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At least 1,297 records · Page 72Linked to original sources
PubMed1996

The 'new' risk factors for SIDS: is there an association with the ethnic and place of birth differences in incidence in Victoria, Australia?

Home interviews and assessments of infant development were carried out in a project examining the family environments of four groups of women and their infants with different risks of sudden infant death syndrome (SIDS): a reference group of 200 Australian-born (Anglo-Celtic) women (SIDS incidence, 2.04/1000), 101 women born in Asia (0.97/1000) and 56 women born in Southern Europe (0.58/1000) whose infants have a very low risk of SIDS and 102 women who chose to give birth at home whose infants have a high risk of SIDS (8.9/1000). As these differences are not explained by the classic social and perinatal risk factors, it was possible that they might be attributable to the 'new' risk factors: prone sleeping position, not fully breast feeding, exposure to cigarette smoke and bed sharing. Analysis of the data did not show this expected association: there were no significant differences between the groups in the use of the prone position; although only two Asian-born women smoked, infant exposure to cigarette smoke was similar in the other three groups; choice of infant feeding method did not fit the expected pattern--homebirth infants were fully breast fed almost exclusively while this was so for only about 50% of infants in both low risk groups; more than 50% of homebirth families slept with their infants, but bed sharing was also significantly more common in the Asian-born group than in the reference group.

Asia↗
PubMed2004

Comparison of risk factors for squamous cell and adenocarcinomas of the cervix: a meta-analysis.

While most cancers of the uterine cervix are squamous cell carcinomas, the relative and absolute incidence of adenocarcinoma of the uterine cervix has risen in recent years. It is not clear to what extent risk factors identified for squamous cell carcinoma of the cervix are shared by cervical adenocarcinomas. We used data from six case-control studies to compare directly risk factors for cervical adenocarcinoma (910 cases) and squamous cell carcinoma (5649 cases) in a published data meta-analysis. The summary odds ratios and tests for differences between these summaries for the two histological types were estimated using empirically weighted least squares. A higher lifetime number of sexual partners, earlier age at first intercourse, higher parity and long duration of oral contraceptive use were risk factors for both histological types. Current smoking was associated with a significantly increased risk of squamous cell carcinoma, with a summary odds ratio of 1.47 (95% confidence interval: 1.15-1.88), but not of adenocarcinoma (summary odds ratio=0.82 (0.60-1.11); test for heterogeneity between squamous cell and adenocarcinoma for current smoking: P=0.001). The results of this meta-analysis of published data suggest that squamous cell and adenocarcinomas of the uterine cervix, while sharing many risk factors, may differ in relation to smoking. Further evidence is needed to confirm this in view of the limited data available.

Adenocarcinoma↗
PubMed2005

Differential membrane localization of ERas and Rheb, two Ras-related proteins involved in the phosphatidylinositol 3-kinase/mTOR pathway.

Two Ras-related proteins, ERas and Rheb, which are involved in the phosphatidylinositol 3-kinase pathway, display high GTP affinity and have atypical CAAX motifs. The factors governing the intracellular localization of ERas and Rheb are incompletely understood. In the current study, we show by confocal microscopy that ERas is localized to the plasma membrane, whereas Rheb is confined to the endomembranes. Membrane localization of the two proteins was abolished by mutation of the cysteine of the CAAX motif. Membrane targeting was also abolished by a farnesyltransferase inhibitor but not by a geranylgeranyltransferase inhibitor. In mouse fibroblasts deficient in either Rce1 (Ras converting enzyme 1) or Icmt (isoprenylcysteine carboxyl methyltransferase), ERas was mislocalized mainly to the Golgi apparatus, whereas Rheb showed diffuse localization. Mutation of cysteines in the hypervariable region of ERas prevented the plasma membrane localization of ERas, very strongly suggesting that palmitoylation of the cysteines is essential for membrane targeting. The hypervariable region of Rheb does not contain cysteines or polybasic residues, and when it was replaced with the hypervariable region of H-Ras, Rheb displayed plasma membrane localization. These data indicate that ERas shares the same posttranslational modifications with H-Ras and N-Ras and is localized at the plasma membrane. Rheb also shares the same membrane-targeting pathway but because of the absence of palmitoylation is located on endomembranes.

