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PubMed2004

Zero-check: a zero-knowledge protocol for reconciling patient identities across institutions.

CONTEXT: Large, multi-institutional studies often involve merging data records that have been de-identified to protect patient privacy. Unless patient identities can be reconciled across institutions, individuals with records held in different institutions will be falsely "counted" as multiple persons when databases are merged. OBJECTIVE: The purpose of this article is to describe a protocol that can reconcile individuals with records in multiple institutions. DESIGN: Institution A and Institution B each create a random character string and send it to the other institution. Each institution receives the random string from the other institution and sums it with their own random string, producing a random string common to both institutions (RandA+B). Each institution takes a unique patient identifier and sums it with RandA+B. The product is a random character string that is identical across institutions when the patient is identical in both institutions. A comparison protocol can be implemented as a zero-knowledge transaction, ensuring that neither institution obtains any knowledge of its own patient or of the patient compared at another institution. RESULTS: The protocol can be executed at high computational speed. No encryption algorithm or 1-way hash algorithm is employed, and there is no need to protect the protocol from discovery. CONCLUSION: A zero-knowledge protocol for reconciling patients across institutions is described. This protocol is one of many computational tools that permit pathologists to safely share clinical and research data.

Confidentiality↗
PubMed1996

Contrasting methods of collecting data on injectors' risk behaviour.

In this paper two contrasting methods of collecting data on drug injectors' needle and syringe sharing practices are considered, namely: direct questions about any previous sharing in the last 6 months, and vignettes in which injectors are asked to indicate whether they would be prepared to share injecting equipment in a range of situations. Injectors' statements of their preparedness to share are far in excess of their reports of actual sharing. The possible reasons for this discrepancy are considered, including that injectors may have under-reported the level of their actual sharing. It is suggested that in future studies aiming to collect risk behaviour data should seek to combine methods rather than to rely solely upon direct questioning of any past sharing.

Adolescent↗
PubMed2006

Inference methods for correlated left truncated lifetimes: parent and offspring relations in an adoption study.

The associations in mortality of adult adoptees and their biological or adoptive parents have been studied in order to separate genetic and environmental influences. The 1003 Danish adoptees born 1924-26 have previously been analysed in a Cox regression model, using dichotomised versions of the parents' lifetimes as covariates. This model will be referred to as the conditional Cox model, as it analyses lifetimes of adoptees conditional on parental lifetimes. Shared frailty models may be more satisfactory by using the entire observed lifetime of the parents. In a simulation study, sample size, distribution of lifetimes, truncation- and censoring patterns were chosen to illustrate aspects of the adoption dataset, and were generated from the conditional Cox model or a shared frailty model with gamma distributed frailties. First, efficiency was compared in the conditional Cox model and a shared frailty model, based on the conditional approach. For data with type 1 censoring the models showed no differences, whereas in data with random or no censoring, the models had different power in favour of the one from which data were generated. Secondly, estimation in the shared frailty model by a conditional approach or a two-stage copula approach was compared. Both approaches worked well, with no sign of dependence upon the truncation pattern, but some sign of bias depending on the censoring. For frailty parameters close to zero, we found bias when the estimation procedure used did not allow negative estimates. Based on this evaluation, we prefer to use frailty models allowing for negative frailty parameter estimates. The conclusions from earlier analyses of the adoption study were confirmed, though without greater precision than using the conditional Cox model. Analyses of associations between parental lifetimes are also presented.

Adoption↗
PubMed2000

Evaluating linkage and linkage disequilibrium: use of excess sharing and transmission disequilibrium methods in affected sib pairs.

