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Biomedical subjects

D R Mitchell

Publications and source records attributed to D R Mitchell.

At least 37 records · Page 2Linked to original sources

Successful treatment of cervical pregnancy with oral etoposide.

Cervical ectopic pregnancy is an uncommon entity associated with significant morbidity and devastating effects on future fertility. A woman with a cervical gestation with quantitative serum beta-hCG levels higher than 46,000 mIU/mL and fetal cardiac activity on ultrasound was treated successfully with one course of oral etoposide, a fetocidal agent, which avoided operative intervention and preserved the patient's fertility.

Abortifacient Agents↗

Effects of adult age and working memory on reasoning and spatial abilities.

Three predictions were derived from the hypothesis that adult age differences in certain measures of cognitive functioning are attributable to age-related reductions in a processing resource such as working-memory capacity. Each prediction received at least some degree of empirical support in a study involving 120 males ranging between 20 and 79 years of age. First, older adults exhibited greater impairments of performance than did young adults when task complexity increased and more demands were placed on the limited processing resources; second, the magnitudes of these complexity effects were highly correlated across verbal (reasoning) and spatial (paper folding) tasks. Finally, statistical control of an index of a working-memory processing resource attenuated the effects of age on the measures of cognitive performance. It was concluded that further progress in understanding the mechanisms of the relation between age and cognitive functioning will require improved conceptualizations of the nature of working memory or other hypothesized mediating constructs.

Adult↗

Structural and operational capacities in integrative spatial ability.

Four experiments were conducted to explore a distinction between structural capacity, the maximum number of informational units that can be temporarily stored, and operational capacity, the number of processing operations that can be executed while simultaneously preserving the products of earlier processing. The results, from a synthesis task requiring the integration of successively presented line segments into a composite stimulus, revealed that there were little or no age differences in structural capacity but large age differences favoring young adults in operational capacity. An attempt was also made to determine how much earlier information was available after each additional processing operation, but equivocal results precluded a definitive conclusion about the exact nature of the age differences in operational capacity.

Adult↗

Memory and age differences in spatial manipulation ability.

Young and old adults were asked, in 3 experiments, to make decisions about the identity of line segment patterns after either adding or subtracting line segments from the original pattern. On some of the trials, the line segments from the initial display were presented again in the second display to minimize the necessity of remembering early information during the processing of later information. Although this manipulation presumably reduced the importance of memory in the tasks, it had little effect on the magnitude of the age differences in any of the experiments. Because the 2 groups were equivalent in accuracy of simple recognition judgments, but older adults were less accurate when the same types of decisions were required in the context of an ongoing task, the results suggested that older adults may be impaired in the ability to retain information while simultaneously processing the same or other information.

Adolescent↗

Homograft replacement of the pulmonary artery bifurcation.

Severe deformity or nonconfluence of the pulmonary arteries was repaired during correction of congenital heart defects by implantation of a complete, fresh, antibiotic-sterilized homograft pulmonary artery bifurcation in 17 patients, aged 15 months to 17 years. Six patients had Fallot's tetralogy; five, pulmonary atresia and ventricular septal defect; three, truncus arteriosus; two, ventricular septal defect; and one, pulmonary atresia with intact ventricular septum. All but one had previously undergone one or more palliative or corrective operations. Thirteen patients survived the operation (76%; 70% confidence interval = 61% to 88%) and were followed up from 2 to 56 months postoperatively (mean = 16 months). All had symmetrical pulmonary perfusion on chest x-ray films and satisfactory homograft function on Doppler echocardiograms. There were no late deaths or reoperations. Four patients (24%; 70% confidence interval = 12% to 39%) died in the hospital of pulmonary or cardiac dysfunction despite a technically satisfactory reconstruction. Comparison of predicted and observed ventricular pressure ratios in nine patients showed that the factor contributed by a right pulmonary artery branch stenois was cancelled in most. The use of a complete, adult-size homograft has thus facilitated reconstruction of the pulmonary artery bifurcation and given encouraging early results.

