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Biomedical subjects

E J Robinson

Publications and source records attributed to E J Robinson.

At least 37 records · Page 2Linked to original sources

Identification of homologs for thioredoxin, peptidyl prolyl cis-trans isomerase, and glycerophosphodiester phosphodiesterase in outer membrane fractions from Treponema pallidum, the syphilis spirochete.

In this study, we characterized candidate rare outer membrane (OM) proteins with apparent molecular masses of 19, 27, 38, and 38.5 kDa, which had been identified previously in OM fractions from Treponema pallidum (J. D. Radolf et al., Infect. Immun. 63:4244-4252, 1995). Using N-terminal and internal amino acid sequences, a probe for the 19-kDa candidate was PCR amplified and used to screen a T. pallidum genomic library in Lambda Zap II. The corresponding gene (tlp) encoded a homolog for periplasmic thioredoxin-like proteins (Tlp), which reduce c-type cytochromes. A degenerate oligonucleotide derived from the N terminus of the 27-kDa protein was used to PCR amplify a duplex probe from a T. pallidum genomic library in pBluescript II SK+. With this probe, the corresponding gene (ppiB) was identified and found to code for a presumptive periplasmic cyclophilin B-type peptidyl prolyl cis-trans isomerase (PpiB). We postulate that PpiB assists the folding of proteins within the T. pallidum periplasmic space. The N terminus of the 38-kDa candidate was blocked to Edman degradation. However, internal sequence data revealed that it was basic membrane protein (Bmp), a previously characterized, signal peptidase I-processed protein. Triton X-114 phase partitioning revealed that despite its name, Bmp is hydrophilic and therefore likely to be periplasmic. The final candidate was also blocked to Edman degradation; as before, a duplex probe was PCR amplified with degenerate primers derived from internal sequences. The corresponding gene (glpQ) coded for a presumptively lipid-modified homolog of glycerophosphodiester phosphodiesterase (GlpQ). Based upon findings with other treponemal lipoproteins, the hydrophilic GlpQ polypeptide is thought to be anchored by N-terminal lipids to the periplasmic leaflet(s) of the cytoplasmic membrane and/or OM. The discovery of T. pallidum periplasmic proteins with potentially defined functions provides fresh insights into a poorly understood aspect of treponemal physiology. At the same time, however, these findings also raise important issues regarding the use of OM preparations for identifying rare OM proteins of T. pallidum.

Amino Acid Sequence↗

Measurement of polyethylene wear in acetabular components inserted with and without cement. A randomized trial.

We measured the three-dimensional wear of polyethylene after total hip arthroplasty with a titanium metal-backed Mallory-Head prosthesis that was inserted with cement in sixty-nine patients (sixty-nine hips) and with a press-fit titanium metal-backed Mallory-Head prosthesis that was inserted without cement in seventy patients (seventy hips). A modular titanium femoral head was used in all of the hips. The patients in the present study were part of a larger double-blind randomized trial comparing the result of total hip arthroplasty performed with cement with that of the same procedure performed without cement in 250 patients. The criterion for inclusion in the study of polyethylene wear was a minimum duration of follow-up of four years, which was met by 148 patients. As adequate radiographs for digitization were not available for nine patients, 139 patients were included in the present study. The age of the patient, the postoperative Harris hip score, the diameter of the femoral head, the thickness of the liner in the polar region of the acetabular component, and the duration of follow-up were similar for the two groups. The mean rate of volumetric wear of the polyethylene was significantly greater in the prostheses that had been inserted without cement than in those that had been inserted with cement (155.1 cubic millimeters per year compared with 98.5 cubic millimeters per year; p = 0.000008). Thirty-four (49 per cent) of the seventy hips in which the prosthesis had been inserted without cement had evidence of osteolysis on radiographs, compared with twelve (17 per cent) of the sixty-nine hips in the other group (p = 0.0002). Osteolysis was associated with an increased rate of polyethylene wear only in the hips in which the prosthesis had been inserted without cement.

Acetabulum↗

Contamination in reasoning about false belief: an instance of realist bias in adults but not children.

