tbuckley/cabot-search huggingface dataset:
A dynamic T cell–limited checkpoint regulates affinity-dependent B cell entry into the germinal center
Authors: Tanja A. Schwickert, Gabriel D. Victora, David R. Fooksman, Alice O. Kamphorst, Monica R. Mugnier, Alexander D. Gitlin, Michael L. Dustin, Michel C. Nussenzweig
Journal: The Journal of Experimental Medicine (2011)

The germinal center (GC) reaction is essential for the generation of the somatically hypermutated, high-affinity antibodies that mediate adaptive immunity. Entry into the GC is limited to a small number of B cell clones; however, the process by which this limited number of clones is selected is unclear. In this study, we demonstrate that low-affinity B cells intrinsically capable of seeding a GC reaction fail to expand and become activated in the presence of higher-affinity B cells even before GC coalescence. Live multiphoton imaging shows that selection is based on the amount of peptide–major histocompatibility complex (pMHC) presented to cognate T cells within clusters of responding B and T cells at the T–B border. We propose a model in which T cell help is restricted to the B cells with the highest amounts of pMHC, thus allowing for a dynamic affinity threshold to be imposed on antigen-binding B cells.
A Multicellular Basis for the Origination of Blast Crisis in Chronic Myeloid Leukemia
Authors: Rainer K. Sachs, Kerstin Johnsson, Philip Hahnfeldt, Janet Luo, Allen Chen, Lynn Hlatky
Journal: Cancer Research (2011)

Abstract Chronic myeloid leukemia (CML) is characterized by a specific chromosome translocation, and its pathobiology is considered comparatively well understood. Thus, quantitative analysis of CML and its progression to blast crisis may help elucidate general mechanisms of carcinogenesis and cancer progression. Hitherto, it has been widely postulated that CML blast crisis originates mainly via cell-autonomous mechanisms such as secondary mutations or genomic instability. However, recent results suggest that carcinogenic transformation may be an inherently multicellular event, in departure from the classic unicellular paradigm. We investigate this possibility in the case of blast crisis origination in CML. A quantitative, mechanistic cell population dynamics model was employed. This model used recent data on imatinib-treated CML; it also used earlier clinical data, not previously incorporated into current mathematical CML/imatinib models. With the pre-imatinib data, which include results on many more blast crises, we obtained evidence that the driving mechanism for blast crisis origination is a cooperation between specific cell types. Assuming leukemic–normal interactions resulted in a statistically significant improvement over assuming either cell-autonomous mechanisms or interactions between leukemic cells. This conclusion was robust with regard to changes in the model's adjustable parameters. Application of the results to patients treated with imatinib suggests that imatinib may act not only on malignant blast precursors, but also, to a limited degree, on the malignant blasts themselves. Cancer Res; 71(8); 2838–47. ©2011 AACR.
Abstract 4090: Akt2-specific signaling in prostate cancer maintenance.
Authors: Yuet Ming Rebecca Chin, Steve Balk, Alex Toker
Journal: Cancer Research (2013)

Abstract Mutations and amplification in genes regulating the PI 3-K/Akt pathway are common in prostate cancer, with deletion or mutations of PTEN being the most frequent. This has led to major efforts in developing anti-cancer drugs targeting the Akt pathway. Although the role of Akt in tumorigenesis has been studied extensively, little is known regarding isoform-specificity, and it is largely assumed that Akt isoforms play redundant roles in regulating cancer cell survival. In this study, we have developed a tet-on inducible system for expressing Akt1/2/3 shRNAs to determine the role of Akt isoforms in prostate cancer progression. Three-dimensional (3D) matrigel cultures are employed to better recapitulate tumors growing in vivo. Administration of doxycycline (dox) in Akt1 or Akt2 shRNA PTEN-deficient LNCaP cells at the start of culture resulted in the inhibition of spheroid formation, suggesting an important role of both Akt1 and Akt2 in the initial growth of spheroids. Conversely, when spheroids were allowed to form for 7 days, followed by dox for further 10 days, no difference was observed between Akt1-depleted and control spheroids. In contrast, silencing of Akt2 resulted in complete disintegration of spheroids. Confocal microscopy studies showed a significant induction of active caspase-3 and fragmented nuclei in Akt2-silenced cells. Moreover, whereas Akt1 is uniformly expressed, Akt2 is localized in the cytoplasm and/or on the plasma membrane. Interestingly, the differences of effect of Akt isoforms on cell survival in conventional 2D culture are considerably more modest. The exclusive requirement of Akt2 for survival is also observed in PC3 prostate cancer cells, which are also PTEN-deficient. Importantly, our preliminary data indicated that Akt2, but not Akt1 knockdown, led to tumor regression in the LnCaP xenograft model. These results indicate that Akt2, but not Akt1, plays a critical role in prostate cancer maintenance. Current efforts are aimed at identifying novel Akt isoform-specific substrates that contribute to prostate cancer progression using a genome-wide proteomic screen. The results of these studies could point to new targets for anti-cancer therapeutics. This work was supported by grants from NIH (A.T., CA122099; R.C., 1K99CA157945-01, T32 CA081156-09) Citation Format: Yuet Ming Rebecca Chin, Steve Balk, Alex Toker. Akt2-specific signaling in prostate cancer maintenance. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4090. doi:10.1158/1538-7445.AM2013-4090
Isolated thrombocytopenia in patients infected with HIV: Treatment with intravenous gammaglobulin
Authors: James B. Bussel, Joseph S. Haimi
Journal: American Journal of Hematology (1988)

