John Snow (1813-1858) and Benjamin Ward Richardson (1828-1896): a notable friendship.
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Anesthesia↗
Biomedical subjects
S Roberts
Publications and source records attributed to S Roberts.
Plantar fascia release through a transverse plantar incision.
A transverse plantar incision for plantar fascial release was assessed for pain relief, numbness, and subsequent heel pad symptoms. Twenty-seven feet in 26 patients who underwent plantar fascia release were reviewed with a minimum follow-up of 2 years after surgery (average, 37.6 months). Comprehensive data were obtained on 25 feet (24 patients) (93% response rate). The plantar fascia origin was completely transected in all cases. This led to complete resolution of symptoms in 19 feet and residual minor symptoms in six feet. After 2 years, four patients had developed recurrent symptoms, two in the area of surgery and two on the dorsum of the foot, in association with a pes planus foot. Two patients had some continued persistence of heel pain after surgery, although significantly less pain than preoperatively.Thus, 76% of patients had complete relieve of there symptoms, 12% of patients had mild symptoms not affecting daily activities, and 12% of patients had moderate symptoms that limited some activities. No patient suffered heel pad symptoms or numbness after surgery. It is concluded that plantar fascia release through a transverse plantar incision is a successful procedure for long-term relief of symptoms which avoids unnecessary heel pad numbness and scar morbidity. The benefits of a transverse incision include greater intraoperative vision, to ensure adequate release and spur excision, and an incision parallel to the medial calcaneal branches of the tibial nerve.
Adult↗
The interaction of TSH receptor autoantibodies with 125I-labelled TSH receptor.
Detergent-solubilized porcine TSH receptor (TSHR) has been labeled with 125I using a monoclonal antibody to the C-terminal domain of the receptor. The ability of sera containing TSHR autoantibody to immunoprecipitate the labeled receptor was then investigated. Sera negative for TSHR autoantibody (as judged by assays based on inhibition of labeled TSH binding to detergent-solubilized porcine TSHR) immunoprecipitated about 4% of the labeled receptor, whereas sera with high levels of receptor autoantibody immunoprecipitated more than 25% of the labeled receptor. The ability to immunoprecipitate labeled TSHR correlated well with ability of the sera to inhibit labeled TSH binding to the receptor (r = 0.92; n = 63), and this is consistent with TSHR autoantibodies in these samples being directed principally to a region of the receptor closely related to the TSH binding site. Preincubation of labeled TSHR with unlabeled TSH before reaction with test sera inhibited the immunoprecipitation reaction, providing further evidence for a close relationship between the TSHR autoantibody binding site(s) and the TSH binding site. This was the case whether the sera had TSH agonist (i.e., thyroid stimulating) or TSH antagonist (i.e., blocking) activities, thus, providing no clear evidence for different regions of the TSHR being involved in forming the binding site(s) for TSHR autoantibodies with stimulating and with blocking activities. The ability of TSHR autoantibodies to stimulate cyclic AMP production in isolated porcine thyroid cells was compared with their ability to immunoprecipitate labeled porcine TSHR. A significant correlation was observed (r = 0.58; n = 50; P < 0.001) and the correlation was improved when stimulation of cyclic AMP production was compared with inhibition of labeled TSH binding to porcine TSHR (r = 0.76). Overall, our results indicate that TSHR autoantibodies bind principally to a region on the TSHR closely related to the TSH binding site, and this seems to be the case whether the autoantibodies act as TSH agonists or antagonists.
Animals↗
Analysis of carbohydrate residues on recombinant human thyrotropin receptor.
