tbuckley/cabot-search huggingface dataset:
Efficacy of an adapted granzyme B-based anti-CD30 cytolytic fusion protein against PI-9-positive classical Hodgkin lymphoma cells in a murine model
Authors: S Schiffer, H P Hansen, G Hehmann-Titt, M Huhn, R Fischer, S Barth, T Thepen
Journal: Blood Cancer Journal (2013)

Tumors develop when infiltrating immune cells contribute growth stimuli, and cancer cells are selected to survive within such a cytotoxic microenvironment. One possible immune-escape mechanism is the upregulation of PI-9 (Serpin B9) within cancer cells. This serine proteinase inhibitor selectively inactivates apoptosis-inducing granzyme B (GrB) from cytotoxic granules of innate immune cells. We demonstrate that most classical Hodgkin lymphoma (cHL)-derived cell lines express PI-9, which protects them against the GrB attack and thereby renders them resistant against GrB-based immunotherapeutics. To circumvent this disadvantage, we developed PI-9-insensitive human GrB mutants as fusion proteins to target the Hodgkin-selective receptor CD30. In contrast to the wild-type GrB, a R201K point-mutated GrB construct most efficiently killed PI-9-positive and -negative cHL cells. This was tested in vitro and also in vivo whereby a novel optical imaging-based tumor model with HL cell line L428 was applied. Therefore, this variant, as part of the next generation immunotherapeutics, also named cytolytic fusion proteins showing reduced immunogenicity, is a promising molecule for (targeted) therapy of patients with relapsing malignancies, such as cHL, and possibly other PI-9-positive malignancies, such as breast or lung carcinoma.
Renal function in fulminant hepatic failure: haemodynamics and renal prostaglandins.
Authors: F Guarner, R D Hughes, A E Gimson, R Williams
Journal: Gut (1987)

Eighteen patients with fulminant liver failure were studied, 10 with normal renal function (group A) and eight with renal failure (group B, plasma creatinine greater than 200 mumol/l). Renal function was assessed by standard clearance techniques and patients in group B had a marked reduction compared with group A in both renal plasma flow and glomerular filtration rate. Raised plasma renin activity was observed in both groups, but levels in group B were significantly higher than in group A. Renal prostacyclin production was estimated by radioimmunoassay (RIA) of 6-keto-prostaglandin F1 alpha in urine, and the excretion rate was markedly increased in group A as compared with nine healthy controls, but was low in group B. The plasma concentrations of 6-keto-prostaglandin F1 alpha and thromboxane B2 were similar in groups A and B and were both significantly higher than in controls. Haemodynamic measurements showed a high cardiac output with low vascular resistance and mean arterial pressure within normal limits in both groups. The pulse pressure, however, was significantly higher in group B than in group A. In conclusion, patients in FHF with renal failure have marked renal vasoconstriction with increased plasma renin activity and reduced renal prostaglandin excretion indicative of an imbalance between vasoactive forces.
Grieving the death of a child
Authors: Beverley Raphael
Journal: BMJ (2006)

Health professionals need to be particularly sensitive to the needs of parents 

T he death of a child brings profound distress and intense grief to the family, challenging all those involved in caring for the family through such times. That such grief can lead to suicide is known, but two cases in this week's BMJ show a particular hazard after a child has died at home: in both cases mothers committed suicide with drugs prescribed for the palliative care of their children (p 647).1

There is substantial evidence from comparative and longitudinal studies that the grief of parents following the loss of a child is more intense and prolonged than that of other losses.2 3 Parental vulner-ability includes a heightened risk of suicide, especially in the first month, as shown in a nested case-control study of Danish longitudinal registers.4 Population based follow-up studies also show that anxiety and depression may last …
Hemodynamic Responses to Oxygen Breathing in Children with Severe Anemia
Authors: GERD J. A. CROPP
Journal: Circulation (1969)

