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Biomedical subjects

M D Thompson

Publications and source records attributed to M D Thompson.

36 records · Page 2Linked to original sources
PubMed1991

Early identification of hearing loss: listen to parents.

Families of 49 hearing-impaired children responded to a questionnaire requesting information about the identification of their child's hearing loss. Parents were the first to suspect the hearing loss in 48 cases but more often than not were told that the child would outgrow it or was too young to test. When professionals agreed with the parents and attended to their concerns, confirmation of the hearing loss occurred significantly more rapidly than when they disagreed with parents and ignored their concerns. A child whose hearing loss is not clearly identified and whose communication is inadequate or nonexistent, causes frustration and stress within the family and prevents the child from receiving the maximum benefit from early language input and amplification. It would benefit both the child and family if professionals would listen to parental concerns regarding their child and assist in the early identification process.

Child, Preschool↗
PubMed1990

Plant cytosolic ribosomal protein S11 and chloroplast ribosomal protein CS17. Their primary structures and evolutionary relationships.

We have isolated cDNA clones specific for Arabidopsis thaliana cytosolic ribosomal protein S11 and plastid ribosomal protein CS17, both of which are encoded in the nuclear genome, through the use of the corresponding soybean and pea cDNAs as probes, respectively. The nucleotide sequences of all four cDNAs were determined. The amino acid sequences derived from these cDNA sequences show that the soybean and A. thaliana S11 cDNAs encode proteins that are homologous to rat ribosomal protein S11 and that the pea and A. thaliana CS17 cDNAs encode proteins that are homologous to Escherichia coli ribosomal protein S17. The plant S11 cytosolic ribosomal proteins also show significant sequence similarity to both E. coli ribosomal protein S17 and plastid CS17 indicating that these are all related proteins. Comparison of A. thaliana CS17 with A. thaliana S11 and with E. coli S17 suggests that CS17 is more related to S17 than it is to S11. These results support the idea that the gene encoding CS17 was derived from a prokaryotic endosymbiont and not from a duplication of the eukaryotic S11 gene.

Amino Acid Sequence↗
PubMed1990

Synthesis, biological profile, and quantitative structure-activity relationship of a series of novel 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors.

A series of 9,9-bis(4-fluorophenyl)-3,5-dihydroxy-8-(alkyltetrazol-5-yl)- 6,8-nonadienoic acid derivatives 1 were synthesized and found to inhibit competitively the enzyme 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase. The analogues having 1N-methyltetrazol-5-yl attached to the C8-position (3a, 4a, R1 = R2 = F) are the most active in suppressing cholesterol biosynthesis in both in vitro and in vivo models: the IC50 for the chiral form of 3a is 19 nM, Ki = 4.3 x 10(-9)M when Km for HMG-CoA is 28 x 10(-6) M;1 the ED50 (oral) value corresponding to the lactone derivative (4a, BMY 22089) is approximately 0.1 mg/kg. Further, BMY 21950 is nearly 2 orders of magnitude more active in parenchymal heptaocytes, from which most of the serum cholesterol originates, than in other cell preparations (such as spleen, testes, ileum, adrenal, and ocular lens epithelial cells; Table III). This apparent tissue specificity may be highly beneficial since the blocking of cholesterol biosynthesis in other vital organs could eventually lead to undesirable side effects. In addition to the chemical synthesis and biological evaluation, a theoretical study aimed at relating the HMG-CoA reductase inhibitory potency to the three-dimensional structure of the inhibitors was undertaken. With a combination of molecular mapping and 3D-QSAR techniques, it was possible to determine a logical candidate for the conformation of the bound inhibitor and to quantitatively relate inhibitory potency to the shape and size of both the binding site and the C8-substituent.

Animals↗
PubMed1989

Structure of the three beta-tubulin-encoding genes of the unicellular alga, Polytomella agilis.

