tbuckley/cabot-search huggingface dataset:
CRC Forum on Bacteriology, sessions 1 and 2: Medically Significant Bacteria; sessions 3 and 4: The Human Host in Bacterial Disease
Authors: George Gee Jackson
Journal: JAMA (1980)

The<i>Forum</i>consists of four loose-leaf volumes, each with four positionpapers on selected topics in medical microbiology and the human as a host for bacterial infections. In addition to the 16 position-papers that were prepared by 12 authors, each volume has four tape cassettes with eight sides (60 cm each) of recorded discussion by the contributors, who are experts in laboratory aspects of medical microbiology. The length of the papers ranges from 16 to 46 double-spaced, 8 1/2×11-in pages (average of 26), including a modest number of references. There are relatively few illustrations and tables. It is suggested that with each volume one first read the four position-papers and then listen to the accompanying discussion tapes. This requires approximately eight hours. At the end, self-assessment materials are provided, and an option is offered the subscriber to register for category 1A continuing medical education (CME) credit. Session 1 (vol 1) considers
Calf pain in the post-thrombotic syndrome.
Authors: D. Negus
Journal: BMJ (1968)

20April 1968 Lung CacrLche n Sireti MEDICALJORA with lung cancer and a control group with no lung cancer.The group mean levels both in the morning and in the after- noon were greater in the lung cancer patients, but the range of individual values within each group does not permit the test to be used diagnostically.Thanks are due to Dr.
Evidence for Transit Peptide Acquisition through Duplication and Subsequent Frameshift Mutation of a Preexisting Protein Gene in Rice
Authors: M. Ueda, M. Fujimoto, S.-i. Arimura, N. Tsutsumi, K.-i. Kadowaki
Journal: Molecular Biology and Evolution (2006)

Many proteins synthesized in the cytosol are delivered to their appropriate compartments in the cell by specific targeting signals. Here, we provide new insight into the generation of the chloroplast-targeting signal (called the transit peptide) in rice. First, we identified the mitochondrial ribosomal protein L13 (mt rpl13) gene on chromosome 5. Downstream of the gene, we identified a DNA fragment of 266 bp: a segment within a duplication of mt rpl13. The duplicated region was transcribed and found to encode an open reading frame (ORF) of 160 amino acids (aa) (orf160). The orf160 gene comprises C-terminal 60 aa derived from the mt rpl13 gene and N-terminal 100 aa derived from another duplicated fragment of a pentatricopeptide repeat (ppr)564 gene that encodes 564 aa with ppr motifs on chromosome 1. Examination of the localization of the ORF160 protein tagged with green fluorescent protein (GFP) showed that it is targeted to the chloroplasts. As such, ORF160 clearly contains a transit peptide. Interestingly, this was translated from the alternative reading frame of the duplicated fragment of ppr564. To confirm this, the reading frame of the ppr564 gene was shifted according to that of the orf160 gene, and the frameshifted ppr564 sequence was fused to the gene for GFP. The expressed GFP-fused protein was also located in the chloroplasts. These results provide clear evidence for the generation of the transit peptide through duplication and subsequent frameshifting of a reading frame of a preexisting protein gene. We also demonstrate the importance of sequence redundancy and frameshift mutation in this evolutionary process.
Roles of TH1 and TH2 cytokines in a murine model of allergic dermatitis
Authors: Jonathan M. Spergel, Emiko Mizoguchi, Hans Oettgen, Atul K. Bhan, Raif S. Geha
Journal: Journal of Clinical Investigation (1999)

Skin lesions in atopic dermatitis (AD) are characterized by hypertrophy of the dermis and epidermis, infiltration by T cells and eosinophils, and expression of the cytokines IL-4, IL-5, and IFN-γ. The role of these cytokines in the pathogenesis of AD is not known. We took advantage of a recently described murine model of AD elicited by epicutaneous sensitization with ovalbumin (OVA) (1) and of the availability of mice with targeted deletions of the IL-4, IL-5, and IFN-γ cytokine genes to assess the role of these cytokines in this model.OVA-sensitized skin from IL-5–/– mice had no detectable eosinophils and exhibited decreased epidermal and dermal thickening. Sensitized skin from IL-4–/– mice displayed normal thickening of the skin layers but had a drastic reduction in eosinophils and a significant increase in infiltrating T cells. These findings were associated with a reduction in eotaxin mRNA and an increase in mRNA for the T-cell chemokines macrophage inflammatory protein-2 (MIP-2), MIP-1β, and RANTES. Sensitized skin from IFN-γ–/– mice was characterized by reduced dermal thickening.These results suggest that both the TH2 cytokines IL-4 and IL-5 and the TH1 cytokine IFN-γ play important roles in the inflammation and hypertrophy of the skin in AD.
Wrongful birth. What is the damage?
Authors: V. R. Greenfield
Journal: JAMA (1982)

