tbuckley/cabot-search huggingface dataset:
Donor Bone Marrow–derived Dendritic Cells Prolong Corneal Allograft Survival and Promote an Intragraft Immunoregulatory Milieu
Authors: Lisa O'Flynn, Oliver Treacy, Aideen E Ryan, Maurice Morcos, Marese Cregg, Jared Gerlach, Lokesh Joshi, Mikhail Nosov, Thomas Ritter
Journal: Molecular Therapy (2013)

Investigations into cell therapies for application in organ transplantation have grown. Here, we describe the ex vivo generation of donor bone marrow-derived dendritic cells (BMDCs) and glucocorticoid-treated BMDCs with potent immunomodulatory properties for application in allogeneic transplantation. BMDCs were treated with dexamethasone (Dexa) to induce an immature, maturation-resistant phenotype. BMDC and Dexa BMDC phenotype, antigen presenting cell function, and immunomodulatory properties were fully characterized. Both populations display significant immunomodulatory properties, including, but not limited to, a significant increase in mRNA expression of programmed death-ligand 1 and indoleamine 2,3-dioxygenase. BMDCs and Dexa BMDCs display a profound impaired capacity to stimulate allogeneic lymphocytes. Moreover, in a fully MHC I/II mismatched rat corneal transplantation model, injection of donor-derived, untreated BMDC or Dexa BMDCs (1 × 10(6) cells, day -7) significantly prolonged corneal allograft survival without the need for additional immunosuppression. Although neovascularization was not reduced and evidence of donor-specific alloantibody response was detected, a significant reduction in allograft cellular infiltration combined with a significant increase in the ratio of intragraft FoxP3-expressing regulatory cells was observed. Our comprehensive analysis demonstrates the novel cellular therapeutic approach and significant effect of donor-derived, untreated BMDCs and Dexa BMDCs in preventing corneal allograft rejection.
Letter: Thromboembolism and oral contraceptives.
Authors: B Astedt, S Jeppsson
Journal: BMJ (1974)

looked in the drug addiction film "The Man with the Golden Arm." Then at my outpatient clinic another patient suffering from neurotic depression told me how very ill she felt after stoppng her regimen of phenelzine and haloperidol to go on to lorazepam.The lorazepam made her excessively drowsy and she stopped it after a day or so but then she felt depressed and irritable and also described this feeling of cold and shivering.This last symptom is quite reminiscent of the "cold turkey" reaction to the with- drawal of narcotics from the habituated, and the reaction followed so swiftly the disoon- tinuation of the drug that I wonder if it might not represent a genuine physical res- ponse to deprival of the drug rather than a purely psychological one or the return of the depression.The medical adviser to the manufacturers tells me that no such with- drawal symptoms have previously been re- ported but I wonder if any of your readers can record similar experiences?-Iam, etc., BRICE PI1-rThe London Hospital (St.Clement's) London E.3 Malaria in the United Kingdom SIR,-In your epidemiological report (5 January, p. 43) you mention 84 cases of malaria in immigrants to the U.K. in 1972.The adult populations of countries where malaria is endemic are generally considered to be inmune to malaria in the sense that they do not suffer overt attacks of the disease.It would be valuable to know if there is any record of the proportion of innigrants in whom malaria was considered to be the cause of their illness rather than simply a concomitant finding, the number of adults, and whether any factors were found, such as acute infections or steroid therapy, which might have been responsible for a temporary lowering of resistance to malaria.-Iam, etc.,
Trimethoprim-Sulfamethoxazole for the Treatment of Pneumocystis carinii Pneumonia
Authors: DREW J. WINSTON
Journal: Annals of Internal Medicine (1980)

Intravenous trimethoprim-sulfamethoxazole therapy was evaluated in 11 consecutive patients with documented Pneumocystis carinii pneumonia and the results compared to those from previously published studies of trimethoprim-sulfamethoxazole therapy for P. carinii pneumonia. Although six patients needed mechanical ventilation, intravenous therapy was successful in seven of 11 patients (64%), and seven of nine patients (78%) receiving 4 or more days of intravenous trimethoprim-sulfamethoxazole therapy were cured. Side effects occurred in two patients (skin rash in one, nausea and vomiting in one). A review of 80 reported cases of confirmed P. carinii pneumonia initially treated with trimethoprim-sulfamethoxazole alone revealed response rates of 67.5% in all treated patients and 85.5% in patients treated for 9 or more days. The clinical response was similar in adults (63.2%) and children (68.9%). Side effects were noted in only 11 of 80 patients (13.8%). Compared to pentamidine, trimethoprim-sulfamethoxazole has a narrower toxic-therapeutic ratio and should be preferred treatment for P. carinii pneumonia in adults as well as children.
Next Patient-Reply
Authors: Blake Rodgers
Journal: JAMA (1987)

