Cowden syndrome and Lhermitte-Duclos disease in a family: a single genetic syndrome with pleiotropy?

Cowden syndrome is an autosomal dominant condition of multiple hamartomas. Patients with this phakomatosis have an increased risk of breast cancer and thyroid tumours. Lhermitte-Duclos disease is usually a sporadic condition of cerebellar ganglion cell hypertrophy, ataxia, mental retardation, and self-limited seizure disorder. We describe a three generation family with Cowden syndrome and Lhermitte-Duclos disease. Karyotyping performed on the peripheral lymphocytes of the proband and her affected mother showed a 46,XX complement. Single strand conformational polymorphism analysis failed to show any germline p53 mutations as a cause of the syndrome in this family.     

Terminal bronchioles harbor a unique airway stem cell population that localizes to the bronchoalveolar duct junction

Cellular mechanisms contributing to renewal of terminal bronchioles remain poorly defined. Our previous studies identified pollutant-resistant Clara cell secretory protein (CCSP)-expressing stem cells that localize to the neuroepithelial body (NEB) and contribute to renewal of the proximal bronchiolar epithelium. However, activation of NEB-associated stem cells is unlikely to contribute to renewal of terminal bronchiolar epithelium because of the paucity of NEBs at this location. Goals of this study were to determine the location and properties of cells contributing to renewal of terminal bronchioles after Clara cell depletion. Pollutant-resistant CCSP-expressing cells were identified that localized to the bronchoalveolar duct junction (BADJ) and contribute to restoration of a phenotypically diverse epithelium. CCSP-expressing cells comprise the predominant proliferative population in initial terminal bronchiolar repair and include a population of label-retaining cells suggesting that they maintain characteristics of a stem cell population. Furthermore, immunohistochemical co-localization studies involving CCSP and the NEB-specific marker calcitonin gene-related peptide indicate that BADJ-associated CCSP-expressing stem cells function independently of NEB microenvironments. These studies identify a BADJ-associated, NEB-independent, CCSP-expressing stem cell population in terminal bronchioles and support the notion that regiospecific stem cell niches function to maintain epithelial diversity after injury.     

P2X receptors in trigeminal subnucleus caudalis modulate central sensitization in trigeminal subnucleus oralis

This study investigated the role of trigeminal subnucleus caudalis (Vc) P2X receptors in the mediation of central sensitization induced in nociceptive neurons in subnucleus oralis (Vo) by mustard oil (MO) application to the tooth pulp in anesthetized rats. MO application produced a long-lasting central sensitization reflected in neuroplastic changes (i.e., increases in neuronal mechanoreceptive field size and responses to innocuous and noxious mechanical stimuli) in Vo nociceptive neurons. Twenty minutes after MO application, the intrathecal (i.t.) administration to the rostral Vc of the selective P2X(1), P2X(3), and P2X(2/3) receptor antagonist, 2'-(or 3'-)O-trinitrophenyl-ATP (TNP-ATP), significantly and reversibly attenuated the MO-induced central sensitization for more than 15 min; saline administration had no effect. Administration to the rostral Vc of the selective P2X(1), P2X(3), and P2X(2/3) receptor agonist, alpha,beta-methylene ATP (alpha,beta-meATP, i.t.) produced abrupt and significant neuroplastic changes in Vo nociceptive neurons, followed by neuronal desensitization as evidenced by the ineffectiveness of a second i.t. application of alpha,beta-meATP and subsequent MO application to the pulp. Administration to the rostral Vc of the selective P2X(1) receptor agonist beta,gamma-methylene ATP (beta,gamma-meATP, i.t.) produced no significant neuroplastic changes per se and did not affect the subsequent MO-induced neuroplastic changes in Vo nociceptive neurons. These results suggest that P2X(3) and possibly also the P2X(2/3) receptor subtypes in Vc may play a role in the initiation and maintenance of central sensitization in Vo nociceptive neurons induced by MO application to the pulp.     

Alzheimer''s disease. Beta-amyloid precursor protein expression in the nucleus basalis of Meynert.

The nucleus basalis of Meynert (nbM) was examined using immunocytochemistry for beta-amyloid precursor protein (beta APP) expression in Alzheimer's disease (AD). In mild AD cases, light labeling of the cell body and proximal processes was observed, and small intracellular structures were labeled rarely. In the more severe cases, intense cytoplasmic beta APP labeling was seen, often along with small beta APP-positive structures. Double-labeling experiments demonstrated that in the more severe cases these small structures were also decorated by a neurofibrillary tangle (NFT) antiserum. Other neurons in the severe cases showed incorporation of beta APP into large inclusions, which were also labeled with the NFT antiserum. However, some large inclusions in the severe cases were labeled by the NFT antiserum but contained no beta APP. Extraneuronal NFTs did not show beta APP labeling and did not react with an antibody to the beta-amyloid peptide. These results suggest that increased expression of beta APP coincides with intracellular NFT formation in the nbM, but that the formation of extraneuronal NFTs results in a loss of beta APP immunoreactivity.     

Bacteremia and fungemia in patients with acquired immune deficiency syndrome

Patients with acquired immune deficiency syndrome (AIDS) are known to have identifiable host defense deficiencies, especially deficiencies in cell-mediated immunity. They are at increased risk for developing infections of the bloodstream caused by Cryptococcus neoformans and Salmonella species. However, bacteremias caused by other enteric gram-negative rods and Pseudomonas aeruginosa are found less frequently in patients with AIDS than in patients without AIDS (P less than 0.001 and P less than 0.01, respectively). The findings of specific organisms in blood is consistent with the known types of host defense deficiencies in these patients.     

Clinical genetic counselling for familial cancers requires reliable data on familial cancer risks and general action plans

Familial cancer clustering, without obvious heritability, poses a major challenge for current cancer risk assessment and management. Reliable determination of familial risks for cancer is important for clinical genetic counselling, but medically verified data on familial risks for many malignancies have been limited. However, the nationwide Swedish Family-Cancer Database allows a reliable characterisation of familial risk for all major neoplasms. Even though alert genetic counsellors and certainly clinical cancer geneticists will consider familial cancer clustering in their purview, the standard medical referral systems, which have already been shown to be poor in capturing and referring families at high risk for heritable cancers, are unlikely to ascertain familial aggregations of other cancers that are not known to belong to an inherited cancer syndrome. The data will be helpful in implementing evidence based guidelines for helping the general medical system to ascertain and refer even familial cancer clusters to cancer genetics professionals.     

Protein absorption and transport by the guinea pig visceral yolk sac placenta

The cytological basis for protein transport across the guinea pig visceral yolk sac at 36–44 days of gestation was studied by means of electron microscopy following injection of horseradish peroxidase and ferritin. These results were compared with those obtained after administration of colloidal thorium dioxide. Distribution of the tracer molecules was studied at 2, 10, 20, 40, and 160 minutes after injection into the uterine lumen. All three tracer molecules were rapidly absorbed by endoderm cells. Although most of the protein appeared to be retained in droplets in endoderm cells, some protein was transmitted. Peroxidase was found to be rapidly transmitted across the yolk sac, ferritin somewhat more slowly, and colloidal thorium was not transmitted at all. Protein which had exited from the endoderm cells followed any of three pathways: (1) it crossed the visceral basement membrane and entered the vitelline capillaries; (2) it crossed the mesodermal compartment, crossed the mesothelial cells and entered the exocoelomic cavity; or (3) some of the protein was sequestered by macrophages in the splanchnic mesoderm. The pathways observed are consistent with those suggested by previous authors for the passage of maternal antibodies and serum proteins to the guinea pig fetus.