Genetics of the apnea hypopnea index in Caucasians and African Americans: I. Segregation analysis

Differences in age of presentation and anatomic risk factors for obstructive sleep apnea (OSA) in Caucasians and African Americans suggest possible racial differences in the genetic underpinnings of the disorder. In this study, we assess transmission patterns in a Caucasian sample consisting of 177 families (N = 1,195) and in an African American sample consisting of 125 families (N = 720) for two variables: 1) apnea hypopnea index (AHI) log transformed and adjusted for age, and 2) AHI log transformed and adjusted for age and body mass index (BMI). We allowed for residual familial correlations and sex-specific means in all models. Analysis of the Caucasian sample showed transmission patterns consistent with that of a major gene that were stronger in the age-adjusted variable than in the age- and BMI-adjusted variable. However, in the African American families, adjusting for BMI in addition to age gave stronger evidence for segregation of a codominant gene with an allele frequency of 0.14, accounting for 35% of the total variance. These results provide support for an underlying genetic basis for OSA that in African Americans is independent of the contribution of BMI.     

The triad of bilateral retinoblastoma, dysplastic naevus syndrome and multiple cutaneous malignant melanomas: a case report and review of the literature

We report a case of a patient with the triad of retinoblastoma, dysplastic naevus syndrome (DNS) and multiple cutaneous melanomas. The combination of retinoblastoma and DNS is a significant risk factor for the development of cutaneous melanoma. This risk extends to family members. We recommend that survivors of (inherited) retinoblastoma and their relatives are closely screened for the presence of dysplastic naevi.     

Progesterone receptors A and B differentially modulate corticotropin-releasing hormone gene expression through a cAMP regulatory element

Corticotrophin-releasing hormone (CRH) plays a major role in mechanisms controlling human pregnancy and parturition. Gene regulation by progesterone may be a key point in the control of placental CRH production. Studies in primary placental ceils show that antagonism of progesterone activity or production by RU486 or trilostane leads to an increase in CRH promoter activity. This effect can be reversed by the addition of progesterone. Overexpression of progesterone receptor A (PRA) or glucocorticoid receptor resulted in a decrease in CRH promoter activity following progesterone treatment, whereas an increase in promoter activity was observed with overexpressed PR-B.     

Estrogen receptor-mediated down-regulation of corticotropin-releasing hormone gene expression is dependent on a cyclic adenosine 3＇ ,5＇-monophosphate regulatory element in human placental syncytiotrophoblast cells

Placental CRH plays a major role in the mechanisms controlling human pregnancy and parturition. Understanding how placental CRH production is regulated is therefore of importance. Previously we have shown that placental expression of CRH peptide and mRNA are inhibited by estrogens, in contrast to the stimulatory effects of estrogen on hypothalamic CRH production. Our current study found that in placental cells cotransfected with a CRH promoter construct and an estrogen receptor-alpha expression vector results in a differential regulation whereby 17beta estradiol (E2) decreased and the putative pure estrogen antagonist, ICI 182780,     

Extent of ductal carcinoma in situ within and surrounding invasive primary breast carcinoma

BACKGROUND: The aim of this study was to evaluate the pathological and morphological features of ductal carcinoma in situ (DCIS) within and surrounding invasive ductal carcinoma, and to investigate its relationship with clinical outcome and established prognostic variables. METHODS: One hundred and seven patients with primary operable invasive breast carcinoma and associated DCIS treated by simple or subcutaneous mastectomy or wide local excision with radiotherapy were assessed. Those with pure DCIS and insufficient tumour available for examination were excluded. The most representative haematoxylin and eosin-stained sections from the remaining 91 samples were selected and examined at x 100 magnification using a 45-point, 2-mm grid graticule. The entire section was assessed and the cell under each point of the graticule was classed as either normal (a), DCIS surrounded by normal tissue (b), invasive tumour (c) or DCIS surrounded by invasive malignancy (d). The volume ratio of DCIS in the normal (b/(a + b)) and invasive (d/(c + d)) tissue was then calculated. RESULTS: The DCIS volume within invasive tumour was not associated with outcome. The DCIS volume within adjacent normal tissue, however, was associated with local recurrence (P = 0.025), disease-free interval (P = 0.048), the occurrence of distant metastases (P = 0.019), death (P = 0.049) and disease-free survival (P = 0.048). Volume ratios of DCIS in normal and invasive tissue were not related to known prognostic factors including lymph node stage, grade, tumour size, vascular invasion or patient age. CONCLUSION: There is a significant prognostic effect relating to the extent of DCIS associated with an invasive cancer, particularly with respect to local recurrence of tumour. This effect is restricted to the volume of DCIS in the tissue surrounding the invasive lesion rather than the intratumoral component.