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Biomedical subjects

J M Clark

Publications and source records attributed to J M Clark.

At least 37 records · Page 2Linked to original sources

Implicit learning of first-, second-, and third-order transition probabilities.

Most sequence-learning studies have confounded different types of information, making it difficult to know precisely what is learned. Addressing many of the confounds, the current study shows that people can learn 1st-, 2nd-, and 3rd-order transition probabilities. Measures directly assessing awareness of the probabilities show that the knowledge is implicit early in training and becomes explicit with extended training.

Adolescent↗

Local flaps in scar revision.

Local and regional skin flaps provide the foundation for reconstructive surgery of the face. When planned and executed properly, local skin flaps provide rapid reconstruction using donor tissue with excellent color and texture match, and a reliable, adequate blood supply. The majority of local skin flaps are utilized for reconstruction after superficial cancer extirpation, however, unfavorable scars from previous trauma, burns, or reconstruction efforts provide the motivated patient and surgeon another opportunity to restore form and function. This article reviews techniques commonly used to reconstruct the face and provides several cases where these techniques were successfully employed.

Cicatrix↗

Emerging perceptions of facial plastic surgery among medical students.

OBJECTIVE: The purpose of this study was to examine the perceptions of medical students regarding facial aesthetic surgery and those specialists most likely to perform aesthetic or reconstructive facial surgery. METHODS: A survey was designed based on a review of the literature to assess the desirable characteristics and the perceived role of the facial plastic and reconstructive surgeon (FPRS). The surveys were distributed to 2 populations: medical students from 4 medical schools and members of the general public. RESULTS: A total of 339 surveys were collected, 217 from medical students and 122 from the general public. Medical students and the public had similar responses. The results demonstrated that respondents preferred a male plastic surgeon from the ages of 41 to 50 years old and would look to their family doctor for a recommendation. Facial aesthetic and reconstructive surgery was considered the domain of maxillofacial and general plastic surgeons, not the FPRS. CONCLUSION: Integration of the FPRS into the medical school curriculum may help to improve the perceived role of the specialty within the medical community. It is important for the specialty to communicate to aspiring physicians the dedicated training of an otolaryngologist specializing in FPRS.

Adult↗

Value of HoNOS in assessing patient change in NHS psychotherapy and psychological treatment services.

BACKGROUND: Little research on the value of Health of the Nation Outcome Scales (HoNOS) has occurred in out-patient settings, particularly psychotherapy services. AIMS: To determine whether HoNOS provides an adequate assessment for psychotherapy services which is sensitive to change. METHODS: HoNOS ratings from 1688 patients from eight out-patient psychotherapy services were collected. Of these, 362 also had ratings post-treatment. Mean scores, pre-to post-treatment differences, and reliable and clinically significant change criteria were calculated for HoNOS items and for total scores. RESULTS: The mean total HoNOS rating was 8.93, which is comparable to psychiatric out-patients. Only three items showed sufficient variability to use in assessing pre- to post-treatment change. CONCLUSIONS: Significant limitations were found in rating items that commonly present to psychotherapists. The lack of variability in most items limits HoNOS's usefulness in this population.

Adult↗

Localized laryngotracheobronchial amyloidosis: case report and review of the literature.

Although localized laryngotracheobronchial amyloidosis is rare, the otolaryngologist--head and neck surgeon should be familiar with this condition. Its characteristic appearance can suggest its presence in a patient who has the typical initial symptoms. Biopsies during direct laryngoscopy and bronchoscopy can play both a diagnostic and therapeutic role. After an appropriate examination to rule out systemic involvement, the patient should be managed with conservative surgery, although the use of a CO2 laser might be more efficacious than conventional surgery. With appropriate diagnosis and treatment, patients should expect a favorable prognosis. In this article, we describe a new case of localized laryngotracheobronchial amyloidosis in a 67-year-old woman, and we review the literature on this subject.

Aged↗

Obesity and approaches to weight in an urban African-American community.

OBJECTIVES: To describe the prevalence of obesity, associated factors, and current approaches to weight in an inner city African-American community. DESIGN: In-home survey by community health interviewers. SETTING: Baltimore, Maryland. PARTICIPANTS: 2196 community residents identified in a probability sample of census blocks. MAIN OUTCOME MEASURES: Self-reported height and weight and calculated Body Mass Index (BMI), category of BMI, and stated weight goals. RESULTS: Sixty percent of participants were overweight (BMI> or =25 kg/m2), and 31% were obese (BMI> or =30 kg/m2). In multivariate analysis, women, those earning $15,000-30,000, and those aged 45-60 were more likely to be obese; less likely to be obese were smokers, daily drinkers, and those with "good" or "excellent" health. Sixty-one percent of obese participants reported trying to lose weight, while 36% of normal weight participants were trying to gain weight. Of those trying to lose weight, 35% were using recommended approaches, and 26% received "the professional help they needed to control their weight." CONCLUSIONS: Although obesity was prevalent, few were using recommended weight loss strategies and a significant minority of normal weight participants were trying to gain weight, indicating a need for improved weight management and obesity prevention in the African-American community.