An investigation of the sugar groups on recombinant human TSH receptors (TSHR) expressed in CHO-K1 cells and solubilized with detergents is described. Western blotting studies with TSHR monoclonal antibodies showed that the receptor was present principally as two bands with approximate molecular masses of 120 and 100 kDa. Further blotting studies using lectins and/or involving treatment with different glycosidases indicated that the 100-kDa band contained about 16 kDa of high mannose-type sugars, and the 120-kDa band contained about 33 kDa of complex-type sugars. It was possible to separate the 120- and 100-kDa components of the TSHRs by lectin affinity chromatography. In particular, Galanthus nivalis lectin, which binds high mannose-type sugars, bound the 100-kDa band, but not the 120-kDa band, whereas Datura stramonium lectin, which binds complex-type sugars, bound the 120-kDa band, but not the 100-kDa band. 125I-Labeled TSH binding studies with the various lectin column fractions showed that TSH-binding activity was principally associated with the complex-type sugar containing the 120-kDa form of the receptor rather than the high mannose-containing 100-kDa form. During peptide chain glycosylation, high mannose-type sugar residues are attached first and then modified by the formation of complex type structures to form the mature glycoprotein. Our data suggest that in the case of the TSH receptor, this type of posttranslational processing has an important role in forming the TSH-binding site.
Animals↗
Repair of human articular cartilage after implantation of autologous chondrocytes.
Tissue engineering is an increasingly popular method of addressing pathological disorders of cartilage. Recent studies have demonstrated its clinical efficacy, but there is little information on the structural organisation and biochemical composition of the repair tissue and its relation to the adjacent normal tissue. We therefore analysed by polarised light microscopy and immunohistochemistry biopsies of repair tissue which had been taken 12 months after implantation of autologous chondrocytes in two patients with defects of articular cartilage. Our findings showed zonal heterogeneity throughout the repair tissue. The deeper zone resembled hyaline-like articular cartilage whereas the upper zone was more fibrocartilaginous. The results indicate that within 12 months autologous chondrocyte implantation successfully produces replacement cartilage tissue, a major part of which resembles normal hyaline cartilage.
Adolescent↗
Changes in collagen cross-linking in degenerative disc disease and scoliosis.
STUDY DESIGN: Biochemical study of the changes in the collagen cross-link profile of human intervertebral discs collected at surgery from patients with either low back pain associated with disc degeneration or scoliosis. OBJECTIVE: To determine whether changes occur in the collagen cross-link profile in the disc of patients with either low back pain associated with disc degeneration or scoliosis, which may well influence matrix integrity. Such changes in the cross-link profile of a tissue indicates increased matrix turnover and tissue remodeling and may have implications for the progression of these disorders. SUMMARY OF BACKGROUND DATA: The diseases of the intervertebral disc, degenerative disc disease and scoliosis, are both characterized by changes in the extracellular matrix components that will affect the mechanical function of the tissue. The stability of the collagenous components and hence the mechanical integrity of connective tissues such as the disc is dependent on the degree and type of cross-links between the collagen molecules. This article reports results on the distribution of the different cross-links in the disc and the changes that occur with age, degenerative disc disease, and scoliosis. METHODS: Thirty-three discs were obtained from patients with degenerative disc disease and 29 discs from patients with scoliosis. Samples were acid hydrolyzed and the collagen cross-links analyzed by either fractionation on an amino acid analyzer configured for cross-link analysis using ninhydrin postcolumn detection or fractionation by high-pressure liquid chromatography with fluorescence detection. RESULTS: The reducible cross-links and the mature cross-link all increased from the outer anulus fibrosus through into the nucleus pulposus. The highest levels of the mature cross-link were found in the cartilage end-plate. The nonenzymic derived cross-link, pentosidine, in contrast, showed little difference across the disc, but did show the expected age-related increase. In degenerative disc disease, no change in the levels of the reducible or mature cross-links was found, but a decrease was observed in the levels of the age-related cross-link pentosidine in the more severe disease samples. In scoliosis, significantly higher levels of the reducible cross-links were found on the convex than on the concave side of the scoliotic disc. CONCLUSIONS: These changes in the cross-link profile of the intervertebral disc in degenerative disc disease and scoliosis are indicative of increased matrix turnover and tissue remodeling and likely to have implications for the progression of these disorders.