Alkyl and Aryl Transferases↗
PubMed1997

Familial cavernous malformations in a large French kindred: mapping of the gene to the CCM1 locus on chromosome 7q.

OBJECTIVES: To characterise clinically a large French family affected with cerebral cavernomas and to check for linkage of this condition to chromosome 7. METHODS: A family, originating from Normandy and in which five members had undergone surgery for cavernomas, was extended. All members older than 18 were studied clinically and by neuroimaging. Genetic linkage analysis was conducted using 11 polymorphic microsatellite markers located between D7S502 and D7S479. RESULTS: The family included three generations. Among the 25 members investigated, 11 had an abnormal cerebral MRI, eight of them being symptomatic, and 12 were asymptomatic with a normal MRI. The status of the two remaining members could not be established on the basis of clinical and MRI data. The family reported shares some striking features with other previously linked families--namely, a high clinical penetrance and the presence of multiple lesions within most of the affected members. A lod score of 4.04 was obtained with marker D7S657 with no recombinant. Significant lod scores were also obtained with D7S524 (Zmax=3.32 at 0=0.00) and D7S630 (Zmax=3.44 at 0=0.00). These results establish linkage of the condition found in this family to chromosome 7. Haplotype analysis strongly suggests that the gene is telomeric to D7S802 and centromeric to D7S479. CONCLUSIONS: These data confirm linkage of cerebral cavernous malformations to chromosome 7 in a non-Hispanic family.

Adolescent↗
PubMed1989

Constitutive endocytosis of HLA class I antigens requires a specific portion of the intracytoplasmic tail that shares structural features with other endocytosed molecules.

HLA class I antigens present in the human leukemia T-cell line HPB-ALL are shown to be endocytosed in the absence of specific antibodies. In 1 hr, approximately 10% of class I molecules initially present at the cell surface are found intracellularly. Genetically engineered mutants of the HLA-A2 gene lacking exon 6 or 7 or both were used to analyze whether the cytoplasmic region contributes to the internalization. The results indicate that amino acids encoded by exon 7 (spanning amino acid residues 323-340) are required for internalization, while deletion of exon 6 had no effect. In addition, a comparison of the cytoplasmic sequences of receptors that are known to be internalized via coated pits and the present data revealed that they share a structural feature that could constitute a specific signal required for endocytosis.

Antigen-Antibody Complex↗
PubMedDate not supplied

Multicenter epidemiologic and health services research on therapeutics in the HMO Research Network Center for Education and Research on Therapeutics.

Research and education programs in therapeutics that combine the data, organizational capabilities, and expertise of several managed care organizations working in concert can serve an important role when a single organization is not large enough to address a question of interest, when diversity in populations or delivery systems is required, and when it is necessary to establish consistency of results in different settings. Nine members of the HMO Research Network, a consortium of health maintenance organizations (HMOs) that perform public domain research, have formed a Center for Education and Research on Therapeutics (CERT), sponsored by the Agency for Healthcare Research and Quality, to conduct multicenter research in therapeutics. The CERT uses a distributed organizational model with shared leadership, in which data reside at the originating organization until they are needed to support a specific study. Extraction of data from the host computer systems, and some manipulation of data, is typically accomplished through computer programs that are developed centrally, then modified for use at each site. For complex studies, pooled analysis files are created by a coordinating center, and then analysed by investigators throughout the HMOs. It is also possible to contact HMO members when necessary. This multicenter environment has several benefits, addressing: (1) a wide array of questions about the safety and effectiveness of therapeutics, (2) the impact of efforts to change clinicians' and patients' behavior, and (3) pharmacoeconomic and pharmacogenetic questions.

