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Biomedical subjects

D C Clark

Publications and source records attributed to D C Clark.

At least 19 recordsLinked to original sources

Measurement of the secondary structure of adsorbed protein by circular dichroism. 1. Measurements of the helix content of adsorbed melittin.

A new circular dichroism (CD) technique is presented which quantifies, in situ, the changes in protein and peptide secondary structure upon adsorption at the quartz/liquid interface. Far-UV CD spectra of adsorbed proteins were recorded from several quartz interfaces contained in a specially constructed cell. Adsorbed, oriented alpha-helical spectra were recorded from hydrophilic and hydrophobic quartz using the bee venom peptide, melittin, which can be induced into an alpha-helical, tetrameric conformation in solution. The hydrophobic quartz provides a model system for oil-in-water emulsions and cell membranes. Surface concentrations were determined by radio-counting and were dependent on the nature of the surface. The characterization of these spectra has been partly achieved using far-UV CD spectra obtained from melittin adsorbed onto hydrophilic colloidal silica particles, where orientation effects are eliminated. Analysis of these spectra reveals considerable denaturation of the helical structures upon adsorption. Surface concentrations from the silica were determined from adsorption isotherms. The surface orientation of adsorbed melittin was dependent on the state of aggregation and hence degree of helicity of the molecule. These results support a model for the mode of action of melittin in lysing membranes.

Adsorption

Secondary structures of a new class of lipid body proteins from oilseeds.

The three main isoforms of the 19-kDa lipid body proteins (oleosin) have been purified to homogeneity from embryos of rapeseed. The secondary structures of these proteins as derived from circular dichroism (CD) and Fourier transform infrared (FTIR) spectroscopy were compared with the secondary structures predicted from the primary sequences. The salient feature of the primary sequence of all oleosins is its division into three defined structural domains: a central hydrophobic domain flanked on either side by relatively hydrophilic domains, respectively. Using a variety of predictive methods based on primary amino acid sequence data, the oleosins exhibited a high probability of beta-strand structure in the 70-residue central hydrophobic domain, with relatively little alpha-helical content. Secondary structure data derived from CD and FTIR were consistent with the predictions from primary sequence, showing that the oleosins contained about 45% beta-strand and 13% alpha-helical structure. Under high salt conditions, a 40-kDa polypeptide was obtained from purified preparations of the 19-kDa oleosins. The 40-kDa polypeptide has a very similar secondary structure, as analyzed by CD and FTIR, to that of the 19-kDa oleosins. This polypeptide is therefore probably a dimer of the 19-kDa oleosins that is formed in high salt environments. A model of the general structure of oleosins is proposed whereby the central hydrophobic domain of the protein with a predominantly beta-strand structure is embedded into the non-aqueous phase of lipid-bodies. This hydrophobic region is flanked by putative alpha-helical structures in the polar N- and C-terminal domains which are probably oriented at the lipid-water interface.

Amino Acid Sequence

MR, CT, and ultrasonography of splanchnic venous thrombosis.

Nine patients with splanchnic venous thrombosis are presented and the value of noninvasive imaging in their initial diagnosis and subsequent follow-up is emphasized. Angiography, traditionally the definitive investigation in such cases, can be reserved for preoperative assessment in those patients considered candidates for surgery. The age of venous thrombi can be estimated by computed tomography (CT) and magnetic resonance imaging (MRI) which aids selection of therapy, and in those anticoagulated, prediction of prognosis.

Adult

Assessment of drug involvement: applications to a sample of physicians in training.