Adolescent↗
Specific cleavage of gamma catenin by caspases during apoptosis.
Caspase-mediated proteolysis of cytoskeletal proteins during apoptosis appears to be commonplace. Enlarging on previous studies we have shown here that gamma catenin, like beta catenin, was degraded during cisplatin-induced apoptosis, initially giving a major product of 75 kDa. This truncated protein could be co-immunoprecipitated with alpha catenin. Addition of caspase inhibitors to cells in the presence of cisplatin appreciably reduced the proteolysis of gamma catenin as well as the level of apoptosis. Only limited degradation of alpha catenin was observed even at very late times when over 90% of cells in the culture were apoptotic. Immunohistochemical staining showed that during apoptosis there was a relocation of alpha, beta, and gamma catenin from the periphery of the cell to the cytoplasm, at the same time as other morphological changes commonly associated with apoptosis occurred. Interestingly, the changes in localisation of the catenins preceded proteolysis by several hours. In the presence of cisplatin and caspase inhibitor no change in distribution of catenins was observed, suggesting that re-localisation requires caspase activity but not necessarily directed against beta and gamma catenins.
Adenovirus E1A Proteins↗
Newly described form of X-linked arthrogryposis maps to the long arm of the human X chromosome.
Arthrogryposis is a heterogeneous birth defect characterized by limitation of movement at multiple joints. One in 3,000 infants is born with arthrogryposis, and at least a third of these cases have a genetic cause. Four distinct types of X-linked arthrogryposis have been reported, and a severe lethal form recently was mapped to Xpll.3-qll.2. We now report an extended family affected with a novel variant of X-linked arthrogryposis that involves only the lower limbs. Linkage analysis with polymorphic DNA markers maps the disease locus in this unique family to the long arm of the human X chromosome between DXS1220 and DXS1205 in Xq23-27.
Alleles↗
The New York High-Risk Project: social and general intelligence in children at risk for schizophrenia.
UNLABELLED: Social deficits, as well as low performance on intelligence tests, are known early symptoms of schizophrenia. We studied whether impairment of social intelligence can be detected before the outbreak of the disorder. In the New York High-Risk Project, children at risk for schizophrenia (HRSz) or affective disorder (HRAff) and a normal control group (NC) were studied over the past 26 years. The children are now in mid-adulthood, with known psychiatric outcomes. Developmental and clinical data from childhood can now be related to adulthood diagnoses. We compared mean WISC (or WISC-R) and WAIS (or WAIS-R) scores from childhood and adolescence, and change of IQ, between the risk groups, as well as between the adulthood outcomes. We were specifically interested in the development of social intelligence (the Picture Arrangement and Comprehension subtests). We used logistic regression analyses to generate a model predicting adulthood schizophrenia. RESULTS: IQ at age 9,7 was lower in children with HRSz than with HRAff. Adulthood schizophrenia, compared with major depressive disorder and no psychiatric diagnosis could not be related conclusively to low IQ. This may be a result of the study design, since children with IQ below 70 or behavioral problems were not eligible as study subjects. There was no evidence of lower scores or more decline in social intelligence related to age or group membership (risk or outcome). Subtest-Scatter, a nondirectional measure of the differences between all subtests and Vocabulary, reflecting a lesser difference between crystallized and fluid intelligence, was identified as a significant predictor of adulthood schizophrenia, in the whole group as well as in the HRSz group alone.
Adolescent↗
Identification of conserved hydrophobic C-terminal residues of the human papillomavirus type 1 E1E4 protein necessary for E4 oligomerisation in vivo.