Community Networks↗
PubMed2004

Avoidance of animal experiments in the new EU Chemicals Regulation - opportunities and problems from the point of view of animal welfare.

On 29 October 2003, the European Commission forwarded the "Proposal for a Regulation of the European Parliament and of the Council concerning the Registration, Evaluation, Authorization and Restriction of Chemicals (REACH), establishing a European Chemicals Agency and amending Directive 1999/45/EC and Regulation (EC) on Persistent Organic Pollutants" to the European Parliament and the Council for adoption under the so-called co-decision procedure. From the point of view of animal welfare it is to be welcomed that it is envisaged better to protect humans and the environment from unknown risks through chemical substances. However, in order to ensure that this goal can be met, extensive amendments to the proposed draft are requested: Instead of continuing to perform animal tests, relevant and reliable non-animal testing strategies should be implemented. Before considering testing, all existing data must be made available, shared and evaluated. This request should be enforced in the new Regulation through an adequate mandatory system. Data requirements must be tailored to the specific substance, to ensure that only such information is collected that is necessary for its safe handling by workers and consumers. Missing data should be determined with non-animal test methods. Finally, the European Union and its Member States are called to provide adequate funding for alternative method research without delay and to call for tenders on those information-gaps that currently prevent the implementation of an entirely non-animal testing strategy, so that such new methods will be available in time for application under the REACH system.

Animal Experimentation↗
PubMed1999

Isolation and molecular characterization of AKAP110, a novel, sperm-specific protein kinase A-anchoring protein.

Agents that increase intracellular cAMP are potent stimulators of sperm motility. Anchoring inhibitor peptides, designed to disrupt the interaction of the cAMP-dependent protein kinase A (PKA) with A kinase-anchoring proteins (AKAPs), are potent inhibitors of sperm motility. These data suggest that PKA anchoring is a key biochemical mechanism controlling motility. We now report the isolation, identification, cloning, and characterization of AKAP110, the predominant AKAP detected in sperm lysates. AKAP110 cDNA was isolated and sequenced from mouse, bovine, and human testis libraries. Using truncated mutants, the RII-binding domain was identified. Alignment of the RII-binding domain on AKAP110 to those from other AKAPs reveals that AKAPs contain eight functionally conserved positions within an amphipathic helix structure that are responsible for RII interaction. Northern analysis of eight different tissues detected AKAP110 only in the testis, and in situ hybridization analysis detected AKAP110 only in round spermatids, suggesting that AKAP110 is a protein found only in male germ cells. Sperm cells contain both RI, located primarily in the acrosomal region of the head, and RII, located exclusively in the tail, regulatory subunits of PKA. Immunocytochemical analysis detected AKAP110 in the acrosomal region of the sperm head and along the entire length of the principal piece. These data suggest that AKAP110 shares compartments with both RI and RII isoforms of PKA and may function as a regulator of both motility- and head-associated functions such as capacitation and the acrosome reaction.

A Kinase Anchor Proteins↗
PubMed1993

A variable-radius measure of local hospital market structure.

OBJECTIVE: To provide a radius measure of the structure of local hospital markets that varies with hospital characteristics and is available for all hospitals in the United States. DATA SOURCES: 1982 American Hospital Association (AHA) Survey of Hospitals, 1982 Area Resource File (ARF), and 1983 California Office of Statewide Health Planning and Development (OSHPD) discharge abstracts. STUDY DESIGN: The OSHPD data were used to measure the radii necessary to capture 75 percent and 90 percent of each hospital's admissions. These radii were used as the dependent variables in regression models in which the independent variables were from the AHA and ARF. To estimate predicted market radii, the estimated parameters from the California models were applied to all nonfederal, short-term, general hospitals in the continental United States. These radii were used to define each hospital's service area, and all other hospitals within the calculated radii were considered potential competitors. Using this definition, we calculated two measures of local market structure: the number of other hospitals within the radius and a Herfindahl-Hirschman Index based on the distribution of hospital bed shares in the market. DATA EXTRACTION METHODS: These measures were calculated for all nonfederal, short-term, acute care hospitals in the continental United States for whom complete data were available (N = 4,884). CONCLUSIONS: These measures are available from the authors on computer-readable diskette, matched to hospital identifiers.