Isolated thrombocytopenia occurs frequently in patients infected with HIV. Studies of mechanisms of thrombocytopenia and clinical response to therapy suggest that the thrombocytopenia is often antibody mediated (ITP). The best approach to treatment of these patients is uncertain in that the routine modalities (steroids, splenectomy, vinca alkaloids) that are used to increase the platelet count in patients with classic ITP are known to be immunosuppressive. We report here the results of intravenous gammaglobulin (IVGG) treatment of 22 patients with HIV-related acute and chronic ITP who had severe thrombocytopenia and bleeding symptoms. Only one patient had an opportunistic infection at the time of treatment. Eight patients were homosexual, eight had hemophilia, three were i.v. drug abusers, two children had congenital acquisition of HIV, and one was the wife of an HIV + i.v. drug abuser. The average pretreatment platelet count was 22,000/microliter (hemophiliacs were treated at higher platelet counts than were the other patients), and the mean peak platelet count measured on days 5 to 8 was 182,000/microliter. Nineteen of 22 patients had peak platelet counts greater than 50,000/microliter following IVGG and 17/22 had peak counts greater than 100,000/microliter. After the initial infusions, all but three refractory patients could maintain adequate platelet counts with IVGG alone infused no more often than once every 2 weeks. The outcomes for the 22 patients after multiple maintenance IVGG infusions were remission, 5; stable without therapy, 1; maintenance, 13; and refractory, 3. The eight hemophiliacs with ITP responded better than did the eight homosexual ITP patients; their mean peak platelet count was 227,000/microliter versus 142,000/microliter in the homosexuals. In summary, patients with HIV-related ITP without opportunistic infections responded well to IVGG, with peak platelet counts comparable to those of ITP patients not infected with HIV. IVGG may be a useful therapy of ITP in HIV+ patients, since it appears to be less immunosuppressive than are conventional therapies, and none of the 22 HIV+ patients developed an opportunistic infection while receiving IVGG alone.
STUDIES ON BACTERIEMIA
Authors: David E. Rogers, Marian Ann Melly
Journal: The Journal of Experimental Medicine (1957)

Intravenous injection of staphylococci produced a marked, transient granulocytopenia inrabbits. Leukopenia was rapidly followed by return of polymorphonuclear leukocytes to the peripheral blood, and normal circulating granulocyte levels were reestablished within 20 to 40 minutes. Differential arterio-venous leukocyte studies showed that polymorphonuclear leukocytes were trapped within the pulmonary vascular bed and, less constantly, in the splanchnic viscera during the initial 10 to 20 minutes following the injection of staphylococci. Granulocytes were subsequently found in larger numbers in blood leaving the lungs and splanchnic tissues, suggesting that entrapped polymorphonuclear leukocytes rapidly reentered the blood stream. This sequence of changes in circulating granulocytes was not significantly altered by splenectomy or the administration of cortisone. It has previously been shown that virtually all staphylococci in the blood stream are found within circulating polymorphonuclear leukocytes 10 to 40 minutes after the injection of culture (9). It is during this period that granulocytes return to the blood stream in large numbers. These observations suggest that staphylococci are phagocyted by polymorphonuclear leucocytes temporarily sequestered in the lungs and splanchnic viscera. It appears probable that some sequestered granulocytes containing living staphylococci subsequently return to the circulation. Such intraleukocytic staphylococci are believed to play a role in the maintenance of bacteriemia.
Staffing of Casualty Departments
Authors: R. Burkitt
Journal: BMJ (1970)

