tbuckley/cabot-search huggingface dataset:
Seneca Valley Virus, a Systemically Deliverable Oncolytic Picornavirus, and the Treatment of Neuroendocrine Cancers
Authors: P. Seshidhar Reddy, Kevin D. Burroughs, Laura M. Hales, Shanthi Ganesh, Brian H. Jones, Neeraja Idamakanti, Carl Hay, Shawn S. Li, Kristine L. Skele, Ann-Jeanette Vasko, Jingping Yang, D. Neil Watkins, Charles M. Rudin, Paul L. Hallenbeck
Journal: JNCI Journal of the National Cancer Institute (2007)

Numerous clinical trials have demonstrated that oncolytic viruses can elicit antitumor responses when they are administered directly into localized cancers. However, the treatment of metastatic disease with oncolytic viruses has been challenging due to the inactivation of viruses by components of human blood and/or to inadequate tumor selectivity. We determined the cytolytic potential and selectivity of Seneca Valley Virus-001 (SVV-001), a newly discovered native picornavirus, in neuroendocrine and pediatric tumor cell lines and normal cells. Suitability of the virus for intravenous delivery in humans was assessed by blood inactivation assays. Safety was evaluated in vivo using an immune-competent mouse model, and efficacy was evaluated in vivo in athymic mice bearing tumors derived from human small-cell lung cancer and retinoblastoma cell lines. Cell lines derived from small-cell lung cancers and solid pediatric cancers were at least 10000-fold more sensitive to the cytolytic activity of SVV-001 than were any of the adult normal human cells tested. Viral infectivity was not inhibited by human blood components. Intravenous doses up to 1 × 1014 virus particles (vp) per kg were well tolerated, and no dose-limiting toxicity was observed in immune-competent mice. A single intravenous dose of 1 × 108 vp per kg into athymic mice bearing preestablished small-cell lung or retinoblastoma tumors resulted in complete, durable responses in ten of ten and five of eight mice, respectively. SVV-001 has potent cytolytic activity and high selectivity for tumor cell lines having neuroendocrine properties versus adult normal cells. Systemically administered SVV-001 has potential for the treatment of metastatic neuroendocrine cancers.
Lactose tolerance in lambs with rotavirus diarrhoea.
Authors: A Ferguson, G Paul, D R Snodgrass
Journal: Gut (1981)

It has been suggested that lactose malabsorption is an important factor in producing the diarrhoea of acute rotavirus infection. Accordingly, the lactose tolerance of gnotobiotic newborn lambs, infected with lamb rotavirus, has been investigated by clinical studies and tissue enzyme assays. Although lactase activity is low in affected areas of the small intestine, rotavirus infected lambs are not lactose intolerant as assessed by the measurement of reducing substances in the faeces, or by the clinical effects and blood glucose levels after a 5.8 mmol (2 g)/kg lactose load on the second day post-infection. Lactose intolerance could be demonstrated by using extremely high (29.2 mmol (10 g)/kg) doses of lactose, three or four times the normal dietary lactose intake. These experiments suggest that lactose-containing feeds (such as maternal milk) are not necessarily contraindicated in patients or animals with rotavirus diarrhoea.
Effectiveness of Mass Oral Cholera Vaccination in Beira, Mozambique
Authors: Marcelino E.S. Lucas, Jacqueline L. Deen, Lorenz von Seidlein, Xuan-Yi Wang, Julia Ampuero, Mahesh Puri, Mohammad Ali, M. Ansaruzzaman, Juvenaldo Amos, Arminda Macuamule, Philippe Cavailler, Philippe J. Guerin, Claude Mahoudeau, Pierre Kahozi-Sangwa, Claire-Lise Chaignat, Avertino Barreto, Francisco F. Songane, John D. Clemens
Journal: New England Journal of Medicine (2005)

New-generation, orally administered cholera vaccines offer the promise of improved control of cholera in sub-Saharan Africa. However, the high prevalence of human immunodeficiency virus (HIV) infection in many cholera-affected African populations has raised doubts about the level of protection possible with vaccination. We evaluated a mass immunization program with recombinant cholera-toxin B subunit, killed whole-cell (rBS-WC) oral cholera vaccine in Beira, Mozambique, a city where the seroprevalence of HIV is 20 to 30 percent.
Limitation to muscular activity in chronic obstructive pulmonary disease
Authors: K.J. Killian
Journal: European Respiratory Journal (2004)

