tbuckley/cabot-search huggingface dataset:
Chronic Mercury Poisoning in Latent Finger-print Development
Authors: G. Forbes, J. White
Journal: BMJ (1952)

That mercury is a highly toxic substance, whether in the form of the pure metal or in combination with an acid radical, has been known from the earliest times, certainly from the days of ancient Rome.Mercury poisoning was first noticed in quicksilver miners, then in gilders, and at the present day there are at least 80 industries in which mercury is used and in which it may be a potential danger to the workmen (Dublin and Vane, 1933).The history of industrial mercurialism and a review of the main industries concerned has been pro- vided by Buckell and his colleagues (1946).It is super- fluous to cover this ground again.To this list, however, there has recently been added another occupation which seems to carry a hazard of chronic mercury poisoning- namely, that of police finger-print expert.An outbreak of chronic mercurialism in the Lanca- shire County Constabulary Finger-print Department was reported by Agate and Buckell (1949).So far as we know, this is the only report of such an incident, and after reading their paper we decided to carry out the present investigation.Agate and Buckell found that of a staff of 32 men 7 exhibited tremor with or without other evidence of mercurialism.The substance respon- sible for the Lancashire outbreak was " grey powder " (hydrargyrum cum creta, B.P.), a preparation which is extensively used for the development of latent finger- prints.As it was known that the City of Sheffield Police Photographic Department had for years used the same powder, it was decided to inquire into the health of the members of that department.The Sheffield City Police Photographic Department is staffed by four men.In addition, one man who was trans- ferred to another branch of the service five years ago was included in the inquiry.
Abstract P2-09-11: Identification of a novel inhibitor of triple-negative breast cancer cell growth by screening of a small molecule library
Authors: T Fujita, T Mizukami, T Okawara, K Inoue, M Fujimori
Journal: Cancer Research (2013)

Abstract Background: Triple-negative breast cancers (TNBC) are defined as not having amplification of the estrogen receptor, progesterone receptor, or epidermal growth factor receptor 2. At present, recovery in patients is severely limited following diagnosis of metastatic TNBC, with less than 30% of patients surviving more than 5 years.. The most effective therapy to date is chemotherapy, which has been unsuccessful due to the lack of therapeutic targets for these aggressive cancers. To identify new molecular targets for TNBC, we have developed a novel method for drug discovery using active compounds for identification of pharmacodynamic biomarkers. Methods: We used chemical informatics to design a small molecule library that has structural diversity. This library was used to screen for compounds that selectively inhibit the proliferation in TNBC cell lines. The differences in gene expression profiles in cell lines before and after the addition of selected compounds were analyzed and compared with control cells. Results: We identified (E)-3-(3,4-dihydroxybenzylidene)-benzofuran-2(3H)-one (DBBF) that exhibited specific inhibition of the proliferation in a TNBC cell line, MDA-MB-468 with IC50 of 2.4 μM. Microarray analysis identified several signaling pathways, including the irinotecan pathway, which changed specifically in the TNBC cell lines by the addition of DBBF. Conclusion: We have developed a novel research strategy that involves screening of selective inhibitors of TNBC cell line proliferation that can be used for identification of pharmacodynamic biomarkers for TNBC. The discovery of new pathways by this technique should lead to the identification of new therapeutic targets for this aggressive cancer. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P2-09-11.
Effects of H1-receptor stimulation on coronary arterial diameter and coronary hemodynamics in humans.
Authors: K Matsuyama, H Yasue, K Okumura, K Matsuyama, H Ogawa, Y Morikami, N Inotsume, M Nakano
Journal: Circulation (1990)