I have a vivid recollection of one of my teachers whose habit was as I was about to divide the second cranial nerve in an enucleation to say, "it was the right eye, wasn't it, Payne?"One knew very well that he would say this, but it never failed to send a shiver down the spine, and I have always felt compelled to verify the laterality by all possible means in the theatre imme- diately before operations of this sort.-Iam, etc., I.
Patient's charter in outpatient services.
Authors: M. P. Corlett
Journal: BMJ (1992)

consent, as they move within the NHS, house officers may be unaware that they are not protected against prescribed diseases such as tuberculosis and hepatitis B. It may well be that Lewisham Hospital's handbook mentions the occupational health department.Luisa Dillner's review of Stress and the Medical Profession seems to confirm my views.2The pen- ultimate paragraph suggests that doctors need an accessible counselling service and an occupational health service that is geared to recognising stress.The standard and quality of occupational health services vary considerably within the NHS, but it is essential that all staff, including doctors, become more aware of the services they offer.
Making Optimum Use of the Microbiology Laboratory
Authors: Raymond C. Bartlett
Journal: JAMA (1982)

PREVIOUS articles in this series have emphasized the need for physicians to review with microbiologists ways of obtaining results from the microbiology laboratory that are more useful. Physicians and microbiologists must work together to facilitate interpretation of laboratory data used to guide antimicrobial therapy. The techniques used and the mode of reporting information should optimize therapy at minimum cost. <h3>ANTIMICROBIAL SUSCEPTIBILITY: 'S-I-R' VS MICs</h3> In recent years, much technological change has occurred in the in vitro testing of antimicrobial susceptibility of bacteria isolated from clinical specimens. The disk method of testing was applied initially in a highly unstandardized manner and led to unreliable results in many instances. More recently, the Kirby-Bauer method has become highly standardized in the majority of laboratories. Still, most physicians are only vaguely aware of how the designations "S," "I," and "R," which stand for<i>sensitive, intermediate (or indeterminate) sensitivity</i>, and<i>resistance</i>, relate to achievable antimicrobial
Cancer of the Head and Neck
Authors: Gregory Matz
Journal: JAMA (1990)

In the second edition of Myers and Suen's book<i>Cancer of the Head and Neck</i>, the editors state that this text is "intended as a contemporary state-of-the-art depiction of the complex field of head and neck surgery." Although the editors have assembled a distinguished group of authors for the 40 chapters of this book, it seems to me to be an introductory text and fails as a comprehensive text of head and neck cancer. In reviewing a number of the chapters, I had the impression I was reading a condensed version of a complete chapter. Some of the material appeared to be incomplete. For example, the chapter "Oral Cavity Tumors" failed to mention any role for laser surgery, a major emerging area of treatment of oral-cavity and tongue cancers. In addition, this chapter failed to delineate well the various surgical approaches to oralcavity cancer, especially those techniques applicable to patients
Epstein-Barr Virus Infection and Persistent Fatigue
Authors: LEO E. HOLLISTER
Journal: Annals of Internal Medicine (1985)

Letters and Corrections1 April 1985Epstein-Barr Virus Infection and Persistent FatigueLEO E. HOLLISTER, M.D.LEO E. HOLLISTER, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-102-4-563_2 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: Those of us who were in the U.S. Navy Medical Corps during World War II and the Korean Conflict remember well a peculiar diagnosis temed "postinfectious mononucleosis asthenia." This diagnosis was made in those persons with definite infectious mononucleosis who complained of fatigue, poor exercise tolerance, and depression after all clinical signs of illness were over. They sometimes remained in hospital for months before they could return to duty. I am sure that many of my colleagues were of the opinion, as I was, that the diagnosis was a brick made of gold. Since the, I have...References1. JONESRAYMINNICKHICKSKIBLERLUCAS JGLMRD. Evidence for active Epstein-Barr virus infection in patients with persistent, unexplained illnesses: elevated anti-early antigen antibodies. Ann Intern Med. 1985;102:1-7. LinkGoogle Scholar2. STRAUSTOSATOARMSTRONG SGG. Persisting illness and fatigue in adults with evidence of Epstein-Barr virus infection. Ann Intern Med. 1985;102:7-16. LinkGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Veterans Administration Medical Center Palo Alto, CA 94304 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 April 1985Volume 102, Issue 4Page: 563-563KeywordsEpstein-Barr virusExerciseFatigue Issue Published: 1 April 1985 PDF downloadLoading ...
An Applicant's Evaluation of a Medical House Officership
Authors: Martin J. Raff, Ira S. Schwartz
Journal: New England Journal of Medicine (1974)