The constellation of laboured breathing, fixed inflated lungs that neither fill nor empty properly was first described in 1685 by Willis 1. Post mortem examination revealed that these lungs failed to deflate on opening of the chest 2, and the term emphysema was introduced 3. Chronic bronchitis was viewed as a separate entity occasionally coexisting with emphysema. Airway obstruction was recognised as the key feature of emphysema and chronic bronchitis at the end of the 1950s. This was formally acknowledged at a Ciba Guest Symposium held in 1959 4 and endorsed by the American Thoracic Society in 1962 5. The functional consequences of airway obstruction progress from a reduced capacity to breathe and exchange respiratory gases, to respiratory failure, pulmonary hypertension, right heart failure and premature death. A reduction in the forced expiratory volume in one second (FEV1) and the FEV1/vital capacity ratio, and failure to improve with treatment are the diagnostic features of what is known today as chronic …
Hepatocellular carcinoma: is current therapy really altering outcome?
Authors: P J Johnson
Journal: Gut (2002)

Progress in the management of hepatocellular carcinoma (HCC) has been slow and has limited impact on outcome. Most patients with HCC have two diseases--chronic liver disease and HCC--and complex interactions between the two have major implications for diagnosis and prognosis as well as the management of HCC. The disease is most prevalent in those areas of the world where the infrastructure for clinical trials is least developed. Also, the aetiology of the disease varies around the world and it is still not known whether HCCs of different aetiologies have different prognoses. Current treatment is making an impact on the management of HCC but further progress awaits not only the development of more effective treatments but also the development of adequate methodologies to assess the impact of these treatments.
Dynamics of GB Virus C viremia early after orthotopic liver transplantation indicates extrahepatic tissues as the predominant site of GB virus C replication
Authors: Thomas Berg, Andrea R. Müller, Klaus P. Platz, Marina Höhne, Wolf-Otto Bechstein, Uwe Hopf, Bertram Wiedenmann, Peter Neuhaus, Eckart Schreier
Journal: Hepatology (1999)

The principal site of GB virus C (GBV–C) replication is unknown. To determine whether hepatic GBV–C replication is important for the maintenance of a measurable viremia level in GBV–C infection, the influence of hepatectomy followed by liver transplantation on GBV–C viremia was investigated. GBV–C RNA levels were determined by a quantitative TaqMan polymerase chain reaction (PCR) in 12 patients with pretransplantation GBV–C infection before and daily after orthotopic liver transplantation (OLT) for 25 to 28 days. Compared with the pretransplantation values (mean, 12.4 ± 3.9 × 10 7 copies/mL), mean GBV–C RNA levels declined significantly by 1 log by day 1 after OLT (mean, 3.5 ± 1.6 × 10 7 copies/mL), but subsequently remained relatively stable on this high level for the entire observation period, indicating ongoing high–level virus replication (mean GBV–C RNA levels on days 7 and 28 were: 1.7 ± 0.5 × 10 7 and 2.8 ± 0.7 × 10 7 copies/mL; P = ns). Thus, at the end of the follow–up, mean GBV–C RNA levels were not significantly different from that of the 1st and 7th postoperative day and remained significantly lower compared with the pretransplantation values. However, in 2 of the 12 patients, different kinetics were observed. Both already had low–level viremia pre–OLT (0.02 and 0.002 × 10 7 copies/mL) and became persistently GBV–C RNA-negative 2 days after OLT. In 5 patients, liver tissues were collected 6 to 9 days after OLT and investigated for GBV–C RNA. All but 1 were GBV–C RNA-negative in the liver, although 2 of them had rather high serum GBV–C RNA levels at this time. The kinetics of GBV–C viremia observed in our study were neither influenced by the immunosuppressive therapy nor by the number of blood and blood product transfusions given after OLT. In addition, they were quite different from those observed in patients with chronic hepatitis C in whom early reinfection of the graft could be demonstrated by a steady increase in HCV RNA levels starting 3 days after OLT and exceeding preoperative levels by day 8. From our data, one can conclude that the liver is certainly not the major site of GBV–C replication in most patients. However, one cannot exclude that host or viral factors exist that predispose GBV–C replication predominantly in the liver.
SURGICAL CLINICS AT THE WESTERN PENNSYLVANIA HOSPITAL BEFORE THE STUDENTS OF THE WESTERN PENNSYLVANIA MEDICAL COLLEGE.
Authors: J. B. MURDOCH
Journal: JAMA (1889)