Effects of H1-receptor stimulation on coronary arterial diameter and coronary hemodynamics were examined in 11 patients with angiographically normal coronary arteries and without variant angina or resting angina. Selective H1-receptor stimulation was achieved by infusing histamine into the left coronary artery at a rate of 2.0 micrograms/min for 5 minutes after pretreatment with cimetidine (25 mg/kg). Plasma histamine concentration in the coronary sinus, coronary sinus blood flow, heart rate, and aortic pressure were measured before, during, and after the histamine infusion. Coronary arterial diameter was measured by cinevideodensitometric analysis of coronary arteriograms performed before and immediately after the histamine infusion. During the histamine infusion, plasma histamine concentration in the coronary sinus increased from 0.33 +/- 0.06 to 5.86 +/- 0.71 ng/ml (p less than 0.01); coronary sinus blood flow increased from 98 +/- 12 to 124 +/- 13 ml/min (p less than 0.01), and coronary vascular resistance decreased from 1,113 +/- 117 to 851 +/- 91 mm Hg.min/l (p less than 0.01). Heart rate and aortic pressure remained unchanged. The mean luminal diameters of the proximal, middle, and distal left anterior descending artery increased by 9.4 +/- 3.6% (p less than 0.05), 19.2 +/- 3.8% (p less than 0.001), and 31.5 +/- 5.6% (p less than 0.001), respectively, after the histamine infusion. The mean luminal diameters of the proximal, middle, and distal left circumflex artery increased by 15.2 +/- 3.6% (p less than 0.01), 17.5 +/- 5.2% (p less than 0.01), and 20.6 +/- 4.3% (p less than 0.001), respectively, after the histamine infusion.(ABSTRACT TRUNCATED AT 250 WORDS)
Heart association advises against HRT for heart protection
Authors: D. Josefson
Journal: BMJ (2001)

The American Heart Association has issued revised guidelines on hormone replacement therapy (HRT) for postmenopausal women.

The new guidelines reverse previous recommendations and advise against the use of hormone replacement therapy for cardiovascular protection alone in postmenopausal women ( Circulation 2001;104:499-503).

The revised recommendations were issued because of conflicting evidence about combined oestrogen and progestogen (known as progestin in the United States) therapy and its effects on the heart. Traditionally, hormone replacement therapy was believed to be good for the heart, and in recent years it has been prescribed not only to ward off menopausal symptoms, but also …
Persistence of interleukin 7 activity and levels on tumour necrosis factor blockade in patients with rheumatoid arthritis
Authors: J. A G van Roon, S. A Y Hartgring, M. Wenting-van Wijk, K. M G Jacobs, P.-P. Tak, J. W J Bijlsma, F. P J G Lafeber
Journal: Annals of the Rheumatic Diseases (2006)

<b>Objectives:</b> To identify the mechanism of interleukin (IL)7-stimulated tumour necrosis factor α (TNFα) production and to determine the relationship between intra-articular IL7 and TNFα expression levels in patients with rheumatoid arthritis (RA). In addition, the effect of TNFα blockade on IL7 activity and on IL7 levels was studied. <b>Methods:</b> The effect of IL7 on isolated CD4 T cells and CD14 monocytes/macrophages was studied. IL7 and TNFα levels were measured in the synovial fluid of patients with RA. In RA synovial tissue, IL7 and TNFα expression was assessed in addition to IL1β, numbers of inflammatory cells and adhesion molecule expression. The extent to which TNFα blockade could prevent IL7-induced lymphocyte responses was studied in vitro. In addition, regulation of serum IL7 levels on anti-TNFα therapy (adalimumab) was studied. <b>Results:</b> IL7 induced cell contact-dependent TNFα production by cocultures of T cells and monocytes, but not by T cells and monocytes cultured separately. IL7 and TNFα levels in RA synovial fluid and synovial tissue significantly correlated. IL7-stimulated lymphocyte responses were not inhibited by TNFα blockade. Circulating IL7 levels were significantly reduced in patients who successfully responded to anti-TNFα treatment. However, IL7 levels persisted in non-responders. <b>Conclusion:</b> The present data suggest that IL7 is an important inducer of T cell-dependent TNFα production in RA joints. This may contribute to the correlation of intra-articular IL7 and TNFα in these joints. Furthermore, the persistence of IL7-induced inflammatory activity on TNFα blockade in vitro and persistence of IL7 levels and disease activity in anti-TNFα non-responders suggest that IL7 might additionally promote TNFα-independent inflammation.
Prevalence of sclerosing cholangitis in adults with autoimmune hepatitis: Evaluating the role of routine magnetic resonance imaging
Authors: Rupert Abdalian, Preeti Dhar, Kartik Jhaveri, Masoom Haider, Maha Guindi, Jenny E. Heathcote
Journal: Hepatology (2008)

