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Biomedical subjects

D Lonsdale

Publications and source records attributed to D Lonsdale.

At least 19 recordsLinked to original sources

Mendel-GFDb and Mendel-ESTS: databases of plant gene families and ESTs annotated with gene family numbers and gene family names.

There is no control over the information provided with sequences when they are deposited in the sequence databases. Consequently mistakes can seed the incorrect annotation of other sequences. Grouping genes into families and applying controlled annotation overcomes the problems of incorrect annotation associated with individual sequences. Two databases (http://www.mendel.ac.uk) were created to apply controlled annotation to plant genes and plant ESTs: Mendel-GFDb is a database of plant protein (gene) families based on gapped-BLAST analysis of all sequences in the SWISS-PROT family of databases. Sequences are aligned (ClustalW) and identical and similar residues shaded. The families are visually curated to ensure that one or more criteria, for example overall relatedness and/or domain similarity relate all sequences within a family. Sequence families are assigned a 'Gene Family Number' and a unified description is developed which best describes the family and its members. If authority exists the gene family is assigned a 'Gene Family Name'. This information is placed in Mendel-GFDb. Mendel-ESTS is primarily a database of plant ESTs, which have been compared to Mendel-GFDb, completely sequenced genomes and domain databases. This approach associated ESTs with individual sequences and the controlled annotation of gene families and protein domains; the information being placed in Mendel-ESTS. The controlled annotation applied to genes and ESTs provides a basis from which a plant transcription database can be developed.

Computational Biology↗

Sudden infant death syndrome requires genetic predisposition, some form of stress and marginal malnutrition.

Over the past 30 years or more, the problem of sudden, unexplained death in infants (SIDS) has made little headway. Many hypotheses have been offered but the basic cause remains elusive. The only successful prevention has been made by the supine sleeping posture. There is still, however, a hard core of unexplained incidents. There is evidence that certain stress factors are involved, and there is good evidence that the tragedy has a familial or genetic tendency. The third factor necessary for the event is inefficient oxidation in brain cells induced most commonly by marginal malnutrition in pregnancy or after birth. The absence of any one or more of these three factors decreases risk to the point of extinction. Anything that impedes healthy oxidation, or accelerates energy utilization through responding to stress, increases the risk greatly. Improving the biochemical mechanisms through appropriate nutrition is by far the best defense.

Autonomic Nervous System Diseases↗

Evaluation of the biochemical effects of administration of intravenous nutrients using erythrocyte ATP/ADP ratios.

Regardless of clinical diagnosis, many acutely and chronically sick patients benefit from intravenous vitamins and minerals, which are usually administered in multiple infusions before observing obvious benefit. We hypothesized this effect was due to improved cellular energy, and attempted to find laboratory evidence via this study. Two groups of patients, chosen at random, received a single infusion of vitamins and minerals in two different dose schedules. Controls received no treatment. Study subjects were patients who presented specifically for a nutritional therapeutic approach, and although all were treated with multiple infusions, a single infusion was selected at random for this study. Thirty patients received a single infusion of a lower dose nutritional formula, sometimes known as a Myer's Cocktail (MC), and 34 had a single infusion of a higher dose nutritional I/V (NIV). Immediately prior to and after the infusion, blood was drawn and an erythrocyte ATP/ADP ratio (EADR) was determined. The results showed that in both infusion groups if the EADR was initially low, it would increase. If it were initially high, it would decrease. This effect was not observed in control subjects. Pre-test EADR boxplot analyses, derived from the results of each protocol, showed these results were statistically predictable. An analysis of variation (ANOVA) calculation indicated the differences were significant. The family error rate used was 0.05. We conclude that this regression of the EADR to the mean, as a result of either of the two infusions and not seen in control subjects, is biochemically significant.

Adenosine Diphosphate↗

Characterization of a birch pollen allergen, Bet v III, representing a novel class of Ca2+ binding proteins: specific expression in mature pollen and dependence of patients' IgE binding on protein-bound Ca2+.

A cDNA coding for a birch pollen allergen, Bet v III, with significant sequence homology to Ca2+ binding proteins was isolated from an expression cDNA library using serum IgE from a patient who was allergic to pollen. The deduced amino acid sequence of the pollen allergen contained three typical Ca2+ binding sites. Peptides mimicking the Ca2+ binding sites of Bet v III were synthesized and shown to bind 45Ca in blot overlays. The binding of patients' IgE to the recombinant allergen depended on the native protein conformation and protein-bound Ca2+. Depletion of Ca2+ led to a reversible loss of the IgE binding thus representing a conformational IgE epitope adopted by a polypeptide upon Ca2+ binding. By RNA hybridization it was demonstrated that Bet v III is expressed preferentially in mature pollen. Bet v III therefore represents a pollen allergen which because of its unique structural features also belongs to a novel class of Ca2+ binding proteins.

