tbuckley/cabot-search huggingface dataset:
Diastolic Heart Sounds during Static (Handgrip) Exercise in Patients with Chest Pain
Authors: PETER F. COHN, PETER THOMPSON, WARREN STRAUSS, JAMES TODD, RICHARD GORLIN
Journal: Circulation (1973)

In order to determine the frequency of third and fourth heart sounds during cardiovascular stress, 61 patients with chest pain syndromes and normal resting phonocardiograms underwent phonocardiography both before and during submaximal handgrip exercise. Cardiac catheterization, selective coronary arteriography, and left ventriculography were performed in all patients. Twenty-nine had phonocardiograms simultaneous with hemodynamic studies. Twenty patients had normal coronary arteriograms; 41 had obstructive coronary artery disease. Fifteen percent of the subjects with normal coronary arteriograms and 54% of the patients with coronary artery disease developed diastolic heart sounds after handgrip exercise ( P &lt; 0.05). Conversely, 88% of the patients developing a diastolic heart sound had coronary artery disease. (If data from the present study are taken together with the previously reported prevalence of diastolic heart sounds at rest, it is estimated that these sounds can be readily demonstrated in approximately 75% of patients with coronary artery disease). Subjects with normal coronary arteriograms who developed postexercise diastolic heart sounds had a greater elevation in LVEDP and a lower EDVI/EDP ratio than did patients without these sounds, although the differences were not statistically significant. However, patients with coronary artery disease who developed abnormal heart sounds had changes which were significantly different from those who did not ( P &lt; 0.001 and P &lt; 0.05, respectively). These findings suggest that (1) the emergence of diastolic heart sounds during handgrip exercise is a useful clinical adjunct in the diagnosis of coronary artery disease and (2) in patients with coronary artery disease, these sounds are associated with significant elevations in LVEDP, which in turn may be related to altered end-diastolic volume-pressure relationships.
STUDIES ON THE IMMUNOLOGICAL RESPONSE TO FOREIGN TUMOR TRANSPLANTS IN THE MOUSE
Authors: N. A. Mitchison, O. L. Dube
Journal: The Journal of Experimental Medicine (1955)

The relation between serum antibody and resistance to tumor homografts in the mouse has been investigated. Production of serum antibody in response to homografts of a transplantable sarcoma (Sarcoma 1) was demonstrated, by cytotoxic action on the cells of the tumor, and also by a hemagglutinin test. The simpler and more repeatable hemagglutinin test was further investigated. Peak hemagglutinin titres were reached after the immunizing homografts underwent breakdown. Following transfer of lymph node cells from immunized mice into hosts of the same strain, hemagglutinin could be detected in the host serum. The course of its production showed that this secondary antibody was not elicited by transferred antigen, nor could it be due to transfer of preformed antibody. The cells developed the capacity to transfer hemagglutinin production later than the power to transfer heightened graft resistance. Spleen cells also transferred hemagglutinin production, at a later stage after immunization and to a lesser extent than cells from the regional lymph nodes. Implantation of the sarcoma in mice pretreated with certain preparations of lyophilized or frozen tissue stimulated hemagglutinin production, although the tumor grew progressively. The regional lymph nodes participated in the response: they could transfer hemagglutinin production into secondary hosts, but not graft resistance, and indeed appeared to diminish resistance. Lymph node cells from immunized donors conferred protection against the tumor on pretreated mice. Lymph nodes from normal donors also appeared in some experiments to confer protection although the effect was obscured by the rapidity with which the growing tumor became immunologically invulnerable. The fate of lymph node cells stained with acriflavine was followed after transfer. No effect of the staining on the power of the cells to confer immunity could be detected. Cells transferred to the peritoneal cavity passed into various host tissues, but were not found in test homografts. The conclusion is drawn that the hemagglutinating antibody is distinct from the antibody effective in combating homografts. The similarity in this respect between the homograft reaction and sensitization is emphasized in discussion.
Medical Problems and the Law
Authors: Blair L. Sadler
Journal: JAMA (1972)