Adolescent↗

High-pressure liquid chromatography fractionation of Chlamydomonas dynein extracts and characterization of inner-arm dynein subunits.

A rapid procedure for fractionating salt-stable dynein subunits from high-salt extracts of Chlamydomonas axonemes has been developed using a high-pressure liquid chromatography system with an anion exchange column and gradient salt elution. Five distinct fractions are shown to be highly enriched for five distinct subunits or subunit complexes by SDS/polyacrylamide gel electrophoresis. ATPase activity and electron microscopy. Peaks 1 and 4 contain, respectively, the single-headed gamma-subunit and the two-headed alpha/beta-heteropolymer that form the outer arm in situ and are dissociated by salt exposure; both peaks are absent from the outer arm-less mutant pf-28. Peaks 2, 3 and 5 contain, respectively, two distinct single-headed species and a double-headed species that derive from inner arms; all three peaks are missing from the inner arm-less mutant pf-23. Sucrose-gradient sedimentation analysis confirms these assignments and provides additional information on the intermediate-chain and light-chain composition of the inner-arm species. Electron microscopy of the purified inner-arm species visualized by the quick-freeze deep-etch technique complements a previous analysis of outer-arm species. Each protein is shown to have a unique morphology, and both the inner- and outer-arm proteins clearly belong to a common family whose structural divergence presumably reflects functional specialization.

Adenosine Triphosphatases↗

Lactate as substrate for glycogen resynthesis after exercise.

Muscle glycogen levels in the perfused rat hemicorpus preparation were reduced two-thirds by electrical stimulation plus exposure to epinephrine (10(-7) M) for 30 min. During the contraction period muscle lactate concentrations increased from a control level of 3.6 +/- 0.6 to a final value of 24.1 +/- 1.6 mumol/g muscle. To determine whether the lactate that had accumulated in muscle during contraction could be used to resynthesize glycogen, glycogen levels were determined after 1-3 h of recovery from the contraction period during which time the perfusion medium (flow-through system) contained low (1.3 mmol/l) or high (10.5 or 18 mmol/l) lactate concentrations but no glucose. With the low perfusate lactate concentration, muscle lactate levels declined to 7.2 +/- 0.8 mumol/g muscle by 3 h after the contraction period and muscle glycogen levels did not increase (1.28 +/- 0.07 at 3 h vs. 1.35 +/- 0.09 mg glucosyl U/g at end of exercise). Lactate disappearance from muscle was accounted for entirely by output into the venous effluent. With the high perfusate lactate concentrations, muscle lactate levels remained high (13.7 +/- 1.7 and 19.3 +/- 2.0 mumol/g) and glycogen levels increased by 1.11 and 0.86 mg glucosyl U/g, respectively, after 1 h of recovery from exercise. No more glycogen was synthesized when the recovery period was extended. Therefore, it appears that limited resynthesis of glycogen from lactate can occur after the contraction period but only when arterial lactate concentrations are high; otherwise the lactate that builds up in muscle during contraction will diffuse into the bloodstream.

Animals↗

Medical treatment of severely impaired infants in New Zealand hospitals.

This study reports on the policies and procedures of paediatricians in 18 New Zealand hospitals with respect to the provision of medical treatment for severely handicapped infants who suffer from a life-threatening illness. None of the hospitals surveyed had specific regulations or codes of conduct that were to be followed by staff in providing medical treatment for such patients. Most of the respondents stated that in making decisions whether or not to provide treatment they gave consideration to the degree of disability, the disabled infant's future quality of life, and the family's quality of life. While almost all of the respondents said that they consulted parents on whether or not to treat their child, many of those who did so made it clear that medical personnel should carry the final responsibility. Few of the subjects said they consulted professionals other than those in the medical or nursing profession when making decisions on treatment. The paper concludes with a recommendation that there be an urgent debate on what policies and practices on treating severely handicapped infants should be followed in New Zealand.

Congenital Abnormalities↗

Protein-protein interactions in the 18S ATPase of Chlamydomonas outer dynein arms.

