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Biomedical subjects

C Leach

Publications and source records attributed to C Leach.

At least 37 records · Page 2Linked to original sources

A K(+)-competitive fluorescent inhibitor of the H,K-ATPase.

The interactions of a novel fluorescent compound, 1-(2-methylphenyl)-4-methylamino-6-methyl-2,3-dihydropyrrolo[3,2-c ]quinoline (MDPQ) with the gastric H,K-ATPase were determined. MDPQ was shown to inhibit the H,K-ATPase and its associated K(+)-phosphatase competitively with K+, with Ki values of 0.22 and 0.65 microM, respectively. It also inhibited H+ transport with an IC50 of 0.29 microM, but at a concentration of 3.5 microM, reduced the steady-state level of phosphoenzyme by only 28%. The fluorescence of the inhibitor increased upon binding to the enzyme. 70% of this increment was quenched by K+, independently of Mg2+. The binding of MgATP to a high affinity site (K0.5(ATP) less than 1 microM) markedly increased the fluorescence due to the formation of an inhibitor-phosphoenzyme complex saturating with a K0.5(MDPQ) of 0.94 microM. The K(+)-dependent fluorescent quench (K0.5(K+) = 1.8 mM) required the ionophore, nigericin, indicating that K+ and MDPQ were competing at an extracytosolic site on the enzyme. Formation also of an enzyme-vanadyl-inhibitor complex was shown by the fact that Mg2+ plus vanadate enhanced MDPQ fluorescence in the absence of MgATP and decreased fluorescence in the presence of MgATP. The minimal stoichiometry of bound MDPQ determined by fluorescence titrations in the presence of MgATP was 1.4 mol/mol phosphoenzyme. The data suggest that this compound can serve as a probe of conformation at an extracytosolic site of the H,K-ATPase.

Adenosine Triphosphatases↗

Pathophysiology of reactions associated with pertussis vaccine.

Many adverse clinical events occur after pertussis immunization in children, but the pathophysiology is not well understood. It has been suggested that some of these adverse events may be due to biologically-active LPF and endotoxin present in DTP vaccines. Fifty-six children were studied who experienced severe reactions (fever greater than or equal to 40.5 degrees C, seizures, persistent crying greater than or equal to 3 hours or hypotonic-hyporesponsive episodes) within 48 hr of DTP immunization. Leukocytosis with neutrophilia was noted acutely (after vaccination) compared to follow-up (approximately one month later). No changes in insulin or glucose values were noted. Utilizing the CHO cell assay, no biologically-active LPF was found in the acute sera of children who had DTP-associated seizures. We found no evidence that biologically-active LPF or altered insulin/glucose metabolism were related to severe DTP-associated reactions.

Blood Glucose↗

Sequence and structure in the concept development of children with emotional and behavioral difficulties.

We investigated the order of acquisition of concepts and cognitive processes in children with emotional and behavioral difficulties and the extent to which these children show similarity to ordinary children in sequence and structure of development. Similarity in developmental sequence was strongly supported by scalogram analyses and has clear implications for organizing teaching, but similarity in structure was less clear. Cognitive processes however, and the nature of the children's reasoning were clarified by the method of exploration used. This was particularly fruitful for providing insight into the difficulties children may have. The findings thus contribute to understanding with a view toward furthering concept development in children with emotional and behavioral difficulties.

Adolescent↗

Similar-sequence and similar-structure in retarded and non-retarded children's development.

Three questions important in relation to the developmental-difference controversy were addressed. The first, to what extent do retarded and non-retarded children show a similar sequence in their development of concepts, was answered using scalogram analyses which supported a common order of acquisition of conservation concepts when intermediate as well as conservation and non-conservation categories were used. There was a high degree of similarity in sequence within as well as between attributes. The second question, how far does the similar-structure hypothesis hold, was answered in the terms set by the developmental theorists. Multiple regression analyses and comparisons of mean mental ages for each of the conservation subgroups supported the similar-structure hypothesis. Non-retarded and retarded children with no known organic condition revealed similar structures. The third question concerned findings of volume conservation in retarded children and how these might be interpreted. It is argued that recognition of conservation in displacement volume tasks need not imply a generalised stage of formal operations nor be interpreted in terms of ceiling in development. Overall the findings have implications for ordering and providing appropriate levels of experiences for retarded children without assuming fixed limits in their development.

