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Biomedical subjects

John Rogers

Publications and source records attributed to John Rogers.

At least 19 recordsLinked to original sources
PubMed2006

Autism spectrum disorder and psychopathy: shared cognitive underpinnings or double hit?

BACKGROUND: We measured psychopathic traits in boys with autism spectrum disorder (ASD) selected for difficult and aggressive behaviour. We asked (i) whether psychopathic tendencies can be measured in ASD independent of the severity of autistic behaviour; (ii) whether individuals with ASD with callous-unemotional (CU) traits differ in their cognitive profile from those without such traits; and (iii) how the cognitive data from this study compare with previous data of youngsters with psychopathic tendencies. METHOD: Twenty-eight ASD boys were rated on psychopathic tendencies, autistic traits and a range of cognitive measures assessing mentalizing ability, executive functions, emotion recognition and ability to make moral-conventional distinction. RESULTS: Our results indicate that psychopathic tendencies are not related to severity of ASD. In addition, such tendencies do not seem to be related to core autistic cognitive deficits, specifically in 'mind-reading' or executive function. Boys with co-occurring ASD and CU tendencies share some behaviours and aspects of cognitive profile with boys who have psychopathic tendencies alone. CONCLUSIONS: Callous/psychopathic acts in a small number of individuals with ASD probably reflect a 'double hit' involving an additional impairment of empathic response to distress cues, which is not part and parcel of ASD itself.

Antisocial Personality Disorder↗
PubMed2006

5-Alkylated thiazolidinones as follicle-stimulating hormone (FSH) receptor agonists.

We prepared analogs of potent thiazolidinone-based follicle-stimulating hormone (FSH) agonists 1, that is, 3 that contained an additional 5-alkyl substituent. This extra substituent was added to reduce synthetic problems that arose during preparation of analogs of 1. These compounds (3) were evaluated in a Chinese hamster ovary (CHO) cell line that expressed recombinant human FSH receptor (FSHR) and a luciferase reporter gene regulated by a cAMP response element (CRE). Selected compounds were also tested on a CHO-cell line that over expressed the FSHR for the ability to induce cAMP production. When the 5-alkyl substituent was a methyl group as in analog 16a, similar FSH activity (i.e., EC(50) = 51 nM, 100% efficacy relative to hFSH) to the analogous 5-hydrogen series compound (e.g., 2) was observed; thus, proving that a small 5-alkyl substituent was well tolerated. New derivatives of 3, in which the potentially hydrolytically labile secondary amide function of 1 (-CONH-) was modified to other moieties (e.g., -CH(2)NH-, -CH(2)S-, and -CH(2)OCONH-), were also prepared and evaluated. These congeners (namely 21, 22, and 24) also displayed good potency in the CRE-luciferase assay.

Alkylation↗
PubMed2005

Fast scanning transmissive delay line for optical coherence tomography.

A novel Fourier domain fast scanning optical delay line is proposed in which the walk-off is eliminated by only two passes through a diffraction grating. Working in transmission, the novel delay line is ideal for balanced optical coherence tomography configurations with recirculation of the reference beam. We evaluate theoretically and experimentally its walk-off and dispersion compensation capabilities.

Equipment Design↗
PubMed2005

Preparation of highly substituted gamma-lactam follicle stimulating hormone receptor agonists.

An unusual combination of Weinreb amidation and Mitsunobu lactam formation was used to prepare highly substituted gamma-lactam analogues of a thiazolidinone follicle stimulating hormone receptor agonist. The analogue synthesis was stereoselective and the final products were chemically stable. Biological properties of the target molecules were nearly identical to those of the lead compound.

Amides↗
PubMed2005

Effective depletion of albumin using a new peptide-based affinity medium.

Blood plasma and serum are very useful samples for the detection, identification and quantitation of proteins associated with both health and disease. However, analysis of plasma and serum is a challenge because traces of interesting polypeptides and proteins can be dominated by the very high concentration of albumin present. Albumin may be depleted by adsorption to immunoaffinity columns or to columns containing dyes such as Cibacron Blue, or by ultrafiltration, but these methods are far from ideal. We describe a new peptide-based affinity medium which is effective for removing albumin and is very specific. The albumin-binding capacity is at least 14 mg per mL of gel. The material may be reused hundreds of times after a simple regeneration step involving NaOH, with full retention of specificity and capacity. The material was tested with human and monkey plasma and serum and rat serum, and has been used to deplete litre volumes of human plasma. The development of other peptide-based affinity media to deplete abundant proteins is briefly discussed.

