tbuckley/cabot-search huggingface dataset:
Primary thrombophilia in Mexico. V. A comprehensive prospective study indicates that most cases are multifactorial
Authors: Guillermo J. Ruiz-Argüelles, Briceida López-Martínez, Patricia Valdés-Tapia, J. David Gómez-Rangel, Virginia Reyes-Núñez, Javier Garcés-Eisele
Journal: American Journal of Hematology (2004)

Over a 36-month period, 46 consecutive Mexican mestizos with a clinical marker associated with a primary hypercoagulable state were prospectively assessed by searching for the sticky platelet syndrome (SPS), the activated protein C resistance (aPCR) phenotype, coagulation protein C activity and antigen, coagulation protein S, antithrombin III, plasminogen, tissue-type plasminogen activator activity, plasminogen activator inhibitor activity, plasminogen activator inhibitor type 1, IgG and IgM isotypes of antiphospholipid antibodies, homocysteine levels, the factor V gene Leiden, Cambridge, Hong Kong, and Liverpool mutations, the 677 C-->T mutation in the 5,10-methylenetetrahydrofolatereductase (MTHFR), and the G20210A polymorphism in the 3'-untranslated region of the prothrombin gene. Of the 46 consecutive patients prospectively accrued in the study, only 12 (26%) were males, the median age being 38 years (range 10-63 years). In only four individuals (8%) could we not record any abnormality. In 5/42 patients with abnormal results (12%), a single abnormality was recorded, whereas in the remaining 37, two to five co-existing abnormalities were identified. We found 22 (48%) patients with the SPS, 11 (24%) with the aPCR phenotype, 5 (11%) with the factor V Leiden mutation, 7 (15%) with the prothrombin gene mutation, 29 (63%) with the MTHFR gene mutation, 11 (24%) with the factor V HR2 haplotype, 11 (24%) with antiphospholipid antibodies, 4 (9%) with PS deficiency, 6 (13%) with PC deficiency, one with the FV Hong Kong mutation, and one with AT-III deficiency. The results are consonant with the idea that most cases of thrombophilia in Mexico are multifactorial.
A DNA vaccine against tumor stromal antigen FAP boosts chemotherapy leading to tumor rejection
Authors: Joerg A. Krueger, Markus Loeffler, Andreas Niethammer, Ralph A. Reisfeld
Journal: Cancer Research (2005)

6174  The tumor stromal compartment is of key importance for tumorigenesis. It also offers an excellent target for cancer immunotherapy through its genetically stable fibroblasts, thereby avoiding the many disadvantages in targeting genetically unstable, frequently mutating tumor cells. We constructed a novel, oral DNA vaccine as a strategy for targeting the serine protease fibroblast activation protein (FAP), which is specifically overexpressed in over 90% of stromal fibroblasts associated with colon, breast and lung carcinoma. To assess the efficacy of our vaccine, we immunized Balb/c mice orally with attenuated Salmonella typhimurium carrying plasmid DNA encoding the complete murine FAP cDNA. After vaccination, we challenged the animals orthotopically with D2F2 breast or s.c. with CT26 colon carcinoma cells and demonstrated a significant decrease in tumor volume in the vaccinated animals. In a therapeutic setting we challenged Balb/c mice i.v. with D2F2 tumor cells and vaccinated three and ten days thereafter. As in the prophylactic setting, we observed a significant reduction of tumor load. To determine which effector cell population accounts for the antitumor response, we immunized mice, challenged i.v. with CT26 colon carcinoma cells, and depleted CD4+ T cells, CD8+ T cells or NK cells with the corresponding antibodies. We demonstrated that the anti-tumor effect relies mainly on CD8+ T cells, a finding that was confirmed by showing that CD8+ splenocytes from immunized mice specifically lyse FAP expressing cells. FAP was also reported to cleave gelatin and type I collagen, which has been shown to inversely correlate to intratumoral uptake of various compounds including chemotherapy. We hypothesized that the combination of the FAP vaccine with chemotherapy could lead to an increased anti-tumor effect due to an enhanced drug uptake in the tumor. To this end we first demonstrated by Western Blot, that the FAP vaccination leads to a decrease of FAP and collagen type I expression in the tumor tissue. Furthermore, the tumor uptake of different compounds such as Evans blue, fluorescein and 14C-5-Fluorouracil was significantly increased in vaccinated mice. We then immunized mice and challenged them orthotopically with D2F2 cells and injected Doxorubicin i.v. on day 5, 10 and 15 after the challenge. Vaccination and chemotherapy alone were able to suppress tumor growth. However, the combination therapy did not only further decrease the tumor load but also lead to tumor rejection in 50% of the animals. In another combinational approach, we first challenged Balb/c mice i.v. with D2F2 tumor cells, and once experimental metastasis had been established after 5d, treated them weekly with the FAP vaccine and Doxorubicin. We observed a significant increase in life span in the combinational group compared to the single treatment groups. This strategy opens a new venue for the combination of immuno- and chemotherapies.
Abstract 789: Parthenolide sensitizes colorectal cancer cells to TRAIL-induced apoptosis by regulating mitochonrial pathway
Authors: Se Lim Kim, Sang-Wook Kim, Soo-Teik Lee, Seong Hun Kim, In Hee Kim, Seung Ok Lee, Dae Ghon Kim
Journal: Cancer Research (2014)