This easily readable book focuses on personal injury litigation in the United States which, in the words of the author, "has become a big business attracting all types of individuals—most of whom are honest, some of whom are not." It is designed for the physician who will be confronted by a variety of such problems during his practice. As stated by Dr. Brown, the aim of the book is to "describe unethical and dishonest practices in personal injury cases so that they may be recognized and, hopefully, eliminated." Using a series of cases drawn on actual experience, the book begins with a thorough discussion of the problem of "overtreatment." Continuing with the illustrative case technique, he reviews in detail the steps in preparing a complete medical history and a comprehensive physical examination to improve patient care and to protect the physician. In the chapter entitled "Questionable Testimony in Medical-Legal Examination,"
microRNA-205 Regulates HER3 in Human Breast Cancer
Authors: Marilena V. Iorio, Patrizia Casalini, Claudia Piovan, Gianpiero Di Leva, Andrea Merlo, Tiziana Triulzi, Sylvie Ménard, Carlo M. Croce, Elda Tagliabue
Journal: Cancer Research (2009)

Abstract An increasing amount of experimental evidence shows that microRNAs can have a causal role in breast cancer tumorigenesis as a novel class of oncogenes or tumor suppressor genes, depending on the targets they regulate. HER2 overexpression is a hallmark of a particularly aggressive subset of breast tumors, and its activation is strictly dependent on the trans-interaction with other members of HER family; in particular, the activation of the PI3K/Akt survival pathway, so critically important in tumorigenesis, is predominantly driven through phosphorylation of the kinase-inactive member HER3. Here, we show that miR-205, down-modulated in breast tumors compared with normal breast tissue, directly targets HER3 receptor, and inhibits the activation of the downstream mediator Akt. The reintroduction of miR-205 in SKBr3 cells inhibits their clonogenic potential and increases the responsiveness to tyrosine-kinase inhibitors Gefitinib and Lapatinib, abrogating the HER3-mediated resistance and restoring a potent proapoptotic activity. Our data describe miR-205 as a new oncosuppressor gene in breast cancer, able to interfere with the proliferative pathway mediated by HER receptor family. Our study also provides experimental evidence suggesting that miR-205 can improve the responsiveness to specific anticancer therapies. [Cancer Res 2009;69(6):2195–200]
Abstract 463: Hypoxia leads to impaired differentiation and sustained global histone acetylation in immortalized mammary epithelial cells cultured as acini
Authors: Marica Vaapil, Karolina Helczynska, Siv Beckman, Sven Påhlman, Annika Jögi
Journal: Cancer Research (2010)

Abstract We study the effect of hypoxia on mammary epithelial cell differentiation at a non-malignant stage as a putative step in early malignant progression. Due to inadequate vasculature solid tumors often contain regions with low oxygen levels (hypoxia). Hypoxia is associated with increased metastatic potential and worse patient outcome. The hypoxic response is in large driven by the two transcription factors hypoxia inducible factor (HIF) 1 and HIF 2. We have reported that hypoxia leads to a less differentiated phenotype in breast cancer and in neuroblastoma, and in the clinic low tumor cell differentiation is related to poor prognosis in these diseases. To investigate the effect of hypoxia on mammary epithelial cell differentiation we employed the model of acinar morphogenesis. In this model immortalized mammary epithelial cells in three-dimensional (3D) culture on a laminin-rich matrix differentiate and form acini-like structures with evacuated lumen surrounded by polarized cells. We have previously seen that hypoxia (1% oxygen) impairs the process of acinar morphogenesis. The hypoxic cells failed to obtain polarity and markers of differentiation were affected at expression level as well as cellular localization. Addressing the mechanism behind the hypoxia-impaired differentiation, we find that hypoxia impairs the global histone deacetylation that is associated with changes in cell morphology and differentiation of the mammary epithelial cells. Three days post-seeding, during the proliferation stage, both normoxic and hypoxic cells stained positive for acetylated histone 4 (AcH4). When the normoxic cells go through morphological changes and acinar formation the acetylation of histone 4 is reduced whereas it is maintained in the hypoxic cell-clusters 10 days after seeding. Transfer of acini from normoxia to hypoxia at this time-point leads to an increase in AcH4. Thus, the hypoxic condition prevents global deacetylation, which is generally associated with high level of transcription and an undifferentiated proliferative cell state, rendering the cells an open chromatin state and hindering acinar formation. These data indicate that hypoxia promotes loss of differentiation also at a non-malignant stage. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 463.
Proximal gastric vagotomy after five years.
Authors: D W Storey, P B Boulos, M W Ward, C G Clark
Journal: Gut (1981)