Adolescent↗

The development of conservation concepts in children with visual impairment.

The investigation was the last in a series examining similarity of sequence and structure in the development of children with different handicapping conditions. It focused on the development of conservation concepts by children who were visually impaired but not blind. Similarity in order of acquisition of conservation concepts for visually impaired and sighted children was found and was supported by scalogram analyses yielding very high coefficients of reproducibility. Similarity in structure or level of understanding of conservation was also evident for these groups of children at comparable chronological ages and was supported by multiple regression analyses. There was no evidence of delay in the visually impaired children's development of conservation concepts.

Adolescent↗

GRAN: a computer program for the cluster analysis of a repertory grid.

A BASIC computer program is described for analysing individual repertory grids. The analysis results in a rearranged version of the grid, with similar constructs and similar elements grouped together. Element and construct similarities are assessed using single-link hierarchical cluster analysis. The program works with rating, ranked or dichotomous grids and copes with missing entries.

Adaptation, Psychological↗

Training general practitioners to improve their recognition of emotional disturbance in the consultation.

The detection of emotional disturbance by general practitioners in the consultation is known to be low. This study measured the detection rates of emotional disturbance among 10 established principals in general practice, as compared with the general health questionnaire, before and after 10 months of training. The training comprised a fortnightly seminar based around video recordings of ordinary consultations. The results showed that nine of the 10 doctors improved their ability to identify cases while one over-diagnosed cases following the training. The general health questionnaire detected emotional disturbance in 51.5% of the patients studied. During the seminars it became apparent that factors both within the doctor and the patient prevented detection of emotional disturbance and these are described. It is concluded that diagnostic accuracy depends on the interaction between doctor and patient, and that this has implications for the organization of general practice both in terms of longer consultation times and of adequate support for the doctor.

Affective Symptoms↗

An ongoing surveillance study of persistent crying and hypotonic-hyporesponsive episodes following routine DTP immunization: a preliminary report.

Hypotonic-hyporesponsive episodes and persistent crying are specific complications of pertussis immunization. Hyperinsulinemia, hypoglycemia, and leukocytosis have been noted after pertussis vaccine administration in a murine model. Five children with hypotonic-hyporesponsive episodes and 6 children with persistent crying following DTP immunization were studied. The children were found to have leukocytosis acutely, similar to findings reported in children following routine DTP immunization. No abnormalities were noted in plasma insulin or serum glucose. Five of 6 children with persistent crying had severe local reactions, suggesting that localized inflammation may be a cause of persistent crying.

Crying↗

Venous pressure in man during weightlessness.

To determine whether the body fluid shift from the lower limbs toward the head that occurs during spaceflight leads to lasting increases of venous pressure in the upper body, venous pressure and hematocrit measurements were made on four astronauts before flight and 1 and 12 hours after recovery and compared with measurements in space. During the mission the hematocrit was elevated and the venous pressure lowered by 1 to 8 centimeters of water as compared with the preflight data. One hour after landing the hematocrit decreased, indicating a hemodilution, venous pressures were unexpectedly high, and a body weight loss of 4 to 5 percent was observed. Twelve hours later the venous pressures were the lowest recorded during the study. The fluid shift apparently takes place during the first several hours of spaceflight. Thereafter, the pressure in the peripheral veins and the central circulation is lower than that measured before flight.

Body Fluids↗

Sheep elastin genes. Isolation and preliminary characterization of a 9.9-kilobase genomic clone.