Abstract Combination therapy utilizing of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) in conjunction with other anticancer agents, is a promising strategy to overcome TRAIL resistance in malignant cells. Recently, parthenolide (PT) has proved to be a promising anticancer agent, and several studies have explored its use in combination therapy. Here, we investigated the molecular mechanisms by which PT sensitizes colorectal cancer (CRC) cells to TRAIL-induced apoptosis. TRAIL inhibited HCT116 cell growth in a dose-dependent manner; however, this reduction did not occur in TRAIL resistant HT-29 cells with an even higher dose of TRAIL. A combination of PT with TRAIL significantly inhibited cell growth of TRAIL resistant HT-29 cells. Consistent with cell growth inhibition, apoptotic cell death was significantly increased by a combination of PT with TRAIL in both of HCT116 and HT-29 cells. Results of flow cytometry analysis demonstrated that TRAIL-sensitive HCT116 cells had much higher death receptor (DR) 5 than TRAIL-resistant HT-29 cells. Interestingly, treatment of PT and/or TRAIL did not affect DR4/DR5, these results indicate that the apoptotic effect of combination is death receptor-independent apoptosis. We observed that the synergistic effect was associated with Bcl-2 family members, p53 and cytochrome C. Moreover, activation of caspase -3, -8 and -9 was increased by combination treatment in both of TRAIL-resistant and -sensitive cells. These results suggest that PT sensitizes TRAIL-induced apoptosis via death receptor-independent and mitochondrial-dependent pathway. Combination treatment using PT and TRAIL might offer an effective strategy to overcome TRAIL resistance in certain CRC cells. Citation Format: Se Lim Kim, Sang-Wook Kim, Soo-Teik Lee, Seong Hun Kim, In Hee Kim, Seung Ok Lee, Dae Ghon Kim. Parthenolide sensitizes colorectal cancer cells to TRAIL-induced apoptosis by regulating mitochonrial pathway. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 789. doi:10.1158/1538-7445.AM2014-789
Fourteen Genetic Misconceptions
Authors: Victor A. Mckusick
Journal: Annals of Internal Medicine (1971)

Editorial Notes1 October 1971Fourteen Genetic MisconceptionsVICTOR A. MCKUSICK, M.D., F.A.C.P.VICTOR A. MCKUSICK, M.D., F.A.C.P.Author, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-75-4-642 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptSome misconceptions* about genetic aspects of medicine are so common that they merit specific comment and correction.Misconception 1. Congenital is synonymous with genetic.Criticism: Congenital merely means present at birth. It has no necessary etiological connotations. Some genetic disorders are not congenital in the usual sense of the word, and many congenital malformations do not have a predominantly genetic cause. For example, Huntington's chorea is genetic but not congenital; rubella embryopathy is congenital but not genetic.Misconception 2. If a disorder is inherited, a chromosome analysis will show abnormality.Criticism: Most mendelian disorders have no chromosome abnormality demonstrable with... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: The John Hopkins Hospital Baltimore, Md.*When an earlier version of this list of misconceptions was unveiled at the 1967 meeting of the Royal College of Physicians and Surgeons of Canada, the President, Professor Robert B. Kerr of Vancouver, made the witticism that all genetic defects are misconceptions! In Kerr's defense, let it be pointed out that he punned in private. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byWhy take part in personalised cancer research? Patients' genetic misconception, genetic responsibility and incomprehension of stratification-an empirical-ethical examinationVictor McKusickPhysician and Patient EducationSyndrome of hypertension and hyperkalemia with normal glomerular filtration rate. 1 October 1971Volume 75, Issue 4Page: 642-643KeywordsBirthChromosomal diseasesGenetic diseasesGeneticsRubellaSurgeons ePublished: 1 December 2008 Issue Published: 1 October 1971 PDF downloadLoading ...
249. New Canine Models of Duchenne Muscular Dystrophy: Identification and Molecular Characterization
Authors: Bruce F. Smith, Lucia Alvarez, Kerriann Sparks
Journal: Molecular Therapy (2004)