A follow-up of 93 patients with chronic duodenal ulceration treated by proximal gastric vagotomy without drainage five to nine years previously shows a high incidence of confirmed recurrent ulceration of 16.1%. In addition, there have been patients with transient recurrent ulceration, and a small group with persistent dyspeptic symptoms but in whom no ulcer has been demonstrated. The operation is commendable for its lack of side-effects, but the high incidence of recurrent or persistent symptoms may lead to some reservations about its general application in the treatment of chronic duodenal ulceration.
LEPROSY FROM A SANITARY STANDPOINT.
Authors: ISADORE DYER
Journal: JAMA (1903)

<h3>SOME ANCIENT METHODS.</h3> Almost the first knowledge of leprosy carried with it methods for its control. No doubt many diseases were called lepra which did not deserve the name. The Hebrews, Arabs, Greeks and Egyptians recognized the disease and named it. With each of these peoples treatment was made subservient, while the sanitary measures were often radical. The Bible (<i>Leviticus, Numbers</i>and<i>Deuteronomy</i>) quite extensively refers to the lepers among the Hebrews. So true is this that the popular conception of leprosy to-day has been derived from the scriptural relation of it. "And the leper in whom the plague is, his clothes shall be rent, and his head bare, and he shall put a covering upon his upper lip and shall cry 'Unclean, Unclean.' All the days wherein the plague shall be in him, he shall be defiled; he is unclean. He shall dwell alone; without the camp shall his
Abstract 2339: Stimulation of sialyl Lewis X carbohydrate expression in lung carcinoma cells by neutrophils: Implications for metastasis
Authors: Catherine A. St. Hill, Mariya Farooqui, Katherine Krieser
Journal: Cancer Research (2010)

Abstract Sialyl Lewis X (sLeX) is a carbohydrate epitope expressed on leukocytes and carcinoma cells that promotes binding of both cell types to vascular endothelium by selectin mediated processes. These binding events are crucial for leukocyte trafficking to lymphoid tissues and sites of inflammation and metastasis of cancer cells. Increased sLeX expression is correlated with advanced disease and a poor prognosis for several types of carcinomas. Synthesis of sLeX is dependent on activity of the enzymes α-(1,3)-fucosyltransferase (FucT-III) and α2,3-sialyltransferase. Exposure to tumor necrosis factor alpha (TNF-α) has been described to upregulate FucT-III resulting in increased sLeX in the airways of patients with respiratory disease, however, little is known about the molecular mechanisms involved in regulation of sLeX expression in the inflammatory tumor microenvironment. We stably transfected lung carcinoma cells with FucT-III to investigate the role of TNF-α in regulation of sLeX expression, selectin binding ability, and metastatic potential of lung carcinoma cells. Stimulation of FucT-III transfected but not mock-transfected H1299 and A549 lung carcinoma cells with recombinant TNF-α resulted in a concentration dependent upregulation of sLeX expression, increased binding of carcinoma cells to E-selectin, and increased migration of transfectants through Matrigel. Lung carcinoma cells transfected with FucT-III demonstrated high secretion of the neutrophil chemoattractant cytokines IL-8, GRO-α and MCP-1. Co-culture of lung carcinoma cells with neutrophil conditioned media and neutrophils isolated from blood at an optimal ratio of 1:5 resulted in significantly increased sLeX expression (p = 0.02 and p = 0.002 respectively). Exposure of transfected carcinoma cells to neutrophil conditioned media and neutrophils resulted in morphological changes consistent with increased invasive potential and a TNF-α dependent increased cellular migration through Matrigel. In patient lung carcinoma specimens but not in normal lung tissues, we observed areas of high sLeX expression that correlated with increased neutrophil infiltration in 80% of tumors. We conclude that FucT-III activity and sLeX expression in lung carcinomas may recruit neutrophils in the tumor microenvironment that enhance the metastatic potential of lung tumor cells. This work was supported in part by funds from the National Institutes of Health/National Cancer Institute grant K08 CA111829-04. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2339.
Twelve-Year Follow-up of Survival in the Randomized European Coronary Surgery Study
Authors: E Varnauskas
Journal: New England Journal of Medicine (1988)

