tbuckley/cabot-search huggingface dataset:
Linkage of combined factors V and VIII deficiency to chromosome 18q by homozygosity mapping.
Authors: W C Nichols, U Seligsohn, A Zivelin, V H Terry, N D Arnold, D R Siemieniak, R J Kaufman, D Ginsburg
Journal: Journal of Clinical Investigation (1997)

Combined Factors V and VIII deficiency is an autosomal recessive bleeding disorder identified in at least 58 families comprising a number of different ethnic groups. Affected patients present with a moderate bleeding tendency and have Factor V and Factor VIII levels in the range of 5-30% of normal. The highest frequency of the mutant gene is found in Jews of Sephardic and Middle Eastern origin living in Israel with an estimated disease frequency of 1:100,000. We sought to identify the gene responsible for combined Factors V and VIII deficiency using a positional cloning approach. Of 14 affected individuals from 8 unrelated Jewish families, 12 were the offspring of first-cousin marriages. After a genome-wide search using 241 highly polymorphic short tandem repeat (STR) markers, 13 of the 14 affected patients were homozygous for two closely linked 18q markers. Patients and all available family members were genotyped for 11 additional STRs spanning approximately 11 cM on the long arm of chromosome 18. Multipoint linkage analysis yielded a maximal log of the odds (LOD) score of 13.22. Haplotype analysis identified a number of recombinant individuals and established a minimum candidate interval of 2.5 cM for the gene responsible for combined Factors V and VIII deficiency. The product of this locus is likely to operate at a common step in the biosynthetic pathway for these two functionally and structurally homologous coagulation proteins. Identification of this gene should provide new insight into the biology of Factor V and Factor VIII production.
Intravenous Magnesium Sulfate in Acute Asthma-Reply
Authors: William H. Spivey
Journal: JAMA (1990)

In Reply.—  We would like to clarify some issues raised by the letter of Dr Kufs. Regarding the dose of the β-agonist used to treat the patients, this was not an arbitrary choice but rather part of an experimental protocol in which all patients were treated in a uniform manner to minimize variables in the study. Metaproterenol and albuterol were used, and all patients received two aerosolized treatments within the first 90 minutes prior to entry into the protocol. Only the patients with initial peak expiratory flow rates less than 200 L/min who failed to double this value by 90 minutes were entered into the study. The design of our study evaluated the bronchodilator activity of magnesium sulfate in a subgroup of asthmatic patients who were severely obstructed and for whom adjunct therapy would be a welcome addition to our therapeutic armamentarium. It would have been possible to adjust the
The Russian radiation legacy: its integrated impact and lessons.
Authors: M Goldman
Journal: Environmental Health Perspectives (1997)

Information about the consequences of human exposure to radiation in the former Soviet Union has recently become available. These data add new insights and provide possible answers to several important questions regarding radiation and its impact on occupational and public health. The 1986 Chernobyl accident initiated a major and early increase in childhood thyroid cancer that resulted from ingestion of iodine-131 (131I) by young children living in the most heavily contaminated areas of Belarus, Ukraine, and Russia. No significant additional cancer or other adverse medical effects have yet been reported in the affected populations and among clean-up workers. Major psychological stress independent of radiation dose has been observed in those people thought to be exposed. During the early days of the atomic energy program in the former Soviet Union, some unfortunate events occurred. The country's first atomic test in Semipalatinsk in 1949 exposed over 25,000 people downwind from the blast to significant doses of fission products, especially 131I. During the late 1940s and the early 1950s nuclear material production facilities were developed near Chelyabinsk in the South Ural Mountains, which resulted in major releases into the environment and significant overexposures for thousands of workers and nearby populations. Chronic radiation sickness was observed early in exposed workers, and increases in leukemia and other cancers were also reported. The series of plutonium inhalation-related lung cancers and fatalities among workers exposed in that first decade appears to be unique. Long-term consequences of chronic radiation sickness and four decades of follow-up are being described for the first time. Villagers downstream from the plant consumed high levels of 137Cs and 90Sr and, it is reported, manifested increases in leukemia from internal and external exposures. Although the 40-year databases for retrospective dosimetry epidemiology studies are just beginning to be integrated and evaluated, preliminary evaluations suggest that there may be graded, significant dose-rate amelioration factors for cancer and leukemia risks in workers and the general population relative to the risk data on the Japanese atomic bomb survivors. Even for plutonium-induced lung cancers in workers, such a dose-rate effect may be evident. These experiences give us insight into the consequences of protracted radiation at high and low doses and rates. If these findings are validated and confirmed, they can provide information that reduces some of the uncertainties in retrospective radiation dosimetry and radiation risk estimates (especially for low-level, chronic exposures) for activities related to medicine as well as the handling of nuclear materials and nuclear facility decommissioning, decontamination, and demilitarization.
Principles of antibody therapy.
Authors: S. J. Russell, M. B. Llewelyn, R. E. Hawkins
Journal: BMJ (1992)