In Reply.—  Drs Henry and McLaughlin raise valid criticisms about my essay. Sadly, my shortcomings as a writer hid some of the meaning I had intended to convey. It was not my purpose to offend or condemn—I certainly did not mean to imply that prejudice resided only in the South—rather, I had hoped to show how quickly I lost sight of my goals and ideals and, without realizing it, became a parody of all I had set out to accomplish. I had also hoped to show that sometimes, in spite of ourselves, good comes from our attempts.  The time I spent in Alabama remains one of my fondest memories. The people of the state opened their homes and lives to me; it is a debt I cannot easily repay. I am honored to call many of them my friends. I am sorry if my story offended: it was intended to
Detection of 2-Hydroxyglutarate in <i>IDH</i> -Mutated Glioma Patients by In Vivo Spectral-Editing and 2D Correlation Magnetic Resonance Spectroscopy
Authors: Ovidiu C. Andronesi, Grace S. Kim, Elizabeth Gerstner, Tracy Batchelor, Aria A. Tzika, Valeria R. Fantin, Matthew G. Vander Heiden, A. Gregory Sorensen
Journal: Science Translational Medicine (2012)

2-Hydroxyglutarate, a metabolite overproduced in IDH -mutated gliomas, can be detected noninvasively in patients with brain tumors by optimized magnetic resonance spectroscopy.
400 MODELING, CLINICAL AND VIROLOGY DATA FROM PHASE 2 AND 3 STUDIES SUPPORT 12-WEEK TELAPREVIR DURATION IN COMBINATION WITH 24- OR 48-WEEK PEGINTERFERON/RIBAVIRIN DURATION
Authors: B. Adiwijaya, T.L. Kieffer, D.J. Bartels, G. Picchio, S. De Meyer, K. Eisenhauer, M. Beumont, N. Adda, C.I. Wright, R.S. Kauffman, V. Garg
Journal: Journal of Hepatology (2011)
Neurophysin biosynthesis in vitro in oat cell carcinoma of the lung with ectopic vasopressin production.
Authors: T Yamaji, M Ishibashi, S Katayama, A Itabashi, N Ohsawa, Y Kondo, Y Mizumoto, K Kosaka
Journal: Journal of Clinical Investigation (1981)

The incorporation of labeled compounds into neurophysins of a transplantable human oat cell carcinoma of the lung with ectopic vasopressin production was studied in vitro. Neurophysins in cell extracts and in incubation media were isolated by immunoprecipitation and analyzed by sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis. When cells were incubated with L-[35S]cysteine for 12 h, SDS-polyacrylamide gel electrophoresis of the immunoprecipitates from cell extract and medium resolved two forms of neurophysins with apparent molecular mass of 10,000 (10K) and 20,000 (20K). Both forms of [35S]-neurophysins were completely displaced from the immunoprecipitates by excess human neurophysin. Incubation of cells with L-[35S]cysteine and D-[3H]-glucosamine hydrochloride revealed that glucosamine was incorporated into the 20K neurophysin region, but not into 10K species. To observe the kinetics of labeling of the two forms of neurophysins, cells were incubated with L[35S]cysteine for varying periods of time. After short labeling periods, most of the radioactivity resided in 20K species, which plateaued after 1 h, whereas 10K neurophysin progressively increased in its height. When cells were chased with unlabeled cysteine after the exposure to a short pulse of labeling, 20K neurophysin peak gradually decreased with an apparent initial half-life of 1 h. In contrast, the label in 10K neurophysin steadily increased, which exceeded the former by 3 h of chase. Analysis of 20K neurophysin in cell extract by isoelectric focusing on polyacrylamide gel demonstrated that it was principally composed of a protein with an apparent isoelectric point (pI) of 5.7. These results suggest that neurophysin is synthesized in ectopic vasopressin-producing tumors by post-translational processing from a glycosylated proneurophysin with an apparent molecular mass of 20,000 daltons and a pI of 5.7.
Commentary: The technology of continuous glucose monitoring
Authors: M. H Charlton
Journal: BMJ (2008)

The continuous glucose monitor used by Murphy and colleagues can be thought of as diabetology’s answer to cardiology’s 24 hour electrocardiography monitor. It is used as an investigative tool, is attached to the patient (usually for 72 hours), and requires the user to return to hospital for its removal. The data are downloaded and examined for abnormal glucose levels and trends.