Children aged around 5 and 9 years and adults were presented with stories and videos about a protagonist who heard a message purporting to provide factual information. Observing subjects knew whether the message was true or false. In some cases, this message contradicted the listener's existing belief based on what he or she had seen previously. Subjects judged whether the listener would believe or disbelieve the message. Child subjects frequently judged that a contradicting message would be disbelieved, irrespective of whether they (the child subjects) knew it to be true or false. In contrast, adult subjects made judgements that were contaminated by their own privileged knowledge of the truth. For three different scenarios, adult subjects judged more frequently that the message would be believed if they (but not the listener protagonist) knew it to be true, than if they thought it was false.

Adolescent↗

Osteolysis in cemented versus cementless acetabular components.

A prospective, randomized, double-blind, clinical trial comparing cemented with cementless total hip arthroplasty was performed to compare the prevalence and pattern of acetabular osteolysis. Both groups were similar before surgery. Acetabular components were metal-backed, titanium implants. Twenty-eight-millimeter modular femoral heads with titanium femoral stems were used. At a minimum 2-year and mean 4-year follow-up period (range, 2-6 years), 224 patients had clinical and radiographic data available. There was no significant difference in the prevalence of acetabular osteolysis between cemented (5%) and cementless (9%) fixation. With or without cement, the use of a titanium femoral head led to osteolysis within a relatively short period after surgery in almost all of the cases, although this was not significant. The pattern of acetabular osteolysis was different. Progressive osteolysis occurred predominantly in acetabular zone 1 in the cemented group and zone 2 in the cementless group. Cementless fixation of acetabular components has been advocated in an attempt to minimize osteolysis that may occur in cemented total hip arthroplasty. This study found no difference in the prevalence of acetabular osteolysis between the two groups.

Acetabulum↗

Benign prostatic stromal cells are regulated by basic fibroblast growth factor and transforming growth factor-beta 1.

The current study was undertaken, using cultures of prostatic epithelial and stromal cells, to determine the functional interactions between androgens, basic fibroblast growth factor (FGF2) and transforming growth factor-beta 1 (TGF beta 1) and their importance in maintaining stromal homeostasis. Treatment of stromal cells with TGF beta 1 significantly increased intracellular FGF2 and FGF2 sequestered to the extracellular matrix. FGF2 was also detected in stromal conditioned medium (SCM), but at levels 70-fold less than found in cell lysates. TGF beta 1 (0.1 ng/ml) treatment caused an initial increase of 86% in secreted FGF2 levels, but high concentrations of TGF beta 1 (5 ng/ml) decreased FGF2 levels by 38%, relative to the untreated control. Further studies showed that epithelial conditioned medium (ECM), androgen-treated, stromal conditioned medium (ASCM), but not SCM were mitogenic for stromal cells. Both ECM and ASCM caused a threefold increase in DNA synthesis. FGF2 may be the mediator of these interactions, since the mitogenic effect of both ECM and ASCM was significantly reduced by the addition of anti-FGF2 neutralising antibody. We hypothesise that the lack of response of stromal cells to SCM is due to TGF beta 1 blocking the mitogenic effect of FGF2. Thus down-regulation of TGF beta 1 synthesis, by androgens, results in stromal proliferation by ASCM.

Cell Division↗

Young children's treating of utterances as unreliable sources of knowledge.

In two investigations (N = 62 and 59), three- and four-year-old children sometimes disbelieved what they were told about the unexpected contents of a deceptive box, even when they had seen the adult speaker look inside the box before s/he told them what s/he saw, and despite being able to recall the utterance: utterances were treated as unreliable sources of knowledge compared with seeing directly. Those who did believe the utterance were no better at recalling their prior belief about the box's contents (now treated as false), than those who saw inside the box. However using a narrative procedure, we replicated Zaitchik's (1991) result that children are more likely to acknowledge another's belief when they are told about reality, than when they see reality for themselves. We argue that these children were acknowledging alternative rather than false belief.

Child Language↗

Characterization of outer membranes isolated from Treponema pallidum, the syphilis spirochete.

