tbuckley/cabot-search huggingface dataset:
Unusual transcriptional and translational regulation of the bacteriophage Mu mom operon
Authors: Stanley Hattman
Journal: Pharmacology & Therapeutics (1999)

The bacteriophage Mu mom gene encodes a novel DNA modification that protects the viral genome against a wide variety of restriction endonucleases. Expression of mom is subject to a series of unusual regulatory controls. Transcription requires the action of a phage-encoded protein, C, which binds (probably as a dimer) the mom promoter from -33 to -52 (with respect to the transcription start site) in two adjacent DNA major grooves on one face of the helix. No apparent direct interaction between C and the host RNA polymerase (RNAP) is evident; however, C binding alters mom DNA conformation. In the absence of C, RNAP binds the mom promoter at a site that results in transcription in a direction away from the mom gene. The function of this transcription is unknown. An additional layer of transcriptional regulation complexity is due to the fact that the host Dam DNA-(N6-adenine)methyltransferase is required. Dam methylation of three closely spaced upstream GATC sequences is necessary to prevent binding by the host protein, OxyR, which acts as a repressor. Repression is not mediated by inhibition of C binding, but rather through interference with C-mediated recruitment of RNAP to the correct site. Translation of mom is regulated by the phage Com protein. Com is only 62 amino acids long and contains a zinc finger-like structure (coordinated by four cysteine residues) in the amino terminal domain. Com binds mom mRNA 5' to the mom open reading frame, whose translation start signals are contained in a stem-loop translation-inhibition-structure. Com binding to its target site (5' to and adjacent to the translation-inhibition-structure) results in a stable change in RNA secondary structure that exposes the translation start signals.
On the Value of Electrolysis in Angioma and Goitre
Authors: J. Duncan
Journal: BMJ (1888)

After this Mr. C. gained steadily in strength, and before he left the country, about the end of December, was able to walk two or three miles at a stretch, his pulse beinig generally aLbout 70.He spent the winter in Edinbuirglh, and about a month of spring in North Wales.He is now at hi.s resi(lence in 'ertlhsliire, and pretty well out of the doctor's handls.He has lately spent the greater part of three days in the Glasgowv exhiibition, which I take to be a pretty severe trial of strength.lie still continues to take the liq.arsenicalis for every alternate month.Dr. AFFLECK thought there was now sufficient clinical evidence to justify an alteration in the nomenclature of this disease.Many of the cases, having all the characteristics of pernicious anemia, recovering completely under treatment by arsenic, in conjunction with a sultable diet.Dr. Affleck had repeatedly had cases of this disease under treatment in the Royal Infirmary, Edinburgh, where hemacytometric observation has shown corpuscles reduced considerably below 1,000,000 per cubic millimUtre completely re- cover under treatment by arsenic and iron.-Dr.M. A. BOYD said that, in a great many cases of chronic dilatation of the stomach, supervening on chronic gastric catarrh and without organic dis- ease, a condition of antemia and exhaustion supervenes, which was often mistaken for pernicious amemia.The history of this case would closely correspond.The persistence of chronic gastro- enteric derangement for so many years would produce all the symptoms enumerated, more especially as the patient improved ultimately with arsenic.
Potassium studies in chronic obstructive airways disease.
Authors: None Semple P d'A, W S Watson, R Hume, G R Sutherland
Journal: Thorax (1978)

Seventeen male patients with chronic obstructive airways disease in remission were separated into two groups according to arterial carbon dioxide tensions. Hypercapnia was associated significantly with hypoxia and increased red cell volume whereas normocapnia was not. Normocapnic patients were significantly lighter than those with hypercapnia. Total body potassium (TBK) measured by the whole body monitor was significantly low in two of the patients studied (P less than 0.005). The mean value for TBK for the normocapnic group as a whole was significantly low (P less than 0.005), but the mean value for the hypercapnic group was not. Serum potassium and erythrocyte potassium concentrations were normal even when TBK was low, and diuretics had no apparent influence on these potassium values. Of four patients (two in the series and two others) who had TBK measured after a recent episode of cor pulmonale, three had significantly low values. The only previous studies using a whole body monitor to measure TBK in chronic obstructive airways disease found no such low values, though other workers estimating exchangeable potassium by isotope dilution techniques had found evidence of gross potassium depletion. It is concluded that low TBK does indeed occur in patients with chronic obstructive airways disease and that gross depletion is more likely to follow an episode of cor pulmonale.
AN ARGYLL ROBERTSON PUPIL BECOMING NORMAL AFTER MERCURY AND SALVARSAN
Authors: J. J. Zaun
Journal: JAMA (1913)

