Faculty Bibliography

Nanomoles of neuropeptide Y (NPY) and noradrenaline (NA), administered i.v. to pentobarbital-anesthetized rats, caused nearly equipotent dose-dependent pressor responses in normotensive rats. However, in renovascular Goldblatt hypertensive rats, the dose-response curves for both NPY and NA were significantly displaced to the left, approximately threefold. Intravenous administration of BIBP 3226 (30-180 microg/kg) did not consistently lower blood pressure, per se, but did evoke competitive antagonism of the NPY pressor response in both rat populations. The magnitude of the NPY antagonism evoked by BIBP 3226 was comparable in normotensive and hypertensive rats. The absence of NA antagonism demonstrates the selectivity of the BIBP 3226 blockade.

Linear streaks of hypopigmentation or hyperpigmentation along Blaschko's lines are currently grouped under the names hypomelanosis of Ito (HI) and linear and whorled hypermelanosis (LWH). Recent studies have suggested that these linear pigmentary anomalies reflect underlying genetic mosaicism. Mosaic individuals are composed of two or more genetically distinct cell populations, a normal and an abnormal population. In HI and LWH, the types of genetic defects that are detectable in the abnormal population are highly variable, including tetraploidy, partial or complete trisomies, translocations, and point mutations. These results, together with recent studies indicating the incidence of extracutaneous anomalies is lower in HI but higher in LWH than previously estimated, have important clinical implications. The need for a revised nomenclature as well as possible modifications in current recommendations for patient management are discussed

During vertebrate limb development, positional information must be specified along three distinct axes. Although much progress has been made in our understanding of the molecular interactions involved in anterior-posterior and proximal-distal limb patterning, less is known about dorsal-ventral patterning. The genes Wnt-7a and Lmx-1, which are expressed in dorsal limb ectoderm and mesoderm, respectively, are thought to be important regulators of dorsal limb differentiation. Whether a complementary set of molecules controls ventral limb development has not been clear. Here we report that Engrailed-1, a homeodomain-containing transcription factor expressed in embryonic ventral limb ectoderm, is essential for ventral limb patterning. Loss of Engrailed-1 function in mice results in dorsal transformations of ventral paw structures, and in subtle alterations along the proximal-distal limb axis. Engrailed-1 seems to act in part by repressing dorsal differentiation induced by Wnt-7a, and is essential for proper formation of the apical ectodermal ridge

BACKGROUND. The antitrichohyalin antibody AE 15 is effective for identifying the cell lineage that undergoes the pathway of inner root sheath-type differentiation. Unfortunately, the AE 15 does not react with trichohyalin in tissue that is formalin-fixed and embedded in paraffin according to routine procedures. METHODS. We attempted to retrieve the trichohyalin antigenicity in formalin-fixed, paraffin-embedded biopsy specimens that included normal skin as well as skin tumors such as trichofolliculoma and pilotricoma. RESULTS. We found that the use of a metal solution in combination with microwave oven heating improves the trichohyalin immunoreactivity substantially. Further, trichohyalin was found to be expressed not only in the secondary hair structure in trichofolliculoma but also in a certain cell lineage that differentiates to squamoid cells in pilomatricoma. CONCLUSIONS. Our findings established that surgical specimens processed under routine procedures can be successfully investigated with AE 15 using the microwave irradiation method. Studies of epidermal diseases expressing trichohyalin should provide valuable insights into our understanding the functional significance of trichohyalin during abnormal keratinization

Male to female sex reversal has been observed in individuals with duplications of the short arm of the X chromosome. The study of Xp duplicated patients demonstrated that sex reversal results from the presence of two active copies of the DSS (dosage sensitive sex reversal) locus. A double dosage of DSS disrupts testis formation whereas its absence is compatible with a male phenotype, suggesting a role for DSS in ovarian development and as a link between ovary and testis formation. DSS was localized to a 160 kb region of Xp21, overlapping the adrenal hypoplasia congenita locus. The search for expressed sequences in the DSS critical region led to the identification of two types of genes: the DAM family and DAX-1, an atypical member of the nuclear receptor superfamily. Although no function is currently known for DAM genes, functional deficiency for DAX-1 has been shown to be responsible for adrenal hypoplasia congenita and hypogonadotropic hypogonadism. The search for the DSS gene(s) is still open and both the DAM genes and DAX-1 represent DSS candidate genes