Sterilization has been used increasingly by married couples as a method of birth control. If the surgical procedure is unsuccessful, what damages can be claimed or recovered against the physician who performed the procedure? Suits for wrongful birth following an unsuccessful sterilization procedure have been based on theories that the procedure was performed negligently or that there was a breach of the contract to ensure sterility or a breach of warranty. Traditionally, life has been regarded as a blessing by the courts. Therefore, until recently, courts have been reluctant to recognize wrongful birth actions. To allow a person to be awarded any amount for damages for the birth of a normal, healthy infant, including those costs incurred during pregnancy and delivery, was considered contrary to public policy. The first case to consider the issue of wrongful birth was<i>Christensen v Thornby</i>, 255 NW 620, Minn App (1934). Christensen engaged the
Proinflammatory consequences of transgenic Fas ligand expression in the heart
Authors: David P. Nelson, Elizabeth Setser, D. Greg Hall, Steven M. Schwartz, Timothy Hewitt, Raisa Klevitsky, Hanna Osinska, Don Bellgrau, Richard C. Duke, Jeffrey Robbins
Journal: Journal of Clinical Investigation (2000)

Expression of Fas ligand (FasL) renders certain tissues immune privileged, but its expression in other tissues can result in severe neutrophil infiltration and tissue destruction. The consequences of enforced FasL expression in striated muscle is particularly controversial. To create a stable reproducible pattern of cardiomyocyte-specific FasL expression, transgenic (Tg) mice were generated that express murine FasL specifically in the heart, where it is not normally expressed. Tg animals are healthy and indistinguishable from nontransgenic littermates. FasL expression in the heart does result in mild leukocyte infiltration, but despite coexpression of Fas and FasL in Tg hearts, neither myocardial tissue apoptosis nor necrosis accompanies the leukocyte infiltration. Instead of tissue destruction, FasL Tg hearts develop mild interstitial fibrosis, functional changes, and cardiac hypertrophy, with corresponding molecular changes in gene expression. Induced expression of the cytokines TNF-α, IL-1β, IL-6, and TGF-β accompanies these proinflammatory changes. The histologic, functional, and molecular proinflammatory consequences of cardiac FasL expression are transgene-dose dependent. Thus, coexpression of Fas and FasL in the heart results in leukocyte infiltration and hypertrophy, but without the severe tissue destruction observed in other examples of FasL-directed proinflammation. The data suggest that the FasL expression level and other tissue-specific microenvironmental factors can modulate the proinflammatory consequences of FasL.
Haemochromatosis after the discovery of HFE (“HLA-H”)
Authors: S GOLDWURM, L W POWELL
Journal: Gut (1997)

See article on page841 

In 1996 the gene and mutation responsible for hereditary haemochromatosis (HHC) were identified.1 In the short time since then, this discovery has greatly changed our knowledge of HHC and has given us new methods for its diagnosis and strategies for its management, together with the potential for greater insight into normal and abnormal iron metabolism.

HHC is a common disorder of iron metabolism which results in iron accumulation in parenchymal cells of the liver, heart, and certain endocrine organs, with eventual organ damage such as cirrhosis. It affects 1 in 300 people of northern European descent with a carrier rate of about 10%. Without treatment, the disease is often fatal, but if treatment starts before tissue injury occurs, patients have a normal life expectancy. An early diagnosis of affected individuals is therefore crucial.

The gene identified by Feder et al 1(“HLA-H” but now defined as HFE2) lies approximately 5 Mb telomeric to HLA-A and shows similarity with MHC class I genes. A single mutation is associated with HHC in 65 to 100% of cases. The mutation is a G to A transition at nucleotide 845 and results in the substitution of a cysteine with tyrosine at position …
Clinical Lecture on Venesection
Authors: W. O. Markham
Journal: BMJ (1865)