H. W., aged 32, married eight years, whose child, aged 3, and wife show no evidence of syphilitic lesions, had gonorrhea years ago, but does not know of ever having had a chancre or initial lesion. I saw him July 30, 1912. He consulted his physician then on account of difficulty in walking and cramps in the calves of his legs. Examination at that time revealed complete loss of patellar reflexes; Argyll Robertson pupil in both eyes (no reaction to light); cramps in the calves; gastric and intestinal crises; marked Romberg sign; testicular reflex increased so that stroking the skin on the inside of thigh caused the testicle to be drawn up into the canal; muscle sense disturbed; gait markedly affected; Wassermann reaction positive. The treatment consisted of mercurial inunctions and potassium iodid until August 20. He was then given 0.6 gm. of salvarsan in the right gluteal region. A
IS THE CONSUMPTIVE CHEST FLAT?.
Authors: WOODS HUTCHINSON
Journal: JAMA (1903)

Some years ago, in the course of a study of the disease liabilities of the human as compared with the animal chest, I was led to take some measurements of the diameters of the human chest at various ages and in certain diseases. The results of these were somewhat unexpected, and led to further researches, of which a preliminary report was read before the Philadelphia meeting of the Association in 1897, and published inThe Journalof the American Medical Association, Sept. 11 of that year. Since that time I have been gradually accumulating further data, though unfortunately delayed by a period of impaired health, and as these are now sufficient in number to give a reasonable probability of correctness to deductions drawn from them, I have ventured to again report progress through the columns ofThe Journal. A short résumé of the position taken in my former paper will
Abstract A55: Inhibition of the heat shock protein receptor CD91 abrogates concomitant antitumor immunity.
Authors: Yu Jerry Zhou, Robert J. Binder
Journal: Cancer Research (2013)

Abstract Most tumors are capable of generating immune response in the bearing host, a phenomenon described as concomitant immunity. Since tumors lack the typical (foreign) PAMPs that provide signal 2 for T cell priming, the mechanism of how concomitant immunity is established remains a mystery. We provide evidence here that, heat shock proteins (HSPs), when released into the tumor microenvironment, is the immunogen necessary for priming concomitant tumor specific immunity. These responses require CD91- the endocytic and signaling receptor for the immunogenic HSPs. In our study, we generated cd11c-specific CD91 knockout mice and showed that tumors grew faster in those knockout mice, compared to CD91+/+ mice. In addition, we abrogated the interaction of tumor-derived HSP with CD91 in vivo by over-expression of Receptor Associated Protein (RAP), an endogenous inhibitor of CD91. The data showed that: first, tumors expressing RAP grew with significantly faster kinetics than the non-RAP expressing counterparts in wild type mice, although this difference was non-existent in immunocompromised mice and the inherent proliferative rates of tumors with or without RAP were identical; second, RAP-expressing tumors, when used as an immunogen in tumor prophylaxis, were significantly less efficient in priming immune responses; third, we examined the competition for CD91 between RAP and tumor-derived HSP in vivo. In the presence of RAP, less amount of tumor-derived EGFP-labeled HSPs were taken up by APCs in draining lymph nodes. In summary, our study demonstrates that the HSP-CD91 pathway is critical for establishment of concomitant immunity. Considering that elevated RAP levels have been reported in colon cancer patients, we propose a novel mechanism of immune evasion for tumors expressing competing ligands for immune receptors such as CD91. Citation Format: Yu Jerry Zhou, Robert J. Binder. Inhibition of the heat shock protein receptor CD91 abrogates concomitant antitumor immunity. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology: Multidisciplinary Science Driving Basic and Clinical Advances; Dec 2-5, 2012; Miami, FL. Philadelphia (PA): AACR; Cancer Res 2013;73(1 Suppl):Abstract nr A55.
A Clinical Review of Autotransfusion and Its Role in Trauma
Authors: Lenworth M. Jacobs
Journal: JAMA (1984)

