Biomedical subjects
P Taylor
Publications and source records attributed to P Taylor.
Isolation of cDNA encoding a newly identified major allergenic protein of rye-grass pollen: intracellular targeting to the amyloplast.
We have identified a major allergenic protein from rye-grass pollen, tentatively designated Lol pIb of 31kDa and with pI 9.0. A cDNA clone encoding Lol pIb has been isolated, sequenced, and characterized. Lol pIb is located mainly in the starch granules. This is a distinct allergen from Lol pI, which is located in the cytosol. Lol pIb is synthesized in pollen as a pre-allergen with a transit peptide targeting the allergen to amyloplasts. Epitope mapping of the fusion protein localized the IgE binding determinant in the C-terminal domain.
Optimal life histories with age dependent tradeoff curves.
Following the approach of Schaffer (1974, Ecology 55, 291-303.) and Charlesworth & Leon (1976, Am. Nat. 110, 449-459.) the tradeoff between fecundity and survival/growth is investigated in an age-structured population with density independent life history parameters. The results of the above authors are generalized by allowing the tradeoff curve to vary with age; the life cycle is assumed to have two stages: an initial stage during which the organism generally improves in her capacity to reproduce, grow and survive, and a final stage during which her general performance remains constant or declines. The principal result is that, during the final stage, RV per unit size should decrease and over the course of the entire life, should either decrease, or increase at first and then decrease. With the additional assumption that the tradeoff curves at different ages are similar in shape, it is shown that unit fecundity should increase throughout the reproductive life of the organism.
Structure comparison and evolutionary relations between elongation factors EF-Tu (EF-1 alpha) and SUP 2 proteins.
On the basis of high homology and structural similarity, three genes, SUP2 Saccharomyces cerevisiae, SUP2 Pichia pinus and GST1 Homo sapiens, might be considered as members of one family named SUP2. Comparison of the primary structure of SUP2 proteins and elongation factors EF-Tu(EF-1 alpha) from 19 different species was performed. It was found that SUP2 proteins bear more homology to eukaryotic elongation factor than to procaryotic EF-Tu, though the degree of sequence conservation in SUP2 proteins is smaller than in EF-1 alpha factors. The extensive phylogenetic analysis of SUP2 and EF-Tu(EF-1 alpha) genes was performed by means of 3 methods, 2 phenetic and one cladystic (maximal parsimony). The data support the close relation of SUP2 genes to other elongation factor genes.
Complement activation during bypass in acquired C1 esterase inhibitor deficiency.
Serial complement estimations during cardiopulmonary bypass are reported in a patient with acquired C1 esterase inhibitor deficiency. Although the extent of classic and alternative pathway activation appeared appropriate, exaggerated common pathway activation with massive increase in the C3d:C3 ratio occurred. A fatal hemostatic disorder, pulmonary edema, and circulatory collapse ensued despite prophylaxis and therapy.
A numerical prognostic index for clinical use in identification of poor-risk patients with Hodgkin's disease at diagnosis. Scotland and Newcastle Lymphoma Group (SNLG) Therapy Working Party.
The aim of this study was to assess the feasibility of using objective data obtained at diagnosis of Hodgkin's disease to predict those patients who were likely to die of progressive disease within 4 years of diagnosis. 92 consecutive patients from one centre (Newcastle upon Tyne) were used to construct a numerical index based on disease stage (Ann Arbor), age, haemoglobin and absolute lymphocyte count. Weight was assigned according to a predictive value in univariate and multivariate analyses based on survival. The index produced was then validated on a separate patient set (455) from other centres within the Scotland and Newcastle Lymphoma Group (SNLG) on whom the same prospective information was available. The index produced provided a useful separation of those patients destined to die of disease. Of 101 patients with index higher than 0.5, 62 (61.4%) were dead at 4 years, whereas with index lower than 0.5, 61 (18%) of 336 patients were dead at 4 years. The index includes Ann Arbor stage but possesses additional practical prognostic value which allows identification of patients with early stage destined to die of disease. Of 149 patients with stage IA and IIA disease 15 patients had index higher than 0.5, and 10 (60%) have died, whereas the remaining patients had survival of 90% and 85% respectively. This numerical index is applicable to all patients at diagnosis and in the SNLG population gives better predictive survival at 4 years than stage alone, and provides a basis for selecting patients for more aggressive therapy.
