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Biomedical subjects

J C Robinson

Publications and source records attributed to J C Robinson.

At least 19 recordsLinked to original sources

Alarm treatment for childhood nocturnal enuresis: an investigation of within-treatment variables.

OBJECTIVE: The enuresis alarm has been widely advocated as an effective intervention in the treatment of childhood nocturnal enuresis. Although there is a body of evidence concerning which pretreatment variables are related to outcome, there is little evidence relating to influential within-treatment variables. This study sought to examine a series of treatment variables against outcome. MATERIAL AND METHODS: A total of 66 children with severe primary nocturnal enuresis but with no day-time wetting were treated with a body-worn enuresis alarm. Pre- and within-treatment variables were collected. Success was considered to be 14 consecutive dry nights during a 16-week period. RESULTS: A total of 54.5% of children achieved the success criterion, with 12.1% being classed as partial successes. Of the pretreatment variables, only low functional bladder capacity was significantly associated with failure. Inability to be woken by the alarm emerged as the most important within-treatment predictor of failure. CONCLUSIONS: The success of alarm treatment is dependent on the child's ability to be aroused by the alarm. Interestingly, of those who successfully became dry, 72.2% slept throughout the night for >80% of nights that they were dry, suggesting that the mode of action of the enuresis alarm is more complex than was previously thought.

Adolescent↗

Structure of the EMAPII domain of human aminoacyl-tRNA synthetase complex reveals evolutionary dimer mimicry.

The EMAPII (endothelial monocyte-activating polypeptide II) domain is a tRNA-binding domain associated with several aminoacyl-tRNA synthetases, which becomes an independent domain with inflammatory cytokine activity upon apoptotic cleavage from the p43 component of the multisynthetase complex. It comprises a domain that is highly homologous to bacterial tRNA-binding proteins (Trbp), followed by an extra domain without homology to known proteins. Trbps, which may represent ancient tRNA chaperones, form dimers and bind one tRNA per dimer. In contrast, EMAPII domains are monomers. Here we report the crystal structure at 1.14 Angstroms of human EMAPII. The structure reveals that the Trbp-like domain, which forms an oligonucleotide-binding (OB) fold, is related by degenerate 2-fold symmetry to the extra-domain. The pseudo-axis coincides with the dyad axis of bacterial TtCsaA, a Trbp whose structure was solved recently. The interdomain interface in EMAPII mimics the intersubunit interface in TtCsaA, and may thus generate a novel OB-fold-based tRNA-binding site. The low sequence homology between the extra domain of EMAPII and either its own OB fold or that of Trbps suggests that dimer mimicry originated from convergent evolution rather than gene duplication.

Amino Acid Sequence↗

Theory and practice in the design of physician payment incentives.

Combining the economic literature on principal-agent relationships with examples of marketplace innovations allows analysis of the evolution of methods for paying physicians. Agency theory and the economic principles of performance-based compensation are applied in the context of imperfect information, risk aversion, multiple interrelated tasks, and team production efficiencies. Fee-for-service and capitation are flawed methods of motivating physicians to achieve specific goals. Payment innovations that blend elements of fee-for-service, capitation, and case rates can preserve the advantages and attenuate the disadvantages of each. These innovations include capitation with fee-for-service carve-outs, department budgets with individual fee-for-service or "contact" capitation, and case rates for defined episodes of illness. The context within which payment incentives are embedded, includes such non-price mechanisms as screening and monitoring and such organizational relationships as employment and ownership. The analysis has implications for health services research and public policy with respect to physician payment incentives.

Capitation Fee↗

Organizational economics and health care markets.

As health policy emphasizes the use of private sector mechanisms to pursue public sector goals, health services research needs to develop stronger conceptual frameworks for the interpretation of empirical studies of health care markets and organizations. Organizational relationships should not be interpreted exclusively in terms of competition among providers of similar services but also in terms of relationships among providers of substitute and complementary services and in terms of upstream suppliers and downstream distributors. This article illustrates the potential applicability of transactions cost economics, agency theory, and organizational economics more broadly to horizontal and vertical markets in health care. Examples are derived from organizational integration between physicians and hospitals and organizational conversions from nonprofit to for-profit ownership.

Data Collection↗

Macromolecular assemblage of aminoacyl-tRNA synthetases: quantitative analysis of protein-protein interactions and mechanism of complex assembly.

