Linkage disequilibrium between mutation and RFLP haplotype at the phenylalanine hydroxylase locus in the German population

Summary Restriction fragment length polymorphism (RFLP) haplotypes at the phenylalanine hydroxylase (PAH) locus have been determined in 60 German families with PAH deficiency. Similar to the Danish population, about 90% of the mutant alleles are confined to four distinct haplotypes. There are however, differences in the frequency distributiion of these haplotypes among the mutant alleles between the two populations. Using an oligonucleotide probe for the splicing mutation associated with mutant haplotype 3 in the Danish population, a tight association between the mutation and the RFLP haplotype has also been observed in Germany. The results provide strong evidence that the splicing mutation occurred on a haplotype 3 chromosome and that the mutant allele has spread into different populations smong Caucasians.     

Immunoelectron microscopic localization of hepatic transferrin receptors in human liver with and without iron overload

The expression of transferrin receptors (TfR's) has been investigated in eight liver biopsy specimens (four from patients without demonstrable iron and four from patients with iron storage due to primary hemochromatosis (HC)) using immunoelectron microscopy to demonstrate TfR's by the simultaneous application of two specific monoclonal antibodies (OKT9 and B3/25) to tissue chopper sections. In the four specimens without iron overload, hepatocytes, but not sinusoidal lining cells, stained positively and immunoreactivity was mainly localized in the cytoplasm. Positively stained cisternae of the endoplasmic reticulum indicated synthesis of the TfR. The presence of TfR's on segments and coated invaginations of the sinusoidal membrane and in small, but otherwise unidentified vesicles in the cytoplasm is compatible with endo-/exocytotic transport and recycling of TfR's as demonstrated by biochemical studies. Occasional positively stained material in canalicular lumina together with positively stained canalicular microvilli and pericanalicular vesicles suggest that transcellular transport may be an additional pathway for TfR's. In three biopsies showing severe iron overload due to HC, TfR immunoreactivity was completely absent. The remaining specimen showing HC, exhibited relatively mild iron overload and showed only a few positively stained hepatocytes. This supports the previously reported disappearance of hepatic TfR expression in HC when iron overload is severe.     

Adhesion of canine and human uropathogenicEscherichia coli andProteus mirabilis strains to canine and human epithelial cells

Escherichia coli strains causing urinary tract infections in dogs produce fimbriae composed of fimbrial subunits closely related to the F12 and F13 fimbriae of human uropathogenic strains [4]. The adhesins carried by the fimbriae of human and canine isolates differ, however, as concluded from a different hemagglutination pattern and from the fact that the dog strains do not agglutinate latex beads coated with P-fimbriae receptor. This possible difference in adhesive specificity was confirmed by experiments in which the adhesion of human and dog isolates to dog kidney epithelial cells (MDCK cells) and human bladder epithelial cells (T24 cells) was compared. Dog uropathogenic strains, in contrast to human uropathogenicE. coli strains, adhere to MDCK cells but hardly to T24 cells. Adhesion to MDCK cells correlates with the presence of F12 or F13 fimbriae on the dog strains. These results suggest that homologous fimbrial subunits can carry different adhesin molecules and that these adhesin molecules can be responsible for species-specific adherence. On the contrary, adhesion of a number of dog uropathogenicProteus mirabilis strains to MDCK and T24 cells was not species specific; it depended on the mere presence of fimbriae.     

Assignment of human platelet GP2B (GPIIb) gene to chromosome 17, region q21.1-q21.3

Summary The platelet GPIIb-IIIa complex functions as a receptor for fibrinogen, fibronectin, and von Willebrand factor on activated platelets. This glycoprotein is a member of a broadly distributed family of structurally and immunologically related membrane receptors involved in cell-cell contact and cell-matrices interactions. GPIIb-IIIa is a heterodimer complex composed of GPIIb (the subunit), which consists of two disulfide-linked heavy and light chains, and GPIIIa (the subunit), which is a single polypeptide chain. Congenital absence of platelet GPIIb-IIIa in Glanzmann's thrombasthenia results in a severe bleeding disorder characterized by defective platelet aggregation and failure of fibrinogen to bind to platelets. The gene coding for GPIIb was located on 17q21.1-17q21.3 as determined by in situ hybridization with a 2650-pb GP2B (GPIIb) cDNA probe prepared from human megakaryocytes.     