We studied survival rates among 767 men with good left ventricular function who participated in the European Coronary Surgery Study, 10 to 12 years after they were randomly assigned to either early coronary bypass surgery or medical therapy. At the projected five-year follow-up interval, we observed a significantly higher survival rate (±95 percent confidence interval) in the group that was assigned to surgical treatment than in the group assigned to medical treatment (92.4±2.7 vs. 83.1±3.9 percent; P = 0.0001). During the subsequent seven years, the percentage of patients who survived decreased more rapidly in the surgically treated than in the medically treated group (70.6±5.8 vs. 66.7±5.3 percent at 12 years). Thus, the improvement in the survival rate among patients with stable angina who were treated surgically appears to have been attenuated after five years. However, the gradually diminishing difference between the two survival curves still favored surgical treatment after 12 years (P = 0.04), despite the fact that 136 patients in the medically treated group had coronary bypass surgery and 23 in the "surgically treated" group did not. The benefit of surgical treatment tended to be greater, but not significantly so, as assessed by interaction analysis in the subgroups of patients who were older or who had signs of ischemia or previous infarction on the resting electrocardiogram, a markedly ischemic response to exercise testing, peripheral arterial disease, an absence of hypertension, and proximal obstruction in the left anterior descending artery. The reasons for the loss of a beneficial effect of surgery after five years are unknown and merit further study. (N Engl J Med 1988; 319:332–7.)
CULTIVATION OF SPIROCHÆTA GALLINARUM
Authors: Hideyo Noguchi
Journal: The Journal of Experimental Medicine (1912)

1. Spirochœta gallinarum can be cultivated in suitable artificial media for many successive generations and probably for indefinite periods. The presence of fresh tissue and a certain amount of oxygen seems to be essential for its growth. No perceptible odor is produced in the cultures. 2. The maximum growth of Spirochœta gallinarum is reached on about the fifth day, but the phase of degeneration commences slowly and gradually, so that in this respect the gallinarum differs from the duttoni, kochi, obermeieri, or novyi, whose cultures are characterized by sudden onset of degeneration soon after the maximum growth is attained. 3. No rod formation resembling bacilli arises in the course of multiplication of Spirochœta gallinarum in cultures. Many round or oval bodies appear in old cultures, but no infection of animals or formation of spiral forms from these granules has been produced. The granules are probably the degeneration products derived from the periblast of the spirochœtœ. 4. Cultures of Spirochœta gallinarum, either old or young, do not contain a form which passes through a Berkefeld filter (V) that infects chickens or grows into spirochætæ. 5. Spirochœta gallinarum remains virulent for chickens after being in cultures for at least thirteen generations, but it may become avirulent under certain cultural conditions. The inoculation of chickens with the attenuated culture renders the birds refractory to the subsequent infection with a virulent strain. 6. When the spirochætæ are cultivated in the media containing rabbit kidney instead of chicken muscle, the individual specimens are somewhat thicker, but otherwise typical. 7. Spirochœta gallinarum multiplies in culture by transverse division. No positive evidence of a longitudinal division has been obtained.
Clinical and family studies in genetic hemochromatosis: Microsatellite and HFE studies in five atypical families
Authors: P C Adams, M L Campion, G Gandon, J LeGall, V David, A M Jouanolle
Journal: Hepatology (1997)

