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Biomedical subjects

D Lonsdale

Publications and source records attributed to D Lonsdale.

At least 19 recordsLinked to original sources

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

Effect of thiamine tetrahydrofurfuryl disulfide on audiogenic seizures in DBA/2J mice.

Weanling mice of the DBA/2J strain are spontaneously audiogenically seizure prone between 19 and 24 days. Thereafter, susceptibility declines rapidly within the next 7-10 days. It was found that thiamine tetrahydrofurfuryl disulfide (TTFD) significantly delayed the natural disappearance of seizure proneness in male animals compared with controls treated with identical doses of saline. There was no significant difference between treated females and controls. Evidence is presented that suggests that TTFD is cholinergic in its action and has pharmacologic effects other than a simple vitamin replacement. The difference between males and females found in this strain of mouse in this experiment is consistent with previous information which indicates that sex-related differences exist in their response to stress.

Acoustic Stimulation

Brainstem dysfunction in the infant apnea syndrome.

Thirty-six infants identified as infant apnea syndrome (IAS) and 25 controls with a comparable age distribution were evaluated with Brainstem Auditory Evoked Potential (BAEP) testing. There was a significant predilection for leftsided BAEP abnormalities in IAS patients. Fifteen IAS patients had bilateral abnormalities, and of the 21 IAS patients with unilateral abnormalities, 17 had abnormalities on the left side (p less than 0.01 by McNemar's test). Significant differences (p less than 0.05 by analysis of covariance adjusting for age) between normal controls and IAS infants were found for peak latencies I, III, and V, and amplitude III. Linear regression analyses of the above parameters versus age in months for normal controls were constructed with 68% and 95% prediction interval bands to permit analysis of individual data points. Data points from the IAS infants with bilateral BAEP abnormalities have been plotted on these linear regression curves. No single measurement of latency or amplitude is abnormal in the majority of IAS infants, but many of the individual points fall outside of the 95% prediction curve.

Brain Stem