Duchenne Muscular Dystrophy (DMD) presents a series of significant challenges to the development of gene therapy approaches, including the frequency of new mutations, the size of the gene and mRNA and the complexity of the mutations involved. Animal models can significantly accelerate the process for development of novel therapies if they accurately mimic the human disease. To date, the only animal that develops disease with a course and severity similar to humans, without requiring additional mutations or manipulations, is the dog. Several canine models have been identified and their mutations characterized, confirming that this disease occurs at a relatively high frequency, can have variable effects, and is the result of many different mutations. Unlike other canine inherited diseases, Duchenne-like Muscular Dystrophy occurs spontaneously in multiple families within in a breed, leading to more than one mutation in a given breed of dog. Using a rapid PCR based screen, we have identified the putative mutations in two canine models of DMD. Data from a Labrador Retriever family and a Welsh Corgi family indicate that the mutations in both families consist of the precise insertion of repetitive DNA elements in the mRNA between exon pairs. The mutations involve different repetitive sequences and different exon pairs in each family. In addition, affected animals from another distinct Labrador Retriever family and a West Highland White family have been identified. Preliminary data supporting the independent nature of these mutations as well as their localization within the gene will be presented. The relatively large size, intact immune system, and potential to measure beneficial effects combined with the assortment of different mutations available provide an excellent resource in which gene therapy approaches for DMD can be tested.
Maintenance of the Mammary-Tumor Agent in Long-Term Cultures of Mouse Mammary Carcinoma
Authors: Katherine K. Sanford, Howard B. Andervont, Gwendolyn L. Hobbs, Wilton R. Earle
Journal: JNCI Journal of the National Cancer Institute (1961)

The object of this study was to determine whether the mammary-tumor agent persists in long-term cell strains cultured from C3H mouse mammary carcinomas. Cell strains and derivative single-cell clones were established in culture from 8 different tumors of mammary-gland origin. At intervals during the period of culture, cells and supernatant fluids were assayed for the mammary-tumor agent. Variations between culture cell strains with respect to maintenance and activity of the agent were noted. In certain cell strains, some activity of the agent could be demonstrated after 6 months to more than a year of rapid cell proliferation in vitro. In other cell strains, the agent disappeared either through cell selection or through diminution or alteration and was no longer detectable by the test system used.
Studies in Blood Volume with the Dye Method
Authors: Leonard G. Rowntree, George E. Brown
Journal: Annals of Internal Medicine (1928)

Article1 May 1928Studies in Blood Volume with the Dye MethodLEONARD G. ROWNTREE, M.D., GEORGE E. BROWN, M.D.LEONARD G. ROWNTREE, M.D.Search for more papers by this author, GEORGE E. BROWN, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-1-11-890 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptNew conceptions concerning blood are urgently needed in medicine, since the routine count of blood cells and the determination of the hemoglobin relate entirely to the concentration of the blood and are in no way related to the important problem of blood quantum. During the last fifteen years we have learned much from the accumulated evidence of studies of blood and plasma volume with the dye method. The results of these studies are now being assembled in monograph form. In this report, we shall present only a brief synopsis of some of our observations in this important but neglected field.... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Division of Medicine Mayo Clinic and the Mayo Foundation Rochester, Minnesota*Read before the American College of Physicians, New Orleans, La., March 5, 1928. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byThe Sterilisation, Stability and Toxicity of Congo Red InjectionsBlutstoffwechsel und Urobilinurie bei Herzinsuffizienz.1Entwicklungsstörungen des Herzgefäßsystems (Dysplasien)Die Nephrosen, die primären Parenehym- und MesenchymdegenerationenDer Wasserversuch und seine klinische Bedeutung 1 May 1928Volume 1, Issue 11Page: 890-901KeywordsAttentionBlood cellsBlood countsBlood plasmaBlood volumeHemoglobinPlasma volume ePublished: 1 December 2008 Issue Published: 1 May 1928 PDF downloadLoading ...
Abstract P2-05-16: Gene expression in synchronous primary, axillary nodal and disseminated breast cancer cells
Authors: Reuben J Broom, Cherie Blenkiron, Richard Harman, Erica Whineray Kelly, Stephen Allpress, Katherine Gale, Sam Rice, Peter Shin, Anna Brown, Annette Lasham, Cristin Print
Journal: Cancer Research (2015)

