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Biomedical subjects

D C Clark

Publications and source records attributed to D C Clark.

At least 145 records · Page 8Linked to original sources

Molecular flexibility in microtubule proteins: proton nuclear magnetic resonance characterization.

Bovine microtubule protein preparations have been examined by proton nuclear magnetic resonance (1H NMR) spectroscopy at 270 MHz. Sharp resonances have been identified as deriving from microtubule-associated proteins. These resonances persist after self-assembly of microtubule protein. Brief tryptic treatment of assembled microtubules, specifically cleaving the microtubule-associated protein HMW2 (Mr = 270 000), releases the pendant portion of HMW2 (Mr = 240 000), three-quarters of which is in a flexible conformation. Isolated tau protein and HMW2 protein both show substantial flexibility; on recombination with tubulin dimer, tau shows considerable decrease in flexibility whereas HMW2 is unaffected. The observations may have important implications for the interactions between microtubules and other cytoskeletal structures.

Amino Acids↗

Assessing anhedonia in psychiatric patients.

In two studies of depressed, manic, schizophrenic, and normal subjects, a scale for measuring the intensity of subjects' pleasureable responses to normally emjoyable situations (the Pleasure Scale) evidenced good internal reliability and moderate agreement with the Chapman Anhedonia Scale and Indexes of depressive symptom severity. Only the depressed patients showed extremely anhedonic responses. Although more than half the depressed patients evidenced pleasure scores in the normal range, about 185 of them seemed more anhedonic than any norma subject. A mixture analysis resolved depressed patient scores into two distinct distributions: a normal-range distribution (88% of depressives) and an extremely anhedonic distribution (12%). The findings provide some support for the existence of a qualitatively distinct subtype of major depression that has been variously defined an "endogenomorphic" or "melancholic."

Bipolar Disorder↗

The core symptoms of depression in medical and psychiatric patients.

The internal consistency of the Beck Depression Inventory (BDI) is assessed in 335 randomly selected medical inpatients, and in another sample of 101 depressed psychiatric inpatients with 104 interviewed normals. The data for the two samples were analyzed separately using a latent trait model. The analysis confirms that the BDI measures a single underlying dimension of depressive severity for both patient samples. Fourteen symptoms discriminate well for severity of depression in the psychiatric-normal sample, seven symptoms in the medical sample, and six symptoms in both samples. The latter six symptoms (suicidal ideation, sense of failure, sense of punishment, loss of social interest, indecision, and dissatisfaction) may represent criteria for depressive severity that are not confounded by the presence of physical illness or the attendant distress.

Adolescent↗

Guilt and conscience in major depressive disorders.

The authors propose definitions of guilt as a self-critical feeling state and of conscience as a set of standards, to permit independent assessment of their prevalence in a sample of 93 depressed, 29 schizophrenic, and 43 normal subjects. Patients with feelings of guilt tended to have a more severe conscience and lower self-esteem. While guilt is prominent in a moderate percentage of depressed patients, negative self-esteem may form one of the cornerstones for depressed patients of all types. The authors propose that the operational definition of psychoanalytic concepts such as guilt and conscience permits a valid and more rigorous test of clinical generalizations.

Adolescent↗

Differences between anhedonic and normally hedonic depressive states.

In this study of 101 patients who met DSM-III criteria for major depression, those with extreme anhedonia (N = 23) were younger, more depressed, and less neurotic than the patients with a normal-range capacity for pleasurable experiences (N = 78). The anhedonic depressed patients recovered more rapidly; at discharge they consequently had levels of symptom severity equal to those of the hedonic patients, yet they remained significantly more anhedonic. The anhedonic patients exhibited loss of pleasure in appetite, sex, social contacts, and work, which suggests a global dulling of the capacity for pleasure.

Adolescent↗

Effectiveness of routine periodontal treatment with and without adjunctive metronidazole therapy in a sample of mentally retarded adolescents.

A sample of mentally retarded adolescents with moderate periodontal disease was given conventional treatment with and without adjunctive metronidazole therapy following consent of guardians. Antibiotics or placebo tables were taken 1 week following prophylaxis in a double blind clinical trial. Six months after the baseline examinations, there were no significant differences between the treatment and control groups in the mean attachment level or the proportions of microorganisms in subgingival pockets.

Adolescent↗

Interactions of tubulin and microtubule-associated proteins. Conformation and stability of the oligomeric species from glycerol-cycled microtubule protein of bovine brain.