Allergens↗

Localization and organization of tRNA genes on the mitochondrial genomes of fertile and male sterile lines of maize.

Maize mitochondrial (mt) tRNA genes were localized on the mt master circles of two fertile lines (WF9-N and B37-N) and of one cytoplasmic male sterile line (B37-cmsT) of maize. The three genomes contain 16 tRNA genes with 14 different anticodons which correspond to 13 amino acids. Out of these 16 tRNA genes, 6 show a high degree of homology with the corresponding chloroplast (cp) tRNA genes and were shown to originate from cp DNA insertions and to be expressed in the mitochondria. The organization of the mt tRNA genes in both fertile lines is similar. The same genes are found, in the same environment, as judged from the restriction maps, in fertile and male sterile lines that have the same nuclear background, but the relative organization of the mt tRNA genes on the master circle is completely different.

Genes, Plant↗

Hypothesis and case reports: possible thiamin deficiency.

Three family members are reported with functional symptoms considered to be caused by intracellular deficiency of thiamin. Persistence of desaturation of erythrocyte transketolase in the face of megadose thiamin hydrochloride (THCl), accompanied by a balanced multivitamin and mineral formula, suggested a familial thiamin dependency state. Each of three individuals responded clinically to the administration of thiamin tetrahydrofurfuryl disulfide (TTFD), and erythrocyte transketolase (TKA) became fully saturated with thiamin pyrophosphate (TPP). Dysautonomic symptoms observed are compared with those seen in classical beriberi, the nutritional prototype for dysautonomia, and changes in blood pressure are described which support this premise. Although there is no proof from the laboratory, it is hypothesized that the biochemical lesion might be due either to malabsorption of thiamin or its inadequate phosphorylation.

Adult↗

Sequence analysis of the tRNA(Tyr) and tRNA(Lys) genes and evidence for the transcription of a chloroplast-like tRNA(Met) in maize mitochondria.

The nucleotide sequences of three tRNA genes and their flanking regions from the maize mitochondrial genome is reported. These genes, which are located in the same region of the genome between the 14-kb inverted repeats, are transcribed in the mitochondria and code for tRNA(Lys) (anticodon UUU) tRNA(Met) (CAU) and tRNA(Tyr) (GUA). The very high homology shown by the tRNA(Met) gene with its chloroplast counterpart indicates that it probably originates from a chloroplast DNA insertion. The analysis of the upstream regions of these genes showed that the tRNA(Tyr) and the tRNA(Lys) genes possess the consensus sequence AAGAANRR, which could act as a promoter sequence in higher plant mitochondria.

Base Sequence↗

Red cell transketolase studies in a private practice specializing in nutritional correction.

Erythrocyte transketolase (TKA) and thiamin pyrophosphate percentage uptake, or effect (TPPE) were performed on 1011 patients between 1983 and 1986. The subjects were drawn from a private practice specializing in nutritional correction as a major therapeutic thrust. Either TKA or TPPE or both were abnormal in 283 (28%). Out of the total number of patients with these abnormal studies 36 have been selected as representative. Their clinical presentation is correlated with subsequent laboratory testing in order to draw attention to the practical value of the test in a clinical setting. These data are presented because of the surprisingly high incidence of abnormal tests, that strongly suggests that there is widespread marginal nutritional deficiency in the United States and that it represents a clinical problem that deserves far more attention than it is presently receiving.

Adolescent↗

Respiratory impairment induced by smoking in children in secondary schools.

A longitudinal study was carried out from 1975 to 1979 in a cohort of 405 secondary school children. At yearly intervals they underwent a series of tests of pulmonary function designed to monitor lung development; some of these tests are relatively sensitive indicators of early abnormalities. A self administered questionnaire provided details of smoking habits and respiratory symptoms. The prevalence of smoking increased with age; most of those smoking at 16 had already been smoking, at least experimentally, at 13. Taking up smoking was clearly associated with the early onset of cough, production of phlegm, and shortness of breath on exertion. After two years of smoking more than a few cigarettes a day the children who smoked appeared considerably less healthy than their non-smoking peers and showed some evidence of early obstruction of the airways.

Adolescent↗