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Hydrolytic endonucleolytic ribozyme (HYER): Systematic identification, characterization and potential application in nucleic acid manipulation.

Group II introns are transposable elements that can propagate in host genomes through the "copy and paste" mechanism. They usually comprise RNA and protein components for effective propagation. Recently, we found that some bacterial GII-C introns without protein components had multiple copies in their resident genomes, implicating their potential transposition activity. We demonstrated that some of these systems are active for hydrolytic DNA cleavage and proved their DNA manipulation capability in bacterial or mammalian cells. These introns are therefore named HYdrolytic Endonucleolytic Ribozymes (HYERs). Here, we provide a detailed protocol for the systematic identification and characterization of HYERs and present our perspectives on its potential application in nucleic acid manipulation.

RNA, Catalytic↗

Hyers-ulam stability of functional equations with a square-symmetric operation.

The stability of the functional equation f(x composite function y) = H(f(x), f(y)) (x, y in S) is investigated, where H is a homogeneous function and composite function is a square-symmetric operation on the set S. The results presented include and generalize the classical theorem of Hyers obtained in 1941 on the stability of the Cauchy functional equation.

Journal Article↗

Health issues and the Pala Indian Reservation, 1903-20.

Joel R. Hyer investigates health conditions on one Indian reservation in Southern California during the first two decades of the twentieth century. Hyer contends that unsanitary conditions on the Pala Reservation actually facilitated the spread of diseases among local Cupeño, Luiseño, and Kumeyaay Indians. He also describes how the United States federal government employed doctors, field matrons, and others to promote good health and combat disease among Indians at Pala. The author asserts that, despite their altruistic intentions, some of these government workers attempted to discourage local indigenous peoples from consulting their shamans for medical attention - Native healers whose extensive knowledge of roots and herbs had cured many forms of illness for years. In addition, the teacher at the reservation's day school sought to prevent the spread of disease among her Indian pupils by exposing them to American modes of health care. Furthermore, Hyer maintains that one national health program, the "Save the Babies" campaign, was successful on the Pala Reservation because Indian mothers believed in it and followed specific guidelines to lower mortality rates among their own children. Throughout his essay, the author addresses the pressures of assimilation and acculturation that were so accute at this time in the United States. Hyer concludes by suggesting that many of his findings reflect broader health trends on Indian reservations throughout the United States during this period.

Acculturation↗

Downregulation of c-FLIP sensitizes DU145 prostate cancer cells to Fas-mediated apoptosis.

Although DU145 prostate cancer cells are resistant to exogenously applied Fas agonist CH-11 (anti-Fas monoclonal antibody), Fas-resistance can be overcome using a FasL expressing adenovirus (AdGFPFasL(TET)) [Hyer et al., Molecular Therapy, 2000; 2:348-58 (ref.12)]. The purpose of this study was to try to understand why DU145 cells are resistant to CH-11 and determine the signaling pathway utilized by AdGFPFasL(TET) to induce apoptosis in these Fas-resistant cells. Using immunoblot analysis, we show that AdGFPFasL(TET) is capable of initiating the classic Fas-mediated apoptotic pathway in DU145 cells, which includes activation of caspases-8, -3, -7, and -9, BID cleavage, cytochrome c release from mitochondria, and PARP cleavage. In contrast, CH-11 binds to Fas, but is unable to transmit the death signal beyond the plasma membrane suggesting a block at the DISC (death inducing signaling complex). The anti-apoptotic protein c-FLIP (cellular Flice-like inhibitory protein), which has been shown to inhibit Fas-mediated apoptosis at the DISC, was down-regulated following AdGFPFasL(TET) treatment prompting us to investigate its role in inhibiting CH-11-induced cell death. Using c-FLIP anti-sense oligonucleotides to down-regulate c-FLIP we sensitized DU145 cells to CH-11-induced apoptosis. These data suggest that c-FLIP may play a critical role in regulating Fas-mediated apoptosis in prostate cancer cells and that modulation of c-FLIP may enhance Fas signaling based therapies.

Apoptosis↗

Lidocaine diffusion in five tissue expanders: an in vitro and in vivo study.

Previous work in our laboratory has demonstrated that tissue expanders are permeable to lidocaine. In this two-part study, we assessed the in vitro lidocaine diffusion in the following five common tissue expanders: Dow Corning, McGhan, Cox-Uphoff, Hyer-Schulte (Mentor), and Surgitek. In part 1, we demonstrated that wall thickness appeared to be the major determinant for diffusion. Part 2 reports an in vivo study of lidocaine diffusion from tissue expanders used for breast reconstruction. We initially determined that there is incomplete mixing between the valve and connecting tubing and the contents of the expanders, over the period of 1 week. We subsequently examined the lidocaine diffusion from seven tissue expanders placed in a submuscular position for breast reconstruction. The rate of lidocaine diffusion was highly variable, but on average was about 3% per day.