Adolescent↗

Crystal structure of human cathepsin V.

Cathepsin V is a lysosomal cysteine protease that is expressed in the thymus, testis and corneal epithelium. We have determined the 1.6 A resolution crystal structure of human cathepsin V associated with an irreversible vinyl sulfone inhibitor. The fold of this enzyme is similar to the fold adopted by other members of the papain superfamily of cysteine proteases. This study provides a framework for understanding the structural basis for cathepsin V's activity and will aid in the design of inhibitors of this enzyme. A comparison of cathepsin V's active site with the active sites of related proteases revealed a number of differences, especially in the S2 and S3 subsites, that could be exploited in identifying specific cathepsin V inhibitors or in identifying inhibitors of other cysteine proteases that would be selective against cathepsin V.

Binding Sites↗

Cloning and characterization of a novel human histone deacetylase, HDAC8.

Histone deacetylases (HDACs) are a growing family of enzymes implicated in transcriptional regulation by affecting the acetylation state of core histones in the nucleus of cells. HDACs are known to have key roles in the regulation of cell proliferation [Brehm, Miska, McCance, Reid, Bannister and Kouzarides (1998) Nature (London) 391, 597-600], and aberrant recruitment of an HDAC complex has been shown to be a key step in the mechanism of cell transformation in acute promyelocytic leukaemia [Grignani, De Matteis, Nervi, Tomassoni, Gelmetti, Cioce, Fanelli, Ruthardt, Ferrara, Zamir et al. (1998) Nature (London) 391, 815-818; Lin, Nagy, Inoue, Shao, Miller and Evans (1998), Nature (London) 391, 811-814]. Here we present the complete nucleotide sequence of a cDNA clone, termed HDAC8, that encodes a protein product with similarity to the RPD3 class (I) of HDACs. The predicted 377-residue HDAC8 product contains a shorter C-terminal extension relative to other members of its class. After expression in two cell systems, immunopurified HDAC8 is shown to possess trichostatin A- and sodium butyrate-inhibitable HDAC activity on histone H4 peptide substrates as well as on core histones. Expression profiling reveals the expression of HDAC8 to various degrees in every tissue tested and also in several tumour lines. Mutation of two adjacent histidine residues within the predicted active site severely decreases activity, confirming these residues as important for HDAC8 enzyme activity. Finally, linkage analysis after radiation hybrid mapping has localized HDAC8 to chromosomal position Xq21.2-Xq21.3. These results confirm HDAC8 as a new member of the HDAC family.

Amino Acid Sequence↗

A novel approach to serine protease inhibition: kinetic characterization of inhibitors whose potencies and selectivities are dramatically enhanced by Zinc(II).

Serine proteases play a role in a variety of disease states and thus are attractive targets for therapeutic intervention. We report the kinetic characterization of a class of serine protease inhibitors whose potencies and selectivities are dramatically enhanced in the presence of Zn(II). The structural basis for Zn(II)-mediated inhibition of trypsin-like proteases has recently been reported [Katz, B. A., Clark, J. M., Finer-Moore, J. S., Jenkins, T. E., Johnson, C. R., Ross, M. J., Luong, C., Moore, W. R., and Stroud, R. M. (1998) Nature 391, 608-612]. A case study of the kinetic behavior of human tryptase inhibitors is provided to illustrate the general phenomenon of Zn(II)-mediated inhibition. Tryptase, Zn(II), and the inhibitor form a ternary complex which exhibits classic tight-binding inhibition. The half-life for release of inhibitor from the tryptase-Zn(II)-inhibitor complex has been measured for a number of inhibitors. Consistent with tight-binding behavior, potent tryptase inhibitors are characterized by extremely slow rates of dissociation from the ternary complex with half-lives on the order of hours. A model of human serum, designed to reproduce physiological levels of Zn(II), has been employed to evaluate the performance of Zn(II)-potentiated tryptase inhibitors under physiological conditions. We demonstrate that Zn(II)-mediated inhibition can be achieved at physiological Zn(II) levels.

Cations, Divalent↗

Lens cytoplasmic phase separation.