Large bile duct injury (that seen on cholangiography) is not usually considered a feature of autoimmune hepatitis (AIH) in adults but is present in up to 50% of children with AIH. The aim of this work was to study the prevalence of large bile duct abnormalities identified by magnetic resonance cholangiography (MRC) in adults given a diagnosis of AIH. Seventy-nine (n = 79) patients given a diagnosis of AIH (mean AIH score: 15.1 +/- 3.4) were screened with MRC for evidence of sclerosing cholangitis (SC). Results were reviewed by two radiologists. Clinical parameters were correlated with MRC findings. A histological review of available liver biopsies (n = 29) was performed. Of the 79 patients surveyed, 8 (10%) had MRC findings consistent with primary sclerosing cholangitis (PSC). The interrater variability was excellent (kappa = 0.87). Younger age at diagnosis (24.3 +/- 11.9), higher baseline alkaline phosphatase (186.4 +/- 98.3), higher bilirubin at time of MRC (45.8 +/- 37.2), and greater lobular activity on initial liver biopsy were significantly associated with the detection of this overlap of SC with AIH (P = 0.024, P = 0.037, P = 0.032, and P = 0.041, respectively), but not alkaline phosphatase/aspartate aminotransferase ratio, time between the initial diagnosis of AIH and the MRC, or the presence of cirrhosis on initial liver histology. Two cases with a normal MRC had histological lesions typical of small duct PSC.The presence of SC detected by MRC and from liver histology in adult patients with AIH may not be clinically overt, and thus the prevalence of this AIH/SC overlap may be higher than previously recognized. Our data suggest that routine radiological evaluation of the biliary tree should be performed in adults given a diagnosis of AIH, as in children the presence of this overlap negatively impacts on survival.
A rare case of shock
Authors: T W Felton
Journal: Annals of the Rheumatic Diseases (2003)

A 48 year old non-smoking women presented with a six hour history of colicky right upper quadrant pain radiating to the back preceded by an episode of syncope. Past history included hyperthyroidism treated by partial thyroidectomy.

Initial examination showed mild right upper quadrant tenderness. Investigations demonstrated a normocytic anaemia (haemoglobin 92 g/l), white cell count 15.3×l09/l, with normal liver function tests and amylase. Twelve hours later she developed shock associated with a distending abdomen.

Emergency laparotomy showed a haemoperitoneum and huge retroperitoneal haematoma with catastrophic bleeding from the duodenojejunal region requiring 13 units of blood and 8 litres of colloid and crystalloid. Haemostasis was achieved with aortic cross suturing around a branch of the superior mesenteric artery (SMA) and packing the peritoneum. Packs were removed 24 hours later without complication.

A postoperative mesenteric angiogram delineated multiple small aneurysms in the gastroduodenal artery and its pancreatic branches, hepatic artery, and ileal branches of the SMA with microaneurysms of the main renal, lobar, and segmental arteries (fig 1). Differential diagnosis included polyarteritis nodosa (PAN) and fibromuscular dysplasia (FMD).



 Figure 1  
Digital subtraction mesenteric angiogram demonstrating “string of beads” of fibromuscular dysplasia



Further investigations, including …
Stretch Reflexes from the Dog's Lung to the Systemic Circulation
Authors: PETER F. SALISBURY, PIERRE-M. GALLETTI, RICHARD J. LEWIN, P. ANDRÉ RIEBEN
Journal: Circulation Research (1959)

Evidence is presented that reflex systemic vasodilatation occurs after stretching dog's lungs by either mechanical traction or positive pressure ventilation under conditions of separate pulmonary and systemic perfusion. This reflex is mediated by the vagus.
Abstract 2818: Aurora B kinase inhibitor barasertib (AZD1152) and cytarabine in combination exert more than additive cytotoxicities against cytarabine-resistant acute myeloid leukemia cells in vitro
Authors: Takahiro Yamauchi, Takanori Ueda
Journal: Cancer Research (2012)