Ancillary Services, Hospital↗
PubMed1992

HEB, a helix-loop-helix protein related to E2A and ITF2 that can modulate the DNA-binding ability of myogenic regulatory factors.

Proteins containing the basic-helix-loop-helix (B-HLH) domain have been shown to be important in regulating cellular differentiation. We have isolated a cDNA for a human B-HLH factor, denoted HEB, that shares nearly complete identity in the B-HLH domain with the immunoglobulin enhancer binding proteins encoded by the E2A and ITF2 genes (E proteins). Functional characterization of the protein expressed from this cDNA indicates that HEB is a third member of the E-protein class of B-HLH factors. HEB mRNA was found to be expressed in several tissues and cell types, including skeletal muscle, thymus, and a B-cell line. HEB, ITF2, and the E12 product of the E2A gene all bound to a similar spectrum of E-box sequences as homo-oligomers. All three factors also formed hetero-oligomers with myogenin, and the DNA-binding specificity and binding off-rates (dissociation rates) were modulated after hetero-oligomerization. Both homo- and hetero-oligomers of these proteins were able to distinguish between very closely related E-box sequences. In addition, HEB was shown to form hetero-oligomers with the E12 and ITF2 proteins. Finally, HEB was able to activate gene expression. These data demonstrate that HEB shares characteristics with other E proteins and show that HEB can interact with members of both the myogenic regulatory class and the E-protein class of B-HLH factors. HEB is therefore likely to play an important role in regulating lineage-specific gene expression.

Amino Acid Sequence↗
PubMed1997

Tc7, a Tc1-hitch hiking transposon in Caenorhabditis elegans.

We have found a novel transposon in the genome of Caenorhabditis elegans. Tc7 is a 921 bp element, made up of two 345 bp inverted repeats separated by a unique, internal sequence. Tc7 does not contain an open reading frame. The outer 38 bp of the inverted repeat show 36 matches with the outer 38 bp of Tc1. This region of Tc1 contains the Tc1-transposase binding site. Furthermore, Tc7 is flanked by TA dinucleotides, just like Tc1, which presumably correspond to the target duplication generated upon integration. Since Tc7 does not encode its own transposase but contains the Tc1-transposase binding site at its extremities, we tested the ability of Tc7 to jump upon forced expression of Tc1 transposase in somatic cells. Under these conditions Tc7 jumps at a frequency similar to Tc1. The target site choice of Tc7 is identical to that of Tc1. These data suggest that Tc7 shares with Tc1 all the sequences minimally required to parasitize upon the Tc1 transposition machinery. The genomic distribution of Tc7 shows a striking clustering on the X chromosome where two thirds of the elements (20 out of 33) are located. Related transposons in C. elegans do not show this asymmetric distribution.

Animals↗
PubMed1999

Name-based surveillance and public health interventions for persons with HIV infection. Multistate Evaluation of Surveillance for HIV Study Group.

