Thrombospondin 4 deficiency in mouse impairs neuronal migration in the early postnatal and adult brain.

In the post-natal rodent brain, neuronal precursors originating from the sub-ventricular zone (SVZ) migrate over a long distance along the rostral migratory stream (RMS) to eventually integrate the olfactory bulb neuronal circuitry. In order to identify new genes specifically expressed in the RMS, we have screened the Allen Brain Atlas Database. We focused our attention on Thrombospondin 4 (Thbs4), one of the 5 members of the Thrombospondin family of large, multidomain, extracellular matrix proteins. In post-natal and adult brain Thbs4 mRNA and protein are specifically expressed in the neurogenic regions, including the SVZ and along the entire RMS. RMS cells expressing Thbs4 are GFAP (Glial Fibrillary Acidic Protein) positive astrocytes. Histological analysis in both wild-type and Thbs4 knock-out mice revealed no major abnormality in the general morphology of these neurogenic regions. Nevertheless, immunostaining for doublecortin demonstrates that in Thbs4-KO, migration of newly formed neurons along the RMS is somehow impaired, with several neurons migrating out of the RMS. This is further supported by a Bromodeoxyuridine-based in vivo approach showing a decrease in the number of newly born neuronal precursors reaching the olfactory bulb, while proliferation in the SVZ is not affected compared to wild-type, both in young animals (P15) and in adults (8 to 12 weeks of age). Corroborating this observation, the number of Parvalbumin- and Calbindin-immunoreactive interneurons in the olfactory bulb is also reduced in Thbs4-KO. Together, these observations support a role for the astrocyte-secreted protein Thbs4 in the migration of newly form neurons within the RMS to the olfactory bulb.

Comparison of a rapid immunoassay for antibodies to the C6 antigen with conventional tests for antibodies to Borrelia burgdorferi in dogs in Europe.

A commercial immunoassay for antibodies to the C6 antigen of Borrelia burgdorferi was evaluated against an IgG in-house ELISA in combination with a Western blot assay to examine 104 samples of serum from 53 healthy Bernese mountain dogs, which were suspected to have a breed predisposition to Lyme borreliosis, and 55 samples from 30 healthy large-breed longhair dogs. The two test methods correlated in 125 (79 per cent) of the samples with an agreement of kappa=0.571 (P<0.001). In comparison with the in-house ELISA in combination with a Western blot, the sensitivity and specificity of the C6 test were 81 per cent and 77 per cent respectively. The agreement between the tests was better with the samples from the Bernese mountain dogs (k=0.681) than with the samples from the control dogs (k=0.347).

[The dilemma with Lyme borreliosis in the dog with particular consideration of "Lyme nephritis"]. / Das Dilemma der Lyme Borreliose beim Hund unter besonderer Berücksichtigung der "Lyme Nephritis"

Lyme borreliosis is the most commonly reported tick-transmitted infectious disease in the northern hemisphere in humans. Certain diseases are associated with Lyme borreliosis in the dog as well, but only intermittent lameness with articular swelling, lymphadenomegaly, fever, and anorexia were experimentally documented. Lyme borreliosis is considered an over diagnosed disease. The term "Lyme nephritis" was introduced for dogs with characteristic renal lesions and typical clinical signs, in which antibodies against Borrelia burgdorferi were found. Different studies have been aimed at showing a relation between renal disease and B. burgdorferi infection; however, this was not possible until now. Reasons for the uncertainty of the effects of B. burgdorferi in the dog are the high prevalence of circulating antibodies, the unspecific clinical picture and the inaccuracy of serologic tests.

Enhanced tumour growth and impaired cellular antitumoural defense in hepatic colorectal carcinoma metastasis in rats after laparoscopy compared to open surgery.

BACKGROUND: This study aims to assess postoperative hepatic growth of colorectal adenocarcinoma metastasis and peritumoural macrophage counts after laparoscopy in an experimental animal model. METHODS: Thirty male syngenic WAG/Rij rats were randomised into two surgical groups: laparoscopy (LS; n = 15) using CO(2) at 12 mmHg and laparotomy (LT; n = 15; negative control) during an operating time of 90 min. At 45 min after setup, CC531s colon adenocarcinoma cells were injected into two liver lobes. Postoperative tumour volumes were determined by abdominal magnetic resonance imaging (MRI) and computed three-dimensional volumetry. Peritumoural macrophages were counted by local stereology using a confocal laser-scanning fluorescence microscope. RESULTS: The median postoperative tumour volume was significantly higher after LS in both lobes (L): after 10, 15 and 20 days in L2 and L5: 24/12, 54/38, 275/62 mm(3) and 0/0, 15/11, 55/24 mm(3) (LS/LT). Significantly fewer peritumoural macrophages were found after LS at all postoperative time points (Mann-Whitney: p < 0.05). CONCLUSIONS: Increased hepatic growth of colorectal adenocarcinoma metastasis and impaired cellular antitumoural defence after LS cast doubt on the use of LS in colorectal cancer and needs further clinical investigation.