The sensor is inserted through the abdominal wall, so that its glucose oxidase tip lies within subcutaneous tissue, where it measures the glucose level of interstitial fluid, not of blood. The sensor is wired to a palm sized monitor, which can be clipped to clothing. The sensor cannot be disconnected, even temporarily—for …
miR-30-5p Functions as a Tumor Suppressor and Novel Therapeutic Tool by Targeting the Oncogenic Wnt/β-Catenin/BCL9 Pathway
Authors: Jian-Jun Zhao, Jianhong Lin, Di Zhu, Xujun Wang, Daniel Brooks, Ming Chen, Zhang-Bo Chu, Kohichi Takada, Bryan Ciccarelli, Samir Admin, Jianguo Tao, Yu-Tzu Tai, Steven Treon, Geraldine Pinkus, Winston Patrick Kuo, Teru Hideshima, Mary Bouxsein, Nikhil Munshi, Kenneth Anderson, Ruben Carrasco
Journal: Cancer Research (2014)

Wnt/β-catenin signaling underlies the pathogenesis of a broad range of human cancers, including the deadly plasma cell cancer multiple myeloma. In this study, we report that downregulation of the tumor suppressor microRNA miR-30-5p is a frequent pathogenetic event in multiple myeloma. Evidence was developed that miR-30-5p downregulation occurs as a result of interaction between multiple myeloma cells and bone marrow stromal cells, which in turn enhances expression of BCL9, a transcriptional coactivator of the Wnt signaling pathway known to promote multiple myeloma cell proliferation, survival, migration, drug resistance, and formation of multiple myeloma cancer stem cells. The potential for clinical translation of strategies to re-express miR-30-5p as a therapeutic approach was further encouraged by the capacity of miR-30c and miR-30 mix to reduce tumor burden and metastatic potential in vivo in three murine xenograft models of human multiple myeloma without adversely affecting associated bone disease. Together, our findings offer a preclinical rationale to explore miR-30-5p delivery as an effective therapeutic strategy to eradicate multiple myeloma cells in vivo.
Lost in the process
Authors: Lynette Wilkinson
Journal: BMJ (2007)

Acknowledging her resilience and creativity and how difficult it must have been, I asked if she could describe how the problem had affected her life. Her response—pain, anger, frustration, and tears were her constant companions. “Feeling dumb” at primary school; this worsened throughout high school. To indicate her attendance at school exams, she would sign and hand in blank papers. Hating reading, she easily became frustrated and emotional, often complaining of “being tired” while reading or studying. Her mother assumed she was avoiding homework, and there would be arguments. Memories of the schoolroom were of fear and trepidation. Oral reading was “torture.”

Remembering her distress and anger when people laughed …
Patching a Leaky Intestine
Authors: Wayne I. Lencer
Journal: New England Journal of Medicine (2008)

In patients with protein-losing enteropathy, the intestinal mucosa completely fails to function as a competent barrier separating the body from the outside world. Serum fluids and proteins quickly leak into the stool, causing diarrhea, hypoalbuminemia, and sometimes death. A recent study by Bode and colleagues1 showed that the disease might be related to the loss of heparin sulfate proteins that are normally expressed on intestinal cells. Remarkably, the investigators also showed that the disease can be successfully treated with novel analogues of heparin sulfate.For the intestine to efficiently absorb nutrient solutes, it first has to effectively separate the lamina . . .
Effect of Medication Adherence on Survival of HIV-Infected Adults Who Start Highly Active Antiretroviral Therapy When the CD4+ Cell Count Is 0.200 to 0.350 × 10<sup>9</sup> cells/L
Authors: Evan Wood, Robert S. Hogg, Benita Yip, P. Richard Harrigan, Michael V. O'Shaughnessy, Julio S.G. Montaner
Journal: Annals of Internal Medicine (2003)