Name-based surveillance of HIV infection is the law in 31 U.S. states but remains controversial. This policy can be advocated solely to support surveillance of the epidemic, but a frequent argument is that it also provides a public health benefit by allowing follow-up of HIV-infected persons. These persons can then receive timely medical care and can be assisted with notifying sex and needle-sharing partners. Few comparative data are available to evaluate the outcomes of these interventions. In five states with name-based surveillance of HIV infection, the Multistate Evaluation of Surveillance for HIV Study Group surveyed a cross-sectional probability sample of persons with AIDS who tested positive for HIV before the date of their AIDS diagnosis. Health department follow-up of a reported HIV infection was not associated with more timely receipt of medical care after a positive HIV test result. Only 8.6% of persons who delayed medical care after their first positive HIV test result gave concern about being reported by name as a reason; no person gave it as the main reason. Persons who were tested anonymously and those who were tested confidentially did not differ in the mean number of sex and needle-sharing partners notified: Those tested anonymously reported personally notifying 3.85 sex and needle-sharing partners, and those tested confidentially reported notifying-personally and through the health department-3.80 partners. Many researchers and policymakers believe that name-based surveillance of HIV infection will have positive or negative effects on partner notification and access to health care. These results suggest that the potential for such effects has been exaggerated.

Anonymous Testing↗
PubMed2001

Differentiation and clonality of lesional lymphocytes in pityriasis lichenoides chronica.

BACKGROUND: Pityriasis lichenoides chronica (PLC) and pityriasis lichenoides et varioliformis acuta (PLEVA) are benign T-cell diseases that share several overlapping clinicopathologic features, leading many to believe that they exist as a spectrum rather than as single entities. Previous molecular studies have shown that PLEVA is a clonal lymphoproliferative disorder. To further characterize the immunohistologic features of PLC and to determine whether PLC demonstrates clonality, we studied 6 cases of PLC using a frozen section-immunoperoxidase technique and polymerase chain reaction/denaturing gradient gel electrophoresis. OBSERVATIONS: All 6 cases showed a mild to moderate superficial and deep perivascular infiltrate composed predominantly of CD4(+) T cells, admixed with Langerhans cells and macrophages; most were associated with an HLA-DR(+) epidermis. Three of 6 cases involved monoclonal T-cell receptor gamma (TCR gamma) gene rearrangements detected by V gamma 1-8/J gamma 1-2 and V gamma 9/J gamma 1-2 primers. CONCLUSIONS: Our findings enhance existing data showing that PLC shares many immunohistologic features with PLEVA and indicating that PLC is frequently a clonal T-cell disease. This provides further evidence that PLC and PLEVA are interrelated processes within the larger group of T-cell lymphoproliferative disorders.

Adult↗
PubMed1984

Nonspecific cytotoxic cells in fish (Ictalurus punctatus). III. Biophysical and biochemical properties affecting cytolysis.

Nonspecific cytotoxic cells (NCC) from the catfish (Ictalurus punctatus) may comprise a population of cells that are responsible for cellular immunity in the fish. NCC kill a wide variety of transformed target cells, and previous studies have indicated that NCC share properties with mammalian natural killer cells. In the present study, many biophysical and biochemical properties of NCC were defined. NCC were nylon wool nonadherent and adherent. NCC activity was also enriched in plastic nonadherent cells. NCC were nonphagocytic (for carbonyl iron), and they did not bind to Sephadex G-10. Characterization of NCC by density gradient centrifugation indicated that they comprise a relatively homogenous population of cytolytic cells that band at 45.5% Percoll. Moderate to high doses (500-2500 R) of X-irradiation produced a stimulatory effect on NCC lysis of labeled target cells. Additional studies indicated that a soluble suppressor protein in catfish serum (CFS) regulated NCC activity. This S. aureus protein A binding component isolated from CFS suppressed NCC activity. Analysis by SDS-PAGE indicated that the soluble regulatory protein had properties similar to immunoglobulin. These data indicate that NCC share some biophysical properties with mammalian natural killer cells. In addition, NCC appear to be under partial cell regulation by a radiation sensitive suppressor cell and also by a soluble regulator serum immunoglobulin component.

Animals↗
PubMed1997

Insulin-induced maturation of Xenopus oocytes is inhibited by microinjection of a Brassica napus cDNA clone with high similarity to a mammalian receptor for activated protein kinase C.