Abstract Disseminated Tumour Cells (DTC) have been found in the bone marrow (BM) of up to 70% of patients with breast cancer metastatic to axillary lymph nodes. They are a biologically and therapeutically interesting tumour cell population. Although there is uncertainty about their relationship to cancer prognosis, DTC provide a valuable window into the processes by which primary tumour (PT) cells disseminate. DTC can be enriched from BM by immunoaffinity using antibodies directed against epithelial cell markers such as EpCAM. To better understand the changing gene expression patterns that may accompany breast cancer metastasis, we have compared the whole genome RNA expression profiles of matched PT, axillary lymph node metastases (LNM), and EpCAM-enriched cells from the BM of seven patients. Compared to PT, axillary LNM had consistently altered expression of RNAs encoding matrix metalloproteinases (MMP), growth factors, transcription factors, as well as downstream targets of Catenin-a, Tumour Necrosis Factor (TNF)-a and miR-22. Once the gene expression patterns of potentially contaminating BM cells were subtracted, compared to PT and LNM EpCAM-enriched MB cells had consistently elevated expression of RNAs encoding metabolic enzymes, ribosomal proteins, and DNA-binding factors such as YB-1. The gene expression changes we identify are candidate mediators of breast cancer metastases and represent attractive targets for further study on a cell by cell basis. Citation Format: Reuben J Broom, Cherie Blenkiron, Richard Harman, Erica Whineray Kelly, Stephen Allpress, Katherine Gale, Sam Rice, Peter Shin, Anna Brown, Annette Lasham, Cristin Print. Gene expression in synchronous primary, axillary nodal and disseminated breast cancer cells [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P2-05-16.
958. Rapid Blockade of Telomerase Activity and Tumor Cell Growth by Ribbon Antisense Oligodeoxynucleotides to hTR
Authors: Jong-Gu Park, Arun Bajpai
Journal: Molecular Therapy (2004)

Telomerase enzyme is up regulated in 80-90% malignant tumors and considered as an attractive target for anti cancer therapy. In the present study, ribbon antisense to the hTR RNA, a component of the telomerase complex, is employed to inhibit telomerase activity and cancer cell growth. The antisense molecule, hTR-RiAS, is shown to effectively inhibit telomerase activity and causes cell cycle arrest, with eventual apoptosis in various cancer cell lines tested. When cancer cells were treated with hTR-RiAS, the cellular level of hTR RNA component of telomerase was reduced by more than 95%, shown by RT-PCR. By contrast, both mismatched and scrambled oligonucleotides failed to reduce the level of hTR RNA and telomerase activity. When checked for cancer cell viability, hTR-RiAS inhibited cell growth up to 90% in 4 days, which is a much rapid response compared to those of earlier reports. Reduced cell viability is found to be due to apoptosis as DNA fragmentation was detected after antisense treatment of cancer cells. Further, when subcutaneous xenografts of a colon cancer cell line were treated intra-tumorally with hTR-RiAS, tumor growth was markedly suppressed. Cells in the tumor tissue were found to undergo apoptosis after hTR-RiAS treatment, detected by in situ apoptosis assay. These results show that hTR-RiAS is a powerful anticancer reagent, with a potential for broad efficacy to diverse malignant tumors.
Dying Well: A Holistic Guide for the Dying and Their Carers, by Richard Reoch
Authors: E. Murray
Journal: BMJ (1997)

Richard Reoch / Gaia Books, £11.99, pp 191 / ISBN 1 85675 019 1

Death comes to us all, and many of us–either in our professional or individual capacities–will have to care for terminally ill people and their carers. This is a book to help all of us with this difficult task. It is a practical guide which sets out the main emotional and physical problems that both dying patients and their carers are likely to experience and suggests ways of helping them to overcome these problems.