When outer-row dynein arms are extracted from Chlamydomonas flagellar axonemes, they dissociate into two ATPase complexes with sedimentation coefficients of 12S and 18S. We immunized mice with 18S dynein and generated a library of monoclonal antibodies against the polypeptides in this complex. Antibodies were selected which specifically recognize the 18S alpha- and beta-heavy chains and the 83,000-dalton and 70,000-dalton intermediate chains. These antibodies were isolated and characterized for their ability to recognize determinants on both denatured antigens and native 18S dynein; 18S dynein was dissociated in stepwise fashion into smaller aggregates with ionic and nonionic detergents and the resulting subcomplexes were isolated by precipitation with specific monoclonal antibodies. The smallest aggregates isolated were heterodimers between the alpha-chain and a 16,000-dalton light chain and between the two intermediate chains. Additional close associations of the beta-heavy chain with an 18,000-dalton light chain and 70,000-dalton intermediate chain, and a weaker interaction between the intermediate chain heterodimer and light chains of 21,000 daltons and 12,500 daltons, were also observed. We present a model of 18S dynein substructure based upon this information.

Adenosine Triphosphatases↗

Molecular cloning and expression of flagellar radial spoke and dynein genes of Chlamydomonas.

Several flagellar dynein ATPase and radial spokehead genes have been isolated from a Chlamydomonas genomic expression library in lambda gt11. The library was probed with polyclonal and monoclonal antibodies raised against purified flagellar polypeptides, and recombinant phage giving positive signals were cloned. In vitro translation of mRNAs hybrid-selected by the cloned sequences from whole cell RNA provided confirmation of identity for three of the four clones. Evidence supporting the identification of the fourth, which encodes a dynein heavy chain, was provided by antibody selection; the fusion protein produced by this clone selected heavy chain-specific antibodies from a complex polyclonal antiserum recognizing many dynein determinants. One of the radial spoke sequences isolated here is of particular interest because it encodes the wild-type allele of a locus which was defined previously by temperature-sensitive paralyzed flagella mutation pf-26ts (Huang, B., G. Piperno, Z. Ramanis, and D. J. L. Luck, 1981, J. Cell Biol., 88:80-88). The cloned sequence was used to hybrid-select mRNA from mutant pf-26ts cells, and when translated in vitro, the selected mRNA produced a mutant spokehead polypeptide with an altered electrophoretic mobility. This confirms that the pf-26ts mutation alters the primary structure of a radial spokehead polypeptide. To quantify spokehead and dynein mRNAs during flagellar regeneration, all of the cloned sequences were used as hybridization probes in RNA dot experiments. Levels increased rapidly and coordinately after deflagellation, peaked 3-10-fold above nondeflagellated controls, and then returned to control values within 2 h. This accumulation pattern was similar to that of flagellar alpha-tubulin mRNA.

Adenosine Triphosphatases↗

A motile Chlamydomonas flagellar mutant that lacks outer dynein arms.

A new Chlamydomonas flagellar mutant, pf-28, which swims more slowly than wild-type cells, was selected. Thin-section electron microscopy revealed the complete absence of outer-row dynein arms in this mutant, whereas inner-row arms and other axonemal structures appeared normal. SDS PAGE analysis also indicated that polypeptides previously identified as outer-arm dynein components are completely absent in pf-28. The two ATPases retained by this mutant sediment at 17.7S and 12.7S on sucrose gradients that contain 0.6 M KCl. Overall swimming patterns of pf-28 differ little from wild-type except that forward swimming speed is reduced to 35% of the wild-type value, and cells show little or no backward movement during photophobic avoidance. Mutant cells will respond to phototactic stimuli, and their flagella will beat in either the forward or reverse mode. This is the first report of a mutant that lacks dynein arms that can swim.

Adenosine Triphosphatases↗

Parents teaching their young mentally handicapped children.

This paper reports a fine-grained analysis of interaction between 21 mothers and fathers and their young mentally handicapped children. Parent-child dyads were videotaped at home on two occasions with a 'roundabout' toy. The sessions were analysed by means of a detailed coding system which reflected the reciprocal nature of interaction and which attended to sequences of behaviour. Results are reported on short-term stability of various features of communication and comparisons of dyads involving mothers and fathers. Implications of the results are outlined for interventions designed to help parents to teach their young mentally handicapped children.

