The genetic defect in multiple endocrine neoplasia type 2A maps next to the centromere of chromosome 10

Multiple endocrine neoplasia type 2A (MEN2A) is a rare cancer syndrome that is inherited in an apparently autosomal dominant fashion. Previous linkage studies had assigned the MEN2A locus to chromosome 10 in the pericentromeric region. We recently have described several new easily scorable RFLPs for the chromosome 10-specific alpha satellite DNA (the D10Z1) locus that is known, on the basis of previous in situ hybridization experiments, to lie at the centromere. We report here tight linkage between MEN2A and D10Z1, as demonstrated by a maximum lod score of 12.02 at the recombination frequency of zero (1-lod-unit support interval 0-4 cM), indicating that the genetic defect in MEN2A lies in the immediate vicinity of the centromere. By means of a set of ordered polymorphic DNA markers from the pericentromeric region, multipoint as well as pairwise linkage analyses place the MEN2A locus at the middle of a small region (approximately 11 cM) bracketing the centromere with FNRB (at 10p11.2) and RBP3 (at 10q11.2) on either side, providing further support for the centromeric location of the MEN2A locus. Marked sex difference in recombination frequencies exists in this pericentromeric region: significantly (P less than .01) more female than male crossovers were observed across all of the adjacent intervals D10S24-FNRB, FNRB-D10Z1, and D10Z1-RBP3. However, a sex difference was not seen in the 7-cM interval from RBP3 to D10S5, suggesting that large variation in the sex difference in recombination can occur over small chromosomal regions.(ABSTRACT TRUNCATED AT 250 WORDS)     

Fibroblast heterogeneity in glucocorticoid regulation of collagen metabolism: Genetic or epigenetic?

Summary Cultured fibroblasts derived from normal human dermis show a consistent 62% inhibition of collagen synthesis by hydrocortisone, whereas cultures derived from keloids average only 30% inhibition and show a much larger strain to strain variation ranging from 75% inhibition to 49% stimulation. Examination of fibroblast clones indicates that this high variation among keloid strains is not due to differences in the proportion of normal and keloid cells in the mass culture populations. Small but significant differences in the effect of hydrocortisone on collagen deposition are also seen among these clonal populations, but are not related to the type of tissue from which cultures were derived. Two to three-fold differences among clones derived from a single individual were observed, possibly suggesting functional heterogeneity of dermal fibroblasts with regard to collagen metabolism under control conditions and in response to hydrocortisone. However, this variation among clones may simply reflect differences in clonal growth, inasmuch as both collagen synthesis and deposition, and the effect of hydrocortisone on these processes, are strongly affected by population density. This work was supported in part by PHS grants, CA-17229 from the National Cancer Institute and AG-02046 from the National Institute on Aging, DHHS; and by Grant RIM 78-17313 from the National Science Foundation.     

Smith degradation of gum exudates from some prosopis species

The polysaccharide of P. hymantophora has been shown to be composed of (1→4)-linked galactopyranosyl, (1→3)-linked galactopyranosyl, (1→3)-linked galactopyranosyl 2- and 4-sulphate and 2,6-disulphate residues. The (1→3)- and (1→4)-linked units are present in approximately equal amounts. The polysaccharide of P. hieroglyphica has been shown to possess (1→4)-linked galactopyranosyl, (1→3)-linked galactopyranosyl, and (1→3)-linked galactopyranosyl 2- and 4-sulphate residues. The (1→3)- and (1→4)-linked units are present in a 4:1 ratio. Both polysaccharides contain small proportions of non-reducing xylosyl end-groups.     

Ultrastructure of the swim bladder of the goldfish,Carassius auratus

Summary The swim bladder of the cyprinid Carassius auratus (goldfish) is a two-chambered organ connected to the esophagus by a pneumatic duct. The anterior chamber is lined by a single type of squamous epithelial cell. Two types of epithelial cells are present in the posterior chamber. Flattened cells with differences in the electron density of the cytoplasm line most of the chamber. Darker cells generally contain large amounts of glycogen. Cuboidal epithelial cells also occur in the posterior chamber. A glandular layer external to the muscularis in the posterior chamber is composed of large cells containing little glycogen, an extensive Golgi apparatus, and numerous mitochondria with single large granules. Capillaries and nerves are present in large numbers in this layer. Blood vessels form micro-retia mirabilia in the submuscular layer external to the glandular layer. Vessels are of two distinct types with wide lumina and flattened endothelium characterizing the venous vessels. Arterial vessels have smaller lumina, thick endothelial cells with prominent pinocytotic vesicles, and surrounding pericytes. Collagen is present in three forms in this swim bladder — large tactoids in the tunica externa of the anterior chamber, smaller tactoids in the lamina propria of the posterior chamber, and small fibrils in all other areas.Supported by a Young Investigator Pulmonary Research Grant # 1 R23 HL 19593-01 and by HL 23338-01 from the National Institutes of Health     

Recent studies of some RNAs and proteins in amoebae

Progress on various aspects of nucleic acids and protein synthesis in amoebae has been reviewed. The RNA molecules involved in the character changes seen after micro-injection of non-homologous cytoplasmic fractions have been isolated after polyacrylamide gel electrophoresis, and their approximate molecular weights calculated. Injection of these RNA molecules was shown to alter the response of recipient cells to growth in streptomycin and neomycin.The relative molecular weights of cytoplasmic ribosomal RNAs have been estimated using both aqueous and formamide gel electrophoresis. Some attempts to characterize the nuclear RNAs seen on aqueous polyacrylamide gels, and to evaluate this data with that published by other workers have been made. Results from assays of DNA- and RNA-directed DNA polymerase activity are considered in relation to those from other eukaryotes.Problems arising after attempts to use rabbit globin messenger RNA to direct globin synthesis in amoebae, and the possibilities of using minature gel systems and small cell numbers to identify proteins and RNAs after various experimental treatments are discussed.     

Inhibitor-“resistant” labelling of rat ventral prostate nuclear proteins : Further evidence consistent with protein synthesis associated with cell nuclei

When minced rat ventral prostate was incubated with labelled amino acids and cycloheximide or puromycin, the specific radioactivity of proteins associated with Triton X 100-washed nuclei exceeded that of the 105 000 g cytosol. The distribution of radioactive proteins from incubated mince, examined by SDS polyacrylamide gel electrophoresis was also consistent with labelling of some nuclear proteins that was resistant to inhibitors. Highly purified prostate nuclei, washed with detergent, labelled proteins of from 1–6 × 10⁴ D with radioactive amino acids. When these proteins were fractionated according to solubility, NaOH-soluble ‘acidic’ proteins, examined by SDS polyacrylamide gel electrophoresis, were highly labelled, with a distribution of radioactivity that differed from the patterns of 0.4 N H₂SO₄-soluble basic proteins (including histones), and proteins soluble in Krebs-Ringer-phosphate buffer. Although these results cannot be interpreted unambiguously, they are consistent with the synthesis of certain nuclear proteins at a site(s) sequestered from cycloheximide and puromycin. Nuclei may represent one such site.