The success of monoclonal antibodies in clinical practice is dependent on good design. Finding a suitable target is the most important part as other properties of the antibody can be altered by genetic engineering. Antibodies that target lymphocyte antigens offer less toxic immunosuppressive treatment than currently available drugs and the first monoclonal antibody approved for human use is an immunosuppressive agent for treating rejection of renal transplants. Human trails of monoclonal antibodies to treat septic shock have been done and antibodies are also being developed to target common pathogens such as herpes simplex virus. Although monoclonal antibodies against cancer have been much heralded, their success has been limited by the poor access to the inside of tumours. Treatment of blood cancers has been more successful and a human antibody against B cell malignancies is being clinically tested. As knowledge about natural immune responses and antibody engineering increases many more monoclonals are likely to feature in clinical practice.
Abstract 3322: Downregulation of XIAP by cord blood stem cells is associated with inhibition of heat shock protein 90 in glioblastoma
Authors: Venkata Ramesh Dasari, Kiran Kumar Velpula, Dzung H. Dinh, Andrew J. Tsung, Jasti S. Rao
Journal: Cancer Research (2011)

Abstract Heat shock protein 90 (HSP90) is highly expressed under stressful conditions in eukaryotic cells showing chaperone activity including the suppression of protein aggregation and signaling pathways. HSP90 is upregulated in various human tumors, including glioblastoma, and targeting its function might provide new therapeutic opportunities. Previously, we have shown that human umbilical cord blood-derived mesenchymal stem cells (hUCBSC) downregulate XIAP in glioblastoma cells in vitro and in vivo. In the present study, we report that downregulation of XIAP by hUCBSC is associated with inhibition of HSP90. Under in vivo conditions, hUCBSC induce apoptosis by downregulation of XIAP in which XIAP migrates from the cytosol to the nucleus in mice brain xenografts. Immunoprecipitation experiments proved that SMAC is associated with Cytochrome C and XIAP in the mitochondria, indicating mitochondrial apoptosis. Simultaneously, cytosolic HSP90 is downregulated and co-localized with TNFR2 in hUCBSC-treated tumors, proving that TRAIL-mediated apoptosis is taking place in hUCBSC-treated tumor xenografts. Also, expression of mitochondrial HSP90 (TRAP-1) is downregulated in glioma cells. The downregulation of XIAP by hUCBSC is shown to be under the transcriptional control of SP1 under both in vitro and in vivo conditions. These results have been confirmed by using shRNA for XIAP. Taken together, these results prove that hUCBSC are efficient in the inhibition of HSP90, and hUCBSC have the potential to be therapeutic tools for the treatment of glioblastoma. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3322. doi:10.1158/1538-7445.AM2011-3322
Role of IgE in hyperresponsiveness induced by passive sensitization of human airways.
Authors: N Watson, K Bodtke, R A Coleman, G Dent, B E Morton, E Rühlmann, H Magnussen, K F Rabe
Journal: American Journal of Respiratory and Critical Care Medicine (1997)

