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Biomedical subjects

D Whitehouse

Publications and source records attributed to D Whitehouse.

At least 19 recordsLinked to original sources
PubMed2001

Funding the GDS.

Explore the source record for details and available documents.

Financing, Government↗
PubMed2001

Congenital disorders of glycosylation type I leads to altered processing of N-linked glycans, as well as underglycosylation.

The N-linked glycans on transferrin and alpha(1)-antitrypsin from patients with congenital disorders of glycosylation type I have increased fucosylation and branching relative to normal controls. The elevated levels of monofucosylated biantennary glycans are probably due to increased alpha-(1-->6) fucosylation. The presence of bi- and trifucosylated triantennary and tetra-antennary glycans indicated that peripheral alpha-(1-->3), as well as core alpha-(1-->6), fucosylation is increased. Altered processing was observed on both the fully and underglycosylated glycoforms.

Amidohydrolases↗
PubMed1998

Specialised sympathetic neuroeffector associations in rat iris arterioles.

Vascular sympathetic neuroeffector associations have been examined in rat iris arterioles using serial section electron microscopy and reconstruction techniques. Examination of random sections showed that, of all profiles of varicosities (199) seen to lie closer than 4 microns to vascular smooth muscle cells, only a small proportion (29/199) were found in close association with vascular smooth muscle cells, where adjacent membranes were separated by less than 100 nm. However, serial section examination, from intervaricose region to intervaricose region, of 79 varicosities similarly observed lying within 4 microns of vascular smooth muscle cells showed that 54 formed close associations with vascular smooth muscle cells. In serial sections, all these varicosities were also closely associated with melanocytes and of the 25 remaining varicosities, 22 formed close associations with melanocytes alone, whilst 3 did not come into close association with any effector cell. The increased observation of close associations with vascular smooth muscle cells in serial sections, compared with random sections, is consistent with the demonstration that the area of contact only occupies, on average, a small percentage (5%) of the total surface area of the varicosity as seen in the 3-dimensional reconstructions. In both random and serial sections, close associations were observed between varicosities and vascular smooth muscle cells or melanocytes irrespective of whether fibres were present singly or in small nerve bundles. Three-dimensional reconstruction of associations of varicosities and vascular smooth muscle cells demonstrated several common features, such as accumulations of synaptic vesicles and loss of Schwann cell covering at the region of membrane facing the effector cell. The similarity in the appearance of the neuroeffector association seen in this study and those described in previous studies provides evidence for the existence of a common sympathetic neuroeffector association, irrespective of the receptor subtype involved in neurotransmission.

Animals↗
PubMed1988

Cloning of the human alpha 1 antichymotrypsin gene and genetic analysis of the gene in relation to alpha 1 antitrypsin deficiency.

Deficiency of alpha 1 antitrypsin (Pi) is clinically heterogeneous and the unpredictability of the clinical manifestation in a person of phenotype PiZ, which may vary from severe childhood liver disease to normal health, is a problem in genetic counselling. This problem may increase as couples at risk who have not had an affected child are identified in screening programmes. One possibility is that genetic variation of other protease inhibitors may influence the prognosis. With this in mind we report the isolation of the human gene for alpha 1 antichymotrypsin (AACT) on a series of cosmid clones, with restriction mapping of about 70 kb around the gene. A probe pACE3.4 derived from the 5' end of the gene defines sequences which have been assigned to chromosome 14 using somatic cell hybrids and has been used to show a common TaqI polymorphism with allele frequencies of AACT6 = 0.7 and AACT3 = 0.3 in Europeans. pACE3.4 is closely linked to alpha 1 antitrypsin (maximum lod score in males +2.29 at theta = 0; in females Z = +6.11 at theta = 0.032). Analysis of Pi-AACT haplotypes in 31 families ascertained through PiZ or PiSZ subjects did not show any linkage disequilibrium. The distribution of AACT6 and AACT3 alleles in 16 unrelated PiZ patients presenting with childhood liver disease and five unrelated PiZ patients with adult chest disease did not differ significantly from each other. These results suggest that if genetic variation at the AACT locus does influence the outcome of alpha 1 antitrypsin deficiency, such variation is not in linkage disequilibrium with the AACT polymorphism reported here.

Cloning, Molecular↗
PubMed1984

Hyperlexia in infantile autism.

Twenty boys meeting the current DSM III criteria for infantile autism at the time of diagnosis were found to be hyperlexic in childhood and have been followed up for 7-17 years. The most striking feature of the group was the compulsion to decode written material without comprehension of its meaning, and this constituted a behavioral phenotype for this population. On word recognition tests such as the WRAT, they scored significantly higher than would be predicted on the basis of intelligence but demonstrated severe reading retardation on tests of reading comprehension such as the Gates-McGinitie. Major differences in intelligence were detected, ranging from severe mental retardation to very superior intelligence. Major differences in verbal and nonverbal abilities were also noted. Many were found to have unusually good memory, both visual and auditory, and the majority possessed an excellent stored vocabulary that could be used with written words despite the poverty of their expressive language. It is suggested that the presence of hyperlexia may identify a subgroup of autistic children.

Adolescent↗
PubMed1983

Encoding and contextual components of word recognition in good and poor readers.

