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PubMed2005

A practical guide to social networks.

Saying that networks are important is stating the obvious. But harnessing the power of these seemingly invisible groups to achieve organizational goals is an elusive undertaking. Most efforts to promote collaboration are haphazard and built on the implicit philosophy that more connectivity is better. In truth, networks create relational demands that sap people's time and energy and can bog down entire organizations. It's crucial for executives to learn how to promote connectivity only where it benefits an organization or individual and to decrease unnecessary connections. In this article, the authors introduce three types of social networks, each of which delivers unique value. The customized response network excels at framing the ambiguous problems involved in innovation. Strategy consulting firms and new-product development groups rely on this format. By contrast, surgical teams and law firms rely mostly on the modular response network, which works best when components of the problem are known but the sequence of those components in the solution is unknown. And the routine response network is best suited for organizations like call centers, where the problems and solutions are fairly predictable but collaboration is still needed. Executives shouldn't simply hope that collaboration will spontaneously occur in the right places atthe right times in their organization. They need to develop a strategic, nuanced view of collaboration, and they must take steps to ensure that their companies support the types of social networks that best fit their goals. Drawing on examples from Novartis, the FAA, and Sallie Mae, the authors offer managers the tools they need to determine which network will deliver the best results for their organizations and which strategic investments will nurture the right degree of connectivity.

Commerce↗
PubMedDate not supplied

[Rheumatologic patient management and research in Berlin at the intersection between East and West].

After the fall of the Berlin Wall in November 1989, there was an immediate need for collaboration between rheumatologists from East- and West-Berlin from the very beginning, which could be taken as an example for the rest of Germany. This was achieved through different activities in patient care and research. The "Regionales Rheumazentrum Berlin" which was started at about that time played a special role in making this enterprise a success.

Berlin↗
PubMed2002

Improving the process through which health plans and providers exchange performance-related mammography data.

The ability of health plans to bring about quality improvement is limited by the fact that physician networks are highly differentiated, with physician groups participating in many plans and plans contracting with many physician groups. The primary purpose of our study was to investigate the problems in the current system of quality monitoring by managed-care organizations (MCOs) at a large integrated health care delivery system (Montefiore Medical Center) and to develop ways of addressing these problems through collaboration among MCOs. The project began by mapping the current system for collecting, reporting, and using performance data to improve performance, using breast cancer screening as an example. We found that neither health plans nor providers were satisfied with the current system. From the perspective of the health plans, the current quality monitoring was costly and, more important, was not yielding appreciable increases in screening rates. From the providers' perspective, multiple health plan requests for chart pulls and other data collection activities cost them substantial amounts of time and money and generated multiple mailings of educational materials and reports, but rarely supplied meaningful information about their performance. From the perspective of the hospital, the current procedure of reporting from MCO to provider or center bypassed the institution's own quality monitoring and management structure and thus limited the institution's ability to assist in quality improvement. This study clearly showed the importance of collaboration among plans at a given provider site. Specifically, it pointed to the need for provider-oriented reporting of data, rather than plan-oriented reporting, to give physicians numbers that they believe. It also showed the need to engage the institution's own quality-management system to assist in bringing about improvements.

Cooperative Behavior↗
PubMed2003

Collaborative everyday problem solving: interpersonal relationships and problem dimensions.

Older adults' preferred partners for collaborative everyday problem solving and the types of everyday problems solved alone and with others were examined in a sample of community dwelling older adults (N = 112, M age = 71.86 yrs., SD = 5.92 yrs.). Family members (i.e., spouses, adult children) were the most frequently nominated partners for collaborative everyday problem solving, but friends, neighbors, and church members also were nominated. Older adults reported that they solved numerous types of problems, including finance, house repair, and health, in collaboration with others. These problems were also prominent when older adults reported the problems that they consulted others for advice on how to solve and the problems they solved alone. Together the results suggest new directions for research on collaborative everyday problem solving in terms of the types of interpersonal relationships and problems to be investigated. Implications of the findings for researchers and practitioners are discussed in terms of how to best understand and promote successful aging.

Activities of Daily Living↗
PubMed2004

A modified screening tool for autism (Checklist for Autism in Toddlers [CHAT-23]) for Chinese children.