Abstract The selection of a house-officership program by senior medical students requires information that can only be obtained through a visit to the institution under consideration. Arrangements to obtain the information can be made through the appropriate directors of house-staff training. In addition to the formal interview, the applicants should direct inquiries to house officers currently in training. These conversations will elicit data concerning the facilities available for patient care, the house officer's involvement with those facilities, and the types and numbers of patients and their diseases. Exploration of educational opportunities can be furthered by questions designed to determine the quantity and quality of the existing house staff, attending staff, and formal instructional programs. Finally, information related to the regional environment and the social and cultural climate into which the house officers and their families will move can best be gained from questions directed to their peers. (N Engl J Med 291:601–605, 1974)
A Comprehensive Investigation of Molecular Features and Prognosis of Lung Adenocarcinoma with Micropapillary Component
Authors: Yang Zhang, Rui Wang, Deng Cai, Yuan Li, Yunjian Pan, Haichuan Hu, Lei Wang, Hang Li, Ting Ye, Xiaoyang Luo, Yiliang Zhang, Bin Li, Lei Shen, Yihua Sun, Haiquan Chen
Journal: Journal of Thoracic Oncology (2014)
WATER-DRIVEN BREAST PUMP
Authors: Isaac A. Abt
Journal: JAMA (1926)

It has frequently occurred to me that a breast pump might be devised in which the suction is produced by water pressure. Such a pump could be used in any home by attaching it to a water faucet. The advantages of this water-power breast pump would obviously be its low cost and ease with which it could be carried about. The first experiments with a water pump, conducted some three years ago, were unsatisfactory. It produces suction only, and, unlike the electric pump, there is no alternate back pressure which relieves the congestion in the nipple occurring during each suction impulse. As a consequence, the nipples became sore in our first experiment with the water-driven pump. Therefore the idea was temporarily abandoned. Subsequent tests have shown that a water-driven pump can be successfully used in conjunction with a suction-regulating device, when it is desired to promote the flow
Airway Pressures and Ventilation in Emphysema during and after Respiratory Infections
Authors: R. S. Jones
Journal: Thorax (1958)

APPARATUS.-Pressures were measured at the mouth during natural breathing by the method of airway interruption (Neegaard and Wirz, 1927; Vuilleumier, 1944; Otis and Proctor, 1948).An apparatus was designed to produce interruption at the points of maximum velocity of airflow in each phase of the respiratory cycle.The equipment was mounted on a trolley, so that observations were possible at the bed- side with a minimum of discomfort to patients ill with acute respiratory infections.In the apparatus shown diagrammatically in Figs.I and 2, the interrupter, I, was placed in the tube between the patient and the spirometer, S, which was of the Bernstein type (Bernstein, D'Silva, and K
Biventricular stimulation in heart failure patients with ICD-indication - First experience with a new implantable cardioverter/defibrillator
Authors: Barbara Lamp, Bert Hansky, Uwe Schulz, Nikola Bogunovic, Gero Tenderich, Axel Meissner, Reiner Körfer, Dieter Horstkotte, Jürgen Vogt
Journal: European Journal of Heart Failure (2000)
Transfer of Carbon Monoxide and Nitrous Oxide in the Artificially Perfused Sheep Placenta
Authors: JAMES METCALFE, WALDEMAR MOLL, HEINZ BARTELS, PETER HILPERT, JULIAN T. PARER
Journal: Circulation Research (1965)

