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Biomedical subjects

K D Smith

Publications and source records attributed to K D Smith.

At least 109 records · Page 6Linked to original sources
PubMed1992

An ocular dynamic study supporting the hypothesis that hypothyroidism is a treatable cause of secondary open-angle glaucoma.

To examine the hypothesis that glaucoma may be a manifestation of unrecognized hypothyroidism, we studied 25 consecutive patients with newly diagnosed hypothyroidism who presented to an endocrinology clinic. Using tonography and tonometry, we demonstrated a reduction in facility of outflow in the hypothyroid state. With treatment of the hypothyroidism alone there was a statistically significant improvement in facility of outflow, intraocular pressure and Po/C (p < 0.002). Our results support the hypothesis that secondary open-angle glaucoma may be a manifestation of hypothyroidism and that the glaucoma will resolve on treatment of the primary disease.

Adolescent↗
PubMed1992

Reversal of poorly controlled glaucoma on diagnosis and treatment of hypothyroidism.

Hypothyroidism was diagnosed in a 62-year-old woman with poorly controlled primary open-angle glaucoma, including a disc hemorrhage and a documented arcuate scotoma. After 1 year of thyroxine therapy the glaucoma was easily controlled, pilocarpine treatment was stopped and the visual fields were completely normal. To our knowledge this is the first report in the modern literature of reversal of open-angle glaucoma with treatment of hypothyroidism.

Female↗
PubMed1992

Frequency of ocular chlamydial infection among young adults.

Young adults are at particular risk for Chlamydia trachomatis infection. To determine whether there is a high rate of asymptomatic ocular chlamydial infection in this population, 131 eyes from 72 patients aged 18 to 30 years with no symptoms of conjunctivitis were tested for C. trachomatis by means of McCoy cell culture and a direct enzyme immunoassay. In addition, 51 of the patients underwent serologic testing to detect systemic chlamydial disease. Ocular chlamydial infection was not found in any of the patients, including the 26 with a positive result of serologic testing. We conclude that routine screening of young adults for ocular chlamydial infection would be of no benefit in detecting systemic chlamydial infection and its sequelae.

Adolescent↗
PubMed1990

Enzyme degradation, high performance liquid chromatography and liquid secondary ion mass spectrometry in the analysis of glycoproteins.

Analysis of small amounts of glycoproteins by high performance liquid chromatography (HPLC) and liquid secondary ion mass spectrometry (LSIMS) together with enzyme digestion has been investigated using fetuin as a model. Preliminary data indicates that 71% of the expected peptides were detected by LSIMS analysis of 200 pmol total digest. HPLC profiles of peptides and glycopeptides were obtained from 2 nmol of digest using a reversed phase (C18) column eluted in a solvent system containing TFA, water and acetonitrile. This has provided glycopeptides for subsequent oligosaccharide analysis. Strategies are reviewed for the chromatographic characterization of oligosaccharides following their release from glycopeptides by chemical and enzymatic procedures.

Amino Acid Sequence↗
PubMed1990

Glucocorticoid therapy in hyperandrogenism.

Hyperandrogenism is a common disorder in the reproductive age female. It is associated with cutaneous manifestations and ovulatory dysfunction. The degree of hyperandrogenaemia is directly related to the severity of ovulatory dysfunction. The ovulatory dysfunction frequently leads to infertility. The most common form of hyperandrogenism is idiopathic glucocorticoid-suppressible hyperandrogenism (IGSH). The management of this disorder involves appropriate use of physiological doses of glucocorticoids. This treatment leads not only to normalization of serum androgen levels but also to amelioration of cutaneous symptoms and improvement in ovulatory function. In infertile women with ovulatory dysfunction secondary to IGSH, occurrence of pregnancy after treatment with glucocorticoids is directly related to the degree of the suppression of serum androgen levels. In other words, this treatment does not 'induce ovulation', but its effectiveness in improving ovulatory function is a result of a correction of the hyperandrogenic state. At physiological doses glucocorticoid therapy does not appear to be associated with significant side-effects. With appropriate management, androgen levels can be maintained within the normal range indefinitely. Furthermore, in a majority of patients, androgen levels remain within the normal range for a long time (years) after discontinuation of chronic glucocorticoid therapy.

Androgens↗
PubMed1990

The estimation of selection coefficients in Afrikaners: Huntington disease, porphyria variegata, and lipoid proteinosis.

