The evolutionary tidal wave Alexander, R.G.“Wick”
American journal of orthodontics and dentofacial orthopedics,
05/2000, Letnik:
117, Številka:
5
Journal Article
One hundred nineteen individuals from 11 families with X-linked ocular albinism (OA1) were studied with respect to both their clinical phenotypes and their linkage genotypes. In a four-generation ...Australian family, two affected males and an obligatory carrier lacked cutaneous melanin macroglobules (MMGs); ocular features were identical to those of Nettleship-Falls OA1. Four other families had more unusual phenotypic features in addition to OA1. All OA1 families were genotyped at DXS16, DXS85, DXS143, STS, and DXS452 and for a CA-repeat polymorphism at the Kallmann syndrome locus (KAL). Separate two-point linkage analyses were performed for the following: group A, six families with biopsy-proved MMGs in at least one affected male; group B, four families whose biopsy status was not known; and group C, OA-9 only (16 samples), the family without MMGs. At the set of loci closest to OA1, there is no clear evidence in our data set for locus heterogeneity between groups A and C or among the four other families with complex phenotypes. Combined multipoint analysis (LINKMAP) in the 11 families and analysis of individual recombination events confirms that the major locus for OA1 resides within the DXS85-DXS143 interval. We suggest that more detailed clinical evaluations of OA1 individuals and families should be performed for future correlation with specific mutations in candidate OA1 genes.
This prospective partly-randomized study assessed the relative efficacy of two strategies of patient management for the replacement of frozen-thawed embryos. A luteinizing hormone-releasing hormone ...(LHRH) agonist was used to induce a temporary hypogonadism in a group of patients who were then prepared for implantation by endometrial priming with hormone replacement therapy (HRT): oral oestradiol valerate and then oestradiol valerate and injections of progesterone. A second group of patients had their frozen-thawed embryos replaced during their natural cycles. Of the 84 patients treated with the LHRH regimen, 80 had embryos replaced and 16 (20%) clinical pregnancies were established. Of the 78 patients treated with natural cycles, 70 had embryos replaced and 14 (20%) achieved clinical pregnancies. There were no statistical differences between the two groups in terms of age, obstetric history, duration of infertility, number of oocytes retrieved and fertilized or the number of embryos frozen following ovarian stimulation in the embryo 'generating' cycle. In terms of pregnancy rates, both protocols were equally effective. However, the LHRH-HRT protocol was of great value in the management of oligomenorrhoeic patients and in establishing standard conditions for implantation in cyclic patients.
The time persistence of monochloramine (levels 0.7-15 ppm) in human saliva and stomach fluid is measured on-line using membrane introduction mass spectrometry.
Early melanoma. Histologic terms Clark, Jr, W H; Evans, H L; Everett, M A ...
The American journal of dermatopathology,
12/1991, Letnik:
13, Številka:
6
Journal Article
How robust are early human embryos? Macnamee, M; Wick, K; Rainsbury, P ...
The Lancet (British edition),
09/1990, Letnik:
336, Številka:
8715
Journal Article
Chickens of the Obese strain (OS) develop a hereditary spontaneous autoimmune thyroiditis (SAT) which closely resembles human Hashimoto's disease. Analysis of the endogenous viruses harboured by ...these animals revealed a new endogenous virus (ev22) detected as a 5.5 kb Sac I fragment. Crossbreeding experiments showed that ev22 is vertically transmitted as an autosomal trait not associated with major histocompatibility (MHC) alleles. Preliminary experiments indicate that ev22 does not necessarily cause SAT, however, it may have a modulatory role in the development of the disease.
Development of organ-specific autoimmune diseases depends on both an abnormal immune regulation and a genetically determined primary susceptibility of the target organ to the autoimmune attack. In ...addition to the essential genetically determined prerequisites there are also facultative, modulating factors that influence the outcome of an autoimmune disease. This concept is exemplified in the Obese strain (OS) chicken model which develops a spontaneous autoimmune thyroiditis closely resembling human Hashimoto disease. Three modulating factors are specifically addressed, viz. (a) the lower threshold of OS thyroid epithelial cells for the gamma-interferon-induced MHC class II antigen expression as compared to normal controls, (b) the decreased glucocorticoid tonus of the OS and (c) the presence of a new endogenous virus (ev 22) locus in the OS that has so far not been found in any normal strain and which seems to influence the glucocorticoid-mediated immunoregulatory process.
A series of "stretched" methotrexate (MTX) analogues containing up to five 4-aminobutyryl (Gab) spacers between the 4-amino-4-deoxy-N10-methylpteroyl (MeAPA) moiety and the glutamate (Glu) side chain ...was prepared. Interest in these compounds stemmed from their relationship to MTX gamma-polyglutamates, from which they differ only in lacking "internal" alpha-carboxyl groups. The ability of the MeAPA-Gabn-Glu derivatives to inhibit dihydrofolate reductase (DHFR) and thymidylate synthase (TS) in vitro and to inhibit the growth of tumor cells in culture was evaluated. The IC50 for DHFR inhibition increased progressively from 0.082 to 0.84 microM as the number of Gab spacers was varied from one to five. At the same time the introduction of Gab spacers was found to produce substantial TS inhibition (Ki 0.1-0.4 microM) similar to that reported for MTX polyglutamates. Despite the activity of the MeAPA-Gabn-Glu derivatives as combined inhibitors of TS and DHFR, there was a steep loss of cell growth inhibitory potency as the number of Gab spacers was increased. This most likely reflects low cell uptake and the fact that when n greater than 1 there is almost total abolition of substrate activity for folylpolyglutamate synthetase, which had previously been observed with n = 1.
Methotrexate (MTX) and aminopterin (AMT) analogues containing L-homocysteic acid or L-cysteic acid in place of L-glutamic acid were synthesized and tested as inhibitors of dihydrofolate reductase ...from L1210 cells and folyl polyglutamate synthetase from mouse liver. The ID50 against dihydrofolate reductase was comparable for the MTX and AMT analogues (0.04-0.07 microM), whereas the ID50 against folyl polyglutamate synthetase was 3- to 4-fold lower for the AMT analogues (40-60 microM) than for the MTX analogues (100-200 microM). Thus, N10-substitution has a greater effect on binding to folyl polyglutamate synthetase than dihydrofolate reductase. The cytotoxicity of these compounds was assayed in vitro against L1210 cells, and the AMT analogues again proved more potent (ID50 = 0.03-0.05 microM) than the MTX analogues (ID50 = 0.1-0.4 microM). A similarly increased potency was observed for the AMT analogues against L1210 leukemia in vivo. Though differential cell uptake cannot be ruled out as the basis of increased potency, it is possible that part of the activity of the AMT analogues involves interference with the intracellular polyglutamation of reduced folate cofactors, i.e., that they are "self-potentiating antifolates". Of the four compounds reported, the most active was N-(4-amino-4- deoxypteroyl )-L-homocysteic acid, which produced a 138% increase in life span (ILS) in L1210 leukemic mice when given on a modified bid X 10 schedule at a dose of 2 mg/kg. A comparable ILS was obtained with AMT itself at 0.24 mg/kg. Thus, replacement of gamma-CO2H by gamma-SO3H in the side chain does not decrease therapeutic effect. However, a higher dose is required, presumably to offset pharmacological differences reflecting the inability of the sulfonate group to be polyglutamated .
