is tightly regulated, by expressing it in peripheral B cells where it is normally absent. To drive expression of leukosialin in mature B cells, the immunoglobulin heavy chain enhancer was fused to the mCD43 gene. mCD43-immunoglobulin heavy chain enhancer transgenic mice display splenomegaly due to increased numbers of B cells. Transgenic B cells show a striking increase in their ability to survive in vitro compared to B cells from nontransgenic control mice. This prolonged survival is reflected in a decreased susceptibility to apoptosis. These observations suggest that mCD43 plays an important role in the regulation of B-cell survival. The alteration of the temporal expression, or "disregulation," of a gene in transgenic mice provides a general strategy for elucidating the in vivo role of other molecules involved in cell signaling and adhesion.

CD43 is expressed normally on Wiskott-Aldrich-derived lymphocytes.

The Wiskott-Aldrich syndrome (WAS) is an X-linked disease characterized by eczema, thrombocytopenia, and profound immunodeficiency in affected males. While the etiology of the syndrome is currently unknown, abnormalities of CD43 have been described as a biochemical marker of the disease. Several investigators have demonstrated alterations in the expression of the CD43 surface antigen on WAS hematopoietic cells, noting either absence, decreased levels or changes in the characteristic molecular weight of the protein on the lymphocytes of affected patients. Biochemical studies have further indicated that glycosylating activity of specific enzymes which may post-translationally modify CD43 is altered in both T cells and Epstein-Barr-virus (EBV)-transformed B cells in WAS patients when compared to unaffected controls. Here we present data on cells derived from two males with a clinical diagnosis of WAS. Analysis of genomic DNA from the mothers of each of these patients (obligate carriers) showed a nonrandom X-chromosome inactivation pattern of nucleated blood cells, confirming the diagnosis of the X-linked syndrome. CD43 was characterized on peripheral blood lymphocytes and long-term EBV-transformed B cell lines, both to further analyze the molecular defects of WAS, as well as to attempt to generate a reproducible method for disease detection. Surprisingly, surface expression, molecular weight and two-dimensional gel analysis failed to demonstrated any reproducible differences in the CD43 expression, whether from disease or normal lymphocytes. Such results suggest possible heterogeneity of this syndrome.

Ultrasound evaluation of the ovarian hyperstimulation syndrome.

282 cycles in 106 women going to be artificially inseminated at the AIED Center in Rome have been studied by means of ultrasound monitoring in order to evaluate the incidence of the ovarian hyperstimulation syndrome. In none of the patients, either in pharmacologically stimulated cycles (82 in 36 women) or in non stimulated cycles (200 in 70 women) moderate or severe hyperstimulation syndrome was reported. Only few mild cases occurred. In the non stimulated group only five cases with mild hyperstimulation occurred (2.5%). 31 pregnancies have been obtained (15.5% of all studied cycles). In the stimulated group 11 cases with signs of mild hyperstimulation occurred (13.4%) and 19 pregnancies were obtained (23.1%) of the stimulated cycles). No twin pregnancy was observed. The only molar pregnancy reported occurred in this group. All signs of hyperstimulation--either in stimulated cycles or in non stimulated patients--regressed spontaneously in the same cycle and anyhow they were not detected by ultrasound monitoring in the subsequent cycle.