[Reported byWill. N. Pringle, M.D., a member of the Graduating Class.]  October 20, 1888.  OPERATION ON A FROST-BITTEN FOOT.  We have here a patient who has had his foot frost-bitten, from which he has lost one toe by amputation, and another one has fallen off, leaving a large and very painful cicatrix. It is not many years since surgeons amputated the leg for injuries involving only the foot. It is not over fifty years since the distinguished French surgeon Velpeau advised amputation at the point of election, as it was called, for such injuries. The point of election was a point about a hand's breadth below the knee. This I suppose was owing to the fact that artificial limbs were not so well known or so much used as they are to-day, and because they only had such artificial limbs as they could use by resting the knee in
Undesirable Effects of Marijuana
Authors: E. G. Wilkins
Journal: BMJ (1967)

MMICJOURIt is, of course, much too early to assess the long-term success rate of such treatment, but so far the resuks have been quite impres- sive and a number of significant facts have emerged from the trial:Proper selection of cases is essntial.Recognition of the end point of treatment is difficult and comes only with appreciable clinical experience of the technique.Adequately treated lesions heal completely with an absolute minimum of scarring.The apparent absence of deep scarring and endarteritis permits the safe use of superficial irradiation at a later date should there be a residue or recurrence within the treated area.Superficial recurrences within previously
The adherence to human endothelium and plastic of neutrophils from psoriatic patients, and the effects of psoriatic patients' sera on normal neutrophils
Authors: S. MAJEWSKI, S. JABŁONSKA, A. LANGNER, M. PAWINSKA, A. SZMURŁO
Journal: British Journal of Dermatology (1985)

Journal Article The adherence to human endothelium and plastic of neutrophils from psoriatic patients, and the effects of psoriatic patients' sera on normal neutrophils Get access S. MAJEWSKI, S. MAJEWSKI Department of Dermatology, Warsaw School of Medicine, Warsaw, Poland Dr S. Majewski, Klinika Dermatologiczna A.M. Koszykowa 82A, 02‐008 Warsaw, Poland. Search for other works by this author on: Oxford Academic Google Scholar S. JABŁONSKA, S. JABŁONSKA Department of Dermatology, Warsaw School of Medicine, Warsaw, Poland Search for other works by this author on: Oxford Academic Google Scholar A. LANGNER, A. LANGNER Department of Dermatology, Warsaw School of Medicine, Warsaw, Poland Search for other works by this author on: Oxford Academic Google Scholar M. PAWINSKA, M. PAWINSKA Department of Dermatology, Warsaw School of Medicine, Warsaw, Poland Search for other works by this author on: Oxford Academic Google Scholar A. SZMURŁO A. SZMURŁO Department of Dermatology, Warsaw School of Medicine, Warsaw, Poland Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 112, Issue 6, 1 June 1985, Pages 655–662, https://doi.org/10.1111/j.1365-2133.1985.tb02333.x Published: 01 June 1985 Article history Accepted: 01 November 1984 Published: 01 June 1985
Caveolin-1 Increases Aerobic Glycolysis in Colorectal Cancers by Stimulating HMGA1-Mediated <i>GLUT3</i> Transcription
Authors: Tae-Kyu Ha, Nam-Gu Her, Min-Goo Lee, Byung-Kyu Ryu, Jin-Hee Lee, Jikhyon Han, Seong-In Jeong, Min-Ju Kang, Nam-Hoon Kim, Hyo-Jong Kim, Sung-Gil Chi
Journal: Cancer Research (2012)