The structure of the mammalian multi-synthetase complex was investigated in vitro using qualitative and quantitative approaches. This macromolecular assemblage comprises the bifunctional glutamyl-prolyl-tRNA synthetase, the seven monospecific isoleucyl, leucyl, methionyl, glutaminyl, lysyl, arginyl and aspartyl-tRNA synthetases, and the three auxiliary p43, p38 and p18 proteins. The scaffold p38 protein was expressed in Escherichia coli and purified to homogeneity as a His-tagged protein. The different components of the complex were shown to associate in vitro with p38 immobilized on Ni(2+)-coated plates. Interactions between peripheral enzymes and p38 are referred to as central interactions, as opposed to lateral interactions between peripheral enzymes. Kinetic parameters of the interactions were determined by the means of a biosensor-based approach. The two dimeric proteins LysRS and AspRS were found to tightly bind to p38, with a K(d) value of 0.3 and 4.7 nM, respectively. These interactions involved the catalytic core of the enzymes. By contrast, binding of ArgRS or GlnRS to p38 was much weaker (>5 microM). ArgRS and p43, two peripheral components, were shown to interact with moderate affinity (K(d)=93 nM). Since all the components of the complex are tightly associated within this particle, lateral interactions were believed to contribute to the stabilization of this assemblage. Using an in vitro binding assay, concomitant association of several components of the complex on immobilized p38 could be demonstrated, and revealed the involvement of synergistic effects for association of weakly interacting proteins. Taking into account the possible synergy between central and lateral contributions, a sub-complex containing p38, p43, ArgRS and GlnRS was reconstituted in vitro. These data provide compelling evidence for an ordered and concerted mechanism of complex assembly.

Amino Acyl-tRNA Synthetases↗

Accuracy of glaucoma detection with frequency-doubling perimetry.

PURPOSE: To determine the accuracy of glaucoma detection by frequency-doubling perimetry. METHODS: Stereoview optic nerve photographs, visual field examination, intraocular pressure measurements, medical and ocular history, and a screening and full threshold frequency-doubling perimetry examination were performed in a prospective study of consecutive subjects. Inclusion criteria included age of 45 years or older, absence of ocular disease other than glaucoma, cataract, or mild drusen, and Snellen visual acuity of 20/60 or better. A total of 125 eyes in 102 glaucoma subjects and 95 eyes of 95 normal subjects were included. Each eye was classified as "normal," "glaucoma," or "uncertain" by each of three ophthalmologists on the basis of all available clinical information with the exception of frequency-doubling perimetry results. Those in the glaucoma group were subclassified as having early (n = 51), moderate (n = 42), or severe (n = 32) glaucoma on the basis of automated Humphrey visual field criteria. In the glaucoma group, two eyes from a subject were allowed to be included (23 of 102 subjects) if they differed in level of damage because they were never analyzed within the same statistical analysis. RESULTS: Several diagnostic algorithms were evaluated. Algorithms based on the most depressed single point, pair of adjacent points, and cluster of three points performed nearly identically. For the screening test, if any abnormality was identified, specificity was 95%, whereas sensitivity was 39%, 86%, and 100% for early, moderate, and severe glaucoma, respectively. For the full threshold test, with at least one point depressed to the P < 0.5% level, specificity measured 91%, whereas sensitivity was 35%, 88%, and 100% for early, moderate, and severe glaucoma, respectively. The two global indices, mean deviation and pattern standard deviation, were also evaluated and were generally less accurate. CONCLUSION: Frequency-doubling perimetry, which is rapid and easily administered, is effective at detecting moderate and severe disease and appears well suited for glaucoma screening.

Aged↗

Blended payment methods in physician organizations under managed care.