Diffusion↗

Stature analysis of Perris Indian school students, 1894-99.

Keller uses anthropometric measurement to examine the health of Native American children attending the Perris Indian School of Southern California during the last decade of the nineteenth century. She compares the mean stature of children at Perris with similar historical and contemporary populations and analyzes their nutrition and linear patterns which reflect on the health of given populations. In accordance with anthropometric research, the taller the population, the better the population's overall health. Keller shows that in comparison to other populations, the children attending Perris Indian School would be considered the "tallest in the world." Such a conclusion contradicts research in this volume by Trafzer and Hyer. Keller questions her findings. She argues that Native parents clearly privileged their children in terms of food, but that the methodology she employs does not take into consideration variables such as genetics, ethnicity, or culture. Administrators screened students attending the school to exclude those with illnesses or physical disabilities. The healthiest children attended Perris while the remainder of the Native population in the region was under stress due to government policies and poverty.

Anthropometry↗

The phase II urokinase-streptokinase pulmonary embolism trial: a national cooperative study.

The controlled clinical trials of thrombolytic agents in the United States have been carried out in two phases, under the auspices of the National Heart and Lung Institute. Phase I was devoted to the comparison of 12-hour Urokinase (12h-UK) followed by heparin (H) with heparin alone in patients with acute pulmonary embolism (Walsh et al. 1969). The results showed that pateints treated with UK had more rapid and gretaer resolution of pulmonary thromboemboli in the first twenty-four hours of therapy than patients treated with H alone, as assessed by serial pulmonary angiography, hemodynamics and lung scanning (The Urokinase Pulmonary Embolism Trial, 1970, 1973; Hyers et al. 1970). Because of the ralatively small size of the Trial and the low mor tality of treated pulmonary embolism, mortality differences were not sought-nor was one found. Although there was early difference in amount of clot resolution, patients treated with H alone showed similar improvement by two weeks. The phase II Urokinase-Streptokinase Pulmonary Embolism Trial (USPET) was begun to assess the comparative results of UK and Streptokinase (SK) therapy. Because of favorable results obtained with SK in other countries, it was deemed necessary to make this comparison (Browse and James, 1964; Hirsh et al. 1968; Miller et al. 1969, 1971; Chesterman et al. 1969). A third group, 12-hour UK, was added to relate this study (24-hour UK and SK) with the Phase I results which employed only a 12-hour infusion of UK. This Phase II Trial represents the first controlled, randomized study of UK and SK in thromboembolic disorders.

Angiography↗

[External ophthalmomyiasis by Oestrus ovis from a beach in Var].

In the month of June, a young women on a beach in Hyeres, France, was afflicted by a sudden burning sensation in both eyes. Emergency room examination of the conjunctiva and conjunctival cul-de-sacs revealed the presence of moving organisms 1 mm. The diagnosis was external ophthalmomyiasis. Subsequent investigation of the site of contamination showed that it was located two kilometers from a herd of sheep. The purpose of this report is to underline the possibility of this albeit rare occurrence in France and to review diagnostic and therapeutic methods. In most cases accidental summertime contamination in man leads to minor clinical manifestations. Examination of the conjunctiva and conjunctival cul-de-sacs is necessary to remove larvae. Larvae can be easily identified on the basis of microscopic examination criteria. Identification is important to allow clinical physician to institute proper symptomatic treatment, attempt complete elimination of all larvae, and reassure the patient. Possible persistence of larvae and potential complications justify follow-up examination.

Adult↗

[The parasite fauna of the chub mackerel (Scombridae: Scomber japonicus Houttuyn, 1782) in the central-eastern Atlantic (Atlantic coast of the Northern Africa and the Azores Archipelago banks)].

The parasite fauna of the chub mackerel Scomber japonicus Houtuym, 1782 was studied from the neritic areas of Morocco, Western Sahara, Mauritania and from the banks of the Azores Archipelago (the Great Meteor Bank, the Hyeres Bank and the Irving Bank) in 1994-2001. Twenty eight species of parasites of following group have been were found: Coccidia (1 species), Microsporidia (1), Myxosporea (4), Monogenea (4), Cestoda (5), Trematoda (5), Acanthocephala (1) and Nematoda (6). The differences between mackerel parasite fauna in the neritic areas and from of the Azores Archipelago banks were established. Peculiarities of the mackerel parasite fauna in two areas (Morocco--Western Sahara and Mauritania) corroborate the hypothesis that two populations of chub mackerel are available: "Sahara-Moroccan" and "Senegal-Mauritanian". Ontogenetic variability of parasite fauna was related to food demands of mackerel and its feeding habits in the areas Morocco and Mauritania. Kudoa histolytica has negative influence on the commercial value of S. japonicus. These parasites were localized in the muscles of mackerel from Mauritania (40%, TL = 20-25 cm). Parasites being dangerous for human health were presented by larvae of Bolbosoma sp. (occurred on the banks of the Azores Archipelago), Anisakis simplex and Contracaecum sp. (occurred in all areas investigated).