Abstract The majority of patients with acute myeloid leukemia (AML) initially achieve complete remission by cytarabine (ara-C)-based chemotherapy, but many relapse with resistant disease. Aurora B kinase is involved in the spindle assembly checkpoint component of the mitotic process. Barasertib (formerly AZD1152), a selective inhibitor of aurora B kinase, provided an overall hematological response rate of 25% in AML patients in a phase I/II study, which warrants further investigation. To see the feasibility of the incorporation of this new agent to the standard induction chemotherapy, we evaluated the combination effect of barasertib with ara-C against leukemic cells in vitro. Cultured human leukemia HL-60 cells and ara-C-resistant variant HL-60/ara-C cells were used. Growth inhibition effects were evaluated by using the XTT assay. The cell cycle distribution and the induction of apoptosis were determined by flowcytometric analysis. Autophosphorylation of aurora B was assessed by Western blotting. The XTT assay determined that the 50%-growth inhibitory concentrations of ara-C were 100 - 300 nM for HL-60 cells and 4,000 - 5,000 nM for HL-60/ara-C cells, respectively. When HL-60 cells were treated with barasertib-hQPA, the active compound of barasertib, the cells exhibited an increase in the percentage of &amp;gt; 4N at 48 h with the subsequent induction of sub-G1 population. Autophosphorylation of aurora B was inhibited by barasertib-hQPA simultaneously. When the cells were treated with ara-C, the accumulation at G2-M phase and the subsequent increase in sub-G1 phase were observed. When the cells were treated with barasertib-hQPA and ara-C in combination, the treatment induced the greater-than-additive induction of sub-G1 population. However, the augmentation was brought about only when the cells were treated with barasertib prior to ara-C or both simultaneously. Barasertib-hQPA similarly altered the cell cycle, inhibited autophosphorylation of auroa B, and induced apoptosis in HL-60/ara-C cells. Low concentrations of ara-C failed to modify cell cycle distribution without the induction of apoptosis in HL-60/ara-C cells. Nevertheless, the sequential combination between barasertib-hQPA and a moderate concentration of ara-C augmented the sub-G1 population. In conclusion, the combination of barasertib with ara-C provided greater cytotoxicity than barasertib alone in both ara-C-sensitive and ara-C-resistant AML cell lines in vitro. The sequential administration of barasertib with ara-C may be promising against ara-C-refractory AML. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2818. doi:1538-7445.AM2012-2818
Coronary stenting for acute coronary dissection after coronary angioplasty: Implications of residual dissection
Authors: Fernando Alfonso, Rosana Hernandez, Javier Goicolea, Javier Segovia, Maria J. Perez-Vizcayno, Camino Bañuelos, Joao C. Silva, Pedro Zarco, Carlos Macaya
Journal: Journal of the American College of Cardiology (1994)
US court finds antiabortionists guilty of violent threats
Authors: F. Charatan
Journal: BMJ (2002)

A federal court in San Francisco has ruled that antiabortionists who distributed “Wanted” posters identifying doctors who performed abortions had illegally threatened the doctors.

The defendants, two antiabortion organisations and a number of individuals, also listed doctors' names and addresses on a website they called “The Nuremberg Files.” The names of doctors who had been killed were lined through in black; the names of wounded doctors were highlighted in grey ( BMJ 1999: 318;214).

An earlier court ruling last year had upheld the rights of the antiabortion campaigners to run such …
P909 POSTTRANSPLANT EVOLUTION OF PATIENTS RECEIVING LIVER GRAFTS FROM DONORS WITH FAMILIAL AMYLOIDOSIS POLYNEUROPATHY (DOMINO LIVER TRANSPLANTATION). A CASE–CONTROL STUDY
Authors: C. Baliellas, J. Castellote, L. Lladó, R. Rota, E. Dueñas, A. Girbau, J. Fabregat, X. Xiol
Journal: Journal of Hepatology (2014)
Use of Mutagenesis to Probe IGF-Binding Protein Structure/Function Relationships
Authors: David R. Clemmons
Journal: Endocrine Reviews (2001)

The IGF-binding proteins (IGFBPs) are multifunctional proteins that modulate IGF actions. To determine whether specific domains within these proteins account for specific functions, we and other laboratories have used in vitro mutagenesis. Prior experiments that used a variety of techniques had identified discrete regions within each protein that were proposed to account for specific functions. Alterations of these regions by substituting charged residues with neutral residues or hydrophobic residues with nonhydrophobic residues as well as domain swapping, i.e., substituting a domain from one specific form of IGFBP for the homologous domain in another form, has resulted in the elucidation of the functions of many of these specific sequences. Because the areas of protein sequence that are altered involve a limited number of amino acids, they generally do not alter the conformation of the entire protein; therefore, these specific substitutions can often be correlated with the functional changes that occur after mutagenesis. Mutants have been particularly useful for performing functional analyses in which the purified mutant protein is added to a biological test system. In some cases it has been possible to overexpress the mutagenized protein and determine whether the constitutively synthesized, mutant form of IGFBP has altered functional activity. These results have revealed that discrete regions of IGFBP sequence can mediate important and specific functional properties of these proteins.
Mechanism of Loss of Kv11.1 K <sup>+</sup> Current in Mutant T421M-Kv11.1–Expressing Rat Ventricular Myocytes
Authors: Sadguna Y. Balijepalli, Evi Lim, Sarah P. Concannon, Chen L. Chew, Kassandra E. Holzem, David J. Tester, Michael J. Ackerman, Brian P. Delisle, Ravi C. Balijepalli, Craig T. January
Journal: Circulation (2012)