BACKGROUND: There is a recent trend of a worldwide increase in the incidence of autistic spectrum disorder. Early identification and intervention have proved to be beneficial. The original version of the Checklist for Autism in Toddlers (CHAT) was a simple screening tool for identification of autistic children at 18 months of age in the United Kingdom. Children with an absence of joint attention (including protodeclarative pointing and gaze monitoring) and pretend play at 18 months were at high risk of autism. Section A of the CHAT was a self-administered questionnaire for parents, with 9 yes/no questions addressing the following areas of child development: rough and tumble play, social interest, motor development, social play, pretend play, protoimperative pointing (pointing to ask for something), protodeclarative pointing, functional play, and showing. Section B of the CHAT consisted of 5 items, which were recorded with observation of the children by general practitioners or health visitors. The 5 items addressed the child's eye contact, ability to follow a point (gaze monitoring), pretend (pretend play), produce a point (protodeclarative pointing), and make a tower of blocks. A 6-year follow-up study of >16,000 children screened with the CHAT at 18 months in the United Kingdom showed a sensitivity of only 0.40 and a specificity of 0.98, with a positive predictive value (PPV) of 0.26. Rescreening using the same instrument at 19 months for those who failed the 18-month screening yielded a higher PPV of 0.75. Therefore, children were likely to have autism if they failed the CHAT at 18 months and failed again at 19 months. It was estimated that consistent failure in 3 key questions (ie, protodeclarative pointing, gaze monitoring, and pretend play) at 18 months indicated an 83.3% risk of having autism. Because of the poor sensitivity of the original CHAT for autism, a Modified Checklist for Autism in Toddlers (M-CHAT), consisting of 23 questions, with 9 questions from the original CHAT and an additional 14 questions addressing core symptoms present among young autistic children, was designed in the United States. The original observational part (ie, section B) was omitted. The M-CHAT was designed as a simple, self-administered, parental questionnaire for use during regular pediatric visits. The more questions children failed, the higher their risk of having autism. Two criteria were used to measure the sensitivity and specificity of M-CHAT. Criterion 1 used any 3 of the 23 questions, and criterion 2 used 2 of the 6 best questions that could be used to discriminate autism from other groups. The sensitivity and specificity for criterion 1 were 0.97 and 0.95 and those for criterion 2 were 0.95 and 0.99, respectively. M-CHAT had a better sensitivity than the original CHAT, because children up to 24 months of age were screened, with the aim of identifying those who might regress between 18 and 24 months. The 6 best questions of the M-CHAT addressed areas of social relatedness (interest in other children and imitation), joint attention (protodeclarative pointing and gaze monitoring), bringing objects to show parents, and responses to calling. Joint attention was addressed in the original CHAT, whereas the other areas were addressed only in the M-CHAT. To date, there has been no study of the application of either the original CHAT or the M-CHAT for Chinese populations. OBJECTIVES: CHAT-23 is a new checklist translated into Chinese, combining the M-CHAT (23 questions) with graded scores and section B (observational section) of the CHAT. We aimed to determine whether CHAT-23 could discriminate autism at mental ages of 18 to 24 months for Chinese children and to determine the best combination of questions to identify autism. METHODS: A cross-sectional cohort study was performed with 212 children with mental ages of 18 to 24 months. The children were categorized into 2 groups, ie, group 1 (N = 87) (autistic disorder: N = 53; pervasive