Acanthocephala↗

Management of venous thromboembolism: past, present, and future.

Venous thromboembolism, including deep vein thrombosis and pulmonary embolism, represents a significant source of morbidity and mortality in the United States and worldwide. The pharmacologic management of venous thromboembolic disease has witnessed significant advances since oral anticoagulant and heparin therapies began to gain widespread use more than 50 years ago. Cumulative clinical experience gained from using these 2 classes of antithrombotic agents for the prevention and treatment of venous thromboembolism in high-risk patients pointed to a number of efficacy and safety limitations. This prompted further research and the eventual introduction, in the 1980s, of low-molecular-weight heparin(s) as a potentially superior therapeutic modality. Within the last decade the pace of development of newer classes of antithrombotic agents for venous thromboembolism prevention and treatment (as well as other indications) has accelerated. Among agents at late stages of investigation are ximelagatran (a direct thrombin inhibitor), nematode anticoagulant peptide c2 (a tissue factor VIIa inhibitor), and sodium N-[8(2-hydroxylbenzoyl)amino]caprylate (SNAC)/heparin (a heparin derivative). The most recently approved agents for venous thromboembolism indications include the heparinoid, danaparoid sodium, and the newly introduced selective factor Xa inhibitor, fondaparinux.

Anticoagulants↗

Antithrombotic therapy practices in US hospitals in an era of practice guidelines.

BACKGROUND: Antithrombotic therapy is efficacious for the prevention of thromboembolic disease, but it necessitates careful risk-benefit assessment. METHODS: Antithrombotic therapy data were retrospectively collected from inpatient medical records at 38 US hospitals. Patients treated for atrial fibrillation, acute myocardial infarction, deep vein thrombosis, or pulmonary embolism and patients given prophylaxis for total knee replacement, total hip replacement, or hip fracture surgery between July 1, 2000, and June 30, 2003, were randomly selected. RESULTS: The medical records of 3778 patients (53.3% men) were included. The mean patient age was 66.1 years. Of patients with atrial fibrillation at high risk for stroke, only 54.7% received warfarin sodium, and 20.6% received neither aspirin nor warfarin. Of patients with acute myocardial infarction, only 75.5% received aspirin on hospital arrival. After orthopedic surgery procedures, only 85.6% of patients received prophylaxis with a parenteral anticoagulant agent or warfarin. In 49.4% of patients with deep vein thrombosis, pulmonary embolism, or both, unfractionated or low-molecular-weight heparin use was discontinued before an international normalized ratio of 2.0 or greater was achieved for 2 consecutive days. Patients with deep vein thrombosis or pulmonary embolism were rarely discharged from the hospital with bridge therapy (an injectable anticoagulant agent plus warfarin), although the length of hospitalization was significantly shorter than if discharged taking warfarin alone (4.0 vs 8.1 days; P < .001). CONCLUSIONS: A significant percentage of hospitalized patients do not receive adequate antithrombotic therapy for the primary and secondary prevention of thromboembolic disease.

Aged↗

Cancer risk in women exposed to diethylstilbestrol in utero.

CONTEXT: The association between in utero exposure to diethylstilbestrol (DES) and clear cell adenocarcinoma (CCA) of the vagina and cervix is well known, yet there has been no systematic study of DES-exposed daughters to determine whether they have an increased risk of other cancers. As many as 3 million women in the United States may have been exposed to DES in utero. OBJECTIVE: To determine whether women exposed to DES in utero have a higher risk of cancer after an average of 16 years of follow-up. DESIGN: A cohort study with mailed questionnaires and medical record review of reported cancer outcomes. PARTICIPANTS: A cohort of 4536 DES-exposed daughters (of whom 81% responded) and 1544 unexposed daughters (of whom 79% responded) who were first identified in the mid-1970s. MAIN OUTCOME MEASURES: Cancer incidence in DES-exposed daughters compared with population-based rates and compared with cancer incidence in unexposed daughters. RESULTS: To date, DES-exposed daughters have not experienced an increased risk for all cancers (rate ratio, 0.96; 95% confidence interval [CI], 0.58-1.56) or for individual cancer sites, except for CCA. Three cases of vaginal CCA occurred among the exposed daughters, resulting in a standardized incidence ratio of 40.7 (95% CI, 13.1-126.2) in comparison with population-based incidence rates. The rate ratio for breast cancer was 1.18 (95% CI, 0.56-2.49); adjustment for known risk factors did not alter this result. CONCLUSIONS: Thus far, DES-exposed daughters show no increased cancer risk, except for CCA. Nevertheless, because exposed daughters included in our study were, on average, only 38 years old at last follow-up, continued surveillance is warranted to determine whether any increases in cancer risk occur during the menopausal years.