Two popular and robust approaches to analysing affected sib pair (ASP) data for linkage are the traditional excess sharing methods and the transmission/disequilibrium test (TDT). Here we derive an overall test of linkage for multi-allelic ASP marker data which comprises two component tests: one for excess sharing and one for transmission disequilibrium. This method has several advantages. Firstly the overall test of linkage is often more powerful than either of the two component tests. Secondly the method makes it possible to determine the contribution of linkage disequilibrium (LD), in addition to linkage, to an overall positive linkage result. This is useful because the presence of LD in addition to linkage may suggest that the marker locus is in very close proximity to a disease susceptibility gene. Thirdly the method provides estimates of the risk associated with transmission of the different marker alleles.

Genetic Diseases, Inborn↗
PubMed1997

Identification of major antigenic proteins of Pasteurella piscicida.

Two different antigenic protein-coding clones (PPA1 and PPA2) were isolated using anti-Pasteurella piscicida rabbit serum from a genomic DNA library of P. piscicida strain KP9038. The PPA1 and PPA2 expressed 7 kDa and 45 kDa proteins in Escherichia coli, respectively, and the molecular sizes of these expressed proteins are the same as these of the major antigenic proteins of P. piscicida. PPA1 encodes a protein of 83 amino acids residues, which is similar to the bacterial lipoprotein. Comparison of the predicted amino acid sequence of the PPA1-encoded 7 kDa protein of P. piscicida with previously reported bacterial lipoprotein sequence data revealed that it shares about 40% amino acid sequence identity. PPA2 has two large open reading frame (ORFs). The larger ORF (encoding 452 amino acid residues) encodes a homolog of DegQ protease, and the smaller ORF (371 amino acid residues) encodes a homolog of DegS protease. The antibodies reacted with the larger ORF-encoded 45 kDa DegQ homolog protein. The DegQ and DegS homolog proteins contain an export signal and a serine protease active site. The structural features of the PPA2-coding locus are similar to those of the loci in E. coli for the degQ and degS serine protease genes. A sequence in the 3' non-coding region of Vibrio hollisae thermostable hemolysin gene that is highly homologous with a similar located sequence in the Pseudomonas putida p-cresol methylhydroxylase gene is also found in the 3' non-coding region of the degS homolog gene of the PPA2.

Amino Acid Sequence↗
PubMed2004

The effect of parity-induced copayment reductions on adolescent utilization of substance use services.

OBJECTIVE: The purpose of this study was to determine if the reduction in copayment amount by a large self-insured state employer increased utilization of adolescent services. Specifically, the study sought to discover if the number of unique adolescent users of substance use outpatient services increased as a result of reductions in cost-sharing arrangements. METHOD: The data utilized in this study were 31,585 records from administrative claims data on utilization of mental health and substance abuse services from members of a state indemnity plan fromJuly 1998 through December 2001, translating to 36 months of pre-intervention data and 6 months of postintervention data. Monthly longitudinal data before and after benefit design change were analyzed using a quasi-experimental time series design, using Box and Jenkins' autoregressive, integrated, moving-average time-series modeling methods. The primary outcome measure was the number of unique users of services. RESULTS: The hypothesis that service utilization would increase following the implementation of a reduction in copayment amount (the intervention) was supported in these analyses for adolescents' substance use service utilization. A significant increase in the number of unique adolescent users of substance use services was detected in the month following the intervention (p < .01). CONCLUSIONS: The results of this study suggest that a reduction in adolescents' substance use service copayment requirements to a level equal to those for general medical services may be a step toward assuring full parity between such types of services. These findings provide potentially important information regarding the possible effects of broader policy changes, as parity in benefit design is a common component of laws that attempt to ensure "full parity."

Adolescent↗
PubMed1998

Protein-tyrosine phosphatases: biological function, structural characteristics, and mechanism of catalysis.