Previous studies have shown that human papillomavirus (HPV) E4 proteins undergo oligomerisation, although the precise sequences involved have not been identified. Using the yeast two-hybrid system we have identified HPV 1 E4 sequences that are critical to multimerisation. Fusion proteins were created by linking wild-type and mutant E4 proteins to a LexA DNA-binding domain or a B42 transactivation domain. HPV 1 E4:E4 interactions were examined by expression of these fusion proteins in Saccharomyces cerevisiae. This assay showed that (1) amino acid residues 95 to 115 at the carboxy-terminus were critical for oligomerisation and (2) hydrophobic residues (isoleucine 107, phenylalanine 114) in this domain are major determinants in the formation of oligomers. Interestingly, the carboxy-terminal domain shares homology with other E4 proteins of cutaneous HPV types and, furthermore, positions 107 and 114 are conserved residues. Substitution of the conserved aspartate amino acids (residues 110 and 112) did not abrogate E4 oligomerisation. Chemical cross-linking of wart and recombinant (baculovirus-expressed) HPV 1 E4 protein indicated that in solution this viral protein forms complexes consistent in size with either trimers or tetramers. These complexes were resistant to urea denaturation and are not dependent on the formation of disulphide linkages. A mutant protein containing a deletion of residues 110 to 115 was unable to form oligomers following cross-linking supporting a role for this region in mediating E4:E4 interactions. We conclude that oligomerisation of the HPV 1 E4 protein is likely to be mediated by carboxy-terminal residues and that conserved hydrophobic residues of this domain play a major role in E4 oligomerisation.
Amino Acid Sequence↗
Expanding yeast knowledge online.
The completion of the Saccharomyces cerevisiae genome sequencing project and the continued development of improved technology for large-scale genome analysis have led to tremendous growth in the amount of new yeast genetics and molecular biology data. Efficient organization, presentation, and dissemination of this information are essential if researchers are to exploit this knowledge. In addition, the development of tools that provide efficient analysis of this information and link it with pertinent information from other systems is becoming increasingly important at a time when the complete genome sequences of other organisms are becoming available. The aim of this review is to familiarize biologists with the type of data resources currently available on the World Wide Web (WWW).
Amino Acid Sequence↗
Type X collagen in the human invertebral disc: an indication of repair or remodelling?
The short-chained type X collagen was once thought to be produced exclusively by hypertrophic chondrocytes during endochondral ossification. More recently, however, it has been found elsewhere, for example in articular cartilage. In the present study, the occurrence of type X collagen in the intervertebral disc has been investigated. Human disc tissues of varying pathologies were examined for the presence of type X collagen and expression of alpha1(X) mRNA by immunohistochemistry and in situ hybridization respectively. All samples of disc contained areas that were immunoreactive but to varying extents. In the disc itself, staining for the protein and alpha1(X) mRNA was seen frequently associated with cells of the nucleus pulposus, which were large and of hypertrophic appearance, most commonly found in degenerate discs, and also in areas of disorganized architecture, such as clefts. In addition, type X collagen, both protein and mRNA, was found in regions of the cartilage end-plate, which calcify ectopically in scoliotic patients. We suggest that type X collagen production may be a response of disc tissue cells to a stimulus, such as altered loading.
Adolescent↗
Retinopathy of prematurity in infants <29 weeks' gestation at birth in New South Wales from 1986-92.