A candidate gene (HFE) has been described for hereditary hemochromatosis on chromosome 6. The study of well-defined atypical hemochromatosis families using genetic markers may increase our understanding of the sensitivity and the specificity of genotyping in hemochromatosis. One hundred and thirteen Canadian families with genetic hemochromatosis were surveyed to find atypical families as possible examples of people with genetic recombinations. All families underwent clinical investigations including iron studies and HLA typing. Each individual was typed at three polymorphic microsatellite loci (D6S105, D6S1260, and D6S299) on chromosome 6. Sixteen subjects were studied for the two missense mutations described for the candidate gene for hemochromatosis (C282Y, H63D). There were eight HLA-identical siblings found in four different families (five men, three women; age range 30-72) with normal transferrin saturation and ferritin levels. There were two patients identified who were homozygous for the C282Y mutation without biochemical evidence of iron overload, and two patients with no evidence of the mutation with significant iron overload. Our conclusions are as follows: 1) finding HLA-identical siblings without iron overload does not confirm a genetic recombination, 2) difficulties in phenotypic definition of disease and the description of new iron overload syndromes that may differ from classical genetic HC cause complicated genetic studies, and 3) finding iron-loaded patients without a C282Y mutation and patients that are homozygous for the C282Y mutation without evidence of iron overload may limit the use of genotyping in population screening for hemochromatosis.
Different pharmacologic treatment for converting recent-onset atrial fibrillation: Evaluation on 377 patients
Authors: Giuseppe Boriani, Alessandro Capucci, Gian Luca Botto, Ida Rubino, Tiziano Lenzi, Maurizio Ongani, Mauro Biffi, Paolo Sabbatani, Mario Sanguinetti, Bruno Magnani
Journal: Journal of the American College of Cardiology (1996)
CT Scans and Tuberous Sclerosis
Authors: Jerome V. Murphy
Journal: JAMA (1976)

<h3>To the Editor.—</h3> The article by Martin et al (235:2323, 1976) indicates that the diagnosis of tuberous sclerosis in a patient may be confirmed by identification of subependymal calcifications on computerized axial tomography (CT). From their series of patients, they imply that a normal CT scan (eg, patient 6) may exclude the diagnosis of tuberous sclerosis. We have performed numerous CT scans on patients at risk for tuberous sclerous. Two patients with the diagnosis of tuberous sclerosis on the basis of retinal astrocytomas, seizures, mental retardation, and depigmented lesions did not have CT evidence of subependymal calcification, whereas an asymptomatic mother of an infant with tuberous sclerosis had an abnormal CT scan (Figure). This mother is a registered nurse and has no stigmata of tuberous sclerosis by history or physical examination. From these and other observations, we have concluded that, like many other laboratory studies, the CT scan is helpful
Multivessel coronary artery spasm.
Authors: R F Dunn, D T Kelly, N Sadick, R Uren
Journal: Circulation (1979)

A 60-year-old patient with variant angina was shown to have myocardial ischemia in two different regions supplied by separate major coronary arteries. Neither artery had significant coronary atherosclerotic obstruction. Ventricular fibrillation was noted during ST-segment elevation in anteroseptal leads. The attacks of pain and arrhythmias disappeared during nifedipine therapy.
Predisposition to Phenytoin Hepatotoxicity Assessed in Vitro
Authors: Stephen P. Spielberg, Gary B. Gordon, David A. Blake, Daniel A. Goldstein, H. Franklin Herlong
Journal: New England Journal of Medicine (1981)

Arene oxide metabolites of phenytoin may be involved in the pathogenesis of drug-induced hepatotoxicity. We examined individual susceptibility to toxicity from such metabolites by exposing human lymphocytes to metabolites generated by a murine hepatic microsomal system. Cells from 17 controls showed no toxicity at concentrations of phenytoin from 31 to 125 μM. Cells from three patients with phenytoin hepatotoxicity manifested dose-dependent toxicity from the metabolites. Phenytoin alone was not toxic to cells. The patients' dose-response curves resembled the response of control cells in which epoxide hydrolase (a detoxification enzyme for arene oxides) was inhibited. Detoxification of non-arene oxide metabolites (e.g., of acetaminophen) was normal in patients' cells. Cells from parents of two patients had intermediate responses. Cells from a sibling of one patient showed no toxicity; a sibling of another patient had a response similar to that of the patient. A heritable defect in response to arene oxides thus may predispose some patients to phenytoin hepatotoxicity. (N Engl J Med. 1981; 305:722–7.)