Albumins↗
PubMed2005

High-risk families: the unequal distribution of infant mortality in nineteenth-century Sweden.

An analysis of infant mortality (based on 133,448 births) in two regions, Sundsvall and Skellefteå, in north-eastern Sweden during the nineteenth century shows that infant mortality was highly clustered with a relatively small number of families accounting for a large proportion of all infant deaths. Using logistic regression, two important factors were found to be associated with high-risk families: (i) a biological component evidenced by an over-representation of women who had experienced stillbirths, and (ii) a social component indicated by an increased risk among women who had remarried. The results strengthen the argument for using the family rather than the single child as the unit of analysis. The clustering of infant deaths points to the need to re-evaluate our interpretations of the causes of infant mortality in the past.

Female↗
PubMed2005

Aspiring to leadership--identifying teacher-leaders.

Educational institutions need effective leaders at many levels. This paper explores the applicability of the Porter/Mazlow need-priority and Herzberg maintenance-motivation models to the challenge of identifying individuals who aspire to leadership. The review includes literature from teaching, engineering, medicine, astronomy, business, and the military. Autonomy need and achievement motivation consistently distinguished leaders from non-leaders in several studies. Affiliation and esteem needs also characterized leaders in two studies. These empirical data support the use of these theoretical models, which are intuitively appealing and have potential for practical applications. One such application could be the identification and recruitment of education "champions" who would be teacher-leaders at dispersed sites. Through self-reflection faculty members could become aware of their needs and motivations and may realize their leadership aspirations and accept the teacher-leader role. For an education "champions" program to be successful, the department leadership would need to attend to the organizational culture and provide release time for the teacher-leaders. A blueprint for the development of teacher-leaders is outlined.

Faculty, Medical↗
PubMed2005

Competency-based assessment and cultural compression in medical education: lessons from educational anthropology.

OBJECTIVE: This paper explores the thesis that medical education is the cultural transmission to learners of specific values, which are increasingly expressed as graduation competencies. As testing is a powerful way to transmit cultural values to learners in a brief period of time, competency-based assessments can be an instrument of cultural compression in medical education. METHODS: The author reviewed medical literature to illustrate the concepts from educational anthropology, led the process one medical school used to develop its list of graduation competencies, and conducted a citation search about competency domains. RESULTS: There is support in the literature for viewing medical education as an example of cultural transmission and compression and for the assertion that testing influences student behaviour. The graduation competency statements developed by the school reflect traditional and emergent values. The citation search data confirmed that some competency domains reflected traditional values, while others reflected more emergent values. CONCLUSION: Concepts from educational anthropology are relevant to medical education and provide perspectives for understanding contemporary issues such as competency-based assessments.

Anthropology, Cultural↗
PubMed2004

CHK2 kinase expression is down-regulated due to promoter methylation in non-small cell lung cancer.

BACKGROUND: CHK2 kinase is a tumor suppressor that plays important role in DNA damage signaling, cell cycle regulation and DNA damage induced apoptosis. CHK2 kinase expression was known to be ubiquitous in mammalian cells. CHK2-/- cells were remarkably resistant to DNA damage induced apoptosis, mimicking the clinical behavior of non-small cell lung cancer to conventional chemo and radiation therapy. RESULT: We reported that the CHK2 expression is diminished or absent in both non-small cell lung cancer (NSCLC) cell lines and clinical lung cancer tumor specimens. The absent CHK2 expression in NSCLC was due to hypermethylation of the CHK2 gene promoter, preventing from binding of a transcriptional factor, leading to silence of the CHK2 gene transcription. CONCLUSION: Since the CHK2 null mice showed a remarkable radioresistance, which bear significant similarity to clinical behavior of NSCLC, down-regulation of CHK2 kinase expression by CHK2 gene silencing and methylation in non-small cell lung cancer suggest a critical role of CHK2 kinase in DNA damage induced apoptosis and a novel mechanism of the resistance of NSCLC to DNA damage based therapy.