Incubation of airways from nonatopic patients with serum from patients with high IgE levels confers responsiveness to "specific" (allergen) and hyperresponsiveness to "nonspecific" (histamine) stimuli. We have tested the hypothesis that the level of IgE determines the degree of specific and nonspecific responsiveness. Bronchial rings from nonatopic patients were sensitized overnight with serum containing high levels of allergen-specific IgE, or with an allergen-specific chimeric IgE (JW8) in physiologic buffer. In vitro responsiveness to allergen and histamine was evaluated and compared with non-sensitized tissues from the same patients. Responses to specific allergen were demonstrated in all tissues sensitized with atopic serum or chimeric IgE, but not in nonsensitized tissues. Allergen responses were specific, since tissues sensitized using serum containing high Dermatohagoides farinae-specific IgE only, did not respond to either horse or dog allergens. The potency and magnitude of the maximal contraction to histamine was significantly (p < 0.05) increased in tissues sensitized using atopic serum with high total IgE concentrations compared with nonsensitized preparations, but was unchanged in tissues sensitized using chimeric IgE or serum with low total IgE levels. Therefore, specific IgE determines allergen responsiveness in passively sensitized human airways, but histamine hyperresponsiveness is independent of specific IgE and appears to be related to some other factor associated with serum containing high concentrations of total IgE.
Furosemide
Authors: WILLIAM B. STASON, PAUL J. CANNON, HENRY O. HEINEMANN, JOHN H. LARAGH
Journal: Circulation (1966)

The physiological effects of furosemide, a new diuretic agent chemically related to thiazide diuretics, have been evaluated in seven normal subjects and in 39 patients with edema of varied origin. The compound exhibited an unusually broad dose-response curve so that increasing diuresis could be induced with oral doses of from 40 mg once daily to 600 mg three times daily. At the higher dosages furosemide was significantly more effective than conventional thiazide diuretics and exhibited an order of potency which can be achieved with ethacrynic acid. In many of its diuretic properties furosemide resembled thiazide agents. The natriuresis and diuresis which it produced was associated with a disproportionate loss of chloride and potassium and the consequent production of degrees of hypokalemic alkalosis. However, physiological studies indicate that furosemide is qualitatively and quantitatively more similar to ethacrynic acid than to thiazide agents. Thus, furosemide, like ethacrynic acid and unlike thiazide diuretics acted to interfere with both urinary concentration (T c H H2 O ) during antidiuresis and to block urinary dilution (C H H2 O ) during water diuresis. It also caused a negative urinary hydrogen balance during diuresis. The data suggest that furosemide acts to block sodium chloride reabsorption in the ascending limb of Henle's loop and in more cortical distal diluting segments. The magnitude of its effects suggests that it also may interfere with proximal sodium chloride reabsorption. Ion exchange sodium reabsorptive mechanisms appear unaffected and become overactive during drug administration thereby accounting for the observed increases in potassium and hydrogen ion excretions. Because of its properties furosemide was especially useful intravenously as an adjunct in the treatment of acute pulmonary edema and for oral maintenance therapy in the treatment of difficult or refractory edematous patients, many of whom exhibit associated electrolyte derangements or azotemias. In these difficult situations, for maximum diuresis and to avoid problems associated with K + , H + and Cl - depletion, intermittent therapy added to a maintenance schedule which utilizes aldosterone antagonists or chloride and potassium supplements appears advisable. Furosemide, also like ethacrynic acid, was capable of adding to the natriuretic action of all other types of diuretic agents. This observation provides additional evidence for the existence of a number of different tubular transport processes located at different sites in the nephron which can participate in sodium conservation.
Body consults to balance public health against private rights
Authors: Michael Day
Journal: BMJ (2006)

Compulsory childhood vaccination and new quarantine measures are among the radical steps that may be needed to protect public health in the United Kingdom, the Nuffield Council on Bioethics warned this week.

