Faculty Bibliography

Modulation of cell adhesion molecule expression plays a key role in melanoma metastasis. In particular, the expression of the cell adhesion molecule L1 has been associated with the metastatic phenotype in a murine model of malignant melanoma. However, no such association between L1 expression and metastasis has been investigated in a clinical study. Therefore, L1 expression was determined immunohistochemically in 100 cases of malignant melanoma and correlated with metastasis in a 10-year retrospective study. Furthermore, nine distant metastases and five sentinel lymph node metastases were analysed for their L1 expression. Additionally, the expression of alpha2,3 sialic acid residues, which are recognised by the siglec domain of L1, was determined by Maackia amurensis agglutinin (MAA) lectin histochemistry. The log-rank test between Kaplan-Meier curves revealed a positive association between L1 expression and metastasis (P<0.0001) and multivariate Cox regression analysis adjusted for tumour thickness, ulceration and mitotic rate confirmed the prognostic power of L1 in malignant melanoma. As alpha2,3 sialic acid residues were absent in melanoma cells, homotypic adhesion between melanoma cells via their siglec domain can be excluded, suggesting a different adhesive function of L1 during melanoma metastasis. The functional role of L1 was further stressed by the fact that its expression was preserved in metastatic lesions.

Muscle-specific kinase (MuSK) is a receptor tyrosine kinase expressed selectively in skeletal muscle. During neuromuscular synapse formation, agrin released from motor neurons stimulates MuSK autophosphorylation in the kinase activation loop and in the juxtamembrane region, leading to clustering of acetylcholine receptors. We have determined the crystal structure of the cytoplasmic domain of unphosphorylated MuSK at 2.05 A resolution. The structure reveals an autoinhibited kinase domain in which the activation loop obstructs ATP and substrate binding. Steady-state kinetic analysis demonstrates that autophosphorylation results in a 200-fold increase in k(cat) and a 10-fold decrease in the K(m) for ATP. These studies provide a molecular basis for understanding the regulation of MuSK catalytic activity and suggest that an additional in vivo component may contribute to regulation via the juxtamembrane region

OBJECTIVE: The emergence of Candida glabrata infections among patients with compromised immunity has become a serious concern, especially at centers caring for individuals with cancer. METHODS: During a prospective evaluation of Candida species associated with either clinically significant colonization or infection, 26.9% of C. glabrata isolates showed in vitro resistance to fluconazole (MIC of > or = 64 microg/ml). RESULTS: Antifungal susceptibility profiles and genetic fingerprinting analysis performed by randomly amplified polymorphic DNA (RAPD) techniques confirmed low-probability of phenotypic and genotypic relatedness among nosocomial C. glabrata isolates. CONCLUSIONS: Presence of polyclonal strains of C. glabrata in patients at our hospital was probably related to selection of resistant yeasts from environmental pool rather than monoclonal expansion or clustering of multi-drug resistant C. glabrata in high-risk patients

The differentiation between atypical variants of Spitz nevus and melanoma is often difficult given the many clinical and histopathologic similarities between the two. We report a case of an infant with a congenital scalp lesion exhibiting clinical features of melanoma, including variegation and regression of pigmentation and a rapidly changing appearance. Histologic examination of the excised lesion revealed a benign congenital Spitz nevus. This case emphasizes the need for clinical and histologic correlation in determining the benign or malignant nature of atypical pigmented lesions in infants

Small bowel obstruction (SBO) is a particularly vexing problem in the postoperative period. The goal of this study was to compare the results of operative versus nonoperative treatment. A secondary goal was to explore risk factors for necessitating reoperation in the immediate postoperative period. We conducted a historical cohort retrospective chart review at a university-affiliated hospital. The medical records of patients treated between 1985 and 2000 at the Sir Mortimer B. Davis Jewish General Hospital (Montreal, Quebec, Canada) who developed SBO after undergoing a laparotomy during that admission were reviewed. Postoperative SBO was defined as cessation of flatus or bowel movements after their resumption following operation. To compare operative versus nonoperative management of early postoperative mechanical SBO we used the following outcome measures: Reoperation rate, time to return of function, length of stay, and mortality. Of 52 patients who developed SBO in the immediate postoperative period 37 were male, 25 had colorectal surgery, and nine had a gastrectomy as the initial operation on admission; five had inflammatory bowel disease, six had a previous SBO, 22 had virgin abdomens before the current operation, and 11 had adhesions noted at the initial operation. The median time to the development of obstructive symptoms was 8 days (range 1-33). The reoperation rate was 42 per cent overall (67% in women and 32% in men, P = 0.02). For operatively treated patients the median time between onset of symptoms and surgery was 5 days [range 1-23, interquartile range (IQR) = 5]. The median time to the return of bowel function was greater in the operatively treated patients compared with nonoperatively treated patients [11.5 days (range 4-37, IQR = 11) vs 6 days (range 1-28, IQR = 7), P < 0.0001] as was median length of stay from onset of obstruction [23 days (range 6-60, IQR = 14) vs 12 days (range 2-45, IQR = 16), P < 0.009]. Operatively treated patients also stayed longer after their obstruction was relieved although not significantly longer [8 days (range 1-35, IQR = 11) vs 4.5 days (range 0-40, IQR = 10), P = 0.15]. There were 11 complications in nine of 22 patients who underwent operative treatment of their SBO. Immediate postoperative SBO can be treated nonoperatively in stable patients resulting in significantly quicker return of bowel function and shorter lengths of hospital stay. Definitive risk factors for immediate SBO could not be identified

Riga-Fede disease presents in early infancy and is characterized by firm, verrucous plaques arising on the oral mucosal surfaces. These histologically benign lesions occur as a result of repetitive trauma of the oral mucosal surfaces by the teeth. Early recognition of this entity is important, because it may be the presenting sign of an underlying neurologic disorder. We report the case of a 10-month-old boy with extensive Riga-Fede disease involving the lip and tongue that prompted a diagnosis of congenital autonomic dysfunction with universal pain loss

OBJECTIVE: Corticotropin-releasing hormone deficient mice (CRH-KO) serve as an interesting model to understand the role of CRH in the regulation of adrenomedullary system. The aim of this study was to compare tyrosine hydroxylase (TH) and phenylethanolamine N-methyltransferase (PNMT) on the levels of gene expression and protein in adrenal medulla of CRH-KO mice, their CRH (+/+) mates and Sprague-Dawley (SD) rats. METHODS: Levels of TH and PNMT mRNA were determined by reverse transcription with subsequent polymerase chain reaction (RT-PCR) and quantified relatively to the housekeeper glyceraldehyde-3-phosphate dehydrogenase. The amount of TH and PNMT protein was determined by Western blot analysis and visualized by enhanced chemiluminiscence. RESULTS: We detected a clear signal of 645 bp for TH mRNA and of 260 bp for PNMT mRNA in adrenal medulla of rats and CRH (+/+) mice, with higher concentration of TH and PNMT mRNA in rat adrenal medulla. Subsequently, TH and PNMT immunoprotein was measured and we found significantly higher amount of TH and also PNMT protein in the rat compared to CRH (+/+) mice. On the other hand, the amount of TH and PNMT immunoprotein in adrenal medulla of CRH-KO mice was significantly lower compared to CRH (+/+) mice. CONCLUSIONS: Our results indicate the lower production of adrenomedullary TH and PNMT protein in CRH (+/+) mice compared to rats, which reflects the lower gene expression of these enzymes in adrenal medulla of mice. We also demonstrated the differences in TH and PNMT protein levels between CRH (+/+) and CRH-KO (-/-) mice.