The quadriflagellate, unicellular, colorless alga, Polytomella agilis, contains several distinct microtubule arrays. To study the genetic basis of microtubule heterogeneity in P. agilis, we characterized its tubulin(Tub)-encoding genes (tub). The three beta tub genes detected in blots of P. agilis DNA were isolated from a genomic library. The structure and organization of the genes were examined by restriction mapping and nucleotide (nt) sequencing. S1 nuclease protection studies showed that all three genes are expressed. The predicted amino acid (aa) sequences are more than 98% conserved with the Chlamydomonas reinhardtii and Volvox carteri beta-Tubs, underscoring the close phylogenetic relationship of these species. Evolutionary divergence among the P. agilis genes is demonstrated by differences in intron number, nt sequences in noncoding regions, and silent nt substitutions in the coding regions. However, the proteins encoded by the beta 1 and beta 3 tub genes are identical; the beta 2 gene product differs by one conservative aa substitution. These results are in striking contrast to the C-terminal aa diversity reported within beta tub gene families in animal, higher plant and fungal systems. The data support the hypothesis that those tub genes whose products assemble into axonemal microtubules are subject

Amino Acid Sequence↗
PubMed1989

Extragenic suppression and synthetic lethality among Chlamydomonas reinhardtii mutants resistant to anti-microtubule drugs.

The antimicrotubule agents oryzalin (ORY), colchicine (COL) and taxol (TAX) were used to select three recessive, conditional lethal (ts-) mutants which defined two new essential loci, ory1 and cor1. The two ory1 mutants conferred resistance to ORY, TAX, and COL; the cor1 mutant conferred resistance only to COL. Each of the mutants displayed wild-type sensitivity to a number of unrelated inhibitors. Assembly and disassembly of flagellar microtubules in the ory1 mutants displayed wild-type sensitivity to ORY and COL, suggesting that the ory1 gene product either does not participate in these processes or the ory1 gene product alone is not sufficient to confer resistance. The ory1 locus mapped to linkage group X; cor1 was mapped to the left arm of linkage group XII. A synthetic lethal interaction was observed between ory1 and cor1 mutations, i.e., inferred ory1 cor1 double mutants were inviable at the permissive temperature. The conditional lethal phenotype of ory1-1 was used to select many spontaneous TS+ revertants, which arose at high frequencies. Genetic and phenotypic characterization of the revertants demonstrated that (1) the revertants fell into four phenotypic classes, including some which conferred supersensitivity to ORY and others which conferred cold-sensitive lethality, (2) reversion was caused in most or all cases by extragenic suppressors, (3) suppressor mutations displayed complex behavior in heterozygous (sup/+) diploids, (4) many different loci may be capable of suppressing ory1 mutants, and (5) suppressors of ory1-1 efficiently suppressed an independently isolated allele, ory1-2. Taken together the ory1, cor1, and suppressor mutations identify a number of interacting loci involved in essential cellular processes which are specifically susceptible to antimicrotubule agents.

Alkaloids↗
PubMed1988

Mapping flagellar genes in Chlamydomonas using restriction fragment length polymorphisms.

To correlate cloned nuclear DNA sequences with previously characterized mutations in Chlamydomonas and, to gain insight into the organization of its nuclear genome, we have begun to map molecular markers using restriction fragment length polymorphisms (RFLPs). A Chlamydomonas reinhardtii strain (CC-29) containing phenotypic markers on nine of the 19 linkage groups was crossed to the interfertile species Chlamydomonas smithii. DNA from each member of 22 randomly selected tetrads was analyzed for the segregation of RFLPs associated with cloned genes detected by hybridization with radioactive DNA probes. The current set of markers allows the detection of linkage to new molecular markers over approximately 54% of the existing genetic map. This study focused on mapping cloned flagellar genes and genes whose transcripts accumulate after deflagellation. Twelve different molecular clones have been assigned to seven linkage groups. The alpha-1 tubulin gene maps to linkage group III and is linked to the genomic sequence homologous to pcf6-100, a cDNA clone whose corresponding transcript accumulates after deflagellation. The alpha-2 tubulin gene maps to linkage group IV. The two beta-tubulin genes are linked, with the beta-1 gene being approximately 12 cM more distal from the centromere than the beta-2 gene. A clone corresponding to a 73-kD dynein protein maps to the opposite arm of the same linkage group. The gene corresponding to the cDNA clone pcf6-187, whose mRNA accumulates after deflagellation, maps very close to the tightly linked pf-26 and pf-1 mutations on linkage group V.