The safety of delaying highly active antiretroviral therapy (HAART) in HIV-infected patients is uncertain when the CD4+ cell count declines below 0.350 x 10(9) cells/L.To evaluate the effect of baseline CD4+ cell count and adherence to HAART on survival rates.Prospective observational study.Province-wide Canadian HIV/AIDS treatment program.1422 HIV-infected persons initiating HAART between 1 August 1996 and 31 July 2000 and followed through 31 March 2002.Patients were stratified by baseline CD4+ cell count and adherence level. Cumulative mortality rates were evaluated by using Kaplan-Meier methods and Cox regression-estimated adjusted relative hazards.Kaplan-Meier analyses showed no survival benefit of starting HAART at a CD4+ count of 0.200 x 10(9) cells/L or greater among adherent patients. Adjusted analysis showed that compared with adherent patients who initiated HAART at a CD4+ cell count of 0.350 x 10(9) cells/L or greater, nonadherent patients who initiated HAART when the CD4+ cell count was 0.200 to 0.349 x 10(9) cells/L had statistically elevated mortality rates (adjusted relative hazard, 2.56 [95% CI, 1.36 to 4.84]; P = 0.004). However, compared with adherent patients who initiated HAART at a CD4+ cell count of 0.350 x 10(9) cells/L or greater, adherent patients who initiated HAART when the CD4+ cell count was 0.200 to 0.349 x 10(9) cells/L had statistically similar mortality rates (adjusted relative hazard, 0.82 [CI, 0.45 to 1.49]; P > 0.2).Delaying HAART until the CD4+ cell count falls to 0.200 x 109 cells/L does not increase the mortality rate in HIV-infected patients with good medication adherence. Mortality rates increase if HAART is initiated below 0.200 x 10(9) cells/L. Also, nonadherent patients have higher mortality rates than adherent patients with similar CD4+ cell counts. Above a CD4+ cell count of 0.200 x 10(9) cells/L, medication adherence is the critical determinant of survival, not the CD4+ cell count at which HAART is begun.
The Duty to Attend Upon the Sick
Authors: Martin L. Proudfoot
Journal: JAMA (1992)

<h3>To the Editor.</h3> —The recent<i>JAMA</i>editorial<sup>1</sup>in regard to care of patients with the acquired immunodeficiency syndrome (AIDS) demonstrates a regrettable attitude of retribution toward practicing physicians. A physician's humanity is indicted as a cause for removing him or her from practice. In response to a research article in the same edition, the authors of the editorial call for removing the license from physicians who refuse to treat AIDS patients. Who is served by this vindictive point of view? Not the reluctant physicians. Not physicians who care for AIDS patients nor AIDS patients themselves. The glib threat of the authors serves only their own sense of indignation. Intimidation plays no part in nurturing compassion in anxious physicians. Who wants care from a personal physician who is motivated by a threat? Persecution of fearful physicians is a help to none. There is no time to waste on adversarial proceedings
Disturbance of the Blood T:B Lymphocyte Ratio in Lepromatous Leprosy
Authors: John M. Dwyer, Ward E. Bullock, James P. Fields
Journal: New England Journal of Medicine (1973)

A significant increase in absolute numbers of bone-marrow-derived (B) lymphocytes and a significant decrease in the absolute numbers of lymphocytes forming spontaneous rosettes with sheep red blood cells (thymus derived [T] lymphocytes) were observed in peripheral blood among a group of 17 patients with lepromatous leprosy. Lymphocyte response to phytohemagglutinin after three days of culture was significantly reduced in the patient group. A generalized impairment of delayed hypersensitivity responses was observed among our patients as manifested by skin-test anergy to lepromin and fungal antigens. These findings suggest that anergy of the cellular immune system in patients with lepromatous leprosy may be secondary to the destruction of T lymphocytes or disturbance of their recirculation. (N Engl J Med 288:1036–1039, 1973)
The genetic background modulates susceptibility to mouse liver Mallory-Denk body formation and liver injury
Authors: Shinichiro Hanada, Pavel Strnad, Elizabeth M. Brunt, Bishr M. Omary
Journal: Hepatology (2008)