developmental disorder: N = 33) and group 2 (N = 125) (nonautistic). The checklist included self-ad25) (nonautistic). The checklist included self-administered questionnaires with 23 questions (part A) and direct observations of 5 items by trained investigators (part B). We performed discriminant function analysis to We found that 7 key questions, addressing areas of joint attention, pretend play, social relatedness, and social referencing, were identified as discriminative for autism. For part A, failing any 2 of 7 key questions, ie, question 13 (does your child imitate you? [eg, you make a face; will your child imitate it?]), question 5 (does your child ever pretend, for example, to talk on the phone or take care of dolls, or pretend other things?), question 7 (does your child ever use his/her index finger to point, to indicate interest in something?), question 23 (does your child look at your face to check your reaction when faced with something unfamiliar?), question 9 (does your child ever bring objects over to you [parent] to show you something?), question 15 (if you point at a toy across the room, does your child look at it?), and question 2 (does your child take an interest in other children?), yielded sensitivity of 0.931 and specificity of 0.768. Failing any 6 of all 23 questions produced sensitivity of 0.839 and specificity of 0.848. For part B, failing any 2 of 4 items produced sensitivity of 0.736, specificity of 0.912, and PPV of 0.853. The 4 observational items were as follows: item B1: during the appointment, has the child made eye contact with you? item B2: does the child look across to see what you are pointing at? item B3: does the child pretend to pour out tea, drink it, etc?; item B4: does the child point with his/her index finger at the light? CONCLUSION: We found that integrating the screening questions of the M-CHAT (from the United States) and observational section B of the original CHAT (from the United Kingdom) yielded high sensitivity and specificity in discriminating autism at 18 to 24 months of age for our Chinese cohort. This new screening instrument (CHAT-23) is simple to administer. We found that a 2-stage screening program for autism can offer a cost-effective method for early detection of autism at 18 to 24 months. For CHAT-23, use of both the parental questionnaire and direct observation and use of the criterion of failing any 2 of 7 key questions yielded the highest sensitivity but a relatively lower specificity, whereas use of part B yielded the highest specificity but a lower sensitivity. We recommend identifying the possible positive cases with part A (parental questionnaire) and then proceeding to part B (observation) with trained assessors. The proposed algorithm for screening for autism is as follows. 1) The parents or chief caretakers complete a 23-item questionnaire when their children are 18 to 24 months of age. 2) The parents mail, fax, or hand this 23-item questionnaire to the local child health agency. 3) Clerical staff members check for and score failure, with the criteria of failing any 2 of 7 key questions or failing any 6 of 23 questions; if either criterion is met, then the staff members highlight the medical records of the suspicious cases. 4) Trained child health care professionals observe the children who failed any 2 of 7 key questions or any 6 of 23 questions. These identified patients are observed for 5 minutes for part B of the CHAT-23. 5) Any child who fails any 2 of 4 items requires direct referral to a comprehensive autism evaluation team, for early diagnostic evaluation and early intervention. The high sensitivity and specificity of the criteria observed in our study suggested that CHAT-23 might be used to differentiate children with autism. Additional international collaboration with the use of the CHAT, M-CHAT, and CHAT-23 could provide more prospective epidemiologic data, to establish whether there is a genuine increase in the worldwide incidence of autism.