Previous freeze-fracture electron microscopy (EM) studies have shown that the outer membrane (OM) of Treponema pallidum contains sparse transmembrane proteins. One strategy for molecular characterization of these rare OM proteins involves isolation of T. pallidum OMs. Here we describe a simple and extremely gentle method for OM isolation based upon isopycnic sucrose density gradient ultracentrifugation of treponemes following plasmolysis in 20% sucrose. Evidence that T. pallidum OMs were isolated included (i) the extremely low protein/lipid ratio of the putative OM fraction, (ii) a paucity of antigenic and/or biochemical markers for periplasmic, cytoplasmic membrane, and cytosolic compartments, and (iii) freeze-fracture EM demonstrating that the putative OMs contained intramembranous particles highly similar in size and density to those in native T. pallidum OMs. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis revealed that the OMs contained a relatively small number of treponemal proteins, including several which did not appear to correspond to previously characterized T. pallidum antigens. Interestingly, these candidate rare OM proteins reacted poorly with syphilitic sera as determined by both conventional immunoblotting and enhanced chemiluminescence. Compared with whole cells, T. pallidum OMs were deficient in cardiolipin, the major lipoidal antigen reactive with antibodies in syphilitic sera. Also noteworthy was that other lipoidal constituents of OMs, including the recently discovered glycolipids, did not react with human syphilitic sera. These latter observations suggest that the poor antigenicity of virulent T. pallidum is a function of both the lipid composition and the low protein content of its OM.

Antigens, Bacterial↗

Catastrophic osteolysis in total knee replacement. A report of 17 cases.

One hundred eighty-five total knee revisions were done by the 2 senior authors from 1988 to 1994. Of these, 17 patients were identified as having severe osteolysis. The average age was 62.7 years, and the average weight was 90.8 g. All patients had osteoarthritis. Preoperative aspiration was negative in all patients. Eight patients had a metal-backed patella, 8 had a cementless implant, 4 had a cemented implant, and 5 had a hybrid implant. The average time interval from the index surgery to radiographic evidence of lysis was 56 months. Radiographic review showed gross polyethylene wear in 10 patients, loose tibial implants in 8, fractured baseplates in 2, and evidence of a metallic synovitis in 2. Retrieved polyethylene liners had a average thickness of 7 mm, and none were conforming. Osteolytic defects were defined and classified according to Engh's criteria. The histology showed a foreign body reaction with intracellular refractile polyethylene particles. Four cases had metallic debris. The exposure at the time of revision required a rectus snip in 4, V-Y-quadricepsplasty in 2, and tibial tubercle osteotomy in 1. Posterior stabilized implants were used in 65% and a constrained implant in 30%. Lytic defects were reconstructed with cement only in 47% of knees, allograft in 30%, and metallic wedges in 35%. Based on this report, the authors conclude that younger, overweight patients seem to be at higher risk of implant failure and that osteolysis is not restricted to cementless implants. Furthermore, because review of the radiographs leads to a constant underestimation of the lytic defect, the surgeon must be prepared to deal with complex revisions.

Aged↗

Measurement of polyethylene wear in metal-backed acetabular cups. II. Clinical application.

The new 3-dimensional technique was applied to the radiographs of 141 patients who had received Porous Coated Anatomic total hip prostheses. Values were obtained for the position of the acetabular cup, the 3-dimensional distance and direction of femoral head displacement, and the minimum volume of polyethylene debris produced. Mean age of the patients at the time of replacement was 61 years old; mean followup was 5.6 years (range, 4-7.2 years). Change in the position of the femoral head between initial and long-term followup films was assumed to represent polyethylene wear, and formulas were used to calculate the minimal volume of polyethylene debris produced. The overall rate of 3-dimensional femoral head displacement was 0.264 mm per year, almost twice that usually quoted in the current literature for 2-dimensional linear wear. A significant contribution to this value was made by anterior and posterior displacement. Two-dimensional femoral head displacement (measured in the plane of anteroposterior radiographs) on the same patients was 0.149 mm per year. The mean minimum volume of polyethylene debris produced after 5.6 years was 0.448 cm3 (range, 0.00-2.83 cm3), giving a mean rate of 0.079 cm3 polyethylene debris produced each year. Thirteen patients in this series had radiologic osteolysis and a significantly greater femoral head displacement and polyethylene volumetric wear than those with no osteolysis. Patients with a 32-mm femoral head diameter and a polyethylene linear < 1 cm thick had a significantly greater amount of polyethylene wear. This series gives previously unavailable data on 3-dimensional femoral head displacement and is the first report that correlates the minimum volume of polyethylene wear produced with radiologic osteolysis.

Acetabulum↗

Intern candidates who withdraw from contracts: incidence and internal medicine program directors' attitudes.

