Mouse homologues of the human AZF candidate gene RBM are expressed in spermatogonia and spermatids, and map to a Y chromosome deletion interval associated with a high incidence of sperm abnormalities

An RNA-binding motif (RBM) gene family has been identified on the human Y chromosome that maps to the same deletion interval as the 'azoospermia factor' (AZF). We have identified the homologous gene family (Rbm) on the mouse Y with a view to investigating the proposal that this gene family plays a role in spermatogenesis. At least 25 and probably >50 copies of Rbm are present on the mouse Y chromosome short arm located between Sry and the centromere. As in the human, a role in spermatogenesis is indicated by a germ cell-specific pattern of expression in the testis, but there are distinct differences in the pattern of expression between the two species. Mice carrying the deletion Yd1, that maps to the proximal Y short arm, are female due to a position effect resulting in non-expression of Sry ; sex-reversing such mice with an Sry transgene produces males with a high incidence of abnormal sperm, making this the third deletion interval on the mouse Y that affects some aspect of spermatogenesis. Most of the copies of Rbm map to this deletion interval, and the Yd1males have markedly reduced Rbm expression, suggesting that RBM deficiency may be responsible for, or contribute to, the abnormal sperm development. In man, deletion of the functional copies of RBM is associated with meiotic arrest rather than sperm anomalies; however, the different effects of deletion are consistent with the differences in expression between the two species.      

Monosomy 7p in meningiomas: a rare constituent of tumor progression

We present karyotypes of 15 meningiomas with structural aberrations of chromosome 7, which were taken from a consecutive series of 400 cytogenetically characterized meningiomas. Twelve of these tumors (80%) displayed partial or complete monosomy 7p with a consensus deleted region of 7p12 approximately pter, in 6 of 15 cases arising from an unbalanced whole-arm t(1;7)(q11;p11), and in 4 of 15 cases from a whole-arm translocation involving other chromosomes. Other types of partial aneusomy 7 (3/15 cases) or balanced aberrations of chromosome 7 (2/15 cases) were relatively rare. In most cases (11/15), the centromeric region of chromosome 7 was involved in the rearrangements. We conclude that in meningiomas, the near-centromeric region of chromosome 7 is particularly prone to structural rearrangements most frequently resulting in monosomy 7p. The investigation of the histopathologic features of this rare cytogenetic subgroup of meningiomas showed no clear genotype/phenotype correlation. As 7 of 11 of the meningiomas with monosomy 7p belonged to World Health Organization grades II or III, which usually comprise less than 20% of all meningiomas, partial loss of 7p appears to be involved in tumor progression in meningiomas. Because monosomy 7p is typically associated with the strongly progression-associated monosomy 1p, however, monosomy 7p represents a cofactor more than a stand-alone feature of meningioma progression.     

Interleukin-18 impairs the pulmonary host response to Pseudomonas aeruginosa

Interleukin-18 (IL-18) is a potent cytokine with many different proinflammatory activities. To study the role of IL-18 in the pathogenesis of Pseudomonas pneumonia, IL-18-deficient (IL-18(-/-)) and wild-type mice were intranasally inoculated with Pseudomonas aeruginosa. IL-18 deficiency was associated with reduced outgrowth of Pseudomonas in the lungs and diminished dissemination of the infection. In addition, pulmonary inflammation (histopathology) and levels of tumor necrosis factor alpha, IL-6, and macrophage inflammatory protein-2 in lungs and plasma were lower in IL-18(-/-) mice. Consistent with results obtained for IL-18(-/-) mice, treatment of wild-type mice with a neutralizing IL-18 binding protein-immunoglobulin G Fc fusion construct also attenuated outgrowth of Pseudomonas compared with that for mice treated with a control protein. These results demonstrate that the presence of endogenous IL-18 activity facilitates inflammatory responses in the lung during Pseudomonas pneumonia, concurrently impairing bacterial clearance.     

