Fabry's disease. An X-linked inherited metabolic disorder.
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Biomedical subjects
Publications and source records attributed to J N Thompson.
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Oligosaccharides were isolated from heparin and heparan sulfate by a procedure consisting of three major steps: (a) acid hydrolysis; (b) gel chromatography; and (c) cation exchange chromatography on an amino acid analyzer. To date, six new oligosaccharides have been isolated by this procedure and have been sequenced by a combination of NaB3H4-labeling and deaminative cleavage with nitrous acid. The structures of these oligosaccharides were as follows: 1. GlcN-GlcUA-GlcN 2. GlcN-IdUA-GlcN 3. GlcN-GlcUA-GlcN-GlcUA-GlcN 4. GlcN-IdUA-GlcN-GlcUA-GlcN 5. GlcN-GlcUA-GlcN-IdUA-GlcN 6. GlcN-IdUA-GlcN-IdUA-GlcN The linkage positions and anomeric configurations were assumed to be the same as in the polysaccharides from which the oligosaccharides originated. The usefulness of some of these oligosaccharides as enzyme substrates was tested after appropriate modifications and radioactive labeling. Oligosaccharides 2 and 3 were N-[35S]sulfated and were found to serve as substrates for heparan N-sulfate sulfatase (heparin sulfamidase), with a homogenate of cultured skin fibroblasts as enzyme source. Similarly, reduction of oligosaccharide 2 with NaB3H4 yielded a substrate for acetyl-CoA:alpha-D-glucosaminide N-acetyltransferase. Finally, the previously known disaccharide, 4-O-alpha-D-glucosaminyl-L-iduronic acid, which was isolated in the course of this work, was N-acetylated with [3H] acetic anhydride and was shown to be a substrate for N-acetyl-alpha-D-glucosaminidase.
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Vitamins D2 and D3 were measured in milk after high performance liquid chromatography of unsaponifiable lipids first on a silica column and then on a reverse-phase column. Milk from cows kept indoors contained barely detectable vitamin (less than 2 IU/100 ml) predominantly in the form of vitamin D3. When cows were given 5 or 10 million IU vitamin D3, maximums were in milk 3 to 7 days after oral doses and up to 10 days after intravenous injections. Maximums ranged from 7 to 90 IU/100 ml. Two cows were given given a mixture of 1 million IU vitamin D2 and 1 million IU vitamin D3 orally, and of the vitamins were maximum 2 to 3 days after the dose in blood plasma and a day later in milk. Equal amounts of the two forms of the vitamins were in milk, but vitamin D3 in plasma was double vitamin D2. Different mechanisms control concentrations of vitamins D2 and D3 in blood and milk after large doses.
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Lipoproteins were removed from human plasma by ultracentrifugation at a density of 1.225. Three classes of lipoproteins were then separated by 4% Agarose-column chromatography: very low density lipoproteins (VLDL), low-density lipoproteins (LDL), and high-density lipoproteins (HDL). A sensitive high performance liquid chromatography method with a fluorescence detector was used to estimate alpha-tocopherol in plasma and in column eluates. Total plasma tocopherol was not significantly different in males (n = 6) and females (n = 6) and almost all of the vitamin was recovered in the isolated lipoproteins. Although LDL and HDL were the main carriers of alpha-tocopherol in both males and females, more tocopherol was found in LDL than in HDL in males but the opposite was true in females. The distribution of alpha-tocopherol in males was: VLDL, 8%; LDL, 59%; and HDL, 33% whereas that in females was VLDL, 2%; LDL, 42%; HDL, 56%. The distribution of protein in lipoprotein from males was: VLDL, 4%, LDL, 37%; and HDL, 59% and in females: VLDL, 2%; LDL, 25%; and HDL, 73%. The alpha-tocopherol concentration (expressed as microgram alpha-tocopherol/mg protein) in lipoproteins differed little between the sexes. The values in males were: VLDL, 7.0; LDL, 4.3; and HDL, 1.5, in females: VLDL, 3.9; LDL, 4.7; and HDL, 2.1. The data suggest that the different distribution of alpha-tocopherol in plasma lipoproteins in males and females is due to the different levels of proteins in those lipoprotein fractions. Overall, tocopherol and protein levels were highly correlated in HDL, a lower correlation was found in LDL.