OBJECTIVE: To study the prevalence of intern candidates accepted through the National Resident Matching Program (NRMP) or after the match who subsequently withdraw and the attitudes of program directors regarding this issue. DESIGN: Mailed survey. SETTING: Four hundred fifty-four internal medicine program directors. MEASUREMENTS: Questionnaires assessing program directors' attitudes toward interns who contract for positions after having verbal or written agreements elsewhere (and the program directors who accept them), the importance of this problem, and the incidence of this problem. MAIN RESULTS: Fifty-five programs (of the 221 responding) experienced intern withdrawals. Programs with larger numbers of open positions after the match had more intern withdrawals (p = 0.03). Eleven of the program directors knew of the prior commitment of the intern, and in all cases the other program director was called for permission to accept the intern. Program directors had negative feelings about both the interns who withdrew and the program directors who accepted them. Community, municipal, and Veterans Affairs hospital program directors were significantly less negative than those in university and university-affiliated hospitals toward interns who withdrew from written commitments (p = 0.001) and the program directors who accepted them (p < 0.05). CONCLUSION: Problems with intern candidate withdrawals from offered/matched programs affect a significant proportion of programs, especially those with larger numbers of unmatched positions. Program directors are generally disapproving.

Analysis of Variance↗

Children's understanding of the evidential connotation of 'know' in relation to overestimation of their own knowledge.

This study examined five- to seven-year-olds' assumptions about the experiential connotation of 'I know that's X'. In Experiment I children tried to identify which of a set of unfamiliar targets had a given name (X), and after they had chosen, we enquired either whether they knew their chosen item was (X) or whether they were sure. Six- to seven-year-olds (N = 39) judged that they were sure more often than they judged that they knew, which suggests that although they experienced confidence that they had chosen correctly, they assumed it would be inappropriate to judge 'know', because this would imply an experiential basis, which was absent. Five- to six-year-olds (N = 36) did not discriminate between the two kinds of question. In Experiment 2, children could infer which item was a named unfamiliar cartoon character by ruling out familiar distractors. Six- to seven-year-olds (N = 35) judged that they knew they had picked the right one much more often than they judged that they knew their chosen picture was (target name). Again, five- to six-year-olds (N = 44) did not discriminate between the two kinds of question. This demonstrates powerfully that the older children held an experiential connotation of 'I know that's X', since they avoided such judgments even when they knew by inference they had chosen correctly.

Child↗

Children's interpretation of messages from a speaker with a false belief.

In 5 investigations we examined a new procedure for assessing children's understanding that messages arise from speakers' internal representations. 3- and 4-year-olds watched the enactment of a message-desire discrepant story in which a speaker doll, who believed wrongly that bag A was in location 1 and that bag B was in location 2, gave a message referring to the bag in location 1. In a message-desire consistent control condition, the speaker had a correct belief about the bags' locations. Children frequently judged correctly in the discrepant story that the speaker (who specified location 1) wanted the bag in location 2, and judged correctly in the consistent story that the speaker wanted the bag in location 1. That is, young children attended to the speaker's internal representations, and not just the real-world referent of the message, when judging what the speaker wanted. In one of the investigations, children performed better on the message-desire discrepant task than on a false belief task. We discuss why they might find it particularly easy to take into account false belief when inferring desire on the basis of behavior.

Child, Preschool↗

Dietary iron overload in southern African rural blacks.

A survey conducted in rural southern African black subjects indicated that dietary iron overload remains a major health problem. A full blood count, erythrocyte sedimentation rate, serum concentrations of iron, total iron-binding capacity, ferritin, C-reactive protein (CRP), gamma-glutamyltransferase (GGT) and serological screening for hepatitis B and human immunodeficiency virus (HIV) infections were carried out in 370 subjects (214 inpatients and 156 ambulatory Mozambican refugees). The fact that the geometric mean (SD range) serum ferritin concentration was much higher in the male hospital patients than in subjects living in the community [1,581 micrograms/l (421-5,944 micrograms/l) and 448 micrograms/l (103-1,945 micrograms/l) respectively] suggested that dietary iron overload was not the only factor raising the serum ferritin concentration. The major additional factor appeared to be inflammation, since the geometric mean (SD range) serum CRP was significantly higher in male hospital patients [21 mg/l (8-53 mg/l)] than in subjects in the community [3 mg/l (1-5 mg)]. Alcohol ingestion, as judged by history and by serum GGT concentrations, was also associated with significantly raised serum ferritin concentrations. This finding was ascribed to the fact that traditional brews are not only associated with alcohol-induced hepatic damage but are also a very rich source of highly bio-available iron. The role of iron overload in the genesis of the raised serum ferritin concentrations are confirmed in the diagnostic liver biopsy study. The majority of biopsies showed heavy siderosis, with varying degrees of hepatic damage.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

When do children overestimate their knowledge of unfamiliar targets?