Abstract Caveolin-1 (CAV1) acts as a growth suppressor in various human malignancies, but its expression is elevated in many advanced cancers, suggesting the oncogenic switch of its role during tumor progression. To understand the molecular basis for the growth-promoting function of CAV1, we characterized its expression status, differential roles for tumor growth, and effect on glucose metabolism in colorectal cancers. Abnormal elevation of CAV1 was detected in a substantial fraction of primary tumors and cell lines and tightly correlated with promoter CpG sites hypomethylation. Depletion of elevated CAV1 led to AMPK activation followed by a p53-dependent G1 cell-cycle arrest and autophagy, suggesting that elevated CAV1 may contribute to ATP generation. Furthermore, CAV1 depletion downregulated glucose uptake, lactate accumulation, and intracellular ATP level, supporting that aerobic glycolysis is enhanced by CAV1. Consistently, CAV1 was shown to stimulate GLUT3 transcription via an HMGA1-binding site within the GLUT3 promoter. HMGA1 was found to interact with and activate the GLUT3 promoter and CAV1 increased the HMGA1 activity by enhancing its nuclear localization. Ectopic expression of HMGA1 increased glucose uptake, whereas its knockdown caused AMPK activation. In addition, GLUT3 expression was strongly induced by cotransfection of CAV1 and HMGA1, and its overexpression was observed predominantly in tumors harboring high levels of CAV1 and HMGA1. Together, these data show that elevated CAV1 upregulates glucose uptake and ATP production through HMGA1-mediated GLUT3 transcription, suggesting that CAV1 may render tumor cells growth advantages by enhancing aerobic glycolysis. Cancer Res; 72(16); 4097–109. ©2012 AACR.
Human ZNF312b Promotes the Progression of Gastric Cancer by Transcriptional Activation of the <i>K-ras</i> Gene
Authors: In-Sung Song, Nang Su Oh, Hyun-Taek Kim, Ga-Hee Ha, So-Young Jeong, Jeong-Min Kim, Dong-Il Kim, Hyang-Sook Yoo, Cheol-Hee Kim, Nam-Soon Kim
Journal: Cancer Research (2009)

Gastric cancer ranks second among the most common causes of cancer deaths worldwide. Recent studies reported target molecules that are candidates for new therapeutic interventions; however, their molecular mechanism has not been clearly defined. In this study, we found that ZNF312b plays a role in tumor progression and metastasis in gastric cancer via transcriptional activation of the K-ras oncogene. ZNF312b seems to be specifically overexpressed in gastric cancer tissues and cell lines. The overexpression of ZNF312b induces cancer-like phenotypes, including accelerated proliferation and increased tumor masses in nude mice, which are completely reversed by its knockdown in gastric cancer cell lines, implying direct involvement in gastric tumor progression. From analyses using deletion mutants of ZNF312b and K-ras promoter-driven luciferase reporters, we found that it translocates into the nucleus via the proline-rich domain of its COOH terminus to activate transcription of the K-ras gene, resulting in an enhancement of the extracellular signal-regulated kinase signaling pathway that governs cell proliferation. Taken together, these results suggest that ZNF312b contributes to the promotion of gastric cancer by triggering K-ras oncogene expression. The current study is the first to report that ZNF312b, a novel transcription factor, was associated with tumorigenicity of gastric cancer. This might be a valuable target that could provide new insight into the development of new therapeutic modalities for patients with gastric cancer.
Comparative Ultrastructure of the Sinus Node in Man and Dog
Authors: THOMAS N. JAMES, LIBI SHERF, GERALD FINE, AZORIDES R. MORALES
Journal: Circulation (1966)

Ultrastructure of the sinus node was studied in human and canine hearts and found to be similar. The principal cell of the sinus node is a small round pale cell with randomly distributed sarcosomes and sparse myofibrils. These cells have been designated as P cells. They occur in elongated clusters and make contact with each other in all directions but do not make direct contact with ordinary working myocardium. Transitional cells, which have features intermediate between P cells and working myocardium, serve as the connections between P cells and the rest of the heart. Each P cell is surrounded by a plasma membrane and groups of them are bound by a basement membrane. The only specialized junction between P cells is the desmosome, which occurs singly and seldom, with most contact being between apposing plasma membranes. P cells exhibit unusually active pinocytosis but have only a sparsely developed sarcoplasmic reticulum. The sarcosomes of P cells are much simpler in internal structure than are those of adjacent working myocardium obtained at the same time in the same heart in the same way, by direct perfusion with glutaraldehyde into the beating sinus node. Correlation of the electron microscopic appearance of the sinus node with that based on light microscopy is discussed, and some of the possible functional significances of the fine structure are considered.
AN IMMUNOLOGICAL RELATIONSHIP BETWEEN THE GROUP A STREPTOCOCCUS AND MAMMALIAN MUSCLE
Authors: John B. Zabriskie, Earl H. Freimer
Journal: The Journal of Experimental Medicine (1966)