1. The sheep placenta was perfused in situ through the umbilical circulation with a dextran solution containing carbon monoxide and nitrous oxide. 2. The concentration of carbon monoxide in the perfusion fluid after passage through the umbilical circulation was found to be 19±3% of its concentration in the entering perfusion fluid. This represents "shunted umbilical flow," the percentage of the perfusion fluid (and presumably of the fetal blood) which does not exchange substances with the maternal blood. 3. The concentration of nitrous oxide in the perfusion fluid after passing the placental membrane and before admixture of shunted perfusion fluid was found to be 14±4% of its original concentration in the perfusion fluid when the maternal arterial concentration was zero. This leads us to the conclusion that the perfusion fluid did not at any time reach the maternal arterial concentration and that no functionally effective countercurrent flow pattern exists in the sheep placenta. 4. Reversal of the flow direction in the fetal umbilical vessels resulted in a slight increase of the N 2 O concentration in the perfusion fluid after passing the placental membrane and before admixture of the shunted perfusion fluid. 5. We suggest that the placenta contains a mixture of countercurrent and concurrent flow units. Diffusion of gases along the capillaries within the comparatively thick placental membrane of the sheep is also presented as a possibility.
Re: Marko Babjuk, Willem Oosterlinck, Richard Sylvester, et al. EAU Guidelines on Non-Muscle-Invasive Urothelial Carcinoma of the Bladder. Eur Urol 2008;54:303–14
Authors: Anna Orsola, Lluís Cecchini, Juan Morote
Journal: European Urology (2008)
Tc-99m HMPAO Labeled White Blood Cell Imaging in a Child With Eosinophilic Lung Disease
Authors: Efstratios Moralidis, Eugenia Papakonstantinou, Georgios Arsos, Nikolaos Boussios, Dimitrios Koliouskas, Constantinos Karakatsanis
Journal: Clinical Nuclear Medicine (2008)

In radiolabeled leukocyte imaging, Tc-99m HMPAO has a significantly higher selectivity for eosinophils than neutrophils, but this may be clinically meaningful in disorders with eosinophilic infiltration. We present the case of a 2-year-old boy with infection who also developed drug-induced eosinophilic lung disease, as established later by bronchoalveolar lavage and discontinuation of the responsible antistaphylococcal agent. In the investigation of sepsis, diffusely increased pulmonary accumulation of Tc-99m HMPAO labeled leukocytes was observed. These findings were consistent with eosinophilic lung infiltration and underline the importance of clinical and laboratory data in the comprehensive interpretation of Tc-99m HMPAO labeled leukocytes scans.
Pneumocystis pneumonia in an HIV-negative patient with no overt risk factors on presentation
Authors: G. Sandhu, R. Dasgupta, A. Ranade, M. Baskin
Journal: European Respiratory Journal (2010)

that seen in asthma.It is tempting to speculate that some individuals are genetically predisposed to over-express HLA-G in response to specific signals.Once secreted, HLA-G could promote a cascade of events that result in worsening inflammation.Several polymorphisms in the promoter region of HLA-G coincide with transcription factor binding sites could account for inter-individual differences in expression of HLA-G [10].We previously identified a polymorphism in the 3' untranslated region of HLA-G which disrupts a microRNA target site and demonstrated allele-specific expression of HLA-G in the presence of microRNAs that bind to that target [5].Therefore, either lack of suppression or over-expression of HLA-G could explain the association we report here with asthma.We note that the small numbers of subjects in this study precludes more detailed analysis of relationships between genetic variation and HLA-G expression.Futuremore, larger studies are required to clarify the potential modulating role of HLA-G on the clinical manifestations of asthma and the role of genetic variation on expression levels.In conclusion, sHLA-G is present in greater concentrations in BAL in mild asthma.We suggest that the overexpression or lack of suppression of HLA-G contributes to the disease process and that sHLA-G represents a novel pathway of asthma pathogenesis.
What's the predicted outcome? Explanatory and predictive properties of the quantum probability framework
Authors: Timothy J. Pleskac, Peter D. Kvam, Shuli Yu
Journal: Behavioral and Brain Sciences (2013)

Abstract Quantum probability (QP) provides a new perspective for cognitive science. However, one must be clear about the outcome the QP model is predicting. We discuss this concern in reference to modeling the subjective probabilities given by people as opposed to modeling the choice proportions of people. These two models would appear to have different cognitive assumptions.