Attention↗
PubMed2002

Partnership for sustainable healthy workplaces: Warner Lecture, British Occupational Hygiene Society, Sheffield 9 April 2002.

The paper sets out a fresh approach to healthy workplaces, laying foundations to meet the demands of the new millennium. Professionals such as occupational hygienists deal with issues at the heart of the economy and society, which are beginning to attract the attention of politicians. Old disciplinary barriers must be crossed and communication improved so that healthy work is accepted as a mainstream concern, integral to sustainable development. This presents challenges both to professionals and to those with responsibilities for policy. As a first step, we need to develop an understanding of how conclusions from research can inform responsible decision making. We will not be able to design and build perfectly safe environments, but real progress can be made in the field of 'workplace health defence', using available human, technical and financial resources. A vital ingredient is partnership in the workplace, involving social partners and professionals working in collaboration.

Employment↗
PubMed1992

[Knowledge of the hygiene habits of schoolchildren: a course of urban collaboration in health].

AIM: To study the hygiene habits of schoolchildren in Santa Maria de Gracia (an urban site) and La Nora (a rural site), both in Murcia. This stemmed from an initiative of the Health Councils of these places, with the aim of later developing an effective project of Health Education. The Community was conceived as the main player in the Health-Illness process: passive behaviour models were thus abandoned. DESIGN: This was a transversal study of the hygiene customs of school-children from Second and Seventh Grade E.G.B. (General Basic Education: from 8 to 13) in the rural area; from Second and Fifth Grade EGB, from Second Grade BUP (Baccalaureate: from 14 to 16) and from the Second Course of Second Grade FP (Professional Formation) in the urban area. Questionnaires covered the whole of the above population. Crosses according to age, sex and the rural or urban environment were made. PARTICIPANTS: Professionals from both the Primary Care Teams, from Educational Centres, from the Department of Socio-Health Sciences of the Faculty of Medicine and schoolchildren interviewed. INTERVENTIONS: Using a participatory methodology, a questionnaire was designed and answered by a total of 1,182 students, belonging to 13 Educational Centres. MAIN FINDINGS: There are shortcomings open to improvement in practically all areas of hygiene habits; with important differences, in particular customs, between boys and girls, between town and country and between younger and older students.

Age Factors↗
PubMed2000

Prophylactic methylxanthine for preventing of apnea in preterm infants.

BACKGROUND: Recurrent apnea is common in preterm infants, particularly at very early gestational ages. These episodes of loss of effective breathing can lead to hypoxemia and bradycardia which may be severe enough to require resuscitation including use of positive pressure ventilation. In infants with apnea, methylxanthines have been successful as treatment to prevent further episodes. It is possible that prophylactic therapy, given to all very preterm infants from soon after birth, might prevent apnea and its associated hypoxemia and bradycardia. OBJECTIVES: In preterm infants, does prophylactic treatment with methylxanthine lead to less apnea, bradycardia, episodes of hypoxemia and use of mechanical ventilation, without clinically important side effects? SEARCH STRATEGY: The standard strategy of the Cochrane Neonatal Review Group was used. This included searches of the Oxford Database of Perinatal Trials, previous reviews including cross references, abstracts, conferences and symposia proceedings, expert informants and journal handsearching mainly in the English language. A search of MEDLINE was made in October 1998 covering the years 1966 -1998. SELECTION CRITERIA: All trials utilising random or quasi-random patient allocation, in which prophylactic methylxanthine (caffeine or theophylline) was compared with placebo or no treatment were eligible. Outcomes sought included the rate of apnea, bradycardia, hypoxemic episodes, use of IPPV, side effects such as tachycardia or feed intolerance, as well as longer term abnormal growth and development. DATA COLLECTION AND ANALYSIS: The standard methods of the Cochrane Collaboration and its Neonatal Review Group were used. The methodological quality of each trial was reviewed independently by each author. Each reviewer extracted data separately, then results were compared and differences resolved. The standard method of the Cochrane Neonatal Review Group was used to analyze the data, utilizing relative risk (RR) and risk difference (RD). MAIN RESULTS: Two studies examining a total of 104 infants were found. Both studied the effects of prophylactic caffeine. There were no meaningful differences between the caffeine and placebo groups in the number of infants with apnea, bradycardia, hypoxemic episodes, use of IPPV or side effects in either of the studies. Only two outcomes (use of IPPV and tachycardia) were common to the two studies and meta-analysis showed no substantive differences between the groups. REVIEWER'S CONCLUSIONS: The results of this review do not support the use of prophylactic caffeine for preterm infants at risk of apnea, bradycardia or hypoxemic episodes. Any future studies need to examine the effects of prophylactic methylxanthines in preterm infants at higher risk of apnea, bradycardia or hypoxemic episodes. This should include examination of important clinical outcomes such as need for IPPV, length of hospital stay and long term development.

Apnea↗
PubMed2000

[Microbiological monitoring in neonatal intensive care].

There is no "ideal" method of infection diseases control, but there are some different methods according to the risk degree of patient, the problems, the information accuracy and also the available resources. Some important points need to be stressed about infectious diseases control in Neonatal Intensive Care Unit:--continuous microbiological surveillance in Neonatal Intensive Care Unit is necessary, because newborns admitted are at very high risk of infection disease;--continuous microbiological data review is needed: therefore criticism and integration with other clinical and laboratory data are necessary to exclude simple colonisation;--critical analysis of data allows more rational use of antimicrobical agents to avoid the selection of multiresistant bacteric streams;--a rational analysis of laboratory data needs necessarily a strict collaboration among neonatologists, microbiologists and the Committee for infectious diseases control;--in epidemics, techniques of bacterial streams typization are needed, and methods of molecular biology (DNA and proteins analysis) are better;--this implies a collection of microbiological data, by database integrating microbiological, clinical and anamnestic data and allowing retrospective studies too.