Good and poor readers from the third and sixth grades (9- and 12-year-olds, respectively), named visually presented words as rapidly as possible. Words were in clear or degraded form, and were preceded by related or unrelated words. Poor readers were hurt more by degradation than were good readers, and showed greater benefit from context. In general, the contextual benefit was greater with degraded words than with intact, and this interaction was especially pronounced in the poor readers. The results are consistent with an interactive-compensatory model of word recognition. Under conditions in which stimulus encoding is slow, contextual factors may compensate for this encoding deficit.

Child↗
PubMed1982

An analysis of fetotoxicity using biochemical endpoints of organ differentiation.

The biochemical differentiation of the brain, lungs, liver, and kidneys of the late gestation rat fetus was examined to characterize the immediate implications of retarded growth on fetal development. Initially, the normative profile of development of the brain (weight, DNA content, and protein content), lungs (weight and surfactant accumulation), liver (weight and glycogen deposition), and kidneys (weight, alkaline phosphatase activity, and protein content) was determined on gestation days 19, 20, 21, and 22 (day 1 = finding of sperm in the vaginal smear). Subsequently, five compounds known to induce fetotoxicity (chlorambucil, methyl salicylate, mirex, nitrofen, and toxaphene) were administered during organogenesis, and the effects on organ differentiation were determined in day 21 fetuses. The effects of fetal growth retardation resulting from exposure to exogenous agents were not equally distributed among the organs studied. The liver and kidney appeared more sensitive to insult by these agents than did the brain and lungs.

Animals↗
PubMed1981

An application of high performance liquid chromatography to analysis of lipids in archaeological samples.

Five samples from three different types of 1500-year-old Mediterranean amphorae, as well as from a contemporary oil lamp found in the same deposit, were analyzed for the presence of lipid residues. Each sample of finely ground amphorae powder weighed 1-2 g. The abundance of interfering secondary products makes thin-layer chromatography (TLC) an essential step of the procedure. The fractionation of the extract into its various lipid components by means of TLC was followed by quantitative recovery of the triglyceride (TG) and free fatty acid (FFA) fractions from the plates and by the measurement of their components by high performance liquid chromatography (HPLC) after esterification. The minimum detectable level is 1 ng. The amphorae samples revealed a more abundant FFA fraction than a TG fraction, which is the reverse of what we know about the composition of fresh oil. Despite the considerable age of the amphorae and their preservation under non-ideal conditions, the lipid residues have retained certain identifiable characteristics that enable one to make valid suggestions as to the type of commodity originally transported in the amphorae. The results of these experiments yield important information that enables the biochemist to observe an aging process irreproducible in the laboratory and provides the archaeologist with previously unavailable information about trade 15 centuries ago.

Africa, Northern↗
PubMed1980

A left-right identification scale for clinical use.

The contribution of this research is a left-right identification scale which is relatively simple to administer, easy to score, and subject to low error rates. The research is unusual in that, rather than use subjective procedures (i.e., inspect data patterns), a probabilistic model was used to access fit to a linear hierarchy to response data. The resulting validated scale should be of use to researchers and clinicians alike.

Child↗
PubMed1980

Comparison of sustained-release and standard methylphenidate in the treatment of minimal brain dysfunction.

In a randomized, double-blind study the effects of the standard form of methylphenidate (10 mg given twice daily) were compared to those of a sustained-release form of methylphenidate (20 mg given once daily) in outpatient children with minimal brain dysfunction. The study was 2 weeks in duration and involved 30 children. Psychometric tests completed by the children, as well as physician, teacher and parent questionnaires were used to measure drug effects. Comparisons between the 2 methylphenidate treatment groups showed no consistent significant changes which could be deemed clinically favorable for one group over the other nor were there significant improvements over pretreatment measurements for either group. Adverse reactions--headache, hyperactivity, restlessness were reported by 5 patients receiving the sustained-release and 2 receiving the standard methylphenidate.

Adolescent↗
PubMed1977

Stereoselectivity and stereospecificity of the alpha,beta-dihydroxyacid dehydratase from Salmonella typhimurium.

1. In addition to the known 2R,3R- and 2R, 3S-2,3-dihydroxy-3-methylpentanoic acids (DHI), the 1S,3S- and sS,DR-isomers were prepared. 2S-2,3-Dihydroxy-3-methylbutanoic acid (DHV) was also prepared in addition to the known 2R-isomer. 2. The six dihydroxy acids were examined for their ability to promote the growth of isoleucine-valine (ilv)-requiring strains of Salmonella typhimurium and to serve as substrates for the alpha,beta-dihydroxyacid dehydratase of the same organism. 3. Only 2R,3R-2,3-dihydroxy-3-methylpentanoic and 2R-2,3-dihydroxy-3-methylbutanoic acids supported growth of the ilv strains of S. typhimurium. 4. alpha,beta-Dihydroxyacid dehydratase utilized the three isomers with the 2R-configuration as substrates but not those with the 2S-configuration. 5. In an additional growth study that utilized the 3R- and 3S-isomers of 3-methyl-2-oxopentanoic acid, the alpha-keto acid analogue of isoleucine, only the 3S-isomer supported growth. 6. It is concluded that the mechanism of action of the dehydratase is stereospecific in that the proton that is attached to C-3 of the substrate occupies the same steriochemical position as the departing hydroxyl group (Fig. 6).

Cell Division↗