The effects of mutation, migration, random drift, and selection on the change in frequency of the alleles associated with Huntington disease, porphyria variegata, and lipoid proteinosis have been assessed in the Afrikaner population of South Africa. Although admixture cannot be completely discounted, it was possible to exclude migration and new mutation as major sources of changes in the frequency of these alleles by limiting analyses to pedigrees descendant from founding families. Calculations which overestimated the possible effect of random drift demonstrated that drift did not account for the observed changes in gene frequencies. Therefore these changes must have been caused by natural selection, and a coefficient of selection was estimated for each trait. For the rare, dominant, deleterious allele associated with Huntington disease, the coefficient of selection was estimated to be .34, indicating that this allele has a selective disadvantage, contrary to some recent studies. For the presumed dominant and probably deleterious allele associated with porphyria variegata, the coefficient of selection lies between .07 and .02. The coefficient of selection for the rare, clinically recessive allele associated with lipoid proteinosis was estimated to be .07. Calculations based on a model system indicate that the observed decrease in allele frequency cannot be explained solely on the basis of selection against the homozygote. Thus, this may be an example of a pleiotropic gene which has a dominant effect in terms of selection even though its known clinical effect is recessive.

Ethnicity↗
PubMed1988

Altered turnover of allelic variants of hypoxanthine phosphoribosyltransferase is associated with N-terminal amino acid sequence variation.

The results of our previous studies suggested that differences in the primary structures of the hypoxanthine phosphoribosyltransferase (HPRT) A and B proteins (EC 2.4.2.8) of mice are associated with altered turnover of these proteins in reticulocytes. On the basis of nucleotide sequence comparisons of their corresponding cDNAs, we show here that the HPRT A and B proteins differ at two positions; there is an alanine/proline substitution at amino acid position 2 and a valine/alanine substitution at amino acid position 29 (HPRT A/B proteins, respectively; total protein length, 218 amino acids). On the basis of results obtained from sequencing of the N termini of the purified HPRT A and B proteins, we also show that these amino acid substitutions are associated with differences in processing of the proteins; HPRT B, which is encoded as N-terminal Met-Pro, has a free N-terminal proline residue; HPRT A, which is encoded as N-terminal Met-Ala, lacks a free N-terminal alpha-amino group and is presumed to be acetylated following removal of the N-terminal methionine (i.e. AcO-Ala). These observations are discussed in reference to the idea that the N terminus of a protein plays a role in determining the rate at which the protein is degraded in erythroid cells.

Alleles↗
PubMed1988

Annual variation in semen characteristics and plasma hormone levels in men undergoing vasectomy.

Prevasectomy levels of plasma luteinizing hormone (LH), follicle-stimulating hormone (FSH), testosterone (T), estradiol (E2), and 20 alpha-dihydroprogesterone (20 alpha-DHP), as well as semen analyses including semen volume, sperm count, and sperm motility from 260 healthy men were evaluated for annual changes. A statistically significant (P less than or equal to 0.015) high-amplitude seasonal variation with the peak in April to May was detected in semen volume, sperm count, and sperm motility. A statistically significant (P less than or equal to 0.04) annual change of moderate T to large FSH amplitude was detected in each of the five plasma endocrine variables as well. Plasma LH, T, and E2 peaked in autumn, while FSH and 20 alpha-DHP peaked in summer. Analysis of postvasectomy LH, FSH, E2, 20 alpha-DHP, and T blood levels for the 3 years following vasectomy revealed loss of seasonal rhythmicity as a group phenomenon in LH, E2, and T. The amplitude of the seasonal variation in FSH was decreased and that in 20 alpha-DHP was unchanged compared with before-vasectomy baselines. For those annual rhythms which persisted following vasectomy, the peak time was unchanged. Compared with the prevasectomy group annual mean, that for each of the endocrine values was unchanged, except for that of LH and T, which was slightly, yet statistically significantly, elevated. The existence of prominent annual variation implicates their consideration in the design of research protocols involving investigation of reproductive phenomena in human beings.

20-alpha-Dihydroprogesterone↗
PubMed1987

Origin of the human L1 elements: proposed progenitor genes deduced from a consensus DNA sequence.

A consensus sequence for the human long interspersed repeated DNA element, L1Hs (LINE or KpnI sequence), is presented. The sequence contains two open reading frames (ORFs) which are homologous to ORFs in corresponding regions of L1 elements in other species. The L1Hs ORFs are separated by a small evolutionarily nonconserved region. The 5' end of the consensus contains frequent terminators in all three reading frames and has a relatively high GC content with numerous stretches of weak homology with AluI repeats. The 5' ORF extends for a minimum of 723 bp (241 codons). The 3' ORF is 3843 bp (1281 codons) and predicts a protein of 149 kD which has regions of weak homology to the polymerase domain of various reverse transcriptases. The 3' end of the consensus has a 208-bp nonconserved region followed by an adenine-rich end. The organization of the L1Hs consensus sequence resembles the structure of eukaryotic mRNAs except for the noncoding region between ORFs. However, due to base substitutions or truncation most elements appear incapable of producing mRNA that can be translated. Our observation that individual elements cluster into subfamilies on the basis of the presence or absence of blocks of sequence, or by the linkage of alternative bases at multiple positions, suggests that most L1 sequences were derived from a small number of structural genes. An estimate of the mammalian L1 substitution rate was derived and used to predict the age of individual human elements. From this it follows that the majority of human L1 sequences have been generated within the last 30 million years. The human elements studied here differ from each other, yet overall the L1Hs sequences demonstrate a pattern of species-specificity when compared to the L1 families of other mammals. Possible mechanisms that may account for the origin and evolution of the L1 family are discussed. These include pseudogene formation (retroposition), transposition, gene conversion, and RNA recombination.