Hemodynamic responses to 100% oxygen inhalation were examined in seven anemic children (hemoglobin 1.9 to 3.8 g/100 ml blood; hematocrit 9 to 14%). During air breathing mean values for cardiac index were 7.71 L/min/m 2 , for heart rate 129/min, for stroke index 61.7 ml/m 2 , and for systemic vascular resistance 11.5 R.U. Oxygen administration significantly decreased mean values of cardiac index to 6.61 L/min/m 2 , of heart rate to 119/min and of stroke index to 56.6 ml/m 2 , and increased mean systemic vascular resistance to 14.2 R.U. Oxygen breathing raised systemic oxygen content 23% and oxygen transport 5%, despite decreases in cardiac ouput. Since oxygen breathing did not change the hematocrit (and thus viscosity), the increase in vascular resistance indicates active vasoconstriction. It is postulated that in anemia tissue hypoxia causes vasodilation of systemic resistance vessels. When anemia is not severe, baroreceptor reflexes prevent significant reductions in blood pressure and systemic vascular resistance by compensatory, neurogenic vasoconstriction. When anemia becomes severe and vasodilation extreme, blood pressure is maintained by an increase in cardiac output. Cardiac output is elevated by decreased vagal inhibition and increased myocardial contractility, which cause tachycardia and increased stroke volumes respectively.
Cyclocreatine treatment improves cognition in mice with creatine transporter deficiency
Authors: Yuko Kurosawa, Ton J. DeGrauw, Diana M. Lindquist, Victor M. Blanco, Gail J. Pyne-Geithman, Takiko Daikoku, James B. Chambers, Stephen C. Benoit, Joseph F. Clark
Journal: Journal of Clinical Investigation (2012)

The second-largest cause of X-linked mental retardation is a deficiency in creatine transporter (CRT; encoded by SLC6A8), which leads to speech and language disorders with severe cognitive impairment. This syndrome, caused by the absence of creatine in the brain, is currently untreatable because CRT is required for creatine entry into brain cells. Here, we developed a brain-specific Slc6a8 knockout mouse (Slc6a8-/y) as an animal model of human CRT deficiency in order to explore potential therapies for this syndrome. The phenotype of the Slc6a8-/y mouse was comparable to that of human patients. We successfully treated the Slc6a8-/y mice with the creatine analog cyclocreatine. Brain cyclocreatine and cyclocreatine phosphate were detected after 9 weeks of cyclocreatine treatment in Slc6a8-/y mice, in contrast to the same mice treated with creatine or placebo. Cyclocreatine-treated Slc6a8-/y mice also exhibited a profound improvement in cognitive abilities, as seen with novel object recognition as well as spatial learning and memory tests. Thus, cyclocreatine appears promising as a potential therapy for CRT deficiency.
OCULAR LESIONS ASSOCIATED WITH CONSTITUTIONAL DIATHESIS.
Authors: H. ISAAC JONES
Journal: JAMA (1902)

In calling your attention to this subject the writer does not desire to create the impression that he has anything purely original to offer, but to call your attention to the fact that the human body is too much of an entity for any one system to be exclusively deranged, while others remain healthy; actions and reactions are the two great rules of organic life. Functional waves of reflex influences are always sweeping to and fro through the body and peripheral irritations of every kind, and every phase of organic disturbances may excite a reflex that will influence the actions and perhaps the nutrition of the eye and its appendages. Sir Thomas Watson said: "We find in the eye more satisfactory and plain illustrations of the general facts and doctrines of pathology than in any other single organ of the body; certain changes in the eye are known to accompany
Oral melphalan, prednisone, and thalidomide in elderly patients with multiple myeloma: updated results of a randomized controlled trial
Authors: Antonio Palumbo, Sara Bringhen, Anna M. Liberati, Tommaso Caravita, Antonietta Falcone, Vincenzo Callea, Marco Montanaro, Roberto Ria, Antonio Capaldi, Renato Zambello, Giulia Benevolo, Daniele Derudas, Fausto Dore, Federica Cavallo, Francesca Gay, Patrizia Falco, Giovannino Ciccone, Pellegrino Musto, Michele Cavo, Mario Boccadoro
Journal: Blood (2008)
Response to Letter Regarding Article, “Usefulness of 64-Slice Cardiac Computed Tomographic Angiography for Diagnosing Acute Coronary Syndromes and Predicting Clinical Outcome in Emergency Department Patients With Chest Pain of Uncertain Origin”
Authors: Ronen Rubinshtein, David A. Halon, Ronen Jaffe, Basheer Karkabi, Moshe Y. Flugelman, Basil S. Lewis, Tamar Gaspar, Nathan Peled, Asia Kogan, Reuma Shapira
Journal: Circulation (2007)
Evaluation of Protocols Used in 2-D Electrophoresis for Proteome Analysis of Young Rice Caryopsis
Authors: Jiang-Lin Liao, Ying-Jin Huang
Journal: Genomics Proteomics & Bioinformatics (2011)