A comparative Raman spectroscopic study of cholinesterases.
We report Raman spectra of various cholinesterases: lytic tetrameric forms (G4) obtained by tryptic digestion of asymmetric acetylcholinesterase (AChE) from Torpedo californica and Electrophorus electricus, a PI-PLC-treated dimeric form (G2) of AChE from T marmorata, and the soluble tetrameric form (G4) of butyrylcholinesterase (BuChE) from human plasma. The contribution of different types of secondary structure was estimated by analyzing the amide I band, using the method of Williams. The spectra of cholinesterases in 10 mM Tris-HCl (pH 7.0) indicate the presence of both alpha-helices (about 50%) and beta-sheets (about 25%), together with 15% turns and 10% undefined structures. In 20 mM phosphate buffer (pH 7.0), the spectra indicated a smaller contribution of alpha-helical structure (about 35%) and an increased beta-sheet content (from 25 to 35%). This shows that the ionic milieu profoundly affects either the conformation of the protein (AChE activity is known to be sensitive to ionic strength), or the evaluation of secondary structure, or both. In addition, we analyzed vibrations corresponding to the side chains of aromatic and aliphatic amino acids. In particular, the analyses of the tyrosine doublet (830-850 cm-1) and of the tryptophan vibration at 880 cm-1 indicated that these residues are predominantly 'exposed' on the surface of the molecules.
Structure/activity and molecular modeling studies of the lophotoxin family of irreversible nicotinic receptor antagonists.
Lophotoxin is a small cyclic diterpene that irreversibly inhibits agonist binding to nicotinic acetylcholine receptors by reacting covalently with Tyr190 in the alpha-subunits of the receptor. Structure/activity and molecular modeling studies were undertaken to investigate the structural and conformational features responsible for this unique biological activity. A total of 18 naturally occurring and 7 chemically modified analogues were evaluated for their ability to inhibit the binding of [125I]-alpha-bungarotoxin to nicotinic acetylcholine receptors on membranes prepared from Torpedo electric organ. When the toxins were incubated with the receptor for short durations they did not slow the initial rate of binding of [125I]-alpha-bungarotoxin, suggesting that they have relatively low reversible affinity. However, their ability to inhibit the equilibrium binding of [125I]-alpha-bungarotoxin increased progressively with longer incubation times, consistent with an irreversible mechanism of action. Comparison of active and inactive analogues allowed identification of a conserved pharmacophore that appeared to be required for irreversible inhibition of the receptor. This pharmacophore contains lactone oxygens and an electron-deficient epoxide that may mimic the acetate oxygens and quaternary ammonium group of acetylcholine, respectively. Computer modeling of the toxins using molecular mechanics and dynamics revealed that the toxins have restricted conformational mobility, thus allowing identification of a minimum-energy conformation. The results allow speculation concerning the site of covalent reaction between Tyr190 and the toxins, the normal function of Tyr190 in binding acetylcholine, and the bound conformation of acetylcholine.
A new method for finding long consensus patterns in nucleic acid sequences.
We describe a fast computer algorithm for identifying consensus patterns in DNA sequences. The method requires no prior assumptions about the consensus pattern other than its length. In particular no previous knowledge of the frequency or spacing of consensus patterns is required. However, a priori information about the shape of the consensus pattern, or invariability of individual positions, or the overall conservation level, can be utilized to enhance the selectivity and sensitivity of search. As the number of all possible consensus words increases very rapidly with length, comprehensive searches have usually been restricted to a maximum of 10-12 nucleotides, even when large mainframes are used. Our algorithm enables searching for consensus patterns of this order on current mid-range and powerful microcomputers. Searches may be conducted on single, long sequences or a set of possibly aligned shorter sequences. We give examples of identified consensus patterns in both prokaryotic and eukaryotic DNA sequences, along with some typical program timings.