The protein-tyrosine phosphatases (PTPases) superfamily consists of tyrosine-specific phosphatases, dual specificity phosphatases, and the low-molecular-weight phosphatases. They are modulators of signal transduction pathways that regulate numerous cell functions. Malfunction of PTPases have been linked to a number of oncogenic and metabolic disease states, and PTPases are also employed by microbes and viruses for pathogenicity. There is little sequence similarity among the three subfamilies of phosphatases. Yet, three-dimensional structural data show that they share similar conserved structural elements, namely, the phosphate-binding loop encompassing the PTPase signature motif (H/V)C(X)5R(S/T) and an essential general acid/base Asp residue on a surface loop. Biochemical experiments demonstrate that phosphatases in the PTPase superfamily utilize a common mechanism for catalysis going through a covalent thiophosphate intermediate that involves the nucleophilic Cys residue in the PTPase signature motif. The transition states for phosphoenzyme intermediate formation and hydrolysis are dissociative in nature and are similar to those of the solution phosphate monoester reactions. One strategy used by these phosphatases for transition state stabilization is to neutralize the developing negative charge in the leaving group. A conformational change that is restricted to the movement of a flexible loop occurs during the catalytic cycle of the PTPases. However, the relationship between loop dynamics and enzyme catalysis remains to be established. The nature and identity of the rate-limiting step in the PTPase catalyzed reaction requires further investigation and may be dependent on the specific experimental conditions such as temperature, pH, buffer, and substrate used. In-depth kinetic and structural analysis of a representative number of phosphatases from each group of the PTPase superfamily will most likely continue to yield insightful mechanistic information that may be applicable to the rest of the family members.

Amino Acid Sequence↗
PubMed1989

Robustness of the unified model to shared environmental effects in the analysis of dichotomous traits.

Simulation studies were conducted to assess to what extent the conclusions of segregation analysis, performed under the unified model, can be affected by the presence of unmeasured environmental factors shared by family members. Dichotomous data were generated on six-member nuclear families under two variants of the mixed model, incorporating environmental effects shared by all family members. When the generating model includes a polygenic component and a shared environmental effect, there is false detection of a major gene, especially when the joint likelihood of parents' and offspring's phenotypes is computed. The proportion of false conclusions increases as the shared environmental effect increases. On the other hand, the presence of a shared environmental effect in addition to a major gene component does not alter the detection of the major gene nor the transmission probability estimates, which are close to the expected Mendelian values. The rejection of the Mendelian transmission hypothesis, as observed in familial analyses of affected disorders, might be the result of mechanisms other than those considered here, such as more complex sources of environmental resemblance or a possible genetic heterogeneity.

Affective Disorders, Psychotic↗
PubMed1988

Development of an inflammatory bowel disease registry.

Inflammatory Bowel Disease is characterized by two major entities, Crohn's Disease and Ulcerative Colitis. These bowel diseases have associated problems involving the eyes, joints, skin, kidneys, immunological system, hepatobiliary system, and psychiatric disturbances. A regional IBD registry encompassing 18 hospitals and IBD specialists in east/northeast Pennsylvania was established to promote awareness of the clinical and epidemiological aspects of the disease. Results of this data collection effort will be shared with patients and physicians through the use of newsletters and symposia. A Basic History (HX) form, an Operative Data (OR) form, and an Annual Follow-up (FU) form was used to collect relevant data. Participation is voluntary and all information is confidential.

Humans↗
PubMed2005

Comparison of HIV-specific CD8 T-cell responses among uninfected individuals exposed to HIV parenterally and mucosally.