Carcinoma, Non-Small-Cell Lung↗
PubMed2004

Industrial-scale proteomics: from liters of plasma to chemically synthesized proteins.

Human blood plasma is a useful source of proteins associated with both health and disease. Analysis of human blood plasma is a challenge due to the large number of peptides and proteins present and the very wide range of concentrations. In order to identify as many proteins as possible for subsequent comparative studies, we developed an industrial-scale (2.5 liter) approach involving sample pooling for the analysis of smaller proteins (M(r) generally < ca. 40 000 and some fragments of very large proteins). Plasma from healthy males was depleted of abundant proteins (albumin and IgG), then smaller proteins and polypeptides were separated into 12 960 fractions by chromatographic techniques. Analysis of proteins and polypeptides was performed by mass spectrometry prior to and after enzymatic digestion. Thousands of peptide identifications were made, permitting the identification of 502 different proteins and polypeptides from a single pool, 405 of which are listed here. The numbers refer to chromatographically separable polypeptide entities present prior to digestion. Combining results from studies with other plasma pools we have identified over 700 different proteins and polypeptides in plasma. Relatively low abundance proteins such as leptin and ghrelin and peptides such as bradykinin, all invisible to two-dimensional gel technology, were clearly identified. Proteins of interest were synthesized by chemical methods for bioassays. We believe that this is the first time that the small proteins in human blood plasma have been separated and analyzed so extensively.

Amino Acid Sequence↗
PubMed2003

Changes to the galactose/mannose ratio in galactomannans during coffee bean ( Coffea arabica L.) development: implications for in vivo modification of galactomannan synthesis.

Endosperm was isolated from Arabica Caturra coffee beans 11, 15, 21, 26, 31 and 37 weeks after flowering, and the chemical composition and relative solubility of its component polysaccharides determined at each growth stage. Chemical analysis of the total mannan content of the cell wall material was done after solubilisation of galactomannans by alkaline extraction of the cell wall material followed by enzymatic digestion of the alkali-insoluble residue with a mixture of endo-mannanse and endo-glucanase. Eleven weeks after flowering, galactomannans accounted for approximately 10% of the polysaccharides but were highly substituted, with galactose/mannose ratios between 1:2 and 1:7. As the bean matured, galactomannan became the predominant polysaccharide, until 31 weeks after flowering it accounted for approximately 50% of the polysaccharides. However, it was less substituted, possessing galactose/mannose ratios between 1:7 and 1:40. Early in bean growth, up to 50% of the cell wall polysaccharides were extractable but as the galactomannan content of the bean increased there was a reduction in the extractability of all polysaccharides. The decrease in the galactose/mannose ratio of the galactomannans commenced between 21 and 26 weeks after flowering and was in synchrony with a rise in the concentration of free galactose in the beans. The results indicated that the degree of substitution of the galactomannans in coffee beans is developmentally regulated and may result, in part, from the modification of a primary synthetic product by the action of an alpha-galactosidase.

Cell Wall↗
PubMed2003

Task-oriented processes in care (TOPIC): a proven model for teaching ambulatory care.

BACKGROUND AND OBJECTIVES: The TOPIC model conceptualizes the work of family physicians as five prototypical visits (new problem, checkup, chronic illness, psychosocial problem, and behavioral change) and four major processes (physician information processing, patient-physician relationship development, integration of information and relationship, and lifelong learning). This paper describes methods for teaching this model to clerkship students and reports 4 years of outcome data. METHODS: The instruction included seminars at the beginning of the rotation, a laminated pocket card as a reminder in clinical sites, a clerkship "passport" with examples of TOPIC verbal presentations, and student self-study for the end-of-rotation Clinical Performance Examination (CPX). Evaluation outcomes include student perceptions of the seminars and student performance on the CPX. RESULTS: Students rated the usefulness of the seminars favorably. The CPX scores showed that students performed most of the tasks expected for each prototypical visit. CONCLUSIONS: Students learned the tasks presented in the seminars and demonstrated them during the CPX. The model is robust since students learned the material despite some changes in teaching methods.