[Leiomyoma of a kidney in a dog: a rare diagnosis]. / Leiomyom einer Niere beim Hund--eine seltene Diagnose.

A five-year-old, neutered male, Bernese Mountain Dog was referred because of a two-week history of hematuria and a one-week history of polydipsia and polyuria. Palpation of the dorsomedial mesogastrium revealed a mass on the left side, which was seen via radiography and ultrasonography to be attached to the left kidney. The left kidney and the attached mass were excised surgically, and the dog had an uneventful recovery. Histological examination of the mass revealed a dense proliferation of non-polymorphic spindle cells, which stained positive for smooth muscle actin via immunohistochemistry. Leiomyoma of the kidney was diagnosed. Postoperatively, there was mild azotaemia, which did not affect the general condition of the dog and was still present 15 months after surgery. Leiomyoma of the kidney is a benign tumor, and hematuria may be the only clinical sign.

Cloned fusion product from a rare t(15;19)(q13.2;p13.1) inhibit S phase in vitro.

BACKGROUND: Somatically acquired chromosomal translocation is a common mechanism of oncogene activation in many haematopoietic tumours and sarcomas. However, very few recurrent chromosomal translocations have been reported in more common epithelial tumours such as lung carcinomas. METHODS: We established a cell line HCC2429 from an aggressive, metastatic lung cancer arising in a young, non-smoking woman, demonstrating a t(15;19)(q13.2;p13.1). The breakpoints on chromosomes 15 and 19 were cloned using long distance inverse PCR and we determined by RT-PCR that the translocation results in a novel fusion transcript in which the 3' end Brd4 on chromosome 19p is fused to the 5' end of NUT on chromosome 15q. RESULTS: In total, 128 lung cancer tissues were screened using fluorescent in situ hybridisation, but none of the tumours screened demonstrated t(15;19), suggesting that this translocation is not commonly found in lung cancer. Consistent with previous literature, ectopic expression of wild type Brd4 was shown to inhibit G(1) to S progression. However, we also found that the Brd4-NUT fusion augments the inhibition of progression to S phase compared with wild type Brd4. CONCLUSION: Alteration in cell cycle kinetics is important in tumorigenesis, although the exact role of Brd4-NUT fusion protein in the pathogenesis of lung cancers remains unclear and need to be further elucidated.

Nonlymphocyte-derived tumor necrosis factor is required for induction of colitis in recombination activating gene (RAG)2(-/-) mice upon transfer of CD4(+)CD45RB(hi) T cells.

In this study, we addressed the role of tumor necrosis factor (TNF)-alpha and lymphotoxin (LT)-alpha in the development of colitis and defined the cellular sources (T cells versus non-T cells) of TNF (TNF-alpha and LT-alpha) relevant to disease development. After adoptive transfer of TNF(+/+) CD4(+)CD45RB(hi) splenocytes into TNF(+/+) recombination activating gene (RAG)2(-/-) mice, the recipients develop massive inflammation of the large intestinal mucosa concurrent with massive weight loss. In contrast, clinical signs of disease are completely absent in TNF(-/-)RAG2(-/-) recipients of TNF(-/-) CD4(+)CD45RB(hi) T cells, although elevated numbers of interferon-gamma-producing cells are present in the colonic mucosa. Surprisingly, upon transfer of TNF(-/-)CD4(+)CD45RB(hi) T cells into TNF(+/+)RAG2(-/-) recipients, colitis develops with kinetics similar to those upon transfer of TNF(+/+)CD4(+)CD45RB(hi) donor cells. In contrast, no clinical signs of colitis are observed in TNF(-/-)RAG2(-/-) recipients of TNF(+/+)CD4(+)CD45RB(hi) T cells. This protection from colitis is not a consequence of the absence of LT-alpha, as TNF-alpha(-/-)RAG2(-/-) recipients of TNF-alpha(-/-) CD4(+)CD45RB(hi) T cells are also protected from colitis induction. These results demonstrate the importance of TNF production by non-T cells of the colonic mucosa in the pathogenesis of colitis and provide direct evidence for a nonredundant role of TNF-alpha in this mouse model of colitis.

Family functions and children's postdivorce adjustment.

Data on school-age children of divorced parents were examined to determine which dimensions of family dynamics were most associated with the children's socioemotional adjustment. Those factors found to be most significant were family roles, behavior control, and affective involvement, as well as children's reaction to and insight into the divorce, and conflict in the home after the divorce. Implications for parent education and early intervention are discussed.