Antisense genes in plants: an overview

Plants are the first multicellular higher eukaryotic organisms in which artificial antisense genes have been shown to down-regulate target gene expression. Manipulations with an antisense gene can serve as a tool to study the effect of a particular plant gene inactivation, the interaction of gene products whose genes are coordinately expressed, or the functional analysis of cryptic genes. Transgenic plants harbouring an antisense gene already gave rise to patentable new characteristics, showing that the technique has great scientific and economic value.     

Relationship between the differential adsorption of odorants by the olfactory mucus and their perception in mixtures

It was proposed recently that the differential adsorption ofodorants by the olfactory mucus may constitute the first stepin the processing of odor mixtures [Laing, D.G. (1988) Ann.NY Acad. Sci., 510, 61–66]. In the present study psychophysicalprocedures were used to determine if there was a relationshipbetween differential adsorption by the olfactory mucus and theperception of odorants of different polarity in binary mixtures.With the eight odor pairs studied, differential adsorption andthe polarity of an odorant were not predictors of how well anodorant would be perceived in a mixture or how it would suppressor enhance the perception of other odorants.     

Subcutaneous implantable infusion device for chronic intravenous pulsatile gonadotropin-releasing hormone treatment

Preliminary data indicate the potential utility of an implantable subcutaneous device that facilitates chronic intravenous infusion of pulsatile gonadotropin-releasing hormone (GnRH) for ovulation induction. GnRH distribution curves were congruent in control monkeys and those with implanted devices. Tissue tolerance was good in this brief trial. These findings suggest that use of this or a similar implantable device be considered for chronic GnRH administration in human pulse therapy.     

Guidelines for the Control of Human Immunodeficiency Virus Infection in Adolescents

Although adolescents account for only 0.4% of reported cases of the acquired immunodeficiency syndrome (AIDS) in the United States, they are sexually active and, therefore, at risk of acquiring human immunodeficiency virus (HIV) infection. To address issues of HIV control in adolescents, we developed guidelines that emphasize education and medical care and deemphasize antibody testing. For adolescents known to be infected with HIV, we recommend no restrictions on access to educational or treatment programs except when their health providers recommend such restrictions to protect them from exposure to opportunistic infections. For adolescents of unknown antibody status with a possible previous exposure to HIV, we recommend that as long as the incidence of HIV infection and clinical AIDS remains low, there should be no restrictions on residential placements and no routine antibody testing.     

Class II genes of miniature swine

Class II genes of miniature swine have been characterized by restriction fragment length polymorphism (RFLP) analysis and by analysis of a series of clones isolated from a lymphocyte genomic library. For RFLP analysis, DNA samples from three independent major histocompatibility complex homozygous lines and three intra-MHC recombinant lines were digested with a variety of restriction enzymes and analyzed in Southern blots using human cDNA probes for DP, DQ, DR, and DZ alpha genes, and DP, DQ, DR, and DO beta genes. One, or at most two, unique fragments were detected by hybridization with each of the human probes tested. In contrast, multiple bands (five to six for most enzymes examined) were detected by each of the human probes tested, the majority of which were found to cross-react with at least three of these probes under conditions of moderate stringency. Genomic DNA from the SLA ^c haplotype was cloned into an EMBL-3 bacteriophage vector, and the corresponding genomic library was screened with each of these human cDNA probes. The class II genes thereby isolated from this library showed characteristics consistent with those anticipated from the RFLP analysis. Thus, unique genes were obtained which showed no evidence of cross-hybridization, while genes showed extensive cross-hybridization and were frequently detected in the library by more than one human gene probe. These data are consistent with early evolutionary divergence of a genes, prior to mammalian speciation, and with continuing evolution of genes, with possible shared usage of these genes by different a loci. The data also imply that genes can readily be assigned to loci homologous to their human counterparts, but that genes will require further mapping and/or sequence analysis to confirm assignments.