Biological Evolution↗
PubMed1987

Repeated DNA of the human Y chromosome.

A significant fraction of the human Y chromosome is composed of DNA sequences which have homologues on the X chromosome or autosomes in humans and non-human primates. However, most human Y-chromosome sequences so far examined do not have homologues on the Y chromosomes of other primates. This observation suggests that a significant proportion of the human Y chromosome is composed of sequences that have acquired their Y-chromosome association since humans diverged from other primates. More than 50% of the human Y chromosome is composed of a variety of repeated DNAs which, with one known exception, can be distinguished from homologues elsewhere in the genome. These include the alphoid repeats, the major human SINE (Alu repeats) and several additional families of repeats which account for the majority of Y-chromosome repeated DNA. The alphoid sequences tandemly clustered near the centromere on the Y chromosome can be distinguished from those on other chromosomes by both sequence and repeat organization, while the majority of Y-chromosome Alu repeats have little homology with genomic consensus Alu sequences. In contrast, the Y-chromosome LINE repeats cannot be distinguished from LINEs found on other chromosomes. It has been proposed that both SINE and LINE repeats have been dispersed throughout the genome by mechanisms that involve RNA intermediates. The difference in the relationship of the Y-chromosome Alu and LINE repeats to their respective family members elsewhere in the genome makes it possible that their dispersal to the Y chromosome has occurred by different mechanisms or at different rates. In addition to the SINE and LINE repeats, the human Y chromosome contains a group of repeated DNA elements originally identified as 3.4 and 2.1 kb fragments in HaeIII digests of male genomic DNA. Although the 3.4 and 2.1 kb Y repeats do not cross-react, both exist as tandem clusters of alternating Y-specific and non-Y-specific sequences. The 3.4 kb Y repeats contain at least three distinct sequences with autosomal homologies interspersed in various ways with a collection of several different Y-specific repeat sequences. Individual recombinant clones derived from isolated 3.4 kb HaeIII Y fragments have been identified which do not cross-react. Thus, the 3.4 kb HaeIII Y fragments are a heterogeneous mixture of sequences which have in common the regular occurrence of HaeIII restriction sites at 3.4 kb intervals and an organization as tandem clusters at various sites along the Y-long arm.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1985

Organization and chromosomal specificity of autosomal homologs of human Y chromosome repeated DNA.

The human Y chromosome contains a group of repeated DNA elements, identified as 3.4-kilobase pair (kb) fragments in Hae III digests of male genomic DNA, which contain both Y-specific and non-Y-specific sequences. We have used these 3.4-kb Hae III Y fragments to explore the organizational properties and chromosomal distribution of the autosomal homologs of the non-Y-specific (NYS) 3.4-kb Hae III Y elements. Three distinct organizations, termed domains, have been identified and shown to have major concentrations on separate chromosomes. We have established that domain K is located on chromosome 15 and domain D on chromosome 16 and suggested that domain R is on chromosome 1. Our findings suggest that each domain is composed of a tandemly arrayed cluster of a regularly repeating unit containing two sets of repeated sequences: one that is homologous to the NYS 3.4-kb Hae III Y sequences and one that does not cross-react with the 3.4-kb Hae III Y repeats. Thus, these autosomal repeated DNA domains, like their Y chromosome counterparts, consist of a complex mixture of repeated DNA elements interspersed among each other in ways that lead to defined periodicities. Although each of the three identified autosomal domains cross-reacts with 3.4-kb Hae III Y fragments purified from genomic DNA, the length periodicities and sequence content of the autosomal domains are chromosome specific. The organizational properties and chromosomal distribution of these NYS 3.4-kb Hae III homologs seem inconsistent with stochastic mechanisms of sequence diffusion between chromosomes.

Animals↗
PubMed1985

Characterization and evolution of a single-copy sequence from the human Y chromosome.

To study the evolution and organization of DNA from the human Y chromosome, we constructed a recombinant library of human Y DNA by using a somatic cell hybrid in which the only cytologically detectable human chromosome is the Y. One recombinant (4B2) contained a 3.3-kilobase EcoRI single-copy fragment which was localized to the proximal portion of the Y long arm. Sequences homologous to this human DNA are present in male gorilla, chimpanzee, and orangutan DNAs but not in female ape DNAs. Under stringent hybridization conditions, the homologous sequence is either a single-copy or a low-order repeat in humans and in the apes. With relaxed hybridization conditions, this human Y probe detected several homologous DNA fragments which are all derived from the Y in that they occur in male DNAs from humans and the apes but not in female DNAs. In contrast, this probe hybridized to highly repeated sequences in both male and female DNAs from old world monkeys. Thus, sequences homologous to this probe underwent a change in copy number and chromosomal distribution during primate evolution.

Adult↗