Cross Infection↗
PubMed1991

Preliminary results from a meta-analysis of drinking behavior in multiple longitudinal studies.

This paper introduces the scope and rationale of The Collaborative Alcohol-Related Longitudinal Project and describes the individual longitudinal studies which contribute to this large collaborative project, representing studies from 15 countries. It also serves as an introduction to four reports of the preliminary findings from the project. The project is distinguished by (1) its interdisciplinary research approach which has assembled a multidisciplinary group of scholars to direct and interpret analyses, (2) its use of primary data from multiple longitudinal studies, (3) the parallel analyses of primary data from multiple studies, using comparable measures across studies recorded to a standard format and common analytic model, and (4) its use of meta-analysis to combine results across studies. Its research objectives include determining the cross-study consistency of findings of (1) the incidence and chronicity of drinking patterns and problems, (2) exogeneous factors which initiate and alter drinking careers, (3) socio-behavioral factors measured in childhood and adolescence which predict adult drinking problems, (4) inter-generational biological and social factors which predict adult drinking problems, and (5) aggregate-level factors which account for study differences. The method of sampling of studies from the world's alcohol-related general population longitudinal research is described.

Alcohol Drinking↗
PubMed2026

The Biobank Rare Variant consortium powers the discovery of rare genetic associations through global collaboration.

Rare coding variants can have large effects on disease risk and provide direct routes from human genetics to disease mechanisms and therapeutic targets, but their discovery is constrained by sample size, particularly for low-prevalence diseases. Here we establish the Biobank Rare Variant Analysis (BRaVa) consortium, a global rare variant association resource that integrates sequencing and linked health-record data from ten biobanks and cohorts comprising over 1.2 million individuals across diverse ancestries. We performed gene-based meta-analyses of rare coding variation across 33 clinical endpoints and 11 quantitative traits. Aggregating evidence across biobanks and ancestries identified 514 gene-trait associations, including 31 not previously reported in prior studies or curated association resources following systematic literature review. Notably, 36.1% of gene-level associations were undetectable in any individual biobank, and 91 emerged only through cross-ancestry meta-analysis, demonstrating that federated integration enables discovery beyond the reach of single cohorts. Similar gains were observed at the variant level, where 25.0% of phenotype-locus associations were detectable only through meta-analysis. Effect size estimates were correlated across ancestries with concordant directions of effect, supporting the generalizability of rare variant associations. The identified signals implicate pathways involved in transcriptional and epigenetic regulation, metabolism, vascular and epithelial biology, and immune function, highlighting rare coding variation as an engine for biological discovery across medical record phenotypes. For example, damaging variation in ANKRD12 implicates inflammatory transcriptional dysregulation in asthma and chronic obstructive pulmonary disease, and ultra-rare predicted loss-of-function variants in NAA15 link protein acetylation processes to type 2 diabetes risk. BRaVa establishes a scalable framework and freely available community resource for rare variant meta-analysis across global biobanks. Public release of gene- and variant-level association summary statistics provides a reference map of rare coding variant associations to support disease gene discovery, biological interpretation, and therapeutic target prioritization as sequencing-linked health-record resources continue to expand.

Journal Article↗
PubMed2005

A Latin American telemedicine social perspective from a Colombian telemedicine center initiative.

This paper describes a collaborative initiative for developing a telemedicine model on for Colombia and Latin America from a social perspective. This was led by the Colombian Telemedicine Center (CTMC) with the participation of teams from Mexico, Costa Rica, Panama, and Argentina, in addition to on-going interaction with academic institutions such as Javeriana University, Icesi University, and Murcia University.

Colombia↗
PubMed2003

Assessing the impact of the green revolution, 1960 to 2000.

We summarize the findings of a recently completed study of the productivity impacts of international crop genetic improvement research in developing countries. Over the period 1960 to 2000, international agricultural research centers, in collaboration with national research programs, contributed to the development of "modern varieties" for many crops. These varieties have contributed to large increases in crop production. Productivity gains, however, have been uneven across crops and regions. Consumers generally benefited from declines in food prices. Farmers benefited only where cost reductions exceeded price reductions.