Abstract In order to obtain a high-resolution electrophorogram of rice young panicle proteome, we evaluated various protocols commonly used in two-dimensional (2D) polyacrylamide gel electrophoresis (PAGE) of proteins, including gel staining protocol, pH range of immobilized pH gradient (IPG) strips and sample loading quantity. Results showed that a silver staining protocol using sensitized solution containing glacial acetic acid, sodium acetate and sodium thiosulfate (reported by Heukeshoven and Dernick in 1988) and a Coomassie Brilliant Blue staining method using solution containing G-250, ammonium sulfate and phosphoric acid (reported by Pink et al. in 2010) demonstrated the superior staining effect. In addition, we also showed that higher resolution was achieved when IPG gel strip with pH range of 5-8 was used, compared to that with pH range of 4-7. Finally, the optimal loading quantity was determined as 130 µg using the 17 cm-long nonlinear IPG strip with pH 5-8 in combination with the silver nitrate staining protocol. The evaluated results would be helpful in proteome analysis of young rice caryopsis.
Evidence for a pivotal role of platelets in vascular reocclusion and restenosis
Authors: H. LeBreton, E. Topol, E. F. Plow
Journal: Cardiovascular Research (1996)

Reocclusion and restenosis continue to be the major clinical complications following emergency and elective coronary interventions. Reocclusion ultimately occurs in more than 25% of patients after successful thrombolysis for acute myocardial infarction [l] and may have major adverse consequences, ranging from mortality to compromised cardiac function. After percutaneous transluminal coronary angioplasty (PTCA), the risk associated with acute occlusion leading to myocardial infarction, emergency repeat PTCA, or coronary bypass surgery, may occur in up to 8% of patients [2]. Even more frequent and to date resistant to therapy is the possibility of restenosis, which occurs in 30-40% of patients after PTCA and requires an additional percutaneous intervention or bypass operation within the following year. Substantial evidence directly implicates platelets in reocclusion and restenosis. In fact, current clinical data suggest that platelets represent the most beneficial therapeutic target to reduce the risk of reocclusion and restenosis. In line with this “controversy series” thrombin is being considered the alternative to platelets in the pathogenesis of vascular reocclusion and restenosis. By virtue of its capacity to mediate fibrin formation, platelet activation and cellular migration and proliferation, thrombin undoubtedly is an important player in reocclusion and restenosis. Nevertheless, thrombin inhibitors have yet to match the dramatic effects of platelet antagonists in patients.
Setting the Record Straight
Authors: Lawrence S. Lewin, Timothy J. Eckels, Linda B. Miller
Journal: New England Journal of Medicine (1988)

IN recent years, questions have been raised about the role of not-for-profit hospitals in providing care to the uninsured and underinsured poor. Traditionally, private hospitals have financed such care largely by charging and collecting more from privately insured patients. This mechanism received relatively little scrutiny until two important trends emerged in the 1980s: an increase in the number of persons without health insurance and increasing price consciousness on the part of both public and private purchasers. The rise in the number of uninsured and underinsured people has increased our nation's dependence on the private sector to finance large increases in . . .
Snoring: Carve the Snorer? Deafen the Snoree?— The Dutch Cheese Wax Solution
Authors: Robert D. Gillette
Journal: JAMA (1989)

<h3>To the Editor. —</h3> The Questions and Answers section in a recent issue ofThe Journalcontained a query on snoring.<sup>1</sup>The response<sup>1</sup>addressed the problem as a disease and advocated various forms of pharmacologic and surgical treatment. Such interventions may be appropriate in a minority of cases, but it might have been useful to state clearly that snoring is so common that it must be considered a normal phenomenon in the vast majority of instances. To demonstrate this point, I recently conducted a simple anonymous poll of the married faculty members, residents, and staff members of our model family practice unit to determine the incidence of snoring in this essentially healthy population. Respondents ranged in age from the early 20s to the late 50s. They were asked to state whether they were aware of their spouses snoring, and also to indicate if the spouses said that they
Creativity and Disease: How Illness Affects Literature, Art and Music
Authors: Tony Miksanek
Journal: JAMA (1983)