GENTLEMIEN, -I have to-day to bring under your notice two cases which, as I think, illustrate in a striking way the beneficial effects of venesection.In both cases, the patients were suffering, and suffering se- verely, from lung-diseases; and in both the symptoms for which the veliesection was practised were those which represent in a marked degree interference with the free play of the heart and lungs.I will, in a few words, relate the history of these cases; and then make a few remarks touching the operation of the venesection in their cure.J. J., aged 36, a healthy man, was seized, about a week before his admission into St.Mary's IIospital, with difficulty of breathing and " stitch" in the right side.These symptoms increased up to the time when he entered the hospital.When I saw him, the morning after his admission, he was sitting up in bed, fighting for breath, and, as he expressed it, felt almost suffocated.His pulse was rapid; his tongue moist and coated; and his face livid.He had been delirous during the night.An examination of his
NVP-BEZ235, a Dual PI3K/mTOR Inhibitor, Prevents PI3K Signaling and Inhibits the Growth of Cancer Cells with Activating PI3K Mutations
Authors: Violeta Serra, Ben Markman, Maurizio Scaltriti, Pieter J.A. Eichhorn, Vanesa Valero, Marta Guzman, Maria Luisa Botero, Elisabeth Llonch, Francesco Atzori, Serena Di Cosimo, Michel Maira, Carlos Garcia-Echeverria, Josep Lluis Parra, Joaquin Arribas, José Baselga
Journal: Cancer Research (2008)

Abstract Phosphatidylinositol-3-kinase (PI3K) pathway deregulation is a common event in human cancer, either through inactivation of the tumor suppressor phosphatase and tensin homologue deleted from chromosome 10 or activating mutations of p110-α. These hotspot mutations result in oncogenic activity of the enzyme and contribute to therapeutic resistance to the anti-HER2 antibody trastuzumab. The PI3K pathway is, therefore, an attractive target for cancer therapy. We have studied NVP-BEZ235, a dual inhibitor of the PI3K and the downstream mammalian target of rapamycin (mTOR). NVP-BEZ235 inhibited the activation of the downstream effectors Akt, S6 ribosomal protein, and 4EBP1 in breast cancer cells. The antiproliferative activity of NVP-BEZ235 was superior to the allosteric selective mTOR complex inhibitor everolimus in a panel of 21 cancer cell lines of different origin and mutation status. The described Akt activation due to mTOR inhibition was prevented by higher doses of NVP-BEZ235. NVP-BEZ235 reversed the hyperactivation of the PI3K/mTOR pathway caused by the oncogenic mutations of p110-α, E545K, and H1047R, and inhibited the proliferation of HER2-amplified BT474 cells exogenously expressing these mutations that render them resistant to trastuzumab. In trastuzumab-resistant BT474 H1047R breast cancer xenografts, NVP-BEZ235 inhibited PI3K signaling and had potent antitumor activity. In treated animals, there was complete inhibition of PI3K signaling in the skin at pharmacologically active doses, suggesting that skin may serve as surrogate tissue for pharmacodynamic studies. In summary, NVP-BEZ235 inhibits the PI3K/mTOR axis and results in antiproliferative and antitumoral activity in cancer cells with both wild-type and mutated p110-α. [Cancer Res 2008;68(19):8022–30]
Glycated high-density lipoprotein regulates reactive oxygen species and reactive nitrogen species in endothelial cells
Authors: Toshiyuki Matsunaga, Takanori Nakajima, Takashi Miyazaki, Iwao Koyama, Shigeru Hokari, Ikuo Inoue, Shin-ichiroh Kawai, Hiroji Shimomura, Shigehiro Katayama, Akira Hara, Tsugikazu Komoda
Journal: Metabolism (2003)
Stromal pleiotrophin regulates repopulation behavior of hematopoietic stem cells
Authors: Rouzanna Istvanffy, Monika Kröger, Christina Eckl, Sylke Gitzelmann, Baiba Vilne, Franziska Bock, Steffi Graf, Matthias Schiemann, Ulrich B. Keller, Christian Peschel, Robert A. J. Oostendorp
Journal: Blood (2011)
DNA–RNA chimeric hammerhead ribozyme to transforming growth factor-β1 mRNA inhibits the exaggerated growth of vascular smooth muscle cells from spontaneously hypertensive rats
Authors: J Teng
Journal: Cardiovascular Research (2000)