The effects of prenatal alcohol use on the growth of children at three years of age.
In this prospective study of substance use during pregnancy, women were interviewed in their 4th and 7th prenatal months, and women and children were assessed at 24 hr, 8, 18, and 36 months postpartum. Data are presented on the outcome of 519 children at age 3. At 3 years, children who were exposed prenatally to alcohol were smaller in weight, length, and head circumference. They also had an increased number of minor physical anomalies. These effects were found even after controlling for nutritional and environmental factors. The persistence of growth effects at age 3 suggests that children exposed to alcohol prenatally may have a diminished capacity for growth.
Prenatal alcohol exposure and offspring growth at 18 months of age: the predictive validity of two measures of drinking.
This is an analysis of the effect of prenatal alcohol exposure on growth of the offspring at 18 months of age. In this prospective study, a cohort of women was interviewed at the end of each trimester of pregnancy, at delivery, and at 8 and 18 months. Offspring were examined at each follow-up point. Two drinking scales, average daily volume (ADV) and frequent heavy drinking (FHD), were used to explore the effect of different patterns of drinking. We found significant relationships between both prenatal FHD and ADV and offspring growth at 18 months. A significant and inverse relationship was found between ADV during the second and the third trimesters of pregnancy and weight, height, and head circumference at 18 months. Frequent heavy drinking during all three trimesters predicted a significant decrease in head circumference at 18 months. FHD during the second trimester was significantly related to weight and height at 18 months. Analyses demonstrated that ADV was a better predictor of growth deficits than FHD.
Distinctions in ligand binding sites on the nicotinic acetylcholine receptor.
Ligand-gated ion channels possess intrinsic binding sites for noncompetitive inhibitors that differ substantially in ligand specificity and structural characteristics from most binding sites found on globular proteins. We have used the nicotinic acetylcholine receptor to examine the characteristics of such diverse sites because the high-affinity binding site in the proximity of the ion channel has unusual binding interactions and ligand specificity, whereas the site of agonist activation exhibits classical structure-activity characteristics. Noncompetitive inhibitors that bind to the former site show a wide degree of structural variation and appear to associate at separate loci and in distinct orientations in the vicinity of the channel. The receptor structure appears to provide a large domain with multiple hydrophobic crevices that can bind noncompetitive inhibitors, yet binding of these inhibitors is mutually exclusive. The mutually exclusive behavior suggests that association of a single ligand is sufficient to prevent access of additional ligands to distinct sites. This could occur either by physical occlusion to the site of binding or by formation of a conformational state that will not allow entry of additional noncompetitive inhibitors.
Androgen associated hepatocellular carcinoma with an aggressive course.
The hepatocellular carcinomas that develop in patients treated with androgens have previously been associated with a benign clinical outcome. We describe a man who developed a hepatocellular carcinoma after 24 years of androgen treatment, whose tumour initially showed partial regression after withdrawal of androgens but subsequently pursued an aggressive and fatal course.
c-erbB-2 expression in different histological types of invasive breast carcinoma.
Sections of 149 breast carcinomas were examined for the over-expression of c-erbB-2 oncoprotein using the avidin-biotin immunoperoxidase technique and two different specific antibodies. These included the polyclonal antibody 21N and the monoclonal antibody 4D5. The tumours were divided into two main groups. The first included 75 cases of invasive ductal and classic invasive lobular carcinomas. The second group consisted of 74 cases with histological types known to have a good prognosis, including mucinous, alveolar variant of invasive lobular, medullary, tubular, cribriform and papillary carcinomas. Fifteen (20%) tumours of the first group were positive with the two antibodies. Fourteen of these were of the ductal type and one was a mixed invasive ductal and lobular carcinoma. Ten of the pure ductal cases had areas of comedo carcinoma. The intraductal elements in a further tumour were positively stained with 21N antibody only. None of the second group of tumours, which included histological types known to have good prognosis, stained with 4D5, although one mucinous carcinoma was positively stained with 21N. These findings suggest that in invasive breast carcinoma immunostaining for c-erbB-2 is mainly seen in a subgroup of ductal tumours, and that almost all other histological types, especially those associated with good prognosis, lack this expression.