<i>Creativity and Disease</i>is a small book with a large mission. It is a successful investigation of the relationship between artistic creativity and illness. The link between disease and creativity is explained in many ways. First, illness may function to motivate the artist. In this sense, the artist compensates for his physical impairment with an artistic creation. His impairment may free him from convention and tradition. Beethoven's hearing loss and musical achievements serve as an example. Second, illness may foster creativity by preventing other activities so that the artist focuses on his work. Creativity becomes therapeutic, and the artist finds refuge from disease in his art, as did Matisse and Montaigne. Finally, illness may directly enhance the senses and amplify the insight of the artist. Dostoevsky, for example, believed that the altered state of mind associated with epilepsy led to supranormal experiences. To a large degree, creativity is dependent on
The endothelium: its role in scleroderma.
Authors: J D Pearson
Journal: Annals of the Rheumatic Diseases (1991)

Vascular dysfunction, in particular micro- vascular pathology perhaps most closely associ- ated with arterioles, is a cardinal sign in the development ofsystemic sclerosis (scleroderma).Altered vascular reactivity and structure provide only one element in a spectrum of pathological alterations associated with the clinical development of the disease.Nonetheless, the almost invariable pre-existence of Raynaud's pheno- menon before the development of scleroderma makes it clear that altered blood vessel respon-
MEDICAL TERMINOLOGY IN GERMANY
Authors: A. N. Tasker
Journal: JAMA (1922)

To the Editor:  —Peculiar results of the European war continue to crop up in unexpected—or at least unforeseen— places, from time to time. This is true not only in politics, geography and finance, but in art and science as well. In 1920, the Vereinigung der deutschen medizinischen Fachpresse designated a commission to collaborate with the Deutsche Gesellschaft fur innere Medizin in selecting German terms which might replace French and English expressions that have been so long in use in medical literature as to have become in many instances a part of the medical language of all nations. TheDeutsche medizinische Wochenschrift(48:493, 1922), theMunchener medizinische Wochenschrift(69:454, 1922) and other medical periodicals from Germany report the results of this collaboration and give the list of the French and English phrases to be interdicted and their German equivalents. Of these new terms, many successfully convey their exact meaning
Autopsy on Abraham Lincoln
Authors: John K. Lattimer
Journal: JAMA (1965)

In recent weeks the press has carried accounts of the discovery, in the files of the New York State Historical Association at Cooperstown, NY, of a further handwritten description of the findings at the autopsy done on Abraham Lincoln. In these notes, Dr. Stone again makes a firm statement that the bullet ended up in the left anterior portion of the brain, above the left eye, instead of above the right eye as stated by two other persons present at the autopsy. It should be noted that the prosector, Dr. E.J.J. Woodward, also stated that the bullet ended up above the left eye.<sup>1</sup> This new report by Dr. Robert King Stone, family physician of President Lincoln, is also accompanied by a small diagram. The newspaper accounts led me to hope that this diagram might show the track of the bullet through the brain. Unfortunately, the diagram appears to me
National standards for diabetes self-management education. Task Force to Review and Revise the National Standards for Diabetes Self-Management Education Programs.
Authors: C Mensing, J Boucher, M Cypress, K Weinger, K Mulcahy, P Barta, G Hosey, W Kopher, A Lasichak, B Lamb, M Mangan, J Norman, J Tanja, L Yauk, K Wisdom, C Adams
Journal: Diabetes Care (2000)
The peeved middle
Authors: Des Spence
Journal: BMJ (2012)

I am a third child. “The older child gets all the awards; the younger gets all the love,” runs the psychological profile of we attention seeking, forgotten middle children. So it is with class. The upper and working classes are socially exclusive because success and money or lack thereof are no key to admission: you must come from a specific background. Both behave badly and care nothing what others think. Neither have time for introspection, and they live for the day.⇑

It is the middle class, so easy …
Cyclosporine for the treatment of granulocytopenia in Felty's syndrome
Authors: Janice M. G. Canvin, Bakul I. Dalal, Fletcher Baragar, James B. Johnston
Journal: American Journal of Hematology (1991)