OBJECTIVE: To assess the influence of route of HIV exposure on the development of HIV-specific CD8 T-cell responses in exposed, uninfected (EU) individuals. DESIGN: Two groups of EU exposed to virus through either sexual or intravenous contact were studied. Group I included subjects (n = 20) who had unprotected sexual contact with known HIV-infected partners and no intravenous HIV exposure; Group II included individuals (n = 27) who had shared needles with HIV-infected partners and had no sexual exposure to this virus. Between-group comparisons were made for the proportion of responders, breadth, magnitude, and specificity of HIV-specific responses. METHODS: : The interferon-gamma ELISPOT assay was used to detect HIV-specific effector activity. Peripheral blood mononuclear cells (PBMC) from each subject were stimulated with a panel of HIV peptides restricted to the MHC class I alleles expressed by the individual. RESULTS: A similar proportion of EU tested from each group (35.0% Group I versus 22.2% Group II) recognized at least one HIV peptide. Group I and II subjects recognized HIV peptides with a similar cumulative intensity of 130 +/- 67.5 and 182.9 +/- 184.2 spot forming cells/1 x 10 PBMC, respectively, and similar magnitude per stimulatory peptide of 82.7 and 78.4 SFC/1 x 10 PBMC, respectively. The proportion of stimulatory peptides derived from HIV Gag, reverse transcriptase, Env, and Nef was not significantly different between the two EU groups. HLA-A*0201 restricted HIV epitopes immunodominant in infected individuals are rarely stimulatory in EU subjects. CONCLUSIONS: Both mucosal and parenteral exposure to HIV can elicit HIV-specific CD8 T-cell responses with similar characteristics.

Adult↗
PubMed1979

Psychotherapy in the goldfish bowl: the role of the indigenous therapist.

The therapeutic advantages and liabilities that accrue to the indigenous therapist (be he professional or paraprofessional) because of the indigenous state were explored, utilizing the five-year experience of ten indigenous therapists in Boston's North End. The current and historical proximity of therapists who live in the same neighborhood as their patients do provides both with increased access to, longitudinal knowledge about, and a blurred role concept of the other that may help or hinder the therapeutic process. Similarities in culture and values can foster alliance formation, differentiation of psychopathology, and therapeutic interventions, but also may interfere when therapy abuts culturally shared blind spots. These data are relevant to the private general psychiatrist as an indigenous therapist in non-metropolitan America.

Allied Health Personnel↗
PubMed1998

Characterization of soybean seed coat peroxidase: resonance Raman evidence for a structure-based classification of plant peroxidases.

Electronic absorption and resonance Raman spectra of ferric and ferrous forms of a peroxidase from soybean seed coat (SBP) at neutral and alkaline pH values together with the spectra of the ferric-fluoride complex are reported. At neutral pH a quantum mechanically mixed spin state, resulting from the admixture of intermediate spin, S = 3/2, and high spin, S = 5/2, configurations, has been identified which coexists with five- and six-coordinate high-spin hemes. A complete conversion to a fluoride-ligated six-coordinate high-spin and a hydroxy-ligated six-coordinate low-spin heme are observed at acid pH in the presence of fluoride and at alkaline pH, respectively. The spectral features suggest that both the fluoride and hydroxo ligands are stabilized by hydrogen-bond interactions with the distal Arg residue and through a water molecule with the distal His residue. The ferrous form shows a single nu(Fe-Im) at 246 cm(-1) at neutral pH. The data indicate that SBP shares many characteristics with peroxidases belonging to class III of the "plant peroxidase" superfamily.

Arginine↗
PubMed2001

Functional anatomy of execution, mental simulation, observation, and verb generation of actions: a meta-analysis.

There is a large body of psychological and neuroimaging experiments that have interpreted their findings in favor of a functional equivalence between action generation, action simulation, action verbalization, and perception of action. On the basis of these data, the concept of shared motor representations has been proposed. Indeed several authors have argued that our capacity to understand other people's behavior and to attribute intention or beliefs to others is rooted in a neural, most likely distributed, execution/observation mechanism. Recent neuroimaging studies have explored the neural network engaged during motor execution, simulation, verbalization, and observation. The focus of this metaanalysis is to evaluate in specific detail to what extent the activated foci elicited by these studies overlap.

Brain Mapping↗
PubMed2005

Growth and nutritional status of male adolescent laborers in Ankara, Turkey.