CONTEXT: Independent practice associations (IPAs) are developing new methods of physician reimbursement to balance the objectives of encouraging individual productivity and clinical cooperation. The economic literature on payment incentives, derived from nonhealth industries, predicts that methods blending elements of fee-for-service and capitation will outperform exclusive reliance on either form of payment. OBJECTIVE: To identify emerging payment methods within IPA physician groups that contract with managed care organizations. DESIGN AND SETTING: Case studies of 7 large IPAs in the San Francisco, Calif, metropolitan region that served 826000 health maintenance organization (HMO) patients during the summer and fall of 1998. MAIN OUTCOME MEASURE: Payment methods of IPAs for primary care physicians, specialists, and physicians grouped by specialty department within the overall IPA structure. RESULTS: All the IPAs contracted with multiple HMOs for the full range of primary and specialty care physicians' services but paid member physicians using methods that blended elements of fee-for-service and subcapitation. For primary care, most IPAs used monthly capitation adjusted for patient age, sex, and selected diagnoses, supplemented with fee-for-service payment for a wide range of visits and procedures, including patient visits in subacute, skilled nursing facility, emergency department, or home settings; for preventive care services; for office procedures requiring expensive supplies; and, most importantly, for borderline primary care procedures that either could be performed directly or referred to specialty care. All the IPAs paid specialty departments on a capitated basis and delegated to the departments responsibility for allocating the budget among individuals. Allocation mechanisms for individual specialists included adjusted fee-for-service, referral-based capitation, and blends of both. CONCLUSION: Our results and case studies indicate that IPAs are developing payment methods that blend elements of fee-for-service and capitation in innovative ways for primary care and specialty physicians.

Budgets↗

Macromolecular assemblage of aminoacyl-tRNA synthetases: identification of protein-protein interactions and characterization of a core protein.

In eukaryotes, from fly to human, nine aminoacyl-tRNA synthetases contribute a multienzyme complex of defined and conserved structural organization. This ubiquitous multiprotein assemblage comprises a unique bifunctional aminoacyl-tRNA synthetase, glutamyl-prolyl-tRNA synthetase, as well as the monospecific isoleucyl, leucyl, glutaminyl, methionyl, lysyl, arginyl, and aspartyl-tRNA synthetases. Three auxiliary proteins of apparent molecular masses of 18, 38 and 43 kDa are invariably associated with the nine tRNA synthetase components of the complex. As part of an inquiry into the molecular and functional organization of this macromolecular assembly, we isolated the cDNA encoding the p38 non-synthetase component and determined its function. The 320 amino acid residue encoded protein has been shown to have no homolog in yeast, bacteria and archaea, according to the examination of the complete genomic sequences available. The p38 protein is a moderately hydrophobic protein, displays a putative leucine-zipper motif, and shares a sequence pattern with protein domains that are involved in protein-protein interactions. We used the yeast two-hybrid system to register protein connections between components of the complex. We performed an exhaustive search of interactive proteins, involving 10 of the 11 components of the complex. Twenty-one protein pairs have been unambiguously identified, leading to a global view of the topological arrangement of the subunits of the multisynthetase complex. In particular, p38 was found to associate with itself to form a dimer, but also with p43, with the class I tRNA synthetases ArgRS and GlnRS, with the class II synthetases AspRS and LysRS, and with the bifunctional GluProRS. We generated a series of deletion mutants to localize the regions of p38 mediating the identified interactions. Mapping the interactive domains in p38 showed the specific association of p38 with its different protein partners. These findings suggest that p38, for which no homologous protein has been identified to date in organisms devoid of multisynthetase complexes, plays a pivotal role for the assembly of the subunits of the eukaryotic tRNA synthetase complex.

Amino Acid Sequence↗

Accuracy of scanning laser polarimetry in the diagnosis of glaucoma.

OBJECTIVE: To determine the diagnostic accuracy of scanning laser polarimetry. SUBJECTS AND METHODS: A total of 95 healthy subjects and 102 patients with glaucoma met all inclusion criteria. Data collected on each participant included an automated visual field examination, stereoview optic nerve head photographs, intraocular pressure measurement, and a screening and full scanning laser polarimetry study. Each participant was classified as "normal," "glaucoma," or "uncertain" by each of 3 ophthalmologists based on all available clinical information, with the exception of the scanning laser polarimetry results. Before data analysis, 4 diagnostic algorithms for the full-test mode and 2 for the screening mode were chosen to be evaluated for their sensitivity and specificity in detecting glaucoma. RESULTS: Of the 4 algorithms tested for the full-test mode, "the number" (abnormal test score, >35) had sensitivities of 57%, 71%, and 81% for early, moderate, and severe glaucoma, respectively. Specificity was 89%. For the screening test, sensitivities were much lower, particularly for those with severe glaucoma damage. CONCLUSIONS AND CLINICAL RELEVANCE: Scanning laser polarimetry can help to differentiate subjects with normal findings from patients with glaucomatous damage. Even the best algorithm tested, however, failed to detect a substantial number of subjects with severe damage. Further study is needed before scanning laser polarimetry can be recommended as a screening method for glaucoma.

Aged↗

Dynamical localization of ultracold sodium atoms.