Cytoplasmic transparency is a unique feature of lens cells. The cytoplasm is a concentrated solution of crystallin proteins with minor constituents that include cytoskeletal proteins and lens specific intermediate filaments. Under normal physiological conditions, the proteins exist as a single transparent phase. With normal aging, progressive modification of the interactions between lens proteins occurs so that conditions within the lens become favorable for phase separation. These conditions produce intracellular inhomogeneities that approach or exceed the dimensions of the wavelength of visible light (400 to 700 nm) and light scattering from lens cells increases. The resulting opacification is the primary factor in the visual loss experienced in cataract, the leading cause of blindness in the world. We study biochemical factors that regulate the cytoplasmic phase separation and maintain normal cellular transparency.

Animals↗

Antiviral efficacy of lobucavir (BMS-180194), a cyclobutyl-guanosine nucleoside analogue, in the woodchuck (Marmota monax) model of chronic hepatitis B virus (HBV) infection.

Lobucavir (BMS-180194), a cyclobutyl-guanosine nucleoside analogue, effectively reduced WHV-viremia in chronically infected carrier woodchucks (Marmota monax) by daily per os treatment. WHV-viremia in the animals was measured by the serum content of hybridizable WHV-genomic DNA. Lobucavir, given at daily doses of 10 and 20 mg/kg body weight, reduced WHV-viremia by a 10- to 200-fold range during therapy. Lobucavir, given at 5 mg/kg, suppressed WHV-viremia by a 10- to 30-fold range, whereas a 0.5 mg/kg dose had no significant effect. WHV-viremia was also measured by hepadnaviral endogenous polymerase activity (EPA) in sera of animals treated for 6 weeks at 5 and 0.5 mg/kg. Changes in EPA in sera of lobucavir treated animals were comparable to changes in WHV DNA levels. Viremia in treated carriers recrudesced to pretreatment levels by 2 weeks of therapy cessation. These results indicated that the minimally effective antiviral daily per os dose of lobucavir in WHV-carrier woodchucks was approximately 5 mg/kg.

Animals↗

The incidence of smoking amongst nurses: a review of the literature.

Over the years there has been an ongoing debate about the implications of the smoking behaviour of nurses in relation to their own health and in the context of their professional role and responsibilities. However it is difficult to determine with any degree of accuracy the current incidence of smoking amongst nurses and most of the available research is based on small samples which embrace nurses of different levels and status. Very few recent studies in the United Kingdom or elsewhere have focused on this issue. A confused picture therefore emerges. This paper presents a critical overview of the literature and where appropriate provides data about the incidence of smoking in comparable groups of the general population.

Adolescent↗

The acute structural changes of loaded articular cartilage following meniscectomy or ACL-transection.

OBJECTIVE: Meniscectomy and anterior cruciate ligament (ACL) rupture have been identified as precursors of osteoarthrosis (OA) in clinical reviews and animal experiments. In this study, the acute effects of these injuries on articular cartilage matrix deformation, preserved in a loaded state using a cryopreservation technique, were studied by scanning electron microscopy (SEM). METHOD: Whole knee joints from adult White New Zealand rabbits (N=87) were loaded ex vivo, using a simulated quadriceps pull under static and cyclic loading conditions, following medial meniscectomy or transection of the ACL. Specimens were plunge-frozen while under load, or following a recovery period, and prepared for SEM by cryofixation. Using SEM and photographic images, the medial tibial plateau cartilage was assessed both qualitatively and quantitatively. RESULTS: After meniscectomy, significantly increased bending and crimping of radial collagen fibers occurred with static loading. Compared to intact knees, the area of tibial cartilage showing an indentation was increased by 80% (P< 0.05), the articular cartilage thickness was significantly more reduced when under load (for high force long duration static loading, intact joints had 53%+/-3 reduction in cartilage thickness compared to 39%+/-4 after meniscectomy, P< 0.05), and it took nearly twice as long for the cartilage thickness to recover following loading. These post-meniscectomy differences were either not present or were minimal when the joint was allowed to extend when loaded. ACL-transection slightly increased collagen deformation in the deeper zones, but only with cyclic loading. CONCLUSION: The findings indicate that, with static loading, significantly increased deformation of articular cartilage collagen structure can occur following meniscectomy, but is minimized by joint motion. This increased deformation may be relevant to the etiology and progression of joint degeneration.

Animals↗

An animal model for the study of genetic predisposition in the pathogenesis of middle ear inflammation.