The investigators examined survey data of lifetime and recent drug use in national samples of 2036 senior medical students and 1772 resident physicians to test whether patterns of lifetime drug use could be characterized adequately by a single underlying dimension of 'drug involvement'. The data analysis was based on a two parameter normal item response theory (IRT) model using the marginal maximum likelihood estimation method. The results showed that a single latent dimension of 'drug involvement' characterized individual drug use differences on the following measures: substances ever used, substances used in the previous year or previous month, and the sequential order of first use for each substance. The dimension was equivalent for students and resident physicians, and for both genders. Those who professed 'no religion' tended to be more drug involved. Physicians-in-training with a higher drug involvement score based on lifetime use were more likely: (a) to have used higher-ranking drugs (such as LSD and prescription opiates) in the past year; and (b) to have used a greater number of different drugs during the past month. Subjects first began to use each of the substances in a relatively invariant sequence corresponding to that predicted by the model. The implications of this model for evaluating the drug use histories of physicians-in-training, for identifying subgroups at greater risk for continued drug involvement after the beginning of medical training, and for further psychological, biological, and sociocultural research on the nature of 'drug involvement' are discussed.

Adult

Chronic dyspnea and suicide in elderly men.

In a structured psychological autopsy study of suicide in older adults, 14 cases in which the subjects experienced chronic dyspnea in the months or weeks before death were examined. Thirteen of the subjects were white men. Most had a diagnosable psychiatric disorder, although none had previous contact with a mental health professional. Other common characteristics were chronic or terminal heart or lung disease, very recent contact with a primary physician, prior experience of self or a significant other suffering a debilitating disease, and a fiercely independent and inflexible personality type. The cases illustrate the intricacy of risk factors associated with suicide and alert other investigators and health care professionals to a possible link between chronic dyspnea and suicide risk.

Aged

An application of item response theory to alexithymia assessment among abstinent alcoholics.

An item response theory (IRT) model identified three dimensions assessed by the Toronto Alexithymia Scale (TAS) in a sample of 130 male applicants for inpatient care at a Veterans Administration (VA) medical center alcoholism treatment program. A unidimensional solution did not capture all of alexithymia's theoretical features. Subjects with lower alexithymia scores gave positive responses to items tapping emotional awareness deficits; only those with higher alexithymia scores gave positive responses to items tapping external, operative cognitive style. Thus, a total TAS score may not represent alexithymia accurately in substance-abusing patient populations.

Adult

The non-psychiatric physician's responsibilities for the suicidal adolescent.

Pediatricians, internists, emergency-room physicians, family practice physicians, and other non-psychiatric physicians, often trusted allies of the child and family, are in an excellent position to assess, manage, and even prevent suicidal behaviors in their younger patients. This is not to suggest that these physicians should necessarily undertake extensive counseling or therapy with self-destructive children and adolescents; rather, they can help to screen and coordinate appropriate referrals and reinforce and/or support corrective efforts.

Adolescent

Changes and challenges in Canadian dental faculties.

Canadian dental faculty were surveyed to determine changing career interests, sources of satisfaction, and professional development needs. The respondents indicated a desire to change the proportion of time allocated to their major responsibilities in ways that could create serious problems for dental faculties, i.e. more time on research, with less time on teaching and administration. While most reported teaching as a source of satisfaction and happiness, relatively few reported it as recognized and rewarded. The different status accorded to teachers, clinicians, and researchers, as reflected in the division of workload and rewards have created dissatisfaction among faculty, perhaps contributing to the fact that over 50 percent of respondents reported considering leaving academia. Faculties of Dentistry must determine what is required to reestablish a productive and enjoyable balance among their roles as teacher, researcher, and clinician and to determine what type of environment will best support the development of today's dental academics and tomorrow's dentists.

Canada

Structural analysis by circular dichroism of some enzymes involved in plant cell wall degradation.

Three enzymes which degrade different polysaccharide components of plant cell walls have been characterized by circular dichroism (CD). A bacterial endoglucanase, which in the native state forms part of a multiprotein cellulase complex, showed a tendency to form aggregates as measured by CD. Depending on its degree of aggregation, this enzyme displayed between 50% and 100% helical structure, whereas a bacterial xylanase and a fungal polygalacturonase exhibited more beta-sheet structure. The polygalacturonase was apparently devoid of helical structure.