This book includes information on a range …
THE PRESENT STATUS OF CLINICAL ELECTROENCEPHALOGRAPHY
Authors: Frederic A. Gibbs
Journal: Annals of Internal Medicine (1943)

Article1 June 1943THE PRESENT STATUS OF CLINICAL ELECTROENCEPHALOGRAPHYFREDERIC A. GIBBS, M.D.FREDERIC A. GIBBS, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-18-6-1012 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptAfter eight years of trial, clinical electroencephalography has gained widespread acceptance. It is being used by neurologists, brain surgeons, psychiatrists, and pediatricians, as an aid in the diagnosis of epilepsy and related disorders and as a painless and entirely safe method of detecting localized damage in the cerebral cortex. Several Army induction centers are using it as part of the medical examination to determine fitness for military service.This widespread acceptance has placed a burden on electroencephalographic standards for diagnosis and prognosis, and various weaknesses have appeared. In the effort to correct these weaknesses, electroencephalographers in this country and abroad...Bibliography1. GIBBSGIBBSLENNOX ELFAWG: Electroencephalographs classification of epileptics and controls, Arch. Neurol. and Psychiat. (In press). Google Scholar2. WILLIAMS D: The electro-encephalogram in chronic posttraumatic states, Jr. Neurol. and Psychiat., 1941, iv, 131-146. CrossrefGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Boston, Massachusetts*Read before the New England Regional Meeting of the American College of Physicians in Boston, Mass., February 5, 1943.From the Department of Neurology, Harvard Medical School, and the Neurological Unit, Boston City Hospital, Boston, Mass. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 June 1943Volume 18, Issue 6Page: 1012-1014KeywordsArmed forcesBrainChild psychiatryClinical trialsElectroencephalographyEpilepsyNeurologySurgeons ePublished: 1 December 2008 Issue Published: 1 June 1943 PDF downloadLoading ...
Magnesium modifies the association between serum phosphate and the risk of progression to end-stage kidney disease in patients with non-diabetic chronic kidney disease
Authors: Yusuke Sakaguchi, Hirotsugu Iwatani, Takayuki Hamano, Kodo Tomida, Hiroaki Kawabata, Yasuo Kusunoki, Akihiro Shimomura, Isao Matsui, Terumasa Hayashi, Yoshiharu Tsubakihara, Yoshitaka Isaka, Hiromi Rakugi
Journal: Kidney International (2015)
Asylum seekers have low rates of vaccination and screening
Authors: Roger Dobson
Journal: BMJ (2002)

A report on the health needs of asylum seekers warns of low rates of vaccination and screening for cervical cancer, poor dental health, high rates of gastrointestinal disorders, and extensive use of drugs for central nervous system disorders.

The report, based on a sample of 397 newly arrived asylum seekers in Sunderland and North Tyneside from 39 different countries, also found that almost 40% of them had seen a doctor and 8% had received hospital treatment since arriving in the United Kingdom.

“Two hundred and sixteen (55%) reported symptoms about which they felt it necessary to consult a doctor and 69% reported needing to consult a dentist,” says the report . 

On vaccination rates the report says, “An issue of public health concern is the overall low rate of immunisation within the asylum seeker population.

“The overall rates for common communicable diseases, in particular for mumps, measles and rubella, were low. Even for BCG the mean rate of the entire sample was below that required to provide adequate population immunity.”
New reporting system for euthanasia shows doctors follow rules
Authors: Tony Sheldon
Journal: BMJ (2000)

Dutch doctors carrying out euthanasia acted with due care in almost all cases according to the first annual report of the Netherlands' “euthanasia appraisal committees.”

But the report, presented to the health and justice ministries, shows no recent improvement in the reporting rate for euthanasia cases, estimated at around 60%.

The committees, made up of doctors, lawyers, and ethicists, were established as part of a new euthanasia reporting procedure and were welcomed by the …