A sheep genomic library containing sheep DNA in the bacteriophage vector Charon 4A was screened for elastin-gene sequences with partially purified, 32P-labelled elastin mRNA (mRNAE). A recombinant containing a 9.9-kb (kilobase) insert was selected from several positive clones by secondary and tertiary screening for further characterization. Positive identification of this elastin clone, designated SE1, was made with radiolabelled mRNAE by hydridization-selected translation and Southern blotting of restriction-enzyme fragments of SE1 DNA. Hybridization of either mRNAE or elastin complementary DNA to restriction fragments of SE1 showed that most of these fragments of SE1 contained elastin-coding sequences. Orientation of the insert was established by preferential hybridization of a short complementary elastin DNA to restriction fragments adjacent to the right arm of Charon 4A. Reciprocal hybridizations of nick-translated SE1 and sheep genomic DNA on Southern blots showed that two restriction fragments of SE1 contained sequence elements which were repeated at high frequency in a restriction-endonuclease-EcoR1 digest of total sheep genomic DNA. In the accompanying paper [Davidson, Shibahara, Boyd, Mason, Tolstoshev & Crystal (1984) Biochem. J. 220, 653-663], it is shown that a subcloned fragment of this elastin gene quantitatively and specifically hybridized to mRNAE sequences in sheep tissue RNA. Electron microscopy of SE1-mRNAE hybrids indicated the presence of at least seven large R-loops. Measurements of these structures indicated that SE1 is likely to contain less than 2 kb of coding sequence and more than 8 kb of intervening sequence, with an average exon size of 120 base-pairs. Thus the elastin gene is distributed over an extended region of the sheep genome and contains numerous intervening and coding sequences.

Animals↗

Five-year follow-up of 101 elderly subjects by means of long-term ambulatory cardiac monitoring.

Long-term follow-up of 101 healthy elderly subjects living independently in the community has been undertaken by means of clinical examination, resting ECG and 24-hour ambulatory cardiac monitoring. It appears that the finding of ventricular premature complexes at the rate of 10 per hour or greater is associated with a significant increase in mortality. The prevalence of atrial fibrillation, initially found to be 11%, rises with age to 17% by the age of 84 years. Long-term ambulatory monitoring is essential in the proper documentation of paroxysmal atrial fibrillation. Bundle branch block also occurs in over 10% of elderly people and the prevalence rises steeply with age, so that at the end of this study more than one quarter of the survivors had evidence of His-Purkinje disease. Over 5% of our subjects had definite indications for pacing during the period of follow-up and lends support to the opinion that the current pacemaker implantation rate in the United Kingdom is below the optimal level.

Aged↗

Longevity comparisons among lithium anode power cells for cardiac pacemakers.

Of over 10,000 lithium-powered pacemakers followed by a commercial transtelephone monitoring service, 148 have been explanted due to rate decline. A breakdown according to the power cell manufactures shows that the longevity is not uniform, indicating that significant differences exist among the power cell designs even though all have lithium anodes. One tenth of all lithium-powered pacemakers in the study were explanted for rate declines within 4 years.

Data Collection↗

The children of psychiatric patients: clinical findings.

Findings are presented on 42 children of school age, the offspring of 26 adult psychiatric patients. Psychiatric disorder was found in 19 (45 per cent) of the children, compared with 12 (26 per cent) of 47 children from a control group of families. Families with disturbed children differed from the remaining families in the following ways: presence of frank marital discord, the diagnosis of personality disorder in the parents, the inability of the father to tolerate angry situations, and the presence of siblings of under 9 years of age. Six months later 9 of the 19 children had improved considerably. In almost every family this was associated with improvement in the condition of the parents. It is suggested that the psychiatric disorder of these children is reactive to the presence of emotional turmoil in the families.

Adolescent↗

Mineral and nitrogen metabolic studies on Skylab flights and comparison with effects of earth long-term recumbency.

A metabolic study of the effects of space flight on various chemical elements, particularly those with special relevance to the musculo-skeletal system, was carried out on the nine astronauts who participated in the three Skylab flights of 28, 59 and 84 days in 1973-1974. The study required of the cooperating crewmen constant dietary intake, continuous 24-hour urine collections and total fecal collections for 21-31 days before each flight, throughout each flight and for 17-18 days post-flight. Increases in urinary calcium and negative calcium balances during space flight were generally similar to those found in previous immobilization and bedrest studies. The persistence of these alterations in calcium metabolism throughout the flights suggested that calcium losses would continue in weightlessness for a very long time. Significant losses of nitrogen and phosphorus occurred, associated with observed reduction in muscle tissue. Both mineral and muscle losses occurred despite vigorous exercise regimens in flight. It was concluded that unless protective measures can be developed, capable musculo-skeletal function is likely to be impaired in space flights, ultimately to be conducted to Mars, of 11/2 to 3 years duration.

Bed Rest↗