We report four investigations in which 5 to 7 year olds judged whether or not they knew familiar- and unfamiliar-named targets. Under some conditions judgments were made in relation to performance on a relevant task, e.g., children judged whether they knew the picture they had picked from a set was the target. Under other conditions, children judged their state of knowledge not in relation to performance, e.g., they answered "Do you know who (target) is?" Under both types of condition, children nearly always made correct "know" judgments when targets were familiar. Correct "don't know" judgments about unfamiliar targets were relatively common when judgments were not made in relation to performance on a task (average scores 80-90% correct), but were less frequent when knowledge was judged in relation to performance on a task (average scores 40-70% correct). Knowledge judged in relation to performance was overestimated even when children did not choose the picture they thought might be the target before making their judgment, when the pictures were face-down, and when children predicted performance on a task not yet present. It seems that although children can make relatively accurate judgments of their own knowledge states, they tend to overestimate their competence when assessing their knowledge in relation to performance on a task. We discuss why this might be.

Attention↗

How internal medicine residents resolve conflicts with attending physicians.

Forty-three of 49 residents in an internal medicine residency answered questionnaires in 1988 about resolving conflicts with attending physicians concerning patient care, using ten case scenarios. The residents indicated their likelihoods of using various methods of addressing the conflicts via Likert-type scales. The residents were most likely to negotiate with the attending physician and least likely to ignore the attending physician or withdraw from the case for all scenarios, though the type of procedure affected the decision. The residents planning careers in general medicine or nonmedical specialties were more likely to agree with the attending physician than were the residents planning medicine subspecialty careers (p less than .005); the graduates from osteopathic schools were more likely to withdraw from the case than were the residents from allopathic schools (p = .05). Conflicts between the residents and attending physicians were resolved by negotiation and interaction with the attending physicians, but the nature of the procedure, medical school attended, and future career plans affected the means of resolving the dilemma chosen by the individual resident.

Conflict, Psychological↗

Molecular cloning and characterization of the 15-kilodalton major immunogen of Treponema pallidum.

Pathogen-specific membrane immunogens of Treponema pallidum subsp. pallidum (T. pallidum) have been identified previously by phase partitioning with the nonionic detergent Triton X-114. One of these antigens, a 15-kilodalton (kDa) polypeptide, is expressed in relatively small quantities in T. pallidum but is highly immunogenic in both human and experimental syphilis. The native T. pallidum antigen was purified to homogeneity from the mixture of Triton X-114 detergent-phase proteins by chromatofocusing. Recombinant Escherichia coli clones were selected from a T. pallidum genomic DNA library by using monoclonal antibodies specific to the 15-kDa antigen; immunoblotting and minicell analyses confirmed expression of the 15-kDa protein in the transformants. Southern hybridization with a 1.1-kilobase fragment of DNA encoding the 15-kDa-antigen gene indicated that the gene is probably present in a single copy within the genomes of both T. pallidum and T. pallidum subsp. pertenue (the agent of yaws), while it is absent from the genome of the nonpathogenic Treponema phagedenis biotype Reiter. Cell fractionation studies with Triton X-114 demonstrated that the recombinant polypeptide possesses hydrophobic properties similar to those of the native antigen and localized the cloned 15-kDa antigen to the inner membrane of E. coli. Protein processing experiments in minicells revealed that a precursor appears to be processed to the mature 15-kDa polypeptide.

Antibodies, Monoclonal↗

A Bristol experience: benefits and cost of an 'asthma nurse' visiting the homes of asthmatic children.

The care of asthmatic children is commonly sub-optimal. Accordingly the costs and benefits of sending a district health authority community nurse, who had specific training in asthma management, into the homes of 43 families with asthmatic children were assessed. During the six months the asthma nurse visited these homes, the children developed and sustained, higher peak expiratory flow rates than 43 control asthmatics. The direct costs of the asthma nurse was 15 pounds/patient/six months.

Asthma↗