Undernutrition, pathogenic agents, and poor living conditions are of primary importance in the evaluation of adverse environmental conditions' effects on human growth; but child labor (an equally significant factor, especially in underdeveloped countries) is generally overlooked or ignored. The aim of this study is to focus on this subject and clarify the effects of labor on the physical growth and nutritional status of child and adolescent laborers. In this study, the height and weight of 532 male adolescent laborers aged 13.5-18.5 years and their non-laboring peers (n = 451) (the control group) were measured by standard anthropometric techniques and equipment. The individuals of both groups come from lower socioeconomic strata and share similar living conditions. Data were transformed to z-scores, using the US Center for Disease Control and Prevention's 2000 growth charts. The analyses show that the z-scores for height-for-age, weight-for-age, and body mass index (BMI)-for-age were negative in both groups. The z-scores of laborers' height-for-age and weight-for-age values lie below the controls', but there is no significant difference between the two groups' BMI-for-age scores. In the laboring group, the percentages of stunting (-2 SD of height-for-age), underweight (-2 SD of weight-for-age), and wasting (-2 SD of BMI-for-age) were 14.3, 2.6, and 0.2, respectively. These values suggest that malnutrition is not a common problem among adolescent laborers living in Ankara; but laboring is an important cause of faltering in growth, particularly in linear growth, in less or underdeveloped economic environments.

Adolescent↗
PubMed1986

Growth-promoting effects of esterolytically inactive thrombin on macrophages.

It has been recognized for many years that alpha-thrombin, like other better known mitogens (eg, PDGF, EGF, etc) is capable of initiating proliferation in quiescent cells belonging to the fibroblast family. However, unlike these other peptides, thrombin is a serine protease whose function as a growth stimulator for fibroblasts is intimately linked to its esterolytic activity. Thus, while native alpha-thrombin is capable of evoking DNA synthesis in G0/G1-arrested cells, neither enzymatically inactive thrombin (eg, iPR2P-alpha-thrombin) nor partially degraded thrombin (eg, gamma-thrombin) shares in this capability. Data from our laboratory have shown that thrombin is chemotactic for peripheral blood monocytes and for cells belonging to the monocyte/macrophage family and that this activity is not dependent upon thrombin's enzymatic properties. Our recent findings demonstrate that thrombin also serves as a growth factor for these cells, and this mitogenic capability is independent of esterolytic function and resides in the same region of the molecule as that responsible for chemotaxis. Additionally, by means of techniques such as computer modeling and peptide synthesis, we have now been able to delineate a distinct mitogenic subsite within this chemotactic thrombin sequence. Thus, the sequence in the thrombin B chain that mediates chemotaxis represents a true cell interactive exosite additionally capable of stimulating growth and possibly other biological functions in cells of macrophage/monocyte lineage.

Amino Acid Sequence↗
PubMed2004

Proteomic analysis of protein changes developing in rat hippocampus after chronic antidepressant treatment: Implications for depressive disorders and future therapies.

It is recognized that monoamine reuptake inhibitors (MARIs) exert beneficial effects in the treatment of major depression and general anxiety disorder. The aim of this study was to identify proteins regulated by this class of antidepressant using a proteome differential profiling approach. Either venlafaxine or fluoxetine was administered systemically to adult rats for 2 weeks, and protein patterns from rat hippocampal cytosolic extracts were compared by two-dimensional gel electrophoresis. Silver-stained protein spots displaying differential expression were identified by mass spectrometry. Thirty-three protein spots were modulated by both drug treatments compared to controls. The classification of several proteins that were sorted by function suggested convergent pathway activities for both MARIs at the post-receptor level. These included proteins associated with neurogenesis (insulin like growth factor 1 (IGF-1), glia maturation factor [GMF]-beta), outgrowth/maintenance of neuronal processes (hippocampal cholinergic neurostimulating peptide [HCNP], PCTAIRE-3), and with neural regeneration/axonal guidance collapsin response mediator protein (CRMP-2) systems. Other modulated proteins indicated an increase in neuronal vesicular cell trafficking and synaptic plasticity (Ras-related protein 4a (Rab4a), Ras-related protein 1b (Rab1b), heat shock protein 10 [HSP10]), as well as neurosteroidogenic (hydroxysteroid sulfotransferase A) and possible anti-apoptotic (dimethylargininase-1 L-N,N-dimethylarginine dimethylaminohydrolase-1 [DDAH-1], pyruvate dehydrogenase-E1 [PDH-E1], antioxidant protein-2 [AOP-2]) pathway-mediated regulatory events. Parallel studies to investigate further the effects of venlafaxine and fluoxetine on adult hippocampal neurogenesis in vivo by quantitative bromodeoxyuridine immunolabeling revealed a significant drug-induced increase in the proliferation rate and long-term survivability of progenitor stem cells located in the subgranular zone. These data suggest that MARIs share wide-ranging proteome changes within the hippocampal formation, beyond 5-HT/NE neurotransmission. This may reflect long-term functional adaptations required for antidepressant activity.