In a wide ranging consultation document, the influential body called for an urgent debate on the pros and cons of mandatory child immunisation in the wake of the debacle involving the measles, mumps, and rubella (MMR) vaccine, in which immunisation rates fell after one unfavourable research report about the vaccine in 1998. It added that new measures may have to …
Fatal embolus during "pill" administration.
Authors: R. G. Allen
Journal: BMJ (1968)

common in the enterobacteria of the infant population of Dublin.Dr. Anderson suggests that the R factors in the Tees-side strains had probably been transferred from non-pathogenic Re+ B. coli.Our findings support his view.One possible method of preventing the spread of R factors within a hospital is to isolate all infants ecreting R+ enterobacteria on admission.As it is a routine practice in most children's hospitals to culture the faeces of infants on admission for pathogenic enterobacteria, I suggest that a direct sensitivity test should also be done on the faeces.All infants carrying R* strains should be isolated within the hospital.It would not be possible or necessary to screen for R factors, because it is most probable that if the organism is multiresistant it is R+.
Gallium Scintigraphy Demonstration of an Appendiceal Mucocele: A Proposed Mechanism of Uptake
Authors: LAURENCE ALPERT, RON FRIEDMAN
Journal: Clinical Nuclear Medicine (1981)

An appendiceal mucocele demonstrated intense early avidity for Ga-67, despite the lack of inflammatory cells to account for the uptake. It is proposed that the acid mucopolysaccharide component of the mucus within the lumen and lining cells accounted for the uptake of the gallium ion, in a similar manner to the uptake of its analogue, the ferric ion, as demonstrated by intense staining of mucus by the colloidal iron technique.
Rhinitis and Asthma
Authors: Michael Kaliner
Journal: JAMA (1987)

ALTHOUGH both rhinitis and asthma can occur without a recognized allergic mechanism, IgE-mediated inflammation should be a major consideration in the differential diagnosis of both entities. It is estimated that 40 million Americans have asthma and other allergic diseases. Other figures compiled by the National Center for Health Statistics underscore the magnitude of this health burden. For example, approximately 9% of all patients seeking medical care at a physician's office do so for one of the common allergic diseases. Furthermore, among chronic illnesses of childhood, asthma is the most frequent cause of school absenteeism. Of the 40 million Americans with allergic disease, an estimated 8.9 million suffer from asthma with or without hay fever, 25 to 30 million have hay fever alone, and 11.8 million have other allergic manifestations such as eczema, urticaria, angioedema, or food, drug, or insect hypersensitivity. Thus, medical students and house officers should familiarize themselves early
Effect of Pressure Support vs Unassisted Breathing Through a Tracheostomy Collar on Weaning Duration in Patients Requiring Prolonged Mechanical Ventilation
Authors: Amal Jubran, Brydon J. B. Grant, Lisa A. Duffner, Eileen G. Collins, Dorothy M. Lanuza, Leslie A. Hoffman, Martin J. Tobin
Journal: JAMA (2013)

