Autosomal Recessive Congenital Ichthyosis in American Bulldogs Is Associated With NIPAL4 (ICHTHYIN) Deficiency.

A minority of patients with nonsyndromic autosomal recessive congenital ichthyosis (ARCI) display mutations in NIPAL4 (ICHTHYIN). This protein plays a role in epidermal lipid metabolism, although the mechanism is unknown. The study describes a moderate form of ARCI in an extended pedigree of American Bulldogs that is linked to the gene encoding ichthyin. The gross phenotype was manifest as a disheveled pelage shortly after birth, generalized scaling, and adherent brown scale with erythema of the abdominal skin. Pedigree analysis indicated an autosomal recessive mode of inheritance. Ultrastructurally, the epidermis showed discontinuous lipid bilayers, unprocessed lipid within corneocytes, and abnormal lamellar bodies. Linkage analysis, performed by choosing simple sequence repeat markers and single-nucleotide polymorphisms near genes known to cause ACRI, revealed an association with NIPAL4. NIPAL4 was identified and sequenced using standard methods. No mutation was identified within the gene, but affected dogs had a SINE element 5' upstream of exon 1 in a highly conserved region. Of 545 DNA samples from American Bulldogs, 32 dogs (17 females, 15 males) were homozygous for the polymerase chain reaction fragment. All affected dogs were homozygous, with parents heterozygous for the insertion. Immunolabeling revealed an absence of ichthyin in the epidermis. This is the first description of ARCI associated with decreased expression of NIPAL4 in nonhuman species.

Evaluation of cyclooxygenase-1 and cyclooxygenase-2 expression and the effect of cyclooxygenase inhibitors in canine prostatic carcinoma.

Prostatic carcinoma occurs primarily in older castrated male dogs and is typically a fatal disease (most dogs die within few months after the initial diagnosis). Surgery, i.e., total prostatectomy, or radiation therapy is often not pursued due to risks of complications and a high rate of distant metastasis. Cyclooxygenase-2 (Cox-2) expression has been documented in several malignancies, including canine prostatic carcinoma. Cox-2 inhibition has been reported to have preventative effects on several human malignancies and has therapeutic effects on both laboratory and spontaneous tumour models. The purpose of this retrospective study was to evaluate Cox expression and the effects of Cox inhibitors on survival in dogs with prostatic carcinoma. 94.1 and 88.2% of the tumours expressed Cox-1 and Cox-2, respectively. Furthermore, dogs treated with Cox inhibitors (piroxicam or carprofen) lived significantly longer than untreated dogs, 6.9 versus 0.7 months (P < 0.0001), suggesting that Cox inhibitors may have an important role in canine prostate cancer therapy.

Immunohistochemical characterization of canine prostatic carcinoma and correlation with castration status and castration time.

The purpose of this study was to characterize canine prostate cancer using immunohistochemical staining specific for acinar and urothelial/ductal tissue and correlate these results with the dogs' castration status/castration time. Seventy dogs with prostate cancer were included, 71% were castrated and 29% were intact. Compared with an age-matched control population, castrated dogs were at increased risk of prostate cancer, odds ratio 3.9. Immunohistochemical staining was performed on 58 cases. Forty-six of the 58 stained positive for cytokeratin 7 (CK 7) (ductal/urothelial origin) and one of the 58 stained positive for prostate-specific antigen. Dogs with CK 7-positive tumours were younger when castrated than dogs with CK 7-negative tumours, 2 versus 7 years (P = 0.03); dogs castrated at

The diagnosis and prognosis of synovial tumors in dogs: 35 cases.

Although synovial cell sarcoma is reported to be the most common neoplasm of the canine synovium, this retrospective study of 35 canine synovial tumors found that the majority were of histiocytic origin. Five (14.3%) synovial cell sarcomas were identified by positive immunohistochemical staining with antibodies to cytokeratin. Eighteen (51.4%) histiocytic sarcomas were identified by cell morphology and immunohistochemical staining with antibodies to CD18. Six (17.1%) synovial myxomas were identified by histologic pattern. The remaining six (17.1%) synovial tumors represented a variety of sarcomas, including two malignant fibrous histiocytomas (actin positive), one fibrosarcoma, one chondrosarcoma, and two undifferentiated sarcomas. Rottweilers were overrepresented in the histiocytic sarcoma category and Doberman Pinschers were overrepresented in the synovial myxoma category. The average survival time was 31.8 months for dogs with synovial cell sarcoma, 5.3 months for dogs with histiocytic sarcoma, 30.7 months for dogs with synovial myxoma, and 3.5 months for dogs with other sarcomas. Among the dogs with follow-up information available, metastatic disease was detected in 25% of dogs with synovial cell sarcoma, in 91% of dogs with histiocytic sarcoma, in none of the dogs with synovial myxoma, and in 100% of dogs with other sarcomas. Immunohistochemical staining for cytokeratin, CD18, and smooth muscle actin is recommended to make the diagnosis and thereby predict the behavior of synovial tumors in dogs.