Objective: The purpose of this study was to develop DNA–RNA chimeric hammerhead ribozyme against transforming growth factor-β1 (TGF-β1) mRNA as a gene therapy agent for arterial proliferative diseases. Methods: A 38-base hammerhead ribozyme against rat TGF-β1 mRNA, to produce cleavage at the GUC sequence at nucleotide 825 according to the secondary structure of rat TGF-β1 mRNA was designed. To enhance its stability, we synthesized a DNA–RNA chimeric ribozyme with two phosphorothioate linkages at the 3′-terminal. We also synthesized a mismatch ribozyme with single base change in the catalytic loop region as a control. These ribozymes were delivered into rat vascular smooth muscle cells (VSMC) from spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) rats by lipofectin-mediated transfection, and their biological effects were investigated. Results: According to in vitro cleavage studies, the synthetic ribozyme can cleave the synthetic substrate RNA into two RNA fragments. Chimeric ribozyme significantly inhibited DNA synthesis in VSMC from SHR but not in cells from WKY rats. Mismatch ribozyme showed only a little effect on growth of VSMC from SHR. Chimeric ribozyme significantly inhibited proliferation of VSMC from SHR; in contrast, the proliferation of VSMC from WKY rats was significantly increased by this chimeric ribozyme. Mismatch ribozyme did not affect proliferation of VSMC from either rat strain. Chimeric hammerhead ribozyme to rat TGF-β1 dose-dependently inhibited TGF-β1 mRNA expression detected by reverse transcription and polymerase chain reaction analysis in VSMC from both rat strains. Chimeric hammerhead ribozyme to rat TGF-β1 also dose-dependently inhibited TGF-β1 protein production detected by Western blot analysis. Conclusions: The present results demonstrated that our designed DNA–RNA chimeric hammerhead ribozyme to TGF-β1 mRNA might be a useful gene therapy agent for hypertensive vascular diseases.
Erythema gyratum repens-like eruption in a patient with epidermolysis bullosa acquisita associated with ulcerative colitis
Authors: A. España, C. Sitaru, M. Pretel, L. Aguado, J. Jimenez
Journal: British Journal of Dermatology (2007)

Journal Article Erythema gyratum repens‐like eruption in a patient with epidermolysis bullosa acquisita associated with ulcerative colitis Get access A. España, A. España Department of Dermatology, University Clinic of Navarra, University of Navarra, School of Medicine, PO Box 4209, Pamplona 31080, Navarra, Spain *Department of Dermatology, University of Lübeck, Germany †Department of Gastroenterology, Hospital of Navarra, Pamplona, Navarra, Spain E‐mail: aespana@unav.es Search for other works by this author on: Oxford Academic Google Scholar C. Sitaru, C. Sitaru Department of Dermatology, University Clinic of Navarra, University of Navarra, School of Medicine, PO Box 4209, Pamplona 31080, Navarra, Spain *Department of Dermatology, University of Lübeck, Germany †Department of Gastroenterology, Hospital of Navarra, Pamplona, Navarra, Spain E‐mail: aespana@unav.es Search for other works by this author on: Oxford Academic Google Scholar M. Pretel, M. Pretel Department of Dermatology, University Clinic of Navarra, University of Navarra, School of Medicine, PO Box 4209, Pamplona 31080, Navarra, Spain *Department of Dermatology, University of Lübeck, Germany †Department of Gastroenterology, Hospital of Navarra, Pamplona, Navarra, Spain E‐mail: aespana@unav.es Search for other works by this author on: Oxford Academic Google Scholar L. Aguado, L. Aguado Department of Dermatology, University Clinic of Navarra, University of Navarra, School of Medicine, PO Box 4209, Pamplona 31080, Navarra, Spain *Department of Dermatology, University of Lübeck, Germany †Department of Gastroenterology, Hospital of Navarra, Pamplona, Navarra, Spain E‐mail: aespana@unav.es Search for other works by this author on: Oxford Academic Google Scholar J. Jimenez J. Jimenez Department of Dermatology, University Clinic of Navarra, University of Navarra, School of Medicine, PO Box 4209, Pamplona 31080, Navarra, Spain *Department of Dermatology, University of Lübeck, Germany †Department of Gastroenterology, Hospital of Navarra, Pamplona, Navarra, Spain E‐mail: aespana@unav.es Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 156, Issue 4, 1 April 2007, Pages 773–775, https://doi.org/10.1111/j.1365-2133.2006.07746.x Published: 01 April 2007
Breast Implants and Connective-Tissue Disease-Reply
Authors: Charles H. Hennekens
Journal: JAMA (1996)

<h3>In Reply.</h3> —Ms Karns and Ms Cullison erroneously suggest that we failed to consider an important point—the possibility of biased selection into the study of only the healthiest women. This is incorrect, because only about 10% of the approximately 400 000 participants in the Women's Health Study are also participating in the Women's Health Study randomized trial of aspirin and vitamin E and signed a consent to avoid taking aspirin or other platelet-active drugs for the duration of the trial. They correctly suggest that the observed 24% increase may be an underestimate, but fail to consider that an overestimate is also plausible.<sup>1</sup>Specifically, among women with breast implants, physicians may be more likely to diagnose and participants may be more likely to report connective-tissue diseases. Dr Romano raises the issue of the importance of considering atypical connective-tissue diseases such as fibromyalgia, an issue that had not been hypothesized when the Mayo Clinic
Altered Relation of Two Collagen Types in Osteogenesis Imperfecta
Authors: Bryan Sykes, Martin J.O. Francis, Roger Smith
Journal: New England Journal of Medicine (1977)