Type 2 long QT syndrome involves mutations in the human ether a-go-go-related gene (hERG or KCNH2). T421M, an S1 domain mutation in the Kv11.1 channel protein, was identified in a resuscitated patient. We assessed its biophysical, protein trafficking, and pharmacological mechanisms in adult rat ventricular myocytes.Isolated adult rat ventricular myocytes were infected with wild-type (WT)-Kv11.1- and T421M-Kv11.1-expressing adenovirus and analyzed with the use of patch clamp, Western blot, and confocal imaging techniques. Expression of WT-Kv11.1 or T421M-Kv11.1 produced peak tail current (I(Kv11.1)) of 8.78±1.18 and 1.91±0.22 pA/pF, respectively. Loss of mutant I(Kv11.1) resulted from (1) a partially trafficking-deficient channel protein with reduced cell surface expression and (2) altered channel gating with a positive shift in the voltage dependence of activation and altered kinetics of activation and deactivation. Coexpression of WT+T421M-Kv11.1 resulted in heterotetrameric channels that remained partially trafficking deficient with only a minimal increase in peak I(Kv11.1) density, whereas the voltage dependence of channel gating became WT-like. In the adult rat ventricular myocyte model, both WT-Kv11.1 and T421M-Kv11.1 channels responded to β-adrenergic stimulation by increasing I(Kv11.1).The T421M-Kv11.1 mutation caused a loss of I(Kv11.1) through interactions of abnormal protein trafficking and channel gating. Furthermore, for coexpressed WT+T421M-Kv11.1 channels, different dominant-negative interactions govern protein trafficking and ion channel gating, and these are likely to be reflected in the clinical phenotype. Our results also show that WT and mutant Kv11.1 channels responded to β-adrenergic stimulation.
Feisty gram-negative aerobes succumb to new antibiotic group
Authors: John Henahan
Journal: JAMA (1982)

ABSTRACT The organism Chromobacterium violaceum was living in relative obscurity in the swamps of southern New Jersey only three years ago. But the new man-made drug that its discovery inspired has already proved quite effective against Pseudomonas aeruginosa and other drug-resistant bacteria involved in hospital-acquired infections throughout the world.Called azthreonam, the first of the new monobactam antibiotics synthesized at the Squibb Institute for Medical Research, Princeton, NJ, received its first clinical airing at the Third Mediterranean Congress of Chemotherapy in Dubrovnik, Yugoslavia. It has shown considerable efficacy against resistant gram-negative infections of the urinary tract, lungs, bone, and soft tissue. It is also efficacious against penicillin-resistant strains of Neisseria gonorrhoeae.In 1979, Squibb scientists found that C violaceum produces substances that are weak antibiotics but are also highly resistant to the β-lactamase enzymes. Such enzymes have effectively neutralized the efficacy of the penicillins and some of the cephalosporin antibiotics against
Cytotoxic-lnduced Ovarian Failure in Hodgkin's Disease
Authors: William F. Thorneloe
Journal: JAMA (1980)

<h3>To the Editor.—</h3> The articles by Chapman et al (242:1877; 1882, 1979) and the one by Sutcliffe (242:1898, 1979) provide lucid descriptions of women who have experienced great emotional trauma as a result of having a potentially fatal disease that must be treated with highly toxic although life-saving medications. These traumas are caused by the illness itself, grief reactions, financial pressure, interruption of lives, relief as the illness abates, among many relevant stresses. The family shares all of these traumas with the patient. Finally, there is the recognition that a patient may become physically and emotionally damaged by this illness and the required treatment. The authors' primary thesis is recognition of ovarian failure and concomitant sexual dysfunction as a result of chemotherapy. Patient education and estrogen replacement are treatments for this perceived iatrogenic disease. These women have other problems related to their illness and treatment, such as dysphoric mood, agitation,