AUTOTRANSFUSION is defined as the collection and reinfusion of a patient's own blood. The first description of autotransfusion dates back to 1818, when Blundell<sup>1</sup>used it in London to counter postpartum hemorrhage, with a mortality of 50%. Autotransfusion in the setting of chest trauma was first recorded by Elmendorf<sup>2</sup>during battle in 1917 and in civilian life in 1931. The earliest reported American application of autotransfusion was attributed to Lockwood<sup>3</sup>intraoperatively during a splenectomy in 1917. Early literature of the 1920s and 1930s reported autotransfusion more commonly used for intra-abdominal hemorrhage, ie, ruptured ectopic pregnancies and traumatic vascular injuries. Its application in chest or pleural cavity injuries was limited to a few sporadic cases. The reluctance for such use stemmed from the fear of contamination of the shed blood. With the advent of blood typing and cross matching, homologous blood from banks became the standard blood replacement
Granulocyte-Macrophage Colony Stimulating Factor and <i>Pneumocystis carinii</i> Pneumonia in Mice
Authors: Jose F. Mandujano, Nympha B. D'Souza, Steve Nelson, Warren R. Summer, Robert C. Beckerman, Judd E. Shellito
Journal: American Journal of Respiratory and Critical Care Medicine (1995)

We hypothesized that therapy with granulocyte-macrophage colony stimulating factor (GM-CSF) would decrease intensity of murine Pneumocystis carinii pneumonia by upregulating alveolar macrophage function. Mice were depleted of CD4+ T lymphocytes and then inoculated intratracheally with P. carinii. Four weeks later, they received recombinant murine GM-CSF (rmGM-CSF) 5 µg/d subcutaneously for 7 and 14 d. At the end of therapy lung tissue was scored for intensity of P. carinii infection by silver methenamine stain and for inflammation by hematoxylin-eosin stain. We found that rmGM-CSF therapy significant decreased the intensity scores of PCP infection in comparison to control mice (1.88 ± 0.47 vs 3.06 ± 0.12, p < 0.01). Inflammation scores were not significantly different in the rmGM-CSF group compared with the control group (1.83 ± 0.47 vs 2.83 ± 0.67). Alveolar macrophages from mice treated with rmGM-CSF released significantly more tumor necrosis factor-alpha (TNF-α) than cells from control mice after in vitro stimulation with lipopolysaccharide (LPS) alone (2.65 ± 0.30 vs 1.45 ± 0.26 ng/ml, p = 0.01) or with LPS plus murine recombinant interferon-γ (4.16 ± 0.51 vs 2.25 ± 0.34 ng/ml, p = 0.01). We conclude that GM-CSF therapy reduces the intensity of PCP and this effect is associated with an enhanced alveolar macrophage TNF-α production.
The NHS reforms revisited
Authors: R. Klein
Journal: BMJ (1996)

Born amid anger and bitterness, the 1991 reforms of the NHS continue to be a subject of controversy. No consensus about the balance of costs and benefits has emerged, and disagreement about the NHS will doubtless feature as prominently in the next general election campaign as it did in the previous two. Not only is the available evidence about the NHS's record since 1991 fragmentary and often ambiguous, but the fiercely partisan positions taken up by advocates and critics when Kenneth Clarke launched Working for Patients1 in 1989 suggest that, even if more had been invested in evaluation, any further evidence would have been used to fuel argument rather than to resolve it.