Abstract Mallory-Denk bodies (MDBs) are hepatocyte inclusions found in several liver diseases and consist primarily of keratins 8 and 18 (K8/K18) and ubiquitin that are cross-linked by transglutaminase-2. We hypothesized that genetic variables contribute to the extent of MDB formation, because not all patients with an MDB-associated liver disease develop inclusions. We tested this hypothesis using five strains of mice (FVB/N, C3H/He, Balb/cAnN, C57BL/6, 129X1/Sv) fed for three months (eight mice per strain) the established MDB-inducing agent 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC). MDB formation was compared using hematoxylin-and-eosin staining, or immunofluorescence staining with antibodies to K8/K18/ubiquitin, or biochemically by blotting with antibodies to transglutaminase-2/p62 proteins and to K8/K18/ubiquitin to detect keratin cross-linking. DDC feeding induced MDBs in all mouse strains, but there were dramatic strain differences that quantitatively varied 2.5-fold ( P &lt; 0.05). MDB formation correlated with hepatocyte ballooning, and most ballooned hepatocytes had MDBs. Immunofluorescence assessment was far more sensitive than hematoxylin-and-eosin staining in detecting small MDBs, which out-numbered (by ˜30-fold to 90-fold) but did not parallel their large counterparts. MDB scores partially reflected the biochemical presence of cross-linked keratin-ubiquitin species but not the changes in liver size or injury in response to DDC. The extent of steatosis correlated with the total (large+small) number of MDBs, and there was a limited correlation between large MDBs and acidophil bodies. Conclusion: Mouse MDB formation has important genetic contributions that do not correlate with the extent of DDC-induced liver injury. If extrapolated to humans, the genetic contributions help explain why some patients develop MDBs whereas others are less likely to do so. Detection and classification of MDBs using MDB-marker-selective staining may offer unique links to specific histological features of DDC-induced liver injury. (Hepatology 2008.)
Cutaneous Granuloma Formations in Crohn's Disease
Authors: Julie K. Billings
Journal: JAMA (1986)

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False Hope on Drug Availability
Authors: Deborah Klapp
Journal: JAMA (1985)

To the Editor.—  The article on adenosine monophosphate (AMP) that appeared in the March 8, 1985, issue ofThe Journaland corresponding editorial led many readers to think that AMP is available for use (albeit with caution) for treating herpes zoster neuralgia.1,2We received almost daily calls from physicians and pharmacists in Florida and at first thought the product was available from several manufacturers.3,4After calling manufacturers, the Food and Drug Administration, and finally the primary author, we discovered that AMP is no longer available except through Dr Sklar, who has a new drug application and a source of supply. We strongly suggest that information about the availability of drugs accompany such articles so that false hopes are not raised.
Estimation of myocardial involvement in patients with acute myocardial infarction by two-dimensional echocardiography.
Authors: J V Nixon, K A Narahara, T C Smitherman
Journal: Circulation (1980)

To determine whether real-time two-dimensional echocardiography (2-D echo) can estimate the extent of myocardial involvement in patients with acute myocardial infarction (MI), regional wall motion on serial short-axis 2-D echo recordings was analyzed and the summed scores were compared with estimates of infarct involvement by thallium-201 reperfusion (Tl) and technetium-99m stannous pyrophosphate (99mTc-PYP) scintigraphy. Thirty-two consecutive male patients admitted with their first MI were studied; 10 patients had anterior, 16 had inferior and six had subendocardial MIs. Two patients were technically unsuitable for 2-D echo studies. Twenty patients had Tl scintigrams and 29 had 99MTc-PYP scintigrams. Summed 2-D echo scores correlated closely with estimates of infarct involvement by Tl (r = 0.87) and with estimates of infarct size by 99mTc-PYP (r = 0.74). The location of MI by 2-D echo agreed with the electrocardiographic location in 26 of 29 patients; discrepancies occurred in one inferior and two subendocardial MIs. Predischarge 2-D echo failed to identify extension of transmural infarction. However, two patients whose subendocardial MIs progressed to transmural MIs were identified. This study shows that 2-D echo is a valid method for the early estimation of the extent of myocardial involvement in patients with acute MI, especially transmural MIs. In particular, 2-D echo correlates closely with Tl reperfusion scintigraphy because both detect areas of ischemia and infarction.