Several important human syndromes provide evidence for the idea that the rate of gene mutation and chromosome breakage is under genetic control. Although not understood in detail, their underlying mechanisms include deficiencies in DNA replication, repair, and increased sensitivity to external agents. The ease of genetic analysis in Drosophila melanogaster offers a number of model systems that may give useful insights into comparable human conditions. For example, some of the many meiotic mutants isolated from natural populations provide information on the genetics of DNA repair in a eukaryote. In addition, complex syndromes affecting mutation rate are available for study. One such system is hybrid dysgenesis in Drosophila. Hybrid dysgenesis refers to a collection of genetic changes, including chromosome breakage, increased mutation rates, and sterility expressed in crosses between independent population lines. Our recent work has focused upon chromosome breakage and mutator activity in this system. The pattern of inheritance and expression of mutator activity implicates a chromosome-cytoplasm interaction for its induction. Furthermore, the genetic elements responsible for this phenomenon appear to move from one location or chromosome to another. Indeed, one can draw a convincing parallel between hybrid dysgenesis and the behavior of transposable, or nomadic, DNA sequences. Thus, one must view the phenotype "mutation rate" as a conglomerate of factors affecting DNA stability, physiological condition, and the behavior of genetic elements.
A 4 1/2-yr.-old stutterer was run on a series of comparative speech tasks and EMG recording periods to assess the potential of using EMG biofeedback-assisted relaxation to reduce stuttering. The basic finding was that the subject was able to reduce the level of tension in the laryngeal area by using EMG biofeedback but not without some difficulty. The effect of EMG biofeedback training on his frequency of stuttering was small but in the direction of less stuttering.
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Fortified milks were saponified overnight at room temperature with 1% ethanolic pyrogallol and KOH. The digest was extracted with hexane after adding water and ethanol, and the extract was washed consecutively with 5% KOH, water, and 55% aqueous ethanol to remove polar lipids. After evaporation, the residue was first chromatographed on a column of 5 micrometer silica. A fraction containing vitamin D was collected, evaporated, and rechromatographed on a reverse phase column for the separation and quantitation of vitamins D2 and D3. Recovery was 96-99% and the coefficient of variation was 3% (8 replicates). Infant formula was diluted and then saponified and extracted as in the analysis of milk. Margarine was saponified by shaking overnight with 1% ethanolic pyrogallol and 80% KOH. Water and ethanol were added to the digest before extraction. Extracts from formula and margarine were chromatographed as milk except, before HPLC, the extract was dissolved in isopropanol-hexane (1 + 99) and passed through 5 cm alumina in a Pasteur pipet, and the concentration of isopropanol in the first high performance liquid chromatographic (HPLC) solvent system was halved to improve the separation of vitamin D from other absorbing lipids. Usually several peaks were obtained during the final HPLC analysis, and the identification of vitamins D2 and D3 was less certain than in the analysis of milk. The coefficients of variation for formula and margarine were 6% (5 replicates) and 9% (6 replicates), respectively.
Transposing genetic elements make up a significant proportion of the DNA of at least some eukaryotes. One of the potential side effects of transposition is a high rate of apparently spontaneous mutation. In this paper we consider some of the evolutionary strategies that might be involved in the suppression of transposition, and we outline a model for the control of spontaneous mutation in terms of the regulation of transposition. Specific predictions are based upon the well-characterized genetics of the mutator system associated with hybrid dysgenesis in Drosophila melanogaster, which has many parallels with the expected behaviour of transposing elements.
Visual loss is a rare and dreaded complication of surgical procedures of the paranasal sinuses. A case of sudden unilateral blindness following irrigation of the frontal sinus is presented and the presumptive pathophysiology is discussed. An awareness of this potential complication as well as early diagnosis with prompt medical and surgical management are essential.
Mutator activity associated with the common male recombination (MR) chromosomes in Drosophila melanogaster appears to be suppressed in natural populations. Crosses between geographically separated populations, however, lead to the release of mutator activity as measured by a significant increase in visible mutations. Such an increase in mutation in hybrid individuals may be a powerful factor in inducing or releasing variation in nature, and in more extreme instances may contribute to the separation of microdifferentiated populations.
Atypical mycobacterium cervical adenitis (AMCA) is a disease primarily of childhood and usually presents as a unilateral mass or draining sinus. The pathogens are mycobacteria which are distinct from Mycobacteria tuberculosis, leprae and bovis (the typical mycobacteria). The atypical mycobacteria are readily recovered from the environment and are generally of low virulence. They are increasingly being recognized as pathogen for man though they are probably not transmissible from human contact. Most commonly these organisms are implicated in either pulmonary disease or lymphadenopathy. Fourteen cases of AMCA occurring in childhood are presented. A review of the bacteriology of the atypical mycobacteria is included. The clinical presentation, differential diagnosis, chemotherapeutic management and role of surgical intervention are discussed.