Cell Wall

Mycetoma: comparison of MR imaging with CT.

Magnetic resonance (MR) images obtained in 18 patients with pathologically confirmed mycetoma in the body (n = 4) or lower extremity (n = 14) were retrospectively reviewed and compared with computed tomographic (CT) scans in 15 patients and surgical findings in 10. T1-weighted images showed an infiltrating mass (same signal intensity as muscle) involving skin, subcutaneous fat, muscles, tendons, and other tissues. On T2-weighted images, the mass and affected structures showed moderately increased signal intensity. Bone marrow involvement was detected in seven patients and was best visualized on T1-weighted images. CT showed moderate enhancement of the infiltrative process in all patients. Bone changes, seen in nine, included coarse trabeculation, periosteal reaction, endosteal proliferation, and patchy destruction. MR imaging and CT were comparable and correlated well with surgery in showing the extent of soft-tissue involvement. Early bone changes (important for therapy planning for pedal mycetoma) were seen only at CT. The study showed that MR imaging is sensitive for assessing the extent of mycetoma in the soft tissues. CT should be the method of choice for staging pedal lesions because it can be used to detect early bone involvement.

Adult

Clinical documentation and occurrence of putative periodontopathic bacteria in human immunodeficiency virus-associated periodontal disease.

Human immunodeficiency virus (HIV)-associated gingivitis (HIV-G) and HIV-associated periodontitis (HIV-P) are two intraoral lesions manifested by patients with HIV infection. Periodontal indices were measured for 87 subjects in 5 study groups: HIV-seropositive patients with healthy periodontium (HIV-H), with HIV-G, or with HIV-P; and non-HIV-infected subjects with healthy periodontium (H) or with adult chronic periodontitis (P). The quantitative clinical parameters were compared and statistically significant intergroup differences were noted. The mean scores on PI and PD do not discriminate between HIV-seropositive and non-HIV-infected seronegative cohorts, but a significant difference in the GI between HIV-H and H was noted. When categories of PD and AL are examined, some differences become apparent. Generally, the PD and AL of HIV-P are not as great as those of P. PI correlates well with GI (r = 0.86) in P, but does not (r = 0.33) in HIV-P. In addition, the occurrence of selected putative periodontopathic bacteria (Porphyromonas gingivalis, spirochetes, and motile eubacteria) in these lesions was determined by brightfield (after staining), darkfield and immunofluorescent microscopy. No difference in microbiological profile in the bacterial groups monitored was found between P and HIV-P. Spirochetes were found to be more abundant than P. gingivalis in the lesions of P and HIV-P. In marked contrast, P. gingivalis was found to be in highest numbers in samples from the gingival crevice of H as determined by indirect immunofluorescence.

Acquired Immunodeficiency Syndrome

The assessment and management of the suicidal patient.

This chapter will be oriented toward the problem faced by the clinician in attempting to prevent suicide in patients under treatment. It will focus on the clinician's difficult task of assessing suicide potential and initiating interventions to prevent suicide in patients at high risk. Specifically, the state of the art in identifying the suicidal patient will be reviewed, and various interventions available to the clinician will be discussed.

Anxiety Disorders

Current research in preventive dentistry and its impact on the future of dental care.

To my mind, preventive dentistry has not changed all that much in the last 10 to 15 years. No miracle drug has come on the scene to prevent periodontal disease. There is no caries vaccine to eliminate dental caries. Interestingly, it has been the traditional technologies that have, given the advantage of time, proven their potential. The reality seems to have surpassed even our most optimistic expectations. But while we have learned how to effectively implement these technologies in many instances, the promotion of water fluoridation has lagged. Nevertheless, the improvements in oral health speak well of the work of our predecessors, who shaped the world of modern dental care. It is up to the profession to use existing preventive technologies to their best advantage and to devise even better preventive measures for the 20 per cent to 30 per cent of the population who are at highest risk of caries and periodontal disease. This paper has focused on some points of interest that have been published in the dental literature on preventive dentistry. Other issues represent concerns of the author. I invite comment and discussion on the topics and issues that were raised. Dialogue is healthy.