Adult↗

Alcohol consumption of high school students in relation to ethnicity, socioeconomic status, and sex.

Fifth form students in three Gisborne city high schools were surveyed in 1968 and 1981. On an item in which they were asked to report on their level of alcohol consumption, 515 responded on the first occasion and 583 on the second. Over time, there were statistically significant shifts in the direction of higher levels of consumption among both Maori and European females, but not for Maoris or European males. Europeans of both low and high socioeconomic status and Maoris of low socioeconomic status increased their level of alcohol consumption, but Maori students from high socioeconomic homes did not. In both 1968 and 1981, Europeans reported higher levels of consumption than did Maoris.

Adolescent↗

A comparison of high school students' smoking behaviours in 1968 and 1981.

A questionnaire survey was carried out among fifth form students in three Gisborne city high schools in 1968 and repeated in 1981. On an item concerned with smoking, 514 students responded on the first occasion and 583 on the second. Over time, there was a shift towards higher levels of smoking among females and lower levels among males, a finding that applied to both Maori and European students. Socioeconomic status was not related to levels of smoking for either ethnic group in 1968 and for Maoris in 1981; on the latter occasion, however, European students from low socioeconomic homes reported higher levels than those from high socioeconomic homes.

Adolescent↗

Binding of dynein 21 S ATPase to microtubules. Effects of ionic conditions and substrate analogs.

Binding of 21 S dynein ATPase isolated from Tetrahymena cilia to B subfibers of microtubule doublets was used as a model system to study dynein-tubulin interactions and their relationship to the microtubule-based sliding filament mechanism. Binding of 21 S dynein to both A and B microtubule subfibers is supported by monovalent as well as divalent ions. Monovalent cation chlorides support dynein binding to B subfibers with the specificity Li greater than Na congruent to K congruent to Rb congruent to Cs congruent to choline. The corresponding sodium or potassium halides follow the order F greater than Cl greater than Br greater than I. However, an optimal binding concentration of 40 mM KCl supports only 55% of the protein binding which takes place in 3 mM MgSO4 and does not stabilize dynein cross-bridges when whole axonemes are fixed for electron microscopy. Divalent metal ion chlorides (MgCl2, CaCl2, SrCl2, and BaCl2) have nearly equivalent effects at a concentration of 6 mM; all support about 140% of the binding observed in 6 mM MgSO4. The binding data suggest negative cooperativity or the presence of more than one class of dynein binding sites on the microtubule lattice. Low concentrations of MgATP2- induce dissociation of dynein bound to B subfibers in either 6 mM MgSO4 or 40 mM KCl. ADP, Pi, PPi, and AMP-PCH2P are unable to induce dynein dissociation, while AMP-PNHP and ATP4- both cause dynein release from B subfiber sites. The half-maximal sensitivities of the tubulin-dynein complex to MgATP2-, ATP4-, and adenylyl-imidodiphosphate (AMP.PNP) are 1.3 X 10(-8) M, 3.6 X 10(-5) M, and 4.7 X 10(-4) M respectively. Incubation of doublets or 21 S dynein in N-ethylmaleimide (NEM), which can inhibit active sliding, has no effect on either association of dynein with the B subfiber or on dissociation of the resulting dynein-B subfiber complex by MgATP2-.

Adenosine Triphosphatases↗

Parents' experiences and views on being told they have a handicapped child: a survey.

This study examines the experiences of 152 parents of young children with special needs of when and how they were first told of their child's condition and their preferences for being told alone or together with their spouse. The point at which parents were first told differed according to the nature of the child's handicap. The medical profession and allied health services bear the brunt of informing parents. There were no significant variations in parents' experiences of who was told or their preferences for being told together or alone when the five independent variables of child's handicap, residence, child's age family size, and socio-economic status were taken into account.

Age Factors↗