OBJECTIVES: Chronic otitis media with effusion (COME) is the most prevalent inflammatory disease in children and is associated with numerous adverse long-term sequelae. Many factors have been associated with an increased risk of developing COME, one of which may be a genetic predisposition to the disease. To study the role that genetics play in the pathogenesis of COME, we used an animal model to compare the middle ear inflammatory responses in two different strains of rats (Lewis and Fisher). METHODS: In earlier studies, we demonstrated that exposure of the middle ear to endotoxin caused early extensive exudation and, later, goblet cell hyperplasia and mucin hypersecretion. In the present study, the animals were divided into six groups. In each group the animals were given transtympanic injection with gram-positive bacterial cell wall product (peptidoglycan-polysaccharide [PG-PS]). The middle ear bullae were studied at 1 week and 3 weeks after infection, and after systemic reinfection. Comparisons were made of the quantity of mucin exudate by enzyme-linked immunosorbent assay and by histological evaluation of the middle ear epithelial thickness. RESULTS: Our data demonstrate a statistically significant difference in middle ear inflammation and effusion formation between the two genetically different strains of rats. CONCLUSIONS: These data support the hypothesis that the middle ear response to PG-PS may be genetically determined and therefore suggest that genetic predisposition may play a role in the pathogenesis of COME.

Acute Disease↗

Effect of mechanical load on articular cartilage collagen structure: a scanning electron-microscopic study.

Little is known about the morphological effect of a mechanical load upon articular cartilage. The objective of this study was to describe and quantify the deformation of the articular cartilage collagen structure of the tibial plateau under static loading. Whole intact rabbit knee joints were loaded in vitro by simulating a quadriceps force of 3x, 1x or 0.5x body weight (high, medium, low) over durations of 30 or 5 min (long, short). Specimens were cryopreserved while under load and prepared for morphological evaluation by field emission scanning electron microscopy. Under high force and long duration loading the collagen fibers exhibited high deformation with an increased thickness of the layer of collagen fibers oriented almost parallel to the surface and a cartilage thickness reduced to 54%. Collagen fiber deformation occurred mostly in the transitional and upper radial zone. The area of tibial indentation and the cartilage thickness reduction increased with magnitude and duration of load. The collagen matrix did show a bulging edge at the border of the meniscus and exhibited remarkable deformation under the meniscus.

Animals↗

Measurement and psychotherapy. Evidence-based practice and practice-based evidence.

BACKGROUND: Measurement is the foundation of evidence-based practice. Advances in measurement procedures should extend to psychotherapy practice. AIMS: To review the developments in measurement relevant to psychotherapy. METHOD: Domains reviewed are: (a) interventions; (b) case formulation; (c) treatment integrity; (d) performance (including adherence, competence and skillfulness); (e) treatment definitions; (f) therapeutic alliance; and (g) routine outcome measurement. RESULTS: Modern methods of measurement can support 'evidence-based practice' for psychological treatments. They also support 'practice-based evidence', a complementary paradigm to improve clinical effectiveness in routine practice via the infrastructure of Practice Research Networks (PRNs). CONCLUSIONS: Advances in measurement derived from psychotherapy research support a model of professional self-management (practice-based evidence) which is widely applicable in psychiatry and medicine.

Clinical Competence↗

Toxicity and residual effectiveness of insecticides on insecticide-treated spheres for controlling females of Rhagoletis pomonella (Diptera: Tephritidae).

This study evaluated the toxicity of five technical-grade insecticides of four different classes to apple maggot females, Rhagoletis pomonella (Walsh), following a 10-min exposure period in insecticide-coated glass jars, with or without a feeding stimulant (sucrose) present. According to LC90 values for toxicity by ingestion and tarsal contact, imidacloprid was 1.5 times more toxic than dimethoate or abamectin, diazinon was less toxic, and phloxine B (a phototoxic dye) least toxic. Based on LC90 values for tarsal contact alone, dimethoate was 2.3, 4.0, and 18.4 times more toxic than imidacloprid, abamectin, and diazinon, respectively. Contact alone with phloxine B caused no mortality. When exposure was assessed using spheres coated with a latex paint mixture containing sucrose and formulated dimethoate (Digon 400 EC) or imidacloprid (Provado 1.6 F) at concentrations ranging from 5 to 70 g (AI)/cm2, both insecticides showed reduced effectiveness compared with toxicities from glass jar tests, with Digon two times more toxic than Provado. After exposure to artificial rainfall and retreatment with sucrose, Digon- and Provado-treated spheres exhibited greatest residual effectiveness, with diazinon-treated spheres less effective. Spheres treated with formulated abamectin (Agri-Mek 0.15 EC) at 1.0% (AI) performed only slightly better than phloxine B-treated spheres, which completely lost effectiveness after exposure to rainfall. Spheres treated with formulated imidacloprid (Merit 75 WP) at 1.5% (AI) showed equal or better residual efficacy in killing apple maggot flies (> 80% mortality, shorter lethal duration of feeding) over a 12-wk exposure period to outdoor weather than spheres treated with Digon at 1.0% (AI) after both types were retreated with sucrose. Our results indicate that imidacloprid is a promising safe substitute for dimethoate as a fly killing agent on lure-kill spheres. Imidacloprid formulated as Merit 75 WP had greater residual efficacy than imidacloprid formulated as Provado 1.6 F.

Animals↗