Abstract A patient with Felty's syndrome was treated with cyclosporine, initially 10 mg/kg/day and then 4 mg/kg/day. The neutrophil count increased by 6 weeks and was normal at 3 months. Over the subsequent 27 months the neutrophil count was closely related to the cyclosporine dosage and there was no evidence of cyclosporine toxicity. This case indicates that cyclosporine may have a role in the treatment of Felty's syndrome.
Commitment to the B Lymphoid Lineage Occurs before DH-JH Recombination
Authors: David Allman, Jin Li, Richard R. Hardy
Journal: The Journal of Experimental Medicine (1999)

Lineage commitment in B lymphopoiesis remains poorly understood due to the inability to clearly define newly committed B lineage progenitors and their multipotential descendants. We examined the potential of three recently described progenitor populations in adult mouse bone marrow to differentiate into each hematopoietic lineage. The earliest of these, termed fraction (Fr.) A0, exhibited myeloid, erythroid, and B and T lymphoid progenitor activity and included individual cells with myeloid/B lymphoid potential. In sharp contrast, two later populations, termed Frs. A1 and A2 and characterized by surface B220 expression and transcription of the germline immunoglobulin heavy chain (IgH) locus, lacked progenitor activity for all hematopoietic lineages except B lymphocytes. These observations, together with single cell polymerase chain reaction analysis showing a lack of DHJH rearrangements in each population and experiments showing identical precursor potentials when these populations were derived from recombination activating gene (Rag)-1(-/-) and JH-/- mice, demonstrate that commitment to the B lymphoid lineage occurs before and independently of VHDHJH recombination.
PUVA-bath photochemotherapy for congenital palmoplantar keratoderma in an 11-year-old girl
Authors: P. Kaskel, U. Leiter, G. Krähn, R. Schiener, H. Pillekamp, R.U. Peter, M. Kerscher
Journal: British Journal of Dermatology (2000)

Journal Article PUVA‐bath photochemotherapy for congenital palmoplantar keratoderma in an 11‐year‐old girl Get access P. Kaskel, P. Kaskel Peter Kaskel and Ulrike Leiter contributed equally to this work. Correspondence: Prof. Dr med. Ralf Uwe Peter. E‐mail: ralf.peter@medizin.uni‐ulm.de Search for other works by this author on: Oxford Academic Google Scholar U. Leiter, U. Leiter Peter Kaskel and Ulrike Leiter contributed equally to this work. Correspondence: Prof. Dr med. Ralf Uwe Peter. E‐mail: ralf.peter@medizin.uni‐ulm.de Search for other works by this author on: Oxford Academic Google Scholar G. Krähn, G. Krähn Department of Dermatology, University of Ulm, 89070 Ulm/Donau, Germany Search for other works by this author on: Oxford Academic Google Scholar R. Schiener, R. Schiener Department of Dermatology, University of Ulm, 89070 Ulm/Donau, Germany Search for other works by this author on: Oxford Academic Google Scholar H. Pillekamp, H. Pillekamp Department of Dermatology, University of Ulm, 89070 Ulm/Donau, Germany Search for other works by this author on: Oxford Academic Google Scholar R.U. Peter, R.U. Peter Department of Dermatology, University of Ulm, 89070 Ulm/Donau, Germany Search for other works by this author on: Oxford Academic Google Scholar M. Kerscher M. Kerscher Department of Dermatology, University of Ulm, 89070 Ulm/Donau, Germany Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 143, Issue 2, 1 August 2000, Pages 464–465, https://doi.org/10.1046/j.1365-2133.2000.03693.x Published: 01 August 2000
The Generalized Epilepsies: A Clinical Electroencephalographic Study
Authors: Louis D. Boshes
Journal: JAMA (1972)

This unique book, the product of 20 years of clinical and electroencephalographic correlation, is an outgrowth of the author's vast experience. He has encountered the most intractable seizure problems especially in children who had not responded to anticonvulsants, and who were considered for selective neurosurgery in the neurosurgical service of Dr. A. Earl Walker.  Three hundred cases, all from the Johns Hopkins Hospital, are presented. They include 125 patients classified as the Lennox-Gastaut syndrome, 72 of common generalized epilepsy of the atypical type, 61 of the pure common generalized epilepsy, 26 with secondary bilateral synchrony, 7 with metabolic disturbances, 5 with deep-seated midline lesions, and 4 with posttraumatic epilepsy with slow spike-wave complexes.  Dr. Niedermeyer presents data from both standard and depth electroencephalographic studies as he investigates patients in each of the categories. These certainly warranted a more complex study than do those patients with focal seizures, where the clinical