Adenocarcinoma, Clear Cell↗

Long-term glycaemic control directly correlates with glomerular filtration rate in early Type 1 diabetes mellitus before the onset of microalbuminuria.

Hyperfiltration occurs early in diabetes mellitus and has been implicated in the development of microalbuminuria. Our aim was to re-examine the controversial relationship between glycaemic control and glomerular filtration (GFR) in normoalbuminuric, normotensive, non-obese patients with short duration Type 1 diabetes mellitus (DM). We studied 75 Type 1 DM patients, 35 male, aged 18-42 years, with a duration of diabetes of 4-8 years. GFR was determined by inulin clearance; hyperfiltration was defined as above 145 ml min(-1) 1.73 m(-2) (equivalent to 2 SD above mean for a control population). Analysis was by paired Student's t-testing and linear regression. GFR correlated significantly with HbA1c (r= 0.47, p < 0.0001) and fructosamine (r= 0.24, p = 0.035). Mean HbA1c and fructosamine in the 13 patients with hyperfiltration was significantly higher than in the rest of the group (HbA1c: 9.2% (95% C.I. 7.9-10.4%) vs 7.6 % (7.2-7.9), p= 0.002; fructosamine: 479 micromol l(-1) (450-507) vs 410 micromol l(-1) (388-432), p = 0.009. This significant difference persisted even when the two highest values of HbA1c or fructosamine were removed from analysis. Effective renal plasma flow, assessed by PAH clearance, also correlated in all patients with HbA1c (r=0.31, p=0.039). We conclude that poor glycaemic control directly correlates with hyperfiltration and renal hyperperfusion in early Type 1 DM.

Adult↗

Effects of Outward Bound Experience as an adjunct to inpatient PTSD treatment of war veterans.

There is a paucity of studies on Outward Bound Experiences (OBE) with adult psychiatric populations and, more notably, with trauma victims. This study evaluates the efficacy of OBE as an adjunct to specialized inpatient PTSD treatment with survivors of chronic combat-related PTSD (N = 219) at two Veterans Administration Medical Centers. On several measures of PTSD and general adaptation, results showed that the five-day OBE did not differ from standard treatment of PTSD survivors. Two other issues were addressed: identification of successful and non-successful subjects as a result of OBE, and exploration of objective versus subjective measures among this chronic group. Finally, as a post-study analysis, inferred curative components of the OBE were discussed as each appeared to impact on the participants.

Adult↗

The interaction of posttraumatic stress disorder and depression among older combat veterans.

The question whether depression is related to trauma as part of posttraumatic stress disorder (PTSD) itself or whether it represents autonomous symptoms occurring separately (from PTSD) has not been answered. We addressed two issues: (a) What is the relationship between PTSD and depression as measured by continuous measures on outcomes? and (b) By removing depression components from the PTSD diagnosis, what is the impact on standard outcomes? Older veterans from World War II or Korea were interviewed and given self-report measures on PTSD and depression. The CAPS-1 and the MMPI-D were used as the continuous measures for PTSD and depression. The outcome measures were health status, overall adjustment, social support, and physiological status. Results showed that depression influenced health status and social support: PTSD did not contribute to the equation. The CAPS-1 also was further divided into CAPS-PTSD and CAPS-D (depression) based on item content. For adjustment and health status, PTSD asserted a greater influence; for social support and heart rate, depression was the greater influence. Discussion addressed the fact that depression is an important consideration in the expression of PTSD.

Adaptation, Psychological↗

Demographic and clinical characteristics as predictors of length of hospitalization and readmission.

The present study investigated demographic and clinical characteristics of psychiatric patients in relation to the two criterion variables of length of hospitalization and readmission within 3 months of discharge. Stepwise multiple regression analysis identified five variables as the optimal set of predictors for length of hospitalization: age, history of commitment, number of prior psychiatric hospitalizations, recent employment history, and past history of suicidal behavior (R = .451). Regression analysis also identified six variables as the optimal set of predictors for readmission within 3 months of discharge: type of discharge, number of prior psychiatric hospitalizations, race, suicide attempt within 1 month prior to admission, subjective report of depression upon admission, and occupational level (R = .452). Implications of the findings for identifying short-term treatment candidates and factors related to readmission are discussed.

Adult↗