A cDNA clone encoding a WD-40 repeat protein (BGB1) was characterized in Brassica napus L. The clone contained an open reading frame of 327 amino acid residues almost entirely composed of seven segments of WD-40 repeats. Among the WD-40 repeat proteins, BGB1 showed high similarity (63% identity) to a rat intracellular receptor for protein kinase C (RACK1) that functions in the translocation of activated protein kinase C (PKC) from the cytosolic fraction to the membrane fraction. BGB1 also had two sequence motifs involved in binding of RACK1 to PKC. The cDNA clone, when carried in a Xenopus oocyte expression vector and injected into Xenopus laevis oocytes, inhibited insulin-induced maturation of the oocytes, a PKC-mediated pathway, and this inhibition was accompanied by reduction of PKC in the membrane fraction, as in the case of mammalian RACKs. The data show that BGB1 shares some common functional characteristics with the mammalian RACK1 along with the structural similarity, suggesting that a mammalian RACK1-related cellular process might be operating in plants. Southern blot analyses of the genome of B. napus and Arabidopsis thaliana (L.) Heynh. revealed that BGB1-related genes constitute a small multigene family in both species. An approximately 1.4-kb transcript was constitutively expressed in all organs examined.

Amino Acid Sequence↗
PubMed1975

SDC experiences with large data bases.

SDC operates a large-data-base system that permits users all over the United States and in several foreign countries to search very large bibliographic files interactively, by means of a terminal and telephone connection. Developing extensive use of such systems requires not only technical considerations--such as proper selection and handling of data base elements--but also a massive educational effort, to help provide the large user community necessary to share the sizable costs of data base acquisition, file development, and storage. The growing acceptance of on-line retrieval services attests to the success of that effort, as well as to their inherent cost-effectiveness.

Computers↗
PubMed2000

Epidemic transmission of human immunodeficiency virus in renal dialysis centers in Egypt.

In 1993 an epidemic of human immunodeficiency virus (HIV) infection occurred among 39 patients at 2 renal dialysis centers in Egypt. The centers, private center A (PCA) and university center A (UCA) were visited, HIV-infected patients were interviewed, seroconversion rates at UCA were calculated, and relatedness of HIV strains was determined by sequence analysis; 34 (62%) of 55 patients from UCA and 5 (42%) of 12 patients from PCA were HIV-infected. The HIV seroconversion risk at UCA varied significantly with day and shift of dialysis session. Practices that resulted in sharing of syringes among patients were observed at both centers. The analyzed V3 loop sequences of the HIV strain of 12 outbreak patients were >96% related to each other. V3 loop sequences from each of 8 HIV-infected Egyptians unrelated to the 1993 epidemic were only 76%-89% related to those from outbreak strains. Dialysis patients may be at risk for HIV infection if infection control guidelines are not followed.

Adolescent↗
PubMed2006

The clinical perspective of large scale projects: a case study of multiparametric MR imaging of pediatric brain tumors.

Current developments in medical information technologies provide the clinical researcher with overwhelming amounts of data that need to be retrieved, organized, analyzed, and shared using secure, efficient, and robust protocols. The development of a local research database can provide an infrastructure for improved data management and detailed data analysis. For example, a pediatric brain tumor database of magnetic resonance imaging data, including conventional MRI imaging, hemodynamic MRI, diffusion weighted MRI and MR spectroscopic imaging, combined with neuropathological and neurological evaluation data, will significantly enhance the assessment and treatment of pediatric brain tumor patients. Furthermore, a negotiation system by which different clinical research facilities can share and combine data will permit re-analyses and meta-analyses of large data arrays that are beyond the focus or time constraints of the original researchers. Such a system will greatly enhance the utility of different data sets to a wide array of scientists. At present, efforts to organize medical data locally and between different sites is limited by diversity, interoperability, security, and accountability difficulties.

Brain Neoplasms↗