It is therefore bold of the BBC to launch its three-part television series Safe with Us, designed to document the genesis, implementation, and impact of the NHS reforms. The series, to be screened over the next three weeks, illustrates both the strengths and weaknesses …
The Whole Truth About Coronary Stents
Authors: Aseem Malhotra
Journal: JAMA Internal Medicine (2014)

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Law will fine German doctors 5000 for failure to advise in abortion cases
Authors: N. Stafford
Journal: BMJ (2009)

Background The prevalence of myopia in Scandinavia seems to differ from other parts of the world and the reasons remain poorly investigated. The current study investigated the incidence of myopia, myopic shift, and associated risk factors in Swedish schoolchildren. This study also investigated the development of refractive error under the effect of COVID-19 restrictions. Methods This longitudinal study was conducted between Jan-2019 and June-2021 in which a cohort of Swedish schoolchildren aged 8-16 years were recruited. Myopia was defined as spherical equivalent refraction (SER) -0.50D. Myopic shift was defined as a minimum change in SER of -0.50D between each visit. Cumulative incidence (CIN) and incidence rate (IRA) were computed. Cox-regression and linear mixed models were used to modulate myopic shift and changes in SER. Results The study enrolled 128 participants, 86% Caucasian, 70 females, mean age 12.0 years (SD=2.4). The CIN of myopia during the two-years follow-up was 5.5%, IRA of myopia was 3.2 cases per 100 person-years. The CIN of myopic shift during the two-years was 21.0%, IRA of myopic shift was 12.4 cases per 100 person-years. Cox regression revealed that the probability of myopic shift reduced with age and increased with axial length/corneal-curvature ratio. Myopic children at the baseline and children with two myopic parents showed a significant faster-paced negative SER change over time. Changes in SER during the first year of the study were more marked than changes during the second year that coincided with the Covid pandemic. Conclusions In the current study the incidence of myopia and myopic shift was low when compared with countries in East Asia. Parental myopia remains a critical factor to consider when predicting myopia progression. Progression of myopia was unaffected by restrictions imposed during COVID-19 in Sweden. In addition to ethnicity, lifestyle and adequate educational pressure might be factors keeping prevalence of myopia under control in Scandinavia. Further studies to investigate these hypotheses are warranted.
Pemetrexed plus Cetuximab in Patients with Recurrent Non-small Cell Lung Cancer (NSCLC): A Phase I/II Study from the Hoosier Oncology Group
Authors: Shadia Jalal, David Waterhouse, Martin J. Edelman, Sreenivasa Nattam, Rafat Ansari, Karuna Koneru, Romnee Clark, Arthur Richards, Jingwei Wu, Menggang Yu, Brian Bottema, Angela White, Nasser Hanna
Journal: Journal of Thoracic Oncology (2009)
Constitutive production of angiotensin converting enzyme from rheumatoid nodule cells under serum free conditions.
Authors: M Goto, M Sasano, M Fuzisawa, T Okabe, K Nishizawa
Journal: Annals of the Rheumatic Diseases (1992)

Angiotensin converting enzyme was assayed in serum free culture supernatants from unstimulated rheumatoid nodule cells. Angiotensin converting enzyme was released spontaneously and the angiotensin converting enzyme derived from rheumatoid nodule cells was suppressed in a dose and time dependent manner by the protein synthesis inhibitor cycloheximide. These data suggest the constitutive de novo synthesis of angiotensin converting enzyme by rheumatoid nodule cells.
Comparative study of calcipotriol (MC 903) ointment and betamethasone 17-valerate ointment in patients with psoriasis vulgaris
Authors: William J. Cunliffe, John Berth-Jones, Alain Claudy, Geoffrey Fairiss, David Goldin, David Gratton, Catriona A. Henderson, Colin A. Holden, W. Stuart Maddin, Jean-Paul Ortonne, Marjorie Young
Journal: Journal of the American Academy of Dermatology (1992)
Ultrasonographic surveillance of hepatocellular carcinoma in cirrhosis: A randomized trial comparing 3- and 6-month periodicities
Authors: Jean-Claude Trinchet, Cendrine Chaffaut, Valérie Bourcier, Françoise Degos, Jean Henrion, Hélène Fontaine, Dominique Roulot, Ariane Mallat, Sophie Hillaire, Paul Cales, Isabelle Ollivier, Jean-Pierre Vinel, Philippe Mathurin, Jean-Pierre Bronowicki, Valérie Vilgrain, Gisèle N'Kontchou, Michel Beaugrand, Sylvie Chevret
Journal: Hepatology (2010)