Chlamydomonas↗
PubMed1987

Synthesis and antiarrhythmic properties of novel 3-selena-7-azabicyclo[3.3.1]nonanes and derivatives. Single-crystal X-ray diffraction analysis of 7-benzyl-3-selena-7-azabicyclo[3.3.1]nonan-9-one and 7-benzyl-3-selena-7-azabicyclo[3.3.1]nonane hydroperchlorate.

Several members of the heterocyclic family 3-selena-7-azabicyclo[3.3.1]nonane have been synthesized and characterized via IR, 1H, 13C, 15N, and 77Se NMR spectroscopy and, in some cases, by X-ray diffraction analysis. Select members, namely the hydroperchlorates of the amines, were examined for antiarrhythmic properties in anesthetized dogs in which myocardial infarctions were induced by techniques previously described. In the predrug, or control state, sustained ventricular tachycardia were induced by ventricular paced beats at rates above 300/min. When 7-benzyl-3-selena-7-azabicyclo[3.3.1]nonane hydroperchlorate was administered at 3 and 6 mg/kg, the sustained ventricular tachycardia could no longer be induced. Similar doses of lidocaine, a commonly used antiarrhythmic, caused slowing of the sustained ventricular tachycardia below 300/min but did not abolish their inducibility. In addition, select members of the hydroperchlorates caused a moderate 10-20% increase in mean blood pressure whereas lidocaine caused either no change in or slightly reduced mean blood pressure. Some general conclusions are delineated concerning the structural requirements that appear to be necessary for activity in this family of heterocycles and that have not been reported previously.

Animals↗
PubMed1985

Synthesis and characterization of selected heteroarotinoids. Pharmacological activity as assessed in vitamin A deficient hamster tracheal organ cultures. Single-crystal X-ray diffraction analysis of 4,4-dimethylthiochroman-6-yl methyl ketone 1,1-dioxide and ethyl (E)-p-[2-(4,4-dimethylthiochroman-6-yl)propenyl]benzoate.

There is reported the first four members of heteroarotinoids, the names of which are ethyl (E)-p-[2-(4,4-dimethylthiochroman-6-yl)propenyl]benzoate (1b), ethyl (E)-p-[2-(4,4-dimethylchroman-6-yl)propenyl]benzoate (1c), ethyl (E)-p-[2-(4,4-dimethyl-1-oxothiochroman-6-yl)propenyl]benzoate (1d), and (E)-p-[2-(4,4-dimethylchroman-6-yl)propenyl]benzoic acid (1e). IR, 1H NMR and 13C NMR data have been recorded for each compound and support the structural assignments. To provide a firm basis for comparison purposes of future analogues, an X-ray analysis was performed on a single crystal of ethyl (E)-p-[2-(4,4-dimethylthiochroman-6-yl)propenyl]benzoate (1b) and a precursor 4,4-dimethylthiochroman-6-yl methyl ketone 1,1-dioxide (18). These data for the heteroarotinoid 1b revealed that the two aryl ring systems were nearly perpendicular in each of the two molecules present in the unit cell (86.37 degrees and 84.17 degrees, respectively). The space group for both molecules was P1 in triclinic systems. Unit cell dimensions (at 15 degrees C) are as follows: for 1b, a = 20.568 (6) A, b = 14.760 (3) A, c = 7.679 (2) A, alpha = 113.33 (2) degrees, beta = 79.45 (2) degrees, gamma = 79.98 (2) degrees, Z = 4; for 18, a = 9.292 (5) A, b = 9.291 (5) A, c = 7.951 (3) A, alpha = 102.16 (3) degrees, beta = 77.49 (3) degrees, gamma = 79.60 (4) degrees, Z = 2. The sulfur-containing ring is in a distorted half-chair in 1b and the methyl carbon C(12) is shown to be trans to H(13) at the C(11)-C(13) bond. The biological activity of these arotinoids was determined in the tracheal organ culture assay and compared with trans-retinoic acid for ability to reverse keratinization in vitamin A deficient hamsters. The ester 1b displayed activity about one-half log unit less than that of the reference while 1c and 1e had activity nearly one log until less than trans-retinoic acid. The sulfoxide was the least active of the heteroretinoids.