Adolescent

De novo design and structure-activity relationships of peptide emulsifiers and foaming agents.

A series of eight amphipathic peptides (8, 11, 15, 2 x 18, 22, 26, 29 amino acids in length) were designed to investigate the effects of amino acid composition, peptide length and secondary structure on surface activity assessed as emulsification and foaming activity. The potential for alpha-helix formation at the hydrophobic/hydrophilic interface was maximized through the use of helix-forming amino acids, a relatively large hydrophobic surface of 200 degrees of arc and ion pairs between basic and acidic amino acids on the hydrophilic surface. Emulsification activity increased rapidly between 11 and 22 residues as alpha-helicity in aqueous solution increased. Despite their small size, the peptides produced exceptionally stable emulsions, compared with proteins. Foaming activity was enhanced by the presence of aromatic amino acids and the activity of the best peptide examined was superior to that of bovine serum albumin and beta-lactoglobulin.

Amino Acid Sequence

A norm-referenced longitudinal study of medical student drinking patterns.

The alcohol consumption patterns of a single class of 121 medical students was assessed at six points over the course of 4 years of medical school training, along with other measures of drinking-related impairment, family history of alcoholism, personality, and psychosocial functioning. Research Diagnostic Criteria were applied to make diagnoses of alcoholism. Eleven percent of the class reported drinking at a level considered "heavy" by class social norms, most transiently. Eighteen percent of the class met criteria for alcohol abuse by virtue of drinking-related impairment during medical school; they were likely to evidence a prior history of alcohol abuse and a family history of alcoholism. Half the excessive drinkers abused alcohol, but two-thirds of the abusers were not excessive drinkers. Alcohol abusers describe themselves as less warm, kind, gentle, and emotionally expressive than their classmates, and were more preoccupied with themes of power in spontaneous fantasy productions. These findings suggest that interpersonal strategies to intervene with alcohol abusing medical students may encounter predictable resistances, and suggest another intervention approach better suited to their psychological concerns.

Adult

A statistical method for evaluating suicide clusters and implementing cluster surveillance.

The absence of any standard definition of suicide cluster events hinders understanding of the prevalence of the problem, hinders the development of appropriate public health responses to observed clusters, and ultimately hinders investigation of the mechanisms underlying contagious communication of suicidal behavior. The authors introduce a Poisson mixture model for assessing potential clusters of adolescent suicide, apply that model to the monthly incidence rates of adolescent suicide for one populous US county over the last 11 years, and generate 99% tolerance limits with 95% confidence for the number of suicides which may occur by chance within specific intervals of time in that county. The suicide incidence data showed a remarkable fit to a single Poisson distribution, suggesting it is not unreasonable to consider the cases as randomly-distributed and independent events. The authors conclude that there is no evidence that adolescent suicides occurred in clusters in the place and in the time frame under study, and recommend the Poisson mixture model for ascertaining clusters as well as implementing cluster surveillance.

Adolescent

Physical recklessness in adolescence. Trait or byproduct of depressive/suicidal states?

The authors assessed adolescents (264 psychiatric inpatients and 742 high school students) with a new instrument (the Sommerfeldt-Clark Adolescent Recklessness Scale) to test whether adolescents show individual differences on a dimension ranging from physical caution to physical recklessness. The three dimensions that emerged reflect an interest in weapons and military dangers, which we have tentatively labeled "foolhardiness"; the combination of dangerous driving and substance abuse; and involvement with smoking, drug use, and "bad company." The personality traits of "venturesomeness" and "impulsiveness" were significantly correlated with all three recklessness factors. The first two factors showed no significant relationship with patient status, diagnosis of mood disorder, or history of suicidal behavior; the third factor was associated with inpatient status and a history of suicide attempts.

Adolescent