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Biomedical subjects

D R Mitchell

Publications and source records attributed to D R Mitchell.

At least 19 recordsLinked to original sources
PubMed1992

The sensitivity of the Mini-Mental State Exam in the white matter dementia of multiple sclerosis.

Fifty-six patients diagnosed with definite multiple sclerosis (MS) according to Poser criteria were administered the Mini-Mental State Examination (MMSE) and a comprehensive battery of neuropsychological tests. Extent of cerebral lesion involvement was determined by quantitative magnetic resonance imaging (MRI) ratings. The MMSE correlated with overall levels of physical disability, but did not correlate with total lesion area on MRI. Sensitivity of the MMSE to the subcortical dementia of MS was low (28%) when performance on the neuropsychological testing battery was used as the criterion. Impairment on tests of memory, speed of information processing, abstract reasoning, naming/verbal fluency, as well as visuoperceptual organization, were correlated highly with total lesion area on MRI. The low sensitivity of the MMSE to cognitive impairment in MS is discussed in terms of its item composition and the characteristic pattern of deficits found in MS.

Adult↗
PubMed1992

Neuropsychological and structural brain lesions in multiple sclerosis: a regional analysis.

Quantified lesion scores derived from MRI correlate significantly with neuropsychological testing in patients with multiple sclerosis (MS). Variables used to reflect disease severity include total lesion area (TLA), ventricular-brain ratio, and size of the corpus callosum. We used these general measures of cerebral lesion involvement as well as specific ratings of lesion involvement by frontal, temporal, and parieto-occipital regions to quantify the topographic distribution of lesions and consequent effects upon cognitive function. Lesions were heavily distributed in the parieto-occipital regions bilaterally. Neuropsychological tests were highly related to all generalized measures of cerebral involvement, with TLA being the best predictor of neuropsychological deficit. Mean TLA for the cognitively impaired group was 28.30 cm2 versus 7.41 cm2 for the cognitively intact group (p less than 0.0001). Multiple regression analyses revealed that left frontal lobe involvement best predicted impaired abstract problem solving, memory, and word fluency. Left parieto-occipital lesion involvement best predicted deficits in verbal learning and complex visual-integrative skills. Analysis of regional cerebral lesion load may assist in understanding the particular pattern and course of cognitive deficits in MS.

Adult↗
PubMed1991

A Chlamydomonas outer arm dynein mutant missing the alpha heavy chain.

A novel Chlamydomonas flagellar mutant (oda-11) missing the alpha heavy chain of outer arm dynein but retaining the beta and gamma heavy chains was isolated. Restriction fragment length polymorphism analysis with an alpha heavy chain locus genomic probe indicated that the oda-11 mutation was genetically linked with the structural gene of the alpha heavy chain. In cross-section electron micrographs, the oda-11 axoneme lacked the outermost appendage of the outer arm, indicating that the alpha heavy chain should be located in this region in the wild-type outer arm. This mutant swam at 119 microns/s at 25 degrees C, i.e., at an intermediate speed between those of wild type (194 microns/s) and of oda-1 (62 microns/s), a mutant missing the entire outer dynein arm. The flagellar beat frequency (approximately 50 Hz) was also between those of wild type (approximately 60 Hz) and oda-1 (approximately 26 Hz). These results indicate that the outer dynein arm of Chlamydomonas can be assembled without the alpha heavy chain, and that the outer arm missing the alpha heavy chain retains partial function.

Cell Movement↗
PubMed1991

Identification of oda6 as a Chlamydomonas dynein mutant by rescue with the wild-type gene.

We find that two Chlamydomonas outer arm dynein assembly loci, oda6 and oda9, are located on the left arm of linkage group XII, in the vicinity of the previously mapped locus for a 70,000 Mr dynein intermediate chain protein. Restriction fragment length polymorphism mapping indicates that this dynein gene is very closely linked to the oda6 locus. A cDNA clone encoding the 70,000 Mr protein was isolated, sequenced, and used to select genomic clones spanning the corresponding locus from both wild-type and oda6 libraries. When wild-type clones were introduced into cells containing an oda6 allele, the mutant phenotype was rescued, while no rescue was observed after transformation with oda6 clones. Genetic analysis further revealed that newly introduced gene copies were responsible for the rescued phenotype and thus confirms that ODA6 encodes the 70,000 Mr dynein intermediate chain protein. The inability of oda6 mutants to assemble any major outer arm dynein subunits shows that this protein is essential for assembly of stable outer dynein arms. This is the first use of transformation with a wild-type gene to identify the product of a Chlamydomonas mutant.

Amino Acid Sequence↗
PubMed1991

Effects of short-term administration of glucocorticoids on bone metabolism in healthy elderly men.

OBJECTIVE: To determine the effects of short-term glucocorticoid administration in healthy elderly men on bone GLA protein (BGP) levels, as well as levels of calcium, phosphorus, immunoreactive parathyroid hormone (PTH), and alkaline phosphatase. DESIGN: Subjects served as own control before and after prednisone treatment. SETTING: Male subjects were recruited by telephone from the Duke University Aging Center Volunteer Registry and the Department of Veterans Affairs Medical Center Gerofit Program (a supervised exercise program). PARTICIPANTS: Healthy males age greater than 60 years with no history of diabetes mellitus, glucose intolerance, or prior glucocorticoid use. Subjects could not be taking diuretic agents and could not have osteoporosis. The seven subjects mean age +/- std dev was 68.6 +/- 5.3 years. INTERVENTIONS: Prednisone 40 mg orally for 5 days. Fasting serum was obtained at baseline, on days 7 through 11, 13, 15, and 17. Assays of BGP, calcium, phosphorus, PTH, and alkaline phosphatase were performed. MAIN OUTCOME MEASURES: Changes in serum BGP levels was the primary outcome measure. Changes in serum calcium, phosphorus, PTH, and alkaline phosphatase levels were secondary outcome measures. RESULTS: Treatment caused reduction in BGP levels within 24 hours of first dose of prednisone, with levels dropping an average of 78% during the 5 days of treatment (P = 0.004). Within 24 hours of stopping treatment, BGP was no different from baseline. Other variables did not change with treatment. CONCLUSION: Glucocorticoid treatment suppresses BGP production in healthy elderly men in the same fashion as it does in younger healthy men.

Administration, Oral↗
PubMed1990

Glucocorticoid-induced osteoporosis: mechanisms for bone loss; evaluation of strategies for prevention.

Osteoporosis is a common complication of chronic glucocorticoid therapy, especially in older patients who already are at risk of having a reduced bone mass. Glucocorticoids cause bone loss by altering the bone remodeling sequence: bone resorption by osteoclasts is increased, and bone formation by osteoblasts is decreased. Serum levels of osteocalcin, a protein made by osteoblasts, are decreased with glucocorticoid therapy, further evidence of decreased osteoblast function. Glucocorticoids decrease calcium absorption by the gastrointestinal tract and increase renal calcium excretion. Several recent studies suggest that low-dose glucocorticoid therapy is not associated with bone loss. Calcium supplementation with vitamin D is recommended. Several short-term studies have shown prevention of glucocorticoid-induced bone loss with bisphosphonates, calcitonin, and progesterone. Long-term clinical trials should be undertaken to determine strategies to prevent this type of osteoporosis.

Aged↗
PubMed1990

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↗
PubMed1989

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↗
PubMed1989

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↗
PubMed1989

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↗
PubMed1989

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↗
PubMed1987

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↗
PubMed1987

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↗
PubMed1986

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↗
PubMed1986

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↗
PubMed1986

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↗
PubMed1985

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↗