We report a study of atomic motion in time-dependent optical potentials. We measure momentum transfer in parameter regimes for which the classical dynamics are chaotic, and observe the quantum suppression of chaos by dynamical localization. The high degree of control over the experimental parameters enables detailed comparisons with theoretical predictions, and opens new avenues for investigating quantum chaos.

Journal Article↗

Consolidation of medical groups into physician practice management organizations.

CONTEXT: Medical groups are growing and merging to improve efficiency and bargaining leverage in the competitive managed care environment. An increasing number are affiliating with physician practice management (PPM) firms that offer capital financing, expertise in utilization management, and global capitation contracts with health insurance entities. These physician organizations provide an alternative to affiliation with a hospital system and to individual physician contracting with health plans. OBJECTIVE: To describe the growth, structure, and strategy of PPM organizations that coordinate medical groups in multiple markets and contract with health maintenance organizations (HMOs). DESIGN: Case studies, including interviews with administrative and clinical leaders, review of company documents, and analysis of documents from investment bankers, the Securities and Exchange Commission, and industry observers. SETTING: Medical groups and independent practice associations (IPAs) in California and New Jersey affiliated with MedPartners, FPA Medical Management, and UniMed. OUTCOME MEASURES: Growth in number of primary care and specialty care physicians employed by and contracting with affiliated medical groups; growth in patient enrollment from commercial, Medicare, and Medicaid HMOs; growth in capitation and noncapitation revenues; structure and governance of affiliated management service organizations and professional corporations; and contracting strategies with HMOs. RESULTS: Between 1994 and 1996, medical groups and IPAs affiliated with 3 PPMs grew from 3787 to 25763 physicians; 65% of employed physicians provide primary care, while the majority of contracting physicians provide specialty care. Patient enrollment in HMOs grew from 285503 to 3028881. Annual capitation revenues grew from $190 million to $2.1 billion. Medical groups affiliated with PPMs are capitated for most professional, hospital, and ancillary clinical services and are increasingly delegated responsibility by HMOs for utilization management and quality assurance. COMMENT: Physician practice management organizations and their affiliated medical groups face the challenge of continuing rapid growth, sustaining stock values, and improving practice efficiencies while maintaining the loyalty of physicians and patients.

California↗

Reproductive health care: services oriented to couples.

Historically, the combination of women's rights to care, population concerns and the development of female-oriented contraceptive methods resulted in family planning programs focusing on women's contraceptive needs and little else. The 1994 United Nations Population Conference in Cairo called for an expansion of programs to cover reproductive health in its broadest interpretation. As this concept has developed and been put into practice it has become evident that a key element in reproductive health services should be the inclusion of the sexually active couple.

Adult↗

Organizational diversification in the American hospital.

This paper outlines a conceptual framework of organizational diversification and assesses the state of empirical research on hospital organizational change. The literature on economic organization of hospitals, one of the most developed branches of health services research, still has only weak ties to economic theory. Evolving physician-hospital organizations do not fit into existing frameworks based on horizontal integration, vertical integration, or diversification. Empirical research has primarily focused on horizontal integration, and cause-effect relationships are often obscured by models that depart from economic theory and lack controls for self-selection bias. Recent empirical studies indicate that hospital mergers had moderate, rather than dramatic, effects on the rate of change in operating costs, staffing, and scale. Mergers rarely resulted in hospital closure, but were as likely to result in acute care consolidation and restructuring as in conversion to non-acute inpatient uses. While administrative costs were higher in for-profit than non-profit system hospitals, total costs were similar. System hospitals had lower marginal and average costs per stay than independent hospitals. Hospital vertical integration into subacute care was largely an artifact of the governmental uniform pricing system, which encouraged vertical integration. Hospitals that shared governance or financial risks with physicians outperformed those with high levels of physician governance and financial integration (e.g. stock ownership). Formal physician-hospital organizational arrangements often served to coordinate managed care contracting or to forge links with primary care group practices. Hospital diversification into related services improved short-term financial performance over unrelated diversification, although long-term performance was similar.

