Background: Germline mutations in mismatch repair (MMR) genes are found in only about half of clinically diagnosed families with hereditary non-polyposis colorectal cancer syndrome (HNPCC) (or Lynch syndrome). Early i...Background: Germline mutations in mismatch repair (MMR) genes are found in only about half of clinically diagnosed families with hereditary non-polyposis colorectal cancer syndrome (HNPCC) (or Lynch syndrome). Early identification of gene carriers is essential to reduce cancer incidence and overall mortality. Aims: Recent evidence indicates an increase in size and number of sebaceous glands following activation of the hedgehog pathway, a crucial signalling pathway for animal development that is aberrantly activated in several types of cancer. Here we sought to assess a possible association between Fordyce granules (FGs-that is, ectopic sebaceous glands on the oral mucosa) and HNPCC. Methods: A total of 15 members of five different genetically unrelated HNPCC kindreds (MLH1 gene mutation n = 8; undetectable MLH1 protein at immunochemistry n = 4; clinical diagnosis n = 3) and 630 genetically unrelated age and sex matched healthy controls were examined. Following examination of the oral mucosa surface, subjects were categorised as either FGs positive or FGs negative. Results: Evidence of FGs was significantly associated with HNPCC (13/15 (86.7% ) affected patients v 6/630 (0.95% ) controls; p< 0.0001), with a relative risk of 91.0 (95% confidence interval 40.05-206.76). The observed difference remained significant when carriers of germline mutations in MMR genes were considered (8/15 v 6/630; p< 0.0001). The most common site for the FGs in HNPCC patients was the lower gingival and vestibular oral mucosa. Conclusions: Our findings suggest that a previously unrecognised activation of the sebaceous glands system occurs in HNPCC. The observation could be of value for attending physicians in identifying affected families and/or increase the accuracy of the currently available molecular genetics screenings.展开更多
An abnormal pulmonary vasculature has been reported as an important component of bronchopulmonary dysplasia (BPD).We tested the hypothesis of an early abnormal vascular network pattern in infants with BPD.Fifteen infa...An abnormal pulmonary vasculature has been reported as an important component of bronchopulmonary dysplasia (BPD).We tested the hypothesis of an early abnormal vascular network pattern in infants with BPD.Fifteen infants with BPD (nine boys and six girls; gestational age 27.5 ±2.0 wk; birth weight 850 ±125 g) and 15 sex-and gestational age-matched infants (nine boys and six girls; gestational age 27.6 ±2.6 wk; birth weight 865 ±135 g) were examined on postnatal days 1 and 28.BPD infants showed a significantly higher prevalence of histologic chorioamnionitis (p = 0.009), as well as higher intubation duration (p = 0.0004), oxygen supplementation (p < 0.0001), and initial illness severity (p = 0.0002) than the BPD-negative population.The lower gingival and vestibular oral mucosa was chosen as the study area.The blood vessel areawas determined, and the oral vascular networks were characterized by analyzing their complexity (D, at two scales: D 1-46, D 1-15), tortuosity (Dmin), and randomness (L-Z) of the vascular loops.Infants with BPD showed a significantly lower blood vessel area aswell as a higher vascular network complexity (D 1-46, D 1-15, and L-Z) than control subjects (p < 0.0001).Our findings provide a new early clinical sign in BPD and stress the importance of an early disorder in the oral mucosal vascularization process in the disease pathogenesis.展开更多
Down syndrome is a leading genetic cause of mental retardation. Here, we show high fractal dimensions and Lempel-Ziv complexity and lower minimum path fractal dimension (P ≤.0006) for the oral vascular networks of pa...Down syndrome is a leading genetic cause of mental retardation. Here, we show high fractal dimensions and Lempel-Ziv complexity and lower minimum path fractal dimension (P ≤.0006) for the oral vascular networks of patients (n = 14)-and their unaffected parents. This newly rec- ognized sign may provide a useful phenotypical marker for identifying couples potentially at risk for offspring with Down syndrome.展开更多
文摘Background: Germline mutations in mismatch repair (MMR) genes are found in only about half of clinically diagnosed families with hereditary non-polyposis colorectal cancer syndrome (HNPCC) (or Lynch syndrome). Early identification of gene carriers is essential to reduce cancer incidence and overall mortality. Aims: Recent evidence indicates an increase in size and number of sebaceous glands following activation of the hedgehog pathway, a crucial signalling pathway for animal development that is aberrantly activated in several types of cancer. Here we sought to assess a possible association between Fordyce granules (FGs-that is, ectopic sebaceous glands on the oral mucosa) and HNPCC. Methods: A total of 15 members of five different genetically unrelated HNPCC kindreds (MLH1 gene mutation n = 8; undetectable MLH1 protein at immunochemistry n = 4; clinical diagnosis n = 3) and 630 genetically unrelated age and sex matched healthy controls were examined. Following examination of the oral mucosa surface, subjects were categorised as either FGs positive or FGs negative. Results: Evidence of FGs was significantly associated with HNPCC (13/15 (86.7% ) affected patients v 6/630 (0.95% ) controls; p< 0.0001), with a relative risk of 91.0 (95% confidence interval 40.05-206.76). The observed difference remained significant when carriers of germline mutations in MMR genes were considered (8/15 v 6/630; p< 0.0001). The most common site for the FGs in HNPCC patients was the lower gingival and vestibular oral mucosa. Conclusions: Our findings suggest that a previously unrecognised activation of the sebaceous glands system occurs in HNPCC. The observation could be of value for attending physicians in identifying affected families and/or increase the accuracy of the currently available molecular genetics screenings.
文摘An abnormal pulmonary vasculature has been reported as an important component of bronchopulmonary dysplasia (BPD).We tested the hypothesis of an early abnormal vascular network pattern in infants with BPD.Fifteen infants with BPD (nine boys and six girls; gestational age 27.5 ±2.0 wk; birth weight 850 ±125 g) and 15 sex-and gestational age-matched infants (nine boys and six girls; gestational age 27.6 ±2.6 wk; birth weight 865 ±135 g) were examined on postnatal days 1 and 28.BPD infants showed a significantly higher prevalence of histologic chorioamnionitis (p = 0.009), as well as higher intubation duration (p = 0.0004), oxygen supplementation (p < 0.0001), and initial illness severity (p = 0.0002) than the BPD-negative population.The lower gingival and vestibular oral mucosa was chosen as the study area.The blood vessel areawas determined, and the oral vascular networks were characterized by analyzing their complexity (D, at two scales: D 1-46, D 1-15), tortuosity (Dmin), and randomness (L-Z) of the vascular loops.Infants with BPD showed a significantly lower blood vessel area aswell as a higher vascular network complexity (D 1-46, D 1-15, and L-Z) than control subjects (p < 0.0001).Our findings provide a new early clinical sign in BPD and stress the importance of an early disorder in the oral mucosal vascularization process in the disease pathogenesis.
文摘Down syndrome is a leading genetic cause of mental retardation. Here, we show high fractal dimensions and Lempel-Ziv complexity and lower minimum path fractal dimension (P ≤.0006) for the oral vascular networks of patients (n = 14)-and their unaffected parents. This newly rec- ognized sign may provide a useful phenotypical marker for identifying couples potentially at risk for offspring with Down syndrome.