Animals↗
PubMed1996

Inhibition of TEA-induced LTP by aluminum.

Brief application of tetraethylammonium (TEA) to hippocampal slices causes long-term potentiation (TEA LTP) at synapses of CA1 pyramidal neurons characterized by a long-lasting increase of field excitatory postsynaptic potential (fEPSP) slope and population spike (PS) amplitude. Since this kind of potentiation requires the activation of voltage-dependent calcium channels, we examined the effect of the inorganic calcium channel blocker aluminum, which has been shown to impair tetanus-induced LTP (eLTP). We found that Al inhibited in a concentration-dependent manner both fEPSP slope and PS amplitude potentiation by TEA; 0.68 microgram/ml A1 attenuated TEA LTP, while a complete block of long-lasting potentiation was obtained for 2.7 micrograms/ml Al. Occlusion experiments revealed that both concentrations of Al allowed the induction of eLTP 60 min after TEA/Al exposure. However, longer application (15 min) of 2.7 micrograms/ml Al before the induction of TEA LTP prevented the subsequent induction of eLTP although no significant differences concerning the action on TEA LTP were observed. This indicates a general loss of neuronal plasticity which might be due to progressive neuronal cell damage. Since the effective concentration range of Al is directly comparable to the action of Al on eLTP, our data provide evidence for shared mechanisms of both potentiations. Although based on different induction mechanisms, Ca2+ is assumed to be a general intracellular trigger for both forms of LTP and thus it can be hypothesized that the neurotoxic action of Al is due to interference with Ca(2+)-dependent processes by inhibition of calcium conductances.

Aluminum↗
PubMed1984

Evidence for polymorphism of MB3 antigens among three HLA-D clusters associated with HLA-DR4.

In a previous study, we showed that the three hitherto serologically indistinguishable HLA-D specificities associated with HLA-DR4, HLA- DYT , HLA- DKT2 , and HLA-Dw4 can be distinguished on the basis of their reactivity with two distinct Ia-like-specific monoclonal antibodies, HU-18 and HU-23. In this study, we attempted to identify and characterize Ia-like molecules recognized by HU-18 and HU-23 on a molecular level because Ia subsets (HLA-DR, MB, MT, or SB) identified by them remained unknown. The results of sequential coprecipitation assays and two-dimensional gel analyses showed that both HU-18 and HU-23 recognize antigenic determinants borne on MB3 but not on HLA-DRw6.2 molecules. Because the two monoclonal antibodies, specific for determinants carried on MB3 molecules, show distinct reactivity against homozygous typing cells defining HLA- DYT , HLA- DKT2 , and HLA-Dw4, all of which share DR4- MB3 , the data indicate that these three HLA-D clusters associated with HLA-DR4 possess distinct MB3 molecules, suggesting the existence of polymorphism in MB3 antigens.

Antibodies, Monoclonal↗