To ascertain if the features of osteogenesis imperfecta could be due to an abnormality in two genetically distinct collagens, Type III and Type I, we measured, in pepsin digests of skin, the ratio of the alpha 1, (III) to alpha 1 (I) chains derived from the two types, using a method of interrupted polyacrylamide-gel electrophoresis. In 40 control subjects this ratio decreased from about 0.45 in early fetal life to a mean (+/-2 S.D.) of 0.14 +/- 0.06 in 14 adults. Seven of nine adult patients with mild osteogenesis imperfecta had ratios of more than 4 S.D., above this mean, as did two of five patients with severe osteogenesis imperfecta. The increased ratio was probably due to a reduction of Type I collagen. If this reduction were generalized it could contribute to the bony fragility of osteogenesis imperfecta, since mineralized bone contains Type I collagen only.
Distribution of cAMP-Activated Chloride Current and CFTR mRNA in the Guinea Pig Heart
Authors: Andrew F. James, Tomoko Tominaga, Yasunobu Okada, Makoto Tominaga
Journal: Circulation Research (1996)

Guinea pig ventricular myocytes exhibit a Cl − -selective current regulated by the cAMP-dependent pathway. We have investigated the distribution of cAMP-activated Cl − channel current density and cystic fibrosis transmembrane-conductance regulator (CFTR) mRNA in three regions of the guinea pig heart: the atrium, and the epicardium and endocardium of the free wall of the left ventricle. The regional differences in the Cl − current density were investigated in enzymatically isolated myocytes using the whole-cell patch-clamp technique. Forskolin (1 μmol/L) activated Cl − -selective currents in all ventricular myocytes and 21% of atrial myocytes examined. The conductance density, estimated as the outward chord conductance normalized to cell capacitance, was greatest in epicardial myocytes (79.8±8.4 pS/pF, n=21) and significantly lower in endocardial (59.8±9.5 pS/pF, n=22) and atrial (10.9±5.0 pS/pF, n=38) myocytes. The regional differences in CFTR mRNA expression levels were investigated by competitive reverse-transcribed polymerase chain reaction. The regional distribution of the mRNA levels was similar to that of the Cl − conductance density, ie, highest in the epicardium (23 230±1840 molecules/μg total RNA, n=3), significantly lower in endocardium (10 610±780 molecules/μg total RNA, n=3), and lowest in atrium (1450±290 molecules/μg total RNA, n=3). The data indicate that regional differences in CFTR mRNA expression in the guinea pig heart are responsible, at least in part, for the regional differences in cAMP-activated Cl − current density.
Aspirin Use and Outcomes in a Community-Based Cohort of 7352 Patients Discharged After First Hospitalization for Heart Failure
Authors: Finlay A. McAlister, William A. Ghali, Yanyan Gong, Jiming Fang, Paul W. Armstrong, Jack V. Tu
Journal: Circulation (2006)

Background— The safety of aspirin in heart failure (HF) has been called into question, particularly in those patients (1) without coronary disease, (2) with renal dysfunction, or (3) treated with low-dose angiotensin-converting enzyme (ACE) inhibitors and high-dose aspirin. Methods and Results— We examined prescription patterns and outcomes (all-cause mortality and/or HF readmission) in patients discharged from 103 Canadian hospitals between April 1999 and March 2001 after a first hospitalization for HF. Of 7352 patients with HF (mean age, 75 years; 44% without coronary disease and 29% with renal dysfunction), 2785 (38%) died or required HF readmission within the first year. Compared with nonusers, aspirin users were no more likely to die or require HF readmission (hazard ratio [HR], 1.02 [0.91 to 1.16]), even in patients without coronary disease (HR, 0.98 [0.78 to 1.22]) or patients with renal dysfunction (HR, 1.13 [0.94 to 1.36]). On the other hand, users of ACE inhibitors were less likely to die or require HF readmission (HR, 0.87 [0.79 to 0.96]), even if they were using aspirin (HR, 0.86 [0.77 to 0.95]). There were no dose-dependent interactions between aspirin and ACE inhibitors. Conclusions— In this observational study, aspirin use was not associated with an increase in mortality rates or HF readmission rates, and aspirin did not attenuate the benefits of ACE inhibitors, even in patients without coronary disease, patients with renal dysfunction, or patients treated with high-dose aspirin and low-dose ACE inhibitors.