Heart disease in native Americans.
Cardiovascular disease is one of the major causes of death among native Americans. Ischemic heart disease has been relatively uncommon in the past, but this entity is rapidly becoming more frequent among Indians as a result of Western acculturation (Western high-fat diet, smoking, sedentary lifestyle). Hypertension remains a major problem in native American populations. Hypertension is often inadequately detected and treated in Indians. Rheumatic fever and rheumatic heart disease are moderately common and apparently in decline among native Americans. Finally, the fetal alcohol syndrome with its accompanying cardiac malformations is all too common among North American Indians. The amount of information available concerning cardiovascular disease in native Americans is rather small. Considerably more attention should be paid to this area in the future.
[Cell number in the medullary substance of hair: a simple and sensitive indicator of exposure to radiation].
The medulla of the lower regions of a growing mouse hair contains a very regularly spaced column of cell nuclei. The total number of nuclei 3 days after irradiation in this column (from its lower recognition point to the point of terminal differentiation and nuclear degradation) proves to be a sensitive indicator of the level of radiation exposure.
Supernatant cell counts from long-term bone marrow culture correlate with the speed of engraftment following autologous bone marrow transplantation.
This study evaluates the relationship between bone marrow growth in a long-term bone marrow culture (LTBMC) system and speed of engraftment of the same marrow following autologous bone marrow transplantation (ABMT). Bone marrow from 21 patients transplanted with unmanipulated, non-cryopreserved autologous marrow was cultured. Samples from 21 normal donors were cultured to establish the normal supernatant cell count range. Supernatant counts from LTBMCs established from marrow taken from patients at the time of bone marrow harvest were compared with the time to neutrophil and platelet engraftment. Supernatant counts, particularly after 1 week in culture, showed close correlation with time to neutrophil and platelet engraftment following ABMT (r = 0.733, p less than 0.01; r = 0.735, p less than 0.01 respectively). Where supernatant cell counts were within the normal range rapid engraftment was predicted (neutrophils greater than 0.5 x 10(9)/l within 21 days, platelets greater than 50 x 10(9)/l within 28 days) and if supernatant counts were below this range, engraftment was predicted to be delayed. After 1 week in culture, the speed of neutrophil and platelet engraftment were correctly predicted in 19 and 18 cases respectively. Preliminary data suggest that LTBMC of marrow obtained 2-6 weeks before harvesting provides similar data, thus allowing the opportunity to intervene, for example with growth factors, in selected patients.
Community control of schistosomiasis in Zimbabwe.
The community-based primary health care approach to control schistosomiasis morbidity is the strategy adopted in Zimbabwe. The paper outlines the results of such a control strategy in a rural community with over 30,000 people in the Madziwa area of Zimbabwe from 1985 to 1989. The community-based control strategy involved diagnosis of infection in school children (seven-15 years of age) using reagent strips followed by treatment with praziquantel. The treatment was linked to programmes aimed at improved sanitation, better water supplies and health education. Following chemotherapy, there was a marked reduction in schistosomiasis prevalence (urinary and intestinal forms combined) (from 60 to 20pc) in the affected groups. Of even greater importance was the significant reduction of 90pc in heavy infections (greater than 50 S. haematobium eggs per 10 ml of urine of greater than 100 S. mansoni eggs per gram of faeces). Progress made through chemotherapy was consolidated by the implementation of intervention measures aimed at reducing human water contact with cercariae infested water. In the last three years of the community-based programme, 2,152 improved ventilated pit latrines were constructed and 104 hand pumps installed at new or existing water points. Drama competitions at schools showed great potential in communicating health education messages. However, technical and organisational difficulties limited the impact of the health education to the general population. A single application of the synthetic molluscicide Bayluscide was carried out in the main streams at the beginning of the programme in support of the initial chemotherapy.(ABSTRACT TRUNCATED AT 250 WORDS)