Animals↗
PubMed1985

Molecular cloning of mouse mammary gland kappa-casein: comparison with rat kappa-casein and rat and human gamma-fibrinogen.

A cDNA clone for kappa-casein mRNA from the lactating mouse mammary gland was isolated and its nucleotide sequence determined. Analysis of the deduced amino acid sequence revealed a precursor protein with a 21-amino-acid signal sequence and a mature protein of 160 amino acids, the mature mouse protein being 3 amino acids longer than the rat kappa-casein. Northern blot analysis of the lactating rat and mouse mammary gland showed a specific mRNA for rat kappa-casein and two distinct mRNAs for mouse kappa-casein. This result is explained by the presence of two putative polyadenylation sites in mouse kappa-casein cDNA, whereas rat kappa-casein cDNA has only one polyadenylation site. Comparison of the nucleotide sequence and of the deduced amino acid sequence of kappa-casein from mouse with that of the rat showed 85% homology between the two sequences. However, when amino acid sequences of kappa-casein from rat and mouse were compared with ovine kappa-casein, only a 45% homology was observed. Amino acid sequences of kappa-casein from rat, mouse, and sheep were 36.53% homologous with rat and human gamma-fibrinogen. The extent of homology was similar (32%) when nucleotide sequences of corresponding cDNAs were compared. The stretches of homology existing at different regions between the two proteins were more confined toward the amino-terminal half of gamma-fibrinogen. However, when nucleotide sequences were compared, mouse kappa-casein cDNA showed homology only with the second half of the rat gamma-fibrinogen cDNA, i.e., between nucleotides 661-1135. The homology with the human gamma-fibrinogen cDNA spanned over two regions, one between nucleotides 1-328 and the second between nucleotides 591-726.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1985

Methylation and expression of rat kappa-casein gene in normal and neoplastic rat mammary gland.

The kappa-casein mRNA was evaluated in the rat mammary gland during functional differentiation and neoplastic growth. Using a dot-blot assay, the mRNA was barely detectable in the virgin gland; it steadily increased from the onset of gestation and leveled off during lactation. In rat mammary tumors, either primary (7,12-dimethylbenz(a)anthracene-induced) or transplanted (MTW9), the level of kappa-casein mRNA was about 2.5-fold lower than in the lactating gland, but an extensive variation among individual tumors was observed. There was no detectable kappa-casein mRNA in rat liver. In the mammary gland of virgin, 10-day pregnant, and nonlactating females, the DNA sequences within and/or around the kappa-casein gene were found to be hypermethylated at the HpaII-MspI sites as compared to 10-day lactating females. In the two tumors studied, the kappa-casein gene was partially methylated at the same sites. Prolactin treatment induced kappa-casein gene expression in the virgin rat mammary gland but did not result in a change of the methylation status at the HpaII-MspI sites. Under similar conditions of prolactin treatment, however, the methylation of the Sau96I sites was reduced, and an inverse correlation between the onset of kappa-casein gene methylation and kappa-casein gene expression was evident in both the virgin gland and the tumors. Thus, the expression of kappa-casein was found to be inversely correlated with the extent of methylation of the kappa-casein gene, except in the case of the prolactin-stimulated virgin gland.

Animals↗
PubMedDate not supplied

Acquiring language through total communication.

Total communication provides an opportunity for very young children to receive training through both visual and auditory systems. Most children with severe hearing loss have auditory discrimination/perceptual problems in addition to a loss of hearing sensitivity. Because sophisticated assessment of auditory perceptual problems is not yet possible in hearing impaired infants, total communication provides immediate and consistent language input regardless of eventual determination of auditory perceptual skills. An illustration of a total communication program is provided.

Auditory Perception↗