Agriculture↗
PubMed1995

The use of molecular techniques in the epidemiology and control of infectious diseases.

The ability to identify specific strains within a given species of pathogen is an important aid in the rational development of effective measures to prevent and control nosocomial infections. The efforts of both microbiologist and hospital epidemiologic are facilitated greatly by the availability of the newer molecular epidemiologic typing techniques. Although these methods clearly have limitations, they generally are a significant improvement over the more conventional typing methods, many of which are too cumbersome, insensitive, and time-consuming to be of practical value for epidemiologic evaluations. Based on current experience, the molecular typing methods that appear to be the most practical and useful for both large and small scale epidemiologic studies are the DNA-based methods of REAP and PFGE. Many questions remain concerning the appropriate role of molecular typing methods in the clinical microbiology laboratory. Often, molecular typing may be performed more efficiently in a reference laboratory. In contrast, selected methods such as plasmid analysis are well within the scope of clinical microbiology laboratories and may be an important adjunct to the hospital infection control effort. Given the limitations of the available methods and the complex nature of patients at risk for nosocomial infections, it is imperative that these methods be employed with clear epidemiologic objectives in mind. Typing should always include unrelated as well as epidemiologically related isolates and, whenever possible, all organisms should be typed under identical conditions, preferably within the same test run. In addition, results are most effectively used to supplement rather than to replace hypotheses and questions thoughtfully developed by the clinician or epidemiologist. Ideally, typing is performed independently by the laboratory to avoid bias, but the results are applied collaboratively to ensure that both the potential insights and the unavoidable ambiguities presented by the results are clearly appreciated. Additional studies based upon sound epidemiologic principles will help clarify the role of the various molecular typing methods as epidemiologic markers and advance our understanding of the epidemiology of nosocomial infections.

Bacterial Infections↗
PubMed1994

A Hebrew version of the Millon Behavioral Health Inventory: preliminary results--brief report. Rakenatti School of Nursing Students.

This study presents a personality questionnaire which was planned to be used with general hospital as well as with psychiatric patients. This questionnaire, the Millon Behavioral Health Inventory (MBHI), is aimed at characterizing the patient's coping style, as well as attitudinal and behavioral correlates with some frequent psychosomatic diseases and prognostic indices. A Hebrew version of the questionnaire was administered to 103 subjects, of whom 64 were medical (non-psychiatric) patients and 39 were healthy controls. The Israeli scores were fairly similar to the American norms presented by Millon and his collaborators. The reliability coefficients seem to be sufficient. The healthy subjects were distinguishable from the patients on the majority of the questionnaire's subscales. However, correlation with an external measure of stress failed to show the expected value. Overall, this study is preliminary. However, the results seem to support the need and usefulness of further research with this instrument.

Cross-Cultural Comparison↗
PubMed2001

Doppler investigation in intrauterine growth restriction--from qualitative indices to flow measurements: a review of the experience of a collaborative group.

In 1997 we started a collaboration among three groups, combining our experience with Doppler examination of the human fetus, blood flow studies on fetal lamb, and mathematical modeling of human circulation. In preliminary investigations on fetal lambs, the same Doppler method designed for the human fetus was used to measure venous blood flow in the umbilical veins of seven fetal lambs. Doppler measurements and diffusion technique groups for umbilical venous flow were 210.8+/-18.8 and 205.7+/-38.5 ml/min/kg, respectively (p = 0.881). In human pregnancy the interobserver variabilities for the vein diameter, mean velocity, and absolute umbilical venous blood were 2.9%, 7.9%, and 12.7%, respectively. A cross-sectional study allowed us to establish normal reference values. Venous blood flow/kg of estimated fetal weight showed a nonsignificant linear reduction with gestational age, from 128.7 ml/min/kg at 20 weeks to 104.2 ml/min/kg at 38 weeks. In a series of 37 growth-restricted fetuses, the UV flow per kilogram was significantly lower in the more severe growth-restricted fetuses (abdominal circumference below the second percentile and abnormal umbilical arterial p.i.) than in normal comparable fetuses (p < 0.001). In a series of 140 normal fetuses, we calculated that the absolute blood flow rate in the ductus venosus (DV) increases significantly with advancing gestational age from 20 to 38 weeks of gestation (from 23.2+/-9.6 ml/min to 43.5+/-21.5 ml/min). This means that the percentage of umbilical blood flow shunted through the DV decreases significantly during gestation (from 50% at midgestation to 20% at 38 weeks). In a series of 45 growthrestricted fetuses, delivered because of nonreactive fetal heart rate (group 2) and for other reasons but still with a normal heart rate pattern (group 1), we measured the ductal inlet diameter. In these fetuses, the diameters at the ductal isthmus, normalized for the dimension of the abdominal circumference (inlet diameter/abdominal circumference), were significantly larger (group 1 = 6.8+/-2.3; group 29.4+/-2.8 ) than in the control group (6.1+/-0.3). This means that in this subset of fetuses the amount of blood shunted can be increased as a compensatory mechanism.