Characterization of FcepsilonRI-bearing CD123 blood dendritic cell antigen-2 plasmacytoid dendritic cells in atopic dermatitis

BACKGROUND: The high-affinity receptor for IgE (FcepsilonRI) on myeloid dendritic cells has been shown to play a major role in atopic dermatitis (AD). Plasmacytoid dendritic cells (pDCs), which are instrumental in the defense of viral infections, are present in reduced amounts in the skin of patients with AD, which is characterized by a high susceptibility to viral infections. OBJECTIVE: We explored phenotypical and functional characteristics of pDC in the peripheral blood of patients with AD and healthy individuals. METHODS: Blood dendritic cell antigen-2+CD123+ pDCs were enriched from the peripheral blood of patients with AD and studied in functional assays. RESULTS: Skin-homing molecules such as cutaneous lymphocyte antigen and L-selectin CD62L were expressed in lower levels on pDCs of patients with AD. pDCs expressed high amounts of IgE-occupied FcepsilonRI. Further, FcepsilonRI aggregation on pDCs impaired the surface expression of MHC I and II, induced the production of IL-10, and enhanced the apoptosis of pDCs. Importantly, FcepsilonRI preactivated pDC produced less IFN-alpha and IFN-beta after stimulation with CpG motifs and enhanced the outcome of immune responses of the TH2 type. CONCLUSION: From these data, we conclude that FcepsilonRI-bearing pDCs from patients with AD (1) are different from pDCs of healthy individuals, (2) might be important in the pathophysiology of AD, and (3) contribute to the enhanced susceptibility of patients with AD to viral infections.     

Impact of maternal age and maternal somatic characteristics on newborn size

Pregnancies during early adolescence were commonly thought to represent special risks, such as preterm delivery or low‐weight newborns, resulting in increased mortality and morbidity of mother and child. An important biopsychosocial interaction can be assumed. In the present study the impact of maternal age and maternal somatic characteristics such as prepregnancy weight, stature, or pregnancy weight gain on newborn somatometric features (birth weight, birth length, head circumference, and arcomial circumference) using a dataset of 8,011 single term births were analyzed. The offspring of 215 extremely young mothers ages 12–16 years were significantly (P < 0.0001) lighter and smaller in all body dimensions than the offspring of older adolescent mothers, ages 17–19 years, and the offspring of adult gravida, ages 20–29 years, although no increased incidence of low‐weight newborns (<2,500g) could be observed. As expected, the youngest mothers were also significantly smaller and lighter than their older, biologically more mature counterparts, although the relative weight gain during pregnancy was highest in the youngest age group (23.4% vs. 22.9 and 22.1%, respectively). In general, age but also pregnancy weight gain and prepregnancy weight status were significantly associated with pregnancy outcome. Within term births taking place under sufficient psychosocial support, maternal somatic features had an important impact on newborn size. Am. J. Hum. Biol. 15:220–228, 2003. ©2003 Wiley‐Liss, Inc.     

Histological,immunohistochemical, and ultrastructural features of a rat medullary thyroid carcinoma transfected with a corticotropin-releasing hormone cDNA expression vector

Clonal cell lines producing corticotropin-releasing hormone (CRH) have been generated by transfection of the W2 rat medullary thyroid carcinoma (MTC) cell with a CRH-encoding CMV/ SV40 expression vector. Here, we report the morphological, immunohistochemical, and ultrastructural features of rat tumors derived by implantation of CRH-producing W2CRH-7 cells and compare them with non-CRH-producing W2 MTCs. Both types of tumors grew rapidly and consisted of sheets and nests of pleomorphic cells infiltrating adjacent adipose tissue. Immunohistochemistry revealed CRH in only W2CRH-7 tumors; scattered cells in these tumors also were immunoreactive for chromogranin and for vasoactive intestinal peptide. Otherwise, the two tumor types exhibited similar profiles of various neuroendocrine markers, including neuron-specific enolase, synaptophysin, calcitonin, and somatostatin. Ultrastructurally, the tumors contained abundant dilated rough endoplasmic reticulum, a prominent Golgi apparatus, and numerous lysosomes. Very few secretory granules were noted in the W2 tumors; by contrast, secretory granules, although still not numerous in the majority of W2CRH-7 cells, were more abundant in scattered cells of those tumors. The positive immunostaining for CRH is consistent with the observations of increased plasma CRH and pituitary-adrenal activation induced by these transplanted tumors. This system provides a valuable model for CRH excess mimicking tumoral CRH-dependent Cushing’s syndrome in human patients.