Ambulatory Care↗
PubMed2003

Loading of the acetabulum by polyethylene and all-ceramic inserts in metal-backed acetabular cups.

Both static and dynamic loads were applied to metal-backed acetabular cups with ceramic or polyethylene inserts and the resulting load transmissions at a simulated bone interface were determined. Perfect fit and under-sized and over-sized cavities were prepared in simulated bone substrates, lined with Fuji pressure sensitive film, and acetabular cups inserted with physiological loads. The magnitude and location of contact forces between the cup and bone were measured. These cups were then subjected to a controlled impact load and the intensity and frequency of the loads transmitted to the substrate were determined. The results suggest that a polyethylene backing for ceramics is not necessary as there were no major differences in the static and dynamic stresses transmitted to the cup-bone interface with all polyethylene or ceramic inserts.

Acetabulum↗
PubMed2002

Laparoscopic adjustable gastric banding for the treatment of morbid obesity.

BACKGROUND: This prospective study evaluated the effectiveness and safety of laparoscopic adjustable gastric banding (LAGB) for morbid obesity. METHODS: Ninety-five consecutive patients (89 female; median age 38 years, range 19 to 69) underwent LAGB for morbid obesity. Median weight and body mass index were 123.2 (88.9 to 228.6) kg and 45 (32.7-76.4) kg/m(2) respectively. Significant coexistent disease was present in 52 (55%) patients. RESULTS: Median excess weight loss was 53% (range 96.9% to 12.1%) and 62% (range 107.5% to 32.3%) at 1 and 2 years respectively (P <0.001). Median operative time was 90 (range 35 to 285) minutes and inpatient stay 2 (range 1 to 10) days. Early complications were seen in 17 (18%) patients most commonly nausea/vomiting or dysphagia. Late complications were seen in 25 (26.3%) patients, most frequently vomiting or reflux due to band slippage or pouch dilatation. There was 1 (1%) operative death. CONCLUSIONS: LAGB is an effective operation for morbid obesity that results in equivalent weight loss to open surgical procedures.

Adult↗
PubMed2002

Multivesicular bodies: a mechanism to package lytic and storage functions in one organelle?

Multivesicular bodies (MVBs) are endosomes or prevacuolar compartments. The lumens of their internal vesicles are thought to be topologically equivalent to cytoplasm and their membranes direct proteins and lipids for degradation. Here, we describe a new MVB function; in certain plant MVBs, the internal vesicles contain lytic enzymes and the surrounding 'soup' is a storage compartment. Separate vesicular pathways deliver proteins to the storage and lytic compartments. Recent data indicate that mammalian secretory lysosomes also have two compartments served by separate vesicular pathways. The formation of separate storage and lytic compartments within MVBs poses problems for membrane organization and topology that have not previously been considered in the literature. We offer a hypothetical model to address these problems.

Animals↗
PubMed2002

Synthesis of (bis)sulfonic acid, (bis)benzamides as follicle-stimulating hormone (FSH) antagonists.

Screening efforts identified (bis)sulfonic acid, (bis)benzamides (1-3) as compounds that interact with the follicle stimulating-hormone receptor (FSHR) and inhibit FSH-stimulated cAMP accumulation with IC(50) values in the low micromolar range. Structure-activity relationship studies using novel analogues of 1-3 revealed that two phenylsulfonic acid moieties were necessary for activity and that the carbon-carbon double bond of the stilbene sub-series was the optimum spacer connecting these groups. Selected analogues (2, 14, and 50) were also able to block FSHR-dependent estradiol production in rat primary ovarian granulosa cells and progesterone secretion in a clonal mouse adrenal Y1 cell line. IC(50) values for these compounds in these assays were in the low micromolar range. Optimization of the benzoic acid side chains of 1-3 led to gains in selectivity versus activity at the thyroid stimulating hormone (TSH) receptor (TSHR). For instance, while stilbene (bis)sulfonic acid congener 2 was only 10-fold selective for FSHR over TSHR, analogue 50 with an IC(50) value of 0.9 microM in the FSHR-cAMP assay was essentially inactive at 30 microM in the TSHR-cAMP assay.

Animals↗