OBJECTIVE: To study the effect of increased survival of infants <29 weeks' gestation on the incidence and severity of retinopathy of prematurity (ROP). METHODOLOGY: Review of prospective records from 1986 to 1992 kept in the New South Wales (NSW) NICUS database on infants admitted to the neonatal intensive care units (NICU) in NSW. The survival rate and the incidence and severity of ROP on all infants <29 weeks' gestation admitted to the NICUs in NSW from 1 July 1986 to 31 December 1987 were compared to a similar group of infants admitted from 1 January 1992 to 31 December 1992. RESULTS: There was a significant difference in the survival rate of infants admitted between the two periods (235 of 376, 62.5% survival vs 255 of 336, 75.9% survival, respectively, P<0.0001). The odds ratio for survival adjusted for gestational age in the second period was 1.76 [1.24, 2.48 (95% confidence interval), P<0.002]. There was a slight increase in ROP in the second period (79 of 172 examined, 45.9% ROP vs 133 of 238 examined, 55.8% ROP, respectively). There was a rise in the number of infants with Stage 3 ROP in the second time period (14 of 172 examined, 8.1% ROP vs 41 of 238 examined, 17.2% ROP, respectively). However, fewer infants had detached retinas or > or = Stage 4 ROP in the second group [7 of 172, (4.1 %) vs 3 of 238, (1.3%), respectively]. This may be a reflection of the increase in the use of cryo- or laser therapy for Stage 3 ROP with 'plus' disease [2 of 172 examined, (1.2%) vs 18 of 238 examined, (7.6%), respectively]. CONCLUSIONS: With the increase in survival of the very preterm infant in recent years, there has been an increase in severe ROP (> or = Stage 3) in NSW. Despite the increased survival of the highest at-risk group (24- to 26-week gestation infants), there have been fewer cases of retinal detachment. There was also a rise in the number of infants receiving cryo- or laser therapy intervention.
Gestational Age↗
Characterisation of cytoplasm-filled processes in cells of the intervertebral disc.
We examined cells from the nucleus pulposus and annulus fibrosus of adult bovine intervertebral discs, using confocal laser scanning microscopy on living unfixed tissue. These cells were visualised using chloromethyl fluorescein diacetate, a membrane-impermeant fluorescent dye. The organisation of cells from the outer annulus was also determined using confocal microscopy after fixation and staining the actin-filaments with FITC-phalloidin. We found that cellular processes were a dominant feature of cells from all regions of the disc including the cells of the nucleus pulposus and inner annulus. These processes were also visible in histological sections of disc examined both at the light and electron microscope level, even though cells from the nucleus and inner annulus appeared chondrocyte-like, being rounded and enclosed in a capsule. The function of these processes is at present unknown. We suggest that they may serve to sense mechanical strain.
Actins↗
Analysis of autoantibody epitopes on steroid 21-hydroxylase using a panel of monoclonal antibodies.
A panel of five mouse monoclonal antibodies (MAbs) to human recombinant steroid 21-hydroxylase (21-OH) were produced, characterized, and used to study the interaction of 21-OH autoantibodies (AAbs) with different epitopes on human 21-OH. AAbs in patients with isolated autoimmune Addison's disease, autoimmune polyglandular syndromes types I and II, and 21-OH antibody-positive patients without overt Addison's disease (25 patients in total) were studied. Four MAbs were IgG1 subclass, one was IgG2a, and all had kappa light chains. The affinities of four of the antibodies were in the range 2.0 x 10(8) M(-1) to 7.0 x 10(8) M(-1), and the affinity of the other was 2.3 x 10(7) M(-1) 21-OH MAbs did not cross-react with 17alpha-hydroxylase (17alpha-OH)) or P450 side chain cleavage enzyme. Studies using a series of 21-OH fragments allowed the identification of short stretches of amino acids (AA) that were involved in forming the MAb binding sites. AA 391-405, defined as epitope region (ER) 1, were found to be important for binding of M21-OH1 and M21-OH2, AA 406-411 (ER2) were important for M21-OH3 and M21-OH4 binding, and AA 335-339 (ER3) for M21-OH5 binding. In addition, MAb Fab or F(ab')2 fragments were used to study 21-OH AAb epitopes in competition experiments. These investigations demonstrated that 21-OH AAbs recognize similar epitopes to the MAbs, with ER2 and ER3 being part of two distinct major epitopes, and ER 1 being part of a minor epitope. Mixtures of M21-OH antibody Fab or F(ab')2 fragments caused almost complete inhibition (80%-95%) of AAb binding in 24 out of 25 sera, and in the case of the remaining serum, the effect was marked but incomplete (67% inhibition). There were no major differences between the binding characteristics of AAbs from patients with different forms of autoimmune adrenal disease. All five 21-OH MAbs reacted with human adrenal tissue in an immunofluorescence test, but only M21-OH1 and M21-OH2 reacted with bovine adrenal tissue in these experiments. None of the MAbs reacted with human ovarian tissue in an immunofluorescence test. Overall, these studies indicate that 21-OH AAbs bind to at least three different epitopes in the C-terminal part of 21-OH, and two of these epitopes appear to be human 21-OH specific.