1. The conformation of bovine microtubule protein prepared by cycles of assembly and disassembly in the presence of glycerol has been studied by near-u.v. circular dichroism (c.d.) over a range of protein concentrations. The effects on the conformational properties of ionic strength and of a pH range from 6 to 7.5 have been correlated with the known oligomeric composition of microtubule protein preparations, as determined by the sedimentation behaviour of this preparation [Bayley, Charlwood, Clark & Martin (1982) Eur. J. Biochem.121, 579-585]. 2. The formation of 30S oligomeric ring species, either by decreasing ionic strength at pH6.5 or by changing pH in the presence of 0.1m-NaCl, correlates with a significant change in tubulin c.d. Formation of 18S oligomer by changing pH at ionic strength 0.2 produced no comparable effect. The c.d. of tubulin dimer itself is not affected by ionic strength and pH over the same range. 3. The results are interpreted as a small conformational adjustment between tubulin and specific microtubule-associated proteins on forming 30S oligomeric species, due to interaction with the high-molecular-weight-group proteins. The possible significance of this is discussed with respect to microtubule assembly in vitro. 4. By using this conformational parameter, together with equilibrium and kinetic light-scattering studies, the sensitivity of glycerol-cycled microtubule protein to dilution is shown to be strongly pH-dependent, the oligomers being much more stable at pH6.4 than at pH6.9. 5. Oligomeric complexes of tubulin with microtubule-associated proteins show marked stability under conditions similar to those for efficient microtubule assembly in vitro. Oligomeric material therefore must be incorporated directly during assembly in vitro from microtubule protein.

Animals↗

A statistical model for the classification of imipramine response in depressed inpatients.

We present a statistical model, recently developed for application in mathematical economics, that yields empirical evidence for the existence of two distinct subtypes of depression. We reanalyze previously reported data on 65 depressed patients treated with imipramine and repeatedly rated on the Hamilton Rating Scale (HRS). The estimated model parameters suggest two underlying response processes. Patients in the first subgroup were initially more severely depressed (as measured by the total HRS score), but exhibited a rapid rate of symptomatic response over time. In contrast, patients in the second subgroup were initially less severely depressed, yet showed a much slower rate of improvement. These findings recommend a refinement of the clinical definitions of endogenous depression. While this model suggests that there are two underlying response processes, it does not classify individual patients. Subject classification was made possible by fitting an item-response model to the data. This model relates the 17 individual symptom ratings, at baseline, to the total post-treatment HRS scores. The results of this analysis suggest that the previously described relationship between high initial severity of depression and more rapid improvement over time is characteristic of subjects who exhibit initial motor retardation and decreased sexual interest. Graphical analysis clearly indicates that subjects who exhibit both motor retardation and decreased sexual interest at baseline have higher total HRS scores at baseline and show more pronounced improvement in total HRS scores in response to treatment with imipramine. Patients not exhibiting motor retardation and decreased sexual interest were less severely depressed initially and show virtually no clinical response over time.

Depressive Disorder↗

A review on fluoride varnishes: an alternative topical fluoride treatment.

The in vitro, in vivo and clinical research on topical fluoride varnishes in surveyed. The probable mechanisms of action for fluoride varnishes is discussed and this effect demonstrated from the results of in vitro and in vivo research. Findings from clinical studies are summarized and selected results are used to estimate expected preventive effects from the treatment. The practical advantages and limitations of fluoride varnishes are also reviewed and indications for the future used of these preventive agents are considered.

Adult↗

A further look at the role of radiographs in trials of caries-prophylactic agents.

To determine the role of bitewing radiographs in clinical trials of caries prophylactic procedures, data from the Chatham flossing study 26 were reanalyzed. The final examination records after 20 months of 147 second grade children were used to assess and compare the separate and combined results from clinical and radiographic examinations. Analysis of paired approximal surfaces from contralateral test and control quadrants revealed that the addition of radiographic findings to clinical data changed the mean increment reduction from 22 to 26 percent. This slight increase was further supported by the results of similar studies which reported either separate or combined radiographic and clinical findings or both. Although the magnitude of the increase of the mean increment reduction remains uncertain, data from these studies indicate that the use of combined radiographic and clinical data might be justified when testing a particular prophylactic procedure which is expected to incur a significant caries reduction to approximal surfaces. Furthermore, findings suggest that clinical trials of certain prophylactic agents that are particularly beneficial to approximal surfaces, but which fail to include radiographic examinations, might actually underestimate the preventive effect of the agent.

Child↗