Female↗
PubMed2004

p53 deficiency provokes urothelial proliferation and synergizes with activated Ha-ras in promoting urothelial tumorigenesis.

Mutation and deletion of the p53 tumor suppressor gene are arguably the most prevalent among the multiple genetic alterations found in human bladder cancer, but these p53 defects are primarily associated with the advanced diseases, and their roles in bladder tumor initiation and in synergizing with oncogenes in tumor progression have yet to be defined. Using the mouse uroplakin II gene promoter, we have targeted into urothelium of transgenic mice a dominant-negative mutant of p53 that lacks the DNA-binding domain but retains the tetramerization domain. Urothelium-expressed p53 mutant binds to and stabilizes the endogenous wild-type p53, induces nuclear abnormality, hyperplasia and occasionally dysplasia, without eliciting frank carcinomas. Concurrent expression of the p53 mutant with an activated Ha-ras, the latter of which alone induces urothelial hyperplasia, fails to accelerate tumor formation. In contrast, the expression of the activated Ha-ras in the absence of p53, as accomplished by crossing the activated Ha-ras transgenic mice with the p53 knockout mice, results in early-onset bladder tumors that are either low-grade superficial papillary or high grade in nature. These results provide the first in vivo experimental evidence that p53 deficiency predisposes the urothelium to hyperproliferation, but is insufficient for bladder tumorigenesis; that the mere reduction of p53 dosage, as produced in transgenic mice expressing the dominant-negative p53 or in heterozygous p53 knockouts, is incapable of synergizing with Ha-ras to induce bladder tumors; and that the complete loss of p53 is a prerequisite for collaborating with activated Ha-ras to promote bladder tumorigenesis.

Animals↗
PubMed1974

Ultrastructural localization of rhodopsin in the vertebrate retina.

Early work by Dewey and collaborators has shown the distribution of rhodopsin in the frog retina. We have repeated these experiments on cow and mouse eyes using antibodies specific to rhodopsin alone. Bovine rhodopsin in emulphogene was purified on an hydroxyapatite column. The purity of this reagent was established by spectrophotometric criteria, by sodium dodecyl sulfate (SDS) gel electrophoresis, and by isoelectric focusing. This rhodopsin was used as an immunoadsorbent to isolate specific antibodies from the antisera of rabbits immunized with bovine rod outer segments solubilized in 2% digitonin. The antibody so prepared was shown by immunoelectrophoresis to be in the IgG class and did not cross-react with lipid extracts of bovine rod outer segments. Papain-digested univalent antibodies (Fab) coupled with peroxidase were used to label rhodopsin in formaldehyde-fixed bovine and murine retinas. In addition to the disk membranes, the plasma membrane of the outer segment, the connecting cilium, and part of the rod inner segment membrane were labeled. We observed staining on both sides of the rod outer segment plasma membrane and the disk membrane. Discrepancies were observed between results of immunolabeling experiments and observations of membrane particles seen in freeze-cleaved specimens. Our experiments indicate that the distribution of membrane particles in freeze cleaving experiments reflects the distribution of membrane proteins. Immunolabeling, on the other hand, can introduce several different types of artifact, unless controlled with extreme care.

Animals↗