Addison Disease↗
Response to Mudford, Hogg, and Roberts on continuous recording of behavior state.
A recently published article by Modford, Hogg, and Roberts (1997) raised concerns about the observation code used by Guess, Rues, and Roberts (1993) in a longitudinal research project to assess emerging behavior state patterns in infants and young children. Specifically, Mudford et al. found low within-state reliability scores when they used the code with 3 adults who had profound mental retardation. From these findings, Mudford et al. questioned whether the state code satisfies the natural science approach for measuring observable behavior and whether behavior state in only a hypothetical construct. In response, we have raised concerns about the thoroughness of the reliability data collected by Mudford et al. and the conclusions and interpretations they derived from these data.
Adult↗
Binding characteristics of antibodies to the TSH receptor.
We have used fragments of the TSH receptor (TSHR) expressed in E. coli as glutathione S-transferase fusion proteins to produce rabbit polyclonal antibodies and a panel (n=5) of monoclonal antibodies to the extracellular fragment of the TSHR. The binding characteristics of the antibodies to linear, conformational, glycosylated and unglycosylated forms of the receptor in different assay systems have been investigated. The reactivity of these antibodies with the TSHR was assessed by Western blotting with both native and recombinant human TSHR expressed in CHO cells, immunoprecipitation of 35S-labelled full-length TSHR produced in an in vitro transcription/ translation system, immunoprecipitation of 125I-TSH/TSHR complexes, inhibition of 125I-TSH binding to the TSHR and fluorescence activated cell sorter (FACS) analysis of binding to CHO-K1 cells expressing the TSHR on their cell surface. Fab fragments of monoclonal antibodies were isolated, labelled with 125I and used to determine the affinity constants of these antibodies with receptor, bound and free Fab being separated by polyethylene glycol (PEG) precipitation. Rabbit polyclonal and mouse monoclonal antibodies reacted with the TSHR in Western blotting and one monoclonal antibody (3C7) was able to inhibit 125I-TSH binding to native human TSHR (74% inhibition), recombinant human TSHR (84% inhibition) and porcine TSHR (65% inhibition). Affinity constant values for TSHR monoclonal antibody Fab fragments calculated using Scatchard analysis were about 10(7) M(-1). Four out of five monoclonal antibodies reacted in FACS analysis with TSHR expressed on the surface of CHO-K1 cells. The FACS unreactive monoclonal (3C7) bound well to detergent solubilised TSH receptors and this emphasised the importance of using a combination of FACS analysis and radioactively-labelled probes in analysis of the TSH receptor. The monoclonal antibodies produced in this study were found to be of relatively low affinity but proved useful for detection of the receptor by Western blotting and by FACS analysis.
Animals↗
Evaluating and improving the delivery of heart care: the University of Michigan experience.
With increasing pressure to curb escalating costs in medical care, there is particular emphasis on the delivery of cardiovascular services, which account for a substantial portion of the current healthcare dollar spent in the United States. A variety of tools were used to improve performance at the University of Michigan Health System, one of the oldest university-affiliated hospitals in the United States. The tools included initiatives to understand outcomes after coronary bypass operations and coronary angioplasty through use of proper risk-adjusted models. Critical pathways and guidelines were implemented to streamline care and improve quality in interventional cardiology, management of myocardial infarction, and preoperative assessment of patients undergoing vascular operations. Strategies to curb unnecessary costs included competitive bidding of vendors for expensive cardiac commodities, pharmacy cost reductions, and changes in nursing staff. Methods were instituted to improve guest services and partnerships with the community in disease prevention and health promotion.
Cardiology Service, Hospital↗