By means of the immunofluorescent staining technique, antisera to a wide variety of serological types of Group A and A variant streptococci were found to contain an antibody which reacted with mammalian striated muscle, both skeletal and cardiac, as well as with smooth muscle in the endocardium and in the media of arterioles. Similar heart-reactive antibodies were not present in antisera to most other groups of hemolytic streptococci and to other Gram-positive cocci. Chemical and serological studies clearly pointed to the cell (protoplast) membrane of the Group A streptococcus as the locus of the antigenic determinant of this heart-reactive antibody. In addition, preliminary studies suggested that the reaction between this streptococcal antibody and cardiac tissue represented an immunological relationship between the sarcolemma, the membrane of a mammalian muscle cell and the cell membrane of a bacterium, the hemolytic streptococcus.
Parental Social Responsiveness and Risk of Autism Spectrum Disorder in Offspring
Authors: Kristen Lyall, John N. Constantino, Marc G. Weisskopf, Andrea L. Roberts, Alberto Ascherio, Susan L. Santangelo
Journal: JAMA Psychiatry (2014)

<h3>Importance</h3> Although autism spectrum disorder (ASD) is known to be heritable, patterns of inheritance of subclinical autistic traits in nonclinical samples are poorly understood. <h3>Objective</h3> To examine the familiality of Social Responsiveness Scale (SRS) scores of individuals with and without ASD. <h3>Design, Setting, and Participants</h3> We performed a nested case-control study (pilot study: July 1, 2007, through June 30, 2009; full-scale study: September 15, 2008, through September 14, 2012) within a population-based longitudinal cohort. Participants were drawn from the Nurses' Health Study II, a cohort of 116 430 female nurses recruited in 1989. Case participants were index children with reported ASD; control participants were frequency matched by year of birth of case participants among those not reporting ASD. Of 3161 eligible participants, 2144 nurses (67.8%) returned SRS forms for a child and at least 1 parent and were included in these analyses. <h3>Exposure</h3> The SRS scores, as reported by nurse mothers and their spouses, were examined in association with risk of ASD using crude and adjusted logistic regression analyses. The SRS scores of the children were examined in association with SRS scores of the parents using crude and adjusted linear regression analyses stratified by case status. <h3>Main Outcomes and Measures</h3> Autism spectrum disorder, assessed by maternal report, validated in a subgroup with the Autism Diagnostic Interview–Revised. <h3>Results</h3> A total of 1649 individuals were included in these analyses, including 256 ASD case participants, 1393 control participants, 1233 mothers, and 1614 fathers. Risk of ASD was increased by 85.0% among children whose parents had concordantly elevated SRS scores (odds ratio [OR], 1.85; 95% CI, 1.08-3.16) and by 52.0% when the score of either parent was elevated (OR, 1.52; 95% CI, 1.11-2.06). Elevated scores of the father significantly increased the risk of ASD in the child (OR, 1.94; 95% CI, 1.38-2.71), but no association was seen with elevated scores of the mother. Elevated parent scores significantly increased child scores in controls, corresponding to an increase in 23 points (<i>P</i> &lt; .001). <h3>Conclusions and Relevance</h3> These findings support the role of additive genetic influences in concentrating inherited ASD susceptibility in successive generations and the potential role of preferential mating, and suggest that typical variation in parental social functioning can produce clinically significant differences in offspring social traits.
The effect of coronary inflow pressure on coronary vascular resistance in the isolated dog heart.
Authors: F L Hanley, L M Messina, M T Grattan, I E Hoffman
Journal: Circulation Research (1984)

The shape of the coronary arterial pressure-flow relationship results from the interaction of a number of poorly understood physiological factors. Experiments in which coronary inflow and outflow pressures were coupled so that driving pressure was held constant showed that changes in inflow or outflow pressures altered coronary blood flow: coronary vascular resistance varied inversely with changes inflow pressure below 50 mm Hg and with changes in outflow pressure below 80 mm Hg. The magnitude of the influence of inflow pressure on resistance also depended on the fixed level of outflow pressure, the influence being large when the outflow pressure was low, and small when it was high. Inflow and outflow pressures, then, are two physiological factors which are determinants of the shape of the pressure-flow relationship, and their interaction contributes to the degree of curvature found in a particular relationship. These findings suggest that the use of linear regression in the interpretation of pressure-flow relationships results in poor estimation of resistance and zero-flow pressure. Other experiments measuring regional coronary blood flow using radionuclide-labeled microspheres resulted in the same inverse relationship between inflow pressure and resistance, regardless of mural depth, indicating that inflow pressure may influence resistance by distending vessels, rather than by causing sequential cessation of perfusion in successive transmural layers.