Delivery of Health Care, Integrated↗

The p43 component of the mammalian multi-synthetase complex is likely to be the precursor of the endothelial monocyte-activating polypeptide II cytokine.

p43 is one of the three auxiliary components invariably associated with nine aminoacyl-tRNA synthetases as a multienzyme complex ubiquitous to all eukaryotic cells from flies to humans. The cDNA encoding the hamster protein was isolated by using mixed oligonucleotides deduced from peptide sequences. The 359-amino acid protein is the hamster homologue of the recently reported murine and human EMAP II cytokine implicated in a variety of inflammatory disorders. The sequence of several proEMAP II proteins suggests that the p43 component of the complex is the precursor of the active mature cytokine after cleavage at a conserved Asp residue. The COOH-terminal moiety of p43 is also homologous to polypeptide domains found in bacterial methionyl- or phenylalanyl-tRNA synthetases and in the yeast Arc1p/G4p1 protein that associates with yeast methionyl-tRNA synthetase. Our results implicate the COOH-terminal moiety of p43 as a RNA binding domain. In the native state, as a component of the multisynthetase complex, p43 may be required for tRNA channeling and, after proteolytic processing occurring in tumor cells, would acquire inflammatory properties possibly related to apoptosis. The release of a truncated p43 from the complex could be involved in mediation of the signaling of tumor cells and stimulation of an acute inflammatory response.

Amino Acid Sequence↗

Cadherin-6, a cell adhesion molecule specifically expressed in the proximal renal tubule and renal cell carcinoma.

Cadherins are a family of calcium-dependent, cell-cell adhesion molecules that play an important morphoregulatory role in a wide variety of tissues. Alterations in cadherin function have been implicated in tumor progression in a number of adenocarcinomas. Despite the increasing number of new cadherins identified, little is known about cadherins in normal renal tissue and renal carcinomas. A novel cadherin transcript, cadherin-6, was recently described to be present in renal cancer cell lines and fetal kidney, but no data on protein expression nor tissue localization has been reported. In this study, we demonstrate that the expression of cadherin-6 is restricted to the proximal tubule epithelium. This finding is critical because these cells give rise to the majority of neoplasms of this organ. Furthermore we demonstrate typical cadherin features of cadherin-6, including cytoplasmic binding to alpha- and beta-catenin. We present data of cadherin-6 expression in a series of 32 primary renal cell cancers. Cadherin-6 expression tended to vary with histology in these samples. Whereas the majority of renal cell cancers with histology-associated poor prognosis (i.e., high grade clear cell carcinomas and sarcomatoid renal tumors) show aberrant expression of cadherin-6, in tumors with a favorable prognosis (i.e., low grade clear cell carcinomas and papillary cancers), normal cadherin-6 expression was predominant. Overall, these findings demonstrate specific expression of cadherin-6 in the proximal renal tubules in normal human kidney and suggest that alterations of cadherin-6 expression are associated with progression of renal cell carcinoma.

Cadherins↗

Superior cervical ganglionectomy in monkeys: light and electron microscopy of the anterior eye segment.

Morphological changes in the anterior eye segment of eight cynomolgus monkeys were investigated 2 days to 2.2 years after unilateral surgical superior cervical ganglionectomy (SCGx). SCGx was confirmed by histologic examination of the excised surgical specimen and persistent ipsilateral miosis. In four short-term monkeys (2, 4, 7 and 11 days), iris, ciliary muscle and trabecular meshwork were studied by electron microscopy. In the other four longer-term monkeys (3 week, 4 week, 5 week, 2.2 year) the anterior eye segment was investigated with tyrosine hydroxylase immunohistochemistry (TH-IR) and catecholamine fluorescence (CF). Electron microscopy of experimental eyes showed characteristic signs of Wallerian degeneration in numerous nerve fibers and terminals in the iris, but to a lesser extent in the ciliary muscle and the trabecular meshwork. TH-IR and CF showed marked interindividual differences. In all experimental eyes, there was a marked reduction, but never a complete absence of adrenergic nerves in the iris. In two animals (4 week and 2.2 years), the adrenergic innervation of the ciliary body and the chamber angle was similarly reduced. In contrast, in the experimental eyes of the other two animals (3 and 5 weeks), changes in adrenergic innervation to the ciliary body and chamber angle were minimal or absent. The results indicate that following apparently complete SCGx in the cynomolgus monkey, reduction of adrenergic innervation to the iris as evidenced by pupillary physiology, electron microscopy, TH-IR and CF does not guarantee reduction in adrenergic innervation to the ciliary body and trabecular meshwork. SCGx may not extirpate all third order sympathetic neurons in the distal stump, or there may be a significant contribution of accessory ganglion cells to the adrenergic innervation of the anterior eye segment.

Adrenergic Fibers↗