Abstract Detection of small hepatocellular carcinoma (HCC) eligible for curative treatment is increased by surveillance, but its optimal periodicity is still debated. Thus, this randomized trial compared two ultrasonographic (US) periodicities: 3 months versus 6 months. A multicenter randomized trial was conducted in France and Belgium (43 sites). Patients with histologically proven compensated cirrhosis were randomized into two groups: US every 6 months (Gr6M) or 3 months (Gr3M). For each focal lesion detected, diagnostic procedures were performed according to European Association for the Study of the Liver guidelines. Cumulative incidence of events was estimated, then compared using Gray's test. The prevalence of HCC ≤30 mm in diameter was the main endpoint. A sample size of 1,200 patients was required. A total of 1,278 patients were randomized (Gr3M, n = 640; Gr6M, n = 638; alcohol 39.2%, hepatitis C virus 44.1%, hepatitis B virus 12.5%). At least one focal lesion was detected in 358 patients (28%) but HCC was confirmed in only 123 (9.6%) (uninodular 58.5%, ≤30 mm in diameter 74%). Focal-lesion incidence was not different between Gr3M and Gr6M groups (2-year estimates, 20.4% versus 13.2%, P = 0.067) but incidence of lesions ≤10 mm was increased (41% in Gr3M versus 28% in Gr6M, P = 0.002). No difference in either HCC incidence ( P = 0.13) or in prevalence of tumors ≤30 mm in diameter (79% versus 70%, P = 0.30) was observed between the randomized groups. Conclusion: US surveillance, performed every 3 months, detects more small focal lesions than US every 6 months, but does not improve detection of small HCC, probably because of limitations in recall procedures. (Hepatology 2011;)
Changes in albumin, α-fetoprotein and collagen gene transcription in ccl4-induced hepatic fibrosis
Authors: Arturo Panduro, Fouad Shalaby, Luis Biempica, David A. Shafritz
Journal: Hepatology (1988)

In efforts to understand mechanisms of liver dysfunction in cirrhosis, transcription of specific genes important to liver function has been measured in the rat model of CCl 4 -induced hepatic fibrosis. The relative transcription rates of albumin, α-fetoprotein and pro-α 1 -collagen genes were studied during development of fibrosis and after fibrosis was established. During the initial phase of CCl 4 administration, there was a decrease in albumin transcription associated with increased α-fetoprotein transcription, indicative of active liver regeneration. However, later during development of fibrosis, the response pattern of these genes was different, as albumin gene transcription was normal or increased and α-fetoprotein gene transcription was no longer increased. Three weeks after completion of CCl 4 treatment (fully established cirrhosis), albumin genes responded normally or hypernormally to an acute regenerative stimulus, but the α-fetoprotein gene was again not measurably responsive. Pro-α 1 -collagen gene transcription increased during the entire fibrogenic process and remained elevated after cirrhosis was established. These studies suggest that a switch from albumin to α-fetoprotein gene transcription can serve as a marker of liver regenerative capacity, and that this process is altered during and after development of hepatic fibrosis. The fibrogenic process is also associated with elevated transcription of collagen genes.
Gliadin peptide specific intestinal T cells in coeliac disease
Authors: K E A Lundin
Journal: Gut (2003)

Can modification of wheat gliadin peptides be used for immunotherapy in coeliac disease?

Despite its heterogeneous clinical appearance, coeliac disease has a remarkable uniform human leucocyte antigen (HLA) association. The majority of coeliac disease patients carry a certain variant of HLA-DQ2, the rest carry HLA-DQ8.1,2 As the physiological role of the HLA system is to present peptide fragments of antigens to T cells, it would seem logical that the HLA-DQ2 and HLA-DQ8 molecules predispose to coeliac disease by presenting peptides to T cells in the intestinal mucosa. The peptides these T cells recognise could derive form gluten peptides as coeliac disease is precipitated by intestinal exposure to wheat gluten and related proteins of other cereals. In fact, this simple concept has gained substantial experimental evidence in recent years.1,2 A paper in this issue of Gut 3 adds further credence to this model [see page 212] .

The small intestinal lesion is characterised by inflammation and infiltration of T cells both in the lamina propria and epithelium. Intraepithelial T cells are …