Patients requiring prolonged mechanical ventilation (>21 days) are commonly weaned at long-term acute care hospitals (LTACHs). The most effective method of weaning such patients has not been investigated.To compare weaning duration with pressure support vs unassisted breathing through a tracheostomy collar in patients transferred to an LTACH for weaning from prolonged ventilation.Between 2000 and 2010, a randomized study was conducted in tracheotomized patients transferred to a single LTACH for weaning from prolonged ventilation. Of 500 patients who underwent a 5-day screening procedure, 316 did not tolerate the procedure and were randomly assigned to receive weaning with pressure support (n = 155) or a tracheostomy collar (n = 161). Survival at 6- and 12-month time points was also determined.Primary outcome was weaning duration. Secondary outcome was survival at 6 and 12 months after enrollment.Of 316 patients, 4 were withdrawn and not included in analysis. Of 152 patients in the pressure-support group, 68 (44.7%) were weaned; 22 (14.5%) died. Of 160 patients in the tracheostomy collar group, 85 (53.1%) were weaned; 16 (10.0%) died. Median weaning time was shorter with tracheostomy collar use (15 days; interquartile range [IQR], 8-25) than with pressure support (19 days; IQR, 12-31), P = .004. The hazard ratio (HR) for successful weaning rate was higher with tracheostomy collar use than with pressure support (HR, 1.43; 95% CI, 1.03-1.98; P = .033) after adjusting for baseline clinical covariates. Use of the tracheostomy collar achieved faster weaning than did pressure support among patients who did not tolerate the screening procedure between 12 and 120 hours (HR, 3.33; 95% CI, 1.44-7.70; P = .005), whereas weaning time was equivalent with the 2 methods in patients who did not tolerate the screening procedure within 0 to 12 hours. Mortality was equivalent in the pressure-support and tracheostomy collar groups at 6 months (55.92% vs 51.25%; 4.67% difference, 95% CI, -6.4% to 15.7%) and at 12 months (66.45% vs 60.00%; 6.45% difference, 95% CI, -4.2% to 17.1%).Among patients requiring prolonged mechanical ventilation and treated at a single long-term care facility, unassisted breathing through a tracheostomy, compared with pressure support, resulted in shorter median weaning time, although weaning mode had no effect on survival at 6 and 12 months.clinicaltrials.gov Identifier: NCT01541462.
Abstract 5737: Parity and lactation in relation to ER-/PR- breast cancer in African American women
Authors: Julie R. Palmer, Deborah A. Boggs, Lucile L. Adams-Campbell, Lynn Rosenberg
Journal: Cancer Research (2010)

Abstract Women of African ancestry are more likely than women of European ancestry to be diagnosed with aggressive tumors characterized by negative staining for estrogen receptors (ER) and progesterone receptors (PR). Reasons for the disparity are unclear, and previous studies have lacked statistical power to investigate risk factors for the more aggressive subtypes. A recent report from the Carolina Breast Cancer Study indicated that basal-like breast cancer, a subtype of breast tumors with ER-, PR-, HER2-, HER1+ and/or CK5/6+ characteristics, was positively associated with increased parity, whereas other subtypes were inversely associated with parity. The increased risk of basal-like cancer was strongest for parous women who had never breastfed. The majority of breast tumors with negative staining for both ER and PR would likely be classified as basal-like. We examined the relation of parity and lactation to risk of ER-/PR- breast cancer among 59,000 African American women from the Black Women's Health Study in 12 years of follow-up data. Reproductive history was obtained by questionnaire at baseline in 1995 and updated every two years. ER and PR status were obtained from pathology reports and state cancer registry records. Included in this analysis were 809 incident breast cancer cases with complete data on ER and PR status, with 285 classified as ER-/PR-, 395 as ER+/PR+, 114 as ER+/PR-, and 15 as ER-/PR+. Incidence rate ratios (IRR) and 95% confidence intervals (CI) were derived from proportional hazard models for the relation of each reproductive factor to risk of specific tumor subtype, with control for all other reproductive factors, age, region, education, body mass index, waist-hip ratio, hormone use, alcohol, smoking, and physical activity. Risk of ER-/PR- breast cancer increased with increasing parity (p trend = 0.02), whereas risk of ER+/PR+ cancer decreased with increasing parity (p trend = 0.0002). For ER-/PR- breast cancer, the IRR for women who had 3+ births and never breastfed relative to nulliparous women was 1.66 (95% CI 1.09-2.54). The increased risk associated with higher parity was ameliorated by breast feeding: the comparable IRR for women who had 3+ births but breastfed at least one of the babies was 1.01 (95% CI 0.63-1.63). These results from a cohort of African American women support findings from the previous study of basal-like breast cancer and are consistent with the hypothesis that pregnancy and breastfeeding may influence risk of ER-/PR- cancer through inflammatory/immune system alterations linked to mammary gland involution. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 5737.